bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attitudes towards deprescribing in patients with multimorbidity and polypharmacy in primary care
Authors: Shantsila Eduard , Woodall Alan , Mair Frances S , Abuzour Aseel S , Bollegala Danushka , Cant Harriet , Clegg Andrew , Gabbay Mark , Griffiths Alan , Hama Layik , Harmsworth-King James , Jones Benedict , Leeming Gary , Lo Emma , Maskell Simon , O’Connell Maurice , Popoola Olusegun , Relton Samuel , Aslam Asra , Ruddle Roy A , Schofield Pieta , Sperrin Matthew , Van Staa Tjeerd , Wilson Samantha , Buchan Iain , Walker Lauren E 
Published: December 2024

AbstractBackgroundPopulation ageing has led to an increase in multimorbidity and polypharmacy. Some medications may need to be stopped, but patient attitudes towards deprescribing are poorly understood. This study explores attitudes towards (de)prescribing in patients with multimorbidity in the UK primary care.MethodsPatients with multimorbidity were invited to complete the Revised Patients’ Attitudes Towards Deprescribing (rPATD) Questionnaire using an Evergreen Life’s Personal Health Record App (Manchester, UK). The responses were linked to electronic health records. Anonymised data were analysed in a trusted research environment (University of Liverpool) for group comparisons and using multivariable logistic regression to identify factors associated with satisfaction with current medications.ResultsA total 1,019 patients participated in the study (n=365 aged <65, 30% males; n=654 ≥65, 57% males). Most patients were satisfied with their current medications (74% aged <65, 70% aged ≥65) but were willing to stop one or more of their regular medicines if their doctor said it was possible (82%, 68% accordingly). Polypharmacy, use of antihypertensive drugs, and antidepressants were associated with patient-reported burden in taking medicines. Frailty did not influence patient deprescribing attitudes. Patients who were satisfied with current medications had fewer medications. Independent predictors of satisfaction with current medications were higher total involvement and appropriateness scores, and lower total burden score.ConclusionsMost patients with multimorbidity would consider stopping some of their medications, even when they are generally satisfied with the treatments they received. Frailty status does not imply willingness to stop medications. Clinicians should discuss medication deprescribing for shared decision.
Qualitative Evaluation of the Work Lifestyle-integrated Functional Exercise Program for Older Employees (wLiFE55+) from Participants’ Perspectives
Authors: Pfister Diana , Ritter Yvonne , Steckhan Greta M. , Voelter-Mahlknecht Susanne , Weber Britta , Augustin Sankt , Ellegast Rolf , Augustin Sankt , Gruber Markus , Schwenk Michael 
Published: December 2024

AbstractBackgroundThe rise in older employees and physical inactivity necessitates targeted health and exercise promotion approaches. Physical training has positive health effects; however, traditional offerings are often underutilized due to time constraints or lack of motivation. The wLiFE55+ program offers a promising approach by integrating neuromotor, strength, and physical activity activities into daily routines with minimal time commitment. There is a high demand for workplace physical activity intervention (WPAI) with sustainable implementation. This study evaluated the wLiFE55+ program, designed for employees aged 55+, focusing on (1) participants’ perspectives on its components and (2) gathering insights for further development.MethodsThe wLiFE55+ program was piloted in a four-week study with a pre-post design. Participants attended four personal trainer sessions and integrated neuromotor, strength, and physical activities into their daily routines. Two focus groups (n=8) were conducted post-program. Half of the focus group participants (mean age 58.5 years, SD = 3.1) were female (5 full-time, 3 part-time), with low to moderate physical activity levels at work and varying functional performance. Audio recordings were transcribed and analyzed using deductive qualitative content analysis. Participants’ statements were categorized into predefined categories, creating a structured analysis system. Three main categories were applied to the transcripts.ResultsThe focus groups demonstrated a balanced distribution of speech contributions, with an average participation rate of 12.5% per participant. In total, 313 statements were categorized into three main areas: “Overall Program” (59), “Program Content” (137), and “Behavioral Change” (117). Participant feedback highlighted requests for more practice time, targeted communication, and precise feedback about progress (“Overall Program”). Personal trainer support and tailoring of activities were evaluated positively (“Program Content”). High motivation existed at the start of the study but challenges in executing the program at the workplace were reported (“Behavioral Change”).ConclusionOverall, the wLiFE55+ program was well-received as a workplace physical activity intervention (WPAI), particularly for the support provided by personal trainers, the activities included, and participants’ progress. The wLiFE55+ program has shown potential as a WPAI, and areas for improvement were identified, such as more communication, digitizing the documentation process, and simplifying activity planning.
Modeling Insights into Potential Mechanisms of Opioid-Induced Respiratory Depression within Medullary and Pontine Networks
Authors: Olsen Wendy L. , Hayes John A. , Shuman Dale , Morris Kendall F. , Bolser Donald C. 
Published: December 2024

