An integrated model of the human cornea as a linear biaxial birefringent medium.

A novel model of human corneal birefringence is presented. The cornea is treated as a homogeneous biaxial linear birefringent medium in which the values of the binormal axes angle and organization of the main refractive indices vary continuously from the apex to the limbus. In its central part, the angle between binormal axes is 35°, and para centrally, it smoothly increases to 83.

Immune heterogeneity in small-cell lung cancer and vulnerability to immune checkpoint blockade.

Atezolizumab (anti-PD-L1), combined with carboplatin and etoposide (CE), is now a standard of care for extensive-stage small-cell lung cancer (ES-SCLC). A clearer understanding of therapeutically relevant SCLC subsets could identify rational combination strategies and improve outcomes. We conduct transcriptomic analyses and non-negative matrix factorization on 271 pre-treatment patient tumor samples from IMpower133 and identify four subsets with general concordance to previously reported SCLC subtypes (SCLC-A, -N, -P, and -I).

Substantial health and economic burden of COVID-19 during the year after acute illness among US adults at high risk of severe COVID-19.

Background: Post-COVID conditions encompass a range of long-term symptoms after SARS-CoV-2 infection. The potential clinical and economic burden in the United States is unclear. We evaluated diagnoses, medications, healthcare use, and medical costs before and after acute COVID-19 illness in US patients at high risk of severe COVID-19.

Investigating the Mechanisms Underlying U46619-Induced Contraction on Porcine Lower Esophageal Sphincter.

Gastroesophageal reflux disease (GERD) is associated with an incompetent lower esophageal sphincter (LES), resulting in the reflux of gastric contents into the esophagus. U46619, a thromboxane A2 (TXA2) receptor agonist, induces contractions in various smooth muscles. Therefore, this study aimed to investigate the effects and mechanisms of action of U46619 on the porcine LES.

Fish consumption and omega-3 polyunsaturated fatty acids from diet are positively associated with cognitive function in older adults even in the presence of exposure to lead, cadmium, selenium, and methylmercury: a cross-sectional study using NHANES 2011-2014 data.

Background: Long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are reported to be beneficial for cognition, but limited consumption of some fish is recommended due to high concentrations of heavy metals and persistent organics.

Objective: We aimed to determine whether dietary ω-3 PUFAs from fish consumption are associated with higher cognitive scores in older adults and explored the associations of mixtures of ω-3 PUFAs and blood concentrations of lead, cadmium, selenium, and methylmercury on cognitive performance.

Methods: We conducted a cross-sectional study with data from the NHANES 2011-2014, assessing cognitive scores of immediate recall, delayed recall, and executive function in adults ≥60 y (n = 3123).

Measurements of the lightest hypernucleus (HΛ3): progress and perspective.

The hyperon-nucleon (Y-N) interaction is important for the description of the equation-of-state of high baryon density matter. Hypernuclei, the cluster object of nucleons and hyperons, serve as cornerstones of a full understanding of the Y-N interaction. Recent measurements of the lightest known hypernucleus, the hypertriton's (HΛ3) and anti-hypertriton's (H¯Λ¯3) lifetime, mass and Λ separation energy have attracted interests on the subject.

Targeting of intracellular oncoproteins with peptide-centric CARs.

The majority of oncogenic drivers are intracellular proteins, constraining their immunotherapeutic targeting to mutated peptides (neoantigens) presented by individual human leukocyte antigen (HLA) allotypes. However, most cancers have a modest mutational burden that is insufficient for generating responses using neoantigen-based therapies. Neuroblastoma is a paediatric cancer that harbours few mutations and is instead driven by epigenetically deregulated transcriptional networks.

Tumor sequencing of African ancestry reveals differences in clinically relevant alterations across common cancers.

Cancer genomes from patients with African (AFR) ancestry have been poorly studied in clinical research. We leverage two large genomic cohorts to investigate the relationship between genomic alterations and AFR ancestry in six common cancers. Cross-cancer type associations, such as an enrichment of MYC amplification with AFR ancestry in lung, breast, and prostate cancers, and depletion of BRAF alterations are observed in colorectal and pancreatic cancers.

Gold(III) derivatives as the noncovalent interaction donors: theoretical study of the π-hole regium bonds.

