bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and central hemodynamic characteristics of early adulthood isolated diastolic hypertension: a comparison with isolated systolic hypertension
Authors: Kim Sunwon , Kim Jin-Seok , Kim Woohyeun , Ahn Jeong-Cheon 
Published: March 2021

Objectives
Knowledge on early adulthood isolated diastolic hypertension (IDH) is limited. We compared the clinical and central hemodynamic characteristics of early adulthood IDH, isolated systolic hypertension (ISH) and normotension.

Methods
A total of 509 untreated young adults (18–35 years) who underwent ambulatory blood pressure monitoring (ABPM; ABPM cohort), 148 who underwent both ABPM and applanation tonometry (ABPM-tonometry cohort) and 26 newly recruited normotensives were analyzed. Their pulse wave images were analyzed after categorizing them into type A vs. B vs. C.

Results
In the ABPM cohort (men, 86.6%), systolic–diastolic hypertension was the most common subtype (68.0%), while IDH was the rarest (5.1%). The subtype composition showed age-dependency; the proportion of IDH and systolic–diastolic hypertension increased across the age tertiles, while that of ISH declined. Patients with IDH were significantly older and shorter than those with ISH. Despite having a significantly lower 24-h average systolic blood pressure (SBP), patients with IDH exhibited discordantly high central systolic blood pressures at levels comparable to those of patients with ISH. Pulse pressure amplification was the lowest in patients with IDH and highest in those with ISH (P < 0.001), accounting for the discordance. Augmentation index differed significantly between them (P < 0.016). The waveform composition differed across the subtypes (type A vs. B/C: IDH = 61.5 vs. 38.5%; ISH = 3.0 vs. 97.0%; normotension = 30.8 vs. 69.2%, P < 0.001); the averaged waveform plots demonstrated a clear morphological disparity between IDH (type A) and ISH (type B/C).

Conclusions
Early adulthood IDH is a unique entity clearly distinguishable from ISH in terms of clinical and central hemodynamic characteristics.
Serrated Lesion Detection in a Population-based Colon Screening Program
Authors: Chu Jenny E. , Hamm Jeremy , Gentile Laura , Telford Jennifer J. , Schaeffer David F. 
Published: March 2021

Background:
Serrated lesions give rise to 15% to 30% of all colorectal cancers, driven predominantly by the sessile serrated polyp (SSP). Fecal immunochemical test (FIT), has low sensitivity for SSPs. SSP detection rate (SSPDR) is influenced by performance of both endoscopists and pathologists, as diagnosis can be subtle both on endoscopy and histology.

Goals:
To evaluate the SSPDR in a population-based screening program, and the influence of subspecialty trained pathologists on provincial reporting practices.

Study:
The colon screening program database was used to identify all FIT-positive patients that received colonoscopy between January 2014 and June 2017. Patient demographics, colonoscopy quality indicators, pathologic diagnoses, and FIT values were collected. This study received IRB approval.

Results:
A total of 74,605 colonoscopies were included and 26.6% had at least 1 serrated polyp removed. The SSPDR was 7.0%, with 59% of the SSPs detected having a concurrent conventional adenoma. The mean FIT value for colonoscopies with only serrated lesions was less than that for colonoscopies with a conventional adenoma or colorectal cancer (P<0.0001). Centers with a gastrointestinal subspecialty pathologist diagnosed proportionally more SSPs (P<0.0001), and right-sided SSPs than centers without subspecialists.

Conclusions:
Serrated lesions often occur in conjunction with conventional adenomas and are associated with lower FIT values. Knowledge of the characteristics of SSPs is essential for pathologists to ensure accurate diagnosis of SSPs.
Rebleeding after hemoclip versus argon plasma coagulation for gastrointestinal angiodysplasias: a retrospective multicenter study
Authors: Ismail Bahaaeldeen , Alayoubi Mhd Suhaib , Abdelwadoud Moaz , Castro Fernando J. 
Published: March 2021

Background
Hemoclips are utilized for treating bleeding gastrointestinal angiodysplastic lesions (GIADs); however, the supporting evidence is limited.

Aims
Our aim is to evaluate the efficacy of hemoclips in preventing bleeding secondary to GIADs compared to argon plasma coagulation (APC).

