The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index; none of the 23 sources its claims cite is checked for support yet.
Macrophage functional polarization (M1/M2) in response to varying fiber and pore dimensions of electrospun scaffolds
Open accessAbstract
In this study, we investigated the effect of fiber and pore size of an electrospun scaffold on the polarization of mouse bone marrow-derived macrophages (BMMΦs) towards regenerative (M2) or inflammatory (M1) phenotypes. BMMΦs were seeded on Polydioxanone (PDO) scaffolds electrospun from varying polymer concentrations (60, 100, and 140 mg/ml). Higher polymer concentrations yielded larger diameter fibers with larger pore sizes and porosity. BMMΦ cultured on these scaffolds showed a correlation between increasing fiber/pore size and increased expression of the M2 marker Arginase 1 (Arg1), along with decreased expression of the M1 marker inducible nitric oxide synthase (iNOS). Secretion of the angiogenic cytokines VEGF, TGF-β1 and bFGF was higher among cultures employing larger fiber/pore size scaffolds (140 mg/ml). Using a 3D in vitro angiogenesis bead assay, we have demonstrated that the M2-like profile of BMMΦ induced by the 140 mg/ml is functional. Furthermore, our results show that the pore size of a scaffold is a more critical regulator of the BMMΦ polarization compared to the fiber diameter. The study also shows a potential role for MyD88 in regulating M1 BMMΦ signaling on the large vs. small fiber/pore size PDO scaffold. These data are instructive for the rationale design of implantable prosthetics designed to promote in situ regeneration.
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53 Own result · 17 Own interpretation · 16 Not checked yet · 3 No basis given · 2 Own method
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In the paper
“The histological evaluation (H&E staining) of PDO scaffolds showed greater BMMΦ (M0s and M2s) infiltration into the fibrous structures of larger fiber/pore size scaffold (Figure 4A).”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.3 Histological Evaluation
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The larger fiber/pore sizes are able to induce statistically higher Arg1 expression.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.4 Arginase and iNOS Expression
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The BMMΦ infiltration was statistically higher in the large fiber/pore size scaffold (140 mg/ml) when compared to the 60 mg/ml scaffold.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.3 Histological Evaluation
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Secretion of the angiogenic cytokines VEGF, TGF-β1 and bFGF was higher among cultures employing larger fiber/pore size scaffolds (140 mg/ml).”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > Abstract
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In the paper
“The M0s and M2s in the case of small fiber/pore size PDO (60 mg/ml) scaffold were found concentrated at the surface.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.3 Histological Evaluation
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The pre-polarized M2 BMMΦs induce statistically higher Arg1 expression on the large fiber/pore sizes on Day 1.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.4 Arginase and iNOS Expression
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The Arg1 expression level by M2s was maintained on the large fiber/pore size.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.4 Arginase and iNOS Expression
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“along with decreased expression of the M1 marker inducible nitric oxide synthase (iNOS).”
- Also stated in: § 3.4 Arginase and iNOS Expression · plain
“The expression of iNOS decreased with increasing fiber/pore sizes.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § 3.4 Arginase and iNOS Expression · plain
None of the sources cited for this claim have been checked yet.
In the paper
“However, in the case of M1s, greater infiltration was observed on the 60 mg/ml.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.3 Histological Evaluation
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“As expected, the results showed that with increasing fiber/pore sizes, BMMΦ infiltration of the scaffold cross-sectional area for M0s and M2s increased linearly.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.3 Histological Evaluation
plaindirect- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 22
- Probably not a substantial claim. 12
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In the paper
“This led to a decrease in the pore size of the scaffold from 14 µm to 9 µm without impacting the fiber size.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 2. Materials and Methods > 2.9 Comparison of Fiber size vs. Pore Size in BMMΦ Phenotype Modulation
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The statistical differences were only observed in the case of 60 mg/ml and 140 mg/ml scaffolds. The properties of 100 mg/ml and 140 mg/ml scaffolds were not statistically different from one another.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.1 Electrospun PDO Properties
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — 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 expression of iNOS in M1 pre-polarized BMMΦ is downregulated by increasing fiber/pore size (Figures 5A and C). However, it should be noted that the statistical difference was only found between 100 mg/ml and 140 mg/ml PDO scaffold.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.4 Arginase and iNOS Expression
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“In order to investigate which property of the PDO scaffolds plays an important role in BMMΦ phenotype modulation, the 60 mg/ml PDO scaffolds were made more porous and the 140 mg/ml PDO scaffolds were made less porous without significantly changing their fiber size.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 2. Materials and Methods > 2.9 Comparison of Fiber size vs. Pore Size in BMMΦ Phenotype Modulation
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Higher polymer concentrations yielded larger diameter fibers with larger pore sizes and porosity.”
- Also stated in: § 3.1 Electrospun PDO Properties · plain
“Increasing the polymer concentration led to a linear increase in the fiber sizes, pore sizes and porosity but decreased the surface area to volume ratio.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § 3.1 Electrospun PDO Properties · plain
A result the paper reports from its own data — 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 air-flow impedance method created a statistically significant increase in the pore size and porosity of the scaffold but did not impact the fiber size and the surface area to volume ratio.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.8 Comparison of Fiber size vs. PoreSize in BMMΦ Phenotype Modulation
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
“BMMΦ conditioned media (especially in the case of 140 mg/ml scaffold) produced greater average length of sprouts and higher percentage density of sprouts compared to the positive control.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.6 Angiogenic Potential of Macrophages of PDO Scaffolds
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“The production of bFGF was statistically higher on the 140 mg/ml scaffold compared to the 60 mg/ml scaffold on Day 1 in the case of M0s and M1s and on Day 3 in the case of M2s.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.5 BMMΦ Mediator Secretion
plaincorrelationaln = 3- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“TNF-α levels decreased on Day 3 and trended lower on the 140 mg/ml scaffold.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.5 BMMΦ Mediator Secretion
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall it was observed that M0s induced a ~200 fold higher and M2s induced a ~2 fold higher length of sprout from the 140 mg/ml compared to the 60 mg/ml PDO scaffolds.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.6 Angiogenic Potential of Macrophages of PDO Scaffolds
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Compared to the 60 mg/ml scaffolds, the 140 mg/ml scaffolds induced a 94 fold higher density of sprouts from M0s, 7 fold higher density of sprouts from M1s and 17 fold higher density of sprouts from M2s.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.6 Angiogenic Potential of Macrophages of PDO Scaffolds
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — 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 production of TGF-β1 was statistically higher on the 140 mg/ml scaffold compared to the 60 mg/ml scaffold on Day 1 in the case of M0s and on both Day 1 and 3 in the case of M1s and M2s.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.5 BMMΦ Mediator Secretion
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similar to TNF-α, the levels of IL-6 were not downregulated by the large fiber/pore size PDO.”
- Also stated in: § 3.5 BMMΦ Mediator Secretion · plain
“IL-6 levels were unaffected by different fiber/pore sizes on either Day 1 or 3.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.5 BMMΦ Mediator Secretion
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § 3.5 BMMΦ Mediator Secretion · plain
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Each experiment was done in triplicates and was reproduced at least twice.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 2. Materials and Methods > 2.10 Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. 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
“These data are instructive for the rationale design of implantable prosthetics designed to promote in situ regeneration.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > Abstract
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may be too vague to check against evidence.
- Rests on an assumption: In vitro BMMΦ responses to PDO scaffolds predict in vivo regeneration.
In the paper
“The actual MΦ phenotype is viewed as a continuum of functional states between these two opposing ends [13].”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 1. Introduction
What the sources say
- Not checked yetcites [13] Kou, 2011, Macrophage and dendritic cell phenotypic diversity in the context of biomaterials, J Biomed Mater Res A source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“It is known that M1s invade tissues by degrading and destroying it in an attempt to clear the tissue of pathogens and debris [13].”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.3 Histological Evaluation
What the sources say
- Not checked yetcites [13] Kou, 2011, Macrophage and dendritic cell phenotypic diversity in the context of biomaterials, J Biomed Mater Res A source
boosteddirect- 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.
