The metabolic and circadian signatures of gestational diabetes in the postpartum period characterised using multiple wearable devices.

Aims/hypothesis: Gestational diabetes mellitus (GDM) affects 14% of all pregnancies worldwide and is associated with cardiometabolic risk. We aimed to exploit high-resolution wearable device time-series data to create a fine-grained physiological characterisation of the postpartum GDM state in free-living conditions, including clinical variables, daily glucose dynamics, food and drink consumption, physical activity, sleep patterns and heart rate.

Methods: In a prospective observational study, we employed continuous glucose monitors (CGMs), a smartphone food diary, triaxial accelerometers and heart rate and heart rate variability monitors over a 2 week period to compare women who had GDM in the previous pregnancy (GDM group) and women who had a pregnancy with normal glucose metabolism (non-GDM group) at 1-2 months after delivery (baseline) and 6 months later (follow-up).

Use of large language models as a scalable approach to understanding public health discourse.

Online public health discourse is becoming more and more important in shaping public health dynamics. Large Language Models (LLMs) offer a scalable solution for analysing the vast amounts of unstructured text found on online platforms. Here, we explore the effectiveness of Large Language Models (LLMs), including GPT models and open-source alternatives, for extracting public stances towards vaccination from social media posts.

Cystic fibrosis.

Cystic fibrosis is a rare genetic disease caused by mutations in CFTR, the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). The discovery of CFTR in 1989 has enabled the unravelling of disease mechanisms and, more recently, the development of CFTR-directed therapeutics that target the underlying molecular defect. The CFTR protein functions as an ion channel that is crucial for correct ion and fluid transport across epithelial cells lining the airways and other organs.

ETD001: A novel inhaled ENaC blocker with an extended duration of action in vivo.

Background: Inhibiting ENaC in the airways of people with cystic fibrosis (pwCF) is hypothesized to enhance mucociliary clearance (MCC) and provide clinical benefit. Historically, inhaled ENaC blockers have failed to show benefit in pwCF challenging this hypothesis. It is however unknown whether the clinical doses were sufficient to provide the required long duration of action in the lungs and questions whether a novel candidate could offer advantages where others have failed?

Methods: Dose-responses with the failed ENaC blockers (VX-371, BI 1265162, AZD5634, QBW276) together with ETD001 (a novel long acting inhaled ENaC blocker) were established in a sheep model of MCC and were used to predict clinically relevant doses that would provide a long-lasting enhancement of MCC in pwCF.

Response to Elexacaftor/Tezacaftor/Ivacaftor in people with cystic fibrosis with the N1303K mutation: Case report and review of the literature.

Cystic fibrosis (CF) is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Thousands of CFTR mutations have been identified, but only a fraction are known to cause CF, with the most common being the prototypical class II CFTR mutation F508del. Elexacaftor-Tezacaftor-Ivacaftor (ETI) is a CFTR modulator that significantly increases ppFEV1 and reduces exacerbation frequencies.

The combination of propylene glycol and vegetable glycerin e-cigarette aerosols induces airway inflammation and mucus hyperconcentration.

Despite concerns over their safety, e-cigarettes (e-cigs) remain a popular tobacco product. Although nicotine and flavors found in e-cig liquids (e-liquids) can cause harm in the airways, whether the delivery vehicles propylene glycol (PG) and vegetable glycerin (VG) are innocuous when inhaled remains unclear. Here, we investigated the effects of e-cig aerosols generated from e-liquid containing only PG/VG on airway inflammation and mucociliary function in primary human bronchial epithelial cells (HBEC) and sheep.

Food & You: A digital cohort on personalized nutrition.

Nutrition is a key contributor to health. Recently, several studies have identified associations between factors such as microbiota composition and health-related responses to dietary intake, raising the potential of personalized nutritional recommendations. To further our understanding of personalized nutrition, detailed individual data must be collected from participants in their day-to-day lives.

SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in cell culture and in mice.

Several coronavirus (CoV) encoded proteins are being evaluated as targets for antiviral therapies for COVID-19. Included in these drug targets is the conserved macrodomain, or Mac1, an ADP-ribosylhydrolase and ADP-ribose binding protein encoded as a small domain at the N terminus of nonstructural protein 3. Utilizing point mutant recombinant viruses, Mac1 was shown to be critical for both murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV virulence.

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Immune dysregulation contributes to poorer outcomes in COVID-19.

Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

Design, Setting, And Participants: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia.

Hits and Misses: Digital Contact Tracing in a Pandemic.

Traditional contact tracing is one of the most powerful weapons people have in the battle against a pandemic, especially when vaccines do not yet exist or do not afford complete protection from infection. But the effectiveness of contact tracing hinges on its ability to find infected people quickly and obtain accurate information from them. Therefore, contact tracing inherits the challenges associated with the fallibilities of memory.

Losartan in hospitalized patients with COVID-19 in North America: An individual participant data meta-analysis.

Background: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) have been hypothesized to benefit patients with COVID-19 via the inhibition of viral entry and other mechanisms. We conducted an individual participant data (IPD) meta-analysis assessing the effect of starting the ARB losartan in recently hospitalized COVID-19 patients.

Methods: We searched ClinicalTrials.

Rev-erbα agonists suppresses TGFβ1-induced fibroblast-to-myofibroblast transition and pro-fibrotic phenotype in human lung fibroblasts.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by excessive scarring of the lungs that can lead to respiratory failure and death. Lungs of patients with IPF demonstrate excessive deposition of extracellular matrix (ECM) and an increased presence of pro-fibrotic mediators such as transforming growth factor-beta 1 (TGFβ1), which is a major driver of fibroblast-to-myofibroblast transition (FMT). Current literature supports that circadian clock dysfunction plays an essential role in the pathophysiology of various chronic inflammatory lung diseases such as asthma, chronic obstructive pulmonary disease, and IPF.

