Exploring the next generation of antibody-drug conjugates.

Antibody-drug conjugates (ADCs) are a promising cancer treatment modality that enables the selective delivery of highly cytotoxic payloads to tumours. However, realizing the full potential of this platform necessitates innovative molecular designs to tackle several clinical challenges such as drug resistance, tumour heterogeneity and treatment-related adverse effects. Several emerging ADC formats exist, including bispecific ADCs, conditionally active ADCs (also known as probody-drug conjugates), immune-stimulating ADCs, protein-degrader ADCs and dual-drug ADCs, and each offers unique capabilities for tackling these various challenges.

Effect of microgravity on mammalian embryo development evaluated at the International Space Station.

Mammalian embryos differentiate into the inner cell mass (ICM) and trophectoderm at the 8-16 cell stage. The ICM forms a single cluster that develops into a single fetus. However, the factors that determine differentiation and single cluster formation are unknown.

Degradation of autotoxic chemicals and maintainence of electrical conductivity recover growth, yield and nutrient absorption of successive lettuce in recycled hydroponics.

In recycled hydroponics, successive crop cultivation by maintaining electrical conductivity (EC) suffers lower growth performance due to accumulating autotoxic root exudates. In this study, the efficiency of alternate current electro degradation (AC-ED) was evaluated for degrading allelochemicals and recovering retarded lettuce yield cultivated in EC-adjusted repeatedly used nutrient solutions. From benzoic acid (BA)-added nutrient solution, BA was completely degraded after 24 h by applying AC-ED at 551 and 940 Hz frequency with 50 and 80% electrical duty.

Non-randomized controlled trial examining the effects of livestock on motivation and anxiety in patients with chronic psychiatric disorders.

Objectives: Patients with chronic schizophrenia exhibit negative symptoms, including decreased work motivation. Animal-assisted therapy programs have been reported to benefit such patients; hence, there is a possibility that sheep-rearing, rather than conventional employment training, may motivate these patients. Therefore, we investigated the effects of a one-day experiential learning program of sheep-rearing on the work motivation and anxiety of patients with chronic schizophrenia.

Discrepancy between invasive and echocardiographic transvalvular gradient after TAVI: Insights from the LAPLACE-TAVI registry.

Background: Echocardiography-based transvalvular mean pressure gradient (ECHO-mPG) used to assess the forward valve function and structural valve deterioration could overestimate the true pressure gradient. This study evaluated the discrepancy between invasive and ECHO-mPG after transcatheter aortic valve implantation (TAVI) with respective valve type and size, its impact on a device success criterion, and predictors of a pressure discrepancy.

Methods: We analyzed 645 patients registered in a multicenter TAVI registry (balloon-expandable valve [BEV]: 500; self-expandable valve [SEV]: 145).

Non-A Blood Type Is a Risk Factor for Poor Cardio-Cerebrovascular Outcomes in Patients Undergoing Dialysis.

The clinical impact of ABO blood type on cardio-cerebrovascular outcomes in patients undergoing dialysis has not been clarified. A total of 365 hemodialysis patients participated in the current study. The primary endpoint was defined as a composite including cardio-cerebrovascular events and cardio-cerebrovascular death.

Understanding Mothers' Worries about the Effects of Disaster Evacuation on Their Children: A Cross-Sectional Study.

In Japan, there is an imminent threat of major earthquakes and floods. Children's health is increasingly at risk from climate-change-related disasters. The purpose of this study was to identify factors related to mothers' worries about the effects of evacuation on their children.

Comprehensive analyses of plant hormones in etiolated pea and maize seedlings grown under microgravity conditions in space: Relevance to the International Space Station experiment "Auxin Transport".

Functional relationships between endogenous levels of plant hormones in the growth and development of shoots in etiolated Alaska pea and etiolated Golden Cross Bantam maize seedlings under different gravities were investigated in the "Auxin Transport" experiment aboard the International Space Station (ISS). Comprehensive analyses of 31 species of plant hormones of pea and maize seedlings grown under microgravity (μg) in space and 1 g conditions were conducted. Principal component analysis (PCA) and a multiple regression analysis with the dataset from the plant hormone analysis of the etiolated pea seedlings grown under μg and 1 g conditions in the presence and absence of 2,3,5-triiodobenzoic acid (TIBA) revealed endogenous levels of auxin correlated positively with bending and length of epicotyls.

