bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accelerated intermittent theta burst as a substitute for patients needing electroconvulsive therapy during the COVID-19 pandemic: study protocol for an open-label clinical trial
Authors: Blumberger Daniel M. , Daskalakis Zafiris J. , Vila-Rodriguez Fidel , Boivin-Lafleur David , Goodman Michelle S. , Kaster Tyler , Knyahnytska Yuliya , Konstantinou Gerasimos , Trevizol Alisson P. , Voineskos Daphne , Weissman Cory R. , Downar Jonathan 
Published: December 2020

Abstract

Background
Treatment resistant depression (TRD) is one of the leading causes of disability in Canada and is associated with significant societal costs. Repetitive transcranial magnetic stimulation (rTMS) is an approved, safe, and well-tolerated intervention for TRD. In the setting of the COVID-19 pandemic, reducing the number of visits to the clinic is a potential approach to significantly minimize exposure and transmission risks to patients. This can be accomplished by administering multiple treatment sessions in a single day, using an rTMS protocol known as accelerated intermittent theta burst stimulation (aiTBS). The objective of this novel study is to assess the feasibility, acceptance and clinical outcomes of a practical high-dose aiTBS protocol, including tapering treatments and symptom-based relapse prevention treatments, in patients with unipolar depression previously responsive to electroconvulsive therapy (ECT) or patients warranting ECT due to symptom severity.

Methods
All patients with unipolar depression referred to the brain stimulation service at the Centre for Addiction and Mental Health (CAMH) who warrant ECT will be offered screening to assess for eligibility to enroll in this trial. This open label, single group trial consists of 3 phases. In the acute treatment phase, treatment will occur 8 times daily for 5 days a week, until symptom remission is achieved or a maximum of 10 days of treatment. In the tapering phase, treatments will be reduced to 2 treatment days per week for 2 weeks, followed by 1 treatment day per week for 2 weeks. Patients will then enter the symptom-based relapse prevention phase including virtual check-ins and a treatment schedule based on symptom level. Remission, response and change in scores on several clinical measures from baseline to the end of the acute, tapering and relapse prevention phases represent the clinical outcomes of interest.

Discussion
Findings from this novel clinical trial may provide support for the use of aiTBS, including tapering treatments and symptom-based relapse prevention treatments, as a safe and effective alternative intervention for patients needing ECT during the COVID-19 pandemic.

Trial registration
Clinicaltrials.gov: NCT04384965
Short-term acute exposure to wildfire smoke and lung function in a Royal Canadian Mounted Police (RCMP) cohort
Authors: Moitra Subhabrata , Tabrizi Ali Farshchi , Fathy Dina , Kamravaei Samineh , Miandashti Noushin , Henderson Linda , Khadour Fadi , Naseem Muhammad T. , Murgia Nicola , Melenka Lyle , Lacy Paige 
Published: December 2020

ABSTRACTRationaleThe increasing incidence of extreme wildfire is becoming a concern for public health. Although long-term exposure to wildfire smoke is associated with respiratory illnesses, reports on the association between short-term occupational exposure to wildfire smoke and lung function remain scarce.MethodsIn this cross-sectional study, we analyzed data of 218 Royal Canadian Mounted Police officers (mean age: 38±9 years) deployed at the Fort McMurray wildfire in 2016. Individual exposure to air pollutants was calculated by integrating the duration of exposure with the air quality parameters obtained from the nearest air quality monitoring station during the phase of deployment. Lung function was measured using spirometry and body plethysmography. Association between exposure and lung function was examined using principal component linear regression analysis, adjusting for potential confounders.ResultsThe participants were predominantly male (71%). Mean forced expiratory volume in 1 second (FEV1), and residual volume (RV) were 76.5±5.9 and 80.1±19.5 (% predicted). A marginal association was observed between air pollution and higher RV [β: 1.55; 95%CI: -0.28 to 3.37 per interquartile change of air pollution index], but not with other lung function indices. The association between air pollution index and RV was significantly higher in participants who were screened within the first three months of deployment [2.80; 0.91 to 4.70] than those screened later [-0.28; -2.58 to 2.03], indicating a more acute effect of air pollution on peripheral airways.ConclusionAcute short-term exposure to wildfire-associated air pollutants may impose subtle but clinically important deleterious respiratory effects, particularly in the peripheral airways.
The Wood equation allows consistent fitting of individual antibody responses profiles in Zika virus or SARS-CoV-2 infected patients
Authors: Denis J. , Garnier A. , Claverie D. , De Laval F. , Attoumani S. , Tenebray B. , Durand G.A. , Coutard B. , Leparc-Goffart I. , Tournier JN. , Briolant S. , Badaut C. 
Published: December 2020

