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Cited by 541Traumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury ResearchSex and Gender in Healthcare

Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know

Open access
Gupte, Raeesa P., Brooks, William M., Vukas, Rachel R., Pierce, Janet D., Harris, Janna L.·2019·Journal of Neurotrauma
DOI 10.1089/neu.2018.6171PMC PMC6818488
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Abstract

There is growing recognition of the problem of male bias in neuroscience research, including in the field of traumatic brain injury (TBI) where fewer women than men are recruited to clinical trials and male rodents have predominantly been used as an experimental injury model. Despite TBI being a leading cause of mortality and disability worldwide, sex differences in pathophysiology and recovery are poorly understood, limiting clinical care and successful drug development. Given growing interest in sex as a biological variable affecting injury outcomes and treatment efficacy, there is a clear need to summarize sex differences in TBI. This scoping review presents an overview of current knowledge of sex differences in TBI and a comparison of human and animal studies. We found that overall, human studies report worse outcomes in women than men, whereas animal studies report better outcomes in females than males. However, closer examination shows that multiple factors including injury severity, sample size, and experimental injury model may differentially interact with sex to affect TBI outcomes. Additionally, we explore how sex differences in mitochondrial structure and function might contribute to possible sex differences in TBI outcomes. We propose recommendations for future investigations of sex differences in TBI, which we hope will lead to improved patient management, prognosis, and translation of therapies from bench to bedside.

AI snapshot

Written from the paper’s full text.

TL;DR

This scoping review compares human and animal TBI studies by sex and finds that human studies most often report worse outcomes in women, whereas animal studies most often report better outcomes in females. Injury severity, sample size, and experimental model interact with sex, and the authors highlight mitochondrial function and chromosomal/hormonal factors as underexplored mechanisms.

Key findings

  • Among 156 human studies, the largest fraction (47%) reported worse outcomes in women than men; 26% reported better outcomes in women, 18% no sex difference, and about 9% mixed results. Among 43 animal studies, 44% reported females fared better than males, 14% females worse, 28% no sex difference, and 14% mixed results.
  • Injury severity mattered: in human mild-moderate TBI, 60% of studies found women fared worse and only 9% better; in moderate-severe TBI, 34% found women worse and 46% better. In animal studies, 17% of mild TBI studies showed better outcomes in females, versus 55% of moderate-severe TBI studies.
  • Study size mattered in humans: 52% of small studies (0–1000 patients) reported worse outcomes in women, while 67% of large studies (>10,000 patients) reported better outcomes in women.
  • Animal model mattered: 55% of controlled cortical impact (CCI) studies reported better outcomes in females and none showed males doing better; in lateral fluid percussion injury, 40% showed females better and 60% females worse.

Methods

  • Scoping review of PubMed searched without publication-date or language limits, using sex/gender and TBI terms; search generated 601 results in July 2018, plus 15 items from manual cross-referencing.
  • Included original research on human adolescents/adults of reproductive age and animal studies; excluded reviews/meta-analyses, pediatric-only or geriatric-only studies, epidemiology-only human studies, non-TBI injuries, and non-English articles.
  • Human and animal studies were classified into four outcome categories: worse in women/females, better in women/females, no difference, or mixed. Human studies were stratified by injury severity (mild-moderate GCS 9–15; moderate-severe GCS <12; nonstratified) and sample size; animal studies were grouped by injury model and severity.

Limitations

  • The paper states that 37% of reviewed human studies provided no data on exclusions, and only 15% specifically reported extracranial injury status, limiting interpretation of sex differences. It also notes that some animal injury models had small numbers of studies, so model-specific trends should be viewed as preliminary.
  • The paper states that mixed results are common and that outcome-measure selection can affect conclusions; it advocates multiple outcome measures and notes that sex and gender terms are often used interchangeably in the literature.
  • Evident from the text: the review is a descriptive scoping synthesis rather than a meta-analysis, relies on PubMed and English-language articles, and excludes pediatric-only and geriatric-only populations, which may limit generalizability across the lifespan.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1089/neu.2018.6171

Cites

297 of 297 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 192 cited sources checked · 0 supported · 0 flagged

  • Findingown data
    § Sex effects on TBI outcomes in humans

    The search found 156 published studies that compared outcomes between men and women following TBI.

    “Using the search criteria outlined above, we found 156 published studies that compared outcomes between men and women following TBI.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Sex effects on TBI outcomes in humans

    Among medium-sized studies, 39% showed women faring worse than men.

    “Among medium-sized studies, 39% showed women faring worse than men”
    Quote in the paperSubstantial claim
  • Findingown data
    § Sex effects on TBI outcomes in humans

    More than 88% of studies of mild-moderate injury used social-behavioral outcome measures including self-reported symptoms.

    “We found that &gt; 88% of studies of mild-moderate injury used SB outcome measures including selfreported symptoms (Table 2).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    In human studies of TBI, studies of mild-moderate TBI that were more likely to use social-behavioral outcomes tended to show worse outcomes in women than men.

    “Studies of mildmoderate TBI that were more likely to use SB outcomes also tended to show worse outcomes in women than men.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Among the studies reviewed, 37% provided no data on exclusions.

    “Although many studies explicitly exclude patients with history of neurological/psychiatric disorders and/or severe comorbidities, a surprising number (37%) of the studies we reviewed provided no data on exclusions.”
    Quote in the paperSubstantial claim
  • May combine two claims. 114
  • Classified as probably not a substantial claim. 90
  • The quote only partly states this claim. 22

  • May combine two claims.

    Findingnone given
    § Abstract

    Overall, human studies report worse outcomes in women than men, whereas animal studies report better outcomes in females than males.

    “We found that overall, human studies report worse outcomes in women than men, whereas animal studies report better outcomes in females than males.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Sex effects on TBI outcomes in humans

    76% of studies of >10,000 patients used either survival or community integration as outcomes, whereas smaller studies relied on social-behavioral measures (66%).

    “For example, 76% of studies of &gt; 10,000 patients used either S or CI as outcomes, whereas smaller studies relied on SB measures (66%, Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Sex effects on TBI outcomes in humans

    Among studies of moderate-severe TBI, 34% found that women fared worse than men and 46% showed that women fared better.

    “In contrast, among studies of moderate-severe TBI, 34% found that women fared worse than men and a greater proportion (46%) showed that women fared better (Fig. 2, lower right).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Sex effects on TBI outcomes in humans

    In studies of moderate-severe injury, 52% used community integration and/or survival as outcomes, whereas only 30% included social-behavioral measures.

    “In studies of moderate-severe injury 52% used CI and/or S as outcomes, whereas only 30% included SB measures (Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Sex effects on TBI outcomes in humans

    Among small studies (0-1000 patients), 52% reported worse outcomes in women compared with men, and 23% reported better outcomes in women.

    “A majority of the smaller studies (52%) reported worse outcomes in women compared with men, with fewer (23%) reporting better outcomes in women (Fig. 3, left).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Sex effects on TBI outcomes in humans

    Across all human studies, 47% reported worse outcomes in women than men, 26% found better outcomes in women, 18% found no sex difference, and about 9% reported mixed results.

    “Across all human studies, the largest fraction (47%) reported worse outcomes in women than men. 26% found better outcomes, in women, 18% found no sex difference, and only about 9% reported mixed results with women performing better on certain outcome measures and men on others (Fig, 2, upper panel).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Sex effects on TBI outcomes in humans

    Among large studies (>10,000 patients), only 13% reported women faring worse, and 67% reported that women did better than men.

    “among large studies only 13% reported women faring worse. Moreover, most large studies reported that women did better than men (67%; Fig. 3, right).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Sex effects on TBI outcomes in humans

    Non-stratified studies were split between those showing women faring better (33%), women faring worse than men (40%), and no sex differences (19%).

    “Non-stratified studies that did not segregate patients by injury severity were split between those that showed women faring better (33%) and those that showed women faring worse than men (40%), with 19% reporting no sex differences in TBI outcomes or pathology (Fig. 2, lower left).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Sex effects on TBI outcomes in humans

    Among studies of mild-moderate TBI, 60% found that women fared worse than men, whereas only 9% reported better outcomes in women.

    “For example, a majority of studies of mild-moderate TBI found that women fared worse than men (60%), whereas only 9% of these reported better outcomes in women (Fig. 2, lower middle).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Sex effects on TBI outcomes in animal studies

    Among animal studies of mild TBI, 17% showed better outcomes in females than males, whereas in moderate-severe TBI, 55% showed better outcomes in females.

    “Specifically, among studies of mild TBI, only 17% showed better outcomes in females than males, whereas in moderate-severe TBI a larger proportion (55%) showed better outcomes in females.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Only 15% of studies specifically reported extracranial injury status, with similar numbers including versus excluding these patients.

    “Further, only 15% of studies specifically reported extracranial injury status, with similar numbers including versus excluding these patients.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Among 156 human studies, functional outcomes were reported in 149, while physiological/neuropathological measures were reported in 24.

    “Although functional outcomes were reported in 149 of the 156 human studies, physiological/neuropathological measures were only reported in 24.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    In human studies of TBI, studies of severe TBI were more likely to use community integration and survival outcomes and to show better outcomes in women.

