Mechanisms of multidrug resistance caused by an Ipi1 mutation in the fungal pathogen Candida glabrata.

Multidrug resistance in the pathogenic fungus Candida glabrata is a growing global threat. Here, we study mechanisms of multidrug resistance in this pathogen. Exposure of C.

Correction: Awahara et al. The Effects of Side-Chain Configurations of a Retro-Inverso-Type Inhibitor on the Human T-Cell Leukemia Virus (HTLV)-1 Protease. 2022, , 1646.

[...

Decoding Codon Bias: The Role of tRNA Modifications in Tissue-Specific Translation.

The tRNA epitranscriptome has been recognized as an important player in mRNA translation regulation. Our knowledge of the role of the tRNA epitranscriptome in fine-tuning translation via codon decoding at tissue or cell levels remains incomplete. We analyzed tRNA expression and modifications as well as codon optimality across seven mouse tissues.

Novel Variants and Clinical Features of Hearing Loss in a Large Japanese Cohort.

Background/objectives: The gene is responsible for autosomal recessive non-syndromic sensorineural hearing loss and is assigned as DFNB18B. To date, 44 causative variants have been reported to cause non-syndromic hearing loss. However, the detailed clinical features for -associated hearing loss remain unclear.

Impact of Hyaluronic Acid on the Cutaneous T-Cell Lymphoma Microenvironment: A Novel Anti-Tumor Mechanism of Bexarotene.

Background: Cutaneous T-cell lymphoma (CTCL) is a type of non-Hodgkin's lymphoma that primarily affects the skin, rich in hyaluronic acid (HA). HA is a component of the extracellular matrix in the dermis and likely affects the development of CTCL, but the mechanism is poorly understood. Here we show that low-molecular-weight HA (LMWHA) possibly exacerbates CTCL, and bexarotene, already used in CTCL treatment, decreases HA production.

Impact of maternal overweight/obesity and high fasting plasma glucose on adverse perinatal outcomes in early gestational diabetes mellitus.

Aim: To elucidate risk factors associated with adverse perinatal outcomes in early-gestational diabetes mellitus (GDM).

Materials And Methods: A dataset of 385 early-GDM cases from a prospective cohort was analyzed. Early-GDM was diagnosed if one or more of the following criteria were met: fasting plasma glucose (PG) levels of 92-125 mg/dL, 1-h PG levels ≥180 mg/dL, and 2-h PG levels ≥153 mg/dL during a 75-g oral glucose tolerance test before 20 weeks of gestation.

Does Osteonecrosis of the Femoral Head Increase Early Complication Rates After Total Hip Arthroplasty? A Japanese Nationwide Medical Claims Database Study.

Background: Osteonecrosis of the femoral head (ONFH) and osteoarthritis (OA) are two common diagnoses for patients undergoing total hip arthroplasty (THA). The early surgical complications in THA for ONFH compared to OA are inconsistently reported. Therefore, this study aimed to evaluate whether THA for ONFH was associated with early postoperative complications in comparison to THA for OA using a large database of Japanese patients.

Pertuzumab Retreatment for Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced/Metastatic Breast Cancer (PRECIOUS Study): Final Overall Survival Analysis.

In the primary analysis of the open-label phase III PRECIOUS study, pertuzumab retreatment combined with trastuzumab plus chemotherapy of physician's choice (PTC) significantly improved investigator-assessed progression-free survival (PFS) compared with trastuzumab plus physician's choice chemotherapy (TC) in patients with human epidermal growth factor receptor 2 (HER2)-positive locally advanced/metastatic breast cancer (LA/mBC). Here, we report final overall survival (OS) at the median follow-up of 25.8 months.

Rspo3-mediated metabolic liver zonation regulates systemic glucose metabolism and body mass in mice.

The unique architecture of the liver consists of hepatic lobules, dividing the hepatic features of metabolism into 2 distinct zones, namely the pericentral and periportal zones, the spatial characteristics of which are broadly defined as metabolic zonation. R-spondin3 (Rspo3), a bioactive protein promoting the Wnt signaling pathway, regulates metabolic features especially around hepatic central veins. However, the functional impact of hepatic metabolic zonation, regulated by the Rspo3/Wnt signaling pathway, on whole-body metabolism homeostasis remains poorly understood.

Transcriptome-wide alternative mRNA splicing analysis reveals post-transcriptional regulation of neuronal differentiation.

Alternative splicing (AS) plays an important role in neuronal development, function, and disease. Efforts to analyze the transcriptome of AS in neurons on a wide scale are currently limited. We characterized the transcriptome-wide AS changes in SH-SY5Y neuronal differentiation model, which is widely used to study neuronal function and disorders.

Lipidomic profiling of plasma from patients with multiple myeloma receiving bortezomib: an exploratory biomarker study of JCOG1105 (JCOG1105A1).

Purpose: A comprehensive analysis of metabolites (metabolomics) has been proposed as a new strategy for analyzing liquid biopsies and has been applied to identify biomarkers predicting clinical responses or adverse events associated with specific treatments. Here, we aimed to identify metabolites associated with bortezomib (Btz)-related toxicities and response to treatment in newly diagnosed multiple myeloma (MM).

Methods: Fifty-four plasma samples from transplant-ineligible MM patients enrolled in a randomized phase II study comparing two less-intensive regimens of melphalan, prednisolone and Btz (MPB) were subjected to the lipidomic profiling analysis.

CUL4-Based Ubiquitin Ligases in Chromatin Regulation: An Evolutionary Perspective.

Ubiquitylation is a post-translational modification that modulates protein function and stability. It is orchestrated by the concerted action of three types of enzymes, with substrate specificity governed by ubiquitin ligases (E3s), which may exist as single proteins or as part of multi-protein complexes. Although Cullin (CUL) proteins lack intrinsic enzymatic activity, they participate in the formation of active ubiquitin ligase complexes, known as Cullin-Ring ubiquitin Ligases (CRLs), through their association with ROC1 or ROC2, along with substrate adaptor and receptor proteins.

Pain detection using biometric information acquired by a wristwatch wearable device: a pilot study of spontaneous menstrual pain in healthy females.

Objective: Pain is subjective, and self-reporting pain might be challenging. Studies conducted to detect pain using biological signals and real-time self-reports pain are limited. We evaluated the feasibility of collecting pain data on healthy females' menstrual pain and conducted preliminary analysis.

Challenges to promoting maternal respiratory syncytial virus vaccination in Japan.

Pfizer's Abrysvo vaccine is highly effective in preventing severe lower respiratory tract illness in those at high risk from the Respiratory Syncytial Virus (RSV). Japan, like other countries, is promoting RSV vaccination among pregnant women, but it needs to do better. However, Japan is enduring a state of broad vaccine hesitancy.

Reproductive and Hormonal Factors and Thyroid Cancer Risk: Pooled Analysis of Prospective Cohort Studies in the Asia Cohort Consortium.

Given the female predominance of thyroid cancer (TC), particularly in the reproductive age range, female sex hormones have been proposed as an aetiology; however, previous epidemiological studies have shown conflicting results. We conducted a pooled analysis using individual data from 9 prospective cohorts in the Asia Cohort Consortium, to explore the association between 10 female reproductive and hormonal factors and TC risk. Using Cox proportional hazards models, cohort-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated and then pooled using a random-effects model.

Sex-specific effects of prenatal bisphenol A exposure on transcriptome-interactome profiles of autism candidate genes in neural stem cells from offspring hippocampus.

Bisphenol A (BPA), an endocrine-disrupting chemical, is increasingly linked to the pathogenesis of autism spectrum disorder (ASD). This study investigates the effects of prenatal BPA exposure on neural stem cells (NSCs) from the hippocampi of rat offspring, a brain region critical for neurodevelopment and implicated in ASD. Pregnant rats were administered with BPA or vehicle control once daily via oral gavage from gestational day 1 until parturition.

A network analysis of postpartum depression and mother-to-infant bonding shows common and unique symptom-level connections across three postpartum periods.

Postpartum depression and mother-to-infant bonding difficulties (MIBD), two issues crucial to maternal and infant mental health, often coexist and affect each other. Our study aims to dissect their complex relationship through a graphical LASSO network analysis of individual symptoms in 5594 Japanese postpartum women, whose geographical distribution was nationally representative. We identified 'fear', 'enjoyment', 'overwhelm', and 'insomnia' as common bridge symptoms linking postpartum depression and MIBD across three distinct postpartum periods.

Phage therapy could be key to conquering persistent bacterial lung infections in children.

Persistent bacterial lung infections in children lead to significant morbidity and mortality due to antibiotic resistance. In this paper, we describe how phage therapy has shown remarkable efficacy in preclinical and clinical studies, demonstrating significant therapeutic benefits through various administration routes. Ongoing trials are evaluating its safety and effectiveness against different pathogens.

Insights into balloon pulmonary angioplasty and the WHO functional class of chronic thromboembolic pulmonary hypertension patients: findings from the CTEPH AC registry.

Advances in chronic thromboembolic pulmonary hypertension (CTEPH) treatment have improved prognosis, shifting focus towards symptom management. This study aimed to identify factors influencing the World Health Organization functional class (WHO-FC) in CTEPH patients. The CTEPH AC registry is a prospective, multicenter database from 35 Japanese institutions, analyzing data from August 2018 to July 2023.

Viral Membrane-Targeting Amphipathic Helical Peptide-Based Fluorogenic Probes for the Analysis of Infectious Titers of Enveloped Viruses.

Enveloped viruses have caused the majority of epidemics and pandemics over the past decade. Direct sensing of virus particles (virions) holds great potential for the functional analysis of enveloped viruses. Here, we explore a series of viral membrane-targeting amphipathic helical (AH) peptide-based molecular probes for the assessment of infectious titers of the human coronavirus 229E virus (HCoV-229E).

Active withdrawal of corticosteroids using tocilizumab and its association with autoantibody profiles in relapsed Takayasu arteritis: a multicentre, single-arm, prospective study (the Ab-TAK study).

Objectives: The feasibility of corticosteroid withdrawal (CW) for Takayasu arteritis (TAK) remains uncertain. Two autoantibodies (Abs) are identified against endothelial protein C receptor (EPCR) and scavenger receptor class B type 1 (SR-BI) in TAK, determining its three subgroups. This study aimed to evaluate CW using tocilizumab (TCZ) and its association with the Ab profile.

Longitudinal associations between informal caring, social network, and psychological distress among adolescents and young adults: modelling within-person effects.

Background: Informal caring is associated with mental health deterioration among young people and impacts their help-seeking ability. Social network can provide social support and mitigate the impact of informal care. However, young carers may avoid identification and withdraw from social networks.

In-hospital mortality of patients admitted to the intermediate care unit in hospitals with and without an intensive care unit: a nationwide inpatient database study.

Background: Intermediate care units (IMCUs) provide care for patients who need more intensive treatment than general wards but less than intensive care units (ICUs). Although the concept of an IMCU requires co-location with an ICU, some hospitals have IMCUs but no ICUs, which potentially worsens patient outcomes. This study aimed to examine the annual trends and care processes, and compare the outcomes of patients admitted to IMCUs in hospitals with and without ICUs using a nationwide inpatient database in Japan.

Real-time trajectory imaging of alpha particles emitted from actinium-225 and its daughter radionuclides.

In targeted alpha-particle therapy, actinium-225 (Ac-225) has emerged as a radionuclide of potential, driving extensive efforts to develop innovative radiopharmaceuticals. High-resolution imaging of alpha particles is required for precisely detecting alpha-emitting radionuclides in cellular environments and small organs. Here, we report real-time trajectory imaging of alpha particles emitted by Ac-225 and its daughter radionuclides, utilizing an alpha particle trajectory imaging system.