bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling the Emotional Turmoil: How Covid-19 impacted researchers and the pursuit of emotional well-being in academia
Authors: Weise Crista , Suñe-Soler Nuria , Corcelles Mariona , Sala-Bubaré Anna , Castelló Monsterrat 
Published: November 2023

AbstractThe Covid-19 crisis unprecedentedly required researchers to adapt to significant changes in their work and personal lives. Our study aims to fill this gap analysing the Covid-19 emotional impact and confinement potential disruptions on researchers’ activity (specifically, those related to working conditions, caring responsibilities, health, balance, and social support) considering the modulating role played by age, gender, and job position. An online survey was distributed during the first lockdown period of the Covid-19 pandemic, and answers from 1301 researchers (ECR %, senior researchers %) working in Sciences (28.1%), Social Sciences (25.9%), Humanities (16.2%), Health (16.2%) and in Engineering and Architecture (13.5%) were collected. The study highlights that the initial lockdown during the Covid-19 pandemic had a significant emotional impact on researchers, exacerbating pre-existing emotional distress and burnout within this group. Factors such as age, health, gender, and difficulties in balancing work and family life were associated with an increased risk of burnout and emotional distress. Lack of social support was identified as a significant risk factor, while the academic culture prioritizing productivity over well-being contributed to the issue. These findings underscore the need for greater support and cultural changes in academia to preserve researchers’ mental health and prevent the chronicization of mental health issues in young academics.
Identification and characterisationof Mansonella perstansin the Volta Region of Ghana
Authors: Opoku Millicent , de Souza Dziedzom K. 
Published: November 2023

AbstractMansonella spp. have been reported to have a wide global distribution. Despite the distribution and occurrence with other filarial parasites likeWuchereria bancrofti, Onchocerca volvulusandLao loa, it is given little attention. Hence, there is no surveillance programme for assessing the distribution or mansonellosis, with mild to no symptoms experienced by infected people. However, addressing this infection is critical to the onchocerciasis control program as current rapid diagnostic tools targetingO. volvulushave the tendency to cross react withMansonella species. In this study we identified and characterisedM. perstansfrom five sites in the Volta region of Ghana and compared them to samples from other regions. Night blood smears and filter blood blots were obtained from individuals as part of a study on lymphatic filariasis. The giemsa stained smears were screened by microscopy for the presence of filarial parasites. Genomic DNA was extracted from blood blots from 39 individuals that were positive forM. perstansand Nested PCR targeting the internal spacer 1 (ITS-1) was conducted. Of these, 30 were sequenced and 24 sequences were kept for further analysis. Phylogenetic analysis of 194 nucleotide positions showed no differences in the samples collected. Samples from Ghana clustered with samples from other reference sequences from Africa and Brazil, possibly supporting the introduction ofM. perstansfrom sub-Saharan Africa, during the trans-Atlantic slave trade. This study draws further attention to a neglected infection and presents the first characterisation ofM. perstansin Ghana and calls for more population-based studies across different geographical zones to ascertain species variations and disease distribution.
Whole genome profiling of short-term hypoxia induced genes and identification of HIF-1 binding sites provide insights into HIF-1 function inCaenorhabditis elegans
Authors: Feng Dingxia , Qu Long 
Published: November 2023

AbstractOxygen is essential to all the aerobic organisms. However, during normal development, disease and homeostasis, organisms are often challenged by hypoxia (oxygen deprivation). Hypoxia-inducible transcription factors (HIFs) are master regulators of hypoxia response and are evolutionarily conserved in metazoans. The homolog of HIF in the genetic model organismC. elegansis HIF-1. In this study, we aimed to understand short-term hypoxia response and to identify HIF-1 direct targets inC. elegans. The central research questions were: (1) which genes are differentially expressed in response to short-term hypoxia? (2) Which of these changes in gene expression are dependent upon HIF-1 function? (3) How do HIF-1-dependent hypoxia-responsive genes affect hypoxia adaptation? (4) Which genes are the direct targets of HIF-1? We combine whole genome gene expression analyses and chromatin immunoprecipitation sequencing (ChIP-seq) experiments to address these questions. In agreement with other published studies, we report that HIF-1-dependent hypoxia-responsive genes are involved in metabolism, oxidation-reduction process, and stress response. Some HIF-1-dependent hypoxia-responsive genes likeefk-1andphy-2dramatically impact survival in hypoxic conditions. HIF-1 co-immunoprecipitates with genomic regions proximal genes involved in stress response, protein processing in endoplasmic reticulum, and cell recognition. Further, some of these potential HIF-1 direct targets are differentially expressed under short-term hypoxia or are differentially regulated by mutations that enhance HIF-1 activity.
Suberoylanilide Hydroxamic Acid Attenuates Cognitive Impairment in Offspring Caused by Maternal Surgery during Mid-pregnancy
Authors: Feng Yunlin , Qin Jia , Lu Yanfei , Wang Mengdie , Wang Shengqiang , Luo Foquan 
Published: November 2023

