Cell lineage-specific immunohistochemical markers in biliary intraepithelial neoplasia: Implications for subclassification and grading.

Biliary intraepithelial neoplasia (BilIN), a precursor to cholangiocarcinoma, is categorized into low- and high-grade based on histological characteristics. Although gastric, intestinal, and biliary phenotypes of BilIN have been identified, detailed analyses of their immunophenotypic profiles using cell lineage-specific markers remain limited. This study aimed to define the immunohistochemical profiles of BilIN lesions, subclassify them based on their immunophenotypes, and correlate these profiles with histological grades.

Potential for reducing confirmation bias using the OMP model "6-microskills" with verbalizing discordance: a cross-sectional study.

Objectives: The "5-microskills" instructional method for clinical reasoning does not incorporate a step for learners' critical reflection on their predicted hypotheses. This study aimed to correct this shortcoming by inserting a third step in which learners conduct critical self-examinations and furnish evidence that contradicts their predicted hypotheses, resulting in the "6-microskills" method.

Methods: In this cross-sectional study, changes in learners' confidence in their predicted hypotheses were measured and examined to modify confirmation bias and diagnoses.

A Novel ELISA System for Measuring Modified LDL-Adiponectin Complex.

Aim: Adiponectin is an anti-diabetic and anti-atherogenic protein secreted primarily from adipose tissue. Adiponectin and modified LDL (mLDL) form a complex to modulate their biological activity. To elucidate the significance of the complex formation, we analyzed its effects on vascular tissue and developed and verified novel quantifying methods for adiponectin.

Vascular E-selectin Expression Recognized by the U12-12 Monoclonal Antibody as a Predictive Marker for Steroid Resistance in Immune Checkpoint Inhibitor-related Colitis.

In immune checkpoint inhibitor (ICI)-related colitis, tumor necrosis factor (TNF)-α blockade is recommended if symptoms are not alleviated with corticosteroids. Although TNF has been shown to be associated with steroid resistance, the early prediction of steroid resistance is challenging in clinical practice. Therefore, in the present study, we evaluated the potential of vascular E-selectin expression, which is induced by TNF, to serve as a predictor of steroid resistance in ICI-related colitis.

Effect of antiemetic corticosteroids on the development of immune-related adverse events caused by chemoimmunotherapy: a multicenter retrospective study.

Purpose: Chemoimmunotherapy is the primary treatment approach for non-small cell lung cancer (NSCLC); however, it is associated with immune-related adverse events (irAEs). Corticosteroids can control irAEs through their anti-inflammatory and immunosuppressive effects. Dexamethasone (DEX) is a potent corticosteroid commonly used to prevent chemotherapy-induced nausea and vomiting (CINV).

Ensitrelvir for the Treatment of Nonhospitalized Adults with COVID-19: Results from the SCORPIO-HR, Phase 3, Randomized, Double-blind, Placebo-Controlled Trial.

Background: Ensitrelvir, a severe acute respiratory syndrome coronavirus-2 main protease inhibitor, has demonstrated clinical and virologic efficacy in previous studies.

Methods: In this global phase 3 trial, nonhospitalized adults with mild-to-moderate coronavirus disease 2019 (COVID-19) and symptom onset within 5 days were randomized (1:1) to receive once-daily ensitrelvir (375 mg day 1, 125 mg days 2-5) or blinded matching placebo. The primary endpoint was the restricted mean time to sustained (≥2 days) resolution of 15 COVID-19 symptoms, recorded in participant daily diaries, through day 29 in participants starting treatment within 3 days after symptom onset.

[The 46th Report on Survey of the Adverse Reaction to Radiopharmaceuticals (The 49th Survey in 2023)].

This survey was performed in order to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2023 in Japan. It was based on responses to questionnaires sent to nuclear medicine institutions. Replies were obtained from 971 institutions out of 1,181 to which the questionnaire had been sent.

Cefepime-taniborbactam and ceftibuten-ledaborbactam maintain activity against KPC variants that lead to ceftazidime-avibactam resistance.

carbapenemases (KPCs) are widespread β-lactamases that are a major cause of clinical non-susceptibility of Gram-negative bacteria to carbapenems and other β-lactam antibiotics. Ceftazidime combined with the β-lactamase inhibitor avibactam (CAZ-AVI) has been effective in treating infections by KPC-producing bacteria, but emerging KPC variants confer resistance to the combination. Taniborbactam and ledaborbactam are bicyclic boronate β-lactamase inhibitors currently under development with cefepime and ceftibuten, respectively, to treat carbapenem-resistant bacterial infections.

Evaluation of the Gly-Phe-Lys Linker to Reduce the Renal Radioactivity of a [Cu]Cu-Labeled Multimeric cRGD Peptide.

Radiometal-labeled peptide-based radiopharmaceuticals (RLPB-radiopharmaceuticals) are promising for cancer imaging and targeted radiotherapy; however, their effectiveness is often compromised by the high retention of nonspecific radioactivity in the kidneys due to renal excretion pathways. Current strategies to address this issue have limitations, highlighting the need for innovative approaches to improve targeting specificity and therapeutic efficacy. We aimed to evaluate the applicability of the Gly-Phe-Lys (GFK) tripeptide, a renal brush border (RBB) enzyme-cleavable linkage, to reduce renal radioactivity in RLPB-radiopharmaceuticals using the integrin-targeting radiopeptide [Cu]Cu-cyclam-RAFT-c(-RGDfK-) ([Cu]Cu-cyclam-RaftRGD).

Survey of Physicians on the Need for Female Chaperones Based on the Body Areas Examined in Female Patients by Male Physicians: A Cross-Sectional Pilot Study.