In the paper
“The values for endotoxin content ranged from 0.03 – 0.09 EU/ml. Therefore, the highest endotoxin level for any scaffold was at least 12,000 times lower than the lowest amount used to activate BMMΦs (100 ng/ml of LPS corresponding to 1100 EU/ml) and well below the acceptable U.S. Pharmacopeia standard for clinical applications (<0.25 EU/ml). This study indicated that the PDO materials used in this”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.2 Endotoxin Content
What the sources say
- Not checked yetcites [31] General chapter <85> bacterial endotoxins test, US pharmacopeia 31-national formulary 26. United States Pharmacopeial Convention, Rockville, MD; 2009.
hedged- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“It exhibits high flexibility, higher strength retention, slower absorption rate, and lower inflammatory response as compared to poly(glycolide lactide) and poly(glycolic acid) [18].”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 1. Introduction
What the sources say
- Not checked yetcites [18] Boland, 2005, Electrospinning polydioxanone for biomedical applications, Acta Biomater source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The surface area to volume ratio of the scaffolds was calculated using the formulas given by Boland et al. [18]”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 2. Materials and Methods > 2.1 Electrospinning of Polydioxanone (PDO) Polymer
What the sources say
- Not checked yetcites [18] Boland, 2005, Electrospinning polydioxanone for biomedical applications, Acta Biomater source
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.
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
“we have demonstrated that increased fiber/pore size shifts the MΦ phenotype to a more M2, tissue regenerative phenotype in vitro, as evidenced by increased Arg1, TGF-β1, VEGF, bFGF expression.”
- Also stated in: § 5. Conclusion · boosted
“BMMΦ acquire a more tissue regenerative M2 phenotype on scaffolds with larger fiber and pore dimensions as evidenced by the increased production of Arg1, VEGF, bFGF and TGF-β1.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 4. Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: An M2 macrophage phenotype promotes healing and integration of the biomaterial with the host tissue, enhancing tissue regeneration.
- Also stated in: § 5. Conclusion · boosted
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 result indicates a potential role for MyD88 in regulating M1 BMMΦ signaling on the large vs. small fiber/pore size PDO scaffold.”
- Also stated in: § 4. Discussion · hedged
“The study indicates a potential role for MyD88 in regulating M1 BMMΦ signaling on the large vs. small fiber/pore size PDO scaffold.”
- Also stated in: § 5. Conclusion · boosted
“We have also shown that the scaffolds with different fiber/pore sizes signal to the BMMΦs differently and have identified MyD88 to be a key component involved in the signaling mechanism.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.7 Role of MyD88 in Arginase Production on PDO Scaffolds
boostedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § 4. Discussion · hedged
In the paper
“Both fiber and pore dimensions increase linearly with concentration [18].”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 4. Discussion
What the sources say
- Not checked yetcites [18] Boland, 2005, Electrospinning polydioxanone for biomedical applications, Acta Biomater 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Pore size has always been a crucial property of tissue engineering scaffolds and a key determinant of a scaffold’s success through their influence on cell infiltration, nutrient/oxygen exchange, and angiogenesis [41, 42].”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 4. Discussion
What the sources say
- Not checked yetcites [41] Yannas, 1989, Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin, Proc Natl Acad Sci USA source
- Not checked yetcites [42] Dagalakis, 1980, Design of an artificial skin. Part III. Control of pore structure, J Biomed Mater Res source
boosteddirect- 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.
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
“These data are instructive for the design and engineering of biomaterials that can promote in situ angiogenesis and tissue regeneration.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 5. Conclusion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check 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 be too vague to check against evidence.
- Rests on an assumption: An M2 macrophage phenotype promotes healing and integration of the biomaterial with the host tissue, enhancing tissue regeneration.
- Rests on an assumption: In vitro macrophage responses to scaffold architecture predict in vivo tissue regeneration outcomes.
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
“we have shown that the BMMΦs of M2 phenotype are functional and can support angiogenesis.”
- Also stated in: § 5. Conclusion · boosted
“We further demonstrated that these BMMΦs of M2 phenotype are functional and support angiogenesis”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 4. Discussion
boosteddirect- 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.
- Also stated in: § 5. Conclusion · boosted
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 140 mg/ml PDO scaffold signal to M1s through a MyD88-dependant mechanism whereas, 60 mg/ml PDO scaffold signals through a MyD88-independent mechanism.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.7 Role of MyD88 in Arginase Production on PDO Scaffolds
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.
