bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary nitrate supplementation for preventing and reducing the severity of winter infections, including COVID-19, in care homes (BEET-Winter)- a randomised placebo-controlled feasibility trial
Authors: Bath Philip M , Skinner Cameron J C , Bath Charlotte S , Woodhouse Lisa J , Korovesi Anastasia Areti Kyriazopoulou , Long Hongjiang , Havard Diane , Coleman Christopher M , England Timothy J , Leyland Valerie , Lim Wei Shen , Montgomery Alan A , Royal Simon , Avery Amanda , Webb Andrew J , Gordon Adam L 
Published: April 2022

Abstract
BackgroundInfections cause considerable care home morbidity and mortality. Nitric oxide (NO) has broad-spectrum anti-viral, bacterial and yeast activity in vitro. We assessed the feasibility of supplementing dietary nitrate (NO substrate) intake in care home residents.MethodsWe performed a cluster-randomised placebo-controlled trial in UK residential and nursing care home residents and compared nitrate containing (400 mg) versus free (0 mg daily) beetroot juice given for 60 days. Outcomes comprised feasibility of recruitment, adherence, salivary and urinary [nitrate], and ordinal infection/clinical events.ResultsOf 30 targeted care homes in late 2020, 16 expressed interest and only 6 participated. 49 residents were recruited (median 8 [interquartile range 7–12] per home), mean (standard deviation) age 82 (8) years, with proxy consent 41 (84%), advance directive for hospital non-admission 8 (16%) and ≥ 1 doses of COVID-19 vaccine 37 (82%). Background dietary nitrate was < 30% of acceptable daily intake. 34 (76%) residents received > 50% of juice. Residents randomised to nitrate vs placebo had higher urinary nitrate levels, median 50 [18–175] v 18 [10–50] mg/L, difference 25 [0–90]. Data paucity precluded clinical between-group comparisons; the outcome distribution was: no infection 32 (67%), uncomplicated infection 0, infection requiring healthcare support 11 (23%), all-cause hospitalisation 5 (10%), all-cause mortality 0. Urinary tract infections were most common.ConclusionsRecruiting UK care homes during the COVID-19 pandemic was partially successful. Supplemented dietary nitrate was tolerated and elevated urinary [nitrate]. Together, infections, hospitalisations and deaths occurred in 33% of residents over 60 days. A larger trial is now required.RegistrationISRCTN51124684
Influence of Prenatal Exercise on the Relationship Between Maternal Overweight and Obesity and Select Delivery Outcomes
Authors: McDonald Samantha M , Mouro Steven , Wisseman Breanna , Isler Christy , DeVente James , Newton Edward , Hildebrand Jason , Kuehn Devon , Kelley George , Chasan-Taber Lisa , Broskey Nicholas T. , May Linda E. 
Published: April 2022

Abstract
Background: Women with overweight or obesity (OWOB) have an increased risk of cesarean birth, preterm birth (PTB), and high birth weight infants. Although regular exercise decreases this risk in healthy weight women, these associations have not been explored in OWOB.Methods: Women were randomized at 13-16 weeks’ gestation to 150-minutes of moderate-intensity exercise (n=131) or non-exercising control (n=61). Delivery mode, gestational age (GA), and birth weight (BW) were obtained via electronic health records.Results: Pregnant exercisers had no differences in risk of cesarean birth, PTB, or BW compared to control participants. OWOB exercisers had higher rates of cesarean birth (27.1% vs. 11.1%), trends of higher PTB (15.3% vs. 5.6%), but normal weight babies relative to normal weight exercisers. Controlling for race and body mass index (BMI), maternal exercise reduced the relative risk (RR) for cesarean birth from 1.63 to 1.43. Cesarean births predicted by pre-pregnancy BMI and fitness level, whereas BW was predicted by race, gestational weight gain (GWG), pre-pregnancy fitness level, and exercise level. Conclusion: Cesarean birth was predicted by pre-pregnancy BMI and fitness level, while maternal exercise reduced the magnitudes of the relative risks of cesarean birth. Maternal exercise, pre-pregnancy fitness level, and GWG predict neonatal BW.Trial Registration: Influence of Maternal Exercise on Infant Skeletal Muscle and Metabolomics- #NCT03838146, 12/02/2019, https://register.clinicaltrials.gov/prs/app/template/EditRecord.vm?epmode=Edit&listmode=Edit&uid=U0003Z0X&ts=8&sid=S0008FWJ&cx=77ud1i
Phytochemical profiling, anti-inﬂammatory, analgesic and antipyretic potentials of Portulacaria afra Jacq: Molecular docking of unexplored bioactive compounds
Authors: Tabassum Sobia , Khan Kashif-ur-Rehman , Ahmad Saeed , Jabeen Qaiser , Rehman M. Sajid-ur , Usman Faisal , Ali Barkat , Iqbal Muhammad Jafar , Tabassum Fouzia , Ghalloo Bilal Ahmad , Ahmad Maqsood , Zubair Hafiz Muhammad 
Published: April 2022