AbstractAntibody kinetic curves obtained during a viral infection are often fitted using aggregated data from patients, hiding the heterogeneity of patient responses. The Wood equation makes it possible to establish the link between an individual’s kinetic profile and the disease, which may be helpful in identifying and studying clusters.
Face masks for preventing respiratory infections in the community: A systematic review
Authors: Saijonkari Maija , Booth Neill , Isojärvi Jaana , Finnilä Jenni , Mäkelä Marjukka 
Published: December 2020

AbstractBackgroundThe Ministry of Social Affairs and Health in Finland commissioned this systematic literature review on the effectiveness and safety of using face masks in public environments in protecting against upper respiratory tract infections, to inform policy. Previous reviews have not clearly distinguished the context of mask use.MethodsThe review was completed within two weeks, adhering to the PRISMA guidelines where possible. The review looks at the effect of face coverings (surgical masks or cloth coverings, excluding FFP2 and FFP3 masks) in protecting against the transmission in droplet-mediated respiratory tract infections. Our review includes controlled trials or previous systematic reviews of mask use by the general public in public spaces, outside homes and healthcare facilities.ResultsThe systematic literature search identified five randomized trials. Use of masks prevented infections in one subgroup of one pilot study, so the effect of face masks on the transmission of infections outside the home appears small or nonexistent. Five of the eight systematic reviews showed no evidence of face masks being helpful in controlling the spread of respiratory infection or preventing exposure in healthy individuals. Meta-analyses often combined very heterogeneous studies and costs were not reported in any studies.ConclusionsRandomized studies on the effect of face coverings in the general population are few. The reported effect of masks used outside the home on transmission of droplet-mediated respiratory infections in the population is minimal or non-existent. It is difficult to distinguish the potential effect of masks from the effects of other protective measures.Summary boxWhat is already known on this subject?Previous reviews on the effectiveness and safety of use of face masks in protecting against upper respiratory tract infections have not clearly distinguished the context of mask use. They have combined very heterogeneous studies done in homes, health care settings, or public environments.What does this study add?Our systematic review on the use of face masks in public environments, done to inform an impending policy decision, found five randomized trials (RCTs) and eight reviews. Use of masks prevented infections in one subgroup of one RCT, so the effect of face masks appears small or nonexistent.
Research Letter: Reactive balance responses after mild traumatic brain injury (mTBI): a scoping review
Authors: Morris Amanda , Casucci Tallie , McFarland Mary M. , Cassidy Benjamin , Pelo Ryan , Kreter Nicholas , Dibble Leland E. , Fino Peter C. 
Published: December 2020

AbstractObjectiveBalance testing after concussion or mild traumatic brain injury (mTBI) can be useful in determining acute and chronic neuromuscular deficits that are unapparent from symptom scores or cognitive testing alone. Current assessments of balance do not comprehensively evaluate all three classes of balance: maintaining a posture, voluntary movement, and reactive postural response. Despite the utility of reactive postural responses in predicting fall risk in other balance impaired populations, the effect of mTBI on reactive postural responses remains unclear. This review sought to (1) examine the extent and range of available research on reactive postural responses in people post-mTBI and (2) determine if reactive postural responses (balance recovery) are affected by mTBI.DesignPRISMA Scoping review.MethodsStudies were identified using Medline, Embase, CINAHL, Cochrane Library, Dissertations and Theses Global, PsycINFO, SportDiscus, and Web of Science. Inclusion criteria were: injury classified as mTBI with no confounding central or peripheral nervous system dysfunction beyond those stemming from the mTBI, quantitative measure of reactive postural response, and a discrete, externally driven perturbation was used to test reactive postural response.ResultsA total of 4,747 publications were identified and a total of three studies (5 publications) were included in the review.ConclusionThe limited number of studies available on this topic highlight the lack of knowledge on reactive postural responses after mTBI. This review provides a new direction for balance assessments after mTBI and recommends incorporating all three classes of postural control in future research.
Bayesian modeling for the detection of adverse events underreporting in clinical trials
Authors: Barmaz Yves , Ménard Timothé 
Published: December 2020

