Uptake and in-vitro bioaccessibility of toxic metals in cocoa beans: Human health risks.

Cocoa-growing areas in Ghana have experienced a rise in mining activities affecting cocoa cultivation and increased concentrations of potentially toxic metals in the soil, which can accumulate in cocoa beans. This study evaluated potential toxic metal contamination in cocoa beans and soils from cocoa farms in mining and non-mining areas in Ghana. We used X-ray fluorescence and an ICP-MS to determine metal concentrations, and a Zeeman mercury analyzer to determine mercury.

Epigenetics and ultraviolet radiation: Implications for skin ageing and carcinogenesis.

Recent published data have highlighted the importance of epigenetics in the response of the skin to recreational and therapeutic ultraviolet radiation (UVR) exposure. 'Epi'-from the Greek επί, meaning over, outside of or around-relates to the chemical modifications that occur on top of the DNA sequence (for example, DNA methylation) and its associated proteins (e.g.

IRF5 Controls Plasma Cell Generation and Antibody Production via Distinct Mechanisms Depending on the Antigenic Trigger.

Elevated levels of serum autoantibodies are a hallmark of systemic lupus erythematosus (SLE) and are produced by plasma cells in response to a variety of antigenic triggers. In SLE, the triggers are complex and may include both T cell-dependent/-independent and TLR-dependent/-independent mechanisms of immune activation, which ultimately contributes to the significant immune dysregulation seen in patients at the level of cytokine production and cellular activation (B cells, T cells, dendritic cells, neutrophils and macrophages). Interferon regulatory factor 5 (IRF5) has been identified as an autoimmune susceptibility gene and polymorphisms in IRF5 associate with altered expression and hyper-activation in distinct SLE immune cell subsets.

Cannabis and the overdose crisis among US adolescents.

Background And Objectives: Since 2019, the drug overdose death rate among adolescents 14-18 years of age in the United States more than doubled. That cannabis legalization may have contributed to this tragedy is investigated by comparing the death rate in jurisdictions that have legalized medicinal or both medicinal and recreational use with those that have not.

Methods: Unintentional drug overdose death data for each state and District of Columbia (jurisdictions) were obtained from CDC WONDER and separately evaluated according to the jurisdiction legalization implementation of cannabis: recreational legalization, medicinal legalization but not recreational legalization, and nonlegalization.

Germline BRCA1/2 status and chemotherapy response score in high-grade serous ovarian cancer.

Background: High-grade serous ovarian cancer (HGSOC) can be treated with platinum-based neoadjuvant chemotherapy (NACT) and delayed primary surgery (DPS). Histopathological response to NACT can be assessed using Böhm's chemotherapy response score (CRS). We investigated whether germline BRCA1/2 (gBRCA1/2) genotype associated with omental CRS phenotype.

Unsupervised machine learning identifies distinct phenotypes in cardiac complications of pediatric patients treated with anthracyclines.

Background: Anthracyclines are essential in pediatric cancer treatment, but patients are at risk cancer therapy-related cardiac dysfunction (CTRCD). Standardized definitions by the International Cardio-Oncology Society (IC-OS) aim to enhance precision in risk assessment.

Objectives: Categorize distinct phenotypes among pediatric patients undergoing anthracycline chemotherapy using unsupervised machine learning.

Generating suspension-adapted human mesenchymal stromal cells (S-hMSCs) for the scalable manufacture of extracellular vesicles.

Backgroud: Human mesenchymal stromal cells (hMSCs) are a naturally adherent cell type and one of the most studied cellular agents used in cell therapy over the last 20 years. Their mechanism of action has been primarily associated with paracrine signaling, which has contributed to an increase in the number of studies focused on hMSC-related extracellular vesicles (EVs).

Methods: In this study, we demonstrate for the first time that human telomerase reverse transcriptase (hTERT) immortalized hMSCs can be adapted to suspension culture, eliminating the need for microcarriers or other matrixes to support cell growth.

IRF5 mediates adaptive immunity via altered glutamine metabolism, mTORC1 signaling and post-transcriptional regulation following T cell receptor activation.

Although dynamic alterations in transcriptional, translational, and metabolic programs have been described in T cells, the factors and pathways guiding these molecular shifts are poorly understood, with recent studies revealing a disassociation between transcriptional responses and protein expression following T cell receptor (TCR) stimulation. Previous studies identified interferon regulatory factor 5 (IRF5) in the transcriptional regulation of cytokines, chemotactic molecules and T effector transcription factors following TCR signaling. In this study, we identified T cell intrinsic IRF5 regulation of mTORC1 activity as a key modulator of CD40L protein expression.