None of the sources cited for this claim have been checked yet.
In the paper
“macrophages play a key role in the success and potential failure of any biomaterial”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 4. Discussion
What the sources say
- Not checked yetcites Greisler et al. [21, 33–36]
- Not checked yetcites Valentin et al. [37] Valentin, 2009, Macrophage participation in the degradation and remodeling of extracellular matrix scaffolds, Tissue Eng Part A source
- Not checked yetcites Brown et al. [4] Brown, 2009, Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component, Biomaterials source
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.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“In general, M1s or classically activated MΦs are pro-inflammatory and microbicidal, whereas M2s or alternatively activated MΦs are immunomodulatory, reparative, and poorly microbicidal [7–12].”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 1. Introduction
What the sources say
- Not checked yetcites [7] Fairweather, 2009, Alternatively activated macrophages in infection and autoimmunity, J Autoimmun source
- Not checked yetcites [8] Gordon, 2003, Alternative activation of macrophages, Nat Rev Immunol source
- Not checked yetcites [9] Gordon, 2010, Alternative activation of macrophages: mechanism and functions, Immunity source
- Not checked yetcites [10] Martinez, 2009, Alternative activation of macrophages: an immunologic functional perspective, Annu Rev Immunol source
- Not checked yetcites [11] Varin, 2009, Alternative activation of macrophages: immune function and cellular biology, Immunobiology source
- Not checked yetcites [12] Galli, 2011, Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils, Nat Immunol source
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.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“This grid has been used in a previous study to quantify the migration of sprouts in a 3D matrix [29].”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 2. Materials and Methods > 2.7 Quantification of Angiogenesis
What the sources say
- Not checked yetcites [29] Vernon, 1999, A novel, quantitative model for study of endothelial cell migration and sprout formation within three-dimensional collagen matrices, Microvasc Res source
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.
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 authors believe that the results of this study can be extrapolated to predict MΦ responses to other biomaterials as well.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 4. Discussion
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
- Rests on an assumption: An M2 macrophage phenotype promotes healing and integration of the biomaterial with the host tissue, enhancing tissue regeneration.
- Rests on an assumption: In vitro macrophage responses to scaffold architecture predict in vivo tissue regeneration outcomes.
In the paper
“The pore size, porosity and surface area to volume ratio of the scaffolds was measured using a method described by Soliman et al. [26].”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 2. Materials and Methods > 2.1 Electrospinning of Polydioxanone (PDO) Polymer
What the sources say
- Not checked yetcites [26] Soliman, 2011, Controlling the porosity of fibrous scaffolds by modulating the fiber diameter and packing density, J Biomed Mater Res A source
plainn = 5- 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.
The paper relies on this without support.
In vitro BMMΦ responses to PDO scaffolds predict in vivo regeneration.
“These data are instructive for the rationale design of implantable prosthetics designed to promote in situ regeneration.”
The paper relies on this without support.
The differences in BMMΦ response across PDO scaffolds are due to fiber/pore size rather than other scaffold properties.
“BMMΦ cultured on these scaffolds showed a correlation between increasing fiber/pore size and increased expression of the M2 marker Arginase 1 (Arg1), along with decreased expression of the M1 marker inducible nitric oxide synthase (iNOS).”
The paper relies on this without support.
An M2 macrophage phenotype promotes healing and integration of the biomaterial with the host tissue, enhancing tissue regeneration.
“Such a functional M2 phenotype is likely to promote healing and integration of the biomaterial with the host tissue to enhance tissue regeneration.”
The paper relies on this without support.
In vitro macrophage responses to scaffold architecture predict in vivo tissue regeneration outcomes.
“These data are instructive for the design and engineering of biomaterials that can promote in situ angiogenesis and tissue regeneration.”
