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.

Characterization of Vortex Vein Drainage System in Healthy Individuals Imaged by Ultra-Widefield Optical Coherence Tomography Angiography.

Purpose: The purpose of this study was to investigate the choroidal characteristics of vortex vein (VV) drainage systems in healthy individuals using ultra-widefield optical coherence tomography angiography.

Methods: The mean choroidal thickness (ChT) and choroidal vascularity index (CVI) of each VV quadrant (24 × 20 mm2 scan mode; superotemporal [ST], superonasal [SN], inferonasal [IN], and inferotemporal [IT] quadrants) were calculated. Furthermore, intervortex venous anastomosis (IVA) was classified into temporal, superior, inferior, and nasal types.

Curcumin-loaded keratin-chitosan hydrogels for enhanced peripheral nerve regeneration.

Peripheral nerve injury often leads to symptoms of motor and sensory impairment, and slow recovery of nerves after injury and limited treatment methods will aggravate symptoms or even lead to lifelong disability. Curcumin can promote peripheral nerve regeneration, but how to accurately deliver the appropriate concentration of curcumin in the local peripheral nerve remains to be solved. In this study, we designed a human hair keratin/chitosan (C/K) hydrogel with sodium tripolyphosphate ions crosslinked to deliver curcumin topically.

Structural transitions enable interleukin-18 maturation and signaling.

Several interleukin-1 (IL-1) family members, including IL-1β and IL-18, require processing by inflammasome-associated caspases to unleash their activities. Here, we unveil, by cryoelectron microscopy (cryo-EM), two major conformations of the complex between caspase-1 and pro-IL-18. One conformation is similar to the complex of caspase-4 and pro-IL-18, with interactions at both the active site and an exosite (closed conformation), and the other only contains interactions at the active site (open conformation).

Therapeutic potential of CBR activation by Qingyangshen glycoside M1 for seizure relief.

Ethnopharmacological Relevance: Cynanchum otophyllum C.K.Schneid.

Secreted clusterin inhibits tumorigenesis by modulating tumor cells and macrophages in human meningioma.

Background: Meningioma is the most common primary intracranial tumor with a high frequency of postoperative recurrence, yet the biology of the meningioma malignancy process is still obscure.

Methods: To identify potential therapeutic targets and tumor suppressors, we performed single-cell transcriptome analysis through meningioma malignancy, which included 18 samples spanning normal meninges, benign and high-grade in situ tumors, and lung metastases, for extensive transcriptome characterization. Tumor suppressor candidate gene and molecular mechanism were functionally validated at the animal model and cellular levels.

Gasdermin D permeabilization of mitochondrial inner and outer membranes accelerates and enhances pyroptosis.

Gasdermin D (GSDMD)-activated inflammatory cell death (pyroptosis) causes mitochondrial damage, but its underlying mechanism and functional consequences are largely unknown. Here, we show that the N-terminal pore-forming GSDMD fragment (GSDMD-NT) rapidly damaged both inner and outer mitochondrial membranes (OMMs) leading to reduced mitochondrial numbers, mitophagy, ROS, loss of transmembrane potential, attenuated oxidative phosphorylation (OXPHOS), and release of mitochondrial proteins and DNA from the matrix and intermembrane space. Mitochondrial damage occurred as soon as GSDMD was cleaved prior to plasma membrane damage.

Observation of New Ω_{c}^{0} States Decaying to the Ξ_{c}^{+}K^{-} Final State.

Two new excited states, Ω_{c}(3185)^{0} and Ω_{c}(3327)^{0}, are observed in the Ξ_{c}^{+}K^{-} invariant-mass spectrum using proton-proton collision data collected by the LHCb experiment, corresponding to an integrated luminosity of 9  fb^{-1}. Five previously observed excited Ω_{c}^{0} states are confirmed, namely Ω_{c}(3000)^{0}, Ω_{c}(3050)^{0}, Ω_{c}(3065)^{0}, Ω_{c}(3090)^{0}, and Ω_{c}(3119)^{0}. The masses and widths of these seven states are measured with the highest precision to date.

Pancreatic Adenocarcinoma: Real World Evidence of Care Delivery in AccessHope Data.

Background: Pancreatic adenocarcinoma is an aggressive disease and the delivery of comprehensive care to individuals with this cancer is critical to achieve appropriate outcomes. The identification of gaps in care delivery facilitates the design of interventions to optimize care delivery and improve outcomes in this population.

Methods: AccessHope™ is a growing organization that connects oncology subspecialists with treating providers through contracts with self-insured employers.