Universalized and robust length separation of carbon and boron nitride nanotubes with improved polymer depletion-based fractionation.

Partitioning nanoparticles by shape and dimension is paramount for advancing nanomaterial standardization, fundamental colloidal investigations, and technologies such as biosensing and digital electronics. Length-separation methods for single-walled carbon nanotubes (SWCNTs) have historically incurred trade-offs in precision and mass throughput, and boron nitride nanotubes (BNNTs) are a rapidly emerging material analogue. We extend and detail a polymer precipitation-based method to fractionate populations of either nanotube type at significant mass scale for four distinct nanotube sources of increasing average diameter (0.

Predicting Hydrocarbon Strain Energy via a Group Equivalent Machine Learning Approach.

Strain energy is a fundamental measure of the steric and configurational properties of organic molecules. The ability to estimate strain energy through quantum chemical simulations requires at minimum the knowledge of an initial set of nuclear coordinates. In general, such knowledge is not categorically known when screening or generating large numbers of molecule candidates in the context of molecular design.

Intrinsic PARG inhibitor sensitivity is mimicked by haploinsufficiency and rescued by nucleoside supplementation.

A subset of cancer cells are intrinsically sensitive to inhibitors targeting PARG, the poly(ADP-ribose) glycohydrolase that degrades PAR chains. Sensitivity is accompanied by persistent DNA replication stress, and can be induced by inhibition of , a replisome accelerator. However, the nature of the vulnerability responsible for intrinsic sensitivity remains undetermined.

IRF5 suppresses metastasis through the regulation of tumor-derived extracellular vesicles and pre-metastatic niche formation.

Metastasis is driven by extensive cooperation between a tumor and its microenvironment, resulting in the adaptation of molecular mechanisms that evade the immune system and enable pre-metastatic niche (PMN) formation. Little is known of the tumor-intrinsic factors that regulate these mechanisms. Here we show that expression of the transcription factor interferon regulatory factor 5 (IRF5) in osteosarcoma (OS) and breast carcinoma (BC) clinically correlates with prolonged survival and decreased secretion of tumor-derived extracellular vesicles (t-dEVs).

Impaired Myocardial Work in Children with Hypertrophic Cardiomyopathy and Left Ventricular Fibrosis on Cardiac Magnetic Resonance Imaging.

Echocardiography is pivotal for diagnosis and monitoring of hypertrophic cardiomyopathy (HCM) and can evaluate myocardial function using myocardial work (MW) calculations. Echocardiography is often supplemented by cardiovascular magnetic resonance (CMR) imaging, which can detect myocardial fibrosis using late gadolinium enhancement (LGE). We sought to study the relationship between baseline LGE and MW at baseline and during follow-up in pediatric HCM patients.

Time course of hypertension and myocardial dysfunction following anthracycline chemotherapy in pediatric patients.

Background: Anthracyclines are associated with cardiac dysfunction. Little is known about the interplay of pre-existing hypertension and treatment response. We aimed to investigate the relationship between hypertension and the development of cancer therapy-related cardiac dysfunction (CTRCD) in pediatric patients treated with anthracycline chemotherapy.

MSA: scalable DNA methylation screening BeadChip for high-throughput trait association studies.

The Infinium DNA Methylation BeadChips have significantly contributed to population-scale epigenetics research by enabling epigenome-wide trait association discoveries. Here, we design, describe, and experimentally verify a new iteration of this technology, the Methylation Screening Array (MSA), to focus on human trait screening and discovery. This array utilizes extensive data from previous Infinium platform-based epigenome-wide association studies (EWAS).

Remodeling of skeletal muscle myosin metabolic states in hibernating mammals.

Hibernation is a period of metabolic suppression utilized by many small and large mammal species to survive during winter periods. As the underlying cellular and molecular mechanisms remain incompletely understood, our study aimed to determine whether skeletal muscle myosin and its metabolic efficiency undergo alterations during hibernation to optimize energy utilization. We isolated muscle fibers from small hibernators, and and larger hibernators, and .

United States marijuana legalization and opioid mortality trends before and during the first year of the COVID-19 pandemic.

