Category: Nevin Manimala

JMIR Med Educ. 2026 Aug 18;12:e92964. doi: 10.2196/92964.

ABSTRACT

BACKGROUND: Psychotherapy training is difficult to scale because manual rating of motivational interviewing (MI) and cognitive behavioral therapy (CBT) sessions is time-intensive, requires trained raters, and is subject to rater variability. Large language models (LLMs) may support simulation-based training and rubric-guided scoring, but early-stage evidence is needed before such systems can be applied to real learners.

OBJECTIVE: This study aimed to conduct a simulation-based evaluation of a multiagent LLM framework for generating and scoring stylized MI and CBT training encounters.

METHODS: We conducted a cross-sectional evaluation of a multiagent framework comprising Student, Patient, Evaluator, and Feedback agents. The Student agent conducted synthetic MI or CBT encounters with Patient agents derived from structured profiles. The Evaluator agent scored transcripts using study-specific MI and CBT scoring forms. Internal discrimination was tested across prompt-engineered novice, intermediate, and expert Student agent profiles using 133 MI and 102 CBT Patient profiles. Preliminary external grounding was assessed using 133 annotated motivational interviewing (AnnoMI) transcripts with coarse, metadata-derived, high/low session-level quality labels. Agreement with a pragmatic human-rater benchmark was evaluated using 16 independent human raters per modality. Criterion-level comparisons used paired Wilcoxon signed-rank tests with Benjamini-Hochberg false discovery rate correction at q<0.05. Agreement analyses used intraclass correlation coefficients (ICCs) with bootstrap 95% CIs. A secondary prompt-augmentation sensitivity analysis tested whether appending criterion-referenced feedback text to the novice Student-agent prompt shifted subsequent Evaluator-assigned scores.

RESULTS: Evaluator scores increased across prompt-defined Student-agent competence levels. For MI, overall mean scores increased from 1.18 (95% CI 1.16-1.20) for novice profiles to 1.75 (95% CI 1.69-1.81) for intermediate profiles and to 3.57 (95% CI 3.48-3.66) for expert profiles. For CBT, overall mean scores increased from 0.83 (95% CI 0.78-0.88) to 2.18 (95% CI 2.10-2.26) and 4.38 (95% CI 4.28-4.48), respectively. Criterion-level planned contrasts were significant after false discovery rate correction. On AnnoMI transcripts, Evaluator scores aligned with metadata-derived high/low session labels, with 91.7% classification accuracy at the prespecified threshold. Human interrater reliability was an ICC(2,1) of 0.866 for MI and 0.769 for CBT. Evaluator-vs-human-consensus agreement was an ICC(2,1) of 0.959 for MI and 0.934 for CBT. In the secondary prompt-augmentation analysis, overall MI scores shifted from 1.18 to 1.44, and CBT scores shifted from 0.83 to 1.01.

CONCLUSIONS: This proof-of-concept study suggests that a rubric-guided multiagent LLM framework can score stylized synthetic MI and CBT transcripts along expected prompt-defined competence gradients and align with preliminary external and human-rater benchmarks. The study is innovative in separating synthetic learner, patient, scoring, and feedback-generation roles within a single simulation workflow, extending prior LLM work from plausible dialogue generation toward rubric-linked scoring. The findings support further development of scalable simulation tools for psychotherapy training research. Prospective studies with human trainees, standardized or real patients, and formal psychometric testing are required.

PMID:42611045 | DOI:10.2196/92964

Syst Biol. 2026 Aug 18:syag065. doi: 10.1093/sysbio/syag065. Online ahead of print.

