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The financial shackling of historically Black universities in the United States
Methanol transfer supports metabolic syntrophy between bacteria and archaea
Promoting language and literacy through shared book reading in the NICU: A scoping review
Background Infants in the neonatal intensive care unit (NICU) are at a heightened risk for language and literacy delays and disorders. Despite the well-established empirical support for early shared reading, the available evidence to date has been scant, revealing mixed results. This study sought to characterize current research on shared reading in the NICU using a scoping review methodology. Methods Studies were eligible for inclusion if they were peer-reviewed, written in the English language, focused on human infants in the NICU, and published between January 1, 2003, and December 31, 2023. No population age range was applied, and quantitative, qualitative, or mixed methods designs were considered. Database searches yielded 338 articles with only eight articles meeting eligibility criteria for inclusion. Conclusion In spite of a modest number of studies on this topic, utilizing limited methodologies, the evidence from this scoping review shows the benefits of shared reading for infants and their caregivers during their NICU stay. Expanding such efforts by embedding shared reading as part of standard practice is recommended.
Fault diagnosis in electric motors using multi-mode time series and ensemble transformers network
Examining the relationship between income and both mental and physical health among adults in the UK: Analysis of 12 waves (2009–2022) of Understanding Society
There is growing evidence of a causal relationship between income and health. At the same time, pressure on reactive health and care services in the UK is increasing. Previous work to quantify the relationship has focused on particular age groups, conditions, or single-item self-rated health. This article reports findings from a study that aimed to provide more comprehensive estimates with an objective of creating an evidential basis for microsimulation modelling of upstream income interventions. We analyse the relationship between income and two health measures – SF-12 Mental Component Summary (MCS-12) and Physical Component Summary (PCS-12) – across 12 waves (2009/11–2020/22) of Understanding Society: The UK Household Longitudinal Study. Using a ‘within-between’ model (Model 1), we find that increases in income compared with an individual’s average and a higher income compared with the sample average is associated with better mental health (higher MCS-12 score) and better functional physical health (higher PCS-12 score). However, for a given increase in household income (say £100 per month), the association with better mental and physical health is smaller at higher incomes. This suggests that redistribution from high-income to lower income households would increase average population physical and mental health, other things being equal. Using a random-effects logistic regression (Model 2), we similarly find that average income quintile is inversely and monotonically associated with the probability of having clinically significant symptoms of depressive disorders (MCS-12 ≤ 45.6) and physical health problems (PCS-12 score ≤ 50.0), with smaller changes in these probabilities from increases in income at higher points in the income distribution. These findings facilitate microsimulation modelling including an estimation of the impact of changes in QALYs, from changes in income, enabling a more detailed and complete understanding of which socioeconomic interventions might begin to address some of the causes of long-term health conditions that are underpinned by socioeconomic determinants.
Sex differences in predicting dyslipidemia using polygenic risk score with fatty liver index and fibrotic nonalcoholic steatohepatitis index
Daily briefing: The second X chromosome isn’t so silent after all
Author Correction: Fetal hepatocytes protect the HSPC genome via fetuin-A
Exploring bioactive compound origins: Profiling gene cluster signatures related to biosynthesis in microbiomes of Sof Umer Cave, Ethiopia
Sof Umer Cave is an unexplored extreme environment that hosts novel microbes and potential genetic resources. Microbiomes from caves have been genetically adapted to produce various bioactive metabolites, allowing them to survive and tolerate harsh conditions. However, the biosynthesis-related gene cluster signatures in the microbiomes of Sof Umer Cave have not been explored. Therefore, high-throughput shotgun sequencing was used to explore biosynthesis-related gene clusters (BGCs) in the microbiomes of Sof Umer Cave. The GeneAll DNA Soil Mini Kit was used to extract high-molecular-weight DNA from homogenized samples, and the purified DNA was sequenced using a NovaSeq PE150. According to the Micro-RN database, the most common microbial genera in Sof Umer Cave are Protobacteria, Actinobacteria, Verrucomicrobiota, and Cyanobacteria. The biosynthesis-related gene clusters were annotated and classified, and the BGCs were predicted using antiSMASH and NAPDOS1. A total of 460 putative regions of BGCs encoding a wide range of secondary metabolites were identified, including RiPP (47.82%), terpene (19.57%), NRPS (13.04%), hybrid (2.18%), and other newly annotated (10.87%) compounds. Additionally, the NAPDOS pipeline identified a calcium-dependent antibiotic gene cluster from Streptomyces coelicolor, an actinomycin gene cluster from Streptomyces chrysomallus, and a bleomycin gene cluster from Streptomyces verticillus. These findings highlight the untapped biosynthetic potential of the Sof Umer Cave microbiome, as well as its potential for the discovery of natural products.
