Recommendations for Design, Execution, and Reporting of Studies on Experimental Thoracic Aortopathy in Preclinical Models.

There is a recent dramatic increase in research on thoracic aortic diseases that includes aneurysms, dissections, and rupture. Experimental studies predominantly use mice in which aortopathy is induced by chemical interventions, genetic manipulations, or both. Many parameters should be deliberated in experimental design in concert with multiple considerations when providing dimensional data and characterization of aortic tissues.

Development of a Calreticulin-targeting Glycan Ligand Based on a Hybrid Binding Concept.

Calreticulin (CRT), a chaperone that possesses both lectin and chaperone domains, is localized in the endoplasmic reticulum (ER). CRT has diverse functions and localizations; thus, CRT is a multifunctional protein. Particularly in the ER, CRT mainly aids in the proper folding of nascent glycoproteins as lectin chaperones.

Innovative therapeutic strategies using ADHD medications tailored to the behavioral characteristics of patients with chronic pain.

Chronic pain affects a significant portion of adults and is linked to psychosocial issues, cognitive dysfunction, and psychiatric disorders, complicating treatment. Attention deficit hyperactivity disorder (ADHD) is increasingly recognized as a contributing factor to chronic pain, particularly nociplastic pain, with a notable prevalence of comorbidity between ADHD and conditions like fibromyalgia and chronic low back pain. ADHD behaviors such as impulsivity and overactivity can exacerbate pain by leading patients to seek risky treatments or discontinue care prematurely.

Approaches to Evaluate Whole Exome Sequencing Data That Incorporate Genetic Intolerance Scores for Congenital Anomalies, Including Intronic Regions Adjacent to Exons.

Background: Whole exome sequencing (WES) aids in diagnosing monogenic diseases, yet > 50% of all cases remain undiagnosed. We aimed to improve diagnostic precision by developing an effective WES-based strategy for detecting congenital anomalies.

Methods: Initially, 128 probands with congenital anomalies were assessed using trio-WES and copy number variation analysis-variant interpretation was for exons and splice sites.

Cost-effectiveness analysis of bispecific antibody faricimab for treatment of neovascular age-related macular degeneration and diabetic macular edema in Japan.

ObjectiveTo assess the cost-effectiveness of faricimab versus other anti-vascular endothelial growth factor (anti-VEGF) drugs for treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) in Japan, while considering societal burden associated with treatment.MethodsA Markov model for cost-effectiveness analysis of anti-VEGF treatment in patients with nAMD and DME was applied based on cost and utility value data from Japan. Faricimab administered through a treat-and-extend (T&E) regimen was compared with ranibizumab administered pro re nata (PRN) and T&E, aflibercept T&E, brolucizumab T&E, and best supportive care (BSC).

Highly multiplexed digital PCR assay for simultaneous quantification of variant allele frequencies and copy number alterations of KRAS and GNAS in pancreatic cancer precursors.

Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMNs) are pancreatic ductal adenocarcinoma (PDAC) precursor lesions. Detecting these precursors and monitoring their progression are crucial for early PDAC diagnosis. Digital PCR (dPCR) is a highly sensitive nucleic acid quantification technique and offers a cost-effective option for patient follow-up.

Polymethoxyflavones and Bone Metabolism.

Phytochemicals, such as flavonoids, are bioactive compounds produced by plants, including citrus fruits, that exhibit antioxidant effects on mammalian cells and tissues. Polymethoxyflavones (PMFs) are a family of flavonoids found in the pulp and peel of citrus fruits, and have been reported to have potent antioxidant activity implicated in the prevention of human diseases. Several studies have shown that PMFs have a protective effect on bone resorption in mouse models of diseases, including osteoporosis, rheumatoid arthritis, and periodontal disease.

Acerola-Derived Photorepair System for Eliminating Ultraviolet-Induced Pyrimidine Dimers in Human Cells.

: Ultraviolet B (UV-B) is a significant risk factor for skin damage, as it induces cyclobutane pyrimidine dimers (CPD), which suppress DNA replication and transcription. Photolyase (PHR) is a blue light-dependent enzyme that repairs DNA damage caused by UV irradiation. While it is absent in human, it plays a crucial role in repairing CPD in other organisms.

Sex Differences in the Relationship Between Nutrient Intake and Mortality Results of the Shika Cohort Study.

: Macronutrients (protein, fat, and carbohydrate) provide sources of energy and play crucial roles in various physiological functions. However, sex differences in the relationships between protein, fat, and carbohydrate intakes and all-cause mortality remain unclear. The present study investigated sex differences in the relationships between protein, fat, and carbohydrate intakes and all-cause mortality using longitudinal epidemiological data.

Influence of Steel Fiber Content on the Long-Term Stability of Slag-Containing UHPC Under Different Environments.

