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Data on toxic effects are at large missing the prevailing understanding of the risks of industrial chemicals. Thyroid hormone (TH) system disruption includes interferences of the life cycle of the thyroid hormones and may occur in various organs. In the current study, high-throughput screening data available for 14 putative molecular initiating events of adverse outcome pathways, related to disruption of the TH system, were used to develop 19 in silico models for identification of potential thyroid hormone system-disrupting chemicals. The conformal prediction framework with the underlying Random Forest was used as a wrapper for the models allowing for setting the desired confidence level and controlling the error rate of predictions. The trained models were then applied to two different databases (i) an in-house database comprising xenobiotics identified in human blood and ii) currently used chemicals registered in the Swedish Product Register, which have been predicted to have a high exposure index to consumers. The application of these models showed that among currently used chemicals, fewer were overall predicted as active compared to chemicals identified in human blood. Chemicals of specific concern for TH disruption were identified from both databases based on their predicted activity.Infrared organic photodiodes have gained increasing attention due to their great application potentials in night vision, optical communication, and all-weather imaging. However, the commonly occurring high dark current and low detectivity impede infrared photodetectors from portable applications at room temperature. Herein, an efficient and generic doping compensation strategy is developed to improve the detectivity of infrared organic photodiodes. A series of n-type organic semiconductors is investigated, and it is found that doping compensation strategy not only reduces the trap density of states and dark currents, but also restrains the nonradiative recombination with improved charge transport and collection. As a result, an ultralow noise spectral density of 8 × 10-15 A Hz-1/2 as well as a high specific detectivity over 1013 Jones in 780-1070 nm is achieved at room temperature. More importantly, the high-performance infrared organic photodiodes can be successfully applied in high-pixel-density image arrays without patterning sensing layers. These findings provide important compensation design insights that will be crucial to further improve the performance of infrared organic photodiodes in the future.Biocatalytic carbene transfer from diazo compounds is a versatile strategy in asymmetric synthesis. However, the limited pool of stable diazo compounds constrains the variety of accessible products. To overcome this restriction, we have engineered variants of Aeropyrum pernix protoglobin (ApePgb) that use diazirines as carbene precursors. While the enhanced stability of diazirines relative to their diazo isomers enables access to a diverse array of carbenes, they have previously resisted catalytic activation. Our engineered ApePgb variants represent the first example of catalysts for selective carbene transfer from these species at room temperature. The structure of an ApePgb variant, determined by microcrystal electron diffraction (MicroED), reveals that evolution has enhanced access to the heme active site to facilitate this new-to-nature catalysis. Using readily prepared aryl diazirines as model substrates, we demonstrate the application of these highly stable carbene precursors in biocatalytic cyclopropanation, N-H insertion, and Si-H insertion reactions.We conducted indoor air quality (IAQ) measurements during a multiyear cookstove randomized control trial in two rural areas in northern and southern India. A total of 1205 days of kitchen PM2.5 were measured in control and intervention households during six ∼3 month long measurement periods across two study locations. Stoves used included traditional solid fuel (TSF), improved biomass, and liquefied petroleum gas (LPG) models. Intent-to-treat analysis indicates that the intervention reduced average 24 h PM2.5 and black carbon in only one of the two follow-up measurement periods in both areas, suggesting mixed effectiveness. Average PM2.5 levels were ∼50% lower in households with LPG (for exclusive LPG use >75% lower) than in those without LPG. PM2.5 was 66% lower in households making exclusive use of an improved chimney stove versus a traditional chimney stove and TSF-exclusive kitchens with a built-in chimney had ∼60% lower PM2.5 than those without a chimney, indicating that kitchen ventilation can be as important as the stove technology in improving IAQ. Diurnal trends in real-time PM2.5 indicate that kitchen chimneys were especially effective at reducing peak concentrations, which leads to decreases in daily PM2.5 in these households. Our data demonstrate a clear hierarchy of IAQ improvement in real world, "stove-stacking" households, driven by different stove technologies and kitchen characteristics.Hypertension (HTN) is a well-established risk factor for cardiovascular diseases (CVDs), including ischemic heart disease, stroke, heart failure, and atrial fibrillation. The prevalence of HTN, as well as mortality rates attributable to HTN, continue to increase, particularly in the United States and among Black populations. The risk of HTN involves a complex interaction of genetics and modifiable risk factors, including dietary patterns. In this regard, there is accumulating evidence that links dietary intake of red meat with a higher risk of poorly controlled blood pressure and HTN. However, research on this topic contains significant methodological limitations, which are described in the review. The report provided below also summarizes the available research reports, with an emphasis on processed red meat consumption and how different dietary patterns among certain populations may contribute to HTN-related health disparities. Finally, this review outlines potential mechanisms and provides recommendations for providers to counsel patients with evidence-based nutritional approaches regarding red meat and the risk of HTN, as well as CVD morbidity and mortality.