ABSTRACTThe opioid epidemic is a pervasive health issue and continues to have a drastic impact on the United States. This is primarily because opioids cause respiratory suppression and the leading cause of death in opioid overdose is respiratory failure (i.e., opioid-induced respiratory depression, OIRD). Opioid administration can affect the frequency and magnitude of inspiratory motor drive by activating µ-opioid receptors that are located throughout the respiratory control network in the brainstem. This can significantly affect ventilation and blunt CO2responsiveness, but the precise neural mechanisms that suppress breathing are not fully understood. Previous research has suggested that opioids affect medullary and pontine inspiratory neuron activity by disrupting upstream elements within this circuit.Inspiratory neurons within this network exhibit synchrony consistent with shared excitation from other neuron populations and recurrent mechanisms. One possible target for opioid suppression of inspiratory drive are excitatory synapses. Reduced excitability of these synaptic elements may result in disfacilitation and reduced synchrony among inspiratory neurons. Downstream effects of disfacilitation may result in abnormal output from phrenic motoneurons resulting in distressed breathing. We tested the plausibility of this hypothesis with a computational model of the respiratory network by targeting the synaptic excitability in fictive medullary and pontine populations. The synaptic conductances were systematically decreased while monitoring the overall respiratory motor pattern and aggregate firing rates of subsets of cell populations. Simulations suggest that highly selective, rather than generalized, actions of opioids on synapses within the inspiratory network may account for different observed breathing mechanics.
Post-transcriptional modifications on tRNA fragments confer functional changes to high-density lipoproteins in atherosclerosis
Authors: Semler Elizabeth M. , Michell Danielle L. , Kingsley Philip J. , Massick Clark , Ramirez Marisol A. , Castleberry Mark A. , Doran Amanda C. , Carr John J. , Marnett Lawrence J. , Sheng Quanhu , Linton MacRae F. , Vickers Kasey C. 
Published: December 2024

SUMMARYEpitranscriptomic modifications on RNA play critical roles in stability, processing, and function, partly by influencing interactions with RNA-binding proteins and receptors. The role of post-transcriptional RNA modifications on cell-free non-coding small RNA (sRNA) remains poorly understood in disease contexts. High-density lipoproteins (HDL), which transport sRNAs, can lose their beneficial properties in atherosclerosis cardiovascular disease (ASCVD). We hypothesize that changes to regulatory modifications on HDL-sRNAs contribute to this dysfunction. To assess changes in HDL-sRNA modification status, HDL-derived RNA from healthy subjects and those with atherosclerotic lesion development were analyzed using LC-MS/MS and AlkB-facilitated RNA (de)Methylation Sequencing. ASVD-HDL showed an enrichment in modified nucleosides including m1A tRNA-derived sRNAs (tDRs), particularly tDR-ArgACG-1. Functional studies revealed that ASCVD-HDL induced cell adhesion genes, including TMEM123, in primary macrophages. Recombinant HDL loaded with m1A-tDR-ArgACG-1 induced immune signaling, and similarly upregulated TMEM123. These findings suggest HDL-delivered-m1A-tDR-ArgACG-1 act on adhesion genes and immune pathways, promoting macrophage activation.
Cell type transcriptional identities are maintained in culturedex vivohuman brain tissue
Authors: McGinnis JP , Ortiz-Guzman Joshua , Mallannagari Sai , Guevara Maria Camila , Belfort Benjamin D. W. , Bao Suyang , Srivastava Snigdha , Morkas Maria , Ji Emily , Katlowitz Kalman A. , Addison Angela , Tantry Evelyne K. , Blessing Melissa M. , Mohila Carrie A. , Gadgil Nisha , McClugage Samuel G. , Bauer David F. , Whitehead William E. , Aldave Guillermo , Tanweer Omar , Jaleel Naser , Jalali Ali , Patel Akash J. , Sheth Sameer A. , Weiner Howard L. , Gopinath Shankar , Rao Ganesh , Harmanci Akdes Serin , Curry Daniel , Arenkiel Benjamin R. 
Published: December 2024

