Building patient-specific models for receptor tyrosine kinase signaling networks.

Cancer progresses due to changes in the dynamic interactions of multidimensional factors associated with gene mutations. Cancer research has actively adopted computational methods, including data-driven and mathematical model-driven approaches, to identify causative factors and regulatory rules that can explain the complexity and diversity of cancers. A data-driven, statistics-based approach revealed correlations between gene alterations and clinical outcomes in many types of cancers.

Overcorrection of fractured vertebrae increases the incidence of adjacent fractures after balloon kyphoplasty: A retrospective study.

Purpose: To investigate whether the correction amount by balloon kyphoplasty (BKP) is associated with the incidence of adjacent vertebral fractures (AVF).

Methods: Data from 61 patients without and 25 patients with AVF were analyzed. A linear regression model was used between vertebral instability and corrected angle or height to divide patients into the overcorrection and undercorrection groups.

Protective effect of Bacteroides fragilis LPS on Escherichia coli LPS-induced inflammatory changes in human monocytic cells and in a rheumatoid arthritis mouse model.

It has been reported that patients with rheumatoid arthritis (RA) have significantly less bacteria belonging to the Bacteroides group in their microbiota. We speculate that inhibition of cytokine production is impaired in patients with RA owing to their low levels of intestinal bacteria belonging to the Bacteroidetes group. Here we investigated the effect of Bacteroides fragilis lipopolysaccharide (B-LPS) on cytokine production in vitro and on the development of collagen antibody-induced arthritis (CAIA) in DBA/1 mice, an animal model of RA.

Clinical outcomes after intravesical bacillus Calmette-Guérin for the highest-risk non-muscle-invasive bladder cancer newly defined in the Japanese Urological Association Guidelines 2019.

Objective: To assess the clinical outcomes of highest-risk non-muscle-invasive bladder cancer patients treated with intravesical bacillus Calmette-Guérin.

Methods: The medical charts of patients with non-muscle-invasive bladder cancer treated with intravesical bacillus Calmette-Guérin between 2000 and 2018 at a single institution were retrospectively reviewed. Patients were stratified into three groups (intermediate-, high- and highest-risk groups) according to the risk classification of the updated Japanese Urological Association guidelines 2019.

Socio-economic impact on epilepsy outside of the nation-wide COVID-19 pandemic area.

Objective: To identify people with epilepsy (PWE) who required extensive care before the novel coronavirus disease 2019 (COVID-19) pandemic that had world-wide impacts on medical care and on socio-economic conditions.

Methods: Consecutive PWE who were treated at the epilepsy center of Hiroshima University Hospital, which was located in the COVID-19 non-pandemic area, between March 2019 and August 2020 were enrolled. We evaluated clinical and socioeconomic factors that were associated with seizure exacerbation (an increase in seizure frequency) during the first 6 months after the COVID-19 pandemic started compared with the previous 6 months.

High J and low anisotropy of hydrogen doped NdFeAsO superconducting thin film.

The recent realisations of hydrogen doped LnFeAsO (Ln = Nd and Sm) superconducting epitaxial thin films call for further investigation of their structural and electrical transport properties. Here, we report on the microstructure of a NdFeAs(O,H) epitaxial thin film and its temperature, field, and orientation dependencies of the resistivity and the critical current density J. The superconducting transition temperature T is comparable to NdFeAs(O,F).

Non-maintenance intravesical Bacillus Calmette-Guérin induction therapy with eight doses in patients with high- or highest-risk non-muscle invasive bladder cancer: a retrospective non-randomized comparative study.

Background: To explore possible solutions to overcome chronic Bacillus Calmette-Guérin (BCG) shortage affecting seriously the management of non-muscle invasive bladder cancer (NMIBC) in Europe and throughout the world, we investigated whether non-maintenance eight-dose induction BCG (iBCG) was comparable to six-dose iBCG plus maintenance BCG (mBCG).

Methods: This observational study evaluated 2669 patients with high- or highest-risk NMIBC who treated with iBCG with or without mBCG during 2000-2019. The patients were classified into five groups according to treatment pattern: 874 (33%) received non-maintenance six-dose iBCG (Group A), 405 (15%) received six-dose iBCG plus mBCG (Group B), 1189 (44%) received non-maintenance seven-/eight-dose iBCG (Group C), 60 (2.