Hepatocellular carcinoma (HCC) is a rare cancer in children, with various histologic subtypes and a paucity of data to guide clinical management and predict prognosis.

A multi-institutional review of children with hepatocellular neoplasms was performed, including demographic, staging, treatment, and outcomes data. Patients were categorized as having conventional HCC (cHCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), and hepatoblastoma with HCC features (HB-HCC). Univariate and multivariate analyses identified predictors of mortality and relapse.

In total, 262 children were identified; and an institutional histologic review revealed 110 cHCCs (42%; 69 normal background liver, 34 inflammatory/cirrhotic, 7 unknown), 119 FLCs (45%), and 33 HB-HCCs (12%). The authors observed notable differences in presentation and behavior among tumor subtypes, including increased lymph node involvement in FLC and higher stage in cHCC. Factors associated with mortality included cHCC (hazard rati different subtypes of hepatocellular carcinoma and identifies key differences between subtypes. This information is pivotal in improving understanding of these rare cancers and may be used to improve clinical management and subsequent outcome in children with these rare malignancies.
This is the largest reported granular data set on children with hepatocellular carcinoma. The study evaluates different subtypes of hepatocellular carcinoma and identifies key differences between subtypes. This information is pivotal in improving understanding of these rare cancers and may be used to improve clinical management and subsequent outcome in children with these rare malignancies.In this study, four tobacco transformants overexpressing the inorganic carbon transporter B gene (ictB) were screened for photosynthetic performance relative to the wild type (WT) in field-based conditions. MS1943 in vitro The WT and transgenic tobacco plants were evaluated for photosynthetic performance to determine the maximum rate of carboxylation (Vc, max), maximum rate of electron transport (Jmax), the photosynthetic compensation point (Γ*), quantum yield of PSII (ΦPSII), and mesophyll conductance (gm). Additionally, all plants were harvested to compare differences in above-ground biomass. Overall, transformants did not perform better than the WT on photosynthesis-, biomass-, and leaf composition-related traits. This is in contrast to previous studies that have suggested significant increases in photosynthesis and yield with the overexpression of ictB, although not widely evaluated under field conditions. These findings suggest that the benefit of ictB is not universal and may only be seen under certain growth conditions. While there is certainly still potential benefit to utilizing ictB in the future, further effort must be concentrated on understanding the underlying function of the gene and in which environmental conditions it offers the greatest benefit to crop performance. As it stands at present, it is possible that ictB overexpression may be largely favorable in controlled environments, such as greenhouses.The transcription factor Nrf2 plays a crucial role in the anti-oxidative stress response, protection of DNA from injury and DNA repair mechanisms. Nrf2 activity reduces cancer initiation, but how Nrf2 affects whole-genome alterations upon carcinogenic stimulus remains unexplored. Although recent genome-wide analysis using next-generation sequencing revealed landscapes of nucleotide mutations and copy number alterations in various human cancers, genomic changes in murine cancer models have not been thoroughly examined. We elucidated the relationship between Nrf2 expression levels and whole exon mutation patterns using an ethyl-carbamate (urethane)-induced lung carcinogenesis model employing Nrf2-deficient and Keap1-kd mice, the latter of which express high levels of Nrf2. Exome analysis demonstrated that single nucleotide and trinucleotide mutation patterns and the Kras mutational signature differed significantly and were dependent on the expression level of Nrf2. The Nrf2-deficient tumors exhibited fewer copy number alterations relative to the Nrf2-wt and Keap1-kd tumors. The observed trend in genomic alterations likely prevented the Nrf2-deficient tumors from progressing into malignancy. For the first time, we present whole-exome sequencing results for chemically-induced lung tumors in the Nrf2 gain or loss of function mouse models. Our results demonstrate that different Nrf2 expression levels lead to distinct gene mutation patterns that underly different oncogenic mechanisms in each tumor genotype.The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.
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