搜索结果：links

Investigators must frequently apportion precious sample volumes between multiple assays to measure the viability, potency, and compositional phenotype of cell therapy products and clinical research samples. However, the use of disparate assay modalities may miss critical information which links the expression profile of cells with functional activity, especially when these activated cell populations are rare. To address this shortcoming, we describe in this short report the creation of a 38-color spectral flow cytometry panel for the phenotypic and functional characterization of antigen reactive T cell populations within cellular therapy products and clinical research samples. Our investigations identified that up to 29 potentially co-expressing markers were able to be identified on mixed sample populations using this panel, including phenotype, activation, and exhaustion markers, as well as intracellular cytokine production. Our calculations also highlight spectral flow cytometry is a more efficient use of technician time, reagent cost, and product sample usage as compared with an equivalent set of traditional flow cytometry panels.

Male infertility is complex, driven by impaired endocrine signalling, germ-somatic cell communication, and epigenetic regulation of spermatogenesis. LH/cAMP/PKA signalling in Leydig cells and FSH-mediated regulation in Sertoli cells have been extensively studied. The combined effects of these pathways on testicular physiology and clinical infertility are unknown. This review integrates hypothalamic-pituitary-gonadal axis signalling, intra-testicular epigenetic oversight, and environmental variables at the systems level. Integrating LH and FSH-dependent signalling with somatic cell activity, epigenetic programming during spermatogenesis, and endocrine disruptor effects on these networks. Despite recent improvements in single-cell and spatial transcriptomics, testicular heterogeneity and its integration processes remain unexplained. This review identifies key barriers that hinder molecular discoveries from becoming clinical diagnoses and therapies. This paradigm links biological pathways to infertility symptoms. It provides new possibilities for biomarker development and targeted therapeutics by including endocrine, epigenetic, and environmental factors on testicular function, prompting future research into translational routes that connect molecular endocrinology and clinical care for infertility.

The glymphatic system is a brain-wide clearance pathway that maintains central nervous system homeostasis by facilitating cerebrospinal fluid (CSF)-interstitial fluid (ISF) exchange and metabolic waste removal. Accumulating evidence links glymphatic dysfunction to neurodegeneration, cerebrovascular disease, and sleep-related disorders, motivating the search for clinically deployable imaging biomarkers. Imaging has become central to this effort, spanning tracer-based approaches and non-invasive MRI methods such as phase-contrast magnetic resonance imaging (MRI), functional MRI-derived CSF dynamics, structural MRI markers including MRI-visible perivascular spaces and parenchymal CSF (pCSF) mapping, and diffusion-based indices including diffusion tensor image analysis along the perivascular space (DTI-ALPS). This review aims toprovide a translation-oriented perspective that reframes the current literature by disentangling what each modality actually measures-such as tracer transport, fluid compartment morphology and distribution, pulsatility-related motion, diffusion-sensitive exchange constraints, or vascular-interface perfusion/exchange physiology-from what it is often interpreted to represent (glymphatic clearance), and by proposing a practical roadmap to improve physiological specificity and clinical utility. Importantly, no truly non-invasive MRI technique can currently directly measure glymphatic transport or CSF-ISF exchange in humans, so existing readouts should be treated as surrogate markers with known confounds. We highlight emerging methods sensitive to slow flow and exchange and outline priorities for clinical translation, including harmonized protocols, cross-site reproducibility, mechanistic validation, and outcome-linked validation in prospective studies.

Fresh mushroom off-flavor (FMOff) is a defect in wines characterized by a mushroom aroma. To date, it has been mainly linked to compounds such as 1-octen-3-one, 1-octen-3-ol, 1-hydroxyoctan-3-one, and octane-1,3-diol. In practice, winemakers have observed changes in FMOff perception during alcoholic (AF) and malolactic fermentations (MLF), suggesting that yeasts and bacteria play a role in aroma modification. To investigate the FMOff metabolism, synthetic must was supplemented with analytical standard molecules (octane-1,3-diol, 1-hydroxyoctan-3-one, and 1-octen-3-one). Their evolution was monitored during AF and after MLF. The effect of the yeast strain was also investigated and validated in natural grape must. The results showed that yeasts and bacteria metabolize 1-octen-3-one into 3-octanone and finally into 3-octanol during fermentation. The production of octane-1,3-diol in must supplemented with 1-hydroxyoctan-3-one confirms a biochemical link between these compounds, which was also verified in natural matrices. Approximately 30% of the 1-hydroxyoctan-3-one was metabolized into octane-1,3-diol, and 70% remained unidentified, opening an avenue for future work.

