PP2A adapter protein IER5 induces dephosphorylation and degradation of MDM2, thereby stabilizing p53.

The tumor suppressor p53 activates transcription of the IER5 gene, which encodes an adapter protein of protein phosphatase PP2A. IER5 binds to both the B55 regulatory subunit of PP2A and PP2A's target proteins, facilitating PP2A/B55-catalyzed dephosphorylation of these proteins. Here, we show that IER5 functions as a positive regulator of p53 by inhibiting its ubiquitination, thereby increasing cellular p53 levels.

Postoperative adjuvant chemotherapy in patients with gastric cancer based on the Nationwide Gastric Cancer Registry in Japan.

The nationwide registry of the Japanese Gastric Cancer Association contains data related to the efficacy of adjuvant chemotherapy and prognostic factors across this patient population; elderly patients with advanced resectable gastric cancer are especially prevalent. Here, we analyzed data from 34,931 patients, who were treated between 2011 and 2013 at 421 hospitals in Japan. Although adjuvant chemotherapy was effective overall, 75 years or older elderly patients had a worse prognosis compared to younger patients.

The association of fasting triglyceride variability with renal dysfunction and proteinuria in medical checkup participants.

Background: The association between the variability of triglyceride (TG) and chronic kidney disease (CKD) progression remains unclear. We examined whether intraindividual variability in fasting TG was associated with the exacerbation of CKD.

Methods: We conducted a retrospective and observational study.

Corrigendum to' The association of agricultural and non-agricultural work on the healthy ageing of older adults in Japan: A 6-year longitudinal study from the Japan Gerontological evaluation study'.

[This corrects the article DOI: 10.1016/j.pmedr.

Design and evaluation of a supramolecular boron compound using a cyclodextrin-based polyrotaxane for boron neutron capture therapy.

Boron neutron capture therapy (BNCT) has recently attracted attention as a new cancer treatment option. In BNCT, boron compounds need to accumulate efficiently in tumor tissues to achieve excellent therapeutic effects. Therefore, it is highly desirable to develop a technology that can selectively and efficiently deliver boron compounds to tumors.

Intrahepatic Cholangiocarcinoma with Mutation Achieved Pathological Complete Response after Neoadjuvant Gemcitabine, Cisplatin, and S-1 Therapy: A Case Report.

Introduction: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant cancer for which surgery is the only curative treatment. The prognosis of ICC is extremely poor, especially in cases of lymph node metastasis (LNM), owing to the high postoperative recurrence rate. Herein, we present a case of advanced ICC with a breast cancer susceptibility gene-2 () mutation, treated with preoperative chemotherapy, including cisplatin, followed by surgery, in which we achieved a pathologic complete response.

Updated insights into the impact of adjuvant chemotherapy on recurrence and survival after curative resection of liver or lung metastases in colorectal cancer: a rapid review and meta-analysis.

Background: Colorectal cancer (CRC) frequently metastasizes to the liver and lungs, leading to poor prognosis. Advances in chemotherapy, minimally invasive surgery, and perioperative care have expanded adjuvant chemotherapy (AC) regimens and eligibility for AC. However, the impact of AC after curative resection of distant metastases on recurrence and prognosis remains uncertain.

Investigating the synergistic effects of immunochemotherapy in esophageal squamous cell carcinoma.

Background: Although combinations of immune-checkpoint inhibitors (ICI) with chemotherapy have been approved for esophageal squamous cell carcinoma (ESCC), it remains unclear whether immunochemotherapy (ICT) offers advantages over the simple addition of individual monotherapies. This study aimed to investigate whether ICT exhibits a synergistic effect in patients with advanced ESCC.

Methods: Reconstructed individual patient data of 3330 patients were electronically extracted from the Kaplan-Meier (KM) curves of eight randomized-controlled trials (ATTRACTION-3, CheckMate648, KEYNOTE-181, KEYNOTE-590, RATIONALE-302, RATIONALE-306, ESCORT, and ESCORT-1st).

Risk of falls associated with non-GABAergic hypnotics and benzodiazepines in hospitalized patients.

Objective: Non-GABAergic hypnotics introduced into clinical practice within the last two decades are pharmacologically presumed to have a lower risk of falls, but clinical investigations are scarce. We aimed to evaluate the risk of falls associated with different classes of hypnotics, namely benzodiazepines, ramelteon, suvorexant, and trazodone, in hospitalized individuals at a general hospital.

Method: In this retrospective cohort study, data on the incidence of falls, hypnotic use, age, sex, body mass index (BMI), activities of daily living (ADL) score, presence of surgery, emergency admission, and ambulance use were collected for hospitalized patients aged 20 years or older who had been discharged from a tertiary general hospital in Japan between April 1, 2014, and March 31, 2019.

Siponimod inhibits microglial inflammasome activation.

Siponimod is the first oral drug approved for active secondary progressive multiple sclerosis. It acts as a functional antagonist of sphingosine-1-phosphate (S1P) receptor 1 (S1P) through S1P internalization, and also serves an agonist of S1P; however, the detailed mechanisms of its therapeutic effects on glial cells have yet to be elucidated. In this study, we investigated the anti-inflammatory mechanism of siponimod in microglia.

Left Atrium Thrombi Extending From Pulmonary Vein Thrombi Are Heterogeneous, Exhibit Calcifications, and Can Cause Acute Myocardial Infarction.

Previous studies have shown that thrombi, upon retrieval, sometimes exhibit calcification and endothelialization, indicating that they are old, and they can be classified as red clots, white clots, or mixed clots according to the degree of heterogeneity of the thrombus. These findings suggest that, prior to the occurrence of acute myocardial infarction (AMI) and acute ischemic stroke (AIS), such large and heterogeneous thrombi may already be present. Pulmonary vein thrombi (PVTs) are common in patients with age-related diseases.