Abstract
Natural products play an important role in novel drug discovery by providing structural leads for the pharmacotherapeutic agents against a variety of diseases. This study aimed to evaluate the possible, anti-inﬂammatory, antipyretic activity and analgesic potential of hydro-methanol extract (HMPA) of Portulacaria afra ( (acq ) in a rat model to support its folk use. The ingredients in HMPA extract were identified by using GC.MS followed by molecular docking of 1-Coprosten-3-one semicarbazone, Phenol, 2, 2-methylenebis,7,9-ditert-butyl-1-oxaspiro [4.5] deca-6,9-diene-2,8-dione against Cyclooxygenase-1 and Cyclooxygenase-2 enzymes. The phytochemical test of HMPA extract showed a positive result for secondary metabolites of tannin, flavonoids, alkaloids, phytosterol, saponins, cardiac glycoside quinolones, triterpenoids, and carbohydrates. The HMPA extract showed a good concentration of total flavonoid content (163.25 ± 2.50 mg GAE/g) and total phenolic contents (153.21 ± 1.17 mg GAE/g). The antioxidant capacity of HMPA extract showed signiﬁcant potential by DPPH, ABTS, and CUPRAC, FRAP methods. The Chromatogram by GC.MS showed compounds with anti-inﬂammatory potentials such as methyl octadeca-9, 12-dienoate, 9, 12, 15-Octadecatrienoic acid, palmitoleic acid, methyl palmitate, hexadecanoic acid, methyl ester, Parthenolide. In carrageenan-induced hind paw edema, assay results showed dose-dependent anti-inﬂammatory action. The different doses (100, 200, and 400 mg/kg) had anti-inflammatory activity in a dose-dependent manner. The analgesic activity by hot-plate, tail flicking, writhing test in rats HMPA extract demonstrated significant (p<0.05) potential. The antipyretic activity was investigated by using yeast-induced pyrexia in albino rats. At the dose of 100 and 200, 400 mg/kg HMPA extract signiﬁcantly decreased the temperature with maximum eﬀect at the 3 rd , 4th, and 5th h. The results of in vitro and in vivo experimental research confirmed the anti-inflammatory, analgesic, and antipyretic capabilities of P.afra and sustained folkloric claims of this plant.
Systematic review of the costs of adverse childhood experiences (ACEs): presenting the evidence on odds ratios and costs.
Authors: Lloyd-Williams Huw , Spencer Llinos Haf , Edwards Rhiannon Tudor 
Published: April 2022

