The DOI matches its Crossref record; 139 of the 139 references it cites were found in a registry or an index; 78 of the 141 sources its claims cite were checked for support.
Fetal hemoglobin in sickle cell anemia
Open accessAbstract
Abstract Fetal hemoglobin (HbF) can blunt the pathophysiology, temper the clinical course, and offer prospects for curative therapy of sickle cell disease. This review focuses on (1) HbF quantitative trait loci and the geography of β-globin gene haplotypes, especially those found in the Middle East; (2) how HbF might differentially impact the pathophysiology and many subphenotypes of sickle cell disease; (3) clinical implications of person-to-person variation in the distribution of HbF among HbF-containing erythrocytes; and (4) reactivation of HbF gene expression using both pharmacologic and cell-based therapeutic approaches. A confluence of detailed understanding of the molecular basis of HbF gene expression, coupled with the ability to precisely target by genomic editing most areas of the genome, is producing important preliminary therapeutic results that could provide new options for cell-based therapeutics with curative intent.
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Claims the paper makes
34 Partly supported · 31 No basis given · 25 No full text of the sources · 19 Supported · 11 Own interpretation · 8 Sources not found · 7 Supported so far · 5 Not supported · 1 Couldn’t confirm · 1 Not checked yet · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“An intronic SNP (rs35685045) in ANTXR1 (TEM8; chr2p13) was associated with HbF in 4 cohorts of adult AI haplotype patients.41,42”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Disputedcites [41] Vathipadiekal, 2016, A candidate transacting modulator of fetal hemoglobin gene expression in the Arab-Indian haplotype of sickle cell anemia, Am J Hematol sourceExperimental — accuracy not yet measured
The Results section identifies rs35685045 as an intronic ANTXR1 SNP associated with HbF, but it does not support association in four AI-haplotype cohorts. The Results report association in the Saudi AI cohorts and explicitly state that it was not found in the Indian AI cohort. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
- Not checked — no full text of the sourcecites [42] Al-Ali, 2018, ANTXR1 intronic variants are associated with fetal hemoglobin in the Arab-Indian haplotype of sickle cell disease, Acta Haematol source
plaincorrelationaln = 4- Asserted: passes — The authors put it forward as true.
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- Disputed
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In the paper
“Therefore, even when started early in life, the HbF response to hydroxyurea might wane.88”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Disputedcites [88] Hankins, 2014, From infancy to adolescence: fifteen years of continuous treatment with hydroxyurea in sickle cell anemia, Medicine (Baltimore) sourceExperimental — accuracy not yet measured
The Results section reports that HbF levels remained above expected values for untreated individuals after 15 years of hydroxyurea therapy. The Discussion says hematologic effects were sustained and found no apparent tolerance among patients with adequate adherence. Rather than reporting a waning HbF response, this cohort's findings point to a sustained one. (LLM, conf=0.86)
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hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“BCL11A is a repressor of HbF gene expression.”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Supportedcites [4] Akinsheye, 2011, Fetal hemoglobin in sickle cell anemia, Blood source
The Introduction describes the suppressive effects of BCL11A on HBG expression. It hedges the mechanism by which BCL11A acts, not its repressive role. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [14] Menzel, 2007, A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15, Nat Genet source
- Partly supportedcites [15] Sedgewick, 2008, BCL11A is a major HbF quantitative trait locus in three different populations with β-hemoglobinopathies, Blood Cells Mol Dis sourceExperimental — accuracy not yet measured
The Results and Discussion section (page unavailable) says BCL11A functions as a transcriptional repressor and that its variants are associated with HbF levels. It also says the mechanism by which BCL11A modulates HbF production was not understood; it does not establish that BCL11A represses HbF gene expression specifically. (LLM, conf=0.89)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Inactivation and activation of genes within the b-globin gene cluster holds the keys to reactivating for therapeutic gain the usually dormant HbF genes.[6][7][8][9][10][11][12]”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Not checked — no full text of the sourcecites [6] Ikawa, 2019, Gene therapy of hemoglobinopathies: progress and future challenges, Hum Mol Genet source
- Supportedcites [7] Vinjamur, 2018, Recent progress in understanding and manipulating haemoglobin switching for the haemoglobinopathies, Br J Haematol source
The ‘Cis-acting sequences that control fetal globin expression’ section says that recruiting transcriptional activators to fetal-globin promoters could reactivate HbF. The ‘Current switching-based therapy efforts’ section describes disrupting sequences in the β-globin locus that silence HBG genes to induce HbF. Page numbers were not supplied in our copy. (LLM, conf=0.91)
- Supportedcites [8] Blobel, 2015, An international effort to cure a global health problem: A report on the 19th Hemoglobin Switching Conference, Exp Hematol source
The section “Transcription factor pathways involved in globin gene switching” describes reactivating fetal γ-globin in adult cells as a potential therapy and reports that a mutation in the γ-globin promoter activates fetal globin genes. It also discusses repression of γ-globin and therapeutic approaches to reversing it. The supplied passages do not give page numbers. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The most efficient means of treatment is interrupting disease pathophysiology by preventing deoxyHbS polymerization.”
§ Fetal hemoglobin in sickle cell anemia > Introduction
What the sources say
- Partly supportedcites [5] Eaton, 2017, Treating sickle cell disease by targeting HbS polymerization, Blood sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) identifies HbS polymerization as the root cause of sickle cell pathology and argues for directing more research and trials toward inhibiting it. It does not establish that preventing polymerization is the most efficient treatment; the Conclusion (page unavailable) says polymerization inhibitors still face hurdles before clinical use. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
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In the paper
“HbF is variably increased in nearly all HbS homozygotes.4”
§ Fetal hemoglobin in sickle cell anemia > Introduction
What the sources say
- Partly supportedcites [4] Akinsheye, 2011, Fetal hemoglobin in sickle cell anemia, Blood sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) defines sickle cell anemia as HbS homozygosity and says HbF levels remain above normal in most patients. It also describes substantial variation in HbF levels. The source says “most,” not “nearly all,” so the claim overstates how many patients have increased HbF. (LLM, conf=0.84)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The rate and extent of polymerization is modified by the erythrocyte HbF concentration. 2”
§ Fetal hemoglobin in sickle cell anemia > Introduction
What the sources say
- Supportedcites [2] Eaton, 1987, Hemoglobin S gelation and sickle cell disease, Blood source
In “Hemoglobin S Gelation and Sickle Cell Disease” (p. 1258, Fig. 9), the paper relates the fraction of HbF in an HbS mixture to the gelation delay time, a measure of polymerization rate. The same section says HbF has a marked effect on gelation, while its discussion of HbS–HbF solubility addresses the amount polymerized at equilibrium. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
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In the paper
“This can be accomplished by inducing sufficiently high levels of HbF in most sickle erythrocytes.5”
§ Fetal hemoglobin in sickle cell anemia > Introduction
What the sources say
- Supportedcites [5] Eaton, 2017, Treating sickle cell disease by targeting HbS polymerization, Blood source
The “Induce HbF synthesis” section says that HbF inhibits HbS polymerization and that treatment would be more effective if increased HbF were distributed among more red cells. It identifies inducing HbF synthesis in as many red cells as possible as a focus of current research. The paper describes inhibition rather than requiring complete elimination of polymerization. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
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In the paper
“The sentinel SNP marking this QTL is rs1427407.”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Supportedcites [19] Bauer, 2013, An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level, Science source
In the passage labeled Abstract (page not provided), the paper identifies rs1427407 as the SNP with the strongest association with fetal hemoglobin level among the common variants tested in the BCL11A enhancer. This supports describing it as the sentinel SNP for that QTL. (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
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In the paper
“Disruption of BCL11A and ZBTB7A binding sites led to 30% to 40% g globin and 75% to 80% F-cells.27”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Partly supportedcites [27] Weber, 2020, Editing a γ-globin repressor binding site restores fetal hemoglobin synthesis and corrects the sickle cell disease phenotype, Sci Adv sourceExperimental — accuracy not yet measured
The Results section (page not available) reports that editing the LRF/ZBTB7A or BCL11A binding sites separately increased γ-globin expression and produced approximately 74–81% F-cells in RBCs derived from sickle-cell HSPCs. It does not establish the stated 30–40% γ-globin range: for the −197 LRF-site edit, it reports 48 ± 3% of β-like globin transcripts. The Discussion describes simultaneous disruption of both sites as a future strategy, not the experiment yielding these results. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Functional variants of BCL11A are marked by single nucleotide polymorphisms (SNPs) in intron 2 that tag an erythroid-specific enhancer.19”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Supportedcites [19] Bauer, 2013, An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level, Science source
The paper states that HbF-associated variants localize to an erythroid enhancer of BCL11A (passage 6, indexed under Abstract). It also reports that the GWAS-marked intron-2 sequences specify erythroid-specific gene expression (passage 4). No page numbers are supplied in our copy. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“This enhancer consists of 3 DNase hypersensitive sites 162, 158, and 155 kb from the transcription initiation site.19”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Partly supportedcites [19] Bauer, 2013, An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level, Science sourceExperimental — accuracy not yet measured
The passage on DNase I hypersensitivity reports three erythroid sites in BCL11A intron 2, supporting the claim's site count. But it places them at +62, +58 and +55 kb from the transcription start site, not 162, 158 and 155 kb. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Partly supported
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In the paper
“Natural mutations and clustered regulary interspaced short palindromic repeat (CRISPR)-Cas9 disruption of the BCL11A and ZBTB7A binding sites are associated with a large effect on expression of the g-globin genes.12,21,27”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Not checked — no full text of the sourcecites [12] Wienert, 2018, Wake-up sleepy gene: reactivating fetal globin for beta-hemoglobinopathies, Trends Genet source
- Not checked — no full text of the sourcecites [21] Martyn, 2018, Natural regulatory mutations elevate the fetal globin gene via disruption of BCL11A or ZBTB7A binding, Nat Genet source
- Supportedcites [27] Weber, 2020, Editing a γ-globin repressor binding site restores fetal hemoglobin synthesis and corrects the sickle cell disease phenotype, Sci Adv source
The Introduction reports that natural mutations in the −200 and −115 promoter regions reduce binding of LRF (ZBTB7A) and BCL11A, respectively, inhibiting γ-globin silencing; it describes CRISPR-Cas9 disruption of these sites. The Results section “Targeting multiple regions in the HBG promoters induces HbF expression in adult HUDEP-2 erythroid cells” reports significant increases in γ-globin production after editing both regions, supporting the claimed large effect. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Every source the paper cites for this claim was checked and supports it.