Methods
This retrospective study included patients with bleeding gastric, small bowel or colonic GIADs that were endoscopically treated between January 2009 and November 2016. Patients that received hemoclips as monotherapy or in combination were compared to a randomly selected similar number of patients treated with APC.

Results
We included 157 patients that underwent APC and 141 who received hemoclips. During a median follow-up of 17 months, those with hemoclips had a 32.6% rebleeding vs. 46.5% in the APC group (P = 0.017). On multivariate regression analysis, use of hemoclips was not a significant predictor of rebleeding when compared to APC; hemoclips monotherapy (HR, 0.92; 95% CI, 0.54–1.59) and hemoclips combination (HR, 0.65; 95% CI, 0.41–1.01). When the multivariate analysis was restricted to subjects that resumed antithrombotics after endoscopy, rebleeding risk was lower when hemoclips were used in combination (HR, 0.46; 95% CI, 0.25–0.84) compared to APC. We noted a similar effect in the antithrombotic subgroup even after propensity score matching (HR, 0.51; 95% CI, 0.27–0.95).

Conclusion
Treatment modality was not a significant predictor of rebleeding when studied for the entire population. However, the risk of rebleeding was lower with hemoclips combination therapy compared to APC in patients that resumed antithrombotic therapy, suggesting a potential role for a combined approach in this subgroup of patients.
Point-of-Care Detection of Nonadherence to Antiretroviral Treatment for HIV-1 in Resource-Limited Settings Using Drug Level Testing for Efavirenz, Lopinavir, and Dolutegravir: A Validation and Pharmacokinetic Simulation Study
Authors: Hermans Lucas E. , Nijhuis Monique , Tempelman Hugo A. , Houts Tom , Schuurman Rob , Burger David M. , Wensing Annemarie M. J. , Heine Rob Ter 
Published: March 2021

Background:
Virological failure during antiretroviral treatment (ART) may indicate the presence of drug resistance, but may also originate from nonadherence. Qualitative detection of ART components using drug level testing may be used to differentiate between these scenarios. We aimed to validate and implement qualitative point-of-care drug level tests for efavirenz (EFV), lopinavir (LPV), and dolutegravir (DTG) in rural South Africa.

Methods:
Qualitative performance of immunoassays for EFV, LPV, and DTG was assessed by calculating limit of detection (LoD), region of uncertainty, and qualitative agreement with a reference test. Minimum duration of nonadherence resulting in a negative drug level test was assessed by simulation of treatment cessation using validated population pharmacokinetic models.

Results:
LoD was 0.05 mg/L for EFV, 0.06 mg/L for LPV, and 0.02 mg/L for DTG. Region of uncertainty was 0.01–0.06 mg/L for EFV, 0.01–0.07 mg/L for LPV, and 0.01–0.02 mg/L for DTG. Qualitative agreement with reference testing at the LoD in patient samples was 95.2% (79/83) for EFV, 99.3% (140/141) for LPV, and 100% (118/118) for DTG. After simulated treatment cessation, median time to undetectability below LoD was 7 days [interquartile range (IQR) 4–13] for EFV, 30 hours (IQR 24–36) for LPV, and 6 days (IQR 4–7) for DTG.

Conclusions:
We demonstrate that qualitative ART drug level testing using immunoassays is feasible in a rural resource-limited setting. Implementation of this technology enables reliable detection of recent nonadherence and may allow for rapid and cost-effective differentiation between patients in need for adherence counseling and patients who require drug resistance testing or alternative treatment.
A Deep Learning Approach to Visualize Aortic Aneurysm Morphology Without the Use of Intravenous Contrast Agents
Authors: Chandrashekar Anirudh , Handa Ashok , Lapolla Pierfrancesco , Shivakumar Natesh , Uberoi Raman , Grau Vicente , Lee Regent 
Published: March 2021

Background:
Intravenous contrast agents are routinely used in CT imaging to enable the visualization of intravascular pathology, such as with abdominal aortic aneurysms. However, the injection is contraindicated in patients with iodine allergy and is associated with renal complications.

Objectives:
In this study, we investigate if the raw data acquired from a noncontrast CT image contains sufficient information to differentiate blood and other soft tissue components. A deep learning pipeline underpinned by generative adversarial networks was developed to simulate contrast enhanced CTA images using noncontrast CTs.