Abstract
BackgroundAdverse childhood experiences (ACEs) are known to cause an array of diseases later in the life course [1]. However, there have been to date no studies that explicitly look at the costs of ACEs to society. Insofar as ACEs have an association with such diseases as cancer it is considered a worthwhile exercise to attempt to put a financial cost on these diseases and to calculate how much of this cost is attributable to ACEs. This is to make the case for investing in early years and linking services across sectors e.g. health, social care, crime and justice etc. so that the balance of spending is shifted towards prevention. Such information is useful for evidence-based policy making.MethodsThis systematic review follows the design, methods and processes of the Campbell and Cochrane Economics Method Group (CCEMG) [2]. The JSTOR, PubMed, Web of Science, Medline, Embase and PsycInfo electronic databases were extensively searched with relevant search terms. ResultsThe review is divided into two parts, the first part looking at odds ratios of the five disease types that link ACEs with these diseases. We then calculate the likelihood of how much of a particular disease is caused by certain ACEs and present these in tables. The second part of the review looks at cost of illness studies for the five highest expenditure disease types in the UK. These are Mental Disorders, Circulatory disorders, cancer, muscoskeletal disorders and genitourinary disorders. The results are presented in a tabular format by taking costs of illness from different studies and presenting them all, converted to GBP and 2020 figures, in an accessible format. The most striking figure in the odds ratios part is the relationship between sexual abuse and psychosis at 15.47 signifying a strong relationship and a suggestion that interventions to reduce psychosis might well benefit from concentrating on tackling sexual abuse. In terms of cost, we see that the lowest costs are those that do not consider indirect costs and only report direct medical expenditure. ConclusionThe information gathered here will serve as the basis to look at the relationship between cost of illness and adverse childhood experiences. The results of this paper will be useful to those who wish to use the odds ratios (after converting into relative risk ratios) to calculate population attributable fractions associated with each ACE so that they are able to calculate the percentage of each disease that is caused by certain ACEs. This percentage can then be applied to the costs gleaned from part 2 of this review to arrive at a cost that can be attributed to certain ACEs.
Phenotypic description of Egyptian endemic centipedes, genus Scolopendra Linnaeus, 1758 with a histological study of its venom glands.
Authors: mona mahy Mohammed , Atlam Aalaa Ibrahim 
Published: April 2022

Abstract
Background: Centipedes are widely distributed over all continents. They have important medicinal value and high toxicity, making it to be an interesting subject for evolutionary studies. Due to the lack of recent taxonomic revision in Egypt, this work and for the first study that is giving a fine report on the geographical distribution and morphometric description of Egyptian Scolopendra species.Result: Two Egyptian Scolopendra species were re-described based on fresh material based on a surveillance study in Egypt. Scolopendra canidens Newport.1844 were found in only one location. Scolopendra moristans Linnaeus,1758 was more abundant. Both venomous glands were histochemically investigated. This study is the first comparative report on the histology, and histochemistry of the venom glands of the Egyptian centipede species the glands in both species are mostly made up of columnar secretory cells that are radially arranged side by side and open through pores in a central chitinous duct. Striated muscular fibers envelop each secretory cell. Except for the size of the glands, which is related to the body dimensions of each species, the secretion takes the shape of small PAS-positive granules, suggesting the presence of neutral polysaccharides.Conclusion: According to this surveillance study the most abundant species was Scolopendra moristans Linnaeus,1758. Scolopendra canidens Newport.1844 were found only on the Northwest coast of Egypt. The findings show also that the analyzed species have a lot in common in terms of morphology and fundamental chemical makeup of their venom.
Shear stress activates P2X4 receptor currents via triggering Cx43 hemichannels in atrial myocytes: possible role on atrial adaptation to pressure overload
Authors: Woo Sun-Hee , Kim Joon-Chul , Do Long Nguyen Hoang , Le Qui Anh , Trinh Tran Nguyet , Kim Luong Phuong 
Published: April 2022

