Emerging HER2 Targeting Immunotherapy for Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a fatal bile duct malignancy. CCA is intrinsically resistant to standard chemotherapy, responds poorly to it, and has a poor prognosis. Effective treatments for cholangiocarcinoma remain elusive, and a breakthrough in CCA treatment is still awaited.

Anatomical pathways and functional implications of the rodent auditory system-basal ganglia interconnectivity.

Sound influences motor functions and sound perception is conversely modulated by locomotion. Accumulating evidence supports an interconnection between the auditory system and the basal ganglia (BG), which has functional implications on the interaction between the two systems. Substantial evidence now supports auditory cortex and auditory thalamus inputs to the tri-laminar region of the tail of the striatum (tTS) in rodents.

Human T-cell leukemia virus type I: modulation of viral gene expression and perturbation of host signaling pathways lead to persistent infection.

Human T-cell leukemia virus type I (HTLV-1) was the first human pathogenic retrovirus to be discovered. HTLV-1 induces a T-cell malignancy, adult T-cell leukemia-lymphoma (ATL), and inflammatory diseases, such as HTLV-1-associated myelopathy (HAM), HTLV-1 uveitis (HU), and HTLV-1-associated pulmonary disease (HAPD). Importantly, HTLV-1 maintains persistent infection by regulating viral gene expression and disrupting host signaling pathways - activities that are closely linked to its pathogenicity.

Clinical impact of mean pulmonary arterial pressure after balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension.

Background: Balloon pulmonary angioplasty (BPA) improves haemodynamics in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Previous studies on BPA have set the treatment objective to achieve a mean pulmonary arterial pressure (mPAP) of <30 mm Hg. However, the clinical impact of mPAP after BPA remains unclear.

Influence of Non-Index Pain Before Radiation Therapy for Bone Metastases on Post-Treatment QOL: Analyses Based on a Prospective Observational Study of 26 Centers.

Purpose: Although pain response is assessed based on the intensity of index pain (pain from the tumor targeted for radiation therapy), few studies have explored non-index pain (pain from other sites not targeted for radiation therapy). We examined the impact of pre-treatment non-index pain on quality of life (QOL) after radiation therapy.

Methods And Materials: Of 232 patients enrolled in the original prospective observational study conducted at 26 centers, 223 were analyzed.

Enantio- and Diastereoselective Synthesis of Tricyclic Lactones Bearing Three Quaternary Stereocenters.

An efficient method for the enantio- and diastereoselective synthesis of tricyclic γ-butyrolactones bearing three quaternary stereocenters has been developed through transformations of achiral alkenoic acid substrates. The target optically active tricyclic lactones were obtained as single diastereomers with good enantioselectivities through a sequence of catalytic asymmetric bromolactonization, azidation, and subsequent 1,3-dipolar cycloaddition. The origin of the complete diastereoselectivity observed in the formation of the tricyclic γ-butyrolactone products was elucidated in this study.

Components of particulate matter as potential risk factors for acute myocardial infarction.

Background: Particulate matter with an aerodynamic diameter of ≤2.5 µm (PM) is a heterogeneous mixture, and specific substances that affect cardiovascular events remain unknown. We aimed to examine the association of short-term exposure to PM and its components with hospital admissions for acute myocardial infarction (AMI).

Periplasmic serine protease Prc is responsible for amyloid subunit CsgA degradation and proteostasis in Escherichia coli.

Escherichia coli synthesizes curli amyloid fibers extracellularly during biofilm formation and host colonization. The proteostasis network regulates the major curli subunit, CsgA, to prevent intracellular amyloid aggregation, yet the degradation mechanism remains elusive. Here, through a comprehensive investigation employing genetically engineered E.

[Disseminated intravascular coagulation associated with sepsis].

Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host responses to infection. The prothrombotic/antithrombotic balance within blood vessels can be shifted toward prothrombotic in infectious diseases. This is a physiological defense mechanism intended to contain the disturbance in peripheral tissues and prevent it from reaching the central systems.

[Current status and challenges of AIDS-related malignant lymphoma].

AIDS-related malignant lymphomas (ARL) are lymphomas that develop in association with HIV infection. Although the introduction of combination antiretroviral therapy (cART) has markedly improved the life expectancy of people living with HIV (PLWH), approximately one-third of PLWH, including some with well controlled disease, still die from HIV-associated malignancies. HIV itself is not tumorigenic, and most of these tumors are due to co-infection with oncogenic viruses.

[Multimodal functions of HTLV-1 in oncogenesis of adult T-cell leukemia-lymphoma].

Adult T-cell leukemia-lymphoma (ATL) is a malignancy of peripheral CD4+ T cells induced by human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 encodes two oncogenic viral factors, Tax and HTLV-1 bZIP factor (HBZ) in the sense and antisense strands of the provirus respectively. Both Tax and HBZ dysregulate the expression and activities of a large number of host genes and cellular signaling pathways via their multimodal functions.

HIV-Associated Multicentric Castleman Disease with Kaposi Sarcoma: A Case Report with 120-Week Follow-Up of HHV-8 After Remission.

HIV-associated multicentric Castleman disease (HIV-MCD) is a rare, life-threatening lymphoproliferative disorder featuring systemic inflammation and marked lymphadenopathy. HIV-MCD is characterized by a human herpesvirus-8 (HHV-8) infection, with an increasing incidence despite advances in antiretroviral therapy (ART). Although HHV-8 viremia is a recognized indicator of disease recurrence, the necessity of intervention for low-level viremia reactivation remains unclear.

Lasting impact of undergraduate operating room shadowing on novice nurses: a ChatGPT-supported qualitative study.

