Insights into xanthine riboswitch structure and metal ion-mediated ligand recognition.

Riboswitches are conserved functional domains in mRNA that mostly exist in bacteria. They regulate gene expression in response to varying concentrations of metabolites or metal ions. Recently, the NMT1 RNA motif has been identified to selectively bind xanthine and uric acid, respectively, both are involved in the metabolic pathway of purine degradation.

Treatment outcomes in HIV infected patients older than 50 years attending an HIV clinic in Harare, Zimbabwe: A cohort study.

There is a growing number of older people living with HIV (OPLHIV). While a significant proportion of this population are adults growing into old age with HIV, there are also new infections among OPLHIV. There is a lack of data describing the outcomes of OPLHIV who commenced antiretroviral therapy (ART) after the age of 50 years in sub-Saharan Africa.

An Improved Staging System for Locally Advanced Pancreatic Cancer: A Critical Need in the Multidisciplinary Era.

Background: Locally-advanced pancreatic cancer (LAPC) is traditionally considered stage III unresectable disease. Advances in induction systemic therapy regimens, surgical technique, and perioperative care have led to successful resection of an increasing number of these tumors with reasonable perioperative outcomes and disease-free intervals. Certain anatomic characteristics that meet criteria for locally-advanced disease, however, are more likely to result in a successful surgical outcome.

A two-stage prediction model for heterogeneous effects of treatments.

Treatment effects vary across different patients, and estimation of this variability is essential for clinical decision-making. We aimed to develop a model estimating the benefit of alternative treatment options for individual patients, extending a risk modeling approach in a network meta-analysis framework. We propose a two-stage prediction model for heterogeneous treatment effects by combining prognosis research and network meta-analysis methods where individual patient data are available.

Tracing People Living With Human Immunodeficiency Virus Who Are Lost to Follow-up at Antiretroviral Therapy Programs in Southern Africa: A Sampling-Based Cohort Study in 6 Countries.

Background: Attrition threatens the success of antiretroviral therapy (ART). In this cohort study, we examined outcomes of people living with human immunodeficiency virus (PLHIV) who were lost to follow-up (LTFU) during 2014-2017 at ART programs in Southern Africa.

Methods: We confirmed LTFU (missed appointment for ≥60 or ≥90 days, according to local guidelines) by checking medical records and used a standardized protocol to trace a weighted random sample of PLHIV who were LTFU in 8 ART programs in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, 2017-2019.

Cervical mucus patterns and the fertile window in women without known subfertility: a pooled analysis of three cohorts.

Study Question: What is the normal range of cervical mucus patterns and number of days with high or moderate day-specific probability of pregnancy (if intercourse occurs on a specific day) based on cervical mucus secretion, in women without known subfertility, and how are these patterns related to parity and age?

Summary Answer: The mean days of peak type (estrogenic) mucus per cycle was 6.4, the mean number of potentially fertile days was 12.1; parous versus nulliparous, and younger nulliparous (<30 years) versus older nulliparous women had more days of peak type mucus, and more potentially fertile days in each cycle.

Longitudinal Relationship between Idylla Plasma ctBRAF V600 Mutation Detection and Tumor Burden in Patients with Metastatic Melanoma.

Background: Circulating tumor DNA (ctDNA) may complement radiography for interim assessment of patients with cancer.

Objective: Our objective was to explore the relationship between changes in plasma ctDNA versus radiographic imaging among patients with metastatic melanoma.

Methods: Using the Idylla system, we measured B-Raf proto-oncogene (BRAF) V600 ctDNA in plasma from 15 patients with BRAF V600E/K-positive primary tumors undergoing standard-of-care monitoring, including cross-sectional computed tomography (CT) imaging.

Face-to-face panel meetings versus remote evaluation of fellowship applications: simulation study at the Swiss National Science Foundation.

Objectives: To trial a simplified, time and cost-saving method for remote evaluation of fellowship applications and compare this with existing panel review processes by analysing concordance between funding decisions, and the use of a lottery-based decision method for proposals of similar quality.

Design: The study involved 134 junior fellowship proposals for postdoctoral research ('Postdoc.Mobility').

A comprehensive antigen production and characterisation study for easy-to-implement, specific and quantitative SARS-CoV-2 serotests.

Background: Antibody tests are essential tools to investigate humoral immunity following SARS-CoV-2 infection or vaccination. While first-generation antibody tests have primarily provided qualitative results, accurate seroprevalence studies and tracking of antibody levels over time require highly specific, sensitive and quantitative test setups.

Methods: We have developed two quantitative, easy-to-implement SARS-CoV-2 antibody tests, based on the spike receptor binding domain and the nucleocapsid protein.

Low Rate of SARS-CoV-2 Infections in Symptomatic Patients Attending a Pediatric Emergency Department.

