Prequalification of genome-based newborn screening for severe childhood genetic diseases through federated training based on purifying hyperselection.

Genome-sequence-based newborn screening (gNBS) has substantial potential to improve outcomes in hundreds of severe childhood genetic disorders (SCGDs). However, a major impediment to gNBS is imprecision due to variants classified as pathogenic (P) or likely pathogenic (LP) that are not SCGD causal. gNBS with 53,855 P/LP variants, 342 genes, 412 SCGDs, and 1,603 therapies was positive in 74% of UK Biobank (UKB470K) adults, suggesting 97% false positives.

Combination of Deep Learning Grad-CAM and Radiomics for Automatic Localization and Diagnosis of Architectural Distortion on DBT.

Rationale And Objectives: Detection and diagnosis of architectural distortion (AD) on digital breast tomosynthesis (DBT) is challenging. This study applied artificial intelligence (AI) using deep learning (DL) algorithms to detect AD, followed by radiomics for classification.

Materials And Methods: 500 cases with AD on DBT reports were identified; the earlier 292 cases for training, and the later 208 cases for testing.

Positive In Vitro Effect of ROCK Pathway Inhibitor Y-27632 on Qualitative Characteristics of Goat Sperm Stored at Low Temperatures.

Y-27632, as a cytoskeleton protector, is commonly used for low-temperature preservation of cells. Goat sperm are prone to damage to the cytoskeleton under low-temperature conditions, leading to a loss of sperm vitality. However, the Y-27632 small molecule has not yet been used in research on low-temperature preservation of goat semen.

Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19 B cell tumors: a phase 1/2 trial.

There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted a phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 chimeric antigen receptor and interleukin-15 (CAR19/IL-15) in 37 patients with CD19 B cell malignancies. The primary objectives were safety and efficacy, defined as day 30 overall response (OR).

Occurrence, seasonal variation and gas/particle partitioning of current used pesticides (CUPs) across 60 °C temperature and 30° latitudes in China.

Gas and particle phases samples were collected at three sites in China in 2019-2020, with 60 °C temperature span and 30° latitude range. Totally, among 76 target current used pesticides (CUPs) with four types, 51 were quantified in at least one sample. The concentrations of individual CUPs ranged from 8 orders of magnitude, indicating different pollution levels.

Pan-cancer proteogenomics connects oncogenic drivers to functional states.

Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying their significant cis-effects and distal trans-effects quantified at the RNA, protein, and phosphoprotein levels. Salient observations include the association of point mutations and copy-number alterations with the rewiring of protein interaction networks, and notably, most cancer genes converge toward similar molecular states denoted by sequence-based kinase activity profiles.

Safety and immunogenicity of a modified COVID-19 mRNA vaccine, SW-BIC-213, as a heterologous booster in healthy adults: an open-labeled, two-centered and multi-arm randomised, phase 1 trial.

Background: We assessed the safety and immunogenicity of a core-shell structured lipopolyplex (LPP) based COVID-19 mRNA vaccine, SW-BIC-213, as a heterologous booster in healthy adults.

Methods: We conducted an open-labeled, two-centered, and three-arm randomised phase 1 trial. Healthy adults, who had completed a two-dose of inactivated COVID-19 vaccine for more than six months, were enrolled and randomized to receive a booster dose of COVILO (inactivated vaccine) (n = 20) or SW-BIC-213-25μg (n = 20), or SW-BIC-213-45μg (n = 20).

Network pharmacology and experiment-based strategy to investigate mechanisms of JingFangFuZiLiZhong formula for ulcerative colitis.

Background: Ulcerative colitis (UC), a chronic inflammatory disease, often cause carcinogenesis, disability, and intestinal perforation. The JingFangFuZiLiZhong formula (JFFZLZ) shows a good effect against UC in the clinic. Hence, we aim to investigate the mechanisms between JFFZLZ and UC network pharmacology data mining and experiments.

Safety and Pharmacokinetics of Islatravir in Individuals with Severe Renal Insufficiency.

Islatravir (MK-8591) is a high-potency reverse transcriptase translocation inhibitor in development for the treatment of HIV-1 infection. Data from preclinical and clinical studies suggest that ~30% to 60% of islatravir is excreted renally and that islatravir is not a substrate of renal transporters. To assess the impact of renal impairment on the pharmacokinetics of islatravir, an open-label phase 1 trial was conducted with individuals with severe renal insufficiency (RI).

Association Between DNA Methylation and Blood Pressure: A 5-Year Longitudinal Twin Study.

Background: Previous EWASs (Epigenome-Wide Association Studies) have reported hundreds of blood pressure (BP) associated 5'-cytosine-phosphate-guanine-3' (CpG) sites. However, their results were inconsistent. Longitudinal observations on the temporal relationship between DNA methylation and BP are lacking.

Effects of short-term continuous and pulse cadmium exposure on gut histology and microbiota of adult male frogs (Pelophylax nigromaculatus) during pre-hibernation.

Cadmium (Cd) is an environmental endocrine-disrupting pollutant which mainly occurs in pulsed manner in natural waters, while traditional toxicology experiments have less examined the effects of pulsed exposure. Here, we studied the effects of short-term (7 days) continuous and pulse exposure to 100 μg/L Cd on gut morphology and microbiota of frogs (Pelophylax nigromaculatus) during pre-hibernation. Compared to continuous exposure, Cd pulse exposure significantly increased individual mortality and decreased the villi height and the ratio of villi height to crypt depth of the gut.

Short-term continuous and pulse Pb exposure causes negative effects on skin histomorphological structure and bacterial composition of adult Pelophylax nigromaculatus.

Lead (Pb) is a toxic heavy metal often present in the environment as a pulse in water. Traditional toxicity tests are usually carried out under conditions of continuous concentration, without considering the impact of pulse exposure on aquatic organisms. This study aimed to evaluate the effects of short-term continuous and pulse Pb exposures on the skin bacteria and histomorphological structure of Pelophylax nigromaculatus.

Atrazine exposure and recovery alter the intestinal structure, bacterial composition and intestinal metabolites of male Pelophylax nigromaculatus.

The pesticide atrazine poses a potential threat to the health of frogs living in farmland areas. The exposure concentration in traditional pesticide experiments is usually constant, while pesticide pollution in actual water may fluctuate due to periodic or seasonal application. We examined the effects of different concentrations of atrazine (50, 100 and 500 μg/L) over a 14-day exposure and a 7-day recovery on intestinal histology, bacterial composition and intestinal metabolites of male Pelophylax nigromaculatus.

Thin-Section Chest CT Imaging of COVID-19 Pneumonia: A Comparison Between Patients with Mild and Severe Disease.

Purpose: To compare radiologic characteristics of coronavirus disease 2019 (COVID-19) pneumonia at thin-section CT on admission between patients with mild and severe disease.

Materials And Methods: Seventy patients with COVID-19 pneumonia who were admitted to Zhongnan Hospital of Wuhan University between January 20, 2020 and January 27, 2020 were enrolled. On the basis of the World Health Organization guidelines, 50 patients were categorized with the mild form and 20 with the severe form based on clinical conditions.

Long non-coding RNA CASC15 promotes nasopharyngeal carcinoma cell proliferation and metastasis by downregulating miR-101-3p.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA CASC15 promotes nasopharyngeal carcinoma cell proliferation and metastasis by downregulating miR-101-3p, by M.-Y. Xue, H.

Six-month Follow-up Chest CT Findings after Severe COVID-19 Pneumonia.

Background Little is known about the long-term lung radiographic changes in patients who have recovered from coronavirus disease 2019 (COVID-19), especially those with severe disease. Purpose To prospectively assess pulmonary sequelae and explore the risk factors for fibrotic-like changes in the lung at 6-month follow-up chest CT of survivors of severe COVID-19 pneumonia. Materials and Methods A total of 114 patients (80 [70%] men; mean age, 54 years ± 12) were studied prospectively.

Unique Subtype of Microglia in Degenerative Thalamus After Cortical Stroke.

Background And Purpose: Stroke disrupts neuronal functions in both local and remotely connected regions, leading to network-wide deficits that can hinder recovery. The thalamus is particularly affected, with progressive development of neurodegeneration accompanied by inflammatory responses. However, the complexity of the involved inflammatory responses is poorly understood.

Nonspecific cleavages arising from reconstitution of trypsin under mildly acidic conditions.

Tryptic digestion of proteins followed by liquid chromatography with tandem mass spectrometry analysis is an extensively used approach in proteomics research and biopharmaceutical product characterization, owing to the high level of cleavage fidelity produced with this technique. However, nonspecific trypsin cleavages have been frequently reported and shown to be related to a number of digestion conditions and predigestion sample treatments. In this work, we reveal that, for a number of commercial trypsins, reconstitution and storage conditions can have a significant impact on the occurrence of trypsin nonspecific cleavages.