bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating multi-system environmental factors to predict brain and behavior in adolescents
Authors: Ramduny Jivesh , Paskewitz Samuel , Brazil Inti A. , Baskin-Sommers Arielle 
Published: January 2025

AbstractObjectiveEnvironmental factors have long been shown to influence brain structure and adolescent psychopathology. However, almost no research has included environmental factors spanning micro-to-macro-systems, brain structure, and psychopathology in an integrated framework. Here, we assessed the ways and degree to which multi-system environmental factors during late childhood predict subcortical volume and psychopathology during early adolescence.MethodWe used the baseline and 2-year follow-up data from the Adolescent Brain Cognitive DevelopmentSMStudy (N= 2,766). A Bayesian latent profile analysis was applied to obtain distinct multi-system environmental profiles during late childhood. The profiles were used in a path analysis to predict their direct and indirect effects on subcortical volume and psychopathology during early adolescence.ResultsBayesian latent profile analysis revealed nine environmental profiles. Two distinct profiles predicted greater externalizing problems in adolescents: (i) adversity across, family, school, and neighborhood systems and (ii) family conflict and low school involvement. In contrast, a profile of family and neighborhood affluence predicted fewer externalizing difficulties. Further, family and neighborhood affluence predicted higher subcortical volume, which in turn, predicted fewer externalizing problems; whereas, family economic and neighborhood adversity predicted lower subcortical volume, which in turn, predicted greater externalizing difficulties.ConclusionWe captured direct and indirect influences of environmental factors across multiple systems on externalizing psychopathology. Specifying the equifinal pathways to externalizing psychopathology serves to provide an evidence base for establishing different types of interventions based on the needs and risk profiles of youth.Diversity and Inclusion StatementThe current study is part of the ongoing Adolescent Brain Cognitive DevelopmentSMStudy (ABCD Study®) for which youth are recruited from elementary schools in the United States that are informed by gender, race, ethnicity, socioeconomic status, and urbanicity. The ABCD Study® aims to recruit youth longitudinally by sampling the sociodemographic makeup of the US population. Two of the authors self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One of the authors identifies as a part of an underrepresented gender group in science. The authors also are representative of the communities for which data was collected and contributed to design, analysis, and/or interpretation of the work. Finally, every effort was made to cite the work of authors from underrepresented and minoritized groups in academic research.
A Diagnostic Blind Spot: Deep intronic SVA_E Insertion identified as the most Common Pathogenic Variant Associated with Canavan Disease
Authors: Dominguez Gonzalez Carlos A. , Bell Katrina M. , Rajagopalan Ramakrishnan , de Silva Michelle G. , Lemes Aída , Zabala Cristina , Pérez Florencia , Cerisola Alfredo , Vossough Arastoo , Whitehead Matthew T. , Cunningham Chloe , Brown Natasha J. , Quin Rebecca , Simons Cas , Conway Thomas , Uebergang Eloise , Rius Rocio , Kumaheri Meutia A. , Kotes Emma , Vohra Ananya , Zalusky Miranda PG , Anderson Zachary B. , Storz Sophie HR , Ward Sydney A. , Goffena Joy , Gustafson Jonas A. , White Susan M. , Vanderver Adeline , Miller Danny E. 
Published: January 2025

AbstractCanavan disease (CD) is a neurodegenerative disorder caused by biallelic disease-causing variants in theASPAgene. Here, we utilized long-read sequencing (LRS) to investigate eight individuals clinically diagnosed with Canavan disease but without definitive genetic diagnoses. Our analyses identified a recurring previously unreported intronic SVA_E retrotransposon insertion withinASPAin all eight individuals. Surprisingly, the frequency of this variant in population databases suggests it is the most common pathogenic variant inASPAand should be evaluated in diagnostic testing and carrier screening for CD. Additionally, this finding has implications for the broader rare disease community, as it highlights a substantial blind spot in standard short-read diagnostic pipelines, which historically have missed or overlooked these types of insertions. This discovery highlights the power of emerging technologies, such as LRS and RNA-sequencing (RNA-seq), to bring new classes of variants into diagnostic utility for genetic disorders like CD.
Measurement of perceived healthcare discrimination and its implications on population health research: A systematic review protocol
Authors: Green Michael D. , Harlow Ashleigh B. , Janek Sarah E. , Weinfert Kevin P. , Skalla Lesley , O’Brien Emily C. , Brookhart M. Alan , Navar Ann Marie , Muhigaba Perusi , Bentley-Edwards Keisha L. , Dupre Matthew E. , Thorpe Roland J. 
Published: January 2025