Background: Operating room (OR) shadowing allows nursing students to observe high-stakes teamwork and clinical decision-making. However, the emotional and professional impact of such experiences on novice nurses remains underexplored.

Methods: This qualitative study explored how a single episode of OR shadowing during undergraduate clinical training influenced novice nurses' emotional responses and professional development.

Genetic and clinical features of hereditary transthyretin amyloidosis: a decade of experience at a Japanese referral center.

Background: Hereditary transthyretin (ATTRv) amyloidosis is a rare, intractable genetic disorder caused by mutations in the transthyretin (TTR) gene. More than 150 TTR mutations have been identified, along with genotype-phenotype correlations. Early diagnosis is critical to facilitate the timely initiation of disease-modifying therapies.

A Rare Case of Bilateral Lateral Ventricular Subependymomas With Complete Resection of the Residual Tumor via Flexible Neuroendoscopy 20 Years After Initial Surgery.

Subependymoma is a benign, slow-growing tumor that arises from the ventricular wall. Although often asymptomatic, it can obstruct cerebrospinal fluid flow, leading to hydrocephalus. Most subependymomas are unilateral, typically located in the fourth ventricle, followed by the lateral ventricles.

Lithium fine-tunes biodegradation of Zn-based implant to promote osseointegration through immunomodulation.

The intricate degradation dynamics exhibited by biodegradable alloys significantly influence host responses during the implantation process, posing challenges in achieving stable osseointegration. It is thus critical to tailor the biodegradation profiles of these implants to establish a conductive tissue microenvironment for bone tissue regeneration. In this study, we demonstrate that Zn-Li alloy forms a layer of Li-containing degradation products at the bone-implant interface to accommodate the bone regeneration process.

Final results of JCOG0601 randomized trial of R-CHOP versus CHOP combined with dose-dense rituximab for diffuse large B-cell lymphoma.

Background: Despite several attempts to improve the prognosis of patients with diffuse large B-cell lymphoma (DLBCL), the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen remains the standard of care in previously untreated DLBCL. A randomized phase II/III study (JCOG0601) was performed to investigate the efficacy of dose-dense weekly rituximab combined with standard CHOP (RW-CHOP). Herein, we report the final results of JCOG0601 as a post hoc assessment after an 8-year follow-up.

Hidden spin state accessed by light irradiation in an iron(III) high-spin complex.

A high-spin (HS) iron(III) complex, [Fe(qsal)]Cl·MeOH·HO, was synthesised, and its crystal structures and photo-induced magnetic properties were characterised. Upon photo-excitation, the HS state is converted into a low-spin (LS) state, revealing a thermally inaccessible metastable state. This photo-induced spin switching behaviour suggests the presence of a light-accessible hidden phase.

Efficacy and safety of esaxerenone with and without sodium-glucose cotransporter-2 inhibitor use in hypertensive patients with type 2 diabetes mellitus: a pooled analysis of five clinical studies.

This pooled subanalysis of five multicenter, prospective, open-label, single-arm studies on esaxerenone aimed to evaluate the efficacy, organ-protective effects, and safety of esaxerenone in hypertensive patients with type 2 diabetes mellitus (T2DM), with and without concomitant sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy. In total, 283 and 279 patients were included in the safety (with SGLT2i, 148; without, 135) and full analysis sets (with SGLT2i; 145; without, 134), respectively. Significant changes in morning home systolic/diastolic blood pressure (SBP/DBP) from baseline to Week 12 were shown in the overall population (mean change: -11.

Ovalbumin-induced asthma leads to bone loss with Piezo channel suppression in mice.

The impact of allergic diseases on bone loss remains unclear because it is considered to result from the use of corticosteroids to ameliorate allergic inflammation. To explore the effects of allergic diseases on bone metabolism, we investigated long bones in ovalbumin (OVA)-induced asthmatic mice. Compared with that of vehicle-treated controls, the bone mass of OVA-induced asthmatic mice was lower.

Low-dose aspirin is not effective as an adjunct treatment for HIV infection among people living with HIV on dolutegravir-based antiretroviral therapy: A randomised double-blind, parallel-group placebo-controlled trial.

Background: Despite virologic suppression with antiretroviral therapy (ART), immune activation (IA) in people living with HIV (PLHIV) remains high and is linked to non-AIDS complications. Alongside its other virologic and immunologic benefits, aspirin promisingly appears to lower the residual IA in PLHIV in small studies.

Methods: We conducted a double-blind, parallel-group randomised trial involving ART-naïve PLHIV initiating ART at recruitment.

The SMARCA5-DMRT1 Pioneer Complex Establishes Epigenetic Priming to Direct Male Germline Development.

The establishment of cell type-specific chromatin landscapes is essential for cellular identity, but how these landscapes are generated remains poorly understood. Here, we demonstrate that the chromatin remodeler SMARCA5 establishes epigenetic priming that is required for retinoic acid (RA)-induced differentiation in the male germline. Germ cell-specific deletion of results in a complete loss of differentiating spermatogonia, phenocopying vitamin A-deficient mice that lack RA signaling.

Harnessing an integrated glyco-nanovaccine technology for enhanced cancer immunotherapy.

Background: Cancer immunotherapy, particularly using immune checkpoint inhibitors, has revolutionized cancer treatment; however, its efficacy remains limited to a subset of patients. Nanoparticles have potential in cancer treatment because they offer advantages such as biocompatibility, greater stability, and precise targeting capabilities.

Method: We synthesized an integrated glyco-nanovaccine (iGN) comprising gold nanoparticles conjugated with a synthetic Toll-like receptor 7 (TLR7) ligand, sugar chains, and peptide antigens for cancer immunotherapy.