bluuebunny/crossref_metadata_2025_split huggingface dataset:
LinguaPhylo: a probabilistic model specification language for reproducible phylogenetic analyses
Authors: Drummond Alexei J. , Chen Kylie , Mendes Fábio K. , Xie Dong 
Published: August 2022

AbstractPhylogenetic models have become increasingly complex, and phylogenetic data sets have expanded in both size and richness. However, current inference tools lack a model specification language that can concisely describe a complete phylogenetic analysis while remaining independent of implementation details. We introduce a new lightweight and concise model specification language, ‘LPhy’, which is designed to be both human and machine-readable. A graphical user interface accompanies ‘LPhy’, allowing users to build models, simulate data, and create natural language narratives describing the models. These narratives can serve as the foundation for manuscript method sections. Additionally, we present a command-line interface for converting LPhy-specified models into analysis specification files (in XML format) compatible with the BEAST2 software platform. Collectively, these tools aim to enhance the clarity of descriptions and reporting of probabilistic models in phylogenetic studies, ultimately promoting reproducibility of results.
Sodium-glucose cotransporter-2 inhibitors and the risk of lung cancer among patients with type 2 diabetes: a retrospective cohort study
Authors: Shapiro Samantha B. , Yin Hui , Yu Oriana H.Y. , Azoulay Laurent 
Published: August 2022

AbstractObjectiveTo determine whether the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, compared to dipeptidyl peptidase 4 (DPP-4) inhibitors, is associated with a decreased risk of incident lung cancers among patients with type 2 diabetes.MethodsWe assembled a new-user, active comparator cohort of SGLT-2 inhibitor and DPP-4 inhibitor users using the United Kingdom Clinical Practice Research Datalink. We fit Cox proportional hazards models with propensity score fine stratification weighting to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for incident lung cancers.ResultsCrude lung cancer incidence rates were 0.92 and 1.37 per 1,000 person-years among 47,517 SGLT-2 inhibitor and 129,807 DPP-4 inhibitor users, respectively. No reduced risk of lung cancer was observed among SGLT-2 inhibitor users after weighting (HR 1.08, 95% CI 0.78–1.48). Conclusions: In this large cohort study, the use of SGLT-2 inhibitors was not associated with a decreased risk of lung cancer.
FGF21 Counteracts Alcohol Intoxication by Activating Noradrenergic Neurons
Authors: Choi Mihwa , Schneeberger Marc , Fan Wei , Bugde Abhijit , Gautron Laurent , Vale Kevin , Zhang Yuan , Friedman Jeffrey M. , Mangelsdorf David J. , Kliewer Steven A. 
Published: August 2022

SUMMARYAnimals that consume fermenting fruit or nectar are exposed to ethanol, thus increasing their risk of injury or predation. This risk is heightened in humans, who have actively imbibed alcohol for thousands of years. In this report, we show that the hormone FGF21, which is strongly induced by ethanol in murine and human liver, exerts sobering or “amethystic” effects on both arousal and motor coordination without changing ethanol catabolism. Mice lacking FGF21 take longer than wild-type littermates to recover their righting reflex and balance following ethanol exposure. Conversely, pharmacologic FGF21 administration reduces the time needed for mice to recover from ethanol-induced unconsciousness and ataxia. FGF21 mediates it amethystic effects by directly activating the noradrenergic nervous system, which regulates arousal and alertness. These results indicate that this FGF21 liver-brain pathway evolved to protect against ethanolinduced intoxication and that it might be targeted pharmaceutically for treating acute alcohol poisoning.
Sex differences in inter-individual gene expression variability across human tissues
Authors: Khodursky Samuel , Jiang Caroline S. , Zheng Eric B. , Vaughan Roger , Schrider Daniel R. , Zhao Li 
Published: August 2022

