bluuebunny/crossref_metadata_2025 huggingface dataset:
Behaviour across the lifespan in Cornelia de Lange syndrome
Authors: Groves Laura , Oliver Chris , Moss Joanna
Published: December 2020

Purpose of review

While previous reviews have extended descriptions of the behavioural phenotype of Cornelia de Lange syndrome (CdLS) significantly, potential changes with age across the lifespan have been neglected. Age-related difference in the behavioural phenotype constitutes preliminary evidence of change with age. Documenting and understanding the developmental trajectories of behaviours is informative as it enables identification of risk periods for behavioural challenges and compromised mental health.

Recent findings

Recent cross sectional, longitudinal and mixed design studies report differing presentations of the behavioural phenotype across the lifespan. Of particular interest are autistic characteristics and behaviours consistent with compromised mental health, particularly anxiety and negative affect, which are reported to be more common and severe in older individuals. Preliminary evidence for identified causal pathways with consideration of biological, cognitive and environmental factors are discussed.

Older individuals with CdLS appear to be at greater risk of poorer psychological wellbeing than younger peers with significant implications for risk informed preventive and early interventions. Further work is required to document the behavioural phenotype across the lifespan with consideration of multiple factors that may influence the trajectory and extent of negative outcomes
Recent developments in Phelan–McDermid syndrome research: an update on cognitive development, communication and psychiatric disorders
Authors: Vogels Annick , Droogmans Gilles , Vergaelen Elfi , Van Buggenhout Griet , Swillen Ann
Published: December 2020

Purpose of review

The purpose of this review is to summarize the literature on cognitive development, communication, behavioral or psychiatric aspects in Phelan–McDermid syndrome (PMS) and to discuss the clinical implications and recommendations of these summarized findings.

Recent findings

PMS is often associated with severe communication impairments, behavioral or psychiatric problems and regression. These challenges may adversely affect and impair the quality of life of the individual with PMS and his family.

Individuals with PMS experience intellectual disability, communication and behavioral/psychiatric challenges, such as catatonia, bipolar disorder and regression across the lifespan. Providing appropriate guidance and support to them and their families demands a better understanding of these challenges.
A cohort study of 223 patients explores the clinical risk factors for the severity diagnosis of COVID-19
Authors: Huang Yongsheng , Lyu Xiaoyu , Li Dan , Wang Yujun , Wang Lin , Zou Wenbin , Wei Yingxin , Wu Xiaowei
Published: December 2020

BACKGROUND

Coronavirus Disease 2019 (COVID-19) has recently become a public emergency and a worldwide pandemic. The clinical symptoms of severe and non-severe patients vary, and the case-fatality rate (CFR) in severe COVID-19 patients is very high. However, the information on the risk factors associated with the severity of COVID-19 and of their prognostic potential is limited.

METHODS

In this retrospective study, the clinical characteristics, laboratory findings, treatment and outcome data were collected and analyzed from 223 COVID-19 patients stratified into 125 non-severe patients and 98 severe patients. In addition, a pooled large-scale meta-analysis of 1646 cases was performed.

RESULTS

We found that the age, gender and comorbidities are the common risk factors associated with the severity of COVID-19. For the diagnosis markers, we found that the levels of D-dimer, C-reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin (PCT) were significantly higher in severe group compared with the non-severe group on admission (D-Dimer: 87.3% vs. 35.3%, P<0.001; CRP, 65.1% vs. 13.5%, P<0.001; LDH: 83.9% vs. 22.2%, P<0.001; PCT: 35.1% vs. 2.2%, P<0.001), while the levels of aspartate aminotransferase (ASP) and creatinine kinase (CK) were only mildly increased. We also made a large scale meta-analysis of 1646 cases combined with 4 related literatures, and further confirmed the relationship between the COVID-19 severity and these risk factors. Moreover, we tracked dynamic changes during the process of COVID-19, and found CRP, D-dimer, LDH, PCT kept in high levels in severe patient. Among all these markers, D-dimer increased remarkably in severe patients and mostly related with the case-fatality rate (CFR). We found adjuvant antithrombotic treatment in some severe patients achieved good therapeutic effect in the cohort.

CONCLUSIONS

The diagnosis markers CRP, D-dimer, LDH and PCT are associated with severity of COVID-19. Among these markers, D-dimer is sensitive for both severity and CFR of COVID-19. Treatment with heparin or other anticoagulants may be beneficial for COVID-19 patients.

Funding

This study was supported by funding from the National Key Research and Development Program of China (2016YFC1302203); Beijing Nova Program (grant number: xx2018040).

