Robust circulating microRNA signature for the diagnosis and early detection of pancreatobiliary cancer.

Background: A new circulating biomarker superior to carbohydrate antigen 19-9 (CA19-9) is needed for diagnosing pancreatobiliary cancer (PBca). The aim of this study was to identify serum microRNA (miRNA) signatures comprising reproducible and disease-related miRNAs.

Methods: This multicenter study involved patients with treatment-naïve PBca and healthy participants.

A Japanese family of hereditary diffuse gastric cancer with a germline pathogenic variant of CTNN1A detected via comprehensive genome profiling.

CTNNA1 codes α-1 catenin, a molecule that functions in intercellular adhesion in combination with E-cadherin (coded by CDH1). A germline pathogenic variant (GPV) of CTNNA1 increases the risk of hereditary diffuse gastric cancer (HDGC); however, this GPV has not been reported in Japan. A 35-year-old Japanese man with an advanced gastric cancer underwent comprehensive genome profiling (CGP), which led to the detection of a CTNNA1 GPV (p.

Efficacy and safety of avalglucosidase alfa in Japanese patients with late-onset and infantile-onset Pompe diseases: A case series from clinical trials.

Background: The efficacy and safety of avalglucosidase alfa for Pompe disease (PD) have been demonstrated in a global Phase 3 trial (COMET) in patients with late-onset PD (LOPD) and a global Phase 2 trial (Mini-COMET) in patients with infantile-onset PD (IOPD). This case series examines the individual results of three Japanese patients enrolled in these trials.

Methods: Case reports were assembled from data collected in the COMET and Mini-COMET trials.

DDX1 is required for non-spliceosomal splicing of tRNAs but not of XBP1 mRNA.

RNA helicase DEAD-box helicase 1 (DDX1) forms a complex with the RNA ligase 2´,3´-cyclic phosphate and 5´-OH ligase (RTCB), which plays a vital role in non-spliceosomal splicing of tRNA and X-box binding protein 1 (XBP1) mRNA. However, the importance of DDX1 in non-spliceosomal splicing has not been clarified. To analyze the functions of DDX1 in mammalian cells, we generated DDX1 cKO cells from the polyploid human U2OS cell line and found that splicing of intron-containing tRNAs was significantly disturbed in DDX1-deficient cells, whereas endoplasmic reticulum (ER) stress-induced splicing of XBP1 mRNA was unaffected.

Immediate effectiveness of condoliase chemonucleolysis for lumbar disc herniation: a comparative study between patients with difficulty walking because of severe leg pain and those who can walk.

Surgery is often the treatment of choice for lumbar disc herniation (LDH) with severe leg pain. This study aimed to investigate the efficacy of Condoliase chemonucleolysis (CC) in patients who were nonambulatory because of severe leg pain. A total of 58 patients who underwent CC for conservative treatment-resistant LDH were included in this study.

Clinical characteristics affecting weight loss in an East Asian population receiving semaglutide: A STEP 6 subgroup analysis.

Objective: To explore the effects of semaglutide versus placebo on body weight (BW) by subgroups of baseline characteristics.

Methods: In STEP 6, Japanese and Korean adults with overweight or obesity were randomized to subcutaneous semaglutide 2.4 mg, semaglutide 1.

Impact of switching from bisphosphonates to denosumab, teriparatide, or romosozumab in patients with postmenopausal osteoporosis: a case-control study.

Unlabelled: This case-control study investigated the impact of switching from bisphosphonates to denosumab, teriparatide, or romosozumab in postmenopausal osteoporosis. Romosozumab demonstrated the most significant improvements in bone mineral density, particularly in the lumbar spine and total hip, by reducing bone resorption and increasing bone formation markers.

Purpose: To investigate the impact of switching from bisphosphonates (BP) to denosumab (DMAb), teriparatide (TPTD), or romosozumab (ROMO) in postmenopausal osteoporosis.

Untreated and uncontrolled hypertension in Japanese patients with spontaneous intracerebral hemorrhage.

Hypertension (HT) is the most attributable and modifiable risk factor for spontaneous intracerebral hemorrhage (SICH). However, epidemiological data on blood pressure (BP) control before SICH and its relationship to patient lifestyles are lacking. This study prospectively enrolled patients with acute SICH from six stroke centers in Tochigi, Japan.

