Tag: pubmed

Genome Res. 2026 Aug 28:gr.282203.126. doi: 10.1101/gr.282203.126. Online ahead of print.

ABSTRACT

Hybridization between species is an important force in evolution, commonly modeled by the network multispecies coalescent. Reconstructing evolutionary histories under this model is computationally challenging, even for level-1 networks where hybridization events are isolated. Divide-and-conquer is a promising path forward, but current methods with statistical guarantees rely on an estimated tree of blobs (TOB) for the network, which compresses each nontree-like part into a single vertex. TOB reconstruction is itself challenging, with the only available method TINNiK having time complexity O(n ⁵ + n ⁴ k) for k genes and n species. Here, we present a new framework for scalable TOB reconstruction with statistical guarantees. Our approach operates by (1) seeking a refinement of the TOB and then (2) contracting edges in it. For step (1), we show that any optimal solution to Weighted Quartet Consensus is a TOB refinement almost surely, as the number of genes goes to infinity, motivating the use of methods, such as ASTRAL or TREE-QMC. For step (2), we show that applying the same hypothesis tests as TINNiK to just O(n) four-taxon subsets around each edge is sufficient for statistically consistent TOB reconstruction when the underlying network is level-1. Leveraging TREE-QMC for the first step gives our method time complexity O(n ³ k) and its name: TOB-QMC. On simulated data, TOB-QMC typically matches or exceeds TINNiK in accuracy while being more scalable. TOB-QMC also enables fast exploration of nontreelike evolution, as demonstrated through reanalysis of three phylogenomic data sets. Lastly, our study clarifies the theoretical utility of quartet-based species tree methods in the context of hybridization, which is critical given the recent result that ASTRAL can be misleading.

PMID:42665444 | DOI:10.1101/gr.282203.126

J Med Genet. 2026 Aug 28:jmg-2025-110787. doi: 10.1136/jmg-2025-110787. Online ahead of print.

ABSTRACT

BACKGROUND: Pathogenic missense variants in the MORC2 gene are associated with two distinct disorders: Charcot-Marie-Tooth disease type 2Z (CMT2Z) and the recently described DIGFAN (developmental delay, impaired growth, dysmorphic facies and axonal neuropathy) phenotype, which encompasses a broad range of clinical manifestations that vary significantly between individuals.

METHODS: Clinical and imaging data from 16 patients were collected. Western blot analysis was performed on 10 identified variants in affected patients as well as on two novel variants without clinical data. Those missense variants were introduced into the wild-type vector transfected into HEK293T cells, and western blot analysis was performed to assess protein expression level.

RESULTS: A total of 11 different missense variants in the MORC2 gene were identified in our cohort, including four novel variants. We demonstrate that early-onset MORC2-associated disorders segregate into two principal neurological phenotypes: a predominantly neuromuscular form and a central nervous system-predominant form. The p.Ser87Leu variant, which defines the neuromuscular cluster, was uniquely characterised by a significant reduction in MORC2 protein levels, distinguishing it mechanistically from other variants. Overall, western blot analysis revealed no statistically significant difference in protein expression levels between variants related to CMT2Z and DIGFAN cases.

CONCLUSION: A comparison of our patients with previously reported cases revealed an intriguing trend suggesting a probable dependence of the leading clinical features on specific variants in the MORC2 gene. Further accumulation of patient data is required to determine whether this observation correlates with other specific variants.

PMID:42665440 | DOI:10.1136/jmg-2025-110787

BMJ Lead. 2026 Aug 28:leader-2026-001625. doi: 10.1136/leader-2026-001625. Online ahead of print.

ABSTRACT

INTRODUCTION: Attitudes and clinical norms are shaped during medical training. Evidence from high-value care education suggests early exposure influences long-term practice patterns, making it an ideal target for curricula interventions. STARS (Students and Trainees Advocating for Resource Stewardship) is a learner-driven programme developed by Choosing Wisely Canada in 2015 and subsequently adopted in the USA. It exposes medical students to high-value care principles and activates them as change agents. We evaluated perceived sustained influence of the US STARS programme on attitudes, behaviours and professional development among medical students.

METHODS: We conducted a mixed-methods programme evaluation of approximately 20% of participants from the first six U.S. cohorts (n=579; 2018-2023). Participants completed an anonymous retrospective pre-post survey assessing familiarity with healthcare value concepts and STARS’ perceived influence. They also submitted annotated CVs reviewed for scholarly activities attributed to programme participation. Survey data were analysed using descriptive statistics.

RESULTS: Ninety-four of 118 invited participants (80% response rate) completed both components. Participants reported that STARS influenced how they consider healthcare costs in clinical decision-making, discuss medical overuse with peers and appreciate the impact of costs on patients. Many attributed subsequent leadership activities and scholarly output to their participation, including quality improvement projects, peer-reviewed publications and locally implemented educational initiatives.

