Deep learning model to diagnose cardiac amyloidosis from haematoxylin/eosin-stained myocardial tissue.

Aims: Amyloid deposition in myocardial tissue is a definitive feature for diagnosing cardiac amyloidosis, though less invasive imaging modalities such as bone tracer cardiac scintigraphy and cardiac magnetic resonance imaging have been established as first steps for its diagnosis. This study aimed to develop a deep learning model to support the diagnosis of cardiac amyloidosis from haematoxylin/eosin (HE)-stained myocardial tissue.

Methods And Results: This single-centre retrospective observational study enrolled 166 patients who underwent myocardial biopsies between 2008 and 2022, including 76 patients diagnosed with cardiac amyloidosis and 90 with other diagnoses.

High Aspect Ratio Polymer Nanocarriers for Gene Delivery and Expression in Plants.

Plant genetic engineering methods are critical for food security and biofuel production and to enable molecular farming. Here, we elucidated how polymeric high aspect ratio nanocarriers can enable DNA delivery to plants and transient expression. We demonstrated that a nanocarrier with 20 nm width, 80 nm length, and a polymer-to-DNA ratio of N/P = 3.

Recommendations for the Safe Application of Temporal Interference Stimulation in the Human Brain Part II: Biophysics, Dosimetry, and Safety Recommendations.

Temporal interference stimulation (TIS) is a new form of transcranial electrical stimulation (tES) that has been proposed as a method for targeted, noninvasive stimulation of deep brain structures. While TIS holds promise for a variety of clinical and nonclinical applications, little data is yet available regarding its effects in humans and its mechanisms of action. To inform the design and safe conduct of experiments involving TIS, researchers require quantitative guidance regarding safe exposure limits and other safety considerations.

Symmetric Diblock Copolymers Form Versatile and Switchable Ultrasmall Nanoparticles.

Block copolymers (BCPs) can form nanoparticles having different morphologies that can be used as photonic nanocrystals and are a platform for drug delivery, sensors, and catalysis. In particular, BCP nanoparticles having disk-like shape have been recently discovered. Such nanodisks can be used as the next-generation antitumor drug delivery carriers; however, the applicability of the existing nanodisks is limited due to their poor or unknown ability to respond to external stimuli.

Considering Comorbidities and Individual Differences in Testing a Gaming Behavioral Activation App for Perinatal Depression and Anxiety: Open Trial Pilot Intervention Study.

Background: There is increasing interest in the development of scalable digital mental health interventions for perinatal populations to increase accessibility. Mobile behavioral activation (BA) is efficacious for the treatment of perinatal depression; however, the effect of comorbid anxiety and depression (CAD) on symptom trajectories remains underexplored. This is important given that at least 10% of women in the perinatal period experience CAD.

In vivo base editing extends lifespan of a humanized mouse model of prion disease.

Prion disease is a fatal neurodegenerative disease caused by the misfolding of prion protein (PrP) encoded by the PRNP gene. While there is currently no cure for the disease, depleting PrP in the brain is an established strategy to prevent or stall templated misfolding of PrP. Here we developed in vivo cytosine and adenine base strategies delivered by adeno-associated viruses to permanently modify the PRNP locus to achieve PrP knockdown in the mouse brain.

Propensity score matched cohort study on magnesium supplementation and mortality in critically ill patients with HFpEF.

Heart failure with preserved ejection fraction (HFpEF) emerges as a singular subclass of heart failure, bereft of specific therapeutic options. Magnesium, an indispensable trace element, is essential to the preservation of cardiac integrity. However, the association between magnesium supplementation and mortality in HFpEF patients remains unclear.

Longitudinal Trends in Physical Activity Among Older Adults With and Without HIV in Uganda.

Introduction: Physical Activity (PA) and its links to frailty, quality of life (QoL), and other comorbidities in older Ugandans living with HIV remain under-explored.

Methods: We analyzed data from three annual assessments of older people living with HIV (PLWH) and age- and sex-similar people not living with HIV (PnLWH). We fitted linear generalized estimating equations (GEE) regression models to estimate the correlates of PA, including demographics, frailty, QoL, HIV, and other comorbidities.

Validation of the multi-day Boston remote assessment of neurocognitive health (BRANCH) among cognitively impaired & unimpaired older adults.

Background: The multi-day Boston Remote Assessment of Neurocognitive Health (BRANCH) is a remote, web-based assessment designed to capture the earliest cognitive changes in the preclinical stage of Alzheimer's disease (AD). It has been validated in unimpaired older adults, but as individuals progress on the AD continuum, assessments need to remain feasible and valid at different clinical stages. The focus of this study was to assess feasibility and validity of multi-day BRANCH in participants with and without cognitive impairment.

Synthesis of Sulfonated Peptides Using a Trifluoromethyltoluene-Protected Amino Acid.

A scalable, seven step synthesis is reported for a trifluoromethyl toluene protected sulfonated phenylalanine building block whose utility was demonstrated in the synthesis of four CXCR4-derived sulfonopeptides. When compared to a conventional trichloroethyl protected building block, overall yield was improved by up to 4-fold. We believe this building block will prove to be of significant value for the synthesis of a variety of peptide targets containing phenylalanine sulfonate, a bioisostere of tyrosine sulfate, enabling orthogonal protection strategies and improving synthetic efficiency and yield.

Estimating the ovarian cancer CA-125 preclinical detectable phase, in-vivo tumour doubling time, and window for detection in early stage: an exploratory analysis of UKCTOCS.

Background: The ovarian cancer (OC) preclinical detectable phase (PCDP), defined as the interval during which cancer is detectable prior to clinical diagnosis, remains poorly characterised. We report exploratory analyses from the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

Methods: In UKCTOCS between Apr-2001 and Sep-2005, 101,314 postmenopausal women were randomised to no screening (NS) and 50,625 to annual multimodal screening (MMS) (until Dec-2011) using serum CA-125 interpreted by the Risk of Ovarian Cancer Algorithm (ROCA).

A Kinetic Enhanced Tuck Jump Assessment Exposes Residual Biomechanical Deficits in Female Athletes 9 Months Post Anterior Cruciate Ligament Reconstruction.

Kember, LS, Riehm, CD, Schille, A, Slaton, JA, Myer, GD, and Lloyd, RS. Residual biomechanical deficits identified with the tuck jump assessment in female athletes 9 months after ACLR surgery. J Strength Cond Res 38(12): 2065-2073, 2024-Addressing biomechanical deficits in female athletes after anterior cruciate ligament reconstruction (ACLR) is crucial for safe return-to-play.

ROMP of Macromonomers Prepared by ROMP: Expanding Access to Complex, Functional Bottlebrush Polymers.

Graft-through ring-opening metathesis polymerization (ROMP) of norbornene-terminated macromonomers (MMs) prepared using various polymerization methods has been extensively used for the synthesis of bottlebrush (co)polymers, yet the potential of ROMP for the synthesis of MMs that can subsequently be polymerized by graft-through ROMP to produce new bottlebrush compositions remains untapped. Here, we report an efficient "ROMP-of-ROMP" method that involves the synthesis of norbornene-terminated poly(norbornene imide) (PNI)-based MMs that, following ROMP, provide new families of bottlebrush (co)polymers and "brush-on-brush" hierarchical architectures. In the bulk state, the organization of the PNI pendants drives bottlebrush backbone extension to enable rapid assembly of asymmetric lamellar morphologies with large asymmetry factors.

Spontaneous Anthropocentric Language Use in University Students' Explanations of Biological Concepts Varies by Topic and Predicts Misconception Agreement.

Previous research has shown that students employ intuitive thinking when understanding scientific concepts. Three types of intuitive thinking-essentialist, teleological, and anthropic thinking-are used in biology learning and can lead to misconceptions. However, it is unknown how commonly these types of intuitive thinking, or cognitive construals, are used spontaneously in students' explanations across biological concepts and whether this usage is related to endorsement of construal-consistent misconceptions.

A Kinetic Enhanced Tuck Jump Assessment Exposes Residual Biomechanical Deficits in Female Athletes 9 Months Post Anterior Cruciate Ligament Reconstruction.

Kember, LS, Riehm, CD, Schille, A, Slaton, JA, Myer, GD, and Lloyd, RS. Residual biomechanical deficits identified with the tuck jump assessment in female athletes 9 months after ACLR surgery. J Strength Cond Res XX(X): 000-000, 2024-Addressing biomechanical deficits in female athletes after anterior cruciate ligament reconstruction (ACLR) is crucial for safe return-to-play.

Exploring the neuroprotective benefits of phytochemicals extracted from indigenous edible fruits in Bangladesh.

The increasing incidence of neurodegenerative diseases (NDs) and the constraints of existing treatment methods have spurred a keen interest in investigating alternative therapies. Medicinal plants, renowned for their long-standing use in traditional medicine, offer a hopeful avenue for discovering new neuroprotective agents. This study emphasizes the potential neuroprotective characteristics of edible fruit plants in Bangladesh, specifically focusing on their traditional folk medicine uses for neurological disorders.

Mitigating matrix effects in oil and gas wastewater analysis: LC-MS/MS method for ethanolamines.

The high salinity and organic content in oil and gas wastewaters can cause ion suppression during liquid chromatography mass spectrometry (LC/MS) analysis, diminishing the sensitivity and accuracy of measurements in available methods. This suppression is severe for low molecular weight organic compounds such as ethanolamines (, monoethanolamine (MEA), diethanolamine (DEA), triethanolamine (TEA), -methyldiethanolamine (MDEA), and ,-ethyldiethanolamine (EDEA)). Here, we deployed solid phase extraction (SPE), mixed-mode LC, triple quadrupole MS with positive electrospray ionization (ESI), and a suite of stable isotope standards (, one per target compound) to correct for ion suppression by salts and organic matter, SPE losses, and instrument variability.

Advancing Principled Pharmacoepidemiologic Research to Support Regulatory and Healthcare Decision Making: The Era of Real-World Evidence.

A compilation of factors over the past decade-including the availability of increasingly large and rich healthcare datasets, advanced technologies to extract unstructured information from health records and digital sources, advancement of principled study design and analytic methods to emulate clinical trials, and frameworks to support transparent study conduct-has ushered in a new era of real-world evidence (RWE). This review article describes the evolution of the RWE era, including pharmacoepidemiologic methods designed to support causal inferences regarding treatment effects, the role of regulators and other health authorities in establishing distributed real-world data networks enabling analytics at scale, and the many global guidance documents on principled methods of producing RWE. This article also highlights the growing opportunity for RWE to support decision making by regulators, health technology assessment groups, clinicians, patients, and other stakeholders and provides examples of influential RWE studies.

Clinical criteria for limbic-predominant age-related TDP-43 encephalopathy.

Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course.

The Environmental and Public Health Benefits of Offshore Wind Power Deployment in China.

With the rapid decline in the levelized cost, offshore wind power offers a new option for the clean energy transition of the power sector in China's coastal areas. Here, we develop a power system capacity expansion and operation optimization model to simulate the penetration of offshore wind power in China and quantify the associated health effects. We find that offshore wind power has great potential in mitigating the negative impacts of existing coal-fired power emissions.

Ni-Catalyzed Enantioselective Desymmetrization: Development of Divergent Acyl and Decarbonylative Cross-Coupling Reactions.

Ni-catalyzed asymmetric reductive cross-coupling reactions provide rapid and modular access to enantioenriched building blocks from simple electrophile precursors. Reductive coupling reactions that can diverge through a common organometallic intermediate to two distinct families of enantioenriched products are particularly versatile but underdeveloped. Here, we describe the development of a bis(oxazoline) ligand that enables the desymmetrization of -anhydrides.

Disentangling emotional source memory: a mega-analysis on the effects of emotion on item-context binding in episodic long-term memory.

Introduction: It has long been known that highly arousing emotional single items are better recollected than low arousing neutral items. Despite the robustness of this memory advantage, emotional arousing events may not always promote the retrieval of source details (i.e.

Prognostic significance of immune reconstitution following CD19 CAR T-cell therapy for relapsed/refractory B-cell lymphoma.

Immune deficits after CD19 chimeric antigen receptor (CAR) T-cell therapy can be long-lasting, predisposing patients to infections and non-relapse mortality. In B-cell non-Hodgkin lymphoma (B-NHL), the prognostic impact of immune reconstitution (IR) remains ill-defined, and detailed cross-product comparisons have not been performed to date. In this retrospective observational study, we longitudinally characterized lymphocyte subsets and immunoglobulin levels in 105 B-NHL patients to assess patterns of immune recovery arising after CD19 CAR-T.