    “Moreover, studies of severe TBI were more likely to use CI and S as outcome measures and to show better outcomes in women.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Sex effects on TBI outcomes in animal studies

    Among all animal studies, 44% reported that females fared better than males, 14% reported that females fared worse, 28% showed no sex differences, and 14% showed mixed results.

    “Among all animal studies, 44% reported that females fared better than males, 14% reported that females fared worse, with the remaining studies showing no sex differences (28%) or mixed results (14%; Fig. 4, top).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Human versus animal studies

    Mild TBI is associated with worse outcomes in women in clinical studies but mixed results in animal studies.

    “In contrast, mild TBI is associated with worse outcomes in women in clinical studies but mixed results in animal studies (Figs. 2 and 4).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The studies included in the review are representative of the literature on sex differences in TBI.

  • May combine two claims.

    Findingown data
    § Sex effects on TBI outcomes in animal studies

    Most CCI studies (55%) reported better outcomes in females than males, with none showing males doing better.

    “Most of the CCI studies (55%) reported better outcomes in females than males, with none showing males doing better (Fig. 5).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given
    § Human versus animal studies

    Among all human studies, women tend to do worse following TBI, whereas in animal studies, females tend to do better.

    “As Figure 6 summarizes, among all human studies, women tend to do worse following TBI, whereas in animal studies, females tend to do better.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The studies included in the review are representative of the literature on sex differences in TBI.

  • May combine two claims.

    Findingown data
    § Sex effects on TBI outcomes in animal studies

    In animal studies using CHI, 31% found females doing better and 23% showed females doing worse.

    “In studies using CHI, 31% found females doing better and 23% showed females doing worse.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Interpreting mixed results

    Figures 2 and 4 indicate that 9% of human studies and 28% of animal studies yielded mixed results per our definition.

    “Figures 2 and 4 indicate that 9% of human studies and 28% of animal studies yielded mixed results per our definition.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The studies included in the review are representative of the literature on sex differences in TBI.

  • May combine two claims.

    Findingown data
    § Interpreting mixed results

    Restricting analysis to studies reporting more than one outcome indicates that 19% of human and 37% of animal studies reported mixed results.

    “Restricting analysis to studies reporting more than one outcome indicates that 19% of human and 37% of animal studies reported mixed results.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The studies included in the review are representative of the literature on sex differences in TBI.

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given
    § Conclusion

    Historically, preclinical studies in neurotrauma have been performed exclusively in males.

    “Historically, preclinical studies in neurotrauma have been performed exclusively in males”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The reviewed human and animal studies are sufficiently representative to support conclusions about sex differences in TBI outcomes.

  • Classified as probably not a substantial claim.

    Findingnone given
    § Conclusion

    An array of outcome measures has been used to study sex differences in TBI in both humans and animals.

    “An array of outcome measures has been used to study sex differences in TBI in both humans and animals.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The reviewed human and animal studies are sufficiently representative to support conclusions about sex differences in TBI outcomes.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given
    § Sex differences in TBI: Do mitochondria play a role?

    Few studies have investigated potential effects of androgens or chromosomal contributions to sex differences in TBI outcomes.

    “Few studies have investigated potential effects of androgens or chromosomal contributions to sex differences in TBI outcomes.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The reviewed human and animal studies are sufficiently representative to support conclusions about sex differences in TBI outcomes.

  • May combine two claims.

    Findingnone given
    § Conclusion

    Most studies using the controlled cortical impact (CCI) model indicate that females do better and none show males with better outcomes.

    “Most studies using the CCI model indicate that females do better and none show males with better outcomes.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The reviewed human and animal studies are sufficiently representative to support conclusions about sex differences in TBI outcomes.

  • May combine two claims.

    Premisecitation
    § Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know

    Fewer women than men are enrolled in clinical trials of TBI, in part because the incidence of TBI in men is far greater than in women.

    “Fewer women than men are enrolled in clinical trials of TBI, in part because the incidence of TBI in men is far greater than in women.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [19] 19. Stein, D.G. (2015). Embracing failure: what the Phase III progesterone studies can teach about TBI clinical trials. Brain Inj. 29, 12591272.

      Not checked in the free run.

    • cites [21] 21. McCarthy, M.M., Pickett, L.A., VanRyzin, J.W., and Kight, K.E. (2015). Surprising origins of sex differences in the brain. Horm. Behav. 76, 3-10.

      Not checked in the free run.

    • cites [22] 22. Soldin, O.P., and Mattison, D.R. (2009). Sex differences in pharmacokinetics and pharmacodynamics. Clin. Pharmacokinet 48, 143-157.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Introduction

    Men are approximately 40% more likely to suffer a TBI compared with women in the general adult population, although the sex difference disappears above 75 years of age.

    “Epidemiological data suggest that men are approximately 40% more likely to suffer a TBI compared with women in the general adult population, although the sex difference disappears above 75 years of age.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] 1. Faul, M., and Coronado, V. (2015). Epidemiology of traumatic brain injury. Handb. Clin. Neurol. 127, 3-13.

      Not checked in the free run.

    • cites [2] 2. Coronado, V.G., McGuire, L.C., Sarmiento, K., Bell, J., Lionbarger, M.R., Jones, C.D., Geller, A.I., Khoury, N., and Xu, L. (2012). Trends in traumatic brain injury in the U.S. and the public health response: 1995-2009. J. Safety Res. 43, 299-307.

      Not checked in the free run.

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    Premisecitation
    § Introduction

    Women are more likely to receive injuries from assault or violence in interpersonal relationships, and men are more likely to receive work-related injuries from falls and motor vehicle collisions.

    “First, are there differences in how men and women acquire their injuries? The answer appears to be yes, with women more likely to receive injuries from assault or violence in interpersonal relationships and men more likely to receive work-related injuries from falls and motor vehicle collisions.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [6] 6. Chang, V.C., Ruseckaite, R., Collie, A., and Colantonio, A. (2014). Examining the epidemiology of work-related traumatic brain injury through a sex/gender lens: analysis of workers' compensation claims in Victoria, Australia. Occup. Environ. Med. 71, 695-703.

      Not checked in the free run.

    • cites [7] 7. Colantonio, A. (2016). Sex, gender, and traumatic brain injury: A commentary. Arch. Physical Med. Rehabil. 97, S1-S4.

      Not checked in the free run.

    • cites [8] 8. Iverson, K.M., Hendricks, A.M., Kimerling, R., Krengel, M., Meterko, M., Stolzmann, K.L., Baker, E., Pogoda, T.K., Vasterling, J.J., and Lew, H.L. (2011). Psychiatric diagnoses and neurobehavioral symptom severity among OEF/OIF VA patients with deploymentrelated traumatic brain injury: a gender comparison. Women Health Iss. 21, S210-S217.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Introduction

    Genetics and sex hormones likely influence inflammation, edema, oxidative stress, excitotoxicity, and mitochondrial function in the brain's response to injury, with sex differences.

    “Second, are there differences in how the brains of men and women respond to an injury at the cellular and molecular level? Again, the answer appears to be yes, with genetics and sex hormones likely to influence inflammation, edema, oxidative stress, excitotoxicity, and mitochondrial function.”
    Quote in the paperSubstantial claim0 of 7 sources checked
    • cites [9] 9. Demarest, T.G., and McCarthy, M.M. (2015). Sex differences in mitochondrial (dys)function: implications for neuroprotection. J. Bioenerg. Biomembr. 47, 173-188.

      Not checked in the free run.

    • cites [10] 10. Gunther, M., Plantman, S., Davidsson, J., Angeria, M., Mathiesen, T., and Risling, M. (2015). COX-2 regulation and TUNEL-positive cell death differ between genders in the secondary inflammatory response following experimental penetrating focal brain injury in rats. Acta Neurochir. (Wien) 157, 649-659.

      Not checked in the free run.

    • cites [11] 11. Roof, R.L., Duvdevani, R., and Stein, D.G. (1993). Gender influences outcome of brain injury: progesterone plays a protective role. Brain Res. 607, 333-336.

      Not checked in the free run.

    • cites [12] 12. Villapol, S., Loane, D.J., and Burns, M.P. (2017). Sexual dimorphism in the inflammatory response to traumatic brain injury. Glia 65, 1423-1438.

      Not checked in the free run.

    • cites [13] 13. Farin, A., Deutsch, R., Biegon, A., and Marshall, L.F. (2003). Sexrelated differences in patients with severe head injury: greater susceptibility to brain swelling in female patients 50 years of age and younger. J. Neurosurg. 98, 32-36.

      Not checked in the free run.

    • cites [14] 14. Wagner, A.K., Bayir, H., Ren, D., Puccio, A., Zafonte, R.D., and Kochanek, P.M. (2004). Relationships between cerebrospinal fluid markers of excitotoxicity, ischemia, and oxidative damage after severe TBI: the impact of gender, age, and hypothermia. J. Neurotrauma 21, 125-136.

      Not checked in the free run.