In the paper
“AI, Senegal, and Benin haplotypes are derived from the CAR and Cameroon haplotypes.32”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Supportedcites [32] Shriner, 2018, Whole-genome-sequence-based haplotypes reveal single origin of the sickle allele during the Holocene wet phase, Am J Hum Genet source
The Results (Phylogenetic Network Analysis) identify a cluster containing HAP1 that accounts for the CAR, Cameroon, and Arabian/Indian haplotypes. They state that two additional clusters associated with Senegal and Benin were derived from HAP1 rather than directly from the ancestral haplotype. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
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In the paper
“Four markers representing the 3 HbF QTL, rs654815 and rs1427407 in BCL11A, rs66650371, the 3-bp deletion in MYB, and rs7482144 in the HBG2 promoter, accounted for 21.8% of HbF variability in 581 HbS homozygotes and patients with HbSb 0 thalassemia.”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Partly supportedcites [31] Gardner, 2018, g(HbF): a genetic model of fetal hemoglobin in sickle cell disease, Blood Adv sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelationaln = 581- Asserted: passes — The authors put it forward as true.
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- Partly supported
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In the paper
“HbF differences among haplotypes were not associated with BCL11A polymorphisms.39”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Partly supportedcites [39] Sebastiani, 2015, BCL11A enhancer haplotypes and fetal hemoglobin in sickle cell anemia, Blood Cells Mol Dis sourceExperimental — accuracy not yet measured
The Discussion says BCL11A enhancer haplotype pairs do not appear to explain the HbF difference between Arab-Indian (AI) and African-origin HBB haplotype populations. But it also says BCL11A polymorphisms are associated with HbF within AI patients, so 'not associated' overstates the finding. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
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- Partly supported
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In the paper
“Similar results were found in 186 patients with compound heterozygosity for HbS and HbC genes (HbSC) disease and 994 Tanzanian HbS homozygotes.31”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Supportedcites [31] Gardner, 2018, g(HbF): a genetic model of fetal hemoglobin in sickle cell disease, Blood Adv source
The Abstract reports that the genetic model explained a similar proportion of HbF variability in two validation cohorts: 27.5% in 186 HbSC patients and 23% in 994 Tanzanian HbSS patients. The Results report the same cohort sizes and findings. (LLM, conf=0.94)
plainn = 186- Asserted: passes — The authors put it forward as true.
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- Supported
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In the paper
“Improved F-cell survival is likely a result of HbF protecting the cell from HbS polymer-induced damage.[44][45][46][47]”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
What the sources say
- Partly supportedcites [44] Bertles, 1968, Irreversibly sickled erythrocytes: a consequence of the heterogeneous distribution of hemoglobin types in sickle-cell anemia, J Clin Invest sourceExperimental — accuracy not yet measured
The Discussion reports preferential survival of Hb SS erythrocytes with higher Hb F and a short lifespan for irreversibly sickled cells. The Abstract describes irreversible sickling as a presumed manifestation of membrane damage, but the paper does not identify HbS polymer-induced damage as the mechanism that HbF prevents. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [45] Dover, 1978, Individual variation in the production and survival of F cells in sickle-cell disease, N Engl J Med source
- Not checked — no full text of the sourcecites [46] Horiuchi, 1995, Survival of F-reticulocytes in sickle cell disease, Biochem Biophys Res Commun source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
- Partly supported
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In the paper
“F-cells do not resemble fetal erythrocytes save for their high levels of HbF.43”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
What the sources say
- Supportedcites [43] Khandros, 2020, Understanding heterogeneity of fetal hemoglobin induction through comparative analysis of F and A-erythroblasts, Blood source
The Discussion says F erythroblasts do not revert to a fetal-like state: their transcriptional differences from A erythroblasts are much smaller than those between fetal and adult erythroblasts, with little overlap in differentially expressed genes. It locates the principal F-cell changes at the β-globin locus, consistent with the claim's contrast between HbF expression and broader fetal-cell resemblance. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
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- Supported
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In the paper
“Unequal protection by HbF across the gamut of sickle cell disease complications might be partially explained by differences in the pathophysiologic roots of these complications.57,58”
§ Fetal hemoglobin in sickle cell anemia > HbF effects on clinical and hematologic phenotypes
What the sources say
- Not checked — no full text of the sourcecites [57] Kato, 2007, Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes, Blood Rev source
- Supportedcites [58] Kato, 2017, Intravascular hemolysis and the pathophysiology of sickle cell disease, J Clin Invest source
In “Evidence that hemolysis modulates SCD subphenotypes” (page unavailable), the review says HbF has its strongest effects on vaso-occlusion-associated complications and may offer less protection against hemolysis-associated complications. This directly supports the proposed explanation that differing pathophysiology may account for unequal protection. (LLM, conf=0.94)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Every source the paper cites for this claim was checked and supports it.
In the paper
“HbF is also associated with higher O 2 saturations.56”
§ Fetal hemoglobin in sickle cell anemia > HbF effects on clinical and hematologic phenotypes
What the sources say
- Supportedcites [56] Nkya, 2017, Fetal hemoglobin is associated with peripheral oxygen saturation in sickle cell disease in Tanzania, EBioMedicine source
The Results section reports that HbF was positively and independently associated with peripheral oxygen saturation (SpO2) in 1,175 individuals with sickle cell disease. The claim accurately paraphrases that association. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Nevertheless, an open-label trial in 606 African children aged 1 to 10 years treated with hydroxyurea found that HbF increased from 10.9% to 23.4%.”
§ Fetal hemoglobin in sickle cell anemia > HbF and malaria
What the sources say
- Partly supportedcites [73] Tshilolo, 2019, Hydroxyurea for children with sickle cell anemia in Sub-Saharan Africa, N Engl J Med sourceExperimental — accuracy not yet measured
Methods > Trial Design describes an open-label trial recruiting children aged 1 to 10 in sub-Saharan Africa, and Results > Enrollment and Retention says 606 began hydroxyurea. Results > Laboratory Benefits reports a 12.5-percentage-point increase in fetal hemoglobin after one year, but the passages in our copy do not give the claimed starting and ending values of 10.9% and 23.4%. (LLM, conf=0.85)
plaindirectn = 606- Asserted: passes — The authors put it forward as true.
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In the paper
“In 3764 patients in the pre-hydroxyurea era, HbF .8.6% was associated with improved survival.60”
§ Fetal hemoglobin in sickle cell anemia > HbF and survival
What the sources say
- Partly supportedcites [60] Platt, 1994, Mortality in sickle cell disease. Life expectancy and risk factors for early death, N Engl J Med sourceExperimental — accuracy not yet measured
The Survival section (p. 2) reports improved survival for patients with sickle cell anemia whose fetal hemoglobin exceeded 8.6%. The Methods (pp. 1–2) say more than 3,764 patients were enrolled in the broader study, but the survival comparison and risk-factor models used smaller groups; the claim incorrectly presents 3,764 as the number in the HbF analysis. Our copy does not explicitly establish the 'pre-hydroxyurea era' qualifier. (LLM, conf=0.87)
plaincorrelationaln = 3,764- Asserted: passes — The authors put it forward as true.
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- Partly supported
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In the paper
“Hydroxyurea is also used effectively in low-resource countries.73,79,80”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Supportedcites [73] Tshilolo, 2019, Hydroxyurea for children with sickle cell anemia in Sub-Saharan Africa, N Engl J Med source
The Discussion reports that hydroxyurea could be administered in low-resource settings and that treatment reduced painful events, infection, malaria, transfusion, and death among children with sickle cell anemia in sub-Saharan Africa. This supports the citing sentence as a broad statement, though the trial's findings concern that specific population and setting. (LLM, conf=0.92)
- Supportedcites [79] Deshpande, 2016, Hydroxyurea in sickle cell disease: our experience in Western India, Indian J Hematol Blood Transfus source
The Abstract (page unavailable) describes a one-year study of 70 sickle cell disease patients in Gujarat, India, and reports statistically significant improvements after hydroxyurea treatment. This supports the claim that hydroxyurea is used effectively in a low-resource-country setting. (LLM, conf=0.88)
- Supportedcites [80] John, 2020, Hydroxyurea dose escalation for sickle cell anemia in Sub-Saharan Africa, N Engl J Med source
The Conclusions report that, among children with sickle cell anemia in sub-Saharan Africa, hydroxyurea with dose escalation had superior clinical efficacy to fixed-dose treatment and equivalent safety. This supports the broad claim that hydroxyurea can be used effectively in low-resource countries; it does not imply that access is routine. (LLM, conf=0.92)
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In the paper
“This was associated with a decrease in the rate of malaria infection by more than 60%.73”
§ Fetal hemoglobin in sickle cell anemia > HbF and malaria
What the sources say
- Partly supportedcites [73] Tshilolo, 2019, Hydroxyurea for children with sickle cell anemia in Sub-Saharan Africa, N Engl J Med sourceExperimental — accuracy not yet measured
The Results (Effects on Survival; page unavailable) report increased fetal hemoglobin during treatment and a lower malaria infection rate, but the reported rates—46.9 versus 22.9 events per 100 patient-years—amount to a reduction of about 51%, not more than 60%. The Discussion (page unavailable) describes the reduction as more than 50% and suggests, rather than establishes, that fetal hemoglobin may explain it. (LLM, conf=0.91)
plaincorrelationaln = 606- Asserted: passes — The authors put it forward as true.
