bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chloroquine and hydroxychloroquine effectiveness in human subjects during coronavirus: a systematic review
Authors: Rawaf Salman , Al-Saffar Mohammed N , Quezada-Yamamoto Harumi , Alshaikh Mashael , Pelly Michael , Rawaf David , Dubois Elizabeth , Majeed Azeem 
Published: May 2020

AbstractIn a search to find effective treatments for COVID-19, chloroquine and hydroxychloroquine have gained attention. We aim to provide evidence to support clinical decision-making regarding medication for the treatment of COVID-19 by carrying out a systematic review of the literature. The electronic databases MEDLINE, EMBASE, Global Health, and HMIC were searched up to April 2020. Eligible study outcomes included: extubation or patient recovery. Relevant data were extracted and analysed by narrative synthesis. Our results included six studies in the review of which four studies were of good or fair quality. All eligible studies included were for coronavirus involving the use of either chloroquine or hydroxychloroquine to treat common symptoms such as fever, cough, shortness of breath and fatigue. Outcomes most commonly reported were improved lung function, viral clearance, and hospital discharge. Strong evidence to support the use of chloroquine and hydroxychloroquine in the treatment of COVID-19 is lacking. Fast track trials are riddled with bias and may not conform to rigorous guidelines which may lead to inadequate data being reported. The use of these drugs in combination with other medications may be useful but without knowing which groups they are suited for and when they may cause more harm than good.
Evaluation of Clinical Trial Data Sharing Policy in Leading Medical Journals
Authors: Danchev Valentin , Min Yan , Borghi John , Baiocchi Mike , Ioannidis John P.A. 
Published: May 2020

AbstractBackgroundThe benefits from responsible sharing of individual-participant data (IPD) from clinical studies are well recognized, but stakeholders often disagree on how to align those benefits with privacy risks, costs, and incentives for clinical trialists and sponsors. Recently, the International Committee of Medical Journal Editors (ICMJE) required a data sharing statement (DSS) from submissions reporting clinical trials effective July 1, 2018. We set out to evaluate the implementation of the policy in three leading medical journals (JAMA, Lancet, and New England Journal of Medicine (NEJM)).MethodsA MEDLINE/PubMed search of clinical trials published in the three journals between July 1, 2018 and April 4, 2020 identified 487 eligible trials (JAMA n = 112, Lancet n = 147, NEJM n = 228). Two reviewers evaluated each of the 487 articles independently. Captured outcomes were declared data availability, data type, access, conditions and reasons for data (un)availability, and funding sources.Findings334 (68.6%, 95% confidence interval (CI), 64.1%–72.5%) articles declared data sharing, with non-industry NIH-funded trials exhibiting the highest rates of declared data sharing (88.9%, 95% CI, 80.0%–97.8) and industry-funded trials the lowest (61.3%, 95% CI, 54.3%–68.3). However, only two IPD datasets were actually deidentified and publicly available as of April 10, 2020. The remaining were supposedly accessible via request to authors (42.8%, 143/334), repository (26.6%, 89/334), and company (23.4%, 78/334). Among the 89 articles declaring to store IPD in repositories, only 17 articles (19.1%) deposited data, mostly due to embargo and regulatory approval. Embargo was set in 47.3% (158/334) of data-sharing articles, and in half of them the period exceeded 1 year or was unspecified.InterpretationMost trials published in JAMA, Lancet, and NEJM after the implementation of the ICMJE policy declared their intent to make clinical data available. However, a wide gap between declared and actual data sharing exists. To improve transparency and data reuse, journals should promote the use of unique pointers to dataset location and standardized choices for embargo periods and access requirements. All data, code, and materials used in this analysis are available on OSF at https://osf.io/s5vbg/.
The critical role of infection prevention overlooked in Ethiopia, only one-half of health-care workers had safe practice: A Systematic Review and Meta-Analysis
Authors: Sahiledengle Biniyam , Tekalegn Yohannes , Woldeyohannes Demelash 
Published: May 2020