    • cites [15] 15. Wagner, A.K., Fabio, A., Puccio, A.M., Hirschberg, R., Li, W., Zafonte, R.D., and Marion, D.W. (2005). Gender associations with cerebrospinal fluid glutamate and lactate/pyruvate levels after severe traumatic brain injury. Crit. Care Med. 33, 407-413.

      Not checked in the free run.

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    Interpretationcitation
    § Introduction

    Women have a lower prevalence of deployment-related TBI than men, but as more women serve in active military duty, their relative risk of sustaining combat-related injuries is likely to increase compared with civilian counterparts.

    “Although women have a lower prevalence of deployment-related TBI than men, as a growing number of women choose to serve in active military duty, their relative risk of sustaining combat-related injuries is likely to increase compared with their civilian counterparts.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [4] 4. Amoroso, T., and Iverson, K.M. (2017). Acknowledging the risk for traumatic brain injury in women veterans. J. Nerv. Ment. Dis. 205, 318-323.

      Not checked in the free run.

    • cites [5] 5. Amara, J.H., Stolzmann, K.L., Iverson, K.M., and Pogoda, T.K. (2018). Predictors of employment status in male and female Post-9/ 11 veterans evaluated for traumatic brain injury. J Head Trauma Rehabil. 34, 11-20.

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Introduction

    Each of the factors of injury acquisition, cellular and molecular response, repair and recovery, and extracerebral trauma might influence outcome in studies of sex differences in TBI.

    “Each and all of these factors might influence outcome in studies of sex differences in TBI.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Adolescent girls have decreased cadence on a dual gait-cognition task indicating impaired executive function up to 2 weeks post-TBI.

    “Decreased cadence on a dual gait-cognition task in adolescent girls indicating impaired executive function up to 2 weeks post-TBI.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no differences in GOS or mortality.

    “No differences GOS or mortality; CI, SB, S”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in symptom severity.

    “No difference in symptom severity; CI”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have lower excitotoxic oxidative damage.

    “Lower excitotoxic oxidative damage in women”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have more post-concussion symptoms and worse GOS-E at 3 months post-injury.

    “More post-concussion symptoms and worse GOS-E in women at 3 months post-injury; SB; CI”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have more nausea, light sensitivity, change in taste/smell and appetite, and poor sleep-related symptoms compared with age-matched men.

    “More nausea, light sensitivity, change in taste/smell and appetite, and poor sleep-related symptoms in women vs. age-matched men;”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women soccer and basketball players have higher rates of injury and longer recovery times.

    “Higher rates of injury and longer recovery times in women soccer basketball players; CI”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no differences in cognitive tests between men and women.

    “No differences in cognitive tests between men and women; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have better executive function.

    “Better executive function in women; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have shorter duration of post-traumatic amnesia.

    “Shorter duration of post-traumatic amnesia in women.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have more verbal memory deficits but no differences on tasks, neurobehavioral symptoms, or chronic stress.

    “More verbal memory deficits in women but no differences on tasks, neurobehavioral symptoms, or chronic stress; SB”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women athletes have greater symptom severity and longer time to return to baseline performance.

    “Greater symptom severity and longer time to return to baseline performance in women athletes; CI, SB”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have better quality of life 8-24 years after TBI.

    “Better quality of life 8-24 years after TBI in women; CI”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning
    § Sex effects on TBI outcomes in humans

    Patients surviving severe TBI are less likely to complete detailed cognitive testing, whereas a study of survival in patients with mild TBI might suffer from ceiling effects because few patients will die.

    “This may be because patients surviving severe TBI are less likely to complete detailed cognitive testing, whereas a study of survival in patients with mild TBI might suffer from ceiling effects because few patients will die.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in sleep disturbance after multiple concussions.

    “difference in sleep disturbance after multiple concussions; SB”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    More post-concussive symptoms occur in women at 3 months post-TBI, mainly in child-bearing age.

    “More post-concussive symptoms in women at 3 months post-TBI, mainly child-bearing age; SB”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women athletes have faster processing speed and reaction time than men.

    “Faster processing speed and reaction time in women athletes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have increased sleep disturbance after a single concussion, especially those above age 15.

    “Increased sleep disturbance after single concussion in women, especially those above age 15.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data
    § Sex effects on TBI outcomes in humans

    Social-behavioral outcome measures used in smaller studies correspond to worse outcomes in women, whereas larger studies that use community integration and survival were more likely to report women faring better than men.

    “When comparing these trends with sex difference findings across study size (Fig. 3), it seems that SB outcome measures used in smaller studies correspond to worse outcomes in women. In contrast, larger studies that use CI and S were more likely to report women faring better than men.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have higher mortality in the ICU and 6 months post-TBI.

    “Higher mortality in the ICU and 6 months post-TBI in women.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no differences in GOS 5 days post-TBI.

    “No differences in GOS 5 days post-TBI; CI”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims. The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Depression is exacerbated over time in women, but resolves over time in men.

    “Depression exacerbated over time in women, but resolved over time men; SB”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning
    § Classification of studies

    The system of classification used in this review is unbiased because it avoids judgments on the relative importance of each outcome or symptom.

    “Such a system of classification is unbiased because it avoids judgments on the relative importance of each outcome/symptom.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have lower risk of mortality compared with men.

    “Lower risk of mortality in women compared with men; S”
    • Also stated in: § Table 1. Human Studies of TBI Comparing Outcomes by Sex · plain
      “Lower mortality in women; S”
    • Also stated in: § Table 1. Human Studies of TBI Comparing Outcomes by Sex · plain
      “Lower risk of post-injury mortality in women; S”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have more post-concussion symptoms, but no differences in rate, loss of consciousness, amnesia, or confusion.

    “More post-concussion symptoms in women, but no differences rate, loss of consciousness, amnesia, or confusion; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    More women experienced post-concussion symptoms and disability, but there are differences in life satisfaction 3 years post-injury.

    “More women experienced post-concussion symptoms and disability, but differences in life satisfaction 3 years post-injury; SB; CI”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have lower mortality after blunt force injury.

    “Lower mortality in women after blunt force injury; S”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women show sustained hypoactivation in fMRI activity during memory tasks.

    “Sustained hypoactivation in fMRI activity during memory tasks”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women in China have a higher risk of mortality.

    “Higher risk of mortality in women in China; S”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Girls have better scores on verbal memory at 1 year post-injury.

    “Better scores on verbal memory in girls at 1 year post-injury;”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have more depressive symptoms.

    “More depressive symptoms in women; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no differences in eye coordination or balance.

    “No differences eye coordination or balance; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Girls have less withdrawal and better social skills 1 year post-TBI.

    “Less withdrawal and better social skills in girls 1 year post-TBI;”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have more vestibulo-oculomotor impairment and longer time to symptom resolution.

    “More vestibulo-oculomotor impairment and longer time to symptom resolution in women.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    More post-concussive symptoms occur in adult women aged 18-59, but not in minor girls aged 4-17, at 3 months post-TBI compared with men.

    “More post-concussive symptoms in adult women (ages 18-59) but not minor girls (ages 4-17), at 3 months post-TBI compared with men: SB”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    More post-concussive symptoms and worse performance on tasks occur in women athletes up to 2 weeks post-TBI.

    “More post-concussive symptoms and worse performance on tasks in women athletes up to 2 weeks post-TBI; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have better visual memory than men.

    “Better visual memory in women.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    More women with minor TBI were depressed and had incomplete return to work 6-12 months post-TBI than men with similar injury severity.

    “More women with minor TBI were depressed and had incomplete return work 6-12 months post-TBI than men with similar injury severity; SB; CI”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no differences in incidence of neuropathic pain following TBI.

    “No differences incidence of neuropathic pain following TBI; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have better work capacity outcomes.

    “Better work capacity outcomes in women; CI”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have more post-traumatic headaches and longer recovery time 1-3 weeks post-TBI.

    “More post-traumatic headaches and longer recovery time 1-3 weeks post- TBI in women; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have prolonged post-concussive symptoms 3 months post-TBI.

    “Prolonged post-concussive symptoms 3 months post-TBI in women;”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have more post-concussive symptoms due to increased anxiety sensitivity.

    “More post-concussive symptoms due to increased anxiety sensitivity”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning
    § Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know

    The paucity of women in clinical trials means that promising treatments are not being tested against the real biological substrate and may hamper translational success.

    “Subsequently, the paucity of women in clinical trials means that promising treatments are not being tested against the real biological substrate and may hamper translational success.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Level of oxidative damage correlates with GOS in women but not men.

    “level of oxidative damage correlated with GOS in women but not men”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Post-menopausal women have better survival rates.

    “Better survival rates in post-menopausal women.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning
    § Sex effects on TBI outcomes in humans

    Smaller studies can collect data prospectively from individual patients, whereas very large studies tend to extract data retrospectively from existing databases including medical records.

    “This is likely because smaller studies can collect data prospectively from individual patients, whereas very large studies tend to extract data retrospectively from existing databases including medical records.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have higher severity and more concussion symptoms.

    “Higher severity and more concussion symptoms in women.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Girls have worse neurocognitive performance and more post-concussion symptoms.