Role of the funding source

The funding listed above supports this study, but had no role in the design and conduct of the study.
Peripheral and lung resident T cell responses against SARS-CoV-2
Authors: Grau-Expósito Judith , Sánchez-Gaona Nerea , Massana Núria , Suppi Marina , Astorga-Gamaza Antonio , Perea David , Rosado Joel , Falcó Anna , Kirkegaard Cristina , Torrella Ariadna , Planas Bibiana , Navarro Jordi , Suanzes Paula , la Sierra Daniel Alvarez-de , Ayora Alfonso , Sansano Irene , Esperalba Juliana , Andrés Cristina , Antón Andrés , Ramón y Cajal Santiago , Almirante Benito , Pujol-Borrell Ricardo , Falcó Vicenç , Burgos Joaquín , Buzón María J. , Genescà Meritxell
Published: December 2020

Considering that SARS-CoV-2 interacts with the host at the respiratory tract mucosal interface, T cells strategically placed within these surfaces, namely resident memory T cells, will be essential to limit viral spread and disease. Importantly, these cells are mostly non-recirculating, which reduces the window of opportunity to examine circulating lymphocytes in blood as they home to the lung parenchyma. Here, we demonstrate that viral specific T cells can migrate and establish in the lung as resident memory T cells remaining detectable up to 10 months after initial infection. Moreover, focusing on the acute phase of the infection, we identified virus-specific T cell responses in blood with functional, migratory and apoptotic patterns modulated by viral proteins and associated with clinical outcome. Our study highlights IL-10 secretion by virus-specific T cells associated to a better outcome and the persistence of resident memory T cells as key players for future protection against SARS-CoV-2 infection.
Sensorimotor cortex forms prism adaptation memories in older adults and stroke patients
Authors: Spitz Gershon , Petitet Pierre , Bultitude Janet , Farnè Alessandro , Luaute Jacques , O’Shea Jacinta
Published: December 2020

Stroke is the largest cause of complex disability in adults. Approximately half of right-hemisphere stroke survivors suffer spatial neglect–an inability to voluntarily orient to people or objects in contralesional space. Neglect is a significant impediment to successful community reintegration. Prism adaptation (PA) is a promising behavioural intervention that can alleviate symptoms of spatial neglect. PA induces a leftward pointing bias–the prism after-effect (AE). In neglect, the prism AE generalises to improve other sensory, motor, and cognitive domains. Although the formation of an AE is a key index in neglect, we do not yet know where it is formed in the brain. Here, we used a novel computational fMRI-based approach to study, for the first time, the brain circuits that mediate the formation of PA in stroke survivors and age matched controls. Healthy individuals (n = 17) and stroke patients (n = 11) performed prism adaptation during fMRI. Temporal signatures of memory formation were extracted from the behavioural data using a state-space model and regressed against the fMRI data. This revealed that, in both groups, fMRI signal in left sensorimotor cortex correlated with the gradual formation of the prism after-effect during adaptation. This indicates that the sensorimotor cortex may be a useful target for neuromodulation that aims to improve the persistence of therapeutic prism after effects.
Tuberculous meningitis in adult patients of a Mexican neurological referral center: A-six-year retrospective cohort study
Authors: Daniela Maldonado-Diaz Ellis , Luis Soto-Hernández José , Citlaltepetl Salinas-Lara , Ashuin Kammar-Garcia , Graciela Cárdenas
Published: December 2020

Introduction

Tuberculosis (TB) remains as an important concern of public health worldwide because the high prevalence and severe sequelae. Tuberculous meningitis (TBM) is the most lethal and disabling form.

Aim

To describe the clinical, laboratory, and neuroimaging characteristics of TBM on admission at neurological center in Mexico City.

Methods

Retrospective cohort study at the third level neurological center from 2010 to 2016. Clinical follow-up was evaluated at hospital discharge, three months, and one-year either due to lack of follow-up or mortality, during the follow-up the adverse events were registered.

Results

One-hundred and six patients were included, 74 (69.8%) males and 32 (30.2%) females. From these 31 (29.2%) were HIV-positive. The median age was 35.5 (IQR:28-51). Pulmonary TB was found in 25% of the population. Alcoholism was observed in a half of the patients while diabetes in 15%, the latter being significant (p=0.04). Abnormalities in neuroimaging were significant among our population (p=0.003). Only one-third of the population had a positive Lowenstein-Jensen culture. There were no differences in clinical outcomes between HIV positive and non-HIV patients.

Conclusion

Our study shows data to those described in the literature. The initiation of empirical treatment in all patients with a high clinical suspicion of tuberculosis mandatory to try to avoid severe neurological sequels.
An evaluation of the accuracy of prehospital eFAST in the assessment of polytrauma by a physician-staffed helicopter emergency medical service
Authors: Partyka Christopher , Miller Matthew , Bliss Jimmy , Burns Brian , Coggins Andrew , Fiorentino Michele , Goorkiz Pierre
Published: December 2020

BACKGROUND

While the accuracy of point of care ultrasound in trauma is well understood, there is limited reporting on the efficacy of prehospital ultrasound by helicopter emergency medical service (HEMS). In severe trauma, early diagnosis and communication of life-threatening injuries has the potential to facilitate timely care. This HEMS ultrasound registry evaluation set out to report the accuracy of the extended focused assessment with sonography in trauma (eFAST) exam.

METHODS

Retrospective review of trauma patients who received a prehospital eFAST by GSA-HEMS clinicians between 1 January 2013 and 31 December 2017. Clinician interpretations of these scans were compared to immediate in-hospital CT imaging or operating room reports as the gold-standard reference. The primary outcome measure was the accuracy of eFAST for intraperitoneal free fluid compared to hospital CT scan. Secondary outcomes included accuracy of eFAST for pneumothorax, haemothorax and pericardial fluid, comparison of clinician seniority and whether prehospital interventions were supported by eFAST results.

