Molecular Determinants of Protein Pathogenicity at the Single-Aggregate Level.

Determining the structure-function relationships of protein aggregates is a fundamental challenge in biology. These aggregates, whether formed in vitro, within cells, or in living organisms, present significant heterogeneity in their molecular features such as size, structure, and composition, making it difficult to determine how their structure influences their functions. Interpreting how these molecular features translate into functional roles is crucial for understanding cellular homeostasis and the pathogenesis of various debilitating diseases like Alzheimer's and Parkinson's.

IP3 receptor depletion in a spontaneous canine model of Charcot-Marie-Tooth disease 1J with amelogenesis imperfecta.

Inositol 1,4,5-trisphosphate receptors (IP3R) mediate Ca2+ release from intracellular stores, contributing to complex regulation of numerous physiological responses. The involvement of the three IP3R genes (ITPR1, ITPR2 and ITPR3) in inherited human diseases has started to shed light on the essential roles of each receptor in different human tissues and cell types. Variants in the ITPR3 gene, which encodes IP3R3, have recently been found to cause demyelinating sensorimotor Charcot-Marie-Tooth neuropathy type 1J (CMT1J).

Self-Assembling of Multilayered Polymorphs with Ion Beams.

Polymorphism determines significant variations in materials' properties by lattice symmetry variation. If they are stacked together into multilayers, polymorphs may work as an alternative approach to the sequential deposition of layers with different chemical compositions. However, selective polymorph crystallization during conventional thin film synthesis is not trivial; changes of temperature or pressure when switching from one polymorph to another during synthesis may cause degradation of the structural quality.

The impact of tuberculosis-induced hyperglycemia on pulmonary microbiota and airway mucus secretion in individuals not previously diabetic: A systematic review and meta-analysis protocol.

The lung environment harbours a community of microbes that play a significant role in health and disease, including innate protection against pathogenic microorganisms. Infection with Mycobacterium tuberculosis, psychological stress associated with the tuberculosis (TB) disease, and the metabolites from the rifampicin treatment regimen have been reported to induce hyperglycemia and consequently type 2 diabetes mellitus (T2DM) in individuals not previously diabetic. The high glucose concentration is proposed to alter the composition of the lung microbiota and airway homeostasis, exerting an influence on TB disease and treatment outcomes.

An Acta Orthopaedica educational article: Treatment of pediatric spondylolysis and spondylolisthesis.

Spondylolysis is defined as a defect or elongation in the pars interarticularis of the lumbar spine, either unilateral or bilateral. Growing children with bilateral spondylolysis may develop spondylolisthesis, i.e.

Three-Year Follow-up After Antiviral Treatment in New-Onset Type 1 Diabetes: Results From the Diabetes Virus Detection and Intervention Trial.

Objective: In the Diabetes Virus Detection and Intervention trial, antiviral treatment with pleconaril and ribavirin decreased the decline, compared with placebo, in endogenous C-peptide 1 year after diagnosis of type 1 diabetes (T1D) in children and adolescents. This article reports the results 2 and 3 years after diagnosis.

Research Design And Methods: This was a multicenter, randomized, placebo-controlled (1:1) trial of 96 children and adolescents aged 6-15.

Post-SELEX modification of quinine aptamers through neoacetalization.

In this article, a neoacetalization-based method for post-SELEX modification of aptamers is introduced. Three modified quinine binding aptamer scaffolds were synthesized by replacing three different nucleosides of the binding site with a (2,3)-4-(methoxyamino)butane-1,2,3-triol residue. These aptamer scaffolds were incubated in different aldehyde mixtures with and without quinine, allowing the reversible formation of -methoxy-1,3-oxazinane (MOANA) nucleoside analogues through dynamic combinatorial chemistry.

First year of in-house forensic neuropathology consultations in Helsinki, Finland.

In July 2023, an in-house forensic neuropathology consultation pilot was established at the Helsinki office of the Forensic Medicine Unit, Finnish Institute for Health and Welfare. This offered an alternative to the previous practice of full outsourcing to a hospital neuropathology department. This paper aims to introduce the first year experiences of the pilot.

Enhancing Psychophysiological Well-Being Through Nature-Based Soundscapes: An Examination of Heart Rate Variability in a Cross-Over Study.

Stress and psychological disorders are substantial public health concerns, necessitating innovative therapeutic strategies. This study investigated the psychophysiological benefits of nature-based soundscapes, drawing on the biophilia hypothesis. Using a randomized, acute cross-over design, 53 healthy participants experienced either a nature-based or a reference soundscape for 10 min, with a 2-min washout period.

Trends in childhood asthma in Denmark, Finland, Norway and Sweden.

Aim: Estimate the incidence of asthma among children aged 0 to 15 years in Denmark, Finland, Norway and Sweden during 2000-2017.

Methods: Cases of preschool asthma (up to 6 years) and school-age asthma (from 6 years) were identified through national registers using an algorithm including hospital diagnoses and prescription medicines. The respective cumulative incidence (CI) was estimated in 1-year age intervals for each country and birth year.

Enhanced neurological anomaly detection in MRI images using deep convolutional neural networks.

Introduction: Neurodegenerative diseases, including Parkinson's, Alzheimer's, and epilepsy, pose significant diagnostic and treatment challenges due to their complexity and the gradual degeneration of central nervous system structures. This study introduces a deep learning framework designed to automate neuro-diagnostics, addressing the limitations of current manual interpretation methods, which are often time-consuming and prone to variability.

Methods: We propose a specialized deep convolutional neural network (DCNN) framework aimed at detecting and classifying neurological anomalies in MRI data.

