bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal renal function tests at presentation in severe COVID 19 pneumonia and its effect on clinical outcomes
Authors: Hanif Mehak , Sumalani Kamran Khan , Mandhan Vishal , Shaikh Zarkesh , Haider Shahbaz 
Published: October 2022

ABSTRACTAimTo determine the incidence of abnormal renal function tests at presentation in South Asian patients admitted with severe COVID 19 pneumonia and determine its effect on disease severity and clinical outcomesMethodsThis was a retrospective cross-sectional study conducted at the COVID Intensive care unit of a large tertiary care government hospital in Karachi, Pakistan. 190 patients admitted over five months from 1/5/2021 till 30/6/2021 were included in the study. Patient demographic characteristics, comorbidities, and clinical manifestations of COVID 19 infection were recorded. Laboratory values at the time of presentation, including Hemoglobin, NLR, platelets, blood urea nitrogen, glomerular filtration rate (GFR), inflammatory markers, liver function tests, and electrolytes were recorded. Patient outcome and need for mechanical ventilation were assessed 28 days after admission and compared with the incidence of abnormal renal functions at presentation.ResultsMean GFR and BUN at presentation were 69.7 and 28.4 respectively. 109 (50.4%) patients had abnormal renal function tests at the time of presentation. 76 (40.0%) patients had low GFR and 33 (17.4%) had only raised BUN with normal GFR. Mean GFR was lower in non-survivors vs survivors (p-value 0.000) and in patients who required mechanical ventilation (p-value 0.008). Patients who had low GFR showed greater mortality than those with normal GFR (p-value 0.04) and were more likely to require mechanical ventilation (p-value 0.04).ConclusionLow GFR at presentation is common in patients with severe COVID 19 pneumonia and is associated with a higher in-hospital mortality rate and need for mechanical ventilation.
Mechanism of targeted killing of P. aeruginosa by pyocins SX1 and SX2
Authors: Premsuriya Jiraphan , Mosbahi Khedidja , Atanaskovic Iva , Kleanthous Colin , Walker Daniel 
Published: October 2022

ABSTRACTPseudomonas aeruginosais a common cause of serious hospital-acquired infections, the leading proven cause of mortality in people with cystic fibrosis and is associated with high levels of antimicrobial resistance. Pyocins are narrow spectrum protein antibiotics produced byP. aeruginosathat kill strains of the same species and have the potential to be developed as therapeutics targeting multi-drug resistant isolates. We have identified two novel pyocins designated SX1 and SX2. Pyocin SX1 is a metal-dependent DNase while pyocin SX2 kills cells through inhibition of protein synthesis. Mapping the uptake pathways of SX1 and SX2 shows these pyocins utilize a combination of the common polysaccharide antigen (CPA) and a previously uncharacterized TonB-dependent transporter (TBDT) PA0434 to traverse the outer membrane. In addition, TonB1 and FtsH are required by both pyocins to energise their transport into cells and catalyse their translocation across the inner membrane, respectively. Expression ofPA0434was found to be specifically regulated by copper availability and we have designated PA0434 as Copper Responsive Transporter A, or CrtA. To our knowledge these are the first S-type pyocins described that utilize a TBDT that is not involved in iron uptake.
Evaluating metabolic and genomic data for predicting grain traits under high night temperature stress in rice
Authors: Bi Ye , Yassue Rafael Massahiro , Paul Puneet , Dhatt Balpreet Kaur , Sandhu Jaspreet , Do Thi Phuc , Walia Harkamal , Obata Toshihiro , Morota Gota 
Published: October 2022

