bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of tocilizumab in the management of COVID-19: A systematic review and meta-analysis of observational studies
Authors: Viswanatha Gollapalle L , Male CH K V L S N Anjana , Shylaja Hanumanthappa 
Published: January 2021

AbstractBackgroundThis systematic review and meta-analysis was aimed to evaluate the efficacy and safety of tocilizumab (TCZ) in treating severe coronavirus disease 2019 (COVID-19).MethodsThe electronic search was performed using PubMed, Scopus, CENTRAL, and Google scholar to identify the retrospective observational reports. The studies published from 01 January 2020 to 30th September 2020. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo/standard of care. The comparison will be between TCZ versus standard of care (SOC)/placebo. Inconsistency between the studies was evaluated with I2 and quality of the evidences were evaluated by Newcastle-Ottawa scale.ResultsBased on the inclusion criteria there were 24 retrospective studies involving 5686 subjects were included. The outcomes of the meta-analysis have revealed that the TCZ has reduced the mortality (M-H,RE-OR −0.11(−0.18 to −0.04) 95% CI, p =0.001, I2 =88%) and increased the incidences of super-infections (M-H, RE-OR 1.49(1.13 to 1.96) 95% CI, p=0.004, I2=47%). However, there is no significant difference in ICU admissions rate (M-H, RE-OR −0.06(−0.23 to 0.12), I2=93%), need of MV (M-H, RE-OR of 0.00(−0.06 to 0.07), I = 74%), LOS (IV −2.86(−0.91 to 3.38), I2=100%), LOS-ICU (IV: −3.93(−12.35 to 4.48), I2=100%), and incidences of pulmonary thrombosis (M-H, RE-OR 1.01 (0.45 to 2.26), I2=0%) compared to SOC/control.ConclusionBased on cumulative low to moderate certainty evidence shows that TCZ could reduce the risk of mortality in hospitalized patients. However, there is no statistically significant difference observed between the TCZ and SOC/control groups in other parameters.
Multidimensional analysis of immune response identified biomarkers of recentMycobacterium tuberculosisinfection
Authors: Lloyd Tessa , Steigler Pia , Mpande Cheleka A.M. , Rozot Virginie , Mosito Boitumelo , Shreuder Constance , Reid Timothy D. , Hatherill Mark , Scriba Thomas J. , Little Francesca , Nemes Elisa ,   the ACS Study Team
Published: January 2021

AbstractThe risk of tuberculosis (TB) disease is higher in individuals with recentMycobacterium tuberculosis(M.tb) infection compared to individuals with more remote, established infection. We aimed to define blood-based biomarkers to distinguish between recent and remote infection, which would allow targeting of recently infected individuals for preventive TB treatment. We hypothesized that integration of multiple immune measurements would outperform the diagnostic performance of a single biomarker. Analysis was performed on different components of the immune system, including adaptive and innate responses to my-cobacteria, measured on recently and remotelyM.tbinfected adolescents. The datasets were standardized using variance stabilizing (vast) scaling and missing values were imputed using a multiple factor analysis-based approach. For data integration, we compared the performance of a Multiple Tuning Parameter Elastic Net (MTP-EN) to a standard EN model, which was built to the single datasets. Biomarkers with non-zero coefficients from the optimal single data EN models were then isolated to build logistic regression models. A decision tree and random forest model were used for statistical validation. We found no difference in the predictive performances of the optimal MTP-EN model and the EN model [average area under the receiver operating curve (AUROC)=0.93]. EN models built to the integrated dataset and the adaptive dataset yielded identically high AUROC values (average AUROC=0.91), while the innate data EN model performed poorly (average AUROC=0.62). Results also indicated that integration of adaptive and innate biomarkers did not outperform the adaptive biomarkers alone (Likelihood Ratio Testχ2=6.09, p=0.808). From a total of 193 variables, the level of HLA-DR on ESAT6/CFP10-specific Th1 cytokine-expressing CD4 cells was the strongest biomarker for recentM.tbinfection. The discriminatory ability of this variable was confirmed in both tree-based models.A single biomarker measuringM.tb-specific T cell activation yielded excellent diagnostic potential to distinguish between recent and remoteM.tbinfection.
Identification and characterization of a biphasic/bidirectional wound-inducibleRHA3Bgene promoter fromArabidopsis thaliana
Authors: Rao Venkateswara , Virupapuram Vijaybhaskar 
Published: January 2021

