Synthesis and biological activity evaluation of azacycloheptane sulfonamide derivatives as potential orexin receptor antagonists.

As the orexin signaling system is crucial for the regulation of the sleep/wake cycle, inhibitors of orexin-1 and orexin-2 receptors are of significant interest in the treatment of insomnia. Herein, a series of novel azacycloheptane sulfonamide derivatives were designed and synthesized, and all the compounds were evaluated as potential orexin receptor inhibitors by FLIPR Tetra calcium assay. A majority of the tested azacycloheptane sulfonamide derivatives showed OX1R and OX2R inhibitory activity.

The risk of bleeding and all-cause mortality with edoxaban versus vitamin K antagonists: A meta-analysis of phase III randomized controlled trials.

Introduction: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. However, the risk of bleeding and all-cause mortality in patients with edoxaban versus vitamin K antagonists (VKAs) is unclear.

Methods: We systematically searched all published studies of edoxaban versus VKAs.

Actionable co-alterations in breast tumors with pathogenic mutations in the homologous recombination DNA damage repair pathway.

Purpose: Homologous recombination (HR)-deficient breast tumors may have genomic alterations that predict response to treatment with PARP inhibitors and other targeted therapies.

Methods: Comprehensive molecular profiles of 4647 breast tumors performed at Caris Life Sciences using 592-gene NGS were reviewed to identify somatic pathogenic mutations in HR genes ARID1A, ATM, ATRX, BAP1, BARD1, BLM, BRCA1/2, BRIP1, CHEK1/2, FANCA/C/D2/E/F/G/L, KMT2D, MRE11, NBN, PALB2, RAD50/51/51B, and WRN, as well as 41 markers that may be associated with treatment response to targeted anticancer therapies.

Results: 17.

Efficacy and safety outcomes in novel oral anticoagulants versus vitamin-K antagonist on post-TAVI patients: a meta-analysis.

Background: Transcatheter aortic valve implantation (TAVI) has been a favored option for the patient who suffered from symptomatic aortic stenosis. However, the efficacy and safety outcomes in novel oral anticoagulants (NOACs) versus Vitamin-K antagonist (VKA) for post-TAVI patients are still controversial. This meta-analysis aims at comparing the clinical outcome and safety of NOACs and VKA in the patients after receiving TAVI.

sp. nov., isolated from the production water of a water-flooded oil reservoir in PR China.

A novel, moderately thermophilic, Gram-stain-negative bacterium, designated strain J18, was isolated from a water-flooded oil reservoir. Cells were aerobic, oxidase- and catalase-positive, with a polar flagellum. Growth occurred at 35-60 °C and at pH 6-8.

Molecular profile of BRCA-mutated biliary tract cancers.

Introduction: Prognosis of biliary tract cancers (BTC) remains dismal and novel treatment strategies are needed to improve survival. mutations are known to occur in BTC but their frequency and the molecular landscape in which they are observed in distinct sites of BTC remain unknown.

Material And Methods: Tumour samples from 1292 patients with BTC, comprising intrahepatic cholangiocarcinoma (IHC, n=746), extrahepatic cholangiocarcinoma (EHC, n=189) and gallbladder cancer (GBC, n=353), were analysed using next-generation sequencing (NGS).

Inverse changes in telomere length between the blood and brain in depressive-like mice.

Background: Telomeres are nucleoprotein complexes located at the end of chromosomes. Previous studies have confirmed that telomere length is reduced in the peripheral blood of depression patients. However, studies regarding whether telomere length is altered in brain regions associated with depression are limited.

Long-term Prognostic Value of Cardiac MRI Left Atrial Strain in ST-Segment Elevation Myocardial Infarction.

Background Left atrial (LA) dysfunction is associated with morbidity and mortality. To the knowledge of the authors, the relationship of LA strain to long-term prognosis in participants with ST-segment elevation myocardial infarction (STEMI) is unknown. Purpose To evaluate LA strain as a long-term outcome predictor in STEMI in a prospective, multicenter cardiac MRI cohort.

-Mutated Colorectal Cancer Is Characterized by a Distinct Genetic Phenotype.

Werner syndrome gene () contributes to DNA repair. In cancer, mutations (-mut) lead to genomic instability. Thus, is a promising target in cancers with microsatellite instability (MSI).

Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors.

Microsatellite instability-high (MSI-H) and tumor mutational burden (TMB) are predictive biomarkers for immune-checkpoint inhibitors (ICIs). Still, the relationship between the underlying cause(s) of MSI and TMB in tumors remains poorly defined. We investigated associations of TMB to mismatch repair (MMR) protein expression patterns by immunohistochemistry (IHC) and MMR mutations in a diverse sample of tumors.

Quantitative toxicological study of dose-dependent arsenic-induced cells via synchrotron-based STXM and FTIR measurement.

Inorganic arsenic (iAs) is a well-known naturally occurring metalloid with abundant hazards to our environment, especially being a human carcinogen through arsenic-contaminated drinking water. The iAs-related contamination is usually examined by a chemical assay system or fluorescence staining technique to investigate iAs accumulation and its deleterious effects. In this work, we present a dual-modality measurement and quantitative analysis methods for the overall evaluation of various dose-dependent iAs-related cytotoxicological manifestations by the combination of the synchrotron-radiation-based scanning transmission soft X-ray microscopy (SR-STXM) and Fourier transform infrared micro-spectroscopy (SR-FTIR) techniques.

Frequent Mutations of POT1 Distinguish Pulmonary Sarcomatoid Carcinoma From Other Lung Cancer Histologies.

Introduction: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small-cell lung cancer (NSCLC) harboring mutations in many canonical NSCLC-driver genes (eg, TP53, KRAS, MET). Protection of telomeres 1 (POT1) mutations are observed in angiosarcoma and chronic lymphocytic leukemia, but their frequency in other solid tumors, including NSCLC subtypes, has not been rigorously explored.

Materials And Methods: We analyzed next-generation sequencing data from 62,368 tumors, including 11,134 NSCLCs and 100 PSCs.

Biomechanical study of space frame structure based on bone cement screw.

Stability of space frame structures with bone cement screw reinforcement by biomechanical testing was analyzed. Seven complete human spine specimens with osteoporosis were selected. Three specimens were separated into 18 vertebral bodies.

Texture analysis of early cerebral tissue damage in magnetic resonance imaging of patients with lung cancer.

Primary tumors can secrete many cytokines, inducing tissue damage or microstructural changes in distant organs. The purpose of this study was to investigate changes in texture features in the cerebral tissue of patients with lung cancer without brain metastasis. In this study, 50 patients with lung cancers underwent 3.

Primary CNS lymphoma commonly expresses immune response biomarkers.

Background: Primary central nervous system lymphoma (PCNSL) is rare and there is limited genomic and immunological information available. Incidental clinical and radiographic responses have been reported in PCNSL patients treated with immune checkpoint inhibitors.

Materials And Methods: To genetically characterize and ascertain if the majority of PCNSL patients may potentially benefit from immune checkpoint inhibitors, we profiled 48 subjects with PCNSL from 2013 to 2018 with (1) next-generation sequencing to detect mutations, gene amplifications, and microsatellite instability (MSI); (2) RNA sequencing to detect gene fusions; and (3) immunohistochemistry to ascertain PD-1 and PD-L1 expression.

Molecular Profiling of the Metaplastic Spindle Cell Carcinoma of the Breast Reveals Potentially Targetable Biomarkers.

Introduction: Spindle cell carcinoma is a rare subtype of metaplastic breast cancer, with triple-negative (TNBC: estrogen receptor-negative/progesterone receptor-negative/human epidermal growth factor receptor 2-negative) phenotype. It is associated with a marked resistance to conventional chemotherapy and has an overall poor outcome.

Materials And Methods: Twenty-three pure spindle cell carcinomas of the breast (18 primary and 5 recurrent/metastatic) were comprehensively explored for biomarkers of immuno-oncology and targeted therapies using immunohistochemistry and DNA/RNA sequencing.

Comprehensive tumor profiling reveals unique molecular differences between peritoneal metastases and primary colorectal adenocarcinoma.

Background And Objectives: Peritoneal metastases (PM) from primary colorectal cancer (pCRC) are associated with poor outcomes; however, molecular differences are not well defined.

Methods: We compared unpaired tumor profiles of patients with pCRC and PM from Caris Life Sciences. Testing included next-generation sequencing of 592 genes, microsatellite instability (MSI) and tumor mutational burden (TMB).

Comparison of direct stenting with conventional strategy on myocardial impairments in ST-segment elevation myocardial infarction: a cardiac magnetic resonance imaging study.

