bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large-scale CSF proteome profiling identifies biomarkers for accurate diagnosis of Frontotemporal Dementia
Authors: Hok-A-Hin Yanaika S. , Vermunt Lisa , Peeters Carel F.W. , van der Ende Emma L. , de Boer Sterre C.M. , Meeter Lieke H. , van Swieten John C. , Hu William T. , Lleó Alberto , Alcolea Daniel , Engelborghs Sebastiaan , Sieben Anne , Chen-Plotkin Alice , Irwin David J. , van der Flier Wiesje M. , Pijnenburg Yolande A.L. , Teunissen Charlotte E. , del Campo Marta 
Published: August 2024

AbstractDiagnosis of Frontotemporal dementia (FTD) and the specific underlying neuropathologies (frontotemporal lobar degeneration; FTLD-Tau and FTLD-TDP) is challenging, and thus fluid biomarkers are needed to improve diagnostic accuracy. We used proximity extension assays to analyze 665 proteins in cerebrospinal fluid (CSF) samples from a multicenter cohort including patients with FTD (n = 189), Alzheimer’s Disease dementia (AD; n = 232), and cognitively unimpaired individuals (n = 196). In a subset, FTLD neuropathology was determined based on phenotype or genotype (FTLD-Tau = 87 and FTLD-TDP = 68). Forty three proteins were differentially regulated in FTD compared to controls and AD, reflecting axon development, regulation of synapse assembly, and cell-cell adhesion mediator activity pathways. Classification analysis identified a 14- and 13-CSF protein panel that discriminated FTD from controls (AUC: 0.96) or AD (AUC: 0.91). Custom multiplex panels confirmed the highly accurate discrimination between FTD and controls (AUCs > 0.96) or AD (AUCs > 0.88) in three validation cohorts, including one with autopsy confirmation (AUCs > 0.90). Six proteins were differentially regulated between FTLD-TDP and FTLD-Tau, but no reproducible classification model could be generated (AUC: 0.80). Overall, this study introduces novel FTD-specific biomarker panels with potential use in diagnostic setting.
Psychometric Evaluation of the Japanese Yale-Brown Obsessive Compulsive Scale Modified for Olfactory Reference Disorder (ORD-YBOCS-J)
Authors: Sano Nanako , Greenberg Jennifer L. , Yoshida Saran 
Published: August 2024

AbstractObjectiveThe Yale-Brown Obsessive Compulsive Scale Modified for Olfactory Reference Syndrome (ORS-YBOCS) is a self-rated measure for assessing the severity of current olfactory reference disorder (ORD) symptoms. This scale has been translated into multiple languages and used in previous studies. However, its psychometric properties have not been investigated. The present study aimed to develop a Japanese ORS-YBOCS (newly named the ORD-YBOCS) and examine its reliability and validity.MethodsA total of 104 individuals with self-reported ORD symptoms were included (mean age = 30.20 years,SD= 10.25). Internal consistency and factor structure were assessed by calculating Cronbach’s alpha and conducting confirmatory factor analysis (CFA) respectively. Convergent and divergent validity were examined via correlations with measures of Jikoshu-Kyofu symptoms, body image concerns, depression, and fear of negative evaluation.ResultsThe Japanese ORD-YBOCS had good internal consistency (α= .81) and acceptable construct validity (r= .43 with Jikoshu-Kyofu symptoms,r= .20 with body image concerns,r= .56 with depression, andr= .27 with fear of negative evaluation). The scree plot suggested a one-factor model, but the CFA results did not support this (CFI = 0.76, TLI = 0.70, RMSEA = 0.14, and SRMR = 0.10).ConclusionThis is the first study to examine the psychometric properties of the self-report ORS-YBOCS. The linguistically validated Japanese ORD-YBOCS showed good internal consistency and acceptable validity. These results suggest that the Japanese ORD-YBOCS is a valid and reliable tool to measure ORD symptom severity.
Physical activity and tobacco smoking in the German adult population
Authors: Acar Zeynep , Jackson Sarah , Klosterhalfen Stephanie , Kotz Daniel 
Published: August 2024