AbstractUnderstanding phenotypic sex differences has long been a goal of biology from both a medical and evolutionary perspective. Although much attention has been paid to mean differences in phenotype between the sexes, little is known about sex differences in phenotypic variability. To gain insight into sex differences in inter-individual variability at the molecular level, we analyzed RNA-seq data from 43 tissues from the Genotype-Tissue Expression project (GTEx). Within each tissue, we identified genes that show sex differences in gene expression variability. We found that these sex-differentially variable (SDV) genes are associated with various important biological functions, including sex hormone response, immune response, and other signaling pathways. By analyzing single-cell RNA sequencing data collected from breast epithelial cells, we found that genes with sex differences in gene expression variability in breast tissue tend to be expressed in a cell-type-specific manner. We looked for an association between SDV expression and Graves’ disease, a well-known heavily female-biased disease, and found a significant enrichment of Graves’ associated genes among genes with higher variability in females in thyroid tissue. This suggests a possible role for SDV expression in the context of sex-biased disease. We then examined the evolutionary constraints acting on genes with sex differences in variability and found that they exhibit evidence of increased selective constraint. Through analysis of sex-biased eQTL data, we found evidence that SDV expression may have a genetic basis. Finally, we propose a simple evolutionary model for the emergence of sex-differentially variable expression from sex-specific constraints.
Urp1 and Urp2 act redundantly to maintain spine shape in zebrafish larvae
Authors: Gaillard Anne-Laure , Mohamad Teddy , Quan Feng B. , de Cian Anne , Mosiman Christian , Tostivint Hervé , Pézeron Guillaume 
Published: August 2022

AbstractUrp1 and Urp2 are two neuropeptides, members of the Urotensin 2 family, that have been recently involved in the control of body axis morphogenesis in zebrafish. They are produced by a population of sensory spinal neurons, called cerebrospinal fluid contacting neurons (CSF-cNs), under the control of signals relying on the Reissner fiber, an extracellular thread bathing in the CSF. Here, we have investigated further the function of Urp1 and Urp2 (Urp1/2) in body axis formation and maintenance. We showed that urp1;urp2 double mutants develop strong body axis defects during larval growth, revealing the redundancy between the two neuropeptides. These defects were similar to those previously reported in uts2r3 mutants. We observed that this phenotype is not associated with bone formation defects nor with increased inflammation status but, by using specific inhibitors, we found that the action of Urp1/2 depends on myosin II contraction. Finally, we provide evidence that while the Urp1/2 signaling is functioning during larval growth but is dispensable for embryonic development. Taken together, our results show that Urp1/2 signaling is required in larvae to promote correct vertebral body axis, most likely by regulating muscle tone.
Spindle F-actin coordinates the first metaphase-anaphase transition in Drosophila meiosis
Authors: Wood Benjamin W. , Weil Timothy T. 
Published: August 2022

ABSTRACTMeiosis is a highly conserved feature of sexual reproduction that ensures germ cells have the correct number of chromosomes prior to fertilization. A subset of microtubules, known as the spindle, are essential for accurate chromosome segregation during meiosis. Building evidence in mammalian systems has recently highlighted the unexpected requirement of the actin cytoskeleton in chromosome segregation; a network of spindle actin filaments appear to regulate many aspects of this process. Here we show that Drosophila oocytes also have a spindle population of actin that regulates the formation of the microtubule spindle and chromosomal movements throughout meiosis. We demonstrate that genetic and pharmacological disruption of the actin cytoskeleton has a significant impact on spindle morphology, dynamics, and chromosome alignment and segregation during the metaphase-anaphase transition. We further reveal the requirement of calcium in maintaining the microtubule spindle and spindle actin. Together, our data highlights the significant conservation of morphology and mechanism of the spindle actin during meiosis.
Urine-based multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS
Authors: Batra Richa , Uni Rie , Akchurin Oleh M. , Alvarez-Mulett Sergio , Gómez-Escobar Luis G. , Patino Edwin , Hoffman Katherine L. , Simmons Will , Chetnik Kelsey , Buyukozkan Mustafa , Benedetti Elisa , Suhre Karsten , Schenck Edward , Cho Soo Jung , Choi Augustine M.K. , Schmidt Frank , Choi Mary E. , Krumsiek Jan 
Published: August 2022