This study investigated the prevalence, genetic diversity, antimicrobial resistance, and virulence characteristics of Campylobacter spp. isolated from retail chicken carcasses in Beijing, China. Overall, Campylobacter was detected in 55.88% of samples, with significantly higher contamination in wet markets compared to supermarkets. A total of 106 non-duplicated isolates were obtained, including 59 C. jejuni and 47 C. coli, exhibiting high genetic diversity with 78 sequence types (STs) and 15 novel STs identified. Antimicrobial susceptibility testing revealed universal resistance to fluoroquinolones and high resistance to tetracycline, while multidrug resistance was prevalent, particularly in C. coli. Genotypic analysis identified 34 resistance genes and 4 point mutations, showing generally strong genotype-phenotype correlation, although notable discrepancies were observed, especially for florfenicol and azithromycin. The health risks to humans posed by tetracycline and macrolide-lincosamide-streptomycin (MLS)-associated antibiotic resistance genes (ARGs) should be given priority attention. Virulence profiling demonstrated that C. jejuni harbored significantly more virulence-associated genes than C. coli, including genes linked to Guillain-Barré syndrome, indicating a substantial potential public health risk from contaminated poultry.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by α-galactosidase A (α-GAL) deficiency, resulting in progressive accumulation of globotriaosylceramide and related glycosphingolipids, leading to progressive organ damage (including the heart, kidney, and brain). The GLA variant c.427G > A p.(Ala143Thr) is currently classified as a "variant of uncertain significance" (VUS). There is no consensus about this variant's significance in the literature and it remains controversial in non-classical FD. We generated a human induced pluripotent stem cell (hiPSC) line derived from dermal fibroblasts of a 64-year-old hemizygous man carrying the p.(Ala143Thr) variant, using an RNA-based reprogramming method.

Clinical biobanks linking electronic health records (EHRs) with genotype data enable the study of genomic risk factors in real-world populations. However, recall-by-genotype (RbG) of psychiatric risk variants in diverse healthcare-system biobanks remains scarce. Leveraging BioMe, a multi-ancestry biobank within the Mount Sinai Health System, we recalled carriers of rare copy number variants (CNVs) that confer increased risk for neurodevelopmental disorders (NDDs) to establish empirical benchmarks for RbG implementation. We recontacted 892 participants: 335 NDD CNV carriers, 217 individuals with schizophrenia without NDD CNVs, and 340 neurotypical controls without NDD CNVs. Participants completed clinical and cognitive assessments. Overall, 18% of recontacted participants responded to recruitment, and 8% completed the study: 30 NDD CNV carriers, 20 individuals with schizophrenia, and 23 controls. The mean age was 48.8 years, 66% were female, and self-reported ancestry was 37% African, 34% Hispanic, and 26% European. Seventy percent of NDD CNV carriers had at least one neuropsychiatric or developmental condition, including mood or anxiety disorders (40%). Among 22 NDD CNV carriers at loci implicated in impaired cognition, performance was lower than controls on Digit Span Backward (β = -1.76, FDR = 0.04) and Digit Span Sequencing (β = -2.01, FDR = 0.04). NDD CNV carriers also outperformed the schizophrenia group on verbal learning (β = 4.5, FDR = 0.05). Recall of individuals-including those with psychiatric illness-yielded phenotypes not captured in EHRs and provides empirical benchmarks relevant to RbG implementation and precision psychiatry in diverse healthcare systems.

The TP53 gene encodes the well-known p53 tumor suppressor protein, which plays a crucial role in preventing cancer development. Germline TP53 variants cause Li-Fraumeni Syndrome (LFS), an autosomal dominant disorder associated with early-onset cancers, including breast cancer, brain tumors, leukemias, bone cancers, and soft tissue sarcomas. Here, we described a germline TP53 variant c.671A>C, located at the penultimate nucleotide of exon 6 and predicted to result in the missense substitution p.E224A. The variant was identified in a 2-year-old child with retroperitoneal rhabdomyosarcoma and with a strong family history suggestive of LFS. Functional assays in yeast and human cells demonstrated wild type-like activity of the protein p.E224A; however, in silico splicing analysis indicated potential splice defects (e.g., SpliceAI score = 0.77). Given this discrepancy, we further investigated this variant using a minigene approach, demonstrating that it causes the skipping of exon 6, likely resulting in a frameshift and the introduction of a premature stop codon. These findings supported the classification of the TP53 germline variant c.671A>C (p.E224A) as likely pathogenic, providing a definitive molecular diagnosis for family counselling. Additionally, the present results sheds light on how certain predicted TP53 missense variants can be linked to disease mechanisms through RNA splicing disruption.

