bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drivers and barriers to promoting self-care in individuals living with multimorbidity: a cross-sectional online survey of health and care professionals
Authors: Barber Susan , Hayhoe Benedict , Richardson Sonia , Norton John , Karki Manisha , El-Osta Austen 
Published: December 2023

AbstractObjectiveInvestigate knowledge, attitudes, and perceptions of health and care professionals (H&CPs) in England concerning drivers and barriers for promoting self-care in service-users with multimorbidity.DesignA cross-sectional online survey of the health and care workforce.SettingHealth and social care workforce.ParticipantsEighty-eight health and social care professionals in England.MethodsA cross-sectional online survey administered via Imperial College Qualtrics platform. Questions were asked about perceived drivers and barriers to promoting self-care in individuals with multimorbidity, including mental health.ResultsExtant barriers associated with service-users ability and opportunity to self-care were feelings of loneliness and social isolation (18.9%; n=61), mobility and access issues (14%; n=45). Strategies deployed by H&CPs to support self-care were social prescribing (17.9%; n=59), helping service-users to monitor their symptoms (15.2%; n=50), referring to recognised programmes to support self-management (13.9%; n=46), knowledge and understanding about the benefits of self-care (91.8%; n=67), the purposes of prescribed medicines (83.3%; n=60), and support for self-care (91.7%; n=66) were considered key drivers of successful self-management and to engagement between service-users and service providers. Service providers’ reported gaps in their knowledge including how to improve practical interactions to sustain health seeking behaviours by service-users (30.6%; n=49), health coaching (21.9%; n=35), improved understanding about effective self-care interventions (21.3%; n=34) and improving self-care in relation to medicines use (20%; n=32). Most respondents (92.2%; n=71) reported that the COVID-19 pandemic had highlighted the need for self-care, and (42.7%; n=32) agreed that the pandemic had a positive impact on their ability to promote self-care among service-users.ConclusionsSelf-care is important for service-users who live with multimorbidity. H&CPs are in a unique position to influence lifestyle choices and health-seeking self-care behaviours. Raising awareness about the importance of self-care, health literacy, knowledge, understanding and skills among service-users and providers is key to improving supported self-care.
Regional-specific calibration enables application of bioinformatic evidence for clinical classification of 5’ cis-regulatory variants in Mendelian disease
Authors: Villani Rehan M. , McKenzie Maddison E. , Davidson Aimee L. , Spurdle Amanda B. 
Published: December 2023

AbstractTo date, clinical genetic testing and approaches to classify genetic variants in Mendelian disease genes have focused heavily on exonic coding and intronic gene regions. This multi-step study was undertaken to provide an evidence base for selecting and applying bioinformatic approaches for use in clinical classification of 5’ cis-regulatory region variants. Curated datasets of rare clinically reported disease-causing 5’ cis-regulatory region variants, and variants from matched genomic regions in population controls, were used to calibrate six bioinformatic tools as predictors of variant pathogenicity. Likelihood ratio estimates were aligned to code weights following ClinGen recommendations for application of the American College of Medical Genetics (ACMG)/American Society of Molecular Pathology (AMP) classification scheme. Considering code assignment across all reference dataset variants, performance was best for CADD (81.2%) and REMM (81.5%). Optimized thresholds provided moderate evidence towards pathogenicity (CADD, REMM), and moderate (CADD) or supporting (REMM) evidence against pathogenicity. Both sensitivity and specificity of prediction were improved when further categorizing variants based on location in an EPDnew-defined promoter region. Combining predictions (CADD, REMM, and location in a promoter region) increased specificity at the expense of sensitivity. Importantly, the optimal CADD thresholds for assigning ACMG/AMP codes PP3 (≥10) and BP4 (≤8) were vastly different to recommendations for protein-coding variants (PP3 ≥ 25.3; BP4 ≤22.7); CADD <22.7 would incorrectly assign BP4 for >90% of reported disease-causing cis-regulatory region variants. Our results demonstrate the need to consider a tiered approach and tailored score thresholds to optimize bioinformatic impact prediction for clinical classification of cis-regulatory region variants.
Incidence and Trends in Ischemic Stroke and Mortality in Patients with and Without Type 2 Diabetes in Taiwan 2000-2018
Authors: Yen Fu-Shun , Wei James Cheng-Chung , Hsu Tzu-Ju , Shih Ying-Hsiu , Yeh Yun Kai , Hsu Chih-Cheng , Hwu Chii-Min 
Published: December 2023

