bluuebunny/crossref_metadata_2025_split huggingface dataset:
The earthquake cycle in the dry lower continental crust: insights from two deeply exhumed terranes (Musgrave Ranges, Australia and Lofoten, Norway)
Authors: Menegon Luca , Campbell Lucy , Mancktelow Neil , Camacho Alfredo , Wex Sebastian , Papa Simone , Toffol Giovanni , Pennacchioni Giorgio 
Published: February 2021

This paper discusses the results of field-based geological investigations of exhumed rocks exposed in the Musgrave Ranges (Central Australia) and in Nusfjord (Lofoten, Norway) that preserve evidence for lower continental crustal earthquakes with focal depths of approximately 25–40 km. These studies have established that deformation of the dry lower continental crust is characterized by a cyclic interplay between viscous creep (mylonitization) and brittle, seismic slip associated with the formation of pseudotachylytes (a solidified melt produced during seismic slip along a fault in silicate rocks). Seismic slip triggers rheological weakening and a transition to viscous creep, which may be already active during the immediate post-seismic deformation along faults initially characterized by frictional melting and wall-rock damage. The cyclical interplay between seismic slip and viscous creep implies transient oscillations in stress and strain rate, which are preserved in the shear zone microstructure. In both localities, the spatial distribution of pseudotachylytes is consistent with a local (deep) source for the transient high stresses required to generate earthquakes in the lower crust. This deep source is the result of localized stress amplification in dry and strong materials generated at the contacts with ductile shear zones, producing multiple generations of pseudotachylyte over geological time. This implies that both the short- and the long-term rheological evolution of the dry lower crust typical of continental interiors is controlled by earthquake cycle deformation.
This article is part of a discussion meeting issue ‘Understanding earthquakes using the geological record’.
Administration of tocilizumab to patients with high concentrations of IL-6 in the course of COVID-19 is associated with a better prognosis
Authors: Flisiak Robert , Jaroszewicz Jerzy , Rogalska Magdalena , Łapiński Tadeusz , Berkan-Kawińska Aleksandra , Bolewska Beata , Tudrujek-Zdunek Magdalena , Kozielewicz Dorota , Rorat Marta , Leszczyński Piotr , Kłos Krzysztof , Kowalska Justyna , Pabjan Paweł , Piekarska Anna , Mozer-Lisewska Iwona , Tomasiewicz Krzysztof , Pawłowska Małgorzata , Simon Krzysztof , Polańska Joanna , Zarębska-Michaluk Dorota 
Published: February 2021

SummaryBackgroundDespite the direct viral activity, the pathogenesis of coronavirus disease 2019 (COVID-19) includes an overproduction of cytokines including interleukin 6 (IL-6). Therefore tocilizumab (TCZ), a monoclonal antibody against IL-6 receptors, became considered as a possible therapeutic option.MethodsPatients were selected from the SARSTer national database, which included 2332 individuals with COVID-19 and the current study included 825 adult patients with moderate to severe course. The retrospective analysis was performed in 170 patients treated with TCZ and 655 without this medication or any other anti-cytokine therapy. The end-points of treatment effectiveness were a rate of death, need for mechanical ventilation, and clinical improvement.ResultsPatients treated with TCZ were balanced compared to non-TCZ regarding gender, age, BMI, and prevalence of coexisting conditions. The reduced death rate was demonstrated in patients treated with TCZ and baseline IL-6 >100 pg/ml (hazard ratio [HR]: 0.27, 95% confidence interval [CI]:0.10-0.78), or those needing oxygen supplementations who worsened within 7 days of hospitalization (HR: 0.38, 95% CI:0.16-0.88). The best effectiveness of TCZ was achieved in patients with a combination of baseline IL-6>100 pg/ml and either SpO2≤90% (HR for death, mechanical ventilation, and clinical improvement after 21 or 28 days: 0.07, 0.14, 5.53, 5.18 respectively) or requiring oxygen supplementation (HR for death and clinical improvement after 21 or 28 days, 0.18, 2.66, 2.85 respectively).ConclusionsTocilizumab administered for COVID-19 in patients with a baseline concentration of IL-6>100 pg/ml is associated with reduced mortality and faster clinical improvement, particularly if there is a need for oxygen supplementation due to SpO2≤90%.
Application of a 27-protein candidate cardiovascular surrogate endpoint to track risk ascendancy and resolution in COVID-19
Authors: Paterson Clare , Hagar Yolanda , Hinterberg Michael A. , Charney Alexander W. , Valle Diane M. Del , Filbin Michael R. , Gnjatic Sacha , Goldman Jason D. , Hacohen Nir , Heath James R. , Hillenbrand Rainer , Jennings Lori L. , Kim-Schulze Seunghee , Magis Andrew T. , Merad Miriam , Mouskas Konstantinos , Simons Nicole W. , Williams Stephen A. 
Published: February 2021

