bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of Water Quality with Cholera in Case-Control Studies: A Systematic Review and Meta-Analysis
Authors: Nguyen Thuy Tien , Kim Chaelin , Goucher Gerard , Kim Jong-Hoon 
Published: September 2023

AbstractCholera is a significant health risk for low- and middle-income countries (LMIC), and the threat of outbreaks is likely to increase due to climate change. To keep up to date with the link between water quality and cholera, we conducted a systematic review and meta-analysis to update a previous review. We searched Embase, Web of Science and PubMed for literature published between 2016 and 2022. Search terms were consistent with the previous review. Study quality was assessed using Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E). Exposures of water were categorized according to the WHO/UNICEF Joint Monitoring Program for Water Supply, Sanitation and Hygiene (JMP) and further divided by the service ladder. Odds ratios were extracted and pooled by performing random-effects meta-analysis. We identified 22 new eligible studies and analysed them together with the 45 studies included in the previous review. Analyses revealed higher odds of cholera when consuming sachet water (OR=1.69, 95% CI: 1.13 to 2.52), unimproved water (OR=2.91, 95% CI: 1.21 to 7.02), surface water (OR=3.40, 95% CI: 2.52 to 4.58), and untreated water (OR=2.51, 95% CI: 2.03 to 3.10). Meanwhile, treating water (OR=0.42, 95% CI: 0.27 to 0.65), by boiling (OR=0.38, 95% CI: 0.17 to 0.84) or chlorination (OR=0.37, 95% CI: 0.17 to 0.83), and drinking basic water (OR=0.44, 95% CI: 0.27 to 0.69) showed protection. Pooled estimates changed with updated evidence while qualitative insights on the protective or risk factors remain valid. Relatively low-cost methods like boiling or chlorinating water provide good protection comparable to providing basic water to the public.Systematic review registration: PROSPERO 2021 CRD42021271881
Prediction of peak oxygen consumption using cardiorespiratory parameters from warm-up and submaximal stage of treadmill cardiopulmonary exercise test
Authors: Rosoł Maciej , Petelczyc Monika , Gąsior Jakub S. , Młyńczak Marcel 
Published: September 2023

AbstractThis study investigates the quality of peak oxygen consumption (VO2peak) prediction based on cardiac and respiratory parameters calculated from warmup and submaximal stages of treadmill cardiopulmonary exercise test (CPET) using machine learning (ML) techniques and assesses the importance of respiratory parameters for the prediction outcome. The database consists of the following parameters: heart rate (HR), respiratory rate (RespRate), pulmonary ventilation (VE), oxygen consumption (VO2) and carbon dioxide production (VCO2) obtained from 369 treadmill CPETs. Combinations of features calculated based on the HR, VE and RespRate time-series from different stages of CPET were used to create 11 datasets for VO2peakprediction. Thirteen ML algorithms were employed, and model performances were evaluated using cross-validation with mean absolute percentage error (MAPE), R2score, mean absolute error (MAE), and root mean squared error (RMSE) calculated after each iteration of the validation. The results demonstrated that incorporating respiratory-based features improves the prediction of VO2peak. The best results in terms of R2score (0.47) and RMSE (5.78) were obtained for the dataset which included both cardiac- and respiratory-based features from CPET up to 85% of age-predicted HRmax, while the best results in terms of MAPE (10.5%) and MAE (4.63) were obtained for the dataset containing cardiorespiratory features from the last 30 seconds of warmup. The study showed the potential of using ML models based on cardiorespiratory features from submaximal tests for prediction of VO2peakand highlights the importance of the monitoring of respiratory signals, enabling to include respiratory parameters into the analysis. Presented approach offers a feasible alternative to direct VO2peakmeasurement, especially when specialized equipment is limited or unavailable.
Severe biventricular cardiomyopathy in both current and former long-term users of anabolic-androgenic steroids
Authors: Abdullah Rang , Bjørnebekk Astrid , Hauger Lisa E. , Hullstein Ingunn R. , Edvardsen Thor , Haugaa Kristina H. , Almaas Vibeke M. 
Published: September 2023