AbstractIntroductionSafety underreporting is a recurrent issue in clinical trials that can impact patient safety and data integrity. Clinical Quality Assurance (QA) practices used to detect underreporting rely on on-site audits, however adverse events underreporting remains a recurrent issue. In a recent project, we developed a predictive model that enables oversight of Adverse Event (AE) reporting for clinical Quality Program Leads (QPL). However, there were limitations to using solely a machine learning model.ObjectiveOur primary objective was to propose a robust method to compute the probability of AE underreporting that could complement our machine learning model. Our model was developed to enhance patients safety while reducing the need for on-site and manual QA activities in clinical trials.MethodsWe used a Bayesian hierarchical model to estimate the site reporting rates and assess the risk of underreporting. We designed the model with Project Data Sphere clinical trial data that is public and anonymized.ResultsWe built a model that infers the site reporting behavior from patient-level observations and compares them across a study to enable a robust detection of outliers between clinical sites.ConclusionThe new model will be integrated into the current dashboard designed for clinical Quality Program Leads. This approach reduces the need for on-site audits, shifting focus from source data verification (SDV) to pre-identified, higher risk areas. It will enhance further quality assurance activities for safety reporting from clinical trials and generate quality evidence during pre-approval inspections.The preprint version of this work is available on MedRxiv: https://doi.org/10.1101/2020.12.18.20245068Key pointsSafety underreporting is a recurrent issue in clinical trials that can impact patient safety and data integrityWe used a Bayesian hierarchical model to estimate the site reporting rates and assess the risk of underreporting.This model complements our previously published machine learning approach and is used by clinical quality professionals to better detect safety underreporting.
Clinically significant estimated glomerular filtration rate decline is common in patients receiving immune checkpoint inhibitors: implications for long-term cancer survivors
Authors: Chute Donald F. , Zhao Sophia , Strohbehn Ian A. , Rusimbayala Nifasha , Seethapathy Harish , Lee Meghan , Zubiri Leyre , Gupta Shruti , Leaf David E. , Rahma Osama , Drobni Zsofia D. , Neilan Tomas G. , Reynolds Kerry L. , Sise Meghan E. 
Published: December 2020

AbstractPurposeImmune checkpoint inhibitors (ICIs) are now indicated in more than one in three cancer patients. Acute kidney injury has emerged as an important complication of ICIs; however, there are no studies characterizing the long-term effects of ICIs on kidney function.MethodsRetrospective cohort study of consecutive adult cancer patients treated with ICIs between 2010–2018 at two major cancer centers. The primary aim was to determine the composite outcome of incident or progressive CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 or a ≥30% decline in eGFR sustained >90 days among patients surviving ≥1 year. The secondary objective was to determine the proportion of patients experiencing rapid eGFR decline defined as >3mL/min/1.73m2 per year decline.ResultsA total of 5004 adult patients with cancer (mean [SD] age, 64 [13] years; 2699 [54%] male; 4529 [91%] White non-Hispanic) were included, and 2563 surviving ≥1 year were analyzed. During a median follow-up of 688 days (interquartile range, 496 to 1031), the overall event rate of the primary composite outcome was 17% and 20% at 3 and 5 years, respectively. Fine-Gray subdistribution multivariable hazard mode demonstrated that age and coronary artery disease were each independently associated with the primary outcome, adjusted HR (95% CI) 1.12 (1.06, 1.19) per 5 years and 1.27 (1.00-1.62), p < 0.001 and p=0.49, respectively.ConclusionNew onset CKD or 30% eGFR decline is common in patients receiving ICIs who survive ≥1 year. As ICIs are increasingly used in earlier stage cancers, the impact of long term kidney function decline among survivors is extremely important. Additional studies are needed to determine the risk factors and potential modifiers for eGFR decline among patients receiving ICIs.
The challenges of the coming mass vaccination and exit strategy in prevention and control of COVID-19, a modelling study
Authors: Tang Biao , Liu Peiyu , Yang Jie , Wu Jianhong , Yanni Xiao , Tang Sanyi 
Published: December 2020

AbstractWith success in the development of COVID-19 vaccines, it is urgent and challenging to analyse how the coming large-scale vaccination in the population and the growing public desire of relaxation of non-pharmaceutical interventions (NPIs) interact to impact the prevention and control of the COVID-19 pandemic. Using mathematical models, we focus on two aspects: 1) how the vaccination program should be designed to balance the dynamic exit of NPIs; 2) how much the vaccination coverage is needed to avoid a second wave of the epidemics when the NPIs exit in stages. We address this issue globally, and take six countries--China, Brazil, Indonesia, Russia, UK, and US—in our case study. We showed that a dynamic vaccination program in three stages can be an effective approach to balance the dynamic exit of the NPIs in terms of mitigating the epidemics. The vaccination rates and the accumulative vaccination coverage in these countries are estimated by fitting the model to the real data. We observed that the required effective vaccination coverages are greatly different to balance the dynamic exit of NPIs in these countries, providing a quantitative criterion for the requirement of an integrative package of NPIs. We predicted the epidemics under different vaccination rates for these countries, and showed that the vaccination can significantly decrease the peak value of a future wave. Furthermore, we found that a lower vaccination coverage can result in a subsequent wave once the NPIs exit. Therefore, there is a critical (minimum) vaccination coverage, depending on effectiveness of NPIs to avoid a subsequent wave. We estimated the critical vaccination coverages for China, Brazil, and Indonesia under different scenarios. In conclusion, we quantitatively showed that the dynamic vaccination program can be the effective approach to supplement or even eventually replace NPIs in mitigating the epidemics and avoiding future waves, and we suggest that country level-based exit strategies of the NPIs should be considered, according to the possible quarantine rate and testing ability, and the accessibility, affordability and efficiency of the vaccines.
A method for prioritizing risk groups for early SARS-CoV-2 Vaccination, By the Numbers
Authors: McDonald Clement J. , Baik Seo H. , Zheng Zhaonian , Amos Liz 
Published: December 2020

AbstractBackgroundGiven the limited supply of two COVID-19 vaccines, it will be important to choose which risk groups to prioritize for vaccination in order to get the most health benefits from that supply.MethodIn order to help decide how to get the maximum health yield from this limited supply, we implemented a logistic regression model to predict COVID-19 death risk by age, race, and sex and did the same to predict COVID-19 case risk.ResultsOur predictive model ranked all demographic groups by COVID-19 death risk. It was highly concentrated in some demographic groups, e.g. 85+ year old Black, Non-Hispanic patients suffered 1,953 deaths per 100,000. If we vaccinated the 17 demographic groups at highest COVID-19 death ranked by our logistic model, it would require only 3.7% of the vaccine supply needed to vaccinate all the United States, and yet prevent 47% of COVID-19 deaths. Nursing home residents had a higher COVID-19 death risk at 5,200 deaths/100,000, more than our highest demographic risk group. Risk of prison residents and health care workers (HCW) were lower than that of our demographic groups with the highest risks.We saw much less concentration of COVID-19 case risk in any demographic groups compared to the high concentration of COVID-19 death in some such groups. We should prioritize vaccinations with the goal of reducing deaths, not cases, while the vaccine supply is low.ConclusionSARS-CoV-2 vaccines protect against severe COVID-19 infection and thus against COVID-19 death per vaccine studies. Allocating at least some of the early vaccine supplies to high risk demographic groups could maximize lives saved. Our model, and the risk estimate it produced, could help states define their vaccine allocation rules.
Cardiac SARS-CoV-2 infection is associated with distinct transcriptomic changes within the heart
Authors: Lindner Diana , Bräuninger Hanna , Stoffers Bastian , Fitzek Antonia , Meißner Kira , Aleshcheva Ganna , Schweizer Michaela , Weimann Jessica , Rotter Björn , Warnke Svenja , Edler Carolin , Braun Fabian , Roedl Kevin , Scherschel Katharina , Escher Felicitas , Kluge Stefan , Huber Tobias B. , Ondruschka Benjamin , Heinz-Peter-Schultheiss  , Kirchhof Paulus , Blankenberg Stefan , Püschel Klaus , Westermann Dirk 
Published: December 2020