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In the paper
“Children aged 12.1 6 2.6 years with the highest HbF were protected from silent infarctions.68”
§ Fetal hemoglobin in sickle cell anemia > HbF and cerebrovascular disease
What the sources say
- Partly supportedcites [68] van der Land, 2016, Risk factor analysis of cerebral white matter hyperintensities in children with sickle cell disease, Br J Haematol sourceExperimental — accuracy not yet measured
The Abstract reports a mean age of 12.1 ± 2.6 years and suggests that high HbF may be protective for white matter hyperintensities. The Results specify a narrower finding: among children who already had these lesions, lower HbF was associated with greater lesion volume. The paper does not establish that children with the highest HbF were protected from developing silent infarctions. (LLM, conf=0.89)
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In 39 Italian patients with HbSb 1 thalassemia receiving more than 15 mg/kg of hydroxyurea, HbF increased from 4.7% to 10.9%.77”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Partly supportedcites [77] Di Maggio, 2018, Chronic administration of hydroxyurea (HU) benefits caucasian patients with sickle-beta thalassemia, Int J Mol Sci sourceExperimental — accuracy not yet measured
Results §2.2 (page unavailable) reports that HbF increased in the hydroxyurea-treated groups, including the ≥15 mg/kg/day group. But it gives a first-to-last HbF ratio of 1.12 for that dose group, not an increase from 4.7% to 10.9%. Methods §4.1 (page unavailable) identifies 60 patients in the ≥15 mg/kg/day group and 56 patients with HbS/β+-thalassemia; it does not identify the claimed subgroup of 39. (LLM, conf=0.88)
plaindirectn = 39- Asserted: passes — The authors put it forward as true.
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In the paper
“HbF did not provide protection from malaria in African (HbF, 5.6%) or Indian (HbF, 18.2%) sickle cell anemia patients.71,72”
§ Fetal hemoglobin in sickle cell anemia > HbF and malaria
What the sources say
- Partly supportedcites [71] Mmbando, 2015, Negative epistasis between sickle and foetal haemoglobin suggests a reduction in protection against malaria, PLoS One sourceExperimental — accuracy not yet measured
The Results report higher HbF among HbSS patients with malaria than among those without it (8.10% versus 5.59%), and the Discussion interprets this as suggesting a loss of malaria protection with increasing HbF. The study population was in Tanzania; the paper does not report malaria outcomes for Indian sickle cell anemia patients or substantiate the claimed 18.2% figure. Page numbers were not available in our copy. (LLM, conf=0.88)
- Partly supportedcites [72] Purohit, 2016, Fetal hemoglobin modifies the disease manifestation of severe Plasmodium Falciparum malaria in adult patients with sickle cell anemia, Mediterr J Hematol Infect Dis sourceExperimental — accuracy not yet measured
In the study text (page unavailable), the Indian cohort had mean HbF of 18.2%, and higher HbF was associated with greater severity of falciparum malaria. The paper does not establish that HbF provided no protection from malaria infection: it also says HbF can diminish parasite growth. It reports no African cohort with HbF of 5.6%. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Increased HbF associated with taking 15 to 35 mg/kg hydroxyurea improved survival in 393 HbS homozygotes (HR: 0.36; 95% CI: 0.17-0.73).62”
§ Fetal hemoglobin in sickle cell anemia > HbF and survival
What the sources say
- Partly supportedcites [62] Fitzhugh, 2015, Hydroxyurea-Increased fetal hemoglobin Is associated with less organ damage and longer survival in adults with sickle cell anemia, PLoS One sourceExperimental — accuracy not yet measured
The Results (Table 3; page unavailable) report the stated hazard ratio and confidence interval for 15–35 mg/kg/day hydroxyurea versus no hydroxyurea. But Table 4 lists 383 patients with HbSS (130 untreated and 253 treated), not 393. The paper describes an association with survival, not a demonstrated causal improvement attributable to increased HbF. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Every source the paper cites for this claim was checked and supports it.
In the paper
“A meta-analysis of 7 studies with 2477 hydroxyurea era cases showed that HbF was associated with reduced mortality (hazard ratio [HR]: 0.97; 95% confidence interval [CI]: 0.94-1.0).61”
§ Fetal hemoglobin in sickle cell anemia > HbF and survival
What the sources say
- Supportedcites [61] Maitra, 2017, Risk factors for mortality in adult patients with sickle cell disease: a meta-analysis of studies in North America and Europe, Haematologica source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelationaln = 2,477- Asserted: passes — The authors put it forward as true.
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In the paper
“In a phase 1/2 study, a similar HbA T87Q -lentiviral construct was introduced into autologous CD34 1 stem and progenitor cells that were infused into myeloablated patients with severe forms b thalassemia.The requirement for chronic transfusion was reduced or eliminated in all patients.116”
§ Fetal hemoglobin in sickle cell anemia > Cell-based HbF-inducing therapeutics
What the sources say
- Partly supportedcites [116] Thompson, 2018, Gene therapy in patients with transfusion-dependent β-thalassemia, N Engl J Med sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
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Every source the paper cites for this claim was checked and supports it.
In the paper
“Dose escalation was also superior to fixed dosing when studied in Ugandan children.80”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Supportedcites [80] John, 2020, Hydroxyurea dose escalation for sickle cell anemia in Sub-Saharan Africa, N Engl J Med source
The Trial Design section places the study at the Mulago Hospital Sickle Cell Clinic in Kampala, Uganda. The Conclusions report that dose escalation had superior clinical efficacy to fixed-dose hydroxyurea in children with sickle cell anemia. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Hydroxyurea was noninferior to transfusion for reducing transcranial Doppler flow velocities in selected children at high risk for stroke.”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Partly supportedcites [90] Ware, 2016, Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial, Lancet sourceExperimental — accuracy not yet measured
The Discussion reports that hydroxyurea was non-inferior to continued transfusions for maintaining TCD velocities in selected children with sickle cell anaemia at high risk for primary stroke. The claim says “reducing” velocities, but the trial tested maintenance after initial transfusion therapy, not whether hydroxyurea was non-inferior at lowering elevated velocities. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, all children seem to have a robust HbF response to hydroxyurea that retards the natural age-related fall in HbF.87”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Partly supportedcites [87] Wang, 2011, Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG), Lancet sourceExperimental — accuracy not yet measured
The Results (Organ Function; page not provided) report that HbF remained relatively stable in the hydroxyurea group while it declined with age in the placebo group, with a 5.3% higher mean HbF at exit. These are group-level findings in very young children; they do not establish a robust response in every child or in children of all ages. (LLM, conf=0.88)
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“By inducing increased levels of HbF through mechanisms that include suppressing erythropoiesis, hydroxyurea was first associated with reduction of morbidity and mortality in adults.81,82”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Partly supportedcites [81] Charache, 1995, Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia, N Engl J Med sourceExperimental — accuracy not yet measured
The Abstract reports fewer painful crises, cases of chest syndrome, and transfusions among adults receiving hydroxyurea, supporting reduced morbidity. Results According to Treatment Assignment states that deaths did not differ significantly between groups, so reduced mortality is not established. The Discussion notes hematopoietic depression but says the mechanism of benefit is unclear; it does not establish suppression of erythropoiesis as the route to increased HbF. Page numbers were not available in our copy. (LLM, conf=0.92)
- Partly supportedcites [82] Steinberg, 2010, The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: a 17.5 year follow-up, Am J Hematol sourceExperimental — accuracy not yet measured
The Introduction reports that hydroxyurea increased HbF and was associated with fewer painful episodes and acute chest syndrome events in an adult trial. The Discussion reports an association with improved survival in the adult follow-up. Neither section identifies suppression of erythropoiesis as a mechanism for increasing HbF. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“More than 40 years ago, Nagel et al 114 showed that the glutamine (Q) at position 87 in the g-globin chain was 1 of 2 residues accounting for the inhibitory effect of HbF on HbS polymerization.”
§ Fetal hemoglobin in sickle cell anemia > Cell-based HbF-inducing therapeutics
What the sources say
- Partly supportedcites [114] Nagel, 1979, Structural bases of the inhibitory effects of hemoglobin F and hemoglobin A2 on the polymerization of hemoglobin S, Proc Natl Acad Sci USA sourceExperimental — accuracy not yet measured
The Results and Discussion identifies γ-chain residues 80 and 87 as contributing to HbF’s inhibition of HbS gelation, and Table 3 identifies residue 87 as glutamine. The paper says these sites are responsible *at least partially* and considers possible contributions from other residues, so it does not establish that exactly two residues account for the effect. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Myeloablative conditioning is required for all cell-based therapeutics but has been associated with myelodysplasia”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Supportedcites [129] Hsieh, 2020, Myelodysplastic syndrome unrelated to lentiviral vector in a patient treated with gene therapy for sickle cell disease, Blood Adv source
The Results and discussion section says that MDS is an identified risk following stem-cell transplantation using alkylating agents and describes a patient who developed MDS after myeloablation. It presents chemotherapy as a possible contributor, supporting the claimed association without establishing that conditioning caused this patient's MDS. (LLM, conf=0.90)
- Partly supportedcites [130] Gao, 2019, Nongenotoxic antibody-drug conjugate conditioning enables safe and effective platelet gene therapy of hemophilia A mice, Blood Adv sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says the irradiation or cytotoxic chemotherapy used in the authors’ prior preconditioning regimens carries potential risks, including secondary malignancy. It does not identify myelodysplasia as an associated outcome, so the specific condition in the claim is unsupported. (LLM, conf=0.78)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“matched-sibling transplants, especially in young children, provide excellent results.127”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Supportedcites [127] Krishnamurti, 2020, Should young children with sickle cell disease and an available human leukocyte antigen identical sibling donor be offered hematopoietic cell transplantation?, Hematol Oncol Stem Cell Ther source
The section “Excellent outcomes after HLA identical sibling bone marrow transplantation in young children” states that overall and event-free survival are excellent in young patients with sickle cell disease receiving transplants from HLA-identical family donors, and that both outcomes worsen with increasing age. The “Additional information” section makes the same point specifically about HLA-identical sibling donors. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
In the paper
“Consistent with the phenotype of most patients with natural or therapy-induced HbF levels of 20%, it is possible for nearly 25% of F-cells to have polymer-inhibiting HbF levels.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
What the sources say
- Not checked — no full text of the sourcecites [52] Steinberg, 2014, Fetal hemoglobin in sickle cell anemia: a glass half full?, Blood source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“DeoxyHbS polymerization drives the disease pathophysiology.”
