Chronic Cerebral Deterioration - A Comprehensive View of Old-Age Cerebral Deterioration.

The current one-dimensional view of pathological brain changes in older persons leading to cognitive complaints, mild cognitive impairment, and ultimately dementia is incomplete. It neglects the earliest, non-cognitive, and multifaceted symptoms of gradually accumulating cerebral damage. Subtle personality changes, balance problems, muscle wasting, weight loss, changing sleep patterns and declining blood pressure and cholesterol, precede memory problems and cognitive impairment.

Plasma Proteomic Signature as a Predictor of Age Advancement in People Living With HIV.

Due to the increased burden of non-AIDS-related comorbidities in people living with HIV (PLHIV), identifying biomarkers and mechanisms underlying premature aging and the risk of developing age-related comorbidities is a priority. Evidence suggests that the plasma proteome is an accurate source for measuring biological age and predicting age-related clinical outcomes. To investigate whether PLHIV on antiretroviral therapy (ART) exhibit a premature aging phenotype, we profiled the plasma proteome of two independent cohorts of virally suppressed PLHIV (200HIV and 2000HIV) and one cohort of people without HIV (200FG) using O-link technology.

Global regulators enable bacterial adaptation to a phenotypic trade-off.

Cellular fitness depends on multiple phenotypes that must be balanced during evolutionary adaptation. For instance, coordinating growth and motility is critical for microbial colonization and cancer invasiveness. In bacteria, these phenotypes are controlled by local regulators that target single operons, as well as by global regulators that impact hundreds of genes.

Cost-effectiveness of follow-up algorithms for chronic thromboembolic pulmonary hypertension in pulmonary embolism survivors.

Introduction: Achieving an early diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) in pulmonary embolism (PE) survivors results in better quality of life and survival. Importantly, dedicated follow-up strategies to achieve an earlier CTEPH diagnosis involve costs that were not explicitly incorporated in the models assessing their cost-effectiveness. We performed an economic evaluation of 11 distinct PE follow-up algorithms to determine which should be preferred.

The effect of active exoskeleton support with different lumbar-to-hip support ratios on spinal musculoskeletal loading and lumbar kinematics during lifting.

While active back-support exoskeletons can reduce mechanical loading of the spine, current designs include only one pair of actuated hip joints combined with a rigid structure between the pelvis and trunk attachments, restricting lumbar flexion and consequently intended lifting behavior. This study presents a novel active exoskeleton including actuated lumbar and hip joints as well as subject-specific exoskeleton control based on a real-time active low-back moment estimation. We evaluated the effect of exoskeleton support with different lumbar-to-hip (L/H) support ratios on spine loading, lumbar kinematics, and back muscle electromyography (EMG).

Perivascular fat attenuation index (FAI) on computed tomography coronary angiography reclassifies individual cardiovascular risk estimation.

Background: The perivascular fat attenuation index (FAI) detects and quantifies coronary inflammation by measuring phenotypic changes in perivascular adipose tissue by using computed tomography coronary angiography images.

Aim: The primary objective of this study was to evaluate the reclassification of cardiovascular (CV) risk after incorporating perivascular FAI assessment in currently used risk score algorithms.

Methods: This was a single-center, retrospective study of 200 patients with suspected coronary artery disease who underwent computed tomography coronary angiography in clinical practice between January 2022 and May 2022.

Extending health equity to people with moderate and mild hemophilia A: revisiting the HAVEN 6 trial.

Congenital hemophilia A (HA) disease severity has traditionally been categorized according to intrinsic factor (F)VIII levels, with <1% of normal indicating severe HA, 1% to 5% moderate HA, and 6% to 40% mild HA. However, mounting evidence illustrates considerable variability in bleeding phenotype regardless of FVIII level. Despite treatment advances, people with moderate or mild HA may be neglected, as treatment guidelines and established norms focus on FVIII levels, and many clinical trials do not include people with FVIII > 1%.

Effectiveness of a stepped-care programme of WHO psychological interventions in a population of migrants: results from the RESPOND randomized controlled trial.

Migrant populations - including labour migrants, undocumented migrants, asylum seekers, refugees, internationally displaced persons, and other populations on the move - are exposed to a variety of stressors that affect their mental health. We designed and tested the effectiveness of a stepped-care programme consisting of two scalable psychological interventions developed by the World Health Organization (WHO) and locally adapted for migrant populations. A parallel-group randomized controlled trial was conducted in Italy.

