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Enhanced Hi-C Capture Analysis reveals complex regulatory architecture at the PICALM_(E)ED locus for Alzheimer’s disease
No full textAccuracy of Autism-Related TikTok Information in Italian: A Comparison Between Human Raters and Large Language Models
No full textPurpose Social networking sites are major channels for sharing information on neurodiversity, including autism spectrum disorder. TikTok has become a particularly influential platform for autism-related communication, yet concerns remain about the scientific accuracy of such content. Most prior studies have focused on English-language videos and have evaluated accuracy with limited granularity. Additionally, the difficulty of achieving consistent expert ratings underscores the need for automated reliability assessment. Methods In this study, we examined 408 informational statements extracted from 148 TikTok videos posted under the hashtag #Autismo (Italian for #Autism). Three clinical experts independently classified each statement as inaccurate, over-generalized, or accurate; their median ratings served as the human-derived ground truth and were compared with classifications from two large language models: ChatGPT 4.0 mini and Gemini 1.5 Flash. Results Human raters showed moderate agreement (kappa(mean) = 0.52) and high specific agreement only for accurate statements, with lower agreement for overgeneralized and inaccurate content. ChatGPT achieved moderate agreement with human ratings (kappa= 0.58), while Gemini reached only fair agreement (kappa= 0.29). ChatGPT also exhibited a more conservative evaluation pattern (accurate information: precision = 0.89, recall = 0.82), whereas Gemini tended to overestimate accuracy (accurate information: precision = 0.76, recall = 0.93). Conclusion These findings suggest that LLMs, particularly ChatGPT, may support cautious and assistive evaluation of online health content. Future research should assess their applicability across online communities and platforms and explore their integration into accuracy-based alert systems that provide users with contextual reliability cues.</p
Supplementing acute care clinical education experiences with simulation-based learning: a pilot study
No full textRationale: Physical therapist (PT) educational programs must prepare students to practice across the continuum of care, but students often lack confidence in the acute care setting. The purpose of this report is to describe a pilot study aimed at exploring a simulation-based learning experience (SBLE) as a complement to an acute care clinical experience (CE) and its effect on student performance and confidence. Methods: In this quasi-experimental cohort pilot study, the performance and confidence of three students (intervention group-IG) participating in a supplemental SBLE, while completing their final CE in an acute care setting, were compared to six students (control group-CG) who did not participate in the SBLE. The Acute Care Confidence Survey and the Clinical Performance Instrument (CPI) 2.0 were utilized to assess four learning competencies: Safety, Communication, Patient Management, and Clinical Reasoning. Results: At midterm and final CPI ratings, the IG showed a trend towards higher scores than the CG in 60% of the relevant categories. Participants in the IG showed similar confidence scores to participants in the CG at the end of the CE. Discussion and conclusion: This project provided an opportunity for students to self-reflect as part of the SBLE on their patient management, in the acute care setting, with guidance by faculty. This project adds to the evidence on how simulation-based learning can complement physical therapy clinical education
Diagnostic accuracy of hysteroscopy for chronic endometritis in reproductive-age and infertile women: a systematic review and latent class meta-analysis
No full textTo evaluate the diagnostic accuracy of hysteroscopy for chronic endometritis (CE) in reproductive-aged women, including those with infertility or recurrent pregnancy loss, considering histopathological, immunohistochemical, and microbiological tests as imperfect reference standards through a Bayesian latent class meta-analysis.
We included peer-reviewed diagnostic accuracy studies, cohort studies, and case series that assessed hysteroscopy as the index test for CE. Eligible studies applied histopathological, immunohistochemical, or microbiological reference standards to endometrial, endocervical, or vaginal samples, providing sufficient quantitative data. Searches across common databases and registries up to October 1st, 2025, were not restricted by language. Study quality was assessed using QUADAS-2.
Pooled estimates of sensitivity, specificity, diagnostic odds ratio (DOR), and likelihood ratios (LR) were obtained using an imperfect-standards Bayesian latent class meta-analysis approach. Subgroup and sensitivity analyses were performed regarding the profile of the studied populations and the risk of bias within and across the studies.
The 28 included studies (12 diagnostic accuracy, 5 cohort, 11 case series) yielded pooled hysteroscopy results of 0.816 sensitivity (95% CI: 0.728–0.882), 0.806 specificity (0.729–0.871), and a DOR of 18.895 (9.364–39.832). Hematoxylin-eosin staining was the most accurate reference standard. Subgroup and sensitivity analyses confirmed results consistency across reproductive-disorder populations and lower-bias studies, with a low estimated risk of reporting bias.
Hysteroscopy demonstrates high diagnostic performance for CE when compared against imperfect reference standards. Despite model-based limitations, evidence supports hysteroscopy as a reliable primary diagnostic tool in clinical assessment and treatment planning.