AbstractIt is known that commonly-used anesthetics can cause long-term neurotoxicity in the developing brain. Some pregnant women have to experience non-obstetric surgery during pregnancy under general anesthesia. It is known that maternal exposure to sevoflurane, isoflurane, propofol and ketamine causes cognitive deficits in offspring. Histone acetylation has been implicated in synaptic plasticity, and abnormal histone acetylation contributes to the neonatal sevoflurane exposure induced deficits in hippocampus-dependent learning and memory. The HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) was shown to attenuate the sevoflurane-induced deficits. Propofol is commonly used in non-obstetric procedures on pregnant women. Recent evidence shows that propofol also causes neurotoxicity in developing brains. For example, previous studies in our laboratory showed that maternal propofol exposure in pregnancy impairs learning and memory in offspring by disturbing histone acetylation. The present study aims to investigate whether SAHA could also attenuate propofol-induced learning and memory deficits in offspring caused by maternal surgery during mid-pregnancy. Maternal rats were exposed to propofol or underwent abdominal surgery under propofol anesthesia during middle pregnancy. The learning and memory abilities of the offspring rats were assessed using Morris water maze (MWM) test. The protein levels of histone deacetylase 2 (HDAC2), phosphorylated cAMP response-element binding (p-CREB),brain derived neurotriphic factor (BDNF) and phosphorylated tyrosine kinase B (p-TrkB) in the hippocampus of the offspring rats were evaluated by immunofluorescence staining and western blot. Hippocampal neuroapoptosis was detected by TUNEL staining. Our results showed that maternal propofol exposure during middle pregnancy impaired the water-maze learning and memory of the offspring rats, increased the protein level of HDAC2 and reduced the protein levels of p-CREB,BDNF and p-TrkB in the hippocampus of the offspring, and such effects were exacerbated by surgery. SAHA alleviated the cognitive dysfunction and rescued the changes in the protein levels of p-CREB, BDNF and p-TrkB induced by maternal propofol exposure alone or maternal propofol exposure plus surgery. Therefore, SAHA could be a potential and promising agent for treating the learning and memory deficits in offspring caused by maternal nonobstetric surgery under propofol aneshtesia.
The proportion of Alzheimer’s disease attributable to apolipoprotein E
Authors: Williams Dylan M. , Davies Neil M. , Anderson Emma L. 
Published: November 2023

AbstractINTRODUCTIONThe extent to which genetic variation at theAPOElocus explains the burden of late-onset Alzheimer’s disease (AD) is poorly understood. We provide new estimates of the proportions of AD and all-cause dementia attributable to carriage of the ε3 and ε4APOEalleles.METHODSWe conducted a cohort study using genetic and electronic health record data from 171,128 participants of UK Biobank, aged ≥60 years at baseline. AD and all-cause dementia were ascertained at baseline and during follow-up for up to 16.8 years.RESULTS74.0% (95% CI: 37.8, 89.1) of AD and 38.1% (95% CI: 9.8, 57.6%) of all-cause dementia burden were attributable to a combination of ε3 and ε4 carriage. Approximately 30% of AD was attributable to ε3 carriage specifically.DISCUSSIONDifferences in apolipoprotein E are responsible for most AD and a large fraction of all dementia. Research into this pathway should be prioritised to facilitate dementia prevention.
Potential Biases in Test-Negative Design Studies of COVID-19 Vaccine Effectiveness Arising from the Inclusion of Asymptomatic Individuals
Authors: Ortiz-Brizuela Edgar , Carabali Mabel , Jiang Cong , Merckx Joanna , Talbot Denis , Schnitzer Mireille E. 
Published: November 2023