Children and adolescents seem to be at lower risk of developing clinical symptoms of COVID-19. We analyzed the rate of SARS-CoV-2 infections among 3,605 symptomatic children and adolescents at 4,402 outpatient visits presenting to a pediatric emergency department. In a total of 1,105 (32.

Impact of 3-deazapurine nucleobases on RNA properties.

Deazapurine nucleosides such as 3-deazaadenosine (c3A) are crucial for atomic mutagenesis studies of functional RNAs. They were the key for our current mechanistic understanding of ribosomal peptide bond formation and of phosphodiester cleavage in recently discovered small ribozymes, such as twister and pistol RNAs. Here, we present a comprehensive study on the impact of c3A and the thus far underinvestigated 3-deazaguanosine (c3G) on RNA properties.

JNK signaling prevents biliary cyst formation through a CASPASE-8-dependent function of RIPK1 during aging.

The c-Jun N-terminal kinase (JNK) signaling pathway mediates adaptation to stress signals and has been associated with cell death, cell proliferation, and malignant transformation in the liver. However, up to now, its function was experimentally studied mainly in young mice. By generating mice with combined conditional ablation of and in liver parenchymal cells (LPCs) (JNK1/2 mice; KO, knockout), we unraveled a function of the JNK pathway in the regulation of liver homeostasis during aging.

Public willingness to participate in personalized health research and biobanking: A large-scale Swiss survey.

This paper reports survey findings on the Swiss public's willingness, attitudes, and concerns regarding personalized health research participation by providing health information and biological material. The survey reached a sample of 15,106 Swiss residents, from which we received 5,156 responses (34.1% response rate).

Storm of Cardiovascular Markers After LPS Administration in Human Volunteers.

Acute infections are associated with an elevated cardiovascular risk. However, little is known about the interactions of acute inflammatory responses and the cardiovascular system. We therefore aimed to evaluate effects of acute inflammatory stimuli mediated by LPS administration on a set of 89 cardiovascular biomarkers.

Outcomes of Esophageal Stent Therapy for the Management of Anastomotic Leaks.

Background: The purpose of this study was to present the optimal patient selection for esophageal stenting after esophageal resection to investigate possible factors leading to treatment success or treatment failure in these patients.

Methods: This was a prospective, observational study of patients from January 2005 to May 2019 with an esophageal anastomotic leak that were treated with a self-expandable stent (SES).

Results: A total of 34 patients were treated.

Effects of National Adoption of Treat-All Guidelines on Pre-Antiretroviral Therapy (ART) CD4 Testing and Viral Load Monitoring After ART initiation: A Regression Discontinuity Analysis.

Background: The World Health Organization's Treat-All guidance recommends CD4 testing before initiating antiretroviral therapy (ART), and routine viral load (VL) monitoring (over CD4 monitoring) for patients on ART.

Methods: We used regression discontinuity analyses to estimate changes in CD4 testing and VL monitoring among 547 837 ART-naive patients enrolling in human immunodeficiency virus (HIV) care during 2006-2018 at 225 clinics in 26 countries where Treat-All policies were adopted. We examined CD4 testing within 12 months before and VL monitoring 6 months after ART initiation among adults (≥20 years), adolescents (10-19 years), and children (0-9 years) in low/lower-middle-income countries (L/LMICs) and high/upper-middle-income countries (H/UMICs).

Losing ground at the wrong time: trends in self-reported influenza vaccination uptake in Switzerland, Swiss Health Survey 2007-2017.

Objectives: We studied time trends in seasonal influenza vaccination and associations with socioeconomic and health-related determinants in Switzerland, overall and in people aged ≥65 years.

Design: Three cross-sectional surveys.

Participants: Individuals who participated in the Swiss Health Surveys 2007, 2012 and 2017.

Immunodeficiency and Cancer in 3.5 Million People Living With Human Immunodeficiency Virus (HIV): The South African HIV Cancer Match Study.

Background: We analyzed associations between immunodeficiency and cancer incidence in a nationwide cohort of people living with human immunodeficiency virus (HIV; PLWH) in South Africa.

Methods: We used data from the South African HIV Cancer Match Study built on HIV-related laboratory measurements from the National Health Laboratory Services and cancer records from the National Cancer Registry. We evaluated associations between time-updated CD4 cell count and cancer incidence rates using Cox proportional hazards models.

A Bayesian dose-response meta-analysis model: A simulations study and application.

Dose-response models express the effect of different dose or exposure levels on a specific outcome. In meta-analysis, where aggregated-level data is available, dose-response evidence is synthesized using either one-stage or two-stage models in a frequentist setting. We propose a hierarchical dose-response model implemented in a Bayesian framework.