Prognostic impact of circulating tumor DNA status post-allogeneic hematopoietic stem cell transplantation in AML and MDS.

This study was performed to assess the utility of tumor-derived fragmentary DNA, or circulating tumor DNA (ctDNA), for identifying high-risk patients for relapse of acute myeloid leukemia and myelodysplastic syndrome (AML/MDS) after undergoing myeloablative allogeneic hematopoietic stem cell transplantation (alloSCT). We retrospectively collected tumor and available matched serum samples at diagnosis and 1 and 3 months post-alloSCT from 53 patients with AML/MDS. After identifying driver mutations in 51 patients using next-generation sequencing, we designed at least 1 personalized digital polymerase chain reaction assay per case.

A Bayesian model integration for mutation calling through data partitioning.

Motivation: Detection of somatic mutations from tumor and matched normal sequencing data has become among the most important analysis methods in cancer research. Some existing mutation callers have focused on additional information, e.g.

Progesterone receptor expression in proliferating cancer cells of hormone-receptor-positive breast cancer.

Breast cancer has been suggested to have two distinct driving mechanisms: the hormone receptor and the growth factor receptor pathways. We hypothesized that each driving system produces a different expression pattern of estrogen-regulated genes, such as progesterone receptor, in proliferating cells. Progesterone receptor and Ki67 expressions were assessed by dual-fluorescence immunohistochemistry in estrogen-receptor-positive breast cancer tissues.

Pressure response of the THz spectrum of bulk liquid water revealed by intermolecular instantaneous normal mode analysis.

The radial distribution functions of liquid water are known to change significantly their shape upon hydrostatic compression from ambient conditions deep into the kbar pressure regime. It has been shown that despite their eye-catching changes, the fundamental locally tetrahedral fourfold H-bonding pattern that characterizes ambient water is preserved up to about 10 kbar (1 GPa), which is the stability limit of liquid water at 300 K. The observed increase in coordination number comes from pushing water molecules into the first coordination sphere without establishing an H-bond, resulting in roughly two such additional interstitial molecules at 10 kbar.

Differential Involvement of Autophagy and Apoptosis in Response to Chemoendocrine and Endocrine Therapy in Breast Cancer: JBCRG-07TR.

Endocrine therapy is an essential component in the curative treatment of hormone receptor (HR)-positive breast cancer. To improve treatment efficacy, the addition of metronomic chemotherapy has been tested and shown to improve therapeutic effects. To better understand cellular reactions to metronomic chemoendocrine therapy, we studied autophagy-related markers, beclin 1 and LC3, and apoptosis-related markers, TUNEL and M30, in pre- and post-treatment cancer tissues from a multicenter neoadjuvant trial, JBCRG-07, in which oral cyclophosphamide plus letrozole were administered to postmenopausal patients with HR-positive breast cancer.

CMCdG, a Novel Nucleoside Analog with Favorable Safety Features, Exerts Potent Activity against Wild-Type and Entecavir-Resistant Hepatitis B Virus.

We designed, synthesized, and characterized a novel nucleoside analog, (1,3,5)-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-5-hydroxy-1-(hydroxymethyl)-2-methylene-cyclopentanecarbonitrile, or 4'-cyano-methylenecarbocyclic-2'-deoxyguanosine (CMCdG), and evaluated its anti-hepatitis B virus (anti-HBV) activity, safety, and related features. CMCdG's activity was determined using quantitative PCR and Southern blotting assays, and its cytotoxicity was determined with a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, while its activity and safety were determined in human liver-chimeric mice infected with wild-type HBV genotype Ce (HBV) and an entecavir (ETV)-resistant HBV variant containing the amino acid substitutions L180M, S202G, and M204V (HBV). CMCdG potently inhibited HBV production in HepG2.

Robust Sample-Specific Stability Selection with Effective Error Control.

Identifying individual characteristics is a crucial issue in personalized genome research. To effectively identify sample-specific characteristics, we propose a novel strategy called robust sample-specific stability selection. Although stability selection shows effective feature selection results and has attractive theoretical property (i.

Antigen delivery targeted to tumor-associated macrophages overcomes tumor immune resistance.

Immune checkpoint inhibitors and adoptive transfer of gene-engineered T cells have emerged as novel therapeutic modalities for hard-to-treat solid tumors; however, many patients are refractory to these immunotherapies, and the mechanisms underlying tumor immune resistance have not been fully elucidated. By comparing the tumor microenvironment of checkpoint inhibition-sensitive and -resistant murine solid tumors, we observed that the resistant tumors had low immunogenicity. We identified antigen presentation by CD11b+F4/80+ tumor-associated macrophages (TAMs) as a key factor correlated with immune resistance.

Synthesis, Anti-HBV, and Anti-HIV Activities of 3'-Halogenated Bis(hydroxymethyl)-cyclopentenyladenines.

Synthesis of 3'-halogeno analogues (-) of 9-[-4,-5-bis(hydroxymethyl)-cyclopent-2-en--1-yl]-9-adenine (BCA, ) was accomplished by means of dual utilization of the vinyl sulfone functional moieties in both and utilizing a S2' conjugate-addition reaction and a sulfur-extrusive stannylation, respectively. Evaluation of the antiviral activities of - revealed that introduction of a halogeno-substituent into the 3'-position of (-)-BCA diminished its anti-HIV-1 activity but increased the inhibitory activity for the reverse transcriptase of HBV in that the 3'-fluorinated BCA exhibited the highest activity without significant cytotoxicity.

Orientational Distribution of Free O-H Groups of Interfacial Water is Exponential.