ABSTRACT

A common assumption in mathematical models of molecular evolution is that mutations are rare. One example is the boundary mutation assumption, which posits that mutations occur so infrequently that, by the time a new one arises, the previous mutation has already been fixed or lost in the population. This assumption, however, ignores recurrent mutations and can be problematic for highly diverse organisms such as bacteria and viruses. In this study, we challenge the assumption of infrequent mutation in phylogenetic inference. To do so, we compare two mutation models: one that incorporates recurrent mutations and another that allows only boundary mutations. Our results show that while tree topologies remain mostly unaffected, branch lengths and estimates of mutation bias and selection are substantially compromised. These patterns hold across both simulations and empirical case studies, including HIV, HCV and IAV viruses. Overall, this study highlights the importance of accounting for recurrent mutations in phylogenetic analyses of highly diverse organisms, many of which have significant epidemiological and medical relevance.

PMID:42611043 | DOI:10.1093/sysbio/syag065

J Alzheimers Dis. 2026 Aug 18:13872877261474020. doi: 10.1177/13872877261474020. Online ahead of print.

ABSTRACT

Anti-amyloid immunotherapies (lecanemab, donanemab) produce statistically significant but clinically modest slowing of decline in early Alzheimer’s disease (AD), with substantial inter-individual response variability that current covariates-antibody titer, baseline amyloid load, apolipoprotein E ε4 (APOE4) status, or tau burden-leave largely unexplained. We propose that a systematically unmeasured upstream variable contributes to this variability: the structural integrity of the locus coeruleus (LC), the principal source of brain norepinephrine (NE), framed as a candidate determinant of amyloid-β (Aβ) clearance efficiency rather than of overall clinical outcome. This hypothesis paper synthesizes three peer-reviewed lines of evidence and derives a hierarchy of falsifiable predictions; no new data are reported. First, tau pathology initiates in LC neurons before any cortical structure, reducing NE output from the earliest preclinical stage. Second, NE governs two complementary Aβ-clearance pathways: glymphatic flow, via aquaporin-4 dynamics driven by slow LC oscillations during non-REM sleep, and microglial phagocytosis, via β2-adrenergic receptor signaling. Third, in Parkinson’s disease, the DTI-ALPS index mediates the relationship between LC integrity on neuromelanin-sensitive MRI and cognition. We term this the Locus Coeruleus Gateway Hypothesis (LCGH). Its mediation chain is testable now in ADNI, which holds research-grade diffusion-tensor imaging; its treatment-response prediction requires immunotherapy cohorts that acquire such imaging, not the existing CLARITY-AD or TRAILBLAZER-ALZ 2 archives, whose safety MRI used diffusion-weighted, not tensor, sequences. We state explicitly that Aβ clearance is only one contributor to clinical benefit, and that the LCGH predicts pharmacodynamic efficiency, not that NE restoration treats AD.

PMID:42611034 | DOI:10.1177/13872877261474020

Acta Radiol. 2026 Aug 18:2841851261477088. doi: 10.1177/02841851261477088. Online ahead of print.

ABSTRACT

BackgroundThe relationship between acute myocardial injury and prognosis in acute myocarditis (AM) is unclear.PurposeTo evaluate myocardial injury characteristics by cardiovascular magnetic resonance (CMR) tissue parameters and their impact on adverse outcomes of AM patients.Material and MethodsThis retrospective study enrolled 41 patients with fulminant myocarditis (FM, including 17 FM patients without mechanical circulatory support [MCS] and 24 FM patients with MCS) and 35 patients with non-fulminant myocarditis (non-FM). Cine, mapping (native T1, T2, and post-T1), and late gadolinium enhancement (LGE) of the left ventricle were performed during CMR. Adverse clinical outcomes consisted of a primary endpoint, major adverse cardiovascular events (MACEs), and a secondary endpoint, a decline in functional status (defined as New York Heart Association [NYHA] functional classes II-IV).ResultsCompared with patients with non-FM, those in FM with MCS exhibited increased native T1 (P = 0.001), extracellular volume (ECV) (P = 0.018), and LGE (P = 0.005) values. After adjusting for the clinical variables (CRP > 67.9 mg/dL), LGE > 8.4% remained independently associated with adverse clinical outcomes and improved the predicting ability of the model (C-statistic improved from 0.74 to 0.82).ConclusionThe burden of necrosis and fibrosis was greatest in FM with MCS, while edema was similar across groups. Higher LGE% adds incremental prognostic value. A new classification using CRP and LGE improved prediction of adverse outcomes. Thus, CMR evaluation of myocardial injury extent offers variable information to improve risk stratification in FM.