ABSTRACTAimsExplore the cardiovascular effects of long-term anabolic-androgenic steroid (AAS)-use in both current and former weightlifting AAS-users, and estimate the occurrence of severe reduced myocardial function and the impact of duration and amount of AAS.MethodsIn this cross-sectional study 101 weightlifting AAS-users with at least one year cumulative AAS-use (mean 11±7 accumulated years of AAS-use) were compared to 71 non-using weightlifting controls (WLC) using clinical data and echocardiography.ResultsSixty-nine were current, 30 former (> 1 year since quitted), and 2 AAS-users were not available for this classification. AAS-users had higher left ventricular mass index (LVMI) (106±26 versus 80±15 g/m2, P<0.001), worse LV ejection fraction (LVEF) (49±7 versus 59±5%, P<0.001) and right ventricular global longitudinal strain (RVGLS) (−17.3±3.5 versus −22.8±2.0%, P<0.001), and higher systolic blood pressure (SBP) (141±17 vs. 133±11 mmHg, p<0.001) compared with WLC. In current users accumulated duration of AAS-use was 12±7 years, and in former 9±6 years (quitted 6±6 years earlier). Compared to WLC, LVMI and LVEF were pathological in current and former users (p<0.05) with equal distribution of severely reduced myocardial function (LVEF ≤40%) (11% vs. 10%, NS). In current users estimated life time AAS-dose correlated with reduced LVEF and LVGLS, p<0.05, but not with LVMI, p=0.12. Regression analyses of the total population showed that the strongest determinant of reduced LVEF were not coexisting strength training or hypertension, but history of AAS-use (β −0.53, P<0.001).ConclusionsLong-term AAS-users showed severely biventricular cardiomyopathy. The reduced systolic function was also found upon discountied use.
Sidedness in unilateral orofacial clefts: A systematic scoping review
Authors: Fell Matthew , Bradley Daniel , Chadha Ambika , Butterworth Sophie , Davies Amy , Russell Craig , Richard Bruce , Wren Yvonne , Lewis Sarah , Chong David 
Published: September 2023

ABSTRACTObjectivesAn overview of the literature relating to the sidedness of unilateral cleft lip with or without cleft palate to map current knowledge on the cause and impact of directional asymmetry in the unilateral cleft lip phenotype.Data SourcesMedline and Embase from inception to May 2023Study selectionStudies including left and right unilateral cleft lip subgroups as a co-occurrence, an outcome or an exposure.Data analysisNarrative synthesis.ResultsForty-one studies were eligible for inclusion; 12 studies reported cleft sidedness co-occurring with another phenotype, 12 studies report sidedness as an outcome and 17 studies as an exposure. Phenotypes which were reported to co-occur with either left or right sided clefts included congenital dental anomalies, handedness and additional congenital anomalies. Variables investigated as a potential cause of left or right sided clefts as an outcome included chromosomal anomalies, genetic variants and environmental factors. Outcomes investigated in relation to cleft sidedness as an exposure included facial anatomical features, facial growth, educational attainment, functional and psychological characteristics. More studies showed worse outcomes in right sided clefts versus left sided clefts than vice versa, although studies were inconsistent, and a quality assessment was not performed.ConclusionsThe field of cleft sidedness research is expanding and there are promising early findings to differentiate cause and outcome by sidedness of the cleft.
Emergence of disease-specific endothelial and stromal cell populations responsible for arterial remodeling during development of pulmonary arterial hypertension
Authors: Cober Nicholas D , McCourt Emma , Godoy Rafael Soares , Deng Yupu , Schlosser Ken , Situ Anu , Cook David P , Lemay Sarah-Eve , Klouda Timothy , Yuan Ke , Bonnet Sébastien , Stewart Duncan J 
Published: September 2023

