bluuebunny/crossref_metadata_2025 huggingface dataset:
Community Led Testing among People Who Inject Drugs: A community centered model to find new cases of HIV and Hepatitis C in Nepal
Authors: Didhiya Rajesh , Pokhrel Tara Nath , Devkota Sudha , Shedain Purusotam Raj , Sharma Mukunda , Shrestha Madan Kumar , Gyenwali Deepak , Imran Muhammad , Kadirov Zakir , Dahal Bhawani Prasad , Rai Amrit Bikram , Prawachan Kumar KC , Ojha Sabir , Pokhrel Khem Narayan
Published: February 2021

Background

People Who Inject Drugs (PWIDs) have sub-optimal HIV and HCV testing as the available testing services are inadequate in low and middle-income countries. We examined a model of Community-Led Testing (CLT) in Nepal, exploring the feasibility of HIV and HCV testing by trained lay service providers who had similar backgrounds to those of PWIDs. We also assessed the prevalence of HIV and HCV within this study population and the associated risk factors among PWIDs.

Methods

A mix-method cross-sectional study was conducted among 1029 PWIDs in five major districts of Nepal from July 2019 to February 2020. Trained PWID peers performed the screening for HIV and HCV using Rapid Diagnostic Test (RDT) kits. Acceptability and feasibility of the testing was assessed. The participants’ sociodemographic characteristics and injecting and non-injecting risk characteristics were determined. The association of risk and prevention characteristics with testing results were assessed using multiple logistic regression.

Results

PWIDs shared that the test providers were friendly and competent in counseling and testing. Of total PWIDs (n=1,029), 20.6% were HCV-positive and 0.2% were HIV-positive. HCV positivity was associated with needle sharing (AOR: 1.83, 95% CI: 1.27,2.64; p=0.001) and reuse of syringe/needle (AOR: 2.26; 95% CI: 1.34, 3.79; p=0.002). In addition, PWIDs were more likely to be HCV-positive who started opioid substitution therapy (OST) (AOR: 1.88, 95% CI: 1.26, 2.80, p=0.002) and attended the rehabilitation center (AOR: 1.66, 95% CI: 1.10, 2.53, p=0.017).

Conclusions

This CLT model was found to be a novel approach of testing of HIV and HCV which was acceptable to PWIDs in Nepal and showed the high prevalence of HCV and its association with injecting-related risk behaviors and being users of OST and rehabilitation. The findings highlight the need of community-led testing in hotspots, OST settings, and rehabilitation centers to screen new HIV and HCV infections.
Telomere shortening as a stress biomarker in children and adolescents affected by natural disasters
Authors: Miranda Débora M. , Magalhães Sabrina S. , Rosa Daniela V. , De Marco Luiz A. , de Paula Jonas J. , Romano-Silva Marco A.
Published: February 2021

Natural disasters have a substantial psychosocial impact. A known biological marker of stress is telomere shortening. In this study, we tested the change in behavior symptoms and telomere length and its shortening in two-time points for about fifteen months, in populations that suffered extreme climate events, comprising flood or drought events. As expected, we observed telomere shortening in children and adolescents after a stressful situation which was directly associated with the worsening of externalizing symptoms and post-traumatic symptoms using a reliable change index. Beyond the psychosocial impact, natural events seem to affect the biology of individuals in development. These findings can help to understand vulnerabilities related to stress impact and to point target populations whose mitigation actions should be addressed in case of a disaster.
Change in burden of disease in UK children and young people (0-24 years) over the past 20 years and estimation of potential burden in 2040: analysis using Global Burden of Disease (GBD) data
Authors: Ward Joseph L. , Hargreaves Dougal , Turner Steve , Viner Russell M.
Published: February 2021

Background

The epidemiological transition and medical innovations have led to changes in causes of ill-health and disability by children and young people (CYP) in many wealthy countries over the past two decades. However this has not been systematically examined at a national level in the UK. Here we examined changes in disability-adjusted life-years (DALYs) by cause for 0-24 year olds by age-group.

Methods

We used data on DALYS by cause, sex and age-group for the UK from 1998 to 2017 from the 2017 Global Burden of Disease (GBD) study. We modified the GBD cause-hierarchy to be more relevant to paediatrics. We assessed current causes of burden in 2017 and change at cause-level for 1998-2007 and 2008-2017 by age. We then used Holt-Winters doubly exponentiated time-series models to forecast change in DALYs by age to 2040.

Results

In 2017, neonatal and congenital disorders were the main causes of DALYS across 0-24 year olds, with other the other large causes being anxiety and depression, endocrine and immune disorders, and lower respiratory tract infections. Total DALYS were highest amongst neonates and lowest amongst 1-9 year olds, rising with age amongst 10-24 year olds. Between 1998-2017, total DALYs fell in each age-group, with the largest falls in infants. The greatest changes in DALYS from 2008 to 2017 were falls in neonatal and congenital causes amongst infants, falls in infectious diseases and injuries in older age-groups, and rises in neonatal causes, mental health, acne and somatic symptoms in all age-groups other than infants. These patterns were forecast to continue to 2040.

