bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the principles of embryonic mammary gland branching morphogenesis
Authors: Lindström Riitta , Satta Jyoti P. , Myllymäki Satu-Marja , Lan Qiang , Trela Ewelina , Prunskaite-Hyyryläinen Renata , Kaczyńska Beata , Voutilainen Maria , Kuure Satu , Vainio Seppo J. , Mikkola Marja L. 
Published: August 2022

AbstractBranching morphogenesis is a characteristic feature of many essential organs such as the lung, kidney, and most glands, and the net result of two tissue behaviors: branch point initiation and elongation. Each branched organ has a distinct architecture customized to its physiological function, but how patterning occurs in these ramified tubular structures is a fundamental problem of development. Here we use quantitative 3D morphometrics, time-lapse imaging, manipulation ofex vivocultured embryonic organs, and mice deficient in the planar cell polarity componentVangl2to address this question in the developing mammary gland. Our results show that the embryonic epithelial trees are highly complex in topology owing to the flexible use of two distinct modes of branch point initiation: lateral branching and tip bifurcation. This non-stereotypy was contrasted by the remarkably constant average branch frequency indicating a ductal growth-invariant, yet stochastic propensity to branch. The probability to branch was malleable and could be tuned by manipulating the Fgf10 and Tgf-β1 pathways. Finally, ourin vivoandex vivotime-lapse imaging suggested the involvement of tissue rearrangements in mammary branch elongation.
Invasion of forested areas in Gabon (Central Africa) by the Asian tiger mosquito and the potential consequences from the One Health perspective
Authors: Obame-Nkoghe Judicaël , Roiz David , Ngangue Marc-Flaubert , Costantini Carlo , Rahola Nil , Jiolle Davy , Lehmann David , Makaga Loïc , Ayala Diego , Kengne Pierre , Paupy Christophe 
Published: August 2022

AbstractSince its first record in urban areas of Central-Africa in 2000s, the invasive mosquito, Aedes albopictus, has continued to spread across the region, including in remote rural areas, and promoted outbreaks of Aedes-borne diseases, such as dengue, chikungunya and Zika. From the One-Health perspective, such invasion might enhance Ae. albopictus interactions with wild animals in forest ecosystems and favor the spillover of zoonotic arboviruses to humans. From 2014 to 2018, we monitored the steady spread of this mosquito species in the wildlife reserve of La Lopé National Park (Gabon), and evaluated the magnitude of its colonization of the rainforest ecosystem using ovitraps, larval surveys, BG-Sentinel traps, and human landing catches following an anthropization gradient. We detected Ae. albopictus in forest galleries up to 15km away from La Lopé village. However, Ae. albopictus was significantly more abundant at anthropogenic sites than in less anthropized areas. The number of eggs laid by Ae. albopictus decreased progressively with the distance from the forest fringe up to 200m inside the forest, showing that its occurrence in forest ecosystems is restricted to anthropized-sylvatic interfaces with dense forest. This suggests that Ae. albopictus may act as bridge vector of zoonotic pathogens between wild and anthropogenic compartments.
BIN1 knockdown rescues systolic dysfunction in the aging heart
Authors: Westhoff Maartje , del Villar Silvia G. , Voelker Taylor L. , Thai Phung N. , Chiamvimonvat Nipavan , Dickson Eamonn J. , Dixon Rose E. 
Published: August 2022

AbstractCardiac dysfunction is a hallmark of aging in humans and mice. Here we report that a two-week treatment to restore youthful Bridging Integrator 1 (BIN1) levels in the hearts of 24-month-old mice rejuvenated cardiac function and substantially reversed the aging phenotype. Our data indicate that age-associated overexpression of BIN1 occurs alongside dysregulated endosomal recycling and disrupted trafficking of cardiac CaV1.2 and type 2 ryanodine receptors. These deficiencies affect channel function at rest and their upregulation during acute stress.In vivoechocardiography revealed reduced systolic function in old mice. BIN1 knockdown using an adeno-associated virus serotype 9 packaged shRNA-mBIN1 restored the nanoscale distribution and clustering plasticity of ryanodine receptors and recovered Ca2+transient amplitudes and cardiac systolic function toward youthful levels. Enhanced systolic function correlated with increased phosphorylation of the myofilament protein cardiac myosin binding protein-C. These results reveal BIN1 knockdown as a novel therapeutic strategy to rejuvenate the aging myocardium.Graphical Abstract
Monocular deprivation during the critical period alters neuronal tuning and the composition of visual circuitry
Authors: Brown Thomas C. , McGee Aaron W. 
Published: August 2022