AbstractThe asymmetric increase in average nighttime temperatures relative to increase in average daytime temperatures due to climate change is decreasing grain yield and quality in rice. Therefore, a better understanding of the impact of higher night temperature on single grain at whole genome level is essential for future development of more resilient rice. We investigated the utility of metabolites obtained from grains to classify high night temperature conditions of genotypes, and metabolites and single nucleotide polymorphisms to predict grain length, width, and perimeter phenotypes using a rice diversity panel. We found that the metabolic profiles of rice genotypes alone could be used to classify control and high night temperature conditions with high accuracy using random forest or extreme gradient boosting. The best linear unbiased prediction and BayesC showed greater metabolic prediction performance than machine learning models for grain-size phenotypes. Metabolic prediction was most effective for grain width, resulting in the highest prediction performance. Genomic prediction performed better than metabolic prediction. Integrating metabolites and genomics simultaneously in a prediction model slightly improved prediction performance. We did not observe a difference in prediction between the control and high night temperature conditions. Several metabolites were identified as auxiliary phenotypes that could be used to enhance the multi-trait genomic prediction of grain-size phenotypes. Our results showed that, in addition to single nucleotide polymorphisms, metabolites collected from grains offer rich information to perform predictive analyses, including classification modeling of high night temperature responses and regression modeling of grain size-related phenotypes in rice.
Flux estimation analysis systematically characterizes the metabolic shifts of the central metabolism pathway in human cancer
Authors: Yang Grace , Huang Shaoyang , Hu Kevin , Lu Alex , Yang Jonathan , Meroueh Noah , Dang Pengtao , Zhu Haiqi , Cao Sha , Zhang Chi 
Published: October 2022

ABSTRACTGlucose and glutamine are major carbon and energy sources that promote the fast proliferation of cancer cells. Metabolic shifs observed on cell line or mouse models may not reflect the general metabolic shifts in real human cancer tissue. In this study, we conducted a computational characterization of the flux distribution and variations of the central energy metabolism and key branches in a pan-cancer analysis, including glycolytic pathway, production of lactate, TCA cycle, nucleic acids synthesis, glutaminolysis, glutaminate, glutamine and glutathione metabolism, amino acids synthesis, in 11 cancer subtypes and 9 matched adjacent normal tissue types, by using TCGA tissue transcriptomics data. Our analysis confirms the increased influx in glucose uptake and glycolysis and decreased upper part of TCA cycle, i.e., Warbug effect in the analyzed cancer types. However, consistently increased lactate production and second half of TCA cycle were only seen in certain cancer types. More interestingly, we did not see cancer tissues have highly shifted glutaminolysis compared to their adjacent normal controls. A systems biology model of metabolic shifts in through cancer and tissue types is further developed and analyzed. We observed that (1) normal tissues have distinct metabolic phenotypes, (2) cancer types have drastically different metabolic shifts compared to their adjacent normal controls, and (3) the different shifts happened to tissue specific metabolic phenotypes result in a converged metabolic phenotype through cancer types and cancer progression. This study strongly suggests the possibility to have a unified framework for studies of cancer-inducing stressors, adaptive metabolic reprogramming, and cancerous behaviors.
Demographically explicit scans for barriers to gene flow using gIMble
Authors: Laetsch Dominik R , Bisschop Gertjan , Martin Simon H , Aeschbacher Simon , Setter Derek , Lohse Konrad 
Published: October 2022