AbstractPulmonary arterial hypertension (PAH) is a severe and lethal pulmonary vascular disease characterized by arteriolar pruning and occlusive vascular remodeling leading to increased pulmonary vascular resistance and eventually right heart failure. While endothelial cell (EC) injury and apoptosis are known triggers for this disease, the mechanisms by which they lead to complex arterial remodeling remain obscure. We employed multiplexed single-cell RNA sequencing (scRNA-seq) at multiple timepoints during the onset and progression of disease in a model of severe PAH to identify mechanisms involved in the development of occlusive arterial lesions. There was significant loss of arterial volume as early as 1-week by microCT, preceding any evidence of occlusive arteriopathy, consistent with early arteriolar dropout. Maximal arterial pruning was seen by 5 to 8 weeks, with signs of progressive occlusive remodeling. Analysis of the scRNA-seq data resolved 44 lung cell populations, with widespread early transcriptomic changes at 1 week affecting endothelial, stromal and immune cell populations. Notably, this included emergence of a relatively dedifferentiated (dD) EC population that was enriched forCd74expression compared to general capillary (gCap) ECs which were primed to undergo endothelial-mesenchymal transition, as evidenced by RNA velocity analysis. However, at late timepoints (5 and 8 weeks), activated arterial ECs (aAECs) were the only cell population exhibiting persistent differential gene expression. This was characterized by a growth regulated state, including high expression ofTm4sf1, a gene implicated in cancer cell growth, which was also expressed by a smooth muscle (SM)-like pericyte cluster. Both these populations were localized to regions of arterial remodeling in the rat model and PAH patients, with aAECs contributing to intimal occlusive lesions and SM-like pericytes forming bands of medial muscularization. Together these findings implicate disease-specific vascular cells in PAH progression and suggest that TM4SF1 may be a novel therapeutic target for arterial remodeling.
Descending control and regulation of spontaneous flight turns inDrosophila
Authors: Ros Ivo G. , Omoto Jaison J. , Dickinson Michael H. 
Published: September 2023

AbstractThe clumped distribution of resources in the world has influenced the pattern of foraging behavior since the origins of life, selecting for a common locomotor search motif in which straight movements through resource-poor regions alternate with zig-zag exploration in resource-rich domains (Berg, 2000). For example, flies execute rapid changes in flight heading called body saccades during local search (Censi et al., 2013; Collett and Land, 1975; Schilstra and van Hateren, 1999; Wagner and Land, 1986), but suppress these turns during long-distance dispersal (Giraldo et al., 2018; Leitch et al., 2021) or when surging upwind after encountering an attractive odor plume (Budick and Dickinson, 2006; van Breugel and Dickinson, 2014). Here, we describe the key cellular components of a neural network in flies that generates spontaneous turns as well as a specialized neuron that inhibits the network to promote straight flight. Using 2-photon imaging, optogenetic activation, and genetic ablation, we show that only four descending neurons appear sufficient to generate the descending commands to execute flight saccades. The network is organized into two functional couplets—one for right turns and one for left—with each couplet consisting of an excitatory (DNae014) and inhibitory (DNb01) neuron that project to the flight motor neuropil within the ventral nerve cord. Using resources from recently published connectomes of the fly brain (Scheffer et al., 2020; Dorkenwald et al., 2023; Schlegel et al., 2023), we identified a large, unique interneuron (VES041) that forms inhibitory connections to all four saccade command neurons and created specific genetic driver lines for this cell. As predicted by its connectivity, activation of VES041 strongly suppresses saccades, suggesting that it regulates the transition between local search and long-distance dispersal. These results thus identify the critical elements of a network that not only structures the locomotor behavior of flies, but may also play a crucial role in their foraging ecology.
CTCF regulates hepatitis B virus cccDNA chromatin topology
Authors: Dobrica Mihaela Olivia , Varghese Christy Susan , Harris James M , Ferguson Jack , Magri Andrea , Arnold Roland , Várnai Csilla , Parish Joanna L , McKeating Jane A 
Published: September 2023

ABSTRACTHepatitis B Virus (HBV) is a small DNA virus that replicates via an episomal covalently closed circular DNA (cccDNA) that serves as the transcriptional template for viral mRNAs. The host protein, CCCTC-binding factor (CTCF), is a key regulator of cellular transcription by maintaining epigenetic boundaries, nucleosome phasing, stabilisation of long-range chromatin loops and directing alternative exon splicing. We previously reported that CTCF binds two conserved motifs within Enhancer I of the HBV genome and represses viral transcripts, however, the underlying mechanisms were not identified. We show that CTCF depletion in cells harbouring cccDNA-like HBV molecules and inde novoinfected cells resulted in an increase in spliced transcripts, which was most notable in the abundant SP1 spliced transcript. In contrast, depletion of CTCF in cell lines with integrated HBV DNA had no effect on the abundance of viral transcripts and in line with this observation there was limited evidence for CTCF binding to viral integrants, suggesting that CTCF-regulation of HBV transcription is specific to episomal cccDNA. Analysis of HBV chromatin topology by Assay for Transposase Accessibility/sequencing (ATAC-Seq) revealed an accessible region spanning Enhancers I and II and the basal core promoter (BCP). Mutating the CTCF binding sites within Enhancer I resulted in a dramatic rearrangement of chromatin accessibility where the open chromatin region was no longer detected, indicating loss of the phased nucleosome up- and down-stream of the HBV enhancer/BCP. These data demonstrate that CTCF functions to regulate HBV chromatin conformation and nucleosomal positioning in episomal maintained cccDNA, which has important consequences for HBV transcription regulation.
The characteristics of CTCF binding sequences contribute to enhancer blocking activity
Authors: Tsang Felice H. , Stolper Rosa J. , Hanifi Muhammad , Cornell Lucy J. , Francis Helena S. , Davies Benjamin , Higgs Douglas R. , Kassouf Mira T. 
Published: September 2023