ABSTRACTBackgroundPhysical inactivity and tobacco smoking remain leading causes of morbidity and mortality worldwide. In Germany, smoking prevalence is high at around 30% and only 45% achieve the World Health Organization recommendation for physical activity (PA). Understanding how smoking and physical inactivity co-occur can inform interventions targeting these behaviours.MethodsWe analysed data from 4,073 adults (≥18 years) participating in a national household survey between April and July 2022. We tested the association between PA level (not=reference/low/medium/very active) and smoking status (never=reference/ex/current smoker). Among current smokers, we tested associations between PA level and cigarettes smoked per day; time spent with, and strength of, urges to smoke; and motivation to stop smoking.ResultsOverall, 29.9% (95%CI=28.5;31.4) reported no leisure time PA; among current smokers it was 39.8% (95% CI=37.3;42.4). Higher PA levels were associated with lower odds of being a current vs. never smoker (OR=0.74, 95%CI=0.69;0.79). Among current smokers, higher PA levels were associated with smoking fewer cigarettes per day (β=-0.98,95%CI=- 1.39;-0.56), weaker urges to smoke (OR=0.81,95%CI=0.74;0.89), and higher motivation to stop smoking (OR=1.13,95%CI=1.02;1.24). Time spent with urges to smoke showed a small overlap in the upper CI (OR=0.93,95%CI=0.85;1.02).ConclusionPeople who are more physically active are less likely to smoke. Current smokers with higher PA levels smoke less, are less dependent, and more motivated to quit. Further research is required to determine whether these associations are causal and, if so, whether interventions to increase PA could help people to quit smoking.What is already known on this topicSmokers are more likely to be physically inactive than non-smokers. The more cigarettes they smoke, the greater their risk of being physically inactive. Therefore, people who are physically inactive and smoke cigarettes have an increased risk of chronic diseases and premature death.What this study addsOur study adds detailed data on the relationships between physical activity (PA) levels and smoking habits in the German adult population. To build on existing studies that have explored the link between PA levels and either smoking status or the amount of cigarettes smoked per day, we also examined the associations between PA levels and both nicotine dependence and the motivation to quit smoking.How this study might affect research, practice or policyThese results indicate a clear need to increase PA levels in the population and reduce smoking prevalence. Understanding the relationships between PA levels and smoking habits can aid in developing prevention strategies and targeting specific groups, such as current smokers. Additionally, this knowledge can inform the design of effective public health campaigns on PA and smoking, highlighting the association between these behaviours. More research is needed to determine whether associations are causal.
Considerations for Equitable Distribution of Digital Healthcare for People Who Use Drugs
Authors: Papalamprakopoulou Zoi , Roussos Sotirios , Ntagianta Elisavet , Triantafyllou Vasiliki , Kalamitsis George , Dharia Arpan , Sypsa Vana , Hatzakis Angelos , Talal Andrew H. 
Published: August 2024

AbstractBackgroundTelehealth holds the potential to expand healthcare access for people who use drugs (PWUD). However, approaches to increase PWUDs’ access to digital healthcare are not well-understood. We studied digital healthcare accessibility among PWUD.MethodsWe employed respondent-driven sampling to recruit 162 PWUD in Athens, Greece to collect data via a structured questionnaire. Participants were aged at least 18 years and had an injection drug use (IDU) history. We assessed current internet and computer access, and experience with telemedicine. We utilized logistic regression to evaluate sociodemographic associations.ResultsParticipants’ mean (standard deviation) age was 45.9 (8.8) years, 84.0% were male, 90.1% Greek, 77.8% reported IDU within the past year, 85.2% were not linked to opioid treatment, and 50.0% were currently experiencing homelessness. Only 1.9% had experience and 46.3% had familiarity with telemedicine. Internet and computer access were reported by 66.0% and 31.5% of participants, respectively. Compared to participants with secure housing, those currently experiencing homelessness reported decreased internet (50.6% vs 81.5%, p<0.001) and computer access (11.1% vs 51.9%, p<0.001). Multivariable analyses revealed that older age (per 1-year increase: odds ratio [OR]=0.94, 95% confidence interval [CI] [0.89, 0.99], p=0.03), IDU within the past year (0.29 [0.10, 0.88], p=0.03), and homelessness (0.29, [0.13, 0.65], p=0.003) were associated with lower odds of internet access. Homelessness was associated with lower odds of computer access (0.17, [0.07, 0.41], p<0.001).ConclusionsInternet and infrastructure challenges, homelessness, and digital literacy gaps should be considered to bridge the digital divide and ensure equitable digital healthcare distribution for PWUD.Clintrials.govregistration number:NCT05794984
Altered neural recruitment despite dual task performance recovery in athletes with repeat concussion
Authors: Hagen Andrew C. , Tracy Brian L , Stephens Jaclyn A. 
Published: August 2024