Low intervention uptake and contamination can dilute effects of cluster randomised trials (CRTs). We investigated the feasibility of digital fingerprints to assess intervention coverage and contamination in a CRT of community-based sexual and reproductive health services for youth (CHIEDZA). 24 clusters in Zimbabwe were randomly allocated to intervention/control. In intervention clusters, CHIEDZA services were provided in community halls for 30 months. A population-based survey of youth aged 18-24 (700/cluster) was conducted to ascertain impact. Digital fingerprints were collected from service attendees and survey participants, and the datasets were linked to assess intervention coverage at population level in intervention clusters and contamination in control clusters. Multilevel logistic regression estimated the association of hall distance with service uptake. Between April 2019 and March 2022, 36 991 clients attended the CHIEDZA service and 99.9% used biometric registration. In the survey 13 675/17 682 (77.3%) participants completed biometric registration: 1182 refused, 1235 bypassed and 1590 could not register.CHIEDZA service coverage in the intervention clusters was 23.1% and contamination was 3.7%. Against biometric registration match, self-reported service attendance had 75.3% sensitivity (95% CI 73.1% to 77.5%) and 92.7% specificity (95% CI 92.0% to 93.4%). Odds of CHIEDZA service use reduced by 52% for every 1km distance (OR: 0.48 95% CI 0.44 to 0.54). Biometric identification was feasible and acceptable in a community setting without time pressure. In population-based surveys additional technological challenges emerged. Biometrics enabled good estimation of intervention coverage and validated self-reported data. Youth community services must overcome distance barriers. Biometric identification is useful for assessment of CRT coverage and contamination. https://clinicaltrials.gov/study/NCT03719521.

Triple-negative breast cancer (TNBC) represents a breast cancer subtype lacking three essential biomarkers: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This biological signature differentiates TNBC from other breast cancer subtypes and acts as an essential diagnostic criterion for clinical identification and constitutes essential diagnostic criteria for clinical identification. Among all subtypes of breast cancer, TNBC exhibits an exceptionally high level of aggressiveness. Its aggressive behavior and paucity of effective treatment options contribute to its notoriously poor prognosis. The immunogenic cell death (ICD) emergence has raised hopes to create fresh treatment approaches to strengthen TNBC patients' immune responses against tumors. However, the correlation between ICD and TNBC prognosis is still unclear. By analyzing transcriptomic data through the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), we discovered the differentially expressed genes (DEGs) and linked to ICD in TNBC. A prognostic model utilizing ICD was developed through LASSO regression. Then, we conducted multivariate Cox proportional hazards analysis on the identified DEGs. We used receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) analysis to evaluate the model's predictive accuracy. To comprehensively evaluate the clinical relevance of the ICD signature, we investigated its associations with genomic alterations, tumor microenvironment (TME) characteristics, and therapeutic responses to both chemotherapy and immunotherapy. Furthermore, functional validation was performed using MDA-MB-231 and BT-549 through various in vitro assays, including CCK-8 proliferation tests, colony formation assays, and Transwell migration experiments to assess HEYL's biological role. A 4-gene ICD signature (HEYL, CXCL13, GBP2, and IL22RA2) was developed and stratified TNBC patients into two categories, showing major distinctions in overall survival (OS). We found that higher-risk patients had less favorable results. Meanwhile, they usually had different TMEs with less immune cell infiltration. By contrast, the low-risk group appeared to react better to immunotherapy, as evidenced by their increased immune cell infiltration level and more favorable outcomes. Analysis via the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) uncovered that DEGs were predominantly involved in immune-related pathways, for example, the receptors on the plasma membrane. Additionally, a lower immunological phenotype score (IPS) and increased susceptibility to various chemotherapeutic medicines, including A-443,654, BAY 61-3606, and CP466722, were detected in the low-risk category. Additionally, HEYL knockdown markedly suppressed TNBC cell growth and metastatic capability, whereas its overexpression produced the opposite outcome, promoting both traits. The prognosis and responsiveness to treatment for TNBC can be anticipated by the ICD-related gene profile, highlighting the significance of the immune microenvironment. It might provide insight into the design of tailored immunotherapies for TNBC.