AbstractIt is becoming more broadly accepted that human-based models are needed to better understand the complexities of the human nervous system and its diseases. The recently developed human brain organotypic culture model is one highly promising model that requires the involvement of neurosurgeons and neurosurgical patients. Studies have investigated the electrophysiological properties of neurons in suchex vivohuman tissues, but the maintenance of other cell types within explanted brain remains largely unknown. Here, using single-nucleus RNA sequencing, we systematically evaluate the transcriptional identities of the various cell types found in six patient samples after fourteen days in culture (83,501 nuclei from day 0 samples and 45,738 nuclei from day 14 samples). We used two pediatric temporal lobectomy samples, an adult frontal cortex sample, two IDH wild-type glioblastoma samples, and one medulloblastoma sample. We found remarkably high correlations of day 14 transcriptional identities to day 0 tissue, especially in tumor cells (r = 0.90 to 0.93), though microglia (r = 0.86), oligodendrocytes (r = 0.80), pericytes (r = 0.77), endothelial cells (r = 0.78), and fibroblasts (r = 0.76) showed strong preservation of their transcriptional profiles as well. Astrocytes and excitatory neurons showed more moderate preservation (r = 0.66 and 0.47, respectively). Because the main difficulty with organotypic brain cultures is the acquisition of human tissue, which is readily available to neurosurgeons, this model is easily accessible to neurosurgeon-scientists and neurosurgeons affiliated with research laboratories. Broad uptake of this more representative model should prompt advances in our understanding of many uniquely human diseases, lead to more reliable clinical trial performance, and ultimately yield better therapies for our patients.
A deep learning method for predicting interactions for intrinsically disordered regions of proteins
Authors: Majila Kartik , Ullanat Varun , Viswanath Shruthi 
Published: December 2024

SummaryIntrinsically disordered proteins or regions (IDPs/IDRs) adopt diverse binding modes with different partners, ranging from ordered to multivalent to fuzzy conformations in the bound state. Characterizing IDR interfaces is challenging experimentally and computationally. Alphafold-multimer and Alphafold3, the state-of-the-art structure prediction methods, are less accurate at predicting IDR binding sites at their benchmarked confidence cutoffs. Their performance improves upon lowering the confidence cutoffs. Here, we developed Disobind, a deep-learning method that predicts inter-protein contact maps and interface residues for an IDR and a partner protein, given their sequences. It outperforms AlphaFold-multimer and AlphaFold3 at multiple confidence cutoffs. Combining the Disobind and AlphaFold-multimer predictions further improves the performance. In contrast to most current methods, Disobind considers the context of the binding partner and does not depend on structures and multiple sequence alignments. Its predictions can be used to localize IDRs in integrative structures of large assemblies and characterize and modulate IDR-mediated interactions.
The TUTase URT1 regulates the transcriptome of seeds and their primary dormancy
Authors: Peter Jackson , Roignant Jeanne , Sacharowski Sebastian , Ubrig Elodie , Lefèvre Benjamin , Swiezewski Szymon , Gagliardi Dominique , Zuber Hélène 
Published: December 2024