AbstractConditional promoters such as wound inducible are important tools for plant biotechnology to selectively express agronomically important genes. From a set of Enhancer trap (DsE-uidA) transposant lines we identified wound inducible ET1075 line by injuring leaf blade and screening for Ds linked GUS gene expression. Earliest GUS stain detected at petiolar region at 2hrs post injury with a progressive attainment of maximum visual intensity between 12 and 24hrs wherein, the transcript expression induced in a bidirectional manner. DsE was found to be inserted in the intergenic region betweenAT4G35480andAT4G35490. To find the essential transcriptional regulatory region, deletion constructs comprising upstream sequences of pRHA3Bfused to GUS reporter gene were functionally tested in Arabidopsis plants by generating stable transgenics. A 481 bp of upstream sequence from ATG is found to be sufficient to promote wound inducible gene expression. Sequence analysis revealed the presence of several regulatory elements implicated in wound inducible gene expression. Comparative analysis with similar wound inducible promoters revealed the presence of commoncis-regulatory elements. This promoter can essentially be used in pest control and in molecular pharming to conditionally express agronomically/commercially important genes in plants.HighlightsDsE enhancer trap transposant lines were generated.Identified a novel wound inducible promoter line ET1075.Wound inducible promoter pRHA3Bis bidirectional and induces the expression ofRHA3BandMRPL11genes.Wound responsive key cis-elements WRKY, W-box, FORCAare present in the pRHA3Bpromoter.
Regional anaesthesia for rib fractures: A pilot study of serratus anterior plane block
Authors: Schnekenburger Marc , Mathew Joseph , Fitzgerald Mark , Hendel Simon , Sekandarzad Mir Wais , Mitra Biswadev 
Published: January 2021

AbstractObjectiveRib fractures are not only painful but are associated with morbidity and mortality, especially in older patients. The serratus anterior plane block (SAPB) is a plane block distant from major neurovascular bundles and may provide anaesthesia to a substantial area of the hemithorax. This pilot study was designed to assess if the SAPB can be safely and efficiently incorporated to the trauma reception workflow of an adult, level 1 trauma centre.MethodsA convenience sample of 20 adult patients with at least two or more unilateral rib fractures received a SAPB performed by an emergency physician in addition to their standard analgesic regime. Time to perform the procedure, the number of attempts and complications were recorded as feasibility measures. Secondary outcome was the safety of the block. Numerical pain scores at pre‐determined time points over 4 h, the diagnosis of hospital‐acquired pneumonia, hospital length of stay and mortality at hospital discharge were collected to provide pilot data on effectiveness.ResultsThe median time to perform the procedure was 5.5 (interquartile range 4.6–10) mins with a range of 2–10.5 min. Most (16; 80%) SAPBs were completed in a single attempt. There were no documented complications. Median pain scores reduced from 6.5 (6–8) and were maintained at 3 (2–5) at 4 h after the SAPB.ConclusionsThe present study demonstrated the feasibility of ultrasound‐guided SAPB among patients with multiple rib fractures in the ED. No complications were observed. Further prospective evaluation of analgesic effects in a larger cohort is indicated.
Baseline carotid intima‐media thickness is associated with cardiovascular morbidity and mortality in peritoneal dialysis patients
Authors: Asicioglu Ebru , Velioglu Arzu , Arikan Hakki , Koc Mehmet , Tuglular Serhan , Ozener Cetin 
Published: January 2021

AbstractCarotid intima‐media thickness (CIMT) is an early marker of atherosclerosis and is increased in peritoneal dialysis (PD) patients. Association of CIMT with cardiovascular disease (CVD) or mortality is less clear. Fibroblast growth factor‐23 (FGF‐23) is a hormone associated with vascular calcification, atherosclerosis, and mortality in the hemodialysis population. We investigated whether baseline CIMT and FGF‐23 are associated with CVD and mortality in PD patients. Fifty‐five PD patients were included. CVD was defined as ischemic heart disease, stroke, or peripheral artery disease. Intact FGF‐23 was measured in plasma. CIMT was measured by ultrasonography. Twenty‐one patients developed CVD and 12 died over 47.1 ± 33.8 months. Patients with CVD were older (55.9 ± 10.5 vs. 42.5 ± 12.9 years, P < .01), had lower albumin (3.8 ± 0.5 vs. 4.2 ± 0.3 g/dL, P < .01) and higher CIMT (0.87 ± 0.22 vs. 0.61 ± 0.11 mm, P < .01). Patients with mortality were also older (53.5 ± 11.5 vs. 45.8 ± 13.8 years, P = .05), had lower albumin (3.7 ± 0.6 vs. 4.1 ± 0.3 g/dL, P < .01), higher CRP (15.0 ± 8.5 vs. 7.6 ± 8.4 mg/L, P < .01) and CIMT (0.9 ± 0.3 vs. 0.6 ± 0.1 mm, P < .01). Albumin and CIMT were associated with CVD and CIMT >  0.75 mm was associated with cardiovascular mortality. FGF‐23 did not show any correlations. CIMT at baseline is associated with CVD and mortality in PD patients.
Cadmium sulfide nanoparticle biomineralization and biofilm formation mediate cadmium resistance of the deep‐sea bacterium Pseudoalteromonas sp. MT33b
Authors: Ma Ning , Sun Chaomin 
Published: January 2021

