Radiomicsmetabolic signature profiles for advanced non-small cell lung cancer with chemoimmunotherapy by reflecting biological function and survival.

Background: Resistance to chemoimmunotherapy in patients with advanced non-small cell lung cancer (NSCLC) necessitates effective prognostic biomarkers. Although F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has shown potential for efficacy assessment, it has been mainly evaluated in immuno-monotherapy setting, lacking elaborations in the scenarios of immunotherapy combined with chemotherapy. To tackle this dilemma, we aimed to build a non-invasive PET/CT-based model for stratifying tumor heterogeneity and predicting survival in advanced NSCLC patients undergoing chemoimmunotherapy.

Construction of stable Cu/Cu sites at the fullerene/Cu(OH)F interface to boost the electroreduction of CO to C products.

Herein, the reduction of the Cu oxidation state during the CO electro-reduction reaction (CORR) is effectively inhibited by depositing C supramolecular clusters onto the Cu(OH)F surface. By utilizing the unique electronic buffering capacity of C, a significant number of Cu/Cu sites are created, leading to a remarkable faradaic efficiency of C products up to 76.9% and exceptional stability.

Targeted LNPs deliver IL-15 superagonists mRNA for precision cancer therapy.

Interleukin-15 (IL-15) emerges as a promising immunotherapeutic candidate, but the therapeutic utility remains concern due to the unexpected systematic stress. Here, we propose that the mRNA lipid nanoparticle (mRNA-LNP) system can balance the issue through targeted delivery to increase IL-15 concentration in the tumor area and reduce leakage into the circulation. In the established Structure-driven TARgeting (STAR) platform, the LNP and LNP can effectively and selectively deliver optimized IL-15 superagonists mRNAs to local and lungs, respectively, in relevant tumor models.

Lymph nodes rather than pleural metabolic activity in F-FDG PET/CT correlates with malignant pleural effusion recurrence in advanced non-small cell lung cancer.

Background: Frequently recurrent malignant pleural effusion (MPE) significantly hampers the life quality of advanced non-small cell lung cancer (NSCLC) patients. We aimed to explore the effects of progression patterns and local intervention on MPE recurrence and apply fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) to establish a predictive model for MPE recurrence in NSCLC.

Methods: We retrospectively recruited two cohorts of patients including treatment-naïve NSCLC diagnosed with MPE at the onset and receiving PET/CT scanning, as well as those with MPE and undergoing first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment.

A human monoclonal antibody targeting the monomeric N6 neuraminidase confers protection against avian H5N6 influenza virus infection.

The influenza neuraminidase (NA) is a potential target for the development of a next-generation influenza vaccine, but its antigenicity is not well understood. Here, we isolate an anti-N6 human monoclonal antibody, named 18_14D, from an H5N6 avian influenza virus (AIV) infected patient. The antibody weakly inhibits enzymatic activity but confers protection in female mice, mainly via ADCC function.

Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection.

Background: Respiratory syncytial virus (RSV) is a leading cause of severe illness in infants, with no effective treatment. Results of a phase 2 trial suggested that ziresovir may have efficacy in the treatment of infants hospitalized with RSV infection.

Methods: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial conducted in China, we enrolled participants 1 to 24 months of age who were hospitalized with RSV infection.

Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer.

Background: Adjuvant therapy with durvalumab, with or without tremelimumab, may have efficacy in patients with limited-stage small-cell lung cancer who do not have disease progression after standard concurrent platinum-based chemoradiotherapy.

Methods: In a phase 3, double-blind, randomized, placebo-controlled trial, we assigned patients to receive durvalumab at a dose of 1500 mg, durvalumab (1500 mg) plus tremelimumab at a dose of 75 mg (four doses only), or placebo every 4 weeks for up to 24 months. Randomization was stratified according to disease stage (I or II vs.

Idiopathic intracranial hypertension in Asians: a retrospective dual-center study.

