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PubMed2026

Financial incentives and social messaging for repeat SARS-CoV-2 antibody testing among the underserved: A randomized trial.

Financial incentives may influence health behavior beyond their expected monetary value, and their effectiveness may depend on how the behavior is framed. Behavioral theories of decision making suggest that individuals may value protection against small-stakes losses more than expected utility predicts, while theories of family-centered health behavior suggest that messages emphasizing benefits to family members may strengthen participation in preventive health activities. We tested these ideas in a 2×2 factorial randomized trial involving 625 households recruited from a Federally Qualified Health Center serving low-income Latino/Hispanic communities. Participants completed repeat SARS-CoV-2 antibody testing. The trial crossed two messaging strategies (Family vs. Personal) with two incentive structures (Loss Protection vs. Lottery) that offered equivalent expected monetary value. Family Messaging emphasized protecting one's family from COVID-19, whereas Personal Messaging emphasized protecting oneself. Loss Protection allowed participants to secure an at-risk reward through repeat testing, whereas the Lottery condition offered a chance of a large reward. Repeat testing was approximately 8 percentage points higher under Family Messaging and 7 percentage points higher under Loss Protection. Baseline trust in medical providers, financial barriers to vaccination, and risk aversion were associated with initial testing, whereas household characteristics were not associated with repeat testing. Incentive design may matter beyond expected monetary value and that framing health behaviors in terms of family welfare may increase participation in repeated healthy activities. Broadly, the results support behavioral theories emphasizing loss aversion, anticipated regret, and family-centered motivations, and suggest practical approaches for improving engagement in repeat health behaviors. CLINICALTRIALS.GOV REGISTRATION NUMBER:: NCT01901624.

Adult↗

PubMed2026

Intentions to use different modalities of long-acting HIV PrEP among men who have sex with men and transgender and gender diverse persons in the Netherlands.

Insight into intentions to use long-acting HIV pre-exposure prophylaxis (PrEP) is essential for successful implementation. We assessed intention to use three hypothetical long-acting PrEP modalities (oral, intramuscular and subdermal) among HIV-negative men who have sex with men (MSM) and transgender and gender diverse persons in Amsterdam, recruited through the Amsterdam Cohort Studies (ACS-participants) and social media (survey-participants). Intention was measured per modality using a 7-point Likert scale. We modeled the probability of high intention to use long-acting PrEP using relative risk regression. Of 1258 participants [1231 (97.9%) MSM; 557 ACS and 701 survey; median age 40 years (IQR 32-50)], 76% had ever used oral short-acting PrEP. Intention to use was highest for monthly oral long-acting PrEP [ACS: median 4.5 (IQR 2-6), 38% high intention; survey: median 7 (IQR 6-7), 81% high intention], followed by 2-monthly intramuscular PrEP [ACS: median 3 (IQR 2-5), 19% high intention; survey: median 5 (IQR 3-7), 47% high intention], and implants [ACS: median 2 (IQR 1-4), 9% high intention; survey: median 4 (IQR 2-7), 37% high intention]. PrEP-experienced participants had higher intention to use oral long-acting PrEP and injectables than PrEP-naïve participants. Offering multiple PrEP modalities may improve the acceptability of HIV prevention strategies and increase PrEP uptake and retention in PrEP care.

Humans↗

PubMed2026

Impact of Contact Lens Use on Clinical Profile and Outcomes of Fungal Keratitis: An 8-Year Retrospective Study.

