bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamics of mask use as a prevention strategy against SARS-Cov-2 in Panama
Authors: Fernández-Marín Hermógenes , Bruner-Montero Gaspar , Portugal-Loayza Ana , Miranda Virginia , Villareal Alcibíades , Ortega Eduardo , Núñez-Samudio Virginia , Landires Iván , Mejia Luis C. , López-Vergès Sandra , Wcislo William T. , Jagannatha Rao K.S. 
Published: September 2021

AbstractBackgroundEarly in the SARS-CoV-2 pandemic, many national public health authorities implemented non-pharmaceutical interventions to mitigate disease outbreaks. Panamá established mandatory mask use two months after its first documented case. Initial compliance was high, but diverse masks were used in public areas. We studied behavioral dynamics of mask use through the first two COVID waves in Panama, to improve implementation of effective, low-cost public health containment measures, when populations are exposed to novel air-borne pathogens.MethodsMask use behavior was recorded from pedestrians in four Panamanian populations (August to December 2020). We recorded facial coverings; and if used, the type of mask, and gender and estimated age of the wearer.FindingsPeople were highly compliant (> 95%) with mask mandates, and demonstrated important population-level behaviours: 1) decreasing use of cloth masks over time, and increasing use of surgical masks; 2) mask use was 3-fold lower in sub-urban neighborhoods than other public areas; and 3) young people were least likely to wear masks.InterpretationResults help focus highly-effective, low-cost, public health interventions for managing and controlling a pandemic. Considerations of behavioural preferences for different masks, relative to pricing and availability, are essential for optimizing public health policies. Policies to increase availability of effective masks, and behavioral nudges to increase acceptance, and to facilitate mask usage, during the on-going SARS-CoV-2 pandemic, and for future pandemics of respiratory pathogens, are key tools, especially for nations lagging in access to expensive vaccines and pharmacological approaches.Funding11-2020 SNI Grant, SENACYT.
High- Versus Low-Dose Dexamethasone for the Treatment of COVID-19-related Acute Respiratory Distress Syndrome: A Multicenter and Randomized Open-label Clinical Trial
Authors: Maskin Luis Patricio , Bonelli Ignacio , Olarte Gabriel Leonardo , Palizas Fernando , Velo Agostina E , Lurbet María Fernanda , Lovazzano Pablo , Kotsias Sophia , Attie Shiry , Saubidet Ignacio Lopez , Baredes Natalio D , Setten Mariano , Rodriguez Pablo Oscar 
Published: September 2021

AbstractPurposeTo determine whether high-dose dexamethasone increases the number of ventilator-free days (VFD) among patients with acute respiratory distress syndrome due to coronavirus disease 2019 (C-ARDS)MaterialsA multicenter randomized controlled trial in adults with C-ARDS. Patients received 16 mg/d of dexamethasone intravenously for five days followed by 8 mg/d of dexamethasone for five days, or 6 mg/d of dexamethasone intravenously for 10 days.ResultsData from 98 patients who received at least one dose of dexamethasone were analyzed. At 28 days after randomization, there was no difference between high- and low-dose dexamethasone groups in VFD (median, 0 d [interquartile range (IQR) 0–14 d] versus 0 d [IQR 0–1 d]; P=0.231). The cumulative hazard of successful discontinuation from mechanical ventilation was increased by the high-dose treatment (adjusted sub-distribution hazard ratio: 1.84; 95% CI: 1.31 to 2.5; P<0.001). None of the prespecified secondary and safety outcomes showed a significant difference between treatment arms.ConclusionsAmong patients with C-ARDS, the use of higher doses of dexamethasone compared with the recommended low-dose treatment did not show an increase in VFD. However, the higher dose significantly improved the time required to liberate them from the ventilatorClinical Trial Registered: NCT04395105
Shatavari Supplementation in Postmenopausal Women Improves Handgrip Strength and Increases Vastus Lateralis Myosin Regulatory Light Chain Phosphorylation But Does Not Alter Markers of Bone Turnover: A Randomised Controlled Trial
Authors: O’Leary Mary F. , Jackman Sarah R. , Sabou Vlad R. , Campbell Matthew I , Tang Jonathan C. Y. , Dutton John , Bowtell Joanna L. 
Published: September 2021

