bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of increased uptake of long-acting injectable antiretroviral therapy on HIV incidence and viral suppression in the United States under 2021 FDA guidelines
Authors: Viguerie Alex , O'Shea Jesse , Johnston Marie , Schreiber Daniel , Adams Joella , Bates Laurel , Carrico Justin , Hicks Katherine A. , Lyles Cynthia M. , Farnham Paul G. 
Published: February 2025

Objectives:
To determine the impact of increased long-acting injectable antiretroviral therapy (Cabotegravir-rilpivirine [CAB/RPV]) use among persons with diagnosed HIV (PWDH) with viral suppression (VLS), per 2021 US Food and Drug Administration (FDA) guidelines, on HIV incidence and levels of VLS in the US.

Methods:
We used the HOPE compartmental model to simulate CAB/RPV use during 2023-2035. We first simulated a baseline scenario (no CAB/RPV), in which 69% of PWDH had VLS. We then introduced CAB/RPV in 2023 under two scenarios: (1) where CAB/RPV improved the duration of VLS post-cessation of ART use compared to oral ART; (2) where CAB/RPV additionally improved adherence. We compared cumulative 2023-35 incidence and percentage of PWDH with VLS at year-end 2035 to baseline.

Results:
When CAB/RPV increased the duration of VLS only, cumulative incidence was reduced up to 9%, and VLS increased up to 4%. When CAB/RPV also improved ART adherence, incidence was reduced up to 19.5%, and VLS increased up to 9%.

Conclusions:
CAB/RPV, even if only used among PWDH with VLS, may reduce HIV incidence and increase VLS, due to longer-lasting VLS post-cessation of usage. If CAB/RPV also improves ART adherence, incidence is further reduced. Improved clinical efficacy of CAB/RPV may translate to improved population-level outcomes, even in limited use cases.
Advancing Optical Coherence Tomography Diagnostic Capabilities: Machine Learning Approaches to Detect Autoimmune Inflammatory Diseases
Authors: Kenney Rachel C. , Flagiello Thomas A. , D' Cunha Anitha , Alva Suhan , Grossman Scott N. , Oertel Frederike C. , Paul Friedemann , Schilling Kurt G. , Balcer Laura J. , Galetta Steven L. , Pandit Lekha 
Published: February 2025

Background:
In many parts of the world including India, the prevalence of autoimmune inflammatory diseases such as neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and multiple sclerosis (MS) is rising. A diagnosis is often delayed due to insufficient diagnostic tools. Machine learning (ML) models have accurately differentiated eyes of patients with MS from those of healthy controls (HCs) using optical coherence tomography (OCT)-based retinal images. Examining OCT characteristics may allow for early differentiation of these conditions. The objective of this study was to determine feasibility of ML analyses to distinguish between patients with different autoimmune inflammatory diseases, other ocular diseases, and HCs based on OCT measurements of the peripapillary retinal nerve fiber layer (pRNFL), ganglion cell-inner plexiform layer (GCIPL), and inner nuclear layers (INLs).

Methods:
Eyes of people with MS (n = 99 patients), NMOSD (n = 40), MOGAD (n = 74), other ocular diseases (OTHER, n = 16), and HCs (n = 54) from the Mangalore Demyelinating Disease Registry were included. Support vector machine (SVM) classification models incorporating age, pRNFL, GCIPL, and INL were performed. Data were split into training (70%) and testing (30%) data and accounted for within-patient correlations. Cross-validation was used in training to choose the best parameters for the SVM model. Accuracy and area under receiver operating characteristic curves (AUROCs) were used to assess model performance.

Results:
The SVM models distinguished between eyes of patients with each condition (i.e., MOGAD vs NMOSD, NMOSD vs HC, MS vs OTHER, etc) with strong discriminatory power demonstrated from the AUROCs for these comparisons ranging from 0.81 to 1.00. These models also performed with moderate to high accuracy, ranging from 0.66 to 0.81, with the exception of the MS vs NMOSD comparison, which had an accuracy of 0.53.