BACKGROUNDStroke has a significant impact on life expectancy, comparable to that of cardiovascular disease in Asia. We conducted this longitudinal study to examine the incidence of ischemic stroke and 30-day mortality among persons with and without type 2 diabetes (T2D). We also compared outcomes between those over and under 60 years and between men and women.METHODSWe enrolled participants from the 2000 to 2018 National Health Insurance Research Database in Taiwan. Cox proportional-hazard models were used to examine the outcomes.RESULTSThe incidence of in-hospital ischemic stroke in patients with and without T2D had significant reductions of 64.42% and 55.63%, respectively. The relative risk of stroke associated with diabetes remained significantly higher (2.01 to 2.33 times) than non-diabetes. The relative risk of stroke in patients under 60 with T2D was 2.56 to 4.36 times higher than in those without T2D. Between 2000 and 2018, there was a significant 83.24% and 88.55% reduction in the risk of 30-day mortality after stroke in patients with and without T2D. There was no significant increase in the risk of 30-day mortality in people with diabetes compared to those without diabetes. However, the relative risk of death from stroke in patients under 60 years with diabetes was 1.63 to 2.49 times higher than in those without diabetes.CONCLUSIONSThis nationwide cohort study showed that the incidence of in-hospital ischemic stroke and 30-day mortality in patients with and without T2D exhibited a significant decreasing trend from 2000 to 2018. Patients with T2D had about twice the relative risk of ischemic stroke compared to those without T2D.
Multipair phase-modulated temporal interference electrical stimulation combined with fMRI
Authors: Savvateev Iurii , Missey Florian , Beliaeva Valeriia , Markicevic Marija , Kindler Diana , Razansky Daniel , Jirsa Viktor , Williamson Adam , Polania Rafael , Zerbi Valerio 
Published: December 2023

AbstractTemporal Interference Stimulation (TI) is a novel brain stimulation technique that aims to integrate the depth characteristic of conventional deep brain stimulation protocols with the non-invasive nature of transcranial electric stimulation. Recent publications in both mice and humans demonstrate that subcortical areas including hippocampus and striatum can be targeted using TI. However, whereas TI stimulation is set to be focused on a specific region of interest, other off-target areas may still be stimulated, including cortical structures. This is a major concern as off-target stimulation carries the risk of modulating unwanted brain structures and circuits. In the present study, we focused on the prefrontal cortex (PFC) in mice and developed a computational modelling approach to identify the best electrode locations for targeting PFC. Usingin-vivoelectrophysiological recordings and functional magnetic resonance imaging (fMRI) combined with TI, we confirmed the presence of induced TI fields and hemodynamic responses in the PFC but also identified off-target stimulated sites. To minimize the occurrence of off-target effects, we propose a new configuration with three electrode pairs, one of which has an active phase shift of 180 degrees in relation to the other two TI-inducing pairs. The use of this phase-canceling field allowed us to improve the focality of TI by reducing off-target stimulations without significantly affecting the TI field in the target area. The proposed design effectively addresses one of TI’s most critical shortcomings and opens new avenues for applications.
Phylogenomics recovers multiple origins of portable case-making in caddisflies (Insecta: Trichoptera), the world’s most common underwater architects
Authors: Frandsen Paul B. , Holzenthal Ralph W. , Espeland Marianne , Breinholt Jesse , Thomas Jessica A. , Simon Sabrina , Kawahara Akito Y. , Plotkin David , Hotaling Scott , Li Yiyuan , Nelson C. Riley , Niehuis Oliver , Mayer Christoph , Podsiadlowski Lars , Donath Alex , Misof Bernhard , Lemmon Emily Moriarty , Lemmon Alan , Morse John C. , Pauls Steffen , Zhou Xin 
Published: December 2023

