bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of COVID-19 vaccines against Omicron and Delta hospitalisation: test negative case-control study
Authors: Stowe Julia , Andrews Nick , Kirsebom Freja , Ramsay Mary , Bernal Jamie Lopez 
Published: April 2022

AbstractBackgroundThe omicron (B.1.1.529) variant has been associated with reduced vaccine effectiveness (VE) against infection and mild disease with rapid waning, even after a third dose, nevertheless omicron has also been associated with milder disease than previous variants. With previous variants protection against severe disease has been substantially higher than protection against infection.MethodsWe used a test-negative case–control design to estimate VE against hospitalisation with the omicron and delta variants using community and in hospital testing linked to hospital records. As a milder disease, there may be an increasing proportion of hospitalised individuals with Omicron as an incidental finding. We therefore investigated the impact of using more specific and more severe hospitalisation indicators on VE.ResultsAmong 18-64 year olds using all Covid-19 cases admitted via emergency care VE after a booster peaked at 82.4% and dropped to 53.6% by 15+ weeks after the booster; using all admissions for >= 2 days stay with a respiratory code in the primary diagnostic field VE ranged from 90.9% down to 67.4%; further restricting to those on oxygen/ventilated/on intensive care VE ranged from 97.1% down to 75.9%. Among 65+ year olds the equivalent VE estimates were 92.4% down to 76.9%; 91.3% down to 85.3% and 95.8% down to 86.8%.ConclusionsWith generally milder disease seen with Omicron, in particular in younger adults, contamination of hospitalisations with incidental cases is likely to reduce VE estimates against hospitalisation. VE estimates improve and waning and waning is more limited when definitions of hospitalisation that are more specific to severe respiratory disease are used.
Effects of Intravenous and Inhaled Anesthetics on the Postoperative Complications for the patients undergoing One Lung Ventilation
Authors: Yang Jing , Huang Qinghua , Cao Rong , Cui Yu 
Published: April 2022

AbstractIntroductionWith the widely used technique of One Lung Ventilation (OLV) in patients throughout thoracic surgery, it’s unclear whether inhaled or intravenous anesthetics were associated with postoperative complications. The purpose of the current study is to compare the effects of intravenous and inhaled anesthetics on the postoperative complications within the patients suffering OLV.MethodsWe searched the related randomized controlled trials in PubMed\EMBASE\Medline and the Cochrane library up to 09\2021.Inclusive criteria were as follows: We included all the randomized controlled trials which compared the effects of intravenous and inhaled anesthetics on the postoperative complications[listed as: (a) major complications; (b)postoperative pulmonary complications (PPCs); (c) postoperative cognitive function (MMSE score); (d) length of hospital stay; (e) 30-days mortality] for the patients undergoing one lung ventilation.ResultsThirteen randomized controlled trials with 2522 patients were included for analysis. Overall, there were no significant differences in the postoperative major complications between inhaled and intravenous anesthetics groups (OR 0.78, 95%CI 0.54 to 1.13, p=0.19; I2=0%). However, more PPCs were detected in intravenous groups when compared to inhaled groups (OR 0.62, 95%CI 0.44 to 0.87, p=0.005; I2=37%). Both the postoperative MMSE scores (SMD -1.94, 95%CI -4.87 to 0.99, p=0.19; I2=100%) and the length of hospital stay (SMD 0.05, 95%CI -0.29 to 0.39, p=0.76; I2=73%) were comparable between two groups. Besides, the 30-day mortality didn’t differ significantly across groups either (OR 0.79, 95%CI 0.03 to 18, p=0.88; I2=63%).ConclusionsIn patients undergoing OLV, generous anesthesia with inhaled anesthetics could reduce PPCs compared with intravenous anesthetics, but no evident advantages were provided over other major complications, cognitive function, hospital stay or mortality.
Characteristics of Kenyan Women Enrolled in a Trial on Doxycycline Postexposure Prophylaxis for Sexually Transmitted Infection Prevention
Authors: Oware Kevin , Adiema Lydia , Rono Bernard , Violette Lauren R. , McClelland R. Scott , Donnell Deborah , Scoville Caitlin W. , Odoyo Josephine , Baeten Jared M. , Bukusi Elizabeth , Stewart Jenell 
Published: April 2022

