Rationale and Ethical Assessment of an Oropharyngeal Gonorrhoea Controlled Human Infection Model.

Infection with Neisseria gonorrhoeae, the causative agent of gonorrhoea, causes significant morbidity worldwide and can have long-term impacts on reproductive health. The greatest global burden of gonorrhoea occurs in low- and middle-income settings. Global public health significance is increasing due to rising antimicrobial resistance (AMR), which threatens future gonorrhoea management.

Inter-Rater Disagreements in Applying the Montreal Classification for Crohn's Disease: The Five-Nations Survey Study.

Background: The Montreal classification has been widely used in Crohn's disease since 2005 to categorize patients by the age of onset (A), disease location (L), behavior (B), and upper gastrointestinal tract and perianal involvement. With evolving management paradigms in Crohn's disease, we aimed to assess the performance of gastroenterologists in applying the Montreal classification.

Methods: An online survey was conducted among participants at an international educational conference on inflammatory bowel diseases.

Study of Children Aged Under 2 Years Admitted With RSV at Four Australian Hospitals [2021-2022].

Aims: Primary aim was to review severe acute respiratory infections (SARI) hospitalisations caused by respiratory syncytial virus (RSV) in children aged < 2 years in paediatric hospitals in Australia. Secondary aims included RSV subtyping, assessing RSV seasonality and contributing to the World Health Organisation's RSV surveillance programme.

Methods: We prospectively reviewed the medical records of children (< 2 years of age) with a confirmed SARI who were admitted to one of four major Australian paediatric hospitals and had a respiratory sample analysed by Polymerase Chain Reaction (PCR).

Immunotherapy-Resistant Neuropathic Pain and Fatigue Predict Quality-of-Life in Contactin-Associated Protein-Like 2 Antibody Disease.

The long-term clinical outcomes and associated prognostic factors in contactin-associated protein-like 2 (CASPR2)-antibody diseases are unknown. A total of 75 participants with CASPR2 antibodies were longitudinally assessed for disability, quality-of-life, and chronic pain. Although most symptoms improved within 6 months of treatment, neuropathic pain and fatigue were the most immunotherapy refractory, and persisted for up to 6 years.

The sulfur-related metabolic status of during infection reveals cytosolic serine hydroxymethyltransferase as a promising antifungal target.

Sulfur metabolism is an essential aspect of fungal physiology and pathogenicity. Fungal sulfur metabolism comprises anabolic and catabolic routes that are not well conserved in mammals, therefore is considered a promising source of prospective novel antifungal targets. To gain insight into sulfur-related metabolism during infection, we used a NanoString custom nCounter-TagSet and compared the expression of 68 key metabolic genes in different murine models of invasive pulmonary aspergillosis, at 3 time-points, and under a variety of conditions.

Management Measures and Trends of Biological Invasions in Europe: A Survey-Based Assessment of Local Managers.

Biological invasions are a major threat to biodiversity, ecosystem functioning and nature's contributions to people worldwide. However, the effectiveness of invasive alien species (IAS) management measures and the progress toward achieving biodiversity targets remain uncertain due to limited and nonuniform data availability. Management success is usually assessed at a local level and documented in technical reports, often written in languages other than English, which makes such data notoriously difficult to collect at large geographic scales.

Pollution, stress response, and obesity: A systematic review.

Limited literature addresses the association between pollution, stress, and obesity, and knowledge synthesis on the associations between these three topics has yet to be made. Two reviewers independently conducted a systematic review of MEDLINE, Embase, and Web of Science Core Collection databases to identify studies dealing with the effects of semi-volatile organic compounds, pesticides, conservatives, and heavy metals on the psychosocial stress response and adiposity in humans, animals, and cells. The quality of papers and risk assessment were evaluated with ToxRTool, BEES-C instrument score, SYRCLE's risk of bias tool, and CAMARADES checklist.