Except for the well-known σ-hole regium bonds formed by metal nanoparticles and M(I) (M = Cu, Ag, and Au) derivatives, the existence of π-hole regions located above and below the Au atom in gold(III) derivatives suggests that gold(III) also functions as an efficient electrophilic site. In this study, a comprehensive analysis was conducted on the electrophilicity of trichloro-(-toluonitrilo-N)-gold(III) derivatives AuL(NCCHX) (L = Cl, Br, CN; X = NH, CH, CF, NC, and CN) and the nature of π-hole regium bonds in the AuL(NCCHX)⋯LB (LB = NH, N(NH), CHO, CH, CH, CH) and (AuCl(NCCHY)) (Y = Cl, CN, NC, NO; = 2, 3)) complexes. The characteristics of the π-hole regium bonds were studied with respect to the influence of ligands and substituents, the strength of intermolecular interactions between Au(III) derivatives and Lewis bases, and those in the polymers.

CD8 cytotoxic T-cell infiltrates and cellular damage in the hypothalamus in human obesity.

Rare cases of paraneoplastic obesity in children suggest sporadic obesity might also arise from an adaptive immune cell-mediated mechanism. Since the hypothalamus is a central regulator of feeding behavior and energy expenditure, we quantified lymphocytic inflammation in this region in a cohort of obese and non-obese human post-mortem brains. We report that CD8-positive cytotoxic T-cells are increased in hypothalamic median eminence/arcuate nucleus (ME/Arc) and bed nucleus of the stria terminalis in 40% of obese compared to non-obese patients, but not in other hypothalamic nuclei or brain regions.

Differentiating Macrovascular and Microvascular Ischemia Using Fractal Analysis of Dynamic Myocardial Perfusion Stress-CT.

Objectives: Fractal analysis of dynamic myocardial stress computed tomography perfusion imaging (4D-CTP) has shown potential to noninvasively differentiate obstructive coronary artery disease (CAD) and coronary microvascular disease (CMD). This study validates fractal analysis of 4D-CTP in a multicenter setting and assesses its diagnostic accuracy in subgroups with ischemia and nonobstructed coronary arteries (INOCA) and with mild to moderate stenosis.

Materials And Methods: From the AMPLIFiED multicenter trial, patients with suspected or known chronic myocardial ischemia and an indication for invasive coronary angiography were included.

Synthesis of Three Families of Titanium Carbonitride MXenes.

Layered MAX phases and two-dimensional (2D) MXenes derived from them are among the most studied materials due to their attractive properties and numerous potential applications. The tunability of their structure and composition allows for every property to be modulated over a wide range. Particularly, elemental replacement and formation of a solid solution without changing the structure allow fine-tuning of material properties.

Optical Properties of ScY (Y = N, P As) Nanoparticles.

In this work, using Density Functional Theory (DFT) and Time Dependent DFT, the absorption spectrum, the optical gap, and the binding energy of scandium pnictogen family nanoparticles (NPs) are examined. The calculated structures are created from an initial cubic-like building block of the form ScY, where Y = N, P, As after elongation along one and two perpendicular directions. The existence of stable structures over a wide range of morphologies was one of the main findings of this research, and this led to the study of several exotic NPs.

Pathways explaining racial/ethnic and socio-economic disparities in dementia incidence: the UK Biobank study.

Background: Pathways explaining racial/ethnic disparities in dementia risk are under-evaluated.

Methods: We examine those disparities and their related pathways among UK Biobank study respondents (50-74 y, = 323,483; 3.6% non-White minorities) using a series of Cox proportional hazards and generalized structural equations models (GSEM).

Triplet maintenance therapy of olaparib, pembrolizumab and bevacizumab in women with BRCA wild-type, platinum-sensitive recurrent ovarian cancer: the multicenter, single-arm phase II study OPEB-01/APGOT-OV4.

In this multicenter, open-label, single-arm, Phase II study with Simon two-stage optimum design (NCT04361370), we investigate the efficacy and safety of triplet maintenance (olaparib, pembrolizumab, bevacizumab) in patients with platinum-sensitive recurrent ovarian cancer who are wild-type for BRCA 1/2. A total of 44 patients were enrolled, and the median follow-up duration was 22.9 months (interquartile range: 17.

iPSC-derived mesenchymal stem cells attenuate cerebral ischemia-reperfusion injury by inhibiting inflammatory signaling and oxidative stress.

Induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) hold great promise as a cell source for transplantation into injured tissues to alleviate inflammation. However, the therapeutic efficacy of iMSC transplantation for ischemic stroke remains unknown. In this study, we evaluated the therapeutic effects of iMSC transplantation on brain injury after ischemia-reperfusion using a rat transient middle cerebral artery occlusion model and compared its therapeutic efficacy with that of bone marrow mesenchymal stem cells (BMMSCs).

Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial.

Idecabtagene vicleucel (ide-cel) is a B-cell-maturation antigen (BCMA)-directed chimeric antigen receptor T cell therapy. We performed a post hoc analysis of a single-arm phase 1 multicenter study in relapsed/refractory multiple myeloma (CRB-401) (n = 62; median follow-up, 18.1 months).

Amorphous Calcium Carbonate Shows Anti-Cancer Properties That are Attributed to Its Buffering Capacity.

Aim: Amorphous calcium carbonate (ACC) is a non-crystalline form of calcium carbonate, and it is composed of aggregated nano-size primary particles. Here, we evaluated its anti-cancer effect postulated relative to its buffering capabilities in lung cancer.

Methods: Tumors were evaluated in vivo using the Lewis lung carcinoma (LLC) mouse cell line and A549 human lung cancer carcinoma cell line.

Sarcopenia in Children With Wilms Tumor: A Marker of Undernutrition Which May Impact Adversely on Clinical Outcomes.

The therapeutic approach to Wilms tumor (WT) is multidisciplinary and leads to significant patient impairment, increasing the risk of nutritional compromise and malnutrition. Children with cancer are vulnerable to sarcopenia which has been recognized as a negative impact of anticancer therapy. Recent studies have highlighted the reduction in the total psoas muscle area (TPMA) to be associated with a poor prognosis in many pediatric diseases, including cancer.

Discovery of a Hidden Spermidine Synthase Binding Site and Inhibitors through , and X-ray Crystallography.

In drug discovery research, the selection of promising binding sites and understanding the binding mode of compounds are crucial fundamental studies. The current understanding of the proteins-ligand binding model extends beyond the simple lock and key model to include the induced-fit model, which alters the conformation to match the shape of the ligand, and the pre-existing equilibrium model, selectively binding structures with high binding affinity from a diverse ensemble of proteins. Although methods for detecting target protein binding sites and virtual screening techniques using docking simulation are well-established, with numerous studies reported, they only consider a very limited number of structures in the diverse ensemble of proteins, as these methods are applied to a single structure.

Crystallographic Study of Product Phases of Carbothermic Reduction and Nitridation of Hafnium Dioxide.

Details of the carbothermic reduction/nitridation to synthesize hafnium nitride (HfN) and hafnium carbide (HfC) are scarce in the literature. Therefore, this current study was carried out to evaluate two pathways for synthesizing these two refractory materials: direct nitridation and carbothermic reduction/nitridation. Two mixtures of hafnium dioxide and carbon with C/HfO molar ratios of 2.

Unilaterally Selective Adrenal Vein Sampling for Identification of Surgically Curable Primary Aldosteronism.

Background: Adrenal venous sampling is recommended for the identification of unilateral surgically curable primary aldosteronism but is often clinically useless, owing to failed bilateral adrenal vein cannulation.

Objectives: To investigate if only unilaterally selective adrenal vein sampling studies can allow the identification of the responsible adrenal.

Methods: Among 1625 patients consecutively submitted to adrenal vein sampling in tertiary referral centers, we selected those with selective adrenal vein sampling results in at least one side; we used surgically cured unilateral primary aldosteronism as gold reference.

A modified CALGB 10403 in adolescents and young adults with acute lymphoblastic leukemia in Central America.

Mexico and Central America have a high incidence of acute lymphoblastic leukemia (ALL) in adolescents and young adults. Historically, this patient group has been treated using adult-based regimens, which entails a high rate of treatment-related mortality and a poor overall survival (OS). The use of the CALGB 10403, a pediatric-inspired regimen, has been proven effective in this patient subgroup.