bluuebunny/crossref_metadata_2025_split huggingface dataset:
ABHD2 activity is not required for the non-genomic action of progesterone on human sperm
Authors: Arnolds Oliver , Carter Eve M. , Edwards Madison , Wigren Edvard , Homan Evert , Ribera Pauline , Bentley Kirsty , Haraldsson Martin , Theo-Emegano Nmesoma , Loppnau Peter , Szewczyk Magdalena M , Cao Michelle A , Barsyte-Lovejoy Dalia , Vester Karen , Thrun Anna , Amaral Alexandra , Lesche Ralf , Münchow Jens , Zhu W. Felix , Temme Louisa , Brenker Christoph , Strünker Timo , Sundström Michael , Todd Matthew H. , Edwards Aled M , Tredup Claudia , Gileadi Opher 
Published: December 2024

AbstractSperm activation is controlled by an influx of calcium ions through the CatSper channel, which is activated in the oviduct by a non-genomic action of progesterone. Progesterone has been hypothesized to act as an activator of ABHD2 activity, which in turn hydrolyses 1- and 2- arachadinoyl glycerol, putative inhibitors of CatSper. To explore the idea of targeting ABHD2 activity as a contraceptive target, we synthesized derivatives of published ABHD2 inhibitors, optimizing for potency and in-cell target engagement, and tested active inhibitors and structurally-related inactive derivatives in sperm motility assays and calcium influx assays. We observed no effect of ABHD2 inhibition on basal or progesterone-induced activity in both assays. We also found no evidence for direct binding of progesterone to purified recombinant ABHD2 protein. We conclude that ABHD2 activity is not required for the non-genomic action of progesterone on human sperm.
Missing what’s right under your nose: failed appetitive and aversive audio-olfactory conditioning in humans
Authors: Menger N.S. , Kotchoubey B. , Ohla K. , Pavlov Y.G. 
Published: December 2024

AbstractThe comparison of physiological mechanisms underlying appetitive and aversive conditioning is often challenging due to the involvement of stimuli from different modalities with potentially disparate effective mechanisms (e.g., pain stimuli versus monetary rewards). The olfactory system offers a unique opportunity to examine both types of conditioning in humans, as isointense odors can serve as comparably pleasant and unpleasant stimuli. To study physiological and behavioral responses during appetitive and aversive learning, we employed odors as unconditioned stimuli (US) in a within-subjects design, measuring various conditioned physiological responses including skin conductance, heart rate, pulse wave amplitude, respiration, fear-potentiated startle, postauricular reflex, facial electromyography as well as event-related potentials, and auditory steady-state responses (ASSR) derived from electroencephalography. We conducted four experiments with a total of 95 participants, presenting three neutral sounds paired with either a pleasant odor, unpleasant odor, or odorless air. The first experiment involved uninstructed participants and frequency-modulated conditioned stimuli (CS) for ASSR analysis. In the second experiment, we omitted the frequency modulation and startle probe. The third experiment included pre-experiment instruction on CS-US contingencies, while the fourth employed a delayed conditioning paradigm in contrast to the other three experiments. Our results revealed differences between CS+ and CS-only in the fear-potentiated startle response in Experiment 3. No other effects were found. The minimal or absent learning effects observed across multiple peripheral and neural physiological measures may be attributed to the extra-thalamic nature of olfactory pathways and the subsequent difficulty in forming associations with auditory stimuli.Impact statementIn a series of 4 experiments, we explored the neurophysiological differences between appetitive and aversive conditioning. Yet, none of the experiments showed effective conditioning. We hypothesize that the lack of learning effects is attributed to the inherent difficulty in forming associations between auditory and olfactory inputs.
The perceptions and roles of teachers and caregivers on play in promoting children’s early learning and development in a rural Kenya
Authors: Otwate Paul , Nampijja Margaret , Langat Nelson , Oloo Linda , Onyango Silas , Mabongah Jesse , Makhapila Erick , Ooko Silas , Odhiambo Brian , Kitsao-Wekulo Patricia 
Published: December 2024