The orientational distribution of free O-H (O-D) groups at the H_{2}O- (D_{2}O-)air interface is investigated using combined molecular dynamics (MD) simulations and sum-frequency generation (SFG) experiments. The average angle of the free O-H groups, relative to the surface normal, is found to be ∼63°, substantially larger than previous estimates of 30°-40°. This discrepancy can be traced to erroneously assumed Gaussian or stepwise orientational distributions of free O-H groups.

Further Evidence Regarding the Important Role of Chlorine Atoms of Aripiprazole on Binding to the Site II Area of Human Albumin.

Previously, we reported on the high-affinity binding of aripiprazole (ARP), an antipsychotic drug, to human albumin and the role of the chlorine atom of ARP on this binding. In this study, we investigated the binding mode of ARP to human albumin in detail using ARP derivatives and several animal-derived albumins. ARP bound strongly to human and dog albumin.

Structure and Dynamics of Water at the Water-Air Interface Using First-Principles Molecular Dynamics Simulations within Generalized Gradient Approximation.

First-principles molecular dynamics simulations within the density functional theory framework have been used to predict the surface structure of water at various aqueous interfaces, but there is no clear consensus on the choice of appropriate simulation parameters, such as exchange-correlation functions and van der Waals corrections yet. Here, we report the systematic survey for the structure and dynamics of water at the water-air interface simulated with various combinations of the exchange-correlation functionals within the generalized gradient approximation and empirical dispersion corrections. Particularly, we focus on the structure and dynamics of the free O-D group of DO, as well as the surface tension of water.

Risk Factors for Skin Flap Necrosis in Breast Cancer Patients Treated with Mastectomy Followed by Immediate Breast Reconstruction.

Background: Skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) are the standard techniques for achieving a cosmetic outcome, but necrosis of a cutaneous flap including the nipple-areolar complex (NAC) is a serious complication. To analyze the risk factors for skin flap necrosis, we retrospectively evaluated a clinical database of breast cancer patients treated with mastectomy followed by immediate breast reconstruction.

Methods: Four hundred and twelve cases were consecutively recorded between 2006 and 2016.

Analysis of the Binding of Aripiprazole to Human Serum Albumin: The Importance of a Chloro-Group in the Chemical Structure.

Aripiprazole (ARP), a quinolinone derivative, is an atypical antipsychotic drug that is used in the treatment of schizophrenia. ARP has an extensive distribution and more than 99% of the ARP and dehydro-ARP, the main active metabolite, is bound to plasma proteins. However, information regarding the protein binding of ARP is limited.

ALPHLARD: a Bayesian method for analyzing HLA genes from whole genome sequence data.

Background: Although human leukocyte antigen (HLA) genotyping based on amplicon, whole exome sequence (WES), and RNA sequence data has been achieved in recent years, accurate genotyping from whole genome sequence (WGS) data remains a challenge due to the low depth. Furthermore, there is no method to identify the sequences of unknown HLA types not registered in HLA databases.

Results: We developed a Bayesian model, called ALPHLARD, that collects reads potentially generated from HLA genes and accurately determines a pair of HLA types for each of HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, and -DRB1 genes at 3rd field resolution.

Detection of activated neutrophils by reactive oxygen species production using a hematology analyzer.

Neutrophils are recruited to infection sites and kill bacteria by phagocytosis and reactive oxygen species (ROS) production. It has been reported that vacuoles are present in neutrophils that produce ROS and are present in large numbers in blood smears of patients with bacterial infections. The leukocyte differentiation function on the Sysmex automated hematology analyzer classifies leukocytes by flow cytometry.

Cell-lineage level-targeted sequencing to identify acute myeloid leukemia with myelodysplasia-related changes.

Acute myeloid leukemia (AML) is a clonal myeloid neoplasm that typically arises de novo; however, some cases evolve from a preleukemic state, such as myelodysplastic syndrome (MDS). Such secondary AMLs and those with typical MDS-related clinical features are known as AMLs with myelodysplasia-related changes (AML-MRC). Because patients with AML-MRC have poor prognosis, more accurate diagnostic approaches are required.

Long-term influence of adjuvant breast radiotherapy on cognitive function in breast cancer patients treated with conservation therapy.

Background: The mechanisms underlying cognitive decline after radiotherapy not directed at brain areas remains unclear. We previously suggested that adjuvant breast radiotherapy in breast conservation therapy could lower memory function soon after therapy, and that the process might be partially mediated by plasma interleukin (IL)-6 levels. The present study investigated how that relationship changes longitudinally.

Circulating tumor DNA dynamically predicts response and/or relapse in patients with hematological malignancies.

A growing body of evidence suggests that tumor-derived fragmentary DNA, known as circulating tumor DNA (ctDNA), has the potential to serve as a non-invasive biomarker for disease monitoring. However, in the setting of hematological malignancy, few published studies support the utility of ctDNA. We retrospectively investigated ctDNA levels of 17 patients with various hematological malignancies who had achieved remission after first-line therapy.

Pharmacokinetic properties of a novel inosine analog, 4'-cyano-2'-deoxyinosine, after oral administration in rats.

4'-cyano-2'-deoxyinosine (SK14-061a), a novel nucleoside analog based on inosine, has antiviral activity against the human immunodeficiency virus type 1 that has the ability to acquire resistance against many types of reverse transcriptase inhibitors based on nucleosides. The aim of this study was to investigate the pharmacokinetics studies after its oral administration to rats. For this purpose, we first developed and validated an analytical method for quantitatively determining SK14-061a levels in biological samples by a UPLC system interfaced with a TOF-MS system.