AbstractThe test-negative design (TND) is a popular method for evaluating vaccine effectiveness (VE). A “classical” TND study includes symptomatic individuals tested for the disease targeted by the vaccine to estimate VE against symptomatic infection. However, recent applications of the TND have attempted to estimate VE against infection by including all tested individuals, regardless of their symptoms. In this article, we use directed acyclic graphs and simulations to investigate potential biases in TND studies of COVID-19 VE arising from the use of this “alternative” approach, particularly when applied during periods of widespread testing. We show that the inclusion of asymptomatic individuals can potentially lead to collider stratification bias, uncontrolled confounding by health and healthcare-seeking behaviors (HSBs), and differential outcome misclassification. While our focus is on the COVID-19 setting, the issues discussed here may also be relevant in the context of other infectious diseases. This may be particularly true in scenarios where there is either a high baseline prevalence of infection, a strong correlation between HSBs and vaccination, different testing practices for vaccinated and unvaccinated individuals, or settings where both the vaccine under study attenuates symptoms of infection and diagnostic accuracy is modified by the presence of symptoms.
Spatiotemporal Trends in Group A Streptococcal Pharyngitis in the United States
Authors: Kline Madeleine C. , Kissler Stephen M. , Whittles Lilith K. , Barnett Michael L. , Grad Yonatan H. 
Published: November 2023

ABSTRACTBackgroundGroup AStreptococcus(GAS) causes an estimated 5.2 million outpatient visits for pharyngitis annually in the United States (U.S.) with incidence peaking in winter, but the annual spatiotemporal pattern of GAS pharyngitis across the U.S. is poorly characterized.MethodsWe used outpatient claims data from individuals with private medical insurance between 2010-2018 to quantify GAS pharyngitis visit rates across U.S. census regions, subregions, and states. We evaluated seasonal and age-based patterns of geographic spread and the association between school start dates and the summertime upward inflection in GAS visits.ResultsThe South had the most visits per person (yearly average 39.11 visits per 1000 people, 95% CI: 36.21-42.01), and the West had the fewest (yearly average 17.63 visits per 1000 people, 95% CI: 16.76-18.49). Visits increased earliest in the South and in school-age children. Differences in visits between the South and other regions were most pronounced in the late summer through early winter. Visits peaked earliest in central southern states, in December to January, and latest on the coasts, in March. The onset of the rise in GAS pharyngitis visits correlated with, but preceded, average school start times.ConclusionsThe burden and timing of GAS pharyngitis varied across the continental U.S., with the South experiencing the highest overall rates and earliest onset and peak in outpatient visits. Understanding the drivers of these regional differences in GAS pharyngitis will help in identifying and targeting prevention measures.SummaryThe incidence of streptococcal pharyngitis varies across the U.S., with highest rates in the South and lowest in the West. On average, the yearly summer increase in cases begins in the South and progresses outwards to adjacent states.
Networks extracted from nonlinear fMRI connectivity exhibit unique spatial variation and enhanced sensitivity to differences between individuals with schizophrenia and controls
Authors: Kinsey Spencer , Kazimierczak Katarzyna , Camazón Pablo Andrés , Chen Jiayu , Adali Tülay , Kochunov Peter , Adhikari Bhim , Ford Judith , van Erp Theo G. M. , Dhamala Mukesh , Calhoun Vince D. , Iraji Armin 
Published: November 2023