Abstract

Increase of afterload induces cardiac hypertrophy leading to contractile failure and dilation. Atria to receive venus return should adapt to such mechanical changes including shear stress. However, the atrial cell responses to shear stress are poorly understood. Recent evidence suggests that atrial myocytes release ATP fast under shear stress via connexin43 (Cx43) hemichannels, which triggers action potentials and Ca2+ waves. We explored cellular mechanism for graded depolarization under shear stress and its implication on atrial pathogenesis during progressive increase in afterload. Using whole-cell patch clamp combined with micro fluid-jet system, we found in rat atrial myocytes that shear stress activates non-selective cation currents (IS,Cs) that were enhanced by zero external Ca2+, but eliminated by La3+, high concentrations of carbenoxolone, anti-Cx43 antibodies, TAT-Gap19 or Cx43 conditional knockout (cKO), suggesting a key role of Cx43 hemichannel. Intracellular calcein fluorescence imaging to assess gap junction hemichannel activity revealed that shear stress induces a calcein efflux from atrial myocytes which was increased by zero external Ca2+ and suppressed by Cx43 hemichannel inhibitions (La3+, Gap19 or Cx43 cKO). The IS,Cs was eliminated by ATP-metabolizing apyrase and suppressed by antagonists of P2 receptors, mainly P2X4 receptor (P2X4R), indicating a role of autocrine P2X4R activation. Furthermore, in a rat model of left atrial (LA) hypertrophy, induced by transverse aortic constriction (TAC) for 5-weeks, IS,Cs and its P2X4R current component, and P2X4R protein level were largely increased with unaltered hemichannel function. In severely dilated left atria following 20-week-TAC, Cx43 hemichannel activity and P2X4R-currents of IS,Cs were attenuated again with lowered protein levels for Cx43 and P2X4R. Cx43 hemichannel-P2X4R signaling could account for increase of atrial excitability under shear stress. Characteristic alterations in this response during progressive pressure overload suggest that it plays a role in atrial compensatory adaptation to hypertension.
GSDMD in the endoplasmic reticulum exacerbates acute pancreatitis through TXNIP/HIF-1α pathway
Authors: Huang Wen , Zhang Cuicui , Niu Hai , Wan Chengyu , Yu Xiuxian , Xin Guang , Zhu Yuda , Wei Zeliang , Li Fan , Wang Yilan , Zhang Kun , Li Shiyi , Dong Yuman , Li Yangying 
Published: April 2022

Abstract
Endoplasmic reticulum stress (ERS) and GSDMD mediate acute pancreatitis (AP), but little is known about their mutual influence in AP. The GSDMD accumulation in ER was firstly found in this study, which caused ERS of acinar cells. GSDMD inhibitor DSF (Disulfiram) notably decreased the expression of GSDMD in ER and TXNIP/HIF-1α signaling. TXNIP inhibitor RES (Resveratrol) significantly inhibited TXNIP/HIF-1α, but not down-regulated the accumulation of GSDMD in ER. The molecular docking study indicated that there was a potential interaction between Drug D (Diosgenin derivative D) and GSDMD. Our results showed that Drug D significantly inhibited necrosis of acinar cells dose dependently, and we also found that Drug D moderated pancreatic necrosis and systemic inflammation with the GSDMD down-accumulation in ER. Furthermore, the level of p-IRE1α (a marker of ERS) was also down-regulated by Drug D in a dose-dependent manner in AP. We also found that Drug D alleviated TXNIP up-regulation and oxidative stress in AP. Moreover, our results revealed that GSDMD−/− mitigated AP by inhibiting TXNIP/HIF-1α. Our study reveals a new pathological mechanism for AP.
Analysis of the concept of nurses’ autonomy in intensive care units: A hybrid model
Authors: Taleghani Fariba , Dehbozorgi Raziye , Babashahi Monire , Monemian Sharife , Masoumi Masoume 
Published: April 2022