PURPOSE: To compare clinical characteristics, microbiological profiles, treatment strategies, and outcomes between contact lens-associated (CL) and noncontact lens-associated (non-CL) fungal keratitis. DESIGN: Retrospective, comparative clinical cohort study. METHODS: A review of culture-proven fungal keratitis treated at a tertiary referral center between 2018 and 2025 was conducted. Cases were categorized as CL or non-CL-associated. Demographic, clinical, microbiological, treatment, and outcome data were analyzed and compared between groups. RESULTS: Thirty-seven eyes were included, comprising 16 CL and 21 non-CL cases. CL users presented earlier than non-CL patients (median 7 vs 14 days, P = .007) and had fewer associated ocular risk factors (31% vs 81%, P = .001). Baseline visual acuity and infiltrate size did not differ significantly between groups. Candida species were isolated in 21% cases, Fusarium in 16% and Aspergillus in 8%. Fusarium (19% vs 13%) and Candida (24% vs 19%) infections were slightly more frequent in non-CL cases. Overall, filamentous fungi were the predominant organism group. Topical voriconazole was the most frequently used antifungal agent (78%). All CL-associated cases resolved with medical therapy alone, with a median time to resolution of 38 days (IQR 22-58). In contrast, 76% of non-CL cases resolved medically (median 42 days, IQR 32-76), while 23% required therapeutic keratoplasty (P = .04). Final visual acuity was comparable between groups (logMAR 0.2 vs 0.5, P = .56). CONCLUSION: Contact lens-associated fungal keratitis is characterized by earlier presentation and fewer underlying ocular comorbidities, with favorable outcomes achieved through medical therapy alone. Despite similar microbiological profiles and treatment approaches, noncontact lens-associated fungal keratitis more frequently follows a complicated course requiring surgical intervention.

Humans↗

PubMed2026

Nebivolol treatment improves hypertension-induced endothelial cell dysfunction by reducing TGF-β1-dependent senescence and normalizing mitochondrial indices.

OBJECTIVES: Serum from patients with hypertension (HT) causes endothelial cell (EC) damage, leading to senescence and dysfunctional phenotype. This study investigated whether serum from patients treated with the antihypertensive drugs could normalize EC activity. METHODS: This study involved 71 patients with newly diagnosed HT, who were randomly assigned to one of three groups based on the antihypertensive treatment: amlodipine, nebivolol, or perindopril. Serum samples collected before and 6 weeks after treatment were applied to ECs in vitro to assess their angiogenic activity, cellular senescence, mitochondrial metabolism, and oxidative stress. RESULTS: Results showed that exposure of ECs to serum from patients treated for 6 weeks significantly altered EC function, with varying effects among the drugs. Serum from nebivolol-treated patients produced the most consistent benefits, reducing EC proliferation and HIF-1α expression, likely due to lower levels of angiogenic factors such as angiopoietin-1, basic fibroblast growth factor (bFGF), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF). Additionally, this serum contained reduced levels of pro-inflammatory cytokines (E-selectin, P-selectin, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNFα)) and lower TGF-β1, which are linked to HT-related EC senescence. Nebivolol treatment decreased senescence biomarkers such as SA-β-Gal, 53BP1, and p16, with SA-β-Gal reduction comparable to that of TGF-β1 neutralizing antibodies. Oxidative stress was reduced, indicated by lower oxidized DNA product levels. CONCLUSIONS: Nebivolol was the most effective at reducing the factors, associated with HT induced cellular senescence of endothelium, through reducing TGF-β1.

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PubMed2026

Faster N1 latency in response to homeostatic-like plasticity of PREPs is impaired during pain: A randomized-placebo capsaicin-pain study.