AbstractFunctional magnetic resonance imaging (fMRI) studies often estimate brain intrinsic connectivity networks (ICNs) from temporal relationships between hemodynamic signals using approaches such as independent component analysis (ICA). While ICNs are thought to represent functional sources that play important roles in various psychological phenomena, current approaches have been tailored to identify ICNs that mainly reflect linear statistical relationships. However, the elements comprising neural systems often exhibit remarkably complex nonlinear interactions that may be involved in cognitive operations and altered in psychiatric conditions such as schizophrenia. Consequently, there is a need to develop methods capable of effectively capturing ICNs from measures that are sensitive to nonlinear relationships. Here, we advance a novel approach to estimate ICNs from explicitly nonlinear whole-brain functional connectivity (ENL-wFC) by transforming resting-state fMRI (rsfMRI) data into the connectivity domain, allowing us to capture unique information from distance correlation patterns that would be missed by linear whole-brain functional connectivity (LIN-wFC) analysis.Our findings provide evidence that ICNs commonly extracted from linear (LIN) relationships are also reflected in explicitly nonlinear (ENL) connectivity patterns. ENL ICN estimates exhibit higher reliability and stability, highlighting our approach’s ability to effectively quantify ICNs from rsfMRI data. Additionally, we observed a consistent spatial gradient pattern between LIN and ENL ICNs with higher ENL weight in core ICN regions, suggesting that ICN function may be subserved by nonlinear processes concentrated within network centers. We also found that a uniquely identified ENL ICN distinguished individuals with schizophrenia from healthy controls while a uniquely identified LIN ICN did not, emphasizing the valuable complementary information that can be gained by incorporating measures that are sensitive to nonlinearity in future analyses. Moreover, the ENL estimates of ICNs associated with auditory, linguistic, sensorimotor, and self-referential processes exhibit heightened sensitivity towards differentiating between individuals with schizophrenia and controls compared to LIN counterparts, demonstrating the translational value of our approach and of the ENL estimates of ICNs that are frequently reported as disrupted in schizophrenia. In summary, our findings underscore the tremendous potential of connectivity domain ICA and nonlinear information in resolving complex brain phenomena and revolutionizing the landscape of clinical FC analysis.
Dynamic neuroinflammatory profiles predict Alzheimer’s disease pathology in microglia-containing cerebral organoids
Authors: Kuhn Madison K. , Kang Rachel Y. , Kim ChaeMin , Tagay Yerbol , Morris Nathan , Tabdanov Erdem D. , Elcheva Irina A. , Proctor Elizabeth A. 
Published: November 2023

AbstractNeuroinflammation and the underlying dysregulated immune responses of microglia actively contribute to the progression and, likely, the initiation of Alzheimer’s disease (AD). Fine-tuned therapeutic modulation of immune dysfunction to ameliorate disease cannot be achieved without the characterization of diverse microglial states that initiate unique, and sometimes contradictory, immune responses that evolve over time in chronic inflammatory environments. Because of the functional differences between human and murine microglia, untangling distinct, disease-relevant reactive states and their corresponding effects on pathology or neuronal health may not be possible without the use of human cells. In order to profile shifting microglial states in early AD and identify microglia-specific drivers of disease, we differentiated human induced pluripotent stem cells (iPSCs) carrying a familial AD PSEN2 mutation or its isogenic control into cerebral organoids and quantified the changes in cytokine concentrations over time with Luminex XMAP technology. We used partial least squares (PLS) modeling to build cytokine signatures predictive of disease and age to identify key differential patterns of cytokine expression that inform the overall organoid immune milieu and quantified the corresponding changes in protein pathology. AD organoids exhibited an overall reduction in cytokine secretion after an initial amplified immune response. We demonstrate that reduced synapse density observed in the AD organoids is prevented with microglial depletion. Crucially, these differential effects of dysregulated immune signaling occurred without the accumulation of pathological proteins. In this study, we used microglia-containing AD organoids to quantitatively characterize an evolving immune milieu, made up of a diverse of collection of activation patterns and immune responses, to identify how a dynamic, overall neuroinflammatory state negatively impacts neuronal health and the cell-specific contribution of microglia.
Macrophage Depletion Protects Against Cisplatin-Induced Ototoxicity and Nephrotoxicity
Authors: Sung Cathy Yea Won , Hayase Naoki , Yuen Peter S.T. , Lee John , Fernandez Katharine , Hu Xuzhen , Cheng Hui , Star Robert A. , Warchol Mark E. , Cunningham Lisa L. 
Published: November 2023

