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Nevin Manimala Statistics

The Gut Microbiome and Diet Interact to Dictate Personalized Response to Broccoli Sprout Consumption

Food Sci Nutr. 2026 Aug 5;14(8):e72211. doi: 10.1002/fsn3.72211. eCollection 2026 Aug.

ABSTRACT

Broccoli sprouts produce sulforaphane (SFN), a dietary isothiocyanate with anti-cancer and anti-inflammatory properties. Human intervention trials observe large variation in metabolite generation and bioactivity with broccoli sprout consumption across individuals. We hypothesize that interactions between pre-intervention diet and personalized gut microbiome composition contribute to this variation. This exploratory analysis leverages a small existing dataset to test novel mediation pathways, with the goal of identifying associations for future validation in larger, prospectively designed studies. In a trial of 38 healthy adults, we analyzed participant-recorded 7-day food diaries, profiled baseline gut microbiome compositions, and quantified urinary SFN metabolites over 72 h after broccoli sprout consumption. Using regression-based mediation analysis, we modeled two complementary predictions: (1) that specific gut bacterial genera mediate how pre-intervention diet composition influences SFN metabolism, and (2) that particular dietary components mediate how gut microbiome composition influences SFN metabolism. These analyses found that seven genera, including Collinsella, Ruminococcus, and Bifidobacterium, mediated relationships between pre-intervention diet and SFN metabolites, particularly the bioactive forms. Unsupervised clustering further revealed three distinct baseline gut microbiome community “types,” each exhibiting differential production of SFN-nitrile, a biologically inert metabolite, with effects mediated by the consumption of specific carbohydrate classes. Together, these findings indicate that microbiome structure, in concert with diet, shapes individual SFN metabolic outcomes. Considering pre-intervention diet and gut microbiome may therefore enhance the design and personalization of cruciferous vegetable interventions.

PMID:42564592 | PMC:PMC13443138 | DOI:10.1002/fsn3.72211

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Intra-articular delivery of VEGF targeting miR-126-3p and miR-140-5p ameliorates synovitis and pain in a rat model of post-traumatic knee osteoarthritis

J Orthop Translat. 2026 Jul 24;60:101184. doi: 10.1016/j.jot.2026.101184. eCollection 2026 Sep.

ABSTRACT

BACKGROUND/OBJECTIVE: Knee osteoarthritis (KOA) is the most common joint disorder and causes pain and functional limitation. Patients who are refractory to conservative treatment or unsuitable for surgery owing to advanced age or comorbidities have limited options. Vascular endothelial growth factor (VEGF) is implicated in synovitis, angiogenesis and pain in KOA. microRNA (miRNA) based therapies have recently attracted attentions. This study aimed to investigate whether intra-articular delivery of VEGF-targeting miRNA can reduce synovitis and pain.

METHODS: Human synovial sarcoma cell line HS-SY-II was used for screening of VEGF-targeting miRNAs and primary synovial fibroblasts derived from KOA patients was used for confirmation of the efficacy. miRNA mimics were transfected and VEGF production was quantified. In vivo analyses, KOA was induced by anterior cruciate ligament transection and medial meniscectomy (ACLT model). Wistar rats were randomly allocated to 5 groups in 2 cohorts (n = 5 per group per cohort): normal (no ACLT), ACLT + negative control miRNA (NC), ACLT + miR-126-3p, ACLT + miR-140-5p, and ACLT + a combination of miR-126-3p and miR-140-5p (miR-Mix). miRNA mimics were injected intra-articularly. Hindlimb weight-bearing was assessed using incapacitance tester. Synovitis and cartilage degeneration were evaluated histologically. VEGF levels in synovial fluid, synovium and cartilage were quantified by Simple Western analysis. Non-parametric tests and repeated-measures analyses were performed, with p < 0.05 considered statistically significant.

RESULTS: Combination of miR-126-3p and miR-140-5p suppressed VEGF production in HS-SY-II cells than either miRNA alone and the suppressive activity on VEGF production was confirmed in primary synovial fibroblasts from KOA patients. In ACLT rats, synovial VEGF levels were increased in NC group compared with normal rats and tended to be lower in all miRNA-treated groups. Hindlimb weight-bearing ratios were reduced to about 30% after ACLT and remained low in the NC group, whereas they gradually improved in the miR-126-3p and miR-140-5p monotherapy groups and almost recovered in the miR-Mix group. At final time point, weight-bearing ratio was significantly higher in miR-Mix group than NC group. Histologically, Krenn scores were tend to lower in miR-126-3p and miR-Mix groups than NC group, indicating amelioration of synovitis, whereas OARSI histopathology scores for femoral cartilage did not differ significantly among groups and tended to be higher in miR-treated groups. There was a strong negative correlation between Krenn synovitis score and hindlimb weight-bearing ratio (Spearman’s ρ = -0.7, p < 0.001).

