Understanding recent advances in non-amyloid/non-tau (NANT) biomarkers and therapeutic targets in Alzheimer's disease.

Unlabelled: The Alzheimer's disease (AD) research community continues to make great strides in expanding approaches for early detection and treatment of the disease, including recent advances in our understanding of fundamental AD pathophysiology beyond the classical targets: beta-amyloid and tau. Recent clinical trial readouts implicate a variety of non-amyloid/non-tau (NANT) approaches that show promise in slowing cognitive decline for people with AD. The Alzheimer's Association Research Roundtable (AARR) meeting held on December 13-14, 2022, reviewed the current state of NANT targets on underlying AD pathophysiology and their contribution to cognitive decline, the current data on a diverse range of NANT biomarkers and therapeutic targets, and the integration of NANT concepts in clinical trial designs.

Alzheimer's disease drug development in an evolving therapeutic landscape.

Unlabelled: The Alzheimer's disease (AD) research field has entered a new era, where our fundamental understanding of the pathophysiology of AD and advances in biomarkers have not only allowed for earlier, timely, and accurate detection and diagnosis of the disease, but that amyloid removal has been shown to be associated with signals of slowing cognitive and functional decline. Although recent FDA-approved amyloid plaque-lowering monoclonal antibody therapies have shifted the trajectory of AD, additional treatment options will be key to further slowing clinical decline or stopping disease progression. Thus, new and emerging therapies for AD have created an evolving therapeutic landscape.

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.

A trial of radiolabeled antibody yttrium-90-FF-21101 for the treatment of advanced ovarian and other cancers.

Background: Yttrium-90 FF-21101 (Y-FF-21101) is a radiopharmaceutical that targets P-cadherin as a therapy against solid tumors. A previously reported, first-in-human study determined that a dose of 25 mCi/m was safe, and a patient with clear cell carcinoma of the ovary achieved a complete response. In this article, the authors report the results of Y-FF-21101 treatment in an ovarian carcinoma expansion cohort and in patients with selected solid tumors who had known high P-cadherin expression.

Exploring Restaurant Worker Mental Models of Injury and Safety Using Pathfinder Networks.

OCCUPATIONAL APPLICATIONSResults from our exploratory study of restaurant worker mental models of injury and safety emphasize the need for improved occupational safety in the culinary industry through targeted interventions for chefs and managers. The analysis we performed showed that managers possess more integrated and coherent mental models of injury and safety than chefs, reflected in network parameters showing better organization of safety concepts. Kitchen training programs should focus on bridging gaps in safety awareness and mitigating hazards such as burns, cuts, slips, and equipment-related risks.

Gender equity in oncology: Progress, challenges, and the path forward in urologic oncology and oncologic specialties.

Women now comprise over 50% of medical school graduates and over one-third of practicing physicians in the United States. Despite this progress, significant barriers to career advancement and leadership persist, particularly in male-dominated fields like urology and oncology. Women physicians are linked to improved patient outcomes and are critical to addressing the projected physician shortage, which is expected to be exaggerated in oncology specialties.

Systemic lupus erythematosus-associated autoantibodies in sickle cell disease: Spontaneous emergence in a patient and in transgenic sickle mice.

We describe a patient with sickle cell disease (SCD) and elevated antiphospholipid antibodies (aPL) who developed multi-organ failure resembling catastrophic antiphospholipid syndrome. Autoimmune screening revealed several autoantibodies characteristic of systemic lupus erythematosus (SLE). Notably, routinely housed and unmanipulated transgenic sickle mice displayed significantly elevated titres of aPL- and SLE-associated autoantibodies.

Where Are All the Clinical Trials for Chronic Rejection?

Chronic rejection is arguably the main obstacle to long-term graft survival. Yet, clinical trials focusing on this condition are disappointingly scarce. Significant advances in treating chronic rejection cannot happen if there is no conduit for testing novel therapies.

Programming scheduled self-assembly of circadian materials.

Active biological molecules present a powerful, yet largely untapped, opportunity to impart autonomous regulation of materials. Because these systems can function robustly to regulate when and where chemical reactions occur, they have the ability to bring complex, life-like behavior to synthetic materials. Here, we achieve this design feat by using functionalized circadian clock proteins, KaiB and KaiC, to engineer time-dependent crosslinking of colloids.

Transition metal vacancy and position engineering enables reversible anionic redox reaction for sodium storage.

Triggering the anionic redox reaction is an effective approach to boost the capacity of layered transition metal (TM) oxides. However, the irreversible oxygen release and structural deterioration at high voltage remain conundrums. Herein, a strategy for Mg ion and vacancy dual doping with partial TM ions pinned in the Na layers is developed to improve both the reversibility of anionic redox reaction and structural stability of layered oxides.

Deep learning-based aberration compensation improves contrast and resolution in fluorescence microscopy.