AbstractAbnormal visual experience during a developmental critical period degrades cortical responsiveness. Yet how experience-dependent plasticity alters the response properties of individual neurons and composition of visual circuitry is unclear. Here we measured with calcium imaging in alert mice how monocular deprivation (MD) during the developmental critical period affects binocularity, orientation, and spatial frequency tuning for neurons in primary visual cortex. Tracking the tuning properties for several hundred neurons revealed that the interconversion of monocular and binocular neurons relies on the quality of visual experience to determine the ratio of monocular neurons responsive to the contralateral and ipsilateral eye. In addition, a population of neurons more responsive to the closed eye were exchanged for neurons with tuning properties more similar to the responsive neurons altered by MD. Thus, plasticity during the critical period adapts to recent experience by both altering the tuning of responsive neurons and recruiting neurons with matching tuning properties.
Model Misspecification Misleads Inference of the Spatial Dynamics of Disease Outbreaks
Authors: Gao Jiansi , May Michael R. , Rannala Bruce , Moore Brian R. 
Published: August 2022

Epidemiology has been transformed by the advent of Bayesian phylodynamic models that allow researchers to infer the geographic history of pathogen dispersal over a set of discrete geographic areas (1, 2). These models provide powerful tools for understanding the spatial dynamics of disease outbreaks, but contain many parameters that are inferred from minimal geographic information (i.e., the single area in which each pathogen was sampled). Consequently, inferences under these models are inherently sensitive to our prior assumptions about the model parameters. Here, we demonstrate that the default priors used in empirical phylodynamic studies make strong and biologically unrealistic assumptions about the underlying geographic process. We provide empirical evidence that these unrealistic priors strongly (and adversely) impact commonly reported aspects of epidemiological studies, including: (1) the relative rates of dispersal between areas; (2) the importance of dispersal routes for the spread of pathogens among areas; (3) the number of dispersal events between areas, and; (4) the ancestral area in which a given outbreak originated. We offer strategies to avoid these problems, and develop tools to help researchers specify more biologically reasonable prior models that will realize the full potential of phylodynamic methods to elucidate pathogen biology and, ultimately, inform surveillance and monitoring policies to mitigate the impacts of disease outbreaks.Significance StatementBayesian phylodynamic models have revolutionized epidemiology by enabling researchers to infer key aspects of the geographic history of disease outbreaks. These models contain many parameters that must be estimated from minimal information (the area from which each pathogen was sampled), rendering inferences under this approach inherently sensitive to the choice of priors on the model parameters. Here, we demonstrate that: (1) the priors assumed in≈93% of surveyed phylodynamic studies make strong and biologically unrealistic assumptions, and; (2) these priors distort the conclusions of epidemiological studies. We offer strategies and tools to specify more reasonable priors that will enhance our ability to understand pathogen biology and, thereby, to mitigate disease.
ETDRS letter scoring method improves the accuracy of 1.25% low-contrast visual acuity measurement in optic neuritis secondary to MS
Authors: You Yuyi , Yan Peng , Graham Stuart L. , Klistorner Alexander 
Published: August 2022

AbstractObjectivesTo examine whether the dynamic range of 1.25% low-contrast visual acuity (LCVA) measurement in MS patients with optic neuritis (ON) can be improved by using the Early Treatment Diabetic Retinopathy Study (ETDRS) letter scoring method.MethodsLCVA was tested using 2.5% and 1.25% low contrast ETDRS-style 4m Sloan letter charts. When ≥20 letters were read correctly, the letter score was equal to letter count plus 30. If <20 letters were read correctly, the letter score was equal to letter count at 4m plus the total number of letters read correctly at 1m.Results51 relapsing-remitting MS patients with unilateral ON were enrolled and 60.8% ON eyes had a 1.25% LCVA letter count worse than 1 line (5 letters). In ON eyes with <20 letter count, ETDRS letter score showed a significantly improved correlation with both macular GCIPL thickness (r=0.71, p<0.0001; vs r=0.31, p=0.08 for letter count) and VEP latency (r=-0.47, p=0.003; vs r=-0.15, p=0.4 for letter count).DiscussionGiven ON with VEP monitoring has been frequently used as a model in MS remyelination clinical trials, our proposed ETDRS-style LCVA letter scoring method may be considered to enhance the functional outcome measure, which is necessary for regulatory approval.
Comparing the Safety and Immunogenicity of homologous (Sputnik V) and heterologous (BNT162B2) COVID-19 prime-boost vaccination
Authors: AlMadhi Marwa , AlAwadhi Abdulla , Stevenson Nigel , Greish Khalid , Jawad Jaleela , Alsayyad Adel , Mirza Afaf , Alsaffar Basma , AlAlawi Ejlal , Fakhroo Khulood , Alalawi Batool , Alabbasi Lana , Aljalahma Noora , AlQahtani Manaf 
Published: August 2022

ABSTRACTStudies have shown increased immunogenicity from heterologous boosting. This study specifically assessed boosting with Pfizer-BioNTech in Sputnik V vaccination regimens. Reactogenicity was assessed through adverse events. Immunogenicity was assessed by comparing serum anti-Spike (Anti-S) protein antibody and neutralizing antibody titers before booster administration and after 30 days. A total of 428 participants were recruited in the heterologous arm and 351 in the homologous arm. Adverse events were more frequent in the heterologous arm (p<0.001). No serious adverse events were reported in either arm. Amongst 577 individuals who completed the study, Anti-S antibodies were 14.8 times higher after heterologous boosting, and 3.1 times higher after homologous boosting (p<0.001). Similarly, heterologous boosting showed a 2 fold increase in neutralizing antibodies, compared to a 1.6 fold increase in homologous boosting (p<0.001). In conclusion, both boosting regimens elicited an immunological response, nonetheless heterologous Pfizer-BioNTech showed a higher immunological response, with more adverse effects.ARTICLE SUMMARY LINEBoth homologous and heterologous boosting are effective in eliciting an immunological response, however heterologous boosting with Pfizer-BioNTech elicited a higher immunological response, with more adverse effects.
Dysphagia and shortness-of-breath as markers for treatment failure and survival in oropharyngeal cancer after radiation
Authors: Wang Jarey H. , McCoy Lance , Salama Vivian , Ajayi Temitayo , Dede Cem , Moreno Amy , Mohamed Abdallah S.R. , Hutcheson Katherine A. , Fuller Clifton David , van Dijk Lisanne V. 
Published: August 2022

AbstractBackgroundPost-treatment symptoms are a focal point of follow-up visits for head and neck cancer patients. While symptoms such as dysphagia and shortness-of-breath early after treatment may motivate additional work up, their precise association with disease control and survival outcomes is not well established.MethodsThis prospective data cohort study of 470 oropharyngeal cancer patients analyzed patient-reported swallowing, choking and shortness-of-breath symptoms at 3-to-6 months following radiotherapy to evaluate their association with overall survival and disease control. Associations between the presence of moderate-to-severe swallowing, choking and mild-to-severe shortness-of-breath and treatment outcomes were analyzed via Cox regression and Kaplan-Meier. The main outcome was overall survival (OS), and the secondary outcomes were local, regional, and distant disease control.ResultsThe majority of patients (91.3%) were HPV-positive. Median follow-up time was 31.7 months (IQR: 21.9-42.1). Univariable analysis showed significant associations between OS and all three symptoms of swallowing, choking, and shortness-of-breath. A composite variable integrating scores of all three symptoms was significantly associated with OS on multivariable Cox regression (p=0.0018). Additionally, this composite symptom score showed the best predictive value for OS (c-index=0.75). Multivariable analysis also revealed that the composite score was significantly associated with local recurrence/progression (p=0.025). Notably, the same significant associations with OS were seen for HPV-positive only subset analysis (p<0.01 for all symptoms).ConclusionsQuantitative patient-reported measures of dysphagia and shortness-of-breath 3-to-6 months post-treatment are significant predictors of OS and disease recurrence/progression in OPC patients and in HPV-positive OPC only.
Phenome-wide Mendelian randomisation analysis identifies causal factors for age-related macular degeneration
Authors: Julian Thomas H , Cooper-Knock Johnathan , MacGregor Stuart , Guo Hui , Aslam Tariq , Sanderson Eleanor , Black Graeme C , Sergouniotis Panagiotis I 
Published: August 2022

