G-cleave LC3B biosensor: monitoring autophagy and assessing resveratrol's synergistic impact on doxorubicin-induced apoptosis in breast cancer cells.

Autophagy, a crucial process in cancer, is closely intertwined with both tumor progression and drug resistance development. However, existing methods used to assess autophagy activity often pose invasiveness and time-related constraints, limiting their applicability in preclinical drug investigations. In this study, we developed a non-invasive autophagy detection system (NIADS-autophagy, also called G-cleave LC3B biosensor) by integrating a split-luciferase-based biosensor with an LC3B cleavage sequence, which swiftly identified classic autophagic triggers, such as Earle's Balanced Salt Solution and serum deprivation, through protease-mediated degradation pathways.

European biologic training course for type 2 inflammation by EUFOREA in 2024: key facts and lessons learned.

The European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized the first European Biologic Training Course (EBTC) in Brussels on 1st March 2024. The aim of this hybrid EBTC including both face-to-face and web-based participation was to address the educational needs of physicians dealing with asthma and Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) on the clinically relevant aspects of diagnosing and treatment with biologics. EUFOREA is an international non-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic respiratory diseases through the implementation of optimal patient care via educational, research, and advocacy activities.

Addition of macrolide antibiotics for hospital treatment of community-acquired pneumonia.

Background: Current guidelines recommend combining a macrolide with a β-lactam antibiotic for the empirical treatment of moderate-to-high severity community-acquired pneumonia (CAP); however macrolide use is associated with potential adverse events and antimicrobial resistance.

Methods: We analysed electronic health data from 8,872 adults in Oxfordshire, UK, hospitalised with CAP between 01-January-2016 and 19-March-2024, who received either amoxicillin or co-amoxiclav as initial treatment. We examined the effects of adjunctive macrolides on 30-day all-cause mortality, time to hospital discharge, and changes in Sequential Organ Failure Assessment (SOFA) score, using inverse probability treatment weighting to address confounding by baseline severity.

Distinct virologic trajectories in chronic hepatitis B identify heterogeneity in response to nucleos(t)ide analogue therapy.

Background & Aims: The dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes.

Methods: Utilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment.

Tumour purity assessment with deep learning in colorectal cancer and impact on molecular analysis.

Tumour content plays a pivotal role in directing the bioinformatic analysis of molecular profiles such as copy number variation (CNV). In clinical application, tumour purity estimation (TPE) is achieved either through visual pathological review [conventional pathology (CP)] or the deconvolution of molecular data. While CP provides a direct measurement, it demonstrates modest reproducibility and lacks standardisation.

Management of partial extensor tendon lacerations of the hand and forearm: A national survey of practice in the United Kingdom.

Background: Partial extensor tendon lacerations of the hand and forearm are common. There is a lack of evidence to guide their management and it is also unclear at what threshold surgeons would consider repair necessary. This study aimed to identify national surgical management of partial extensor tendon lacerations of the hand and forearm (zones 2-8) and assess surgeons' willingness to randomise in a future trial.

Safety and immunogenicity of an acellular pertussis vaccine containing genetically detoxified pertussis toxin administered to pregnant women living with and without HIV and their newborns (WoMANPOWER): a randomised controlled trial in Uganda.

Background: Immunisation in pregnancy against pertussis can reduce severe disease in infancy. There are few data on the safety and immunogenicity of vaccines given to pregnant women living with HIV and their infants. We aimed to describe the safety and immunogenicity of a tetanus-diphtheria-acellular pertussis (TdaP) vaccine containing genetically detoxified pertussis toxin given to pregnant women living with HIV and the effect of the vaccine on infant whole-cell pertussis vaccine responses.

The epithelial era of asthma research: knowledge gaps and future direction for patient care.

The Epithelial Science Expert Group convened on 18-19 October 2023, in Naples, Italy, to discuss the current understanding of the fundamental role of the airway epithelium in asthma and other respiratory diseases and to explore the future direction of patient care. This review summarises the key concepts and research questions that were raised. As an introduction to the epithelial era of research, the evolution of asthma management throughout the ages was discussed and the role of the epithelium as an immune-functioning organ was elucidated.

Effects of azithromycin in severe eosinophilic asthma with concomitant monoclonal antibody treatment.

Macrolides reduce exacerbations when added to inhaled therapy in severe asthma. However, there is little published evidence for effectiveness in patients treated with biologics. We conducted a retrospective audit of all patients who started azithromycin while on biologics in our centre.

Hypercoagulation after Hospital Discharge in Acute Severe Ulcerative Colitis: A Prospective Study.

Background & Aims: Venous thromboembolism is a serious complication during and following hospitalization with acute severe ulcerative colitis (ASUC). We evaluated serial thrombotic profiles of patients with ASUC from the point of hospitalization up to 12 weeks post-discharge and compared these with control patients with quiescent UC.

Methods: Twenty-seven patients with ASUC and 25 control patients with quiescent ulcerative colitis (UC) were recruited.

Clinical and genetic characterization of a progressive RBL2-associated neurodevelopmental disorder.