AbstractBackgroundEffective infection prevention and control measures, such as such hand hygiene, the use of personal protective equipment, instrument processing, safe injection, and safe disposal of infectious wastes in the healthcare facilities maximize patient outcomes and are essential to providing effective, efficient, and quality health care services. In Ethiopia, findings regarding infection prevention practices among healthcare workers have been highly variable and uncertain. Therefore, this systematic review and meta-analysis estimate the pooled prevalence of safe infection prevention practices and summarize the associated factors among healthcare workers in Ethiopia.MethodsPubMed, Science Direct, Google Scholar, and the Cochrane library were systematically searched. We included all observational studies reporting the prevalence of safe infection prevention practices among healthcare workers in Ethiopia. Two authors independently extracted all necessary data using a standardized data extraction format. Qualitative and quantitative analyses were employed. The Cochrane Q test statistics and I2 tests were used to assess the heterogeneity of the studies. A random-effects meta-analysis model was used to estimate the pooled prevalence of safe infection prevention practice.ResultsOf the 187 articles identified through our search, 10 studies fulfilled the inclusion criteria and were included in the meta-analysis. The pooled prevalence of safe infection prevention practice in Ethiopia was 52.2% (95%CI: 40.9-63.4). The highest prevalence of safe practice was observed in Addis Ababa (capital city) 66.2% (95%CI: 60.6-71.8), followed by Amhara region 54.6% (95%CI: 51.1-58.1), and then Oromia region 48.5% (95%CI: 24.2-72.8), and the least safe practices were reported from South Nation Nationalities and People (SNNP) and Tigray regions with a pooled prevalence of 39.4% (95%CI: 13.9-64.8). In our qualitative syntheses, healthcare workers socio-demographic factors (young age, female gender), behavioral-related factors (being knowledgeable and having a positive attitude towards infection prevention), and healthcare facility-related factors (presence of running water supply, availability of infection prevention guideline, and receiving training) were important variables associated with safe infection prevention practice.ConclusionsOnly half of the healthcare workers in Ethiopia practiced safe infection prevention. Furthermore, the study found out that there were regional and professional variations in the prevalence of safe infection prevention practices. Therefore, the need to step-up efforts to intensify the current national infection prevention and patient safety initiative as key policy direction is 41 strongly recommended, along with more attempts to increase healthcare worker’s adherence towards infection prevention guidelines.
A generic white pupae sex selection phenotype for insect pest control
Authors: Ward CM , Aumann RA , Whitehead MA , Nikolouli K , Leveque G , Gouvi G , Fung E , Reiling SJ , Djambazian H , Hughes MA , Whiteford S , Caceres-Barrios C , Nguyen TNM , Choo A , Crisp P , Sim S , Geib S , Marec F , Häcker I , Ragoussis J , Darby AC , Bourtzis K , Baxter SW , Schetelig MF 
Published: May 2020

AbstractMass releases of sterilized male insects, in the frame of sterile insect technique programs, have helped suppress insect pest populations since the 1950s. In the major horticultural pestsBactrocera dorsalis, Ceratitis capitata, andZeugodacus cucurbitae, a key phenotype white pupae (wp) has been used for decades to selectively remove females before releases, yet the gene responsible remained unknown. Here we use classical and modern genetic approaches to identify and functionally characterize causalwp−mutations in these distantly related fruit fly species. We find that the wp phenotype is produced by parallel mutations in a single, conserved gene. CRISPR/Cas9-mediated knockout of thewpgene leads to the rapid generation of novel white pupae strains inC. capitataandB. tryoni. The conserved phenotype and independent nature of thewp−mutations suggest that this technique can provide a generic approach to produce sexing strains in other major medical and agricultural insect pests.
A series of five population-specific Indian brain templates and atlases spanning ages 6 to 60 years
Authors: Holla Bharath , Taylor Paul A. , Glen Daniel R. , Lee John A. , Vaidya Nilakshi , Mehta Urvakhsh Meherwan , Venkatasubramanian Ganesan , Pal Pramod , Saini Jitender , Rao Naren P. , Ahuja Chirag , Kuriyan Rebecca , Krishna Murali , Basu Debashish , Kalyanram Kartik , Chakrabarti Amit , Orfanos Dimitri Papadopoulos , Barker Gareth J. , Cox Robert W. , Schumann Gunter , Bharath Rose Dawn , Benegal Vivek 
Published: May 2020