Methods and Results:
Two generative models (cycle- and conditional) are trained with paired noncontrast and contrast enhanced CTs from seventy-five patients (total of 11,243 pairs of images) with abdominal aortic aneurysms in a 3-fold cross-validation approach with a training/testing split of 50:25 patients. Subsequently, models were evaluated on an independent validation cohort of 200 patients (total of 29,468 pairs of images). Both deep learning generative models are able to perform this image transformation task with the Cycle-generative adversarial network (GAN) model outperforming the Conditional-GAN model as measured by aneurysm lumen segmentation accuracy (Cycle-GAN: 86.1% ± 12.2% vs Con-GAN: 85.7% ± 10.4%) and thrombus spatial morphology classification accuracy (Cycle-GAN: 93.5% vs Con-GAN: 85.7%).

Conclusion:
This pipeline implements deep learning methods to generate CTAs from noncontrast images, without the need of contrast injection, that bear strong concordance to the ground truth and enable the assessment of
important clinical metrics. Our pipeline is poised to disrupt clinical pathways requiring intravenous contrast.
Prevention of Firearm Violence Through Specific Types of Community-based Programming
Authors: Bonne Stephanie L. , Violano Pina , Duncan Thomas K. , Pappas Peter A. , Baltazar Gerard A. , Dultz Linda A. , Schroeder Mary E. , Capella Jeanette , Hirsh Michael , Conrad-Schnetz Kristen , Rattan Rishi , Como John J. , Jewell Sarah , Crandall Marie L. 
Published: March 2021

Objective:
The purpose of this review was to provide an evidence-based recommendation for community-based programs to mitigate gun violence, from the Eastern Association for the Surgery of Trauma (EAST).

Summary Background Data:
Firearm Injury leads to >40,000 annual deaths and >115,000 injuries annually in the United States. Communities have adopted culturally relevant strategies to mitigate gun related injury and death. Two such strategies are gun buyback programs and community-based violence prevention programs.

Methods:
The Injury Control and Violence Prevention Committee of EAST developed Population, Intervention, Comparator, Outcomes (PICO) questions and performed a comprehensive literature and gray web literature search. Using GRADE methodology, they reviewed and graded the literature and provided consensus recommendations informed by the literature.

Results:
A total of 19 studies were included for analysis of gun buyback programs. Twenty-six studies were reviewed for analysis for community-based violence prevention programs. Gray literature was added to the discussion of PICO questions from selected websites. A conditional recommendation is made for the implementation of community-based gun buyback programs and a conditional recommendation for community-based violence prevention programs, with special emphasis on cultural appropriateness and community input.

Conclusions:
Gun violence may be mitigated by community-based efforts, such as gun buybacks or violence prevention programs. These programs come with caveats, notably community cultural relevance and proper support and funding from local leadership.
Level of Evidence: Review, Decision, level III.
The MEK Inhibitor Trametinib Suppresses Major Histocompatibility Antigen-mismatched Rejection Following Pancreatic Islet Transplantation
Authors: Tada Seiichiro , Anazawa Takayuki , Shindo Takero , Yamane Kei , Inoguchi Kenta , Fujimoto Nanae , Nagai Kazuyuki , Masui Toshihiko , Okajima Hideaki , Takaori Kyoichi , Sumi Shoichiro , Uemoto Shinji 
Published: March 2021

Background.
Potential adverse effects, such as functional impairment of islets, render conventional immunosuppressive drugs unsuitable for use in islet transplantation. In addition, as a single therapy, they cannot prolong islet allograft survival. Here, we investigated the utility of the mitogen-activated protein kinase inhibitor trametinib and asked whether it ameliorates acute rejection of transplanted islets without the need for conventional immunosuppressants.

Methods.
Islets from fully major histocompatibility complex-mismatched BALB/c mice were transplanted into streptozotocin-induced diabetic C57BL/6 mice via the portal vein. These mice received trametinib or vehicle (orally) for 28 days. Isolated islets from BALB/c mice were incubated in vitro with different concentrations of trametinib to determine viability and function.

Results.
Trametinib (0.1 and 0.3 mg/kg) prolonged graft survival significantly (P = 0.0007 and P = 0.005, respectively) when compared with vehicle. Histologic analyses revealed that cellular infiltration of the graft by lymphocytes was inhibited significantly on day 7 (P < 0.05). In addition, trametinib suppressed functional differentiation of naive CD4+ T cells in recipients. Expression of mRNA encoding inflammatory cytokines interleukin (IL)-2, tumor necrosis factor α, and interferon γ in recipients treated with trametinib was also inhibited (P < 0.001, P < 0.05, and P < 0.01, respectively). Trametinib also increased production of IL-4 and IL-10 (P < 0.05 and P = 0.20, respectively). In vitro, islets incubated with different concentrations of trametinib exhibited no harmful effects with respect to viability and function.

Conclusions.
Trametinib delayed islet graft rejection by inhibiting functional differentiation of naive CD4+ T cells and regulating inflammatory cytokines. Trametinib might be a promising candidate for maintenance immunosuppressive therapy after allogeneic islet transplantation.
The causal effect of serum vitamin D concentration on COVID-19 susceptibility, severity and hospitalization traits: a Mendelian randomization study
Authors: Cui Zhiyong , Tian Yun 
Published: March 2021

AbstractBackgroundEvidence supporting the role of vitamin D in the coronavirus disease 2019 (COVID-19) pandemic remains controversial.MethodsWe performed a two-sample Mendelian randomization (MR) analysis to analyze the causal effect of the 25-hydroxyvitamin D [25(OH)D] concentration on COVID-19 susceptibility, severity and hospitalization traits by using summary-level GWAS data. The causal associations were estimated with inverse variance weighted (IVW) with fixed effects (IVW-fixed) and random effects (IVW-random), MR-Egger, weighted median and MR Robust Adjusted Profile Score (MR.RAPS) methods. We further applied the MR Steiger filtering method, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test and PhenoScanner tool to check and remove single nucleotide polymorphisms (SNPs) that were horizontally pleiotropic.ResultsWe found no evidence to support the causal associations between the serum 25(OH)D concentration and the risk of COVID-19 susceptibility (IVW-fixed: odds ratio [OR] = 0.9049, 95% confidence interval [CI] 0.8197∼0.9988, p = 0.0473), severity (IVW-fixed: OR = 1.0298, 95% CI 0.7699∼1.3775, p = 0.8432) and hospitalized traits (IVW-fixed: OR = 1.0713, 95% CI 0.8819∼1.3013, p = 0.4878) using outlier removed sets at a Bonferroni-corrected p threshold of 0.0167. Sensitivity analyses did not reveal any sign of horizontal pleiotropy.ConclusionsOur MR analysis provided precise evidence that genetically lowered serum 25(OH)D concentrations were not causally associated with COVID-19 susceptibility, severity or hospitalized traits. Our study therefore did not provide evidence assessing the role of vitamin D supplementation during the COVID-19 pandemic. High-quality randomized controlled trials are necessary to explore and define the role of vitamin D supplementation in the prevention and treatment of COVID-19.
Explanatory latent representation of heterogeneous spatial maps of task-fMRI in large-scale datasets
Authors: Zabihi Mariam , Kia Seyed Mostafa , Wolfers Thomas , de Boer Stijn , Fraza Charlotte , Soheili-Nezhad Sourena , Dinga Richard , Llera Arenas Alberto , Bzdok Danilo , Beckmann Christian F. , Marquand Andre 
Published: March 2021

AbstractFinding an interpretable and compact representation of complex neuroimage data can be extremely useful for understanding brain behavioral mapping and hence for explaining the biological underpinnings of mental disorders. Hand-crafted representations, as well as linear transformations, may not accurately reflect the significant variability across individuals. Here, we applied a data-driven approach to learn interpretable and generalizable latent representations that link cognition with underlying brain systems; we applied a three-dimensional autoencoder to two large-scale datasets to find an interpretable latent representation of high dimensional task fMRI image data. This representation also accounts for demographic characteristics, achieved by solving a joint optimization problem that simultaneously reconstructs the data and predicts clinical or demographic variables. We then applied normative modeling to the latent variables to define summary statistics (‘latent indices’) to find a multivariate mapping to non-imaging measures. We trained our model with multi-task fMRI data derived from the Human Connectome Project (HCP) that provides whole-brain coverage across a range of cognitive tasks. Next, in a transfer learning setting, we tested the generalization of our latent space on UK Biobank data as an independent dataset. Our model showed high performance in terms of age and predictions and was capable of capturing complex behavioral characteristics and preserving the individualized variabilities using a highly interpretable latent representation.
Rapid review of social contact patterns during the COVID-19 pandemic
Authors: Liu Carol Y. , Berlin Juliette , Kiti Moses C. , Fava Emanuele Del , Grow André , Zagheni Emilio , Melegaro Alessia , Jenness Samuel M. , Omer Saad , Lopman Benjamin , Nelson Kristin 
Published: March 2021