INTRODUCTION: Homeostatic-like plasticity (HP-like) stabilizes cortical excitability through long-term potentiation and depression-like mechanisms. The efficacy of homeostatic regulation in the corticomotor system is impaired during pain, which may have functional relevance for chronic pain. This study investigated whether a cortical HP-like response could be assessed by nociceptive stimulation, and if such response was impaired by experimental tonic pain. METHODS: Twenty-eight healthy participants completed placebo and capsaicin sessions, with 11 sham controls for time and design. HP-like plasticity was induced with two blocks of anodal tDCS over the primary motor cortex. The N1 (TP7) and N2P2 (Cz) components of electrically induced pain-related evoked potentials (PREPs) were assessed from the volar forearm before and after patch application, and again immediately and 20 min after HP-like induction. An HP-like response was defined by PREP decrease after induction, and further normalization to baseline. RESULTS: Anodal tDCS did not induce an HP-like regulation of PREP amplitudes. Interestingly, an HP-like response was observed as a fastening of N1 latency after HP-like induction, which returned to baseline values after 20 min. The latter effect was impaired during capsaicin-induced pain, where N1 was slower. The N2P2 component showed habituation over time in all sessions. CONCLUSION: This is the first study that investigates the HP-like regulation of nociceptive-evoked responses. An HP-like response was observed as a shortening of N1 latency, suggesting that early nociceptive processing may be susceptible to homeostatic regulation. In contrast, the later component, N2P2, showed habituation over time, which prevented evaluation of HP-like effects.

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PubMed2026

The Animal Variant Classification Guidelines v2: An Update With New Criteria and Improved Clarifications.

The Animal Variant Classification Guidelines (AVCG) were developed to standardize and objectify the classification of putative disease-causing variants. These guidelines are sufficiently reproducible and are used to classify previously published and new disease-causing variants across species. Here, the guidelines are updated (AVCG.v2), based on a three-phase decision process. Overall, four new criteria and seven clarifying comments were added. The number of criteria has increased from 23 to 27, with three new criteria supporting pathogenicity and one new criterion supporting benign classification. Pharmacogenomic variants were determined to fall within the scope of the guidelines. These updated guidelines are being used by the Variant Pathogenicity Working Group (VPWG), part of the Animal Genetic Testing Standardization standing committee, which is a committee of elected members of the International Society for Animal Genetics (ISAG). Under the auspices of ISAG, the VPWG retrospectively classifies published putative disease-causing variants. The pathogenicity label for a variant will be presented in the variant tables of Online Mendelian Inheritance in Animals (OMIA; https://omia.org/). The AVCGv.2 criteria and recommendations were developed by the expertise of the animal genetics community and the ISAG Executive Committee through the Animal Genetics Testing Standardization Committee endorses and strongly encourages their use to evaluate the evidence supporting pathogenicity of putative disease-causing variants.

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PubMed2026

Association of ERBB4 and SHBG gene polymorphisms with polycystic ovarian syndrome in South Indian women: a case-control genetic analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a multifactorial endocrinological disorder with a substantial genetic component. However, the role of genes involved in follicular development and androgen regulation remains incompletely understood, particularly in South Indian populations. This study aimed to evaluate how variations in the ERBB4 and SHBG genes affect PCOS risk. METHODOLOGY: A hospital-based case-control study was conducted among 400 South Indian women, comprising 200 women with PCOS and 200 age-matched healthy controls. Genomic DNA was extracted to study SNPs at ERBB4 (rs2178575 and rs1351592) and SHBG (rs1799941 and rs727428) using ARMS-PCR genotyping. The study compared genotype and allele frequencies between cases and controls while assessing their associations with allelic, homozygous, heterozygous, dominant, recessive, and over-dominant genetic models. Genotyping accuracy was confirmed by re-genotyping and Sanger sequencing of a subset of samples. RESULTS: The ERBB4 rs2178575 polymorphism demonstrated a significant association with PCOS, as the AA genotype and A allele combination increased risk across all three genetic models, including homozygous, recessive, and allelic models. The ERBB4 rs1351592 variant was associated with 3-fold higher risk of PCOS in heterozygous and GC carriers. The SHBG rs1799941 polymorphism showed a significant link to PCOS through its effects on heterozygous and allelic states, whereas rs727428 displayed no significant connection due to its monomorphic distribution. CONCLUSION: These findings suggest that polymorphisms in ERBB4 and SHBG may contribute to PCOS susceptibility in South Indian women in a locus- and model-specific manner, revealing the intricate genetic structure that defines this medical condition.

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PubMed2026

The Effect of Breastfeeding on Cervical Dysplasias.

