Refractory phenotype of -sensitized asthma with bronchiectasis and allergic bronchopulmonary aspergillosis.

Background: Sensitization to mucus plugs, and bacterial colonization may coexist and relate to a refractory phenotype during follow-up in asthma with bronchiectasis and allergic bronchopulmonary aspergillosis (ABPA).

Objective: This study aimed to clarify the features of -sensitized refractory asthma with bronchiectasis and determine the refractory phenotype in this population and ABPA.

Methods: This study included cases of the oldest available -specific IgE data and chest computed tomography images from a nationwide survey of refractory asthma with bronchiectasis.

UGGT1-mediated reglucosylation of -glycan competes with ER-associated degradation of unstable and misfolded glycoproteins.

How the fate (folding versus degradation) of glycoproteins is determined in the endoplasmic reticulum (ER) is an intriguing question. Monoglucosylated glycoproteins are recognized by lectin chaperones to facilitate their folding, whereas glycoproteins exposing well-trimmed mannoses are subjected to glycoprotein ER-associated degradation (gpERAD); we have elucidated how mannoses are sequentially trimmed by EDEM family members (George et al., 2020; 2021 eLife).

Clonal hematopoiesis-related mutant ASXL1 promotes atherosclerosis in mice via dysregulated innate immunity.

Certain somatic mutations provide a fitness advantage to hematopoietic stem cells and lead to clonal expansion of mutant blood cells, known as clonal hematopoiesis (CH). Among the most common CH mutations, ASXL1 mutations pose the highest risk for cardiovascular diseases (CVDs), yet the mechanisms by which they contribute to CVDs are unclear. Here we show that hematopoietic cells harboring C-terminally truncated ASXL1 mutant (ASXL1-MT) accelerate the development of atherosclerosis in Ldlr mice.

Protein corona formation on different-shaped CdSe/CdS semiconductor nanocrystals.

Nanoparticles (NPs) have been widely studied and applied in medical and pharmaceutical fields. When NPs enter the environment, they are covered with protein molecules to form the so-called "protein corona". Because NPs and proteins are comparable in size, the shape of NPs has a significant impact on NP-protein interactions.

Red-light Emitting Orthogonally Trireactive Gold Nanoclusters for the Synthesis of Multifunctionalized Nanomaterials.

For the development of highly multifunctionalized nanomaterials, the introduction of functional molecules on gold nanoclusters containing thiols preinstalled with connecting groupsconstitutes a promising approach. However, the uniform introduction of multiple connecting groups while avoiding side reactions is a challenging task. Herein, the synthesis of gold nanoclusters (ca.

Potential of boron neutron capture therapy (BNCT) for myxofibrosarcoma.

Myxofibrosarcoma, a rare malignant tumor, predominantly affects the extremities of the elderly. Because of its invasive nature amputation is sometimes required, resulting in serious deterioration of quality of life. Therefore, cell lines established from amputated surgical specimens of myxofibrosarcoma in the upper limbs of elderly patients were used to create a myxofibrosarcoma-bearing animal model and to investigate the therapeutic effect of BNCT thereon.

Comparison of outcomes between surgery and chemoradiotherapy after endoscopic resection for pT1a-MM with lymphovascular invasion or pT1b esophageal squamous cell carcinoma: Japanese multicenter propensity score-matched study.

Background: Lymphovascular invasion (LVI) or pT1b is noncurative after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC), and therefore surgery or chemoradiotherapy (CRT) is recommended. However, there has been debate regarding which treatment has better outcomes and whether individual risks should be considered.

Methods: This was a multicenter, retrospective study conducted at 65 hospitals in Japan.

Association between the COVID-19 pandemic and short-term outcomes after esophagectomy for esophageal cancer in facilities with and without board-certified esophageal surgeons: a nationwide retrospective cohort study.

Background: The COVID-19 pandemic had a profound impact on cancer screening, diagnosis, and treatment procedures. We speculated that during the COVID-19 pandemic, sufficient medical resources were maintained in board-certified hospitals, resulting in favorable short-term outcomes, whereas hospital functions in non-board-certified hospitals declined, leading to mortality increase. The aim of this study is to investigate the impact of COVID-19 pandemic on short-term outcomes after esophagectomy, based on the scale of the facilities.

Can the agrochemical Oryzemate treatment control the uptake of pyrene by Cucurbita pepo through the regulation of major latex-like proteins?

Members of the Cucurbitaceae family accumulate several hydrophobic organic pollutants in their above-ground parts at high concentrations. Major latex-like proteins (MLPs) identified in Cucurbita pepo bind to hydrophobic organic pollutants, such as pyrene and dieldrin, in roots, forming complexes that are transported via xylem vessels to the above-ground plant parts. However, soil remediation of hydrophobic organic pollutants utilizing MLPs has not been established.

How much progress has been made toward a smoke-free environment in the restaurants and bars of Japan? Limitations of partial bans and their enforcement.

Background: In April 2020, the revised Health Promotion Act and Tokyo Metropolitan Ordinance to prevent second-hand smoke (SHS) exposure was fully enforced. The government has provided an exemption for small-scale, existing establishments by allowing them 'unregulated' status, and it is unclear to what extent indoor smoking bans have been applied in these small bars and restaurants. In this study, we report on indoor smoking status before/after the enforcement of the current legislation both regulated and unregulated restaurants and bars.

Resistance exercise has an antihypertensive effect comparable to that of aerobic exercise in hypertensive patients: a meta-analysis of randomized controlled trials.

Hypertension increases the risk of cerebrovascular disease and death. In addition to aerobic exercise, which is currently recommended for its antihypertensive effects, recent studies have suggested that dynamic and isometric resistance exercises also have antihypertensive effects. However, the magnitude of the antihypertensive effect of such resistance exercises is not well known.

Anti-integrin αvβ6 antibody as a biomarker for diagnosing ulcerative colitis: a nationwide multicenter validation study.

Background: A serum biomarker for diagnosing ulcerative colitis (UC) remains to be established. Although we recently reported an anti-integrin αvβ6 antibody (V6 Ab) for diagnosing UC with high sensitivity and specificity, no large-scale validation study exists. This study aimed to validate the diagnostic value of V6 Ab for UC using a nationwide multicenter cohort study.

Proximal tubule cell maturation rate and function are controlled by PPARα signaling in kidney organoids.

Human pluripotent stem cell-derived kidney organoids are expected to be a useful tool for new drug discoveries, however, the immaturation of kidney organoids causes difficulties in recapitulating renal pharmacokinetics using organoids. Here, we performed time-course single-cell RNA sequencing of kidney organoids and revealed cell heterogeneity in the maturation rate of the proximal tubule. An unbiased analysis to identify upstream targets of genes that are expressed differentially between cells with low and high maturation rates revealed a higher activation of PPARα signaling in rapidly maturing cells.

Body Composition in Cases with Normal Alanine Aminotransferase Values in Medical Health Checkups.

Background And Aims: We aimed to clarify the relationship between alanine aminotransferase (ALT) level and body composition in Japanese medical health checkups, especially in cases with ALT ≤ 30 IU/L (7569 men and 9497 women).

Methods: We categorized our study cohort into four groups: type A (ALT value ≤ 10 IU/L), type B (11 ≤ ALT value ≤ 20 IU/L), type C (21 ≤ ALT value ≤ 30 IU/L) and type D (ALT value > 30 IU/L (ALT over 30)). We retrospectively compared body composition-related parameters (body mass index (BMI), waist circumference (WC), fat (F) index, fatty liver index (FLI), fat-free (FF) index and F-FF ratio) among the four types.

Efficacy and Safety of Rivaroxaban, Apixaban, and Edoxaban for Nonvalvular Atrial Fibrillation Based on Blood Coagulation Activity and Drug Plasma Concentration: SETtsu and North Osaka Multicenter Direct Oral AntiCoagulant (SET DOAC) Registry.

The therapeutic effects of oral anticoagulant drugs for nonvalvular atrial fibrillation (NVAF) suggest that the three factor Xa (FXa) inhibitors may have distinct safety profiles, though this is not yet fully conclusive. This study investigated the current dosing of rivaroxaban, apixaban, and edoxaban by monitoring drug plasma concentration (PC) and coagulation activity from the viewpoint of the safety. This multicenter clinical study monitored the drug PC and two coagulation biomarkers (fibrinogen and fibrin monomer complex [FMC]) at peak and trough timing in 268 outpatients taking rivaroxaban (n = 72), apixaban (n = 71), and edoxaban (n = 125) for NVAF.

The Clinical Significance of Interstitial Pneumonia with Autoimmune Features in Cryptogenic Organizing Pneumonia: A Prospective Multicenter Observational Study.

There are cases of idiopathic interstitial pneumonias (IIPs) that do not meet the diagnostic criteria for connective tissue disease but have clinical features suggestive of autoimmune process. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept for these patients. Although several prospective studies on IPAF have been conducted, its clinical significance in cryptogenic organizing pneumonia (COP) remains unclear.

Modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: a randomized phase II DEEPER trial.

The clinical significance of FOLFOXIRI (5-FU, leucovorin, oxaliplatin, and irinotecan) plus anti-EGFR monoclonal antibody using cetuximab for metastatic colorectal cancer (mCRC) remains controversial. We report results from a randomized phase 2 DEEPER trial (UMIN000018217, jRCTs061180022) to test the superiority of modified (m)-FOLFOXIRI plus weekly cetuximab over bevacizumab in patients with RAS wild-type (wt) mCRC. Primary endpoint was depth of response (DpR).