Auditory sequence learning with degraded input: children with cochlear implants (‘nature effect’) compared to children from low and high socio-economic backgrounds (‘nurture effect’)
Human capital and regional disparities: Advancing accounting frameworks with education, health, and population dynamics
This study advances the inclusive wealth accounting of human capital (HC) to improve global research on the valuation of HC for sustainability. By innovatively integrating complex population dynamics, including schooling and labor force participation, and using a net present value (NPV) valuation method aligned with capital budgeting principles, we quantitatively measure HC in 165 countries. As a methodological advancement, we use a unified framework that incorporates education, health and economic participation via the measurement of life expectancy in different life stages to inform sustainable development investments. Our analysis from 1990 to 2020 reveals significant differences in HC development across countries. While education is strongly correlated with GDP growth, disparities in health and economic participation are critical barriers to long-term HC accumulation. Our findings argue for a comprehensive policy approach that goes beyond investing in education for its financial benefits and includes substantial improvements in health and economic opportunities to promote more equitable HC growth. We emphasize the need to incorporate complex population dynamics into HC assessments to better understand and strengthen the interdependencies between these critical factors, with the aim of reducing global development gaps.
Exploring the active ingredients and potential mechanisms of Pingchan granules in Parkinson’s disease treatment through network pharmacology and transcriptomics
Amazonian deforestation makes the wet season wetter, and the dry season drier
Indications of the SERPINE 1 variant rs1799768’s role in anti-VEGF therapy resistance in neovascular age-related macular degeneration
Age-related macular degeneration (AMD) is a retinal disease prevalent in the elderly population, with two main subtypes: dry (non-exudative) and neovascular (wet or exudative). Neovascular AMD (nAMD) has a more debilitating prognosis than dry AMD, making it the third leading cause of blindness. Intravitreal injections of anti-vascular endothelial growth factor (IV anti-VEGF) are the most effective and widely accepted treatment for nAMD. However, a significant number of nAMD patients exhibit suboptimal responses to IV anti-VEGF therapy, with the underlying mechanisms not yet fully understood. We hypothesized that genetic polymorphisms associated with blood hypercoagulation may also contribute to suboptimal responses to IV anti-VEGF therapy. This study recruited 20 nAMD patients, who were divided into two groups based on their treatment responses after four years: 10 patients with suboptimal responses to IV anti-VEGF therapy and 10 patients with optimal responses. After obtaining institutional ethics board approval, we retrospectively evaluated relevant clinical records of twenty patients diagnosed with nAMD. Patient clinical data were accessed between 20th March 2021 -1st April 2021 for research purposes only. We genotyped peripheral blood DNA from each patient for hypercoagulation-related polymorphisms, including Factor V Leiden (rs6025), prothrombin c.20210G>A (rs1799963), MTHFR A1298C (rs1801131), MTHFR C677T (rs1801133), and SERPINE 1 (PAI-1-675 4G/5G) (rs1799768), and statistically compared the frequencies. Heterozygous and homozygous mutations in the SERPINE1 gene specifically PAI-1 promoter region PAI-1-675 4G/5G (rs1799768) were identified as risk factors for resistance to IV anti-VEGF therapy in nAMD patients (χ² test, p = 0.006). No other polymorphisms of the above-mentioned genes were statistically significant (p > 0.05). The failure of IV anti-VEGF therapy in nAMD patients may be influenced by various factors, one of which may be the inherited PAI-1-675 4G/5G (rs1799768) polymorphisms which normally known to contribute hypercoagulation. Further research involving a larger cohort is necessary to uncover the interplay between hereditary factors and other elements contributing to the inefficacy of IV anti-VEGF therapy in nAMD.
