bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detailed mapping of mesothelioma cases in Denmark to identify areas with elevated risk: a nationwide population-based study
Authors: Christensen Heidi Søgaard , Jensen Rikke Hedegaard , Nielsen Lars Hernández , Bertelsen Lise Dueholm , Teglgaard Christian , Bønløkke Jakob , Severinsen Marianne Tang , Bøgsted Martin 
Published: January 2025

AbstractObjectivesPrevious studies mapping pleural mesothelioma in Denmark have found that the risk varies between Danish regions. However, evaluating disease risk for such relatively large geographical units ignores any heterogeneity within the unit and can thus diminish more local spikes in risk, missing smaller areas of excess risk. In this study, we examined the distribution of pleural mesothelioma in Denmark on an unprecedented detailed scale, mapping cases to each of the Danish parishes.MethodsWe identified individuals diagnosed with pleural mesothelioma between 1990 and 2021 in the Danish Cancer Registry. Considering age- and sex-standardised incidence rate ratios, we used a conditional autoregressive random effects model to smooth incidence rate ratios across parishes. Parishes with a smoothed parish-to-national incidence rate ratio higher than 1.25 or 2.0 with a posterior probability of more than 95% were flagged as parishes with an excess risk of pleural mesothelioma.ResultsWe identified 3105 incident cases of pleural mesothelioma in the study period. A total of 73 and 14 parishes were flagged with incidence rate ratios significantly above 1.25 and 2.0, respectively. The flagged parishes had smoothed incidence rate ratios ranging from 1.80 to 4.65.ConclusionsWe provided a detailed mapping of pleural mesothelioma cases in Denmark and found five distinct areas, each covering several parishes, with a significantly elevated risk. All these areas were in the proximity of previous asbestos-using industries.
Explanatory factors for the occurrence of the cholera epidemic in the Kadutu health zone, city of Bukavu in the Democratic Republic of Congo
Authors: Kachelewa Bonhomme Kalimira , Ngondo Denise , Mata Henry , Kokolomami Jack , Bobanga Thiery Lengu , Kyloka Jean Nyandwe 
Published: January 2025

AbstractBackgroundThe Kadutu Health Zone (HZK) in Bukavu, located in the east of the Democratic Republic of Congo, is one of the areas most affected by cholera. This study aims to identify the factors explaining the occurrence of cholera epidemics in this region.MethodsA case-control study was conducted between January and June 2024, with a sample drawn from cholera cases of the 2023 outbreak. A questionnaire was administered to 112 cases and 224 controls. Data were analyzed using SPSS v 25 software.ResultsThe results revealed nine factors significantly associated with the onset of the epidemic: low monthly income (OR = 2.49; p = 0.010), non-washing of hands before eating (OR = 25.85; p < 0.001) and before breastfeeding (OR = 3.06; p = 0.006), lack of hygiene of soiled hands (OR = 19.37; p < 0.001), defecation outside the toilet (OR = 4.54; p < 0.001), recourse to traditional practitioners (OR = 3.28; p = 0.033), lack of toilets (OR = 2.07; p = 0.017), and lack of knowledge of the modes of transmission (OR = 2.94; p = 0.032) and prevention (OR = 1.75; p = 0.037).ConclusionCholera prevention in the HZK requires a multisectoral approach, taking into account sociodemographic, economic, environmental, cultural and health factors.
A pragmatic randomized controlled trial of artificial intelligence (AI)-based predictive analytics monitoring for early detection of clinical deterioration
Authors: Keim-Malpass Jessica , Ratcliffe Sarah J , Clark Matthew T , Krahn Katy N , Monfredi Oliver J , Hamil Susan , Yousevfand Gholamreza , Jones Marieke K , Nelson Ashley , Moorman Liza P , Moorman J. Randall , Bourque Jamieson M 
Published: January 2025

