Population pharmacokinetic and exposure-response analysis to support a dosing regimen of CPX-351 (NS-87) in Japanese adult and pediatric patients with untreated high-risk acute myeloid leukemia.

CPX-351 (NS-87; Vyxeos®) has a characteristic liposomal formulation and contains cytarabine and daunorubicin at a 5:1 molar ratio, which demonstrates synergistic activity in both in vitro and in vivo animal models. It has been approved in several countries for the treatment of newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). Since there are very few Asian patients, especially Japanese adult and pediatric patients, only a small clinical study has been conducted in Japanese adult patients and no study in Japanese pediatric patients.

Reappraisal of carcinoma in situ residue at the bile duct margin: a single-center review of 681 patients with perihilar cholangiocarcinoma.

Background: A histologically involved surgical margin (R1) is often observed after resection for cholangiocarcinoma. Compared with a negative margin (R0), R1 with invasive carcinoma (R1inv) markedly worsens survival, whereas the prognostic effect of R1 with carcinoma in situ (R1cis) remains controversial.

Methods: Patients who underwent resection for perihilar cholangiocarcinoma between 2002 and 2019 were retrospectively reviewed.

Combined quantitative analysis of the nigro-striata system in multiple system atrophy and Parkinson's disease.

Degeneration of the nigrostriatal system occurs in multiple system atrophy (MSA) and Parkinson's disease (PD) via distinct pathological mechanisms. Here, we investigated nigrostriatal degeneration in MSA and PD by combining a newly developed method for evaluating the regional accumulation of dopamine transporter single-photon emission computed tomography (DAT SPECT) and individual voxel-based morphometry adjusting covariates (iVAC). We recruited 17 MSA patients and 13 PD patients, and compared their clinical and imaging indices.

WO Nanofibers Functionalized with Graphene as a Selective Sensing of NO Gas at Room Temperature.

Recent trends in two-dimensional (2D) graphene have demonstrated significant potential for gas-sensing applications with significantly enhanced sensitivity even at room temperature. Herein, this study presents fabrication of distinctive gas sensor based on one-dimensional (1D) WO nanofibers decorated 2D graphene, specifically coated on copper (Cu)-based interdigitated electrodes formed by DC sputtering, which can selectively detect NO gas at room temperature. The sensor device fabricated using WO/Gr1.

Effects of ankle joint degree of freedom of knee-ankle-foot orthoses on loading patterns and triceps surae muscle activity on the paretic side in individuals with subacute severe hemiplegia: a retrospective study.

Background: Individuals with subacute severe hemiplegia often undergo alternate gait training to overcome challenges in achieving walking independence. However, the ankle joint setting in a knee-ankle-foot orthosis (KAFO) depends on trunk function or paralysis stage for alternate gait training with a KAFO. The optimal degree of ankle joint freedom in a KAFO and the specific ankle joint conditions for effective rehabilitation remain unclear.

Loss of Trefoil Factor 1 Accelerates the Immune Response to Colorectal Cancer.

Background/aim: Recent studies suggest that PD-L1 expression in immune cells, rather than tumor cells, plays a key role in tumor immunity. Trefoil factor family 1 (TFF1) is a secreted protein expressed mainly by the gastrointestinal epithelium and is related to the development of malignant disease. This study investigated the effects of TFF1 on tumor immunity in a xenograft mouse model of colorectal cancer (CRC).

Neuro-mesenchymal interaction mediated by a β2 adrenergic-nerve growth factor feedforward loop promotes colorectal cancer progression.

Cancer-associated fibroblasts (CAFs) and nerves, components of the tumor microenvironment, have each been shown to directly promote gastrointestinal cancers. However, it remains unknown whether these cells interact with each other to regulate cancer progression. We found that in colorectal cancer (CRC) norepinephrine induces ADRB2-dependent nerve growth factor (NGF) secretion from CAFs, which in turn increases intra-tumor sympathetic innervation and norepinephrine accumulation.

Disruption of insulin receptor substrate 2 (IRS2) causes non-obese type 2 diabetes with β-cell dysfunction in the golden (Syrian) hamster.

Because of the advent of genome-editing technology, gene knockout (KO) hamsters have become attractive research models for diverse diseases in humans. This study established a new KO model of diabetes by disrupting the insulin receptor substrate-2 (Irs2) gene in the golden (Syrian) hamster. Homozygous KO animals were born alive but with delayed postnatal growth until adulthood.

An Infant With COVID-19 Presenting With a Bulging Fontanel: A Case Report and Literature Review.

A bulging fontanel is a sign of elevated intracranial pressure, which can be caused by diseases with intracranial fluid retention or swelling of the cerebral parenchyma. We experienced a case of an infant with a typical course of mild coronavirus disease 2019 (COVID-19) but with a bulging fontanel as a finding at presentation. The patient, a three-month-old boy with no underlying conditions, presented to the emergency clinic with fever, vomiting, and loss of appetite.

TLK1 Inhibition Enhances the Anticancer Effect of Deep UV Irradiation Through CHK1 Activation.