Pharmacovigilance Pregnancy Data in a Population of Japanese Patients With Chronic Inflammatory Disease Exposed to Certolizumab Pegol.

Aim: Uncontrolled chronic inflammatory diseases (CIDs) before, during, and after pregnancy, as well as some CID medications, can increase the risk of impaired fertility in addition to adverse maternal/pregnancy outcomes in women of childbearing age. We report pregnancy outcomes from prospectively reported pregnancies in Japanese women treated with certolizumab pegol (CZP).

Methods: Data from July 2001 to November 2020 on CZP-exposed pregnancies from the CZP Pharmacovigilance safety database were reviewed.

-A152T mutation drives neuronal hyperactivity through Fyn-NMDAR signaling in human iPSC-Derived neurons: Insights into Alzheimer's pathogenesis.

Introduction: Tau protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) and in regulating neuronal excitability. Among tau-coding microtubule associated protein tau () gene mutations, the A152T mutation is reported to increase the risk of AD and neuronal excitability in mouse models.

Methods: To investigate the effects of gene expression and its mutations on neuronal activity in human neurons, we employed genome editing technology to introduce the A152T or P301S mutations into induced pluripotent stem cells (iPSCs).

Urolithin A Modulates PER2 Degradation via SIRT1 and Enhances the Amplitude of Circadian Clocks in Human Senescent Cells.

Background/objectives: Circadian clocks are endogenous systems that regulate numerous biological, physiological, and behavioral events in living organisms. Aging attenuates the precision and robustness of circadian clocks, leading to prolonged and dampened circadian gene oscillation rhythms and amplitudes. This study investigated the effects of food-derived polyphenols such as ellagic acid and its metabolites (urolithin A, B, and C) on the aging clock at the cellular level using senescent human fibroblast cells, TIG-3 cells.

Detection of Human GPCR Activity in Drosophila S2 Cells Using the Tango System.

G protein-coupled receptors (GPCRs) are essential cell surface proteins involved in transducing extracellular signals into intracellular responses, regulating various physiological processes. This study validated the use of the Tango assay, a sensitive method for detecting GPCR activation, in Schneider 2 (S2) cells, focusing on the human Dopamine Receptor D4 (DRD4). Plasmids encoding the LexA-tagged human DRD4 receptor and a luciferase reporter were co-transfected into S2 cells and stimulated with dopamine.

Serial Changes in Cranial Asymmetry During Helmet Therapy for Deformational Plagiocephaly.

Background: To analyze the serial changes in cranial asymmetry (CA) during helmet therapy for deformational plagiocephaly (DP).

Methods: The subjects were 159 patients with DP who visited National Center for Child Health and Development between October 2011 and March 2014 and completed helmet therapy. The authors retrospectively collected information from medical records and analyzed the rate of improvement of deformation.

A mixed-methods study comparing human-led and ChatGPT-driven qualitative analysis in medical education research.

Qualitative research, used to analyse non-numerical data including interview texts, is crucial in understanding medical education processes. However, it is often complex and time-consuming, leading to an interest in technology for streamlining the analysis. This study investigated the applicability of ChatGPT, a large language model, in thematic analysis for medical qualitative research.

Management, biomarkers and prognosis in people developing endocrinopathies associated with immune checkpoint inhibitors.

Immune-related adverse events (irAEs), including endocrine irAEs, can occur in response to cancer immunotherapy using immune checkpoint inhibitors (ICIs). Of the endocrine irAEs, pituitary and thyroid irAEs are most frequently observed, followed by primary adrenal insufficiency, type 1 diabetes mellitus and hypoparathyroidism. Notably, pituitary irAEs and type 1 diabetes mellitus can be lethal if overlooked, potentially leading to adrenal crisis and diabetic ketoacidosis, respectively.

The real-world efficacy and safety of frontline therapy of obinutuzumab plus bendamustine for untreated high-tumor-burden follicular lymphoma.