ABSTRACTWhile the elements encoding enhancers and promoters have been relatively well studied, the full spectrum of insulator elements which bind the CCCTC binding factor (CTCF), is relatively poorly characterised. This is partly due to the genomic context of CTCF sites greatly influencing their roles and activity. Here we have developed an experimental system to determine the ability of consistently sized, individual CTCF elements to interpose between enhancers and promoters and thereby reduce gene expression during differentiation. Importantly, each element is tested in the identical location thereby minimising the effect of genomic context. We found no correlation between the ability of CTCF elements to block enhancer-promoter activity with the amount of CTCF or cohesin bound at the natural genomic sites of these elements; the degree of evolutionary conservation; or their resemblance to the consensus core sequences. Nevertheless, we have shown that the strongest enhancer-promoter blockers include a previously described bound element lying upstream of the CTCF core motif. In addition, we found other uncharacterised DNaseI footprints located close to the core motif that may affect function. We have developed an assay of CTCF sequences which will enable researchers to sub-classify CTCF elements in a uniform and unbiased way.
ATAD1 and the integrated stress response prevent clogging of TOM and damage caused by un-imported mitochondrial proteins
Authors: Kim John , Goldstein Madeleine , Zecchel Lauren , Weidberg Hilla 
Published: September 2023

AbstractMitochondria require the constant import of nuclear-encoded proteins for proper functioning. Impaired protein import not only depletes mitochondria of essential factors but also leads to toxic accumulation of un-imported proteins outside the organelle. Defects in mitochondrial protein import are associated with neurodegenerative and bioenergetic diseases. Here, we investigated the consequences of mitochondrial protein import stress in human cells. We demonstrated that un-imported proteins can clog the mitochondria by stalling inside the translocase of the outer membrane (TOM). We found that the integrated stress response (ISR) acted as the first line of defense to mitochondrial clogging by attenuating global protein translation and preventing excessive accumulation of un-imported proteins. A second mechanism, mediated by a mitochondrial ATPase, ATAD1, acted specifically to remove proteins from TOM and clear the entry gate into the mitochondria. ATAD1 interacted with both TOM and stalled proteins, and its knockout resulted in extensive accumulation of mitochondrial precursors as well as decreased protein import. Increased ATAD1 expression improved tolerance of cells to defective mitochondrial protein import, demonstrating the importance of this quality control pathway in surveilling protein import and its contribution to cellular health.
The brain’s topographical organization shapes dynamic interaction patterns to support flexible behavior
Authors: Wang Xiuyi , Krieger-Redwood Katya , Lyu Baihan , Lowndes Rebecca , Wu Guowei , Souter Nicholas E. , Wang Xiaokang , Kong Ru , Shafiei Golia , Bernhardt Boris C. , Cui Zaixu , Smallwood Jonathan , Du Yi , Jefferies Elizabeth 
Published: September 2023

AbstractUnderstanding how human cognition flexibly supports distinct forms of behavior is a key goal of neuroscience. Adaptive behavior relies on context-specific rules that vary across situations, as well as on stable knowledge gained from experience. However, the mechanisms that allow these influences to be appropriately balanced remain elusive. Here, we show that this cognitive flexibility is partly supported by the topographical organization of the cortex. The frontoparietal control network (FPCN) is located between regions implicated in top-down attention and memory-guided cognition. We hypothesized that the FPCN is topographically divided into discrete systems that support these distinct forms of behavior. These FPCN subsystems exhibit multiple anatomical and functional similarities to their neighboring systems (the dorsal attention network and default mode network respectively). This topographic architecture is also mirrored in the functional patterns that emerge in different situations: the FPCN subnetworks act as a unified system when long-term memory can support behavior, but they segregate into discrete units when working memory, rather than long term memory, is necessary for behavioral control. In this way, the topographic organization of brain function provides crucial insights into how the human cortex supports flexible behavior.
Oral immunization of goats and foxes with a recombinant NDV vectored rabies vaccine
Authors: Murr Magdalena , Freuling Conrad , Pérez-Bravo David , Grund Christian , Mettenleiter Thomas C. , Römer-Oberdörfer Angela , Müller Thomas , Finke Stefan 
Published: September 2023