Cell-free microRNA-1246 in different body fluids as a diagnostic biomarker for esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma is a malignant tumor with unfavorable prognosis. In this study, we investigated the usefulness of microRNA (miR)-1246 detection in various body fluids as a biomarker for this disease. A total of 72 patients with esophageal squamous cell carcinoma were enrolled, and their blood, urine, and saliva samples were collected prior to treatment.

Clinical Heterogeneity of Acquired Idiopathic Isolated Adrenocorticotropic Hormone Deficiency.

Objective: Heterogeneous clinical characteristics are observed in acquired isolated adrenocorticotropic hormone (ACTH) deficiency (IAD); however, its classification remains to be established because of its largely unknown pathophysiology. In IAD, anti-pituitary antibodies have been detected in some patients, although their significance remains unclear. Therefore, this study aimed to classify patients with IAD and to clarify the significance of anti-pituitary antibodies.

Initiating an epilepsy surgery program with limited resources in Indonesia.

To share the experiences of organizing the epilepsy surgery program in Indonesia. This study was divided into two periods based on the presurgical evaluation method: the first period (1999-2004), when interictal electroencephalogram (EEG) and magnetic resonance imaging (MRI) were used mainly for confirmation, and the second period (2005-2017), when long-term non-invasive and invasive video-EEG was involved in the evaluation. Long-term outcomes were recorded up to December 2019 based on the Engel scale.

[Consideration on Industry-Academia Partnering in Drug Discovery Development: Based on a Questionnaire Survey of Pharmaceutical Companies and Academia].

Japanese pharmaceutical products continue to experience a trade deficit, since import values exceed export values. In drug discovery development, given the pace of technological innovations, there has been a major shift from low-molecular-weight compounds to biomedicine. It is anticipated that industry, academia and government will work more closely together in support of the pharmaceutical industry.

Venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome due to an acute type B aortic dissection: a case report.

Acute type B aortic dissection is sometimes complicated by acute respiratory failure requiring mechanical ventilation. Herein, we describe our experience in a rare acute type B aortic dissection-associated respiratory failure case culminating in acute respiratory distress syndrome. The patient was a 45-year-old man admitted with a complaint of sudden chest pain radiating to his back.

Crystal structure of 1,2-bis-(4-fluoro-phen-yl)-1-hy-droxy-2,3,8-tri-meth-oxy-acenaphthene: formation of a five-membered intra-molecular O-H⋯O hydrogen-bonded ring.

The structure of the title compound, CHFO, at 193 K has triclinic ( ) symmetry. The hy-droxy and meth-oxy groups at the 1,2-positions of the acenaphthene core display a configuration. Both substituents are involved in the formation of a five-membered intra-molecular O-H⋯O hydrogen-bonded ring.

Quercetin 3,5,7,3',4'-pentamethyl ether from Kaempferia parviflora directly and effectively activates human SIRT1.

Sirtuin 1 (SIRT1), an NAD-dependent deacetylase, is a crucial regulator that produces multiple physiological benefits, such as the prevention of cancer and age-related diseases. SIRT1 is activated by sirtuin-activating compounds (STACs). Here, we report that quercetin 3,5,7,3',4'-pentamethyl ether (KPMF-8), a natural STAC from Thai black ginger Kaempferia parviflora, interacts with SIRT1 directly and stimulates SIRT1 activity by enhancing the binding affinity of SIRT1 with Ac-p53 peptide, a native substrate peptide without a fluorogenic moiety.

Relationship between vitamin D receptor gene polymorphisms (BsmI, TaqI, ApaI, and FokI) and calcium intake on bone mass in young Japanese women.

Background: The high prevalence of low bone mass in young women in Japan has emerged as a serious health issue in recent years. Therefore, the aim of the present study was to reevaluate the relationship between genetic and dietary factors, as well as its influence on bone mass in young Japanese women, with particular emphasis on vitamin D receptor (VDR) gene polymorphisms and calcium intake.

Methods: A total of 499 Japanese women aged 20-24 years were enrolled in the study.

Identification and Therapeutic Targeting of GPR20, Selectively Expressed in Gastrointestinal Stromal Tumors, with DS-6157a, a First-in-Class Antibody-Drug Conjugate.

Currently, the only approved treatments for gastrointestinal stromal tumor (GIST) are tyrosine kinase inhibitors (TKI), which eventually lead to the development of secondary resistance mutations in KIT or PDGFRA and disease progression. Herein, we identified G protein-coupled receptor 20 (GPR20) as a novel non-tyrosine kinase target in GIST, developed new GPR20 IHC, and assessed GPR20 expression in cell lines, patient-derived xenografts, and clinical samples from two institutes (United States and Japan). We studied GPR20 expression stratified by treatment line, KIT expression, GIST molecular subtype, and primary tumor location.

