bluuebunny/crossref_metadata_2025 huggingface dataset:
A golden decade for ocean science (2021–2030): from knowledge to solutions and actions
Authors: Zhao Weijie
Published: February 2021

‘It is planning, it is science, it is management, and it is a huge change of human relations with the ocean.’ As introduced by Dr Vladimir Ryabinin, the Intergovernmental Oceanographic Commission (IOC) Executive Secretary and Assistant Director-General of the United Nations Educational, Scientific and Cultural Organization (UNESCO), the UN Decade of Ocean Science for Sustainable Development (the Decade, 2021–2030) got underway this January.

To echo that, on 14 January 2021, a Special Forum on the Decade was held in hybrid mode as part of the Fifth Xiamen Symposium on Marine Environmental Science (XMAS-V) in Xiamen University, China. The Forum was organized to promote the Decade through insightful talks and in-depth discussions with international and regional representatives who have been actively involved in the planning of the Decade. In addition to Dr Ryabinin, Zhanhai Zhang, Chief Engineer of the Ministry of Natural Resources of China, gave an inspiring opening speech. What followed were presentations by invited speakers. They then joined a panel discussion chaired by Dr Minhan Dai from Xiamen University. This article is edited and re-organized from the record of this Special Forum.
Opioid Prescribing After Implementation of Single Click Access to a State Prescription Drug Monitoring Program Database in a Health System’s Electronic Health Record
Authors: Weiner Scott G , Kobayashi Kimiyoshi , Reynolds Joshua , Chan Kit , Kelly Rodd , Wakeman Sarah , Reddy Prabashni , Young Leonard D
Published: February 2021

Objectives

To determine the effect of one-click integration of a state’s prescription drug monitoring program (PDMP) on the number of PDMP searches and opioid prescriptions, stratified by specialty.

Methods

Our large health system worked with the state department of public health to integrate the PDMP with the electronic health record (EHR), which enabled providers to query the data with a single click inside the EHR environment. We evaluated Schedule II or III opioid prescriptions reported to the Massachusetts PDMP 6 months before (November 15, 2017-May 15, 2018) and 6 months after (May 16, 2018, to November 16, 2018) integration. Search counts, prescriptions, patients, morphine milligram equivalents, as well as prescriber specialty were compared.

Results

There were 3,185 unique prescribers with a record of a Schedule II and/or III opioid prescription in both study periods that met inclusion criteria. After integration, the number of PDMP searches increased from 208,684 in the pre-integration phase to 298,478 searches in the post-integration phase (+43.0%). The number of opioid prescriptions dispensed decreased by 4.8%, the number of patients receiving a prescription decreased by 5.1%, and the mean morphine milligram equivalents (MMEs) per prescriber decreased by 5.4%. There were some notable specialty-specific differences in these measures.

Conclusions

Integration of the PDMP into the EHR markedly increased the number of searches but was associated with modest decreases in opioids prescribed and patients receiving a prescription. Single click EHR integration of the PDMP, if implemented broadly, may be a way for states to significantly increase PDMP utilization.
Association of clinical characteristics, disease activity and health-related quality of life in SLE patients with major depressive disorder
Authors: Parperis Konstantinos , Psarelis Savvas , Chatzittofis Andreas , Michaelides Michalis , Nikiforou Dimitra , Antoniade Elpida , Bhattarai Bikash
Published: February 2021

Objective

To determine the contributing factors associated with major depressive disorder (MDD) in SLE patients and examine the association between disease-specific health-related quality of life [lupus quality of life (LupusQoL)] domains and MDD.

Methods

Depression was assessed by the patient health questionnaire (PHQ)-9, and scores ≥10 indicate MDD. Demographic data, LupusQoL domains, clinical and other features of the SLE patients were described and compared between MDD (PHQ-9 ≥10) and non-MDD (PHQ-9 <10) groups using χ2 tests for categorical variables and Wilcoxon rank sum tests for non-normal continuous variables. The risk of MDD was evaluated for the patient and physician-reported features individually using log-binomial models to estimate relative risks and 95% confidence limits.

Results

Eighty-eight patients with SLE met eligibility criteria, with a mean (range) age of 48.6 (19–80), mostly female (80%) and with a mean disease duration of 13.2 years. Compared with the non-MDD group, patients with MDD (n = 32, 36%) were more likely to have the following SLE manifestations: mucocutaneous, vascular, ocular, pulmonary and musculoskeletal involvement. Self-rated health described as poor/fair was markedly associated with MDD (P < 0.001, relative risk = 0.48). Based on relative risks, higher pain visual analogue score, and patient and physician global assessment scores were also linked to MDD. The LupusQoL domain scores were notably lower in the MDD patients, with a statistically significant reduction in all LupusQoL domains.

Conclusion

Predictors of MDD in SLE patients include higher scores in pain and global assessment, poor or fair self-reported health, and specific organ involvement. These findings may help clinicians to recognize and manage MDD promptly.
Safety of recombinant zoster vaccine: a retrospective study of 622 rheumatology patients
Authors: Lenfant Tiphaine , Jin Yuxuan , Kirchner Elizabeth , Hajj-Ali Rula A , Calabrese Leonard H , Calabrese Cassandra
Published: February 2021

Objectives

To provide insight into the safety of recombinant zoster vaccine (RZV) in patients with immune-mediated inflammatory diseases (IMID).