AbstractCisplatin is a widely used and highly effective anti-cancer drug with significant side effects including ototoxicity and nephrotoxicity. Macrophages, the major resident immune cells in the cochlea and kidney, are important drivers of both inflammatory and tissue repair responses. To investigate the roles of macrophages in cisplatin-induced ototoxicity and nephrotoxicity, we used PLX3397, an FDA-approved inhibitor of the colony-stimulating factor 1 receptor (CSF1R), to eliminate tissue-resident macrophages during the course of cisplatin administration. Mice treated with cisplatin alone (cisplatin/vehicle) had significant hearing loss (ototoxicity) as well as kidney injury (nephrotoxicity). Macrophage ablation using PLX3397 resulted in significantly reduced hearing loss measured by auditory brainstem responses (ABR) and distortion-product otoacoustic emissions (DPOAE). Sensory hair cells in the cochlea were protected against cisplatin-induced death in mice treated with PLX3397. Macrophage ablation also protected against cisplatin-induced nephrotoxicity, as evidenced by markedly reduced tubular injury and fibrosis as well as reduced plasma blood urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) levels. Mechanistically, our data suggest that the protective effect of macrophage ablation against cisplatin-induced ototoxicity and nephrotoxicity is mediated by reduced platinum accumulation in both the inner ear and the kidney. Together our data indicate that ablation of tissue-resident macrophages represents a novel strategy for mitigating cisplatin-induced ototoxicity and nephrotoxicity.Brief summaryMacrophage ablation using PLX3397 was protective against cisplatin-induced ototoxicity and nephrotoxicity by limiting platinum accumulation in the inner ear and kidney.
De novotranscriptome assembly and genome annotation of the fat-tailed dunnart (Sminthopsis crassicaudata)
Authors: Ibeh Neke , Feigin Charles Y. , Frankenberg Stephen R. , McCarthy Davis J. , Pask Andrew J. , Romero Irene Gallego 
Published: November 2023

AbstractMarsupials exhibit highly specialized patterns of reproduction and development, making them uniquely valuable for comparative genomics studies with their sister lineage, eutherian (also known as placental) mammals. However, marsupial genomic resources still lag far behind those of eutherian mammals, limiting our insight into mammalian diversity. Here, we present a series of novel genomic resources for the fat-tailed dunnart (Sminthopsis crassicaudata), a mouse-like marsupial that, due to its ease of husbandry andex-uterodevelopment, is emerging as a laboratory model. To enable wider use, we have generated a multi-tissuede novotranscriptome assembly of dunnart RNA-seq reads spanning 12 tissues. This highly representative transcriptome is comprised of 2,093,982 assembled transcripts, with a mean transcript length of 830 bp. The transcriptome mammalian BUSCO completeness score of 93% is the highest amongst all other published marsupial transcriptomes. Additionally, we report an improved fat-tailed dunnart genome assembly which is 3.23 Gb long, organized into 1,848 scaffolds, with a scaffold N50 of 72.64 Mb. The genome annotation, supported by assembled transcripts andab initiopredictions, revealed 21,622 protein-coding genes. Altogether, these resources will contribute greatly towards characterizing marsupial biology and mammalian genome evolution.
The Wolfram-like variant WFS1E864Kdestabilizes MAM and compromises autophagy and mitophagy in human and mice
Authors: Patergnani Simone , Bataillard Méghane S. , Danese Alberto , Alves Stacy , Cazevieille Chantal , Valéro René , Tranebjærg Lisbeth , Maurice Tangui , Pinton Paolo , Delprat Benjamin , Richard Elodie M. 
Published: November 2023

AbstractDominant variants inWFS1, a gene coding for the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) resident protein Wolframin, have been associated with Wolfram-like syndrome (WLS).In vitroandin vivo, WFS1 loss results in reduced ER to mitochondria calcium (Ca2+) transfer, mitochondrial dysfunction, and enhanced autophagy and mitophagy. However, in WLS pathological context, whether the mutant protein triggers the same cellular processes is unknown. Here, we show that, in human fibroblasts and murine neuronal cultures, WLS protein WFS1E864Kleads to decreases in mitochondria bioenergetics and Ca2+uptake, deregulation of the mitochondrial quality system mechanisms, and alteration of the autophagic flux. Moreover, in theWfs1E864Kmouse, these alterations are concomitant with a decrease of MAM number. These findings reveal pathophysiological similarities between WS and WLS, highlighting the importance of WFS1 for MAM’s integrity and functionality. It may open new treatment perspectives, until now non-existent, for patients with WLS.