bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between overcrowded households, multigenerational households, and COVID-19: a cohort study
Authors: Ghosh Arnab K. , Venkatraman Sara , Soroka Orysya , Reshetnyak Evgeniya , Rajan Mangala , An Anjile , Chae John K. , Gonzalez Christopher , Prince Jonathan , DiMaggio Charles , Ibrahim Said , Safford Monika M. , Hupert Nathaniel 
Published: June 2021

AbstractIntroductionThe role of overcrowded and multigenerational households as a risk factor for COVID-19 remains unmeasured. The objective of this study is to examine and quantify the association between overcrowded and multigenerational households, and COVID-19 in New York City (NYC).MethodsWe conducted a Bayesian ecological time series analysis at the ZIP Code Tabulation Area (ZCTA) level in NYC to assess whether ZCTAs with higher proportions of overcrowded (defined as proportion of estimated number of housing units with more than one occupant per room) and multigenerational households (defined as the estimated percentage of residences occupied by a grandparent and a grandchild less than 18 years of age) were independently associated with higher suspected COVID-19 case rates (from NYC Department of Health Syndromic Surveillance data for March 1 to 30, 2020). Our main measure was adjusted incidence rate ratio (IRR) of suspected COVID-19 cases per 10,000 population. Our final model controlled for ZCTA-level sociodemographic factors (median income, poverty status, White race, essential workers), prevalence of clinical conditions related to COVID-19 severity (obesity, hypertension, coronary heart disease, diabetes, asthma, smoking status, and chronic obstructive pulmonary disease), and spatial clustering.Results39,923 suspected COVID-19 cases presented to emergency departments across 173 ZCTAs in NYC. Adjusted COVID-19 case rates increased by 67% (IRR 1.67, 95% CI = 1.12, 2.52) in ZCTAs in quartile four (versus one) for percent overcrowdedness and increased by 77% (IRR 1.77, 95% CI = 1.11, 2.79) in quartile four (versus one) for percent living in multigenerational housing. Interaction between both exposures was not significant (βinteraction = 0.99, 95% CI: 0.99-1.00).ConclusionsOver-crowdedness and multigenerational housing are independent risk factors for suspected COVID-19. In the early phase of surge in COVID cases, social distancing measures that increase house-bound populations may inadvertently but temporarily increase SARS-CoV-2 transmission risk and COVID-19 disease in these populations.
Statistical tests for heterogeneity of clusters and composite endpoints
Authors: Webster Anthony J. 
Published: June 2021

AbstractClinical trials and epidemiological cohort studies often group similar diseases together into a composite endpoint, to increase statistical power. A common example is to use a 3-digit code from the International Classification of Diseases (ICD), to represent a collection of several 4-digit coded diseases. More recently, data-driven studies are using associations with risk factors to cluster diseases, leading this article to reconsider the assumptions needed to study a composite endpoint of several potentially distinct diseases. An important assumption is that the (possibly multivariate) associations are the same for all diseases in a composite endpoint (not heterogeneous). Therefore, multivariate measures of heterogeneity from meta-analysis are considered, including multi-variate versions of the I2 and Q statistics. Whereas meta-analysis offers tools to test heterogeneity of clustering studies, clustering models suggest an alternative heterogeneity test, of whether the data are better described by one, or more, clusters of elements with the same mean. The assumptions needed to model composite endpoints with a proportional hazards model are also considered. It is found that the model can fail if one or more diseases in the composite endpoint have different associations. Tests of the proportional hazards assumption can help identify when this occurs. It is emphasised that in multi-stage diseases such as cancer, some germline genetic variants can strongly modify the baseline hazard function and cannot be adjusted for, but must instead be used to stratify the data.
Train-the-Trainer as an Effective Approach to Building Global Networks of Experts in Genomic Surveillance of AMR
Authors: Abrudan Monica , Matimba Alice , Nikolic Dusanka , Hughes Darren , Argimón Silvia , Kekre Mihir , Underwood Anthony , Aanensen David ,   The NIHR Global Health Research Unit (GHRU) on Genomic Surveillance of Antimicrobial Resistance
Published: June 2021

