Tag: pubmed

N Engl J Med. 2025 Mar 13;392(11):1089-1099. doi: 10.1056/NEJMoa2408645.

ABSTRACT

BACKGROUND: Hospital studies suggest that scrub typhus is a leading cause of severe undifferentiated fever in regions across Asia where the disease is endemic, but the population-based incidence of infection and illness has been little studied.

METHODS: We conducted a population-based cohort study to assess epidemiologic and clinical characteristics of scrub typhus in 37 villages in Tamil Nadu, India, where the disease is highly endemic. Study participants were visited every 6 to 8 weeks over a period of 2 years; a venous blood sample was obtained from those who had had fever since the last visit. A subcohort of participants underwent blood sampling to estimate the incidence of serologically confirmed Orientia tsutsugamushi infection.

RESULTS: We systematically assessed 32,279 participants from 7619 households for acute febrile illness. During 54,588 person-years of follow-up, we observed 6175 episodes of fever. A blood sample was obtained in 4474 episodes (72.5%), of which 328 (7.3%) met the clinical case definition of scrub typhus (detection of IgM against O. tsutsugamushi on enzyme-linked immunosorbent assay [ELISA] or detection of O. tsutsugamushi on polymerase-chain-reaction assay). The incidence of clinical infection was 6.0 cases per 1000 person-years (95% confidence interval [CI], 4.8 to 7.5). A total of 71 clinical cases (21.6%) resulted in hospitalization (incidence, 1.3 events per 1000 person-years; 95% CI, 1.0 to 1.7). A total of 29 clinical cases (8.8%) were severe, as indicated by the presence of organ dysfunction or adverse pregnancy outcomes (incidence, 0.5 cases per 1000 person-years; 95% CI, 0.4 to 0.8). Among 2128 participants in the subcohort who provided samples at the beginning and end of a study year, the incidence of seroconversion independent of any symptoms was 81.2 events per 1000 person-years (95% CI, 70.8 to 91.6). The incidence of clinical infection was higher in older age groups than in younger age groups and higher among female participants than among male participants. By contrast, the age-adjusted rate of severe infection was similar among male and female participants. Among 5602 participants assessed at the start of the first year of the study, the seroprevalence of IgG as assessed with ELISA was 42.8% (95% CI, 35.8 to 50.2). IgG seropositivity at the beginning of years 1 or 2 did not protect against clinical illness during the subsequent year but was associated with less severe disease than IgG seronegativity.

CONCLUSIONS: We describe the burden of scrub typhus, including the incidence of asymptomatic infection, in a region of Asia where the disease is endemic. (Funded by the U.K. Medical Research Council; ClinicalTrials.gov number, NCT04506944.).

PMID:40073309 | DOI:10.1056/NEJMoa2408645

Neurology. 2025 Apr 8;104(7):e213374. doi: 10.1212/WNL.0000000000213374. Epub 2025 Mar 12.

ABSTRACT

BACKGROUND AND OBJECTIVES: Medical clearance for return to play (RTP) after sports-related concussion is based on clinical assessment. It is unknown whether brain physiology has entirely returned to preinjury baseline at the time of clearance. In this longitudinal study, we assessed whether concussed individuals show functional and structural MRI brain changes relative to preinjury levels that persist beyond medical clearance. Secondary objectives were to test whether postconcussion changes exceed uninjured brain variability and to correlate MRI findings with clinical recovery time.

METHODS: For this prospective observational study, healthy athletes without a history of psychiatric, neurologic, or sensory-motor conditions were recruited from a single university sport medicine clinic. Clinical and MRI data were collected at preseason baseline, and those who were later concussed were reassessed at 1-7 days after injury, RTP, 1-3 months after RTP, and 1 year after RTP. A demographically matched control cohort of uninjured athletes was also reassessed at their subsequent preseason baseline. Primary outcomes were postconcussion changes in MRI measures of cerebral blood flow (CBF), white matter mean diffusivity (MD), and fractional anisotropy (FA), evaluated using mixed models. Secondary outcomes were group differences in MRI change scores and correlations of change scores with days to RTP.

RESULTS: Of the 187 athletes enrolled in the study, 25 had concussion with follow-up imaging (20.3 ± 1.5 years, 56% male, 44% female) and were compared with 27 controls (19.7 ± 1.8 years, 44% male, 56% female). Concussed athletes showed statistically significant changes from baseline, including decreased frontoinsular CBF (mean and 95% CI -8.97 [-12.80, -5.01] mL/100 g/minute, z = -4.53), along with increased MD (1.94 × 10^-5 [1.26, 2.69] × 10^-5, z = 5.48) and reduced FA (-7.30 × 10^-3 [-9.80, -5.05] × 10^-3, z = -6.07) in the corona radiata and internal capsule. Effects persisted beyond RTP, although only CBF changes exceeded longitudinal variability in controls. For participants with longer recovery periods, significantly greater changes in medial temporal CBF were also seen (ρ = 0.64 [0.44, 0.81], z = 6.80).

DISCUSSION: This study provides direct evidence of persistent postconcussion changes in CBF and white matter at RTP and up to 1 year later. These results support incomplete recovery of brain physiology at medical clearance, with secondary analyses emphasizing the sensitivity of CBF to clinical recovery.

PMID:40073308 | DOI:10.1212/WNL.0000000000213374

Dentomaxillofac Radiol. 2025 Mar 12:twaf015. doi: 10.1093/dmfr/twaf015. Online ahead of print.

ABSTRACT

OBJECTIVE: To quantitatively and qualitatively compare directly two types of cisternography images for diagnosing trigeminal neuralgia (TN) using 3-T magnetic resonance imaging.

METHODS: This prospective study recruited 64 patients with a clinical diagnosis or suspicion of TN. Patients were examined through the three-dimensional (3D) Constructive Interference in Steady State (CISS) and Sampling Perfection with Application-optimized Contrasts using different flip angle Evolutions (SPACE) sequences. Three radiologists quantitatively measured the signal intensity of the trigeminal nerve (cranial nerve V, CN5) (SICN5), cerebrospinal fluid (CSF) (SICSF), and contrast between CN5 and CSF (Cont.). Additionally, two radiologists qualitatively evaluated the basilar artery (BA), CN5, CSF, image artefacts, and overall image quality. Statistical analyses included paired-sample t-tests, non-parametric McNemar tests, and the Friedman test (significance set at p < 0.05).

RESULTS: Mean SICN5 (p < 0.001), SICSF (p = 0.679), and Cont. (p < 0.001) were as follows: 203.08 ± 26.68, 936.03 ± 91, and 3.68 ± 0.74 in CISS; 46.80 ± 16.88, 940.61 ± 71.39, and 23.19 ± 14.52 in SPACE. Low-to-moderate CN5 and BA visibility was observed in all cases in CISS, while it was noted in one case for CN5 and in none for BA in SPACE (p < 0.001). Homogenous CSF and minor artefacts were observed in 14 cases in CISS, while it was seen in 52 cases for CN5 and 59 for BA in SPACE (p < 0.001). The overall image quality was scored as four in 57 cases in SPACE, while no cases received this score in CISS (p < 0.001).

CONCLUSIONS: SPACE provided better images than CISS for evaluating CN5 and prepontine cistern vascularity, indicating a valuable sequence for TN diagnosis.

ADVANCES IN KNOWLEDGE: This study indicates that SPACE should be selected for TN diagnosis instead of CISS sequence.

PMID:40073237 | DOI:10.1093/dmfr/twaf015

Bioinformatics. 2025 Mar 12:btaf096. doi: 10.1093/bioinformatics/btaf096. Online ahead of print.

ABSTRACT

MOTIVATION: Inferring gene networks provides insights into biological pathways and functional relationships among genes. When gene expression samples exhibit heterogeneity, they may originate from unknown subtypes, prompting the utilization of mixture Gaussian graphical model for simultaneous subclassification and gene network inference. However, this method overlooks the heterogeneity of network relationships across subtypes and does not sufficiently emphasize shared relationships. Additionally, GGM assumes data follows a multivariate Gaussian distribution, which is often not the case with zero-inflated scRNA-seq data.

RESULTS: We propose an Adaptive Joint Graphical Model (AJGM) for estimating multiple gene networks from single-cell or bulk data with unknown heterogeneity. In AJGM, an overall network is introduced to capture relationships shared by all samples. The model establishes connections between the subtype networks and the overall network through adaptive weights, enabling it to focus more effectively on gene relationships shared across all networks, thereby enhancing the accuracy of network estimation. On synthetic data, the proposed approach outperforms existing methods in terms of sample classification and network inference, particularly excelling in the identification of shared relationships. Applying this method to gene expression data from triple-negative breast cancer confirms known gene pathways and hub genes, while also revealing novel biological insights.

AVAILABILITY AND IMPLEMENTATION: The Python code and demonstrations of the proposed approaches are available at https://github.com/yyytim/AJGM, and the software is archived in Zenodo with DOI: 10.5281/zenodo.14740972.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:40073230 | DOI:10.1093/bioinformatics/btaf096

Elife. 2025 Mar 12;13:RP95802. doi: 10.7554/eLife.95802.