ABSTRACTBackgroundThere is an urgent need for tools allowing the early prognosis and subsequent monitoring of individuals with heterogeneous COVID-19 disease trajectories. Pre-existing cardiovascular (CV) disease is a leading risk factor for COVID-19 susceptibility and poor outcomes, and cardiac involvement is prevalent in COVID-19 patients both during the acute phase as well as in convalescence. The utility of traditional CV risk biomarkers in mild COVID-19 disease or across disease course is poorly understood. We sought to determine if a previously validated 27-protein predictor of CV outcomes served a purpose in COVID-19.MethodsThe 27-protein test of residual CV (RCV) risk was applied without modification to n=860 plasma samples from hospitalized and non-hospitalized SARS-CoV-2 infected individuals at disease presentation from three independent cohorts to predict COVID-19 severity and mortality. The same test was applied to an additional n=991 longitudinal samples to assess sensitivity to change in CV risk throughout the course of infection into convalescence.ResultsIn each independent cohort, RCV predictions were significantly related to maximal subsequent COVID-19 severity and to mortality. At the baseline blood draw, the mean protein-predicted likelihood of an event in subjects who died during the study period ranged from 88-99% while it ranged from 8-36% in subjects who were not admitted to hospital. Additionally, the test outperformed existing risk predictors based on commonly used laboratory chemistry values or presence of comorbidities. Application of the RCV test to sequential samples showed dramatic increases in risk during the first few days of infection followed by risk reduction in the survivors; a period of catastrophically high cardiovascular risk (above 50%) typically lasted 8-12 days and had not resolved to normal levels in most people within that timescale.ConclusionsThe finding that a 27-protein candidate CV surrogate endpoint developed in multi-morbid patients prior to the pandemic is both prognostic and acutely sensitive to the adverse effects of COVID-19 suggests that this disease activates the same biologic risk-related mechanisms. The test may be useful for monitoring recovery and drug response.
Unmet need of essential treatments for critical illness in Malawi
Authors: Kayambankadzanja Raphael Kazidule , Schell Carl Otto , Mbingwani Isaac , Mndolo Samson Kwazizira , Castegren Markus , Baker Tim 
Published: February 2021

AbstractBackgroundCritical illness is common throughout the world and has been the focus of a dramatic increase in attention in the COVID-19 pandemic. Severely deranged vital signs can identify critical illness, are simple to check and treatments that aim to correct derangements are established, basic and low-cost. The aim of the study was to estimate the unmet need of essential treatments for severely deranged vital signs in all adults admitted to hospitals in Malawi.MethodsWe conducted a cross-sectional study with follow-up of adult hospitalized patients in Malawi. All in-patients aged ≥18 on single days Queen Elizabeth Central Hospital (QECH) and Chiradzulu District Hospital (CDH) were screened.. Patients with hypoxia (oxygen saturation <90%), hypotension (systolic blood pressure <90mmHg) and reduced conscious level (Glasgow Coma Score <9) were included in the study. The a-priori defined essential treatments were oxygen therapy for hypoxia, intravenous fluid for hypotension and an action to protect the airway for reduced consciousness (placing the patient in the lateral position, insertion of an oropharyngeal airway or endo-tracheal tube or manual airway protection).ResultsOf the 1135 hospital in-patients screened, 45 (4.0%) had hypoxia, 103 (9.1%) had hypotension, and 17 (1.5%) had a reduced conscious level. Of those with hypoxia, 40 were not receiving oxygen (88.9%). Of those with hypotension, 94 were not receiving intravenous fluids (91.3%). Of those with a reduced conscious level, nine were not receiving an action to protect the airway (53.0%).ConclusionThere was a large unmet need of essential treatments for critical illness in two hospitals in Malawi.
Identification of Nonverbal Communication Tools for Use in Dementia
Authors: Khan Zunera , Da Silva Miguel Vasconcelos , Eno-Amooquaye Jemuwem , Nowicki Steven , Nunez Kayleigh , Francis Paul , Ballard Clive 
Published: February 2021