Background: There have been limited data on idiopathic intracranial hypertension (IIH) in Asians and there remain uncertainties whether a cerebrospinal fluid (CSF) pressure of 250 mm CSF is an optimum diagnostic cutoff. The aims of the present study included (1) characterization of IIH patients in Taiwan, (2) comparisons among different diagnostic criteria for IIH, and (3) comparisons between patients with CSF pressures of > 250 and 200-250 mm CSF.

Methods: This retrospective study involved IIH patients based on the modified Dandy criteria from two tertiary medical centers in Taiwan.

Exposure-response modeling for nausea incidence for cotadutide using a Markov modeling approach.

Cotadutide is a dual glucagon-like peptide-1 (GLP-1)/glucagon receptor agonist. Gastrointestinal adverse effects are known to be associated with GLP-1 receptor agonism and can be mitigated through tolerance development via a gradual up-titration. This analysis aimed to characterize the relationship between exposure and nausea incidence and to optimize titration schemes.

Inhibition of Vascular Smooth Muscle Cell Proliferation by ENPP1: The Role of CD73 and the Adenosine Signaling Axis.

The Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) ectoenzyme regulates vascular intimal proliferation and mineralization of bone and soft tissues. variants cause Generalized Arterial Calcification of Infancy (GACI), a rare genetic disorder characterized by ectopic calcification, intimal proliferation, and stenosis of large- and medium-sized arteries. ENPP1 hydrolyzes extracellular ATP to pyrophosphate (PP) and AMP.

Seizure, Motor, and Cognitive Outcomes After Epilepsy Surgery for Patients With Sturge-Weber Syndrome: Results From a Multicenter Study.

Background And Objectives: Surgery is widely performed for refractory epilepsy in patients with Sturge-Weber syndrome (SWS), but reports on its effectiveness are limited. This study aimed to analyze seizure, motor, and cognitive outcomes of surgery in these patients and to identify factors associated with the outcomes.

Methods: This was a multicenter retrospective observational study using data from patients with SWS and refractory epilepsy who underwent epilepsy surgery between 2000 and 2020 at 16 centers throughout China.

Multi-dimensional cell-free DNA-based liquid biopsy for sensitive early detection of gastric cancer.

Background: Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality.

Strain and Electric Field Engineering of G-ZnO/SnXY (X, Y = S, Se) S-Scheme Heterostructures for Photocatalyst and Electronic Device Applications: A Hybrid DFT Calculation.

Using hybrid density functional theory calculations, we systematically study the biaxial strain and electric field modulated electronic properties of g-ZnO/SnS, g-ZnO/SnSe, and g-ZnO/SnSSe S-scheme van der Waals heterostructures (vdWHs). g-ZnO/SnS and g-ZnO/SnSSe are found to be promising photocatalysts for water splitting with high solar-to-hydrogen efficiencies, even under acidic, alkaline, and high-stress conditions. The strain effect on the bandgaps of g-ZnO/SnXY is explained in detail according to the correlation between geometry structure and orbital hybridization of SnXY, which could help understand the strain-induced band structure evolutions in other SnXY (X, Y = S, Se)-based vdWHs.

Subtype-Specific Association of Mitochondrial DNA Copy Number With Poststroke/TIA Outcomes in 10 241 Patients in China.

Background: Mitochondrial DNA copy number (mtDNA-CN) is associated with the severity and mortality in patients with stroke, but the associations in different stroke subtypes remain unexplored.

Methods: We conducted an observational prospective cohort analysis on patients with ischemic stroke or transient ischemic attack enrolled in the Third China National Stroke Registry. We applied logistic models to assess the association of mtDNA-CN with functional outcome (modified Rankin Scale score, 3-6 versus 0-2) and Cox proportional hazard models to assess the association with stroke recurrence (treating mortality as a competing risk) and mortality during a 12-month follow-up, adjusting for sex, age, physical activity, National Institutes of Health Stroke Scale at admission, history of stroke and peripheral artery disease, small artery occlusion, and interleukin-6.

