Predicting Microvascular Invasion and Early Recurrence in Hepatocellular Carcinoma Using DeepLab V3+ Segmentation of Multiregional MR Habitat Images.

Rationale And Objectives: Accurate identification of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is crucial for treatment and prognosis. Single-modality and feature fusion models using manual segmentation fail to provide insights into MVI. This study aims to develop a DeepLab V3+ model for automated segmentation of HCC magnetic resonance (MR) images and a decision fusion model to predict MVI and early recurrence (ER).

A new species of Isonychia Eaton, 1871 (Ephemeroptera: Isonychiidae) from Taishun, China based on morphological characteristics and COX1 gene.

Isonychia taishunensis Huang, Shen, Zhang & Cheng sp. nov. is described based on larval samples from Taishun County, Zhejiang Province, China.

Chip-scale sensor for spectroscopic metrology.

Miniaturized spectrometers hold great promise for in situ, in vitro, and even in vivo sensing applications. However, their size reduction imposes vital performance constraints in meeting the rigorous demands of spectroscopy, including fine resolution, high accuracy, and ultra-wide observation window. The prevailing view in the community holds that miniaturized spectrometers are most suitable for coarse identification of signature peaks.

Decision Fusion Model for Predicting Microvascular Invasion in Hepatocellular Carcinoma Based on Multi-MR Habitat Imaging and Machine-Learning Classifiers.

Rationale And Objectives: Accurate prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is crucial for guiding treatment. This study evaluates and compares the performance of clinicoradiologic, traditional radiomics, deep-learning radiomics, feature fusion, and decision fusion models based on multi-region MR habitat imaging using six machine-learning classifiers.

Materials And Methods: We retrospectively included 300 HCC patients.

Outcomes of inadequate empiric therapy and timing of newer antibacterial therapy in hospitalized adults with culture-positive Enterobacterales and Pseudomonas aeruginosa: a multicenter analysis.

Background: Infections caused by multi-drug resistant Gram-negative pathogens are associated with worse clinical outcomes in critically ill patients. We evaluated hospital outcomes based on adequacy of overall and newer antibacterial therapy for Enterobacterales (ENT) and Pseudomonas aeruginosa (PsA) in US patients.

Methods: Hospitalized adults ≥ 18 years old with facility-reported antibiotic susceptibility from 2018-2022 across 161 facilities in the BD Insights Research Database were identified as ENT- or PsA-positive.

Novel Quantitative Contrast Sensitivity Function Enhances the Prediction of Treatment Outcome and Recurrence in Amblyopia.

Purpose: Although effective amblyopia treatments are available, treatment outcome is unpredictable, and the condition recurs in up to 25% of the patients. We aimed to evaluate whether a large-scale quantitative contrast sensitivity function (CSF) data source, coupled with machine learning (ML) algorithms, can predict amblyopia treatment response and recurrence in individuals.

Methods: Visual function measures from traditional chart vision acuity (VA) and novel CSF assessments were used as the main predictive variables in the models.

FRAX predicts cardiovascular risk in women undergoing osteoporosis screening: the Manitoba bone mineral density registry.

Osteoporosis and cardiovascular disease (CVD) are highly prevalent in older women, with increasing evidence for shared risk factors and pathogenesis. Although FRAX was developed for the assessment of fracture risk, we hypothesized that it might also provide information on CVD risk. To test the ability of the FRAX tool and FRAX-defined risk factors to predict incident CVD in women undergoing osteoporosis screening with DXA, we performed a retrospective prognostic cohort study which included women aged 50 yr or older with a baseline DXA scan in the Manitoba Bone Mineral Density Registry between March 31, 1999 and March 31, 2018.

Intravenous administration of IL-12 encoding self-replicating RNA-lipid nanoparticle complex leads to safe and effective antitumor responses.

Interleukin 12 (IL-12) is a potent immunostimulatory cytokine mainly produced by antigen-presenting cells (e.g., dendritic cells, macrophages) and plays an important role in innate and adaptive immunity against cancers.

Novel Angiogenesis Role of GLP-1(32-36) to Rescue Diabetic Ischemic Lower Limbs via GLP-1R-Dependent Glycolysis in Mice.

Background: Restoring the capacity of endothelial progenitor cells (EPCs) to promote angiogenesis is the major therapeutic strategy of diabetic peripheral artery disease. The aim of this study was to investigate the effects of GLP-1 (glucagon-like peptide 1; 32-36)-an end product of GLP-1-on angiogenesis of EPCs and T1DM (type 1 diabetes) mice, as well as its interaction with the classical GLP-1R (GLP-1 receptor) pathway and its effect on mitochondrial metabolism.

Methods: In in vivo experiments, we conducted streptozocin-induced type 1 diabetic mice as a murine model of unilateral hind limb ischemia to examine the therapeutic potential of GLP-1(32-36) on angiogenesis.

Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes several proteins that inhibit host interferon responses. Among these, ORF6 antagonizes interferon signaling by disrupting nucleocytoplasmic trafficking through interactions with the nuclear pore complex components Nup98-Rae1. However, the roles and contributions of ORF6 during physiological infection remain unexplored.

SARS-CoV-2 variants evolve convergent strategies to remodel the host response.

SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions.

Treated, hospital-onset infection: An evaluation of predictors and feasibility of benchmarking comparing 2 risk-adjusted models among 265 hospitals.

Objectives: To evaluate the incidence of a candidate definition of healthcare facility-onset, treated (CD) infection (cHT-CDI) and to identify variables and best model fit of a risk-adjusted cHT-CDI metric using extractable electronic heath data.

Methods: We analyzed 9,134,276 admissions from 265 hospitals during 2015-2020. The cHT-CDI events were defined based on the first positive laboratory final identification of CD after day 3 of hospitalization, accompanied by use of a CD drug.

Highly Regioselective Dichalcogenation of Alkenyl Sulfonium Salts to Access 1,1-Dichalcogenalkenes.

An unprecedented geminal olefinic dichalcogenation of alkenyl sulfonium salts with dichalcogenides ArYYAr (Y = S, Se, Te) is reported, providing various trisubstituted 1,1-dichalcogenalkenes [ArCH = C(YAr)] in a highly selective manner under mild and catalyst-free conditions. The key process involves the formation of two geminal olefinic C-Y bonds via sequential C-Y cross-coupling and C-H chalcogenation. A mechanistic rationale is further supported by control experiments and density functional theory calculations.

Novel Frizzled-specific antibody-based Wnt mimetics and Wnt superagonists selectively activate WNT/β-catenin signaling in target tissues.

WNTs are essential factors for stem cell biology, embryonic development, and for maintaining homeostasis and tissue repair in adults. Difficulties in purifying WNTs and their lack of receptor selectivity have hampered research and regenerative medicine development. While breakthroughs in WNT mimetic development have overcome some of these difficulties, the tools developed so far are incomplete and mimetics alone are often not sufficient.

Activation of Platelet mTORC2/Akt Pathway by Anti-β2GP1 Antibody Promotes Thrombosis in Antiphospholipid Syndrome.

Background: Anti-β2GP1 (β2-glycoprotein 1) antibodies are the primary pathogenic antibody to promote thrombosis in antiphospholipid syndrome (APS), yet the underlying mechanism remains obscure. We aimed to explore the intracellular pathway that mediated platelet activation.

Methods: Platelets were isolated from patients with APS and subjected to RNA sequencing.

Immunization with Recombinant Accessory Protein-Deficient SARS-CoV-2 Protects against Lethal Challenge and Viral Transmission.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a worldwide coronavirus disease 2019 (COVID-19) pandemic. Despite the high efficacy of the authorized vaccines, there may be uncertain and unknown side effects or disadvantages associated with current vaccination approaches. Live-attenuated vaccines (LAVs) have been shown to elicit robust and long-term protection by the induction of host innate and adaptive immune responses.

Objective Pharyngeal Phenotyping in Obstructive Sleep Apnea With High-Resolution Manometry.

Objective: Drug-induced sleep endoscopy (DISE) is a commonly used diagnostic tool for surgical procedural selection in obstructive sleep apnea (OSA), but it is expensive, subjective, and requires sedation. Here we present an initial investigation of high-resolution pharyngeal manometry (HRM) for upper airway phenotyping in OSA, developing a software system that reliably predicts pharyngeal sites of collapse based solely on manometric recordings.

Study Design: Prospective cross-sectional study.

A Phase 1, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics of Iberdomide in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared with Healthy Subjects.

Introduction: Iberdomide, a novel cereblon modulator (CELMoD), is currently under clinical investigation for hematology indications. To evaluate the influence of hepatic impairment on the pharmacokinetics (PK) of iberdomide and its major active metabolite M12, a phase 1, multicenter, open-label study was conducted in healthy subjects and subjects with mild, moderate, and severe hepatic impairment.