Background: While R-CHOP has been one of the standard therapies for untreated high-tumor-burden (HTB) follicular lymphoma (FL) for over 2 decades, obinutuzumab plus bendamustine (OB) is also currently regarded as the standard of care since its approval in 2018 in Japan; however, the long-term efficacy and safety of OB in the daily clinical practice has not been thoroughly evaluated.

Methods: We conducted a multicenter retrospective study for the clinical outcome of 53 patients with HTB FL treated by OB as the frontline therapy between 2018 and 2021 in the Kyoto Hematology Clinical Study Group (KOTOSG). All patients had at least 2-year follow-up period.

MARCH8 Restricts RSV Replication by Promoting Cellular Apoptosis Through Ubiquitin-Mediated Proteolysis of Viral SH Protein.

Numerous host factors function as intrinsic antiviral effectors to attenuate viral replication. MARCH8 is an E3 ubiquitin ligase that has been identified as a host restriction factor that inhibits the replication of various viruses. This study elucidated the mechanism by which MARCH8 restricts respiratory syncytial virus (RSV) replication through selective degradation of the viral small hydrophobic (SH) protein.

A Mutation in the Herpes Simplex Virus Type 1 (HSV-1) UL29 Gene is Associated with Anti-Herpesvirus Drugs' Susceptibility.

Herpes simplex virus type 1 (HSV-1) acyclovir (ACV) resistance is acquired by mutations in the viral thymidine kinase (TK) or DNA polymerase (DNApol) genes. We previously obtained an ACV-resistant clone (HSV-1_VZV_TK_clone α) by sequential passages of HSV-1_VZV-TK, a recombinant virus which lacked its endogenous TK activity and instead expressed the varicella-zoster virus (VZV) TK ectopically. HSV-1_VZV_TK_clone α had been generated using an HSV-1_BAC in the presence of increasing concentrations of ACV.

Development of Hemispherical 3D Models of Human Brain and B Cell Lymphomas Using On-Chip Cell Dome System.

Lymphocytes are generally non-adherent. This makes it challenging to fabricate three-dimensional (3D) structures mimicking the three-dimensional lymphoma microenvironment in vivo. This study presents the fabrication of a hemispherical 3D lymphoma model using the on-chip Cell Dome system with a hemispherical cavity (1 mm in diameter and almost 300 µm in height).

Cutoffs on severity metrics for minimal manifestations or better status in patients with generalized myasthenia gravis.

International consensus guidance and Japanese clinical guidelines for myasthenia gravis (MG) recommend achieving minimal manifestations or better status (MM-or-better) as the severity component of the treatment goal. However, the subjective nature of determining MM can result in ambiguity regarding this category in clinical practice and clinical trials. This study analyzed severity metrics in a large number of MG patients to propose criteria for MM-or-better.

Four-dimensional anatomical spinal reconstruction using pre-bent rods in thoracic adolescent idiopathic scoliosis.

A four-dimensional (4D) anatomical spinal reconstruction (ASR) technique and anatomical notch-free, pre-bent rods have been developed for thoracic adolescent idiopathic scoliosis (AIS) surgery. We aimed to evaluate the outcomes of ASR using notch-free rods through multiple comparisons with conventional methods, including the simultaneous double-rod rotation technique (SDRRT) and ASR using manually bent notched rods. Three consecutive series of 126 patients who underwent surgery for Lenke 1 AIS curves were prospectively followed up for 2 years after surgery.

Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study.

Background: Vosoritide is a C-type natriuretic peptide analog that addresses an underlying pathway causing reduced bone growth in achondroplasia. Understanding the vosoritide treatment effect requires evaluation over an extended duration and comparison with outcomes in untreated children.

Methods: After completing ≥6 months of a baseline observational growth study and 52 weeks in a double-blind, placebo-controlled study (ClinicalTrials.

Downregulation of semaphorin 4A in keratinocytes reflects the features of non-lesional psoriasis.

Psoriasis is a multifactorial disorder mediated by IL-17-producing T cells, involving immune cells and skin-constituting cells. Semaphorin 4A (Sema4A), an immune semaphorin, is known to take part in T helper type 1/17 differentiation and activation. However, Sema4A is also crucial for maintaining peripheral tissue homeostasis and its involvement in skin remains unknown.