Highly sensitive spatial transcriptomics using FISHnCHIPs of multiple co-expressed genes.

High-dimensional, spatially resolved analysis of intact tissue samples promises to transform biomedical research and diagnostics, but existing spatial omics technologies are costly and labor-intensive. We present Fluorescence In Situ Hybridization of Cellular HeterogeneIty and gene expression Programs (FISHnCHIPs) for highly sensitive in situ profiling of cell types and gene expression programs. FISHnCHIPs achieves this by simultaneously imaging ~2-35 co-expressed genes (clustered into modules) that are spatially co-localized in tissues, resulting in similar spatial information as single-gene Fluorescence In Situ Hybridization (FISH), but with ~2-20-fold higher sensitivity.

Factors Contributing to Non-Concordance Between End-of-Life Care and Advance Care Planning.

Context: Despite making do-not-resuscitate or comfort care decisions during advance care planning, terminally ill patients sometimes receive life-sustaining treatments as they approach end of life.

Objectives: To examine factors contributing to nonconcordance between end-of-life care and advance care planning.

Methods: In this longitudinal retrospective cohort study, terminally ill patients with a life expectancy shorter than six months, who had previously expressed a preference for do-not-resuscitate or comfort care, were followed up after palliative shared care intervention.

Hypermethylation Loci of ZNF671, IRF8, and OTX1 as Potential Urine-Based Predictive Biomarkers for Bladder Cancer.

Bladder cancer (BCa) is a significant health issue and poses a healthcare burden on patients, highlighting the importance of an effective detection method. Here, we developed a urine DNA methylation diagnostic panel for distinguishing between BCa and non-BCa. In the discovery stage, an analysis of the TCGA database was conducted to identify BCa-specific DNA hypermethylation markers.

Cleavage-intermediate Lassa virus trimer elicits neutralizing responses, identifies neutralizing nanobodies, and reveals an apex-situated site-of-vulnerability.

Lassa virus (LASV) infection is expanding outside its traditionally endemic areas in West Africa, posing a pandemic biothreat. LASV-neutralizing antibodies, moreover, have proven difficult to elicit. To gain insight into LASV neutralization, here we develop a prefusion-stabilized LASV glycoprotein trimer (GPC), pan it against phage libraries comprising single-domain antibodies (nanobodies) from shark and camel, and identify one, D5, which neutralizes LASV.

Lung SORT LNPs enable precise homology-directed repair mediated CRISPR/Cas genome correction in cystic fibrosis models.

Approximately 10% of Cystic Fibrosis (CF) patients, particularly those with CF transmembrane conductance regulator (CFTR) gene nonsense mutations, lack effective treatments. The potential of gene correction therapy through delivery of the CRISPR/Cas system to CF-relevant organs/cells is hindered by the lack of efficient genome editor delivery carriers. Herein, we report improved Lung Selective Organ Targeting Lipid Nanoparticles (SORT LNPs) for efficient delivery of Cas9 mRNA, sgRNA, and donor ssDNA templates, enabling precise homology-directed repair-mediated gene correction in CF models.

FAM222A, Part of the BET-Regulated Basal Endothelial Transcriptome, Is a Novel Determinant of Endothelial Biology and Angiogenesis-Brief Report.

Background: BETs (bromodomain and extraterminal domain-containing epigenetic reader proteins), including BRD4 (bromodomain-containing protein 4), orchestrate transcriptional programs induced by pathogenic stimuli, as intensively studied in cardiovascular disease and elsewhere. In endothelial cells (ECs), BRD4 directs induced proinflammatory, proatherosclerotic transcriptional responses; BET inhibitors, like JQ1, repress these effects and decrease atherosclerosis. While BET effects in pathogenic conditions have prompted therapeutic BET inhibitor development, BET action under basal conditions, including ECs, has remained understudied.