AbstractBackgroundShatavari has long been used as an Ayurvedic herb for women’s health, but empirical evidence for its effectiveness has been lacking. Shatavari contains phytoestrogenic compounds that bind to the estradiol receptor, and may therefore benefit postmenopausal women since postmenopausal estradiol deficiency contributes to sarcopenia and osteoporosis.MethodsIn a randomised double-blind trial, 20 postmenopausal women (68.5 ± 6 y) ingested either placebo (N=10) or shatavari (N=10; 1000 mg/d, equivalent to 26,500 mg/d fresh weight shatavari) for 6 weeks. Handgrip and knee extensor strength were measured at baseline and at 6 weeks. Vastus lateralis (VL) biopsy samples were obtained. Data are presented and analysed (t test/Mann Whitney U) as difference scores (Week 6 – baseline, median ± interquartile range).ResultsHandgrip, (but not knee extensor) strength was improved by shatavari supplementation (shatavari +0.7 ± 1.1 kg, placebo -0.4 ± 1.3 kg; p=0.04). Myosin regulatory light chain phosphorylation, a known marker of improved myosin contractile function, was increased in VL following shatavari supplementation (immunoblotting; placebo -0.08 ± 0.5 a.u. shatavari +0.3 ± 1 arbitrary units (a.u.); p=0.03). Shatavari increased phosphorylation of Aktser473 (Aktser473 (placebo -0.6 ± 0.6 a.u. shatavari +0.2 ± 1.3 a.u; p=0.03) in VL. Shatavari supplementation did not alter plasma markers of bone turnover (P1NP, β-CTX) and stimulation of human osteoblasts with pooled sera (N=8 per condition) from placebo and shatavari supplementation conditions did not alter cytokine or metabolic markers of osteoblast activity.ConclusionsShatavari may improve muscle function and contractility via myosin conformational change and warrants further investigation of its utility in conserving musculoskeletal function in postmenopausal women.Trial RegistrationRetrospectively registered at clinicaltrials.gov as NCT05025917 on 30/08/21.
Deleterious drugs in COVID-19: a rapid systematic review and meta-analysis
Authors: Holder Michael , Heeney Catherine , Malden Stephen , Perera Uditha , Sheikh Aziz 
Published: September 2021

AbstractBackgroundConcerns have been expressed about a number of drugs that potentially worsen outcomes in patients with COVID-19. We sought to identify all potentially deleterious drug groups in COVID-19 and critically assess the underpinning strength of evidence pertaining to the harmful effects of these drugs.Methods and findingsWe performed a rapid systematic review, searching Medline, Embase and two COVID-19 portfolios (WHO COVID-19 database and NIH iSearch COVID-19 portfolio) for papers and preprints related to primary studies investigating drugs identified as potentially deleterious. Primary outcomes were direct measures of susceptibility to infection, disease severity and mortality. Study quality was assessed using the National Heart, Lung, and Blood Institute quality assessment tools. Random-effects meta-analyses were used for data synthesis with further subgroup analyses where possible for specific outcome, study design, statistical adjustment and drug groups when two were combined. Sensitivity analyses were performed by removing any studies at high risk of bias and by publication status.49 observational studies (15 peer-reviewed papers and 34 preprints) reported primary outcomes for eight drug groups hypothesised to be deleterious. Meta-analysis showed that acute inpatient corticosteroid use was associated with increased mortality (OR 2.22, 95% CI 1.26-3.90), however this result appeared to have been biased by confounding via indication. One subgroup analysis indicated an association between immunosuppressant use and susceptibility to COVID-19 among case control and cross-sectional studies (OR 1.29, 95% CI 1.19-1.40) but this was not found with cohort studies (OR 1.11, 95% CI 0.86-1.43). Studies which adjusted for multiple confounders showed that people taking angiotensin-converting-enzyme inhibitors (ACEIs) or angiotensin-II-receptor blockers (ARBs) required a lower level of care (OR 0.85, 95% CI 0.74-0.98). Furthermore, studies which combined these two drug groups in their analysis demonstrated an association with a lower mortality (OR 0.68, 95% CI 0.55-0.85).ConclusionsWe found minimal high quality or consistent evidence that any drug groups increase susceptibility, severity or mortality in COVID-19. Converse to initial hypotheses, we found some evidence that regular use of ACEIs and ARBs prior to infection may be effective in reducing the level of care required, such as requiring intensive care, in patients with COVID-19.
Nurse staffing levels and patient outcomes: a systematic review of longitudinal studies
Authors: Dall’Ora Chiara , Saville Christina , Rubbo Bruna , Turner Lesley Y , Jones Jeremy , Griffiths Peter 
Published: September 2021