Background: To determine if marijuana legalization was associated with reduced opioid mortality.

Study Design: The United States (US) opioid mortality trend during the 2010-2019 decade was compared in states and District of Columbia (jurisdictions) that had implemented marijuana legalization with states that had not. Acceleration of opioid mortality during 2020, the first year of the coronavirus disease 2019 (COVID-19) pandemic, was also compared in recreational and medicinal-only legalizing jurisdictions.

Evolution of the clinical-stage hyperactive TcBuster transposase as a platform for robust non-viral production of adoptive cellular therapies.

Cellular therapies for the treatment of human diseases, such as chimeric antigen receptor (CAR) T and natural killer (NK) cells have shown remarkable clinical efficacy in treating hematological malignancies; however, current methods mainly utilize viral vectors that are limited by their cargo size capacities, high cost, and long timelines for production of clinical reagent. Delivery of genetic cargo via DNA transposon engineering is a more timely and cost-effective approach, yet has been held back by less efficient integration rates. Here, we report the development of a novel hyperactive TcBuster (TcB-M) transposase engineered through structure-guided and in vitro evolution approaches that achieves high-efficiency integration of large, multicistronic CAR-expression cassettes in primary human cells.

Potential for a minor pine bark beetle pest, Dendroctonus terebrans (Coleoptera: Curculionidae: Scolytinae), to mediate host location by a major pine killer, Dendroctonus frontalis.

The southern pine beetle, Dendroctonus frontalis Zimmermann is an important mortality agent of Pinus in the eastern United States of America where it commonly shares hosts with the black turpentine beetle, Dendroctonus terebrans (Olivier), which infrequently kills trees. Unlike D. frontalis, which must kill its hosts to become established in the bark and reproduce, D.

The Royal College of Ophthalmologists' National ophthalmology database study of cataract surgery: Report 14, cohort analysis - the impact of CapsuleGuard® utilisation on cataract surgery posterior capsule rupture rates.

Background/objectives: The aim of this study was to investigate whether the use of the silicone tipped irrigation/aspiration (I/A) handpiece CapsuleGuard® (Bausch + Lomb, Laval, Canada) reduced rates of posterior capsule rupture (PCR) during cataract surgery.

Methods: Royal College of Ophthalmologists' National Ophthalmology Database (NOD) Cataract Audit data from 01/04/2010 and 31/03/2021 and Bausch + Lomb sales figures were combined to identify centres participating in national cataract audit who have routinely adopted the silicone tipped I/A handpiece, CapsuleGuard®. Data were included only from centres with eligible cataract operations recorded on the NOD both before and after adopting CapsuleGuard®.

Specialized replication mechanisms maintain genome stability at human centromeres.

The high incidence of whole-arm chromosome aneuploidy and translocations in tumors suggests instability of centromeres, unique loci built on repetitive sequences and essential for chromosome separation. The causes behind this fragility and the mechanisms preserving centromere integrity remain elusive. We show that replication stress, hallmark of pre-cancerous lesions, promotes centromeric breakage in mitosis, due to spindle forces and endonuclease activities.

Pelagic Sargassum in the Gulf of Mexico driven by ocean currents and eddies.

Pelagic Sargassum in the Gulf of Mexico (GoM) plays an important role in ocean biology and ecology, yet our knowledge of its origins and transport pathways is limited. Here, using satellite observations of Sargassum areal density and ocean surface currents between 2000 and 2023, we show that large amounts of Sargassum in the GoM can either originate from the northwestern GoM or be a result of physical transport from the northwestern Caribbean Sea, both with specific transport pathways. Sargassum of the northwestern GoM can be transported to the eastern GoM by ocean currents and eddies, eventually entering the Sargasso Sea.

ATI-1777, a Topical Jak1/3 Inhibitor, May Benefit Atopic Dermatitis without Systemic Drug Exposure: Results from Preclinical Development and Phase 2a Randomized Control Study ATI-1777-AD-201.

Introduction: Atopic dermatitis, a chronic, pruritic skin disease, affects 10-30% of children and up to 14% of adults in developed countries. ATI-1777, a potent and selective Jak1/3 inhibitor, was designed with multiple sites of metabolism to deliver local efficacy in the skin and limit systemic exposure. In preclinical studies, ATI-1777 selectively inhibited Jak1/3 with limited systemic exposure and without any adverse effects.