ABSTRACTBackgroundThis pragmatic randomized controlled trial aimed to assess the effect of a passive display of artificial intelligence (AI)-based predictive analytics on hours free of clinical deterioration events among medical and surgical patients in an acute care cardiology medical-surgical ward.Methods10,422 inpatient visits were randomly assigned by cluster to the intervention group of a display of risk trajectories or to a control group of usual medical care. The trial was undertaken on an 85-bed inpatient cardiology and cardiac surgery ward of an academic hospital with a substantial implementation and education plan. This was a passive display with no specific response mandated. The primary analysis compared events of clinical deterioration (death, emergent ICU transfer, emergent endotracheal intubation, cardiac arrest, or emergent surgery) and compared mortality 21 days after admission.ResultsPatients with a large spike in risk score had, on average, twice the length of hospital stay (6.8 compared to 3.4 days). There was no change in the primary outcome between groups. Among those who had a clinical event, there were more event-free hours in the intervention/display-on group compared to the standard-of-care/display-off, but this did not approach statistical significance. 11% of patients were transferred into or out of display beds, a censoring event removing them from the analysis, thereby undermining aspects of the randomized nature of the study.ConclusionPredictive analytics monitoring incorporating continuous cardiorespiratory monitoring and displays of risk trajectories coupled with an education plan did not improve patient outcomes or reduce deaths. While necessary to conduct the study, the pragmatic design allowed for significant movement towards intervention/displayed beds for sicker patients. Design considerations in the future must focus on understanding clinicians’ interpretation, care processes, and communication practices.Trial registrationNCT04359641
Sparks fade with distance: The effect of electric field distribution on global motion perception using different tES techniques
Authors: Pavan Andrea , Ghin Filippo , Contillo Adriano , Akyuz Sibel , Campana Gianluca 
Published: January 2025

AbstractPrevious evidence has shown that high frequency transcranial random noise stimulation (hf-tRNS) decreases motion coherence thresholds when a cephalic montage (i.e., return over Cz) is used. Extracephalic montages have also been employed to modulate behavioral performance, eliminating stimulation of regions under the return electrode. In this study, we examined the effects of different transcranial electrical stimulation (tES) protocols on visual motion discrimination, placing the return electrode on the ipsilateral arm. We assessed the impact of electrode localization using hf-tRNS, anodal, cathodal transcranial direct current stimulation (tDCS), and Sham stimulation over hMT+, a brain region involved in global motion perception. Motion direction discrimination was measured using random dot kinematograms (RDKs). Due to the increased distance between the stimulation and return electrodes in this montage, we expected a smaller reduction in motion discrimination thresholds compared to our previous study. The results suggest that increased interelectrode distance mitigates the efficacy of hf-tRNS. Additionally, no significant effects were observed with the other tES protocols tested. Our findings imply that the positioning of the two electrodes affects current flow characteristics, leading to reduced neuromodulation. These results underscore the importance of stimulation configuration, particularly the effect of interelectrode distance on performance. Given the widespread application of brain stimulation techniques in clinical and cognitive research, our results can guide future studies in carefully considering this further aspect of stimulation montage configurations.
Delayed copulation and mating in the malaria vectorAnopheles funestuscompared toAnopheles arabiensis
Authors: Hape Emmanuel Elirehema , Ngonyani Alex Thadei , Mabula Daniel Mathias , Nkya Joel Daniel , Thomas Claus Augustino , Omari Mohamed Jumanne , Siria Doreen Josen , Ngowo Halfan Said , Koekemoer Lizette Leonie , Okumu Fredros Oketch 
Published: January 2025

AbstractMating is a vital behavior for mosquito reproduction, yet it remains poorly understood under captive conditions. We examined the copulation dynamics of two key malaria vectors,Anopheles funestus, andAnopheles arabiensis, in controlled laboratory settings in Tanzania. We observed how variations in mosquito age and artificial lighting influence mating success for these two mosquito species within cages under controlled conditions. We conducted observations in 24-hour cycles, monitoring copulation events and insemination in females. We used generalized linear mixed models (GLMMs) for statistical analyses to assess how environmental conditions influence mating behavior. We found thatAnopheles arabiensisexhibited rapid copulation, with 32.4% of individuals mating by Day 3 post-emergence, whileAn. funestusshowed delayed activity, reaching a similar mating rate by Day 8. The introduction of artificial red light significantly accelerated copulation inAn. funestusbut did not affectAn. arabiensis. Dissection confirmed successful sperm transfer and mating plug delivery in over 92% of copulating pairs for both species. Mating occurred primarily at night, with distinct peaks at 22:00 forAn. arabiensisand 23:00 forAn. funestus. In conclusion, our findings reveal species-specific differences in reproductive behavior, which could improve the colonization ofAn. funestus, a species historically challenging to rear in captivity. These insights may also inform the development of new vector control technologies, such as sterile insect techniques and genetic-based approaches, that exploit mosquito mating behaviors.
Variation in genome architecture and epigenetic modification across the microsporidia phylogeny
Authors: Angst Pascal , Ebert Dieter , Fields Peter D. 
Published: January 2025