§ Fetal hemoglobin in sickle cell anemia > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“ree quantitative trait loci (QTL), BCL11A, MYB, and a locus in the promotor of HBG2 modify HbF gene expression.”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
plaindirect- Asserted: passes — The authors put it forward as true.
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Reducing bcl11a expression in transgenic sickle mice derepressed g-globin genes.17,18”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Not checked — no full text of the sourcecites [17] Sankaran, 2008, Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A, Science source
- Not checked — no full text of the sourcecites [18] Xu, 2011, Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing, Science source
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Reduced KLF1 expression or activity is associated with HbF derepression.”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
plaincorrelational- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“ZBTB7A (LRF) is another zinc finger HbF gene silencer.”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The C-T polymorphism 158 bp 59 of HBG2, a cleavage site for Xmn1, is associated with increased HbF in the Senegal and Arab-Indian HbS gene haplotypes.”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
plaincorrelational- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Variants associated with increased HbF are present in ;20% of sickle cell anemia patients.”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
plaincorrelational- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“CRISPR-Cas9 disruption of this site in sickle cell CD34 1 cells caused ;25% g globin and 55 6 5% F-cells.”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Children with the AI haplotype have HbF of ;30%.37”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Not checked — no full text of the sourcecites [37] Perrine, 1972, Benign sickle-cell anaemia, Lancet source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Saudi patients with Bantu and Cameroon haplotypes have HbF of ;8% compared with ;5% in their African counterparts.35”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Not checked — no full text of the sourcecites [35] Al-Ali, 2020, Prevalence and diversity of haplotypes of sickle cell disease in the Eastern Province of Saudi Arabia, Hemoglobin source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“HBG2 levels fall from ;70% at birth to ;40% 6 months postnatally, making it unsurprising that targeting the HBG2 site had a smaller effect on HbF.”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Malaria, in turn, provided the selective pressure driving the rise of the HbS gene.”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Like BCL11A and MYB, ANTXR1 appeared to be a repressor of HbF.”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
hedgedconditionaln = 4- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“With the possible exception of the AI and Senegal haplotypes, the genetic basis of the variance of HbF levels among HbS gene haplotypes remains undefined.”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The number of F-cells with polymer-inhibiting concentrations of HbF is likely to be a more important determinant of the features of sickle cell anemia than the total number of F-cells or the concentration of HbF in the hemolysate.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
hedgedconditional- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“These cells arise stochastically from erythroid precursors that can give rise to both HbF-containing and non-HbF-containing erythrocytes.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Any protection afforded by HbF against the development of priapism, renal functional impairment, cerebrovascular disease, and perhaps sickle vasculopathy is questionable.”
§ Fetal hemoglobin in sickle cell anemia > HbF effects on clinical and hematologic phenotypes
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“BCL11A and ZBTB7A are not differentially expressed in F-erythroblasts compared with non-HbF-expressing erythroid precursors.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The threshold for F-cell detection by fluorescent activated cell sorting (FACS) using an antibody reactive with HbF is ;6 pg of HbF/F-cell.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“This is consistent with disease severity in most patients with these HbF levels and individuals with Bantu/Benin/Cameroon haplotypes.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
What the sources say
- Not checked — no full text of the sourcecites [52] Steinberg, 2014, Fetal hemoglobin in sickle cell anemia: a glass half full?, Blood source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In compound heterozygotes for HbS and the common gene deletions HPFH-1 and HPFH-2 that cause hereditary persistence of HbF (HPFH), total HbF level is ;30%.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plain- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Malarial parasites grow poorly in HbF-containing erythrocytes.”
§ Fetal hemoglobin in sickle cell anemia > HbF and malaria
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Using the PedsQL Sickle Cell Disease Module, health-related quality of life in 123 Omani children with sickle cell disease was predicted by HbF independent of other measured elements (95% CI: 0.15-1.12).63”
§ Fetal hemoglobin in sickle cell anemia > HbF and survival
What the sources say
- Not checked — no full text of the sourcecites [63] Boulassel, 2019, Hemoglobin F as a predictor of health-related quality of life in children with sickle cell anemia, Qual Life Res source
plaincorrelationaln = 123- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Greek adults with HbS-b 1 thalassemia treated with hydroxyurea showed a HbF increase from a median of ;6.8% to a median of ;20%.78”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Not checked — no full text of the sourcecites [78] Voskaridou, 2010, The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: results of a 17-year, single-center trial (LaSHS), Blood source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The stability of the HbF compared with the HbA tetramer might account for part of this effect.74”
§ Fetal hemoglobin in sickle cell anemia > HbF and malaria
What the sources say
- Not checked — no full text of the sourcecites [74] Manning, 2020, Embryonic and fetal human hemoglobins: structures, oxygen binding, and physiological roles, Subcell Biochem source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In early childhood, high HbF is likely to be associated with more F-cells containing protective HbF levels.”
§ Fetal hemoglobin in sickle cell anemia > HbF and cerebrovascular disease
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Eighty-three neurologically intact adults with sickle cell anemia had silent white matter changes that were associated with low HbF.70”
§ Fetal hemoglobin in sickle cell anemia > HbF and cerebrovascular disease
What the sources say
- Not checked — no full text of the sourcecites [70] Calvet, 2017, Low fetal hemoglobin percentage is associated with silent brain lesions in adults with homozygous sickle cell disease, Blood Adv source
plaincorrelationaln = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Fourteen children with HbSC disease, mean age 11 years, were given hydroxyurea at the maximum tolerated dose.HbF increased from 1.7 6 1.9% to 6.3 6 6.7%.75”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Not checked — no full text of the sourcecites [75] Summarell, 2016, Original Research: Use of hydroxyurea and phlebotomy in pediatric patients with hemoglobin SC disease, Exp Biol Med (Maywood) source
plaindirectn = 14- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“After 12 months, HbF increased from ;2.8% to 5.5% in 133 hydroxyureatreated HbSC disease patients.76”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Not checked — no full text of the sourcecites [76] Luchtman-Jones, 2016, Effects of hydroxyurea treatment for patients with hemoglobin SC disease, Am J Hematol source
plaindirectn = 133- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Following 2 years of hydroxyurea in adults with baseline HbF of ;5%, the top quartile of HbF responders had ;12% HbF.86”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Not checked — no full text of the sourcecites [86] Steinberg, 1997, Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea, Blood source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“When hydroxyurea was started at 9 to 18 months of age, HbF remained at its baseline level of 25%.”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Hydroxyurea treatment was associated with progressive increases in the polymerization delay time, coincident with the increase of F-cells.83”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Not checked — no full text of the sourcecites [83] Bridges, 1996, A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy, Blood source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Clinical trials are targeting BCL11A with CRISPR/Cas and zinc finger nucleases (NCT03745287, NCT03655 678, and NCT03653247).”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Not matchedcites NCT03745287
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites NCT03655 678
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites NCT03653247
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“Replacing b 87 threonine (T) with Q (HbA T87Q ) and incorporating this gene into a lentiviral vector that was transferred into hematopoietic stem cells corrected the main features of sickle cell disease in transgenic mice.115”
§ Fetal hemoglobin in sickle cell anemia > Cell-based HbF-inducing therapeutics
What the sources say
- Not checked — no full text of the sourcecites [115] Pawliuk, 2001, Correction of sickle cell disease in transgenic mouse models by gene therapy, Science source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“HbF induction by hydroxyurea depends in part on a proliferating erythroid bone marrow, which is most vigorous in childhood.”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“At a fixed dose of 20 mg/kg, after at least 18 months of observation, the percent decrease in HbF in hydroxyurea-treated patients was 13% compared with 37% in placebo-treated controls.”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“With time, intramedullary sickling and marrow infarction reduce the erythroid capacity of the marrow.84,85”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Not checked — no full text of the sourcecites [84] Hayes, 1985, The haematology of steady state homozygous sickle cell disease: frequency distributions, variation with age and sex, longitudinal observations, Br J Haematol source
- Not checked — no full text of the sourcecites [85] West, 1992, Laboratory profile of sickle cell disease: a cross-sectional analysis, J Clin Epidemiol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In the context of sickle cell disease treatment discussed below, CRISPR-Cas9 disrupts specific enhancer motifs or binding sites for HbF repressor proteins.”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Some benefits of hydroxyurea might also be unrelated to HbF induction.83”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Not checked — no full text of the sourcecites [83] Bridges, 1996, A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy, Blood source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cure of sickle cell anemias is possible if enough HbF can be induced in enough sickle erythrocytes to thwart their premature destruction and inhibit sickle vasoocclusion.”