OBJECTIVE: This study aimed to investigate the relationship between breastfeeding and precancerous cervical lesions. MATERIALS AND METHODS: A case control study was conducted at a tertiary training and research hospital between September 1 and November 1, 2023. A total of 168 patients who attended the gynecology outpatient clinic and reported their breastfeeding experiences were included. Patients with abnormal cervical cytology formed the study group (n = 37), while patients with normal cytology formed the control group (n = 131). Breastfeeding duration and patterns were compared between groups. RESULTS: The control group had normal smear results. In the study group, 15 patients had high-grade squamous intraepithelial lesions, and 22 patients had low-grade squamous intraepithelial lesions. Human papillomavirus (HPV) was positive in 54.1% of the study group versus 9.2% of the control group. The mean breastfeeding duration was shorter in the study group (9.18 ± 3.43 months) than the control group (23.6 ± 3.35 months; p < 0.05). Most control group patients breastfed for 13-36 months (35.1%), while most study group patients breastfed for <6 months (48.6%; p < 0.05). Shorter breastfeeding (<6 months) and HPV positivity were the strongest predictors of abnormal cytology. Breastfeeding <6 months increased the risk 9.883-fold compared with >36 months, while HPV positivity increased the risk 27.612-fold. CONCLUSION: Breastfeeding and longer breastfeeding duration appear to be associated with a lower risk of cervical intraepithelial neoplasia. Given its multiple health benefits, including prevention of gynecological cancers, promoting breastfeeding through public health policies is strongly recommended. Early recognition and prevention of precancerous lesions remain essential to reducing the risk of cervical cancer.

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PubMed2026

Associations Between Routine Vaccinations and the Risk of New-Onset Idiopathic Uveitis.

OBJECTIVE: To evaluate the association between vaccination and the risk of new-onset idiopathic uveitis (NIU). DESIGN: Retrospective cohort study of aggregated electronic health records from multiple health systems across the United States. SUBJECTS: Subjects who received the coronavirus disease 2019 (COVID-19), human papillomavirus (HPV), varicella, recombinant herpes zoster, or live herpes zoster vaccinations from 2006 to 2025 and propensity-score matched controls. INTERVENTION: Vaccines against COVID-19, HPV, varicella, recombinant herpes zoster, or live herpes zoster. MAIN OUTCOMES AND MEASURES: The main outcome was the incidence of NIU at 3, 6, and 12 months following vaccination. Vaccinated patients were compared with matched controls who did not receive the respective vaccines. Analyses were repeated, excluding patients with previous diagnosis of the respective viral infection. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated for overall NIU and constituent subtypes (anterior, intermediate, posterior, and panuveitis). RESULTS: All tested vaccinations were associated with reduced risk of NIU through 12 months compared with matched controls. Relative risk reductions were 65% for COVID-19 (RR, 0.35; CI, 0.33-0.37), 56% for HPV (RR, 0.44; CI, 0.35-0.54), 71% for varicella (RR, 0.29; CI, 0.25-0.33), 68% for live zoster (RR, 0.32; CI, 0.23-0.43), and 69% for recombinant zoster vaccination (RR, 0.31; CI, 0.26-0.37). Similar reductions were observed after excluding patients with prior diagnoses of the respective viral infections. CONCLUSIONS: Vaccination was associated with a lower risk of idiopathic uveitis, representing the complex interplay between immune modulation and the development of NIU.

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PubMed2026

Acceptability of capillary point-of-care testing: a systematic review.

OBJECTIVE: To identify and synthesise evidence on the acceptability and perceived experience of finger-prick point-of-care testing (POCT) among patients and clinicians across healthcare settings. DESIGN: Systematic review conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. DATA SOURCES: Medline, Embase, PsycInfo, CINAHL, Cochrane and Web of Science were searched from inception to January 2024 and re-run in July 2025, supplemented by citation tracking of relevant studies. ELIGIBILITY CRITERIA: Studies reporting patient and clinicians' experiences, perceptions, satisfaction or acceptability relating to finger-prick POCT for any health condition or blood parameter were eligible. Quantitative, qualitative and mixed-methods designs were included. DATA EXTRACTION AND SYNTHESIS: Data were extracted independently by two reviewers and synthesised using thematic analysis and narrative synthesis. Methodological quality was appraised using the Mixed-Methods Appraisal Tool. RESULTS: 21 studies met the inclusion criteria, encompassing 9128 participants (17 quantitative, 3 qualitative, 1 mixed methods). Across diverse clinical contexts, finger-prick POCT was reported as generally acceptable, less distressing and perceived as a convenient alternative to venous sampling in comparative studies. Thematic synthesis identified two major themes: (1) enhancing the patient-clinician relationship through improved engagement, communication and understanding of care and (2) clinical implications of finger-prick POCT on clinicians' workflow, confidence and skill acquisition. Finger-prick POCT was perceived to promote personalised consultations, enable immediate discussion of results and streamline decision-making. Clinicians highlighted its potential to expand task sharing, improve efficiency and strengthen continuity of care, although concerns regarding training, reliability and quality assurance were identified. CONCLUSIONS: Finger-prick POCT is generally acceptable to patients and clinicians, improving comfort, convenience, engagement and perceived efficiency. Implementation should prioritise training, infrastructure and quality assurance frameworks to maximise clinical and experiential benefits. PROSPERO REGISTRATION NUMBER: CRD42024512130.

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PubMed2026

Sex-stratified analyses of femoral intercondylar notch morphology and ACL injury risk: a systematic review and meta-analysis.

BACKGROUND: Anterior cruciate ligament (ACL) injury is more common in females. Although ACL injury risk is multifactorial, involving neuromuscular, hormonal, and biomechanical factors, femoral intercondylar notch morphology is a proposed non-modifiable anatomical contributor that may help explain this disparity. This review synthesizes evidence on its association with ACL injury risk, analyses stratified by male and female sex. METHODS: A literature search of PubMed, Web of Science, and Scopus was conducted through January 2026. After duplicate removal, 527 unique records were screened and 134 full texts assessed for eligibility. Twenty-four studies met inclusion criteria, with 22 providing quantitative data. Data were extracted on ACL-injured (ACLi) and control (ACLc) knees, stratified by sex. RESULTS: ACLi knees had narrower notch widths than ACLc knees in both females (MD -1.74 mm, 95% CI -2.54 to -0.95) and males (MD -1.31 mm, 95% CI -1.94 to -0.68), with substantial heterogeneity (I2 81-95%). NWI differences were significant in males (MD -0.01, 95% CI -0.02 to 0.00) but not females. Limited notch shape data suggested higher ACL injury odds with A-shaped notches in females (OR 2.85, 95% CI 0.07-110.66) and males (OR 1.67, 95% CI 0.00-3.98 × 105). CONCLUSION: Narrower femoral intercondylar notch width was consistently associated with ACL injury in both sexes, whereas findings for NWI and notch shape were limited by heterogeneity and sparse data. These results provide a structured synthesis of sex-specific anatomical risk factors and support femoral notch narrowing as a shared contributor, while highlighting the need for prospective, standardized studies in the future.

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PubMed2026

Venous Sinus Stenting for Pulsatile Tinnitus: A Systematic Review and Meta-Analysis.

