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Nevin Manimala Statistics

“Can We Trust Them?” An Expert Evaluation of Large Language Models to Provide Sleep and Jet Lag Recommendations for Athletes

Sports Med. 2025 Oct 3. doi: 10.1007/s40279-025-02303-5. Online ahead of print.

ABSTRACT

BACKGROUND: With the increasing use of artificial intelligence in healthcare and sports science, large language models (LLMs) are being explored as tools for delivering personalized, evidence-based guidance to athletes.

OBJECTIVE: This study evaluated the capabilities of LLMs (ChatGPT-3.5, ChatGPT-4, and Google Bard) to deliver evidence-based advice on sleep and jet lag for athletes.

METHODS: Conducted in two phases between January and June 2024, the study first identified ten frequently asked questions on these topics with input from experts and LLMs. In the second phase, 20 experts (mean age 43.9 ± 9.0 years; ten females, ten males) assessed LLM responses using Google Forms surveys administered at two intervals (T1 and T2). Inter-rater reliability was evaluated using Fleiss’ Kappa, and intra-rater agreement using the Jaccard Similarity Index (JSI), and content validity through the content validity ratio (CVR). Differences among LLMs were analyzed using Friedman and Chi-square tests.

RESULTS: Experts’ response rates were high (100% at T1 and 95% at T2). Inter-rater reliability was minimal (Fleiss’ Kappa: 0.21-0.39), while intra-rater agreement was high, with 53% of experts achieving a JSI ≥ 0.75. ChatGPT-4 had the highest CVR for sleep (0.67) and was the only model with a valid CVR for jet lag (0.68). Google Bard showed the lowest CVR for jet lag (0%), with significant differences compared to ChatGPT-3.5 (p = 0.0073) and ChatGPT-4 (p < 0.0001). Reasons for inappropriate responses varied significantly for jet lag (p < 0.0001), with Google Bard criticized for insufficient information and frequent errors. ChatGPT-4 outperformed other models overall.

CONCLUSIONS: This study highlights the potential of LLMs, particularly ChatGPT-4, to provide evidence-based advice on sleep but underscores the need for improved accuracy and validation for jet lag recommendations.

PMID:41042486 | DOI:10.1007/s40279-025-02303-5

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Normative Data for Single- and Dual-Task Tandem Gait Performance in Collegiate Athletes

Sports Med. 2025 Oct 3. doi: 10.1007/s40279-025-02306-2. Online ahead of print.

ABSTRACT

BACKGROUND: Normative dual-task (concurrent cognitive and motor task) tandem gait has not been developed. Currently, only individual baseline data are used for tandem gait assessment post concussion.

OBJECTIVE: The object was to (1) determine factors associated with single-task and dual-task tandem gait time among collegiate athletes across multiple institutions, and (2) provide robust normative data for single-task and dual-task tandem gait time based on clinically relevant factors.

METHODS: Data were analyzed from 2,137 unique collegiate athletes (19.0 ± 1.1 years, 48.9% female, 23.7% with concussion history) from 2015 to 2022 during pre-injury baseline concussion testing from three universities. Tandem gait was performed under single- and dual-task conditions (serial subtraction by sixes/sevens, spelling five-letter words backward, reciting the months backward). The criteria for being a clinically relevant independent variable was (a) p value < 0.05, and (b) effect estimate of ≥ 1 s. Normative data based on established percentile thresholds were derived and stratified by clinically relevant factors.

RESULTS: None of the single-task tandem gait times were clinically relevant, while sex and contact level were for dual task. Mean (95% confidence interval) for overall single- and dual-task tandem gait times were 12.07 s (11.95, 12.19) and 16.51 s (16.29, 16.73), respectively.

CONCLUSION: Our results provide robust normative data for single- and dual-task tandem gait stratified by relevant patient factors that can be immediately used by clinicians and future researchers. Future research should compare the use of individual baseline versus normative data for acute concussion tracking.

PMID:41042485 | DOI:10.1007/s40279-025-02306-2

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Polycystic Ovary Syndrome: Unraveling the Minor Shifts in Fatty Acid Composition of Follicular Fluid Phospholipids and Triglycerides

Reprod Sci. 2025 Oct 3. doi: 10.1007/s43032-025-01992-7. Online ahead of print.