PMID:42611031 | DOI:10.1177/02841851261477088

J Back Musculoskelet Rehabil. 2026 Aug 18:10538127261477947. doi: 10.1177/10538127261477947. Online ahead of print.

ABSTRACT

BackgroundFrozen shoulder (FS), commonly known as adhesive capsulitis, is a disabling musculoskeletal condition frequently accompanied by psychological distress. This meta-analysis aimed to evaluate the association between FS and depression.MethodsFor this meta-analysis, a systematic literature search of EMBASE, PubMed, and the Cochrane Library was conducted through 2025 using the keywords “frozen shoulder”, “adhesive capsulitis” and “depression.” Data regarding study characteristics, participant information, and depression-related outcomes were extracted. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS). Pooled odds ratios (ORs), mean differences (MDs), and corresponding 95% confidence intervals (CIs) were calculated. Statistical heterogeneity and potential publication bias were also assessed.ResultsNine studies including 122,378 participants met the inclusion criteria. The pooled prevalence of depression among patients with FS was 25.5% (95% CI: 16.7-36.8%). Patients with FS showed significantly higher odds of depression compared with individuals without FS (OR = 2.15, 95% CI: 1.57-2.94). In addition, FS patients had significantly higher HADS-D scores (MD = 2.97, 95% CI: 0.66-5.28). Substantial heterogeneity was observed across studies, while no significant publication bias was detected.ConclusionFS is associated with an increased risk of depression. These findings emphasize the importance of incorporating psychological assessment and management into the clinical care of patients with FS to improve overall outcomes.

PMID:42611029 | DOI:10.1177/10538127261477947

Orthopedics. 2026 Jul-Aug;49(4):e275-e283. doi: 10.3928/01477447-20260625-01. Epub 2026 Aug 14.

ABSTRACT

BACKGROUND: This meta-analysis compared the clinical efficacy of unilateral biportal endoscopic diskectomy (UBE) and percutaneous endoscopic lumbar diskectomy (PELD) for lumbar disk herniation.

MATERIALS AND METHODS: A systematic search of PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and Wanfang was conducted from inception to May 2025. Comparative studies in adults undergoing UBE or PELD were included. Outcomes included operative and recovery parameters, complications, reoperation, Macnab outcomes, visual analog scale (VAS) scores, Oswestry Disability Index (ODI), fluoroscopy exposure, and total cost. Pooled effects were calculated as mean differences or odds ratios with 95% confidence intervals. Prespecified subgroup analyses (PELD approach and operative level) and sensitivity analyses (leave-one-out/model switching) were performed. Clinical relevance was interpreted using commonly cited minimal clinically important difference thresholds for VAS and ODI.

RESULTS: A total of 25 studies involving 2,087 patients were included. Compared with PELD, UBE was associated with longer operative time, greater intraoperative blood loss, larger incisions, longer hospital stays, and higher hospitalization costs, but significantly fewer intraoperative fluoroscopy exposures. No significant differences were observed in complication or reoperation rates. Although some statistically significant differences were detected in early perioperative metrics, all between-group differences in VAS pain and ODI functional scores were far below the minimal clinically important difference thresholds, confirming clinically equivalent mid-term outcomes. Subgroup analyses identified that PELD approach and operative level were key contributors to between-study heterogeneity, and sensitivity analyses confirmed that our main conclusions remained stable.

CONCLUSION: Both UBE and PELD are safe and effective minimally invasive strategies for lumbar disk herniation, with comparable clinical efficacy. PELD offers advantages in lower surgical trauma and cost effectiveness, whereas UBE reduces intraoperative radiation exposure. Surgical selection should be individualized based on patient pathology and surgeon expertise.

PMID:42611015 | DOI:10.3928/01477447-20260625-01

Orthopedics. 2026 Jul-Aug;49(4):e368-e375. doi: 10.3928/01477447-20260722-01. Epub 2026 Aug 14.

ABSTRACT

BACKGROUND: Orthopedic surgery fellowships have evolved from optional to nearly mandatory since accreditation in 1981, yet factors influencing subspecialty selection remain incompletely defined. We evaluated orthopedic residency program director (PD) and department chair demographics and training backgrounds, resident fellowship match patterns, fellowship availability, and concordance between leadership training and resident subspecialty selection.

MATERIALS AND METHODS: Using programs accredited by the Accreditation Council for Graduate Medical Education, we analyzed available PD and department chair demographics and fellowship training. Five years of alumni fellowship data and fellowship availability at each institution were collected from program websites. Descriptive statistics, chi-squared tests, and crude odds ratios (ORs) were used, with P < .05 considered significant.

RESULTS: Among 109 residency programs and 5,443 recent graduates, residents most often matched into sports medicine (24.44%), arthroplasty (17.86%), and hand surgery (16.57%). PDs were most commonly trained in trauma, sports medicine, and hand surgery; chairs were most commonly trained in sports medicine, trauma, and spine surgery. Leadership was predominantly male and White (PDs: 87.16% male, 78.90% White; chairs: 93.58% male, 88.07% White). Programs offering spine, hand, or orthopedic oncology fellowships had higher match rates into those specialties than programs without them (OR: 1.20, 1.42, and 1.94; all P < .05). Residents were also more likely to enter arthroplasty when their PD was arthroplasty trained and to enter hand surgery or orthopedic oncology when their chair had concordant training.

CONCLUSION: Fellowship availability and leadership training background were each associated with resident subspecialty selection. Applicants with subspecialty interests should consider both factors when evaluating residency programs.

PMID:42611012 | DOI:10.3928/01477447-20260722-01

J Speech Lang Hear Res. 2026 Aug 18:1-13. doi: 10.1044/2026_JSLHR-25-00740. Online ahead of print.

ABSTRACT

PURPOSE: The minimally detectable change (MDC) provides a threshold for interpreting changes in outcome measures that are outside of measurement error. There is emerging evidence that dysarthria etiology and speech severity impact the MDC of speech intelligibility; however, an investigation of these factors is needed to determine the unique effects of dysarthria etiology and speech severity. The purpose of the current study was to calculate and compare MDCs of speech intelligibility across five dysarthria etiology groups and four severity levels.

METHOD: Speech Intelligibility Test recordings from 200 speakers were used as stimuli, including recordings from healthy controls (n = 40) and individuals with neurodegenerative diseases such as amyotrophic lateral sclerosis (n = 16), Huntington’s disease (n = 44), multiple sclerosis (n = 60), and Parkinson’s disease (n = 40). Thirty inexperienced listeners provided orthographic transcriptions of 20 speakers each. MDCs were calculated, and speech severity levels were categorized based on empirically defined speech severity levels reported in Stipancic et al. (2021). Statistical analyses, including multiple linear regression, assessed the effects of etiology and severity on MDCs.

RESULTS: Speech severity was a significant predictor of MDCs, with greater impairments to speech intelligibility resulting in higher MDCs. Dysarthria etiology was not a significant predictor of MDCs.

CONCLUSION: The impact of speech severity on MDCs of intelligibility in dysarthria underscores the need to calculate and provide MDCs across severity ranges to enhance the interpretation of patient outcomes.

PMID:42611011 | DOI:10.1044/2026_JSLHR-25-00740

Biol Psychiatry. 2026 Aug 18:S0006-3223(26)01385-5. doi: 10.1016/j.biopsych.2026.06.025. Online ahead of print.