ABSTRACTBackgroundAge-related macular degeneration (AMD) is a leading cause of blindness in the industrialised world and is projected to affect >280 million people worldwide by 2040. Aiming to identify causal factors and potential therapeutic targets for this common condition, we designed and undertook a phenome-wide Mendelian randomisation (MR) study.MethodsWe evaluated the effect of 4,591 exposure traits on early AMD using univariable MR. Statistically significant results were explored further using: validation in an advanced AMD cohort; MR Bayesian model averaging (MR-BMA); and multivariable MR.ResultsOverall, 44 traits were found to be putatively causal for early AMD in univariable analysis. Serum proteins that were found to have significant relationships with AMD included S100-A5 (odds ratio [OR]=1.07, p-value=6.80E-06), cathepsin F (OR=1.10, p-value=7.16E-05) and serine palmitoyltransferase 2 (OR=0.86, p-value=1.00E-03). Univariable MR analysis also supported roles for complement and immune cell traits. Although numerous lipid traits were found to be significantly related to AMD, MR-BMA suggested a driving causal role for serum sphingomyelin (marginal inclusion probability [MIP]=0.76; model-averaged causal effect [MACE]=0.29).ConclusionsThe results of this MR study support several putative causal factors for AMD and highlight avenues for future translational research.FundingThis project was funded by the Wellcome Trust (224643/Z/21/Z); the University of Manchester’s Wellcome Institutional Strategic Support Fund (Wellcome ISSF) grant (204796/Z/16/Z); the UK National Institute for Health Research (NIHR) Academic Clinical Fellow and Clinical Lecturer Programmes; Retina UK and Fight for Sight (GR586); the Australian National Health and Medical Research Council (NHMRC) (1150144).IMPACT STATEMENTA phenome-wide Mendelian randomisation analysis revealed a causal link between age-related macular degeneration and a number of lipid, complement, immune cell, and serum protein traits, highlighting potential treatment targets.
Sex-stratified RNA-seq analysis reveals traumatic brain injury-induced transcriptional changes in the female hippocampus conducive to dementia
Authors: Fiorini Michael R. , Dilliott Allison A. , Farhan Sali M.K. 
Published: August 2022

AbstractTraumatic brain injury (TBI), resulting from a violent force that causes functional changes in the brain, is the foremost environmental risk factor for developing dementia. While previous studies have identified specific candidate genes that may instigate worse outcomes following TBI when mutated, TBI-induced changes in gene expression conducive to dementia are critically understudied. Additionally, biological sex seemingly influences TBI outcomes, but the discrepancies in post-TBI gene expression leading to progressive neurodegeneration between the sexes have yet to be investigated. We conducted a whole-genome RNA sequencing analysis of post-mortem brain tissue from the parietal neocortex, temporal neocortex, frontal white matter, and hippocampus of 107 donors characterized by the Aging, Dementia, and Traumatic Brain Injury Project. Our analysis was sex-stratified and compared gene expression patterns between TBI donors and controls, a subset of which presented with dementia. Here we report three candidate gene modules from the female hippocampus whose expression correlated with dementia in female TBI donors. Enrichment analyses revealed that the candidate modules were notably enriched in cardiac processes and the immune-inflammatory response, among other biological processes. In addition, multiple candidate module genes showed a significant positive correlation with hippocampal concentrations of monocyte chemoattractant protein-1 in females with post-TBI dementia, which has been previously described as a potential biomarker for TBI and susceptibility to post-injury dementia. We concurrently examined the expression profiles of these candidate modules in the hippocampus of males with TBI and found no apparent indicator that the identified candidate modules contribute to post-TBI dementia in males. Here, we present the first sex-stratified RNA sequencing analysis of TBI-induced changes to the transcriptome that may be conducive to dementia. This work contributes to our current understanding of the pathophysiological link between TBI and dementia and emphasizes the growing interest in sex as a biological variable affecting TBI outcomes.
Identification of novel plasma lipid markers of cardiovascular disease risk in White and Black women
Authors: Jain Raghav , Davidson Jessica , Gonzalez Paula , Coe Chris , King Camille , Ryff Carol , Bersh Andrew , Mohsin Sheher , Love Gayle D. , Nimityongskul Francesca , Malecki Kristen , Simcox Judith 
Published: August 2022

AbstractRationaleCardiovascular disease (CVD) is the leading cause of mortality for women in the USA. Current clinical biomarkers are inadequate to determine CVD risk in women, especially Black women, who disproportionately suffer from CVD.MethodsClinical data and LC-MS lipidomics from two independent study cohorts were used to identify novel circulating markers of CVD risk in White and Black women. Machine learning assessed predictive efficacy of identified lipids, and targeted oxylipid analysis provided insight into dysregulated inflammatory pathways.ResultsSelect phospholipids and triglycerides containing acyl chains in the arachidonic acid (ARA) pathway were predictive of systolic blood pressure (BP) after adjusting for biological factors including age, obesity, and glycemic status in White and Black women. Oxylipid levels indicated increased conversion of ARA through the COX and LOX enzymes to pro-inflammatory cytokines in Black women.ConclusionARA-containing phospholipid are independent predictors of CVD risk in White and Black women. Predisposition to CVD risk in Black women may further be explained by increased production of pro-inflammatory oxylipids relative to White women, regardless of blood pressure status. Future studies investigating the clinical utility of phospholipid ARA abundance as a marker of CVD risk in White and Black women are warranted.
TRENDS IN CASES, HOSPITALISATION AND MORTALITY RELATED TO THE OMICRON BA.4/BA.5 SUB-VARIANTS IN SOUTH AFRICA
Authors: Jassat Waasila , Abdool Karim Salim S , Ozougwu Lovelyn , Welch Richard , Mudara Caroline , Masha Maureen , Rousseau Petro , Wolmarans Milani , Selikow Anthony , Govender Nevashan , Walaza Sibongile , Gottberg Anne von , Wolter Nicole , Pisa Pedro Terrence , Sanne Ian , Govender Sharlene ,   DATCOV author group, Blumberg Lucille , Cohen Cheryl , Groome Michelle J. 
Published: August 2022

ABSTRACTIntroductionThe Omicron BA.1/BA.2 wave in South Africa had lower hospitalisation and mortality than previous SARS-CoV-2 variants and was followed by an Omicron BA.4/BA.5 wave. This study compared admission incidence risk across waves, and the risk of mortality in the Omicron BA.4/BA.5 wave, to the Omicron BA.1/BA.2 and Delta waves.MethodsData from South Africa’s national hospital surveillance system, SARS-CoV-2 case linelist and Electronic Vaccine Data System were linked and analysed. Wave periods were defined when the country passed a weekly incidence of 30 cases/100,000 people. Mortality rates in the Delta, Omicron BA.1/BA.2 and Omicron BA.4/BA.5 wave periods were compared by post-imputation random effect multivariable logistic regression models.ResultsIn-hospital deaths declined 6-fold from 37,537 in the Delta wave to 6,074 in the Omicron BA.1/BA.2 wave and a further 7-fold to 837 in the Omicron BA.4/BA.5 wave. The case fatality ratio (CFR) was 25.9% (N=144,798), 10.9% (N=55,966) and 7.1% (N=11,860) in the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves respectively. After adjusting for age, sex, race, comorbidities, health sector and province, compared to the Omicron BA.4/BA.5 wave, patients had higher risk of mortality in the Omicron BA.1/BA.2 wave (adjusted odds ratio [aOR] 1.43; 95% confidence interval [CI] 1.32-1.56) and Delta (aOR 3.22; 95% CI 2.98-3.49) wave. Being partially vaccinated (aOR 0.89, CI 0.86-0.93), fully vaccinated (aOR 0.63, CI 0.60-0.66) and boosted (aOR 0.31, CI 0.24-0.41); and prior laboratory-confirmed infection (aOR 0.38, CI 0.35-0.42) were associated with reduced risks of mortality.ConclusionOverall, admission incidence risk and in-hospital mortality, which had increased progressively in South Africa’s first three waves, decreased in the fourth Omicron BA.1/BA.2 wave and declined even further in the fifth Omicron BA.4/BA.5 wave. Mortality risk was lower in those with natural infection and vaccination, declining further as the number of vaccine doses increased.