ABSTRACTBackgroundThe contribution of registered nurses (RN) towards safe patient care has been demonstrated by several studies. However, most of the evidence is cross-sectional, hence the inability to demonstrate that staffing levels precede patient outcomes. No reviews have summarised longitudinal studies considering nurse staffing and patient outcomes.ObjectivesTo synthesise longitudinal studies focusing on associations between nurse staffing levels and patient outcomes.MethodsSystematic review. We conducted our search in 2020 and updated it in July 2021. We searched Medline, CINAHL, Embase and the Cochrane Library. We used the ROBINS-I tool for assessing risk of bias. We reported results narratively grouped by outcome.Results28 papers were included. Most studies were either at serious (n=12) or critical (n=6) risk of bias, with 3 studies at low risk of bias. Studies were conducted in a variety of settings and populations. Notwithstanding the limitations, findings are consistent with an overall picture of a beneficial effect from higher RN staffing on preventing patient death. Studies with the greatest risk of bias were judged as most likely to underestimate the effect of higher RN staffing. The evidence is less clear for other patient outcomes, but estimates, though at moderate or serious risk of bias, indicate that higher RN staffing is likely to lead to better patient outcomes. Evidence about the contribution of other nursing staff groups and skill mix of the team is unclear.ConclusionThere is a likely causal relationship between low RN staffing and harm to patients, although uncertainties remain regarding the magnitude of effect. To address these uncertainties, future studies should be conducted in more than one hospital and using standardised measures when reporting staffing levels.
A tetracycline antibiotic minocycline prevents early aging phenotypes in mice heterozygous for RP58
Authors: Tanaka Tomoko , Hirai Shinobu , Manabe Hiroyuki , Endo Kentaro , Nishito Yasumasa , Shimbo Hiroko , Yoshitane Hikari , Okado Haruo 
Published: September 2021

SummaryIn humans, cognitive and motor functions develop in association with maturation, followed by a decline in advancing age. In this study, we aimed to provide a method for extending healthy lifespan by preventing age-related phenomena. Therefore, we focused on RP58, a transcriptional repressor, whose expression is reduced during aging in the human cortex. In the Rp58 hetero-knockout (KO) mice, object location memory was impaired even at 4–5 months, while it was normal in the wild-type mice at 4–5 months but was impaired at 12–18 months. These results indicate an early onset of impaired spatial memory in the mutant mice. As the underlying mechanism, the Rp58 hetero-KO mice showed early onset of DNA damage accumulation and microglial activation in the dentate gyrus due to a DNA repair defect that is generally observed with aging. As another hallmark of aging, we focused on mitochondrial function and detected mitochondrial abnormalities in the Rp58 hetero-KO mice at 4–5 months. Notably, continuous treatments with minocycline, a neuroprotective and anti-inflammatory antibiotic, prevented the facilitation of age-related phenomena in the Rp58 hetero-KO mice. These results suggest the availability of the Rp58 hetero-KO mice as a novel mouse model of human-like early aging and provide a therapeutic strategy to prevent age-related phenomena using minocycline.HighlightRp58 hetero-KO mice exhibit early aging phenotypes including impairment of spatial cognitionRp58 hetero-KO mice show early accumulation of DNA damage due to a defect in the DNA repair systemTreatment with minocycline prevented cognitive dysfunction observed in Rp58 hetero-KO mice
Microbial induced calcite precipitation can consolidate martian and lunar regolith simulants
Authors: Dikshit Rashmi , Gupta Nitin , Dey Arjun , Viswanathan Koushik , Kumar Aloke 
Published: September 2021

AbstractWe demonstrate that Microbial Induced Calcite Precipitation (MICP) can be utilized for creation of consolidates of Martian Simulant Soil (MSS) and Lunar Simulant Soil (LSS) in the form of a ‘brick’. A urease producer bacteria, Sporosarcina pasteurii, was used to induce the MICP process for the both simulant soils. An admixture of guar gum as an organic polymer and NiCl2, as bio-catalyst to enhance urease activity, was introduced to increase the compressive strength of the biologically grown bricks. A casting method was utilized for a slurry consisting of the appropriate simulant soil and microbe; the slurry over a few days consolidated in the form of a ‘brick’ of the desired shape. In case of MSS, maximum strength of 3.3 MPa was obtained with 10mM NiCl2 and 1% guar gum supplementation whereas in case of LSS maximum strength of 5.65 MPa was obtained with 1% guar gum supplementation and 10mM NiCl2. MICP mediated consolidation of the simulant soil was confirmed with field emission scanning electron microscopy (FESEM) and X-ray diffraction (XRD). Our work demonstrates a biological approach with an explicit casting method towards manufacturing of consolidated structures using extra-terrestrial regolith simulant; this is a promising route for in situ development of structural elements on the extra-terrestrial habitats.
A novel eukaryotic RdRP-dependent small RNA pathway represses antiviral immunity by controlling an ERK pathway component in the black-legged tick
Authors: Feng Canran , Torimaru Kyosuke , Lim Mandy Yu Theng , Chak Li-Ling , Shiimori Masami , Tsuji Kosuke , Tanaka Tetsuya , Iida Junko , Okamura Katsutomo 
Published: September 2021

AbstractSmall regulatory RNAs (sRNAs) are involved in antiviral defense and gene regulation. Although roles of RNA-dependent RNA Polymerases (RdRPs) in sRNA biology are extensively studied in nematodes, plants and fungi, understanding of RdRP homologs in other animals is still lacking. Here, we study sRNAs in the ISE6 cell line, which is derived from the black-legged tick, an important vector of human and animal pathogens. We find abundant classes of ∼22nt sRNAs that require specific combinations of RdRPs and sRNA effector proteins (Argonautes or AGOs). RdRP-dependent sRNAs possess 5’- monophosphates and are mainly derived from RNA polymerase III-transcribed genes and repetitive elements. Knockdown of RdRPs misregulates genes including RNAi-related genes and the regulator of immune response Dsor1. Sensor assays demonstrate that Dsor1 is downregulated by RdRP through the 3’UTR that contains a target site of RdRP-dependent repeat-derived sRNAs. Consistent with viral gene repression by the RNAi mechanism using virus-derived small interfering RNAs, viral transcripts are upregulated by AGO knockdown. On the other hand, RdRP knockdown unexpectedly results in downregulation of viral transcripts. This effect is dependent on Dsor1, suggesting that antiviral immunity is enhanced by RdRP knockdown through Dsor1 upregulation. We propose that tick sRNA pathways control multiple aspects of immune response via RNAi and regulation of signaling pathways.Author summaryRNA-dependent RNA Polymerases (RdRPs) are essential for biogenesis of small regulatory RNAs (sRNAs) in many organisms such as plants and fungi, but its general importance in animals besides nematodes remains controversial because experimental evidence is lacking. By using a tick cell line, we demonstrate that RdRP-dependent sRNAs are abundantly expressed and tick RdRPs regulate gene expression. These results indicate that ticks have unexpectedly complex sRNA biogenesis pathways that are essential for proper gene regulation. Interestingly, we show that RdRP negatively regulates immune response by changing expression of a gene that is essential in an immunity-related signaling pathway. Because ticks are important vectors of human and animal pathogens, studying the novel tick sRNA pathways and their effects on immune signaling may lead to a better understanding of vector-virus interactions.
pcnaDeep: A Fast and Robust Single-Cell Tracking Method Using Deep-Learning Mediated Cell Cycle Profiling
Authors: Gui Yifan , Xie Shuangshuang , Wang Yanan , Wang Ping , Yao Renzhi , Gao Xukai , Dong Yutian , Wang Gaoang , Chan Kuan Yoow 
Published: September 2021

AbstractMotivationComputational methods that track single-cells and quantify fluorescent biosensors in time-lapse microscopy images have revolutionised our approach in studying the molecular control of cellular decisions. One barrier that limits the adoption of single-cell analysis in biomedical research is the lack of efficient methods to robustly track single-cells over cell division events.ResultsHere, we developed an application that automatically tracks and assigns mother-daughter relationships of single-cells. By incorporating cell cycle information from a well-established fluorescent cell cycle reporter, we associate mitosis relationships enabling high fidelity long-term single-cell tracking. This was achieved by integrating a deep-learning based fluorescent PCNA signal instance segmentation module with a cell tracking and cell cycle resolving pipeline. The application offers a user-friendly interface and extensible APIs for customized cell cycle analysis and manual correction for various imaging configurations.Availability and ImplementationpcnaDeep is an open-source Python application under the Apache 2.0 licence. The source code, documentation and tutorials are available at https://github.com/chan-labsite/PCNAdeep.Supplementary InformationSupplementary data are available online.
Chronic hM4Di-DREADD mediated chemogenetic inhibition of forebrain excitatory neurons in postnatal or juvenile life does not alter adult mood-related behavior
Authors: Tiwari Praachi , Kapri Darshana , Pradhan Amartya , Balakrishnan Angarika , Chaudhari Pratik R. , Vaidya Vidita A. 
Published: September 2021