AbstractIntroductionThe global incidence of sexually transmitted infections (STIs) has been rapidly increasing over the past decade, with more than one million curable STIs being acquired daily. Young women in sub-Saharan Africa have a high prevalence and incidence of both curable STIs and HIV. The use of doxycycline as a prophylaxis to prevent STI infections is promising; however, clinical trials, to date, have only been conducted among men who have sex with men (MSM) in high-income settings. We describe the characteristics of participants enrolled in the first trial to determine the efficacy of doxycycline post-exposure prophylaxis (PEP) to reduce STI incidence among women.MethodsThis is an open-label 1:1 randomized clinical trial of doxycycline PEP efficacy to reduce incident bacterial STIs – Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum – among Kenyan women aged ≥18 and ≤30 years. All were also taking HIV pre-exposure prophylaxis (PrEP). We describe the baseline characteristics of participants.ResultsBetween February 2020 and November 2021, 449 women were enrolled. The median age was 24 years (IQR 21-27), the majority were never married (66.1%), 370 women (82.4%) reported having a primary sex partner, and 33% had sex with new partners in the 3 months prior to enrolment. Two-thirds (67.5%, 268 women) did not use condoms, 36.7% reported transactional sex, and 43.2% suspected their male partners of having sex with other women. Slightly less than half (45.9%, 206 women) were recently concerned about being exposed to an STI. The prevalence of STIs was 17.9%, with C. trachomatis accounting for the majority of infections.ConclusionYoung cisgender women using HIV PrEP in Kenya and enrolled in a trial of doxycycline postexposure prophylaxis had a high prevalence of curable STIs and represent a target population for an STI prevention intervention.
Recurrent aphthous stomatitis affects quality of life
Authors: Rivera César , Muñoz-Pastén Mariagrazia , Muñoz-Núñez Esteban , Hernández-Olivos Romina 
Published: April 2022

ABSTRACTRecurrent aphthous stomatitis are recurrent oral ulcers that can affect important daily activities, such as oral hygiene and eating. In this prospective case-control study (n=62), we show that, during ulcer episodes, patients report a poorer quality of life compared to ulcer-free periods, and that this impact is positively associated with the number and size of lesions. Our results suggest that, if intervened locally, general relief of the condition could be achieved.
Metabolic Disturbances, Hemoglobin A1c, and Social Cognition Impairment in Schizophrenia Spectrum Disorders
Authors: Tang Sunny X. , Oliver Lindsay D. , Hänsel Katrin , DeRosse Pamela , John Majnu , Khairullah Ammar , Gold James M. , Buchanan Robert W. , Voineskos Aristotle , Malhotra Anil K. 
Published: April 2022

AbstractSocial cognitive impairments are core features of schizophrenia spectrum disorders (SSD) and are associated with greater functional impairment and decreased quality of life. Metabolic disturbances have been related to greater impairment in general neurocognition, but their relationship to social cognition has not been previously reported. In this study, metabolic measures and social cognition were assessed in 245 participants with SSD and 165 healthy comparison subjects (HC), excluding those with hemoglobin A1c (HA1c)>6.5%. Tasks assessed emotion processing, theory of mind, and social perception. Functional connectivity within and between social cognitive networks was measured during a naturalistic social task. Among SSD, a significant inverse relationship was found between social cognition and cumulative metabolic burden (β=-0.38,p<0.001) and HA1c (β=-0.37,p<0.001). The relationship between social cognition and HA1c was robust across domains and measures of social cognition and after accounting for age, sex, race, non-social neurocognition, hospitalization, and treatment with different antipsychotic medications. Negative connectivity between affect sharing and motor resonance networks was a partial mediator of this relationship across SSD and HC groups (β=-0.05,p=0.008). There was a group x HA1c effect indicating that SSD participants were more adversely affected by increasing HA1c. Thus, we provide the first report of a robust relationship in SSD between social cognition and abnormal glucose metabolism. If replicated and found to be causal, insulin sensitivity and blood glucose may present as promising targets for improving social cognition, functional outcomes, and quality of life in SSD.
Automated development of clinical prediction models enables real-time risk stratification with exemplar application to hypoxic-ischaemic encephalopathy
Authors: Lyon Matthew S. , White Heather , Gaunt Tom R. , Lawlor Deborah , Odd David 
Published: April 2022