Hypochondroplasia is a rare genetic condition that causes disproportionate short stature. This retrospective, real-world, matched-cohort study used electronic health records data from the Clinical Practice Research Datalink Aurum primary care database, linked to Hospital Episode Statistics and Office of National Statistics mortality records, to assess the natural history of hypochondroplasia in England from 1998 to 2019. A total of 549 participants with hypochondroplasia and 2196 matched controls were included. Mean follow-up time was 7.50 years for participants with hypochondroplasia and 11.68 years for controls. Approximately 60% of participants were aged >18 years at start of follow-up. Mean age (standard deviation) at first recorded hypochondroplasia code was 29.20 (20.2) years. The highest event rates for participants with hypochondroplasia involved cardiovascular, orthopaedic, respiratory, mental health, and ear, nose and throat (ENT) systems. Event rates for the selected comorbidities combined were higher in participants with hypochondroplasia versus controls (rate ratio [RR] 2.13, 95% confidence interval [CI] 1.98-2.28). Participants with hypochondroplasia had higher healthcare visit rates, including a median of 10.91 annual general practitioner visits versus 5.52 for controls (RR 1.63, 95% CI 1.48-1.80). Mortality rates were more than double for participants with hypochondroplasia versus controls (RR 2.64, 95% CI 1.33-5.26), mainly driven by cohorts aged ≥30 years and by cardiovascular and respiratory diseases. Rates for procedures, particularly orthopaedic and ENT, and medication use were also higher among participants with hypochondroplasia versus controls. These results highlight the medical burden of hypochondroplasia and need for coordinated, multidisciplinary management starting early in life.

Congenital disorders of glycosylation (CDG) comprise a diverse group of inherited metabolic diseases caused by defects in glycan biosynthesis. SSR4-CDG is an ultra-rare X-linked disorder caused by pathogenic variants in SSR4, which encodes a subunit of the translocon-associated protein (TRAP) complex involved in endoplasmic reticulum N-linked glycosylation. To date, only a limited number of patients have been reported, and all previously reported pathogenic variants have been truncating or splice-altering variants. Here, we report two unrelated patients with SSR4-CDG identified by trio-based whole-exome sequencing. Patient 1 carried a de novo nonsense variant and presented with severe intellectual disability and autism spectrum disorder. Notably, he is currently alive at age 56, providing insight into the long-term clinical course of this condition. Patient 2 harbored a maternally inherited in-frame insertion-deletion variant that was initially classified as a variant of uncertain significance. He showed severe developmental delay, failure to thrive, epilepsy, and hyperkinetic movements. Repeat glycan analysis revealed a CDG type I pattern, transcript analysis demonstrated aberrant transcripts with an expanded deletion, and structural modeling suggested destabilization of the β-barrel domain of SSR4, together supporting reclassification as likely pathogenic. These findings expand the clinical and molecular spectrum of SSR4-CDG, including survival into adulthood and diverse neurological manifestations. Our study also illustrates the challenges in interpreting variants associated with subtle biochemical abnormalities and underscores the importance of integrating biochemical, genetic, transcript, and modeling-based structural assessment for accurate diagnosis of rare CDG subtypes.

Early temperament, particularly regulation and reactivity, is critical to neurodevelopment and can be shaped by early biological and environmental factors. Prenatal substance exposure is one such influencing factor, often associated with lower regulation and heightened reactivity in infants. However, positive parenting may help mitigate these effects. This study examined how prenatal exposure to alcohol, tobacco, and marijuana influences infant temperament at 24 months, and whether maternal warmth at 12- and 24-months moderates or mediates these relationships. Participants were 404 mother-child dyads from a prospective, ethnically diverse urban cohort. Results showed prenatal alcohol and tobacco exposure was directly associated with poorer child regulation and reactivity, while marijuana was not independently linked to these outcomes. Maternal warmth at 12 and 24 months moderated some of the negative effects of prenatal tobacco and marijuana exposure, but not alcohol. These moderating effects varied by child outcome, timing, and frequency of substance use. No evidence was found for maternal warmth mediating any of the associations between prenatal substance use and child outcomes. Findings highlight the differential impact of substance type, timing, and frequency on child outcomes and underscore the importance of early parenting support as a resilience factor.