AbstractAdults, including teachers and parents have an important role in supporting children’s learning and development through play. This paper aimed to explore parents’ and teachers’ viewpoints and roles on play in promoting early learning and development in children, which has little emphasis in existing studies. This paper employed a cross-sectional study using a mixed-method approach to gather data from preschool teachers (n=96), parents (n=126), and policy implementers (n=6) in Kenya. We used questionnaires, focus group discussions, and interview guides to collect qualitative and quantitative data through face-to-face interviews with teachers and parents and mobile interviews with policy stakeholders. We performed qualitative analysis through reviewing the study transcripts, coding, and generating emerging themes that later guided the draft of the narrative report. Quantitative data were coded, cleaned, and reviewed before they were descriptively computed on the Stata version 18 to generate graphic representations. Our findings revealed that teachers and parents jointly perceived play to be pivotal on children’s learning and development. In addition, parents and teachers recognized that it is their role to engage children in play, provide play materials, and supervise children. Based on our results, we suggest that preschool teachers and parents collaboratively identify days to jointly develop play materials in preschool centers. This strategy may present a better understanding of the adults’ primary role of facilitating play and play-based learning. Our findings may serve as a resource and source of information for preschool teachers, parents, and policy stakeholders to consider play not only as a development pathway but also an element of learning and contributor to school readiness in children.
Prevalence and predictors of anemia in children under 5 years of age in sub-Saharan Africa: a systematic review and meta-analysis
Authors: Gotine Ana Raquel Ernesto Manuel , Xavier Sancho Pedro , Vasco Melsequisete Daniel , Alfane Nerys Wendy Antonieta , Victor Audêncio 
Published: December 2024

AbstractBackgroundAnemia is a significant public health challenge in Sub-Saharan Africa, particularly affecting children under five years old and posing serious health and developmental consequences. This systematic review and meta-analysis aim to quantify the prevalence and identify the predictors of anemia in this vulnerable age group across the region.MethodsA systematic review and meta-analysis were conducted in adherence to PRISMA guidelines. Observational studies reporting on the prevalence and predictors of anemia among children under five in Sub-Saharan Africa were included. Comprehensive searches were performed in PubMed, Scopus, Web of Science, and Embase databases. The Joanna Briggs Institute (JBI) tools were used for critical appraisal. A random-effects model was applied to estimate pooled prevalence, while heterogeneity and publication bias were assessed using R software.ResultsA total of 32 studies comprising 93,388 children were included. The pooled prevalence of anemia was 55%, reflecting a widespread public health issue, with significant heterogeneity (I² = 99.7%). Key predictors included younger age (particularly 0–23 months), male gender, and indicators of poor nutritional status such as stunting. Socioeconomic and environmental factors, including rural residency and low maternal education, were also strongly associated with higher anemia rates. The observed variability across studies highlights the multifaceted nature of anemia’s determinants in the region.ConclusionThe consistently high prevalence of anemia among children under five in Sub-Saharan Africa underscores the need for integrated public health strategies. Efforts to address nutritional deficiencies, improve maternal education, and enhance living conditions are essential to mitigate the burden of anemia and improve child health outcomes in the region.
Phylogenetic relatedness rather than aquatic habitat fosters horizontal transfer of transposable elements in animals
Authors: Muller Héloïse , Savisaar Rosina , Peccoud Jean , Charlat Sylvain , Gilbert Clément 
Published: December 2024