RESULTS

We included 896 patients who underwent eFAST by prehospital clinicians. 411 patients had adequate in-hospital data available for comparison. For the primary outcome of IPFF, eFAST had a sensitivity of 25% [95% CI 16-36%] and specificity of 96% [95% CI 93-98%]. Sensitivities and specificities were calculated for pneumothorax (38% and 96% respectively), haemothorax (17% and 97% respectively) and pericardial effusion (17% and 100% respectively). Fifty percent of patients had thoracostomies supported by lung US whilst 24% of patients who received a prehospital blood transfusion had an eFAST negative for haemorrhage.

CONCLUSION

This study shows that prehospital eFAST is a reliable tool for ruling in the diagnoses of intraperitoneal free fluid, pneumothorax, haemothorax and pericardial effusion and as expected less reliable than CT imaging for these injuries.

What is already known about this subject?

Extended Focused Abdominal Sonography in Trauma (eFAST) is widely used in an in hospital setting for the assessment of blunt and penetrating injury.

Point of care sonography in the prehospital setting has become feasible due to advances in technology, widespread physician training and availability of scanning devices.

What does this study add?

Our study demonstrates that prehospital eFAST is highly specific for the diagnosis of significant abdominal haemorrhage.

Prehospital eFAST is less accurate for other injuries including haemothorax and pneumothorax. The explanation for this finding is unclear, but may be associated with scanning earlier in the clinical course, diminishing sensitivity, environmental factors or human factors.

Further studies are required to understand the optimal role of point of care ultrasound in the prehospital setting.
Protocol for longitudinal assessment of SARS-CoV-2-specific immune responses in healthcare professionals in Hannover, Germany: the prospective, longitudinal, observational COVID-19 Contact (CoCo) study
Authors: Jablonka Alexandra , Happle Christine , Cossmann Anne , Stankov Metodi V. , Scharff Anna Zychlinsky , Ernst Diana , Behrens Georg M.N.
Published: December 2020

Background

During the current pandemic, healthcare professionals (HCP) have been at the frontline of the crisis. Serological screening may help in identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence. However, given the rapidly evolving situation in spring 2020, many questions regarding coronavirus disease 2019 (COVID-19) infection risk and utility of serological testing remained unanswered. To address these questions, we initiated the COVID-19 Contact (CoCo) study at Hannover Medical School, a large university hospital in Northern Germany and affiliated care providers.

Methods

The CoCo study is an ongoing, prospective, longitudinal, observational study in HCP and individuals with potential contact to SARS-CoV-2. It monitors anti-SARS-CoV-2 immunoglobulin serum levels and collects information on symptoms of respiratory infection, work and home environment, and self-perceived SARS-CoV-2 infection risk. Inclusion criteria are (1) working as HCP in clinical care at our university centre, affiliated hospitals or private practices, (2) written informed consent and (3) age >18 years. Exclusion criteria are (1) refusal to give informed consent and (2) contraindication to venepuncture. Study participants are asked to provide weekly to six-monthly samples (7.5 ml serum and 7.5 ml EDTA blood) and fill out a questionnaire. Since March 2020, around 1250 HCP have been included in the study. At each study visit, sera are screened for anti-SARS-CoV-2 spike protein 1 (S1) immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA). Positive or borderline positive samples are re-assessed with an alternative serological test. Individual results for each study participant are made available online via a dedicated study website. This study also aims to compare different serological testing assays, as well as explore further humoral and cellular immune markers. Study protocols are continually adapted to the rapidly evolving situation of the current pandemic.

Discussion

This ongoing prospective study will aim to answer central questions on the prevalence and kinetics of anti-SARS-CoV-2-humoral immune responses and the validity of serological testing of HCP in a region with high healthcare standard and comparatively low COVID-19 prevalence. As such, our results are highly relevant to other regions and may support HCP around the world in managing this unprecedented situation.

Trial registration

German Clinical Trial Registry, DRKS00021152. Registered 4th April 2020 -retrospectively registered,https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021152

Protocol summary
Top 100 cited systematic reviews and meta-analyses in the major journals of oral and maxillofacial surgery : a bibliometric analysis
Authors: Almoraissi Essam Ahmed , Galvão Endi Lanza , Nikolaos Christidis Saulo , Falci Gabriel Moreira
Published: December 2020

The aim of this bibliometric research was to identify and analyze the top 100 cited systematic reviews in the field of oral and maxillofacial surgery. Using the Web of Science-database without restrictions on publication year or language, a bibliometric analysis was performed for the five major journals of oral and maxillofacial surgery: International Journal of Oral and Maxillofacial Surgery, Journal of Oral and Maxillofacial Surgery, Journal of Cranio-maxillofacial Surgery, British Journal of Oral & Maxillofacial Surgery and Oral Surgery Oral medicine Oral pathology Oral radiology. The most top-cited systematic review was published in 2015 with a total of 200 citations on survival and success rates of dental implants, consistent with the finding that “pre- and peri-implant surgery and dental implantology”, and “craniomaxillofacial deformities and cosmetic surgery” were the most frequently-cited topics (22% each). The International Journal of Oral and Maxillofacial Surgery and Journal of Oral and Maxillofacial Surgery displayed have got most citations in total and in average per publication. The outcome of this article can be used as a source of information not just for researchers but also for clinicians and students, and of which areas have a large impact on the field of oral and maxillofacial surgery but cannot reflect the quality of the included systematic reviews.
The Moderating Role of Parental Sleep Knowledge on Children with Developmental Disabilities and Their Parents’ Sleep
Authors: Halstead Elizabeth J. , Jones Alexandra , Esposito Gianluca , Dimitriou Dagmara
Published: December 2020

Background

Children with intellectual and developmental difficulties often experience 2 sleep problems, which in turn may impact parental sleep patterns. This study explored the role of parental sleep knowledge as a moderator on the relationship between child sleep and parental sleep impairment.

Methods

582 parents or caregivers (92.6% mothers) of children with different developmental disabilities (Age M = 9.34, 29.5 % females) such as Down’s syndrome, participated in an online survey. Multiple regression analysis was conducted.

Results

Parental sleep knowledge of child sleep was a moderating variable in the relationship between child sleep nocturnal duration and parental sleep impairment. Although overall, sleep knowledge was high in this sample, two specific knowledge gaps were identified namely child sleep duration requirements, and the recognition of signs of a well-rested child.

Conclusion

This study has provided evidence that increased parental sleep knowledge can positively impact both child and parental sleep outcomes.
McQ – An open-source multiplexed SARS-CoV-2 quantification platform
Authors: Vonesch Sibylle C , Bredikhin Danila , Dobrev Nikolay , Villacorta Laura , Kleinendorst Rozemarijn , Cacace Elisabetta , Flock Julia , Frank Max , Jung Ferris , Kornienko Julia , Mitosch Karin , Osuna-López Mireia , Zimmermann Jürgen , Göttig Stephan , Hamprecht Axel , Kräusslich Hans-Georg , Knop Michael , Typas Athanasios , Steinmetz Lars M , Benes Vladimir , Remans Kim , Krebs Arnaud R
Published: December 2020

McQ is a SARS-CoV-2 quantification assay that couples early-stage barcoding with high-throughput sequencing to enable multiplexed processing of thousands of samples. McQ is based on homemade enzymes to enable low-cost testing of large sample pools, circumventing supply chain shortages.

Implementation of cost-efficient high-throughput methods for detection of RNA viruses such as SARS-CoV-2 is a potent strategy to curb ongoing and future pandemics. Here we describe Multiplexed SARS-CoV-2 Quantification platform (McQ), an in-expensive scalable framework for SARS-CoV-2 quantification in saliva samples. McQ is based on the parallel sequencing of barcoded amplicons generated from SARS- CoV-2 genomic RNA. McQ uses indexed, target-specific reverse transcription (RT) to generate barcoded cDNA for amplifying viral- and human-specific regions. The barcoding system enables early sample pooling to reduce hands-on time and makes the ap-proach scalable to thousands of samples per sequencing run. Robust and accurate quantification of viral load is achieved by measuring the abundance of Unique Molecular Identifiers (UMIs) introduced during reverse transcription. The use of homemade reverse transcriptase and polymerase enzymes and non-proprietary buffers reduces RNA to library reagent costs to 92 cents/sample and circumvents potential supply chain short-ages. We demonstrate the ability of McQ to robustly quantify various levels of viral RNA in 838 clinical samples and accu-rately diagnose positive and negative control samples in a test-ing workflow entailing self-sampling and automated RNA ex-traction from saliva. The implementation of McQ is modular, scalable and could be extended to other pathogenic targets in future.
An Accurate Model for SARS-CoV-2 Pooled RT-PCR Test Errors
Authors: Daon Yair , Huppert Amit , Obolski Uri
Published: December 2020

PCR testing is an important tool to mitigate outbreaks of infectious diseases. One way of increasing testing throughput is by simultaneously testing multiple samples for the presence of a pathogen, a technique known aspooling. During the current COVID-19 pandemic, rapidly testing individuals for the presence of SARS-CoV-2 is conducted in large amounts. Since testing is often a bottleneck in mitigating the spread of SARS-CoV-2, pooling is increasing in popularity. Most analyses of the error rates of pooling schemes assume that including more than a single infected sample in a pooled test does not increase the probability of a positive outcome. We challenge this assumption with experimental data and suggest a novel probabilistic model for the outcomes of pooled tests. As an application, we analyze the false-negative rates of one common pooling scheme known as Dorfman pooling. We show that the false-negative rates of Dorfman pooling increase when the prevalence of infection decreases. However, low infection prevalence is exactly the condition under which Dorfman pooling achieves highest throughput. We therefore implore the cautious use of pooling and development of pooling schemes that consider correctly accounting for tests’ error rates.
FarmApp: a new cognitive assessment method for young people with intellectual disability
Authors: Brkić Diandra , Ng-Cordell Elise , O’Brien Sinéad , Martin Jessica , Scerif Gaia , Astle Duncan , Baker Kate
Published: December 2020

Background

A major challenge when investigating intellectual disability (ID) is the selection of assessment tools that are sensitive to cognitive diversity within the ID population. This study introduces a new touchscreen-based method, FarmApp, which aims to measure competence in relatively low-level cognitive processes (selective attention, short-term visuospatial memory, longer-term recognition memory) which contribute to complex aspects of learning and behaviour.

