Redefining ALS: Large-scale proteomic profiling reveals a prolonged pre-diagnostic phase with immune, muscular, metabolic, and brain involvement.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a largely unknown duration and pathophysiology of the pre-diagnostic phase, especially for the common non-monogenic form.

Methods: We leveraged the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with up to 30 years of follow-up to identify incident ALS cases across five European countries. Pre-diagnostic plasma samples from initially healthy participants underwent high-throughput proteomic profiling (7,285 protein markers, SomaScan).

Moving beyond word error rate to evaluate automatic speech recognition in clinical samples: Lessons from research into schizophrenia-spectrum disorders.

Natural language processing applications to mental health research depend on automatic speech recognition (ASR) to study large samples and develop scalable clinical tools. To ensure safe and effective implementation, it is crucial to understand performance patterns of ASR for speech from clinical populations. Therefore, this study evaluated ASR performance in N=50 speech samples from individuals with schizophrenia-spectrum disorders, identifying word error rates (WER) ranging from 0.

Pseudomonas infections persisting after CFTR modulators are widespread throughout the lungs and drive lung inflammation.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve the physiological defect causing cystic fibrosis, but the lungs of most people remain infected and inflamed. A leading hypothesis implicates damaged segments as the cause of persistent infection and predicts that mildly diseased segments within an individual's lungs will clear after treatment, whereas severely diseased segments will not. Our findings contradict this hypothesis.

Large-scale plasma proteomics uncovers preclinical molecular signatures of Parkinson's disease and overlap with other neurodegenerative disorders.

Parkinson's disease (PD) remains incurable, with a long preclinical phase currently undetectable by existing methods. In the largest proteomic study in neurodegenerative diseases to date, we analyzed blood samples from ~74,000 individuals across discovery and validation cohorts. In the EPIC4PD discovery case-cohort, large-scale profiling of 7,285 proteins (SomaScan-7K) in 4,538 initially unaffected participants (574 incident cases) identified 17 proteins that predict PD up to 28 years before diagnosis.

Influence of the Saccharide Structure on Cargo Loading, Thermal Properties, and Lectin Binding of Amphiphilic Glycopolymer-Polylactic Acid Block Copolymer Nanoparticles.

Stereospecific arrangements of saccharide molecules control biological recognition and binding with proteins. These properties can also be utilized in the design of biomaterials for applications such as polymeric drug delivery, where saccharides may enhance the ability to target specific cells. Glycopolymer block copolymers incorporating pendant saccharides at high concentration have potential for use in applications; however, there is a need for further evaluation of their structure-property relationships.

A PKCη missense mutation enhances Golgi-localized signaling and is associated with recessively inherited familial Alzheimer's disease.

The identification of Alzheimer's disease (AD)-associated genomic variants has provided powerful insight into disease etiology. Genome-wide association studies (GWASs) of AD have successfully identified previously unidentified targets but have almost exclusively used additive genetic models. Here, we performed a family-based GWAS of a recessive inheritance model using whole-genome sequencing from families affected by AD.

Structural Similarity Networks Reveal Brain Vulnerability in Dementia.

Introduction: Alzheimer's disease (AD) is characterised by inter-individual heterogeneity in brain degeneration, limiting diagnostic and prognostic precision. We present a novel framework integrating Morphometric Inverse Divergence (MIND) networks with hierarchical Bayesian large-scale population modelling to identify individual-level neuroanatomical deviations.

Methods: MIND networks quantify similarity between brain regions using multivariate MRI features.

Clinical Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor in 6 to 11-Year-Olds with Cystic Fibrosis.