Methods

Patients who received RZV in a single-centre rheumatology department were retrospectively included. An IMID flare was defined as (i) a documentation of flare in the office notes or patient portal communication or (ii) new prednisone prescription, in the 12 weeks after each dose.

Results

Six-hundred and twenty-two patients were included (67% female, median age 67 years), 8.5% of them experienced adverse events (AEs) and herpes zoster (HZ) incidence was 0.6% after median follow-up of 36 weeks. Of 359 IMID patients: 88 had RA (25%), 50 vasculitis (14%) and 29 PMR (8%). At vaccination, 35% were on glucocorticoids (GC). Fifty-nine patients (16%) experienced a flare, 18 flares occurred in temporal relation to a treatment change (31%). RA patients had the highest flare rate (n = 21, 24%), 25% of patients who flared required adjustment of immunosuppression. In a multivariate analysis, use of GC at time of vaccination was associated with flare after vaccination [odds ratio (OR) 2.31 (1.3–4.1), P =0.004]. A time-to-flare survival analysis (Cox-model) showed that GC was a significant predictor of IMID flare after first RZV dose [hazard ratio (HR) 2.4 (1.3–4.5), P =0.0039] and that a flare after the first dose was associated with flaring after the second RZV dose [HR 3.9 (1.7–9), P =0.0015].

Conclusion

RZV administration in patients with IMIDs was generally well-tolerated, though mild flares were not uncommon in the first 12 weeks after vaccination. These data may provide useful information for patient education when considering RZV administration.
State Variation in TANF Expenditures: Implications for Social Work and Social Policy
Authors: Fusaro Vincent A.
Published: February 2021

The Temporary Assistance for Needy Families (TANF) program is a federal block grant to the states, with a required state contribution. Although often viewed as a cash assistance program with work requirements and services targeted at extremely low-income families with children, only about one-quarter of all state and federal TANF funds are now used for traditional cash aid. Uses of funds vary widely by state, and alternatives range from refundable tax credits to support of state child welfare systems. In this article, the author examines the relationship between state categorical TANF spending and key social, political, and economic characteristics using data from 2015 to 2017 and multilevel linear models. Racial and ethnic demographics of the cash assistance caseload are associated with differences in spending, with states with larger proportions of the caseload composed of people of color devoting a lower percentage of effort to traditional benefits and more to alternative cash transfers. Changes in unemployment rate within states are associated with greater spending on basic assistance and reduced spending on alternative transfers. These findings indicate that, although TANF cash benefits spending may be economically responsive within the program’s overall flexible structure, spending patterns raise issues of equity for disadvantaged families.
Gene Tree Discord, Simplex Plots, and Statistical Tests under the Coalescent
Authors: Allman Elizabeth S , Mitchell Jonathan D , Rhodes John A
Published: February 2021

A simple graphical device, the simplex plot of quartet concordance factors, is introduced to aid in the exploration of a collection of gene trees on a common set of taxa. A single plot summarizes all gene tree discord and allows for visual comparison to the expected discord from the multispecies coalescent model (MSC) of incomplete lineage sorting on a species tree. A formal statistical procedure is described that can quantify the deviation from expectation for each subset of four taxa, suggesting when the data are not in accord with the MSC, and thus that either gene tree inference error is substantial or a more complex model such as that on a network may be required. If the collection of gene trees is in accord with the MSC, the plots reveal when substantial incomplete lineage sorting is present. Applications to both simulated and empirical multilocus data sets illustrate the insights provided. [Gene tree discordance; hypothesis test; multispecies coalescent model; quartet concordance factor; simplex plot; species tree].
Microbial Colonization of Oxygenator and Clinical Outcomes in Extracorporeal Membrane Oxygenation
Authors: Kim Taehwa , Cho Woo Hyun , Kim Dohyung , Jeon Doosoo , Kim Yun Seong , Yeo Hye Ju
Published: February 2021

The importance of microbial colonization during extracorporeal membrane oxygenation (ECMO) is unclear. We prospectively cultured ECMO oxygenators and retrospectively reviewed the culture results, clinical outcomes, and associated factors in 112 ECMO patients (122 oxygenators, 1,196 ECMO days). Of the oxygenators, 11.6% (n = 13) had positive cultures. The most common pathogen was Klebsiella pneumoniae, followed by Acinetobacter baumannii and Staphylococcus epidermidis. Nine (69%) cases showed catheter colonization, and five (38%) bloodstream infection (BSI) with the same microorganism. Most of the microorganisms were multidrug resistant. BSI tended to be associated with oxygenator colonization (r = 0.172, p = 0.070). The patients were divided into oxygenator colonization (n = 13) and no colonization groups (n = 99). Successful weaning from ECMO and survival to discharge were significantly lower in the oxygenator colonization group (weaning 30.8% vs. 90.9%, p < 0.001, survival 23.1% vs. 76.8%; p < 0.001). In multivariate analyses, age (per decade) (odds ratio [OR] = 1.95, 95% CI = 1.28–2.95; p = 0.002), oxygenator colonization (OR = 15.49, 95% CI = 3.31–72.46; p < 0.001), and renal replacement therapy (OR = 4.61, 95% CI = 1.69–12.58; p = 0.003) were significantly associated with mortality. Oxygenator colonization was associated with poor outcomes in ECMO patients. These results support the early exchange and culture of oxygenators in patients with persisting bacteremia.
Management of Intracranial Hemorrhage During Pulsatile Long-Term Biventricular Support: When Necessity Is the Mother of Invention
Authors: Martínez-Solano Jorge , Ortiz-Bautista Carlos , Zatarain-Nicolás Eduardo , Sousa-Casasnovas Iago , Pedraz-Prieto Álvaro , Barrio-Gutiérrez José M. , Pascual-Izquierdo Cristina , Fernández-Avilés Francisco
Published: February 2021

Despite improvements in device design and hemocompatibility, intracranial hemorrhage and stroke remain the most feared and devastating complications in patients under mechanical circulatory support. We present the case of a 48 year old man with advanced heart failure (INTERMACS 3) and severe biventricular dysfunction who underwent biventricular pulsatile paracorporeal device implantation (Berlin Heart Excor) as a bridge to candidacy. Although on the heart transplantation waiting list, the patient experienced an intracranial hemorrhage, which was successfully managed by switching to a less thrombogenic biventricular assist device (Levitronix Centrimag) using the Excor cannulae, thus enabling temporary withdrawal of antithrombotic therapy. Heart transplant was performed successfully with no significant complications.
Health workers’ psychological distress during early phase of the covid-19 pandemic in Morocco
Authors: Belayachi Jihane , Benammi Sarah , Chippo Hasnae , Bennis Rhita Nechba , Madani Naoufel , Hrora Abdelmalek , Abouqal Redouane
Published: February 2021

Introduction

The mental being of healthcare workers with the COVID 19 pandemic is a determinant of their resilience. We investigated the psychological impact of health workers during early phase of Covid 19 pandemic in Morocco.

Methods

This was a cross-sectional study based on a survey of health workers of the Rabat University Hospital Ibn-Sina in Morocco. Data were collected during the first week of health emergency state –between 23 and 30 march-related to the covid-19 pandemic declaration in Morocco. Sociodemographic, health characteristics and professional characteristics of each health worker were collected. We also evaluated the knowledge of health workers concerning the protective measures against COVID 19. The mental health status of the health workers was investigated using the Arabic validated version of HADS 14 items, evaluating hospital anxiety and depression

Results

Two hundred eighty-seven health workers were included.The mean age was 34.4±12.18 year; and 64.5% were female, 54% have been trained regarding protection procedures, and 94.8% declared that they are aware of individual protection measures. The incidence of anxiety and depression was respectively 77.4% and 73.9%. High degree of anxiety and depression was associated with female gender. However, Higher degree of anxiety was also related to function, specialty of practice, and knowledge of the protective measures against COVID-19.

Conclusion

We reported the result of the first evaluation of psychological burden of health worker during early period of COVID-19 pandemic in a developing country. The study showed high frequency of anxiety and depression among Moroccan health worker in a hospital faced to COVID-19 patient management.
Infection and mRNA-1273 vaccine antibodies neutralize SARS-CoV-2 UK variant
Authors: Edara Venkata Viswanadh , Floyd Katharine , Lai Lilin , Gardner Meredith , Hudson William , Piantadosi Anne , Waggoner Jesse J. , Babiker Ahmed , Ahmed Rafi , Xie Xuping , Lokugamage Kumari , Menachery Vineet , Shi Pei-Yong , Suthar Mehul S. ,   for the COVID-19 Neutralization Study Group
Published: February 2021

Antibody responses against the SARS-CoV-2 Spike protein correlate with protection against COVID-19. Serum neutralizing antibodies appear early after symptom onset following SARS-CoV-2 infection and can last for several months. Similarly, the messenger RNA vaccine, mRNA-1273, generates serum neutralizing antibodies that are detected through at least day 119. However, the recent emergence of the B.1.1.7 variant has raised significant concerns about the breadth of these neutralizing antibody responses. In this study, we used a live virus neutralization assay to compare the neutralization potency of sera from infected and vaccinated individuals against a panel of SARS-CoV-2 variants, including SARS-CoV-2 B.1.1.7. We found that both infection- and vaccine-induced antibodies were effective at neutralizing the SARS-CoV-2 B.1.1.7 variant. These findings support the notion that in the context of the UK variant, vaccine-induced immunity can provide protection against COVID-19. As additional SARS-CoV-2 viral variants continue to emerge, it is crucial to monitor their impact on neutralizing antibody responses following infection and vaccination.
IgA autoantibodies target pulmonary surfactant in patients with severe COVID-19
Authors: Sinnberg Tobias , Lichtensteiger Christa , Ali Omar Hasan , Pop Oltin T. , Gilardi Mara , Risch Lorenz , Bomze David , Kohler Philipp , Vernazza Pietro , Albrich Werner C. , Kahlert Christian R. , Brugger Silvio D. , Abdou Marie-Therese , Zinner Carl , Tzankov Alexandar , Röcken Martin , Kern Lukas , Brutsche Martin H. , Kalbacher Hubert , Velic Ana , Maček Boris , Penninger Josef M. , Matter Matthias S. , Flatz Lukas
Published: February 2021

