Epitope-focused immunogen design based on the ebolavirus glycoprotein HR2-MPER region.

The three human pathogenic ebolaviruses: Zaire (EBOV), Bundibugyo (BDBV), and Sudan (SUDV) virus, cause severe disease with high fatality rates. Epitopes of ebolavirus glycoprotein (GP) recognized by antibodies with binding breadth for all three ebolaviruses are of major interest for rational vaccine design. In particular, the heptad repeat 2 -membrane-proximal external region (HR2-MPER) epitope is relatively conserved between EBOV, BDBV, and SUDV GP and targeted by human broadly-neutralizing antibodies.

Qualitative assessment of caregiver experiences when navigating childhood immunisation in urban communities in Sierra Leone.

Objective: To gain in-depth understanding of the caregiver experience when navigating urban immunisation services for their children.

Design: An exploratory qualitative assessment comprising 16 in-depth interviews using an interpretative phenomenology approach.

Setting: Caregivers were purposively recruited from slums (n=8) and other urban communities (n=8) in the capital city of Sierra Leone.

Suspect Screening and Chemical Profile Analysis of Storm-Water Runoff Following 2017 Wildfires in Northern California.

The combustion of structures and household materials as well as firefighting during wildfires lead to releases of potentially hazardous chemicals directly into the landscape. Subsequent storm-water runoff events can transport wildfire-related contaminants to downstream receiving waters, where they may pose water quality concerns. To evaluate the environmental hazards of northern California fires on the types of contaminants in storm water discharging to San Francisco Bay and the coastal marine environment, we analyzed storm water collected after the northern California wildfires (October 2017) using a nontargeted analytical (NTA) approach.

Leveraging EHR Data to Evaluate the Association of Late Recognition of Deterioration With Outcomes.

Objectives: Emergency transfers (ETs), deterioration events with late recognition requiring ICU interventions within 1 hour of transfer, are associated with adverse outcomes. We leveraged electronic health record (EHR) data to assess the association between ETs and outcomes. We also evaluated the association between intervention timing (urgency) and outcomes.

Predicting the Need for Therapeutic Intervention and Mortality in Acute Pancreatitis: A Two-Center International Study Using Machine Learning.

Background: Current approaches to predicting intervention needs and mortality have reached 65-85% accuracy, which falls below clinical decision-making requirements in patients with acute pancreatitis (AP). We aimed to accurately predict therapeutic intervention needs and mortality on admission, in AP patients, using machine learning (ML).

Methods: Data were obtained from three databases of patients admitted with AP: one retrospective (Chengdu) and two prospective (Liverpool and Chengdu) databases.

The Benefit of Routine Axillary Sonographic Assessment in cN0 Breast Cancer Patients.

Objective: Axillary ultrasound (US) is often part of the routine assessment of the clinically negative axilla in primary breast cancer, which determines the extent of axillary surgery to be performed. This study aims to ascertain the burden of disease in the axilla of patients with a normal clinical examination (cN0) but with US detected metastatic axillary lymph nodes.

Materials And Methods: We retrospectively identified 345 female patients who underwent axillary lymph node dissection, following a positive lymph node biopsy, between January 2015 and August 2019.

Sensitive Measurement of Minimal Residual Disease in Blood by HAT-PCR.

PCR is widely used to measure minimal residual disease (MRD) in lymphoid neoplasms, but its sensitivity is limited. High Adenine/Thymine PCR and High Annealing Temperature PCR (HAT-PCR) is a modified PCR designed to minimize nonspecificity and hence increase sensitivity. It was evaluated in the laboratory and the clinic, using samples from 58 patients.

Isolation of a Potently Neutralizing and Protective Human Monoclonal Antibody Targeting Yellow Fever Virus.

Yellow fever virus (YFV) causes sporadic outbreaks of infection in South America and sub-Saharan Africa. While live-attenuated yellow fever virus vaccines based on three substrains of 17D are considered some of the most effective vaccines in use, problems with production and distribution have created large populations of unvaccinated, vulnerable individuals in areas of endemicity. To date, specific antiviral therapeutics have not been licensed for human use against YFV or any other related flavivirus.

Clinical Variables Correlate with Serum Neutralizing Antibody Titers after COVID-19 mRNA Vaccination in an Adult, US-based Population.

Background: We studied whether comorbid conditions impact strength and duration of immune responses after SARS-CoV-2 mRNA vaccination in a US-based, adult population.

Methods: Sera (pre-and-post-BNT162b2 vaccination) were tested serially up to 12 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Post-booster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects respectively.

Outcomes of Primary vs. Delayed Strategy of Implanting a Cardiac Monitor for Unexplained Syncope.

Objective: Implantable cardiac monitors (ILR) have an important role in diagnosing unexplained syncope. However, outcomes of primary vs. delayed ILR implantation after initial syncope evaluation have not been explored.

Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617.

COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical.

Near-infrared spectroscopy during cardiopulmonary resuscitation for pediatric cardiac arrest: A prospective, observational study.

Aim: Cerebral oxygenation (rSO2) is not routinely measured during pediatric cardiopulmonary resuscitation (CPR). We aimed to determine whether higher intra-arrest rSO2 was associated with return of spontaneous circulation (ROSC) and survival to hospital discharge.

Methods: Prospective, single-center observational study of cerebral oximetry using near-infrared spectroscopy (NIRS) during pediatric cardiac arrest from 2016 to 2020.

COVID-19 stressors and health behaviors: A multilevel longitudinal study across 86 countries.