AbstractIntroductionNon-verbal communication remains a relatively unexplored area in dementia care with a lack of validated assessment tools available to measure non-verbal communication function in dementia.MethodsThis scoping review identifies assessment scales of nonverbal communication in dementia and evaluates the psychometric properties and clinical utility of these instruments. Relevant publications in English, from 1947 to 2017, were identified through an extensive search strategy in Medline, Psychinfo and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Cochrane and generic search engines (Google) and available off-line resources. Quality judgement criteria was formulated and used to evaluate the psychometric aspects of the scales.ResultsForty-one tools were identified measuring various communication channels including verbal, nonverbal (e.g., facial expressions, gestures, eye contact) and functional, communication means; within various settings and populations, for instance, those assessing cognition and verbal language difficulties secondary to stroke, aphasia and nonverbal cues associated with pain. A number of tools presented psychometrics qualities; only nine of the forty-one tools specifically focussed on nonverbal communication, however, comprehensive assessment of nonverbal communication function was not presented in majority of the identified tools. Two tools provided a detailed assessment of nonverbal communication, the Emory dyssemia Index (EDI) and the Threadgold Communication Tool (TCT).ConclusionBased on the psychometric qualities and criteria regarding sensitivity and clinical utility, we concluded that although it is difficult to recommend one particular tool, the EDI and TCT are the most appropriate scales currently available. Further research should focus on improving these scales by further testing their validity, reliability and clinical utility in dementia.
Effect of RBD mutations in spike glycoprotein of SARS-CoV-2 on neutralizing IgG affinity
Authors: Hayashi Takuma , Yaegashi Nobuo , Konishi Ikuo 
Published: February 2021

AbstractBackgroundCertain mutant strains of SARS-CoV-2 are known to spread widely among humans, including the receptor binding domain (RBD) mutant, Y453F, from farmed minks, and the RBD mutant, N501Y, a mutation common to three major SARS-CoV-2 subspecies (B.1.1.7, B.1.351, and B.1.1.248).MethodsWe investigated the characteristics of the RBD mutants, Y453F and N501Y, using three-dimensional structural analysis. We also investigated the effect of Y453F and N501Y on neutralizing antibodies in serum derived from COVID-19-positive patients.ResultsOur results suggest that SARS-CoV-2 subspecies with the RBD mutations Y453F or N501Y partially escaped detection by 4 neutralizing monoclonal antibodies and 21 neutralizing antibodies in serums derived from COVID-19-positive patients.ConclusionsInfection with SARS-CoV-2 subspecies that cause serious symptoms in humans may spread globally.
The mobility gap: estimating mobility levels required to control Canada’s winter COVID-19 surge
Authors: Brown Kevin A. , Soucy Jean-Paul R. , Buchan Sarah A. , Sturrock Shelby L. , Berry Isha , Stall Nathan M. , Jüni Peter , Ghasemi Amir , Gibb Nicholas , MacFadden Derek R. , Daneman Nick 
Published: February 2021

AbstractBackgroundNon-pharmaceutical interventions remain a primary means of suppressing COVID-19 until vaccination coverage is sufficient to achieve herd immunity. We used anonymized smartphone mobility measures in seven Canadian provinces to quantify the mobility level needed to suppress COVID-19 (mobility threshold), and the difference relative to current mobility levels (mobility gap).MethodsWe conducted a longitudinal study of weekly COVID-19 incidence from March 15, 2020 to January 16, 2021, among provinces with 20 COVID-19 cases in at least 10 weeks. The outcome was weekly growth rate defined as the ratio of current cases compared to the previous week. We examined the effects of average time spent outside the home (non-residential mobility) in the prior three weeks using a lognormal regression model accounting for province, season, and mean temperature. We calculated the COVID-19 mobility threshold and gap.ResultsAcross the 44-week study period, a total of 704,294 persons were infected with COVID-19. Non-residential mobility dropped rapidly in the spring and reached a median of 36% (IQR: 31,40) in April 2020. After adjustment, each 5% increase in non-residential mobility was associated with a 9% increase in the COVID-19 weekly growth rate (ratio=1.09, 95%CI: 1.07,1.12). The mobility gap increased through the fall months, which was associated with increasing case growth.InterpretationMobility strongly and consistently predicts weekly case growth, and low levels of mobility are needed to control COVID-19 through winter 2021. Mobility measures from anonymized smartphone data can be used to guide the provincial and regional implementation and loosening of physical distancing measures.
Stochastic social behavior coupled to COVID-19 dynamics leads to waves, plateaus and an endemic state
Authors: Tkachenko Alexei V. , Maslov Sergei , Wang Tong , Elbanna Ahmed , Wong George N. , Goldenfeld Nigel 
Published: February 2021

