Tag: pubmed

J Alzheimers Dis. 2026 Apr 15:13872877261440972. doi: 10.1177/13872877261440972. Online ahead of print.

ABSTRACT

BackgroundArgyrophilic grain disease (AGD) is a common tauopathy in the elderly, but its neuroimaging features remain less well characterized compared with Alzheimer’s disease (AD). Notably, structural covariance network (SCN) analysis has not previously been applied to AGD.ObjectiveThis study aimed to investigate SCN alterations in pathologically confirmed AGD and AD and to characterize disease-specific patterns of network disruption.MethodsWe examined 12 AGD, 13 AD, and 18 healthy controls (HC). Individualized structural covariance matrices were constructed from regional gray matter volumes, and global and nodal graph-theoretical metrics were computed for each participant. Group differences were assessed using analysis of covariance adjusting for age and sex, and partial correlations were performed to examine associations between global metrics and Mini-Mental State Examination (MMSE) scores.ResultsGlobal SCN metrics showed a graded pattern, with strength, clustering coefficient, and efficiency lowest in AD, highest in HC, and intermediate in AGD. All global metrics except modularity were significantly correlated with MMSE. Nodal analyses revealed widespread reductions in closeness centrality in AD, with more limited decreases in AGD. Betweenness centrality showed an AD > AGD > HC pattern, whereas closeness centrality showed the opposite trend. Eigenvector centrality also suggested a graded trend (AD < AGD < HC), despite regional variability.ConclusionsSCN-derived metrics were consistent with disease-related volume patterns and revealed that AGD exhibits an intermediate network profile between AD and healthy aging. These findings suggest that SCN-based measures offer complementary insights into disease-related patterns of network disruption.

PMID:41984506 | DOI:10.1177/13872877261440972

J Alzheimers Dis. 2026 Apr 15:13872877261441603. doi: 10.1177/13872877261441603. Online ahead of print.

ABSTRACT

BackgroundAlzheimer’s disease (AD) is a complex, multifactorial neurodegenerative disorder involving dysfunction across multiple brain regions. While accumulating evidence has implicated the roles of diverse cell types, including neurons, glia, and vascular cells in AD pathogenesis, it is still poorly understood how cell type interactions drive or respond to the disease progression and severity.ObjectiveThis study aimed to systematically characterize cell-type-specific alterations and intercellular communication changes associated with AD progression.MethodsWe leveraged the transcriptome profiling and a previously established statistical framework to present a comprehensive mapping of the cellular interaction landscape in the human brain of AD.ResultsWe identified a wide array of AD-associated cell-cell interactions (CCIs), including not only between the non-neuronal and neuron cells, but also among different neuron subtypes. These patterns were further supported by cell-type signature scoring. Moreover, due to the flexibility of the framework, we further examined CCIs associated with clinical dementia rating across multiple cortical regions. Our findings revealed that the temporal and frontal cortices showed a stronger correlation with dementia severity. However, the subregions of the temporal area show specific dementia-associated CCIs, especially between the inferior and middle temporal gyrus.ConclusionsOur work advances our understanding of the cellular microenvironment in AD, offering novel insights into how intercellular interactions shape disease trajectory and cognitive outcomes.

PMID:41984490 | DOI:10.1177/13872877261441603

JAMA Netw Open. 2026 Apr 1;9(4):e264881. doi: 10.1001/jamanetworkopen.2026.4881.

ABSTRACT

IMPORTANCE: Computer-aided detection (CAD) systems can enhance adenoma detection, but their effectiveness in high-performance settings and among patients with positive fecal immunochemical test (FIT) results remains uncertain.

OBJECTIVE: To evaluate the impact of CAD on adenoma detection in routine practice, focusing on patients with positive FIT results.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label, randomized clinical trial was conducted at 4 tertiary hospitals in Taiwan from February 23, 2022, to November 27, 2024. Adults aged 40 to 79 years who were scheduled for a colonoscopy owing to FIT positivity, symptoms, screening, or surveillance were randomized 1:1 to CAD-assisted or standard colonoscopy. Data were analyzed from December 1, 2024, to February 28, 2025.

