Pathway Polygenic Risk Scores (pPRS) for the Analysis of Gene-environment Interaction.

Unlabelled: A polygenic risk score (PRS) is used to quantify the combined disease risk of many genetic variants. For complex human traits there is interest in determining whether the PRS modifies, i.e.

Unique bibenzyl cannabinoids in the liverwort Radula marginata: parallels with Cannabis chemistry.

The potential of cannabinoids to address public health challenges has stimulated exploration into alternative sources and production technologies. Radula marginata, an endemic Aotearoa/New Zealand liverwort, produces the bibenzyl cannabinoid perrottetinene (PET), analogous to Cannabis psychoactive tetrahydrocannabinol (THC). Structural differences between PET and THC could alter therapeutic interactions and mitigate adverse side effects.

Antibiotic Use and Subsequent Cognitive Decline and Dementia Risk in Healthy Older Adults.

Background And Objectives: Antibiotics rapidly reduce intestinal bacterial diversity, leading to dysbiosis that persists for months to years. Although emerging evidence from retrospective and claims-based studies has linked dysbiosis to cognitive function, prospective data are lacking. We aim to examine the prospective association of antibiotics with cognitive aging among initially healthy older adults.

Switching from natalizumab to antiCD20 monoclonal antibodies: Short transition interval is associated with improved outcome.

Objective: To investigate the impact of transition interval length when switching from natalizumab (NTZ) to anti-CD20 monoclonal antibodies (antiCD20) on recurrent disease activity and safety in relapsing multiple sclerosis (RMS).

Methods: Aggregating data from 8 MS centres in Austria, Switzerland, and Germany, we included RMS patients who (i) continuously received NTZ for ≥3 months, (ii) were switched to antiCD20, and (iii) had ≥12 months follow-up after switch. The primary endpoint was occurrence of relapse after switch, secondary endpoints included severe infections (CTCAE grade ≥3).

Shared Genetics of Migraine and Gastrointestinal Disorders Implicates Underlying Neurologic Mechanisms Yet Heterogeneous Etiologies.

Background And Objectives: Migraine is strongly comorbid with irritable bowel syndrome (IBS), one of several gastrointestinal (GI) conditions that are distinguished by symptomatic profiles that are partly overlapping. Potential shared mechanisms of migraine and the GI conditions were investigated by assessing shared genetics on a genome-wide basis.

Methods: Analyses leveraged genome-wide summary statistics from large-scale genetic studies for migraine, including by aura status, IBS, peptic ulcer disease (PUD), gastrointestinal reflux (GERD), functional dyspepsia (FD), diverticular disease (DD), and the immune-related inflammatory bowel disease (IBD) or its constituents, ulcerative colitis (UC) and Crohn disease (CD).

Utility of cardiac implantable electronic device algorithm for detecting severe sleep-disordered breathing in cardiomyopathy.

Background: Half of patients with heart failure are estimated to have sleep-disordered breathing (SDB). However, many are undiagnosed as they do not report typical symptoms. This study aims to evaluate the implantable cardiac defibrillator (ICD) sleep-disordered breathing algorithm in a cohort of multi-racial Asian patients for detection of SDB against polysomnography (PSG).

Disability progression is a question of definition-A methodological reappraisal by example of primary progressive multiple sclerosis.

Background: Different definitions of disability progression by Expanded Disability Status Scale (EDSS) may influence frequency and/or time to event.

Methods: In this multicenter cohort study, we included PPMS patients with follow-up ≥24 months and ≥3 available EDSS scores overall (≥1 per year). We applied 672 definitions of disability progression including different minimal EDSS increase, required confirmation and fixed/roving-baseline score.

Next-generation immunotherapy: igniting new hope for lung cancer.

Adoption of immunotherapy has completely transformed the treatment landscape of cancer. Patients with advanced cancer treated with immunotherapy may benefit from durable tumor response and long-term survival. The most widely used immunotherapy in solid tumors is anti-programmed-death (ligand) protein (PD-(L)1), which is now an integral part of non-small cell lung cancer (NSCLC) treatment irrespective of histological cell types and tumor stage.

Levels of evidence supporting recommendations in gastroenterology.

Introduction: We aimed to analyze gastrointestinal guidelines to assess quality of evidence and strength of recommendation.

Methods: We abstracted clinical practice guidelines and guidance statements from 4 American GI societies (ACG, AGA, ASGE and AASLD) and the United States Multi-Society Task Forc.

Results: Of the 3,609 statements analyzed, only 13% were supported by high level of evidence.

Associations between MASLD, atrial fibrillation, cardiovascular events, mortality and aspirin use in older adults.

The impact of metabolic dysfunction-associated steatotic liver disease (MASLD), the preferred nomenclature for NAFLD, on cardiovascular health and mortality among older adults is uncertain. As such, we aimed to identify whether MASLD increases the risk of Major Adverse Cardiovascular Events (MACE) (a composite of fatal coronary heart disease [excluding heart failure], nonfatal myocardial infarction, or fatal or nonfatal ischemic stroke), Atrial Fibrillation (AF), or all-cause mortality in older adults, and whether aspirin attenuates these risks in individuals with MASLD. This is a non-prespecified post-hoc analysis of the ASPREE (ASPirin in Reducing Events in the Elderly) randomized trial.

Colorectal Cancer Incidence and Mortality After Negative Colonoscopy Screening Results.

Importance: The current recommendation for a 10-year rescreening interval after a negative colonoscopy screening (NCS) result has been questioned, with some studies showing a persistently lower risk of colorectal cancer (CRC) after NCS results.