Anxiety associated with the COVID-19 pandemic and home confinement has been associated with adverse health behaviors, such as unhealthy eating, smoking, and drinking. However, most studies have been limited by regional sampling, which precludes the examination of behavioral consequences associated with the pandemic at a global level. Further, few studies operationalized pandemic-related stressors to enable the investigation of the impact of different types of stressors on health outcomes.

Using machine learning to identify important predictors of COVID-19 infection prevention behaviors during the early phase of the pandemic.

Before vaccines for coronavirus disease 2019 (COVID-19) became available, a set of infection-prevention behaviors constituted the primary means to mitigate the virus spread. Our study aimed to identify important predictors of this set of behaviors. Whereas social and health psychological theories suggest a limited set of predictors, machine-learning analyses can identify correlates from a larger pool of candidate predictors.

Predictors of adherence to public health behaviors for fighting COVID-19 derived from longitudinal data.

The present paper examines longitudinally how subjective perceptions about COVID-19, one's community, and the government predict adherence to public health measures to reduce the spread of the virus. Using an international survey (N = 3040), we test how infection risk perception, trust in the governmental response and communications about COVID-19, conspiracy beliefs, social norms on distancing, tightness of culture, and community punishment predict various containment-related attitudes and behavior. Autoregressive analyses indicate that, at the personal level, personal hygiene behavior was predicted by personal infection risk perception.

Effect of Physiologic Point-of-Care Cardiopulmonary Resuscitation Training on Survival With Favorable Neurologic Outcome in Cardiac Arrest in Pediatric ICUs: A Randomized Clinical Trial.

Importance: Approximately 40% of children who experience an in-hospital cardiac arrest survive to hospital discharge. Achieving threshold intra-arrest diastolic blood pressure (BP) targets during cardiopulmonary resuscitation (CPR) and systolic BP targets after the return of circulation may be associated with improved outcomes.

Objective: To evaluate the effectiveness of a bundled intervention comprising physiologically focused CPR training at the point of care and structured clinical event debriefings.

Recent decadal weakening of the summer Eurasian westerly jet attributable to anthropogenic aerosol emissions.

The Eurasian subtropical westerly jet (ESWJ) is a major feature of the summertime atmospheric circulation in the Northern Hemisphere. Here, we demonstrate a robust weakening trend in the summer ESWJ over the last four decades, linked to significant impacts on extreme weather. Analysis of climate model simulations from the Coupled Model Intercomparison Project Phase 6 (CMIP6) suggests that anthropogenic aerosols were likely the primary driver of the weakening ESWJ.

Randomized controlled trial: neostigmine for intra-abdominal hypertension in acute pancreatitis.

Background: Intra-abdominal hypertension (IAH) in acute pancreatitis (AP) is associated with deterioration in organ function. This trial aimed to assess the efficacy of neostigmine for IAH in patients with AP.

Methods: In this single-center, randomized trial, consenting patients with IAH within 2 weeks of AP onset received conventional treatment for 24 h.

The FDA-Approved Drug Cobicistat Synergizes with Remdesivir To Inhibit SARS-CoV-2 Replication and Decreases Viral Titers and Disease Progression in Syrian Hamsters.

Combinations of direct-acting antivirals are needed to minimize drug resistance mutations and stably suppress replication of RNA viruses. Currently, there are limited therapeutic options against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and testing of a number of drug regimens has led to conflicting results. Here, we show that cobicistat, which is an FDA-approved drug booster that blocks the activity of the drug-metabolizing proteins cytochrome P450-3As (CYP3As) and P-glycoprotein (P-gp), inhibits SARS-CoV-2 replication.

Cumulative Intraarticular Injections Are Not a Risk Factor for Periprosthetic Joint Infection Following total Knee Arthroplasty.

Background: While injections within 90 days prior to total knee arthroplasty (TKA) are associated with an increased risk of periprosthetic joint infection (PJI), there is a paucity of literature regarding the impact of cumulative injections on PJI risk. This study was conducted to assess the association between cumulative corticosteroid and hyaluronic acid (HA) injections and PJI risk following TKA.

Methods: This retrospective study using an injection database included patients undergoing TKA with a minimum 1-year follow-up from 2015 to 2020.

Artificial intelligence enabled automated diagnosis and grading of ulcerative colitis endoscopy images.

Endoscopic evaluation to reliably grade disease activity, detect complications including cancer and verification of mucosal healing are paramount in the care of patients with ulcerative colitis (UC); but this evaluation is hampered by substantial intra- and interobserver variability. Recently, artificial intelligence methodologies have been proposed to facilitate more objective, reproducible endoscopic assessment. In a first step, we compared how well several deep learning convolutional neural network architectures (CNNs) applied to a diverse subset of 8000 labeled endoscopic still images derived from HyperKvasir, the largest multi-class image and video dataset from the gastrointestinal tract available today.

Early and late-onset syncope: insight into mechanisms.

Aims: Unexplained syncope is an important clinical challenge. The influence of age at first syncope on the final syncope diagnosis is not well studied.

Methods And Results: Consecutive head-up tilt patients (n = 1928) evaluated for unexplained syncope were stratified into age groups <30, 30-59, and ≥60 years based on age at first syncope.

Concern with COVID-19 pandemic threat and attitudes towards immigrants: The mediating effect of the desire for tightness.

Tightening social norms is thought to be adaptive for dealing with collective threat yet it may have negative consequences for increasing prejudice. The present research investigated the role of desire for cultural tightness, triggered by the COVID-19 pandemic, in increasing negative attitudes towards immigrants. We used participant-level data from 41 countries ( = 55,015) collected as part of the PsyCorona project, a cross-national longitudinal study on responses to COVID-19.