AbstractIdentifying regions of the genome that act as barriers to gene flow between recently diverged taxa has remained challenging given the many evolutionary forces that generate variation in genetic diversity and divergence along the genome, and the stochastic nature of this variation. Progress has been impeded by a conceptual and methodological divide between analyses that infer the demographic history of speciation and genome scans aimed at identifying locally maladaptive alleles i.e. genomic barriers to gene flow. Here we implement genomewide IM blockwise likelihood estimation (gIMble), a composite likelihood approach for the quantification of barriers, that bridges this divide. This analytic framework captures background selection and selection against barriers in a model of isolation with migration (IM) as heterogeneity in effective population size (Ne) and effective migration rate (me), respectively. Variation in both effective demographic parameters is estimated in sliding windows via pre-computed likelihood grids.gIMbleincludes modules for pre-processing/filtering of genomic data and performing parametric bootstraps using coalescent simulations. To demonstrate the new approach, we analyse data from a well-studied pair of sister species of tropical butterflies with a known history of post-divergence gene flow:Heliconius melpomeneandH. cydno. Our analyses uncover both large-effect barrier loci (including well-known wing-pattern genes) and a genome-wide signal of a polygenic barrier architecture.Author summaryAs a fundamental process generating biological diversity, speciation involves the evolution of reproductive isolation and thus the build-up of barriers to genetic exchange among organismal groups. While population genomic data are arguably the only source of information we have about most recent speciation events, the way such data are analysed remains depressingly superficial: population genomic studies of speciation are phrased either as scans for outliers of genetic differentiation, or are based on models of neutral evolution under the constraint of a single genome-wide demography. Here we introduce a new statistical framework calledgIMbleto estimate the effective rate of gene flow and the effective population sizes along the genome from population genomic data. By capturing genome-wide variation in these two effective demographic parameters,gIMbledisentangles the genomic footprints of different modes of selection and provides a direct quantification of the species barrier. To illustrate this framework, we analyse a classic speciation genomic dataset fromHeliconiusbutterflies. We show that barriers to gene flow in this system include both large effect loci – most, but not all, of which were known from functional work – as well as a genome-wide signature of weak-effect polygenic barriers.
RAPTOR: A Five-Safes approach to a secure, cloud native and serverless genomics data repository
Authors: Shih Chih Chuan , Chen Jieqi , Lee Ai Shan , Bertin Nicolas , Hebrard Maxime , Khor Chiea Chuen , Li Zheng , Juan Tan Joanna Hui , Meah Wee Yang , Peh Su Qin , Mok Shi Qi , Sim Kar Seng , Liu Jianjun , Wang Ling , Wong Eleanor , Li Jingmei , Tin Aung , Cheng Ching-Yu , Heng Chew-Kiat , Yuan Jian-Min , Koh Woon-Puay , Saw Seang Mei , Friedlander Yechiel , Sim Xueling , Chai Jin Fang , Chong Yap Seng , Davila Sonia , Goh Liuh Ling , Lee Eng Sing , Wong Tien Yin , Karnani Neerja , Leong Khai Pang , Yeo Khung Keong , Chambers John C , Chi Lim Su , Mong Goh Rick Siow , Tan Patrick , Dorajoo Rajkumar 
Published: October 2022

AbstractGenomic researchers are increasingly utilizing commercial cloud platforms (CCPs) to manage their data and analytics needs. Commercial clouds allow researchers to grow their storage and analytics capacity on demand, keeping pace with expanding project data footprints and enabling researchers to avoid large capital expenditures while paying only for IT capacity consumed by their project. Cloud computing also allows researchers to overcome common network and storage bottlenecks encountered when combining or re-analysing large datasets. However, cloud computing presents a new set of challenges. Without adequate security controls, the risk of unauthorised access may be higher for data stored on the cloud. In addition, regulators are increasingly mandating data access patterns and specific security protocols on the storage and use of genomic data to safeguard rights of the study participants. While CCPs provide tools for security and regulatory compliance, utilising these tools to build the necessary controls required for cloud solutions is not trivial as such skill sets are not commonly found in a genomics lab. The Research Assets Provisioning and Tracking Online Repository (RAPTOR) by the Genome Institute of Singapore is a cloud native genomics data repository and analytics platform focusing on security and regulatory compliance. Using a “five-safes” framework (Safe Purpose, Safe People, Safe Settings, Safe Data and Safe Output), RAPTOR provides security and governance controls to data contributors and users leveraging cloud computing for sharing and analysis of large genomic datasets without the risk of security breaches or running afoul of regulations. RAPTOR can also enable data federation with other genomic data repositories using GA4GH community-defined standards, allowing researchers to boost the statistical power of their work and overcome geographic and ancestry limitations of data sets
Clarifying Microbial Nitrous Oxide Reduction Under Aerobic Conditions: Tolerant, Intolerant, and Sensitive
Authors: Wang Zhiyue , Vishwanathan Nisha , Kowaliczko Sophie , Ishii Satoshi 
Published: October 2022