CONCLUSION: This evaluation highlights the potential of learner-driven, longitudinal models such as STARS to foster durable engagement with high-value care education and catalyse professional development among medical trainees.

PMID:42665435 | DOI:10.1136/leader-2026-001625

J Obstet Gynaecol. 2026 Dec;46(1):2721701. doi: 10.1080/01443615.2026.2721701. Epub 2026 Aug 28.

ABSTRACT

BACKGROUND: Cross-sectional associations of high-density lipoprotein-related inflammatory indices (HIRIs) – white-blood-cell-, lymphocyte-, monocyte-, neutrophil-, and platelet-to-high-density lipoprotein cholesterol (HDL-C) ratios (WHR, LHR, MHR, NHR, and PHR) – with self-reported gynaecological cancer (GC) history are unclear.

METHODS: We analysed 12,955 women from six National Health and Nutrition Examination Survey cycles (2007-2008 to 2017-March 2020 pre-pandemic), including 369 with GC history; cervical cancer (CC), 184; uterine cancer (UC), 127; and ovarian cancer (OC), 70. Primary analyses used survey-weighted logistic regression and restricted cubic spline (RCS) models with Benjamini-Hochberg false discovery rate (BH-FDR) correction; component-resolved and sensitivity analyses were supportive, and other secondary analyses were exploratory.

RESULTS: In fully adjusted models, overall GC history was nominally associated with PHR (odds ratio [OR] 1.26, 95% confidence interval [CI] 1.01-1.59; p = 0.045), the highest NHR tertile (OR 1.67, 95% CI 1.12-2.50; p = 0.013), and the highest WHR tertile (OR 1.56, 95% CI 1.04-2.34; p = 0.032). Subtype analyses showed selected nominal patterns, including an NHR tertile gradient for CC and WHR/LHR/PHR associations for UC; OC estimates were less stable. No primary logistic or RCS result survived BH-FDR correction. In supportive component-resolved analyses, the OC WHR white-blood-cell component met the BH-FDR threshold within the prespecified WHR-specific eight-test family (OR 2.40, 95% CI 1.35-4.25; p = 0.003; q = 0.025).

CONCLUSIONS: HIRIs showed modest, heterogeneous cross-sectional associations with self-reported GC history, but the primary findings were not retained after multiplicity correction. These ratios appear to reflect both shared HDL-C and numerator-cell information and should be interpreted as descriptive, hypothesis-generating phenotypes rather than diagnostic, prognostic, or causal markers.

PMID:42665432 | DOI:10.1080/01443615.2026.2721701

Cutan Ocul Toxicol. 2026 Aug 28:1-8. doi: 10.1080/15569527.2026.2725116. Online ahead of print.

ABSTRACT

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening mucocutaneous reactions. Although SCORTEN remains the most widely used prognostic tool, its performance in real-world settings may vary according to patient population and clinical context. This study evaluated clinical variables associated with in-hospital mortality in SJS/TEN.

MATERIALS AND METHODS: We conducted a single-center retrospective cohort study including 20 patients diagnosed with SJS, SJS/TEN overlap, or TEN between January 2010 and December 2024. Clinical and demographic data were extracted, including SCORTEN, mucosal involvement, etiology, comorbidities, treatment modalities, need for intensive care unit (ICU) admission, organ failure, ICU and ward length of stay. Due to the small sample size, statistical comparisons were exploratory and were performed using appropriate exact and non-parametric tests.

RESULTS: The in-hospital mortality rate was 40.0% (8/20; exact 95% CI, 19.1%-63.9%). ICU admission occurred in 8/8 non-survivors and 4/12 survivors (absolute difference, 66.7 percentage points; 95% CI, 24.1 to 86.2; p = 0.005). Respiratory failure, dialysis-requiring renal failure, and malignancy each occurred in 4/8 non-survivors and 0/12 survivors (absolute difference for each, 50.0 percentage points; 95% CI, 12.6 to 78.5; p = 0.014 for each), although these outcomes partly overlapped. Among ICU-admitted patients, the median ICU length of stay was 8.5 days in both outcome groups (Hodges-Lehmann difference, 0 days; 95% CI, -9 to 11; p = 0.958). Neither SCORTEN nor TBSA category was significantly associated with mortality.

CONCLUSIONS: In this retrospective single-center cohort, ICU requirement, acute organ failure, and underlying malignancy were more frequent among non-survivors with SJS/TEN. Given the limited sample size and absence of multivariable analysis, these findings should be interpreted cautiously. Larger multicenter studies are needed to clarify prognostic factors and real-world clinical course in SJS/TEN.