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
“The collection of secreted cytokines creates an anti‐proliferative environment, destroys local matrix, and induces tissue reorganization, which allows for an increased migratory process and improved pathogen clearance.[ 36 ]”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [36]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Increased fiber/pore size (0.35 ± 0.2 to 2.8 ± 0.5 µm fiber diameter; 0.96 ± 0.09 to 14.73 ± 0.63 µm pore size) increased expression of M2 marker Arg1 and angiogenic cytokines, VEGF, TGF‐β1, and basic fibroblast growth factor (bFGF), while decreasing the M1 marker iNOS.”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [36]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Garg et al. supported M2 polarization results when using mouse bone marrow‐derived macrophages (BMDMs), showing that larger fiber diameter of polydioxanone‐enhanced M2 macrophage polarization.[ 36 ]”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [36]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Hence, predictable angiogenesis can be identified by upregulation and secretion of VEGF by macrophages as seen in the FBR in vitro models.[ 36 , 41 ]”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [36]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Macrophages that are exposed to foreign biomaterials take part in various processes, including fibrous encapsulation, remodeling, and angiogenesis.[ 36 ]”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [36]
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, VEGF, TGF‐β, and bFGF were also upregulated, indicating that a larger pore size may also promote angiogenesis.[ 36 ]”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [36]
The cited source says what the claim attributes to it.
In the citing paper
“Cells seeded on scaffolds with a higher fiber diameter and pore size showed a clear switch toward an M2 phenotype through the expression of the M2 marker Arginase 1, while displaying decreased levels of iNOS.”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [36]
In the citing paper
“nanofibers elicit significantly less macrophage adhesion and inflammatory activation, and minimize the host response, when compared to microfibers.14-16”
From Micro- and Nanopatterned Topographical Cues for Regulating Macrophage Cell Shape and Phenotype (2015) · cites this paper as [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.6 Angiogenic Potential of Macrophages of PDO Scaffolds
“Overall it was observed that M0s induced a ~200 fold higher and M2s induced a ~2 fold higher length of sprout from the 140 mg/ml compared to the 60 mg/ml PDO scaffolds.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.6 Angiogenic Potential of Macrophages of PDO Scaffolds
“No sprouting was observed from the conditioned media of M0s cultured on the 60 mg/ml scaffold.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.6 Angiogenic Potential of Macrophages of PDO Scaffolds
“Compared to the 60 mg/ml scaffolds, the 140 mg/ml scaffolds induced a 94 fold higher density of sprouts from M0s, 7 fold higher density of sprouts from M1s and 17 fold higher density of sprouts from M2s.”
§ MACROPHAGE FUNCTIONAL POLARIZATION (M1/M2) IN RESPONSE TO VARYING FIBER AND PORE DIMENSIONS OF ELECTROSPUN SCAFFOLDS > 3. Results > 3.6 Angiogenic Potential of Macrophages of PDO Scaffolds
“No sprouting was observed from the conditioned media of M0s cultured on the 60 mg/ml scaffold.”
Citations
Cites
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144 · cited 1×
“MF are grouped into three primary phenotypes: classically activated MF for microbicidal activity, woundhealing MF for tissue repair, and regulatory MF for antiinflammatory activity [15].”
The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534 · cited 1×
“M2c phenotype is induced by IL-10 or glucocorticoids, produces elevated levels of IL-10 and Transforming Growth Factor-beta 1 (TGF-b1), and is associated with immune suppression and remodeling [13,14].”
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189
Foreign body reaction to biomaterials
Anderson, J. M., Rodriguez, A., & Chang, D. T. (2008) · Seminars in Immunology · doi:10.1016/j.smim.2007.11.004 · Cited by 5,138 · cited 2×
“Upon exposure to implanted biomaterials, macrophages (MFs) fuse intomultinucleated giant cells called foreign-body giant cells (FBGCs), leading to fibrous encapsulation [1,2].”
Alternative activation of macrophages: mechanism and functions
Gordon, S., & Martinez, F. O. (2010) · Immunity · doi:10.1016/j.immuni.2010.05.007 · Cited by 4,197
Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm
Biswas, S. K., & Mantovani, A. (2010) · Nature Immunology · doi:10.1038/ni.1937 · Cited by 3,840 · cited 1×
“endothelial cells), as well as factors within the local environment [5,6].”
Alternative Activation of Macrophages: An Immunologic Functional Perspective
Martinez, F. O., Helming, L., & Gordon, S. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132532 · Cited by 2,745 · cited 1×
“Scaffold pore size can also alter the MF response and subsequent angiogenic functions [10,11].”