Conclusions

We forecast falls in causes that have historically dominated disease in CYP, particularly congenital disorders, infectious diseases, cancers and injuries, representing falls in the prevalence of many infectious diseases and improvements in road safety and also improvements in survival from cancer and many congenital conditions. Forecast increases in DALYS from mental health problems, other adolescent health issues and the consequences of neonatal survival, such as neuro-disability and epilepsy, have potential implications for the training of paediatricians and workforce needs over the next two decades. The impact of the COVID-19 pandemic, climate change and changes in child poverty require further research.
Modeling the evolution of SARS-CoV-2 under non-pharmaceutical interventions
Authors: Gurevich Yael , Ram Yoav , Hadany Lilach
Published: February 2021

Social and behavioral non-pharmaceutical interventions (NPIs), such as mask-wearing, social distancing, and travel restrictions, as well as diagnostic tests, have been broadly implemented in response to the COVID-19 pandemic. Epidemiological models and data analysis affirm that wide adoption of NPIs helps to control the pandemic. However, SARS-CoV-2 has extensively demonstrated its ability to evolve. Therefore, it is crucial to examine how NPIs may affect the evolution of the virus. Such evolution could have important effects on the spread and impact of the pandemic.

We used evo-epidemiological models to examine the effect of non-pharmaceutical interventions and testing on two evolutionary trajectories for SARS-CoV-2: attenuation and test evasion. Our results show that when stronger measures are taken, selection may act to reduce virulence. Additionally, the timely application of NPIs could significantly affect the competition between viral strains, favoring reduced virulence. Furthermore, a higher testing rate can select for a test-evasive viral strain, even if that strain is less infectious than the detectable competing strain. Importantly, if a less detectable strain evolves, epidemiological metrics such as confirmed daily cases may distort our assessment of the pandemic. Our results highlight the important implications NPIs can have on the evolution of SARS-CoV-2.
A novel benchmark for COVID-19 pandemic testing effectiveness enables the accurate prediction of new Intensive Care Unit admissions
Authors: Nikoloudis Dimitris , Kountouras Dimitrios , Hiona Asimina
Published: February 2021

The positivity rate of testing is currently used both as a benchmark of testing adequacy and for assessing the evolution of the COVID-19 pandemic. However, since the former is a prerequisite for the latter, its interpretation is often conflicting. We propose as a benchmark for COVID-19 testing effectiveness a new metric, termed ‘Severity Detection Rate’ (SDR), that represents the daily needs for new Intensive Care Unit (ICU) admissions, per 100 cases detected (t-i) days ago, per 10,000 tests performed (t-i) days ago. Based on the announced COVID-19 monitoring data in Greece from May 2020 until August 2021, we show that beyond a certain threshold of daily tests, SDR reaches a plateau of very low variability that begins to reflect testing adequacy. Due to the stabilization of SDR, it was possible to predict with great accuracy the daily needs for new ICU admissions, 12 days ahead of each testing data point, over a period of 10 months, with Pearson r = 0.98 (p = 10−197), RMSE = 7,16. We strongly believe that this metric will help guide the timely decisions of both scientists and government officials to tackle pandemic spread and prevent ICU overload by setting effective testing requirements for accurate pandemic monitoring. We propose further study of this novel metric with data from more countries to confirm the validity of the current findings.
Nanoceutical Fabric Prevents COVID-19 Spread through Expelled Respiratory Droplets: A Combined Computational, Spectroscopic and Anti-microbial Study
Authors: Adhikari Aniruddha , Pal Uttam , Bayan Sayan , Mondal Susmita , Ghosh Ria , Darbar Soumendra , Saha-Dasgupta Tanusri , Ray Samit Kumar , Pal Samir Kumar
Published: February 2021

Centers for Disease Control and Prevention (CDC) warns the use of one-way valves or vents in free masks for potential threat of spreading COVID-19 through expelled respiratory droplets. Here, we have developed a nanoceutical cotton fabric duly sensitized with non-toxic zinc oxide nanomaterial for potential use as membrane filter in the one way valve for the ease of breathing without the threat of COVID-19 spreading. A detailed computational study revealed that zinc oxide nanoflowers (ZnO NF) with almost two-dimensional petals trap SARS-CoV-2 spike proteins, responsible to attach to ACE-2 receptors in human lung epithelial cells. The study also confirm significant denaturation of the spike proteins on the ZnO surface, revealing removal of virus upon efficient trapping. Following the computational study, we have synthesized ZnO NF on cotton matrix using hydrothermal assisted strategy. Electron microscopic, steady-state and picosecond resolved spectroscopic studies confirm attachment of ZnO NF to the cotton (i.e., cellulose) matrix at atomic level to develop the nanoceutical fabric. A detailed antimicrobial assay using Pseudomonas aeruginosa bacteria (model SARS-CoV-2 mimic) reveals excellent anti-microbial efficiency of the developed nanoceutical fabric. To our understanding the novel nanoceutical fabric used in one-way valve of a face mask would be the choice to assure breathing comfort along with source control of COVID-19 infection. The developed nanosensitized cloth can also be used as antibacterial/anti CoV-2 washable dress material in general.

GRAPHICAL ABSTRACT

A novel nanoceutical cotton fabric duly sensitized with non-toxic zinc oxide nanoflower can potentially be used as membrane filter in the one way valve of face mask to assure breathing comfort along with source control of COVID-19 infection. The nanoceutical fabric denatures the SARS-CoV-2 spike protein and makes the microorganism ineffective.
Estimating VO2peak in 18-91 year-old adults: Development and Validation of the FitMáx© - Questionnaire
Authors: Meijer Renske , Hooff Martijn van , Papen-Botterhuis Nicole E. , Molenaar Charlotte J.L. , Regis Marta , Timmers Thomas , van de Poll-Franse Lonneke V. , Savelberg Hans H.C.M. , Schep Goof
Published: February 2021

Objectives

Cardiorespiratory fitness plays an essential role in health outcomes and quality of life. Objective assessment of cardiorespiratory fitness is costly, labour intensive and not widely available. Although patient-reported outcome measures estimate cardiorespiratory fitness more cost-efficiently, the current questionnaires lack accuracy. The aim of this study is to develop and validate the FitMáx©-questionnaire, a self-reported questionnaire to estimate cardiorespiratory fitness in healthcare.

Methods

We developed the FitMáx©-questionnaire, consisting of three questions assessing walking, stair climbing, and cycling capacity. A comparison on estimating VO2peak was made with the Duke Activity Status Index (DASI), Veterans Specific Activity Questionnaire (VSAQ) and cardiopulmonary exercise testing as the gold standard. A total of 716 patients and athletes (520 men, 196 women) aged 18□91 performed a CPET in our hospital. We randomly selected 70% of the subjects to fit a linear regression model to estimate VO2peak based on the FitMáx© scores. The remaining 30% of participants was used for validation of this model.

Results

The VO2peak estimated by the FitMáx© strongly correlates with the VO2peak measured objectively with CPET; r=0.95 (0.93□0.96) SEE=3.94 ml·kg-1·min-1. Bias between predicted and measured VO2peak was 0.32 ml·kg-1·min-1 and the 95% limits of agreement were −8.11 □ 9.40 ml·kg-1·min-1. In our sample, the FitMáx scored superiorly on correlation and SEE compared with those from the DASI and VSAQ, r=0.80 (0.73□0.86) SEE=4.22 ml·kg-1·min-1 and r=0.88 (0.84□0.91) SEE=6.61 ml·kg-1·min-1, respectively.

Conclusion

FitMáx© is a valid and accessible questionnaire to estimate cardiorespiratory fitness expressed as VO2peak and shows substantial improvement compared to currently used questionnaires.

Key points

FitMáx© relies on three simple single-answer questions, which are recognizable for a large population, to accurately estimate cardiorespiratory fitness.

The FitMáx© is a self-reported instrument in which involvement of physicians, healthcare providers or other instrumentation is not necessary.

Cardiorespiratory fitness estimated by the FitMáx© may serve as an easily applicable measure in clinical and non-clinical settings.
Subphenotyping of COVID-19 patients at pre-admission towards anticipated severity stratification: an analysis of 778 692 Mexican patients through an age-gender unbiased meta-clustering technique
Authors: Zhou Lexin , Romero Nekane , Martínez-Miranda Juan , Conejero J Alberto , García-Gómez Juan M , Sáez Carlos
Published: February 2021

We apply a meta-clustering technique to discover age-gender unbiased COVID-19 patient subphenotypes based on phenotypical before admission, including pre-existing comorbidities, habits and demographic features, to study the potential early severity stratification capabilities of the discovered subgroups through characterizing their severity patterns including prognostic, ICU and morbimortality outcomes. We used the Mexican Government COVID-19 open data including 778,692 SARS-CoV-2 population-based patient-level data as of September 2020. The meta-clustering technique consists of a two-stage clustering approach combining dimensionality reduction and hierarchical clustering: 56 clusters from independent age-gender clustering analyses supported 11 clinically distinguishable meta-clusters (MCs). MCs 1-3 showed high recovery rates (90.27-95.22%), including healthy patients of all ages; children with comorbidities alongside priority in medical resources; and young obese smokers. MCs 4-5 showed moderate recovery rates (81.3-82.81%): patients with hypertension or diabetes of all ages; and obese patients with pneumonia, hypertension and diabetes. MCs 6-11 showed low recovery rates (53.96-66.94%): immunosuppressed patients with high comorbidity rate; CKD patients with poor survival length and recovery; elderly smokers with COPD; severe diabetic elderly with hypertension; and oldest obese smokers with COPD and mild cardiovascular disease. Group outcomes conformed to the recent literature on dedicated age-gender groups. These results can potentially help in the clinical patient understanding and their stratification towards automated early triage, prior to further tests and laboratory results are available, or help decide priority in vaccination or resource allocation among vulnerable subgroups or locations where additional tests are not available.

Code available at:https://github.com/bdslab-upv/covid19-metaclustering
Dominant Clade-featured SARS-CoV-2 Co-occurring Mutations Reveals Plausible Epistasis: An in silico based Hypothetical Model
Authors: Alam A. S. M. Rubayet Ul , Islam Ovinu Kibria , Hasan Md. Shazid , Islam Mir Raihanul , Mahmud Shafi , Al□Emran Hassan M. , Jahid Iqbal Kabir , Crandall Keith A. , Hossain M. Anwar
Published: February 2021