PMID:42665431 | DOI:10.1080/15569527.2026.2725116

In Vivo. 2026 Sep-Oct;40(5):3137-3145. doi: 10.21873/invivo.14462.

ABSTRACT

BACKGROUND/AIM: TROP2 has become a therapeutic target in urothelial carcinoma following the approval of TROP2-directed antibody-drug conjugates (ADCs), yet its expression in transurethral resection (TURBT) material remains poorly characterized. This study aimed to evaluate TROP2 protein expression using immunohistochemistry (IHC) in bladder TURBT samples and to investigate its association with histological grade, tumor stage, lymphovascular invasion (LVI), carcinoma in situ (CIS), recurrence, and survival outcomes.

MATERIALS AND METHODS: A total of 79 bladder TURBT specimens were included. Histological grading was performed according to the WHO/ISUP two-tier classification system (low grade / high grade) and pathological staging was based on the AJCC/UICC TNM Classification, 8th edition. TROP2 expression was assessed using IHC and quantified using the H-score method. Statistical analyses were performed using the chi-square test, Fisher’s exact test, Mann-Whitney U and Kruskal-Wallis tests, Spearman’s correlation analysis, receiver operating characteristic analysis, Kaplan-Meier estimates with log-rank tests, and Cox proportional hazards regression.

RESULTS: Mean age was 65.87±11.46 years (91.1% male). Mean TROP2 H-score was 173.99±48.15 (median 160.0; range 30-280). A significant negative correlation was identified between TROP2 and histological grade (rho=-0.410; p=0.0003); median H-scores were 200.0 in low-grade versus 150.0 in high-grade tumors. Receiver operating characteristic analysis yielded an area under the curve (AUC) of 0.736 (sensitivity 92.3%, specificity 45.0%; cut-off 200). No significant association was found with pT stage, LVI, CIS, recurrence, disease-free survival (log-rank p=0.886), or overall survival (log-rank p=0.752). Cox regression confirmed no independent prognostic effect on survival.

CONCLUSION: TROP2 inversely correlates with histological grade in bladder TURBT specimens (AUC=0.736) and may guide pathologists in diagnostically challenging cases – limited tissue, cautery artifact, or incomplete resection – where a low H-score suggests high-grade disease. TROP2 may complement WHO/ISUP grading and serve as a candidate predictive biomarker for TROP2-targeted ADC therapies.

PMID:42665429 | DOI:10.21873/invivo.14462

In Vivo. 2026 Sep-Oct;40(5):2881-2893. doi: 10.21873/invivo.14438.

ABSTRACT

BACKGROUND/AIM: To compare two different devices for computed tomography (CT)-guided preoperative localization of impalpable pulmonary nodules in terms of effectiveness, technical and clinical success and complications rate.

PATIENTS AND METHODS: CT-guided preoperative localization procedures of small or ground glass (i.e., impalpable) pulmonary nodules performed in our center from April 2018 to December 2021 before lung resection with video-assisted thoracic surgery (VATS) were retrospectively analyzed. Two different markers were used: spiral-wire (SpW) and hydrogel plug (HyP). For each nodule the density, size and pleural distance were evaluated. Technical (correct CT-guided positioning of the marker) and clinical (its correct localization in VATS) success were assessed for each device. Complications as displacement, pneumothorax and parenchymal hemorrhage (PH) were registered. Statistical analysis was made by Chi-square, Wilcoxon and Fisher tests.

RESULTS: Eighty-five consecutive patients (46/39 males/female; mean age 42 years, range=4-80 years) with 85 pulmonary nodules (maximum diameter: 8.5±6.4 mm in the SpW group and 17.0±4.2 mm in the HyP group) underwent preoperative CT-guided localization with SpW (65/85, 76.5%) or HyP (20/85, 23.5%) device. Correct CT-guided landmark positioning was obtained in 100% of cases. VATS revealed 4/65 (6.2%) cases of marker displacement in the SpW group and 3/17 (17.6%) cases in the HyP group (p=0.0353). Pneumothorax occurred in 40/65 (61.5%) cases in the SpW group and in 11/20 (55.0%) cases in the HyP group (p=0.602); no drainage tube was needed. PH occurred in 34/65 (52.3%) cases in SpW group and in 14/20 (70.0%) cases in HyP group (p=0.0163).

CONCLUSION: Both markers are effective for the preoperative localization of impalpable pulmonary nodules in VATS. SpW seems to be slightly more stable and safer than HyP lung marker in relation to the displacement and PH rate.

PMID:42665416 | DOI:10.21873/invivo.14438

In Vivo. 2026 Sep-Oct;40(5):2894-2907. doi: 10.21873/invivo.14439.