Complications affecting the lung are hallmarks of severe coronavirus disease 2019 (COVID-19). While there is evidence for autoimmunity in severe COVID-19, the exact mechanisms remain unknown. Here, we established a prospective observational cohort to study lung specific autoantibodies (auto-Abs). Incubation of plasma from severe COVID-19 patients with healthy human lung tissue revealed the presence of IgA antibodies binding to surfactant-producing pneumocytes. Enzyme-linked immunosorbent assays (ELISA) and protein pull-downs using porcine surfactant confirmed the presence of auto-Abs binding to surfactant proteins in severe COVID-19 patients. Mass spectrometry and ELISAs with recombinant proteins identified IgA auto-Abs that target human surfactant proteins B and C. In line with these findings, lungs of deceased COVID-19 patients showed reduced pulmonary surfactant. Our data suggest that IgA-driven autoimmunity against surfactant may result in disease progression of COVID-19.
Could the new COVID-19 mutant strain undermine vaccination efforts? A mathematical modelling approach for estimating the spread of the UK mutant strain using Ontario, Canada, as a case study
Authors: Betti Matthew , Bragazzi Nicola Luigi , Heffernan Jane Marie , Kong Jude , Raad Angie
Published: February 2021

Background

Infections represent highly dynamic processes, characterized by evolutionary changes and events that involve both the pathogen and the host. Among infectious agents, viruses, such as the “Severe Acute Respiratory Syndrome-related Coronavirus type 2” (SARS-CoV-2), the infectious agent responsible for the currently ongoing “Coronavirus disease 2019” (COVID-2019) pandemic, have a particularly high mutation rate. Taking into account the mutational landscape of an infectious agent, it is important to shed light on its evolution capability over time. As new, more infectious strains of COVID-19 emerge around the world, it is imperative to estimate when these new strains may overtake the wild-type strain in different populations. Therefore, we developed a general-purpose framework to estimate the time at which a mutant variant is able to takeover a wild-type strain during an emerging infectious diseases outbreak. In this study, we used COVID-19 as a case-study, but the model is adaptable to any emerging pathogens.

Methods and findings

We devise a two-strain mathematical framework, to model a wild- and a mutant-type viral population and fit cumulative case data to parameterize the model, using Ontario as a case study. We found that, in the context of under-reporting and the current case levels, a variant strain is unlikely to dominate until March/April 2021. Current non-pharmaceutical interventions in Ontario need to be kept in place longer even with vaccination in order to prevent another outbreak. The spread of a variant strain in Ontario will mostly likely be observed by a widened peak of the daily reported cases. If vaccine efficacy is maintained across strains, then it is still possible to have an immune population by end of 2021.

Conclusions

Our findings have important practical implications in terms of public health as policy-and decision-makers are equipped with a mathematical tool that can enable the estimation of the take-over of a mutant strain of an emerging infectious disease.
Impact of Vaccination and Testing in an Urban Campus model for the SARS-CoV-2 Pandemic *
Authors: Zhang Yi , Kapoor Sanjiv
Published: February 2021

The crisis induced by the Coronavirus pandemic has severely impacted educational institutes. Even with vaccination efforts underway, it is not clear that sufficient confidence will be achieved for schools to reopen soon.

This paper considers the impact of vaccination rates and testing rates to reduce infections and hospitalizations and evaluates strategies that will allow educational institute in urban settings to reopen. These strategies are also applicable to businesses and would help plan reopening in order to help the economy.

Our analysis is based on a graph model where nodes represent population groups and edges represent population exchanges due to commuting populations. The commuting population is associated with edges and is associated with one of the end nodes of the edge during part of the time period and with the other node during the remainder of the time period. The progression of the disease at each node is determined via compartment models, that include vaccination rates and testing to place infected people in quarantine along with consideration of asymptomatic and symptomatic populations. Applying this to a university population in Chicago with a substantial commuter population, chosen to be 80% as an illustration, provides an analysis which specifies benefits of testing and vaccination strategies over a time period of 150 days.
Experience of clinical services shapes attitudes to mental health data sharing: Findings from a UK-wide survey
Authors: Kirkham E.J. , Lawrie S. M. , Crompton C.J. , Iveson M.H. , Jenkins N. D. , Goerdten J. , Beange I. , Chan S.W.Y. , McIntosh A. , Fletcher-Watson S.
Published: February 2021

Background

Routinely-collected mental health data could deliver novel insights for mental health research. However, patients’ willingness to share their mental health data remains largely unknown. We investigated factors influencing likelihood of sharing these data for research purposes amongst people with experience of mental illness.

Methods

We collected responses from a diverse sample of UK National Health Service (NHS) users (n = 2187) of which about half (n = 1087) had lifetime experience of mental illness. Ordinal logistic regression was used to examine the influence of demographic factors, clinical service experience, and primary mental illness on willingness to share mental health data, contrasted against physical health data.

Results

There was a high level of willingness to share mental (89.7%) and physical (92.8%) health data for research purposes. Higher levels of satisfaction with the NHS were associated with greater willingness to share mental health data. Furthermore, people with personal experience of mental illness were more willing than those without to share mental health data, once the effect of NHS satisfaction had been controlled for. Of the mental illnesses recorded, people with depression, obsessive-compulsive disorder (OCD), personality disorder or bipolar disorder were significantly more likely to share their mental health data than people without mental illness.