SARS-CoV-2 is evolved into eight fundamental clades where four (G, GH, GR, and GV) are globally prevalent in 2020. How the featured co-occurring mutations of these clades are linked with viral fitness is the main question here and we thus proposed a hypothetical model using in silico approach to explain the plausible epistatic effects of those mutations on viral replication and transmission. Molecular docking and dynamics analyses showed the higher infectiousness of a spike mutant through more favorable binding of G614 with the elastase-2. RdRp mutation p.P323L significantly increased genome-wide mutations (p<0.0001) since more flexible RdRp (mutated)-NSP8 interaction may accelerate replication. Superior RNA stability and structural variation at NSP3:C241T might impact protein and/or RNA interactions. Another silent 5’UTR:C241T mutation might affect translational efficiency and viral packaging. These four G-clade-featured co-occurring mutations might increase viral replication. Sentinel GH-clade ORF3a:p.Q57H constricted ion-channel through inter-transmembrane-domain interaction of cysteine(C81)-histidine(H57) and GR-clade N:p.RG203-204KR would stabilize RNA interaction by a more flexible and hypo-phosphorylated SR-rich region. GV-clade viruses seemingly gained the evolutionary advantage of the confounding factors; nevertheless, N:p.A220V might modulate RNA binding with no phenotypic effect. Our hypothetical model needs further retrospective and prospective studies to understand detailed molecular events featuring the fitness of SARS-CoV-2.
Neurophobia: A study of Australian medical students and junior doctors
Authors: Yeung Alex , Karimi Leila , Wijeratne Tissa
Published: February 2021

Background

Neurological disorders are the leading cause disability in Australia and the world. Combating the perceived difficulty of neurology or “neurophobia” and improving physician education is a key component in addressing this problem. We aim to conduct the first study to identify whether neurophobia exists in medical students and junior doctors in an Australian population and try to identify factors that may contribute to this in this population.

Methods

A 24 question online validated survey was distributed via email broadcast to all medical students and junior doctors at a metropolitan tertiary care centre in Australia. Responses were collected over 6 weeks with weekly reminder emails for 4 weeks after the initial invitation email.

Results

114 medical students and junior doctors participated in the study. Participants perceived neurology as the most difficult medical speciality compared to 10 other medical specialties (p=0.001). The top three factors contributing to this perceived difficulty were: a lack of understanding of neuroanatomy, lack of diagnostic certainty and lack of clinical exposure. 65% of the participants stated that they had too little planned teaching in neurology with only 36% of the participants having performed a neurology rotation during medical school.

Conclusion

The prevalence of neurophobia in this Australian cohort of medical students and junior doctors is consistent with previous findings from around the world. This concerning finding requires further examination into the contributing factors in order to created trials of targeted interventions in order to resolve this.
A Second Wave? What Do People Mean By COVID Waves? – A Working Definition of Epidemic Waves
Authors: Zhang Stephen X. , Marioli Francisco Arroyo , Gao Renfei
Published: February 2021

Policymakers and researchers describe the COVID-19 epidemics by waves without a common vocabulary on what constitutes an epidemic wave, either in terms of a working definition or operationalization, causing inconsistencies and confusions. A working definition and operationalization can be helpful to characterize and communicate about epidemics. We propose a working definition of epidemic waves in the ongoing COVID-19 pandemic and an operationalization based on the public data of the effective reproduction number R. Our operationalization characterizes the numbers and durations of waves (upward and downward) in 179 countries and reveals patterns that can enable healthcare organizations and policymakers to make better description and assessment of the COVID crisis to make more informed resource planning, mobilization, and allocation temporally in the continued COVID-19 pandemic.

ONE SENTENCE SUMMARY

A working definition and operationalization of waves to enable common ground to understand and communicate COVID-19 crisis.
Risk of plague transmission from human cadavers: a systematic review
Authors: Jullien Sophie , de Silva Nipun Lakshitha , Garner Paul
Published: February 2021

Plague can be fatal. Ebola has raised concern of the risk of infection from bodies of people that have died from other dangerous infectious diseases. We sought to estimate the risk of human remains from someone who was infected with plague transmitting Yersinia pestis. With no clear direct evidence, we developed a causal chain and carefully searched and assessed the literature at each step: we assessed the infectiousness of body fluids of people ill with plague; we sought for reported infection acquired from human and animal cadavers; and examined evidence of body fluid infectiousness of cadavers, seeking any information about the length of infectiousness. We concluded that pneumonic plague can occur after intense manipulation of the cadaver, presumably from inhalation of respiratory droplets; and that bubonic plague can occur after contact with infected blood in people with skin cuts or abrasions. Establishing a quantitative measure of risk was not possible from the evidence available.

Author summary

Plague is an infectious disease that is of particular concern due to its high risk for human outbreaks. Understanding the level and duration of infectiousness of the body of someone who was infected with plague is essential to establish adequate preventive measures while handling corpses. We found limited evidence that human cadavers who have died from plague remain infectious, both from inhalation of particles generated by handling and by direct skin contact.
A Complex Model of Clinical Narrative Information for the Diagnostic Act
Authors: Chartash David , Rosenman Marc B , Bollen Johan , Dickinson Markus , Downs Stephen M
Published: February 2021

Background

The act of diagnosis is one which precipitates semiotic closure, the complex integration of signs and symptoms through cognitive perspectives to ultimately activate causal reasoning and calibrate the assignment of a disease entity to the patient. In writing about this act, physicians encode both structured and unstructured information into the medical record. Unstructured information contains a latent structure which entwines both the cognitive components of the diagnostic act and the linguistic patterns associated with clinical documentation. Existing models of clinical language primarily use a physical or dialogic model of information as their basis, and do not adequately account for the complexity inherent in the diagnostic act.