Conclusions:
ML models are useful for distinguishing between autoimmune inflammatory diseases and for distinguishing these from HCs and other ocular diseases based on OCT measures. This study lays the groundwork for future deep learning studies that use analyses of raw OCT images for identifying eyes of patients with such disorders and other etiologies of optic neuropathy.
Predicting molecular recognition features in protein sequences with MoRFchibi 2.0
Authors: Malhis Nawar , Gsponer Jörg 
Published: February 2025

AbstractIdentifying sites within intrinsically disordered regions (IDR) that bind to other proteins remains a significant challenge. Molecular Recognition Features (MoRFs) are a subset of segments in IDR that bind to other proteins, undergoing a disorder-to-order transition upon binding. This paper introduces MoRFchibi 2.0, a specialized prediction tool designed to identify the locations of MoRFs within protein sequences. Our results show that MoRFchibi 2.0 outperforms all existing MoRF and general predictors of protein-binding sites within IDRs, including top-performing models from CAID rounds 1, 2, and 3. Remarkably, MoRFchibi 2.0 surpasses predictors that utilize AlphaFold data and state-of-the-art protein language models, achieving superior ROC and Precision-Recall curves and higher success rates. MoRFchibi 2.0 generates output scores using an ensemble of convolutional neural network logistic regression models, followed by a reverse Bayes Rule to adjust for priors in the training data. These scores reflect MoRF probabilities normalized for the priors in the training data, making them individually interpretable and compatible with other tools utilizing the same scoring framework.Availabilityhttps://mc2.msl.ubc.ca/index.xhtml
Sources of nutrition information used and preferred by older people: A scoping review
Authors: McClinchy Jane , Dickinson Angela , Barnes Emily , Ibitoye Tai , Jackson John , Wellings Amander 
Published: February 2025

AbstractA nutritionally adequate diet is needed for older people to optimise their nutritional status and promote healthy ageing. Making use of nutrition information can inform in people’s food choices to help them improve their health and food experience.Over a million older people in the UK are at risk of or experience malnutrition. This number is likely to increase as the population ages. Understanding where older people source their nutrition information could help inform public health interventions to reduce the prevalence of malnutrition.This scoping review aims to summarise studies that examined sources of nutrition information used by older people. A scoping review in order to map and explore studies that examine the current sources of nutritional knowledge used by older people was undertaken using PUBMED, Scopus and CINAHL databases during March 2023. Of the 8819 studies identified, 13 studies reporting on 12 research projects met the inclusion criteria of exposure to, impact by, or preference for at least one source of nutrition information.Eight studies showed that older people used magazines; 6 studies showed that TV, dietitians, embodied knowledge, family and friends and GPs were the main sources of nutrition information. Educational level, gender and trust in the messages influenced their ability to use these sources to inform their food choices.Research is needed to further explore the impact of nutritional information in order to identify ways in which to support older adults to make use of nutrition information to help make food choices that would facilitate healthy ageing.
Enhanced Detection of Glioblastoma Vasculature with Superparamagnetic Iron Oxide Nanoparticles and MRI
Authors: Janowicz Phillip W. , Boele Thomas , Maschmeyer Richard T. , Gholami Yaser H. , Kempe Emma G. , Stringer Brett W. , Stoner Shihani P. , Zhang Marie , Thompson Taymin du-Toit , Williams Fern , Touffu Aude , Munoz Lenka , Kuncic Zdenka , Brighi Caterina , Waddington David E. J. 
Published: February 2025

AbstractDetecting glioblastoma infiltration in the brain is challenging due to limited MRI contrast beyond the enhancing tumour core. This study aims to investigate the potential of superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents for improved detection of diffuse brain cancer. We examine the distribution and pharmacokinetics of SPIONs in glioblastoma models with intact and disrupted blood-brain barriers. Using MRI, we imaged RN1-luc and U87MG mice injected with Gadovist and SPIONs, observing differences in blood-brain barrier permeability. Peripheral imaging showed strong uptake of nanoparticles in the liver and spleen, while vascular and renal signals were transient. Susceptibility gradient mapping enabled positive nanoparticle contrast within tumours and provided additional information on tumour angiogenesis. This approach offers a novel method for detecting diffuse brain cancer. Our findings demonstrate that SPIONs enhance glioblastoma detection beyond conventional MRI, providing insights into tumour angiogenesis and opening new avenues for early diagnosis and targeted treatment strategies.
Individuals withPMS2pathogenic variants are at average risk of cancer before age 60
Authors: Schiabor Barrett Kelly M. , Hajek Catherine , Lu James , Lynch Kate , Cauwels Jeremy , Stoller Douglas , Chapman Christopher N. , Chahal C. Anwar A. , Judge Daniel P. , Olson Douglas A. , Grzymski Joseph J. , Lee William , Cirulli Elizabeth T. , Bolze Alexandre 
Published: February 2025

AbstractImportanceScreening Lynch syndrome in the general population, including healthy individuals, aims to detect and prevent cancers early. Current clinical recommendations for those with pathogenic variants are based on studies of patients with cancer or strong family history. It is essential to ensure guidelines are based on accurate assumptions regarding the impact of pathogenic variants in Lynch syndrome genes.ObjectiveTo determine the risk of cancer associated with pathogenic variants inMLH1, MSH2, MSH6, orPMS2in the general population.Design, Setting, and ParticipantsThis retrospective case-control study utilizes Helix Research Network™data from 144,852 participants across seven US health systems sequenced between 2018 and 2024.Main outcomes and measuresAn automated pipeline based on the ACMG-AMP guidelines was developed for variant interpretations. Clinical diagnoses were identified from electronic health records for 11 cancer types associated with Lynch syndrome including colorectal and endometrial cancers.ResultsIndividuals with pathogenic variants inMLH1, MSH2, andMSH6were at significantly increased risk for Lynch syndrome-associated cancers with Hazard Ratios (HR) of 16.5 (95% Cl: 8.9-30.8) forMLH1, 17.3 (7.8-38.6) forMSH2and 4.7 (3.2-6.9) forMSH6. No significant risk was associated withPMS2pathogenic variants when considering all 11 cancers combined.PMS2pathogenic variants were only associated with colorectal cancer (HR of 4.3, 1.6-11.4); however, this risk was observed only after the age of 60, 10 years after clinical guidelines recommend starting colonoscopies for the average population. Up to age 60, 0.6% of individuals withPMS2pathogenic variants were diagnosed with colorectal cancer, similar to 0.4% in the general population but lower thanMLH1(41.0%),MSH2(17.9%) orMSH6(4.5%) pathogenic variants.Conclusion and relevanceThe findings underscore the benefits of screening the entire population forMLH1, MSH2andMSH6. They also highlight significantly lower cancer risk for those harboringPMS2pathogenic variants. This study provides data to support tailored surveillance and prevention strategies by gene and highlights the importance of deriving clinical recommendations from relevant populations.
Contribution of an under-recognized adversity to child health risk: large-scale, population-based ACEs screening
Authors: Glynn Laura M. , Liu Sabrina R. , Golden Charles , Weiss Michael , Lucas Candice Taylor , Cooper Dan M. , Ehwerhemuepha Louis , Stern Hal S. , Baram Tallie Z. 
Published: February 2025

AbstractBackground and ObjectivesWhereas adverse early life experiences (ACEs) correlate with cognitive, emotional and physical health at the population level, existing ACEs screens are only weakly predictive of outcomes for an individual child. This raises the possibility that important elements of the early-life experiences that drive vulnerability and resilience are not being captured. We previously demonstrated that unpredictable parental and household signals constitute an ACE with cross-cultural relevance. We created the 5-item Questionnaire of Unpredictability in Childhood (QUIC-5) that can be readily administered in pediatric clinics. Here, we tested if combined screening with the QUIC-5 and an ACEs measure in this real-world setting significantly improved prediction of child health outcomes.MethodsLeveraging existing screening with the Pediatric ACEs and Related Life Events Screener (PEARLS) at annual well-child visits, we implemented QUIC-5 screening in 19 pediatric clinics spanning the diverse sociodemographic constituency of Orange County, CA. Children (12yr+) and caregivers (for children 0-17years) completed both screens. Health diagnoses were abstracted from electronic health records (N=29,305 children).ResultsFor both screeners, increasing exposures were associated with a higher probability of a mental (ADHD, anxiety, depression, externalizing problems, sleep disorder) or physical (obesity abdominal pain, asthma, headache) health diagnosis. Across most diagnoses, PEARLS and QUIC provided unique predictive contributions. Importantly, for three outcomes (depression, obesity, sleep disorders) QUIC-5 identified vulnerable individuals that were missed by PEARLS alone.ConclusionsScreening for unpredictability as an additional ACE in primary care is feasible, acceptable and provides unique, actionable information about child psychopathology and physical health.What’s Known on This SubjectWhereas ACEs correlate with neurodevelopmental and physical health of children at the population level, ACEs scales (e.g., PEARLS) are only weakly predictive at the level of the individual child. Are important elements of early-life adversity missed by these scales?What This Study AddsBecause unpredictable signals constitute a unique ACE, we developed the Questionnaire of Unpredictability in Childhood (QUIC-5). Administering QUIC-5 and PEARLS to 30,000 families identified youth at risk for depression, obesity and other health problems, who would be missed by PEARLS alone.
From cyst to tapeworm: Transcriptome ofTaenia solium in vitroactivation and growth
Authors: Castaneda-Carpio David , Gutierrez-Loli Renzo , Maravi-Jaime Jose , Del Aguila Segundo W , Villar-Davila Valeria , Moyano Luz M , Tapia-Limonchi Rafael , Chenet Stella M , Guerra-Giraldez Cristina 
Published: February 2025

AbstractThe cestodeTaenia soliumdevelops as a tapeworm solely in the human intestine, starting from a larva (cyst). Upon maturing, it produces hundreds of thousands of infectious eggs. When ingested by pigs or humans, the eggs develop as cysts that lodge in various tissues, including the brain, leading to neurocysticercosis. Despite advances in understanding cestode biology through genomic and transcriptomic studies, particularly in model organisms, much remains unknown about the activation ofT. soliumcysts in the human digestive tract and the events that drive the development into adult worms—the stage responsible for dispersing the parasite. We present a transcriptome generated by Next Generation Sequencing fromT. soliumcysts activated in culture and collected at three different in vitro growth phases, as defined by their morphology. We identified differentially expressed genes and biological processes relevant to growth phases, which can be further explored with the dataset. The information is valuable for identifying genes that regulate the molecular, metabolic, and cellular events leading to parasite maturation or elements driving its transmission.
Neural signatures of stream segregation: From childhood to adulthood
Authors: Benocci Elena , Alain Claude , Calcus Axelle 
Published: February 2025

ABSTRACTWhen faced with noisy environments, listeners perform auditory scene analysis, which allows them to parse the auditory target from concurrent interferences. Stream segregation involves organizing similar sound waves into a coherent stream, while distinguishing dissimilar acoustic components and attributing them to distinct sources. Two event-related potential components have been identified as “neural signatures” of stream segregation: the Object-Related Negativity (ORN) and the P400. Our study aims to examine (i) the maturation of neural and behavioural correlates of stream segregation and (ii) the development of the relationship between stream segregation and speech perception in noise. ORN/P400 were recorded while 8-23 year-olds performed an active stream segregation task based on temporal coherence. Participants also performed speech identification in noise tasks (behaviourally). Behavioral results indicate an improvement in both stream segregation and speech perception in noise from childhood to adulthood. Amplitude of the ORN (but not P400) decreases, and latency of both ORN and P400 decreases throughout development. Critically, P400 amplitude significantly predicts stream segregation performance. Overall, our results suggest that the neural mechanisms underlying stream segregation follow a prolonged maturation trajectory, and support the progressive maturation of auditory scene analysis and speech perception in noise.RESEARCH HIGHLIGHTS- Neurophysiological indices of stream segregation mature from childhood to adulthood- Neural indices of top-down attentive processing of complex auditory sequences predict stream segregation, irrespective of the listeners age- In adults (but not in children or adolescents), stream segregation predicts speech perception in noise- Stream segregation may thus operate as a bottleneck to speech in noise difficulties in children and adolescents
Friend Request Accepted: Fundamental Features of Social Environments Determine Rate of Social Affiliation
Authors: Garud Sankalp , Rascu Miruna , Hamilton Sorcha , Yu Ingrid , Rushworth Matthew F.S. , Klein-Flügge Miriam C. 
Published: February 2025

AbstractHumans start new friendships and social connections throughout their lives and such relationships foster mental and physical well-being. While friendship initiation may depend on alignment of subtle and complex personal variables, here we investigated whether it also depends on basic features of social environments. This would be analogous to other fundamental behaviours like foraging which depend on basic features of the environment such as the density of opportunities and the likelihood of success. In a pre-registered online study (n=783), we found people were more likely to send friend requests as the density of friendship opportunities decreased and frequency of success increased. Further, we found task-related measures, like overall friend requests, were correlated with personality-related factors like social thriving and anhedonia. Next, in an ultra-high-field fMRI study (n=24), we found that both fundamental features of social environments – opportunity density and frequency of success – affected neural activity across a network of regions linked to foraging including dorsal raphe nucleus, substantia nigra, and anterior insula. Finally, in resting-state fMRI data (n=400), we showed that model predicted estimates of anhedonia were related to functional connectivity between components of the same network. Thus, humans consider the background statistics of an environment while making social decisions and these decisions are linked to activity in ancient subcortical circuits mediating the influence of environmental statistics on other aspects of behaviour. Moreover, individual differences in how environmental features influence social behaviour are associated with variation in personality and psychiatric traits, offering new insights into inter-individual variability in social functioning.
Survival of the “unfittest”: clinical emergence of hyper-multidrug-resistantNakaseomyces glabratuswith rare nonfunctional Erg3 and Erg11 and severely impaired fitness
Authors: Carolus Hans , Biriukov Vladislav , Vreys Jolien , Lobo Romero Celia , Paulo Herrera Avila Juan , Vergauwen Rudy , Sofras Dimitrios , Vanreppelen Giel , Vinken Lore , Britto Xavier Basil , Gabaldón Toni , Lagrou Katrien , Naesens Reinout , Van Dijck Patrick 
Published: February 2025

AbstractBackgroundNakaseomyces glabratus(Candida gabrata) poses a significant clinical challenge due to common drug resistance. We report a case of a complicated urinary tract infection (UTI) progressing to prostatitis and urosepsis, with the emergence of a hyper-multidrug-resistant isolate with low stress tolerance, slow growth and a short life span. This study elucidates the genetic mechanisms and phenotypic characteristics underlying antifungal hyper-resistance with strong fitness trade-offs, and explores potential alternative therapies for resistant UTI’s.MethodsWhole-genome sequencing was performed to identify resistance-associated mutations and gene knock-out strains were generated to assess the relative impact of putative loss-of-function (LoF) mutations on antifungal resistance, fitness and membrane sterol composition. Drug susceptibility testing of the antibiotic nitroxoline and related compounds was conducted to evaluate it as a therapeutic alternative and study the mechanism of action.FindingsLoss-of-function mutations inERG3andERG11were identified and linked to the accumulation of 4,14-dimethylzymosterol and lanosterol instead of ergosterol. EngineeredERG3Δ+ERG11Δstrains recapitulated the clinical isolate’s hyper-multidrug resistance and associated fitness deficits. WhileERG3Δstrains showed no resistance but enhanced thermotolerance,ERG11ΔandERG3Δ+ERG11Δstrains exhibited multidrug resistance with severe fitness trade-offs. Interestingly,ERG3Δ+ERG11Δstrains showed mild resistance to flucytosine, but an additionalFUR1mutation in the clinical isolate most probably underlies hyper-resistance to flucytosine. The UTI antibiotic nitroxoline demonstrated high antifungal activity against all strains, and the LoF ofERG3and/orERG11induced collateral sensitivity to this drug. Testing of related compounds suggest a mode of action beyond iron chelation.InterpretationThis case demonstrates that hyper-resistant strains ofN. glabratuscan emerge despite significant fitness costs and persist under prolonged antifungal therapy in specific clinical settings. These findings underscore the importance of vigilant antifungal resistance monitoring and highlight nitroxoline as a promising alternative treatment for complicated fungal UTIs. These results challenge the notion that strains with fitness deficits are clinically irrelevant and emphasize the need for novel therapeutic strategies including repurposed agents.