Abstract
Purpose: This study aimed to analyze the concept of autonomy among ICU nurses in the third populous city in Iran using the hybrid model and to explain the characteristics of this concept.Background: Autonomy is a relatively new concept in Intensive Care Unit nurses, it can have great outcomes for improving cooperation and autonomous performance in healthcare. Nonetheless, lack of theoretical and conceptual clarity for this concept has resulted in an incorrect perception amongst health staff and policymakers.Methods: this study was conducted using Schwartz-Barcott and Kim’s hybrid model including theoretical, field work, and analytical phases and according to COREQ checklist. Results: Based on the results, the antecedents of this concept were powerful human workforce, organizational platform, and the society’s sociocultural platform. Its attributes were professionalism and having personal capabilities. Finally, the consequences included personal competencies, promotion of care quality, improvement of the view towards the profession, and professional outcomes. Conclusion: Nurses’ autonomy in ICUs can facilitate their empowerment that results in the promotion of their care behaviors followed by the improvement of patients’ outcomes and care quality.
A comprehensive analysis of Simple Sequence Repeats in Picornaviruses
Authors: Sahu Basanta Pravas , George Biju , Majee Prativa , Singh Ravi Raj , Mishra Anurag , Tiwari Ritudhwaj , Nayak Debasis 
Published: April 2022

Abstract
Genome-wide identification of simple sequence repeats (SSRs) of Picornaviruses was carried out to investigate type, distribution, and potential role in genome evolution. Investigation on 88 Picornavirus species revealed the presence of 2,488 SSRs and 100 compound SSRs. The relative abundance and relative density of SSR varied between 1.953 bp/kb-5.763 bp/kb and 13.39 bp/kb-45.02 bp/kb, while that of cSSR ranged from 0.108 bp/kb-0.636 bp/kb and 1.36 bp/kb-26.84 bp/kb. Regression analysis revealed a significant correlation of genome size and GC content with the incidence of SSRs. Motif duplication pattern, such as (C)-x-(C), (TG)-x-(TG), etc. and self-complementary motifs, such as (GC)-x-(CG), (TC)-x-(AG), etc. were observed in cSSR. Polymorphism analysis revealed that most of the cSSR were prone to instability, followed by consensus motifs. Finally, recombination analysis revealed that the breakpoints were rich in dinucleotide repeat, especially GT. However, further experimental validation is needed to elucidate the correlation between recombination hotspots and microsatellites.
MicroRNA-588 regulates the invasive, migratory and vasculogenic mimicry-forming abilities of hypoxic glioma cells by targeting ROBO1
Authors: Yu Rui , Zhao Rongrong , Sun Xiaopeng , Zhang Zongpu , Wang Shaobo , Gao Xiao , Sun Zhongzheng , Xue Hao , Li Gang 
Published: April 2022

Abstract
BackgroundGlioma is an intracranial malignancy that is the most challenging tumor to treat. The hypoxic microenvironment is an important factor contributing to tumor development, while the migration, invasion and vasculogenic mimicry (VM) of glioma cells are the main causes of the increasing treatment difficulty.Materials and methodsA microarray was leveraged to identify differentially expressed microRNAs in U251 glioma cells cultured under normoxic and hypoxic conditions. The expression of miR-588 was assessed using quantitative real-time PCR (qRT-PCR). Gain- and loss-of-function studies were used to evaluated the role of miR-588 under hypoxic and normoxic conditions. Cell invasive, migratory, proliferation, as well as VM formation experiments were performed. The relationship between miR-588 and ROBO1 was confirmed using western blot and luciferase reporter assays. Intracranial xenograft tumor mouse models were applied to study the function of miR-588 in vivo.ResultsThe expression of miR-588 was obviously upregulated in hypoxic glioma cells in comparison with normoxic glioma cells. miR-588 inhibited the invasive, migratory and VM-forming abilities of glioma cells in vitro and in vivo. Mechanistically, Roundabout guidance receptor 1 (ROBO1) is a direct, functionally relevant target of miR-588 in glioma. ROBO1 knockdown suppressed the expression of matrix metallopeptidase 2 (MMP2) and matrix metallopeptidase 9 (MMP9), thereby inhibiting the invasive, migratory and VM-forming abilities of glioma.ConclusionsMiR-588 regulated the malignant behaviors of hypoxic glioma cells by targeting ROBO1. miR-588 can be used as a prognostic marker for glioma and has potential implications in glioma gene therapy.
Pyruvate kinase M2 promotes hair regeneration by connecting metabolic and Wnt/β- catenin signaling
Authors: Ryu Yeong Chan , Kim You-Rin , Park Jiyeon , Choi Sehee , Ryu Won-Ji , Kim Geon-Uk , Kim Eunhwan , Hwang Yumi , Kim Heejene , Han Gyoonhee , Lee Soung-Hoon , Choi Kang-Yell 
Published: April 2022