BACKGROUND: Pulsatile tinnitus (PT) is frequently caused by venous sinus stenosis and may be associated with idiopathic intracranial hypertension (IIH). Venous sinus stenting (VSS) directly addresses venous outflow obstruction and has emerged as a therapeutic option; however, outcome data remain heterogeneous. We performed an updated systematic review and meta-analysis to evaluate the efficacy and durability of VSS for PT and to compare outcomes between IIH-associated and isolated PT. METHODS: MEDLINE, Scopus, and Web of Science were searched from inception through December 2025 following PRISMA guidelines. Clinical studies reporting PT outcomes after VSS were included. Random-effects meta-analyses of proportions were conducted to estimate pooled rates of overall improvement, complete resolution, and recurrence. Prespecified subgroup analyses compared IIH versus isolated PT. RESULTS: Thirty-two studies comprising 850 patients were included (641 with IIH; 209 with isolated PT). Venous sinus stenosis accounted for 90.3% of treated etiologies. The pooled rate of overall PT improvement was 89.8% (95% CI, 85.5-92.9). Complete resolution occurred in 87.1% (95% CI, 82.5-90.6). Recurrence at last follow-up was 10.9% (95% CI, 8.3-14.2). Improvement and complete resolution rates did not differ significantly between IIH and isolated PT. Recurrence was higher in IIH (12.0%) than in isolated PT (5.7%), without reaching statistical significance. CONCLUSIONS: VSS is associated with high rates of PT improvement and complete resolution with low recurrence. Recurrence trends appear higher in IIH, suggesting underlying pathophysiology may influence durability.

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PubMed2026

Linking women leaving jail to medications for opioid use disorder: Costs to implement pre-release telehealth and peer navigation services.

AIMS: Telehealth and peer navigation are feasible strategies for connecting women in the criminal-legal system with medications for opioid use disorder (MOUD), yet implementation costs are not well understood. This study conducted a microcosting analysis of two interventions for women leaving jail in Kentucky: pre-release, PreTreatment Telehealth with a MOUD provider (TH-Only) and PreTreatment Telehealth combined with peer navigation (TH+PN) through the Justice Community Opioid Innovation Network (JCOIN). METHODS: From the provider perspective, we estimated total start-up costs, total intervention costs, and average cost per participant. Women participating in the clinical trial were randomly assigned to TH-Only (n=299) or TH+PN (n=301). Start-up costs were incurred primarily in 2019 - 2020; intervention costs represent expenses in 2021 - 2023. Cost data were collected from study and agency financial records and interviews with research staff and analyzed using Microsoft Excel (version 16.90.2). RESULTS: Start-up costs were $36,320, comprising planning, meetings, travel, and supplies. The total cost of TH-Only was $60,767, representing 259 telehealth sessions with an average duration of 47 minutes. Total cost of TH+PN was $472,148 based on 270 telehealth sessions (48 minutes), 268 peer navigation (PN) sessions (30 minutes), and 12 weeks of PN support post-release per participant. Average cost per TH-Only participant was $235 and per TH+PN participant was $1,760. CONCLUSIONS: Telehealth may be a relatively low-cost approach for jails lacking on-site MOUD services. Although more costly, combining telehealth with PN may add value by supporting service continuity and facilitating linkage to treatment during the jail to community transition.

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PubMed2026

The Addition of Concurrent Immune Checkpoint Inhibitors for Chemoradiotherapy With Consolidative Immune Checkpoint Inhibitors in Unresectable Cancers: A Systematic Review and Meta-Analysis.

Following the success of chemoradiotherapy (CRT) combined with consolidative immune checkpoint inhibitors (ICIs) in locally advanced tumors, over 30 ongoing randomized controlled trials (RCTs) are investigating the potential benefits of adding concurrent ICIs. To investigate the differences in efficacy and safety between adding and not adding concurrent ICIs to CRT followed by consolidative ICIs, a literature search was conducted in PubMed, Embase, and the Cochrane Library, incorporating RCTs comparing CRT combined with consolidative ICIs versus CRT alone, or CRT with both concurrent and consolidative ICIs versus CRT alone. The primary outcomes were overall survival (OS) and progression-free survival (PFS). To reduce potential bias, an additional mirror-design analysis was performed through network meta-analysis. A total of 13 RCTs comprising 6868 patients and 14 cohort studies comprising 4724 patients were included. While patients treated with CRT and consolidative ICIs demonstrated significantly superior OS and PFS to patients treated with CRT alone in RCTs (HR of OS, 0.743, 95% CI, 0.654-0.843; HR of PFS, 0.674, 95% CI, 0.577-0.786), CRT and concurrent-plus-consolidative ICIs did not improve OS and PFS compared with CRT alone (HR of OS, 0.942, 95% CI, 0.782-1.134; HR of PFS, 0.880, 95% CI, 0.752-1.030). Significant differences were detected in OS (p = 0.038) and PFS (p = 0.017) between CRT combined with consolidative ICIs treatment versus CRT combined with concurrent and consolidative ICIs treatment from RCTs. In conclusion, adding concurrent ICIs may dampen the survival benefits of CRT combined with consolidative ICIs. This evidence informs future RCT design strategies.