ABSTRACT

The effect of polycystic ovary syndrome (PCOS) on the fatty acid (FA) content of follicular fluid (FF) is not fully understood. The present study aimed to determine whether the FA composition of FF phospholipids (PLs) and triglycerides (TGs) undergoes alterations in women with PCOS. A total of 40 subjects, including 20 PCOS patients and 20 controls, were enrolled. Thin-layer chromatography followed by gas chromatography was carried out to isolate FF lipid fractions and measure relative concentrations of their FAs, respectively. Percentages of individual FAs in FF PLs and TGs did not statistically differ between the control and PCOS groups (p > 0.05), other than palmitoleic acid, which significantly decreased and increased in PLs and TGs of women with PCOS, respectively (p < 0.05). There were positive correlations between intrafollicular levels of androgens and PL levels of several n-6 polyunsaturated FAs in the PCOS group (r > 0.4, p < 0.05). In addition, relative concentrations of eicosapentaenoic acid in both PL and TG fractions were inversely correlated with the fertilization rate (r < -0.4, p < 0.05). PCOS women with positive pregnancy outcomes also had higher PL and TG stearic acid with concomitant lower docosahexaenoic acid and peroxidizability index in PL and TG fractions, respectively (p < 0.05). It could be concluded that PCOS was associated with minor alterations in the FA composition of FF PLs and TGs. Furthermore, there were differential fraction-dependent associations between FF FA profile and biochemical and reproductive parameters in women with PCOS.

PMID:41042473 | DOI:10.1007/s43032-025-01992-7

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ASO Visual Abstract: Surgery for Retroperitoneal Soft Tissue Sarcoma is Safe Following Multimodal Treatment with Regional Hyperthermia

Ann Surg Oncol. 2025 Oct 3. doi: 10.1245/s10434-025-18365-8. Online ahead of print.

NO ABSTRACT

PMID:41042464 | DOI:10.1245/s10434-025-18365-8

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Estimation of the Respiratory Syncytial Virus Hospitalization Burden in Older Adults in the Veneto Region, Italy: A Modeling Study

Infect Dis Ther. 2025 Oct 3. doi: 10.1007/s40121-025-01241-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Respiratory syncytial virus (RSV) in older adults can cause a variable spectrum of symptoms, ranging from mild manifestations to hospitalization and sometimes adverse outcomes. However, its true epidemiological burden is underestimated due to non-specific symptoms, lack of standardized diagnostic criteria, limited lab confirmation, and inadequate attribution in administrative datasets.

METHODS: We conducted a time-series analysis using hospital discharge data from the Veneto Region, Italy, between 2018 and 2024. Respiratory infections (RI) and RSV-related hospitalizations were identified using International Classification of Diseases codes. A generalized additive mixed model (GAMM) was applied to weekly RI admissions, incorporating circulating pathogen data from the RespiVirNet surveillance system. Seasonal patterns and age-stratified risk were modeled using smoothing terms.

RESULTS: Among individuals aged ≥ 65 years, RSV accounted for an estimated 3.0% to 4.6% of RI hospitalizations. Age-specific hospitalization rates attributable to RSV were 26.8, 109.4, and 317.4 per 100,000 person-years in the 65-74, 75-84, and ≥ 85 age groups, respectively. Explicit RSV coding underestimated the true burden by a factor of up to 7.6. Incidence rates and underreporting were highest in post-acute COVID-19 seasons.

CONCLUSIONS: RSV-related hospitalizations in older adults are substantially underreported in administrative data. Improved surveillance and prospective clinical studies are needed to validate model estimates and assess diagnostic test performance. Statistical modeling represents a valid approach to estimate the burden of RSV hospitalizations in underdiagnosed populations, such as the elderly, when direct data are lacking.

PMID:41042450 | DOI:10.1007/s40121-025-01241-z

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Superior Effectiveness and Estimated Public Health Impact of Cell- Versus Egg-Based Influenza Vaccines in Children and Adults During the US 2023-2024 Season

Infect Dis Ther. 2025 Oct 3. doi: 10.1007/s40121-025-01230-2. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of this study was to assess the relative vaccine effectiveness (rVE) of cell-based versus egg-based quadrivalent influenza vaccines (QIVc versus QIVe) in preventing test-confirmed influenza during the 2023-2024 US influenza season.

METHODS: rVE was estimated using a test-negative design applied to a large, linked, real-world dataset. QIVc or QIVe recipients aged 6 months-64 years who were tested for influenza within ± 7 days of an acute respiratory or febrile illness were included. rVE was estimated using doubly robust logistic regression. Analyses were performed for the full, pediatric, adult, outpatient and high-risk populations and by influenza type. Public health impact was assessed using a compartmental influenza burden averted model.

RESULTS: The analysis included 2119 QIVc-cases, 14,750 QIVc-controls, 14,559 QIVe-cases, and 75,351 QIVe-controls. QIVc was superior to QIVe in preventing test-confirmed influenza with an rVE of 19.8% (95% CI 15.7-23.8%) in the full population, and with rVEs of 19.6% (13.6-25.3%) in the pediatric population aged 6 months-17 years and 18.5% (12.1-24.5%) in adults aged 18-64 years. Consistent results were observed for all sensitivity and subgroup analyses against any influenza. If all vaccinated individuals aged 6 months-64 years in the US received QIVc over QIVe, an estimated 2,379,395 additional symptomatic illnesses would have been prevented, with proportionate reductions in related complications.