AbstractRNA uridylation is a pervasive mechanism that regulates the degradation of eukaryotic mRNAs. In Arabidopsis, uridylation influences mRNA decay both by favoring 5’ to 3’ degradation and by preventing excessive deadenylation. Yet, the significance of mRNA uridylation during plant development remains largely unknown. Here, we adapted FLEP-seq2, a method based on nanopore sequencing, to generate a comprehensive inventory of mRNA uridylation events in different Arabidopsis tissues. We also evaluated the respective contribution of the two known Arabidopsis uridylyltransferases, URT1 and HESO1, in mRNA uridylation. Our transcriptome-wide analysis showed that, URT1 is the main enzyme responsible for mRNA uridylation, in all analyzed tissues, while HESO1 can marginally uridylate mRNAs. Importantly, our results revealed the singularity of mRNA uridylation pattern in seeds and the dual function of URT1-dependent uridylation in shaping the transcriptome during seed maturation. We propose that during seed maturation, URT1-dependent uridylation promotes the elimination of unnecessary translation-associated mRNAs, by facilitating their degradation, while also promoting the accumulation of mRNAs associated with the maturation program, by hindering their deadenylation. In line with its important function in shaping the seed transcriptome, our study also identifies URT1 as a novel regulator of seed dormancy. Overall, our study reveals the biological relevance of mRNA uridylation during seed maturation.
Tonic sound-evoked motility of cochlear outer hair cells in mice with impaired mechanotransduction
Authors: Dewey James B. 
Published: December 2024

ABSTRACTCochlear outer hair cells (OHCs) transduce sound-induced vibrations of their stereociliary bundles into receptor potentials that drive changes in cell length. While fast, phasic OHC length changes are thought to underlie an amplification process required for sensitive hearing, OHCs also exhibit large tonic length changes. The origins and functional significance of this tonic motility are unclear. Here,in vivocochlear vibration measurements reveal tonic, sound-induced OHC motility in mice with stereociliary defects that impair mechanotransduction and eliminate cochlear amplification. Tonic motility in impaired mice was physiologically vulnerable but weakly related to any residual phasic motility, possibly suggesting a dissociation between the underlying mechanisms. Nevertheless, a simple model demonstrates how tonic responses in both normal and impaired mice can result from asymmetric mechanotransduction currents and be large even when phasic motility is undetectable. Tonic OHC responses are therefore not unique to sensitive ears, though their potential functional role remains uncertain.
Distinct Microbiomes Underlie Divergent Responses of Methane Emissions from Diverse Wetland soils to Oxygen Shifts
Authors: Reji Linta , Duan Jianshu , Myneni Satish , Zhang Xinning 
Published: December 2024

ABSTRACTHydrological shifts in wetlands, a globally important methane (CH4) source, are critical constraints on CH4emissions and carbon-climate feedbacks. A limited understanding of how hydrologically driven oxygen (O2) variability affects microbial CH4cycling in diverse wetlands makes wetland CH4emissions uncertain. Transient O2exposure significantly stimulated anoxic CH4production in incubations ofSphagnumpeat from a temperate bog by enriching for polyphenol oxidizers and polysaccharide degraders, enhancing substrate flow toward methanogenesis under subsequent anoxic conditions. To assess whether shifts in soil microbiome structure and function operate similarly across wetland types, here we examined the sensitivity of different wetland soils to transient oxygenation. In slurry incubations ofSphagnumpeat from a minerotrophic fen, and sediments from a freshwater marsh and saltmarsh, we examined temporal shifts in microbiomes coupled with geochemical characterization of slurries and incubation headspaces. Oxygenation did not affect microbiome structure and anoxic CH4production in mineral-rich fen-origin peat and freshwater marsh soils. Key taxa linked to O2-stimulated CH4production in the bog-origin peat were notably rare in the fen-origin peat, supporting microbiome structure as a primary determinant of wetland response to O2shifts. In contrast to freshwater wetland experiments, saltmarsh geochemistry—particularly pH—and microbiome structure were persistently and significantly altered post-oxygenation, albeit with no significant impact on greenhouse gas emissions. These divergent responses suggest wetlands may be differentially resilient to O2fluctuations. With climate change driving greater O2variability in wetlands, our results inform mechanisms of wetland resiliency and highlight microbiome structure as a potential resiliency biomarker.
Quantitative Characterization and Prediction of the Binding Determinants and Immune Escape Hotspots for Groups of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling of the SARS-CoV-2 Spike Complexes with Antibodies
Authors: Alshahrani Mohammed , Parikh Vedant , Foley Brandon , Raisinghani Nishank , Verkhivker Gennady 
Published: December 2024

