Oral amoxicillin treatment disrupts the gut microbiome and metabolome without interfering with luminal redox potential in the intestine of Wistar Han rats.

Oral antibiotic treatment is well known to be one of the main factors affecting gut microbiota composition by altering bacterial diversity. It decreases the abundance of butyrate-producing bacteria such as Lachnospiraceae and Ruminococcaceae, while increasing abundance of Enterobacteriaceae. The recovery time of commensal bacteria post-antibiotic treatment varies among individuals, and often, complete recovery is not achieved.

Enhancing intestinal absorption of a macromolecule through engineered probiotic yeast in the murine gastrointestinal tract.

Oral administration of therapeutic peptides is limited by poor intestinal absorption. Use of engineered microorganisms as drug delivery vehicles can overcome the challenges faced by conventional delivery methods. The potential of engineered microorganisms to act synergistically with the therapeutics they deliver opens new horizons for noninvasive treatment modalities.

Structure-dependent stimulation of gut bacteria by arabinoxylo-oligosaccharides (AXOS): a review.

Arabinoxylo-oligosaccharides (AXOS) are non-digestible dietary fibers that potentially confer a health benefit by stimulating beneficial bacteria in the gut. Still, a detailed overview of the diversity of gut bacteria and their specificity to utilize structurally different AXOS has not been provided to date and was aimed for in this study. Moreover, we assessed the genetic information of summarized bacteria, and we extracted genes expected to encode for enzymes that are involved in AXOS hydrolysis (based on the CAZy database).

Gut physiology and environment explain variations in human gut microbiome composition and metabolism.

The human gut microbiome is highly personal. However, the contribution of gut physiology and environment to variations in the gut microbiome remains understudied. Here we performed an observational trial using multi-omics to profile microbiome composition and metabolism in 61 healthy adults for 9 consecutive days.

Individual risk assessment for rupture of abdominal aortic aneurysm using artificial intelligence.

Objective: This study aimed to develop a prediction tool to identify abdominal aortic aneurysms (AAAs) at increased risk of rupture incorporating demographic, clinical, imaging, and medication data using artificial intelligence (AI).

Design: A development and validation study for individual prognosis using AI in a case-control design.

Methods: From two Danish hospitals, all available ruptured AAA cases between January 2009 and December 2016 were included in a ratio of 1:2 with elective surgery controls.

Validation of anorexia nervosa and Bulimia nervosa diagnosis coding in Danish hospitals assisted by a natural language processing model.

Introduction: The Danish Health Care Registers rely on the International Statistical Classification of Diseases and Related Health Problems (ICD)-classification and stand as a widely utilized resource for health epidemiological research. Eating disorders are multifaceted syndromes where two distinctive diagnoses are defined, anorexia nervosa (AN) and bulimia nervosa (BN). However, the validity of the registered diagnoses remains to be verified.

Dietary fibre directs microbial tryptophan metabolism via metabolic interactions in the gut microbiota.

Tryptophan is catabolized by gut microorganisms resulting in a wide range of metabolites implicated in both beneficial and adverse host effects. How gut microbial tryptophan metabolism is directed towards indole, associated with chronic kidney disease, or towards protective indolelactic acid (ILA) and indolepropionic acid (IPA) is unclear. Here we used in vitro culturing and animal experiments to assess gut microbial competition for tryptophan and the resulting metabolites in a controlled three-species defined community and in complex undefined human faecal communities.

Structural analysis of light chain-driven bispecific antibodies targeting CD47 and PD-L1.

In contrast to natural antibodies that rely mainly on the heavy chain to establish contacts with their cognate antigen, we have developed a bispecific antibody format in which the light chain (LC) drives antigen binding and specificity. To better understand epitope-paratope interactions in this context, we determined the X-ray crystallographic structures of an antigen binding fragment (Fab) in complex with human CD47 and another Fab in complex with human PD-L1. These Fabs contain a κ-LC and a λ-LC, respectively, which are paired with an identical heavy chain (HC).

Exercise and Pain Neuroscience Education for Patients With Chronic Pain After Total Knee Arthroplasty: A Randomized Clinical Trial.

Importance: Up to 20% of patients develop chronic pain after total knee arthroplasty (TKA), yet there is a scarcity of effective interventions for this population.

Objective: To evaluate whether neuromuscular exercise and pain neuroscience education were superior to pain neuroscience education alone for patients with chronic pain after TKA.

Design, Setting, And Participants: A superiority randomized clinical trial was conducted at 3 outpatient clinics at Aalborg University Hospital in Denmark.