Methods

Framing the diagnostic information collected in clinical care as a narrative, we developed a model representative of said information, accounting for its content and structure, as well as the inherent complexity therein. Using an exemplar text, we present the use of known predication and semantic relations from ontological (the Unified Medical Language System) and linguistic theory (Rhetorical Structure Theory) to facilitate the operationalization of the model, and analyze the result.

Results

The resulting model is demonstrated to be complex, representative of the clinical narrative text, and is fundamentally aligned with the clinical acts of both documentation and diagnosis. We find the model’s representation of the cognitive aspects of narrative consistent with models of reading, as well as an adequate model of information as presented by clinical medicine and the clinical sub-language.

Conclusions

We present a model to represent diagnostic information in the physician’s note which accounts for the clinical and textual narrative precipitated by the cognition involved in encoding said information into the unstructured medical record. This model prepends the development of (computational) linguistic models of the clinical sublanguage within the physician’s note as it relates to diagnosis, beyond the information level of the lexical unit. Such analysis would facilitate better reflection on the structure and meaning of the clinical note, offering improvements to medical education and care.
Antibiotics and hospital-associatedClostridioides difficileinfection: systematic review and meta-analysis 2020 update
Authors: Slimings Claudia , Riley Thomas V.
Published: February 2021

Background

Clostridioides difficileinfection (CDI) is the most common cause of healthcare facility-associated (HCFA) infectious diarrhoea in high-income countries. Antibiotic use is the most important modifiable risk factor for CDI. The most recent systematic review covered studies published until 31stDecember 2012.

Objectives

To update the evidence for epidemiological associations between specific antibiotic classes and HCFA-CDI for the period 1stJanuary 2013 to 31stDecember 2020.

Data sources

PubMed, Scopus, Web of Science Core Collection, WorldCat, and Proquest Dissertations and Theses.

Study eligibility criteria, participants and exposures

Eligible studies were those conducted among adult hospital inpatients, measured exposure to individual antibiotics or antibiotic classes, included a comparison group, and measured the occurrence of HCFA-CDI as an outcome.

Study appraisal and synthesis methods

The Newcastle–Ottawa Scale for the Assessment of Quality was used to appraise study quality. To assess the association between each antibiotic class and HA-CDI, a pooled random effects meta-analysis was undertaken. Metaregression and sub-group analysis was used to investigate study characteristics identifieda priorias potential sources of heterogeneity.

Results

Carbapenems, and 3rdand 4thgeneration cephalosporin antibiotics remain most strongly associated with HCFA-CDI, with cases more than twice as likely to have recent exposure to these antibiotics prior to developing CDI. Modest associations were observed for fluoroquinolones clindamycin, and beta-lactamase inhibitor combination penicillin antibiotics.

Limitations

Individual study effect sizes were variable and heterogeneity was observed for most antibiotic classes. Availability of a single reviewer to select, extract and critically appraise the studies.

Conclusions

This review provides the most up to date synthesis of evidence in relation to the risk of HCFA-CDI associated with exposure to specific antibiotic classes. Studies were predominantly conducted in North America or Europe and more studies outside of these settings are needed.

Registration number

Prospero CRD42020181817
Widespread Cortical Thickness Reductions Following Non-medical Use of Ketamine: a Structural MRI Study of Individuals with Ketamine Dependence
Authors: Tang Jinsong , Wu Qiuxia , Qi Chang , Xie An , Liu Jianbin , Sun Yunkai , Yuan Tifei , Chen Wei , Liu Tieqiao , Hao Wei , Liao Yanhui
Published: February 2021

Background

A version of ketamine, called Esketamine has been approved for treatment-resistant depression (TRD). Ketamine (“K powder”), a “dissociative” anesthetic agent, however, has been used non-medically alone or with other illicit substances. Our previous studies showed a link between non-medical ketamine use and brain structural and functional alterations. We found dorsal prefrontal gray matter reduction in chronic ketamine users. It is unknown, however, whether these observations might parallel findings of cortical thickness alterations. This study aimed at exploring cortical thickness abnormalities following non-medical, long-term use of ketamine.

Methods

Structural brain images were acquired for 95 patients with ketamine dependence, and 169 drug-free healthy controls. FreeSurfer software was used to measure cortical thickness for 68 brain regions. Cortical thickness was compared between the two groups using analysis of covariance (ANCOVA) with covariates of age, gender, educational level, smoking, drinking, and whole brain mean cortical thickness. Results were considered significant if the Bonferroni corrected P-value < 0.01.

Results

Compared to healthy controls, patients with ketamine dependence have widespread decreased cortical thickness, with the most extensive reductions in the frontal (including the dorsolateral prefrontal cortex, DLPFC) and parietal (including the precuneus) lobes. Increased cortical thickness was not observed in ketamine users relative to comparison subjects. Estimated total lifetime ketamine consumption is correlated with the right inferior parietal and the right rostral middle frontal cortical thickness reductions.

Conclusions

This study provides first evidence that, compared with healthy controls, chronic ketamine users had cortical thickness reductions.
The Good, the Bad and the Stochastic: How Living in Groups Innately Supports Cooperation
Authors: Steiner Klaus F.
Published: February 2021

Based on theoretical considerations and computer simulations, I show that living in groups brings advantages for cooperative traits through purely stochastic effects that result from the division of a population into groups. These advantages can be sufficient to compensate individual selection pressures that may be associated with the cooperative traits. In more complex agent-based simulation models, this effect combined with some migration between the groups leads to stable dynamic equilibria between cooperative and defective replicators in the population.
Excess Serum Interleukin-18 Distinguishes Patients with Pathogenic Mutations in PSTPIP1
Authors: Stone Deborah L. , Ombrello Amanda , Arostegui Juan I. , Schneider Corinne , Jesus Adriana de , Girard-Guyonvarc’h Charlotte , Gabay Cem , Lee Wonyong , Chae Jae Jin , Aksentijevich Ivona , Goldbach-Mansky Raphaela , Kastner Daniel L. , Canna Scott W.
Published: February 2021

Objective

Dominantly-inherited mutations in PSTPIP1 cause a family of monogenic autoinflammatory diseases epitomized by Pyogenic Arthritis, Pyoderma gangrenosum, and Acne (PAPA) syndrome. The connections between PSTPIP1 and PAPA are poorly understood, although in vitro evidence suggests increased activation of the pyrin-inflammasome. We sought to identify biomarkers of potential mechanistic, diagnostic, and therapeutic utility specific to autoinflammatory diseases.

Methods

Clinical and genetic data and sera were obtained from patients referred with concern for PAPA syndrome, as well as relevant disease controls. Serum Interleukin-18 (IL-18) and related biomarkers were assessed by bead-based assay.

Results

Symptoms in PSTPIP1 mutation-positive PAPA patients overlapped with those of mutation-negative PAPA-like patients, but the former were younger at onset and had more arthritis. We found uniform elevation of total IL-18 in PAPA patients at a level approaching NLRC4-associated Macrophage Activation Syndrome (MAS) and well beyond Familial Mediterranean Fever. IL-18 elevation in PAPA patients’ sera persisted despite fluctuations in disease activity. IL-18 Binding Protein (IL-18BP) was modestly elevated, and as such PAPA patients had detectable free IL-18. PAPA patients did not develop MAS, and CXCL9 (an indicator of Interferon-gamma activity) was rarely elevated in their sera.

Conclusion

PAPA syndrome is a refractory, and often disabling monogenic autoinflammatory disease associated with chronic elevation of serum IL-18, but not risk for MAS. This finding instructs our understanding of the origins of excess IL-18, its potential spectrum of pathogenic effects, and the possible role for IL-18 blockade in refractory PAPA syndrome.
Examining sex differences in neurodevelopmental and psychiatric genetic risk in anxiety and depression
Authors: Martin Joanna , Asjadi Kimiya , Hubbard Leon , Kendall Kimberley , Pardiñas Antonio F. , Jermy Bradley , Lewis Cathryn M. , Baune Bernhard T. , Boomsma Dorret I. , Hamilton Steven P. , Lucae Susanne , Magnusson Patrik K. , Martin Nicholas G. , McIntosh Andrew M. , Mehta Divya , Mors Ole , Mullins Niamh , Penninx Brenda W. J. H. , Preisig Martin , Rietschel Marcella ,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Jones Ian , Walters James T. R. , Rice Frances , Thapar Anita , O’Donovan Michael
Published: February 2021

Anxiety and depression are common mental health disorders and have a higher prevalence in females. They are modestly heritable, share genetic liability with other psychiatric disorders, and are highly heterogeneous. There is evidence that genetic liability to neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) is associated with anxiety and depression, particularly in females. We investigated sex differences in family history for neurodevelopmental and psychiatric disorders and neurodevelopmental genetic risk burden (indexed by ADHD polygenic risk scores (PRS) and rare copy number variants; CNVs) in individuals with anxiety and depression, also taking into account age at onset.

We used two complementary datasets: 1) participants with a self-reported diagnosis of anxiety or depression (N=4,178, 65.5% female; mean age=41.5 years; N=1,315 with genetic data) from the National Centre for Mental Health (NCMH) cohort and 2) a clinical sample of 13,273 (67.6% female; mean age=45.2 years) patients with major depressive disorder (MDD) from the Psychiatric Genomics Consortium (PGC). We tested for sex differences in family history of psychiatric problems and presence of rare CNVs (neurodevelopmental and >500kb loci) in NCMH only and for sex differences in ADHD PRS in both datasets.

In the NCMH cohort, females were more likely to report family history of neurodevelopmental and psychiatric disorders, but there were no robust sex differences in ADHD PRS or presence of rare CNVs. There was weak evidence of higher ADHD PRS in females compared to males in the PGC MDD sample, particularly in those with an early onset of MDD.