    “Worse neurocognitive performance and more post-concussion symptoms girls; SB”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know

    Biological sex can affect brain anatomy, cellular pathways, and drug pharmacokinetics.

    “Because brain anatomy, cellular pathways, and drug pharmacokinetics can be affected by biological sex, 21,22”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [21] 21. McCarthy, M.M., Pickett, L.A., VanRyzin, J.W., and Kight, K.E. (2015). Surprising origins of sex differences in the brain. Horm. Behav. 76, 3-10.

      Not checked in the free run.

    • cites [22] 22. Soldin, O.P., and Mattison, D.R. (2009). Sex differences in pharmacokinetics and pharmacodynamics. Clin. Pharmacokinet 48, 143-157.

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisereasoning
    § Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know

    The NIH workshop acknowledged that findings to date have been mixed and concluded that numerous knowledge gaps still exist regarding the effects of sex in TBI.

    “The workshop acknowledged that findings to date have been mixed, and concluded that numerous knowledge gaps still exist regarding the effects of sex in TBI.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Girls have more post-concussion symptoms and greater impairment in vestibular reflexes up to 3 weeks post-TBI.

    “More post-concussion symptoms and greater in vestibular reflexes in girls up to 3 weeks post-TBI.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have shorter length of hospital stay and better outcomes at 3 months.

    “Shorter length of hospital stay and better outcomes on 3-month women; CI”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have more impaired empathy post-TBI.

    “More impaired empathy in women post-TBI; SB”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have more severe post-concussion symptoms and anxiety.

    “More severe post-concussion symptoms and anxiety in women; SB”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Men have shorter comprehension times than women.

    “Shorter comprehension times in men;”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have better emotion recognition than men.

    “Better emotion recognition in women.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in symptom recovery or cognitive recovery between women and men.

    “No difference in symptom recovery or cognitive recovery; SB”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have more headaches and dizziness than men.

    “More headaches and dizziness in women;”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no differences in neurocognitive abilities between women and men.

    “No differences in neurocognitive abilities; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in sleep architecture between women and men.

    “No difference in sleep architecture; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims. The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have better memory and immediate recall than men.

    “better memory and immediate recall women; SB”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Lower cerebral perfusion pressure, higher intracranial pressure, and greater frequency of cerebral edema may contribute to higher mortality and unfavorable GOS at 1 month post-TBI in women.

    “Lower cerebral perfusion pressure, higher intracranial pressure, and greater frequency of cerebral edema may contribute to higher mortality and unfavorable GOS 1 month postTBI in women. 13,24,25”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [13] 13. Farin, A., Deutsch, R., Biegon, A., and Marshall, L.F. (2003). Sexrelated differences in patients with severe head injury: greater susceptibility to brain swelling in female patients 50 years of age and younger. J. Neurosurg. 98, 32-36.

      Not checked in the free run.

    • cites [24] 24. Balestreri, M., Steiner, L.A., and Czosnyka, M. (2003). Sex-related differences and traumatic brain injury. J. Neurosurg. 99, 616; author reply 616-617.

      Not checked in the free run.

    • cites [25] 25. Czosnyka, M., Radolovich, D., Balestreri, M., Lavinio, A., Hutchinson, P., Timofeev, I., Smielewski, P., and Pickard, J.D. (2008). Gender-related differences in intracranial hypertension and outcome after traumatic brain injury. Acta Neurochir. Suppl. 102, 25-28.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in 6-month GOS between women and men.

    “No difference in 6-month GOS; S”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have higher levels of dopamine metabolites in CSF.

    “Higher levels of dopamine metabolites in CSF of women”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Systolic blood pressure is lower in pubescent and pre-pubescent girls than in boys.

    “Systolic blood pressure was in pubescent and pre- pubescent girls than in boys;”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims. The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no differences in frequency or severity of chronic pain between women and men.

    “No differences in frequency or severity of chronic pain; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no incidence of hyponatremia post-TBI.

    “No incidence hyponatremia post-TBI”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women hockey players have fewer cerebral micro-bleeds post-concussion.

    “Fewer cerebral micro-bleeds post- concussion in women hockey players”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Race may interact with sex to influence TBI outcomes, with a study of nearly 3000 patients with mild to severe TBI finding higher incidence of brain edema in women sampled in Hong Kong but not those in Australia.

    “Additionally, race may interact with sex to influence TBI outcomes, with a study of nearly 3000 patients with mild to severe TBI finding higher incidence of brain edema in women sampled in Hong Kong but not those in Australia. 30”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] 30. Yeung, J.H., Mikocka-Walus, A.A., Cameron, P.A., Poon, W.S., Ho, H.F., Chang, A., Graham, C.A., and Rainer, T.H. (2011). Protection from traumatic brain injury in hormonally active women vs. men of a similar age: a retrospective international study. Arch. Surg. 146, 436-442.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in insomnia prevalence or severity 3 months post-TBI between women and men.

    “No difference in insomnia prevalence or severity 3 months post-TBI;”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in serum markers of oxidative stress trauma between women and men.

    “No difference in serum of oxidative stress trauma”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in mortality or GOS at discharge between women and men.

    “No difference in mortality or GOS at discharge.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in unemployment rate between men and women veterans.

    “No difference in unemployment rate between men and women veterans;”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no sex difference in diffuse axonal injury, brain edema, hypoxia, ICP, or contusional bleeding.

    “No sex difference in diffuse axonal injury, brain edema, hypoxia, ICP, contusional bleeding;”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in duration of symptoms between women and men.

    “No difference in duration of symptoms, or SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no sex differences in lesions on CT scans.

    “sex differences in lesions on CT scans”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no differences in mortality, injury severity, or incidence of acute complications post-TBI between women and men.

    “No differences in mortality, injury severity, or incidence of acute complications post-TBI; SB, S”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    These differences could be attributed to race-specific single nucleotide polymorphisms in genes affecting inflammation and predisposition to genetic diseases.

    “These differences could be attributed to race-specific single nucleotide polymorphisms in genes affecting inflammation and predisposition to genetic diseases. 31,32”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [31] 31. Huang, T., Shu, Y., and Cai, Y.D. (2015). Genetic differences among ethnic groups. BMC Genomics 16, 1093.

      Not checked in the free run.

    • cites [32] 32. Van Dyke, A.L., Cote, M.L., Wenzlaff, A.S., Land, S., and Schwartz, A.G. (2009). Cytokine SNPs: comparison of allele frequencies by race and implications for future studies. Cytokine 46, 236-244.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no differences in number of post-concussive symptoms, neurocognitive scores, or depression up to 2 weeks post-injury between women and men.

    “No differences in number of post-concussive symptoms, neurocognitive scores or depression up to 2 weeks post-injury; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no differences in concussion symptom reporting or cognition in hockey players 6 months post-injury.

    “No differences in concussion symptom reporting or cognition in hockey players 6 months post-injury; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims. The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have lower rates of fogginess, memory impairment, and concentration problems.

    “Lower rates fogginess, memory impairment, and concentration problems”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Girls have lower mortality than boys.

    “Lower mortalityin girls; S”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no differences in mild depression 1-year post-injury between women and men.

    “No differences in mild depression 1-year post-injury; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have shorter hospital stay and better attention, working memory, and language skills 1 year post-TBI.

    “Shorter hospital stay and better attention, working memory, and language skills 1 year post-TBI in women;”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no sex differences in motor outcomes or perceived life satisfaction.

    “No motor outcomes or perceived life satisfaction; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have better executive function due to greater self-awareness related deficits.

    “Better executive function in women due to greater self-awareness related deficits; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in visuo-spatial abilities between women and men.

    “No difference in visuo-spatial abilities; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in postural control and balance post-TBI between women and men.

    “No difference in postural control and balance post-TBI; CI”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in cognition or symptoms in soccer players 6 months post-TBI between women and men.

    “No difference in cognition or symptoms in soccer players 6 months post- TBI; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have higher fractional anisotropy (indicative of white matter integrity) than men.

    “Higher fractional anisotropy (indicative of white matter integrity) in women”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in symptom reporting between women and men.

    “No difference in symptom reporting in women.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in neuropsychological performance 2 years post-TBI between women and men.

    “No difference in neuropsychological performance 2 post-TBI;”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in neurocognitive ability or number of symptoms in high school soccer players.

    “No difference in neurocognitive ability or number of symptoms in high school soccer players; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women veterans have less physical aggression than men veterans.

    “Less physical aggression in women veterans”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no differences in depression between women and men veterans.

    “but no differences depression; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Men athletes have better visual memory than women athletes.

    “Better visual memory in men athletes;”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no differences in injury severity, GOS, or length of stay in rehabilitation between women and men.

    “No differences in injury severity, GOS, or length of stay in rehabilitation;”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    Women have better post-concussion performance than men.

    “Better post-concussion performance in women; SB”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There is no difference in balance and postural stability between women and men.

    “No difference in balance and postural stability; CI”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given
    § Table 1. Human Studies of TBI Comparing Outcomes by Sex

    There are no differences in length of hospital stay, GOS-E, or functional independence 3.5 years post-TBI.