Direct oral anticoagulants (DOACs) - dabigatran (a thrombin inhibitor) and rivaroxaban, apixaban, and edoxaban (factor Xa [FXa] inhibitors) - modify oxidative stress, endothelial inflammation, and barrier integrity beyond anticoagulation. We ask whether this reflects distinct pharmacology or silencing of proteases at protease-activated receptors (PARs), and propose a three-condition framework for when it becomes clinically measurable. Narrative review (PubMed, Scopus, Web of Science; primary search 2019-2026, with foundational earlier references retained) with claims graded on a six-tier hierarchy; A‡ marks trials formally negative or inconclusive owing to insufficient statistical power. DOAC effects largely converge on one node - reduced PAR-1 signalling under thrombin inhibition and dual PAR-1/PAR-2 blockade under FXa inhibition - rather than independent targets; the FXa-PAR-2 axis is cross-validated across macrophages, liver sinusoidal endothelial cells, and neutrophils; and dabigatran plausibly differs qualitatively rather than only in degree - a working hypothesis whose mechanistic linchpin (residual exosite-I signalling) currently rests on a single unreplicated in-vitro study (level D). Clinically the signal sorts by phenotype and disease phase, not class: low-dose rivaroxaban benefits stable atherosclerosis (COMPASS) but not heart failure in sinus rhythm (COMMANDER-HF), and COVID-19 benefit appears only in convalescence (MICHELLE), not acutely or in outpatients (ACTIV-4B, A‡). A nationwide cohort linked DOACs to lower acute kidney injury and chronic kidney disease progression than vitamin K antagonists, pending separation from their nephrotoxicity. Pleiotropy emerges where three conditions coincide - the protease is available at PARs, its generation is chronic, and PAR signalling is rate-limiting. This supports within-indication molecule selection (selection, not extension) and biomarker co-primary trials, not extension of indications.

The functional properties of pectin are closely related to its molecular structure. In addition to the carbohydrate backbone, non-carbohydrate components such as intrinsic protein also play a significant role in influencing pectin properties both directly and indirectly. In this study, pepsin and papain were used to remove protein in high methoxyl pectin (HMP) extracted from citrus, achieving protein removal rates of 72.59% and 89.40%, respectively. Structural analyses from FTIR, XRD, and NMR confirmed that protein removal did not alter the fundamental functional groups of pectin. However, monosaccharide composition and atomic force microscopy (AFM) revealed that protein was linked to both the homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) domains. Gel analysis showed that protein removal led to a 50°SAG reduction in gel strength at pH 2.5, whereas its impact at pH 6.0 was negligible. Additionally, the rheological characterization further demonstrated the positive role of protein in deformation stability in pectin gels.

Age-related impairments in balance and gait are strongly linked to deficits in plantarflexion, yet the underlying changes in force control and their neural and muscle-tendon determinants remain poorly understood. The purpose of this study was to determine whether central and/or peripheral mechanisms contribute to age-related declines in rapid, goal-directed plantar flexions. Twenty-two young (22 ± 2 years) and twenty-two older adults (72 ± 6 years) performed 3 sets of 10 plantar flexions to match force targets of 30% and 80% MVC as accurately and quickly as possible. Rapid force control was assessed using force error, time to peak force (TPF), force variability, and TPF variability. Surface EMG from plantar flexor and dorsiflexor muscles quantified neuromuscular activation and coordination, while Achilles tendon stiffness was measured to evaluate peripheral contributions. Older adults exhibited longer TPF, greater force error, and greater force and temporal variability compared with young adults, indicating impaired rapid force control relevant to mobility. They also demonstrated altered activation patterns and impaired coordination between agonist and antagonist muscles, whereas Achilles tendon stiffness did not differ between groups. Age-related slowing and increased variability were largely predicted by slower and more variable activation of the lateral gastrocnemius. These deficits were also associated with greater delays between antagonistic muscles and increased coactivation among synergistic plantar flexors. Together, these findings suggest that neural activation and coordination deficits may contribute more substantially than Achilles tendon stiffness to age-related declines in ballistic plantarflexion and identify candidate neural markers of mobility decline and fall risk.