ABSTRACTAdvanced genomics and sequencing technologies are increasingly becoming critical for global health applications such as pathogen and antimicrobial resistance (AMR) surveillance. Limited resources challenge capacity development in low- and middle-income countries (LMICs), with few countries having genomics facilities and adequately trained staff. Training research and public health experts who are directly involved in the establishment of such facilities offers an effective, but limited, solution to a growing need. Instead, training them to impart their knowledge and skills to others provides a sustainable model for scaling up the much needed capacity and capability for genomic sequencing and analysis locally with global impact. We designed and developed a Train-the-Trainer course integrating pedagogical aspects with genomic and bioinformatics activities. The course was delivered to 18 participants from 12 countries in Africa, Asia, and Latin America. A combination of teaching strategies culminating in a group project created a foundation for continued development at home institutions. Upon follow-up after 6 months, at least 40% of trainees had initiated training programs and collaborations to build capacity at local, national, and regional level. This work provides a framework for implementing a training and capacity building program for the application of genomics tools and resources in AMR surveillance.40-word summaryThis work provides a framework for implementing a training and capacity building program for the application of genomics tools and resources in AMR surveillance. We outline a Train-the-Trainer course integrating pedagogical aspects with genomic and bioinformatics activities.
Modelling, Simulations and Analysis of the First COVID-19 Epidemic in Shanghai
Authors: Min Lequan 
Published: June 2021

AbstractTo date, over 178 million people on infected with COVID-19. It causes more 3.8 millions deaths. Based on a previous symptomatic-asymptomatic-recoverer-dead differential equation model (SARDDE) and the clinic data of the first COVID-19 epidemic in Shanghai, this paper determines the parameters of SARDDE. Numerical simulations of SARDDE describe well the outcomes of current symptomatic individuals, recovered symptomatic individuals, and died individuals, respectively. The numerical simulations suggest that both symptomatic and asymptomatic individuals cause lesser asymptomatic spread than symptomatic spread; blocking rate of about 95.5% cannot prevent the spread of the COVID19 epidemic in Shanghai. The strict prevention and control strategies implemented by Shanghai government is not only very effective but also completely necessary. The numerical simulations suggest also that using the data from the beginning to the day after about 19 days at the turning point can estimate well the following outcomes of the COVID-19 academic. It is expected that the research can provide better understanding, explaining, and dominating for epidemic spreads, prevention and control measures.
The AMIGO1 adhesion protein activates Kv2.1 voltage sensors
Authors: Sepela R.J. , Stewart R.G. , Valencia L.A. , Thapa P. , Wang Z. , Cohen B.E. , Sack J.T. 
Published: June 2021

AbstractKv2 voltage-gated potassium channels are modulated by AMIGO neuronal adhesion proteins. Here, we identify steps in the conductance activation pathway of Kv2.1 channels that are modulated by AMIGO1 using voltage clamp recordings and spectroscopy of heterologously expressed Kv2.1 and AMIGO1 in mammalian cell lines. AMIGO1 speeds early voltage sensor movements and shifts the gating charge–voltage relationship to more negative voltages. The gating charge–voltage relationship indicates that AMIGO1 exerts a larger energetic effect on voltage sensor movement than apparent from the midpoint of the conductance–voltage relationship. When voltage sensors are detained at rest by voltage sensor toxins, AMIGO1 has a greater impact on the conductance–voltage relationship. Fluorescence measurements from voltage sensor toxins bound to Kv2.1 indicate that with AMIGO1, the voltage sensors enter their earliest resting conformation, yet this conformation is less stable upon voltage stimulation. We conclude that AMIGO1 modulates the Kv2.1 conductance activation pathway by destabilizing the earliest resting state of the voltage sensors.Statement of SignificanceKv2 potassium channels activate a potassium conductance that shapes neuronal action potentials. The AMIGO family of adhesion proteins modulate activation of Kv2 conductances, yet, which activation steps are modified is unknown. This study finds that AMIGO1 destabilizes the earliest resting conformation of the Kv2.1 voltage sensors to promote activation of channel conductance.
Phytochrome gene expression studies: PHYE is required for FR-induced expression of PHYA and PHYD suppresses expression of PHYA
Authors: Shapulatov Umidjon , Meisenburg Mara , van Hoogdalem Mark , van Hall Alexander , van Ieperen Wim , van Wassenaar Maarten , van der Krol Alexander 
Published: June 2021