Effect of Maillard reaction on the quality of clarified butter, ghee.

In Ayurveda, a traditional Indian medicine system, clarified butter is called ghee and is used for food and medicinal purposes. Since butter is subjected to heat to prepare ghee, the heating process affects the ghee quality, such as oxidation, flavor, nutritional value, and biological activity. Therefore, this study focused on the Maillard reaction progress and free-radical scavenging activity with temperature and time during ghee preparation.

Development of a new device for manipulating frozen mouse 2-cell embryos on the International Space Station.

Whether mammalian embryos develop normally under microgravity remains to be determined. However, embryos are too small to be handled by inexperienced astronauts who orbit Earth on the International Space Station (ISS). Here we describe the development of a new device that allows astronauts to thaw and culture frozen mouse 2-cell embryos on the ISS without directly contacting the embryos.

Development of a New Radiation Shield for the Face and Neck of IVR Physicians.

Interventional radiology (IVR) procedures are associated with increased radiation exposure and injury risk. Furthermore, radiation eye injury (i.e.

An Enzymatically Cleavable Tripeptide Linker for Maximizing the Therapeutic Index of Antibody-Drug Conjugates.

Valine-citrulline is a protease-cleavable linker commonly used in many drug delivery systems, including antibody-drug conjugates (ADC) for cancer therapy. However, its suboptimal in vivo stability can cause various adverse effects such as neutropenia and hepatotoxicity, leading to dose delays or treatment discontinuation. Here, we report that glutamic acid-glycine-citrulline (EGCit) linkers have the potential to solve this clinical issue without compromising the ability of traceless drug release and ADC therapeutic efficacy.

Indole-3-pyruvic acid regulates TAA1 activity, which plays a key role in coordinating the two steps of auxin biosynthesis.

Auxin biosynthesis involves two types of enzymes: the Trp aminotransferases (TAA/TARs) and the flavin monooxygenases (YUCCAs). This two-step pathway is highly conserved throughout the plant kingdom and is essential for almost all of the major developmental processes. Despite their importance, it is unclear how these enzymes are regulated and how their activities are coordinated.

Childhood Tuberculosis in Mongolia: Trends and Estimates, 2010-2030.

Mongolia was listed among the 30 countries with a high tuberculosis burden in 2021. Approximately 10-11% of the tuberculosis cases are of children, which is higher than the global average (6.0%).

Impact of left ventricular hypertrophy on clinical outcomes in patients with dialysis: a single-center study in Japan.

Purpose: Left ventricular hypertrophy (LVH) is a well-known risk factor for poor clinical outcomes in patients undergoing dialysis. However, little evidence supports the above notion in Japan, and the influence of subtypes of LVH on prognosis.

Methods: We investigated 367 patients undergoing dialysis who underwent routine echocardiographic examinations between April and September 2018.

Antibody-drug conjugates with dual payloads for combating breast tumor heterogeneity and drug resistance.

Breast tumors generally consist of a diverse population of cells with varying gene expression profiles. Breast tumor heterogeneity is a major factor contributing to drug resistance, recurrence, and metastasis after chemotherapy. Antibody-drug conjugates (ADCs) are emerging chemotherapeutic agents with striking clinical success, including T-DM1 for HER2-positive breast cancer.

Impact of serum magnesium and bone mineral density on systemic fractures in chronic hemodialysis patients.

Introduction: Bone mineral density (BMD) measured with dual-energy X-ray absorptiometry (DXA) can be used to predict fractures, but its clinical utility has not been fully established in chronic kidney disease (CKD) patients. Magnesium is an essential trace element. Although magnesium is associated with the risk of fractures in non-CKD populations, the relationship is unknown in CKD patients.

Recent advances in clinical studies of selenium supplementation in radiotherapy.

Background: Radiotherapy is one of the most important and common therapies for cancer patients. Selenium has been shown to be capable of reducing the side effects of radiotherapy because selenoproteins have anti-oxidative functions against reactive oxygen species that are induced by the radiation. They also function in DNA-repair and cytokine control.