AbstractSports-related concussions (SRCs) pose significant challenges to college-aged athletes, eliciting both immediate symptoms and subacute cognitive and motor function impairment. While most symptoms and impairments resolve within weeks, athletes with repeat SRCs may experience heightened risk for prolonged recovery trajectories, future musculoskeletal injuries, and long-term neurocognitive deficits. This includes impaired dual task performance and altered neurophysiology that could persist across the lifespan and elicit future pathophysiology and neurodegeneration. Thus, it is imperative to improve our understanding of neurophysiology after SRC. This study aimed to investigate the impact of repeat SRCs on dual task performance and associated neural recruitment using functional near-infrared spectroscopy (fNIRS).A total of 37 college-aged athletes (ages 18-24) participated in this cross-sectional observational study. Among these athletes, 20 had a history of two or more SRCs, while 17 had never sustained a SRC and served as controls. Participants completed the Neuroimaging-Compatible Dual Task Screen (NC-DTS) while fNIRS measured neural recruitment in the frontoparietal attention network and the primary motor and sensory cortices.Behavioral analysis revealed that athletes with repeat SRCs exhibited comparable single task and dual task performance to control athletes. Additionally, dual task effects (DTE), which capture performance declines in dual tasks versus single tasks, did not significantly differ between groups. Notably, the cohort of athletes with repeat SRC in this study had a longer time since their last SRC (mean = 1.75 years) than majority of previous SRC studies. Neuroimaging results indicated altered neural recruitment patterns in athletes with multiple repeat SRCs during both single and dual tasks. Specifically, athletes with repeat SRCs demonstrated increased prefrontal cortex (PFC) activation during single motor tasks compared to controls (P< 0.001,d= 0.47). Conversely, during dual tasks, these same athletes exhibited reduced PFC activation (P< 0.001,d= 0.29) and primary motor cortex (M1) activation (P= 0.038,d= 0.16) compared to their single task activation.These findings emphasize the complex relationship between SRC history, dual task performance, and changes in neurophysiology. While athletes with repeat SRCs demonstrate recovery in behavioral dual task performance, persistent alterations in neural recruitment patterns suggest ongoing neurophysiological changes, possibly indicating compensatory neural strategies and inefficient neural resource allocation, even beyond symptom resolution and medical clearance. Understanding the compensatory neural recruitment strategies that support behavioral performance following repeat SRCs can inform return-to-play decisions, future musculoskeletal injury risk, and the long-term impact of SRCs on neurocognitive function.
The Detection of Xylazine in Tijuana, Mexico: Triangulating Drug Checking and Clinical Urine Testing Data
Authors: Friedman Joseph R. , Montoya Alejando González , Ruiz Carmina , González Tejeda Mariana Alejandra , Segovia Luis A. , Godvin Morgan E. , Sisco Edward , Pyfrom Elise M. , Appley Meghan G. , Shover Chelsea L. , Bufanda Lilia Pacheco 
Published: August 2024

AbstractIntroductionXylazine is a veterinary anesthetic increasingly present alongside illicit fentanyl in the US and Canada, presenting novel health risks. Although xylazine remains less common in the Western US, Mexican border cities serve as key trafficking hubs and may have higher prevalence of novel substances, but surveillance has been limited.MethodsWe examined deidentified records from the Prevencasa harm reduction clinic in Tijuana, describing urine and paraphernalia testing from patients reporting using illicit opioids within 24 hr. Xylazine (two types), fentanyl, opiate, methamphetamine, amphetamine, benzodiazepine, and nitazene test strips were used to test urine and paraphernalia samples. Paraphernalia samples were also analyzed with mass spectrometry.ResultsThe study consisted of 23 participants that provided both urine and paraphernalia samples. Of the participants studied, 100 %, 91.3 %, and 69.6 % reported using China White/fentanyl, methamphetamine, and tar heroin, respectively. The mean age was 41.7 years, 95.7 % were male, 65.2 % were unhoused, and 30.4 % had skin wounds at the time of sample collection.Xylazine positivity in urine, for the two types used, was 82.6 % and 65.2 %. For paraphernalia testing, the xylazine positivity was 65.2 % and 47.8 %. Confirmatory testing of paraphernalia samples by mass spectrometry indicated a 52.2 % xylazine positivity. This testing also revealed positivity rates for fentanyl (73.9 %), fluorofentanyl (30.4 %), tramadol (30.4 %), and lidocaine (30.4 %).The mass spectrometry results suggest lidocaine triggeredn= 3 andn= 0 false positives among the xylazine test strip types. A total ofn= 0 andn= 1 false negatives were also observed.DiscussionXylazine is present on the U.S.-Mexico border, requiring public health intervention. High lidocaine positivity complicates the clinical detection of xylazine via testing strips. Xylazine was found to be more prevalent in urine than in paraphernalia samples. Confirmatory urine studies are needed to better understand possible complications of using test strips for toxicological testing.
Enhanced Diversifying Selection on Polymerase Genes in H5N1 Clade 2.3.4.4b: A Key Driver of Altered Species Tropism and Host Range Expansion
Authors: Misra Sougat , Gilbride Elizabeth , Ramasamy Santhamani , Pond Sergei L. Kosakovsky , Kuchipudi Suresh V. 
Published: August 2024