AbstractVaccination of the reservoir species is a key component in the global fight against rabies. For wildlife reservoir species and hard to reach spillover species (e. g. ruminant farm animals), oral vaccination is the only solution. In search for a novel potent and safe oral rabies vaccine, we generated a recombinant vector virus based on lentogenic Newcastle disease virus (NDV) strain Clone 30 that expresses the glycoprotein G of rabies virus (RABV) vaccine strain SAD L16 (rNDV_GRABV). Transgene expression and virus replication was verified in avian and mammalian cells.To test immunogenicity and viral shedding, in a proof-of-concept study six goats and foxes, representing herbivore and carnivore species susceptible to rabies, each received a single dose of rNDV_GRABV(108.5TCID50/animal) by direct oral application. For comparison, three animals received the similar dose of the empty viral vector (rNDV). All animals remained clinically inconspicuous during the trial. Viral RNA could be isolated from oral and nasal swabs until four (goats) or seven days (foxes) post vaccination, while infectious NDV could not be re-isolated. After four weeks, three out of six rNDV_GRABVvaccinated foxes developed RABV binding and virus neutralizing antibodies. Five out of six rNDV_GRABVvaccinated goats displayed RABV G specific antibodies either detected by ELISA or RFFIT. Additionally, NDV and RABV specific T cell activity was demonstrated in some of the vaccinated animals by detecting antigen specific interferon γ secretion in lymphocytes isolated from pharyngeal lymph nodes. In conclusion, the NDV vectored rabies vaccine rNDV_GRABVwas safe and immunogenic after a single oral application in goats and foxes, and highlight the potential of NDV as vector for oral vaccines in mammals.Author SummaryOral vaccination of rabies reservoir and spill-over species is the key to control the disease and prevent human rabies. In the past, baits containing live-attenuated rabies vaccines decreased significantly carnivore-mediated rabies in Central and Western Europe as well as North America. However, certain susceptible species are refractory to the oral immunization using so far licensed vaccines. Our vector vaccine based on avian Newcastle disease virus (NDV) has the potential to contribute to the targeted rabies eradication as it was safe and immunogenic after oral administration in goats and foxes. A single vaccine application elicited a rabies virus (RABV) specific systemic humoral immune response in the majority of the vaccinated animals as well as RABV specific T cells in some of the vaccinated animals. NDV can be manufactured at low-cost using already existing infrastructure of influenza vaccines, opening new possibilities especially for middle- and low-income countries that suffer under the economically burden of rabies.
The glucocorticoid receptor as a master regulator of Müller cell gliosis in the diabetic retina
Authors: Pfaller Anna M. , Kaplan Lew , Carido Madalena , Grassmann Felix , Díaz-Lezama Nundehui , Ghaseminejad Farhad , Wunderlich Kirsten A. , Glänzer Sarah , Pannicke Thomas , Weber Bernhard H.F. , Koch Susanne F. , Bonev Boyan , Hauck Stefanie M. , Grosche Antje 
Published: September 2023

AbstractDiabetic retinopathy (DR) is considered a primarily microvascular complication of diabetes. Müller glia cells are at the center of the retinal neurovascular unit and play a critical role in DR. We therefore investigated Müller cell-specific signaling pathways that are altered in DR to identify novel targets for gene therapy. Using a multi-omics approach on purified Müller cells from diabetic db/db mice, we found the mRNA and protein expression of the glucocorticoid receptor (GR) to be significantly decreased, while its target gene cluster was down-regulated. Further, oPOSSUM TF analysis and ATAC-sequencing identified the GR as a master regulator of Müller cell gliosis in DR. Cortisol not only increased GR phosphorylation. It also induced changes in the expression of known GR target genes in retinal explants. Finally, retinal functionality was improved by AAV-mediated overexpression of GR in Müller cells. Our study demonstrates an important role of the glial GR in DR and implies that therapeutic approaches targeting this signalling pathway should be aimed at increasing GR expression rather than the addition of more ligand.Graphical abstract