Ultra-high-performance concrete (UHPC) is an advanced material known for its high strength and durability. This study investigates the long-term stability of slag-containing UHPC exposed to outdoor, tap water, and seawater environments over 720 days, focusing on the impact of steel fiber content. The results show that UHPC in tap water exhibits higher compressive strength compared to seawater and outdoor environments.

Differential Effects of Adding Graphene Nanoplatelets on the Mechanical Properties and Crystalline Behavior of Polypropylene Composites Reinforced with Carbon Fiber or Glass Fiber.

Short fiber-reinforced thermoplastic composites (SFRTPs) have excellent recyclability and processability, but their mechanical properties are weak compared to continuous fiber products. Various studies have reported that the addition of GNPs improves the mechanical properties of SFRTPs, but it is unclear what effect different types of reinforcing fibers have on a hybrid composite system. In this study, the effect of adding a small amount (1 wt%) of graphene nanoplatelets (GNPs) to fiber-reinforced polypropylene composites on their mechanical properties was investigated from a crystallinity perspective.

Aspirin Eugenol Ester Alleviates Energy Metabolism Disorders by Reducing Oxidative Damage and Inflammation in the Livers of Broilers Under High-Stocking-Density Stress.

This study aimed to evaluate the effects of aspirin eugenol ester (AEE) on growth performance, oxidative liver damage, inflammation, and liver metabolomics in broilers under high-stocking-density (HSD) stress. A total of 360 broilers were divided into four groups: normal density (ND, 14/m), high density (HD, 22/m), ND-AEE (ND + 0.01% AEE), and HD-AEE (HD + 0.

Trends in Efficacy Endpoints in Phase II Glioblastoma Trials: A Regulatory Science Analysis (FY2020-FY2022).

: In glioblastoma trials, efficacy evaluation often deviates from the standard Response Evaluation Criteria in Solid Tumors (RECIST), an objective response rate (ORR) method, because of the unique nature of brain tumors. In phase II trials from the fiscal years (FYs) 2017-2019, primary endpoints (PEs) were overall survival (OS) at 29%, ORR at 20%, progression-free survival (PFS) at 17%, and OS rate at 10%. Clinical trial methodologies have likely evolved in recent years.

Proteogenomic Profiling of Treatment-Naïve Metastatic Malignant Melanoma.

Background: Melanoma is a highly heterogeneous disease, and a deeper molecular classification is essential for improving patient stratification and treatment approaches. Here, we describe the histopathology-driven proteogenomic landscape of 142 treatment-naïve metastatic melanoma samples to uncover molecular subtypes and clinically relevant biomarkers.

Methods: We performed an integrative proteogenomic analysis to identify proteomic subtypes, assess the impact of BRAF V600 mutations, and study the molecular profiles and cellular composition of the tumor microenvironment.

The current status of cancer rehabilitation provided by palliative care units in Japan: a nationwide survey.

Background: To our knowledge, the current status of and barriers to cancer rehabilitation in palliative care units (PCUs) in Japan remain to be elucidated. If clarified, this information could help develop rehabilitation strategies to improve the quality of life of patients with cancer who need palliative care. Hence, this study aimed to clarify the current status of and barriers to cancer rehabilitation in PCUs in Japan by conducting a nationwide questionnaire survey.

XFEL crystallography reveals catalytic cycle dynamics during non-native substrate oxidation by cytochrome P450BM3.

Cytochrome P450s are haem-containing enzymes, catalysing the regio- and stereospecific oxidation of non-activated hydrocarbons. Among these, the bacterial P450BM3 is a promising biocatalyst due to its high enzymatic activity. Given the significant conformational flexibility of this enzyme, understanding protein-substrate interactions and associated structural dynamics are crucial for designing P450BM3-based biocatalysts.

Receptor mechanism producing a sweet taste from plant aroma compounds.

Fruits and vegetables contain highly volatile hydrophobic small molecules responsible for their aroma, taste, and pungency. Empirically, we understand that these compounds can evoke a sweet taste; however, their specific interactions with sweet taste receptors are unclear. To address this issue, HEK293 cells expressing human and mouse sweet taste receptors TAS1R2/TAS1R3 were used to identify trans-2-hexenal (a novel sweetener) in human and cinnamyl alcohol (a sweetness inhibitor) in mice.

Uptake of small extracellular vesicles by recipient cells is facilitated by paracrine adhesion signaling.

Small extracellular vesicles (sEVs) play crucial roles in intercellular communication. However, the internalization of individual sEVs by recipient cells has not been directly observed. Here, we examined these mechanisms using state-of-the-art imaging techniques.

Development and Validation of the Scale of Motives for Faith in Japan.