AbstractMicrosporidia are a model clade for studying intracellular parasitism, being well-known for their streamlined genomes and their extreme life history. Although microsporidia are highly diverse and ecologically important to a broad range of hosts, previous research on genome architecture has focused primarily on the mammal-infecting genusEncephalitozoon. Here, we expand that work, testing the universality of the patterns observed inEncephalitozoonby investigating and comparing variation in genetic and epigenetic architectures in the high-quality genome assemblies of several major microsporidia clades. Our comparison of nine genomes, including the first genome assemblies ofBinucleata daphniae,Gurleya vavrai, andConglomerata obtusa, and revised, improved assemblies ofGlugoides intestinalisandOrdospora colligata, found limited conservation of genetic and epigenetic architecture across all microsporidia, although many genomic characteristics, such as nucleotide composition and repeat content, were shared between genomes of the same or related clades. For example, rRNA genes were hypermethylated in all species, but their position close to chromosome ends was only found in theEncephalitozoonand its sister clade. GC- content varied widely, linked to genome size, phylogenetic position and activity of repeat elements. These findings enhance our insight into genome evolution and, consistent with findings from other systems, suggest epigenetic modification as a regulatory mechanism of gene expression and repeat element activity in microsporidia. Our comparative genome analysis reveals higher variation among microsporidia than previously supposed.
Valosin-containing Protein is Cargo in Amyloid Precursor Protein Extracellular Vesicles
Authors: Lu Yue , Abdullah Mohammad , Healy Liam R. , Tambini Marc D. 
Published: January 2025

ABSTRACTThe Amyloid Precursor Protein (APP), a genetic cause of Alzheimer’s disease (AD), is a type-I transmembrane protein that is metabolized by proteolysis in the endolysomal system. APP and its metabolites are secreted by cells in extracellular vesicles (EVs). To study the function of APP-containing EVs, we isolated App-EVs from rat primary neuronal conditioned media and proteomic analysis identified the Valosin-containing protein (Vcp) as molecular cargo. Pharmacological modulation of Vcp activity was found to alter App processing and global EV secretion in rat primary neurons. AD-associated knock-inAppmutations were found to alter the abundance of App-EVs and the trafficking of App metabolites within App-EVs, in a manner related to the epitopes generated by the nonamyloidogenic processing of App. The presence of Vcp suggests a role for App-EVs in the clearance of protein aggregates.
Phosphoinositide- and Collybistin-Dependent Synaptic Clustering of Gephyrin
Authors: Burdina Nele , Liebsch Filip , Macha Arthur , Ortuño Gil Joaquín Lucas , Frommelt Pia , Rais Irina , Basler Fabian , Pöpsel Simon , Schwarz Guenter 
Published: January 2025

ABSTRACTGephyrin is the main scaffolding protein at inhibitory synapses clustering glycine and GABA type A receptors. At specific GABAergic synapses, the nucleotide exchange factor collybistin recruits gephyrin to the postsynaptic membrane via interaction with phosphoinositides. However, the molecular mechanisms underlying the formation, maintenance and regulation of collybistin-dependent gephyrin clusters remain poorly understood.This study sheds light on the molecular mechanism of gephyrin cluster formation based on gephyrin self-oligomerization induced by collybistin, leading to the formation of a high-molecular weight (>5 MDa) gephyrin-collybistin complex, which is regulated in two ways: First, plasma-membrane phosphoinositides promote complex formation demonstrating their critical role in membrane targeting and stabilization of gephyrin-collybistin clusters at postsynaptic sites. Second, gephyrin phosphorylation at Ser325 abolishes complex formation with collybistin thus impairing collybistin-dependent gephyrin clustering at GABAergic synapses. Collectively, our data demonstrates a molecular mechanism for synaptic clustering of gephyrin which involves collybistin- and phosphoinositide-dependent formation of high-molecular gephyrin oligomers.
Identifying mood instability and circadian rest-activity patterns using digital remote monitoring and actigraphy in participants at risk for bipolar disorder
Authors: Panchal Priyanka , Nelissen Natalie , McGowan Niall M. , Atkinson Lauren Z. , Saunders Kate E. A. , Harrison Paul J. , Rushworth Matthew , Draschkow Dejan , Geddes John , Nobre Anna C. , Harmer Catherine J. 
Published: January 2025