EXPOSURES: Colonoscopy performed with a real-time CAD system or standard high-definition colonoscopy.

MAIN OUTCOMES AND MEASURES: The primary outcome was adenoma detection rate (ADR), defined as the proportion of patients with at least 1 histologically confirmed adenoma. Secondary outcomes included adenomas per colonoscopy (APC), sessile serrated lesion detection rate (SSLDR), and postpolypectomy surveillance intervals according to the US Multi-Society Task Force (USMSTF) and European Society of Gastrointestinal Endoscopy criteria.

RESULTS: Of 1356 randomized participants (mean [SD] age, 60.0 [9.4] years; 678 [50.0%] female and 678 [50.0%] male), CAD-assisted colonoscopy met noninferiority criteria for ADR compared with standard colonoscopy (395 of 675 [58.5%] vs 363 of 681 [53.3%]; absolute difference, 5.2 percentage points [95% CI, -0.1 to 10.5 percentage points]). Superiority was not statistically significant. CAD significantly increased mean (SD) APC (1.41 [1.95] vs 1.20 [1.88]; P = .01), driven mainly by detection of diminutive adenomas. In exploratory analyses of 864 patients with FIT-positive findings, CAD significantly increased ADR (288 of 441 [65.3%] vs 243 of 423 [57.4%]; P = .02; adjusted odds ratio [AOR], 1.39 [95% CI, 1.05-1.86]) and APC (mean [SD], 1.64 [2.08] vs 1.39 [2.09]; P = .01). SSLDR did not differ between groups. Consequently, CAD led to more intensive surveillance recommendations under USMSTF criteria, particularly in patients with FIT-positive findings (58 of 441 [13.2%] vs 31 of 423 [7.3%]; AOR, 1.94 [95% CI, 1.22-3.09]).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, CAD-assisted colonoscopy met noninferiority criteria for adenoma detection. Superiority was not statistically significant overall, with significant improvements limited to the exploratory FIT-positive subgroup, driven largely by diminutive adenomas. CAD also increased intensive surveillance assignments. The incremental benefit of CAD in reducing interval cancer risk requires further investigation.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03842059.

PMID:41984482 | DOI:10.1001/jamanetworkopen.2026.4881

JAMA Netw Open. 2026 Apr 1;9(4):e267242. doi: 10.1001/jamanetworkopen.2026.7242.

ABSTRACT

IMPORTANCE: American Indian and Alaska Native people have higher hepatitis C virus (HCV) incidence and mortality rates compared with other racial and ethnic groups. With the point-of-care HCV RNA diagnostic test recently approved for use in the US, the Cherokee Nation integrated diagnostic testing within existing community-based screening efforts to reach underserved community members.

OBJECTIVE: To describe the lessons learned from implementing community-based point-of-care HCV RNA testing, including same-day HCV treatment uptake, in a tribal health setting.

DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study, conducted on the Cherokee Nation reservation in northeastern Oklahoma, collected quantitative data through paper-based surveys and electronic medical records from Cherokee Nation’s Infectious Disease Department and harm reduction site, as well as qualitative data from staff meetings. Eligible participants included people aged 22 years or older who visited participating sites from October 30, 2024, to May 28, 2025, and provided informed consent.

EXPOSURE: The Cherokee Nation Hepatitis C Engagement and Linkage Program.

MAIN OUTCOME AND MEASURES: Test acceptance, completion, validity, and results; HCV treatment uptake; and implementation lessons learned.

RESULTS: Of the 400 participants (mean [SD] age, 42.5 [12.6] years; 209 [52%] women), 247 of 377 (66%) had a high school degree or less, 309 of 374 (83%) had an annual income of $15 000 or less, and 149 of 385 (39%) reported ever injecting drugs. There were 405 point-of-care HCV RNA tests offered, and 348 (86%) accepted. Of these, 23 (7%) were not performed due to insufficient sample volume. An additional 51 samples (15%) tested were invalid. Of the 274 valid tests, 26 (10%) detected HCV. Of the samples with HCV, 12 (46%) were from American Indian and Alaska Native participants and 14 (54%) were not. Nine participants (35%) with detectable HCV initiated treatment, 6 (67%) the same day, and all who initiated treatment were American Indian and Alaska Native. Most invalid tests occurred within 2 months of implementation. Test validity increased after introducing techniques to improve volume collection.