Direct stenting (DS) without pre-dilatation of the culprit lesion might improve myocardial perfusion and prognosis in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI); however, some studies report conflicting results. We investigated whether DS provides incremental myocardial benefits over conventional stenting (CS) in STEMI patients based on cardiac magnetic resonance imaging (CMR) measures. Reperfused patients who underwent CMR examinations within 1 week of STEMI onset were selected from a multicenter CMR registry of STEMI (NCT: 03768453).

Radiomics analysis of lung CT image for the early detection of metastases in patients with breast cancer: preliminary findings from a retrospective cohort study.

Objectives: To investigate whether subtle changes in radiomics features are present in lung CT images prior to the development of CT-detectable lung metastases in patients with breast cancer.

Methods: Thirty-three radiomics features were measured in the metastasis region (MR) and in matched contralateral tissues (non-metastasis region, NMR) of 29 breast cancer patients at the last CT scan, as well as in the corresponding regions of the patients' pre-metastasis scan (pre-MR and pre-NMR). We also compared them with normal lung tissues (control group, CG) from 29 healthy volunteers.

[Effect of NO produced by indigenous denitrifiers in oil reservoir on the physical properties of crude oil].

The success of microbial enhanced oil recovery (MEOR) relies on complex microbial processes. Nevertheless, the contribution and mechanism of in-situ denitrification to microbial oil recovery remain unclear. In this study, eight denitrifying bacterial strains, designated T1, D1, D44, D46, D15, S1, S2 and S6, were isolated from the produced water of Xinjiang Oilfield, China, by a double layered plate method.

mutation spectrum in tumour types commonly diagnosed among -associated hereditary cancer syndrome families.

Background: The shelterin complex is composed of six proteins that protect and regulate telomere length, including protection of telomeres 1 (POT1). Germline mutations are associated with an autosomal dominant familial cancer syndrome presenting with diverse malignancies, including glioma, angiosarcoma, colorectal cancer and melanoma. Although somatic mutations promote telomere elongation and genome instability in chronic lymphocytic leukaemia, the contribution of mutations to development of other sporadic cancers is largely unexplored.

Immune checkpoint expression, microsatellite instability, and mutational burden: Identifying immune biomarker phenotypes in uterine cancer.

Objectives: Increasing grade of endometrioid endometrial cancer (EEC) is associated with aggressive behavior and poor prognosis. The traditional classification system is limited in its ability to guide treatment planning and prognostication. We identify distinct immune biomarker phenotypes using known markers of immunogenicity to identify patients who may benefit from immune therapy (IT).

Antifungal Activity and Physicochemical Properties of a Novel Antimicrobial Protein AMP-17 from .

Antimicrobial peptides (AMPs) are cationic small peptide chains that have good antimicrobial activity against a variety of bacteria, fungi, and viruses. AMP-17 is a recombinant insect AMP obtained by a prokaryotic expression system. However, the full antifungal activity, physicochemical characteristics, and cytotoxicity of AMP-17 were previously unknown.

A 3D Printed Hanging Drop Dripper for Tumor Spheroids Analysis Without Recovery.

Compared with traditional monolayer cell culture, the three-dimensional tumor spheroid has emerged as an essential in vitro model for cancer research due to the recapitulation of the architecture and physiology of solid human tumors. Herein, by implementing the rapid prototyping of a benchtop 3D printer, we developed a new strategy to generate and analyze tumor spheroids on a commonly used multi-well plate. In this method, the printed artifact can be directly mounted on a 96/384-well plate, enables hanging drop-based spheroid formation, avoiding the tedious fabrication process from micromechanical systems.

Syntheses, Structures, and Characteristics of Three Metal Complexes Constructed Using Hexacarboxylic Acid.

In this study, three new 3D coordination polymers (CPs), {[Cd(L)(HO)]·HO} (), {[Cu(L)(bimb)]·5HO·DMF} (), and {[Mn(HL)(bibp)(HO)]·3HO} () (= 1,3-bis(imidazol-1-yl)benzene, = 1,4-bis((4-imidazol-1-yl)benzyl)piperazine), were prepared under solvothermal or hydrothermal conditions based on a hexadentate ligand (1,3,5-triazine-2,4,6-triamine hexa-acetic acid (HL)). Structural elucidations were carried out by IR spectra along with single-crystal X-ray diffraction analysis, while thermogravimetric analysis (TGA) (dynamic and isothermal) and XRD techniques were used for property evaluations of the polymers. Furthermore, the fluorescence properties and detection of the Fe ions in were tested at room temperature, and the electrochemical behavior of is also stated in this article.