AbstractHorizontal transfer of transposable elements (HTT) is an important driver of genome evolution, yet the factors conditioning this phenomenon remain poorly characterized. Here, we screened 247 animal genomes from four phyla (annelids, arthropods, mollusks, chordates), spanning 19 independent transitions between aquatic and terrestrial lifestyles, to evaluate the suspected positive effects of aquatic habitat and of phylogenetic relatedness on HTT. Among the 5,952 independent HTT events recovered, the vast majority (>85%) involve DNA transposons, of which Mariner-like and hAT-like elements have the highest rates of horizontal transfer, and of intra-genomic amplification. Using a novel approach that circumvents putative biases linked to phylogenetic inertia and taxon sampling, we found that HTT rates positively correlate with similarity in habitat type but were not significantly higher in aquatic than in terrestrial animals. However, modelling the number of HTT events as a function of divergence time in a Bayesian framework revealed a clear positive effect of phylogenetic relatedness on HTT rates in most of the animal species studied (162 out of 247). The effect is very pronounced: a typical species is expected to show 10 times more transfers with a species it diverged from 125 million years (My) ago than with a species it diverged from 375 My ago. Overall, our study underscores the pervasiveness of HTT throughout animals and the impact of evolutionary relatedness on its dynamics.Significance statementGenetic material can be transmitted between organisms through other means than reproduction, in a process called horizontal transfer. The mechanisms and factors underlying this phenomenon in animals remain unclear, although it often involves transposable elements (TEs). TEs are DNA segments capable of jumping within genomes, but also occasionally between individuals. Here, we show evidence for nearly 6,000 transfers of TEs among animals, based on genomic comparisons among 247 species of annelids, arthropods, chordates and mollusks. Contrarily to expectations, we found no excess in the rates of transfers in aquaticversusterrestrial animals. By contrast, most analyzed species appeared engaged in many more horizontal transfers with close than with distant relatives, highlighting the strong impact of phylogenetic relatedness on horizontal transfers of TEs.
Learning the Language of Phylogeny with MSA Transformer
Authors: Chen Ruyi , Foley Gabriel , Bodén Mikael 
Published: December 2024

AbstractClassical phylogenetic inference assumes independence between sites, potentially undermining the accuracy of evolutionary analyses in the presence of epistasis. Some protein language models have the capacity to encode dependencies between sites in conserved structural and functional domains across the protein universe. We employ the MSA Transformer, which takes a multiple sequence alignment (MSA) as an input, and is trained with masked language modeling objectives, to investigate if and how effects of epistasis can be captured to enhance the analysis of phylogenetic relationships.We test whether the MSA Transformer internally encodes evolutionary distances between the sequences in the MSA despite this information not being explicitly available during training. We investigate the model’s reliance on information available in columns as opposed to rows in the MSA, by systematically shuffling sequence content. We then use MSA Transformer on both natural and simulated MSAs to reconstruct entire phylogenetic trees with implied ancestral branchpoints, and assess their consistency with trees from maximum likelihood inference.We demonstrate how both previously known and novel evolutionary relationships are available from a “non-classical” approach with very different computational requirements, by reconstructing phylogenetic trees for the RNA virus RNAdependent RNA polymerase and the nucleo-cytoplasmic large DNA virus domain. We anticipate that MSA Transformer will not replace but rather complement classical phylogenetic inference, to accurately recover the evolutionary history of protein families.
Risk assessment of zoonotic viruses in urban-adapted wildlife
Authors: Wei Xuemin , Li Hongfeng , Huang Zheng Y.X. , Li Shuo , Wang Yuhao , Lan Jie , Hu Li , Li Yang , Becker Daniel J. , Wei Fuwen , Xu Yifei 
Published: December 2024

AbstractThe repeated emergence of pandemic viruses underscores the linkages between land-use change and wildlife disease, and urban-adapted wildlife are of special interest due to their close proximity to humans. However, viral diversity within urban-adapted species and their zoonotic potential remains largely unexplored. We compiled a large dataset on seven priority urban-adapted mammal species and their viruses covering over 115 countries from 1574 to 2023. These urban-adapted species host 286 virus species spanning 24 orders and 38 families, 14 of which are potentially high risk for human infection. Raccoons carried the most high-risk viruses, while raccoon dogs had increased viral positivity in urban habitats compared to raccoons, wild boars, and red foxes. Many viruses in urban-adapted species were phylogenetically related to those found in humans, and we also observed evidence of possible viral spillback. These results highlight zoonotic risks associated with urban-adapted species and suggest enhanced surveillance to mitigate future outbreaks.
Benchmarking scRNA-seq copy number variation callers
Authors: Schmid Katharina T. , Symeonidi Aikaterini , Hlushchenko Dmytro , Richter Maria L. , Colomé-Tatché Maria 
Published: December 2024

