Guanidyl-rich highly branched poly(β-amino ester)s for the delivery of dual CRISPR ribonucleoprotein for efficient large DNA fragment deletion.

Gene editing technologies, particularly clustered regularly interspersed short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins, have revolutionized the ability to modify gene sequences in living cells for therapeutic purposes. Delivery of CRISPR/Cas ribonucleoprotein (RNP) is preferred over its DNA and RNA formats in terms of gene editing effectiveness and low risk of off-target events. However, the intracellular delivery of RNP poses significant challenges and necessitates the development of non-viral vectors.

Physical Activity and Life Expectancy Free of Cancer: Prospective Evidence From the UK Biobank Study.

Background: Life expectancy free of cancer (LEFC) is a novel measure that considers both morbidity and mortality and could be a useful metric for disease surveillance and risk communication. We aimed to examine the association between physical activity and LEFC in British adults.

Methods: This was a prospective cohort study of 292,559 apparently healthy UK Biobank participants (mean [SD] age, 56.

WBP1L, a transmembrane adaptor protein involved in the regulation of hematopoiesis, is controlled by CRL1 ubiquitin ligases.

WBP1L is a broadly expressed transmembrane adaptor protein involved in regulating hematopoietic stem cell function and T cell development. It interacts with NEDD4-family E3 ubiquitin ligases and regulates important chemokine receptor CXCR4. Using tandem affinity purification coupled with mass spectrometry, we identified novel WBP1L interactions with the IFNγ receptor and the Cullin-RING ubiquitin ligases CRL1.

Double Povidone-Iodine 5% Preparation Before Cataract Surgery for Endophthalmitis Prevention.

Objective: To compare endophthalmitis rates after cataract extraction in patients with different preoperative prophylaxis: double povidone-iodine preparation with topical antibiotics versus a control group.

Methods: All cases of postoperative endophthalmitis over the last 17 years were reviewed. Incidence rates of endophthalmitis for all cataract surgeries (current procedural terminology codes 66982 and 66984) performed by 26 surgeons were calculated.

Future Directions in the Management of Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.

Context: The traditional management of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is difficult and often suboptimal.

Objective: To review improvements in the diagnosis and management of 21OHD.

Design: Literature review, synthesis, and authors' experience.

Safety of Human USH1C Transgene Expression Following Subretinal Injection in Wild-Type Pigs.

Purpose: This study aimed to evaluate early-phase safety of subretinal application of AAVanc80.CAG.USH1Ca1 (OT_USH_101) in wild-type (WT) pigs, examining the effects of a vehicle control, low dose, and high dose.

Immunohistochemical analysis of 147 cases of low-grade endometrial stromal sarcoma: refining the immunohistochemical profile of LG-ESS on a large, molecularly confirmed series.

Low-grade endometrial stromal sarcoma (LG-ESS) can present diagnostic challenges, due to its overlapping morphological features with other uterine mesenchymal tumors. Misdiagnosis rates remain significant, and immunohistochemical data for LG-ESS are limited to small series and inconsistent antibody panels. This study aimed to refine the IHC profile of LG-ESS by analyzing a large, molecularly confirmed series of 147 cases using a panel of 24 antibodies, including newer markers like transgelin and smoothelin.

Geometrically constrained cytoskeletal reorganisation modulates DNA nanostructures uptake.

DNA nanostructures (DNs) have gained popularity in various biomedical applications due to their unique properties, including structural programmability, ease of synthesis and functionalization, and low cytotoxicity. Effective utilization of DNs in biomedical applications requires a fundamental understanding of their interactions with living cells and the mechanics of cellular uptake. Current knowledge primarily focuses on how the physicochemical properties of DNs, such as mass, shape, size, and surface functionalization, affect uptake efficacy.

AI-Enhanced Understanding of Retention Interactions in Supercritical Fluid Chromatography: Neural Network Insights into Retention on Selected Non-Polar Stationary Phases.

The retention behavior in supercritical fluid chromatography (SFC) remains a complex and poorly understood phenomenon despite the development of various models to explain retention mechanisms. This study aims to deepen the understanding of retention by investigating three distinct stationary phases: high-strength silica octadecyl (HSS C18 SB), charged surface hybrid pentafluorophenyl (CSH PFP), and porous graphitic carbon (PGC) as a nonsilica-based phase. Three mobile phase compositions, i.

Antimicrobial and Antiproliferative Properties of 2-Phenyl-N-(Pyridin-2-yl)acetamides.

Infectious diseases, including bacterial, fungal, and viral, have once again gained urgency in the drug development pipeline after the recent COVID-19 pandemic. Tuberculosis (TB) is an old infectious disease for which eradication has not yet been successful. Novel agents are required to have potential activity against both drug-sensitive and drug-resistant strains of Mycobacterium tuberculosis (Mtb), the causative agent of TB.

A Multicentre Evaluation of a Ceramide-Containing Hydrating Cream-to-Foam Cleanser and Facial Moisturizing Lotion for Improving Topical Treatment Tolerability in Facial Acne.

Acne vulgaris (AV) is a common skin condition that can cause substantial psychosocial impact. Treatments of AV target clearing and prevention of lesions and reducing scarring and dyspigmentation. Numerous medications are used to target one or more of the pathogenetic factors contributing to AV.

An immunosenescent CD8+ T cell subset in patients with axial Spondyloarthritis and Psoriatic Arthritis links spontaneous motility to telomere shortening and dysfunction.

Objective: A pathogenetic role of CD8+ T lymphocytes in radiographic axial spondyloarthritis (r-axSpA) and other spondyloarthritis (SpA) is sustained by genome-wide association studies (GWAS) and by the expansion of public T cell clonotypes in the target tissues. This study investigates the migration of CD8+ T cells, along with their phenotype and functions in patients with r-axSpA and psoriatic arthritis (PsA).

Methods: Peripheral blood CD8+ and CD4+ T cells were isolated from r-axSpA (n= 128), PsA (n= 60) and rheumatoid arthritis (RA, n= 74) patients and healthy donors (HD, n= 79).

The pattern and burden of non-communicable diseases in armed conflict-exposed populations in Northeastern Nigeria.

Background: The risk of non-communicable diseases (NCDs) in conflict and post-conflict settings in Northeastern Nigeria has not been evaluated to date. As this region undergoes recovery, understanding the prevalence of NCDs, such as hypertension, diabetes, depression, and obesity, and the associated behavioral coping mechanisms, is crucial for developing tailored healthcare solutions. Therefore, this study aimed to assess the impact of conflict on the prevalence of NCDs in conflict-exposed areas in Northeastern Nigeria compared with non-conflict regions.

Direct detection of phycocyanin in sediments by hyperspectral imaging.

Unlabelled: Cyanobacteria are ubiquitous aquatic organisms with a remarkable evolutionary history reaching as far as 1.9 Ga. They play a vital role in ecosystems yet also raise concerns due to their association with harmful algal blooms.

Dynamic retinal vessel analysis: flickering a light into the brain.

Introduction: Growing aging populations pose new challenges to public health as the number of people living with dementia grows in tandem. To alleviate the burden of dementia, prodromal signs of cognitive impairment must be recognized and risk factors reduced. In this context, non-invasive techniques may be used to identify early changes and monitor disease progression.

Integrating microfluidics, hydrogels, and 3D bioprinting for personalized vessel-on-a-chip platforms.

Thrombosis, a major cause of morbidity and mortality worldwide, presents a complex challenge in cardiovascular medicine due to the intricacy of clotting mechanisms in living organisms. Traditional research approaches, including clinical studies and animal models, often yield conflicting results due to the inability to control variables in these complex systems, highlighting the need for more precise investigative tools. This review explores the evolution of thrombosis models, from conventional polydimethylsiloxane (PDMS)-based microfluidic devices to advanced hydrogel-based systems and cutting-edge 3D bioprinted vascular constructs.

A practical guide for choosing an optimal spatial transcriptomics technology from seven major commercially available options.

Spatial transcriptomics technology enables the mapping of gene expression within tissues, allowing researchers to visualize the spatial distribution of RNA molecules and gain insights into cellular organization, interactions, and functions in their native environments. A variety of spatial technologies are now commercially available, each offering distinct technical parameters such as cellular resolution, detection sensitivity, gene coverage, and throughput. This wide range of options can make it challenges or create confusion for researchers to select the most appropriate platform for their specific research objectives.

Implementation of a Faith Community Nursing Transition of Care Program in the USA: A Propensity Score Matching Analysis.

Faith community nursing (FCN) is a specialty nursing practice that integrates spiritual and religious practices into patient care. This study aimed to quantitatively assess the impact of the standardized FCN transition of care (TOC) program on the rate of hospital readmission and length of stay (LOS) through propensity score matching and difference-in-differences methods. Compared with those in the non-FCN group (n = 409), patients in the FCN group (n = 66) had a reduced likelihood of hospital readmission at 30, 90, and 180 days after discharge (by 8.

Trust in scientists and their role in society across 68 countries.

Science is crucial for evidence-based decision-making. Public trust in scientists can help decision makers act on the basis of the best available evidence, especially during crises. However, in recent years the epistemic authority of science has been challenged, causing concerns about low public trust in scientists.

Machine learning validation of the AVAS classification compared to ultrasound mapping in a multicentre study.

The Arteriovenous Access Stage (AVAS) classification simplifies information about suitability of vessels for vascular access (VA). It's been previously validated in a clinical study. Here, AVAS performance was tested against multiple ultrasound mapping measurements using machine learning.

Perceptions of science, science communication, and climate change attitudes in 68 countries - the TISP dataset.

Science is integral to society because it can inform individual, government, corporate, and civil society decision-making on issues such as public health, new technologies or climate change. Yet, public distrust and populist sentiment challenge the relationship between science and society. To help researchers analyse the science-society nexus across different geographical and cultural contexts, we undertook a cross-sectional population survey resulting in a dataset of 71,922 participants in 68 countries.

Elevated serum neurofilament light chain levels in patients with neuropsychiatric systemic lupus erythematosus: a cross-sectional study.

Background: The neurofilament light chain (NfL) in cerebrospinal fluid (CSF) and serum as a marker of neuronal damage may be a potential biomarker of neuropsychiatric involvement in SLE (NPSLE).

Methods: 80 patients with SLE were included.We obtained paired serum and CSF samples from 48 patients (NPSLE n=32, non-NPSLE n=16) and 31 controls.

Outcomes of extremely preterm infants who participated in a randomised trial of dopamine for treatment of hypotension (the HIP trial) at 2 years corrected age.

Objective: To determine survival and neurodevelopmental outcomes in the Hypotension in Preterm (HIP) trial.

Design: Prospective follow-up of infants enrolled in randomised controlled trial.

Participants: 58 infants born before 28 weeks of gestation with low mean arterial blood pressure.