AbstractAnatomical brain templates are commonly used as references in neurological MRI studies, for bringing data into a common space for group-level statistics and coordinate reporting. Given the inherent variability in brain morphology across age and geography, it is important to have templates that are as representative as possible for both age and population. A representative-template increases the accuracy of alignment, decreases distortions as well as potential biases in final coordinate reports. In this study, we developed and validated a new set of T1w Indian brain templates (IBT) from a large number of brain scans (total n=466) acquired across different locations and multiple 3T MRI scanners in India. A new tool in AFNI, make_template_dask.py, was created to efficiently make five age-specific IBTs (ages 6-60 years) as well as maximum probability map (MPM) atlases for each template; for each age-group’s template-atlas pair, there is both a “population-average” and a “typical” version. Validation experiments on an independent Indian structural and functional-MRI dataset show the appropriateness of IBTs for spatial normalization of Indian brains. The results indicate significant structural differences when comparing the IBTs and MNI template, with these differences being maximal along the Anterior-Posterior and Inferior-Superior axes, but minimal Left-Right. For each age-group, the MPM brain atlases provide reasonably good representation of the native-space volumes in the IBT space, except in a few regions with high inter-subject variability. These findings provide evidence to support the use of age and population-specific templates in human brain mapping studies. This dataset is made publicly available (https://hollabharath.github.io/IndiaBrainTemplates).HighlightsA new set of age-specific T1w Indian brain templates for ages 6-60 yr are developed and validated.A new AFNI tool, make_template_dask.py, for the creation of group-based templates.Maximum probability map atlases are also provided for each template.Results indicate the appropriateness of Indian templates for spatial normalization of Indian brains
Rapid Assembly and Screening of Multivalent Immune Cell-Redirecting Therapies for Leukemia
Authors: Do Priscilla , Perdue Lacey A , Chyong Andrew , Hunter Rae , Dougan Jodi , Henry Curtis J , Porter Christopher C , Dreaden Erik C 
Published: May 2020

ABSTRACTTherapies that bind with immune cells and redirect their cytotoxic activity towards diseased cells represent a promising and versatile approach to immunotherapy with applications in cancer, lupus, and other diseases; traditional methods for discovering these therapies, however, are often time-intensive and lack the throughput of related target-based discovery approaches. Inspired by the observation that the cytokine, IL-12, can enhance antileukemic activity of the clinically approved T cell redirecting therapy, blinatumomab, here we describe the structure and assembly of a chimeric immune cell-redirecting agent which redirects the lytic activity of primary human T cells towards leukemic B cells and simultaneously co-targets the delivery of T cell-stimulating IL-12. We further describe a novel method for the parallel assembly of compositionally diverse libraries of these bi-specific T cell engaging cytokines (BiTEokines) and their high-throughput phenotypic screening, requiring just days for hit identification and the analysis of structure-function relationships. Using this approach, we identified CD19 × CD3 × IL12 compounds that exhibitex vivolytic activity comparable to current FDA-approved therapies for leukemia and correlated drug treatment with specific cell-cell contact, cytokine delivery, and leukemia cell lysis. Given the modular nature of these multivalent compounds and their rapid assembly/screening, we anticipate facile extension of this therapeutic approach to a wide range of immune cells, diseased cells, and soluble protein combinations in the future.
Arousal levels explain inter-subject variability of neuromodulation effects
Authors: Esposito Marco , Ferrari Clarissa , Fracassi Claudia , Miniussi Carlo , Brignani Debora 
Published: May 2020

AbstractOver the past two decades, the postulated modulatory effects of transcranial direct current stimulation (tDCS) on the human brain have been extensively investigated, with attractive real-world applications. However, recent concerns on reliability of tDCS effects have been raised, principally due to reduced replicability and to the great interindividual variability in response to tDCS. These inconsistencies are likely due to the interplay between the level of induced cortical excitability and unaccounted individual state-dependent factors. On these grounds, we aimed to verify whether the behavioural effects induced by a common prefrontal tDCS montage were dependent on the participants’ arousal levels. Pupillary dynamics were recorded during an auditory oddball task while applying either a sham or real tDCS. The tDCS effects on reaction times and pupil dilation were evaluated as a function of subjective and physiological arousal predictors. Both predictors significantly explained performance during real tDCS, namely reaction times improved only with moderate arousal levels; likewise, pupil dilation was affected according to the ongoing levels of arousal. These findings highlight the critical role of arousal in shaping the neuromodulatory outcome, and thus encourage a more careful interpretation of null or negative results.
Testing for context-dependent effects of maternal thyroid hormones on offspring survival and physiology: an experimental approach manipulating temperature in a wild bird species
Authors: Hsu Bin-Yan , Sarraude Tom , Cossin-Sevrin Nina , Crombecque Melanie , Stier Antoine , Ruuskanen Suvi 
Published: May 2020

