PARP inhibition-associated heterochromatin confers increased DNA replication stress and vulnerability to ATR inhibition in SMARCA4-deficient cells.

DNA replication stress (RS), a prevalent feature of various malignancies, arises from both genetic mutations and genotoxic exposure. Elevated RS levels increase the vulnerability of cancer cells to ataxia telangiectasia and Rad3-related kinase inhibitors (ATRis). Here, we screened for DNA damage response inhibitors that enhance ATRi-induced cytotoxicity using SWI/SNF complex-deficient cells and identified a potent synergy between ATRi and poly(ADP-ribose) polymerase inhibitor (PARPi), particularly in SMARCA4-deficient cells.

Chromosome-scale genome assembly reveals how repeat elements shape non-coding RNA landscapes active during newt limb regeneration.

Newts have large genomes harboring many repeat elements. How these elements shape the genome and relate to newts' unique regeneration ability remains unknown. We present here the chromosome-scale assembly of the 20.

The Arabidopsis Basic-Helix-Loop-Helix Transcription Factor LRL1 Activates Cell Wall-Related Genes during Root Hair Development.

Lotus japonicus-ROOT HAIR LESS1-LIKE1 (LRL1) of Arabidopsis thaliana encodes a basic helix-loop-helix (bHLH) transcription factor (TF) involved in root hair development. Root hair development is regulated by an elaborate transcriptional network, in which GLABRA2 (GL2), a key negative regulator, directly represses bHLH TF genes, including LRL1 and ROOT HAIR DEFECTIVE6 (RHD6). Although RHD6 and its paralogous TFs have been shown to connect downstream to genes involved in cell morphological events such as endomembrane and cell wall modification, the network downstream of LRL1 remains elusive.

[Guidelines for presymptomatic genetic testing for adult-onset hereditary neuromuscular diseases in Japan].

In Japan, there are no nationwide guidelines for presymptomatic testing for hereditary neuromuscular diseases. Although each institution has been dealing with this situation by using their own procedures to date, it is necessary to develop a standardized guidelines based on the Japanese medical system, because the development of disease-modifying therapies has progressed, and we are entering an era in which early diagnosis and early treatment are necessary. The guidelines presented here were devised by the Committee on Medical Genetics of the Japan Neurological Society.

Lactoferrin Modulates Radiation Response Under Hypoxic Conditions, Possibly Through the Regulation of ROS Production in a Cell Type-Specific Manner.

Lactoferrin (LF) is an iron-binding glycoprotein of the transferrin family and has been suggested to have a variety of biological functions, including anticancer activity. However, the effects of LF and its mechanisms in anticancer therapies, especially in radiotherapy against cancer cells under hypoxic conditions, are not well-determined. In this study, we focused on the molecular mechanisms of LF functions in cells under hypoxic conditions.

Imaging characteristics and treatment of recurrent germinoma.

Objective: An MRI protocol for germinoma surveillance after complete remission has not been established. Moreover, the standard treatment for recurrent or refractory germinoma has not been determined. In this study, the authors explored the imaging characteristics of recurrent germinoma and discuss their institution's experience with multidisciplinary treatment of this malignancy.

Influence of Nursing Time and Staffing on Medication Errors: A Cross-Sectional Analysis of Administrative Data.

: Medication errors cause adverse events; however, studies have yet to examine medication errors related to nursing hours while considering ward characteristics in Japan. Purpose: This study investigated medication errors caused by nurses to quantitatively assess ward activity as busyness in nursing duties. : This study considered patients hospitalized in the general wards of 10 National Hospital Organization institutions between April 2019 and March 2020.

Suppressive effect of vitamin K (menatetrenone) against bone mineral density loss after radiotherapy in uterine cancer patients.

Purpose: This study aimed to investigate whether vitamin K (menatetrenone) suppresses bone mineral density (BMD) loss in the irradiated region after radiotherapy (RT) in uterine cancer patients.

Materials And Methods: Our study included 34 patients who underwent whole pelvic irradiation for uterine cancer between 2001 and 2010. The patients were categorized in two groups: (1) Vitamin K (45 mg/day) administration group (group A) with 18 cases and (2) non-administered group (group B) with 16 cases.

Associations of objectively measured physical activity and sedentary time with all-cause mortality in Japanese older adults: a 10-year prospective study.

Objective: To examine the associations of accelerometer-measured physical activity and sedentary time with all-cause mortality in older Japanese adults.

Methods: A total of 1723 independent Japanese adults aged ≥65 years were followed from 2011 to 2021. Moderate-to-vigorous physical activity (MVPA), light physical activity (LPA) and sedentary time were measured using a triaxial accelerometer secured to participants' waists.

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.

PI5P4K inhibitors: promising opportunities and challenges.

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4K), also known as type II PIPKs or PIPKIIs, convert the lipid second messenger PI5P to PI(4,5)P. The PI5P4K family consists of three isozymes in mammals-PI5P4Kα, β, and γ-which notably utilize both GTP and ATP as phosphodonors. Unlike the other two isozymes, which can utilize both ATP and GTP, PI5P4Kβ exhibits a marked preference for GTP over ATP, acting as an intracellular GTP sensor that alters its kinase activity in response to physiological changes in GTP concentration.

Unfolded protein response modulates Tyrosinase levels and melanin production during melanogenesis.

Background: Melanocytes protect the body from ultraviolet radiation by synthesizing melanin. Tyrosinase, a key enzyme in melanin production, accumulates in the endoplasmic reticulum (ER) during melanin synthesis, potentially causing ER stress. However, regulating ER function for melanin synthesis has been less studied than controlling Tyrosinase activity.

The microcephaly-associated transcriptional regulator AUTS2 cooperates with Polycomb complex PRC2 to produce upper-layer neurons in mice.

AUTS2 syndrome is characterized by intellectual disability and microcephaly, and is often associated with autism spectrum disorder, but the underlying mechanisms, particularly concerning microcephaly, remain incompletely understood. Here, we analyze mice mutated for the transcriptional regulator AUTS2, which recapitulate microcephaly. Their brains exhibit reduced division of intermediate progenitor cells (IPCs), leading to fewer neurons and decreased thickness in the upper-layer cortex.

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.

Purpose: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.

Background: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.

New future dental material: Antimicrobial material "cetylpyridinium chloride-montmorillonite" and implantable material "phosphorylated pullulan".

In dental practice, there are two major diseases: dental caries and periodontal disease. Although dental treatment techniques have advanced along with advances in dental materials, some diseases such as root surface caries and horizontal bone resorption have not yet achieved satisfactory treatment results. Since these diseases are infections caused by oral bacteria, we believe that materials with long-lasting antimicrobial properties would help control these diseases.

Advocacy in Action: International Patient Group Improves Hereditary Angioedema Diagnosis and Care Across the Asia-Pacific.

This study demonstrates that patient advocacy groups significantly enhance medication availability and improve diagnosis of hereditary angioedema (HAE), particularly in emerging economies within the Asia-Pacific region. This study supports integrating patient advocacy group involvement into management guidelines, emphasising their role in improving access to diagnostics and treatment for HAE.

Methylglyoxal compromises callus mineralization and impairs fracture healing through suppression of osteoblast terminal differentiation.

Impaired fracture healing in diabetic patients leads to prolonged morbidity and increased healthcare costs. Methylglyoxal (MG), a reactive metabolite elevated in diabetes, is implicated in various complications, but its direct impact on bone healing remains unclear. Here, using a non-diabetic murine tibial fracture model, we demonstrate that MG directly impairs fracture healing.

Effectiveness for remission maintenance rate and safety of different rituximab regimens for treating anti-neutrophil cytoplasmic antibody-associated vasculitis in Japan: a J-CANVAS study.

Rituximab (RTX) has been reported to effectively maintain remission in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). In this multicenter study involving 57 patients who achieved remission after 24 weeks, we evaluated the effectiveness of RTX in maintaining remission in patients with AAV. Patients were divided into three groups based on RTX administration: continuous, induction phase-only, and maintenance phase-only groups.

Impact of Nurse Staffing Levels on Patient Fall Rates: A Retrospective Cross-Sectional Study in General Wards in Japan.

: Falls are common adverse events among hospitalized patients, affecting outcomes and placing a financial burden on patients and hospitals. This study investigated the relationship between nurse staffing/workload and patient falls during hospitalization. : The patients studied were hospitalized in the general wards (excluding pediatrics and obstetrics/gynecology) of 11 National Hospital Organization institutions between April 2019 and March 2020.

Untargeted Mutation Triggered by Ribonucleoside Embedded in DNA.

DNA polymerases frequently misincorporate ribonucleoside 5'-triphosphates into nascent DNA strands. This study examined the effects of an incorporated ribonucleoside on untargeted mutations in human cells. Riboguanosine (rG) was introduced into the downstream region of the gene to preferentially detect the untargeted mutations.

Saliva in Balancing Oral and Systemic Health, Oral Cancer, and Beyond: A Narrative Review.

Saliva plays a multifaceted role in oral health and systemic well-being. It supports digestion, protects oral tissues, maintains a healthy oral microbiome, and facilitates wound healing. Additionally, saliva serves as a diagnostic tool that reflects systemic health and disease/therapeutic states.

Effect of abdominal aortic calcification on long-term outcomes after the first liver resection in very old patients with hepatocellular carcinoma.

Aim: We previously reported that abdominal aortic calcification is associated with poor overall and recurrence-free survival after hepatectomy for hepatocellular carcinoma (HCC). However, the effect of abdominal aortic calcification on cancer-specific prognosis in very old patients with several comorbidities remains unknown. This multicenter study aimed to evaluate the impact of abdominal aortic calcification on the cumulative recurrence rate and recurrence-free survival in patients with HCC aged >80 years.

Predicting Antidepressant Treatment Response From Cortical Structure on MRI: A Mega-Analysis From the ENIGMA-MDD Working Group.

Accurately predicting individual antidepressant treatment response could expedite the lengthy trial-and-error process of finding an effective treatment for major depressive disorder (MDD). We tested and compared machine learning-based methods that predict individual-level pharmacotherapeutic treatment response using cortical morphometry from multisite longitudinal cohorts. We conducted an international analysis of pooled data from six sites of the ENIGMA-MDD consortium (n = 262 MDD patients; age = 36.