C-reactive protein and association with disease severity in hospitalized adult patients with Lassa fever in Nigeria.

Objectives: Lassa fever (LF) poses a significant health burden in West Africa. The pathophysiology of LF and determinants of clinical spectrum of disease remain poorly understood. We performed a study to understand the correlation of blood inflammatory marker C-reactive protein (CRP), with LF disease severity.

Patients with neurological or psychiatric complications of COVID-19 have worse long-term functional outcomes: COVID-CNS-A multicentre case-control study.

It is established that patients hospitalised with COVID-19 often have ongoing morbidity affecting activity of daily living (ADL), employment, and mental health. However, little is known about the relative outcomes in patients with COVID-19 neurological or psychiatric complications. We conducted a UK multicentre case-control study of patients hospitalised with COVID-19 (controls) and those who developed COVID-19 associated acute neurological or psychiatric complications (cases).

Splicing accuracy varies across human introns, tissues, age and disease.

Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we investigate splicing accuracy using RNA-sequencing data from >14k control samples and 40 human body sites, focusing on split reads partially mapping to known transcripts in annotation.

An MRI assessment of mechanisms underlying lesion growth and shrinkage in multiple sclerosis.

Objective: To assess the pathological mechanisms contributing to white matter (WM) lesion expansion or contraction and remyelination in multiple sclerosis (MS).

Methods: We assessed 1,613 lesions in 49 people with relapsing-remitting MS in the CCMR-One bexarotene trial (EudraCT 2014-003145-99). We measured lesion orientation relative to WM tracts, surface-in gradients and veins.

Protocol for a systematic review and individual participant data meta-analysis for risk factors for lung cancer in individuals with lung nodules identified by low-dose CT screening.

Background: Worldwide, lung cancer (LC) is the second most frequent cancer and the leading cause of cancer related mortality. Low-dose CT (LDCT) screening reduced LC mortality by 20-24% in randomised trials of high-risk populations. A significant proportion of those screened have nodules detected that are found to be benign.

Prognostic performance of the two-step clinical care pathway in metabolic dysfunction-associated steatotic liver disease.

Background & Aims: Current guidelines recommend a 2-step approach for risk stratification in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) with Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) or similar second-line tests. This study aimed to examine to prognostic performance of this approach.

Methods: The VCTE-Prognosis Study was a longitudinal study of patients with MASLD who had undergone VCTE examinations at 16 centres from the US, Europe and Asia with subsequent follow-up for clinical events.

Leveraging Epigenetic Alterations in Pancreatic Ductal Adenocarcinoma for Clinical Applications.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by late detection and poor prognosis. Recent research highlights the pivotal role of epigenetic alter- ations in driving PDAC development and progression. These changes, in conjunction with genetic mutations, contribute to the intricate molecular landscape of the disease.

Congenital Titinopathy: Comprehensive Characterization of the Most Severe End of the Disease Spectrum.

Unlabelled: Congenital titinopathy has recently emerged as one of the most common congenital muscle disorders.

Objective: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.

Methods: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.

Conventional MRI-Based Structural Disconnection and Morphometric Similarity Networks and Their Clinical Correlates in Multiple Sclerosis.

Background And Objectives: Although multiple sclerosis (MS) can be conceptualized as a network disorder, brain network analyses typically require advanced MRI sequences not commonly acquired in clinical practice. Using conventional MRI, we assessed cross-sectional and longitudinal structural disconnection and morphometric similarity networks in people with MS (pwMS), along with their relationship with clinical disability.

Methods: In this longitudinal monocentric study, 3T structural MRI of pwMS and healthy controls (HC) was retrospectively analyzed.

Determinants of physical function, as measured using PROMIS PF-10a, in patients with rheumatoid arthritis: results from the international COVID-19 Vaccination in Autoimmune Diseases (COVAD) study.

Objectives: Physical function in RA is largely influenced by multiple clinical factors, however, there is a growing body of evidence that psychological state and other comorbidities also play an essential role. Using data obtained in the COVID-19 Vaccination in Autoimmune Diseases study, an international self-reported e-survey, we aimed to explore the predictive ability of sociodemographic and clinical variables on Patient-Reported Outcomes Measurement Information System Physical Function Short Form 10a (PROMIS PF-10a) in RA and to investigate variation in disease activity and functional outcomes based on country-level socio-economic parameters.

Methods: Patient demographics, disease characteristics including current symptom status, functional status and treatment variables, as well as income level of the country of residence, were extracted from survey responses.

Identify biological Alzheimer's disease using a novel nucleic acid-linked protein immunoassay.

Blood-based biomarkers have been revolutionizing the detection, diagnosis and screening of Alzheimer's disease. Specifically, phosphorylated-tau variants (p-tau, p-tau and p-tau) are promising biomarkers for identifying Alzheimer's disease pathology. Antibody-based assays such as single molecule arrays immunoassays are powerful tools to investigate pathological changes indicated by blood-based biomarkers and have been studied extensively in the Alzheimer's disease research field.

Myosin-based nucleation of actin filaments contributes to stereocilia development critical for hearing.

Assembly of actin-based stereocilia is critical for cochlear hair cells to detect sound. To tune their mechanosensivity, stereocilia form bundles composed of graded rows of ascending height, necessitating the precise control of actin polymerization. Myosin 15 (MYO15A) drives hair bundle development by delivering critical proteins to growing stereocilia that regulate actin polymerization via an unknown mechanism.