AbstractHighly pathogenic avian influenza H5N1 clade 2.3.4.4b viruses have shown unprecedented host range and pathogenicity, including infections in cattle, previously not susceptible to H5N1. We investigated whether selection pressures on clade 2.3.4.4b viral genes could shed light on their unique epidemiological features. Our analysis revealed that while the gene products of clade 2.3.4.4b H5N1 primarily undergo purifying selection, there are notable instances of episodic diversifying selection. Specifically, the polymerase genes PB2, PB1, and PA exhibit significantly greater selection pressures in clade 2.3.4.4b than all earlier H5N1 virus clades. Polymerases play critical roles in influenza virus adaptation, including viral fitness, interspecies transmission, and virulence. Our findings provide evidence that significant selection pressures have shaped the evolution of the H5N1 clade 2.3.4.4b viruses, facilitating their expanded host tropism and the potential for further adaptation to mammalian hosts. We discuss how exogenous factors, such as altered bird migration patterns and increased host susceptibility, may have contributed to the expanded host range. As H5N1 viruses continue to infect new hosts, there is a greater risk of emergent novel variants with increased pathogenicity in humans and animals. Thus, comprehensive One Health surveillance is critical to monitor transmission among avian and mammalian hosts.
mobileRNA: a tool for efficient analysis of mobile RNA molecules in multiple genomes
Authors: Jeynes-Cupper Katie , Catoni Marco 
Published: August 2024

AbstractIn plants, mobile RNA molecules play a significant role in long distance signalling, with evidence of transport mechanisms and functional roles for both mobile messenger RNA (mRNA) and small RNA (sRNA) molecules. The movement of RNAs between distant tissues can be revealed in plant grafting experiments involving different genotypes (hetero-grafting) associated to genomic analysis, using the natural polymorphisms between the genotypes to discriminate between RNAs produced in the sampled tissue from those which have travelled from distant organs. However, the hight level of noise in the analyses of RNA sequencing datasets involving two different genotypes, and the lack of a standardised pipeline for the analysis of grafted plants, make the identification of natural mobile RNA molecules a challenge. Here, we introduce a pipeline integrated into an R package,mobileRNA, which performs simultaneous alignment of RNA sequencing samples on a merged reference genome. Using simulated datasets, we show thatmobileRNAcan identify putative mobile RNAs with unprecedented efficiency in absence of post-processing steps.
Using Functional Genomic Data in Monocytes/Macrophages and Genotyping to Nominate Disease-Driving Single Nucleotide Polymorphisms and Target Genes in Juvenile Idiopathic Arthritis
Authors: Haley Emma K. , Barshad Gilad , He Adam , Rice Edward , Sudman Marc , Thompson Susan D. , Crinzi Elizabeth A. , Jiang Kaiyu , Danko Charles G. , Jarvis James N. 
Published: August 2024

AbstractIntroductionGWAS have identified multiple regions that confer risk for juvenile idiopathic arthritis (JIA). However, identifying the single nucleotide polymorphisms (SNPs) that drive disease risk is impeded by the SNPs’ that identify risk loci being in linkage disequilibrium (LD) with hundreds of other SNPs. Since the causal SNPs remain unknown, it is difficult to identify target genes and use genetic information to inform patient care. We used genotyping and functional data in primary human monocytes/macrophages to nominate disease-driving SNPs on JIA risk haplotypes and identify their likely target genes.MethodsWe identified JIA risk haplotypes using Immunochip data from Hinks et al (Nature Gen 2013) and the meta-analysis from McIntosh et al (Arthritis Rheum 2017). We used genotyping data from 3,939 children with JIA and 14,412 healthy controls to identify SNPs that: (1) were situated within open chromatin in multiple immune cell types and (2) were more common in children with JIA than the controls (p< 0.05). We intersected the chosen SNPs (n=846) with regions of bi-directional transcription initiation characteristic of non-coding regulatory regions detected using dREG to analyze GRO-seq data. Finally, we used MicroC data to identify gene promoters interacting with the regulatory regions harboring the candidate causal SNPs.ResultsWe identified 190 SNPs that overlap with dREG peaks in monocytes and126 SNPs that overlap with dREG peaks in macrophages. Of these SNPs, 101 were situated within dREG peaks in both monocytes and macrophages, suggesting that these SNPs exert their effects independent of the cellular activation state. MicroC data in monocytes identified 20 genes/transcripts whose promoters interact with the enhancers harboring the SNPs of interest.ConclusionSNPs in JIA risk regions that are candidate causal variants can be further screened using functional data such as GRO-seq. This process identifies a finite number of candidate causal SNPs, the majority of which are likely to exert their biological effects independent of cellular activation state in monocytes. Three-dimensional chromatin data generated with MicroC identifies genes likely to be influenced by these SNPs. These studies demonstrate the importance of investigations into the role of innate immunity in JIA.
Molecular Visualization of Neuronal TDP43 PathologyIn Situ
Authors: Erwin Amanda L. , Chang Matthew L. , Fernandez Martin G. , Attili Durga , Russ Jennifer E. , Sutanto Renaldo , Pinarbasi Emile S. , Bekier Michael , Brant Tyler S. , Hahn Terry , Dykstra Megan , Thomas Dafydd , Li Xingli , Baldridge Ryan D. , Tank Elizabeth M. H. , Barmada Sami J. , Mosalaganti Shyamal 
Published: August 2024

AbstractNuclear exclusion and cytoplasmic accumulation of the RNA-binding protein TDP43 are characteristic of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite this, the origin and ultrastructure of cytosolic TDP43 deposits remain unknown. Accumulating evidence suggests that abnormal RNA homeostasis can drive pathological TDP43 mislocalization, enhancing RNA misprocessing due to loss of nuclear TDP43 and engendering a cycle that ends in cell death. Here, we show that adding small monovalent oligonucleotides successfully recapitulates pathological TDP43 mislocalization and aggregation in iPSC-derived neurons (iNeurons). By employing a multimodalin situcryo-correlative light and electron microscopy pipeline, we examine how RNA influences the localization and aggregation of TDP43 in near-native conditions. We find that mislocalized TDP43 forms ordered fibrils within lysosomes and autophagosomes in iNeurons as well as in patient tissue, and provide the first high-resolution snapshots of TDP43 aggregatesin situ. In so doing, we provide a cellular model for studying initial pathogenic events underlying ALS, FTLD, and related TDP43-proteinopathies.
Towards Digital Quantification of Ploidy from Pan-Cancer Digital Pathology Slides using Deep Learning
Authors: Carrillo-Perez Francisco , Cramer Eric M. , Pizurica Marija , Andor Noemi , Gevaert Olivier 
Published: August 2024

ABSTRACTAbnormal DNA ploidy, found in numerous cancers, is increasingly being recognized as a contributor in driving chromosomal instability, genome evolution, and the heterogeneity that fuels cancer cell progression. Furthermore, it has been linked with poor prognosis of cancer patients. While next-generation sequencing can be used to approximate tumor ploidy, it has a high error rate for near-euploid states, a high cost and is time consuming, motivating alternative rapid quantification methods. We introduce PloiViT, a transformer-based model for tumor ploidy quantification that outperforms traditional machine learning models, enabling rapid and cost-effective quantification directly from pathology slides. We trained PloiViT on a dataset of fifteen cancer types from The Cancer Genome Atlas and validated its performance in multiple independent cohorts. Additionally, we explored the impact of self-supervised feature extraction on performance. PloiViT, using self-supervised features, achieved the lowest prediction error in multiple independent cohorts, exhibiting better generalization capabilities. Our findings demonstrate that PloiViT predicts higher ploidy values in aggressive cancer groups and patients with specific mutations, validating PloiViT potential as complementary for ploidy assessment to next-generation sequencing data. To further promote its use, we release our models as a user-friendly inference application and a Python package for easy adoption and use.