Application of the revised criteria for diagnosis and staging of Alzheimer's disease: Drug development and clinical practice.

Unlabelled: The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the Alzheimer's Association (AA) Workgroup represent a significant milestone in the field. These criteria offer objective measures for diagnosing and staging biological AD, bridging the gap between research and clinical care. Although implementation feasibility may vary across regions and settings, improving the availability and accuracy of biomarkers, especially plasma biomarkers, is expected to enhance the applicability of these criteria in clinical practice.

Chemical Probes for Investigating the Endocannabinoid System.

Cannabis sativa has been used therapeutically since early civilizations, with key cannabinoids Δ-tetrahydrocannabinol (THC) 3.1 and cannabidiol characterized in the 1960s, leading to the discovery of cannabinoid receptors type 1 (CBR) and type 2 (CBR) and the endocannabinoid system (ECS) in the 1990s. The ECS, involving endogenous ligands like 2-arachidonoylglycerol (2-AG) 1.

A stratified treatment algorithm in psychiatry: a program on stratified pharmacogenomics in severe mental illness (Psych-STRATA): concept, objectives and methodologies of a multidisciplinary project funded by Horizon Europe.

Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal.

How Does Deep Neural Network-Based Noise Reduction in Hearing Aids Impact Cochlear Implant Candidacy?

Background/objectives: Adult hearing-impaired patients qualifying for cochlear implants typically exhibit less than 60% sentence recognition under the best hearing aid conditions, either in quiet or noisy environments, with speech and noise presented through a single speaker. This study examines the influence of deep neural network-based (DNN-based) noise reduction on cochlear implant evaluation.

Methods: Speech perception was assessed using AzBio sentences in both quiet and noisy conditions (multi-talker babble) at 5 and 10 dB signal-to-noise ratios (SNRs) through one loudspeaker.

Salivary oxytocin and amygdalar alterations in functional neurological disorders.

Individuals diagnosed with functional neurological disorder experience abnormal movement, gait, sensory processing or functional seizures, for which research into the pathophysiology identified psychosocial contributing factors as well as promising biomarkers. Recent pilot studies suggested that (epi-)genetic variants may act as vulnerability factors, for example, on the oxytocin pathway. This study set out to explore endogenous oxytocin hormone levels in saliva in a cohort of 59 functional neurological disorder patients and 65 healthy controls comparable in sex and age.

Building global collaborative research networks in paediatric critical care: a roadmap.

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups.

Virus adaptation to heparan sulfate comes with capsid stability tradeoff.

Because of high mutation rates, viruses constantly adapt to new environments. When propagated in cell lines, certain viruses acquire positively charged amino acids on their surface proteins, enabling them to utilize negatively charged heparan sulfate (HS) as an attachment receptor. In this study, we used enterovirus A71 (EV-A71) as model and demonstrated that unlike the parental MP4 variant, the cell-adapted strong HS-binder MP4-97R/167G does not require acidification for uncoating and releases its genome in the neutral or weakly acidic environment of early endosomes.

Origin of the Suppression of Magnetic Order in MnSi under Hydrostatic Pressure.

We experimentally study the evolution of the magnetic moment m and exchange interaction J as a function of hydrostatic pressure in the zero-field helimagnetic phase of the strongly correlated electron system MnSi. The suppression of magnetic order at ≈1.5  GPa is shown to arise from the J collapse and not from a quantum fluctuations induced reduction of m.

Plasma Aβ/Aβ is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum.

Introduction: The availability of amyloid beta (Aβ) targeting therapies for Alzheimer's disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aβ accumulation.

Methods: We evaluated fully-automated Lumipulse plasma Aβ/Aβ immunoassays for detecting cerebral Aβ in 457 clinically unimpaired (CU) and clinically impaired (CI) Stanford Alzheimer's Disease Research Center (Stanford ADRC) participants and 186 CU in the Stanford Aging and Memory Study (SAMS). Longitudinal change in ADRC plasma Aβ/Aβ and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined.

The Safety of Recently Approved Therapeutics in Age-Related Macular Degeneration.

Recent developments in treatments for both forms of advanced age-related macular degeneration (AMD) have led to the approval of multiple agents and modalities within the last few years. Five new medications for both neovascular AMD (nAMD) and geographic atrophy (GA) secondary to nonexudative AMD (neAMD) have been FDA-approved within the last 5 years, along with a new device designed for sustained drug delivery for nAMD. In nAMD, the newest agents approved by the FDA are brolucizumab (Novartis Pharmaceuticals, Basel, Switzerland), faricimab (F.

ExerG - an exergame-based training device for the rehabilitation of older adults: a functional model usability study.

Background: Exergames are interactive technology-based exercise programs. By combining physical and cognitive training components, they aim to preserve independence in older adults and reduce their risk of falling. This study explored whether primary end users (PEU, healthy older adults and patients with neurological and geriatric diagnoses) and secondary end users (SEU, health professionals) evaluated the ExerG functional model to be usable, providing a positive experience and therefore acceptable.

Impact of gender on the willingness to participate in clinical trials and undergo related procedures in individuals from an Alzheimer's prevention research cohort.

Background: Although there is growing evidence of the association between gender and early diagnosis of preclinical Alzheimer's disease, little attention has been given to the enrolment ratio of men and women in clinical trials and data reporting.

Methods: This study aims to analyze gender differences in sociodemographic factors associated with the willingness to participate in clinical trials and undergo specific procedures in the context of an Alzheimer's disease prevention research cohort. 2544 cognitively unimpaired participants from the ALFA parent cohort (age 45-75 years) of the Barcelonaβeta Brain Research Center were contacted through a structured phone call to determine their willingness to participate in Alzheimer's disease clinical trials and undergo trial-related procedures (magnetic resonance imaging, lumbar puncture, positron emission tomography, and cognitive assessment).