SummaryCadmium (Cd) is a common toxic heavy metal in the environment, and bacteria have evolved different strategies to deal with Cd toxicity. Here, a bacterium designated Pseudoalteromonas sp. MT33b possessing strong Cd resistance was isolated from the Mariana Trench sediments. Supplement of cysteine significantly increased bacterial Cd resistance and removal rate. Biofilm formation was demonstrated to play a positive role toward bacterial Cd resistance. Transcriptome analysis showed the supplement of cysteine effectively prevented Cd2+ from entering bacterial cells, promoted saccharide metabolism and thereby facilitating energy production, which consists well with bacterial growth trend analysed under the same conditions. Notably, the expressions of many biofilm formation related genes including flagellar assembly, signal transduction, bacterial secretion and TonB‐dependent transfer system were significantly upregulated when facing Cd stress, indicating their important roles in determining bacterial biofilm formation and enhancing Cd resistance. Overall, this study indicates the formation of insoluble CdS precipitates and massive biofilm is the major strategy adopted by Pseudoalteromonas sp. MT33b to eliminate Cd stress. Our results provide a good model to investigate how heavy metals impact biofilm formation in the deep‐sea ecosystems, which may facilitate a deeper understanding of microbial environmental adaptability and better utilization of these microbes for bioremediation purposes in the future.
The Enlarged Global Financial Safety Net
Authors: Vinokurov Evgeny , Levenkov Artem 
Published: January 2021

AbstractThe institutions and instruments of the Global Financial Safety Net (GFSN) represent the part of the global financial architecture that is responsible for providing an anti‐crisis and stabilization support to the countries in need. We argue that the standard understanding of the GFSN as a system consisting of four layers – national reserves, bilateral swaps, regional financing arrangements and the IMF – demands rethinking. We suggest the concept of an enlarged GFSN, namely its expansion by two additional elements – multilateral development banks and bilateral financial support. Both elements of the international financial architecture are partly involved in providing an anti‐crisis and macroeconomic stabilization support at concessional terms. We demonstrate how the enlarged GFSN functions, including at the time of the COVID‐19 crisis.
A systemic review of intravenous immunoglobulin G treatment in women with recurrent implantation failures and recurrent pregnancy losses
Authors: Saab Wael , Seshadri Srividya , Huang Changsheng , Alsubki Lujain , Sung Nayoung , Kwak‐Kim Joanne 
Published: January 2021

AbstractOver the last few decades, the advancement in reproductive technologies and protocols to improve embryo quality through culture techniques and genetic testing to eliminate chromosomally abnormal embryos resulted in better pregnancy rates and outcomes after fertility treatments. Unfortunately, some patients still struggle with recurrent implantation failures (RIFs) and recurrent pregnancy losses (RPLs). Immune etiologies have been attributed to play an important role in some of those patients. Maintaining a pre‐conceptional anti‐inflammatory environment for implantation and pregnancy continuation yields superior results. Intravenous immunoglobulin G (IVIG) treatment has been reported to enhance reproductive outcome in patients with RIF and RPL with immune dysregulations. In this systemic review, we analyzed outcomes of IVIG trials for RIF and RPL, its mechanism of action, dosing, administration, side‐effects, and evidence for its use in women with RIF and RPL.
Lithium from breast‐milk inhibits thyroid iodine uptake and hormone production, which are remedied by maternal iodine supplementation
Authors: Ahmed Irfan , Ma Victor , Liu Yuanchao , Khan Muhammad Shehzad , Liu Zhenhui , Zhang Chi , Paidi Santosh Kumar , Manno Francis A. M. , Amjad Noreen , Manno Sinai H. C. , Ahmed Rafay , Law Alan W. L. , Ali Ahmed , Raza Faizan , Zhang Yanpeng , Cho William C. S , Barman Ishan , Alda Martin , Bergink Veerle , Lau Condon 
Published: January 2021