1AbstractBackgroundAnalyses in hospitalized patients and small autopsy series suggest that severe SARS-CoV-2 infection may affect the heart. We investigated heart tissue by in situ hybridization, immunohistochemistry and RNA sequencing in consecutive autopsy cases to quantify virus load and characterize cardiac involvement in COVID-19.MethodsLeft ventricular tissue from 95 deceased with diagnosed SARS-CoV-2 infection undergoing autopsy was analyzed and clinical data were collected. RNA was isolated to examine virus load of SARS- CoV-2 and its replication in the heart. A virus load >1000 copies per µg RNA was defined as relevant. Viral RNA and inflammatory cells were assessed using histology. RNA sequencing and gene ontology (GO) enrichment were performed in 10 cases with high cardiac virus load and 10 age-matched cases without cardiac infection.ResultsA relevant SARS-CoV-2 virus load was detected in 41 out of 95 deceased (43%). The median cardiac virus load was 7952 copies per µg RNA (IQR 2507, 32 005). In situ hybridization revealed SARS- CoV-2 RNA primarily in the interstitium or interstitial cells. Virus detection was not associated with increased inflammatory cells. Relevant cardiac infection was associated with increased expression of the entry factor TMPRSS2. Cardiac virus replication was found in 14/95 hearts (15%). Remarkably, cardiac virus replication was associated with shorter time between diagnosis and death. RNA sequencing revealed clear activation of immune response pathways to virus infection and destruction of cardiomyocytes. Hearts with high virus load showed activation of the GO term “extracellular exosomes”.ConclusionSARS-CoV-2 infection including virus replication and distinct transcriptomic alterations without signs of myocarditis demonstrate a cardiac involvement. In this autopsy series, cardiac replication of SARS-CoV-2 was associated with early death.
The ratio of exhausted to resident infiltrating lymphocytes is prognostic for colorectal cancer patient outcome
Authors: Foroutan Momeneh , Molania Ramyar , Pfefferle Aline , Behrenbruch Corina , Kallies Axel , Speed Terence P , Cursons Joseph , Huntington Nicholas D 
Published: December 2020

AbstractImmunotherapy success in colorectal cancer (CRC) is mainly limited to patients whose tumours exhibit high microsatellite instability (MSI). However, there is variability in treatment outcomes within this group, which is in part driven by the frequency and characteristics of tumour infiltrating immune cells. Indeed, the presence of specific infiltrating immune cell subsets has been shown to correlate with immunotherapy responses and is in many cases prognostic of treatment outcome. Tumour-infiltrating lymphocytes (TILs) can undergo distinct differentiation programs, acquiring features of tissue-residency or exhaustion, a process during which T cells upregulate inhibitory receptors such as PD-1 and loose functionality. While residency and exhaustion programs of CD8 T cells are relatively well-studied, these programs have only recently been appreciated in CD4 T cells and remain largely unknown in tumour-infiltrating natural killer (NK) cells. In this study, we use single cell RNA-seq data to identify signatures of residency and exhaustion in CRC infiltrating lymphocytes, including CD8, CD4 and NK cells. We then test these signatures in independent single cell data from tumour and normal tissue infiltrating immune cells. Further, we use versions of these signatures designed for bulk RNA-seq data to explore tumour intrinsic mutations associated with residency and exhaustion from TCGA data. Finally, using two independent transcriptomic data sets from patients with colon adenocarcinoma, we show that combinations of these signatures, in particular combinations of NK activity signatures, together with tumour-associated signatures, such as TGF-β signalling, are associated with distinct survival outcomes in colorectal cancer patients.