PROSPERO registration number: CRD42025108754
Overturning Circulation of the North Atlantic Subtropical Gyre Computed in Density Coordinates at 26°N
No full textThe RAPID‐MOCHA‐WBTS array in the subtropical gyre of the North Atlantic has measured the Atlantic Meridional Overturning Circulation (AMOC) and the overturning streamfunction in depth coordinates since 2004. Here we show that the overturning streamfunction in density coordinates can be estimated by combining data from the RAPID‐MOCHA‐WBTS array with repeated shipboard measurements from the Florida Straits and Argo data. The streamfunction in density coordinates highlights the shallow overturning cell associated with the subtropical gyre circulation, a feature that is obscured in depth coordinates. The AMOC calculated in density space is slightly greater than in depth space, but the variability of the time series are very similar with differences occurring when the streamfunction maximum occasionally switches from the main overturning cell to the shallow cell. Plain Language Summary The Atlantic Meridional Overturning Circulation (AMOC) is a large system of ocean currents in the Atlantic Ocean that transports warm water northward near the surface and returns colder, deeper water southward. As such, it plays an important role in global and regional variability. In this paper we compare two different calculations of the AMOC, one is determined from the distribution of ocean currents with depth in the ocean and the other analyses the distribution of ocean currents according to the density of sea water. The results of the two analyses are similar, but the use of density reveals aspects of the circulation within the subtropical ocean that are obscured when depth is used. Key Points A method for calculating overturning circulation in density coordinates from the data available at 26°N is presented Use of density coordinates highlights the shallow cell associated with overturning in the subtropical gyre The Atlantic Meridional Overturning Circulation calculated in density space is slightly greater than in depth space, but the time series are very simila
A sensitivity analysis of non-fungible tokens (NFTs) and comparative assets using time series forecasting
No full textFinancial assets are central to economic stability, yet the macroeconomic sensitivity and predictability of emerging digital assets, particularly non-fungible tokens (NFTs), remain unclear. This study evaluates the responsiveness of NFTs, cryptocurrencies, and traditional assets to interest rate and inflation fluctuations using time series forecasting and sensitivity analysis. ARIMAX, Partial Least Squares, Ridge Regression, and Long Short-Term Memory (LSTM) models are employed to capture linear and nonlinear dynamics across asset classes. Using daily data from July 2017 to November 2024, results indicate that LSTM achieves superior predictive accuracy for highly volatile and nonlinear assets, although forecast reliability is limited by structural breaks and thin trading. Traditional assets such as bonds and gold display stable sensitivities to macroeconomic variables, reinforcing their hedging role. In contrast, digital assets exhibit higher volatility and weaker, less stable macroeconomic linkages. NFTs show low correlations with traditional assets, suggesting diversification potential, but low forecast error variance does not imply low risk. Cryptocurrencies demonstrate stronger macroeconomic sensitivity alongside greater instability. Overall, the findings reveal a trade-off between diversification benefits and forecast reliability when integrating digital assets into portfolios
Vascular Destabilization and Pericyte Detachment are Mediated by hIAPP Aggregation in Transgenic Mice
No full textAims/hypothesis: Human islet amyloid polypeptide (hIAPP) deposition is a common feature of type-2 diabetes (T2D). Previous studies have demonstrated hIAPP-mediated endothelial cell (EC) dysfunction and inflammation, but little is known about islet microvascular stability or pericyte function in hIAPP-containing islets. This study investigates how islet endothelial cells and pericytes are influenced by hIAPP aggregation. Methods: Bulk RNAseq and qPCR were conducted on hIAPP or vehicle treated MS-1 cells and bead-purified human islet CD31+ cells from donors with or without T2D to determine how islet ECs respond to hIAPP exposure. Confocal imaging of living pancreatic slices obtained from hIAPP transgenic mice was conducted to evaluate the effect of hIAPP deposition on islet pericyte function and vasomotor responses. Results: hIAPP-treated MS-1 cells and ECs purified from T2D islets demonstrate downregulation of leading-edge genes associated with extracellular matrix and cell adhesion pathways. Pericytes from hIAPP-expressing mouse islets appear detached from underlying endothelial cells, which was associated with impaired vasomotor responses to constrictive or dilatory stimuli. Conclusions/interpretation: hIAPP induces vascular destabilization by downregulating mRNA of key extracellular matrix and cell adhesion molecules in ECs, likely promoting the breakdown of EC-EC and EC-pericyte coupling. hIAPP disrupts EC-pericyte connections, and pericyte detachment ultimately impairs pericytes' ability to modulate capillary diameter without impairing intracellular Ca2+ dynamics. Our data suggest that amyloid deposition compromises EC health and survival by altering islet microvascular morphology, stability, and function. This, in turn, may disrupt islet microvascular stability and exacerbate endocrine cell dysfunction in T2D.Competing Interest StatementThe authors have declared no competing interest.Funder Information DeclaredDepartment of Veterans Affairs, VA Puget Sound Health Care System, I01-BX004063Canada Excellence Research Chairs, https://ror.org/02tvrwm90, CERC-22-0023NIH Common Fund, https://ror.org/001d55x84, NIH T32 HL00702