Flometoquin, a novel insecticide, acts on mitochondrial complex III as a Q inhibitor.

Flometoquin (FLO) is a novel quinoline-type insecticide that elicits a quick knock-down effect against target pests; however, its mode of action (MoA) remains unknown. In this study, we investigated its MoA systematically, using varying biochemical techniques. Since FLO-treated insects exhibited symptoms similar to those induced by respiratory inhibitors, we examined the effect of FLO on respiratory enzyme complexes using mitochondria isolated from different insects (housefly, diamondback moth, and western flower thrips).

Risk Factors Preventing Identification of the Microorganism Causing Vertebral Osteomyelitis.

Study Design: Retrospective study.

Objective: To elucidate the factors influencing the identification of causative microorganisms in vertebral osteomyelitis (VO) and the effectiveness of different culture methods in increasing the identification rate.

Methods: A total of 252 patients diagnosed with and treated for VO at a single hospital were enrolled.

Association Between Trauma-Induced Vertebral Fractures and Motor Weakness in Patients With Diffuse Idiopathic Skeletal Hyperostosis.

Background Diffuse idiopathic skeletal hyperostosis (DISH) is an age-related condition involving abnormal ossification of soft tissues, including ligaments and joint capsules. Patients with DISH have an increased risk of fractures, especially in ankylosed spines, which increases susceptibility to spinal cord injury. This study aimed to explore the risk factors for neurological symptoms in patients with DISH-related fractures.

Formulation Design of Orally Disintegrating Film Using Two Cellulose Derivatives as a Blend Polymer.

: Orally disintegrating film (ODF) is prepared using water-soluble polymers as film-forming agents. To improve mechanical and disintegration properties, some polymers need to be blended with others. This study aimed to investigate the utility of hydroxypropyl cellulose (HPC) and hydroxypropyl methyl cellulose (HPMC) as blend film-forming components for ODFs.

Nonapoptotic caspase-3 guides C1q-dependent synaptic phagocytosis by microglia.

Caspases are known to mediate neuronal apoptosis during brain development. However, here we show that nonapoptotic activation of caspase-3 at presynapses drives microglial synaptic phagocytosis. Real-time observation and spatiotemporal manipulation of synaptic caspase-3 in the newly established, mouse-derived culture system demonstrate that increased neuronal activity triggers localized presynaptic caspase-3 activation, facilitating synaptic tagging by complements.

Effects of Intravenous Hydroxyzine Versus Haloperidol Monotherapy for Delirium: A Retrospective Study.

Although antipsychotics are used commonly for delirium, they increase the risk of mortality in elderly patients and those with dementia. As hydroxyzine has sedative and anxiolytic effects, it can be used in the treatment of delirium. We performed a retrospective study to compare the effects of intravenous hydroxyzine and haloperidol monotherapy on delirium.

Dynamic switching between brain networks predicts creative ability.

Creativity is hypothesized to arise from a mental state which balances spontaneous thought and cognitive control, corresponding to functional connectivity between the brain's Default Mode (DMN) and Executive Control (ECN) Networks. Here, we conduct a large-scale, multi-center examination of this hypothesis. Employing a meta-analytic network neuroscience approach, we analyze resting-state fMRI and creative task performance across 10 independent samples from Austria, Canada, China, Japan, and the United States (N = 2433)-constituting the largest and most ethnically diverse creativity neuroscience study to date.

Microwave ablation single-needle radiofrequency ablation for the treatment of HCC up to 4 cm: A randomized-controlled trial.

Background & Aims: Radiofrequency ablation (RFA) is the standard treatment for small hepatocellular carcinoma (HCC), specifically for tumors <3 cm in size and numbering fewer than three, excluding surgical candidates. Microwave ablation (MWA) is an innovative approach believed to have theoretical benefits over RFA; however, these advantages are yet to be empirically verified. Therefore, we evaluated and compared the effectiveness of MWA and RFA in managing HCC tumors up to 4 cm in size.

The association of agricultural and non-agricultural work on the healthy ageing of older adults in Japan: A 6-year longitudinal study from the Japan Gerontological evaluation study.

Objectives: Many studies have examined the impact of employment on health, but few large-scale longitudinal studies specifically investigate the impact of agricultural labor on the health of older adults. This study aims to identify the health effects of employment on older Japanese adults, focusing on agricultural workers.

Methods: This study uses longitudinal data collected by the Japan Gerontological Evaluation Study (JAGES) from 2013 to 2019.

A new classification for dislocated and displaced proximal humeral fractures.

Background: Although the Neer and AO/OTA classifications have been widely accepted, observer reliability studies of these two classifications have questioned their reliability and reproducibility to date. We developed an entirely new classification, the Mitsuzawa classification, for dislocated and displaced proximal humeral fractures and tested all three classifications for their intra- and interobserver reliability.

Methods: Two experienced shoulder surgeons and two orthopedic residents independently evaluated the Xray (xR) values of 100 proximal humeral fractures (PHFs).

Annual report on National Clinical Database 2021 for gastroenterological surgery in Japan.

Aim: The Japanese National Clinical Database, which covers more than 95% of the surgeries performed in Japan, is the largest nationwide database. This is the 2021 annual report of the Gastroenterological Section of the National Clinical Database, which aims to present the short-term outcomes of cases registered in 2021 and discuss significant changes and insights into gastroenterological surgeries observed over the decade.

Methods: We reviewed the data of patients registered in the National Clinical Database between 2012 and 2021.