AbstractCopy number variations (CNVs), the gain or loss of genomic regions, are associated with different diseases and cancer types, where they are related to tumor progression and treatment outcome. Single cell technologies offer new possibilities to measure CNVs in individual cells, allowing to assess population heterogeneity and to delineate subclonal structures. Single cell whole-genome sequencing is considered the gold-standard for the quantification of CNVs in single cells. However, the majority of existing single cell datasets interrogate gene expression, using scRNA-seq. Consequently, several computational approaches have been developed to identify CNVs from that data modality. Nevertheless, an independent benchmarking of these methods is lacking. We used 15 scRNA-seq datasets and evaluated six popular computational methods in their ability to recover the ground truth CNVs using a large set of performance metrics. Additionally, we explored whether they could correctly identify euploid cells, especially also in fully diploid samples, and subclonal structures in heterogeneous tumor samples. We discovered several dataset-specific factors that influence the performance of the methods, such as the dataset size and the number and type of CNVs in the analyzed sample. We found that the choice of the reference dataset can have a large impact on the performance. Methods which included additional allelic information from the scRNA-seq reads performed more robustly across scenarios, but at the cost of higher runtime. Furthermore, the methods differed substantially in their additional functionalities and resource requirements. We offer a benchmarking pipeline to help identify the optimal CNV calling method for newly generated scRNA-seq datasets, and to benchmark and improve new methods performance.
Incidence of acute ischemic stroke after COVID-19 or influenza among older adults, findings from PCORnet and HealthVerity, 2022
Authors: Koumans Emilia H. , Raykin Julia , Boehmer Tegan K. , Saydah Sharon , Wiltz Jennifer , Garg Shikha , DeSantis Carol E. , Carton Thomas W. , Cowell Lindsay G. , Thacker Deepika , Arnold Jonathan , Rasmussen Sonja A. , Smith Samantha J. , Barrett Kimberly , Draper Christine , Coronado Fátima , Lundeen Elizabeth A. , Woodruff Rebecca C. , Block Jason P. 
Published: December 2024

AbstractBackgroundAlthough COVID-19 is a known risk factor for thrombotic conditions including embolism, stroke, and myocardial infarction, stroke incidence after implementation of thromboprophylaxis during COVID-19 hospitalization in 2021 and how incidence may differ from influenza is unknown.MethodsPCORnet and HealthVerity (HV) data assets were used to identify patients aged ≥65 years with no prior stroke and COVID-19 or influenza during January 1-December 31, 2022, and AIS from 3 days before to 28 days after COVID-19 or influenza diagnosis. Overall demographic information (age [for HV], sex, race/ethnicity), underlying conditions, level of care, outcomes, and incidence were described and compared between those with early (-3 to 7 days from diagnosis date) and late (8 to 28 days) AIS.ResultsAmong 245,352 (PC) and 639,396 (HV) patients aged ≥65 years with COVID-19, the incidence of ischemic stroke in the 3 days prior to 7 days after diagnosis of COVID-19 (PC: 962/100,000 and HV: 447/100,000) and influenza (PC: 589/100,000 and HV: 387/100,000) was significantly higher than in the 8 to 28 days after diagnosis (COVID PC: 81/100,000 and HV: 141/100,000)(influenza PC:75/100,000 and HV: 15/100,000)(all P<0.01).ConclusionsContinued risk for AIS with acute COVID-19 and influenza underscore the importance of monitoring and prevention measures for older adults.
Cadmium and Lead Attributable Burden of Cancers in Skipjack (Katsuwonus pelamis) and Yellowfin (Thunnus albacares) in Ghana
Authors: Nkansah J. A. , Lutterodt H.E. , Dodoo A. , Ofosu I.W. 
Published: December 2024