Cannabis Use Cessation and the Risk of Psychotic Disorders: A Case-Control Analysis from the First Episode Case-Control EU-GEI WP2 Study: L'arrêt de l'utilisation du cannabis et le risque de troubles psychotiques: Une analyse cas-témoins tirée de l'étude cas-témoins EU-GEI WP2 centrée sur les premiers épisodes psychotiques.

Objectives: To establish whether the risk of psychotic disorders in cannabis users changes with time following cannabis cessation using data from the European Network of National Networks studying Gene-Environment Interactions in Schizophrenia (EU-GEI) case-control study.

Methods: The EU-GEI case-control study collected data from first episode psychosis patients and population controls across sites in Europe and Brazil between May 2010 and April 2015. Adjusted logistic regressions were applied to examine whether the odd of psychosis case status changed: (1) with time following cannabis cessation and (2) across different cannabis use groups.

Investigator-Initiated Clinical Pharmacokinetic Studies in Resource-Limited Settings: Minimal Requirements and Practical Guidance.

Clinical pharmacology studies are critical for determining the efficacy and safety of drugs. Due to the resource-intensive nature of these studies, most have been conducted in high-income countries, leading to a significant gap in clinical pharmacology data for patients in low- and middle-income countries. This paper provides an overview of the minimal requirements for performing a clinical pharmacology investigator-initiated trial (IIT), including pharmacokinetic sampling.

Mapping Trajectories of Gait Recovery in Clinical Stroke Rehabilitation.

Background: How gait changes during the early stages of stoke rehabilitation, and which patient characteristics are associated with these changes is still largely unknown.

Objective: he first objective was to describe the changes in gait during stroke rehabilitation. Secondly, we determined how various patient characteristics were associated with the rate of change of gait over time.

Discovery of robust and highly specific microbiome signatures of non-alcoholic fatty liver disease.

Background: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) with a global prevalence of 30% is multifactorial and the involvement of gut bacteria has been recently proposed. However, finding robust bacterial signatures of NAFLD has been a great challenge, mainly due to its co-occurrence with other metabolic diseases.

Results: Here, we collected public metagenomic data and integrated the taxonomy profiles with in silico generated community metabolic outputs, and detailed clinical data, of 1206 Chinese subjects w/wo metabolic diseases, including NAFLD (obese and lean), obesity, T2D, hypertension, and atherosclerosis.

F-Prostate-Specific Membrane Antigen PET/CT imaging for potentially resectable pancreatic cancer (PANSCAN-2): a phase I/II study.

Background: Current diagnostic imaging modalities have limited ability to differentiate between malignant and benign pancreaticobiliary disease, and lack accuracy in detecting lymph node metastases. F-Prostate-Specific Membrane Antigen (PSMA) PET/CT is an imaging modality used for staging of prostate cancer, but has incidentally also identified PSMA-avid pancreatic lesions, histologically characterized as pancreatic ductal adenocarcinoma (PDAC). This phase I/II study aimed to assess the feasibility of F-PSMA PET/CT to detect PDAC.

Enabling next-generation engineered TCR-T therapies based on high-throughput TCR discovery from diagnostic tumor biopsies.

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) can mediate tumor regression, including complete and durable responses, in a range of solid cancers, most notably in melanoma. However, its wider application and efficacy has been restricted by the limited accessibility, proliferative capacity and effector function of tumor-specific TIL. Here, we develop a platform for the efficient identification of tumor-specific TCR genes from diagnostic tumor biopsies, including core-needle biopsies frozen in a non-viable format, to enable engineered T cell therapy.

A diagnostic host-specific transcriptome response for Mycoplasma pneumoniae pneumonia to guide pediatric patient treatment.

Mycoplasma pneumoniae causes atypical pneumonia in children and young adults. Its lack of a cell wall makes it resistant to beta-lactams, which are the first-line treatment for typical pneumonia. Current diagnostic tests are time-consuming and have low specificity, leading clinicians to administer empirical antibiotics.

The TRPV1-PKM2-SREBP1 axis maintains microglial lipid homeostasis in Alzheimer's disease.