AbstractAcute respiratory distress syndrome (ARDS), a life-threatening condition during critical illness, is a common complication of COVID-19. It can originate from various disease etiologies, including severe infections, major injury, or inhalation of irritants. ARDS poses substantial clinical challenges due to a lack of etiology-specific therapies, multisystem involvement, and heterogeneous, poor patient outcomes. A molecular comparison of ARDS groups holds the potential to reveal common and distinct mechanisms underlying ARDS pathogenesis. In this study, we performed a comparative analysis of urine-based metabolomics and proteomics profiles from COVID-19 ARDS patients (n = 42) and bacterial sepsis-induced ARDS patients (n = 17). The comparison of these ARDS etiologies identified 150 metabolites and 70 proteins that were differentially abundant between the two groups. Based on these findings, we interrogated the interplay of cell adhesion/extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis through a multi-omic network approach. Moreover, we identified a proteomic signature associated with mortality in COVID-19 ARDS patients, which contained several proteins that had previously been implicated in clinical manifestations frequently linked with ARDS pathogenesis. In summary, our results provide evidence for significant molecular differences in ARDS patients from different etiologies and a potential synergy of extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis. The proteomic mortality signature should be further investigated in future studies to develop prediction models for COVID-19 patient outcomes.
Public relations strategies employed by healthcare organizations to address vaccine hesitancy: the case of the Ghana Health Service
Authors: McCarthy Ruth , Donkoh Emmanuel Timmy , De Graft Arthur Dominic , Dassah Edward Tieru , Boadu Kwame Ofori , Otoo John Ekow , Ofori Boadu Ivy Wina , Fosu-Gyasi Samuel 
Published: August 2022

AbstractBackgroundStrategies for developing and advancing good public relations can be recognized in nearly all fields of life without making an exception for the healthcare industry. In the wake of the COVID-19 pandemic, matters of public health have gathered more force. The importance of effective public relations for improving healthcare is highlighted by the position that immediate access to reliable health information should be the hallmark of a just society. However, the strategies available for addressing major threats to the uptake of public health services such as mass vaccination campaigns are not properly studied and documented in the Ghanaian context.MethodsSemi-structured interviews were conducted with officials of the Ghana Health Service (GHS). Participants were recruited through purposive sampling. Data collected included demographic characteristics, perspectives on public relations strategies used in the past year to improve vaccine uptake as well as successes and pitfalls. Thematic content analysis was performed on data collected using the NVIVO software.ResultsHealthcare workers perceived vaccine hesitancy to be a threat with the potential to undermine an important strategic organizational goal related to COVID-19 illness. A combination of informative, motivational, persuasive and coercive public relations strategies was employed by the Ghana Health Service to address the challenge of vaccine hesitancy. These strategies were deployed across both traditional (print, radio, TV) and emerging/social media networks. Officials were optimistic that the strategies would produce results but were uncertain whether they could attribute current successes or failures to the PR strategies used.ConclusionSince the onset of the COVID-19 pandemic, several public relations strategies have been evidently employed by the Ghana Health Service to address vaccine hesitancy. The nature of the audience and PR strategies employed suggests that the effect of these strategies may be short-lived unless they are constantly reinforced by the GHS.
Humoral immune responses remain quantitatively impaired but improve qualitatively in anti-CD20 treated patients with multiple sclerosis after three or four COVID-19 vaccinations
Authors: Otto Carolin , Schwarz Tatjana , Jeworowski Lara M. , Schmidt Marie L. , Walper Felix , Pache Florence , Schindler Patrick , Niederschweiberer Moritz , Krumbholz Andi , Rose Ruben , Drosten Christian , Ruprecht Klemens , Corman Victor M 
Published: August 2022