CONCLUSIONS AND RELEVANCE: In this quality improvement study conducted in a tribal clinic and harm reduction site, point-of-care HCV RNA testing was feasible and effective, with high acceptance and same-day treatment among American Indian and Alaska Native participants. Staff training, addressing logistical barriers, and broadening the population reached supported equitable access to testing. This study supports expanding point-of-care HCV RNA testing and integrated treatment to advance HCV elimination.

PMID:41984476 | DOI:10.1001/jamanetworkopen.2026.7242

JAMA Netw Open. 2026 Apr 1;9(4):e267424. doi: 10.1001/jamanetworkopen.2026.7424.

ABSTRACT

IMPORTANCE: Multiple retractions from the same author often uncover issues affecting their entire work, such as having systematically altered or fabricated data.

OBJECTIVES: To evaluate the contribution of authors with the most retractions (ie, superretractors) and top-cited scientists with multiple retractions to the retracted randomized clinical trial (RCT) literature.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study linked an openly available cohort of retracted RCTs (VITALITY) to 3 lists of scientists: (1) superretractors, totaling most retractions in the Retraction Watch Leaderboard; (2) scientists in the top 100 000 or 2% of their subfield in terms of citations (ie, top-cited scientists) over their entire careers who accumulated 10 or more retractions not due to editor or publisher errors; and (3) top-cited scientists in the most recent year (ie, 2024) who accumulated 10 or more retractions not due to editor or publisher errors. The VITALITY cohort was updated up to November 2024. The 3 author lists were updated in August 2025.

MAIN OUTCOMES AND MEASURES: The main outcomes were authorship and the characteristics of retracted RCTs (publication and retraction year, time between publication and retraction, number of citations).

RESULTS: A total of 30 superretractors, 163 career-long top-cited scientists with 10 or more retractions, and 174 recent-year top-cited scientists with 10 or more retractions were included; 1330 retracted RCTs were included. Overall, 6 superretractors (20%), representing anesthesiology as well as endocrinology and metabolism, coauthored 290 retracted RCTs (22%); 18 career-long top-cited scientists with at least 10 retractions, representing 10 fields, coauthored 327 trials (25%), 275 (84%) of which were also coauthored by a superretractor; 7 single-year top-cited scientists with at least 10 retractions coauthored 50 retracted RCTs (4%), all of which were also included in the list of articles authored by career-long top-cited scientists with at least 10 retractions. Articles with superretractor authors vs not were published earlier (median [IQR], 2000 [1997-2005] vs 2020 [2014-2022]); retracted earlier (median [IQR], 2013 [2012-2019] vs 2023 [2018.5-2023]); had a longer lag between publication and retraction (median [IQR], 5111 [3560-6820] days vs 482 [330-1119] days); and accrued more citations (median [IQR], 21 [12-42] vs 5 [1-19]). In multivariable regression models, only time to retraction (β = 0.02; P < .001) was significantly and positively associated with total citations. Results were similar when comparing retracted articles from top-cited scientists with at least 10 retractions vs other articles.

CONCLUSIONS AND RELEVANCE: In this cohort study of 1330 retracted RCTs, a small number of influential authors, often coauthors and concentrated across few fields of medicine, accounted for a significant proportion of retracted clinical trials.

PMID:41984475 | DOI:10.1001/jamanetworkopen.2026.7424

J Phys Chem B. 2026 Apr 15. doi: 10.1021/acs.jpcb.6c00165. Online ahead of print.