AbstractMaternal effects via hormonal transfer from the mother to the offspring provide a tool to translate environmental cues to the offspring. Experimental manipulations of maternally transferred hormones have yielded increasingly contradictory results, which may be explained by environment-dependent effects of hormones. Yet context-dependent effects have rarely been experimentally tested. We therefore studied whether maternally transferred thyroid hormones (THs) exert context-dependent effects on offspring survival and physiology by manipulating both egg TH levels and post-hatching nest temperature in wild pied flycatchers (Ficedula hypoleuca) using a full factorial design. We found no clear evidence for context-dependent effects of prenatal THs related to postnatal temperature on growth, survival and potential underlying physiological responses (plasma TH levels, oxidative stress and mitochondrial density). We conclude that future studies should test for other key environmental conditions, such as food availability, to understand potential context-dependent effects of maternally transmitted hormones on offspring, and their role in adapting to changing environments.
Novel antiproliferative tripeptides block AP-1 transcriptional complex by in silico approach
Authors: Raj Ajay Kumar , Kothari Jainish , Sinchana Sethamma TN , Lokhande Kiran , Swamy K. V. , Sharma Nilesh Kumar 
Published: May 2020

ABSTRACTBACKGROUNDThe complexity and heterogeneity at genetic, epigenetic and microenvironment levels are key attributes of tumors. Genetic heterogeneity encompasses one of key factors at transcriptional gene regulation that promote abnormal proliferation, invasiveness and metastasis. Among various key pro-tumor transcriptional complexes, activating protein-1 (AP-1) transcriptional complex controls the transcriptional expression of key oncogenes in cancer cells. Therefore, an avenue to search for a chemical inhibition approach of the AP-1 transcriptional complex is warranted in cancer therapeutics.METHODSTo achieve chemical inhibition of AP-1 transcriptional complex, we report novel tripeptides identified from the goat urine DMSO fraction as potential agents that bind to AP-1 responsive TPA element and heterodimer c-Jun:c-Fos. Novel tripeptides enriched GUDF were tested against DNA substrates to assess DNA metabolizing activity. Further, Novel tripeptides enriched GUDF were treated upon HCT-116 cells to estimate the nature of tripeptides entered into the intracellular compartment of HCT-116 cells. Here, we report on a novel methodology that employ VTGE assisted intracellular metabolite purification and is analyzed with the help of LC-HRMS technique. Post purification of intracellular metabolites that included tripeptides of GUDF, these tripeptides from DMSO and GUDF treated HCT-116 cells were subjected to molecular docking and ligand-DNA:AP-1 (PDB ID: 1FOS) interaction study by using bioinformatics tools AutoDock Vina and PyMol.RESULTSGUDF enriched with tripeptides and other metabolites show appreciable instability of DNA substrates plasmid and genomic DNA to an extent of 90%. Interestingly, LC-HRMS analysis of intracellular metabolite profiling of GUDF treated HCT-116 cells reveal the appreciable abundance of tripeptides Glu-Glu-Arg, Gly-Arg-Pro, Gln-Lys-Arg, Glu-Glu-Lys, Trp-Trp-Val. On the other hand, DMSO treated HCT-116 cells show the presence of Ser-Trp-Lys, Glu-Glu-Gln, Glu-Glu-Lys, Ser-Leu-Ser. Interestingly, GUDF treated HCT-116 cells show inhibition of proliferation by more than 70%. Among the identified intracellular tripeptides, Glu-Glu-Arg (9.1 Kcal/Mol), Gly-Arg-Pro (8.8 Kcal/Mol), and Gln-Lys-Arg (6.8) show a precise and strong binding to heptameric TPA response element 5’ TGAGTCA 3’ and key amino acid residue within the AP-1 transcriptional complex.CONCLUSIONIn summary, this study suggests the potential of novel tripeptides, those are reported from GUDF intracellularly in HCT-116 cells to destabilize the AP-1 transcriptional complex. Data indicate that cellular arrest in HCT-116 cells treated by GUDF is well supported by the molecular docking observations that destabilization of AP-1 complex is linked to reduced growth and proliferation.
An experimental test of information use by North American wood ducks (Aix sponsa): external habitat cues, not social visual cues, influence initial nest-site selection
Authors: Berg Elena C. , Eadie John M. 
Published: May 2020