Retinoblastoma (RB) proteins are highly conserved transcriptional regulators that play important roles during development by regulating cell-cycle gene expression. RBL2 dysfunction has been linked to a severe neurodevelopmental disorder. However, to date, clinical features have only been described in six individuals carrying five biallelic predicted loss of function (pLOF) variants.

Non-invasive assessment of portal hypertension in patients with primary biliary cholangitis is affected by severity of cholestasis.

Background&aims: Non-invasive tests (NITs) for ruling-out clinical significant portal hypertension (CSPH) and high-risk varices (HRV) in patients with primary biliary cholangitis(PBC) and compensated advanced chronic liver disease (cACLD) are lacking. We evaluated NITs in these patients and the influence of cholestasis on their performance.

Methods: Consecutive patients from the "Italian PBC registry" and two UK large-volume PBC referral centres with upper endoscopy within 6 months from biochemical evaluation and transient elastography were included.

Promoting Prevention and Targeting Remission of Asthma A EUFOREA Consensus Statement on Raising the Bar in Asthma Care.

Topic Importance: Asthma is a common multifaceted respiratory disease with a major impact on quality of life. Despite increased insights into mechanisms underlying various asthma phenotypes/endotypes and the availability of targeted biologic treatment options, a substantial proportion of patients remains uncontrolled with risk of exacerbations, requiring systemic corticosteroids, and progressive disease. Current international guidelines advocate a personalized management approach to patients with uncontrolled severe asthma.

Safety and efficacy of the blood-stage malaria vaccine RH5.1/Matrix-M in Burkina Faso: interim results of a double-blind, randomised, controlled, phase 2b trial in children.

Background: Two pre-erythrocytic vaccines (R21/Matrix-M and RTS,S/AS01) are now approved for Plasmodium falciparum malaria. However, neither induces blood-stage immunity against parasites that break through from the liver. RH5.

Asparagine availability controls germinal center B cell homeostasis.

The rapid proliferation of germinal center (GC) B cells requires metabolic reprogramming to meet energy demands, yet these metabolic processes are poorly understood. By integrating metabolomic and transcriptomic profiling of GC B cells, we identified that asparagine (Asn) metabolism was highly up-regulated and essential for B cell function. Asparagine synthetase (ASNS) was up-regulated after B cell activation through the integrated stress response sensor GCN2.

Impact of Female Sex and Mild Cortisol Secretion on Coagulation Profile in Adrenal Incidentalomas.

Context: Studies describing the coagulation profile in adrenal adenomas still need to be added.

Objective: We explored how sex and mild autonomous cortisol secretion (MACS) affect coagulation parameters in patients with adrenal adenomas.

Design: Cross-sectional study.

Genomic perspective on the bacillus causing paratyphoid B fever.

Paratyphoid B fever (PTB) is caused by an invasive lineage (phylogroup 1, PG1) of Salmonella enterica serotype Paratyphi B (SPB). However, little was known about the global population structure, geographic distribution, and evolution of this pathogen. Here, we report a whole-genome analysis of 568 historical and contemporary SPB PG1 isolates, obtained globally, between 1898 and 2021.

Treatments for RYR1-related disorders.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: Primary objective To analyse the benefits and harms of pharmacological or other interventions (e.g.

The respiratory microbiome is linked to the severity of RSV infections and the persistence of symptoms in children.

Respiratory syncytial virus (RSV) is the leading cause of infant respiratory infections and hospitalizations. To investigate the relationship between the respiratory microbiome and RSV infection, we sequence nasopharyngeal samples from a birth cohort and a pediatric case-control study (Respiratory Syncytial virus Consortium in Europe [RESCEU]). 1,537 samples are collected shortly after birth ("baseline"), during RSV infection and convalescence, and from healthy controls.

Glucocorticoid treatment and new-onset hyperglycaemia and diabetes in people living with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

Introduction: In people living with chronic obstructive pulmonary disease (COPD), we aimed to estimate: (1) the prevalence of glucocorticoid-induced hyperglycaemia (GIH); (2) whether the prevalence of GIH varies by age, baseline diabetes status, treatment duration, ascertainment of glycaemia, definition of hyperglycaemia, study design and year of publication; and (3) the relative risk (RR) of new-onset hyperglycaemia in exposed vs non-exposed to systemic glucocorticoids.

Methods: We searched electronic databases until 9 November 2023 for randomised controlled trials and observational studies including adults diagnosed with COPD, with or without diabetes at baseline, using systemic glucocorticoids equivalent to prednisolone ≥5 mg/day for ≥3 days if exposed. Hyperglycaemia was defined as a blood glucose above a study-specific cut-off.

Systems Immunology Approaches to Understanding Immune Responses in Acute Infection of Yellow Fever Patients.

In the 2018 yellow fever (YF) outbreak in Brazil, we generated new transcriptomic data and combined it with clinical and immunological data to decode the pathogenesis of YF. Analyzing 79 patients, we found distinct gene expression patterns between acute YF, other viral infections, and the milder YF-17D vaccine infection. We identified a critical role for low-density, immature neutrophils in severe outcomes, marked by the downregulation of genes essential for neutrophil migration and maturation, such as PADI4, CSF3R, and ICAM1, in deceased patients.