AbstractReal-time updated risk prediction of disease outcomes could lead to improvements in patient care and better resource management. Established monitoring during pregnancy at antenatal and intrapartum periods could be particularly amenable to benefits of this approach. This proof-of-concept study compared automated and manual prediction modelling approaches using data from the Collaborative Perinatal Project with exemplar application to hypoxic-ischaemic encephalopathy (HIE). Using manually selected predictors identified from previously published studies we obtained high HIE discrimination with logistic regression applied to antenatal only (0.71 AUC [95% CI 0.64-0.77]), antenatal and intrapartum (0.70 AUC [95% CI 0.64-0.77]), and antenatal, intrapartum and birthweight (0.73 AUC [95% CI 0.67-0.79]) data. In parallel, we applied a range of automated modelling methods and found penalised logistic regression had best discrimination and was equivalent to the manual approach but required little human input giving 0.75 AUC for antenatal only (95% CI 0.69, 0.81), 0.70 AUC for antenatal and intrapartum (95% CI 0.63, 0.78), and 0.74 AUC using antenatal, intrapartum, and infant birthweight (95% CI 0.65, 0.81). These results demonstrate the feasibility of developing automated prediction models which could be applied to produce disease risk estimates in real-time. This approach may be especially useful in pregnancy care but could be applied to any disease.
Modeling and Global Sensitivity Analysis of Strategies to Mitigate Covid-19 Transmission on a Structured College Campus
Authors: Zhao Lihong , Santiago Fabian , Rutter Erica M. , Khatri Shilpa , Sindi Suzanne 
Published: April 2022

AbstractIn response to the COVID-19 pandemic, many higher educational institutions moved their courses on-line in hopes of slowing disease spread. The advent of multiple highly-effective vaccines offers the promise of a return to “normal” in-person operations, but it is not clear if—or for how long—campuses should employ non-pharmaceutical interventions such as requiring masks or capping the size of in-person courses. In this study, we develop and fine-tune a model of COVID-19 spread to UC Merced’s student and faculty population. We perform a global sensitivity analysis to consider how both pharmaceutical and non-pharmaceutical interventions impact disease spread. Our work reveals that vaccines alone may not be sufficient to eradicate disease dynamics and that significant contact with an infectious surrounding community will maintain infections on-campus. Our work provides a foundation for higher-education planning allowing campuses to balance the benefits of in-person instruction with the ability to quarantine/isolate infectious individuals.
In vivoprenylomic profiling in the brain of a transgenic mouse model of Alzheimer’s disease reveals increased prenylation of a key set of proteins
Authors: Jeong Angela , Auger Shelby A. , Maity Sanjay , Li Ling , Distefano Mark D. 
Published: April 2022

AbstractDysregulation of protein prenylation has been implicated in many diseases, including Alzheimer’s disease (AD). Prenylomic analysis, the combination of metabolic incorporation of an isoprenoid analogue (C15AlkOPP) into prenylated proteins with a bottom-up proteomic analysis, has allowed identification of prenylated proteins in various cellular models. Here, transgenic AD mice were administered with C15AlkOPP through intracerebroventricular (ICV) infusion over 13 days. Using prenylomic analysis, 36 prenylated proteins were enriched in the brains of AD mice. Importantly, the prenylated forms of 15 proteins were consistently upregulated in AD mice compared to non-transgenic wild-type controls. These results highlight the power of this in vivo metabolic labeling approach to identify multiple post-translationally modified proteins that may serve as potential therapeutic targets for a disease that has proved refractory to treatment thus far. Moreover, this method should be applicable to many other types of protein modifications, significantly broadening its scope.
Overexpression of the WAPO-A1 gene increases the number of spikelets per spike in bread wheat
Authors: Wittern Lukas M. , Barrero Jose M. , Bovill William D. , Verbyla Klara L. , Hughes Trijntje , Swain Steve M. , Steed Gareth , Webb Alex A.R. , Gardner Keith , Greenland Andy , Jacobs John , Frohberg Claus , Schmidt Ralf-Christian , Cavanagh Colin , Rohde Antje , Davey Mark , Hannah Matthew A. 
Published: April 2022