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PubMed2026

Comparison of summative assessments between simulated electronic health records versus traditional paper-based patient cases: A non-inferiority randomized controlled trial.

INTRODUCTION: Electronic health records are fundamental to contemporary pharmacy practice, yet evidence supporting their use in pharmacy education is lacking. This single-center, non-inferiority randomized controlled trial with blinded outcome assessment evaluated whether delivering patient cases via a simulated academic EHR (aEHR) was non-inferior to a traditional paper-based format in student exam performance. METHODS: 53 third-year PharmD students at the University of British Columbia were randomized 1:1 to complete a mock summative examination using either the aEHR or paper-based case delivery, stratified by self-reported EHR comfort level. The primary outcome was mean written exam score (%). Non-inferiority was pre-specified at a margin of 14%. Adjusted linear regression was used for the primary analysis, with a multiple imputation sensitivity analysis. Student perceptions were explored through post-exam focus groups analyzed using inductive thematic analysis. RESULTS: 42 students (21 per group) completed the exam and were included in the primary analysis. Mean scores were 66% (SD 11) in the aEHR group and 68% (SD 10) in the paper group. The adjusted mean difference (paper minus aEHR) was -2.2% (95% CI -9.2% to +4.8%), satisfying non-inferiority but not superiority. Sensitivity analysis (n = 53) yielded consistent results (-2.3%; 95% CI -7.1% to +4.1%). Focus groups revealed initial student anxiety with the aEHR but recognized its alignment with clinical practice. DISCUSSION: These findings support the feasibility of integrating simulated EHRs into summative pharmacy assessments without compromising performance. CONCLUSION: Simulated EHRs are a non-inferior assessment medium compared with paper-based formats and represent a viable step toward technology-driven pharmacy practice environments.

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PubMed2026

Polygenic risk scores in major depressive disorder: A systematic review across diagnostic, treatment, course/severity, and subtype domains.

BACKGROUND: Major depressive disorder (MDD) is heterogeneous across diagnostic, treatment-related, course/severity, and subtype domains. Polygenic risk score (PRS) studies have examined these domains, but differences in PRS sources, samples, methods, and endpoint definitions have fragmented the evidence. We synthesised findings and examined potential contributors to heterogeneity. METHODS: PubMed/MEDLINE, Embase, PsycINFO, and Web of Science were searched for studies published from January 2016 through 25 November 2025. Result records were synthesised using SWiM, and certainty was assessed with an adapted GRADE framework. RESULTS: Sixty studies contributed 493 retained records; 450 were descriptively classified as positive, null, or reverse, although records were not independent. Positive findings accounted for 44/56 diagnostic, 61/273 treatment-related, 64/100 course/severity, and 14/21 subtype records. For MDD/depression-derived PRSs and case-control MDD status, all 10 contributing studies showed higher liability in cases (exploratory exact sign test p = 0.002; FDR q = 0.004). The same PRS group showed positive findings for overall depressive symptom severity (14/18), although the study-level test was imprecise (5/5 studies; p = 0.063). Pharmacological response/remission findings for these PRSs were mostly null or directionally mixed (10 positive, 18 null, and 9 reverse). Treatment-resistant depression (TRD) findings differed by operational definition. Atypical and psychotic subtype signals arose mainly from single-study PRS and endpoint contrasts. CONCLUSIONS: PRS evidence was clearest for MDD diagnostic status and showed a tentative pattern for overall symptom burden. Treatment and subtype findings were less consistent or less replicated. Larger, ancestrally diverse studies with standardised endpoints and transparent PRS methods are needed.

