Transmission dynamics of Norovirus GII and Enterovirus in Switzerland during the COVID-19 pandemic (2021-2022) as evidenced in wastewater.

Noroviruses and enteroviruses are major causes of endemic gastrointestinal disease associated with substantial disease burden. However, viral gastroenteritis is often diagnosed based on symptoms, with etiology infrequently tested or reported, so little information exists on community-level transmission dynamics. In this study, we demonstrate that norovirus (NoV) genogroup II and enterovirus (EV) viral loads in wastewater reveal transmission dynamics of these viruses.

Inactivation of SARS-CoV-2 at acidic pH is driven by partial unfolding of spike.

SARS-CoV-2, the causative agent of COVID-19, is predominantly transmitted by respiratory aerosol and contaminated surfaces. Recent studies demonstrated that aerosols can become acidic, and acidification has been proposed as decontamination method. Here, we investigate how SARS-CoV-2 reacts to acidic pH and by which mechanism the virus is inactivated.

The Influence of Hospital Policies on Clinicians' Decisions to Withhold or Withdraw Life-Sustaining Treatment.

Background: There is considerable variation in clinicians' approaches to decisions to withhold or withdraw life sustaining treatment (LST) across US hospitals. These differences are not explained by patient preferences alone and are likely influenced by other factors (eg, hospital policies, hospital culture, state laws, medical society guidelines).

Research Question: How do hospital policies influence clinician approaches to decisions to withhold or withdraw LST among patients admitted to an ICU?

Study Design And Methods: We conducted semistructured interviews with ICU nurses and physicians at 3 geographically diverse hospital systems across the United States between July and October 2024.

Emergence of Bictegravir Resistance in a Treatment-Experienced PWH on Functional Monotherapy and Rapid Replacement by an Ancient Wild-Type Strain Following Transient Treatment Interruption.

A treatment-experienced, highly adherent person living with HIV for over 25 years developed resistance mutations against all four major ART classes, including bictegravir (BIC). This led to viral failure on a quadruple regimen including BIC and doravirine (DOR). Resistance emergence was associated with M184V, thymidine analog mutations (TAMs), NNRTI mutations (108I, 234I, 318F), and INSTI mutations (T97A, G140S, Q148H, G149A), likely driven by suboptimal BIC levels due to divalent cation interactions.

Generation of Neutron Airy Beams.

The Airy wave packet is a solution to the potential-free Schrödinger equation that exhibits remarkable properties such as self-acceleration, nondiffraction, and self-healing. Although Airy beams are now routinely realized with electromagnetic waves and electrons, the implementation with neutrons has remained elusive due to small transverse coherence lengths, low fluence rates, and the absence of neutron lenses. In this Letter, we overcome these challenges through a holographic approach and present the first experimental demonstration of neutron Airy beams.

Addressing data management and analysis challenges in viral genomics: The Swiss HIV cohort study viral next generation sequencing database.

Numerous HIV related outcomes can be determined on the viral genome, for example, resistance associated mutations, population transmission dynamics, viral heritability traits, or time since infection. Viral sequences of people with HIV (PWH) are therefore essential for therapeutic and research purposes. While in the first three decades of the HIV pandemic viral genomes were mainly sequenced using Sanger sequencing, the last decade has seen a shift towards next-generation sequencing (NGS) as the preferred method.

Patient Activation and Shared Decision-Making Among Hispanics/Latinos With Metastatic Cancer: A Qualitative Study.

Background: Patient activation is established when patients are equipped with the necessary knowledge, skills, and motivation to meaningfully participate in managing their health and, along with shared decision-making, improves clinical outcomes like treatment adherence. Little is known regarding patient activation among Hispanics/Latinos with metastatic cancer, who report worse quality of life and symptom burden compared to non-Hispanic/Latino Whites.

Aims: This study aimed to characterize barriers and facilitators to patient activation and shared decision-making among English- and Spanish-speaking Hispanics/Latinos with metastatic cancer.

TGF-β1 Induces Mucosal Mast Cell Genes and is Negatively Regulated by the IL-3/ERK1/2 Axis.

Mast cells develop from the myeloid lineage and are released from the bone marrow as immature cells, which then differentiate at the destination tissue based on cues from the local environment. In the liver, mast cells are recruited in diseased states to fibrogenic surroundings rich in TGF-β1. The aim of this study was to investigate TGF-β1 signaling in primary and permanent mast cells to identify common and unique mechanisms.

Rare twin cysteine residues in the HIV-1 envelope variable region 1 link to neutralization escape and breadth development.

Identifying HIV-1 envelope (Env) traits associated with neutralization cross-reactivity is crucial for vaccine design. Variable loops 1 and 2 (V1V2), positioned at the Env trimer apex, are key regions linked to neutralization. We describe non-canonical cysteine (Cys) residues in V1 that are enriched in individuals with elite neutralization breadth.