§ Fetal hemoglobin in sickle cell anemia > Cell-based HbF-inducing therapeutics
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“vaso-occlusive episodes stopped.”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Not matchedcites [125] Corbacioglu, 2020, Initial safety and efficacy results with a single dose of autologous crispr-cas9 modified CD34+ hematopoietic stem and progenitor cells in transfusion-dependent β-thalassemia and sickle cell disease, Eur Soc Haematol
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“F-cells increased from 33.9% to 99.7%”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Not matchedcites [125] Corbacioglu, 2020, Initial safety and efficacy results with a single dose of autologous crispr-cas9 modified CD34+ hematopoietic stem and progenitor cells in transfusion-dependent β-thalassemia and sickle cell disease, Eur Soc Haematol
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“All cell-based modalities had similar results with close to 50% HbF or HbA T87Q .”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Engraftment occurred after 30 days.”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Not matchedcites [125] Corbacioglu, 2020, Initial safety and efficacy results with a single dose of autologous crispr-cas9 modified CD34+ hematopoietic stem and progenitor cells in transfusion-dependent β-thalassemia and sickle cell disease, Eur Soc Haematol
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggests that stress erythropoiesis contributes minimally, if at all, to high HbF.”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
hedgedn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“total hemoglobin stabilized at 11 to 12 g/dL”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Not matchedcites [125] Corbacioglu, 2020, Initial safety and efficacy results with a single dose of autologous crispr-cas9 modified CD34+ hematopoietic stem and progenitor cells in transfusion-dependent β-thalassemia and sickle cell disease, Eur Soc Haematol
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
- Probably not a substantial claim. 12
- It may state two separate claims as one. 48
- The quote only partly states this claim. 1
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“When HbF/F-cell is 9 to 12 pg, calculations suggested that deoxyHbS polymerization should be prevented at physiologic venous and capillary O 2 saturations of 40% to 70%, affording the sickle erythrocyte nearly total protection from HbS polymerinduced damage, although recent studies call into question this observation.3,48,49”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
What the sources say
- Disputedcites [3] Henry, 2020, Allosteric control of hemoglobin S fiber formation by oxygen and its relation to the pathophysiology of sickle cell disease, Proc Natl Acad Sci USA sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 0 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
- Disputedcites [48] Maier-Redelsperger, 1994, Variation in fetal hemoglobin parameters and predicted hemoglobin S polymerization in sickle cell children in the first two years of life: Parisian Prospective Study on Sickle Cell Disease, Blood sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
- Not checked — no full text of the sourcecites [49] Horiuchi, 1995, Estimation of fetal hemoglobin levels in individual red cells via fluorescence image cytometry, Cytometry source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Disputed
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“As HbF falls and fewer F-cells are protected from HbS polymer damage, the propensity for vascular occlusion and intravascular hemolysis increases with the release of heme products into the circulation that scavenge nitric oxide causing endothelial damage and vasculopathy.[57][58][59]”
§ Fetal hemoglobin in sickle cell anemia > HbF and cerebrovascular disease
What the sources say
- Not checked — no full text of the sourcecites [57] Kato, 2007, Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes, Blood Rev source
- Disputedcites [58] Kato, 2017, Intravascular hemolysis and the pathophysiology of sickle cell disease, J Clin Invest sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
- Not checked — no full text of the sourcecites [59] Reiter, 2002, Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease, Nat Med source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Several approaches to reducing the expression of HbF suppressors in CD34 1 cells have entered clinical trials, including the first use of CRISPR-Cas9 in humans (Figure 2).123-125”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Not checked — no full text of the sourcecites [123] Porteus, 2017, Genome Editing for the β-Hemoglobinopathies, Adv Exp Med Biol source
- Disputedcites [124] Hoban, 2016, Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease, Blood sourceExperimental — accuracy not yet measured
The 'Current SCD gene therapy clinical trials' section describes trials using globin gene-addition vectors, including one treatment with an antisickling β-globin vector. The paper discusses BCL11A suppression and CRISPR-based editing as novel approaches, not as approaches that had entered clinical trials; it does not report a first use of CRISPR-Cas9 in humans. Page numbers were not available in our copy. (LLM, conf=0.87)
Checked by a reasoning model — may be wrong.
- Not matchedcites [125] Corbacioglu, 2020, Initial safety and efficacy results with a single dose of autologous crispr-cas9 modified CD34+ hematopoietic stem and progenitor cells in transfusion-dependent β-thalassemia and sickle cell disease, Eur Soc Haematol
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“HbF prolongs the time needed for HbS polymerization (delay time), allowing the escape of sickle erythrocytes from the microcirculation into larger veins and hence the lungs, where on reoxygenation, HbS polymer melts.3”
§ Fetal hemoglobin in sickle cell anemia > Introduction
What the sources say
- Supportedcites [3] Henry, 2020, Allosteric control of hemoglobin S fiber formation by oxygen and its relation to the pathophysiology of sickle cell disease, Proc Natl Acad Sci USA source
The Discussion (Fig. 12; page unavailable) describes a delay that lets red cells pass through narrow vessels, followed by fiber melting when they return to the lungs and are reoxygenated. It also says delay times are much longer in S/HPFH, the HbF-containing condition compared in the Results (Fig. 11; page unavailable). (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“BCL11A expression is controlled by transcriptional and/or translational mechanisms.[22][23][24]”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Supportedcites [22] Basak, 2020, Control of human hemoglobin switching by LIN28B-mediated regulation of BCL11A translation, Nat Genet source
The Abstract states that BCL11A is regulated at the level of mRNA translation during human hematopoietic development and identifies LIN28B-mediated suppression of that translation. This supports the claim’s “and/or” formulation through its translational component. (LLM, conf=0.92)
- Supportedcites [23] Lessard, 2018, 14q32 and let-7 microRNAs regulate transcriptional networks in fetal and adult human erythroblasts, Hum Mol Genet source
The Introduction (page not provided) says variants disrupt a developmental-stage-specific enhancer of BCL11A, supporting transcriptional control of its expression. It also reports that miR-486-3p directly targets BCL11A in erythroid cells, consistent with the claim’s broader description of regulatory mechanisms. (LLM, conf=0.87)
- Could not verifycites [24] Huang, 2017, Comparative analysis of three-dimensional chromosomal architecture identifies a novel fetal hemoglobin regulatory element, Genes Dev sourceExperimental — accuracy not yet measured
The Abstract describes BCL11A as a repressor of γ-globin transcription, and the Results examine what happens when BCL11A is knocked out. Neither passage addresses whether BCL11A’s own expression is controlled transcriptionally or translationally; searches for those mechanisms found no supporting passage in our copy. (LLM, conf=0.77)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“ZBTB7A is not polymorphic and does not account for HbF variation in patients with sickle cell anemia.26”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Partly supportedcites [26] Shaikho, 2016, Variants of ZBTB7A (LRF) and its β-globin gene cluster binding motifs in sickle cell anemia, Blood Cells Mol Dis sourceExperimental — accuracy not yet measured
In the paper’s discussion of ZBTB7A variants (page unavailable), the authors conclude that common variants in ZBTB7A or its nearby regulatory regions are unlikely to account for HbF variation in sickle cell anemia. But they report a CGC insertion polymorphism in two patients, so the claim that ZBTB7A is not polymorphic is incorrect. The claim also states the HbF conclusion more definitively than the paper does. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Its inactivation in HUDEP-2 cells led to ;50% HbF; BCL11A plus ZBTB7A knockout caused .90% HbF. 25”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Partly supportedcites [25] Masuda, 2016, Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin, Science sourceExperimental — accuracy not yet measured
The HUDEP-2 results report HbF above 60% in all three ZBTB7A-knockout clones, not approximately 50%. The double-knockout results report HbF at 91–94% of total hemoglobin, supporting the second figure. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“BCL11A binds TGACCA motifs in the HBB gene cluster, preferentially binding to position 2115 in the HBG2 and HBG1 promoters.20,21”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Supportedcites [20] Liu, 2018, Direct promoter repression by BCL11A controls the fetal to adult hemoglobin switch, Cell source
The Results section, “High-resolution localization of BCL11A at the γ-globin promoters” (page not supplied), reports preferential binding to the distal TGACCA motif at −118 to −113, which includes position −115. The Methods section identifies the duplicated promoters as HBG1 and HBG2. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [21] Martyn, 2018, Natural regulatory mutations elevate the fetal globin gene via disruption of BCL11A or ZBTB7A binding, Nat Genet source
plaindirect- Asserted: unclear — It is unclear whether the authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Kr üppel-like factor 1 (KLF1) binds to the promoter of ZBTB7A increasing its expression; KLF1 also activates the expression of BCL11A.28,29”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Not checked — no full text of the sourcecites [28] Norton, 2017, KLF1 directly activates expression of the novel fetal globin repressor ZBTB7A/LRF in erythroid cells, Blood Adv source