ABSTRACTOne of the major challenges for the bioremediation application of microbial N2O reduction is its oxygen sensitivity. While a few strains were reported capable of reducing N2O under aerobic conditions, the N2O reduction kinetics of phylogenetically diverse N2O reducers are not well understood. Here we analyzed and compared the kinetics of Clade I and Clade II N2O-reducing bacteria in the presence or absence of O2by using a whole-cell assay with N2O and O2microsensors. Among the seven strains tested, N2O reduction ofStutzerimonas stutzeriTR2 and ZoBell were not inhibited by oxygen (i.e., oxygen tolerant).Paracoccus denitrificans, Azospirillum brasilense, andGemmatimonas aurantiacareduced N2O in the presence of O2but slower than in the absence of O2(i.e., oxygen sensitive). N2O reduction ofPseudomonas aeruginosaandDechloromonas aromaticadid not occur when O2was present (i.e., oxygen intolerant). Amino acid sequences and predicted structures of NosZ were highly similar among these strains, whereas oxygen-tolerant N2O reducers had higher oxygen consumption rates. The results suggest that the mechanism of O2tolerance is not directly related to NosZ structure but rather related to the scavenging of O2in the cells and/or accessory proteins encoded by thenoscluster.IMPORTANCESome bacteria can reduce N2O in the presence of O2, whereas others cannot. It is unclear whether this trait of aerobic N2O reduction is related to the phylogeny and structure of N2O reductase. The understanding of aerobic N2O reduction is critical in guiding emission control, due to the common concurrence of N2O and O2in natural and engineered systems. This study provided the N2O reduction kinetics of various bacteria under aerobic and anaerobic conditions and classified the bacteria into oxygen-tolerant, -sensitive, and -intolerant N2O reducers. Oxygen-tolerant N2O reducers rapidly consumed O2, which could help maintain the low O2concentration in the cells and keep their N2O reductase active. These findings are important and useful when selecting N2O reducers for bioremediation applications.
Acquisition of a large virulence plasmid (pINV) promoted temperature-dependent virulence and global dispersal of O96:H19 enteroinvasiveEscherichia coli
Authors: Miles Sydney L. , Torraca Vincenzo , Dyson Zoe A. , López-Jiménez Ana Teresa , Foster-Nyarko Ebenezer , Jenkins Claire , Holt Kathryn E. , Mostowy Serge 
Published: October 2022

AbstractEnteroinvasiveEscherichia coli(EIEC) andShigellaare closely related agents of bacillary dysentery. It is widely viewed that EIEC andShigellaspecies evolved fromE. colivia independent acquisitions of a large virulence plasmid (pINV) encoding a type three secretion system (T3SS). Sequence Type (ST)99 O96:H19E. coliis an emergent clone of EIEC responsible for recent outbreaks in Europe and South America. Here, we reconstruct the evolutionary history of ST99E. coliusing BactDating, revealing distinct phylogenomic clusters of pINV-positive and -negative isolates. To study the impact of pINV acquisition on the virulence of this clone, we developed an EIEC-zebrafish infection model showing that virulence of ST99 EIEC is thermoregulated. Strikingly, zebrafish infection using the oldest available pINV-negative isolate reveals a separate, temperature-independent mechanism of virulence, indicating that ST99 non-EIEC strains were virulent before pINV acquisition. Taken together, these results suggest that an already pathogenicE. coliacquired pINV and that virulence of ST99 isolates became thermoregulated once pINV was acquired.ImportanceEnteroinvasiveEscherichia coli(EIEC) andShigellaare etiological agents of bacillary dysentery. Sequence Type (ST)99 is an emergent clone of EIEC hypothesised to cause human disease by the recent acquisition of pINV, a large plasmid encoding a type three secretion system (T3SS) that confers the ability to invade human cells. Here, using phylogenomic reconstruction and zebrafish larvae infection, we show that the virulence of ST99 EIEC isolates is highly dependent on temperature, while pINV-negative isolates encode a separate temperature-independent mechanism of virulence. These results highlight that ST99 non-EIEC isolates may have been virulent before pINV acquisition and highlight an important role for pINV acquisition in the emergence of ST99 EIEC in humans, allowing wider dissemination across Europe and South America.
Multiscale Hybrid Fabrication: Volumetric Printing Meets Two-Photon Ablation
Authors: Rizzo Riccardo , Ruetsche Dominic , Liu Hao , Chansoria Parth , Wang Anny , Hasenauer Amelia , Zenobi-Wong Marcy 
Published: October 2022