Methods

Here we describe the FarmApp design, testing and analysis procedures. We report the feasibility and validity of the method, and demonstrate its utility for measuring change over time, and for comparing groups defined by aetiology.

Results

We found that FarmApp can be completed by a higher proportion of young people with ID than traditional psychometric tests. FarmApp performance correlates with standardised neuropsychological tests of attention and working memory, and with questionnaire measures of ADHD-relevant behavioural difficulties. Individual performance slopes over a two-week period correlate with general ability and behavioural difficulties, indicating that FarmApp is sensitive to meaningful dynamic variation in cognitive performance. Finally, we compared the FarmApp performance of two groups of young people with ID, defined by the physiological function of ID-associated genetic variants (functional network groups: chromatin-related and synaptic-related), and found that groups differ on attention parameters but not on memory ones.

Conclusion

FarmApp is a feasible, valid and useful alternative to traditional neuropsychological tests. It can increase access to cognitive assessment for individuals with ID. It adds the opportunity to monitor variation in performance over time and determine capacity to acquire task competence in addition to baseline ability. Our comparison between functional network groups supports the proposal that cognitive processes contributing to ID are differentially influenced by specific genetic aetiologies. In summary, we introduce a new tool for cognitive assessment in ID, with the potential for multiple future applications in clinical practice and research.
The epidemiology and direct medical costs of diseases associated with human papillomavirus infection among men in Manitoba, Canada
Authors: Righolt Christiaan H. , Pabla Gurpreet , Mahmud Salaheddin M.
Published: December 2020

Background

There is little information on the economic burden of human papillomavirus-related diseases (HPV-RDs) among men. We used province-wide clinical, administrative and accounting databases to measure the direct medical costs of HPV infections in men in Manitoba (Canada).

Methods

We included all males aged 9 years and older with health insurance coverage in Manitoba between January 1997 and December 2016. We identified HPV-RD patient cohorts and matched each patient to HPV-RD-free men. We estimated the net direct medical cost (excess cost of hospitalizations, outpatient visits, and prescription drugs) of patients compared to their matches for anogenital warts (AGWs) and HPV-caused cancers. We adjusted costs to 2017 Canadian dollars. For each condition, we attributed costs to HPV based on the etiological fraction caused by HPV infection.

Results

We found that the median net direct medical cost was about $250 for AGW patients and $16,000 for invasive cancer patients. The total cost was about $49 million or $2.6 million per year. Overall, 54%-67% ($26-$33 million) was attributable to HPV infection according different estimates of the attributable fraction. The net annual attributable cost was $2.37-$2.95 per male resident and $161-$200 per male newborn. The estimated potential savings was 30% for the bivalent vaccine and 56%-60% for the quadrivalent and nonavalent vaccines.

Conclusions

Overall, HPV’s economic burden on males remains significant, the average cost of treating all conditions attributable to HPV was about $180 per male newborn. Invasive cancer accounted for the majority of these costs.
Treatment of Severe COVID-19 with Convalescent Plasma in the Bronx, NYC
Authors: Yoon Hyun ah , Bartash Rachel , Gendlina Inessa , Rivera Johanna , Nakouzi Antonio , Bortz Robert H. , Wirchnianski Ariel S. , Paroder Monika , Fehn Karen , Serrano-Rahman Leana , Babb Rachelle , Sarwar Uzma N. , Haslwanter Denise , Laudermilch Ethan , Florez Catalina , Dieterle M. Eugenia , Jangra Rohit K. , Fels J. Maximilian , Tong Karen , Mariano Margarette C. , Vergnolle Olivia , Georgiev George I. , Herrera Natalia G. , Malonis Ryan J. , Quiroz Jose A. , Morano Nicholas C. , Krause Gregory J. , Sweeney Joseph M. , Cowman Kelsie , Allen Stephanie , Annam Jayabhargav , Applebaum Ariella , Barboto Daniel , Khokhar Ahmed , Lally Brianna J. , Lee Audrey , Lee Max , Malaviya Avinash , Sample Reise , Yang Xiuyi A. , Li Yang , Ruiz Rafael , Thota Raja , Barnhill Jason , Goldstein Doctor Y. , Uehlinger Joan , Garforth Scott J. , Almo Steven C. , Lai Jonathan R. , Gil Morayma Reyes , Fox Amy S. , Chandran Kartik , Wang Tao , Daily Johanna P. , Pirofski Liise-anne
Published: December 2020

Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as treatment for Coronavirus Disease 2019 (COVID-19). We compared the mortality and clinical outcome of patients with COVID-19 who received 200mL of CCP with a Spike protein IgG titer ≥1:2,430 (median 1:47,385) within 72 hours of admission to propensity score-matched controls cared for at a medical center in the Bronx, between April 13 to May 4, 2020. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroids, and anticoagulation use. There was no difference in mortality or oxygenation between CCP recipients and controls at day 28. When stratified by age, compared to matched controls, CCP recipients <65 years had 4-fold lower mortality and 4-fold lower deterioration in oxygenation or mortality at day 28. For CCP recipients, pre-transfusion Spike protein IgG, IgM and IgA titers were associated with mortality at day 28 in univariate analyses. No adverse effects of CCP were observed. Our results suggest CCP may be beneficial for hospitalized patients <65 years, but data from controlled trials is needed to validate this finding and establish the effect of ageing on CCP efficacy.
Pre-existing cardiovascular disease rather than cardiovascular risk factors drives mortality in COVID-19
Authors: O’Gallagher Kevin , Shek Anthony , Bean Daniel M. , Bendayan Rebecca , Teo James T. H. , Dobson Richard J. B. , Shah Ajay M. , Zakeri Rosita
Published: December 2020

Background

The association between cardiovascular (CV) risk factors, such as hypertension and diabetes, established CV disease (CVD), and susceptibility to CV complications or mortality in COVID-19 remains unclear.

Methods

We conducted a cohort study of consecutive adults hospitalised for severe COVID-19 between 1stMarch and 30thJune 2020. Pre-existing CVD, CV risk factors and associations with mortality and CV complications were ascertained.

Findings

Among 1,721 patients (median age 71 years, 57% male), 349 (20.3%) had pre-existing CVD (CVD), 888 (51.6%) had CV risk factors without CVD (RF-CVD), 484 (28.1%) had neither. Patients with CVD were older with a higher burden of non-CV comorbidities. During follow-up, 438 (25.5%) patients died: 37% with CVD, 25.7% with RF-CVD and 16.5% with neither. CVD was independently associated with in-hospital mortality among patients <70 years of age (adjusted HR 2.43 [95%CI 1.16-5.07]), but not in those ≥70 years (aHR 1.14 [95%CI 0.77-1.69]). RF-CVD were not independently associated with mortality in either age group (<70y aHR 1.21 [95%CI 0.72-2.01], ≥70y aHR 1.07 [95%CI 0.76-1.52]). Most CV complications occurred in patients with CVD (66%) versus RF-CVD (17%) or neither (11%; p<0.001). 213 [12.4%] patients developed venous thromboembolism (VTE). CVD was not an independent predictor of VTE.

Interpretation

In patients hospitalised with COVID-19, pre-existing established CVD appears to be a more important contributor to mortality than CV risk factors in the absence of CVD. CVD-related hazard may be mediated, in part, by new CV complications. Optimal care and vigilance for destabilised CVD are essential in this patient group.
Can non-disabled adults reproduce the stiff-knee gait of individuals with stroke?
Authors: Bacca Odair , Celestino Melissa , Barela José , Lima Anna , Barela Ana
Published: December 2020

This study investigated whether a mechanical constraint of knee flexion in non-disabled individuals could help with reproducing the gait pattern of individuals with stroke. Eleven non-disabled adults (26.6±6.5 years old) and 12 individuals with stroke (52.0±12.8 years old) walked at a self-selected comfortable speed as kinematic and electromyographic data were acquired. Non-disabled adults also walked with an orthosis that limited to 45 degrees of knee flexion. The hip, knee, and ankle joint angles and the muscle activation of the rectus femoris, vastus medialis and lateralis, tibialis anterior, semitendinosus, biceps femoris, and gastrocnemius medialis and lateralis were analyzed. The results demonstrated that non-disabled adults presented similar lower limb excursion to individuals with stroke that affects most joints, although, they displayed a different muscle activation level for most muscles. These results suggest that a mechanical constraint of knee flexion leads to temporal and joint excursion alterations in the lower limb of non-disabled individuals, thereby enabling the reproduction of a gait pattern similar to individuals with stroke. It is also observed that these individuals use different strategies to control muscle activation, which might be related to the lack of control in coordinating muscle activation during gait that is present in individuals with stroke.
Analgesic α-conotoxins modulate GIRK1/2 channels via GABABreceptor activation and reduce neuroexcitability
Authors: Bony Anuja R. , McArthur Jeffrey R. , Finol-Urdaneta Rocio K. , Adams David J.
Published: December 2020

Activation of G protein-coupled inwardly rectifying potassium (GIRK or Kir3) channels leads to membrane hyperpolarization and dampening of neuronal excitability. Here we show that the analgesic α-conotoxin Vc1.1 potentiates inwardly rectifying K+currents (IKir) mediated through native and recombinant GIRK1/2 channels by activation of the G protein-coupled GABABreceptor (GABABR) via aPertussistoxin (PTX)-sensitive G protein. Recombinant co-expression of human GIRK1/2 subunits and GABABR in HEK293T cells resulted in a Ba2+-sensitive IKirpotentiated by baclofen and Vc1.1 which was inhibited by PTX, intracellular GDP-β-S, or the GABABR-selective antagonist CGP 55845. In adult mouse DRG neurons, GABABR-dependent GIRK channel potentiation by Vc1.1 and baclofen hyperpolarizes the cell resting membrane potential with concomitant reduction of excitability consistent with Vc1.1 and baclofen analgesic effectsin vivo. This study provides new insight into Vc1.1 as an allosteric agonist for GABABR-mediated potentiation of GIRK channels and may aid in the development of novel non-opioid treatments for chronic pain.
Antiherpetic medication and incident dementia: observational cohort studies in four countries
Authors: Schnier Christian , Janbek Janet , Williams Linda , Wilkinson Tim , Laursen Thomas Munk , Waldemar Gunhild , Richter Hartmut , Kostev Karel , Lathe Richard , Haas Jürgen
Published: December 2020

Introduction

Recent meta-analysis of the association between herpesvirus infection and dementia concluded that the evidence for an association to date is insufficient.

Methods

2.5 million individuals aged ≥65 years were followed up using linked electronic health records in four national observational cohort studies. Exposure and outcome were classified using coded data from primary and secondary care. Data were analyzed using survival analysis with time-dependent covariates.

Results

Results were heterogeneous, with a tendency towards decreased dementia risk in individuals exposed to antiherpetic medication. Associations were not affected by treatment number, herpes subtype, dementia subtype, or specific medication. In one cohort, individuals diagnosed with herpes but not exposed to antiherpetic medication were at higher dementia risk.

Discussion

Short-term antiherpetic medication is not markedly associated with incident dementia. Because neither dementia subtype nor herpes subtype modified the association, the small but significant decrease in dementia incidence with antiherpetic adminstration may reflect confounding and misclassification.
Survival analysis in breast cancer using proteomic data from four independent datasets
Authors: Ősz Ágnes , Lánczky András , Győrffy Balázs
Published: December 2020

Breast cancer clinical treatment selection is based on the immunohistochemical determination of four proteins: ESR1, PGR, HER2, and MKI67. Our aim was to correlate immunohistochemical results to proteome-level technologies in measuring the expression of these markers. We also aimed to integrate available proteome-level breast cancer datasets to identify and validate new prognostic biomarker candidates.

We identified protein studies involving breast cancer patient cohorts with published survival and proteomic information. Immunohistochemistry and proteomic technologies were compared using the Mann-Whitney test. Receiver operating characteristics (ROC) curves were generated to validate discriminative power. Cox regression and Kaplan-Meier survival analysiss were calculated to assess prognostic power. The false discovery rate was computed to correct for multiple hypothesis testing.

The complete database contains protein expression data and survival information from four independent cohorts for 1,229 breast cancer patients. In all four studies combined, a total of 7,342 unique proteins were identified, and 1,417 of these were identified in at least three datasets. ESR1, PGR, HER2 protein expression levels determined by RPPA or LC-MS/MS methods showed a significant correlation with the levels determined by immunohistochemistry (p<0.0001). PGR and ESR1 levels showed a moderate correlation (correlation coefficient=0.17, p=0.0399). A panel of candidate proteins, including apoptosis-related proteins (BCL2,), adhesion markers (CDH1, CLDN3, CLDN7) and basal markers (cytokeratins), were validated as prognostic biomarkers. We expanded our established web tool to validate survival-associated biomarkers to include the proteomic datasets analyzed in this study (https://kmplot.com/analysis/).

Large proteomic studies now provide sufficient data enabling the validation and ranking of new protein biomarkers.
Mental health problems in the general population during and after the first lockdown phase due to the SARS-Cov-2 pandemic: Rapid review of multi-wave studies
Authors: Richter Dirk , Riedel-Heller Steffi , Zuercher Simeon
Published: December 2020

Aims

The SARS-Cov-2 pandemic and the lockdown response are assumed to have increased mental health problems in general populations compared to pre-pandemic times. The aim of this paper is to review studies on the course of mental health problems during and after the first lockdown phase.

Methods

We conducted a rapid review of multi-wave studies in general populations with time points during and after the first lockdown phase. Repeated cross-sectional and longitudinal studies that utilized validated instruments were included. The main outcome was whether indicators of mental health problems have changed during and after the first lockdown phase. The study was registered with PROSPERO No. CRD42020218640.

Results

23 studies with 56 indicators were included in the qualitative review. Studies that reported data from pre-pandemic assessments through lockdown indicated an increase in mental health problems. During lockdown no uniform trend could be identified. After lockdown mental health problems decreased slightly.

Conclusions

As mental health care utilization indicators and data on suicides do not suggest an increase in demand during the first lockdown phase, we regard the increase in mental health problems as general distress that is to be expected during a global health crisis. Several methodological, pandemic-related, response-related and health policy-related factors need to be considered when trying to gain a broader perspective on the impact of the first wave of the pandemic and the first phase of lockdown on general populations’ mental health.
Novel Approach for Monte Carlo Simulation of the new COVID-19 Spread Dynamics
Authors: Maltezos Stavros , Georgakopoulou Angelika
Published: December 2020

A Monte Carlo simulation in a novel approach is used for studying the problem of the outbreak and spread dynamics of the new COVID-19 pandemic in this work. In particular, our goal was to generate epidemiological data based on natural mechanism of transmission of this disease assuming random interactions of a large-finite number of individuals in very short distance ranges. In the simulation we also take into account the stochastic character of the individuals in a finite population and given densities of people. On the other hand, we include in the simulation the appropriate statistical distributions for the parameters characterizing this disease. An important outcome of our work, besides the generated epidemic curves, is the methodology of determining of the effective reproductive number during the main part of the new daily cases of the epidemic. Since this quantity constitutes a fundamental parameter of the SIR-based epidemic models, we also studied how it is affected by small variations of the incubation time and the crucial distance distributions, and furthermore, by the degree of quarantine measures. In addition, we compare our qualitative results with those of selected real epidemiological data.
The impact of the COVID-19 pandemic on mental health and well-being of people living with a long-term physical health condition: a qualitative study
Authors: Fisher A , Roberts A , McKinlay A.R. , Fancourt D , Burton A
Published: December 2020

Background

The COVID-19 pandemic and associated restrictions caused major global disruption. Individuals with long-term physical health conditions (LTCs) are at higher risk of severe illness and often subject to the strictest pandemic guidance, so may be disproportionally affected. The aim of this study was to qualitatively explore how living with a LTC during the COVID-19 pandemic affected people’s mental health and wellbeing.