Lower respiratory tract microbiome composition and community interactions in smokers.

The lung microbiome impacts on lung function, making any smoking-induced changes in the lung microbiome potentially significant. The complex co-occurrence and co-avoidance patterns between the bacterial taxa in the lower respiratory tract (LRT) microbiome were explored for a cohort of active (AS), former (FS) and never (NS) smokers. Bronchoalveolar lavages (BALs) were collected from 55 volunteer subjects (9 NS, 24 FS and 22 AS).

Transport of Designed Ankyrin Repeat Proteins through reconstituted human bronchial epithelia and protection against SARS-CoV-2.

Clinical studies have proven antiviral effectiveness of treatment with a Designed Ankyrin Repeat Protein (DARPin) specific against the spike protein of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). More information on transport mechanisms and efficiency to the site of action is desirable. Transepithelial migration through air-liquid interface (ALI) cultures of reconstituted human bronchial epithelia (HBE) was assessed by Enzyme-Linked Immunosorbent Assays and Confocal Laser Scanning Microscopy for different DARPin designs in comparison to a monoclonal antibody.

COVID-Twitter-BERT: A natural language processing model to analyse COVID-19 content on Twitter.

Introduction: This study presents COVID-Twitter-BERT (CT-BERT), a transformer-based model that is pre-trained on a large corpus of COVID-19 related Twitter messages. CT-BERT is specifically designed to be used on COVID-19 content, particularly from social media, and can be utilized for various natural language processing tasks such as classification, question-answering, and chatbots. This paper aims to evaluate the performance of CT-BERT on different classification datasets and compare it with BERT-LARGE, its base model.

Dynamics of social media behavior before and after SARS-CoV-2 infection.

Introduction: Online social media have been both a field of research and a source of data for research since the beginning of the COVID-19 pandemic. In this study, we aimed to determine how and whether the content of tweets by Twitter users reporting SARS-CoV-2 infections changed over time.

Methods: We built a regular expression to detect users reporting being infected, and we applied several Natural Language Processing methods to assess the emotions, topics, and self-reports of symptoms present in the timelines of the users.

E-cigarette aerosols of propylene glycol impair BK channel activity and parameters of mucociliary function.

Propylene glycol (PG) is a common delivery vehicle for nicotine and flavorings in e-cigarette (e-cig) liquids and is largely considered safe for ingestion. However, little is known about its effects as an e-cig aerosol on the airway. Here, we investigated whether pure PG e-cig aerosols in realistic daily amounts impact parameters of mucociliary function and airway inflammation in a large animal model (sheep) in vivo and primary human bronchial epithelial cells (HBECs) in vitro.

Timeliness of online COVID-19 reports from official sources.

Introduction: Making epidemiological indicators for COVID-19 publicly available through websites and social media can support public health experts in the near-real-time monitoring of the situation worldwide, and in the establishment of rapid response and public health measures to reduce the consequences of the pandemic. Little is known, however, about the timeliness of such sources. Here, we assess the timeliness of official public COVID-19 sources for the WHO regions of Europe and Africa.

Nebulized Menthol Impairs Mucociliary Clearance via TRPM8 and MUC5AC/MUC5B in Primary Airway Epithelial Cells.

Flavorings enhance the palatability of e-cigarettes (e-cigs), with menthol remaining a popular choice among e-cig users. Menthol flavor remains one of the only flavors approved by the United States FDA for use in commercially available, pod-based e-cigs. However, the safety of inhaled menthol at the high concentrations used in e-cigs remains unclear.

Differences Between Centers in Psychosocial Evaluations for Living Kidney Donors Do Not Influence Outcome: Results From an Observational Multicenter Study.

Unlabelled: Rather little is known about how psychosocial evaluations for living kidney donation (LKD) are performed. We aimed to explore whether Swiss transplant centers (STCs) vary regarding the rate of living kidney donors refused for psychosocial reasons, the psychosocial evaluation process, and the characteristics of the donors.

Methods: We investigated 310 consecutive candidates for LKD in 4 of 6 existing STC during mandatory psychosocial evaluations.

Role of Secondary Organic Matter on Soot Particle Toxicity in Reconstituted Human Bronchial Epithelia Exposed at the Air-Liquid Interface.

Secondary organic matter (SOM) formed from gaseous precursors constitutes a major mass fraction of fine particulate matter. However, there is only limited evidence on its toxicological impact. In this study, air-liquid interface cultures of human bronchial epithelia were exposed to different series of fresh and aged soot particles generated by a miniCAST burner combined with a micro smog chamber (MSC).

Vegetable glycerin e-cigarette aerosols cause airway inflammation and ion channel dysfunction.

Vegetable glycerin (VG) and propylene glycol (PG) serve as delivery vehicles for nicotine and flavorings in most e-cigarette (e-cig) liquids. Here, we investigated whether VG e-cig aerosols, in the absence of nicotine and flavors, impact parameters of mucociliary function in human volunteers, a large animal model (sheep), and air-liquid interface (ALI) cultures of primary human bronchial epithelial cells (HBECs). We found that VG-containing (VG or PG/VG), but not sole PG-containing, e-cig aerosols reduced the activity of nasal cystic fibrosis transmembrane conductance regulator (CFTR) in human volunteers who vaped for seven days.