Trastuzumab-Pertuzumab Plus Eribulin or Taxane as First-Line Chemotherapy for Human Epidermal Growth Factor 2-Positive Locally Advanced/Metastatic Breast Cancer: The Randomized Noninferiority Phase III EMERALD Trial.

Purpose: Trastuzumab-pertuzumab (HP) plus taxane is a current standard first-line therapy for recurrent or metastatic human epidermal growth factor 2 (HER2)+ breast cancer (BC). We investigated noninferiority of eribulin to a taxane when combined with dual HER2 blockade as first-line systemic treatment for locally advanced/metastatic HER2+ BC.

Methods: In the phase III EMERALD trial (target sample size, 480; ClinicalTrials.

Prediction of cccDNA dynamics in hepatitis B patients by a combination of serum surrogate markers.

Quantification of intrahepatic covalently closed circular DNA (cccDNA) is a key for evaluating an elimination of hepatitis B virus (HBV) in infected patients. However, quantifying cccDNA requires invasive methods such as a liver biopsy, which makes it impractical to access the dynamics of cccDNA in patients. Although HBV RNA and HBV core-related antigens (HBcrAg) have been proposed as surrogate markers for evaluating cccDNA activity, they do not necessarily estimate the amount of cccDNA.

Differences in Phenotypes, Treatments, and Outcomes of ANCA-associated Vasculitis across Europe, Japan, and the United States in 2020.

Objectives: To clarify the differences in clinical phenotypes, therapeutic patterns, and outcomes of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) across geographic regions using a multinational cohort.

Methods: Data were collected from patients with newly diagnosed or relapsing GPA or MPA in Europe, Japan, and the United States (US) from January to July 2020. The composite outcome of kidney failure and/or death within 52 weeks after treatment was evaluated, and the hazard ratios across the regions were estimated using the Cox proportional hazard model.

Automated quantification of anterior chamber cells using swept-source anterior segment optical coherence tomography.

Purpose: To validate automated counts of presumed anterior chamber (AC) cells in eyes with histories of uveitis involving the anterior segment using swept-source (SS) anterior segment optical coherence tomography (AS-OCT) against manual counts and compare automated counts against Standardized Uveitis Nomenclature (SUN) criteria.

Methods: Eyes were imaged with the ANTERION SS AS-OCT device (Heidelberg Engineering). A fully automated custom algorithm quantified the number of hyper-reflective foci (HRF) in line-scan images.

Sonic Hedgehog signaling regulates the optimal differentiation pace from early-stage mesoderm to cardiogenic mesoderm in mice.

Sonic Hedgehog (Shh), encoding an extracellular signaling molecule, is vital for heart development. Shh null mutants show congenital heart disease due to left-right asymmetry defects stemming from functional anomaly in the midline structure in mice. Shh signaling is also known to affect cardiomyocyte differentiation, endocardium development, and heart morphogenesis, particularly in second heart field (SHF) cardiac progenitor cells that contribute to the right ventricle, outflow tract, and parts of the atrium.

Sustained inhibition of CSF1R signaling augments antitumor immunity through inhibiting tumor-associated macrophages.

Tumor-associated macrophages (TAMs) are one of the key immunosuppressive components in the tumor microenvironment (TME) and contribute to tumor development, progression, and resistance to cancer immunotherapy. Several reagents targeting TAMs have been tested in preclinical and clinical studies, but they have had limited success. Here, we show that a unique reagent, FF-10101, exhibited a sustained inhibitory effect against colony-stimulating factor 1 receptor by forming a covalent bond and reduced immunosuppressive TAMs in the TME, which led to strong antitumor immunity.

Prevalence and Clinical Outcomes of Discordant Lesions Between Fractional Flow Reserve and Nonhyperemic Pressure Ratios in Clinical Practice: The J-PRIDE Registry.

Background: Limited large-scale, real-world data exist on the prevalence and clinical impact of discordance between fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs).

Methods: The J-PRIDE registry (Clinical Outcomes of Japanese Patients With Coronary Artery Disease Assessed by Resting Indices and Fractional Flow Reserve: A Prospective Multicenter Registry) prospectively enrolled 4304 lesions in 3200 patients from 20 Japanese centers. The lesions were classified into FFR+/NHPR-, FFR-/NHPR+, FFR+/NHPR+, or FFR-/NHPR groups according to cutoff values of 0.

Genome Analysis of Japanese Yersinia pseudotuberculosis Strains Isolated From Kawasaki Disease Patients and Other Sources and Their Phylogenetic Positions in the Global Y. pseudotuberculosis Population.

Yersinia pseudotuberculosis (Ypt) is a gram-negative bacterium that infects both humans and animals primarily through fecal‒oral transmission. While Ypt causes acute gastroenteritis in humans, an association with Kawasaki disease (KD), a disease that primarily affects infants and young children and causes multisystemic vasculitis, has also been suspected. Although KD represents a significant health concern worldwide, the highest annual incidence rate is reported in Japan.

Long-term intake of Tamogi-take mushroom (Pleurotus cornucopiae) mitigates age-related cardiovascular dysfunction and extends healthy life expectancy.

Age-related declines in cardiac function and exercise tolerance interfere with healthy living and decrease healthy life expectancy in older individuals. Tamogi-take mushrooms (Pleurotus cornucopiae) are known to contain high levels of Ergothioneine (EGT), an antioxidant with potential health benefits. In this study, we assessed the possibility that long-term consumption of Tamogi-take mushrooms might attenuate age-related decline in cardiac and vascular endothelial function in mice.

Prognostic significance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio in uterine carcinosarcoma.

Introduction: Uterine carcinosarcoma (UCS) and uterine sarcomas (US) are rare but aggressive cancer with poor prognoses. The prognostic value of systemic inflammatory response (SIR) indicators, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), in predicting outcomes of UCS and US remains unclear. This study investigated the prognostic significance of SIR indicators for UCS and US.

Questionnaire on the surgical indications for intrahepatic cholangiocarcinoma administered to Japanese board-certified expert hepatobiliary and pancreatic surgeons and instructors.

Background: Treatment of intrahepatic cholangiocarcinoma (ICC) remains challenging owing to the lack of clear guidelines on surgical resection. The 2021 ICC guidelines have not fully resolved the ongoing debate between surgical and nonsurgical treatment options. This study aimed to identify trends and issues in ICC treatment strategies in the clinical field by surveying the attitudes of hepatobiliary and pancreatic (HBP) surgeons.

[Graft-versus-host disease-like gastroenteritis after autologous stem cell transplantation with busulfan/thiotepa conditioning for primary central nervous system lymphoma].

Graft-versus-host disease (GVHD) is less common in autologous stem cell transplantation (ASCT) recipients than in allogeneic SCT recipients. However, some cases of severe GVHD, especially involving the gastrointestinal (GI) tract, have been documented. We present a patient with primary central nervous system lymphoma (PCNSL) exhibiting severe GI-GVHD after ASCT with busulfan/thiotepa conditioning.

Efficacy and Safety of a Novel Tapered-Tip Sheath System for Biliary-Lesion Tissue Sampling: A Randomized Controlled Trial.

Background/aims: Pathological evaluation is crucial for diagnosing biliary lesions and determining appropriate treatment strategies. However, tissue sampling via the transpapillary route can be difficult. In this study, we aimed to assess the efficacy and safety of a novel tapered-tip sheath system for tissue sampling from biliary strictures.

Medical Student Evaluations of Medical Faculty: Characteristics of Highly and Lower-Rated Teachers.

Purpose: Our purpose was to evaluate the characteristics of highly and poorly rated teachers as well as to assess the validity and reliability of those evaluations.

Methods: We downloaded 14 years of medicine faculty evaluations completed by 3rd and 4 year medical students. We dichotomized overall teaching effectiveness as outstanding (receiving "outstanding") or inferior (rated as a "unsatisfactory," "marginal," or "acceptable").

Outcomes and Role of Lymphadenectomy in Hypervascular Intrahepatic Cholangiocarcinoma Based on CT-Vascularity.

Background: This study aimed to evaluate the outcomes and role of lymphadenectomy in hypervascular intrahepatic cholangiocarcinoma (ICC) quantified using the arterial phase of contrast-enhanced computed tomography (CT).

Methods: Consecutive patients with mass-forming (MF) or predominantly MF type ICC who underwent surgical resection from 2000 to 2019 were retrospectively analyzed. Using the image of the late arterial phase, CT-vascularity was calculated by dividing the CT value of the tumor (Hounsfield units) with that of the liver parenchyma.

Association Between Antibiotic Exposure During Pregnancy and Postpartum Depressive Symptoms: The Japan Environment and Children's Study.

Postpartum depressive symptoms (PDS) are a common mental health condition among women after delivery. Although various causative factors have been reported, PDS remains a challenging condition to predict and prevent. The disruption of the gut microbiota due to antibiotic exposure has been reported to affect psychiatric conditions.

Enhancing quality of care for older adults: The age-friendly health system (4Ms framework) and the role of general medicine physicians as system-based complexologists.

The aging population presents critical challenges to global healthcare systems, with Japan expected to have 35% of its population aged 65 or older by 2040. Older adults often experience multimorbidity, cognitive impairments, and physical frailties, increasing healthcare utilization and costs. Traditional medical approaches that focus on organ-specific diagnoses are insufficient for addressing these multifaceted needs.

Effectiveness of the educational training program for Japanese chief residents: A one-year pilot study.

Background: Multi-institutional faculty development programs for chief residents were lacking in Japan. This study evaluated the effectiveness of the program for enhancing the knowledge and behaviors of chief residents at the national level.

Methods: Six participants completed self-assessment questionnaires at three points: before, immediately after, and 6 months post-program.

Plantar cutaneous sensation is independently associated with postural balance and lower limb motor function in older adults: the Shizuoka study.

Purpose: A relationship between decreased plantar cutaneous sensation and impaired balance function has been reported in patients with peripheral neuropathy and diabetes. This cross-sectional study aimed to investigate the relationship between plantar sensation and postural balance, as well as the association between plantar sensation and sarcopenia-related motor function in community-dwelling older adults.

Methods: The participants included 1659 community-dwelling older adults with a mean age of 74 ± 5 years, of which 43% were male patients.

Selenoprotein-Mediated Redox Regulation Shapes the Cell Fate of HSCs and Mature Lineages.

The maintenance of cellular redox balance is crucial for cell survival and homeostasis and is disrupted with aging. Selenoproteins, comprising essential antioxidant enzymes, raise intriguing questions about their involvement in hematopoietic aging and potential reversibility. Motivated by our observation of mRNA downregulation of key antioxidant selenoproteins in aged human hematopoietic stem cells (HSCs) and previous findings of increased lipid peroxidation in aged hematopoiesis, we employed tRNASec gene (Trsp) knockout (KO) mouse model to simulate disrupted selenoprotein synthesis.

Associations Between Anticipatory Grief and Post-Bereavement Depression and Post-Loss Grief of Family Members of Dying Patients With Cancer in Palliative Care Units: A Cohort Study.

Anticipatory grief is associated with post-bereavement grief; however, reports on the influence of pre-loss depression are limited. Therefore, we investigated the association between the anticipatory grief of family members and post-loss and post-depression grief adjusted for pre-loss depression. This cohort study included the family members of dying patients with cancer.