AbstractBackgroundHumoral immune responses to COVID-19 vaccination are diminished in anti-CD20 treated patients with multiple sclerosis (pwMS). In healthy individuals, neutralizing antibodies against the SARS-CoV-2 Omicron variant are only detected after three COVID-19 vaccinations. It was hitherto unknown whether a third or fourth COVID-19 vaccination of anti-CD20 treated pwMS improves SARS-CoV-2 specific humoral immune responses, including neutralizing antibodies against Omicron.MethodsAnti-CD20 treated pwMS vaccinated two (n=61), three (n=57) or four (n=15) times and healthy controls (n=10) vaccinated thrice were included in a prospective cohort study. Anti-SARS-CoV-2 spike S1 IgG and IgA levels, maturation of SARS-CoV-2 IgG avidity, neutralizing capacity against the SARS-CoV-2 Omicron BA.2 variant and SARS-CoV-2 specific T cell responses were analyzed.ResultsThe proportion of anti-CD20 treated pwMS with detectable SARS-CoV-2 S1 IgG was similar after the second (31/61, 50.8%), third (31/57, 54.4%) and fourth (8/15, 53.3%) vaccination. In pwMS with detectable SARS-CoV-2 IgG, the proportion with high affinity antibodies increased from the second (6/31, 19.4%) to the third (17/31, 54.8%) and fourth (6/8, 75%) vaccination. While none (0/10) of the anti-CD20 treated pwMS vaccinated twice had Omicron specific neutralizing antibodies, 3/10 (30%) pwMS vaccinated thrice and 3/5 (60%) pwMS vaccinated four times generated Omicron specific neutralizing antibodies.ConclusionAlthough SARS-CoV-2 specific humoral immune responses remain quantitatively impaired, in those anti-CD20 treated pwMS who do develop SARS-CoV-2 antibodies, the functionality of SARS-CoV-2 antibodies, including neutralizing antibodies against Omicron, improves after three and four SARS-CoV-2 vaccinations, supporting current recommendations for one or two booster vaccination in anti-CD20 treated pwMS.
Defining and phenotyping gastric abnormalities in long-term type 1 diabetes using body surface gastric mapping
Authors: Xu William , Gharibans Armen A. , Calder Stefan , Schamberg Gabriel , Walters Anthony , Jang Jia , Varghese Chris , Carson Daniel , Daker Charlotte , Waite Stephen , Andrews Christopher N , Cundy Tim , O’Grady Gregory 
Published: August 2022

AbstractObjectiveTo define phenotypes of gastric myoelectrical abnormalities and relation to symptoms in people with longstanding T1D, compared to matched healthy controls, using a novel non-invasive body surface gastric mapping (BSGM) device.Research design and methodsBSGM was performed on people with T1D of >10 years duration and matched controls, employing Gastric Alimetry (Alimetry, New Zealand), comprising a high-resolution 64-channel array, validated symptom logging App, and wearable reader.Results32 people with T1D were recruited (15 with a high symptom burden), and 32 controls. Those with symptoms showed more unstable gastric myoelectrical activity, (Gastric Alimetry Rhythm Index 0.39 vs 0.51, p=0.017; and lower average spatial covariance 0.48 vs 0.51, p=0.009) compared with controls. Those with T1D and symptoms also had higher prevalence of peripheral neuropathy (67% vs 6%, p=0.001), anxiety/depression diagnoses (27% vs 0%, p=0.001), and mean HbA1c levels (76 vs 56 mmol/mol, p<0.001). BSGM defined distinct phenotypes in participants including those with markedly unstable gastric rhythms (4/32, 12.5%), and abnormally high gastric frequencies (10/32, 31%). Deviation in gastric frequency was positively correlated with symptoms of bloating, upper gut pain, nausea and vomiting, and fullness and early satiation (r>0.35, p<0.05)ConclusionGastroduodenal symptoms in people with longstanding T1D correlate with gastric myoelectrical abnormalities on BSGM evaluation, in addition to glycemic control, psychological comorbidities, and peripheral neuropathy. BSGM using the Gastric Alimetry device identified a range of myoelectrical phenotypes, representing both myogenic and neurogenic mechanisms, which represent targets for diagnosis, monitoring and therapy.
Proteome capacity constraints favor respiratory ATP generation
Authors: Shen Yihui , Dinh Hoang V. , Cruz Edward , Call Catherine M. , Baron Heide , Ryseck Rolf-Peter , Pratas Jimmy , Subramanian Arjuna , Fatma Zia , Weilandt Daniel , Dwaraknath Sudharsan , Xiao Tianxia , Hendry John I. , Tran Vinh , Yang Lifeng , Yoshikuni Yasuo , Zhao Huimin , Maranas Costas D. , Wühr Martin , Rabinowitz Joshua D. 
Published: August 2022