Biomaterials: Where We Have Been and Where We Are Going
Ratner, B. D., & Bryant, S. J. (2004) · Annual Review of Biomedical Engineering · doi:10.1146/annurev.bioeng.6.040803.140027 · Cited by 1,507 · cited 1×
“In an attempt to invade they may undergo “frustrated phagocytosis” and acquire tissue destructive roles which are typically associated with the M1s [17,43].”
Biological Responses to Materials
Anderson, J. M. (2001) · Annual Review of Materials Research · doi:10.1146/annurev.matsci.31.1.81 · Cited by 1,465
Galli, S. J., Borregaard, N., & Wynn, T. A. (2011) · Nature Immunology · doi:10.1038/ni.2109 · Cited by 1,055
Research works printed but not linked: 1
- General chapter <85> bacterial endotoxins test, US pharmacopeia 31-national formulary 26. United States Pharmacopeial Convention, Rockville, MD; 2009.
Cited by
Sorted by citations
Modulation of macrophage phenotype by cell shape
McWhorter, F. Y., Wang, T., Nguyen, P., Chung, T., & Liu, W. F. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1308887110 · Cited by 1,482
Osteoimmunomodulation for the development of advanced bone biomaterials
Chen, Z., Klein, T. J., Murray, R. Z., Crawford, R., Chang, J., Wu, C., & Xiao, Y. (2015) · Materials Today · doi:10.1016/j.mattod.2015.11.004 · Cited by 752
Biomaterials: Foreign Bodies or Tuners for the Immune Response?
Mariani, E., Lisignoli, G., Borzì, R. M., & Pulsatelli, L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030636 · Cited by 706
“Similar to the wound healing process [74], adherent macrophages eventually shift to the “M2” phenotype [75], secreting anti-inflammatory cytokines (such as IL-10) presenting a reduced degradative capacity and achieving tissue remodeling activity, also inducing the migration and proliferation of fibroblasts toward effe…”
BackgroundCurrent Advances in Immunomodulatory Biomaterials for Bone Regeneration
Lee, J., Byun, H., Perikamana, S. K. M., Lee, S., & Shin, H. (2018) · Advanced Healthcare Materials · doi:10.1002/adhm.201801106 · Cited by 462
Material stiffness influences the polarization state, function and migration mode of macrophages
Sridharan, R., Cavanagh, B., Cameron, A. R., Kelly, D. J., & O'Brien, F. J. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.02.048 · Cited by 450
Metadata
- Authors
- Garg, K., Pullen, N. A., Oskeritzian, C. A., Ryan, J. J., & Bowlin, G. L.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- Bowlin, Gary L.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 34
- Issue
- 18
- Pages
- 4439-4451
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC3623371
- OpenAlex
- W2070438219
- Cited by
- 457
- References
- 43
- Citations by year
- 2026: 28 · 2025: 35 · 2024: 40 · 2023: 35 · 2022: 48 · 2021: 65 · 2020: 55 · 2019: 39 · 2018: 24 · 2017: 26 · 2016: 32 · 2015: 12 · 2014: 17 · 2013: 1
- FWCI
- 7.34
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (K12GM093857)
- National Institute of Allergy and Infectious Diseases (R01AI059638, R01AI095494)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- macrophage polarization, M1/M2 macrophages, electrospun scaffolds, fiber diameter, pore size, polydioxanone, bone marrow-derived macrophages, arginase-1, inducible nitric oxide synthase, angiogenic cytokines, vascular endothelial growth factor, TGF-β1, basic fibroblast growth factor, MyD88, scaffold porosity, tissue regeneration
- MeSH terms
- Animals, Arginase, Bone Marrow Cells, Endotoxins, Macrophages, Mice, Inbred C57BL, Microscopy, Electron, Scanning, Phenotype, Signal Transduction, Porosity, Polydioxanone, Cell Polarity, Culture Media, Conditioned, Neovascularization, Physiologic, Tissue Engineering, Endothelial Cells, Mice, Nitric Oxide Synthase Type II, Myeloid Differentiation Factor 88, Tissue Scaffolds
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 2026-10-05, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-05 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
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