: Elexacaftor/tezacaftor/ivacaftor (ETI) provided substantial health benefits to children with cystic fibrosis (CF) in clinical trials; there is less information about its effectiveness in a "real world" setting. The pediatric PROMISE substudy enrolled CF children 6 to <12 years of age starting ETI. Outcomes measured at baseline (pre-ETI), 1, 3, 6 and 12 months after ETI initiation included the lung clearance index (LCI), % predicted forced expiratory volume in 1 second (ppFEV), the CFQ-R respiratory domain symptom score (CFQ-R RD), height, weight, oropharyngeal (OP) cultures, culture and DNA-based analysis of sputum microbiology (when sputum available).

Protein kinase C eta enhances Golgi-localized signaling and is associated with Alzheimer's disease using a recessive mode of inheritance.

The identification of Alzheimer's disease (AD)-associated genomic variants has provided powerful insight into disease etiology. Genome-wide association studies (GWAS) for AD have successfully identified new targets but have almost exclusively utilized additive genetic models. Here, we performed a family-based GWAS under a recessive inheritance model using whole genome sequencing from families affected by AD.

Disrupted functional brain network associated with presence of hallucinations in Parkinson's disease.

Hallucinations negatively impact quality of life in Parkinson's disease, yet their neural mechanisms remain poorly understood, particularly in early disease stages. This study aimed to identify functional connectivity differences associated with visual hallucinations in early Parkinson's disease and to validate these findings across independent datasets. Resting-state functional MRI data from two independent studies were used: the 'Parkinson's Progression Markers Initiative' dataset was used as a discovery cohort ( = 25 hallucinators, = 56 non-hallucinators) and the 'Incidence of Cognitive Impairments in Cohorts with Longitudinal Evaluation' dataset as replication ( = 49 hallucinators, = 55 non-hallucinators overall).

Shame and Experiences of Psychosis: A Qualitative Inquiry.

Research reports a strong association between the experience of psychosis and shame, but there is a paucity of detailed information on the nature of this relationship. This qualitative study explored the relationship between shame and psychosis from the perspectives of people with lived experience of psychosis. Using a trauma-informed and shame-sensitive approach to research, fourteen adults from three mental health services completed semi-structured face-to-face interviews.

Antiresorptive Therapy to Reduce Fracture Risk and Effects on Dental Implant Outcomes in Patients With Osteoporosis: A Systematic Review and Osteonecrosis of the Jaw Taskforce Consensus Statement.

Objective: Placement of a dental implant in a patient on antiresorptive therapy has been hypothesized to increase the risk of medication-related osteonecrosis of the jaw (MRONJ) and/or impact implant survival. In patients with osteoporosis, the risk of MRONJ with antiresorptive therapy is only marginally higher than observed in the general population.

Methods: The International ONJ Taskforce conducted a systematic review of the literature and evaluated the outcomes of implant placement in individuals with osteoporosis receiving antiresorptive therapy.

Morphology Control in Waterborne Polyurethane Dispersion Nanocomposites through Tailored Structure, Formulation, and Processing.

Waterborne polyurethane dispersions (PUDs) have garnered increasing interest in recent years due to the growing demand for environmentally friendly materials. The unique phase-separated morphologies exhibited in PUD films and coatings provide opportunities for directing the distribution of functional additives and controlling properties. Although there has been extensive research on polyurethanes for several decades, the mechanisms underlying the PUD morphology formation are poorly understood.

Grief Among Oncology Providers: Prevalence and Association with Burnout.

International research shows that oncology providers frequently experience grief and that grief is linked to burnout. Evidence on the prevalence of grief and its link to burnout is limited, especially in the United States (US). We investigated the prevalence of grief and its association with burnout at our institution.

Amyloid Peptide-Polymer Blends with Enhanced Mechanical and Biological Properties.

Amyloid peptides are structurally diverse materials that exhibit different properties depending on their self-assembly. While they are often associated with neurodegenerative diseases, functional amyloids play important roles in nature and exhibit properties with high relevance for biomedical applications, including remarkable strength, mechanical stability, antimicrobial and antioxidant properties, low cytotoxicity, and adhesion to biotic and abiotic surfaces. Challenges in developing amyloid biomaterials include the complexity of peptide chemistry and the practical techniques required for processing amyloids into bulk materials.