AbstractToxic heavy metal contamination in fish sources poses significant health risks, particularly in populations that rely on fish as a primary dietary component. Thus, this study aimed to assess the concentrations of cadmium (Cd) and lead (Pb) in selected tuna species and evaluate the associated health risks and cancer burdens to consumers in Ghana through a systematic review and meta-analysis of data covering the period 2015 to 2019. A Disability Adjusted Life Year (DALY) approach was used to quantify the health burden with secondary data from the Institute of Health Metrics and Evaluation (IHME). Median contaminant exposure was 1.26 × 10-5mg/kg(bw)-day for Cd, and 1.04 × 10-4mg/kg(bw)-day for Pb. The highest DALY was found in the elderly age group (55-89) and it ranged from 10-5- 10-3. The results indicate that in the elderly age group, stomach cancer was the most prevalent for both males and females, reflecting a significant cancer burden. For elderly males, prostate cancer was also a severe concern, contributing to the overall cancer burden, although its prevalence was lower than that of stomach cancer. In elderly females, however, pancreatic cancer was observed to have a higher prevalence compared to males, indicating gender-specific differences in cancer risk among older adults. The findings underscore the need for public health interventions to mitigate the risks of heavy metal contamination in fish.
Comparative analysis of dietary iron deprivation and supplementation in a murine model of colitis
Authors: Medjbeur Thanina , Sardo Ugo , Perrier Prunelle , Cormier Kevin , Roy Marilyne , Dumay Anne , Kautz Léon 
Published: December 2024

ABSTRACTInflammatory bowel diseases are chronic inflammatory conditions with growing prevalence in western populations. Iron is an essential component of erythrocytes hemoglobin. Under the influence of elevated hepcidin production, iron is sequestered in cells during inflammation which, in turn, leads to iron restriction for red blood cells synthesis. As a consequence, iron deficiency and anemia of inflammation are the most prevalent extraintestinal complications in IBD patients. Patients are thus treated with oral iron supplements that have limited efficacy as iron absorption is blunted during intestinal inflammation. Moreover, iron supplementation can cause intestinal complications and previous studies have shown that iron supplementation worsens the inflammatory response. However, a comparative analysis of the effects of low, adequate and high dietary iron content matching iron the supplementation given to patients has not been performed in mice. We therefore tested the impact of dietary iron deprivation and supplementation in a murine model of colitis induced by dextran sodium sulfate. We found that both dietary iron deprivation and supplementation were accompanied by a more severe inflammation with earlier signs of gastrointestinal bleeding compared to mice fed an iron adequate diet. The manipulation of dietary iron led to a comparable oxidative stress and a pronounced dysbiosis in the colon of control mice that differed depending on the dietary iron content. Analysis of these dysbiosis is in line with a pronounced susceptibility to colonic inflammation thus questioning the benefit/risk balance of oral iron supplementation for IBD patients.
Transcriptomic disruption and functional hypoactivity in DYT-SGCEMGE-patterned inhibitory neurons
Authors: Li Zongze , Abram Laura , Cruz-Santos Maria , Petter Olena , Peall Kathryn J 
Published: December 2024

AbstractMyoclonus Dystonia is a dystonic movement disorder caused bySGCEmutations, the underlying pathophysiology for which remains unclear. Here, we evaluated the impact ofSGCEmutations on medial ganglionic eminence (MGE)-derived GABAergic neurons using patient-derived induced pluripotent and gene edited embryonic stem cell lines, each compared to their isogenic wild-type control. No significant differences were observed in markers of neuronal development however, single-cell RNA sequencing demonstrated transcriptomic dysregulation in genes related to axonal organization, synaptic signalling, and action potential generation in theSGCE-mutation harbouring neurons. Functional assays demonstrated reduced neurite outgrowth, lower calcium responses to GABA, and decreased neuronal excitability and network activity in theSGCE-mutant neurons. These findings contrast with the hyperexcitable phenotype previously observed inSGCE-mutant cortical glutamatergic neurons. Collectively, this supports loss of neuronal inhibitory activity, and disruption to the neuronal excitatory/inhibitory balance in motor circuits, in contributing to the overall hyperkinetic clinical phenotype in Myoclonus Dystonia.