ABSTRACT

Electron transfer (ET) in protein receptor-ligand complexes is governed by environmental structure, memory, and fluctuation statistics. We investigate ET dynamics within a non-Markovian open-quantum-systems framework using a non-Markovian stochastic Schrödinger equation (NMSSE), contrasting the conventional harmonic (Gaussian) bath approximation with an anharmonic, non-Gaussian environment modeled by discrete Poisson (shot-noise) events. The model consists of a two-state donor-acceptor dimer coupled to a discrete vibrational mode and embedded in a structured protein-membrane environment. To represent anharmonicity beyond harmonic-bath theory, we introduce a finite-memory shot-noise description at the level of the second cumulant that implements instantaneous kicks on the coupled electronic-vibrational manifold. Ensemble-averaged trajectory simulations yield populations and coherences across broad parameter ranges. Three robust regimes emerge: (i) a weakly anharmonic regime, where many small events per correlation time render the compound-Poisson bath effectively Gaussian and harmonic, and non-Gaussian predictions are quantitatively close; (ii) an intermediate anharmonic regime, where intermittency and higher-order statistics become dynamically relevant, enhancing ET and qualitatively reshaping population and coherence dynamics, particularly at weak electronic coupling; and (iii) a strongly anharmonic sparse-event regime, where impulsive events drive pronounced, irregular energy exchange and the largest deviations from harmonic-bath behavior. These results delineate when harmonic approximations are sufficient and when explicit anharmonic, non-Gaussian bath models are required for faithful ET dynamics in biomolecular environments.

PMID:41984468 | DOI:10.1021/acs.jpcb.6c00165

JAMA Dermatol. 2026 Apr 15. doi: 10.1001/jamadermatol.2026.0605. Online ahead of print.

ABSTRACT

IMPORTANCE: Lifileucel is a first-in-class autologous tumor-infiltrating lymphocyte (TIL) therapy for advanced/metastatic melanoma with progression after anti-programmed cell death protein 1 (PD-1) therapy and/or BRAF inhibitor therapy, if BRAF V600 mutations are present. In the C-144-01 phase 2 trial of lymphodepleting chemotherapy, lifileucel, and interleukin 2 (IL-2), cutaneous eruption occurred in 37.2% of individuals. These eruptions remain clinically and prognostically unknown.

OBJECTIVE: To examine cutaneous toxic effects development in the setting of lifileucel therapy, abstract clinical and histopathologic eruption features, and test for association with objective radiographic tumor response.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was performed at Mass General Brigham (MGB)/Dana-Farber Cancer Institute (DFCI) that included all patients treated with lifileucel, outside of active clinical trials. The analysis was completed in December 2025.

EXPOSURES: All individuals received cyclophosphamide/fludarabine lymphodepletion, lifileucel, and 6 or fewer IL-2 infusions. Demographics, melanoma-specific factors (M stage, pre-TIL lactate dehydrogenase levels, and number of lines of prior systemic therapy), number of IL-2 doses received, eruption features, photography, and dermatopathologic findings were abstracted.

MAIN OUTCOMES AND MEASURES: Radiographic responses 30 to 41 days, 42 to 89 days, and 90 days or longer from TIL infusion per Response Evaluation Criteria in Solid Tumors (RECIST) were abstracted. Individuals were stratified as high IL-2 (4-6 doses) or low IL-2 (1-3 doses), for objective response rate (ORR) comparison as a descriptive sensitivity analysis. An unadjusted logistic regression modeled tumor response as a binary outcome with lifileucel-associated eruption occurrence as a binary predictor. Three adjusted models included IL-2 doses (age, sex, and demographic differences) and melanoma-specific factors as covariates.

RESULTS: Per retrospective electronic medical health record review, among 44 individuals (34.1% female individuals; mean [SD] age, 54.8 [14.5] years), treated with lifileucel (median, 4.5 IL-2 doses), 22 (50.0%) developed an associated cutaneous eruption while hospitalized, after a median of 4 post-TIL days. Photographs from 14 of 22 individuals (63.6%) with available images demonstrated central-predominant, frequently purpuric morbilliform eruptions. ORRs did not significantly differ by IL-2 stratification (high IL-2: 50.0% vs low IL-2: 37.5%; P = .53). Cutaneous eruption development was associated with a 42-day response across analyses (analysis 1: OR, 7.29; 95% CI, 1.91-27.86; P = .004; OR, 7.65; 95% CI, 1.79-32.69; P = .006; analysis 2: OR, 11.95; 95% CI, 1.90-75.39; P = .008; analysis 3: OR, 9.73; 95% CI, 2.12-44.74; P = .003); 30-day responses were statistically similarly associated. All 90-day cutaneous eruption response analyses did not detect statistical significance.