AbstractCaddisflies (Trichoptera) are among the most diverse groups of freshwater animals with more than 16,000 described species. They play an outsized role in freshwater ecology and environmental engineering in streams, rivers, and lakes. Because of this, they are frequently used as indicator organisms in biomonitoring programs. Despite their importance, key questions concerning the evolutionary history of caddisflies, such as the timing and origin of larval case-making, have been unanswered due to the lack of a well-resolved phylogenetic tree. To shed light on these questions in Trichoptera, we estimated a phylogenetic tree using a combination of transcriptomes and targeted enrichment data for 206 species, representing 48 of 52 extant families and 174 genera. We calibrated and dated the tree with a set of 33 carefully selected fossils. The first caddisflies originated in the Permian and the major suborders began to diversify in the Triassic. Ancestral state reconstruction and diversification analysis revealed that portable case-making evolved in three separate lineages and shifts in diversification occurred in concert with key evolutionary innovations other than case-making.
A comparative analysis of planarian genomes reveals regulatory conservation in the face of rapid structural divergence
Authors: Ivankovic Mario , Brand Jeremias N. , Pandolfini Luca , Brown Tom , Pippel Martin , Rozanski Andrei , Schubert Til , Grohme Markus A. , Winkler Sylke , Robledillo Laura , Zhang Meng , Codino Azzurra , Gustincich Stefano , Vila-Farré Miquel , Zhang Shu , Papantonis Argyris , Marques André , Rink Jochen C. 
Published: December 2023

AbstractThe planarianSchmidtea mediterraneacan regenerate its entire body from small tissue fragments and is studied as regeneration model species. The assembly and functional analysis of planarian genomes has proven challenging due its high A/T content (70% A/T), repetitive nature, and limited transferability of routine laboratory protocols due to their divergent biochemistry. Only few and often fragmented genome assemblies are currently available, and open challenges include the provision of well-annotated chromosome-scale reference assemblies of the model species and other planarians for a comparative genome evolution perspective. Here we report a haplotype-phased, chromosome-scale genome assembly and high-quality gene annotations of the sexual S2 strain ofS. mediterraneaand provide putative regulatory region annotations via optimized ATAC-seq and ChIP-seq protocols. To additionally leverage sequence conservation for regulatory element annotations, we generated chromosome-scale genome assemblies and chromatin accessibility data for the three closest relatives ofS. mediterranea:S. polychroa,S. nova, andS. lugubris. We find substantial divergence in protein-coding sequences and regulatory regions, yet reveal remarkable conservation in ChIP-mark bearing open chromatin regions identified as promoters and enhancers inS. mediterranea. The resulting high-confidence set of evolutionary conserved enhancers and promoters provides a valuable resource for the analysis of gene regulatory circuits and their evolution within the taxon. In addition, our four chromosome-scale genome assemblies provide a first comparative perspective on planarian genome evolution. Our analyses reveal frequent retrotransposon-associated chromosomal inversions and inter-chromosomal translocations that lead to a degradation of synteny across the genus. Interestingly, we further find independent and near-complete losses of the ancestral metazoan synteny acrossSchmidteaand two other flatworm groups, indicating that platyhelminth genomes largely evolve without syntenic constraints. Our work provides valuable genome resources for the planarian research community and sets a foundation for the comparative genomics of planarians. We reveal a contrast between the fast structural evolution of planarian genomes and the conservation of their regulatory elements, suggesting a unique genome evolution in flatworms where gene positioning may not be essential.
Comparative genomic analysis reveals novel phylogenetically intermediate Streptococci with high phenotypic diversity in the human distal lung microbiota
Authors: Kanungo Slipa , Bonilla-Rosso Germán , Sarton-Lohéac Garance , Kuffer Marianne , Hilty Markus , Geiser Thomas , Engel Philipp , Das Sudip 
Published: December 2023

AbstractStreptococci are one of the predominant and the most diverse genus in the human lung. Previously, we isolated human distal lung Streptococci from bronchoalvolear lavage fluid (BALF) as part of the human Lung Microbiota culture Collection (LuMiCol). Here, we performed whole genome sequencing, comparative phylogenomics and phenotypic characterization of six Streptococcal isolates representing the phylogenetic diversity of the genus in distal human lung. Here, we report five new species and one new subspecies including phylogenetic intermediates of commonly found Streptococci not limited to human lung. Pangenome analysis reveals gene content, evolutionary relationships, and metabolic functions shedding light on contribution of these Streptococci to lung microbial metabolism. Antimicrobial resistance gene analysis followed by MIC determination revealed macrolide, lincosamide and tetracycline resistance in lung Streptococci. We show the presence of capsular genes in lung streptococci both matching to the prototypical capsular genes (cps) and unique genes. Interestingly, the newStreptococcusisolate sp. nov. P2E5, genetically identical to the most prevalentStreptococcusin the human distal lung was revealed to be a phylogenetic intermediate between theS. mitisgroup andS. pneumoniae.It also harbors the pneumolysin (ply) gene and was found to have the serotype 21E. Finally, core genome phylogeny reveals that lung Streptococci the are evolutionary distinct from oral Streptococcal isolates in expanded Human Oral Microbiome Database (eHOMD). Hence, these findings we reveal new phylogenetically distinct Streptococcal species from the human distal lung microbiota and its genetic diversity and metabolism to understand the microbial ecology of human lung.ImportanceA healthy human distal lung harbour characteristic microbial communities mostly composed of oropharyngeal taxa, which are facultative or obligative anaerobes despite lung being the medium of oxygen intake. However, little is known about the genetic and functional diversity of these bacteria owing to the lack of resources including availability of primary lung isolate from human samples. Therefore, we have established a large bacterial collection that covers all major phyla by cultivating human bronchoalveolar lavage fluid (BALF) under various conditions.Streptococcusis the most prevalent and diverse genera in the human lung microbiota. Using genetic and biochemical approaches, we studied six diverse lung isolates from our collection representing the actual Streptococcal diversity and identify these as new species and subspecies. We hypothesize that learning about the phylogenetic genetic diversity, preferred metabolism and molecular structures of these Streptococci will provide with new insights on the understudied microbial ecosystem of the human lung.
Antibody-mediated depletion of select T cell subsets in blood and tissue of nonhuman primates
Authors: Sutton Matthew S. , Bucsan Allison N. , Lehman Chelsea C. , Kamath Megha , Pokkali Supriya , Magnani Diogo M. , Seder Robert , Darrah Patricia A. , Roederer Mario 
Published: December 2023

AbstractUnderstanding the immunological control of pathogens requires a detailed evaluation of the mechanistic contributions of individual cell types within the immune system. While knockout mouse models that lack certain cell types have been used to help define the role of those cells, the biological and physiological characteristics of mice do not necessarily recapitulate that of a human. To overcome some of these differences, studies often look towards nonhuman primates (NHPs) due to their close phylogenetic relationship to humans.To evaluate the immunological role of select cell types, the NHP model provides distinct advantages since NHP more closely mirror the disease manifestations and immunological characteristics of humans. However, many of the experimental manipulations routinely used in mice (e.g., gene knock-out) cannot be used with the NHP model. As an alternative, thein vivoinfusion of monoclonal antibodies that target surface proteins on specific cells to either functionally inhibit or deplete cells can be a useful tool. Such depleting antibodies have been used in NHP studies to address immunological mechanisms of action. In these studies, the extent of depletion has generally been reported for blood, but not thoroughly assessed in tissues.Here, we evaluated four depleting regimens that primarily target T cells in NHP: anti-CD4, anti-CD8α, anti-CD8β, and immunotoxin-conjugated anti-CD3. We evaluated these treatments in healthy unvaccinated and IV BCG-vaccinated NHP to measure the extent that vaccine-elicited T cells – which may be activated, increased in number, or resident in specific tissues – are depleted compared to resting populations in unvaccinated NHPs. We report quantitative measurements ofin vivodepletion at multiple tissue sites providing insight into the range of cell types depleted by a given mAb. While we found substantial depletion of target cell types in blood and tissue of many animals, residual cells remained, often residing within tissue. Notably, we find that animal-to-animal variation is substantial and consequently studies that use these reagents should be powered accordingly.
Suppression of piriform cortex alters brain-wide dynamics and alleviates seizures in temporal lobe epilepsy
Authors: Zhang Huiqi , Chiu Arthur , Jiang Hehai , Choi Harry M. C. , Huang Zhuo , Lau Chunyue Geoffrey 
Published: December 2023