AbstractThe vascular tree spans length scales from centimeter to micrometer. Engineering multiscale vasculature, in particular from millimeter vessels to micrometer-size capillaries, represents an unmet challenge and may require the convergence of two or more printing modalities. Leveraging the great advances in light-based biofabrication, we herein introduce a hybrid strategy to tackle this challenge. By combining volumetric printing (VP) and high-resolution two-photon ablation (2PA), we demonstrate the possibility to create complex multiscale organotypic perfusable models with features ranging from mesoscale (VP) to microscale (2PA). To successfully combine these two methods, we first eliminated micrometer-size defects generated during VP process. Due to optical modulation instability of the laser source and selffocusing phenomenon that occurs when the light triggers the photoresin crosslinking, VP printed constructs feature micrometer-size filaments and channels. By optical tuning the refractive index of the photoresin, we demonstrate defect-free VP that can then be combined with 2PA. To facilitate the 2PA process and meet VP requirements, we introduce a purely protein-based photoclick photoresin combining gelatin-norbornene and gelatin-thiol. By optimizing defect-free VP and 2PA processes, we finally demonstrate the possibility to generate complex 3D vasculature-like constructs with features ranging from ~400 μm of VP to ~2 μm of 2PA. This hybrid strategy opens new possibilities to better recapitulate microtissues vasculature and complex architectures, with particular potential for microfluidics and organ/tissue-on-a-chip technologies.
Assessing the impacts of various factors related to identification, conservation, biogenesis, and function on circular RNA reliability
Authors: Chuang Trees-Juen , Chiang Tai-Wei , Chen Chia-Ying 
Published: October 2022

AbstractCircular RNAs (circRNAs) are non-polyadenylated RNAs with a continuous loop structure characterized by a non-co-linear back-splice junction (BSJ). While dozens of computational tools have been developed and identified millions of circRNA candidates in diverse species, it remains a major challenge for determining circRNA reliability due to various types of false positives. Here, we systematically assess the impacts of numerous factors related to identification, conservation, biogenesis, and function on circRNA reliability by comparisons of circRNA expression from mock (total RNAs) and the corresponding co-linear/polyadenylated RNA-depleted datasets based on three different RNA treatment approaches. Eight important indicators of circRNA reliability are determined. The relative contribution to variability explained analyses further reveal that the relative importance of these factors in affecting circRNA reliability is conservation level of circRNA > full-length circular sequences > supporting BSJ read count > both BSJ donor and acceptor splice sites at the same co-linear transcript isoforms > both BSJ donor and acceptor splice sites at the annotated exon boundaries > BSJs detected by multiple tools > supporting functional features > both BSJ donor and acceptor splice sites undergoing alternative splicing. By extracting RT-independent circRNAs, circRNAs passing multiple experimental validations, and database-specific circRNAs, we showed the additive effects of these important factors in determining circRNA reliability. This study thus provides a useful guideline and an important resource for selecting high-confidence circRNAs for further investigations.
A multi-enhancer hub at theEts1locus controls T cell differentiation and allergic inflammation through 3D genome topology
Authors: Chandra Aditi , Yoon Sora , Michieletto Michael F. , Goldman Naomi , Ferrari Emily K. , Fasolino Maria , Joannas Leonel , Kee Barbara L. , Henao-Mejia Jorge , Vahedi Golnaz 
Published: October 2022

AbstractMulti-enhancer hubs are spatial clusters of enhancers which have been recently characterized across numerous developmental programs. Yet, the functional relevance of these three-dimensional (3D) structures is poorly understood. Here we show that the multiplicity of enhancers interacting with the transcription factorEts1is essential to control the precise expression level of this gene in response to cellular cues, and the failure to do so can lead to allergic diseases. Focusing on T cells as a model, we identified a highly connected multi-enhancer hub at theEts1locus, comprising a noncoding regulatory element that is a hotspot for sequence variation associated with allergic diseases. We deleted this hotspot and found that the multi-enhancer connectivity is dispensable for T cell development but required for CD4+T helper (Th1) differentiation in response to changes in the cytokine milieu. Mice lacking this hotspot are thus protected from Th1-mediated colitis but demonstrate an overt allergic response to house dust mites, a T cell-mediated response which is dampened by Th1 cells. Mechanistically, the multi-enhancer hub controls the expression level ofEts1that is dispensable for the active enhancer landscape but required for the Th1-specific genome topology through recruitment of CTCF. Together, we establish a paradigm for the functional and mechanistic relevance of multi-enhancer hubs controlling cellular competence to respond specifically to an inductive cue.