AbstractArabidopsis has five phytochrome (PHY) genes for sensing the Red:Far Red (R:FR) ratio in ambient light, of which PHYA has an established role in responses to FR. To study whether and how PHYs may influence each other’s transcription, PHY-Luciferase reporter plants (pPHYA:LUC, pPHYB:LUC, pPHYC:LUC, pPHYD:LUC and pPHYE:LUC) were constructed. Subsequently, reporter lines representative for each PHY were crossed into each of the five single phy-mutant backgrounds. Reporter activities in WT and phy mutant was studied under diurnal mixed (R, B, FR), R, FR or B LED light in seedling or rosette plants. Both pPHYA:LUC and pPHYB:LUC show strong induction under FR. Full FR upregulation of both PHYA and PHYB is dependent on PHYE, identifying PHYE as a novel sensor for FR light responses. Results also show that PHYA expression is strongly suppressed by PHYD. Results were confirmed for expression of endogenous PHYA and PHYB, albeit with different dynamics compared to the LUC reporters. Profiling of pPHYA:LUC and pPHYB:LUC reporters suggest gating of FR responses. Manipulation of PHY expression levels by FR may provide a novel basis for manipulating plant growth in controlled environments.
WEE1 kinase is a therapeutic vulnerability in CIC-DUX4 undifferentiated sarcoma
Authors: Ponce Rovingaile Kriska , Thomas Nicholas J. , Bui Nam Q. , Kondo Tadashi , Okimoto Ross A. 
Published: June 2021

AbstractCIC-DUX4 rearrangements define an aggressive and chemotherapy-insensitive subset of undifferentiated sarcomas. The CIC-DUX4 fusion drives oncogenesis through direct transcriptional upregulation of cell cycle and DNA replication genes. Notably, CIC-DUX4- mediated CCNE1 upregulation compromises the G1/S transition, conferring a potential survival dependence on the G2/M cell cycle checkpoint. Through an integrative transcriptional and kinase activity screen using patient-derived specimens, we now show that CIC-DUX4 sarcomas depend on the G2/M checkpoint regulator, WEE1, as an adaptive survival mechanism. Specifically, CIC-DUX4 sarcomas depend on WEE1 activity to limit DNA damage and unscheduled mitotic entry. Consequently, genetic or pharmacologic WEE1 inhibition in vitro and in vivo leads to rapid DNA damage-associated apoptotic induction of patient-derived CIC-DUX4 sarcomas. Thus, we identify WEE1 as an actionable therapeutic vulnerability in CIC-DUX4 sarcomas.
Ecological memory of prior nutrient exposure in the human gut microbiome
Authors: Letourneau Jeffrey , Holmes Zachary C , Dallow Eric P , Durand Heather K , Jiang Sharon , Gupta Savita K , Mincey Adam C , Muehlbauer Michael J , Bain James R , David Lawrence A 
Published: June 2021

AbstractMany ecosystems retain an ecological memory of past conditions that affects responses to future stimuli. However, it remains unknown what mechanisms and dynamics may govern such a memory in microbial communities. Here, in both a human dietary intervention cohort and an artificial gut, we show that the human gut microbiome encodes a memory of past carbohydrate exposures. Changes in the relative abundance of primary degraders were sufficient to enhance metabolism, and these changes were mediated by transcriptional changes within hours of initial exposure. We further found that ecological memory of one carbohydrate species impacted metabolism of others. These findings demonstrate that the human gut microbiome’s metabolic potential reflects dietary exposures over preceding days and changes within hours of exposure to a novel nutrient.One Sentence SummaryRecent nutrient exposures are encoded into the structure and activity of human gut microbial communities, which enables more efficient future metabolic responses.
Inflammation induces pro-NETotic neutrophils via TNFR2 signaling
Authors: Neuenfeldt Friederike , Schumacher Jan Christoph , Grieshaber-Bouyer Ricardo , Habicht Jüri , Schröder-Braunstein Jutta , Gauss Annika , Niesler Beate , Heineken Niko , Dalpke Alexander , Gaida Matthias M. , Giese Thomas , Meuer Stefan , Samstag Yvonne , Wabnitz Guido 
Published: June 2021

AbstractCytokines released during chronic inflammatory diseases induce pro-inflammatory properties in polymorphonuclear neutrophils (PMN). Here we show that in vitro cytokine treatment leads to the development of a subgroup of human PMN expressing CCR5, termed CCR5+ cytokine-induced PMN (CCR5+ cPMN). Auto/paracrine TNF signaling increases intracellular neutrophil elastase (ELANE) abundance and induces NETosis in CCR5+ cPMN. Triggering of CCR5 amplifies NETosis. Membranous TNF (mTNF) outside-in signaling induces the formation of reactive oxygen species, a known activator of NETosis. In vivo, we find an increased number of CCR5+ cPMN in the peripheral blood and inflamed lamina propria of patients with ulcerative colitis (UC) but not Crohn’s disease (CD). Notably, failure of anti-TNF therapy is associated with higher frequencies of CCR5+ cPMN. In conclusion, we identify a phenotype of pro-NETotic, CCR5 positive PMN present in inflamed tissue in vivo and inducible in vitro. These cells may reflect an important component of tissue damage during chronic inflammation and could be of diagnostic value.
Antibiotics drive expansion of rare pathogens in a chronic infection microbiome model
Authors: Varga John J. , Zhao Conan , Davis Jacob D. , Hao Yiqi , Farrell Jennifer M. , Gurney James R. , Voit Eberhard , Brown Sam P 
Published: June 2021

AbstractChronic (long-lasting) infections are globally a major and rising cause of morbidity and mortality. Unlike typical acute infections, chronic infections are ecologically diverse, characterized by the presence of a polymicrobial mix of opportunistic pathogens and human-associated commensals. To address the challenge of chronic infection microbiomes, we focus on a particularly well-characterized disease, cystic fibrosis (CF), where polymicrobial lung infections persist for decades despite frequent exposure to antibiotics. Epidemiological analyses point to conflicting results on the benefits of antibiotic treatment, and are confounded by the dependency of antibiotic exposures on prior pathogen presence, limiting their ability to draw causal inferences on the relationships between antibiotic exposure and pathogen dynamics. To address this limitation, we develop a synthetic infection microbiome model, and benchmark on clinical data. We show that, in the absence of antibiotics, the microbiome structure in a synthetic sputum medium is highly repeatable and dominated by oral commensals. In contrast, challenge with physiologically relevant antibiotic doses leads to substantial community perturbation characterized by multiple alternate pathogen-dominant states and enrichment of drug-resistant species. These results provide evidence that antibiotics can drive the expansion (via competitive release) of previously rare opportunistic pathogens and offer a path towards microbiome-informed conditional treatment strategies.
Analysis of the H-Ras mobility patternin vivoshows cellular heterogeneity inside epidermal tissue
Authors: Gora Radoslaw J. , de Jong Babette , van Hage Patrick , Rhiemus Mary A. , van Steenis Fjodor , van Noort John , Schmidt Thomas , Schaaf Marcel J.M. 
Published: June 2021

ABSTRACTOver the last two decades, developments in single-molecule microscopy (SMM) have enabled imaging and tracking of individual, fluorescently labelled proteins in biological systems, and most of these studies have focused on the analysis of protein mobility patterns inside cultured cells. In the present study, SMM was appliedin vivo, using the zebrafish embryo model. We studied the protein dynamics of the membrane protein H-Ras, mutants of this protein, and its membrane-anchoring domain, C10H-Ras, in epidermal cells of living two-day-old embryos, using a total internal reflection fluorescence microscopy (TIRFM) setup. For all proteins studied, our results consistently confirm the presence of a fast- and a slow-diffusing subpopulations of molecules, which both confine to microdomains within the plasma membrane. Although the mobility patterns of H-Ras, mutants of this proteins and its membrane-anchoring domain were remarkably similar, the constitutively active H-Ras mutant, H-RasV12, exhibited significantly higher diffusion rates than the wild-type H-Ras and its inactive mutant, H-RasN17. Ultimately, we characterized variability in our data obtained using the zebrafish embryo model and demonstrated that differences between cells within the same embryo are the largest source of variation in our data. Our findings are in line with a model in which the cellular architecture of individual cells within a tissue determine the mobility of H-Ras proteins anchored in the plasma membrane cytoplasmic leaflet. Thereby, our results underline the growing importance of performing SMM imagingin vivoin order to better understand factors influencing the protein dynamics in an intact living organism.SUMMARY STATEMENTBy application of single-molecule microscopy to living zebrafish embryos, factors altering thein vivodynamics of H-Ras proteins in epidermal cells were analyzed.
Immunological features that determine the strength of antibody responses to BNT162b2 mRNA vaccine against SARS-CoV-2
Authors: Kageyama Takahiro , Tanaka Shigeru , Etori Keishi , Hattori Koto , Miyachi Kazusa , Kasuya Tadamichi , Iwamoto Taro , Ikeda Kei , Igari Hidetoshi , Yokote Koutaro , Nakajima Hiroshi 
Published: June 2021

ABSTRACTWe analyzed peripheral blood mononuclear cells (PBMCs) of each 20 individuals with a high anti-SARS-CoV-2 antibody titer and a low antibody titer out of 1,774 healthcare workers who received BNT162b2 mRNA vaccine. A higher antibody titer was associated with the frequencies of naïve and transitional B cells before vaccination. In addition, fold changes in the frequency of activated CD8+ T cells upon vaccination were correlated with the antibody titers.
A ligated intestinal loop mouse model protocol to study the interactions of Clostridioides difficile spores with the intestinal mucosa during aging
Authors: Castro-Córdova Pablo , Mendoza-Leon María José , Paredes-Sabja Daniel 
Published: June 2021

ABSTRACTThe interaction of the Clostridioides difficile spores with the intestinal mucosa contribute to the persistence and recurrence of the infection. Advanced age is one of the main risk factors to manifest C. difficile infection and recurrence. However, the interaction of C. difficile spores with the intestinal mucosa during aging has not been evaluated. In the present work, we provide a detailed protocol with all the critical information to perform an intestinal ligated loop. Using this technique in a mouse model, we evaluated C. difficile spore adherence and internalization to the ileum and colonic mucosa during aging. Consequently, our data suggest that spore internalization in the ileum and colonic mucosa is higher in elderly than in adults or young mice. Also, our data suggest that spore-adherence to the ileum and colonic mucosa decreases with aging.
One viral sequence for each host? – The neglected within-host diversity as the main stage of SARS-CoV-2 evolution
Authors: Ruan Yongsen , Hou Mei , Li Jiarui , Song Yangzi , Wang Hurng-YI , He Xionglei , Zeng Hui , Lu Jian , Wen Haijun , Chen Chen , Wu Chung-I 
Published: June 2021

AbstractThe standard practice of presenting one viral sequence for each infected individual implicitly assumes low within-host genetic diversity. It places the emphasis on the viral evolution between, rather than within, hosts. To determine this diversity, we collect SARS-CoV-2 samples from the same patient multiple times. Our own data in conjunction with previous reports show that two viral samples collected from the same individual are often very different due to the substantial within-host diversity. Each sample captures only a small part of the total diversity that is transiently and locally released from infected cells. Hence, the global SARS-CoV-2 population is a meta-population consisting of the viruses in all the infected hosts, each of which harboring a genetically diverse sub-population. Advantageous mutations must be present first as the within-host diversity before they are revealed as between-host polymorphism. The early detection of such diversity in multiple hosts could be an alarm for potentially dangerous mutations. In conclusion, the main forces of viral evolution, i.e., mutation, drift, recombination and selection, all operate within hosts and should be studied accordingly. Several significant implications are discussed.
Introduction of probiotic bacterial consortia promotes plant growth via impacts on the resident rhizosphere microbiome
Authors: Hu Jie , Yang Tianjie , Friman Ville-Petri , Kowalchuk George A. , Hautier Yann , Li Mei , Wei Zhong , Xu Yangchun , Shen Qirong , Jousset Alexandre 
Published: June 2021

AbstractPlant growth depends on a range of functions provided by their associated rhizosphere microbiome, including nutrient mineralization, hormone co-regulation and pathogen suppression. Improving the ability of plant associated microbiome to deliver these functions is thus important for developing robust and sustainable crop production. However, it is yet unclear how beneficial effects of probiotic microbial inoculants can be optimised and how they are mediated. Here, we sought to enhance the tomato plant growth by targeted introduction of probiotic bacterial consortia consisting of up to eight plant-associated Pseudomonas strains. We found that the effect of probiotic consortium inoculation was richness-dependent: consortia that contained more Pseudomonas strains, reached higher densities in the tomato rhizosphere and had clearer beneficial effects on multiple plant growth characteristics. Crucially, these effects were best explained by changes in the resident community diversity, composition and increase in the relative abundance of initially rare taxa, instead of introduction of plant-beneficial traits into the existing community along with probiotic consortia. Together, our results suggest that beneficial effects of microbial introductions can be driven indirectly through effects on the diversity and composition of resident plant rhizosphere microbiome.