ABSTRACT

BACKGROUND/AIM: Type II odontoid fractures in elderly patients are associated with high rates of nonunion and substantial morbidity. However, the clinical relevance of radiographic nonunion following anterior odontoid screw fixation remains unclear. This study aimed to evaluate long-term functional outcomes and health-related quality of life, with particular focus on the impact of fracture healing.

PATIENTS AND METHODS: This retrospective single-center study included 82 patients (mean age 75.7 years) treated with anterior odontoid screw fixation between 2011 and 2019. Radiographic union was assessed using postoperative imaging. Patient-reported outcome measures (PROMs), including Visual Analog Scale (VAS), Neck Disability Index (NDI), EQ-5D-5L, and SF-36, were obtained at long-term follow-up. Outcomes were compared between patients with and without radiographic union.

RESULTS: Radiographic nonunion was observed in 44% of patients. A total of 27 patients completed follow-up assessments. Overall outcomes were favorable, with low pain levels (mean VAS score of 2), minimal disability (NDI mean 7), and good quality of life (EQ-5D-5L mean 0.79). Patients with nonunion demonstrated consistently worse PROMs; however, differences did not reach statistical significance. A significant difference was observed in the EQ-5D-5L anxiety/depression domain (p=0.018), indicating increased psychological burden in the nonunion group.

CONCLUSION: Anterior odontoid screw fixation provides satisfactory long-term clinical outcomes in elderly patients with type II odontoid fractures. Despite a high rate of radiographic nonunion, functional outcomes and quality of life were not significantly impaired. These findings suggest that mechanical stability may be more clinically relevant than complete osseous union. Larger prospective studies are required to confirm these results.

PMID:42665394 | DOI:10.21873/invivo.14439

In Vivo. 2026 Sep-Oct;40(5):2947-2959. doi: 10.21873/invivo.14444.

ABSTRACT

BACKGROUND/AIM: Hospital stays are often associated with emotional strain, influenced by environmental, procedural, and communication factors. While supportive interventions hold promise for improving patient well-being, understanding the lived experiences and needs of patients is essential for designing effective, patient-centered solutions. This study seeks to explore these factors to inform future strategies for enhancing emotional support during hospital stays.

PATIENTS AND METHODS: A 2023 cross-sectional survey at the Department of Radiology and Nuclear Medicine at the University Hospital Mannheim was conducted as an exploratory assessment to characterize patient-reported emotional stressors and care experiences during hospitalization. The survey employed a mixed-methods approach. The data was analyzed using descriptive and inferential statistics, with qualitative responses coded for thematic patterns.

RESULTS: The survey revealed that prolonged waiting times (>1 hour, 74% of participants) and communication problems were associated with lower self-reported mental well-being (mean score dropped from 4.45 to 3.57 out of 5, p<0.001). Language barriers and organizational inefficiencies exacerbated distress, while staff empathy and social visits improved well-being. Prior to procedures, the most common stated emotions by participants were apprehension (68% therapeutic procedure and 58% diagnostic procedure) and anxiety (47% therapeutic, 21% diagnostic), with these emotions shifting to confidence (78% therapeutic, 57% diagnostic) and hope (44% therapeutic, 43% diagnostic) post-procedure.

CONCLUSION: Communication delays and procedural anxiety are important contributors to emotional distress during hospitalization. These findings delineate empirically grounded stress domains that may guide structured investigation of supportive intervention strategies. By integrating such innovations alongside the irreplaceable value of human-centered care, future research can build on these insights to create holistic, patient-tailored solutions. Co-design with patients and clinicians, followed by rigorous validation, will be key to unlocking this potential.

PMID:42665371 | DOI:10.21873/invivo.14444

BMJ Glob Health. 2026 Aug 28;11(8):e024344. doi: 10.1136/bmjgh-2026-024344.

ABSTRACT

Cluster randomised trials (CRTs) remain key for evaluating the community-wide impact of interventions against infectious diseases such as malaria. Randomising by cluster prevents contamination and enables both the direct and indirect effects of the intervention to be estimated. Although these trials are extremely informative, they can be logistically demanding and costly to carry out, which means it is important that these trials are well powered. Here, we present a framework for planning CRTs that measure malaria prevalence as the outcome using an established mathematical model of malaria transmission. In this way, we explicitly consider the epidemiology of the individual trial clusters. The framework can be used alongside a baseline prevalence survey to help inform the sample size calculations for the trial. We use a case study to illustrate the framework, where we simulate a CRT in which a next-generation pyrethroid-pyrrole insecticide-treated net (ITN) is compared against a standard pyrethroid-only ITN. We show how the malaria endemicity of the trial location and timing of the follow-up surveys can affect the results obtained. We also highlight how other active interventions against malaria can reduce study power by increasing the amount of between-cluster heterogeneity in malaria prevalence.

PMID:42665358 | DOI:10.1136/bmjgh-2026-024344