AbstractTwo homoeologous QTLs for number of spikelets per spike (SPS) were mapped on chromosomes 7AL and 7BL using two wheat MAGIC populations. Sets of lines contrasting for the QTL on 7AL were developed which allowed for the validation and fine mapping of the 7AL QTL and for the identification of a previously described candidate gene, WHEAT ORTHOLOG OF APO1 (WAPO1). Using transgenic overexpression in both a low and a high SPS line, we provide a functional validation for the role of this gene in determining SPS also in hexaploid wheat. We show that the expression levels of this gene positively correlate with SPS in multiple MAGIC founder lines under field conditions as well as in transgenic lines grown in the greenhouse. This work highlights the potential use of WAPO1 in hexaploid wheat for further yield increases. The impact of WAPO1 and SPS on yield depends on other genetic and environmental factors, hence, will require a finely balanced expression level to avoid the development of detrimental pleiotropic phenotypes.
Feedback linking cell envelope stiffness, curvature, and synthesis enables robust rod-shaped bacterial growth
Authors: al-Mosleh Salem , Gopinathan Ajay , Santangelo Christian , Huang Kerwyn Casey , Rojas Enrique 
Published: April 2022

Bacterial growth is remarkably robust to environmental fluctuations, yet the mechanisms of growth-rate homeostasis are poorly understood. Here, we combine theory and experiment to infer mechanisms by which Escherichia coli adapts its growth rate in response to changes in osmolarity, a fundamental physicochemical property of the environment. The central tenet of our theoretical model is that cell-envelope expansion is only sensitive to local information such as enzyme concentrations, cell-envelope curvature, and mechanical strain in the envelope. We constrained this model with quantitative measurements of the dynamics of E. coli elongation rate and cell width after hyperosmotic shock. Our analysis demonstrated that adaptive cell-envelope softening is a key process underlying growth-rate homeostasis. Furthermore, our model correctly predicted that softening does not occur above a critical hyperosmotic shock magnitude and precisely recapitulated the elongation-rate dynamics in response to shocks with magnitude larger than this threshold. Finally, we found that to coordinately achieve growth-rate and cell-width homeostasis, cells employ direct feedback between cell-envelope curvature and envelope expansion. In sum, our analysis points to new cellular mechanisms of bacterial growth-rate homeostasis and provides a practical theoretical framework for understanding this process.Significance StatementThe bacterial cell envelope is the critical structure that defines cell size and shape, and its expansion therefore defines cell growth. Although size, shape, and growth rate are important cellular variables that are robust to environmental fluctuations, the feedback mechanisms by which these variables influence cell-envelope expansion are unknown. Here, we explore how E. coli cells achieve growth-rate and cell-width homeostasis during fluctuations in osmolarity, a key environmental property. A biophysical model in which the cell envelope softens after an osmotic shock and envelope expansion depends directly on local curvature quantitatively recapitulated all experimental observations. Our study elucidates new mechanisms of bacterial cell morphogenesis and highlights the deep interplay between global cellular variables and the mechanisms of cell-envelope expansion.
HSD3B1 is an Oxysterol 3β-Hydroxysteroid Dehydrogenase in Human Placenta
Authors: Dickson Alison , Yutuc Eylan , Thornton Catherine A , Dunford James E , Oppermann Udo , Wang Yuqin , Griffiths William J 
Published: April 2022