Exploring the molecular landscape of cancer of unknown primary: A comparative analysis with other metastatic cancers.

Cancer of unknown primary (CUP) tumors are biologically very heterogeneous, which complicates stratification of patients for treatment. Consequently, these patients face limited treatment options and a poor prognosis. With this study, we aim to expand on the current knowledge of CUP biology by analyzing two cohorts: a well-characterized cohort of 44 CUP patients, and 213 metastatic patients with known primary.

Cholesterol-binding motifs in STING that control endoplasmic reticulum retention mediate anti-tumoral activity of cholesterol-lowering compounds.

The cGAS-STING pathway plays a crucial role in anti-tumoral responses by activating inflammation and reprogramming the tumour microenvironment. Upon activation, STING traffics from the endoplasmic reticulum (ER) to Golgi, allowing signalling complex assembly and induction of interferon and inflammatory cytokines. Here we report that cGAMP stimulation leads to a transient decline in ER cholesterol levels, mediated by Sterol O-Acyltransferase 1-dependent cholesterol esterification.

Novel nucleotide-packaging vaccine delivers antigen and poly(I:C) to dendritic cells and generate a potent antibody response in vivo.

An issue with many current vaccines is the dependency on broadly inflammatory adjuvants, such as aluminum hydroxide or aluminum salts that affect many immune- and non-immune cells. These adjuvants are not necessarily activating all antigen-presenting cells (APCs) that take up the antigen and most likely they also activate APCs with no antigen uptake, as well as many non-immune cells. Conjugation of antigen and adjuvant would enable the use of smaller amounts of adjuvant and avoid unnecessary tissue damage and activation of bystander cells.

Stable fixation of an ultra-short femoral neck-preserving hip prosthesis: a 5-year RSA, DXA, and clinical prospective outcome study of 48 patients.

Background And Purpose: We previously showed promising primary stability and preservation of bone stock with the ultra-short neck-loading hip implant in total hip arthroplasty (THA). The aim of this study was to evaluate clinical outcome, implant stability, and bone mineral density (BMD).

Methods: 50 patients were treated with the ultra-short neck Primoris hip implant at baseline and 48 were available for evaluation at 5-year follow-up.

Applying valency-based immuno-selection to generate broadly cross-reactive antibodies against influenza hemagglutinins.

Conserved epitopes shared between virus subtypes are often subdominant, making it difficult to induce broadly reactive antibodies by immunization. Here, we generate a plasmid DNA mix vaccine that encodes protein heterodimers with sixteen different influenza A virus hemagglutinins (HA) representing all HA subtypes except H1 (group 1) and H7 (group 2). Each single heterodimer expresses two different HA subtypes and is targeted to MHC class II on antigen presenting cells (APC).

microbeMASST: a taxonomically informed mass spectrometry search tool for microbial metabolomics data.

microbeMASST, a taxonomically informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbe-derived metabolites and relative producers without a priori knowledge will vastly enhance the understanding of microorganisms' role in ecology and human health.

Activation and substrate specificity of the human P4-ATPase ATP8B1.

Asymmetric distribution of phospholipids in eukaryotic membranes is essential for cell integrity, signaling pathways, and vesicular trafficking. P4-ATPases, also known as flippases, participate in creating and maintaining this asymmetry through active transport of phospholipids from the exoplasmic to the cytosolic leaflet. Here, we present a total of nine cryo-electron microscopy structures of the human flippase ATP8B1-CDC50A complex at 2.

Machine-learning analysis of cross-study samples according to the gut microbiome in 12 infant cohorts.

There are challenges in merging microbiome data from diverse research groups due to the intricate and multifaceted nature of such data. To address this, we utilized a combination of machine-learning (ML) models to analyze 16S sequencing data from a substantial set of gut microbiome samples, sourced from 12 distinct infant cohorts that were gathered prospectively. Our initial focus was on the mode of delivery due to its prior association with changes in infant gut microbiomes.

Experiences of young people living with type 1 diabetes in transition to adulthood: The importance of care provider familiarity and support.

Background: During the developmental transition from childhood to adulthood, young people living with type 1 diabetes (T1D) are more likely to take less care of their chronic disease. Alongside the developmental transition, young people with T1D also experience an organisational transition in which the care responsibility changes from a family-based approach in paediatric care to an individualised approach in adult care. Little is known from the perspective of the young people about what their interactions with the healthcare providers mean during these transitions.