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PubMed2026

Quantitative susceptibility mapping in neurodegenerative diseases: An umbrella review of iron-related biomarkers and mechanisms.

Pathological iron accumulation is a common pathophysiological hallmark across multiple neurodegenerative diseases (NDDs), motivating the need for accurate, non-invasive quantification methods. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique that enables in vivo measurement of tissue magnetic susceptibility (χ), providing a sensitive proxy for iron content. This umbrella review systematically evaluates the diagnostic accuracy, clinical correlations, and distinct iron distribution patterns of QSM in major NDDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and atypical Parkinsonism. We included 15 (13/15 were rated Low or Critically Low on AMSTAR 2) systematic reviews and meta-analyses (through July 15, 2026); however, the findings should be interpreted cautiously because of heterogeneity and the low methodological quality. A Corrected Covered Area (CCA) analysis demonstrated only slight overlap of primary studies across the included reviews (CCA = 5.42%). Collectively, the evidence indicates that QSM provides comparable or higher diagnostic sensitivity and reliability than conventional R2* and SWI techniques, particularly for deep gray matter structures. The findings support significant iron overload in the substantia nigra, particularly in the pars compacta, as a robust biomarker for PD that correlates with motor severity and disease duration. Furthermore, regional iron profiling in the basal ganglia is critical for differential diagnosis; specifically, elevated χ in the putamen and globus pallidus effectively distinguishes multiple system atrophy and progressive supranuclear palsy from idiopathic PD. Distinctively, AD and ALS exhibit specific χ alterations in the thalamus, motor cortex, and hippocampus, reflecting divergent iron-related pathophysiological mechanisms, which correlate with cognitive impairment and upper motor neuron signs. Overall, QSM shows diagnostic promise and offers mechanistic insights into iron-related neurodegenerative processes.

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PubMed2026

Natural products alleviate exercise-induced fatigue by modulating gut microbiota: a systematic review.

BACKGROUND: Exercise-induced fatigue critically impairs athletic performance and training quality. The gut microbiota, as a key regulator of the "gut-muscle axis," has emerged as a promising anti-fatigue target. Natural products - owing to their diverse sources, structural complexity, and favorable safety profiles - have attracted growing research interest. However, a systematic synthesis comparing their anti-fatigue effects via gut microbiota modulation across different sources is lacking. SCOPE AND APPROACH: We systematically searched PubMed, Web of Science, the Cochrane Library, and CNKI for original studies that administered natural products and concurrently assessed gut microbiota changes and anti-fatigue outcomes. Twenty-six studies (25 animal experiments and 1 human trial) were included and categorized into seven groups by source and chemical characteristics. A descriptive systematic review was conducted to identify common mechanisms and source-specific differentiations. KEY FINDINGS AND CONCLUSIONS: The enrichment of short-chain fatty acid (SCFA)-producing bacteria and the activation of the SCFA-AMPK/PGC-1α axis were shared core events across all product categories. However, source-dependent mechanistic divergences emerged: polysaccharides acted primarily as fermentable substrates with an optimal dose window; polyphenols and saponins exerted dual modulation on both microbiota and host signaling pathways; compound extracts achieved systemic synergy through functional complementation; marine- and animal-derived products exhibited unique targeting profiles and rapid action. Intestinal barrier maintenance and brain-gut axis regulation further extended the anti-fatigue repertoire. Collectively, natural products possess a solid mechanistic basis for alleviating exercise-induced fatigue via gut microbiota remodeling. The differentiated characteristics of these methods in targeting precision and pathway engagement provide a theoretical foundation for designing precision intervention strategies tailored to specific fatigue contexts.

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