CONCLUSIONS: Our analysis showed superior effectiveness of QIVc over QIVe in preventing test-confirmed influenza among persons aged 6 months-64 years, and provided the first demonstration of superiority in pediatric populations from 6 months of age. A Graphical Abstract is availible for this article.

PMID:41042449 | DOI:10.1007/s40121-025-01230-2

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Buprenorphine Substitution as a Tapering Strategy for Opioid Discontinuation in Patients with Chronic Pain: A Nonrandomized and Proof of Concept Study

Pain Ther. 2025 Oct 3. doi: 10.1007/s40122-025-00781-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Long-term use (≥ 3 months) of opioids for chronic noncancer pain (CNCP) shows limited benefit and often leads to dependence, especially when tapered too quickly. Standard opioid discontinuation typically involves gradual dose reduction, yet many patients fail to complete it. Meta-analyses show buprenorphine reduces withdrawal severity, increases treatment retention and completion rates, and facilitates analgesia and smoother transitions in patients with chronic pain, with low adverse effects and high initiation success.

METHODS: This single-center, prospective, nonrandomized proof-of-concept study assessed the efficacy of an outpatient buprenorphine-based discontinuation strategy in patients with CNCP and opioid dependence who had failed standard tapering. Participants first attempted gradual tapering; those unsuccessful transitioned to buprenorphine: 4-8 mg/day for 1 month, followed by tapering over up to 9 months. Success was defined as complete opioid cessation at 9 months, confirmed by urine analysis (including buprenorphine). The primary outcome was the success rate of the buprenorphine strategy, with ≥ 60% considered effective. A secondary outcome compared success rates between strategies.

RESULTS: Of 20 patients, six (30.0%) successfully withdrew using standard tapering. Fourteen failed; 11 of them transitioned to buprenorphine. Of these, seven (63.6%) achieved full discontinuation. While not statistically significant, the buprenorphine group showed a higher success rate than standard tapering (p = 0.076; OR = 4.08 [0.90-21.23]).

CONCLUSIONS: Buprenorphine substitution appears at least as effective as conventional tapering and may benefit patients unable to succeed with tapering alone. These preliminary results support further investigation in larger trials.

TRIAL REGISTRATION: ClinicalTrials. gov identifier, NCT03156907.

PMID:41042438 | DOI:10.1007/s40122-025-00781-z

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PLANTA Protocol for the Direct Detection and Identification of Bioactive Compounds in Complex Mixtures via Combined NMR-HPTLC-Based Heterocovariance

Anal Chem. 2025 Oct 3. doi: 10.1021/acs.analchem.5c02192. Online ahead of print.

ABSTRACT

The assignment of bioactivity to compounds within complex natural product (NPs) mixtures remains a significant challenge in NPs research. The present research introduces a comprehensive protocol, named “PLANTA (PhytochemicaL Analysis for NaTural bioActives)” protocol, for the detection and identification of bioactive compounds in complex natural extracts prior to isolation combining the NMRHeteroCovariance Approach (NMR-HetCA), high-performance thin-layer chromatography (HPTLC), and chemometric techniques. This study emphasizes two novel components: STOCSY-guided targeted spectral depletion, adapted to resolve overlapping NMR signals in complex matrices, improve minor component detection, and facilitate identification through NMR databases, as well as a new SHY variant termed SH-SCY (Statistical Heterocovariance – SpectroChromatographY), a new cross-correlation method linking orthogonal datasets by identifying the corresponding HPTLC spot from a single NMR peak and reconstructing of the 1H NMR spectrum from a specific HPTLC spot, enhancing dereplication confidence. In this proof-of-concept study, an artificial extract (ArtExtr) composed of 59 standard compounds was evaluated for the detection of compounds active against the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). Statistical approaches were applied to the spectral, chromatographic, and bioactivity data to identify the highly correlated bioactive compounds. The PLANTA protocol achieved an 89.5% detection rate of active metabolites and 73.7% correct identification of them. The integration of NMR and HPTLC with HetCA provides a robust and sensitive strategy for preisolation identification of bioactive constituents. This methodology addresses core challenges in metabolite profiling of complex mixtures and offers a streamlined, reproducible workflow for natural product dereplication and discovery.

PMID:41041709 | DOI:10.1021/acs.analchem.5c02192

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High-definition brain stimulation targeting separate regions leads to differential word retrieval outcomes in patients with primary progressive aphasia: a pilot study

Front Neurol. 2025 Sep 17;16:1630103. doi: 10.3389/fneur.2025.1630103. eCollection 2025.