Microglia are progressively activated by inflammation and exhibit phagocytic dysfunction in the pathogenesis of neurodegenerative diseases. Lipid-droplet-accumulating microglia were identified in the aging mouse and human brain; however, little is known about the formation and role of lipid droplets in microglial neuroinflammation of Alzheimer's disease (AD). Here, we report a striking buildup of lipid droplets accumulation in microglia in the 3xTg mouse brain.

Predictive performance of ROX index and its variations for NIV failure.

Objective: To determine whether the ROX index and its variations can predict the risk of intubation in ICU patients receiving NIV ventilation using large public ICU databases.

Design: Retrospective observational cohort study.

Setting: Patient data was extracted from both the AmsterdamUMCdb and the MIMIC-IV ICU databases, which contained data related to 20,109 and 50,920 unique patients.

An extensive dataset of spiking activity to reveal the syntax of the ventral stream.

Visual neuroscience benefits from high-quality datasets with neuronal responses to many images. Several neuroimaging datasets have been published in recent years, but no comparable dataset with spiking activity exists. Here, we introduce the THINGS ventral stream spiking dataset (TVSD).

A Patient-Oriented Implementation Strategy for a Perioperative mHealth Intervention: Feasibility Cohort Study.

Background: Day surgery is being increasingly implemented across Europe, driven in part by capacity problems. Patients recovering at home could benefit from tools tailored to their new care setting to effectively manage their convalescence. The mHealth application ikHerstel is one such tool, but although it administers its functions in the home, its implementation hinges on health care professionals within the hospital.

Identifying depression subtypes and investigating their consistency and transitions in a 1-year cohort analysis.

Major depressive disorder (MDD) is defined by an array of symptoms that make it challenging to understand the condition at a population level. Subtyping offers a way to unpick this phenotypic diversity for improved disorder characterisation. We aimed to identify depression subtypes longitudinally using the Inventory of Depressive Symptomatology: Self-Report (IDS-SR).

Adverse health outcomes and health-related quality of life (HRQoL) among long-term adolescent and young adult (AYA) brain tumour survivors: results from the population-based SURVAYA study.

Purpose: Adolescent and young adult (AYA) malignant brain tumour (BT) survivors are at risk of adverse health outcomes, which may impact their health-related quality of life (HRQoL). This study aimed to investigate the (1) prevalence of physical and psychological adverse health outcomes, (2) the HRQoL, and (3) the association of adverse health outcomes and HRQoL among long-term AYA-BT survivors. Adverse health outcomes and HRQoL were compared to other AYA cancer (AYAC) survivors.

Machine learning prediction model for oral mucositis risk in head and neck radiotherapy: a preliminary study.

Purpose: Oral mucositis (OM) reflects a complex interplay of several risk factors. Machine learning (ML) is a promising frontier in science, capable of processing dense information. This study aims to assess the performance of ML in predicting OM risk in patients undergoing head and neck radiotherapy.

Predictors of Bilateral Disease in Low-Risk Papillary Thyroid Cancer: Histopathologic Insights and Preoperative Ultrasonography.

Background: With the current shift toward de-escalation of surgical management in low-risk papillary thyroid cancer (PTC), understanding predictors and the clinical significance of additional tumors in the contralateral lobe is important. This study investigated the histopathologic predictors of bilateral disease in low-risk PTC patients and the utility of preoperative ultrasonography in guiding completion thyroidectomy decisions.

Methods: Patients treated with total thyroidectomy (TT) for low-risk PTCs (< 4 cm) at the Endocrine Surgical Unit of the Royal North Shore Hospital, University of Sydney from 2013 to 2020 were identified from a prospectively maintained database.

Tenascin-X deficiency causing classical-like Ehlers Danlos syndrome type 1 in humans is a significant risk factor for GI and tracheal ruptures.

Background: Classical-like Ehlers Danlos Syndrome type 1 (clEDS1) is a very rare form of Ehlers Danlos Syndrome (EDS) caused by tenascin-X (TNX) deficiency, with only 56 individuals reported. TNX is an extracellular matrix protein needed for collagen stability. Previous publications propose that individuals with clEDS1 might be at risk for gastrointestinal (GI) tract perforations and/or tracheal ruptures.