Conclusions

These findings suggest that positive experiences of health services and personal experience of mental illness are associated with greater willingness to share mental health data. NHS satisfaction is a potentially modifiable factor that could foster public support for increased use of NHS mental health data in research.
Increased SAR-CoV-2 shedding associated with reduced disease severity despite continually emerging genetic variants
Authors: Tang Cynthia Y. , Wang Yang , Gao Cheng , Smith David R. , McElroy Jane A. , Li Tao , Segovia Karen , Haynes Tricia , Hammer Richard , Sampson Christopher , Ritter Detlef , Schulze Christopher , Trotman Robin , Lidl Grace M , Webby Richard , Hang Jun , Wan Xiu-Feng
Published: February 2021

Since the first report of SARS-CoV-2 in December 2019, genetic variants have continued to emerge, complicating strategies for mitigating the disease burden of COVID-19. Positive SARS-CoV-2 nasopharyngeal swabs (n=8,735) were collected from Missouri, USA, from March-October 2020, and viral genomes (n=178) were sequenced. Hospitalization status and length of stay were extracted from medical charts of 1,335 patients and integrated with emerging genetic variants and viral shedding analyses for assessment of clinical impacts. Multiple introductions of SARS-CoV-2 into Missouri, primarily from Australia, Europe, and domestic states, were observed. Four local lineages rapidly emerged and spread across urban and rural regions in Missouri. While the majority of Missouri viruses harbored Spike-D614G mutations, a large number of unreported mutations were identified among Missouri viruses, including seven in the RNA-dependent RNA polymerase complex and Spike protein that were positively selected. A 15.6-fold increase in viral RNA levels in swab samples occurred from March to May and remained elevated. Accounting for other comorbidities, individuals test-positive for COVID-19 with high viral loads were less likely to be hospitalized (odds ratio=0.39, 95% confidence interval [CI]=0.20, 0.77) and had shorter hospital stays (hazard ratio=0.34, p=0.003) than those with low viral loads. Overall, the first eight months of the pandemic in Missouri saw multiple locally acquired mutants emerge and dominate in urban and rural locations. Although we were unable to find associations between specific variants and greater disease severity, Missouri COVID-positive individuals that presented with increased viral shedding had less severe disease by several measures.
Extubation generates lung volume inhomogeneity in preterm infants
Authors: Bhatia R , Carlisle HR , Armstrong RK , Kamlin COF , Davis PG , Tingay DG
Published: February 2021

Objective

To evaluate the feasibility of EIT to describe the regional tidal ventilation (VT) and change in end-expiratory lung volume (EELV) patterns in preterm infants during the process of extubation from invasive to non-invasive respiratory support.

Design

Prospective observational study

Setting

Single-centre tertiary neonatal intensive care unit

Patients

Preterm infants born <32 weeks gestation who were being extubated to nasal continuous positive airway pressure (nCPAP) as per clinician discretion.

Interventions

Electrical Impedance Tomography measurements were taken in supine infants during elective extubation from synchronised positive pressure ventilation (SIPPV) before extubation, during and then at 2 and 20 minutes after commencing nCPAP. Extubation and pressure settings were determined by clinicians.

Main outcome measures

Global and regional ΔEELV and ΔVTwere measured. Heart rate, respiratory rate and oxygen saturation were measured throughout.

Results

Thirty infants of median (range) 2 (1, 21) days were extubated to a median (range) CPAP 7 (6, 8) cmH2O. SpO2/FiO2ratio was mean (95% CI) 50 (35, 65) lower 20 minutes after nCPAP compared with SIPPV. EELV was lower at all points after extubation compared to SIPPV, and EELV loss was primarily in the ventral lung (p=0.04). VTwas increased immediately after extubation, especially in the central and ventral regions of the lung, but the application of nCPAP returned VTto pre-extubation patterns.

Conclusions

Lung behaviour during the transition from invasive positive pressure ventilation to CPAP at moderate distending pressures is variable and associated with lung volume loss in the ventral lung.
Impact of systemic corticosteroids on hospitalized patients with COVID-19: January 2021 Meta-analysis of randomized controlled trials
Authors: Robinson Robert , Prakash Vidhya , Tamimi Raad Al , Albast Nour , Al-Bast Basma
Published: February 2021

Background

The COVID-19 pandemic has stimulated worldwide investigation into a myriad of potential therapeutic agents, including corticosteroids. The first RCT reporting results on the impact of systemic corticosteroids on COVID-19 in a peer reviewed journal was the RECOVERY trial published in July, 2020. The RECOVERY trial showed a reduced risk of 28-day mortality in patients who received oral or intravenous dexamethasone for 10 days.

This study is a meta-analysis of peer reviewed RCTs aims to estimate the association of systemic corticosteroid therapy compared to the usual care or placebo on all-cause mortality in hospitalized patients with COVID-19. Software based tools to accelerate the analysis process.

Methods

Meta-analysis of peer reviewed RCTs comparing systemic corticosteroids to usual care or placebo.

Results

Five English language RCTs were identified, including data from 7645 hospitalized patients worldwide using systemic dexamethasone, hydrocortisone and methylprednisolone in COVID-19 positive patients. Three RCTs were discontinued when preliminary results from the RECOVERY trial became available.

Meta-analysis of all identified RCTs showed no difference in survival in patients who received systemic corticosteroid therapy compared to usual care or placebo (Odds ratio 0.82, 95% CI 0.64-1.05, p = 0.09). Subgroup analysis from the 1967 critically ill patients in the identified RCTs showed improved survival in patients who received systemic corticosteroid therapy (Odds ratio 0.67, 95% CI 0.51-0.87, p = 0.01).

Conclusions

This meta-analysis of randomized controlled trials published in peer-reviewed literature by January 1, 2021 showed reduced mortality in critically ill patients but not all hospitalized patients with COVID-19 who received systemic corticosteroids. The early termination of three of the included RCTs because of the preliminary results of the RECOVERY trial is likely to have dramatically influenced the results of this meta-analysis. Further research is needed to clarify the role of systemic corticosteroid therapy in the management of COVID-19.
Ultrasound-Guided Needling and Lidocaine Plus Sterile Water Injection in Lumbar Spinal Stenosis
Authors: Chen Carl PC , Suputtitada Areerat , Pongpirul Krit
Published: February 2021

Objective

To study the effect of ultrasound-guided (USG) needling and lidocaine plus sterile water injections in lumbar spinal stenosis (LSS).

Method

This retrospective study examined data of LSS patients who received USG lidocaine injection to lumbar facets, medial branches to facet joints, and multifidus muscles with one needle insertion at 4 spinal levels.

Results

A total of 213 lumbar spinal stenosis patients—104 patients received USG needling and 1% lidocaine without adrenaline 2 ml plus sterile water 10 ml injection (Group A) and 109 patients received 1% lidocaine without adrenaline 6 ml injection (Group B)—for 4 times, once per week. The VAS of chronic low back pain, radicular pain, claudication, and walking ability of both groups at 3, 6, and 12 months were significantly better than the baseline. Group A reported significantly better chronic low back pain, radicular pain, claudication, and walking ability at 3, 6, and 12 months than Group B.

Conclusions

USG needling and 1% lidocaine without adrenaline 2 ml plus sterile water 10 ml injection to lumbar facets, medial branches to facet joints, and multifidus muscles with one needle insertion at 4 spinal levels, once a week for 4 weeks can improve low back pain, radicular pain and gait ability in LSS with long term pain relief at least 12 months.

Highlights

There is evidence of the long-lasting effectiveness of local anesthetic alone for chronic spinal pain on noxious peripheral stimulation, phenotypic changes for neuronal plasticity, and neurotransmitter release responsible for secondary hyperalgesia.

USG needling and amount of safety solution as 1% lidocaine without adrenaline 2 ml plus sterile water 10 ml is effective for treating chronic low back pain, radicular pain, and claudication in LSS at least 12 months.

These clinical outcomes should be the effects of peripheral and central desensitization. The other possible effect is the mechanical removal of fibrosis and calcification at lumbar facets, medial branches to facet joints, and multifidus muscles.
How did COVID-19 measures impact sexual behaviour and access to HIV/STI services in Panama? Results from a national cross-sectional online survey
Authors: Gabster Amanda , Erausquin Jennifer Toller , Michielsen Kristien , Mayaud Philippe , Pascale Juan Miguel , Escalé Carles Pericas , Marks Michael , Katz Jennifer , Talavero Gonzalo Cabezas , de Argote Marilu , Murillo Anet , Tucker Joseph D.
Published: February 2021

Objectives

To describe perceived changes in sexual behaviours, including virtual sex (sexting and cybersex), and access to HIV/STI testing and care during COVID-19 measures in Panama. Methods We conducted an online cross-sectional survey from August 8 to September 12, 2020, among adults (≥18 years) residing in Panama. Participants were recruited through social media. Questions included demographics, access to HIV/STI testing and HIV care and sexual behaviours three months before COVID-19 social distancing measures and during social distancing measures (COVID-19 measures). Logistic regression was used to identify associations between variables and behavioural changes.

Results

We recruited 960 participants; 526 (54.8%) identified as cis-women, 366 (38.1%) cis-men, and 68 (7.1%) non-binary or another gender; median age was 28y (IQR:23-37y), 531/957 (55.5%) were of mixed-ethnicity (mixed-Indigenous/European/Afro-descendant ancestry). Before COVID-19 measures, virtual sex was reported by 38.5% (181/470) cis-women, 58.4% (184/315) cis-men and 45.0% (27/60) non-binary participants; during COVID-19 measures, virtual sex increased among 17.2% cis-women, 24.7% cis-men and 8.9% non-binary participants. During COVID-19 measures, 230/800 [28.8%] of participants reported decreased casual sex compared to pre-COVID-19 measures. Compared to pre-COVID-19 measures, decreased casual sex were reported more frequently during COVID-19 measures by cis-men compared to cis-women (39.2% versus 22.9%, urban/rural adjusted odds ratio [AOR]=2.17, 95% confidence interval [CI]:1.57-3.01); and by Afro-descendant compared to mixed-ethnicity participants (40.0% versus 29.8%, AOR=1.78, 95%CI:1.07-2.94). Compared to no change in virtual sex (16.8%), increase in virtual sex (38.5%, AOR=1.78, 95%CI:1.10-2.88); and decreased virtual sex (86.7%, AOR=16.53, 95%CI:7.74-35.27) were associated with decreased casual sex encounters. During COVID-19 measures, HIV/STI testing could not be obtained by 58.0%(58/100) participants who needed a test, and interrupted HIV care was reported by 53.3% (8/15) HIV-positive participants.

Conclusions

COVID-19 measures in Panama were associated with a decrease in casual sex among cis-men and Afro-descendant peoples, whilst access to HIV/STI testing and care was seriously disrupted.
Outcomes following out-of-hours cholecystectomy: A systematic review and meta-analysis
Authors: Bhat Sameer , Varghese Chris , Xu William , Barazanchi Ahmed W.H. , Ratnayake Bathiya , O’Grady Gregory , Windsor John A. , Wells Cameron I.
Published: February 2021

Background

Cholecystectomy is one of the most commonly performed abdominal operations. Demands on acute operating theatre availability have led to out-of-hours (evenings, nights, or weekend) cholecystectomy being performed, although it is not known whether outcomes differ between out-of-hours and in-hours (daytime on weekdays) cholecystectomy.

Objective

This systematic review and meta-analysis aimed to compare outcomes following out-of-hoursversusin-hours urgent cholecystectomy.

Methods

MEDLINE, EMBASE and Scopus databases were systematically searched from inception to December 2020 for studies comparing outcomes from out-of-hours and in-hours urgent cholecystectomy in adults. The outcomes of interest were rates of bile leakage, bile duct injury (BDI), overall post-operative complications, conversion to open cholecystectomy, specific intra- and post-operative complications, length of stay (LOS), readmission and mortality. Sensitivity analysis of adjusted multivariate results was also performed.

Results

In total, 194,135 urgent cholecystectomies (30,001 out-of-hours; 164,134 in-hours) from 11 studies were included. Most studies were of high (64%) or medium (18%) quality. There were no differences between out-of-hours and in-hours cholecystectomy for rates of bile leakage, BDI, overall post-operative complications, conversion to open cholecystectomy, operative duration, readmission, mortality, and post-operative LOS. Higher rates of post-operative sepsis (odds ratio (OR) 1.58, 95% CI: 1.04-2.41; p=0.03) and pneumonia (OR 1.55, 95% CI: 1.06-2.26; p=0.02) were observed following out-of-hours cholecystectomy on univariate meta-analysis but not on adjusted multivariate meta-analysis.

Conclusions

There was no increased risk or difference in specific complications associated with out-of-hours compared with in-hours urgent cholecystectomy.
DMRscaler: A Scale-Aware Method to Identify Regions of Differential DNA Methylation Spanning Basepair to Multi-Megabase Features
Authors: Bondhus Leroy , Wei Angela , Arboleda Valerie A.
Published: February 2021

Background

Pathogenic mutations in genes that control chromatin function have been implicated in rare genetic syndromes. These chromatin modifiers exhibit extraordinary diversity in the scale of the epigenetic changes they affect, from single basepair modifications by DNMT1 to whole genome structural changes by PRM1/2. Patterns of DNA methylation are related to a diverse set of epigenetic features across this full range of epigenetic scale, making DNA methylation valuable for mapping regions of general epigenetic dysregulation. However,existing methods are unable to accurately identify regions of differential methylation across this full range of epigenetic scale directly from DNA methylation data.

Results

To address this, we developed DMRscaler, a novel method that uses an iterative windowing procedure to capture regions of differential DNA methylation (DMRs) ranging in size from single basepairs to whole chromosomes. We benchmarked DMRscaler against several DMR callers in simulated and natural data comparing XX and XY peripheral blood samples. DMRscaler was the only method that accurately called DMRs ranging in size from 100 bp to 1 Mb (pearson’s r = 0.96) and up to 152 Mb on the X-chromosome. We then analyzed methylation data from rare-disease cohorts that harbor chromatin modifier gene mutations in NSD1, EZH2, and KAT6A where DMRscaler identified novel DMRs spanning gene clusters involved in development.

Conclusion

Taken together, our results show DMRscaler is uniquely able to capture the size of DMR features across the full range of epigenetic scale and identify novel, co-regulated regions that drive epigenetic dysregulation in human disease.
A novel capsid protein network allows the characteristic inner membrane structure of Marseilleviridae giant viruses
Authors: Chihara Akane , Burton-Smith Raymond N. , Kajimura Naoko , Mitsuoka Kaoru , Okamoto Kenta , Song Chihong , Murata Kazuyoshi
Published: February 2021

Marseilleviridae is a family of the new order of giant viruses, which exhibit a characteristic inner membrane. Here, we investigated the entire structure of tokyovirus, a species of Marseillevirus at 7.7 Å resolution using 1 MV high-voltage cryo-EM and single particle analysis. The minor capsid lattice formed by five proteins, shows a novel structure compared to other icosahedral giant viruses. Under the minor capsid proteins, scaffold proteins connect two five-fold vertices and interact with the inner membrane. Previously reported giant viruses utilise “tape measure” proteins, proposed to control its capsid size, which could not be identified in tokyovirus, but scaffold proteins appear to perform a similar role. A density on top of the major capsid protein was identified, which suggested to be a 14kDa glycoprotein. Our observations suggest that the icosahedral particle of Marseilleviridae is constructed with a novel capsid protein network, which allows the characteristic inner membrane structure.
Cold-acclimation induces life stage-specific responses in the cardiac proteome of Western painted turtles (Chrysemys picta bellii): implications for anoxia tolerance
Authors: Alderman Sarah L. , Riggs Claire L. , Bullingham Oliver , Gillis Todd E. , Warren Daniel E.
Published: February 2021