AbstractBackgroundPhysical distancing measures aim to reduce person-to-person contact, a key driver of transmission of respiratory infections such as SARS-CoV-2. In response to unprecedented restrictions on human contact during the COVID-19 pandemic, a number of studies measured social contact patterns under the implementation of physical distancing measures. This rapid review aims to synthesize empirical data on the changing social contact patterns during the COVID-19 pandemic.MethodWe conducted a systematic review using PubMed, Medline, Embase and Google Scholar following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We descriptively compared the distribution of contacts observed during the pandemic to pre-COVID data across countries to explore changes in contact patterns during physical distancing measures.ResultsWe identified 12 studies that reported social contact patterns during the COVID-19 pandemic. The majority of studies (11/12) collected data during the initial mitigation period in the spring of 2020 marked by government-declared lockdowns and the most stringent physical distancing measures. Some studies collected additional data after relaxation of initial mitigation. Most study settings reported a mean of between 2-5 contacts per person per day, a substantial reduction compared to pre-COVID rates which ranged from 7-26 contacts per day in similar settings. This reduction was particularly pronounced for contacts outside of the home. Consequently, levels of assortative mixing by age substantially declined. After relaxation of initial mitigation, mean contact rates subsequently increased but did not return to pre-COVID levels. Increases in contacts post-relaxation were driven by working-age adults.ConclusionInformation on changes in contact patterns during physical distancing measures can guide more realistic representations of contact patterns in mathematical models for SARS-CoV-2 transmission.
The efficacy and safety of remdesivir in the treatment of patients with COVID-19: a systematic review and meta-analysis
Authors: Lou Lixiang , Zhang Hui , Li Zeqing , Tang Baoming , Li Zhaowei 
Published: March 2021

AbstractBackgroundThe global total of COVID-19 cases will reach 20 million this week, with 750,000 deaths. It has spread to more than 200 countries and regions around the world. At present, the global pandemic continues to rise and continues to spread worldwide. It is necessary to explore the effective and safe treatment of COVID-19 as soon as possible. Remdesiviras was an antiviral agent with therapeutic potential, but it was still controversial.ObjectiveThrough systematic review and meta-analysis, to evaluate the effect and safety of remdesivir in the treatment of patients with COVID-19, and will provide a reliable reference for the treatment of COVID-19.MethodsWe used the following search string: “COVID-19” [Mesh], “remdesivir” [Mesh], “randomized controlled trial” [Mesh]. We used the Medical Subject Heading (MeSH) terms and corresponding keywords to make the search strategy. We searched six databases, PubMed, EMBASE, Cochrane Library, Web of Science, clinical trials.gov and chictr.org.cn. Data analyses were conducted by using the software Review Manager 5.3 and STATA version 14.0.ResultsOur systematic search identified 5 meta-analyses of RCTs, including 1782 patients with COVID-19.The clinical improvement of remdesivir in the treatment of COVID-19 was superior to the placebo-controlled group (relative risk (RR) =1.17, 95% confidence interval (CI)=1.07-1.29, p=0.0009). The following are the Single-Arm Study, Meta-analysis results. The pooled prevalence of clinical improvement significant findings was 62% (95% CI = 59-65%, p=0.00), during treatment of COVID-19 with remdesivir. The incidence rates of Acute kidney injury, Hepatic enzyme increased, Any serious adverse event were 5% (95%CI=3-7%, p=0.00), 11%(95%CI=5-16%, p=0.00), 22%(95%CI=18-27%, p=0.00), respectively, and the mortality was 13%(95%CI=8-19%, p=0.00), during treatment of COVID-19 with remdesivir.ConclusionThis analysis confirms that remdesivir is effective in the clinical improvement of COVID-19 patients, and the rate of clinical improvement was 62%. In addition, adverse events and mortality should also be paid attention to. Future research should aim that more large-scale studies were needed to confirm the results, to further elucidate the underlying mechanisms.