bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of adiposity, kidney stone disease, and serum calcium concentrations; observational and genetic epidemiological studies
Authors: Lovegrove Catherine E , Bešević Jelena , Wiberg Akira , Lacey Ben , Littlejohns Thomas J , Allen Naomi E , Goldsworthy Michelle , Kim Jihye , Hannan Fadil , Curhan Gary C , Turney Ben , McCarthy Mark , Mahajan Anubha , Thakker Rajesh V , Holmes Michael V , Furniss Dominic , Howles Sarah A 
Published: June 2022

AbstractBackgroundKidney stone disease (KSD) is linked to obesity, metabolic syndrome and biochemical alterations including higher serum calcium concentration. The mechanisms by which these phenotypes associate with KSD are uncertain. We aimed to establish the effects of adiposity on KSD using conventional and genetic epidemiological techniques.MethodsWe assessed observational associations between measures of adiposity and incident KSD in 479,405 people from the UK Biobank. To facilitate Mendelian randomization (MR) analyses, we undertook genome-wide association studies (GWAS) of KSD in the UK Biobank in combined and sex-specific subsets. Univariable, multivariable and mediation MR analyses were used to calculate odds ratio (OR) or beta coefficient (ß) for risk of KSD per genetically instrumented higher marker of adiposity, metabolic syndrome parameter, biochemical phenotype, and inflammation and identify violations of MR assumptions.FindingsObservational analyses demonstrated that measures of central adiposity (waist-to-hip ratio (WHR) and waist circumference (WC)) are more strongly associated with incident KSD than measures of general adiposity (body mass index (BMI)). Three novel KSD-GWAS loci were identified (SLC2A12, TRPV5, and SLC28A1); no sex-specific loci were detected. MR analyses established that higher central adiposity is causally linked to both KSD and higher adjusted serum calcium concentrations independent of BMI (one standard deviation higher WHR: OR for KSD=1·43, p=4·1×10−6; ß for serum calcium concentration=0·11mmol/L, p=2·7×10−7). Mediation analyses indicated that 12% of the effect of WHR on KSD is due its role in elevating serum calcium concentration. Our MR studies indicated that other components of the metabolic syndrome, serum uric acid levels, and biomarkers of inflammation are unlikely to be implicated in the causation of KSD.InterpretationOur study indicates that visceral adipose depots elevate serum calcium concentration and cause an increased risk of KSD. Therapies targeting central adipose deposition may affect calcium homeostasis and have utility for the prevention of KSD.
Metabolomics and transcriptomics reveal the response mechanisms of Mikania micrantha to Puccinia spegazzinii infection
Authors: Ren Xinghai , Zhang Guangzhong , Gu Yujuan , Jin Mengjiao , Day Michael D. , Liu Huai , Qian Wanqiang , Liu Bo 
Published: June 2022

AbstractMikania micrantha is one of the 100 worst invasive species globally and can cause significant negative impacts to agricultural and forestry economics, particularly in Asia and the Pacific region. The rust Puccinia spegazzinii has been used successfully as a biological control agent in several countries to help manage M. micrantha. However, the response mechanisms of M. micrantha to P. spegazzinii infection have never been studied. To investigate the response of M. micrantha to infection by P. spegazzinii, an integrated analysis of metabolomics and transcriptomics was performed. The levels of 101 metabolites, including organic acids, amino acids and secondary metabolites in M. micrantha infected with P. spegazzinii, were significantly different compared to those in plants that were not infected. The relative amounts of L-leucine, L-ioleucine, L-tryptophan, histidine, L-phenylalanine and L-citrulline were increased under P. spegazzinii infection. These may convert to intermediates within the TCA cycle, participating in energy biosynthesis. In addition, phytoalexins, such as maackiain, nobiletin, vasicin, arachidonic acid and JA-Ile, were synthesized and accumulated in M. micrantha in response to P. spegazzinii infection. A total of 4,978 differentially expressed genes were identified in M. micrantha infected by P. spegazzinii. Many key genes of the Mitogen-activated protein kinase (MAPK) signalling pathway, showed significantly higher expression under P. spegazzinii infection. These results not only help us to understand the response of metabolites and gene expression in M. micrantha following infection by P. spegazzinii, but also help us understand the potential for the continuous biological control of M. micrantha using P. spegazzinii.
Nervous system reduction in branched-chain amino acid metabolism disrupts hippocampal neurogenesis and memory
Authors: Abdi Khadar , Rodriguiz Ramona M. , Wetsel William C. , Arlotto Michelle E. , McGarrah Robert W. , White Phillip J. 
Published: June 2022

SUMMARYA role for macronutrient metabolism in learning and memory is supported by numerous epidemiological studies. The Ppm1k gene encodes the branched-chain keto acid dehydrogenase (BCKDH) phosphatase that promotes the metabolism of branched-chain amino acids (BCAA). Here we show that nervous system deletion of Ppm1k in mice increases BCAA levels in brain tissue but not in plasma. These mice have significant impairments in working memory accompanied by a robust accumulation of DCX+/NeuroD1+ immature neurons within the dentate gyrus granule cell layer. Through single cell RNA sequencing and pathway analysis we identified substantial increases in transit-amplifying cells and immature neurons along with activated hedgehog signaling in Ppm1k deficient primary neural stem cells (NSCs). Inhibition of mTOR signaling reversed the effects of Ppm1k deletion on neuronal progenitor gene activation in primary NSCs. Together our findings uncover a new molecular link between BCAA metabolism, hippocampal neurogenesis, and cognitive performance.
Kidney patients remain at increased risk for succumbing to COVID-19
Authors: Hendrickx Rodinde , Jellingsø Mads , Sommer Morten OA 
Published: June 2022

AbstractImmunocompromised patients have been at an increased risk of succumbing to COVID-19 already since the beginning of the pandemic. Here we analyzed data from patients with end stage renal disease, including those on dialysis and patients with a kidney transplant, and compared them to the general population. We found that kidney patients remain at increased risk of succumbing to COVID-19 despite all available countermeasures. The analyses underline the need for additional protection for this vulnerable population.
Occupation, Worker Vulnerability, and COVID-19 Vaccination Uptake: Analysis of the Virus Watch prospective cohort study
Authors: Beale Sarah , Burns Rachel , Braithwaite Isobel , Byrne Thomas , Erica Fong Wing Lam , Fragaszy Ellen , Geismar Cyril , Hoskins Susan , Kovar Jana , Navaratnam Annalan M D , Nguyen Vincent , Patel Parth , Yavlinsky Alexei , Van Tongeren Martie , Aldridge Robert W , Hayward Andrew 
Published: June 2022

AbstractBackgroundOccupational disparities in COVID-19 vaccine uptake can impact the effectiveness of vaccination programmes and introduce particular risk for vulnerable workers and those with high workplace exposure. This study aimed to investigate COVID-19 vaccine uptake by occupation, including for vulnerable groups and by occupational exposure status.MethodsWe used data from employed or self-employed adults who provided occupational information as part of the Virus Watch prospective cohort study (n=19,595) and linked this to study-obtained information about vulnerability-relevant characteristics (age, medical conditions, obesity status) and work-related COVID-19 exposure based on the Job Exposure Matrix. Participant vaccination status for the first, second, and third dose of any COVID-19 vaccine was obtained based on linkage to national records and study records. We calculated proportions and Sison-Glaz multinomial 95% confidence intervals for vaccine uptake by occupation overall, by vulnerability-relevant characteristics, and by job exposure.FindingsVaccination uptake across occupations ranged from 89-96% for the first dose, 87-94% for the second dose, and 75-86% for the third dose, with transport, trade, service and sales workers persistently demonstrating the lowest uptake. Vulnerable workers tended to demonstrate fewer between-occupational differences in uptake than non-vulnerable workers, although clinically vulnerable transport workers (76%-89% across doses) had lower uptake than several other occupational groups (maximum across doses 86-96%). Workers with low SARS-CoV-2 exposure risk had higher vaccine uptake (86%-96% across doses) than those with elevated or high risk (81-94% across doses).InterpretationDifferential vaccination uptake by occupation, particularly amongst vulnerable and highly-exposed workers, is likely to worsen occupational and related socioeconomic inequalities in infection outcomes. Further investigation into occupational and non-occupational factors influencing differential uptake is required to inform relevant interventions for future COVID-19 booster rollouts and similar vaccination programmes.
An attenuated vaccinia vaccine encoding the SARS-CoV-2 spike protein elicits broad and durable immune responses, and protects cynomolgus macaques and human ACE2 transgenic mice from SARS-CoV-2 and its variants
Authors: Ishigaki Hirohito , Yasui Fumihiko , Nakayama Misako , Endo Akinori , Yamamoto Naoki , Yamaji Kenzaburo , Nguyen Cong Thanh , Kitagawa Yoshinori , Sanada Takahiro , Honda Tomoko , Munakata Tsubasa , Higa Masahiko , Toyama Sakiko , Kono Risa , Takagi Asako , Matsumoto Yusuke , Hayashi Kaori , Shiohara Masanori , Ishii Koji , Saeki Yasushi , Itoh Yasushi , Kohara Michinori 
Published: June 2022

AbstractAs long as the coronavirus disease 2019 (COVID-19) pandemic continues, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with altered antigenicity will emerge. The development of vaccines that elicit robust, broad, and durable protection against SARS-CoV-2 variants is urgently needed. We have developed a vaccine (rDIs-S) consisting of the attenuated vaccinia virus DIs strain platform carrying the SARS-CoV-2 S gene. rDIs-S induced neutralizing antibody and T-lymphocyte responses in cynomolgus macaques and human angiotensin converting enzyme 2 (hACE2) transgenic mice, and showed broad protection against SARS-CoV-2 isolates ranging from the early-pandemic strain (WK-521) to the recent Omicron BA. 1 variant (TY38-839). Using a tandem mass tag (TMT) -based quantitative proteomic analysis of lung homogenates from hACE2 transgenic mice, we found that, among mice subjected to challenge infection with WK-521, vaccination with rDIs-S prevented protein expression related to the severe pathogenic effects of SARS-CoV-2 infection (tissue destruction, inflammation, coagulation, fibrosis, and angiogenesis) and restored protein expression related to immune responses (antigen presentation and cellular response to stress). Furthermore, long-term studies in mice showed that rDIs-S maintains S protein-specific antibody titers for at least 6 months after a 1st vaccination. Thus, rDIs-S appears to provide broad and durable protective immunity against SARS-CoV-2, including current and possibly future variants.
Male-killing-associated bacteriophage WO identified from comparisons of Wolbachia endosymbionts of Homona magnanima
Authors: Arai Hiroshi , Anbutsu Hisashi , Nishikawa Yohei , Kogawa Masato , Ishii Kazuo , Hosokawa Masahito , Lin Shiou-Ruei , Ueda Masatoshi , Nakai Madoka , Kunimi Yasuhisa , Harumoto Toshiyuki , Kageyama Daisuke , Takeyama Haruko , Inoue Maki N. 
Published: June 2022

AbstractThe origin and mechanism of male-killing, an advantageous strategy employed by maternally transmitted symbionts such as Wolbachia, remain unclear. We compared genomes of four Wolbachia strains derived from Homona magnanima, a male-killing strain wHm-t (1.5 Mb), and three non-male-killing strains, wHm-a (1.1 Mb), wHm-b (1.3 Mb), and wHm-c (1.4 Mb). A wHm-t-specific 76-kbp prophage region harboured two tandemly arrayed WO-mediated killing (wmk) gene homologs (wmk-1/wmk-2 and wmk-3/wmk-4). Of these, wmk-1 or wmk-3 killed almost all Drosophila melanogaster individuals when transgenically overexpressed. Dual expression of wmk-3 and wmk-4 killed all males and rescued females. We propose a novel hypothesis wherein horizontally transmitted proto-Wolbachia with a single wmk killed both sexes, and tandem duplication of wmk allowed an evolutionary transition to a vertically transmitted symbiont, causing male-killing. Our study highlights the bacteriophage as a critical driver of the evolution of male-killing and argues for a conserved male-killing mechanism in diverse insects.
Epidemiological Correlates of Overweight and Obesity in the Northern Cape Province, South Africa
Authors: Smith Mackenzie H , Myrick Justin W , Oyageshio Oshiomah , Uren Caitlin , Saayman Jamie , Boolay Sihaam , van der Westhuizen Lena , Werely Cedric , Möller Marlo , Henn Brenna M , Reynolds Austin W 
Published: June 2022

AbstractBackgroundIn the past several decades, obesity has become a major public health issue worldwide, associated with increased rates of chronic disease and death. Like many developing nations, South Africa is experiencing rapid increases in BMI, and as a result, evidence-based preventive strategies are needed to reduce the increasing burden of overweight and obesity. This study aimed to determine the prevalence and predictors of overweight and obesity among a multi-ethnic cohort from the rural Northern Cape of South Africa.MethodsThese data were collected as part of a tuberculosis (TB) case-control study, with 395 healthy control participants included in the final analysis. Overweight and obesity were defined according to WHO classification. Multivariate linear models of BMI were generated using sex, age, education level, smoking, alcohol consumption, and diabetes as predictor variables. We also used multivariable logistic regression analysis to assess the relationship of these factors with overweight and obesity.ResultsThe average BMI in our study cohort was 25.1. The prevalence overweight was 18.6% and the prevalence of obesity was 23.5%. We find that female gender, being older, and having more years of formal education are all positively associated with BMI in our dataset. Women (OR = 5.4, CI = 3.2-9.4), older individuals (OR = 1.02, CI = 1-1.04), and those with more years of education (OR = 1.18, CI = 1.07-1.29) were all more likely to be overweight or obese. Alternatively, being a smoker is negatively associated with BMI and decreases one’s odds of being overweight or obese (OR = 0.25, CI = 0.15-0.42).ConclusionsWe observed a high prevalence of overweight and obesity in this study. The odds of being overweight and obesity was higher in women and those with more education and increases with age. Community-based interventions to control obesity in these communities should pay special attention to these groups.
Repeated mass testing of staff and residents in prison outbreaks of Covid-19: an enhanced outbreak investigation in two adult prisons in England, 2021
Authors: Czachorowski Maciej , Bashton Matthew , O’Moore Eamonn , McGrath Nuala , Smith Darren , Gutridge Kerry , Parkes Julie , Plugge Emma 
Published: June 2022

AbstractBackgroundThe management of Covid-19 outbreaks presented particular challenges in the prison setting. In this study we describe the results from the implementation of a serial mass testing approach in two adult prisons in northern England. The overall aim was to examine the epidemiology of Covid-19 outbreaks in prisons and help inform public health policy and practice during the pandemic.MethodsRepeat mass testing was offered to all eligible staff and residents in a women’s (nresidents=239; nstaff=246) and a men’s (nresidents=703; nstaff=340) prison in February and March 2021 at days 0, 7 and 28 after Covid-19 outbreaks were declared. Positive swab samples were sent for viral whole genome sequencing by COG-UK.FindingsParticipation in at least one testing round ranged from a low of 67% of staff in the men’s prison to a high of 98% of residents in the women’s prison. The largest outbreak, in the men’s prison (261 cases in residents and 37 cases in staff), continued to see new cases identified at the last testing round on day 28. Test positivity in residents of both prisons was significantly lower (p<0.05) at day 28 than on preceding test days, but no significant difference was observed for staff (p>0.05). Epidemiological data in conjunction with sequencing information provided evidence for multiple introductions of the SARS-CoV-2 virus from the local community into the prisons, with transmission identified both within wings and between wings among residents and staff. Two distinct SARS-CoV-2 lineages were identified in the women’s and men’s prisons, B.1.177 and B.1.17, respectively.ConclusionsDuring a Covid-19 outbreak, timely implementation of a whole prison testing regime can serve to inform a targeted approach to infection prevention and control by identifying the true extent of disease transmission in all (including asymptomatic) individuals. Staff, in particular, should be tested regularly and testing uptake should be as high as possible to minimise the risk of infection incursion. Ensuring high testing uptake across all testing rounds remains a challenge.
Telemedicine Ready or Not? a cross-sectional assessment of telemedicine maturity of federally funded tertiary health institutions in Nigeria
Authors: Olufunlayo Tolulope F. , Ojo Oluwadamilola O. , Ozoh Obianuju B. , Agabi Osigwe P. , Opara Chuks R. , Taiwo Funlola T. , Fasanmade Olufemi A. , Okubadejo Njideka U. 
Published: June 2022

ABSTRACTBackground and ObjectiveTelemedicine (TM) has solidified its place as a means for continuity of healthcare services and a cost-effective approach for improving health equity as demonstrated during the COVID-19 pandemic. Preparedness of health systems for telemedicine is an indicator of the scalability of their services, especially during disasters. We aimed to assess the maturity and preparedness of federally funded tertiary health institutions (FFTHIs) in Nigeria, to deploy and integrate telemedicineMethodsWe conducted a cross-sectional study of randomly selected FFTHIs in Nigeria using PAHO’s tool for assessing the maturity level of health institutions to implement telemedicine services. Descriptive statistics were used for overall maturity levels and non-parametric tests to compare scores for overall maturity and specific PAHO domains per region. The level of significance was set at p value <0.05.ResultsTwenty-four of thirty randomly polled FFTHIs responded (response rate of 77.4%). Overall, the median TM maturity level was 2.0 (1.75) indicating beginner level. No significant inter-zonal difference in median overall maturity level (p=0.87). The median maturity levels for telemedicine readiness in specific domains were organizational readiness - 2.0 (2.0), processes 1.0 (1.0), digital environment 2.0 (3.0), human resources 2.0 (1.0), regulatory issues- 1.5 (1.0) and expertise 2.0 (2.0); mostly at beginner level, with no inter-zonal differences. Most participating institutions had no initiatives in place for domains of processes and regulatory issues.ConclusionsThe current status of telemedicine maturity of FFTHIs in Nigeria behoves policy makers to advance the implementation of telemedicine across the country as part of national digital quality healthcare.
High-throughput engineering of cytoplasmic- and nuclear-replicating large dsDNA viruses by CRISPR/Cas9
Authors: López-Muñoz Alberto Domingo , Rastrojo Alberto , Martín Rocío , Alcamí Antonio 
Published: June 2022

ABSTRACTThe application of CRISPR/Cas9 to improve genome engineering efficiency of large dsDNA viruses has been extensively described, but a robust and versatile method for high-throughput generation of marker-free recombinants for a desire locus has not been reported yet. Cytoplasmic-replicating viruses use their own repair enzymes for homologous recombination, while nuclear-replicating viruses use the host repair machinery. This is translated into a wide range of Cas9-induced homologous recombination efficiency depending on the virus replication compartment and viral/host repair machinery characteristics and accessibility. However, the use of Cas9 as a selection agent to target parental virus genomes robustly improves the selection of desired recombinants across large dsDNA viruses. We used ectromelia virus (ECTV) and herpes simplex viruses (HSV) type 1 and 2, to optimize a CRISPR/Cas9 method that can be versatilely used for efficient genome editing and selection of both cytoplasmic- and nuclear-replicating viruses. We performed a genome-wide genetic variant analysis of mutations located at predicted off-target sequences for 20 different recombinants, showing off-target-free accuracy by deep-sequencing. Our results support this optimized method as an efficient, accurate and versatile approach to enhance the two critical factors of high-throughput viral genome engineering: generation and color-based selection of recombinants. This application of CRISPR/Cas9 reduces time and labor of screening of desired recombinants, allowing for high-throughput generation of large collections of mutant dsDNA viruses for a desire locus in less than two weeks.DATA SUMMARYRaw sequence reads are available at the European Bioinformatics Institute (EMBL-EBI) European Nucleotide Archive (ENA) as Bioproject ID PRJEB32151 and PRJEB32152.Six supplementary figures, eleven supplementary tables and supplementary methods are available with the online version of this article. The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.
Elucidating dynamic anaerobe metabolism with Live Cell HRMAS 13C NMR and genome-scale metabolic modeling
Authors: Pavao Aidan , Girinathan Brintha , Peltier Johann , Silva Pamela Altamirano , Dupuy Bruno , Muti Isabella H. , Malloy Craig , Cheng Leo L. , Bry Lynn 
Published: June 2022

AbstractAnaerobic microbial metabolism drives critical functions within global ecosystems, host-microbiota interactions, and industrial applications, yet remains ill-defined. Here we advance versatile approaches to elaborate dynamic metabolism in living cells of obligate anaerobes, using the pathogen Clostridioides difficile, an amino acid and carbohydrate-fermenting Clostridia. High-Resolution Magic Angle Spinning (HRMAS) Nuclear Magnetic Resonance (NMR) spectroscopy of C. difficile grown with uniformly labeled 13C substrates informed dynamic flux balance analysis (dFBA) of the pathogen’s genome-scale metabolism. Predictions identified metabolic integration of glycolytic and amino acid fermentation pathways at alanine’s biosynthesis, to support efficient energy generation, maintenance of redox balance, nitrogen handling, and biomass generation. Model predictions advanced an approach using the sensitivity of 13C NMR spectroscopy to simultaneously track cellular carbon and nitrogen flow, from [U-13C]glucose and [15N] leucine, confirming the formation of [13C,15N]alanine. We illustrate experimental and computational approaches to elaborate complex anaerobic metabolism for diverse applications.