AbstractThe growing body of experimental and computational studies suggested that the cross-neutralization antibody activity against Omicron variants may be driven by balance and tradeoff of multiple energetic factors and interaction contributions of the evolving escape hotspots involved in antigenic drift and convergent evolution. However, the dynamic and energetic details quantifying the balance and contribution of these factors, particularly the balancing nature of specific interactions formed by antibodies with the epitope residues remain scarcely characterized. In this study, we performed molecular dynamics simulations, ensemble-based deep mutational scanning of SARS-CoV-2 spike residues and binding free energy computations for two distinct groups of broadly neutralizing antibodies : E1 group (BD55-3152, BD55-3546 and BD5-5840) and F3 group (BD55-3372, BD55-4637 and BD55-5514). Using these approaches, we examine the energetic determinants by which broadly potent antibodies can largely evade immune resistance. Our analysis revealed the emergence of a small number of immune escape positions for E1 group antibodies that correspond to R346 and K444 positions in which the strong van der Waals and interactions act synchronously leading to the large binding contribution. According to our results, E1 and F3 groups of Abs effectively exploit binding hotspot clusters of hydrophobic sites critical for spike functions along with selective complementary targeting of positively charged sites that are important for ACE2 binding. Together with targeting conserved epitopes, these groups of antibodies can lead to the expanded neutralization breadth and resilience to antigenic shift associated with viral evolution. The results of this study and the energetic analysis demonstrate excellent qualitative agreement between the predicted binding hotspots and critical mutations with respect to the latest experiments on average antibody escape scores. We argue that E1 and F3 groups of antibodies targeting binding epitopes may leverage strong hydrophobic interactions with the binding epitope hotspots critical for the spike stability and ACE2 binding, while escape mutations tend to emerge in sites associated with synergistically strong hydrophobic and electrostatic interactions.
Simpler predictive models provide higher accuracy for ovarian cancer detection
Authors: Wood Derrick E. , Roy Joseph , Ballew Bari J. 
Published: December 2024

AbstractOvarian cancer remains a danger to women’s health, and accurate screening tests would likely increase survival. Two established protein biomarkers, CA125 and HE4, have been shown to work well in isolation, but achieve even higher accuracy when combined using logistic regression (LR). We show here that this LR-based combination of protein concentrations achieves high accuracy when distinguishing healthy samples from cancer samples (AUC = 0.99) and benign masses from cancer (AUC = 0.86). This approach exhibits superior performance on an external validation cohort compared to a more complex method, which was published with the dataset we use here and tested on the same data. While our method only uses proteins, the more complex method also uses features derived from cell-free DNA (cfDNA). We show that many of that method’s cfDNA features are affected by confounding technical variation, which impacts the previously reported results. Our results are in line with the principle that simpler machine learning models will tend to exhibit better generalizability on new data.
To Peck or Not To Peck: The influence of early-life social environment on response inhibition and impulsive aggression in Japanese quails
Authors: Vernouillet Alizée , Willcox Kathryn , Allaert Reinoud , Dewulf Anneleen , Zhang Wen , Troisi Camille A. , Knoch Sophia , Martel An , Lens Luc , Verbruggen Frederick 
Published: December 2024

1SummaryDeficits in response inhibition (i.e., the ability to suppress inappropriate responses) may contribute to increased impulsive aggression (i.e., unplanned behaviors that harm others). Since early-life environment might influence the development of response inhibition, it could also indirectly affect impulsive aggression. However, this relationship has rarely been directly examined. Here, we investigated whether response inhibition is associated with impulsive aggression and whether this relationship explains the effects of early-life social environments on impulsive aggression in Japanese quails (Coturnix japonica). Quails (n= 120) were raised in two social conditions: Small groups of five birds or Large groups of 15 birds. Response inhibition was assessed using the Barrier and Cylinder tasks, while impulsive aggression was measured in two contexts - within a group of five familiar individuals and in a dyad with an unfamiliar individual. We found that some aspects of response inhibition were related to impulsive aggression. Furthermore, quails reared in small groups showed significantly poorer response inhibition than those reared in large groups. Yet, impulsive aggression did not significantly differ between the two conditions. These findings suggest that, while impulsive aggression is partly related to response inhibition, other factors mitigate the effects of early social environments on its expression.