AbstractPurposeDiscrimination in healthcare settings significantly impacts population health, affecting individuals of racial and ethnic minoritized identities, sexual and gender minoritized identities, and individuals with disabilities. Most measures of discrimination are derived from instruments assessing everyday discrimination experiences and do not adequately capture the specific nuances of healthcare-related discrimination. This systematic review protocol outlines a planned study that will evaluate and synthesize tools designed to measure discrimination in healthcare settings in the United States (U.S.). By providing a detailed overview of these measurement tools and their psychometric properties, this review will enhance understanding of healthcare discrimination and guide policy and practice towards improving health equity.MethodsA comprehensive search will be conducted across four databases (PubMed, Embase, PsycINFO, and Web of Science) and supplemented by citation tracking of reviewed articles. The review will focus on studies involving measurements of perceived discrimination within healthcare settings in the United States. The primary outcomes include the reliability, validity, and specificity of discrimination measurement instruments. Quality assessment will use the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) Risk of Bias tool. Our systematic review will be present findings based on the Preferred Reporting Items for Systematic Review and Meta-Analyses COnsensus-based Standards for the selection of Health Measurment INstruments of outcome measurements 2024 (PRISMA-COSMIN for OMIs 2024) reporting standard. The protocol is registered with PROSPERO (Registration number: CRD42024592267.DiscussionThis review will synthesize existing literature and offer a comprehensive evaluation of discrimination measurement tools to guide future health equity research. This review aims to contribute to the mitigation of healthcare inequities and the promotion of health equity by offering actionable insights into the measurement of discrimination in healthcare settings.
Novel Biomarkers of Immune Toxicity from CAR-T Cell Therapy Using Ultrasensitive NULISA™ Proteome Technology
Authors: Kirkpatrick Riley , Beer Joanne C. , Blaum Emily M. , Mian Agrima , Patel Manishkumar S. , Jalota Akansha , Ariyapala Ishara S. , Hao Qinyu , Feng Wei , Ma Xiao-Jun , Luo Yuling , Hill Brian T. , Gupta Neetu 
Published: January 2025

AbstractTranslational relevanceUsing serial samples from patients undergoing anti-CD19 CAR T-cell therapy and NULISATM, an assay with attomolar sensitivity, we identify novel plasma proteins associated with severe treatment-associated toxicities. This study not only reveals the evolution of proteomic biomarkers before and during therapy and their association with toxicities, it distinguishes between the induction and recovery phases, and provides insights into factors that may mediate chronic sequelae of CAR T-cell therapy. As the use of CAR T-cell therapy is limited by toxicities, especially in elderly patients or those with pre-existing comorbidities, being able to identify the patients who are at the highest risk for severe toxicities will allow for stratification strategies that would ultimately enable more widespread application of this cutting-edge therapy. Finally, this investigation reveals several potential therapeutic candidates to enable better management and pre-emptive mitigation of acute toxicities.PurposeThe efficacy of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL) patients is limited by acute toxicities, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Previous biomarker studies have been constrained by narrow protein panels and limited time points. We employed NULISATM, a novel ultrasensitive assay capable of simultaneously quantifying 204 proteins, to identify temporal proteome associations with acute toxicities in LBCL patients treated with anti-CD19 CAR T-cell therapy.Experimental DesignPlasma samples from 80 LBCL patients who underwent anti-CD19 CAR T-cell therapy, collected before and after cell infusion, were analyzed with NULISATM. Baseline demographics and treatment toxicities, including CRS and ICANS, were graded according to ASTCT consensus criteria. Differential protein abundance, pathway enrichment, and network analysis were performed.ResultsOur analysis revealed higher levels of the chemokines CXCL1, CX3CL1, and CCL8 associated with severe toxicity within the first two days of treatment. Thereafter, severe toxicity was marked by more abundant Th2 cell effector cytokines, IL4, IL5 and IL-13, markers of exhaustion, and TNF receptor superfamily proteins CTLA4, PDCD1, CD274, LAG3, TNFRSF1A, TNFRSF1B, and CD40. Finally, patients with severe toxicities showed lower levels of cell growth factors PDGFA and EGF, and the neuronal repair protein BDNF at the resolution stage.ConclusionsThis study represents the most comprehensive characterization of proteomic immune response to CAR T-cell therapy to date and identifies novel proteins, pathways, and networks associated with acute toxicity in the initiation and resolution phases, implicating them as potential biomarkers.
Physical activity and favourable adiposity genetic liability reduce the risk of hypertension among high body mass individuals
Authors: Hezekiah Chukwueloka , Pazoki Raha 
Published: January 2025

AbstractBackground and PurposeHypertension is a global health issue, and the risk factors include genetics, physical inactivity, and excess body fat (adiposity). Genetic predisposition to adiposity generally increases risk of hypertension. Several genetic variants have been identified to increase adiposity but unexpectedly reduce hypertension (favourable adiposity genes). Here, we tested the effect of these genetic variants on risk of hypertension in European ancestry participants under various scenarios of physical activity and body mass index.MethodsFavourable adiposity genetic liability was estimated using previously identified genetic variants and their effect sizes. The study analysed data from 230,027 unrelated participants in the UK Biobank. Logistic regression was used to examine the association between this genetic liability and hypertension (defined as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, or the use of anti-hypertensive medications). The analyses were conducted separately based on physical activity status (physically active and inactive) within low and high body mass groups.ResultsIndividuals with high body mass, could reduce their risk of hypertension by up to 16% depending on the favourable adiposity genetic liability and physical activity status (Padjusted= 1.32 x10-8). In high body mass individuals, physical activity alone contributes to 6-9% reduction in risk of hypertension.ConclusionThe study provides evidence that the protective effect of favourable adiposity on hypertension risk varies according to body mass composition and physical activity status.
Design and Validation of a Wearable Imaging System for Automated Wound Monitoring in Porcine Model
Authors: Hee Wan Shen , Tebyani Maryam , Baniya Prabhat , Franco Celeste , Keller Gordon , Lu Fan , Li Houpu , Asefifeyzabadi Narges , Yang Hsin-ya , Villa-Martinez Guillermo , Schorger Kaelan , Devarajan Koushik , Barbee Alexie , Hernandez Cristian , Nguyen Tiffany , Gomez Marcella , Isseroff Roslyn Rivkah , Rolandi Marco , Teodorescu Mircea 
Published: January 2025

AbstractEffective wound monitoring has the potential to guide treatment regiments and improve healing outcomes, yet current clinical assessment methods remain largely subjective and labor-intensive. To address this challenge, we present a high-resolution wearable imaging system designed for continuous wound monitoring. The system integrates a 64 MP camera with a plano-convex lens housed in an enclosure measuring 73 mm in diameter and 36.1 mm in height, and features a custom printed circuit board (PCB) for programmable LED illumination. The 3D-printed device enclosure is designed to accommodate a silicone bioelectronic device and can be securely attached using a commercially available ostomy skin barrier. In porcine model validation studies, the system successfully captured daily wound progression over periods up to 7 days. The captured images were wirelessly transmitted to a processing unit where DeepMapper, a machine learning algorithm, processed z-stacked images and performed multi-level feature extraction to predict wound healing stages and indicate potential complications such as infection. This imaging system enables automated analysis of wound progression and supports the development of smart wound care platforms for personalized treatment strategies. The integrated design approach demonstrates the feasibility of creating compact, high-resolution imaging systems suitable for clinical wound monitoring applications.
Defective DcpS Decapping Manifests in Creatine Deficiency Syndrome and Neurological impairment
Authors: Yang Jun , Palsule Geeta , Jiao Xinfu , Hart Ronald P. , Kiledjian Megerditch 
Published: January 2025