CONCLUSION: Intra-articular administration of VEGF-suppressive miR-Mix ameliorated synovitis and pain-related behaviour. In highly unstable traumatic model, however, structural protection of articular cartilage was not observed and cartilage degeneration even tended to be worse in miR-treated groups, possibly due to increased weight-bearing following pain relief.

THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: These findings suggest intra-articular delivery of VEGF-suppresive miRNAs may represent novel analgesic strategies for KOA by reducing synovitis within joint. miRNA-based modulation of VEGF production could potentially be translated into future disease-modifying and analgesic treatments, however further studies using non-traumatic KOA models, safety evaluation and clarifying molecular mechanisms are required.

PMID:42564586 | PMC:PMC13444623 | DOI:10.1016/j.jot.2026.101184

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Nevin Manimala Statistics

Multidimensional Depressive Symptom Exposure and Incident Cognitive Decline: A Prospective Cohort Study

Depress Anxiety. 2026 Aug 6;2026:8846772. doi: 10.1155/da/8846772. eCollection 2026.

ABSTRACT

BACKGROUND: Despite being a modifiable risk factor for cognitive decline, the influence of depressive symptoms on cognitive decline lacks a systematic assessment of its cumulative exposure intensity, temporal dimensions, and dynamic change.

AIM: To systematically evaluate the multidimensional associations of depressive symptom exposure-including cumulative exposure, burden, duration, and dynamic change patterns-with incident cognitive decline, by adopting an analytical framework that integrates “static accumulation and dynamic evolution.”

METHODS: Among 8847 Health and Retirement Study (HRS) participants free of cognitive decline at baseline, cumulative depressive symptoms were quantified as the area under the curve (AUC) across 2012-2016 waves. A cut-point was identified by maximizing the log-rank statistic for cognitive decline risk within a clinically relevant range (2.5-3.5) and used to define cumulative burden and high-exposure duration. Dynamic symptom patterns across three waves were identified, and their interaction with cumulative burden was examined. Multivariable Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cognitive decline risk associated with these exposure metrics.

RESULTS: During 3.67 median follow-up years, 2311 incident cognitive decline cases occurred. Cognitive decline risk rose with escalating cumulative depressive exposure: the highest tertile (HR 1.42; 1.28-1.58), cumulative burden ≥0 (HR 1.34; 1.21-1.49), longest duration (HR 1.29; 1.12-1.48), and a progressively worsening trend (HR 1.52; 1.25-1.84) all significantly increased risk.

CONCLUSIONS: Our findings demonstrate that the effect of depressive symptoms on cognitive decline is cumulative, time-dependent, and dynamic. These results emphasize that sustaining a stable, low-severity depressive symptom profile is essential for lifelong cognitive health.

PMID:42564581 | PMC:PMC13444727 | DOI:10.1155/da/8846772

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Artificial intelligence in psychiatry: clinical applications, limitations, and ethical challenges

Front Behav Neurosci. 2026 Jul 23;20:1864429. doi: 10.3389/fnbeh.2026.1864429. eCollection 2026.

ABSTRACT

Artificial intelligence (AI) is rapidly transforming psychiatric research and clinical practice, offering new capabilities in areas such as diagnosis, risk prediction, digital phenotyping, and treatment personalization. In the domain of diagnostic classification, machine learning models have demonstrated classification accuracy across major psychiatric disorders in internally validated research settings. In a distinct and non-equivalent domain, large language model-assisted clinical decision support has shown performance comparable to expert clinicians in a specific, structured benchmark task; this finding should not be generalized to open-ended clinical practice. However, this technological promise is shadowed by profound methodological, clinical, and ethical limitations. The majority of AI models in neuroimaging-based psychiatry carry a high risk of bias, external validation remains rare, and evidence of real-world clinical impact is scarce. Critically, the field is developing in a context where vast repositories of sensitive mental health data are increasingly controlled by large technology corporations. This trend raises urgent, yet underexplored, questions about data governance and commercial use, as well as broader concerns around accountability and long-term behavioral surveillance. Furthermore, the reliance of AI systems on statistical distributions to define normality risks encoding a historically unstable and culturally contingent concept as a medical standard, with particular consequences for the pathologization of human diversity. This perspective article argues that the psychiatric community must assume an active governance role, advocating for patient-centered data frameworks that do not reduce human suffering to a monetizable data stream.