Sample and methods

32 participants, mean age 57 (SD 13) years, 66% female and 72% white British, who reported having LTCS (most commonly cancer, respiratory conditions or cardiovascular diseases), participated in telephone/video call interviews based on a semi-structured topic guide. Key themes and subthemes were determined using deductive and inductive thematic analysis.

Results

There were four overarching themes specific to living with a LTC. These were 1) high levels of fear and anxiety related to perceived consequences of catching COVID-19, 2) impact of shielding/isolation on mental health and wellbeing, 3) experience of healthcare during the pandemic and 4) anxiety created by uncertainty about the future. Fourteen subthemes were identified, including concerns about accessing essential supplies and the importance of social support. Individuals who lived alone and were advised to shield could be profoundly negatively affected.

Conclusions

This study found that there were a number of aspects of living with a LTC during the pandemic that had a significant impact on mental health and well-being. There should be focus on how best to provide practical and social support to people with LTCs during a pandemic, particularly if they have to shield or isolate.
Reduced frequency of perforin-positive CD8+ T cells in menstrual effluent of endometriosis patients compared to healthy controls
Authors: Schmitz Timo , Hoffmann Verena , Olliges Elisabeth , Bobinger Alina , Popovici Roxana , Nößner Elfriede , Meissner Karin
Published: December 2020

Background

Endometriosis is widespread among women in reproductive age and quite commonly reduces life quality of those affected by symptoms like dysmenorrhea, dyspareunia or infertility. The scientific literature indicates many immunological changes like reduced cytotoxicity of natural killer cells or altered concentrations of cytokines and cell adhesion molecules. Frequently examined tissues are peripheral blood, endometrial tissue and peritoneal fluid. Yet, knowledge on immunological differences in menstrual effluent (ME) is scarce.

Methods

12 women with endometriosis and 11 healthy controls were included in this study. ME was collected using menstrual cups and venous blood samples (PB) were taken. Mononuclear cells were obtained from ME (MMC) and PB (PBMC) and analyzed using flow cytometry. Furthermore, concentrations of cell adhesion molecules (ICAM-I and VCAM-I) and cytokines (IL-6, IL-8 and TNF-α) were measured in ME and PB.

Results

CD8+ T cells obtained from ME were significantly less often perforin-positive in women with endometriosis compared to healthy controls. Additionally, plasma ICAM-I concentrations were significantly lower in the endometriosis group. A comparison between MMC and PBMC revealed that MMC contained significantly less T cells and more B cells. The CD4/CD8 ratio was significantly higher in MMC, and Tregs were significantly less frequently in MMC. In ME, T cells and NK cells expressed significantly more CD69. NK cells obtained from ME were predominantly CD56bright/CD16dim and had a lower frequency of perforin+ cells compared to PBMC NK cells. NKp46 was significantly more expressed on NK cells from PBMC.

Conclusion

CD8+ T cells obtained from the ME were significantly less perforin-positive in endometriosis patients indicating a reduced cytotoxic potential. MMC are distinctively different from PBMC and, thus, seem to be of endometrial origin.
Supervised Image Classification Algorithm Using Representative Spatial Texture Features: Application to COVID-19 Diagnosis Using CT Images
Authors: Belkhatir Zehor , Estépar Raúl San José , Tannenbaum Allen R.
Published: December 2020

Although there is no universal definition for texture, the concept in various forms is nevertheless widely used and a key element of visual perception to analyze images in different fields. The present work’s main idea relies on the assumption that there exist representative samples, which we refer to as references as well, i.e., “good or bad” samples that represent a given dataset investigated in a particular data analysis problem. These representative samples need to be accounted for when designing predictive models with the aim of improving their performance. In particular, based on a selected subset of texture gray-level co-occurrence matrices (GLCMs) from the training cohort, we propose new representative spatial texture features, which we incorporate into a supervised image classification pipeline. The pipeline relies on the support vector machine (SVM) algorithm along with Bayesian optimization and the Wasserstein metric from optimal mass transport (OMT) theory. The selection of the best, “good and bad,” GLCM references is considered for each classification label and performed during the training phase of the SVM classifier using a Bayesian optimizer. We assume that sample fitness is defined based on closeness (in the sense of the Wasserstein metric) and high correlation (Spearman’s rank sense) with other samples in the same class. Moreover, the newly defined spatial texture features consist of the Wasserstein distance between the optimally selected references and the remaining samples. We assessed the performance of the proposed classification pipeline in diagnosing the corona virus disease 2019 (COVID-19) from computed tomographic (CT) images.