Amyloid-associated hyperconnectivity drives tau spread across connected brain regions in Alzheimer's disease.

In Alzheimer's disease (AD), amyloid-β (Aβ) triggers the aggregation and spreading of tau pathology, which drives neurodegeneration and cognitive decline. However, the pathophysiological link between Aβ and tau remains unclear, which hinders therapeutic efforts to attenuate Aβ-related tau accumulation. Aβ has been found to trigger neuronal hyperactivity and hyperconnectivity, and preclinical research has shown that tau spreads across connected neurons in an activity-dependent manner.

A Non-Centrifugation Method to Concentrate and Purify Extracellular Vesicles Using Superabsorbent Polymer Followed by Size Exclusion Chromatography.

Extracellular vesicles (EVs) can be isolated and purified from cell cultures and biofluids using different methodologies. Here, we explored a novel EV isolation approach by combining superabsorbent polymers (SAP) in a dialysis membrane with size exclusion chromatography (SEC) to achieve high concentration and purity of EVs without the use of ultracentrifugation (UC). Suspension HEK293 cells transfected with CD63 coupled with Thermo Luciferase were used to quantify the EV yield and purity.

Compositional data analysis enables statistical rigor in comparative glycomics.

Comparative glycomics data are compositional data, where measured glycans are parts of a whole, indicated by relative abundances. Applying traditional statistical analyses to these data often results in misleading conclusions, such as spurious "decreases" of glycans when other structures increase in abundance, or high false-positive rates for differential abundance. Our work introduces a compositional data analysis framework, tailored to comparative glycomics, to account for these data dependencies.

Cutting through the noise: A narrative review of Alzheimer's disease plasma biomarkers for routine clinical use.

As novel, anti-amyloid therapies have become more widely available, access to timely and accurate diagnosis has become integral to ensuring optimal treatment of patients with early-stage Alzheimer's disease (AD). Plasma biomarkers are a promising tool for identifying AD pathology; however, several technical and clinical factors need to be considered prior to their implementation in routine clinical use. Given the rapid pace of advancements in the field and the wide array of available biomarkers and tests, this review aims to summarize these considerations, evaluate available platforms, and discuss the steps needed to bring plasma biomarker testing to the clinic.

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.

Influenza A Virus H7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protection.

Influenza remains a persistent global health challenge, largely due to the virus' continuous antigenic drift and occasional shift, which impede the development of a universal vaccine. To address this, the identification of broadly neutralizing antibodies and their epitopes is crucial. Nanobodies, with their unique characteristics and binding capacity, offer a promising avenue to identify such epitopes.

Machine learning-derived asthma and allergy trajectories in children: a systematic review and meta-analysis.

Introduction: Numerous studies have characterised trajectories of asthma and allergy in children using machine learning, but with different techniques and mixed findings. The present work aimed to summarise the evidence and critically appraise the methodology.

Methods: 10 databases were searched.

Data-driven CSF biomarker profiling: imaging and clinical outcomes in a cohort at risk of Alzheimer's disease.

Background: Cerebrospinal fluid (CSF) biomarkers of synaptic dysfunction, neuroinflammation, and glial response, complementing Alzheimer's disease (AD) core biomarkers, have improved the pathophysiological characterization of the disease. Here, we tested the hypothesis that the co-expression of multiple CSF biomarkers will help the identification of AD-like phenotypes when biomarker positivity thresholds are not met yet.

Methods: Two hundred and seventy cognitively unimpaired adults with family history (FH) of sporadic AD (mean age = 60.

Artificial intelligence in pediatric allergy research.

Unlabelled: Atopic dermatitis, food allergy, allergic rhinitis, and asthma are among the most common diseases in childhood. They are heterogeneous diseases, can co-exist in their development, and manifest complex associations with other disorders and environmental and hereditary factors. Elucidating these intricacies by identifying clinically distinguishable groups and actionable risk factors will allow for better understanding of the diseases, which will enhance clinical management and benefit society and affected individuals and families.

Integration of personalised ultrasensitive ctDNA monitoring of patients with metastatic breast cancer to reduce imaging requirements.

Circulating tumour DNA (ctDNA) is an emerging biomarker for monitoring cancers. The personalised disease monitoring in metastatic breast cancer (PDM-MBC) study is an ongoing study instigated to evaluate ctDNA as a biomarker to individualise imaging requirements in patients with MBC. Patients receiving first-line endocrine therapy (aromatase inhibitor + cyclin-dependent kinase 4/6 inhibitor) had plasma samples collected pre-treatment, weeks 2 and 4, and concurrently with imaging until progressive disease (PD).

Magnetic Sentinel Lymph Node Biopsy in Early Breast Cancer Patients: An Individual Patient Data Meta-analysis of Tracer Uptake.

Background: Superparamagnetic iron oxide nanoparticles (SPIO) are emerging as a viable alternative to technetium and blue dye. Our study was designed to evaluate the correlation between SPIO dose, injection site, and timing with sentinel lymph node (SLN) detection and iron content in retrieved SLNs.

Methods: This study combined individual patient data from three Dutch and five Swedish studies.

Rituximab Treatment as Second-Line Therapy in Glucocorticoid Nonresponsive Graves' Orbitopathy: A Nonrandomized, Controlled, Interventional Study.

Objective: In moderate-to-severe Graves' orbitopathy, rituximab is recommended as second-line therapy in patients nonresponsive to intravenous glucocorticoids. We aimed to evaluate rituximab as early second-line therapy, as data are scarce and contradictory.

Methods: In this nonrandomized, controlled, interventional study, patients with Graves' orbitopathy started on intravenous glucocorticoids.

Cortical hypometabolism in Parkinson's disease is linked to cholinergic basal forebrain atrophy.

Cortical hypometabolism on FDG-PET is a well-established neuroimaging biomarker of cognitive impairment in Parkinson's disease (PD), but its pathophysiologic origins are incompletely understood. Cholinergic basal forebrain (cBF) degeneration is a prominent pathological feature of PD-related cognitive impairment and may contribute to cortical hypometabolism through cholinergic denervation of cortical projection areas. Here, we investigated in-vivo associations between subregional cBF volumes on 3T-MRI, cortical hypometabolism on [F]FDG-PET, and cognitive deficits in a cohort of 95 PD participants with varying degrees of cognitive impairment.

Development of an optimized MRI protocol for a rapid preoperative identification of sentinel lymph nodes using superparamagnetic iron oxide - The Gothenburg fast acquisition sentinel lymph node tracking magnetic resonance imaging protocol (GO-FAST-MRI).

Introduction: Determining sentinel lymph node (SLN) status is important for treatment decisions in patients with melanoma. Superparamagnetic iron oxide nanoparticles (SPIO) combined with MRI have emerged as an alternative to Technetium lymphoscintigraphy for preoperative mapping of SLN, however, the MRI protocols so far are extensive with long in-camera time. This study aimed to evaluate an optimized MRI protocol for rapid identification of SLNs using SPIO as a tracer, without compromising diagnostic quality, the GOthenburg Fast Acquisition Sentinel lymph node Tracking MRI (GO-FAST-MRI).

Personalized circulating tumor DNA analysis for sensitive disease monitoring and detection of relapse in neuroblastoma.

Circulating tumor DNA (ctDNA) has shown potential as a non-invasive tumor biomarker in neuroblastoma. Previous studies used generic assays for detection of selected predefined oncogenic variants as markers of ctDNA, which limits the sensitivity and excludes a subset of patients from analysis. Here we assessed patient-specific ctDNA analysis for treatment evaluation and detection of relapse in neuroblastoma.

Mechanistic basis of atypical TERT promoter mutations.

Non-coding mutations in the TERT promoter (TERTp), typically at one of two bases -124 and -146 bp upstream of the start codon, are among the most prevalent driver mutations in human cancer. Several additional recurrent TERTp mutations have been reported but their functions and origins remain largely unexplained. Here, we show that atypical TERTp mutations arise secondary to canonical TERTp mutations in a two-step process.

Efficient Gene-Editing in Human Pluripotent Stem Cells Through Simplified Assembly of Adeno-Associated Viral (AAV) Donor Templates.

Gene-edited human pluripotent stem cells provide attractive model systems to functionally interrogate the role of specific genetic variants in relevant cell types. However, the need to isolate and screen edited clones often remains a bottleneck, in particular when recombination rates are sub-optimal. Here, we present a protocol for flexible gene editing combining Cas9 ribonucleoprotein with donor templates delivered by adeno-associated virus (AAV) vectors to yield high rates of homologous recombination.

Comparative Analysis of Plasma Protein Dynamics in Women with ST-Elevation Myocardial Infarction and Takotsubo Syndrome.

Background: ST-elevation myocardial infarction (STEMI) and Takotsubo syndrome (TS) are two distinct cardiac conditions that both result in sudden loss of cardiac dysfunction and that are difficult to distinguish clinically. This study compared plasma protein changes in 24 women with STEMI and 12 women with TS in the acute phase (days 0-3 post symptom onset) and the stabilization phase (days 7, 14, and 30) to examine the molecular differences between these conditions.

Methods: Plasma proteins from STEMI and TS patients were extracted during the acute and stabilization phases and analyzed via quantitative proteomics.