PMID:42564577 | PMC:PMC13443063 | DOI:10.3389/fnbeh.2026.1864429

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Health-related quality of life with linvoseltamab treatment for relapsed/refractory multiple myeloma in LINKER-MM1

Blood Neoplasia. 2026 Mar 27;3(3):100225. doi: 10.1016/j.bneo.2026.100225. eCollection 2026 Aug.

ABSTRACT

Linvoseltamab, a human B-cell maturation antigen × CD3 bispecific antibody, showed high efficacy and a generally manageable safety profile in 117 patients with relapsed/refractory multiple myeloma (R/RMM) over a median follow-up of 21.3 months in the LINKER-MM1 trial. Patient-reported health-related quality of life (HRQoL) was assessed at baseline, week 4, and then every 4 weeks, using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30); the 20-item MM module (QLQ-MY20); and the EuroQol 5-dimension, 3-level (EQ-5D-3L) questionnaire. Changes from baseline were estimated overall and at each assessment using mixed models for repeated-measures analysis; clinically meaningful change thresholds were based on previous literature. Results were evaluated by objective response status (at least partial response). Nominal statistically significant improvements from baseline on all QLQ-C30/QLQ-MY20 scales and the EQ-5D-3L visual analog scale were observed overall and at multiple assessments. Improvements in QLQ-C30 Global Health Status/quality of life, fatigue, and pain observed by week 16 were maintained at most subsequent assessments; pain improvement reached the clinically meaningful threshold at week 20 and was generally maintained through week 104. Among 83 treatment responders, nominal statistically significant overall improvements were observed on all scales; nonresponders (n = 34) reported numerical worsening on most scales. Through treatment week 104, improvements in HRQoL measures, including pain, fatigue, and functioning, were reported in patients with triple-class-exposed R/RMM receiving linvoseltamab. Patient-reported benefits were consistent with clinical response, supporting linvoseltamab’s favorable benefit-risk profile. This trial was registered at www.clinicaltrials.gov as NCT03761108.

PMID:42564571 | PMC:PMC13443898 | DOI:10.1016/j.bneo.2026.100225

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Nevin Manimala Statistics

Association between BDNF and postoperative cognitive dysfunction across surgical stages: a systematic review and meta-analysis

Front Aging Neurosci. 2026 Jul 23;18:1864037. doi: 10.3389/fnagi.2026.1864037. eCollection 2026.

ABSTRACT

Postoperative cognitive dysfunction (POCD) is a frequent complication after surgery, particularly among older adults, and its underlying mechanisms remain incompletely understood. Brain-derived neurotrophic factor (BDNF) is a key regulator of neuronal survival and synaptic plasticity, and has been implicated in POCD but published findings are inconsistent. We therefore performed a systematic review and meta-analysis to evaluate the association between perioperative BDNF levels and POCD across surgical time points. Following PRISMA guidelines, we searched PubMed, EMBASE, Web of Science, and Scopus were searched for observational studies that reported perioperative BDNF levels in patients with and without POCD. Two reviewers independently extraction data and assessed study quality using the Newcastle-Ottawa Scale. Statistical analyses were conducted in RevMan 5.3, with mean differences (MD) with 95% confidence intervals (CI) were calculated for absolute BDNF levels and perioperative changes (ΔBDNF) at preoperative, intraoperative, and postoperative stages. Six studies including 135 patients with POCD and 247 without POCD met the inclusion criteria. The fixed-effects meta-analysis showed lower intraoperative BDNF levels in the POCD group (MD = -5.62, 95% CI[-8.95, -2.29], P = 0.0009; I 2 = 0%). Similarly, intraoperative ΔBDNF was reduced in the POCD group under a fixed-effects meta-model (MD = -9.73, 95% CI[-16.08, -3.38], P = 0.003; I 2 = 0%). The subgroup analysis indicated that the type of surgery may contribute to the high heterogeneity observed in 24-h postoperative BDNF and in 24-h postoperative ΔBDNF. These findings suggest that intraoperative BDNF levels and their dynamic changes may serve as preliminary exploratory biomarker for POCD. The intraoperative phase appears to be a critical window for BDNF monitoring, yet prospective cohort studies are urgently needed to externally validate its uesfulness for screening patients at high risk of POCD before clinical implementation. Current evidence remains preliminary, since only six small observational studies were included and substantial statistical heterogeneity was present in multiple postoperative subgroup analyses. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251265921.

PMID:42564570 | PMC:PMC13443294 | DOI:10.3389/fnagi.2026.1864037

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Effectiveness of a Home-Based Video-Guided Hip Muscle Exercise Program in Elderly Patients Following Bipolar Hemiarthroplasty for Femoral Neck Fracture: A Randomized Controlled Trial

Cureus. 2026 Jul 6;18(7):e112184. doi: 10.7759/cureus.112184. eCollection 2026 Jul.

ABSTRACT

BACKGROUND: Physical therapy after a femoral neck fracture is essential but is limited by poor compliance and incorrect exercise. To improve this, we developed the home-based video-guided music program (HBW-MV) program. We hypothesize that this program will improve functional outcome.

STUDY DESIGN AND METHODS: This was a randomized controlled trial from 2023 to 2024 on elderly patients with cementless bipolar hemiarthroplasty after femoral neck fracture. Thirty patients were equally allocated into the intervention group and the control group. Both received pre-discharge physical therapy instructions from an orthopedic trainee. Functional outcomes were assessed using Harris Hip Score (HHS) from two to 12 weeks. Hip strength was measured by a handheld dynamometer. Anxiety and pain were assessed using a visual analog scale. Compliance was assessed by a record table.

RESULTS: Both groups showed an increase in HHS at two, six, and 12 weeks postoperatively. The intervention group demonstrated significantly higher HHS compared with the control group at all time points, with mean scores of 49.40±6.10, 65.20±6.09, and 82.30±5.85 versus 39.73±7.80, 53.53±5.84, and 67.67±6.33, respectively (p<0.05). At the 12-week follow-up, significantly higher hip muscle strength in abduction, adduction, and flexion was observed in the intervention group relative to the control group (p < 0.05), whereas hip extension strength, although improved in both groups, did not show a statistically significant between-group difference. At both six and 12 weeks postoperatively, anxiety scores were significantly reduced in the intervention group relative to the control group (six weeks: 2.87±0.91 vs 3.47±0.64, p=0.023; 12 weeks: 1.47±0.51 vs 2.27±0.96, p=0.004). Postoperative pain scores were also significantly lower in the intervention group at 12 weeks (1.20±0.41 vs 1.93±0.88, p=0.004). Patient compliance with the rehabilitation program was significantly higher in the intervention group at six and 12 weeks.

CONCLUSIONS: This research shows the HBW-MV program significantly improved functional outcomes, hip strength, and compliance. Additionally, it reduced anxiety and postoperative pain effectively.

PMID:42564554 | PMC:PMC13442973 | DOI:10.7759/cureus.112184

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Multi-trait multi-environment genomic prediction strategies for Miscanthus sacchariflorus

Front Plant Sci. 2026 Jul 23;17:1835247. doi: 10.3389/fpls.2026.1835247. eCollection 2026.

ABSTRACT

Genomic selection holds the potential to serve as a strategic tool to enhance the genetic gain of complex traits in Miscanthus breeding programs. The development of improved cultivars requires their assessment for various traits across diverse environments to ensure suitable overall performance. Hence, the multi-trait multi-environment (MTME) genomic prediction (GP) models offer an opportunity to improve selection accuracy. This study aims to evaluate the potential of five GP models: (1) three MTME models including genotype-by-trait-by-environment interaction (G×E×T) and (2) two single-trait multi-environment (STME) models (with and without G×E interaction). A Miscanthus sacchariflorus population comprising 336 genotypes evaluated in three environments and scored for four traits (biomass yield YDY, total culm number TCM, average internode length AIL, and culm node number CNN) was analyzed. The predictive ability of the models was evaluated considering three cross-validation schemes resembling realistic scenarios (CV1: predicting new genotypes, CVP: predicting missing traits in a given environment, and CV2: predicting partially observed genotypes). On average, in all cross-validation schemes compared to the STME the predictive ability of the MTME models was 10% to 70% higher for TCM and AIL. On the other hand, for YDY and CNN, both STME models performed similarly or slightly better (between 5 to 64%) than the MTME models in most environments. While the MTME models were not successful for all traits when compared to their STME counterparts, MTME models improved the prediction of the performance of genotypes that were untested across environments or lacked trait information in a specific environment. Overall, our study suggests that MTME GP models can be implemented in Miscanthus breeding programs to improve the predictive ability of the complex traits, shorten breeding cycles, and accelerate selection decisions.