AbstractBirds may use a variety of cues to select a nest site, including external information on habitat structure and nest site characteristics, or they may rely instead on social information obtained directly or indirectly from the actions of conspecifics. We used an experimental manipulation to determine the extent to which a California population of the wood duck (Aix sponsa) used social information gleaned from visual cues inside nest boxes that might indicate the quality or occupancy of that site. Over two nesting seasons, we manipulated the contents of newly installed boxes to simulate one of three states: (1) presence of wood duck eggs, indicating current use of a nest site; (2) presence of down and shell membranes, indicating a previously successful nest; and (3) control nests with fresh shavings indicating an unused box. In addition, we measured habitat characteristics of the area surrounding each box to assess the use of external, non-social information about each nest site. We found no evidence that females laid eggs preferentially, or that conspecific brood parasitism was more likely to occur, in any of the treatments. In contrast, nest site use and reproductive traits of wood ducks did vary with vegetation cover, and orientation and distance of the box from water. Our results suggest that personal information, not social information, influence initial nest site selection decisions when females are unfamiliar with a site. Social cues likely become increasingly important once nest sites develop their own history, and a population becomes well established.Significance StatementIn selecting a nest site, birds may use many types of information, including habitat characteristics, their own previous breeding experience, or social cues inadvertently provided by other individuals of the same or different species. We examined information use in a Californian population of wood ducks by experimentally manipulating the visual cues within nest boxes and found that females did not use internal box cues to direct their nesting behaviors, appearing to rely on key habitat characteristics instead. These results contrast with previous studies of this system, suggesting that females may change the cues they use depending on their prior experience with a particular area. In the nest-site selection literature, there appears to be a divergence between research on passerines versus waterfowl, and we advocate unifying these perspectives.
Bursting mitral cells time the oscillatory coupling between olfactory bulb and entorhinal networks in neonatal mice
Authors: Kostka Johanna K. , Gretenkord Sabine , Hanganu-Opatz Ileana L. 
Published: May 2020

ABSTRACTShortly after birth, the olfactory system provides to blind, deaf, non-whisking and motorically-limited rodents not only the main source of environmental inputs, but also the drive boosting the functional entrainment of limbic circuits. However, the cellular substrate of this early communication remains largely unknown. Here we combinein vivoandin vitropatch-clamp and extracellular recordings to reveal the contribution of mitral cell (MC) firing to the early patterns of network activity in the neonatal olfactory bulb (OB) and lateral entorhinal cortex (LEC), the gatekeeper of limbic circuits. We show that MCs predominantly fire either in an irregular bursting or non-bursting pattern during discontinuous theta events in OB. However, the temporal spike-theta phase coupling is stronger for bursting MCs when compared to non-bursting cells. In line with the direct OB projections to LEC, both bursting and non-bursting firing augments during coordinated patterns of entorhinal activity, yet to a higher magnitude for bursting MCs. These cells are stronger temporally coupled to the discontinuous theta events in LEC. Thus, bursting MCs might drive the entrainment of OB-LEC network during neonatal development.KEY POINTSDuring early postnatal development mitral cells show either irregular bursting or non-bursting firing patternsBursting mitral cells preferentially fire during theta bursts in the neonatal OB, being locked to the theta phaseBursting mitral cells preferentially fire during theta bursts in the neonatal lateral entorhinal cortex and are temporally related to both respiration rhythm- and theta phaseBursting mitral cells act as cellular substrate of the olfactory drive promoting the oscillatory entrainment of entorhinal networks