AbstractMood instability and circadian rhythm disruptions are both of increasing interest with regard to a number of psychiatric disorders, notably bipolar disorder (BD), but understanding of their nature and their interrelationship are incomplete. By definition, both have an integral temporal component and, as such, measuring them longitudinally and remotely is desirable.We conducted the Cognition and Mood Evolution across Time (COMET) study to assess the feasibility and value of digital devices to capture mood, its instability, and daily rest-activity patterns, over a 10-week period, in two groups of participants. The first group (n=37) were selected as scoring>7 on the Mood Disorder Questionnaire (MDQ) (‘high MDQ’), thereby having a history of mood elevation and being at risk for BD. They were compared with a group (n=37) scoring<5 on the MDQ (‘low MDQ’). Over a 10-week period, using a tablet, mood was rated daily, clinical ratings of depression, mania, and anxiety were captured weekly via the True Colours app, and a GENEactiv actigraph was worn to capture rest-activity pattern data.The main findings are that (1) MDQ score predicts mood instability; (2) high MDQ score is associated with more negative affect and mood symptoms than people with low MDQ, and with a different circadian activity profile; and (3) mood instability and circadian indices appear uncorrelated.The implications are that (1) remote monitoring of these domains is feasible and valuable; (2) selection of participants based on MDQ score is useful for studying mood (in)stability; and (3) the approach has potential for studies of clinical populations and for experimental medicine studies assessing interventions to reduce mood instability.
Local nucleolar surveillance mechanisms maintain rDNA stability
Authors: Liu Ruofei , Xuan Jiachen , Pan Junqi , Chelliah Shalini Sundramurthi , Dmello Rhynelle , Cowley Karla J. , Mendez Shannon , Zhang Yangyi , Gitareja Kezia , Wakefield Matthew , Deans Andrew , Scott Clare , Chan Keefe T. , Simpson Kaylene J. , Kang Jian , Sanij Elaine 
Published: January 2025

AbstractThe nucleoli are subdomains of the nucleus that form around actively transcribed ribosomal RNA (rRNA) genes. The highly repetitive and transcribed nature of the rRNA genes (rDNA) by RNA polymerase I (Pol I) poses a challenge for DNA repair and replication machineries. Here, we profile the nucleolar proteome and the chromatin landscape of stalled replication sites upon rDNA damage to characterize the early steps of nucleolar DNA damage response (nDDR). We observed early dynamics in nucleolar-nucleoplasmic proteome localization and identified nucleolar replication stress signatures involving chromatin remodeling networks, transcription-replication conflicts and DNA repair. Our findings define localized surveillance mechanisms that activate the nDDR. Further, we identified that upon rDNA damage, nucleolar RNA Polymerase (Pol) II binds to intergenic rDNA sequences and generates R-loops (DNA:RNA hybrid structures) that are essential for recruiting nDDR factors. Using a boutique CRISPR-Cas9 synthetic lethal screen of DNA repair factors with inhibitors of RNA Pol I transcription, we identified an unexpected protective role for the DNA translocase RAD54L in nDDR. Loss of Rad54L increases nucleolar R-loops and rDNA damage leading to defects in nucleolar structure and enhanced sensitivity to PARP and RNA Pol I inhibitors. Altogether, our study uncovers localized surveillance networks within the nucleolus that respond to rDNA damage. These insights expand our understanding of the molecular mechanisms governing nDDR and opens new avenues for developing nDDR-targeting therapies.
Autism-Associated Genes and Neighboring lncRNAs Converge on Key Gene Regulatory Networks
Authors: Andersen Rebecca E. , Talukdar Maya , Sakamoto Tyler , Song Janet H.T. , Qian Xuyu , Lee Seungil , Delgado Ryan N. , Zhao Sijing , Eichfeld Gwenyth , Harms Julia , Walsh Christopher A. 
Published: January 2025