AbstractIt is well recognized that population heterogeneity plays an important role in the spread of epidemics. While individual variations in social activity are often assumed to be persistent, i.e. constant in time, here we discuss the consequences of dynamic heterogeneity. By integrating the stochastic dynamics of social activity into traditional epidemiological models we demonstrate the emergence of a new long timescale governing the epidemic, in broad agreement with empirical data. Our Stochastic Social Activity model captures multiple features of real-life epidemics such as COVID-19, including prolonged plateaus and multiple waves, which are transiently suppressed due to the dynamic nature of social activity. The existence of a long timescale due to the interplay between epidemic and social dynamics provides a unifying picture of how a fast-paced epidemic typically will transition to an endemic state.
Socioeconomic Disparities and COVID-19 Vaccination Acceptance: Experience from Israel
Authors: Caspi Gil , Dayan Avshalom , Eshal Yael , Liverant-Taub Sigal , Twig Gilad , Shalit Uri , Lewis Yair , Shina Avi , Caspi Oren 
Published: February 2021

AbstractCOVID-19 vaccination acceptance has a key role in mitigating the pandemic. Concern has been raised that vaccination rates will be limited in demographically defined areas of lower income. Israel’s rapid vaccination campaign may allow to assess these assumptions in real-world and to devise tools for effectively focusing the vaccination efforts. We analyzed the correlation between COVID-19 vaccination rates, socioeconomic status (SES) and active COVID-19 disease burden. We carried out a nationwide study, based on data provided by Ministry of Health of COVID-19 vaccination rates in all municipalities in Israel up to January 12th, 2021. Municipal Vaccination rates of population older than 60 significantly correlated with the socioeconomic status (r=0.83, 95% confidence interval [0.79 to 0.87]). Finally, we established a novel metric for focusing the vaccination efforts based on % vaccinations and active disease burden. In Israel, a case-model country for COVD-19 vaccinations, vaccination rates were strongly correlated with SES. The study findings demonstrate the need to directly target vaccination acceptance to socio-economically disadvantaged populations and suggest potential tools for policymakers to focus their efforts.
Prediction Models for Severe Manifestations and Mortality due to COVID-19: A Rapid Systematic Review
Authors: Miller Jamie L. , Tada Masafumi , Goto Michihiko , Mohr Nicholas , Lee Sangil 
Published: February 2021