- Partly supportedcites [29] Bieker, 2010, Putting a finger on the switch, Nat Genet sourceExperimental — accuracy not yet measured
The Common ties section reports that KLF1 binds the BCL11A gene and that BCL11A levels rise with KLF1 levels, supporting the BCL11A part of the claim. Our copy does not mention ZBTB7A or say that KLF1 binds its promoter or increases its expression. (LLM, conf=0.89)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The HbS gene had a single origin in West Central Africa or in the Sahara during the Holocene Wet Phase between 3400 and 11 100 years ago or in agriculturists ;22 000 years ago, which was introduced into rainforest dwellers within the last 6000 years.32,33”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Partly supportedcites [32] Shriner, 2018, Whole-genome-sequence-based haplotypes reveal single origin of the sickle allele during the Holocene wet phase, Am J Hum Genet sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [33] Laval, 2019, Recent adaptive acquisition by African rainforest hunter-gatherers of the late Pleistocene sickle-cell mutation suggests past differences in malaria exposure, Am J Hum Genet source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“This variant explained ;10% of HbF variability compared with ;8% for BCL11A.”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Supportedcites [41] Vathipadiekal, 2016, A candidate transacting modulator of fetal hemoglobin gene expression in the Arab-Indian haplotype of sickle cell anemia, Am J Hematol source
The Results section reports that, in Arab-Indian haplotype sickle cell patients, the regression model for ANTXR1 rs4527238 explained about 10% of HbF variability, compared with about 8% for BCL11A rs1427407. These are the figures attributed to the source; the finding is specific to that patient group. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [42] Al-Ali, 2018, ANTXR1 intronic variants are associated with fetal hemoglobin in the Arab-Indian haplotype of sickle cell disease, Acta Haematol source
plaincorrelationaln = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The AI haplotype in Saudi patients is associated with a unique pattern of SNPs in putative cis-acting globin regulatory elements and is linked to a novel variant in ANTXR1.40,41”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Partly supportedcites [40] Vathipadiekal, 2016, Homozygosity for a haplotype in the HBG2-OR51B4 region is exclusive to Arab-Indian haplotype sickle cell anemia, Am J Hematol sourceExperimental — accuracy not yet measured
The Results (“A unique AI haplotype”) and Discussion describe a distinctive SNP haplotype in Saudi AI patients that may involve cis-acting globin regulatory elements. The paper does not report a link to a novel ANTXR1 variant; a search for ANTXR1 found no matching passage in our copy. Page numbers were not provided. (LLM, conf=0.88)
- Partly supportedcites [41] Vathipadiekal, 2016, A candidate transacting modulator of fetal hemoglobin gene expression in the Arab-Indian haplotype of sickle cell anemia, Am J Hematol sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) describes a unique cis-acting sub-haplotype containing putative functional elements in the AI haplotype, but does not establish the claimed pattern of SNPs in Saudi patients. The Results (page unavailable) identify ANTXR1 SNPs associated with fetal hemoglobin specifically in Saudi AI-haplotype patients; they do not show that the AI haplotype itself is linked to a novel ANTXR1 variant. (LLM, conf=0.84)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“The earlier origin in agriculturists might have resulted from destruction of the rain forest canopy that created conditions favorable for malaria.”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Could not verifycites [32] Shriner, 2018, Whole-genome-sequence-based haplotypes reveal single origin of the sickle allele during the Holocene wet phase, Am J Hum Genet sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) estimates that the sickle allele arose about 7,300 years ago and mentions the equatorial rainforest as a possible place of origin. It does not address an earlier origin in agriculturists or propose that destruction of the rainforest canopy created conditions favorable for malaria. Searches for agriculturists and forest clearing found no supporting passage. (LLM, conf=0.72)
- Not checked — no full text of the sourcecites [33] Laval, 2019, Recent adaptive acquisition by African rainforest hunter-gatherers of the late Pleistocene sickle-cell mutation suggests past differences in malaria exposure, Am J Hum Genet source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“As HbF levels decline, AI haplotype adults have more numerous symptoms, and their disease begins to resemble that of African patients, but with a lower incidence of stroke, no leg ulcers, and .70%prevalence of splenomegaly.37,38”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Not checked — no full text of the sourcecites [37] Perrine, 1972, Benign sickle-cell anaemia, Lancet source
- Partly supportedcites [38] Alsultan, 2014, Sickle cell disease in Saudi Arabia: the phenotype in adults with the Arab-Indian haplotype is not benign, Br J Haematol sourceExperimental — accuracy not yet measured
The Discussion (page not provided) says the adult Arab–Indian haplotype phenotype is broadly similar to that of African-haplotype patients, except for fewer overt strokes, no leg ulcers, and more persistent splenomegaly. It proposes declining HbF as an explanation for the change from the milder childhood phenotype, but the Results report only that a majority had a palpable spleen; the copy does not establish prevalence above 70%. (LLM, conf=0.87)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Individuals with this genotype do not have hemolytic anemia and are usually asymptomatic.50”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
What the sources say
- Supportedcites [50] Ngo, 2012, Fetal haemoglobin levels and haematological characteristics of compound heterozygotes for haemoglobin S and deletional hereditary persistence of fetal haemoglobin, Br J Haematol source
The Discussion states that HbS-HPFH has “little or no haemolysis” and nearly normal haematological values. The Results report an absence of symptoms due to sickle cell anaemia. Page numbers were not provided for these passages. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“When HbF is near 30%, disease can be relatively benign and 70% of cells can be protected.[52][53][54]”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
What the sources say
- Not checked — no full text of the sourcecites [52] Steinberg, 2014, Fetal hemoglobin in sickle cell anemia: a glass half full?, Blood source
- Not checked — no full text of the sourcecites [53] Perrine, 1978, Natural history of sickle cell anemia in Saudi Arabs. A study of 270 subjects, Ann Intern Med source
- Partly supportedcites [54] Perrine, 1981, Sickle cell disease in Saudi Arabs in early childhood, Arch Dis Child sourceExperimental — accuracy not yet measured
The Results report a mean HbF level of 29% in one group of Saudi Arab infants with HbSS, and the introductory passage says the unusually high HbF is believed to account for their relatively mild clinical course. The paper does not report that 70% of cells were protected; the Subjects and methods passage describes HbF distribution as heterocellular without giving a protected-cell percentage. Page numbers were not available in our copy. (LLM, conf=0.87)
plainconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“High HbF is strongly associated with a reduced rate of acute painful episodes, fewer leg ulcers, and longevity.55”
§ Fetal hemoglobin in sickle cell anemia > HbF effects on clinical and hematologic phenotypes
What the sources say
- Supportedcites [55] Steinberg, 2012, Genetic modifiers of sickle cell disease, Am J Hematol source
The HbF section states the cited claim verbatim: high HbF is strongly associated with fewer acute painful episodes, fewer leg ulcers, and longevity. The paper notes some studies with differing results but presents this as its overall assessment. (LLM, conf=0.95)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Of 375 children with sickle cell anemia or Figure 1.HbF distribution in sickle erythrocytes from 3 patients with 20% HbF.An example of 3 possible distributions of HbF/F-cell in 1000 cells from 3 individuals with mean HbF levels of 20%.The y axis represents numbers of cells, and the x axis represents HbF concentration in 5-pg increments.In red are cells likely to be least protected from HbS polymer”
§ Fetal hemoglobin in sickle cell anemia > HbF and cerebrovascular disease
What the sources say
- Partly supportedcites [69] Sommet, 2016, Clinical and haematological risk factors for cerebral macrovasculopathy in a sickle cell disease newborn cohort: a prospective study, Br J Haematol sourceExperimental — accuracy not yet measured
The cohort table lists 375 children, and the Cerebral vasculopathy and stroke section reports 59 with cerebral vasculopathy, including seven who had a stroke. The paper gives 4.4 years as the median age at cerebral vasculopathy diagnosis, not the mean. Its risk-factor table reports HbF as protective against cerebral vasculopathy (HR 0.68, 95% CI 0.48–0.96, per 5% increase). (LLM, conf=0.90)
plaindirectn = 375 ·- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Acute painful episodes and acute chest syndrome are a result of sickle vasoocclusion; HbF has the most noticeable beneficial effect on these subphenotypes.”
§ Fetal hemoglobin in sickle cell anemia > HbF effects on clinical and hematologic phenotypes
What the sources say
- Not checked — no full text of the sourcecites [57] Kato, 2007, Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes, Blood Rev source
- Supportedcites [58] Kato, 2017, Intravascular hemolysis and the pathophysiology of sickle cell disease, J Clin Invest source
The “Evidence that hemolysis modulates SCD subphenotypes” section identifies subphenotypes associated with sickle vaso-occlusion and says HbF has its most robust effects on them, including acute chest syndrome. Table 1 in “The hemolysis hypothesis” lists HbF as protective against both painful episodes and acute chest syndrome. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Priapism, nephropathy, and sickle vasculopathy are associated with hemolysis.”