AbstractMost biologically active oxysterols have a 3β-hydroxy-5-ene function in the ring system with an additional site of oxidation at C-7 or on the side-chain. In blood plasma oxysterols with a 7α-hydroxy group are also observed with the alternative 3-oxo-4-ene function in the ring system formed by ubiquitously expressed 3β-hydroxy-Δ5-C27-steroid oxidoreductase Δ5-isomerase, HSD3B7. However, oxysterols without a 7α-hydroxy group are not substrates for HSD3B7 and are not usually observed with the 3-oxo-4-ene function. Here we report the unexpected identification of oxysterols in plasma derived from umbilical cord blood and blood from pregnant women taken before delivery at 37+ weeks of gestation, of side-chain oxysterols with a 3-oxo-4-ene function but no 7α-hydroxy group. These 3-oxo-4-ene oxysterols were also identified in placenta, leading to the hypothesis that they may be formed by a previously unrecognised 3β-hydroxy-Δ5-C27-steroid oxidoreductase Δ5-isomerase activity of HSD3B1, an enzyme which is highly expressed in placenta. Proof of principle experiments confirmed that HSD3B1 has this activity. We speculate that HSD3B1 in placenta is the source of the unexpected 3-oxo-4-ene oxysterols in cord and pregnant women’s plasma and may have a role in controlling the abundance of biologically active oxysterols delivered to the fetus.
GTP-bound E. coli FtsZ filaments are composed of Tense monomers: A DNP NMR study using interface detection
Authors: McCoy Kelsey M. , McDermott Ann E. 
Published: April 2022

ABSTRACTFtsZ filaments are the major structural component of the bacterial Z-ring and are drivers of bacterial division. While crystal structures for FtsZ from some gram positive bacteria in the presence of GTP-analog like compounds suggest the possibility of a high energy “Tense” conformation, to date it remains an important question to elucidate whether this Tense form is the dominant form in filaments. Using dynamic nuclear polarization (DNP) solid-state NMR and differential isotopic labelling, we directly detect residues located at the inter-monomer interface of GTP-bound WT Escherichia coli FtsZ filaments. We combine chemical shift prediction, homology modelling, and heteronuclear dipolar recoupling techniques to characterize the E. coli FtsZ filament interface and demonstrate that the monomers in active filaments assume a Tense conformation.
Rapid loss of fine motor skills after low dose space radiation exposure
Authors: Blackwell Ashley A , Fesshaye Arriyam , Tidmore Alyssa , Lake Rami I , Wallace Douglas G , Britten Richard A 
Published: April 2022

AbstractSensorimotor function, motivation, and attentional processes are fundamental aspects of behavioral organization during skilled tasks. NASA’s planned expedition to Mars will expose astronauts to space radiation (SR) that has the potential to impair performance in mission critical tasks. Impairments in task accuracy and movement kinematics have been previously reported during string-pulling behavior ~7 months after SR exposure. If similar SR-induced sensorimotor deficits emerge at earlier times, then astronauts may have compromised in-flight performance disruptions while performing skilled tasks in critical situations, such as when manipulating controls or performing seat egress. Due to the possibility that such performance losses may compromise mission success, it is critical to determine if sensorimotor, motivation, or attentional deficits occur acutely after SR exposure at a time point that corresponds to in-flight performance. Male Wistar rats were thus exposed to either 10 cGy simplified galactic cosmic radiation (GCRsim), 10 cGy 4Helium (4He), or no radiation at all (Sham), and string-pulling behavior was assessed approximately 72 hours later. Following exposure to SR, rats (4He) took more time to approach the string to initiate string-pulling behavior and to pull in the string to reach the Cheerio (4He and GCRsim) relative to Sham rats. 4He-exposed rats also exhibited a greater number of misses and less contacts relative to both Sham and GCRsim-exposed rats. Further, rats exposed to 4He demonstrated less concentrated reach endpoints with both the left and right hands compared to GCR-exposed rats. This work suggests that sensorimotor function and motivation and/or attentional processes were impaired 72 hours after 4He-radiation exposure.