Validation of prognostic models predicting mortality or ICU admission in patients with COVID-19 in low- and middle-income countries: a global individual participant data meta-analysis.

Background: We evaluated the performance of prognostic models for predicting mortality or ICU admission in hospitalized patients with COVID-19 in the World Health Organization (WHO) Global Clinical Platform, a repository of individual-level clinical data of patients hospitalized with COVID-19, including in low- and middle-income countries (LMICs).

Methods: We identified eligible multivariable prognostic models for predicting overall mortality and ICU admission during hospital stay in patients with confirmed or suspected COVID-19 from a living review of COVID-19 prediction models. These models were evaluated using data contributed to the WHO Global Clinical Platform for COVID-19 from nine LMICs (Burkina Faso, Cameroon, Democratic Republic of Congo, Guinea, India, Niger, Nigeria, Zambia, and Zimbabwe).

Asciminib add-on to imatinib demonstrates sustained high rates of ongoing therapy and deep molecular responses with prolonged follow-up in the ASC4MORE study.

Background: Up to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, which is required to attempt treatment-free remission. Asciminib is the only approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket. This unique mechanism of action allows asciminib to be combined with adenosine triphosphate-competitive tyrosine kinase inhibitors to prevent resistance and enhance efficacy.

Strength of clinical evidence supporting the United States Food and Drug Administration Accelerated Approvals from 2015 to 2022.

Background: The Food and Drug Administration (FDA)'s Accelerated Approval (AA) pathway has increasingly used to authorize market approval of new drugs amid controversy. The present study aims to inform the most recent data on the strength of clinical evidence supporting such approvals.

Methods: Evidentiary characteristics of pre-approval pivotal clinical studies and regulator-required post-approval confirmatory studies supporting AAs between 2015 and 2022 were extracted from publicly available FDA documents.

Intracorneal iontophoretic delivery of triamcinolone acetonide prodrugs: Physicochemical parameters guiding electrotransport.

Intracorneal delivery of ten amino acid (alanine, arginine, asparagine, glutamine, glycine, histidine, isoleucine, lysine, methionine and valine) ester prodrugs of triamcinolone acetonide (TA-AA) was investigated in vitro, using a corneal iontophoresis device (IONTOFOR-CXL; SOOFT Italia S.p.A.

A Prospective Evaluation of Chemokine Receptor-4 (CXCR4) Overexpression in High-grade Glioma Using Ga-Pentixafor (Pars-Cixafor™) PET/CT Imaging.

Background: While magnetic resonance imaging (MRI) remains the gold standard for morphological imaging, its ability to differentiate between tumor tissue and treatment-induced changes on the cellular level is insufficient. Notably, glioma cells, particularly glioblastoma multiforme (GBM), demonstrate overexpression of chemokine receptor-4 (CXCR4). This study aims to evaluate the feasibility of non-invasive Ga-Cixafor™ PET/CT as a tool to improve diagnostic accuracy in patients with high-grade glioma.

Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours.

Cancer immunotherapies with antibodies blocking immune checkpoint molecules are clinically active across multiple cancer entities and have markedly improved cancer treatment. Yet, response rates are still limited, and tumour progression commonly occurs. Soluble and cell-bound factors in the tumour microenvironment negatively affect cancer immunity.

Prognostic relevance of treatment deviations in children with relapsed acute lymphoblastic leukemia who were treated in the ALL-REZ BFM 2002 study.

Relapsed Acute Lymphoblastic Leukemia (ALL) is among the most common causes of cancer-associated deaths in children. However, little is known about the implications of deviations from ALL treatment protocols on survival rates. The present study elucidates the various characteristics of treatment deviations in children with relapsed ALL included in the ALL-REZ BFM 2002 (i.

Estimated global and regional incidence and prevalence of herpes simplex virus infections and genital ulcer disease in 2020: mathematical modelling analyses.

Objectives: Genital herpes simplex virus (HSV) type 1 and 2 infections are lifelong and can cause symptomatic genital ulcer disease (GUD). HSV-2 almost always causes sexually transmitted genital infection, while HSV-1 mainly causes oral infection but can be sexually transmitted to cause genital infection. This study estimated genital infection with both HSV types and associated GUD globally in 2020, breaking down the data by WHO region and sex for females and males.

Type 2 responses determine skin rash during recombinant interleukin-2 therapy.

The skin is the organ most often affected by adverse drug reactions. Although these cutaneous adverse drug reactions (CADRs) often are mild, they represent a major burden for patients. One of the drugs inducing CADRs is aldesleukin, a recombinant interleukin-2 (recIL-2) originally approved to treat malignant melanoma and metastatic renal cell carcinoma which frequently led to skin rashes when applied in high doses for anti-cancer therapy.

Microplastic analysis in soils: A comparative assessment.

Microplastic (MiP) contamination poses environmental risks, but harmonizing data from different quantification methods and sample matrices remains challenging. We compared analytical protocols for MiP quantification in soil, consisting of Digital, Fluorescence, Fourier-transform infrared (FTIR), and Raman Microscopy as well as quantitative Pyrolysis-Gas Chromatography-Mass Spectroscopy (Py-GC-MS) and 1-proton nuclear magnetic resonance (H NMR) spectroscopy as detection techniques. Each technique was coupled with a specific extraction procedure and evaluated for three soils with different textures and organic carbon contents, amended with eight types of large MiPs (0.