Background/aim: A deep ultraviolet (DUV) light-emitting diode (LED) is a device that can irradiate electromagnetic waves from 250 nm to 350 nm. Tousled-like kinase 1 (TLK1) encodes a nuclear serine/threonine kinase, which is thought to influence the effects of DUV irradiation in cancer. The aim of this study was to clarify the interaction of TLK1 with DUV irradiation-induced DNA damage in cancer cells.

Sedentary behaviour may cause differences in physical outcomes and activities of daily living in older cardiovascular disease patients participating in phase I cardiac rehabilitation.

This study aimed to investigate the rate of sedentary behaviour and differences in physical outcomes and activities of daily living (ADL) based on sedentary behaviour time of hospitalized older cardiovascular disease patients undergoing phase I cardiac rehabilitation. Older cardiovascular disease patients were enrolled from October 2020 to September 2023 and were divided into the high sedentary behaviour group (≥ 480 min/day) and low sedentary behaviour group (< 480 min/day). Patients' clinical characteristics, usual gait speed, and Five Times Sit to Stand Test time were compared as indices of physical outcomes.

Trefoil factor 1 suppresses stemness and enhances chemosensitivity of pancreatic cancer.

Background And Aims: Pancreatic cancer is one of the most lethal malignancies, partly due to resistance to conventional chemotherapy. The chemoresistance of malignant tumors is associated with epithelial-mesenchymal transition (EMT) and the stemness of cancer cells. The aim of this study is to investigate the availability and functional mechanisms of trefoil factor family 1 (TFF1), a tumor-suppressive protein in pancreatic carcinogenesis, to treat pancreatic cancer.

promotes zygotic genome activation upon loss of .

Once fertilized, mouse zygotes rapidly proceed to zygotic genome activation (ZGA), during which long terminal repeats (LTRs) of murine endogenous retroviruses with leucine tRNA primer (MERVL) are activated by a conserved homeodomain-containing transcription factor, DUX. However, -knockout embryos produce fertile mice, suggesting that ZGA is redundantly driven by an unknown factor(s). Here, we present multiple lines of evidence that the multicopy homeobox gene, , encodes a transcription factor that is highly expressed in mouse two-cell embryos and redundantly drives ZGA.

Reduction of H3K9 methylation by G9a inhibitors improves the development of mouse SCNT embryos.

Removal of somatic histone H3 lysine 9 trimethylation (H3K9me3) from the embryonic genome can improve the efficiency of mammalian cloning using somatic cell nuclear transfer (SCNT). However, this strategy involves the injection of histone demethylase mRNA into embryos, which is limiting because of its invasive and labor-consuming nature. Here, we report that treatment with an inhibitor of G9a (G9ai), the major histone methyltransferase that introduces H3K9me1/2 in mammals, greatly improved the development of mouse SCNT embryos.

Superovulation with an anti-inhibin monoclonal antibody improves the reproductive performance of rat strains by increasing the pregnancy rate and the litter size.

Rats are multiparous rodents that have been used extensively in research; however, the low reproductive performance of some rat strains hampers the broader use of rats as a biomedical model. In this study, the possibility of increasing the litter size after natural mating in rats through superovulation using an anti-inhibin monoclonal antibody (AIMA) was examined. In outbred Wistar rats, AIMA increased the number of ovulated oocytes by 1.

Antiproliferative activities through accelerating autophagic flux by basidalin and its analogs in human cancer cells.

Basidalin, isolated from the basidiomycete Leucoagaricus naucina, has previously demonstrated antibacterial and antitumor properties against murine cancer cells in vivo, but its effects on human cancer cells remain unknown. In this study, we found that basidalin possesses antiproliferative activity against human cancer cell lines. To elucidate the antiproliferative mechanism of basidalin, we focused on autophagy.

Restoration of fertility in nonablated recipient mice after spermatogonial stem cell transplantation.

Spermatogonial stem cell (SSC) transplantation is a valuable tool for studying stem cell-niche interaction. However, the conventional approach requires the removal of endogenous SSCs, causing damage to the niche. Here we introduce WIN18,446, an ALDH1A2 inhibitor, to enhance SSC colonization in nonablated recipients.

Prediction model of the risk for lateral local recurrence in locally advanced rectal cancer without enlarged lateral lymph nodes: Lessons from a Japanese multicenter pooled analysis of 812 patients.

Aim: Although the oncological impact of lateral lymph node dissection on enlarged lateral lymph nodes has been gradually accepted over the last decade, that on lateral lymph nodes without swelling remains doubtful. This study aimed to develop a prediction model for the future risk of lateral local recurrence and to clarify the value of adding lateral lymph node dissection in locally advanced rectal cancer without enlarged lateral lymph nodes.

Methods: This retrospective, multi-institutional study recruited 812 patients with cStage II/III low rectal cancer without enlarged lateral lymph nodes <7 mm.

Inter-subspecies mouse F1 hybrid embryonic stem cell lines newly established for studies of allelic imbalance in gene expression.

Allele-specific monoallelic gene expression is a unique phenomenon and a great resource for analyzing gene regulation. To study this phenomenon, we established new embryonic stem (ES) cell lines derived from F1 hybrid blastocysts from crosses between four mouse subspecies (Mus musculus domesticus, C57BL/6; M. musculus molossinus, MSM/Ms; M.