These results do not provide strong evidence of sex differences in neurodevelopmental genetic risk burden in adults with anxiety and depression. This indicates that sex may not be a major index of neurodevelopmental genetic heterogeneity, that is captured by ADHD PRS and rare CNV burden, in adults with anxiety and depression.
Seven-month kinetics of SARS-CoV-2 antibodies and protective role of pre-existing antibodies to seasonal human coronaviruses on COVID-19
Authors: Ortega Natalia , Ribes Marta , Vidal Marta , Rubio Rocío , Aguilar Ruth , Williams Sarah , Barrios Diana , Alonso Selena , Hernández-Luis Pablo , Mitchell Robert A. , Jairoce Chenjerai , Cruz Angeline , Jimenez Alfons , Santano Rebeca , Méndez Susana , Lamoglia Montserrat , Rosell Neus , Llupià Anna , Puyol Laura , Chi Jordi , Rodrigo Melero Natalia , Parras Daniel , Serra Pau , Pradenas Edwards , Trinité Benjamin , Blanco Julià , Mayor Alfredo , Barroso Sonia , Varela Pilar , Vilella Anna , Trilla Antoni , Santamaria Pere , Carolis Carlo , Tortajada Marta , Izquierdo Luis , Angulo Ana , Engel Pablo , García-Basteiro Alberto L. , Moncunill Gemma , Dobaño Carlota
Published: February 2021

Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and its determinants, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E,NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed-up for 6 months (N = 578). Seroprevalence increased over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, were stable over time, except IgG to nucleocapsid antigen and IgM levels that waned. After the peak response, anti-spike antibody levels increased from ∼150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. Pre-existing antibodies to alpha-HCoV were lower in individuals who subsequently seroconverted for SARS-CoV-2. IgG and IgA to HCoV were significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease.
Modelling the Impact of Delaying Vaccination Against SARS-CoV-2 Assuming Unlimited Vaccines Supply
Authors: Amaku Marcos , Covas Dimas Tadeu , Bezerra Coutinho Francisco Antonio , Azevedo Raymundo Soares , Massad Eduardo
Published: February 2021

Background

At the moment we have more than 109 million cases and 2.4 million deaths around the world and vaccination represents the only hope to control the pandemic. Imperfections in planning vaccine acquisition and difficulties in implementing distribution among the population, however, have hampered the control of the virus so far.

Methods

We propose a new mathematical model to estimate the impact of vaccination delay against COVID-19 on the number of cases and deaths by the disease in Brazil. We apply the model to Brazil as a whole and to the State of Sao Paulo, the most affected by COVID-19 in Brazil. We simulated the model for the populations of the State of Sao Paulo and Brazil as a whole, varying the scenarios related to vaccine efficacy and compliance from the populations.

Results

The model projects that, in the absence of vaccination, almost 170 thousand deaths and more than 350 thousand deaths until the end of 2021 for Sao Paulo and Brazil, respectively. If in contrast, Sao Paulo and Brazil had enough vaccine supply and so started a vaccination campaign in January with the maximum vaccination rate, compliance and efficacy, they could have averted more than 112 thousand deaths and 127 thousand deaths, respectively. In addition, that for each month of delay the number of deaths increases monotonically in a logarithm fashion, for both the State of Sao Paulo and Brazil as a whole.

Conclusions

Our model shows that the current delay in the vaccination schedules that is observed in many countries has serious consequences in terms of mortality by the disease and should serve as an alert to health authorities to speed the process up such that the highest number of people to be immunized is reached in the shortest period of time.
Lower respiratory tract sampling via bronchoscopy in COVID-19 ARDS: A focus on microbiology, cellular morphology, cytology and management impact
Authors: Bansal Sameer , Kalpakam Hariprasad , Kumar Ashwin , Thorbole Anmol , Varsha Amogha , Mehta Ravindra M
Published: February 2021

Background

Lower respiratory tract (LRT) sampling via bronchoscopy has been done sparingly in COVID-19 ARDS due to the high aerosol risk for the health care workers (HCW). Valuable information can be gained by detailed evaluation of bronchoscopic LRT samples.

Methods

LRT samples were obtained by bedside bronchoscopy performed in suspected or confirmed severe COVID-19 ARDS patients on mechanical ventilation. Only positive cases were included in the study. Microbiological, cellular and cytological studies including LRT COVID-19 RT-PCR were performed and analysed.

Results

100 samples were collected from 63 patients, 53 were males (84%). 43 patients (68%) had at least 1 comorbidity. 55% cases had secondary bacterial infection as demonstrated by positive culture. Most of these infections were due to multi-drug resistant organisms (94.5%). The most common organisms were Klebsiella pneumoniae and Acinetobacter baumanii in 56.3% and 14.5% cases respectively. Fungal superinfection was observed in 9 patients (14.3%). Bronchoscopy helped confirm COVID-19 diagnosis in 1 patient and helped rule out COVID-19 in 3 patients who were eventually excluded from the study. The median BAL fluid (BALF) WBC count was 953 (IQR; 400-2717), with mean neutrophil count 85.2% (±13.9), and mean lymphocyte count 14.8% (±13.9). Repeat sampling done in some patients showed a progressive increase in the total WBC count in BALF, an increase in neutrophil percentage, and a higher chance of isolating an organism on the culture (81% repeat procedures were culture positive). The rate of super-infection increased with longer duration of illness. Patients with superinfection also had an increased WBC count (1001 vs 400), and lower lymphocyte percentage (19% vs 12% - OR - 6.8 [95%CI −14.3 − 0.7]). Bronchoscopic LRT sampling contributed significantly to modifying antibiotic coverage and discontinuing steroids in 37% cases.