Methods: Forty subjects were enrolled in the study and divided into five groups based on hepatic function.

Automated Classification of Intramedullary Spinal Cord Tumors and Inflammatory Demyelinating Lesions Using Deep Learning.

Accurate differentiation of intramedullary spinal cord tumors and inflammatory demyelinating lesions and their subtypes are warranted because of their overlapping characteristics at MRI but with different treatments and prognosis. The authors aimed to develop a pipeline for spinal cord lesion segmentation and classification using two-dimensional MultiResUNet and DenseNet121 networks based on T2-weighted images. A retrospective cohort of 490 patients (118 patients with astrocytoma, 130 with ependymoma, 101 with multiple sclerosis [MS], and 141 with neuromyelitis optica spectrum disorders [NMOSD]) was used for model development, and a prospective cohort of 157 patients (34 patients with astrocytoma, 45 with ependymoma, 33 with MS, and 45 with NMOSD) was used for model testing.

Independent Associations of Education, Intelligence, and Cognition With Hypertension and the Mediating Effects of Cardiometabolic Risk Factors: A Mendelian Randomization Study.

Background: Education, intelligence, and cognition are associated with hypertension, but which one plays the most prominent role in the pathogenesis of hypertension and which modifiable risk factors mediate the causal effects remains unknown.

Methods: Using summary statistics of genome-wide association studies of predominantly European ancestry, we conducted 2-sample multivariable Mendelian randomization to estimate the independent effects of education, intelligence, or cognition on hypertension (FinnGen study, 70 651 cases/223 663 controls; UK Biobank, 77 723 cases/330 366 controls) and blood pressure (International Consortium of Blood Pressure, 757 601 participants), and used 2-step Mendelian randomization to evaluate 25 potential mediators of the association and calculate the mediated proportions.

Results: Meta-analysis of inverse variance weighted Mendelian randomization results from FinnGen and UK Biobank showed that genetically predicted 1-SD (4.

Use of a Bacterial Artificial Chromosome to Generate Recombinant SARS-CoV-2 Expressing Robust Levels of Reporter Genes.

Reporter-expressing recombinant virus represents an excellent option and a powerful tool to investigate, among others, viral infection, pathogenicity, and transmission, as well as to identify therapeutic compounds that inhibit viral infection and prophylactic vaccines. To combat the ongoing coronavirus disease 2019 (COVID-19) pandemic, we have established a robust bacterial artificial chromosome (BAC)-based reverse genetics (RG) system to rapidly generate recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) to study the contribution of viral proteins in viral pathogenesis. In addition, we have engineered reporter-expressing recombinant viruses in which we placed the reporter genes upstream of the viral nucleocapsid (N) gene to promote high levels of reporter gene expression, which facilitates the study of SARS-CoV-2 and .

Trial of Thrombectomy 6 to 24 Hours after Stroke Due to Basilar-Artery Occlusion.

Background: The effects and risks of endovascular thrombectomy 6 to 24 hours after stroke onset due to basilar-artery occlusion have not been extensively studied.

Methods: In a trial conducted over a 5-year period in China, we randomly assigned, in a 1:1 ratio, patients with basilar-artery stroke who presented between 6 to 24 hours after symptom onset to receive either medical therapy plus thrombectomy or medical therapy only (control). The original primary outcome, a score of 0 to 4 on the modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 4 moderately severe disability, and 6 death) at 90 days, was changed to a good functional status (a modified Rankin scale score of 0 to 3, with a score of 3 indicating moderate disability).

Monitoring SARS-CoV-2 Infection Using a Double Reporter-Expressing Virus.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the highly contagious agent responsible for the coronavirus disease 2019 (COVID-19) pandemic. An essential requirement for understanding SARS-CoV-2 biology and the impact of antiviral therapeutics is a robust method to detect the presence of the virus in infected cells or animal models. Despite the development and successful generation of recombinant (r)SARS-CoV-2-expressing fluorescent or luciferase reporter genes, knowledge acquired from their use in assays and/or in live animals is limited to the properties of the fluorescent or luciferase reporter genes.

GMP Manufacturing and IND-Enabling Studies of a Recombinant Hyperimmune Globulin Targeting SARS-CoV-2.

Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope neutralization is required to prevent the development of immune-evading viral mutants that can emerge upon treatment with monoclonal antibodies. Using microfluidics, flow sorting, and a targeted integration cell line, a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 (GIGA-2050) was generated.