Efficacy and safety of pharmacological treatments in inclusion body myositis: a systematic review.

Objective: To identify the best evidence on the efficacy of treatment interventions for inclusion body myositis (IBM) and to describe their safety.

Methods: Systematic review of randomised controlled trials (RCTs) of pharmacological treatments of adults with IBM, conducted according to the Cochrane Handbook, updating a previous Cochrane review. The search strategy was run on Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE, ClinicalTrials.

Effect of ethnicity and other sociodemographic factors on attendance at ophthalmology appointments following referral from a Diabetic Eye Screening Programme: a retrospective cohort study.

Background/aims: To examine the association between sociodemographic characteristics and attendance at Hospital Eye Service (HES) referrals from the Diabetic Eye Screening Programme (DESP), in a large, ethnically diverse urban population.

Methods: Retrospective cohort study (4 January 2016-12 August 2019) of people with diabetic retinopathy (DR) referred from an English DESP to a tertiary referral eye hospital. We conducted a multivariable logistic regression with attendance as the primary outcome, controlling for age, sex, ethnicity, Index of Multiple Deprivation, best eye visual acuity and baseline DR grade.

Cerebral Microbleeds and Amyloid Pathology Estimates From the Amyloid Biomarker Study.

Importance: Baseline cerebral microbleeds (CMBs) and APOE ε4 allele copy number are important risk factors for amyloid-related imaging abnormalities in patients with Alzheimer disease (AD) receiving therapies to lower amyloid-β plaque levels.

Objective: To provide prevalence estimates of any, no more than 4, or fewer than 2 CMBs in association with amyloid status, APOE ε4 copy number, and age.

Design, Setting, And Participants: This cross-sectional study used data included in the Amyloid Biomarker Study data pooling initiative (January 1, 2012, to the present [data collection is ongoing]).

Emergence of SARS-CoV-2 subgenomic RNAs that enhance viral fitness and immune evasion.

Coronaviruses express their structural and accessory genes via a set of subgenomic RNAs, whose synthesis is directed by transcription regulatory sequences (TRSs) in the 5' genomic leader and upstream of each body open reading frame. In SARS-CoV-2, the TRS has the consensus AAACGAAC; upon searching for emergence of this motif in the global SARS-CoV-2 sequences, we find that it evolves frequently, especially in the 3' end of the genome. We show well-supported examples upstream of the Spike gene-within the nsp16 coding region of ORF1b-which is expressed during human infection, and upstream of the canonical Envelope gene TRS, both of which have evolved convergently in multiple lineages.

Early detection and management of hearing loss to reduce dementia risk in older adults with mild cognitive impairment: findings from the treating auditory impairment and cognition trial (TACT).

Background: Age-related hearing loss and mild cognitive impairment (MCI) independently increase dementia risk. The Ageing and Cognitive Health Evaluation in Elders randomised controlled trial (RCT) found hearing aids reduce cognitive decline in high-risk older adults with poor hearing.

Methods: This pilot RCT in London memory clinics randomised people with MCI (aged ≥55, untreated hearing loss defined as Pure Tone Average 0.

De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.

The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together with U5 and ~30 proteins, is part of the U4/U6.U5 tri-snRNP complex, located at the core of the major spliceosome. Recently, recurrent variants in the U4 RNA, transcribed from the gene, and in at least two other genes were discovered to cause neurodevelopmental disorder.

The Cognitive Footprint of Medication Use.

Introduction: The cognitive side-effects of medication are common, but often overlooked in practice, and not routinely considered in interventional trials or post-market surveillance. The cognitive footprint of a medication seeks to quantify the impact of its cognitive effects based on magnitude, duration, and interaction with other factors, evaluated across the exposed population.

Methods: Bayesian multivariable regression analysis of retrospective population-based cross-sectional cohorts.

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.

Bi-allelic KICS2 mutations impair KICSTOR complex-mediated mTORC1 regulation, causing intellectual disability and epilepsy.

Nutrient-dependent mTORC1 regulation upon amino acid deprivation is mediated by the KICSTOR complex, comprising SZT2, KPTN, ITFG2, and KICS2, recruiting GATOR1 to lysosomes. Previously, pathogenic SZT2 and KPTN variants have been associated with autosomal recessive intellectual disability and epileptic encephalopathy. We identified bi-allelic KICS2 variants in eleven affected individuals presenting with intellectual disability and epilepsy.

The Future Hospital in Global Health Systems: The Future Hospital Within the Healthcare System.

Future hospitals must be able to adapt in many ways to the changing demands on their roles and functions within evolving healthcare delivery infrastructures. These include changing population structures and needs, new models of healthcare provision, technological advances, and innovations in design, all while enhancing their environmental sustainability. This article sets out the issues that those determining healthcare policy and designing future hospitals must consider if they are to become and remain fit for purpose within the wider health and social care system.

Macular, choroidal and disc associations across women's reproductive life stages: a scoping review from menarche to post-menopause.

Oestrogen and progesterone fluctuate cyclically in women throughout their adult lives. Although these hormones cross the blood-retinal barrier and bind to intraocular receptors, their effects remain unclear. We present the first review to date on associations between posterior pole structures-specifically the macula, choroid, and optic disc-and both the menstrual cycle and post-menopausal period, utilising multimodal imaging techniques in healthy adult non-pregnant women.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD).