Phase-separated protein droplets of amyotrophic lateral sclerosis-associated p62/SQSTM1 mutants show reduced inner fluidity.

Several amyotrophic lateral sclerosis (ALS)-related proteins such as FUS, TDP-43, and hnRNPA1 demonstrate liquid-liquid phase separation, and their disease-related mutations correlate with a transition of their liquid droplet form into aggregates. Missense mutations in SQSTM1/p62, which have been identified throughout the gene, are associated with ALS, frontotemporal degeneration (FTD), and Paget's disease of bone. SQSTM1/p62 protein forms liquid droplets through interaction with ubiquitinated proteins, and these droplets serve as a platform for autophagosome formation and the antioxidative stress response via the LC3-interacting region (LIR) and KEAP1-interacting region (KIR) of p62, respectively.

Changes in the Functional Range of Motion of the Thumb Metacarpophalangeal Joint After Trapeziometacarpal Arthrodesis for Patients With Advanced Trapeziometacarpal Osteoarthritis.

Purpose: Advanced-stage trapeziometacarpal (TMC) osteoarthritis of the thumb often presents with concomitant hyperextension deformity of the metacarpophalangeal (MCP) joint. Although several studies have reported simultaneous procedures to correct this deformity, the indication for these procedures remains controversial. The purpose of this study was to evaluate changes in the range of motion (ROM) of the thumb MCP joint before and after TMC arthrodesis.

BHLHE41/DEC2 Expression Induces Autophagic Cell Death in Lung Cancer Cells and Is Associated with Favorable Prognosis for Patients with Lung Adenocarcinoma.

Lung cancer constitutes a threat to human health. BHLHE41 plays important roles in circadian rhythm and cell differentiation as a negative regulatory transcription factor. This study investigates the role of BHLHE41 in lung cancer progression.

Effect of Early vs Delayed Surgical Treatment on Motor Recovery in Incomplete Cervical Spinal Cord Injury With Preexisting Cervical Stenosis: A Randomized Clinical Trial.

Importance: The optimal management for acute traumatic cervical spinal cord injury (SCI) is unknown.

Objective: To determine whether early surgical decompression results in better motor recovery than delayed surgical treatment in patients with acute traumatic incomplete cervical SCI associated with preexisting canal stenosis but without bone injury.

Design, Setting, And Participants: This multicenter randomized clinical trial was conducted in 43 tertiary referral centers in Japan from December 2011 through November 2019.

Loss of and Impairs the Maintenance of the Hematopoietic Stem Cell Pool Size.

A germ line copy number duplication of chromosome 14q32, which contains and , was identified in families with myeloproliferative neoplasm (MPN). Here, we show that mice lacking both and , but not either alone, exhibited decreased hematopoiesis, resulting in death accompanied by anemia. In marked contrast to MPN patients with duplication of and , the number of hematopoietic stem cells (HSCs), in particular long-term HSCs, in double-knockout fetal livers was significantly decreased due to increased cell death.

Cell-cycle dependent GATA2 subcellular localization in mouse 2-cell embryos.

GATA factors are essential transcription factors for embryonic development that broadly control the transcription of other genes. This study aimed to examine GATA2 protein localization in mouse embryos at the 2-cell stage, when drastic transformation in gene expression occurs for subsequent development in early embryos. We first analyzed GATA2 localization in 2-cell embryos at the interphase and mitotic phases by immunofluorescence analysis.

Expressions of PD-L1 and Nectin-4 in urothelial cancer patients treated with pembrolizumab.

Objectives: Recently, the standard of care for advanced urothelial cancer (UC) has been changed by developing immune-checkpoint inhibitors (ICIs). However, its response rate is limited to 20-30%. The identification of biomarkers to predict the therapeutic effects of ICIs is urgently needed.

Magnetic resonance imaging of diffusion characteristics following collagenase clostridium histolyticum injection in Dupuytren's contracture.

PurposeWe aimed to evaluate the extent of collagenase clostridium histolyticum (CCH) diffusion in Dupuytren's contracture (DC) for tissues outside of the contracture cord using Magnetic Resonance Imaging (MRI) immediately after CCH injection. 10 male patients aged 57-79 with DC of the metacarpophalangeal (MCP) joints were examined. Extension deficits were 10-60°(mean, 34.

Broadband Dynamics Rather than Frequency-Specific Rhythms Underlie Prediction Error in the Primate Auditory Cortex.

Detection of statistical irregularities, measured as a prediction error response, is fundamental to the perceptual monitoring of the environment. We studied whether prediction error response is associated with neural oscillations or asynchronous broadband activity. Electrocorticography was conducted in three male monkeys, who passively listened to the auditory roving oddball stimuli.

Changes in serum uric acid levels as a predictor of future decline in renal function in older adults with type 2 diabetes.

Given that factors affecting renal function remain unknown, this study aimed to identify key predictors of estimated glomerular filtration rate (eGFR) deterioration, which is a representative of renal function decline in older adults with type 2 diabetes (T2DM). In an exploratory prospective observational study, we enrolled 268 Japanese people with T2DM aged ≥20 years who were followed up at Shinshu University Hospital. Among those, 112 eligible individuals aged ≥65 years were included in the present study.

Prognostic implication of erector spinae muscles in non-small-cell lung cancer patients treated with immuno-oncology combinatorial chemotherapy.

Background: The quantity of skeletal muscles has recently been reported to have prognostic value in patients with non-small-cell lung cancer (NSCLC) treated with second-line immunotherapy. However, the prognostic role of skeletal muscle assessment in NSCLC patients undergoing first-line immuno-oncology (IO) combinatorial treatment (IO-chemotherapy) has not been elucidated.

Methods: We retrospectively reviewed 36 patients with NSCLC undergoing first-line IO-chemotherapy between April 2018 and June 2021 in our hospital.

Application of Artificial Intelligence in COVID-19 Diagnosis and Therapeutics.

The coronavirus disease 2019 (COVID-19) pandemic began at the end of December 2019, giving rise to a high rate of infections and causing COVID-19-associated deaths worldwide. It was first reported in Wuhan, China, and since then, not only global leaders, organizations, and pharmaceutical/biotech companies, but also researchers, have directed their efforts toward overcoming this threat. The use of artificial intelligence (AI) has recently surged internationally and has been applied to diverse aspects of many problems.

Epigenetic Mechanisms Underlying COVID-19 Pathogenesis.

In 2019, a novel severe acute respiratory syndrome called coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported and was declared a pandemic by the World Health Organization (WHO) in March 2020. With the advancing development of COVID-19 vaccines and their administration globally, it is expected that COVID-19 will converge in the future; however, the situation remains unpredictable because of a series of reports regarding SARS-CoV-2 variants. Currently, there are still few specific effective treatments for COVID-19, as many unanswered questions remain regarding the pathogenic mechanism of COVID-19.

A first case report of nasopharyngeal Mycobacterium abscessus subspecies massiliense infection.

Background: Mycobacterium abscessus subspecies massiliense is a non-tuberculous mycobacteriosis and was subdivided from Mycobacterium abscessus in 2006. This article is the first report on nasopharyngitis caused by Mycobacterium abscessus subspecies massiliense.

Case Presentation: A 45-year-old woman had an 18-month history of recurrent nasopharyngitis and presented with pain in the throat.

Mitochondrial reactive oxygen species trigger metformin-dependent antitumor immunity via activation of Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8T lymphocytes.

Background: Metformin (Met) is the first-line treatment for type 2 diabetes mellitus and plays an effective role in treating various diseases, such as cardiovascular disease, neurodegenerative disease, cancer, and aging. However, the underlying mechanism of Met-dependent antitumor immunity remains to be elucidated.

Methods: MitoTEMPO, a scavenger of mitochondrial superoxide, abolished the antitumor effect of Met, but not antiprogrammed cell death (PD-1) antibody (Ab) treatment.

Dynamics of radiocaesium within forests in Fukushima-results and analysis of a model inter-comparison.

Forests cover approximately 70% of the area contaminated by the Fukushima Daiichi Nuclear Power Plant accident in 2011. Following this severe contamination event, radiocaesium (Cs) is anticipated to circulate within these forest ecosystems for several decades. Since the accident, a number of models have been constructed to evaluate the past and future dynamics of Cs in these forests.

Genomic Characterization of ESBL- and Carbapenemase-Positive Enterobacteriaceae Co-harboring in Japan.

Worldwide spread of Enterobacteriaceae resistant to colistin, a polypeptide antibacterial drug for last-resort treatment of carbapenemase-producing Enterobacteriaceae (CPE) infections, is concerning. This study aimed to elucidate colistin MICs and molecular characteristics of to of ESBL-producing (ESBL-Ec) and CPE in Japan and clarify the genomic structure of strains harboring genes (especially ). This study included 168 ESBL-Ec and 126 CPE strains isolated at Japanese medical facilities.

Clinical characteristics of immunoglobulin G-positive interstitial pneumonia.

https://bit.ly/3dUo2cu.

Pineal gland differentiation in mature teratoma: An under-recognized condition and potential pitfalls for overdiagnosis.

We herein report three cases of mature teratomas with pineal gland differentiation, which is a less recognized phenomenon. Case 1 was a 6-year-old male with a neck mass, Case 2 was a 23-year-old female with a retroperitoneal mass, and Case 3 was a 45-year-old female with a retroperitoneal mass. Each case showed the typical macroscopic and histological findings of mature teratoma, such as solid and cystic lesions mainly lined with a mature squamous epithelium.

A rare case of nivolumab-related myasthenia gravis and myocarditis in a patient with metastatic gastric cancer.

Background: Although rare, several immune-related adverse effects can be life-threatening. Here, we describe a metastatic gastric cancer patient presenting with nivolumab-related myasthenia gravis and myocarditis, a previously unreported adverse effect of gastric cancer treatment.

Case Presentation: A 66-year-old man with metastatic gastric cancer visited the emergency department because of dizziness after the first dose of nivolumab.

Selective autophagy.

While starvation-induced autophagy is thought to randomly degrade cellular components, under certain circumstances autophagy selectively recognizes, sequesters, and degrades specific targets via autophagosomes. This process is called selective autophagy, and it contributes to cellular homeostasis by degrading specific soluble proteins, supramolecular complexes, liquid-liquid phase-separated droplets, abnormal or excess organelles, and pathogenic invasive bacteria. This means that autophagy, like the ubiquitin-proteasome system, strictly regulates diverse cellular functions through its selectivity.

Nosocomial infections caused by vancomycin-resistant Enterococcus in a Japanese general hospital and molecular genetic analysis.

Introduction: Vancomycin-resistant Enterococcus (VRE) is a rare bacterium in Japan, but an outbreak due to nosocomial transmission in medical facilities has been reported in recent years. Here, we report the outbreak of vanA vancomycin-resistant Enterococcus faecium (VREfm) in multiple wards of Nara Prefectural General Medical Center in 2019 and results of the molecular epidemiology analysis.

Methods: An aggressive screening program was conducted after the first VREfm was detected in a patient in the A ward.