ABSTRACT

Fiber photometry has become a popular technique to measure neural activity in vivo, but common analysis strategies can reduce the detection of effects because they condense within-trial signals into summary measures, and discard trial-level information by averaging across-trials. We propose a novel photometry statistical framework based on functional linear mixed modeling, which enables hypothesis testing of variable effects at every trial time-point, and uses trial-level signals without averaging. This makes it possible to compare the timing and magnitude of signals across conditions while accounting for between-animal differences. Our framework produces a series of plots that illustrate covariate effect estimates and statistical significance at each trial time-point. By exploiting signal autocorrelation, our methodology yields joint 95% confidence intervals that account for inspecting effects across the entire trial and improve the detection of event-related signal changes over common multiple comparisons correction strategies. We reanalyze data from a recent study proposing a theory for the role of mesolimbic dopamine in reward learning, and show the capability of our framework to reveal significant effects obscured by standard analysis approaches. For example, our method identifies two dopamine components with distinct temporal dynamics in response to reward delivery. In simulation experiments, our methodology yields improved statistical power over common analysis approaches. Finally, we provide an open-source package and analysis guide for applying our framework.

PMID:40073228 | DOI:10.7554/eLife.95802

JBRA Assist Reprod. 2025 Mar 12;29(1):167-190. doi: 10.5935/1518-0557.20240107.

ABSTRACT

RESEARCH QUESTION: What are the trends and impact of new technologies on the effectiveness and safety of assisted reproductive technology (ART) performed in Latin America during 2021?

DESIGN: This was a retrospective collection of cycle-based multinational data obtained from ART procedures performed by 204 accredited institutions in 16 countries.

RESULTS: In total 127,351 initiated cycles resulted in 20,032 deliveries and 22,708 births. ART utilization showed great variability, from 623.5 cycles/million inhabitants in Uruguay to fewer than 35 in Guatemala and El Salvador. The proportion of women aged ≥40 years increased to 35.8%, while that of women ≤34 years dropped to 23.9%. Nonetheless, the proportion of single-embryo transfers (SET) increased from 11.9% in the previous decade to 42.4% in 2021. Of 22,708 babies born, 76.8% were singletons, 22.3% twins and 1.0% triplets or more. Intracytoplasmic sperm injection represented 84.5% of fertilization techniques, and blastocyst transfer increased from 49.6% in 2016 to 79.3% in 2021. The delivery rate after fresh blastocyst elective SET was significantly higher than after the transfer of one frozen embryo from a freeze-all cycle (p<0.0001). The number of aspirations leading to preimplantation genetic testing has increased 2.8 times in 5 years and significantly increased delivery rates/transfer at all ages, including in oocyte donation (p≤0.002), and reduced miscarriage in women ≥35 years old. In oocyte donation, delivery rates after the fresh transfer of embryos from vitrified-warmed oocyte cycles generated similar outcomes to frozen embryo transfer. Perinatal mortality increased from 7.7 ‰ in singletons to 21.3 ‰ in twins.

CONCLUSIONS: The systematic collection of cycle-based multinational data contributes to cooperative sustained development and helps implement evidence-based reproductive decisions.

PMID:40073223 | DOI:10.5935/1518-0557.20240107

Health Promot Chronic Dis Prev Can. 2025 Mar;45(3):112-138. doi: 10.24095/hpcdp.45.3.02.

ABSTRACT

INTRODUCTION: We investigated the prevalence of new or persistent manifestations experienced by COVID-19 survivors at 3 or more months after their initial infection, collectively known as post-COVID-19 condition (PCC).

METHODS: We searched four electronic databases and major grey literature resources for prospective studies, systematic reviews, authoritative reports and population surveys. A random-effects meta-analysis pooled the prevalence data of 22 symptoms and outcomes. The GRADE approach was used to assess the certainty of evidence. PROSPERO CRD42021231476.

RESULTS: Of 20 731 identified references, 194 met our inclusion criteria. These studies followed 483 531 individuals with confirmed COVID-19 diagnosis over periods of up to 2 years. Most focused on adults, nearly two-thirds were conducted in Europe and 63% were of high or moderate quality. The supplementary search identified 17 systematic reviews, five authoritative reports and four population surveys that reported on PCC prevalence. Our analysis revealed that more than half of COVID-19 survivors experienced one or more symptoms more than a year after their initial infection. The most common symptoms were fatiguedyspneamemory, sleep or concentration disturbances; depressionand pain. Limitation in returning to work was the most common outcome. Prevalence tended to be higher among females, individuals hospitalized during their initial infection and those who experienced severe COVID-19 illness.

CONCLUSION: PCC presents a significant health burden, affecting some groups more than others. This information will help inform health care system policies and services for people living with PCC and those caring for them.

PMID:40073162 | DOI:10.24095/hpcdp.45.3.02

J Cutan Med Surg. 2025 Mar 12:12034754251324941. doi: 10.1177/12034754251324941. Online ahead of print.

ABSTRACT

BACKGROUND: The Ontario Health Insurance Plan (OHIP) insures appointments for the assessment and diagnosis of hair loss, or alopecia. Although anecdotal, discussion suggests that, increasingly, dermatologists decline to see referrals of this nature. There has been a lack of objective surveillance to determine the proportion of dermatologists in practice who accept referrals for this concern.

OBJECTIVES: This study investigated the proportion of dermatologists in Ontario accepting OHIP referrals for hair loss. Secondary objectives included wait times, consultation fees for non-OHIP visits, and factors affecting referral acceptance or rejection.

METHODS: A cross-sectional telephone survey was conducted, in which 284 dermatologists’ offices listed by the College of Physicians and Surgeons of Ontario (CPSO) were contacted. The study investigated the acceptance of OHIP referrals for hair loss, wait times, additional referral requirements, and private consultation fees. Descriptive statistics were employed to summarize data.

RESULTS: Of the 284 offices contacted, 38.38% (109/284) accepted OHIP referrals for hair loss, 48.59% (138/284) did not, and 13.03% (37/284) were unavailable for contact. The average wait time for offices that accepted referrals was 4.51 ± 4.07 months. Non-OHIP consultation fees ranged from $135 to $299 CAD. Some offices limited acceptance to specific conditions such as alopecia areata and male androgenetic alopecia.

CONCLUSION: A total of 48.59% of dermatologists in Ontario do not accept OHIP referrals for hair loss, while the status of 13.03% remains unknown. This reality raises concerns about accessibility to care. Further research is needed to investigate factors influencing referral acceptance.

PMID:40072492 | DOI:10.1177/12034754251324941

Biometrics. 2025 Jan 7;81(1):ujaf022. doi: 10.1093/biomtc/ujaf022.

ABSTRACT

The segmented model has significant applications in scientific research when the change-point effect exists. In this article, we propose a comprehensive semiparametric framework in segmented models to test the existence and estimate the location of change points in the generalized outcome setting. The proposed framework is based on a semismooth estimating equation for the change-point estimation and an average score-type test for hypothesis testing. The root-n consistency, asymptotic normality, and asymptotic efficiency of estimators for all parameters in the segmented model are rigorously studied. The distribution of the average score-type test statistics under the null hypothesis is rigorously derived. Extensive simulation studies are conducted to assess the numerical performance of the proposed change-point estimation method and the average score-type test. We investigate change-point effects of baseline glomerular filtration rate and body mass index on bleeding after intervention using data from Blue Cross Blue Shield. This application study successfully identifies statistically significant change-point effects, with the estimated values providing clinically meaningful insights.

PMID:40072490 | DOI:10.1093/biomtc/ujaf022

Epilepsia. 2025 Mar 12. doi: 10.1111/epi.18342. Online ahead of print.

ABSTRACT

OBJECTIVE: We analyzed the long-term safety and effectiveness of fenfluramine (FFA) in patients with Dravet syndrome (DS) in an open-label extension (OLE) study after participating in randomized controlled trials (RCTs) or commencing FFA de novo as adults.

METHODS: Patients with DS who participated in one of three RCTs or were 19 to 35 years of age and started FFA de novo were included. Key endpoints were: incidence of treatment-emergent adverse events (TEAEs) in the safety population, and median percentage change in monthly convulsive seizure frequency (MCSF) from the RCT baseline to end of study (EOS) in the modified intent-to-treat (mITT) population. Post hoc analyses compared effectiveness in patients on concomitant stiripentol (STP) vs those not taking STP, and assessed safety (TEAEs) and effectiveness (Clinical Global Impression-Improvement [CGI-I] scale ratings) in patients enrolled as adults.

RESULTS: A total of 374 patients, including 45 adults, received ≥1 FFA dose. Median FFA exposure was 824 days (range, 7-1280). TEAEs occurring in ≥10% of patients were pyrexia, nasopharyngitis, decreased appetite, seizure, decreased blood glucose, diarrhea, abnormal echocardiography (only physiologic regurgitation), upper respiratory tract infection, influenza, vomiting, and ear infection; no valvular heart disease or pulmonary arterial hypertension was observed over the OLE. In the mITT population (n = 324), median percentage change in MCSF from baseline to EOS was -66.8% (p < .001). The post hoc analyses of MCSF change from baseline to EOS in patients on concomitant STP (n = 75) was -36.2% vs -71.6% in those not on concomitant STP (n = 234) (p < .0001). In adult patients, 29 of 41 (70.7%) and 29 of 42 patients (69.1%) demonstrated clinically meaningful improvement on CGI-I at last visit as rated by caregivers and investigators, respectively.

SIGNIFICANCE: Our OLE study of FFA in patients with DS confirmed previous positive findings and extended the exposure up to 3.5 years. No new or unexpected safety signals were observed and FFA demonstrated sustained and clinically meaningful reduction in MCSF.

PMID:40072476 | DOI:10.1111/epi.18342