AbstractG-protein coupled receptors (GPCRs) coupled to Gi-signaling, in particular downstream of monoaminergic neurotransmission, are posited to play a key role during developmental epochs (postnatal and juvenile), in shaping the emergence of adult anxio-depressive behaviors and sensorimotor gating. To address the role of Gi-signaling in these developmental windows, we used a CamKIIα-tTA::TRE hM4Di bigenic mouse line to express the hM4Di-DREADD in forebrain excitatory neurons and enhanced Gi-signaling via chronic administration of the DREADD agonist, CNO in the postnatal (PNCNO: postnatal day 2-14) or juvenile (JCNO: postnatal day 28-40) window. We confirmed that the expression of the HA-tagged hM4Di-DREADD was restricted to CamKII-positive neurons in the forebrain, and administration of CNO in postnatal or juvenile windows evoked inhibition in forebrain circuits of the hippocampus and cortex, as indicated by a decline in expression of the neuronal activity marker, c-fos. hM4Di-DREADD mediated inhibition of CamKIIα-positive forebrain excitatory neurons in postnatal or juvenile life did not impact the weight profile of mouse pups, and also did not influence the normal ontogeny of sensory reflexes. Further, postnatal or juvenile hM4Di-DREADD mediated inhibition of CamKIIα-positive forebrain excitatory neurons did not alter anxiety or despair-like behaviors in adulthood, and did not impact sensorimotor gating. Collectively, these results indicate that chemogenetic induction of Gi-signaling in CamKIIα-positive forebrain excitatory neurons in postnatal and juvenile temporal windows does not appear to impinge on the programming of anxio-depressive behaviors in adulthood.
Genome wide profiling of histone H3 lysine 4 methylation during the Chlamydomonas cell cycle reveals stable and dynamic properties of lysine 4 trimethylation at gene promoters and near ubiquitous lysine 4 monomethylation
Authors: Strenkert Daniela , Yildirim Asli , Yan Juying , Yoshinaga Yuko , Pellegrini Matteo , O’Malley Ronan C. , Merchant Sabeeha S. , Umen James G. 
Published: September 2021

ABSTRACTChromatin modifications are key epigenetic regulatory features with roles in various cellular events, yet histone mark identification, gene wide distribution and relationship to gene expression remains understudied in green algae. Histone lysine methylation is regarded as an active chromatin mark in many organisms, and is implicated in mediating active euchromatin. We interrogated the genome wide distribution pattern of mono- and trimethylated H3K4 using Chromatin-Immunoprecipitation followed by deep-sequencing (ChIP-Seq) during key phases of the Chlamydomonas cell cycle: early G1 phase (ZT1) when cells initiate biomass accumulation, S/M phase (ZT13) when cells are undergoing DNA replication and mitosis, and late G0 phase (ZT23) when they are quiescent. Tri-methylated H3K4 was predominantly enriched at TSSs of the majority of protein coding genes (85%). The likelihood of a gene being marked by H3K4me3 correlated with it being transcribed at one or more time points during the cell cycle but not necessarily by continuous active transcription. This finding even applied to early zygotic genes whose expression may be dormant for hundreds or thousands of generations between sexual cycles; but core meiotic genes were completely missing H3K4me3 peaks at their TSS. In addition, bi-directional promoters regulating expression of replication dependent histone genes, had transient H3K4me3 peaks that were present only during S/M phase when their expression peaked. In agreement with biochemical studies, mono-methylated H3K4 was the default state for the vast majority of histones that were outside of TSS and terminator regions of genes. A small fraction of the genome which was depleted of any H3 lysine methylation was enriched for DNA cytosine methylation and the genes within these DNA methylation islands were poorly expressed. Genome wide H3K4me3 ChIP-Seq data will be a valuable resource, facilitating gene structural annotation, as exemplified by our validation of hundreds of long non-coding RNA genes.