Conclusion

This study describes a detailed analysis of bronchoscopic LRT sampling in critically ill COVID-19 patients. This provided important basic and applied information augmenting disease understanding and contributing to clinical management when there was scant information available in the pandemic.
Vaccination efforts in Brazil: scenarios and perspectives under a mathematical modeling approach
Authors: Vilches Thomas Nogueira , Rubio Felipe Alves , Forti Perroni Rafael Augusto , de Almeida Gabriel Berg , Branco Fortaleza Carlos Magno Castelo , Ferreira Cláudia Pio
Published: February 2021

An agent-based model is proposed to access the impact of vaccination strategies to halt the COVID-19 spread. The model is parameterized using data from São Paulo State, Brazil. It was considered the two vaccines that are already approved for emergency use in Brazil, the CoronaVac vaccine developed by the Chinese bio-pharmaceutical company Sinovac and the Oxford-AstraZeneca vaccine (ChadOx1) developed by Oxford University and the British laboratory AstraZeneca. Both of them are two-dose schemes, but the efficacy and the interval between doses are different. We found that even in the worst scenario, in which the vaccine does not prevent infection either severe symptoms, the number of deaths decreases from 122 to 99 for CoronaVac application and to 80 for ChadOx1 administration. The same patterns have been seen in hospitalizations. Nevertheless, we show that when a low risk perception occurs, the reduction values decrease between 2% to 4%. Moreover, the increase of disease prevalence also jeopardizes immunization, showing the importance of the mitigation measures maintenance. On the other hand, doubling the vaccination rate would be able to significantly decrease the disease outcomes, reducing deaths by up to 74.4%. In conclusion, vaccination, along with non-pharmaceutical measures, is key to the control of COVID-19 in Brazil.
COVID-19 Spreading Dynamics in an Age-Structured Population with Selective Relaxation of Restrictions for Vaccinated Individuals : a Mathematical Modeling Study
Authors: Shayak B , Sharma Mohit M , Mishra Anand K
Published: February 2021

Background

COVID-19 vaccination of healthcare and other essential workers is underway in many countries while immunization of the general public is expected to begin in the next several weeks. We consider the question of whether people who have received the vaccine can be selectively and immediately permitted to return to normal activities.

Methods

We use a delay differential equation model to calculate the effects of vaccinee “immunity passports” on the epidemic spreading trajectories. The model incorporates age-structuring to account for children who are ineligible for vaccination, and senior citizens who are especially vulnerable to the disease. We consider consensus strains of virus as well as high-transmissibility variants such as B1.1.7 and B1.351 in our analysis.

Results

We find that with high vaccine efficacy of 80 percent or greater, unrestricted vaccinee—vaccinee interactions do not derail the epidemic from a path towards elimination. Vaccinee—non-vaccinee interactions should however be treated with far more caution. At current vaccine administration rates, it may be the better part of a year before COVID-19 transmission is significantly reduced or ceased. With lower vaccine efficacy of approximately 60 percent, restrictions for vaccinees may need to remain in place until the elimination of the disease is achieved. In all cases, the death tolls can be reduced by vaccinating the vulnerable population first.

Conclusions

Designing high-efficacy vaccines with easily scalable manufacturing and distribution capacity should remain on the priority list in academic as well as industrial circles. Performance of all vaccines should continue to be monitored in real time during vaccination drives with a view to analysing socio-demographic determinants of efficacy, if any, and optimizing distribution accordingly. A speedy and efficacious vaccination drive augmented with selective relaxations for vaccinees will provide the smoothest path out of the pandemic with the least additional caseloads, death tolls and socio-economic cost.
An evolutionarily conserved coreceptor gene is essential for CLAVATA signaling inMarchantia polymorpha
Authors: Takahashi Go , Betsuyaku Shigeyuki , Okuzumi Natsuki , Kiyosue Tomohiro , Hirakawa Yuki
Published: February 2021

Growth and development of land plants are controlled by CLAVATA3/EMBRYO SURROUNDING REGION-related (CLE) family of peptide hormones. In contrast to the genetic diversity of CLE family in flowering plants, the liverwortMarchantia polymorphapossesses a minimal set of CLE, MpCLE1(TDIF homolog) and MpCLE2 (CLV3 homolog). MpCLE1 and MpCLE2 peptides exert distinct function at the apical meristem ofM. polymorphagametophyte via specific receptors, MpTDIF RECEPTOR (MpTDR) and MpCLAVATA1 (MpCLV1), respectively, both belonging to the subclass XI of leucine-rich repeat receptor-like kinases (LRR-RLKs). Biochemical and genetic studies in Arabidopsis have shown that TDR/PXY family and CLV1/BAM family recognize the CLE peptide ligand in a heterodimeric complex with a member of subclass-II coreceptors. Here we show that three LRR-RLK genes ofM. polymorphaare classified into subclass II, representing three distinct subgroups evolutionarily conserved in land plants. To address the involvement of subclass-II coreceptors inM. polymorphaCLE signaling, we performed molecular genetic analysis on one of them, MpCLAVATA3 INSENSITIVE RECEPTOR KINASE(MpCIK). Two knockout alleles for MpCIKformed narrow apical meristems marked bypromMpYUC2:GUSmarker, which were not expanded by MpCLE2 peptide treatment, phenocopying Mpclv1. Loss of sensitivity to MpCLE2 peptide was also observed in gemma cup formation in both Mpclv1and Mpcik. Biochemical analysis using aNicotiana benthamianatransient expression system revealed weak association between MpCIK and MpCLV1, as well as MpCIK and MpTDR. While MpCIK may also participate in MpCLE1 signaling, our data show that the conserved CLV3-CLV1-CIK module functions inM. polymorpha, controlling meristem activity for development and organ formation for asexual reproduction.