Previous religiousness scales have been developed in Christian contexts; we developed in Japan, where diverse religions coexist, the Scale of Motives for Faith comprising novel dimensions to facilitate intercultural comparison studies between Western and Eastern religions including monotheistic, polytheistic, and atheistic ones. In Phase 1, items were extracted using an adapted Delphi method; in Phase 2, validity and reliability were tested in a nationwide survey. In Phase 1, twenty experts representing Buddhism, Christianity, Shinto, Islam, and new religions extracted 16 items; in Phase 2 using a pilot scale, 1093 respondents' beliefs were analyzed.

First-Line Tislelizumab Plus Chemotherapy for Advanced Gastric Cancer with Programmed Death-Ligand 1 Expression ≥ 1%: A Retrospective Analysis of RATIONALE-305.

Introduction: Tislelizumab plus investigator-chosen chemotherapy (ICC) demonstrated a statistically significant improvement in overall survival (OS) versus placebo plus ICC in RATIONALE-305 in patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric cancer/gastroesophageal junction cancer (GC/GEJC) in the intent-to-treat population and in patients with programmed death-ligand 1 (PD-L1) Tumor Area Positivity (TAP) score ≥ 5%. The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against first-line treatment with programmed cell death protein-1 inhibitors in this setting in patients with a PD-L1 combined positive score < 1 or TAP score < 1%, due to an unfavorable benefit-risk profile. Thus, we retrospectively analyzed data from RATIONALE-305 in patients with a PD-L1 TAP score ≥ 1%.

First-Line Tislelizumab Plus Chemotherapy for Esophageal Squamous Cell Carcinoma with Programmed Death-Ligand 1 Expression ≥ 1%: A Retrospective Analysis of RATIONALE-306.

Introduction: The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against the use of programmed cell death protein-1 inhibitors for first-line treatment of advanced or metastatic unresectable esophageal squamous cell carcinoma (ESCC) with a programmed death-ligand 1 (PD-L1) expression Tumor Area Positivity (TAP) score < 1% or combined positive score < 1 due to an unfavorable benefit-risk profile observed across the phase 3 CheckMate 648, KEYNOTE-590, and RATIONALE-306 trials. Therefore, we conducted a retrospective analysis of RATIONALE-306 to evaluate the efficacy and safety of tislelizumab plus investigator-chosen chemotherapy (ICC) versus placebo plus ICC in patients with advanced or metastatic unresectable ESCC and a PD-L1 TAP score ≥ 1%.

Methods: Adult patients with advanced or metastatic unresectable ESCC enrolled in the global, randomized, phase 3 RATIONALE-306 trial randomly received tislelizumab 200 mg every 3 weeks plus ICC or matched placebo plus ICC.

Prevalence of Comorbid Hyperparathyroidism and Its Association with Renal Dysfunction in Asian Patients with X-Linked Hypophosphatemic Rickets/Osteomalacia.

In patients with X-linked hypophosphatemic rickets/osteomalacia (XLH) in Asia, the current prevalence of hyperparathyroidism and its association with renal dysfunction have not been determined. We used patient data retrospectively collected up to the time of informed consent in the SUNFLOWER study, a long-term observational study, to investigate the current treatment status and prevalence of comorbid hyperparathyroidism and its association with renal dysfunction in patients with XLH in Japan and South Korea. Of 69 patients who met the eligibility criteria, 32 (46.

Long-term clinical significance of the presence of puff-chandelier ruptures detected by non-obstructive aortic angioscopy.

Although studies have reported various patterns of atherosclerotic aortic plaques (AAPs) detected by non-obstructive aortic angioscopy (NOA), the long-term outcomes associated with AAPs such as puff-chandelier rupture atheromatous plaque (PCR), remain unclear. This study investigated the long-term prognostic significance of AAPs detected by NOA in patients who underwent percutaneous coronary intervention (PCI). This retrospective multicenter cohort study included 167 patients who underwent PCI and NOA.

Foxa2-dependent uterine glandular cell differentiation is essential for successful implantation.

Uterine receptivity is essential for successful implantation. In mice, uterine receptivity begins with the secretion of LIF from uterine glands stimulated by estrogen on the morning of day 4 pregnancy. We hypothesize that gland readiness for estrogen stimulation is indispensable for uterine receptivity.

Best Practices for Imaging of Transcatheter Valve Failure: An Update From the Heart Valve Collaboratory.

This updated Heart Valve Collaboratory framework addresses the growing concern for transcatheter valve failure (TVF) following transcatheter aortic valve replacement (TAVR). With the increasing volume of redo-TAV and surgical TAV explantation, there is a critical need for standardized pathways and protocols for evaluating TVF using echocardiography and cardiac computed tomography (CT) angiography. This document clarifies prior definitions of bioprosthetic valve deterioration and bioprosthetic valve failure in a practical, imaging directed context for TAVR.