PMID:42564547 | PMC:PMC13443311 | DOI:10.3389/fpls.2026.1835247

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Major discrepancy between clinical and autopsy diagnosis: a descriptive single-center analysis and its implications for the South African public health system

Front Med (Lausanne). 2026 Jul 23;13:1884301. doi: 10.3389/fmed.2026.1884301. eCollection 2026.

ABSTRACT

BACKGROUND: A global decline in the number of clinical post-mortems sought and conducted indicates a diminishing necessity for post-mortem exams. Notwithstanding advancements in medical technology, autopsies continue to serve as a pertinent method for ascertaining the cause of death.

OBJECTIVES: This study aimed to identify prevalent major misdiagnoses in clinical settings through autopsy and to investigate potential contributing factors.

METHODS: A retrospective cross-sectional study was conducted, including 51 autopsies retrieved from the NHLS Laboratory Information System (LIS) and classified as either Class I or Class II discrepancies according to the Goldman criteria. Stata-18 was used to analyse descriptive data and examine the associations between clinicopathological factors and the major discrepancy classes.

RESULTS: Of the 51 autopsies included in the study, 68.63% (n = 35) were female in contrast to 31.37% (n = 16) of males, with a mean death age of 39.3 years. A total of 88.24% (n = 45) of the cases were classified as Class I discrepancies, and 11.76% (n = 6) were Class II. There was no evidence of an association between discrepancies and age, sex and disease type. However, autopsy diagnosis showed a statistically significant association with Class I discrepancies (p ≤ 0.05) accounted for the largest proportion of misdiagnoses, with pulmonary disease being the most frequently misdiagnosed condition at 44.44% (n = 20).

CONCLUSIONS: Autopsies remain a pertinent clinical audit tool despite advances in medical technology. The hospital should provide funds for autopsies and encourage doctors to utilize them as a clinical audit instrument to enhance patient management.

PMID:42564546 | PMC:PMC13444749 | DOI:10.3389/fmed.2026.1884301

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Comparative analysis of COVID-19 vaccine and booster acceptance among healthcare workers in public and private sectors in KwaZulu-Natal, South Africa

Health SA. 2026 Jul 7;31:3331. doi: 10.4102/hsag.v31i0.3331. eCollection 2026.

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic posed unprecedented global health challenges, necessitating accelerated COVID-19 vaccine development. However, vaccine and booster hesitancy among healthcare workers (HCWs) presented a barrier globally and in South Africa (SA).

AIM: This study aimed to determine the level of vaccine and booster acceptance among HCWs in public, private and public-private sectors in KwaZulu-Natal (KZN), SA, and to identify the key reasons of vaccine and booster acceptance and refusal.

SETTING: This study was conducted across KZN.

METHODS: A quantitative, descriptive, cross-sectional survey was conducted from October 2024 to April 2025 among doctors, nurses and pharmacists using an online questionnaire. Three hundred and thirty-one HCWs participated in this study with a reliable and standardised questionnaire. Data analysis included descriptive and inferential statistics. Relevant ethics committees and participants provided ethical approval.

RESULTS: Average vaccine acceptance rate for vaccine and booster was 92.4% (n = 306) and 73.7% (n = 244), respectively. Public-private recorded the highest acceptance rates for vaccine (96.3%) and booster (85.1%). Primary reasons for vaccine refusal included vaccine-related illness in family (52.4%, n = 11) and rapid development and safety concerns (64%, n = 16), predominantly among private sector. Main booster refusal reasons included safety of multiple booster doses (50%, n = 32) and antibodies from previous COVID-19 infection, mostly in the public sector.

CONCLUSION: Addressing complex determinants of vaccine hesitancy across healthcare sectors necessitates an integrated and sustained approach reinforced by multidisciplinary stakeholder engagement.

CONTRIBUTION: This study contributes to future pandemic preparedness and vaccination programmes by elucidating reasons influencing vaccine acceptance and refusal among HCWs.

PMID:42564541 | PMC:PMC13443733 | DOI:10.4102/hsag.v31i0.3331