Objective: To examine long-term CRC incidence and mortality after NCS results (ie, no presence of CRC or polyps) and according to a risk score based on major demographic and lifestyle risk factors.

Design, Setting, And Participants: In this cohort study, 3 prospective US population-based cohorts from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study were followed up from 1988 and 1991 to 2020.

Associations of blood lipids and LDL cholesterol lowering drug-targets with colorectal cancer risk: a Mendelian randomisation study.

Background: Whether blood lipids are causally associated with colorectal cancer (CRC) risk remains unclear.

Methods: Using two-sample Mendelian randomisation (MR), our study examined the associations of genetically-predicted blood concentrations of lipids and lipoproteins (primary: LDL-C, HDL-C, triglycerides, and total cholesterol), and genetically-proxied inhibition of HMGCR, NPC1L1, and PCSK9 (which mimic therapeutic effects of LDL-lowering drugs), with risks of CRC and its subsites. Genetic associations with lipids were obtained from the Global Lipids Genetics Consortium (n = 1,320,016), while genetic associations with CRC were obtained from the largest existing CRC consortium (n = 58,221 cases and 67,694 controls).

Coffee consumption is associated with intestinal Lawsonibacter asaccharolyticus abundance and prevalence across multiple cohorts.

Although diet is a substantial determinant of the human gut microbiome, the interplay between specific foods and microbial community structure remains poorly understood. Coffee is a habitually consumed beverage with established metabolic and health benefits. We previously found that coffee is, among >150 items, the food showing the highest correlation with microbiome components.

Rising Prevalence of Multiple Sclerosis in Switzerland: Results from the Swiss Multiple Sclerosis Registry.

Introduction: Understanding the prevalence of multiple sclerosis (MS) provides information for healthcare planning and helps identify trends and patterns of disease occurrence. For Switzerland, the number of persons with MS (pwMS) was last estimated at approximately 15,000 in 2016. The study's objectives were to update estimates of MS prevalence and characterise the change in MS prevalence in Switzerland between 2016 and 2021, the last year with complete administrative data.

F. prausnitzii potentially modulates the association between citrus intake and depression.

Background: The gut microbiome modulates the effects of diet on host health, but it remains unclear which specific foods and microbial features interact to influence risk of depression. To understand this interplay, we leveraged decades of dietary and depression data from a longitudinal cohort of women (n = 32,427), along with fecal metagenomics and plasma metabolomics from a substudy (n = 207) nested in this cohort, as well as an independent validation cohort of men (n = 307).

Results: We report that citrus intake and its components are prospectively associated with a lower risk of depression and altered abundance of 15 gut microbial species, including enriched Faecalibacterium prausnitzii.

Prevalence and Prognosis of Coronal Malalignment Following Lateral Lumbar Interbody Fusion for Minimally Invasive Treatment of Adult Spinal Deformity.

Study Design: Retrospective analysis of prospective multicenter adult spinal deformity (ASD) database.

Objective: To determine the prevalence and prognosis of postoperative coronal malalignment following LLIF for ASD with Qiu type A coronal alignment.

Summary Of Background Data: Qiu Type A coronal alignment is defined as coronal vertical axis (CVA) <30mm.

Updated 5-Year Institutional Bibliometric Profiles for United States Neurosurgery Residency Programs and the Relationship Between Social Media Presence and Objective Departmental Metrics.

Background And Objectives: The authors report current 3-year and 5-year institutional bibliometric profiles and investigate the correlations between objective metrics of neurosurgical residency programs and social media presence, including residency program size, faculty count, Doximity rankings, and measures of research output.

Methods: A list of neurosurgery residency programs was obtained through the Doximity Residency Navigator. Publication history of faculty members was compiled using Scopus and analyzed to create institutional bibliometric profiles from 2018-2022 to 2020-2022.

Metatranscriptomics-guided discovery and characterization of a polyphenol-metabolizing gut microbial enzyme.

Gut microbial catechol dehydroxylases are a largely uncharacterized family of metalloenzymes that potentially impact human health by metabolizing dietary polyphenols. Here, we use metatranscriptomics (MTX) to identify highly transcribed catechol-dehydroxylase-encoding genes in human gut microbiomes. We discover a prevalent, previously uncharacterized catechol dehydroxylase (Gp Hcdh) from Gordonibacter pamelaeae that dehydroxylates hydrocaffeic acid (HCA), an anti-inflammatory gut microbial metabolite derived from plant-based foods.

Novel metabolomic predictors of incident colorectal cancer in men and women.

Background: Metabolomic profiles may influence colorectal cancer (CRC) development. Few studies have performed pre-diagnostic metabolome-wide analyses with CRC risk.

Methods: We conducted a nested case-control study among women (Nurses' Health Study (NHS)) and men (Health Professionals Follow-up Study (HPFS)) who provided blood between 1989 and 1995.

Diagnosis and Management of Thoracolumbar Spinal Disorders Presenting as Cardiac, Gastrointestinal, and Other False Pain Syndromes.

Summary Of Background Data: Although pseudoangina is most commonly caused by cervical disc herniation, several cases have been described where thoracic herniation produced symptoms of pseudoangina. If thoracic herniation can produce angina-like pain, then it is important to consider whether pathology of the thoracolumbar spine, in general, can trigger false pain syndromes distinct from pseudoangina.

Objective: We seek to provide the most comprehensive study regarding the diagnosis and treatment of spinal conditions causing false pain syndromes.