Background In the United States (US), most physicians who commit sexual misconduct are male, and such misconduct is associated with the absence of chaperones. Several organizations recommend a chaperone during all intimate examinations (breast, genital, and rectal exams). However, in Japan, guidelines are not clearly defined, and hospitals and medical societies have not established standardized protocols.

Ensitrelvir treatment-emergent amino acid substitutions in SARS-CoV-2 3CL detected in the SCORPIO-SR phase 3 trial.

The impact of treatment-emergent amino acid substitutions (TEAASs) in severe acute respiratory syndome coronavirus 2 (SARS-CoV-2) 3C-like protease (3CL) on clinical and virologic outcomes was evaluated in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) who received ensitrelvir 125 mg in the SCORPIO-SR trial. Individuals were randomised to ensitrelvir or matched placebo once daily for 5 days (first dose <72 h after disease onset). 3CL-TEAASs were identified by sequencing nsp5 encoding 3CL from pre- and post-treatment nasopharyngeal swabs.

An At-labeled alpha-melanocyte stimulating hormone peptide analog for targeted alpha therapy of metastatic melanoma.

Purpose: Patients who develop metastatic melanoma have a very poor prognosis, and new treatments are needed to improve the response rates. Melanocortin-1 receptor (MC1R) is a promising target for radionuclide therapy of metastatic melanoma, and alpha-melanocyte stimulating hormone (α-MSH) peptide analogs show high affinities to MC1Rs. Because targeted alpha therapy (TAT) can be a desirable treatment for metastatic melanoma, this study aimed to develop an At-labeled α-MSH peptide analog for TAT of metastatic melanoma.

Intensity-modulated radiation therapy can reduce acute toxicities in long-course neoadjuvant radiation therapy combined with S-1 for locally advanced rectal cancer.

Background: The purpose of this study was to compare outcomes and adverse events between three-dimensional conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) in patients undergoing long-course neoadjuvant radiation therapy (NA-RT) for locally advanced rectal adenocarcinoma (LARC).

Methods: We retrospectively analyzed a total of 47 consecutive patients who received NA-RT for LARC between January 2011 and September 2022. Seven and 40 patients were diagnosed with clinical stages II and III, respectively.

Aberrant Methylation of is Associated with the Pathogenesis of Autoimmune Pancreatitis.

IgG4-related disease (IgG4-RD) is an autoimmune disease of unknown cause. is a transcription factor involved in immune responses, and its dysfunction leads to uncontrolled immune responses. We performed, to our knowledge, the first methylation analysis in type 1 autoimmune pancreatitis (denoted simply as AIP), a representative IgG4-RD.

A Case of Small-Cell Lung Cancer With Novel Anaplastic Lymphoma Kinase Gene Rearrangement That Developed Intradural Extramedullary Spinal Metastases With Myelitis.

( gene rearrangement-positive small-cell lung cancer (SCLC) is extremely rare. A 73-year-old man was diagnosed with SCLC. Standard treatments were not effective.

A new class of penicillin-binding protein inhibitors to address drug-resistant .

β-Lactams are the most widely used antibiotics for the treatment of bacterial infections because of their proven track record of safety and efficacy. However, susceptibility to β-lactam antibiotics is continually eroded by resistance mechanisms. Emerging multidrug-resistant (MDR) strains possessing altered alleles (encoding PBP2) pose a global health emergency as they threaten the utility of ceftriaxone, the last remaining outpatient antibiotic.

Gut-brain Axis and Irritable Bowel Syndrome During the Lockdown due to the SARS-CoV-2 Pandemic: A Survey-based Study.

Background: Irritable bowel syndrome (IBS) is influenced by various factors, including socioemotional stressors. The COVID-19 lockdown created a unique environment characterized by reduced social interactions, potentially impacting IBS symptoms.

Aim: To assess how lockdown measures affected symptoms related to the gut-brain axis in IBS patients in Buenos Aires, Argentina.

Proteomic serum profiles before and after lipoprotein apheresis in patients with peripheral artery disease with ulceration.

Introduction: The efficacy of lipoprotein apheresis (LA) in peripheral arterial disease (PAD) has been primarily attributed to its anti-atherosclerotic effects through the adsorption of lipoproteins. However, the other potential effects of LA remain unknown. We evaluated changes in serum profiles before and after LA using a comprehensive analysis to explore the underlying mechanism.

Leptin on the apical surface inhibits casein production and STAT5 phosphorylation in mammary epithelial cells.

Leptin is a peptide hormone present in both the blood and milk. A close relationship between leptin and milk production in lactating mammary glands has been previously reported. However, how leptin influences milk production in lactating mammary glands remains unclear.

Discovery of a Compound That Inhibits IRE1α -Nitrosylation and Preserves the Endoplasmic Reticulum Stress Response under Nitrosative Stress.

Inositol-requiring enzyme 1α (IRE1α) is a sensor of endoplasmic reticulum (ER) stress and drives ER stress response pathways. Activated IRE1α exhibits RNase activity and cleaves mRNA encoding X-box binding protein 1, a transcription factor that induces the expression of genes that maintain ER proteostasis for cell survival. Previously, we showed that IRE1α undergoes -nitrosylation, a post-translational modification induced by nitric oxide (NO), resulting in reduced RNase activity.

Epigenetic Regulation of CXC Chemokine Expression by Environmental Electrophiles Through DNA Methyltransferase Inhibition.

Ubiquitously distributed environmental electrophiles covalently modify DNA and proteins, potentially leading to adverse health effects. However, the impacts of specific electrophiles on target proteins and their physiological roles remain largely unknown. In the present study, we focused on DNA methylation, which regulates gene expression and physiological responses.