Pathological complete response with cocktail chemotherapy in mediastinal seminoma.

A mediastinal mass can present a diagnostic challenge, especially when symptoms necessitate urgent treatment. Mediastinal seminoma, a rare extragonadal germ cell tumour, shares clinical features with testicular seminoma, such as slow growth and high sensitivity to chemotherapy and radiotherapy. This case is of a man in his 40s presenting with cough and chest discomfort, with imaging revealing a large anterior mediastinal mass that was causing left diaphragmatic paralysis due to phrenic nerve involvement.

Molecular hallmarks of excitatory and inhibitory neuronal resilience and resistance to Alzheimer's disease.

Background: A significant proportion of individuals maintain healthy cognitive function despite having extensive Alzheimer's disease (AD) pathology, known as cognitive resilience. Understanding the molecular mechanisms that protect these individuals can identify therapeutic targets for AD dementia. This study aims to define molecular and cellular signatures of cognitive resilience, protection and resistance, by integrating genetics, bulk RNA, and single-nucleus RNA sequencing data across multiple brain regions from AD, resilient, and control individuals.

The ISCB competency framework v. 3: a revised and extended standard for bioinformatics education and training.

Motivation: Developing competency in the broad area of bioinformatics is challenging globally, owing to the breadth of the field and the diversity of its audiences for education and training. Course design can be facilitated by the use of a competency framework-a set of competency requirements that define the knowledge, skills and attitudes needed by individuals in (or aspiring to be in) a particular profession or role. These competency requirements can help to define curricula as they can inform both the content and level to which competency needs to be developed.

Structural MRI of brain similarity networks.

Recent advances in structural MRI analytics now allow the network organization of individual brains to be comprehensively mapped through the use of the biologically principled metric of anatomical similarity. In this Review, we offer an overview of the measurement and meaning of structural MRI similarity, especially in relation to two key assumptions that often underlie its interpretation: (i) that MRI similarity can be representative of architectonic similarity between cortical areas and (ii) that similar areas are more likely to be axonally connected, as predicted by the homophily principle. We first introduce the historical roots and technical foundations of MRI similarity analysis and compare it with the distinct MRI techniques of structural covariance and tractography analysis.

The Camden and Islington Viral Hepatitis Identification Tool (CIVHIT): Use of a Clinical Database Case-Finding Tool for Hepatitis B, Hepatitis C and HIV in Primary Care.

Despite the availability of effective treatment and vaccines for hepatitis B virus (HBV) and C virus (HCV), many people are still infected and remain unaware of their infection. The Camden and Islington Viral Hepatitis Identification Tool (CIVHIT), a computer-based search tool, was introduced in 60 general practices (GPs) in April 2014 to support identification, testing and treatment of individuals at high risk for blood-borne viruses (BBVs). CIVHIT searched electronic medical records (EMRs), flagging all those with codes linked to risk factors or medical conditions associated with BBVs.

Mechanochemically responsive polymer enables shockwave visualization.

Understanding the physical and chemical response of materials to impulsive deformation is crucial for applications ranging from soft robotic locomotion to space exploration to seismology. However, investigating material properties at extreme strain rates remains challenging due to temporal and spatial resolution limitations. Combining high-strain-rate testing with mechanochemistry encodes the molecular-level deformation within the material itself, thus enabling the direct quantification of the material response.

Assessing bioactivity of environmental water samples filtered using nanomembrane technology and mammalian cell lines.

This project reports on the use of a novel nanomembrane filtering technology to isolate and analyze the bioactivity of microplastic (MP)-containing debris from Lake Ontario water samples. Environmental MPs are a complex mixture of polymers and sorbed chemicals that are persistent and can exhibit a wide range of toxic effects. Since human exposure to MPs is unavoidable, it is necessary to characterize their bioactivity to assess potential health risks.