ABSTRACTThe diversity of genes implicated in autism spectrum disorder (ASD) creates challenges for identifying core pathophysiological mechanisms. Aggregation of seven different classes of genetic variants implicated in ASD, in a database we callConsensus-ASD, reveals shared features across distinct types of ASD variants. Functional interrogation of 19 ASD genes and 9 neighboring long non-coding RNAs (lncRNAs) using CRISPR-Cas13 strikingly revealed differential gene expression profiles that were significantly enriched for other ASD genes. Furthermore, construction of a gene regulatory network (GRN) enabled the identification of central regulators that exhibit convergently altered activity upon ASD gene disruption. Thus, this study reveals how perturbing distinct ASD-associated genes can lead to shared, broad dysregulation of GRNs with critical relevance to ASD. This provides a crucial framework for understanding how diverse genes, including lncRNAs, can play convergent roles in key neurodevelopmental processes and ultimately contribute to ASD.
Retinal and Optic Nerve Lesions Correspond to Amyloid in Autosomal Dominant Alzheimer’s Disease
Authors: Kashani Amir H , Koronyo-Hamaoui Maya , Koronyo Yosef , Shi Haoshen , Alluwimi Muhammed , Singer Maxwell , Sagare Abhay , Hawes Debra , Tang Anna , Jiang Xuejuan , Collazo Martinez Ana , Ross-Cisneros Fred N. , Sadun Alfredo A. , Ringman John M. 
Published: January 2025

AbstractAutosomal dominant Alzheimer’s disease (ADAD) is a rare form of Alzheimer’s disease (AD) in which the biology of the disease can be explored during the presymptomatic phase of the illness. The retina is an outgrowth of the central nervous system and therefore provides the opportunity for direct observation of neural tissue and its vasculature during life. Retinal thinning measuredin vivohas been previously described in persons carrying ADAD mutations through fundoscopy but its pathologic correlates have not been reported.We describe retinal lesions detected using fundoscopyin vivoin a patient homozygous for the A431E mutation inPSEN1and its pathological correlates. Retinal lesions seen with fundoscopy during life corresponded to intraretinal and prelaminar optic nerve head amyloid β42-protein that were surrounded by perivascular anti-11A50-B10-Aβ40and gliosis. We then performed a cross-sectional, observational study of forty-one Latinos in three cohorts consisting of (1) persons with ADAD causing mutations, (2) at 50% risk for, but testing negative for ADAD mutations, and (3) elderly subjects not at-risk for ADAD.Clinical exam demonstrated novel, yellow, intraretinal lesions in Cohort 1 in absence of drusen. Fifty-six percent of Cohort 1 subjects had >10 retinal lesions compared to 0% and 25% for Cohorts 2 and 3, respectively (P< 0.04). There has been some controversy as to the detectability of Aβ in the retina of persons with AD during life and our findings verify the presence of intraretinal, prelaminar, and perivascular amyloidosis detectable during life in a subset of AD patients.
Modelling the impact of changes to prescription medicine cost-sharing schemes among middle aged and older adults
Authors: Larkin James , Prendergast Ciaran , Murry Logan T. , Flood Michelle , Clyne Barbara , Burke Sara , Keegan Conor , Boland Fiona , Fahey Tom , Persaud Nav , Kenny Rose Anne , Moriarty Frank 
Published: January 2025

AbstractObjectiveTo assess impacts of government changes to prescription medicine co-payments on individuals’ out-of-pocket prescription medicine expenditure.MethodsData from The Irish Longitudinal Study on Ageing were used. Participants were community-dwelling adults aged ≥56 years. Ireland has two prescription cost-sharing schemes: the General Medical Services (GMS) scheme (primarily for low-income populations), involving a low monthly payment cap and low co-payments, and the Drugs Payment Scheme (DPS) (for others), with a higher cap and no co-payment limit. We modelled changes to these schemes implemented between 2016-2022 using 2016 data, assessing impacts on out-of-pocket prescription medicine expenditure across participant characteristics.ResultsAmong 4,155 participants with out-of-pocket prescription medicine expenditure, estimated mean annual prescription medicine expenditure for GMS-eligible participants reduced from €117 (95%CI=€114-120) to €55 (95%CI=€54-€56) due to post-2016 scheme changes. For DPS-eligible participants it reduced from €719 (95%CI=€694-€744) to €555 (95%CI=€541-€569). Those on more medicines had greater savings, with similar savings across income groups.ConclusionsCo-payment changes led to average savings of €62 for GMS-eligible participants and €174 for DPS-eligible participants. Although absolute savings were smaller for GMS participants, these were likely more impactful for this low-income population. Further reductions in monthly caps and co-payment charges, particularly for low-income populations, warrant consideration.