    “No differences in length of hospital stay, GOS-E, or functional independence 3.5 years post-TBI; CI, S”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Sex effects on TBI outcomes in animal studies

    Severe CCI did not show significant difference in time-course of neurodegeneration or in overall tissue damage between males and females.

    “However, severe CCI did not show significant difference in time-course of neurodegeneration or in overall tissue damage between males and females. 43”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] 43. Hall, E.D., Gibson, T.R., and Pavel, K.M. (2005). Lack of a gender difference in post-traumatic neurodegeneration in the mouse controlled cortical impact injury model. J. Neurotrauma 22, 669-679.

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisenone given
    § Sex effects on TBI outcomes in animal studies

    Animal studies offer the ability to control many experimental variables, to study cellular and molecular mechanisms, and to directly test the link between mechanisms and functional outcomes.

    “Animal studies offer the ability to control many experimental variables, to study cellular and molecular mechanisms, and to directly test the link between mechanisms and functional outcomes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Human versus animal studies

    Cell death following brain injury is triggered by caspase activation in females but by caspase-independent mechanisms in males.

    “For instance, cell death following brain injury is triggered by caspase activation in females but by caspase-independent mechanisms in males. 9”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] 9. Demarest, T.G., and McCarthy, M.M. (2015). Sex differences in mitochondrial (dys)function: implications for neuroprotection. J. Bioenerg. Biomembr. 47, 173-188.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Hormonal versus non-hormonal factors

    Normally cycling females had significantly better survival rates, blood-brain barrier integrity, improved cortical blood flow, fewer sensorimotor deficits, less brain edema, and smaller contusion volumes than age-matched males after TBI.

    “Normally cycling females had significantly better survival rates, blood-brain barrier integrity, improved cortical blood flow, fewer sensorimotor deficits, less brain edema, and smaller contusion volumes than age-matched males after TBI. 11,60-62”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [11] 11. Roof, R.L., Duvdevani, R., and Stein, D.G. (1993). Gender influences outcome of brain injury: progesterone plays a protective role. Brain Res. 607, 333-336.

      Not checked in the free run.

    • cites [60] 60. Roof, R.L., and Hall, E.D. (2000). Estrogen-related gender difference in survival rate and cortical blood flow after impact-acceleration head injury in rats. J. Neurotrauma 17, 1155-1169.

      Not checked in the free run.

    • cites [61] 61. Bramlett, H.M., and Dietrich, W.D. (2001). Neuropathological protection after traumatic brain injury in intact female rats versus males or ovariectomized females. J. Neurotrauma 18, 891-900.

      Not checked in the free run.

    • cites [62] 62. Clevenger, A.C., Kim, H., Salcedo, E., Yonchek, J.C., Rodgers, K.M., Orfila, J.E., Dietz, R.M., Quillinan, N., Traystman, R.J., and Herson, P.S. (2018). Endogenous sex steroids dampen neuroinflammation and improve outcome of traumatic brain injury in mice. J. Mol. Neurosci. 64, 410-420.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Hormonal versus non-hormonal factors

    Female rats in the proestrous phase of their cycles had less brain edema and lower intracranial pressure after TBI compared with non-proestrous females presumably due to elevated serum levels of estrogen and progesterone.

    “Similarly, female rats in the proestrous phase of their cycles had less brain edema and lower intracranial pressure after TBI compared with non-proestrous females presumably due to elevated serum levels of estrogen and progesterone. 64”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [64] 64. Maghool, F., Khaksari, M., and Siahposht Khachki, A. (2013). Differences in brain edema and intracranial pressure following traumatic brain injury across the estrous cycle: involvement of female sex steroid hormones. Brain Res. 1497, 61-72.

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given
    § Discussion

    The overall picture of sex differences in TBI is not straightforward; findings from human and animal studies are complicated and often contradictory.

    “Considering the current body of research on sex differences in TBI, the overall picture is not a straightforward one that points to better outcomes in one sex versus the other. Rather, the findings we have reviewed from human and animal studies are complicated and often contradictory.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given
    § Human versus animal studies

    Human studies more commonly report functional outcomes after TBI, whereas animal studies more frequently report measures related to cellular or molecular mechanism.

    “As noted above, human studies more commonly report functional outcomes after TBI, whereas animal studies more frequently report measures related to cellular or molecular mechanism.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation
    § Human versus animal studies

    Post-concussive symptoms in human mild TBI studies are usually self-reported and may be influenced by societal gender stereotypes resulting in men reporting symptoms differently from women.

    “Such symptoms are usually self-reported and may be influenced by societal gender stereotypes resulting in men reporting symptoms differently from women. 53,54”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [53] 53. Maclean, A., Sweeting, H., and Hunt, K. (2010). 'Rules' for boys, 'guidelines' for girls: gender differences in symptom reporting during childhood and adolescence. Soc. Sci. Med. 70, 597-604.

      Not checked in the free run.

    • cites [54] 54. Wallace, J., Covassin, T., and Beidler, E. (2017). Sex differences in high school athletes' knowledge of sport-related concussion symptoms and reporting behaviors. J. Athl. Train. 52, 682-688.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Sex effects on TBI outcomes in animal studies

    Females performed better than males on sensorimotor tasks but not on cognitive tasks following moderate to severe CCI.

    “Females performed better than males on sensorimotor tasks but not on cognitive tasks following moderate to severe CCI. 37-40”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [37] 37. Free, K.E., Greene, A.M., Bondi, C.O., Lajud, N., de la Tremblaye, P.B., and Kline, A.E. (2017). Comparable impediment of cognitive function in female and male rats subsequent to daily administration of haloperidol after traumatic brain injury. Exp. Neurol. 296, 62-68.

      Not checked in the free run.

    • cites [38] 38. Wagner, A.K., Willard, L.A., Kline, A.E., Wenger, M.K., Bolinger, B.D., Ren, D., Zafonte, R.D., and Dixon, C.E. (2004). Evaluation of estrous cycle stage and gender on behavioral outcome after experimental traumatic brain injury. Brain Res. 998, 113-121.

      Not checked in the free run.

    • cites [39] 39. Xu, X., Cao, S., Chao, H., Liu, Y., and Ji, J. (2016). Sex-related differences in striatal dopaminergic system after traumatic brain injury. Brain Res. Bull. 124, 214-221.

      Not checked in the free run.

    • cites [40] 40. Xiong, Y., Mahmood, A., Lu, D., Qu, C., Goussev, A., Schallert, T., and Chopp, M. (2007). Role of gender in outcome after traumatic brain injury and therapeutic effect of erythropoietin in mice. Brain Res. 1185, 301-312.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Hormonal versus non-hormonal factors

    In adolescent male mice with TBI, progesterone improved motor performance but exacerbated deficits in female mice.

    “In adolescent male mice with TBI, progesterone improved motor performance but exacerbated deficits in female mice. 66”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [66] 66. Mannix, R., Berglass, J., Berkner, J., Moleus, P., Qiu, J., Jantzie, L.L., Meehan, W.P., 3rd, Stanley, R.M., and Robinson, S. (2014). Sex differences in the effect of progesterone after controlled cortical impact in adolescent mice: a preliminary study. J. Neurosurg. 121, 1337-1341.

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationcitation
    § Hormonal versus non-hormonal factors

    One study suggests that the better post-injury outcome in pseudopregnant females compared with both males and intact females might be due to their 50-100 times higher levels of progesterone and its metabolites at the time of injury.

    “One study suggests that the better post-injury outcome in pseudopregnant females compared with both males and intact females might be due to their 50-100 times higher levels of progesterone and its metabolites at the time of injury. 63”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [63] 63. Meffre, D., Pianos, A., Liere, P., Eychenne, B., Cambourg, A., Schumacher, M., Stein, D.G., and Guennoun, R. (2007). Steroid profiling in brain and plasma of male and pseudopregnant female rats after traumatic brain injury: analysis by gas chromatography/mass spectrometry. Endocrinology 148, 2505-2517.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Sex effects on TBI outcomes in animal studies

    Females showed less edema than males at 5 h, 3 days, and 5 days after impact acceleration injury, but more edema at 24 h post-injury.

    “Regarding timecourse, females showed less edema than males at 5 h, 3 days, and 5 days after impact acceleration injury, but more edema at 24 h post-injury. 41”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] 41. O'Connor, C.A., Cernak, I., and Vink, R. (2006). The temporal profile of edema formation differs between male and female rats following diffuse traumatic brain injury. Acta Neurochir. Suppl. 96, 121-124.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Human versus animal studies

    In mice, dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis following blast TBI is caused by dysregulation of pre-autonomic neurons in females, but by disruption of limbic pathways in males.

    “In mice, dysfunction of the hypothalamic-pituitaryadrenal (HPA) axis following blast TBI is caused by dysregulation of pre-autonomic neurons in females, but by disruption of limbic pathways in males. 58”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [58] 58. Russell, A.L., Richardson, M.R., Bauman, B.M., Hernandez, I.M., Saperstein, S., Handa, R.J., and Wu, T.J. (2018). Differential responses of the HPA axis to mild blast traumatic brain injury in male and female mice. Endocrinology 159, 2363-2375.