ABSTRACTBackgroundThroughout 2020, the coronavirus disease 2019 (COVID-19) has become a threat to public health on national and global level. There has been an immediate need for research to understand the clinical signs and symptoms of COVID-19 that can help predict deterioration including mechanical ventilation, organ support, and death. Studies thus far have addressed the epidemiology of the disease, common presentations, and susceptibility to acquisition and transmission of the virus; however, an accurate prognostic model for severe manifestations of COVID-19 is still needed because of the limited healthcare resources available.ObjectiveThis systematic review aims to evaluate published reports of prediction models for severe illnesses caused COVID-19.MethodsSearches were developed by the primary author and a medical librarian using an iterative process of gathering and evaluating terms. Comprehensive strategies, including both index and keyword methods, were devised for PubMed and EMBASE. The data of confirmed COVID-19 patients from randomized control studies, cohort studies, and case-control studies published between January 2020 and July 2020 were retrieved. Studies were independently assessed for risk of bias and applicability using the Prediction Model Risk Of Bias Assessment Tool (PROBAST). We collected study type, setting, sample size, type of validation, and outcome including intubation, ventilation, any other type of organ support, or death. The combination of the prediction model, scoring system, performance of predictive models, and geographic locations were summarized.ResultsA primary review found 292 articles relevant based on title and abstract. After further review, 246 were excluded based on the defined inclusion and exclusion criteria. Forty-six articles were included in the qualitative analysis. Inter observer agreement on inclusion was 0.86 (95% confidence interval: 0.79 - 0.93). When the PROBAST tool was applied, 44 of the 46 articles were identified to have high or unclear risk of bias, or high or unclear concern for applicability. Two studied reported prediction models, 4C Mortality Score from hospital data and QCOVID from general public data from UK, and were rated as low risk of bias and low concerns for applicability.ConclusionSeveral prognostic models are reported in the literature, but many of them had concerning risks of biases and applicability. For most of the studies, caution is needed before use, as many of them will require external validation before dissemination. However, two articles were found to have low risk of bias and low applicability can be useful tools.
High variability in transmission of SARS-CoV-2 within households and implications for control
Authors: Toth Damon J.A. , Beams Alexander B. , Keegan Lindsay T. , Zhang Yue , Greene Tom , Orleans Brian , Seegert Nathan , Looney Adam , Alder Stephen C. , Samore Matthew H. 
Published: February 2021

AbstractBackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a high risk of transmission in close-contact indoor settings, which may include households. Prior studies have found a wide range of household secondary attack rates and may contain biases due to simplifying assumptions about transmission variability and test accuracy.MethodsWe compiled serological SARS-CoV-2 antibody test data and prior SARS-CoV-2 test reporting from members of 9,224 Utah households. We paired these data with a probabilistic model of household importation and transmission. We calculated a maximum likelihood estimate of the importation probability, mean and variability of household transmission probability, and sensitivity and specificity of test data. Given our household transmission estimates, we estimated the threshold of non-household transmission required for epidemic growth in the population.ResultsWe estimated that individuals in our study households had a 0.41% (95% CI 0.32% – 0.51%) chance of acquiring SARS-CoV-2 infection outside their household. Our household secondary attack rate estimate was 36% (27% – 48%), substantially higher than the crude estimate of 16% unadjusted for imperfect serological test specificity and other factors. We found evidence for high variability in individual transmissibility, with higher probability of no transmissions or many transmissions compared to standard models. With household transmission at our estimates, the average number of non-household transmissions per case must be kept below 0.41 (0.33 – 0.52) to avoid continued growth of the pandemic in Utah.ConclusionsOur findings suggest that crude estimates of household secondary attack rate based on serology data without accounting for false positive tests may underestimate the true average transmissibility, even when test specificity is high. Our finding of potential high variability (overdispersion) in transmissibility of infected individuals is consistent with characterizing SARS-CoV-2 transmission being largely driven by superspreading from a minority of infected individuals. Mitigation efforts targeting large households and other locations where many people congregate indoors might curb continued spread of the virus.
Cholesterol-lowering Decreased mTOR Complex 2 Signaling and Enhanced Antitumor Immunity
Authors: Wang Yanping , You Sungyong , Su Shengchen , Yeon Austin , Lo Eric M. , Kim Sungjin , Mohler James L. , Freeman Michael R. , Kim Hyung L. 
Published: February 2021

SummaryCholesterol-lowering interventions are employed widely and safely to reduce risk of cardiovascular disease. Cholesterol may have complex and opposing effects on immunity. We lowered serum cholesterol to clinically relevant levels in mice and evaluated the final adaptive immune response. Mice treated with oral ezetimibe exhibited enhanced antitumor immunity against syngeneic cancers in a CD8+ lymphocyte-dependent manner, produced immunity that was transferrable through lymphocytes, and enhanced central CD8+ T cell memory. In both mice and patients undergoing prostatectomy, lowering serum cholesterol inhibited mTORC2 signaling in lymphocytes and increased infiltration of CD8+ lymphocytes into prostate tumors. Lymphocyte-specific mTORC2 knockout mice demonstrated enhanced CD8+ lymphocyte function and antitumor capacity. In a prospective clinical trial, cholesterol-lowering intervention prior to prostatectomy decreased the proliferation of normal prostate and low-grade adenocarcinomas. Here, we show that lowering serum cholesterol may be an effective strategy to decrease signaling through mTORC2 and enhance antitumor CD8+ T cell memory.