Abstract
The hair follicle stem cells (HFSCs) utilize glycolytic metabolism during their activation and anagen induction. However, the role of pyruvate kinase M2 (PKM2), which catalyzes the final step of glycolysis, in hair regeneration has not been elucidated. In this study, we investigated the expression pattern and activity of PKM2 during the depilation-induced anagen progression in mice. We found that TEPP-46, a selective activator of PKM2, enhanced hair re-growth and proliferation of HFSCs. PKM2 expression was increased via up-regulation of the Wnt/β-catenin signaling, which is involved in hair regeneration. Moreover, a combined treatment with KY19382, a small molecule that activates the Wnt/β-catenin signaling, and TEPP-46 significantly enhanced hair re-growth and wound-induced hair follicle neogenesis (WIHN). These results indicate that simultaneous activation of the PKM2 and Wnt/β-catenin signaling could be a potential strategy for treating alopecia patients.
Treatment and control of invasive Gram-negative bacterial infection in eight hospitals across sub-Saharan Africa: a cross-sectional study
Authors: Aiken Alexander M. , Nyamwaya Brian , Madrid Lola , Edessa Dumessa , Labi Appiah-Korang , Obeng-Nkrumah Noah , Mwabaya William , Chimenya Mabvuto , Cocker Derek , Iregbu Kenneth C. , Nwajobi-Princewill Philip I. P. , Dramowski Angela , Sonda Tolbert , Mmbaga Blandina Theophil , Ojok David , Fwoloshi Sombo , Scott J. Anthony G. , Whitelaw Andrew , Sisay Mekonnnen , Aliye Jabir , Dankwah Thomas , Osei Mary M. , Mulunda Caroline , Karani Bernard , Feasey Nicholas , Lester Rebecca , Medugu Nubwa , Okonkwo Chinelo H. , Hemedi Asia , Ng'unda Neema , Mutemba Charles , Chirwa Uchizi 
Published: April 2022

Abstract
Background: Bloodstream infections caused by Enterobacterales show high frequency of antimicrobial resistance (AMR) in many Low- and Middle-Income Countries. We aimed to describe the variation in circumstances for management of such resistant infections in public-sector hospitals across sub-Saharan Africa. Methods: We gathered data from eight hospitals across sub-Saharan Africa to describe hospital services, infection prevention and antibiotic stewardship activities, using two WHO-generated tools. We collected monthly cross-sectional data on availability of antibiotics in the hospital pharmacies for bloodstream infections caused by Enterobacterales. Results: Hospital circumstances for institutional management of resistant BSI varied markedly. This included self-evaluated infection prevention level (WHO-IPCAF score: median 428, range 155 to 687.5) and antibiotic stewardship activities (WHO stewardship toolkit questions: median 14.5, range 2 to 23). These results did not correlate with national income levels. Across all sites, ceftriaxone and ciprofloxacin were the most consistently available antibiotic agents, followed by amoxicillin, co-amoxiclav, gentamicin and co-trimoxazole. There was substantial variation in the availability of some antibiotics, especially carbapenems, amikacin and piperacillin-tazobactam with degree of access linked to national income level. Investigators described out-of-pocket payments for access to additional antibiotics at 7/8 sites. Conclusion: There was wide variation between these African hospitals for a range of important circumstances relating to treatment and control of severe bacterial infections, though these did not all correspond to national income level. Antimicrobial resistant bacterial infections could plausibly show different clinical impacts across sub-Saharan Africa due to this contextual variation. More estimates of the impact of AMR are needed from countries of different income levels to account for these differences.