      Not checked in the free run.

    • Rests on an assumption: Animal models of TBI can inform the pathophysiology of human TBI.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given
    § Sex effects on TBI outcomes in animal studies

    Mixed results within an animal study may result from pre-set group sizes that are powered to detect sex differences in some assessments but might be inadequate for others.

    “Mixed results within an animal study may also result from pre-set group sizes that are powered to detect sex differences in some assessments but might be inadequate for others.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Human versus animal studies

    Female mice had better ambulation and displayed less anxiety post-TBI although sex differences in brain lesion volumes were not detected.

    “In addition, female mice had better ambulation and displayed less anxiety post-TBI although sex differences in brain lesion volumes were not detected. 49,51”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [49] 49. Tucker, L.B., Fu, A.H., and McCabe, J.T. (2016). Performance of male and female C57BL/6J mice on motor and cognitive tasks commonly used in pre-clinical traumatic brain injury research. J. Neurotrauma 33, 880-894.

      Not checked in the free run.

    • cites [51] 51. Tucker, L.B., Burke, J.F., Fu, A.H., and McCabe, J.T. (2017). Neuropsychiatric symptom modeling in male and female C57BL/6J mice after experimental traumatic brain injury. J. Neurotrauma 34, 890-905.

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation
    § Hormonal versus non-hormonal factors

    In pseudo-pregnant rats, post-TBI cerebral edema was even lower than in normally cycling females, suggesting that female sex hormones may exert a dose-dependent neuroprotective response.

    “In pseudo-pregnant rats, post-TBI cerebral edema was even lower than in normally cycling females, suggesting that female sex hormones may exert a dose-dependent neuroprotective response. 11”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] 11. Roof, R.L., Duvdevani, R., and Stein, D.G. (1993). Gender influences outcome of brain injury: progesterone plays a protective role. Brain Res. 607, 333-336.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Hormonal versus non-hormonal factors

    Sex-dependent neuroprotective effects were extinguished in ovariectomized females with low levels of circulating estrogen and progesterone, but rescued by exogenous treatment with these hormones.

    “Conversely, sex-dependent neuroprotective effects were extinguished in ovariectomized females with low levels of circulating estrogen and progesterone, but rescued by exogenous treatment with these hormones. 11,60,61”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [11] 11. Roof, R.L., Duvdevani, R., and Stein, D.G. (1993). Gender influences outcome of brain injury: progesterone plays a protective role. Brain Res. 607, 333-336.

      Not checked in the free run.

    • cites [60] 60. Roof, R.L., and Hall, E.D. (2000). Estrogen-related gender difference in survival rate and cortical blood flow after impact-acceleration head injury in rats. J. Neurotrauma 17, 1155-1169.

      Not checked in the free run.

    • cites [61] 61. Bramlett, H.M., and Dietrich, W.D. (2001). Neuropathological protection after traumatic brain injury in intact female rats versus males or ovariectomized females. J. Neurotrauma 18, 891-900.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Hormonal versus non-hormonal factors

    At the ultrastructural level, axons of cultured neurons isolated from females were consistently smaller and contained fewer microtubules than those from males.

    “At the ultrastructural level, axons of cultured neurons isolated from females were consistently smaller and contained fewer microtubules than those from males.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [102] 102. Dolle, J.P., Jaye, A., Anderson, S.A., Ahmadzadeh, H., Shenoy, V.B., and Smith, D.H. (2018). Newfound sex differences in axonal structure underlie differential outcomes from in vitro traumatic axonal injury. Exp. Neurol. 300, 121-134.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Hormonal versus non-hormonal factors

    Chronically treating mice with an androgenic-anabolic steroid cocktail containing testosterone prior to induction of repeated, mild TBI exacerbated TBI-mediated axonal injury and white matter microgliosis but not behavioral deficits.

    “In contrast, chronically treating mice with an androgenic-anabolic steroid cocktail containing testosterone prior to induction of repeated, mild TBI exacerbated TBI-mediated axonal injury and white matter microgliosis but not behavioral deficits. 85”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [85] 85. Namjoshi, D.R., Cheng, W.H., Carr, M., Martens, K.M., Zareyan, S., Wilkinson, A., McInnes, K.A., Cripton, P.A., and Wellington, C.L. (2016). Chronic exposure to androgenic-anabolic steroids exacerbates axonal injury and microgliosis in the CHIMERA mouse model of repetitive concussion. PLoS One 11, e0146540.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Interpreting mixed results

    Age interacted with sex leading to better verbal abilities in women than men in their twenties but slower processing speed in women than men in their forties.

    “Further, age interacted with sex leading to better verbal abilities in women than men in their twenties but slower processing speed in women than men in their forties. 110”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [110] 110. Eramudugolla, R., Bielak, A.A., Bunce, D., Easteal, S., Cherbuin, N., and Anstey, K.J. (2014). Long-term cognitive correlates of traumatic brain injury across adulthood and interactions with APOE genotype, sex, and age cohorts. J. Int. Neuropsychol. Soc. 20, 444-454.

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning
    § Interpreting mixed results

    These studies, which show within a given population sample that males fare better on some outcome measures and females better on others, encourage us to think about sex effects in TBI beyond a single dimension.

    “These studies, which show within a given population sample that males fare better on some outcome measures and females better on others, encourage us to think about sex effects in TBI beyond a single dimension.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning
    § Interpreting mixed results

    The selection of outcome measures clearly matters and can affect conclusions.

    “In addition, the selection of outcome measures clearly matters and can affect conclusions.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning
    § Hormonal versus non-hormonal factors

    Because testosterone is converted to estradiol by aromatase, there is a possibility that the observed effects are at least partly conferred by its estrogenic metabolite.

    “However, because testosterone is converted to estradiol by aromatase, there is a possibility that the observed effects are at least partly conferred by its estrogenic metabolite.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given
    § Hormonal versus non-hormonal factors

    Although many studies have focused on the hormonal basis of sex differences in TBI, chromosomal differences remain underexplored.

    “Although many studies have focused on the hormonal basis of sex differences in TBI, chromosomal differences remain underexplored.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Interpreting mixed results

    Women veterans were less likely to be diagnosed with post-traumatic stress disorder following TBI, but they were more likely to suffer from depression or anxiety.

    “For example, although women veterans were less likely to be diagnosed with post-traumatic stress disorder following TBI, they were more likely to suffer from depression or anxiety. 8”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] 8. Iverson, K.M., Hendricks, A.M., Kimerling, R., Krengel, M., Meterko, M., Stolzmann, K.L., Baker, E., Pogoda, T.K., Vasterling, J.J., and Lew, H.L. (2011). Psychiatric diagnoses and neurobehavioral symptom severity among OEF/OIF VA patients with deploymentrelated traumatic brain injury: a gender comparison. Women Health Iss. 21, S210-S217.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Interpreting mixed results

    Post-TBI symptoms differed between sexes with women reporting more headaches, dizziness, and drowsiness and men reporting more amnesia and confusion.

    “Post-TBI symptoms differed between sexes with women reporting more headaches, dizziness, and drowsiness and men reporting more amnesia and confusion. 100,109”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [100] 100. Frommer, L.J., Gurka, K.K., Cross, K.M., Ingersoll, C.D., Comstock, R.D., and Saliba, S.A. (2011). Sex differences in concussion symptoms of high school athletes. J. Athl. Train. 46, 76-84.

      Not checked in the free run.

    • cites [109] 109. Colantonio, A., Harris, J.E., Ratcliff, G., Chase, S., and Ellis, K. (2010). Gender differences in self reported long term outcomes following moderate to severe traumatic brain injury. BMC Neurol. 10, 102.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Interpreting mixed results

    Behavioral studies in the same rats also found increased depression-like behaviors in females and working memory deficits in males.

    “Behavioral studies in the same rats also found increased depression-like behaviors in females and working memory deficits in males. 45”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] 45. Wright, D.K., O'Brien, T.J., Shultz, S.R., and Mychasiuk, R. (2017). Sex matters: repetitive mild traumatic brain injury in adolescent rats. Ann. Clin. Transl. Neurol. 4, 640-654.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Hormonal versus non-hormonal factors

    High-resolution MRI in these mice found that sex differences in the volumes of certain brain regions were influenced exclusively by gonadal hormones, whereas differences in others were exclusively under chromosomal control.

    “High-resolution MRI in these mice found that sex differences in the volumes of certain brain regions were influenced exclusively by gonadal hormones, whereas differences in others were exclusively under chromosomal control.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [92] 92. Corre, C., Friedel, M., Vousden, D.A., Metcalf, A., Spring, S., Qiu, L.R., Lerch, J.P., and Palmert, M.R. (2016). Separate effects of sex hormones and sex chromosomes on brain structure and function revealed by high-resolution magnetic resonance imaging and spatial navigation assessment of the Four Core Genotype mouse model. Brain Struct. Funct. 221, 997-1016.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Interpreting mixed results

    Female mice had fewer deficits in social recognition, but increased sociosexual avoidance compared with males following CCI, and also showed greater ambulation but more severely depleted striatal dopamine compared with males.

    “For example, female mice had fewer deficits in social recognition, but increased sociosexual avoidance compared with males following CCI, 51 and also showed greater ambulation but more severely depleted striatal dopamine compared with males. 39”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [51] 51. Tucker, L.B., Burke, J.F., Fu, A.H., and McCabe, J.T. (2017). Neuropsychiatric symptom modeling in male and female C57BL/6J mice after experimental traumatic brain injury. J. Neurotrauma 34, 890-905.

      Not checked in the free run.

    • cites [39] 39. Xu, X., Cao, S., Chao, H., Liu, Y., and Ji, J. (2016). Sex-related differences in striatal dopaminergic system after traumatic brain injury. Brain Res. Bull. 124, 214-221.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Hormonal versus non-hormonal factors

    Testosterone promotes neurogenesis in uninjured male rats and neuronal survival in male and female rats following axonal injury.

    “Testosterone promotes neurogenesis in uninjured male rats 82 and neuronal survival in male and female rats following axonal injury. 83,84”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [82] 82. Spritzer, M.D., and Galea, L.A. (2007). Testosterone and dihydrotestosterone, but not estradiol, enhance survival of new hippocampal neurons in adult male rats. Dev. Neurobiol. 67, 13211333.

      Not checked in the free run.

    • cites [83] 83. Yu, W.H. (1989). Administration of testosterone attenuates neuronal loss following axotomy in the brain-stem motor nuclei of female rats. J. Neurosci. 9, 3908-3914.

      Not checked in the free run.

    • cites [84] 84. Tehranipour, M., and Moghimi, A. (2010). Neuroprotective effects of testosterone on regenerating spinal cord motoneurons in rats. J. Mot. Behav. 42, 151-155.

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation
    § Hormonal versus non-hormonal factors

    The effect of sex hormones on neurogenesis and spine density has also been studied, and could modulate synaptic plasticity during recovery from TBI.

    “The effect of sex hormones on neurogenesis and spine density has also been studied, 103-105 and could modulate synaptic plasticity during recovery from TBI.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [103] 103. Galea, L.A., Spritzer, M.D., Barker, J.M., and Pawluski, J.L. (2006). Gonadal hormone modulation of hippocampal neurogenesis in the adult. Hippocampus 16, 225-232.

      Not checked in the free run.

    • cites [104] 104. Keil, K.P., Sethi, S., Wilson, M.D., Chen, H., and Lein, P.J. (2017). In vivo and in vitro sex differences in the dendritic morphology of developing murine hippocampal and cortical neurons. Sci. Rep. 7, 8486.

      Not checked in the free run.

    • cites [105] 105. Shors, T.J., Chua, C., and Falduto, J. (2001). Sex differences and opposite effects of stress on dendritic spine density in the male versus female hippocampus. J. Neurosci. 21, 6292-6297. source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning
    § Hormonal versus non-hormonal factors

    Given the importance of the amygdala, hippocampus, and prefrontal cortex for stress responses and mood, it is possible that anatomical differences in these regions may contribute to post-TBI symptoms, as women report greater anxiety and depression and men report more amnesia and confusion.

    “Given the importance of the amygdala, hippocampus, and prefrontal cortex for stress responses and mood, 97-99 it is possible that anatomical differences in these regions may contribute to post-TBI symptoms, as women report greater anxiety and depression and men report more amnesia and confusion. 8,100,101”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [97] 97. Bangasser, D.A., and Valentino, R.J. (2014). Sex differences in stress-related psychiatric disorders: neurobiological perspectives. Front. Neuroendocrinol. 35, 303-319. source

      Not checked in the free run.

    • cites [98] 98. Gobinath, A.R., Mahmoud, R., and Galea, L.A. (2014). Influence of sex and stress exposure across the lifespan on endophenotypes of depression: focus on behavior, glucocorticoids, and hippocampus. Front. Neurosci. 8, 420.

      Not checked in the free run.

    • cites [99] 99. McEwen, B.S. (2010). Stress, sex, and neural adaptation to a changing environment: mechanisms of neuronal remodeling. Ann. N Y Acad. Sci. 1204 Suppl., E38-E59.

      Not checked in the free run.

    • cites [8] 8. Iverson, K.M., Hendricks, A.M., Kimerling, R., Krengel, M., Meterko, M., Stolzmann, K.L., Baker, E., Pogoda, T.K., Vasterling, J.J., and Lew, H.L. (2011). Psychiatric diagnoses and neurobehavioral symptom severity among OEF/OIF VA patients with deploymentrelated traumatic brain injury: a gender comparison. Women Health Iss. 21, S210-S217.

      Not checked in the free run.

    • cites [100] 100. Frommer, L.J., Gurka, K.K., Cross, K.M., Ingersoll, C.D., Comstock, R.D., and Saliba, S.A. (2011). Sex differences in concussion symptoms of high school athletes. J. Athl. Train. 46, 76-84.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Hormonal versus non-hormonal factors

    Sex differences in cerebellar and pre-central gray matter volumes were associated with X-chromosome load, whereas sex differences in the amygdala, parahippocampus, and occipital cortex were linked to testosterone levels.

    “Accordingly, sex differences in cerebellar and pre-central gray matter volumes were associated with X-chromosome load, whereas sex differences in the amygdala, parahippocampus, and occipital cortex were linked to testosterone levels. 96”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [96] 96. Lentini, E., Kasahara, M., Arver, S., and Savic, I. (2013). Sex differences in the human brain and the impact of sex chromosomes and sex hormones. Cereb. Cortex 23, 2322-2336.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Sex differences in TBI: Do mitochondria play a role?

    Neuroprotective effects of testosterone, including inhibition of apoptosis, reduction in oxidative stress, improved mitochondrial respiration, and maintenance of mitochondrial membrane potential, have been reported.

    “neuroprotective effects of testosterone including inhibition of apoptosis, reduction in oxidative stress, improved mitochondrial respiration, and maintenance of mitochondrial membrane potential have also been reported.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [144] 144. Chisu, V., Manca, P., Lepore, G., Gadau, S., Zedda, M., and Farina, V. (2006). Testosterone induces neuroprotection from oxidative stress. Effects on catalase activity and 3-nitro-L-tyrosine incorporation into alpha-tubulin in a mouse neuroblastoma cell line. Arch. Ital. Biol. 144, 63-73.

      Not checked in the free run.

    • cites [145] 145. Fanaei, H., Karimian, S.M., Sadeghipour, H.R., Hassanzade, G., Kasaeian, A., Attari, F., Khayat, S., Ramezani, V., and Javadimehr, M. (2014). Testosterone enhances functional recovery after stroke through promotion of antioxidant defenses, BDNF levels and neurogenesis in male rats. Brain Res. 1558, 74-83.

      Not checked in the free run.

    • cites [146] 146. Toro-Urrego, N., Garcia-Segura, L.M., Echeverria, V., and Barreto, G.E. (2016). Testosterone protects mitochondrial function and regulates neuroglobin expression in astrocytic cells exposed to glucose deprivation. Front. Aging Neurosci. 8, 152.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Sex differences in TBI: Do mitochondria play a role?

    During high-stress conditions, males preferentially rely on carbohydrates and amino acids as a fuel source for energy production, whereas females use fats.

    “during high-stress conditions males preferentially rely on carbohydrates and amino acids as a fuel source for energy production, whereas females use fats.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [116] 116. Manole, M.D., Tehranian-DePasquale, R., Du, L., Bayir, H., Kochanek, P.M., and Clark, R.S. (2011). Unmasking sex-based disparity in neuronal metabolism. Curr. Pharm. Des. 17, 3854-3860.

      Not checked in the free run.

    • cites [126] 126. Widdowson, E.M. (1976). The response of the sexes to nutritional stress. Proc. Nutr. Soc. 35, 175-180.

      Not checked in the free run.

    • cites [127] 127. Lamont, L.S. (2005). Gender differences in amino acid use during endurance exercise. Nutr. Rev. 63, 419-422.

      Not checked in the free run.

    • cites [128] 128. Du, L., Hickey, R.W., Bayir, H., Watkins, S.C., Tyurin, V.A., Guo, F., Kochanek, P.M., Jenkins, L.W., Ren, J., Gibson, G., Chu, C.T., Kagan, V.E., and Clark, R.S. (2009). Starving neurons show sex difference in autophagy. J. Biol. Chem. 284, 2383-2396.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Sex differences in TBI: Do mitochondria play a role?

    Mitochondria are crucial to energy production, calcium homeostasis, free radical production, neurotransmitter synthesis, and apoptosis in neurons and glia.

    “Mitochondria are crucial to energy production, as well as calcium homeostasis, free radical production, neurotransmitter synthesis, and apoptosis in neurons and glia.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [115] 115. Mattson, M.P., Gleichmann, M., and Cheng, A. (2008). Mitochondria in neuroplasticity and neurological disorders. Neuron 60, 748-766. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning
    § Interpreting mixed results

    A useful framework for understanding sex differences in TBI may be a 'mosaic' model in which distinct anatomical/functional domains may each respond differently to injury in males versus females.