ABSTRACT

BACKGROUND: Increases in cannabis use, potency, and legal liberalization have raised concerns about psychiatric consequences. Previous studies suggest an association between cannabis use and earlier age at onset (AAO) of psychosis, but an updated meta-analysis is needed.

METHODS: MEDLINE, Embase, and PsycInfo were searched from inception to April 2025. Peer-reviewed cohort and case-control studies reporting mean and standard deviation of AAO of psychosis in cannabis users and nonusers or other effect size data were included. Pooled standardized mean difference was calculated using random-effects meta-analysis. Subgroup analyses used mixed effects models, and between-study heterogeneity was examined with random-effects meta-regression.

RESULTS: The main meta-analysis included 181 samples from 149 studies, comprising 18,272 cannabis users and 52,801 nonusers. Cannabis use was associated with a mean earlier AAO of 2.50 years. Subgroup analysis by sample mean onset age found no difference in AAO of psychosis between cannabis users and nonusers in the <20-year-old group, but there was a progressive age-related difference; cannabis users in the 20 to <25, 25 to <30, and ≥30 groups had an earlier AAO of 1.60, 4.43, and 6.30 years, respectively. Multiple meta-regression indicated that sample mean onset age was a strong and statistically independent moderator of earlier AAO effect size (z = -7.59, p < .0001).

CONCLUSIONS: The association between cannabis use and earlier psychosis onset is robust, with larger effect sizes in samples with later mean age of psychosis onset. These findings support consideration of public health warnings of the potential psychiatric risks associated with cannabis use across the lifespan.

PMID:42610992 | DOI:10.1016/j.biopsych.2026.06.025

BJS Open. 2026 Jul 3;10(4):zrag092. doi: 10.1093/bjsopen/zrag092.

ABSTRACT

BACKGROUND: Debate continues about the need for prophylactic concomitant cholecystectomy (CC) at the time of Roux-en-Y gastric bypass (RYGB). The concerns over higher complication rates should be balanced against the risk of future biliary events. This pilot trial compared RYGB with CC to RYGB alone in patients without preoperative gallstones to inform a future large randomized trial.

METHODS: Eligible patients without gallstones scheduled to undergo RYGB were randomized before surgery using a 1 : 1 allocation ratio. Surgeons and patients were not blinded. The primary outcome was a composite of intraoperative adverse events and 30-day postoperative complications. In addition, feasibility (time to enrolment, completion of follow-up) was added as a co-primary endpoint after the study started, driven by prolonged enrolment times and independent of trial results. Secondary outcomes included late complications, biliary events, length of operation, length of hospital stay, and quality of life.

RESULTS: In all, 96 patients were randomized between July 2018 and January 2023, and 95 were included in the full analysis due to one withdrawal. There were 49 and 46 patients in the RYGB with and without CC arms, respectively. The feasibility endpoint was met with regard to the completion of follow-up (95/95, 100% at 1 month; 88/95 93% at 18 months), but not the time to enrolment (21 patients randomized per year). The composite outcome of intraoperative and postoperative complications occurred in 44.9% and 26.1% of patients with and without CC, respectively (difference 18.8%; 95% confidence interval (c.i.) -0.6 to 36.8; P = 0.098). Patients with CC had a higher early comprehensive complication index score (mean 6.09 versus 2.06; difference 4.03; 95% c.i. 0.23 to 7.83; P = 0.047). Late (> 30 days) complications, length of hospital stay, and quality of life were similar between the two groups. During the 18-month follow-up, biliary events occurred in 3 patients without CC (6.5%), of whom 2 required biliary intervention (4.4%) compared with 1 patient with CC (2%), with no biliary interventions required.

CONCLUSION: The debate over performing CC during RYGB remains unresolved. The incidence of subsequent biliary interventions was low when CC was not performed. As a pilot study, this investigation sets the stage for a large randomized trial. Registration number: NCT04324515 (https://www.clinicaltrials.gov).

PMID:42610981 | DOI:10.1093/bjsopen/zrag092