AbstractBiallelic mutations in theDCPSgene disrupting the decapping activity of the scavenger decapping protein DcpS, leads to neurodevelopmental deficiencies and intellectual disability. However, the molecular basis for the neurogenesis defects in these individuals remains unknown. Here we show that cells derived from individuals with aDCPSmutation harbor a creatine deficiency and a corresponding elevation of the creatine precursor, guanidinoacetate (GAA). The altered metabolite levels are a consequence of a reduction in both the mRNA and protein levels for the enzyme that converts GAA into creatine, guanidinoacetate methyltransferase. Importantly, the compromised neurogenesis and neurite outgrowth phenotypes observed during the differentiation of DcpS mutant patient derived induced pluripotent stem cell differentiation into neurons was reversed upon supplementation of creatine monohydrate. These findings suggest creatine deficiency as the major underlying factor for the neurogenetic defect detected in DcpS mutant cells and a potential driver of the neurological deficiencies in affected individuals.
Unique spatiotemporal synchronization solutions of heterogeneous local Ca2+dynamics underlie the formation of each impulse that emerges from the cardiac sinoatrial node
Authors: Tagirova Syevda , Maltsev Alexander V. , Baca Georgiana L. , Bychkov Rostislav , Maltsev Victor A. , Lakatta Edward G. 
Published: January 2025

AbstractSpontaneous, stochastic, local Ca2+oscillations (LCOs) that are heterogeneous in phase, frequency, and amplitude incessantly occur throughout the neuronal-like cytoarchitecture of the heart’s pacemaker, the sinoatrial node (SAN). How information encoded within ensembles of these heterogeneous LCOs is linked to the incessant emergence of the formation of rhythmic SAN impulses, however, is an unsolved problem. We applied a wide range of analytical techniques adapted from dynamical systems and neuroscience to map fine details of spatiotemporal distributions of local Ca2+dynamics in time-series of high-speed acquisition panoramic images of mouse SANsex vivo.Phase analysis delineated a network of functional pacemaker cell clusters, in which Ca2+dynamic amplitudes, kinetics, and phases were similar, but still differed from each other, and differed from those of other clusters. Local Ca2+dynamics within the network of clusters formed rhythmic global Ca2+impulses, with a mean rate identical to that recorded by the reference sharp electrode in the right atria. Initial conditions of each impulse initiation differed from each other, due mostly to stochastic nature of Ca2+dynamics within a small cluster located near the crista terminalis, having the highest intrinsic power, earliest rotor-like energy transfer, most frequent point-to-point instability, earliest acrophase, and greatest impulse-to-impulse variability within the network of functional clusters. A spontaneous, slowly increasing ensemble Ca2+signal within this cluster forms a foot of each CaT. Following this foot, the amplitude of the global CaT increased rapidly, due to rapid increases in the kinetics and amplitudes of Ca2+dynamics in some adjacent clusters. In other clusters near to the inter-atrial septum, a delayed, but rapid increase in the Ca2+dynamic occurred when the relaxation phase of the CaT had already begun.Orbit plots and Lyapunov exponent analyses detected both deterministic and stochastic features within the SAN Ca2+ dynamics. Correlation analyses detected cross-talk among the Ca2+dynamics withindifferent clustersthat varied, not only throughout an impulse, but also from one impulse to the next, forming unique dynamic small-world networks, assessed as ratios of the highest correlation coefficientsand shortest path lengths, ultimately creatinga uniquespatiotemporal Ca2+dynamic synchronization solution for each CaT. Thus, the emergence of each CaT from individual LCOs during each cycle is unique underlies cycle length variability in SAN, recapitulating the emergence of spontaneous CaTs in isolated, single, SAN pacemaker cells.
Left-right cortical interactions drive intracellular pattern formation in the ciliateTetrahymena
Authors: Lee Chinkyu , Joachimiak Ewa , Maier Wolfgang , Jiang Yu-Yang , Lechtreck Karl F. , Cole Eric S. , Gaertig Jacek 
Published: January 2025

SummaryIn ciliates, cortical organelles are positioned at precise locations along two polarity axes: anterior-posterior and circumferential (lateral). We explored the poorly understood mechanism of circumferential patterning, which generates left-right asymmetry. The model ciliateTetrahymenahas a single anteriorly-located oral apparatus. During cell division, a single new oral apparatus forms near the equator of the parental cell and along the longitude of the parental organelle. Cells homozygous forhypoangular 1(hpo1) alleles, assemble multiple oral apparatuses positioned either to the left or right flanking the normal oral longitude. We identifiedHPO1as a gene encoding an ARMC9-like protein. Hpo1 colocalizes with ciliary basal bodies, forming a bilateral concentration gradient with the high point on the cell’s right side and a sharp drop-off that marks the longitude at which oral development initiates on the ventral side. Hpo1 acts to exclude oral development from the cell’s right side. Hpo1 interacts with the Beige-Beach domain protein Bcd1, a cell’s left side-enriched factor, whose loss also confers formation of multiple oral apparatuses. A loss of both Hpo1 and Bcd1 is lethal and profoundly disrupts both positioning and organization of the forming oral apparatus (including its internal left-right polarity). We conclude that in ciliates, the circumferential/chiral patterning involves gradient-forming factors that are concentrated on either the cell’s right or left side and that the two sides of the cortex interact to create boundary effects that induce, position and shape developing cortical organelles.
Probabilistic Annotations of Protein Sequences for Intrinsically Disordered Features
Authors: Malhis Nawar 
Published: January 2025

AbstractThis paper introduces a novel platform for IDR Probabilistic Annotation (IPA). The IPA platform now encompasses tools for predicting ‘Linker’ regions and ‘nucleic’, ‘protein’, and ‘all’ (protein or nucleic) IDR binding sites within protein amino acid sequences. Despite its simplicity and computational efficiency, results demonstrate that IPA performs competitively with leading tools in predicting ‘protein’ and ‘all’ IDR binding sites while considerably outperforming all tools in identifying Linker regions and nucleic binding sites. An important contribution of this work is the introduction of a new output paradigm for computational feature predictions. Traditional tools typically express predictions as scores, with higher values indicating greater probabilities. However, these scores lack true probabilistic meaning and interpretability, even derived from logistic regression models. This limitation arises primarily because training data priors differ from broader populations’ unknown priors. This paper proposes applying a reverse Bayes Rule to logistic regression outputs, effectively normalizing for the priors in the training data. This adjustment produces scores representing actual probabilities, assuming 50% priors in the general population. Such scores are interpretable in isolation and enable comparability and integration across different tools, marking a significant step toward standardization in feature prediction methodologies.Availabilityorca.msl.ubc.ca/nmshare/ipa.tar.gz
The use of iconPCR for 16S library preparation improves data quality and workflow
Authors: Jouvenot Yann , Obert Caroline , Hale Brett , Metcalfe Kyle , Kaur Gagneet , Boddicker Andrew , Krivet Marielle , Zhao Junhua , Ben-Yehezkel Tuval , Patel Pranav 
Published: January 2025

AbstractPolymerase Chain Reaction (PCR) is a cornerstone of contemporary biological research, enabling the amplification of specific DNA sequences for various applications. However, suboptimal cycling conditions often undermine its efficacy, which can generate chimeric products, exacerbate PCR duplication rates, and skew species representation in metabarcoding experiments due to the preferential amplification of dominant populations.To address these limitations, we present iconPCR—Individually Controlled PCR—a novel technology that allows each reaction in a 96-well plate to be cycled independently and programmatically. By setting a predefined fluorescence threshold, iconPCR ensures that all Next Generation Sequencing (NGS) libraries are amplified to equivalent levels, thereby eliminating the risks of over- or under-amplification through a process known as “Auto-Normalization.”In this study, we applied iconPCR to generate V3, V4, and full-length 16S rRNA gene libraries using Avidite sequencing. The V1-V9 variable region libraries were also evaluated with HiFi sequencing, which significantly demonstrated its potential to improve microbial community analysis accuracy and reliability.