Cullin-5 controls the number of megakaryocyte-committed stem cells to prevent thrombocytosis in mice
Abstract Cullin-5 (Cul5) coordinates the assembly of cullin-RING-E3 ubiquitin ligase complexes that include the suppressors of cytokine signaling (SOCS)-box–containing proteins. The SOCS-box proteins function to recruit specific substrates to the complex for ubiquitination and degradation. In hematopoiesis, SOCS-box proteins are best known for regulating the actions of cytokines that utilize the JAK-STAT signaling pathway. However, the roles of most SOCS-box proteins have not been studied in physiological contexts and any actions for Cul5/SOCS complexes in signaling by several hematopoietic cytokines, including thrombopoietin (TPO) and interleukin-3 (IL-3), remain unknown. To define additional potential roles for Cul5/SOCS complexes, we generated mice lacking Cul5 in hematopoiesis; the absence of Cul5 is predicted to impair the SOCS-box–dependent actions of all proteins that contain this motif. Here, we show that Cul5-deficient mice develop excess megakaryopoiesis and thrombocytosis revealing a novel mechanism of negative regulation of megakaryocyte-committed stem cells, a distinct population within the hematopoietic stem cell pool that have been shown to rapidly, perhaps directly, generate megakaryocytes, and which are produced in excess in the absence of Cul5. Cul5-deficient megakaryopoiesis is distinctive in being largely independent of TPO/myeloproliferative leukemia protein and involves signaling via the β-common and/or β-IL-3 receptors, with evidence of deregulated responses to IL-3. This process is independent of the interferon-α/β receptor, previously implicated in inflammation-induced activation of stem-like megakaryocyte progenitor cells.
Influence of fractal fabric on the shear characteristics of large scale accumulation bodies
Nanobody-based naturally selected CD7-targeted CAR-T therapy for acute myeloid leukemia
Abstract Approximately 30% of patients with acute myeloid leukemia (AML) express CD7 on their myeloblasts. We have previously demonstrated that single-chain variable fragment (scFv)–based “naturally selected” CD7 chimeric antigen receptor T-cell (NS7CAR-T) therapy shows significant efficacy, with a favorable safety profile in T-cell lymphoid malignancies. Here, we derived dual variable heavy-chain domain of a heavy-chain antibody (dVHH) NS7CAR-Ts that have superior CD7 binding specificity, affinity to their scFv-based counterparts, and improved proliferative capability. In this phase 1 clinical trial, we evaluated the efficacy and safety of nanobody-based dVHH NS7CAR-Ts for patients with CD7+ refractory/relapsed AML. A cohort of 10 patients received dVHH NS7CAR-Ts across 2 dosage levels of 5 × 105/kg and 1 × 106/kg. Before enrollment, patients had undergone a median of 8 (range, 3-17) prior lines of therapy. Seven patients had prior transplants. After NS7CAR-T infusion, 7 of 10 (70%) patients achieved complete remission (CR). The median observation time was 178 days (range, 28-776). Among 7 patients who achieved CR, 3 who relapsed from prior transplants underwent a second allogeneic hematopoietic stem cell transplant (allo-HSCT). One patient remained leukemia free on day 401, and the other 2 died on day 241 and day 776, respectively, from nonrelapse-related causes. Three CR patients without consolidative (allo-HSCT) relapsed within 90 days. All the nonresponders and relapsed patients had CD7 loss. The treatment was well tolerated, with 80% experiencing mild cytokine release syndrome and none had neurotoxicity. This trial underscores the potential promising treatment of dVHH NS7CAR-Ts in providing clinical benefits with a manageable safety profile to patients with CD7+ AML, warranting further investigation. This trial was registered at www.clinicaltrials.gov as #NCT04938115.