CONCLUSIONS AND RELEVANCE: In this cohort study, lifileucel treatment was frequently complicated by purpuric morbilliform eruptions, which were prognostically favorable and associated with short-term response. The lifileucel-associated eruption may be a peritreatment efficacy marker, assessable during the TIL treatment hospitalization prior to traditional 42-day restaging.

PMID:41984455 | DOI:10.1001/jamadermatol.2026.0605

Pain Ther. 2026 Apr 15. doi: 10.1007/s40122-026-00835-w. Online ahead of print.

ABSTRACT

INTRODUCTION: The objective of this study was to utilize real-world data from National Poison Data System (NPDS) to evaluate the relative risk of intentional use and subsequent outcomes following exposures to buprenorphine buccal film (BBF) compared to immediate-release (IR) and extended-release (ER) full agonist opioid (FAO) formulations, and buprenorphine transdermal patch (BTP).

METHODS: A cross-sectional study design compared exposures that involved BBF to those that involved IR FAO, ER FAO, and BTP using real-world data from NPDS. Data included individuals age 18 years and older involved in exposures managed by US poison centers from 2020 to 2023. Descriptive statistics were used to summarize study groups, exposures, and outcomes. Relative risk was calculated for exposure reasons and clinical outcomes using BBF as reference group.

RESULTS: Dataset included 276 BBF, 43,322 IR FAO, 2453 ER FAO, and 134 BTP exposures. Compared to BBF, significantly higher risks were found for both IR FAO and ER FAO for intentional abuse, intentional suspected suicide, significant medical outcome, hospital admission, and treated/evaluated and released level of care.

CONCLUSION: Findings from this study suggest that, compared to FAO, exposures to BBF managed by US poison centers were less likely to involve intentional abuse or suspected suicide, have a decreased risk of resulting in a life-threatening effect or death, and have a lower likelihood of subsequent hospital admission and emergency department visits. Along with published guidelines and medication labels (including boxed warnings), relative risks of intentional exposures and associated clinical outcomes should be considered when determining opioid therapy for pain management.

PMID:41984416 | DOI:10.1007/s40122-026-00835-w

J Hist Biol. 2026 Apr 15. doi: 10.1007/s10739-026-09854-x. Online ahead of print.

NO ABSTRACT

PMID:41984382 | DOI:10.1007/s10739-026-09854-x

Hepatol Res. 2026 Apr 15. doi: 10.1111/hepr.70187. Online ahead of print.

ABSTRACT

AIM: This study investigated the effects of the subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI) on the overall survival (OS) of patients with hepatocellular carcinoma (HCC).

METHODS: This study included 587 patients with HCC. The Cox proportional hazards model was used to identify independent prognostic factors. The optimal SATI cutoff value that yielded the most significant differences in OS was determined using the maximally selected statistics. Survival was estimated using the Kaplan-Meier method, and differences between survival curves were evaluated using the log-rank test.

RESULTS: SATI (hazard ratio, 0.99; 95% confidence interval, 0.98-0.99; p < 0.001) was significantly associated with improved OS after adjustment for potential confounders. The high-SATI group (≥ 41.1 cm²/m² for males and ≥ 48.9 cm²/m² for females) demonstrated significantly longer survival than those in the low-SATI group (p < 0.001; median survival: 87.0 vs. 40.4 months). The results of the decision tree analysis showed that patients with SATI ≥ 41.0 cm²/m² who received curative treatment demonstrated the best survival (median survival: 191.8 months). Subgroup analyses revealed that the survival advantage of the high-SATI group was consistent across most subgroups, except for patients with metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, body mass index > 25 kg/m², VATI ≥ 85 cm²/m², or hyperlipidemia.

CONCLUSIONS: In the absence of findings indicative of ectopic lipid accumulation, SAT accumulation is associated with an improved prognosis in patients with HCC.

PMID:41984354 | DOI:10.1111/hepr.70187