Looking at Infrared Background Radiation Anisotropies with Spitzer. II. Small Scale Anisotropies and their Implications for New and Upcoming Space Surveys
No full textSpitzer-based source-subtracted cosmic infrared background (CIB) fluctuations at arcminute-to-degree scales indicate the presence of new populations, whereas subarcminute power arises from known z ≲ 6 galaxies. We reconstruct the evolution of the near-IR CIB anisotropies on subarcminute scales by known galaxy populations. This method is based on, and significantly advanced over, the empirical reconstruction by Helgason et al. which is combined with the halo model connecting galaxies to their host dark matter halos. The modeled CIB fluctuations from known galaxies produce the majority of the observed small-scale signal down to statistical uncertainties of <10% and we constrain the evolution of the halo mass regime hosting such galaxies. Thus, the large-scale CIB fluctuations from new populations are produced by sources with negligible small-scale power. This appears to conflict with the presented intra-halo light models, but is accounted for if the new sources are at high z . Our analysis spanning several Spitzer datasets allows us to narrow the estimated contributions of remaining known galaxies to the CIB anisotropies to be probed potentially from surveys by new and upcoming space missions such as Euclid, SPHEREx, and Roman. Of these, the Roman surveys have the best prospects for measuring the source-subtracted CIB and probing the nature of the underlying new populations at λ < 2 μ m, followed by Euclid’s surveys, while for SPHEREx the source-subtracted CIB signal from them appears significantly overwhelmed by the CIB from remaining known galaxies
The Management of Severe Isolated Traumatic Brain Injury in Pregnancy: A Joint Consensus Statement from the European Association of Neurosurgical Societies (EANS) and the World Society of Emergency Surgery (WSES)
No full textSevere traumatic brain injury (TBI) during pregnancy is a rare but challenging condition. There is scarce evidence in this population, and severe TBI management during gestation remains empirical and extrapolated from data on non-pregnant women.
The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) collaborated to establish a multidisciplinary consensus panel of 115 physicians with vast expertise in the management of severe TBI, including cases of pregnant women. A modified Delphi approach was adopted. Two online questionnaires were conducted between February and June 2025. The list of statements (36) was distributed to the panelists to allow voting and to propose any comments and/or changes. The analysis of results was performed by an experienced non-voting methodologist. Statements were classified as strong suggestion, weak suggestion or no suggestion when > 85%, 75–85% and < 75% of votes were in favor, respectively.
A consensus was reached, generating 36 strong suggestions regarding several important aspects in the care of isolated severe TBI during pregnancy.
This consensus provides practical suggestions to support a clinician’s decision-making in the management of severe isolated TBI during pregnancy in high-income countries. However, these statements are based mainly on expert opinion, and further evidence is required in this field
PO:05:141 Measurement of mucocutaneous domain activity in a novel treatment response measure for systemic lupus erythematosus clinical trials
No full textObjectives Previous work by an international taskforce delivered consensus to include rash, mucosal ulcers and alopecia in the mucocutaneous domain of a novel multi-domain clinical outcome measure for systemic lupus erythematosus (SLE) clinical trials, the Treatment Response Measure for SLE (TRM-SLE). (1) Here we report results of a consensus process to define a fit for purpose clinical outcome assessment and entry and response thresholds for assessment of mucocutaneous activity.Methods A multi-step consensus process was completed by a 18-person working group comprising rheumatologists, dermatologists, and patients with lived experience of mucocutaneous SLE. The domain scope for rash, mucosal ulcers and alopecia for the SLE clinical trial context was defined. Candidate outcome measures were nominated via an online survey. After structured discussion and review of results from the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) working group of the Lupus Accelerating Breakthroughs Consortium (Lupus ABC) addressing outcome measures for trials in cutaneous lupus (CLE), the working group selected a response measure and proceeded to nominal group technique (NGT) to reach consensus on thresholds defining entry and clinically meaningful minimum response.Results 100% consensus was achieved to define the scopes (figure 1). Rash includes SLE-specific rashes such as acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus and chronic cutaneous lupus erythematosus. Mucosal ulcers are limited to oral ulcers confirmed by assessor examination. Alopecia includes CLE-related alopecia and non-scarring alopecia, limited to the scalp. Potential measures of each domain were nominated, with CLASI featuring for all three. After discussion and review of the evidence, including outcomes from the Lupus ABC CLASI working group, there was unanimous agreement to adopt CLASI as the response measure for the mucocutaneous domain in TRM-SLE. Potential CLASI-A thresholds for entry and response were nominated, discussed and ranked via NGT, resulting in consensus on thresholds for entry (CLASI-A >=8) and minimum clinically meaningful response (CLASI-50: CLASI-A reduction by >50%) for use in TRM-SLE. Discussions will be held pending further evidence to define thresholds reflecting complete response