Choroidal Vortex Vein Drainage System in Central Serous Chorioretinopathy Using Ultra-Widefield Optical Coherence Tomography Angiography.

Purpose: To evaluate differences in the choroidal vortex vein drainage system (VV) in eyes between patients with central serous chorioretinopathy (CSC) and unaffected individuals using ultra-widefield optical coherence tomography angiography (UWF-OCTA).

Methods: In this cross-sectional observational study, 40 eyes of patients with CSC and 28 eyes of healthy volunteers were included. The analysis involved the use of UWF-OCTA to analyze the proportion of the choroidal vortex vein drainage system (VV%), choroidal thickness, choroidal vascular volume (CVV), and choroidal vascularity index (CVI) of the VV in each drainage quadrant.

[Effects of Balanced Fertilization and Straw Mulching on Soil Nutrients and Stoichiometry in Purple Soil Slope].

To explore the effects of long-term balanced fertilization and straw mulching on soil nutrients and stoichiometric ratios in purple soil sloping cropland, nine plots (length 7 m×width 3 m) were established in Dianjiang County as the research sample area of long-term farmland nitrogen and phosphorus loss monitoring. The following three treatments were set up:conventional mode (CK), balanced fertilization mode (M1), and balanced fertilization+straw mulching mode (M2), with three replications for each treatment to compare the contents of carbon (C), nitrogen (N), phosphorus (P), and potassium (K) and their stoichiometric changes under different treatments from 2018 to 2020. The results showed:K contents showed significant differences among the three treatments in 2018, in the order of CK>M2>M1.

Provenance variation of root C, N, P, and K stoichiometric characteristics under different diameter classes of .

For exploring the difference of root stoichiometric characteristics among diameter classes and provenances, we examined the contents and stoichiometric ratios of carbon (C), nitrogen (N), phosphorus (P), and potassium (K) in three diameter classes of roots (0-1, 1-2 and 2-5 mm, respectively) of 39-year-old grown in a common garden. The results showed that root element contents and their stoichiometric ratios had significant difference among three diameter classes of roots. C content, C:N, C:P, C:K were the lowest, and N, P, K contents, N:P, and N:K were the highest in 0-1 mm diameter class roots.

Investigating the NRAS 5' UTR as a target for small molecules.

Neuroblastoma RAS (NRAS) is an oncogene that is deregulated and highly mutated in cancers including melanomas and acute myeloid leukemias. The 5' untranslated region (UTR) (5' UTR) of the NRAS mRNA contains a G-quadruplex (G4) that regulates translation. Here we report a novel class of small molecule that binds to the G4 structure located in the 5' UTR of the NRAS mRNA.

Coordinated pattern of multiple element variability in Aegiceras corniculatum propagule in shrimp aquaculture effluent habitats.

Human activities and environment changes have changed river estuary ecosystems, which impacts element changes in coastal sediments and mangroves. Mangrove propagule chemical traits showed a systematic shift along environmental gradients. But knowledge about how the pattern of multi-element variability is coordinated in propagule remains limited, and the conservation of macro and trace elements in propagules is also unknown.

Steroid-induced fibroblast growth factors drive an epithelial-mesenchymal inflammatory axis in severe asthma.

Asthma and inflammatory airway diseases restrict airflow in the lung, compromising gas exchange and lung function. Inhaled corticosteroids (ICSs) can reduce inflammation, control symptoms, and improve lung function; however, a growing number of patients with severe asthma do not benefit from ICS. Using bronchial airway epithelial brushings from patients with severe asthma or primary human cells, we delineated a corticosteroid-driven fibroblast growth factor (FGF)-dependent inflammatory axis, with FGF-responsive fibroblasts promoting downstream granulocyte colony-stimulating factor (G-CSF) production, hyaluronan secretion, and neutrophilic inflammation.

The FUS::DDIT3 fusion oncoprotein inhibits BAF complex targeting and activity in myxoid liposarcoma.

Mammalian SWI/SNF (mSWI/SNF or BAF) ATP-dependent chromatin remodeling complexes play critical roles in governing genomic architecture and gene expression and are frequently perturbed in human cancers. Transcription factors (TFs), including fusion oncoproteins, can bind to BAF complex surfaces to direct chromatin targeting and accessibility, often activating oncogenic gene loci. Here, we demonstrate that the FUS::DDIT3 fusion oncoprotein hallmark to myxoid liposarcoma (MLPS) inhibits BAF complex-mediated remodeling of adipogenic enhancer sites via sequestration of the adipogenic TF, CEBPB, from the genome.