The incidence of radiologically verified community-acquired pneumonia requiring hospitalisation in adults living in southern Sweden, 2016-2018: a population-based study.

Background: Community-acquired pneumonia (CAP) was one of the most common causes of death in the European Union in 2017. Severity and mortality of CAP increase with age and an aging European population will require increased planning for prevention, control, and management of CAP. The purpose of this study was to provide an updated population-based estimate of the incidence of CAP requiring hospitalization in Northern Europe.

Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

Molecular architecture of human LYCHOS involved in lysosomal cholesterol signaling.

Lysosomal membrane protein LYCHOS (lysosomal cholesterol signaling) translates cholesterol abundance to mammalian target of rapamycin activation. Here we report the 2.11-Å structure of human LYCHOS, revealing a unique fusion architecture comprising a G-protein-coupled receptor (GPCR)-like domain and a transporter domain that mediates homodimer assembly.

Streptococcus abundance and oral site tropism in humans and non-human primates reflects host and lifestyle differences.

The genus Streptococcus is highly diverse and a core member of the primate oral microbiome. Streptococcus species are grouped into at least eight phylogenetically-supported clades, five of which are found almost exclusively in the oral cavity. We explored the dominant Streptococcus phylogenetic clades in samples from multiple oral sites and from ancient and modern-day humans and non-human primates and found that clade dominance is conserved across human oral sites, with most Streptococcus reads assigned to species falling in the Sanguinis or Mitis clades.

High-throughput method characterizes hundreds of previously unknown antibiotic resistance mutations.

A fundamental obstacle to tackling the antimicrobial resistance crisis is identifying mutations that lead to resistance in a given genomic background and environment. We present a high-throughput technique - Quantitative Mutational Scan sequencing (QMS-seq) - that enables quantitative comparison of which genes are under antibiotic selection and captures how genetic background influences resistance evolution. We compare four E.

Evaluation of the diagnostic accuracy of Xpert® Mpox and STANDARD™ M10 MPX/OPX for the detection of monkeypox virus.

Objectives: Evaluation of diagnostic accuracy of two point-of-care (POC) molecular diagnostic tests for the detection of monkeypox virus (MPXV): Xpert® Mpox (Cepheid, Inc., USA) and STANDARD™ M10 MPX/OPX (SD Biosensor, Inc., Korea).

The incidence and risk factor for febrile urinary tract infection after robot-assisted laparoscopic radical cystectomy in bladder cancer patients.

Introduction: Febrile urinary tract infections are major complications of radical cystectomy; however, their characteristics after robot-assisted radical cystectomy remain unclear. Thus, we investigated the rate, severity, pathogens, and risk factors of febrile urinary tract infections after robot-assisted radical cystectomy.

Patients And Methods: Patients who underwent robot-assisted radical cystectomy at three institutions between April 2018 and March 2022 were retrospectively analyzed.

Metabolic tug-of-war: Microbial metabolism shapes colonization resistance against enteric pathogens.

A widely recognized benefit of gut microbiota is that it provides colonization resistance against enteric pathogens. The gut microbiota and their products can protect the host from invading microbes directly via microbe-pathogen interactions and indirectly by host-microbiota interactions, which regulate immune system function. In contrast, enteric pathogens have evolved mechanisms to utilize microbiota-derived metabolites to overcome colonization resistance and increase their pathogenic potential.

Regulatory workshop on standardisation of clinical procedures, endpoints and data robustness of human challenge studies - A stakeholder meeting report.

Inno4Vac, a public-private partnership funded by the IMI2/EU/EFPIA Joint Undertaking (IMI2 JU), brings together academic institutions, SMEs, and pharmaceutical companies to accelerate and de-risk vaccine development. The project has made significant strides in the selection and production of challenge agents for influenza, respiratory syncytial virus (RSV), and toxigenic Clostridioides difficile for controlled human infection model studies (CHIMs). A regulatory workshop held on March 20, 2024, addressed the standardisation of clinical procedures, ethical considerations, endpoints, and data integrity, highlighting the ongoing initiatives related to these CHIMs.