§ Fetal hemoglobin in sickle cell anemia > HbF effects on clinical and hematologic phenotypes
What the sources say
- Not checked — no full text of the sourcecites [57] Kato, 2007, Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes, Blood Rev source
- Supportedcites [58] Kato, 2017, Intravascular hemolysis and the pathophysiology of sickle cell disease, J Clin Invest source
The Abstract links products of hemolysis to vasculopathy and lists priapism and chronic kidney disease among its complications. The section “Hemolytic anemia and vasculopathic complications” also describes hemolytic anemia as a risk factor for vasculopathic complications and associates indices of hemolytic anemia with priapism. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [59] Reiter, 2002, Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease, Nat Med source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“To identify prognostic factors for clinical complications, 57 infants were studied at 4.4 6 1 months of age and followed for ;19 months.HbF, which fell from 42% to 21% during the observation period, was the strongest prognostic factor for disease complications.64”
§ Fetal hemoglobin in sickle cell anemia > HbF and survival
What the sources say
- Supportedcites [64] Brousse, 2018, Prognostic factors of disease severity in infants with sickle cell anemia: A comprehensive longitudinal cohort study, Am J Hematol source
The Abstract reports 57 infants enrolled at a mean age of 4.4 ± 1 months and a median follow-up of 19.4 months. Table 1 gives HbF as 42% at enrollment; the Biological data discussion reports 21% at 24 months and calls early HbF the most robust predictor of severe outcomes in the first two years. Page numbers are unavailable in our copy. (LLM, conf=0.94)
plaincorrelationaln = 57- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Of 230 children treated with hydroxyurea with 510 patient-years of follow-up, patients with HbF less than 20% had twice the risk of hospitalization for pain and acute chest syndrome and 2 times the risk of fever as patients with .20%HbF.65”
§ Fetal hemoglobin in sickle cell anemia > HbF and survival
What the sources say
- Partly supportedcites [65] Estepp, 2017, A clinically meaningful fetal hemoglobin threshold for children with sickle cell anemia during hydroxyurea therapy, Am J Hematol sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelationaln = 230- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“CRISPR-Cas dominates the field because of the ease of using guide RNAs directing the CRISPR complex to specific DNA sequences and the increasing ability to target most sites in the genome.121,122”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Partly supportedcites [121] Doudna, 2020, The promise and challenge of therapeutic genome editing, Nature sourceExperimental — accuracy not yet measured
The GENOME EDITING STRATEGIES section (page unavailable) says CRISPR-Cas9 was widely adopted because its DNA-binding and editing capabilities are easy to program, and explains how guide RNA directs it to a complementary DNA sequence. It also describes an expanding collection of enzymes, but does not establish that most genomic sites can be targeted; the section notes a PAM requirement for Cas9 binding. (LLM, conf=0.83)
- Partly supportedcites [122] Walton, 2020, Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants, Science sourceExperimental — accuracy not yet measured
The Discussion (page not provided) says that SpRY makes the vast majority of the genome targetable, supporting the claim about increasing targeting range. The passages do not say that CRISPR-Cas dominates genome editing because guide RNAs make it easy to direct the complex to specific sequences. (LLM, conf=0.82)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Preclinical testing in sickle CD34 1 cells transduced with this shRNA miR achieved a vector copy .5 and gene marking of .80%, resulting in a three-to fivefold induction of HbF.Growth, differentiation, and engraftment of gene-modified cells in vitro or in vivo were unaffected.”
§ Fetal hemoglobin in sickle cell anemia > Cell-based HbF-inducing therapeutics
What the sources say
- Partly supportedcites [119] Brendel, 2020, Preclinical evaluation of a novel lentiviral vector driving lineage-specific BCL11A knockdown for sickle cell gene therapy, Mol Ther Methods Clin Dev sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Hydroxyurea started at ;11 months at a dose of ;27 mg/kg was associated with HbF levels of 33.3 6 9.1%; 33% of patients had HbF .40% with a hemoglobin concentration of 10.1 6 1.3 g/dL; acute events were markedly reduced; and toxicity was minimal.89”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Partly supportedcites [89] McGann, 2019, Robust clinical and laboratory response to hydroxyurea using pharmacokinetically guided dosing for young children with sickle cell anemia, Am J Hematol sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“They include disrupting the erythroid enhancer of BCL11A or the binding sites for BCL11A in the g-globin gene promoters.126”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Supportedcites [126] Métais, 2019, Genome editing of HBG1 and HBG2 to induce fetal hemoglobin, Blood Adv source
The Introduction identifies disruption of BCL11A-binding sites in the HBG1 and HBG2 (γ-globin) promoters as the strategy studied. The Discussion also describes editing an erythroid-specific enhancer in BCL11A as a comparable approach. No page numbers are available in our copy. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“This same approach was used in a patient with sickle cell anemia.About 1 copy of this vector was present in each cell.After 15 months, total hemoglobin level was 11 to 12 g/dL; HbA T87Q formed about half of the total hemoglobin; and the patient was asymptomatic.117”
§ Fetal hemoglobin in sickle cell anemia > Cell-based HbF-inducing therapeutics
What the sources say
- Supportedcites [117] Ribeil, 2017, Gene therapy in a patient with sickle cell disease, N Engl J Med source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Gene therapy will also have to compete with the improving prospects for haploidentical allogeneic transplantation that could extend the proven effectiveness of allogeneic transplantation.128”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Supportedcites [128] Leonard, 2020, Curative options for sickle cell disease: haploidentical stem cell transplantation or gene therapy?, Br J Haematol source
The “Haploidentical transplantation versus gene therapy” section compares the two curative strategies as haploidentical HSCT methods are refined. The “Haploidentical transplantation results in sickle cell disease” section says improved engraftment could expand this curative option to nearly all patients with SCD. Together, these passages support the claim that improving haploidentical transplantation presents an alternative with which gene therapy must compete. (LLM, conf=0.92)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
In the paper
“It is nearly impossible to have a clinically important number of fully protected F-cells when HbF is 5%; no more than 15% of cells can be protected when HbF is 10%.52”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
What the sources say
- Not checked — no full text of the sourcecites [52] Steinberg, 2014, Fetal hemoglobin in sickle cell anemia: a glass half full?, Blood source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Reduction of let-7 or overexpression of its regulator LIN28B is associated with increased HBG expression. 13”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Not checked — no full text of the sourcecites [13] Lee, 2013, LIN28B-mediated expression of fetal hemoglobin and production of fetal-like erythrocytes from adult human erythroblasts ex vivo, Blood source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Sickle cell disease is caused by homozygosity for the sickle hemoglobin (HbS) gene (b 7glu-val , GAG-GTG) or compound heterozygosity of the HbS gene and other HBB disorders.1”
§ Fetal hemoglobin in sickle cell anemia > Introduction
What the sources say
- Not checked — no full text of the sourcecites [1] Piel, 2017, Sickle cell disease, N Engl J Med source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Fetal hemoglobin (HbF) can blunt the pathophysiology, temper the clinical course, and offer prospects for curative therapy of sickle cell disease.”
§ Fetal hemoglobin in sickle cell anemia > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Only HBG2 expression is affected by the 2158 polymorphism; both HbF genes are affected by BCL11A polymorphisms.30”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Not checked — no full text of the sourcecites [30] Shaikho, 2018, Cis- and trans-acting expression quantitative trait loci differentially regulate gamma-globin gene expression, bioRxiv source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“From the primordial haplotype the HbS gene subsequently became associated with 5 common HBB haplotypes: Bantu (CAR or Central African Republic), Cameroon, Arab-Indian (AI), Senegal, and Benin.34”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Not matchedcites [34] Nagel RL , SteinbergMH. Genetics of the βs gene: origins, genetic epidemiology, and epistasis in sickle cell anemia. In: SteinbergM, ForgetBG, HiggsDR, NagelRL, eds.Disorders of Hemoglobin: Genetics, Pathophysiology, Clinical Management, Cambridge, United Kingdom: Cambridge University Press; 2001:711-755.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Benin haplotype patients of African descent have HbF of ;6%; Saudi Arab patients with the Benin haplotype have HbF of ;11%.36”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Not checked — no full text of the sourcecites [36] Alsultan, 2011, Fetal hemoglobin in sickle cell anemia: Saudi patients from the Southwestern province have similar HBB haplotypes but higher HbF levels than African Americans, Am J Hematol source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“making it unsurprising that targeting the HBG2 site had a smaller effect on HbF.”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Each haplotype is associated with a distinctive mean HbF level, albeit with wide dispersion, making ascertainment of haplotype in individuals of little prognostic value.”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Adult HbS homozygotes with the AI haplotype have a mean baseline HbF of 17% 35 ; Senegal haplotype patients have HbF of ;10%.”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Not checked — no full text of the sourcecites [35] Al-Ali, 2020, Prevalence and diversity of haplotypes of sickle cell disease in the Eastern Province of Saudi Arabia, Hemoglobin source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“This protection provided by HbF can be nearly absolute or only partial.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“HbF is distributed nearly evenly, or pancellularly, in HbS-HPFH erythrocytes, endowing each cell with ;10 pg HbF; HbS polymer is not present in these erythrocytes.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Treatment with hydroxyurea increases the number of F-cells and the concentration of HbF/F-cell.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In sickle cell anemia, HbS polymer is present at 70% O 2 saturation, and the polymer fraction rises steeply as O 2 saturation falls.51”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
What the sources say
- Not checked — no full text of the sourcecites [51] Brittenham, 1985, Hemoglobin S polymerization: primary determinant of the hemolytic and clinical severity of the sickling syndromes, Blood source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Patients with untreated sickle cell anemia, sickle cell anemia treated with hydroxyurea or HbS-db thalassemia, who can have total HbF levels similar to those found in HbS-HPFH, are usually symptomatic; all have hemolytic anemia.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Each erythrocyte contains ;30 pg hemoglobin.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Patients with sickle cell anemia have 2% to 80% F-cells, which survive longer than non-HbF cells.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In these complications HbF has a less obvious beneficial effect, perhaps because only a small number of lysed sickle erythrocytes are needed to trigger these subphenotypes.59”
§ Fetal hemoglobin in sickle cell anemia > HbF effects on clinical and hematologic phenotypes
What the sources say
- Not checked — no full text of the sourcecites [59] Reiter, 2002, Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease, Nat Med source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Pre-hydroxyurea era studies of patients with a mean age of 14.1 6 12.7 years suggested that neither stroke nor silent cerebrovascular disease was associated with HbF.66,67”
§ Fetal hemoglobin in sickle cell anemia > HbF and cerebrovascular disease
What the sources say
- Not matchedcites [66] Ohene-Frempong, 1998, Cerebrovascular accidents in sickle cell disease: rates and risk factors, Blood
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [67] Kinney, 1999, Silent cerebral infarcts in sickle cell anemia: a risk factor analysis, Pediatrics source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Correcting the HbS mutation itself requires a slightly different approach relying on homology-directed repair, which as currently used, is a less efficient reparative pathway.”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Cell-mediated therapy either adds a b-globin gene with a HbF-like substitution or reverses the silencing of the HbF genes by curbing HbF repressors or disrupting their binding motifs in g-globin gene promoters.”
§ Fetal hemoglobin in sickle cell anemia > Cell-based HbF-inducing therapeutics
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This has not yet been achieved with drug therapy but might be possible with cell-based therapeutics.”