AbstractBackgroundLithium is especially taken as a maintenance medication for Bipolar Disorder. In women with bipolar disorder, lithium is often effective during postpartum period, but breast‐feeding for medicated mothers is controversial because of harmful effects for her child. At present, the biological mechanisms of lithium are not well‐understood, affecting its usage and overall health implications.ProcedureWe developed a rat lithium and breast‐feeding model at human therapeutic levels to study the effects of lithium exposure through breast‐milk on pups’ thyroid function. Novel laser analytical spectroscopy, along with traditional blood and immunohistochemical tests, were applied to further investigate the mechanisms behind the thyroid dysfunction. Maternal iodine supplementation was evaluated as a therapeutic method to address the pups’ thyroid dysfunction.ResultsPups exposed to lithium via breastmilk, even with the dam on a sub‐therapeutic level, experienced weight gain, reduced blood thyroxine (T4), and elevated blood urea nitrogen, indicating effects on thyroid and kidney function. We show that lithium inhibited iodine uptake by thyroid follicles, initiating a mechanism that reduced iodination of tyrosine, thyroglobulin cleavage, and thyroid hormone production. Importantly, infant thyroid function can be significantly improved by administering supplementary iodine to the medicated dam's diet during breast‐feeding.ConclusionThese results elucidate the mechanisms of lithium in thyroid function, provide valuable information on use postpartum, and suggest a clinically applicable remedy to side‐effects. The results are particularly important for patients (and their infants) who respond well to lithium and need, or choose, to breast‐feed.
Introduction: The Politics of Open Access — Decolonizing Research or Corporate Capture?
Authors: Meagher Kate 
Published: January 2021

ABSTRACTThis introductory article looks beyond the conventional framing of open access (OA) debates in terms of paywalls and copyrights, to examine the historical processes, institutional and digital infrastructures, and political dynamics shaping the effects of OA in development research. From a historical perspective, it focuses on tensions and crises in the relationship between scholarly and corporate publishing ecosystems. The spectrum of open access models is also examined, with a focus on green, gold, diamond and black, which tend to obscure the underlying scholarly publishing infrastructures that shape the parameters of openness and access. A closer look at distinctive for‐profit and non‐profit OA infrastructures reveals the inequitable and often neo‐colonial effects of for‐profit models on Southern researchers and the social sciences. Accounts of the politics of OA highlight processes of political capture of the OA agenda by Northern corporate and state interests and draw attention to alternative interest coalitions which are more suited to prioritizing the global public good over private profit. Reflecting on the requirements of OA in low‐resource environments, this article echoes calls for more equitable forms of openness and access in development research ecosystems, with a view to decolonizing as well as advancing OA.
Cerebral blood flow and acute episodes of Leigh syndrome in neurometabolic disorders
Authors: Loiselet Klervie , Ruzzenente Benedetta , Roux Charles‐Joris , Barcia Giulia , Pennisi Alessandra , Desguerre Isabelle , Rötig Agnès , Munnich Arnold , Boddaert Nathalie ,   Paediatric Radiology and Metabolics Group
Published: January 2021

AimTo investigate cerebral blood flow (CBF) in acute episodes of Leigh syndrome compared with basal state in patients carrying pathogenic mitochondrial disease gene variants responsible for neurometabolic disorders.MethodArterial spin labelling (ASL) magnetic resonance imaging (MRI) sequences were used to measure CBF in 27 patients with mitochondrial respiratory chain enzyme deficiencies, ascribed to pathogenic variants of reported disease genes who were undergoing either urgent neuroimaging for acute episodes of Leigh syndrome (Group I: 15 MRI, seven females, eight males; mean age 7y; range 7mo–14y) or routine brain MRI (Group II: 15 MRI, eight females, seven males; mean age 5y 2mo; range 2mo–12y).ResultsPatients displayed markedly increased CBF in the striatum (2.8‐fold greater, p<0.001 [1.05–2.53]) during acute episodes of Leigh syndrome compared to basal conditions. Detection of elevated CBF preceded identification of structural MRI lesions in four out of 15 cases.InterpretationOur results suggest that increased CBF is an overt hallmark of Leigh syndrome episodes and ASL MRI sequences should facilitate early diagnosis of acute episodes of Leigh syndrome, especially during the first attack in young children, when structural MRI is insufficiently informative.
Linking range wide energetic tradeoffs to breeding performance in a long‐distance migrant
Authors: Carneiro Camilo , Gunnarsson Tómas G. , Méndez Verónica , Soares Amadeu M. V. M. , Alves José A. 
Published: January 2021