Microfluidics-enabled core/shell nanostructure assembly: Understanding encapsulation processes via particle characterization and molecular dynamics.

In the realm of hybrid nanomaterials, the construction of core/shell nanoparticles offer an effective strategy for encompassing a particle by a polymeric or other suitable material, leading to a nanocomposite with distinct features within its structure. The polymer shell can be formed via nanoprecipitation, optimized by manipulating fluid flow, fluid mixing, modulating device features in microfluidics. In addition to the process optimization, success of polymer assembly in encapsulation strongly lies upon the favorable molecular interactions originating from the diverse chemical environment shared between core and shell materials facilitating formation of core/shell nanostructure.

Shortened SARS-CoV-2 viral RNA shedding in saliva during early Omicron compared to wild-type pandemic phase.

This study compared the dynamics of SARS-CoV-2 viral shedding in saliva between wild-type virus-infected and Omicron-infected household cohorts. Pre-existing immunity in participants likely shortens the viral RNA shedding duration and lowers viral load peaks. Frequent saliva sampling can be a convenient tool to study viral load dynamics.

KSHV hijacks the antiviral kinase IKKε to initiate lytic replication.

IKKε is a traditional antiviral kinase known for positively regulating the production of type I interferon (IFN) and the expression of IFN-stimulated genes (ISGs) during various virus infections. However, through an inhibitor screen targeting cellular kinases, we found that IKKε plays a crucial role in the lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV). Mechanistically, during KSHV lytic replication, IKKε undergoes significant SUMOylation at both Lys321 and Lys549 by the viral SUMO E3 ligase ORF45.

Reaching Syrian migrants through Dutch municipal registries for hepatitis B and C point-of-care testing.

Undetected chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections can lead to cirrhosis and liver cancer. Syrian migrants are the largest non-European migrant group in the Netherlands with HBV and HCV prevalence rates above 2%. This study aimed to reach Syrian migrants for HBV and HCV testing using point-of-care tests (POCT).

Comparison of mortality in people with type 2 diabetes between different ethnic groups: Systematic review and meta-analysis of longitudinal studies.

Aims: Type 2 diabetes (T2D) is more common in certain ethnic groups. This systematic review compares mortality risk between people with T2D from different ethnic groups and includes recent larger studies.

Methods: We searched nine databases using PRISMA guidelines (PROSPERO CRD42022372542).

Anti-immune complex antibodies are elicited during repeated immunization with HIV Env immunogens.

Vaccination strategies against HIV-1 aim to elicit broadly neutralizing antibodies (bnAbs) using prime-boost regimens with HIV envelope (Env) immunogens. Epitope mapping has shown that early antibody responses are directed to easily accessible nonneutralizing epitopes on Env instead of bnAb epitopes. Autologously neutralizing antibody responses appear upon boosting, once immunodominant epitopes are saturated.

Nutritional and Sensory Properties of Meat Analogues: A Current Overview and Future Considerations.

For centuries, meat has been a staple in the human diet, cherished for its rich protein content, vitamins, appealing texture, and umami flavor. The future supply is, however, tenuous as the global population continues to grow. Additional issues regarding animal welfare, adverse health effects, and the environmental impact of meat production have accelerated the development of meat analogues (MAs) over the last decades.

Reduction of elevated Gli3 does not alter the progression of autosomal recessive polycystic kidney disease.

Polycystic kidney diseases (PKD) are genetic disorders which disrupt kidney architecture and function. Autosomal recessive PKD (ARPKD) is a rare form of PKD, caused by mutations in PKHD1, and clinically more severe than the more common autosomal dominant PKD (ADPKD). Prior studies have implicated Hedgehog (Hh) signaling in ADPKD, with increased levels of Hh components in experimental ADPKD and reduced cystogenesis following pharmacological Hh inhibition.