Western painted turtles(Chrysemys picta bellii)are the most anoxia-tolerant tetrapod. Survival time improves at low temperature and during ontogeny, such that adults acclimated to 3°C survive far longer without oxygen than either warm-acclimated adults or cold-acclimated hatchlings. Since protein synthesis is rapidly suppressed to save energy at the onset of anoxia exposure, this study tested the hypothesis that cold-acclimation would evoke preparatory changes in protein expression that would support enhanced anoxia survival in adult but not hatchling turtles. To test this, adult and hatchling turtles were acclimated to either 20°C (warm) or 3°C (cold) for 5 weeks, and then the heart ventricles were collected for quantitative proteomic analysis using labeled isobaric tags and mass spectrometry. The relative abundances of 1316 identified proteins were compared between temperatures and developmental stages. The effect of cold-acclimation on the cardiac proteome was most evident when life stage was included as a covariable, suggesting that ontogenic differences in anoxia tolerance may be predicated on successful maturation of the heart from its hatchling to adult form and, only after this maturation occurs, will cold-acclimation induce protein expression changes appropriate for supporting heart function during prolonged anoxia. The main differences between the hatchling and adult cardiac proteomes reflect an increase in metabolic scope that included more myoglobin and increased investment in both aerobic and anaerobic energy pathways. Mitochondrial structure and function were key targets of life stage- and temperature-induced changes to the cardiac proteome, including reduced complex II proteins in cold-acclimated adults that may help down-regulate the electron transport system and avoid succinate accumulation during anoxia. Therefore, targeted cold-induced changes to the cardiac proteome may be a contributing mechanism for stagespecific anoxia tolerance in turtles.
Extensive recombination-driven coronavirus diversification expands the pool of potential pandemic pathogens
Authors: Goldstein Stephen A. , Brown Joe , Pedersen Brent S. , Quinlan Aaron R. , Elde Nels C.
Published: February 2021

The ongoing SARS-CoV-2 pandemic is the third zoonotic coronavirus identified in the last twenty years. Enzootic and epizootic coronaviruses of diverse lineages also pose a significant threat to livestock, as most recently observed for virulent strains of porcine epidemic diarrhea virus (PEDV) and swine acute diarrhea-associated coronavirus (SADS-CoV). Unique to RNA viruses, coronaviruses encode a proofreading exonuclease (ExoN) that lowers point mutation rates to increase the viability of large RNA virus genomes, which comes with the cost of limiting virus adaptation via point mutation. This limitation can be overcome by high rates of recombination that facilitate rapid increases in genetic diversification. To compare dynamics of recombination between related sequences, we developed an open-source computational workflow (IDPlot) to measure nucleotide identity, locate recombination breakpoints, and infer phylogenetic relationships. We analyzed recombination dynamics among three groups of coronaviruses with noteworthy impacts on human health and agriculture:SARSr-CoV, Betacoronavirus-1, and SADSr-CoV. We found that all three groups undergo recombination with highly diverged viruses from sparsely sampled or undescribed lineages, which can disrupt the inference of phylogenetic relationships. In most cases, no parental origin of recombinant regions could be found in genetic databases, suggesting that much coronavirus diversity remains unknown. These patterns of recombination expand the genetic pool that may contribute to future zoonotic events. Our results also illustrate the limitations of current sampling approaches for anticipating zoonotic threats to human and animal health.
The yeast eIF2 kinase Gcn2 facilitates H2O2-mediated feedback inhibition of both protein synthesis and ER oxidative folding during recombinant protein production
Authors: Gast Veronica , Campbell Kate , Campos Cecilia Picazo , Engqvist Martin , Siewers Verena , Molin Mikael
Published: February 2021

Recombinant protein production is a known source of oxidative stress. Knowledge of which ROS are involved or the specific growth phase in which stress occurs however remains lacking. Using modern, hypersensitive genetic H2O2-specific probes, micro-cultivation and continuous measurements in batch culture, we observed H2O2accumulation during and following the diauxic shift in engineeredSaccharomyces cerevisiae, correlating with peak α-amylase production. In agreement with previous studies supporting a role of the translation initiation factor kinase Gcn2 in the response to H2O2, we find Gcn2-dependent phosphorylation of eIF2α to increase alongside translational attenuation in strains engineered to produce large amounts of α-amylase. Gcn2 removal significantly improved α-amylase production in two previously optimized high-producing strains, but not in the wild-type. Gcn2-deficiency furthermore reduced intracellular H2O2levels and the unfolded protein response whilst expression of antioxidants and the ER disulfide isomerasePDI1increased. These results suggest protein synthesis and ER oxidative folding to be coupled and subject to feedback inhibition by H2O2.

Importance

Reactive oxygen species (ROS) accumulate during recombinant protein production both in yeast and Chinese hamster ovary cells, two of the most popular organisms used in the multi-million dollar protein production industry. Here we document increased H2O2in the cytosol of yeast cells producing α-amylase. Since H2O2predominantly targets the protein synthesis machinery and activates the translation initiation factor kinase Gcn2, we removed Gcn2, resulting in increased recombinant α-amylase production in two different previously engineered high-producing protein production strains. Removal of this negative feed-back loop thus represents a complementary strategy for improving recombinant protein production efforts currently used in yeast. Gcn2-deficiency also increased the expression of antioxidant genes and the ER-foldasePDI1, suggesting that protein synthesis and ER oxidative folding are linked and feed-back regulated via H2O2. Identification of additional components in this complex regulation may further improve protein production and contribute to the development of novel protein-based therapeutic strategies.