Understanding how individual tradeoffs and carry‐over effects along the annual cycle influence fitness is fundamental to unravel population dynamics, but such data is particularly challenging to collect in long‐distance migrants. Here, with a full annual cycle perspective of Icelandic whimbrels Numenius phaeopus islandicus, we investigate tradeoffs across the entire distribution, assessing migration costs and wintering energetic balance experienced throughout the wintering range (from temperate to tropical regions), and link these to breeding parameters for two wintering regions.We found that Icelandic whimbrels traded off higher costs of migration with more favourable wintering conditions, in terms of energetic balance. By migrating further, whimbrels experience lower thermoregulatory costs and higher net energetic intake rates, resulting in a more positive energetic balance during winter. However, these differences did not appear to carry‐over into the breeding season in terms of measurable effects on laying date (and, consequently, fledging success) or egg volume, suggesting that individual fitness is unlikely to be significantly influenced by previous wintering conditions, although effects on other traits may potentially occur. Nevertheless, Icelandic whimbrels seem to favour wintering locations where the conditions are more advantageous, as the abundance of individuals at the wintering sites reflects the variation in site quality.
An innovative interprofessional dental clinical learning environment using entrustable professional activities
Authors: Hissink Elske , Fokkinga Wietske A. , Leunissen Ronald R. M. , Lia Fluit C. R. M. G. , Loek Nieuwenhuis A. F. M. , Creugers Nico H. J. 
Published: January 2021

AbstractIntroductionChanges in society, new public demands for dental care and contemporary educational insights have influenced dental education worldwide and demand a renewed perspective. Following this perspective, an innovative interprofessional dental Master curriculum was developed at Radboud University Nijmegen in the Netherlands.Educational principlesThe curriculum is based on five contemporary educational principles and the core of the curriculum consists of a Student Run Dental Clinic that is fully run by students under professional supervision.The new curriculumIn the Student Run Dental Clinic, Master dental students and Bachelor oral hygiene students are responsible for the care of approximately 750 patients. The students work within the same clinic for 3 years and patients receive oral health care from the same students over a long period. The clinic is a longitudinal cross‐disciplinary clinic with different dental subdisciplines.Entrustable professional activities (also known as EPAs), to our knowledge not yet widely used in dental education, were introduced to facilitate learning and assessment. Fourteen EPAs have been developed to stimulate interprofessional education and learning. Of these, five EPAs are identical for the dental and oral hygiene curriculum, leading to extended interprofessional education and learning in the Student Run Dental Clinic.DiscussionPreliminary results show that EPAs are generally well received by supervisors and students.ConclusionTo monitor and investigate the exact effect of the interventions and underlying mechanisms, a research programme on interprofessional learning, practice‐based learning and EPAs and entrustment in dental education was recently set up.
Parental relatedness and parasitoid sex ratios under local mate competition
Authors: Du Kai , Abdi Mohamed Khadar , Hardy Ian CW 
Published: January 2021

AbstractSex ratio theory predicts that, under local mate competition, a more female‐biased offspring sex ratio will be produced by females when their relatedness to their mates is closer. We assess how the sexual composition of broods responds to mother–mate relatedness using Goniozus legneri Gordh (Hymenoptera: Bethylidae), a parasitoid wasp that has biased sex ratios due to local mate competition. Relatedness was varied by providing virgin females with a mate that was either a sibling, a non‐sibling from the same strain, from a strain with geographically similar origin or from a strain with geographically distant origin. The sex ratios among broods produced by mothers that had mated with a sibling or a same‐strain male were similar and were more biased than broods produced by females mated with males from a different strain. Brood sex variances were higher after mating with different‐strain males. Previous evaluations of parasitoid sex ratio responses to mate relatedness have not found the patterns predicted, possibly because the species investigated can control progeny sex ratio but cannot discriminate kin. In contrast, female G. legneri appear to possess both these abilities and appears to respond to mate relatedness in qualitative agreement with theoretical predictions.