S1PR3-G-biased agonist ALESIA targets cancer metabolism and promotes glucose starvation.

Metabolic activities are altered in cancer cells compared with those in normal cells, and the cancer-specific pathway becomes a potential therapeutic target. Higher cellular glucose consumption, which leads to lower glucose levels, is a hallmark of cancer cells. In an objective screening for chemicals that induce cell death under low-glucose conditions, we discovered a compound, denoted as ALESIA (Anticancer Ligand Enhancing Starvation-induced Apoptosis).

Examining the Beneficial Aspects of Nutritional Guidance Using Estimated Daily Salt Intake in Cancer Patients with Ischemic Heart Disease.

BACKGROUND The outcomes associated with nutritional guidance for patients with ischemic heart disease undergoing cancer treatment have not been explored. We examined the effects of nutritional guidance using estimated daily salt intake in cancer patients with ischemic heart disease. MATERIAL AND METHODS We examined the data from physical examinations and laboratory assessments of 27 patients with suspected excessive salt intake who underwent coronary angiography for the first time and received nutritional guidance on their next visit to the Department of Cardiology of Shizuoka Cancer Center between May 2018 and March 2020.

Dispersal history of Miniopterus fuliginosus bats and their associated viruses in east Asia.

In this study, we examined the role of the eastern bent-winged bat (Miniopterus fuliginosus) in the dispersion of bat adenovirus and bat alphacoronavirus in east Asia, considering their gene flows and divergence times (based on deep-sequencing data), using bat fecal guano samples. Bats in China moved to Jeju Island and/or Taiwan in the last 20,000 years via the Korean Peninsula and/or Japan. The phylogenies of host mitochondrial D-loop DNA was not significantly congruent with those of bat adenovirus (m2XY = 0.

Novel candidates of pathogenic variants of the BRCA1 and BRCA2 genes from a dataset of 3,552 Japanese whole genomes (3.5KJPNv2).

Identification of the population frequencies of definitely pathogenic germline variants in two major hereditary breast and ovarian cancer syndrome (HBOC) genes, BRCA1/2, is essential to estimate the number of HBOC patients. In addition, the identification of moderately penetrant HBOC gene variants that contribute to increasing the risk of breast and ovarian cancers in a population is critical to establish personalized health care. A prospective cohort subjected to genome analysis can provide both sets of information.

Shape Factor of the Spinal Cord: A Possible Predictor of Surgical Outcome for Intradural Extramedullary Spinal Tumors in the Thoracic Spine.

Study Design: Retrospective diagnostic analysis.

Objectives: To establish a new predictor of surgical outcome after surgery for intradural extramedullary spinal tumor (IDEMT) in the thoracic spine, we introduced shape factor (SF), a mathematical description of the morphology of the spinal cord. SF was calculated by dividing object area by the square of perimeter.

External validation of a genitourinary cancer-specific prognostic scoring system to predict survival for patients with bone metastasis (modified B-FOM scoring model): Comparison with other scoring models in terms of accuracy.

Objective: We previously developed genitourinary (GU) cancer-specific scoring system for prediction of survival in patients with bone metastasis (the Bone-Fujimoto-Owari-Miyake [B-FOM] scoring model) based on five prognostic factors: the type of primary tumor (prostate cancer (PCa) renal cell carcinoma (RCC) and PCa urothelial carcinoma (UC)), poor performance status (PS), visceral metastasis, high Glasgow-prognostic score (GPS), elevated neutrophil-to-lymphocyte ratio (NLR). The aim of this study was to externally validate and further improve the performance of the B-FOM score.

Methods: The external validation cohort comprised 309 patients with GU cancer with bone metastasis from multiple institutions.

Anti-sortilin1 Antibody Up-Regulates Progranulin Sortilin1 Down-Regulation.

Progranulin (PGRN) haploinsufficiency associated with loss-of-function mutations in the granulin gene causes frontotemporal dementia (FTD). This suggests that increasing PGRN levels could have promising therapeutic implications for patients carrying mutations. In this study, we explored the therapeutic potential of sortilin1 (SORT1), a clearance receptor of PGRN, by generating and characterizing monoclonal antibodies against SORT1.