AbstractTemporal lobe epilepsy (TLE) is a pathological state that involves altered excitation-inhibition (E-I) in the brain and exhibits recurrent seizures. Many circuit studies of TLE have focused on the hippocampus. Anterior piriform cortex (APC) is also a limbic area closely associated with TLE, but is understudied. In the APC, parvalbumin-expressing (PV+) interneurons provide strong inhibition and help maintain E-I balance. However, whether APCPVneurons play a causal role in TLE is unclear.We used the systemic pilocarpine and intrahippocampal kainic acid (KA) mouse models, which showed pathological changes and spontaneous recurrent seizures (SRSs) akin to those observed in patients with TLE. Whole-cell patch clamp recording and immunohistochemistry were used to examine inhibitory synaptic transmission in the pilocarpine model. Then, using chemogenetics and multi-site local field potential (LFP) recording, we manipulated APCPVneurons at different periods, before applying convulsant, during status epilepticus (SE) and in chronic epileptic phase, and examined the efficacy of APCPVneuronal activation on seizures. For chronic period experiments, KA-injected mice underwent four-site longitudinal LFP recordings. We quantified SRSs based on the frequency and duration of epileptic discharges (> 2 Hz, 10 seconds). For the underlying functional network dynamics, we analyzed the power of each recording site and functional connectivity of each pair of regions in four epileptic states, preictal, ictal, postictal and interictal.In the pilocarpine model, we found impaired synaptic inhibition and loss of PV synapses in the APC. APCPVneuronal pre-activation decreased seizure susceptibility and mortality, but could not stop an ongoing SE. In the chronic KA model, activation of APCPVneurons reduced the frequency and duration of SRSs in the hippocampus. Interestingly, APCPVneuronal activation altered the brain-wide dynamics of seizure network and afforded differential modulation based on epileptic states, brain regions and frequency bands.Our work demonstrates the causal role of APCPVin TLE and provides detailed functional characterization of mechanisms underlying the effectiveness of APCPVactivation. We reveal how a cortical microcircuit can alter neural activity in multiple brain regions and exert antiepileptic benefits. These findings strengthen the idea that large-scale connections from APC play a key role in maintaining the E-I balance of the entire seizure network and thus provide the basis for future circuit-based therapies.
Piezo1-induced durotaxis of pancreatic stellate cells depends on TRPC1 and TRPV4 channels
Authors: Budde Ilka , Schlichting André , Ing David , Schimmelpfennig Sandra , Kuntze Anna , Fels Benedikt , Romac Joelle M-J , Swain Sandip M , Liddle Rodger A , Stevens Angela , Schwab Albrecht , Pethő Zoltán 
Published: December 2023

AbstractPancreatic stellate cells (PSCs) are primarily responsible for producing the stiff tumor tissue in pancreatic ductal adenocarcinoma (PDAC). Thereby, PSCs generate a stiffness gradient between the healthy pancreas and the tumor. This gradient induces durotaxis, a form of directional cell migration driven by differential stiffness. The molecular sensors behind durotaxis are still unclear. To investigate the role of mechanosensitive ion channels in PSC durotaxis, we established a two-dimensional stiffness gradient mimicking PDAC. Using pharmacological and genetic methods, we investigated the role of the ion channels Piezo1, TRPC1, and TRPV4 in PSC durotaxis. We found that PSC migration towards a stiffer substrate is diminished by altering Piezo1 activity. Moreover, disrupting TRPC1 along with TRPV4 abolishes PSC durotaxis even when Piezo1 is functional. Hence, PSC durotaxis is optimal with an intermediary level of mechanosensitive channel activity, which we simulated using a numerically discretized mathematical model. Our findings suggest that mechanosensitive ion channels, particularly Piezo1, detect the mechanical microenvironment to guide PSC migration.SummaryCells move towards regions with higher stiffness in a process called durotaxis. This study shows that ion channels Piezo1, TRPV4, and TRPC1 are crucial sensors in pancreatic stellate cells. They act together to orchestrate durotaxis of pancreatic stellate cells which may be relevant in pancreatic cancer.