Neuroinflammation is a key factor contributing to cognitive decline in Alzheimer's disease (AD). This study aims to investigate the mechanistic associations among neuroinflammation, glymphatic dysfunction, tau pathology, and cognitive decline in AD spectrum. The study included 355 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and a supportive cohort of 59 individuals from Wuhan Union Hospital (WHUH). Tau pathology was quantified using 18F-AV1451 positron emission tomography (PET). Glymphatic function was estimated through diffusion tensor image analysis along the perivascular space (DTI-ALPS). Neuroinflammation was assessed via plasma glial fibrillary acidic protein (GFAP) in two cohorts and translocator protein (TSPO) PET imaging with 18F-DPA-714 in supportive cohort. Correlation analyses and mediation models were employed to evaluate the directional relationships among tau deposition, inflammation, glymphatic function, and cognition. Higher levels of inflammation were significantly associated with lower DTI-ALPS index (β = -0.171, P = 0.046), which in turn was associated with higher tau burden (β = 0.162, P = 0.010). Path analysis revealed significant indirect associations linking neuroinflammation to cognitive performance through glymphatic dysfunction and tau pathology, with total indirect effects of - 0.165 (95% CI, - 0.266 to - 0.105) in ADNI and - 0.143 (95% CI, - 0.386 to - 0.013) in WHUH. These findings support a hypothesized inflammation-glymphatic-tau pathway rather than a definitive causal cascade. Our findings are consistent with a hypothesized inflammation-glymphatic-tau association in which greater neuroinflammation is linked to reduced glymphatic function and higher regional tau burden, particularly in preclinical and prodromal stages. This study obtained ethical approval from the Institutional Review Committee of Nanjing Drum Tower Hospital (ChiCTR-BRC-17011316, date:20170506; ChiCTR1900022526, date:20190415).

Hypertrophic scars often cause functional impairment and aesthetic damage, thereby affecting patients' daily life and comfort. Moreover, existing therapies have limited efficacy and are prone to recurrence. To achieve precise genetic intervention, this study constructed a time-controlled release polysaccharide hydrogel dressing for the targeted delivery of IL-11 siRNA. This dressing is based on a chitosan quaternary ammonium (QCS)/sodium alginate (SA) double-network structure hydrogel (SQG) and loaded with cationic lipid nanoparticles (siIL11@NPs), forming an "integrated drug-loading and cross-linking" system. SQG hydrogel also shows good antibacterial activity and anti-inflammatory properties, which is helpful to establish a wound microenvironment that inhibits scar hyperplasia. It continuously releases siRNA during the mid-to-late stage of wound healing (days 5-9). Cell experiments showed that the released nanoparticles were efficiently internalized by TGF-β1-induced myofibroblasts, significantly inhibiting their migration and proliferation and downregulating the expression of IL-11 and the typical fibrotic genes COL1A1, FN1, and ACTA2. In the rabbit ear scar model, this dressing promoted wound healing, inhibited late-stage hypertrophy, reduced the scar elevation index and thickness, improved collagen alignment and the type I/III collagen ratio, and downregulated the expression of α-SMA and TGF-β1. In summary, the SQG/siIL11@NPs hydrogel dressing shows good potential and provides a new option for inhibiting hypertrophic scar formation in wound treatment.

The aim of this study was evaluate the extent to which women are represented and reported within the scientific evidence supporting the clinical practice guidelines on peripheral arterial disease (PAD) and chronic limb threatening ischaemia (CLTI). Data were extracted from all studies supporting recommendation statements within the European Society for Vascular Surgery (ESVS) 2024 clinical practice guidelines on the management of PAD and the 2019 global vascular guidelines on the management of CLTI, including study type, journal impact factor, year of publication, country, sex of authors, participant sex, use of a sex stratified main outcome, and sex disaggregated reporting. The protocol was registered with PROSPERO (CRD42024559537) and conducted in accordance with PRISMA-Equity guidelines. Analyses were performed using RStudio. Under enrolment was defined as a participation prevalence ratio (PPR) <&#x2009;0.8. Binary logistic regression evaluated factors associated with reporting sex stratified outcomes; weighted linear regression assessed factors linked to increased PPR. Of 89 PAD and 113 CLTI recommendations, 213 and 116 unique studies were analysed. The remaining references were consensus documents or were excluded due to reasons such as single sex populations. Only 21% and &#x223c;10% of the studies reported sex disaggregated data, while only 10% and 2% reported sex stratified outcomes in PAD and CLTI, respectively. Participants' sex was unreported in &#x223c;42% (PAD) and &#x223c;39% (CLTI). Women were under enrolled in &#x223c;63% (PAD) and &#x223c;55% (CLTI) of studies. Multinational studies, higher proportion of women authors, and stronger evidence levels were associated with better women's enrolment. Women first authorship was associated with increased odds of sex stratified reporting. Other factors that influenced sex stratified reporting included more women participants, a higher proportion of women authors, and recent publication year. Women are under represented and under reported in the evidence underpinning ESVS PAD and CLTI guidelines. Future societal guidelines should be based on research with balanced inclusion and consistent sex specific reporting.