    “A useful framework for understanding sex differences in TBI may be a ''mosaic'' model in which distinct anatomical/functional domains may each respond differently to injury in males versus females.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Sex differences in TBI: Do mitochondria play a role?

    Cellular stressors such as nutrient deprivation may elicit a differential response in mitochondria from males and females, resulting in decreased mitochondrial respiration, increased autophagy, and enhanced neuronal death in male rats.

    “Cellular stressors such as nutrient deprivation may elicit a differential response in mitochondria from males and females resulting in decreased mitochondrial respiration, increased autophagy, and enhanced neuronal death in male rats.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [128] 128. Du, L., Hickey, R.W., Bayir, H., Watkins, S.C., Tyurin, V.A., Guo, F., Kochanek, P.M., Jenkins, L.W., Ren, J., Gibson, G., Chu, C.T., Kagan, V.E., and Clark, R.S. (2009). Starving neurons show sex difference in autophagy. J. Biol. Chem. 284, 2383-2396.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Sex differences in TBI: Do mitochondria play a role?

    Brain mitochondria of female rodents had lower oxidative stress than those from males, associated with greater expression and activity of antioxidant enzymes.

    “brain mitochondria of female rodents had lower oxidative stress than those from males associated with greater expression and activity of antioxidant enzymes.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [119] 119. Gaignard, P., Savouroux, S., Liere, P., Pianos, A., Therond, P., Schumacher, M., Slama, A., and Guennoun, R. (2015). Effect of sex differences on brain mitochondrial function and its suppression by ovariectomy and in aged mice. Endocrinology 156, 2893-2904.

      Not checked in the free run.

    • cites [124] 124. Borras, C., Sastre, J., Garcia-Sala, D., Lloret, A., Pallardo, F.V., and Vina, J. (2003). Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radic. Biol. Med. 34, 546-552. source

      Not checked in the free run.

    • cites [125] 125. Pinto, R.E., and Bartley, W. (1969). The effect of age and sex on glutathione reductase and glutathione peroxidase activities and on aerobic glutathione oxidation in rat liver homogenates. Biochem. J112, 109-115.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning
    § Interpreting mixed results

    Although studies relying on a single outcome measure might be useful for gross outcomes such as mortality and are easier to interpret, they do not fully represent the anatomical and physiological complexity of sex effects in TBI.

    “Although studies relying on a single outcome measure might be useful for gross outcomes such as mortality and are easier to interpret, they do not fully represent the anatomical and physiological complexity of sex effects in TBI.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Sex differences in TBI: Do mitochondria play a role?

    Mitochondrial fission facilitates transport of mitochondria to regions of high energy demand and removal of damaged mitochondria by autophagy.

    “fission facilitates transport of mitochondria to regions of high energy demand and removal of damaged mitochondria by autophagy.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [132] 132. Bereiter-Hahn, J., and Voth, M. (1994). Dynamics of mitochondria in living cells: shape changes, dislocations, fusion, and fission of mitochondria. Microsc. Res. Tech. 27, 198-219.

      Not checked in the free run.

    • cites [133] 133. Chan, D.C. (2006). Mitochondrial fusion and fission in mammals. Annu. Rev. Cell Dev. Biol. 22, 79-99. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning
    § Interpreting mixed results

    Such a model can account for mixed results, and highlights the benefits of study design that includes multiple outcome measurements.

    “Such a model can account for mixed results, and highlights the benefits of study design that includes multiple outcome measurements. 48,111”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [48] 48. McCarthy, M.M., Arnold, A.P., Ball, G.F., Blaustein, J.D., and De Vries, G.J. (2012). Sex differences in the brain: the not so inconvenient truth. J. Neurosci. 32, 2241-2247. source

      Not checked in the free run.

    • cites [111] 111. Joel, D., and Fausto-Sterling, A. (2016). Beyond sex differences: new approaches for thinking about variation in brain structure and function. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 371, 20150451.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Sex differences in TBI: Do mitochondria play a role?

    Progesterone treatment reversed TBI-mediated impairment in mitochondrial respiration and neuron loss in ovariectomized adult females.

    “Progesterone treatment reversed TBI-mediated impairment in mitochondrial respiration and neuron loss in ovariectomized adult females”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [65] 65. Robertson, C.L., and Saraswati, M. (2015). Progesterone protects mitochondrial function in a rat model of pediatric traumatic brain injury. J. Bioenerg. Biomembr. 47, 43-51.

      Not checked in the free run.

    • cites [143] 143. Robertson, C.L., Puskar, A., Hoffman, G.E., Murphy, A.Z., Saraswati, M., and Fiskum, G. (2006). Physiologic progesterone reduces mitochondrial dysfunction and hippocampal cell loss after traumatic brain injury in female rats. Exp. Neurol. 197, 235-243.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given
    § Sex differences in TBI: Do mitochondria play a role?

    Comorbidities and extracerebral injuries may have different prevalence in women and men.

    “which may have different prevalence in women and men”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning
    § Sex differences in TBI: Do mitochondria play a role?

    Injury severity, genetic factors, and age may interact with biological sex to determine TBI outcomes.

    “Injury severity, genetic factors, and age may interact with biological sex to determine TBI outcomes.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning
    § Sex differences in TBI: Do mitochondria play a role?

    Sex differences in mitochondrial function and dynamics may be important sources of sex differences in TBI.

    “Sex differences in mitochondrial function and dynamics may be important sources of sex differences in TBI.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given
    § Conclusion

    Larger sample size affords greater statistical power and might better represent the general population.

    “Because larger sample size affords greater statistical power and might better represent the general population”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning
    § Conclusion

    Under-representation of women in clinical studies likely has a negative impact on clinical care and limits successful drug development.

    “such under-representation likely has a negative impact on clinical care and limits successful drug development.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Disease etiology, underlying neuropathology, and cellular mechanisms of recovery differ between sexes.
179 of 179

  • The paper relies on this without support.

    Across the scientific literature, the terms sex and gender are often used interchangeably.

    “However, across the scientific literature the terms sex and gender are often used interchangeably.”

  • The paper relies on this without support.

    Animal models of TBI can inform the pathophysiology of human TBI.

    “Because therapeutic interventions are targeted toward underlying mechanisms, elucidating the role of sex in TBI pathophysiology is crucial.”

  • The paper relies on this without support.

    The studies included in the review are representative of the literature on sex differences in TBI.

    “All animal studies identified by our search criteria were classified based on post-TBI outcomes (upper panel).”

  • The paper relies on this without support.

    Disease etiology, underlying neuropathology, and cellular mechanisms of recovery differ between sexes.

    “Because disease etiology, underlying neuropathology, and cellular mechanisms of recovery differ between sexes”

  • The paper relies on this without support.

    The reviewed human and animal studies are sufficiently representative to support conclusions about sex differences in TBI outcomes.

    “This review of the literature in humans and animal models suggests that sex differences in TBI outcomes are likely”
5 of 5

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?

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.

  • Conflicting percentages for mixed results in animal studies

    Major

    The results section says 14% of animal studies had mixed results and 28% found no sex differences. The discussion instead assigns 28% to mixed results, doubling the stated fraction behind its discussion of mixed findings.

1 of 1

Cites

1 retracted

Flagged first, then by citations

1 of the 298 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Taylor A.N., , Tio D.L., , Paydar A., , and Sutton R.L. (2017). Sex differences in thermal, stress and inflammatory responses to minocycline administration in rats with traumatic brain injury. J. Neurotrauma, 35, 630–638.

Cited by

Sorted by citations

Related

Authors
Gupte, R. P., Brooks, W. M., Vukas, R. R., Pierce, J. D., & Harris, J. L.
Affiliations
  • University of Kansas Medical Center (US)
  • University of Kansas (US)
Corresponding author
Harris, Janna L.
ORCID
Venue
Journal of Neurotrauma
Publisher
SAGE Publications
Published
2019-10-23
Volume
36
Issue
22
Pages
3063-3091
ISSN
  • 0897-7151 (ISSN-L)
  • 1557-9042
DOI
10.1089/neu.2018.6171
PMC
PMC6818488
OpenAlex
W2915478013
Semantic Scholar
df6dea32c0f453621f674193fcab8f821850d6d1
Cited by
533
References
298
Citations by year
2026: 94 · 2025: 84 · 2024: 84 · 2023: 81 · 2022: 85 · 2021: 62 · 2020: 35 · 2019: 6
FWCI
31.80
Type
journal article
Language
en
Open access
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Journal of Neurotrauma (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (UL1TR002366)
  • National Institute on Aging (R21AG058052, P30AG035982, P30AG072973)
  • National Institute of Neurological Disorders and Stroke (R21NS091920)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
Keywords
traumatic brain injury, sex differences, women in clinical trials, injury severity, mitochondrial function, sex as a biological variable, sex differences in recovery, translational research
MeSH terms
Brain Injuries, Traumatic, Animals, Female, Humans, Male, Sex Characteristics

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

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