Optical aberrations hinder fluorescence microscopy of thick samples, reducing image signal, contrast, and resolution. Here we introduce a deep learning-based strategy for aberration compensation, improving image quality without slowing image acquisition, applying additional dose, or introducing more optics. Our method (i) introduces synthetic aberrations to images acquired on the shallow side of image stacks, making them resemble those acquired deeper into the volume and (ii) trains neural networks to reverse the effect of these aberrations.

Antibiotic Length of Therapy: Is Shorter Better in Older Adults?

Antibiotic lengths of therapy (LOT) vary widely, based on infection type, antibiotic regimen, and patient characteristics. Longer LOT are associated with increased risk of antibiotic resistance, adverse effects, and health care costs. There are increasing data supporting shorter LOT for many infections based on randomized, controlled trials (RCTs).

An evaluation framework for clinical use of large language models in patient interaction tasks.

The integration of large language models (LLMs) into clinical diagnostics has the potential to transform doctor-patient interactions. However, the readiness of these models for real-world clinical application remains inadequately tested. This paper introduces the Conversational Reasoning Assessment Framework for Testing in Medicine (CRAFT-MD) approach for evaluating clinical LLMs.

Standardized workflow for multiplexed charge detection mass spectrometry on orbitrap analyzers.

Individual ion mass spectrometry (IMS) is the Orbitrap-based extension of the niche mass spectrometry technique known as charge detection mass spectrometry (CDMS). While traditional CDMS analysis is performed on in-house-built instruments such as the electrostatic linear ion trap, IMS extends CDMS analysis to Orbitrap analyzers, allowing charge detection analysis to be available to the scientific community at large. IMS simultaneously measures the mass-to-charge ratios (m/z) and charges (z) of hundreds to thousands of individual ions within one acquisition event, creating a spectral output directly into the mass domain without the need for further spectral deconvolution.

Dissecting tumor transcriptional heterogeneity from single-cell RNA-seq data by generalized binary covariance decomposition.

Profiling tumors with single-cell RNA sequencing has the potential to identify recurrent patterns of transcription variation related to cancer progression, and to produce therapeutically relevant insights. However, strong intertumor heterogeneity can obscure more subtle patterns that are shared across tumors. Here we introduce a statistical method, generalized binary covariance decomposition (GBCD), to address this problem.

Repairing a deleterious domestication variant in a floral regulator gene of tomato by base editing.

Crop genomes accumulate deleterious mutations-a phenomenon known as the cost of domestication. Precision genome editing has been proposed to eliminate such potentially harmful mutations; however, experimental demonstration is lacking. Here we identified a deleterious mutation in the tomato transcription factor SUPPRESSOR OF SP2 (SSP2), which became prevalent in the domesticated germplasm and diminished DNA binding to genome-wide targets.

The impact of common and rare genetic variants on bradyarrhythmia development.

To broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively.

Mechanical regulation of macrophage metabolism by allograft inflammatory factor 1 leads to adverse remodeling after cardiac injury.

Myocardial infarction (MI) mobilizes macrophages, the central protagonists of tissue repair in the infarcted heart. Although necessary for repair, macrophages also contribute to adverse remodeling and progression to heart failure. In this context, specific targeting of inflammatory macrophage activation may attenuate maladaptive responses and enhance cardiac repair.

Cell-free biodegradable electroactive scaffold for urinary bladder tissue regeneration.

Tissue engineering heavily relies on cell-seeded scaffolds to support the complex biological and mechanical requirements of a target organ. However, in addition to safety and efficacy, translation of tissue engineering technology will depend on manufacturability, affordability, and ease of adoption. Therefore, there is a need to develop scalable biomaterial scaffolds with sufficient bioactivity to eliminate the need for exogenous cell seeding.

A soft thermal sensor for the continuous assessment of flow in vascular access.

Hemodialysis for chronic kidney disease (CKD) relies on vascular access (VA) devices, such as arteriovenous fistulas (AVF), grafts (AVG), or catheters, to maintain blood flow. Nonetheless, unpredictable progressive vascular stenosis due to neointimal formation or complete occlusion from acute thrombosis remains the primary cause of mature VA failure. Despite emergent surgical intervention efforts, the lack of a reliable early detection tool significantly reduces patient outcomes and survival rates.

Prevalence of indications of alcohol and drug use among patients treated for injurious falls by Emergency Medical Services in the USA.

Objective: The association between alcohol consumption and increased injuries from falls is well established, but there is a lack of data on the prevalence of substance use by fall type. This study aims to describe the distribution of alcohol and drug involvement in injurious falls.

Methods: Using the 2019 National Emergency Medical Services (EMS) Information System data set, we identified 1 854 909 patients injured from falls requiring an EMS response and determined the fall location (eg, indoors or on street/sidewalk).