Low agreement and frequent invalid controls in two SARS-CoV-2 T-cell assays in people with compromised immune function.

T-cell response plays an important role in SARS-CoV-2 immunogenicity. For people living with HIV (PWH) and solid organ transplant (SOT) recipients there is limited evidence on the reliability of commercially available T-cell tests. We assessed 173 blood samples from 81 participants (62 samples from 35 PWH; 111 samples from 46 SOT recipients [lung and kidney]) with two commercial SARS-CoV-2 Interferon-γ (IFN-γ) release assays (IGRA; SARS-CoV-2 IGRA by Euroimmun, and IGRA SARS-CoV-2 by Roche).

Small-angle scattering interferometry with neutron orbital angular momentum states.

Methods to prepare and characterize neutron helical waves carrying orbital angular momentum (OAM) were recently demonstrated at small-angle neutron scattering (SANS) facilities. These methods enable access to the neutron orbital degree of freedom which provides new avenues of exploration in fundamental science experiments as well as in material characterization applications. However, it remains a challenge to recover phase profiles from SANS measurements.

KIRA6 is an Effective and Versatile Mast Cell Inhibitor of IgE-mediated Activation.

Mast cell (MC)-driven allergic diseases are constantly expanding and require the development of novel pharmacological MC stabilizers. Allergen/antigen (Ag)-triggered activation via crosslinking of the high-affinity receptor for IgE (FcεRI) is fundamentally regulated by SRC family kinases, for example, LYN and FYN, exhibiting positive and negative functions. We report that KIRA6, an inhibitor for the endoplasmic reticulum stress sensor IRE1α, suppresses IgE-mediated MC activation by inhibiting both LYN and FYN.

Highly sensitive reporter cell line for detection of interferon types I-III and their neutralization by antibodies.

Interferons (IFNs) are a critical component of innate immune defenses and limit viral disease severity. To advance studies on IFNs and their neutralization by pathogenic autoantibodies, we generated a Renilla luciferase-based reporter cell line capable of detecting the activities of IFN-Is, IFN-II, and IFN-IIIs. The reporter cell line exhibits a 125- to 2000-fold higher sensitivity to IFNs than a commonly used alternative biological reporter system and allows for a rapid and simple live-cell workflow for detecting low titer amounts of neutralizing anti-IFN antibodies.

Decoupling HIV-1 antiretroviral drug inhibition from plasma antibody activity to evaluate broadly neutralizing antibody therapeutics and vaccines.

The development of broadly neutralizing antibody (bnAb)-based therapeutic HIV-1 vaccines and cure concepts depends on monitoring bnAb plasma activity in people with HIV (PWH) on suppressive antiretroviral therapy (ART). To enable this, analytical strategies must be defined to reliably distinguish antibody-based neutralization from drug inhibition. Here, we explore strategies that either utilize drug-resistant viruses or remove drugs from plasma.

Enzyme Is the Name-Adapter Is the Game.

Signaling proteins in eukaryotes usually comprise a catalytic domain coupled to one or several interaction domains, such as SH2 and SH3 domains. An additional class of proteins critically involved in cellular communication are adapter or scaffold proteins, which fulfill their purely non-enzymatic functions by organizing protein-protein interactions. Intriguingly, certain signaling enzymes, e.

Using viral diversity to identify HIV-1 variants under HLA-dependent selection in a systematic viral genome-wide screen.

The pathogenesis of HIV-1 infection is governed by a highly dynamic, time-dependent interaction between the host and the viral genome. In this study, we developed a novel systematic approach to assess the host-virus interaction, using average pairwise viral diversity as a proxy for time since infection, and applied this method to nearly whole viral genome sequences (n = 4,464), human leukocyte antigen (HLA) genotyping data (n = 1,044), and viral RNA load (VL) measurements during the untreated chronic phase (n = 829) of Swiss HIV Cohort Study participants. Our systematic genome-wide screen revealed for 98 HLA/viral-variant pairs a signature of immune-driven selection in the form of an HLA-dependent effect of infection time on the presence of HIV amino acid variants.

Loss of tolerance precedes triggering and lifelong persistence of pathogenic type I interferon autoantibodies.

Autoantibodies neutralizing type I interferons (IFN-Is) can underlie infection severity. Here, we trace the development of these autoantibodies at high-resolution using longitudinal samples from 1,876 well-treated individuals living with HIV over a 35-year period. Similar to general populations, ∼1.

Self-reported neurocognitive complaints in the Swiss HIV Cohort Study: a viral genome-wide association study.

People with HIV may report neurocognitive complaints, with or without associated neurocognitive impairment, varying between individuals and populations. While the HIV genome could play a major role, large systematic viral genome-wide screens to date are lacking. The Swiss HIV Cohort Study biannually enquires neurocognitive complaints.