ABSTRACT

BACKGROUND: Word retrieval deficits are the most prominent symptoms reported in primary progressive aphasia (PPA) and related syndromes. Current treatments, such as speech and language therapy, have shown limited success, highlighting the need for alternative non-pharmacological interventions with high-definition transcranial direct current stimulation (HD-tDCS) emerging as a promising tool.

OBJECTIVE: This study aimed to evaluate the effects of HD-tDCS on word retrieval function in individuals with PPA by comparing two stimulation sites: the pre-supplementary motor area (pre-SMA) and the left inferior frontal gyrus (LIFG), and to assess the relative benefits of each site.

METHODS: Eight individuals with PPA underwent 10 sessions of open-label HD-tDCS targeting either the LIFG (n = 4) or pre-SMA (n = 4). Word retrieval was assessed at baseline, immediately post-stimulation, and at 8-week follow-up. Electrophysiological measures, including event-related potentials during a non-verbal Go-NoGo task, were also collected to explore neural mechanisms.

RESULTS: LIFG stimulation yielded statistically significant improvements in phonemic fluency at immediate post testing compared to baseline, with 25-50% showing clinically meaningful improvement. Clinically meaningful improvement was observed in category fluency in 25-50% of the patients receiving stimulation at either site. Lastly, electrophysiological measures indicated HD-tDCS targeting LIFG differentially modulated event-related potential effects during non-verbal Go-NoGo tasks.

CONCLUSION: This research provides preliminary evidence supporting the use of both traditional (LIFG) and alternative (pre-SMA) stimulation sites for treating word retrieval deficits in individuals with PPA. The findings also suggest potential neural mechanisms of HD-tDCS intervention, which can inform future designs of non-invasive brain stimulation for cognitive symptoms in PPA.

CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT05368350.

PMID:41041680 | PMC:PMC12484069 | DOI:10.3389/fneur.2025.1630103

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Dexmedetomidine decreases cerebral hyperperfusion syndrome incidence following mechanical thrombectomy in acute ischemic stroke: a double-blind, randomized controlled trial

Front Neurol. 2025 Sep 17;16:1680268. doi: 10.3389/fneur.2025.1680268. eCollection 2025.

ABSTRACT

BACKGROUND: Cerebral hyperperfusion syndrome (CHS) is a serious complication that can follow intravascular mechanical thrombectomy for acute ischemic stroke (AIS). Dexmedetomidine (Dex), a selective α₂-adrenoceptor agonist used as a sedative, has known neuroprotective effects in ischemic cerebral injury. This double-blind, randomized, placebo-controlled clinical trial (ChiCTR 2500105088) aimed to evaluate the preventive impact of low-dose Dex on CHS after AIS.

METHODS: Patients with AIS and anterior circulation occlusion scheduled for endovascular mechanical thrombectomy from August 2023 to October 2024 were included. The occluded vessels were the internal carotid artery intracranial portion, M1, or M2 segments of the middle cerebral artery. After obtaining informed consent, patients were randomly allocated to two groups: one group (n = 70) received intravenous Dex with a 10-min preoperative loading dose of 0.5 μg/kg, followed by postoperative maintenance infusion at 0.1 μg/kg/h until 72 h postoperatively. The other group (n = 71) received an equal volume of placebo (normal saline) via the same intravenous route and schedule. The principal outcome was the occurrence of CHS evaluated through the seventh day post-operation. Subsidiary outcomes comprised the National Institutes of Health Stroke Scale (NIHSS) score within 24 h post-operation, Modified Rankin Scale (mRS) scores at discharge, within 30 days and 90 days post-operation, the duration of ICU stay, total hospital stay length, and the 30-day all-cause mortality rate.

RESULTS: A statistically significant reduction in the occurrence of CHS was observed in the Dex group relative to the placebo group: among 70 patients in the Dex group, only 2 cases of CHS were identified (2.9%), whereas 10 cases occurred in the placebo group (14.1%) from a total of 71 patients. This difference was confirmed by both odds ratio (OR: 0.203; 95% confidence interval [CI]: 0.046-0.893; p = 0.017) and hazard ratio (HR: 0.194; 95% CI: 0.043-0.887; p = 0.018) analyses. Additionally, the Dex group showed significantly lower postoperative pain scores assessed via the Numeric Rating Scale (NRS) on postoperative day 1 and day 3 compared with the placebo group (p < 0.0001).

CONCLUSION: Dex significantly reduced 7-day CHS occurrence after mechanical thrombectomy in AIS patients and lowered postoperative pain scores.

CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, identifier ChiCTR 2500105088.

PMID:41041673 | PMC:PMC12483894 | DOI:10.3389/fneur.2025.1680268