§ Fetal hemoglobin in sickle cell anemia > Cell-based HbF-inducing therapeutics
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Using a modified manufacturing process, 13 patients had plerixafor mobilized CD34 1 cells transfected with the HbA T87Q -containing vector and were followed for 3 to 15 months.The vector copy number was 3.8, HbA T87Q was nearly 50% of total hemoglobin, and hemoglobin levels were 10.2 to 15 g/dL; patients became asymptomatic.118”
§ Fetal hemoglobin in sickle cell anemia > Cell-based HbF-inducing therapeutics
What the sources say
- Not checked — no full text of the sourcecites [118] Kanter, 2019, Resolution of sickle cell disease manifestations in patients treated with lentiglobin gene therapy: updates results from the phase 1/2 HGB-206 group C study, Blood source
plaindirectn = 13- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Other drugs that act epigenetically or with novel mechanisms of action have increased HbF levels in preclinical and early-phase clinical trials; none are approved for treatment.”
§ Fetal hemoglobin in sickle cell anemia > Novel agents and targets
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The baseline HbF of 9.1% increased to 25.9% after 2 months and appeared to stabilize between 46% and 48% when tested at 4 through 9 months”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Not matchedcites [125] Corbacioglu, 2020, Initial safety and efficacy results with a single dose of autologous crispr-cas9 modified CD34+ hematopoietic stem and progenitor cells in transfusion-dependent β-thalassemia and sickle cell disease, Eur Soc Haematol
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgeddirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Many of these studies had follow-up of more than 1 year, with near normalization of the hematologic findings.”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cell-based therapeutics are developing rapidly.”
§ Fetal hemoglobin in sickle cell anemia > Conclusion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Genomic editing and shRNA-mediated knockdown of BCL11A should erase lingering doubts that the clinical and hematologic phenotypes of sickle cell anemia can be reversed by high HbF levels in most sickle erythrocytes.”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Rests on an assumption: BCL11A is one of two major repressors of HbF gene expression.
- Rests on an assumption: BCL11A expression is controlled by an erythroid-specific enhancer.
- Rests on an assumption: BCL11A binds to a TGACCA motif centered at position 2115 in the promoters of both HBG2 and HBG1.
- Rests on an assumption: CRISPR-Cas9 editing of either the BCL11A erythroid-specific enhancer or its binding sites in the HbF gene promoters reverses the repression of these genes increasing HbF.
In the paper
“Two patients with b thalassemia treated similarly achieved HbF .97% of the hemolysate with a hemoglobin concentration at 15 months of 14 g/dL.125”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Not matchedcites [125] Corbacioglu, 2020, Initial safety and efficacy results with a single dose of autologous crispr-cas9 modified CD34+ hematopoietic stem and progenitor cells in transfusion-dependent β-thalassemia and sickle cell disease, Eur Soc Haematol
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper relies on this without support.
Gene therapy does not require immunosuppression.
“Gene therapy does not require the immunosuppression.”
The paper relies on this without support.
Experience with allogeneic transplantation is far greater than with gene therapy.
“Nevertheless, experience with allogeneic transplantation is far greater”
The paper relies on this without support.
Myeloablative conditioning is required for all cell-based therapeutics.
“Myeloablative conditioning is required for all cell-based therapeutics”
The paper relies on this without support.
Genomic editing does not use lentiviral transduction.
“Genomic editing does not use lentiviral transduction.”
The paper relies on this without support.
BCL11A is one of two major repressors of HbF gene expression.
“The expression of BCL11A, 1 of 2 major repressors of HbF gene expression, is controlled by an erythroid-specific enhancer.”
The paper relies on this without support.
BCL11A expression is controlled by an erythroid-specific enhancer.
“The expression of BCL11A, 1 of 2 major repressors of HbF gene expression, is controlled by an erythroid-specific enhancer.”
The paper relies on this without support.
BCL11A binds to a TGACCA motif centered at position 2115 in the promoters of both HBG2 and HBG1.
“BCL11A binds to a TGACCA motif centered at position 2115 in the promoters of both HBG2 and HBG1.”
The paper relies on this without support.
CRISPR-Cas9 editing of either the BCL11A erythroid-specific enhancer or its binding sites in the HbF gene promoters reverses the repression of these genes increasing HbF.
“CRISPR-Cas9 editing of either the BCL11A erythroid-specific enhancer, shown as a double-strand break, or its binding sites in the HbF gene promoters, shown before editing, reverses the repression of these genes increasing HbF.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Patients with TDT or SCD who co-inherit hereditary persistence of fetal hemoglobin, in which fetal expression continues into adulthood, have little or no disease.25”
From CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia (2021) · cites this paper as [25]
Experimental — accuracy not yet measured
Citations
Cites
Mortality in sickle cell disease. Life expectancy and risk factors for early death
Platt, O. S., Brambilla, D. J., Rosse, W. F., Milner, P. F., Castro, O., Steinberg, M. H., & Klug, P. P. (1994) · New England Journal of Medicine · doi:10.1056/nejm199406093302303 · Cited by 3,320
Self-citationEffect of hydroxyurea on the frequency of painful crises in sickle cell anemia
Charache, S., Terrin, M. L., Moore, R. D., Dover, G. J., Barton, F. B., Eckert, S. V., McMahon, R. P., & Bonds, D. R. (1995) · New England Journal of Medicine · doi:10.1056/nejm199505183322001 · Cited by 2,340
Cerebrovascular accidents in sickle cell disease: rates and risk factors.
(1998) · PubMed · doi:10.1182/blood.v91.1.288 · Cited by 1,694
Piel, F. B., Steinberg, M. H., & Rees, D. C. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1510865 · Cited by 1,488
Self-citationCell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease
Reiter, C. D., Wang, X., Tanus-Santos, J. E., Hogg, N., Cannon, R. O., Schechter, A. N., & Gladwin, M. T. (2002) · Nature Medicine · doi:10.1038/nm1202-799 · Cited by 1,330
Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants
Walton, R. T., Christie, K. A., Whittaker, M. N., & Kleinstiver, B. P. (2020) · Science · doi:10.1126/science.aba8853 · Cited by 1,233
The promise and challenge of therapeutic genome editing
Doudna, J. A. (2020) · Nature · doi:10.1038/s41586-020-1978-5 · Cited by 1,126
Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease
Reiter, C. D., Wang, X., Tanus-Santos, J. E., et al. (2002) · Nature Medicine · doi:10.1038/nm799 · Cited by 1,097
Human Fetal Hemoglobin Expression Is Regulated by the Developmental Stage-Specific Repressor BCL11A
Sankaran, V. G., Menne, T. F., Xu, J., Akie, T. E., Lettre, G., Van Handel, B., Mikkola, H. K. A., Hirschhorn, J. N., Cantor, A. B., & Orkin, S. H. (2008) · Science · doi:10.1126/science.1165409 · Cited by 919
Kato, G. J., Gladwin, M. T., & Steinberg, M. H. (2007) · Blood Reviews · doi:10.1016/j.blre.2006.07.001 · Cited by 876
Self-citation
Research works printed but not linked: 1
- Nagel RL , SteinbergMH. Genetics of the βs gene: origins, genetic epidemiology, and epistasis in sickle cell anemia. In: SteinbergM, ForgetBG, HiggsDR, NagelRL, eds.Disorders of Hemoglobin: Genetics, Pathophysiology, Clinical Management, Cambridge, United Kingdom: Cambridge University Press; 2001:711-755.
Cited by
Sorted by citations
CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia
Frangoul, H., Altshuler, D., Cappellini, M. D., Chen, Y.-S., Domm, J., Eustace, B. K., Foell, J., de la Fuente, J., Grupp, S., Handgretinger, R., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2031054 · Cited by 1,962
Self-citationExagamglogene Autotemcel for Severe Sickle Cell Disease
Frangoul, H., Locatelli, F., Sharma, A., Bhatia, M., Mapara, M., Molinari, L., Wall, D., Liem, R. I., Telfer, P., Shah, A. J., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2309676 · Cited by 493
Self-citationBiologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease
Kanter, J., Walters, M. C., Krishnamurti, L., Mapara, M. Y., Kwiatkowski, J. L., Rifkin-Zenenberg, S., Aygun, B., Kasow, K. A., Pierciey, F. J., Bonner, M., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2117175 · Cited by 442
Exagamglogene Autotemcel for Transfusion-Dependent β-Thalassemia
Locatelli, F., Lang, P., Wall, D., Meisel, R., Corbacioglu, S., Li, A. M., de la Fuente, J., Shah, A. J., Carpenter, B., Kwiatkowski, J. L., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2309673 · Cited by 253
Identification of non-coding silencer elements and their regulation of gene expression
Pang, B., van Weerd, J. H., Hamoen, F. L., & Snyder, M. P. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00549-9 · Cited by 103
Metadata
- Authors
- Steinberg, M. H.
- Affiliations
- Boston University (US)
- Corresponding author
- Steinberg, Martin H.
- ORCID
- Steinberg, Martin H.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2020-11-19
- Volume
- 136
- Issue
- 21
- Pages
- 2392-2400
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W4211089719
- Cited by
- 136
- References
- 135
- Citations by year
- 2026: 27 · 2025: 28 · 2024: 35 · 2023: 11 · 2022: 21 · 2021: 11 · 2020: 2
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- Funders
- University of Dammam (SP 11/2011)
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL133350, R01HL068970)
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Keywords
- fetal hemoglobin, sickle cell disease, quantitative trait loci, beta-globin gene haplotypes, cell therapy, genome editing, curative treatment, Middle Eastern populations
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
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Statistics and arithmetic are recomputed, not judged.
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