AbstractCells face competing metabolic demands. These include efficient use of both limited substrates and limited proteome capacity, as well as flexibility to deal with different environments. Flexibility requires spare enzyme capacity, which is proteome inefficient. ATP generation can occur via fermentation or respiration. Fermentation is much less substrate-efficient, but often assumed to be more proteome efficient 1–3, thereby favoring fast-growing cells engaging in aerobic glycolysis 4–8. Here, however, we show that mitochondrial respiration is actually more proteome-efficient than aerobic glycolysis. Instead, aerobic glycolysis arises from cells maintaining the flexibility to grow also anaerobically. These conclusions emerged from an unbiased assessment of metabolic regulatory mechanisms, integrating quantitative metabolomics, proteomics, and fluxomics, of two budding yeasts, Saccharomyces cerevisiae and Issatchenkia orientalis, the former more fermentative and the latter respiratory. Their energy pathway usage is largely explained by differences in proteome allocation. Each organism’s proteome allocation is remarkably stable across environmental conditions, with metabolic fluxes predominantly regulated at the level of metabolite concentrations. This leaves extensive spare biosynthetic capacity during slow growth and spare capacity of their preferred bioenergetic machinery when it is not essential. The greater proteome-efficiency of respiration is also observed in mammals, with aerobic glycolysis occurring in yeast or mammalian cells that maintain a fermentation-capable proteome conducive to both aerobic and anaerobic growth.
Fgf9-Nolz-1-Wnt2 Signaling Axis Regulates Morphogenesis of the Lung
Authors: Chen Shih-Yun , Liu Fu-Chin 
Published: August 2022

AbstractMorphological development of the lung requires complex signal crosstalk between the mesenchymal and epithelial progenitors. Elucidating the genetic cascades underlying the signal crosstalk is essential to understanding the morphogenesis of the lung. Here, we have identified Nolz-1/Znf503 as a mesenchymal lineage-specific transcriptional regulator that plays a key role in lung morphogenesis. The null mutation of Nolz-1 resulted in a severe hypoplasia phenotype, including decreased proliferation of mesenchymal cells, aberrant differentiation of epithelial cells, and defective growth of epithelial branches. The deletion of Nolz-1 also downregulated the expressions of Wnt2, Lef1, Fgf10, Gli3 and Bmp4. Mechanistically, we found that Nolz-1 regulated lung morphogenesis primarily through Wnt2 signaling. Loss of function and overexpression studies demonstrated that Nolz-1 transcriptionally activated Wnt2 and downstream β-catenin signaling to control mesenchymal cell proliferation and epithelial branching. The Nolz-1-Wnt2 axis was also supported by evidence that exogenous Wnt2 could causally rescue defective proliferation and epithelial branching in Nolz-1 knockout lungs. Finally, we have identified Fgf9 as an upstream regulator of Nolz-1. Collectively, Fgf9-Nolz-1-Wnt2 signaling represents a novel signaling axis in the control of lung morphogenesis. These findings are also relevant to lung tumorigenesis in which a pathological function of Nolz-1 is involved.
Deciphering transcriptional networks during human cardiac development
Authors: Canac Robin , Cimarosti Bastien , Girardeau Aurore , Forest Virginie , Olchesqui Pierre , Poschmann Jeremie , Redon Richard , Lemarchand Patricia , Gaborit Nathalie , Lamirault Guillaume 
Published: August 2022

AbstractHuman heart development is governed by transcription factor (TF) networks controlling dynamic and temporal gene expression alterations. Therefore, to comprehensively characterize these transcriptional regulations, day-to-day transcriptomic profiles were generated throughout the directed cardiac differentiation, starting from three distinct human induced pluripotent stem cell lines from healthy donors (32 days). We applied an expression-based correlation score to the chronological expression profiles of the TF genes, and clustered them into 12 sequential gene expression waves. We then identified a regulatory network of more than 23 000 activation and inhibition links between 216 TFs. Within this network, we observed previously unknown inferred transcriptional activations linking IRX3 and IRX5 TFs to three master cardiac TFs: GATA4, NKX2-5 and TBX5. Luciferase and co-immunoprecipitation assays demonstrated that these 5 TFs could (1) activate each other’s expression, (2) interact physically as multiprotein complexes and (3) together, finely regulate the expression of SCN5A, encoding the major cardiac sodium channel. Altogether, these results unveiled thousands of interactions between TFs, generating multiple robust hypotheses governing human cardiac development.