High nature value farming systems in Europe: A dataset encompassing the environmental impact assessment of farms and extensive ruminant food products.

High Nature Value (HNV) farming systems occur in areas where the major land use is agriculture and are characterized by their significance in promoting biodiversity and ecosystem services due to their extensive land use. Despite their importance for ecological and socio-economic resilience of rural regions, these systems are often overlooked in Life Cycle Assessment (LCA) studies due to challenges in data compilation, especially from small local farms and because of the diversity of production. To address this gap, we established an international collaborative network across Europe, involving professionals directly engaged with farmers, farmer associations, and researchers to collect data on HNV farms employing a developed questionnaire examining inputs and outputs, farm structures, and herd characteristics.

Circadian rhythms of microbial communities and their role in regulating nitrogen and phosphorus cycling in the rhizosphere of tea plants.

The circadian clock mediates metabolic functions of plants and rhythmically shapes structure and function of microbial communities in the rhizosphere. However, it is unclear how the circadian rhythm of plant hosts regulates changes in rhizosphere bacterial and fungal communities and nutrient cycles. In the present study, we measured diel changes in the rhizosphere of bacterial and fungal communities, and in nitrogen (N) and phosphorus (P) cycling in 20-year-old tea plantations.

Self-Reported Performance and Hormonal-Cycle-Related Symptoms in Competitive Female Athletes.

Introduction: The present scientific consensus is that the menstrual cycle (MC) and hormonal contraceptive (HC) cycle only influence performance trivially. Nevertheless, athletes perceive changes in performance that they associate with different phases of their hormonal cycle.

Methods: A total of 959 female athletes completed a questionnaire, of which 750 were included in the present analysis.

Non-targeted LC-MS metabolomics reveal shifts from wound-induced enzymatic browning to lignification during extended storage of fresh-cut lettuce in modified atmosphere packaging.

Modified Atmosphere Packaging (MAP) is a conventional method used to prolong the shelf-life of fresh-cut vegetables, including lettuce. However, MAP-stored lettuce remains perishable, and its deterioration mechanism is not fully understood. Here, we utilized non-targeted LC-MS metabolomics to evaluate the effects of cutting and extended storage time on metabolite profiles of lettuce stored in MAP.

Outcomes of kidney transplantation in patients with lysinuric protein intolerance.

Background: Lysinuric protein intolerance (LPI) is a metabolic disorder that leads to dysfunctional intestinal absorption and kidney clearance of cationic amino acids. Chronic kidney disease develops in many LPI patients and leads to end-stage kidney disease in at least 10% of patients. Since data on kidney transplants in LPI patients are limited, we analysed the outcomes of LPI patients after transplantation in Finland.

Direct measurement of three different deformations near the ground state in an atomic nucleus.

Atomic nuclei serve as prime laboratories for investigations of complex quantum phenomena, where minor nucleon rearrangements cause significant structural changes. Pb is the heaviest known neutron-deficient Pb isotope that can exhibit three distinct shapes: prolate, oblate, and spherical, with nearly degenerate excitation energies. Here we report on the combined results from three state-of-the-art measurements to directly observe these deformations in Pb.

Identifying biomarker-driven subphenotypes of cardiogenic shock: analysis of prospective cohorts and randomized controlled trials.

Background: Cardiogenic shock (CS) is a heterogeneous clinical syndrome, making it challenging to predict patient trajectory and response to treatment. This study aims to identify biological/molecular CS subphenotypes, evaluate their association with outcome, and explore their impact on heterogeneity of treatment effect (ShockCO-OP, NCT06376318).

Methods: We used unsupervised clustering to integrate plasma biomarker data from two prospective cohorts of CS patients: CardShock (N = 205 [2010-2012, NCT01374867]) and the French and European Outcome reGistry in Intensive Care Units (FROG-ICU) (N = 228 [2011-2013, NCT01367093]) to determine the optimal number of classes.

Fat Grafting With Lymphedema Fat: From Trash to Treasure?

Liposuction is a common procedure for patients with lymphedema with nonpitting adipose tissue hypertrophy. However, routinely, the lipoaspirate is discarded. Experimental studies have shown that adipose-derived stem cells in fat may enhance the regenerative and lymphangiogenic effects of the fat.

Durable complete response after combined treatment with tumor-infiltrating lymphocytes and oncolytic adenovirus (TILT-123) in a patient with metastatic mucosal melanoma.

Background: Despite significant advancements in the treatment of malignant melanoma, metastatic mucosal melanoma remains a therapeutic challenge due to its complex pathogenesis, distinct pathological characteristics, and limited response to immunotherapy. Combining different immunotherapeutic approaches offers a potential strategy to address these challenges. Tumor-infiltrating lymphocyte (TIL) therapy and oncolytic virus therapy represent promising treatment modalities that may synergize with each other.

Sentience and Beyond-A Representative Interview With Peter Singer AI.

This interview with Peter Singer AI serves a dual purpose. It is an exploration of certain-utilitarian and related-views on sentience and its ethical implications. It is also an exercise in the emerging interaction between natural and artificial intelligence, presented not as just ethics of AI but perhaps more importantly, as ethics with AI.

Anorexia nervosa is associated with higher brain mu-opioid receptor availability.

Anorexia nervosa (AN) is a severe psychiatric disorder, characterized by restricted eating, fear to gain weight, and a distorted body image. Mu-opioid receptor (MOR) functions as a part of complex opioid system and supports both homeostatic and hedonic control of eating behavior. Thirteen patients with AN and thirteen healthy controls (HC) were included in this study.

Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.

The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists.