Design and in vitro anticancer assessment of a click chemistry-derived dinuclear copper artificial metallo-nuclease.

Copper compounds with artificial metallo-nuclease (AMN) activity are mechanistically unique compared to established metallodrugs. Here, we describe the development of a new dinuclear copper AMN, Cu2-BPL-C6 (BPL-C6 = bis-1,10-phenanthroline-carbon-6), prepared using click chemistry that demonstrates site-specific DNA recognition with low micromolar cleavage activity. The BPL-C6 ligand was designed to force two redox-active copper centres-central for enhancing AMN activity-to bind DNA, via two phenanthroline ligands separated by an aliphatic linker.

Navigating new threats: Prey naïveté in native mammals.

Invasive predators pose a substantial threat to global biodiversity. Native prey species frequently exhibit naïveté to the cues of invasive predators, and this phenomenon may contribute to the disproportionate impact of invasive predators on prey populations. However, not all species exhibit naïveté, which has led to the generation of many hypotheses to explain patterns in prey responses.

The Future Hospital in Global Health Systems: The Future Hospital as an Entity.

Health care is changing rapidly. Hospitals are, and will remain, an essential setting to deliver it. We discuss how to maximise the benefits of hospitals in the future in different geographic and health system settings, highlighting a series of cross-cutting issues.

Predicting sinonasal inverted papilloma attachment using machine learning: Current lessons and future directions.

Background: Hyperostosis is a common radiographic feature of inverted papilloma (IP) tumor origin on computed tomography (CT). Herein, we developed a machine learning (ML) model capable of analyzing CT images and identifying IP attachment sites.

Methods: A retrospective review of patients treated for IP at our institution was performed.

US mortality trends from alcohol-associated hepatitis by sex, age, race, and ethnicity, 1999-2020.

Background: Alcohol-associated hepatitis (AH) is a subtype of alcohol-associated liver disease (ALD) resulting in severe acute liver inflammation. This study aims to examine longitudinal trends in mortality from AH in the United States (US) from 1999 to 2020, stratifying the data by sex, age, and racial/ethnic groups.

Methods: We performed a cross-sectional study using data from the US Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (WONDER) to determine annual AH-related mortality rates (MR) in adults ≥21 years between 1999 and 2020.

Spatial proteomic differences in chronic traumatic encephalopathy, Alzheimer's disease, and primary age-related tauopathy hippocampi.

Introduction: Alzheimer's disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)-immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (Aβ) deposition.

Methods: We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)-bearing and non-NFT-bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy-confirmed AD (n = 8), PART (n = 7), and CTE (n = 5).

Results: There were numerous subregion-specific differences related to Aβ processing, autophagy/proteostasis, inflammation, gliosis, oxidative stress, neuronal/synaptic integrity, and p-tau epitopes among these different disorders.

Factors Associated with Pediatric Drowning-Associated Lung Injury.

Objective: To identify risk factors for clinically-important drowning-associated lung injury (ciDALI) in children.

Study Design: This was a cross-sectional study of children (0 through18 years) who presented to 32 pediatric emergency departments (EDs) from 2010 through 2017. We reviewed demographics, comorbidities, prehospital data, chest radiographs reports, and ED course from emergency medical services, medical, and fatality records.

Pathways to Hypertension Control: Unfinished Journeys of Low-Income Individuals in Malaysia and the Philippines.

Background: Reducing inequities in hypertension control among those affected in low- and middle-income countries requires person-centred health system responses based on a contextualised understanding of the choices and care pathways taken by those who rely on the services provided, particularly those from poor and marginalised communities. We examine patterns of care seeking and pathways followed by individuals with hypertension from low-income households in the Philippines and Malaysia. This study aims to fill a significant gap in the literature by analysing the stages at which individuals make decisions that may affect the successful control of their blood pressure.

Improving colonoscopy quality in the national VA healthcare system.

Background: Colorectal cancer (CRC) prevention is a Veterans Affairs (VA) priority. Colonoscopy quality, especially adenoma detection rate (ADR), is critical for effective screening. Our research indicates considerable variation in ADR among VA providers.

Qualitative Findings from a Pilot Trial of Mindfulness for Low Sexual Desire in Midlife and Older Women.

Low libido is a common and potentially distressing problem among midlife and older women. We recently reported results from a pilot randomized controlled trial of a mindfulness intervention for midlife and older cisgender women with low libido; the purpose of this qualitative investigation is to illustrate women's experiences with being recruited for, enrolling in, and participating in the trial. We conducted individual interviews with a subset of trial participants, some of whom attended a group-based mindfulness intervention and some attended an educational control group (N = 25).

Consensus Preconception Educational Domains for People With Mobility Disabilities: A Delphi Study.

Background: Preconception health education is critical to improve pregnancy and neonatal outcomes, but people with mobility disabilities have specific, often unique issues related to preparing for pregnancy. This study sought to develop consensus-based domains for a preconception education curriculum for people with mobility disabilities.

Methods: We used a mixed methods approach, including a literature review and a Delphi method to develop consensus.

Chromosome X-wide common variant association study in autism spectrum disorder.

Autism spectrum disorder (ASD) displays a notable male bias in prevalence. Research into rare (<0.1) genetic variants on the X chromosome has implicated over 20 genes in ASD pathogenesis, such as MECP2, DDX3X, and DMD.

Case Series of Traumatic Peripheral Nerve Injuries in Pediatric Patients Treated with Allograft Repair.

Purpose: In the adult literature, allograft reconstruction of gapped peripheral nerve injuries has gained popularity over autologous nerve grafting. Allografts have demonstrated similar recovery while eliminating donor site morbidity. There is no well-defined incidence or treatment of such injuries in children.

BRCA2 germline mutation carrier with five malignancies: a case report.

Background: BRCA2 germline mutations are known to predispose carriers to various cancer types, including breast, ovarian, pancreatic and prostate cancer. An association with melanoma has also been reported. However, the full tumour spectrum associated with BRCA2 mutations, particularly in patients with other concurrent pathogenetic mutations, is unexplored.

Chronic conditions among transgender Medicare beneficiaries: Variation by race, ethnicity, and Medicaid dual-enrollment.

Background: Transgender and gender diverse (TGD) adults experience disability at twice the rate of cisgender (non-TGD) adults in the US. TGD people of color and low-income TGD people experience intersecting discrimination that may compound chronic conditions and disability. To our knowledge, no research has focused on chronic conditions among TGD Medicare beneficiaries with disabilities.

Delphi-Based Global Consensus on Adopting Endothelial Keratoplasty: An Endothelial Keratoplasty Learners Group Initiative.

Purpose: To identify areas of consensus among experts on the performance of endothelial keratoplasty by using a modified Delphi approach, to help create a framework for novice surgeons to adopt these procedures.

Methods: Thirty-one international experts in endothelial keratoplasty participated. Two rounds of electronic survey were followed by a hybrid, virtual meeting.

Correction: Ádány et al. Discrepancies between the Spatial Distribution of Cancer Incidence and Mortality as an Indicator of Unmet Needs in Cancer Prevention and/or Treatment in Hungary. 2024, , 2917.

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Independent SAGE as an example of effective public dialogue on scientific research.

The World Health Organization declared COVID-19 to be a public health emergency of international concern on 30 January 2020 and then a pandemic on 11 March 2020. In early 2020, a group of UK scientists volunteered to provide the public with up-to-date and transparent scientific information. The group formed the Independent Scientific Advisory Group for Emergencies (Independent SAGE) and provided live weekly briefings to the public via YouTube.

Further delineation of the SCAF4-associated neurodevelopmental disorder.

While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4 variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder.

Safety, tolerability, pharmacokinetics, and neutralisation activities of the anti-HIV-1 monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS in adults without HIV in the USA (HVTN 136/HPTN 092): a first-in-human, open-label, randomised controlled phase 1 trial.

Background: Multiple broadly neutralising monoclonal antibodies (mAbs) are in development for HIV-1 prevention. The aim of this trial was to test the PGT121.414.

Neurodegeneration in the cortical sulcus is a feature of chronic traumatic encephalopathy and associated with repetitive head impacts.

Neurodegeneration is a seminal feature of many neurological disorders. Chronic traumatic encephalopathy (CTE) is caused by repetitive head impacts (RHI) and is characterized by sulcal tau pathology. However, quantitative assessments of regional neurodegeneration in CTE have not been described.