Preclinical pharmacokinetic, pharmacodynamic, and safety profile of OBI-992: a novel TROP2-targeted antibody-drug conjugate.

OBI-992, a novel TROP2-targeted ADC, is composed of an anti-TROP2 antibody conjugated to exatecan, a topoisomerase 1 (TOP1) inhibitor, via an enzyme-cleavable hydrophilic linker. The stability, pharmacokinetics, pharmacodynamics, and off-target toxicity of OBI-992 were evaluated and compared with a benchmark ADC datopotamab deruxtecan (Dato-DXd). OBI-992 exhibited better stability in human and monkey serum than Dato-DXd, which was further supported by in-vivo PK study in rats.

Factors Associated With Potentially Inappropriate Medication Use and Deprescribing Among Patients Receiving Home-Based Hospice Care.

PurposeThis study aimed to examine the factors associated with potentially inappropriate medication (PIM) use and the deprescribing among home hospice patients in Taipei, Taiwan.MethodsWe analyzed 101 home hospice patients from a Taipei City hospital from 2016 to 2022, using 2 significant PIMs which are identified by the OncPal guideline and STOPPFrail version 2 respectively. Logistic regression and Cox proportional hazards regression were used to analyze factors associated with PIMs and the deprescribing.

Home-based, short-duration, high-intensity interval inspiratory muscle training improves exercise capacity of patients with chronic heart failure: a double-blind study.

Aims: To explore effects of home-based, short-duration, high-intensity interval inspiratory muscle training (IMT) on exercise capacity, inspiratory muscle function, and quality of life (QoL) in patients with chronic heart failure (CHF).

Methods And Results: Thirty-six adult patients with diagnosed CHF with NYHA II-III were randomly assigned to the high-intensity interval inspiratory muscle training group (H-IMT; n = 17) and sham inspiratory muscle training group (S-IMT; n = 19). All participants received home-based training 1 session/day, 6 days/week for 12 weeks.

Development of Autonomous Electric USV for Water Quality Detection.

With the rise of industry, river pollution has become increasingly severe. Countries worldwide now face the challenge of effectively and promptly detecting river pollution. Traditional river detection methods rely on manual sampling and subsequent data analysis at various sampling sites, requiring significant time and labor costs.

Preclinical evaluation of a novel antibody-drug conjugate OBI-992 for Cancer therapy.

Trophoblast cell surface antigen 2 (TROP2), a transmembrane glycoprotein highly expressed in a variety of epithelial cancers, has been considered as a primary therapeutic target for the development of antibody-drug conjugates (ADCs). OBI-992, an investigational TROP2-targeted ADC, is composed of a novel TROP2 antibody (R4702) conjugated to the topoisomerase I (TOP1) inhibitor exatecan through a hydrophilic enzyme-cleavable linker. This study aimed to characterize R4702 and OBI-992 in vitro.

Comparative analysis of frailty identification tools in community services across the Asia-Pacific: A systematic review and meta-analysis.

Objectives: This study aimed to compare various frailty screening and assessment tools with the Frailty Phenotype (FP), Frailty Index (FI), and Comprehensive Geriatric Assessment (CGA), which are considered the current gold standards, among the Asia-Pacific population in community settings.

Design: Systematic review and meta-analysis.

Setting And Participants: This review included studies evaluating frailty identification tools based on the criteria of population, index and reference tests, and diagnosis of interest.

Geometric construction of relativistic and non-relativistic distortion.

To an observer moving through a scene with a relativistic velocity, the scene appears distorted. Here we present a simple geometric interpretation of this relativistic distortion. This interpretation is exact for pinhole cameras whose shutter coincides with the pinhole, and it can easily be modified to take into account time-of-flight effects only that lead to a "non-relativistic distortion," allowing a separation of the relativistic distortion into time-of-flight effects and "truly relativistic" effects.

Deep Convolutional Neural Networks on Multiclass Classification of Three-Dimensional Brain Images for Parkinson's Disease Stage Prediction.

Parkinson's disease (PD), a degenerative disorder of the central nervous system, is commonly diagnosed using functional medical imaging techniques such as single-photon emission computed tomography (SPECT). In this study, we utilized two SPECT data sets (n = 634 and n = 202) from different hospitals to develop a model capable of accurately predicting PD stages, a multiclass classification task. We used the entire three-dimensional (3D) brain images as input and experimented with various model architectures.

Soy Protein and Safflower-Seed Oil Attenuate Inflammation and Immune Dysfunction in Rats with Hyperuricemia.

A plant-based diet is considered a promising approach for managing hyperuricemia (HUA). This study examined the effects of soy protein and plant-based oils on HUA-induced inflammation and immune dysfunction. Male Wistar rats, induced with HUA using oxonic acid and uric acid (UA), were fed casein or soy protein with palm or safflower oil (2 × 2 factorial design) for 8 weeks.

Structural Diversity and Dimensionality of Three Cu(II)-dpds-CO Coordination Polymers Controlled by the Coordination Sphere of Cu(II) Centers and the Coordination Modes of CO (dpds = 4,4'-Dipyridyldisulfide).

Three supramolecular architectures, [Cu(dpds)(CO)(HO)]·3HO (), [Cu(dpds)(CO)]·3HO (), and [Cu(dpds)(CO)]·9HO·CHOH () (dpds = 4,4'-dipyridyldisulfide and CO (croconate) = dianion of 4,5-dihydroxycyclopent-4-ene-1,2,3-trione), have been synthesized and structurally characterized. Compound contains two crystallographically independent Cu(II) ions, which are both distorted octahedral geometry with elongation along the croconate- and HO-bound axial positions and bonded with two N atoms of two dpds, two O atoms of one CO , and two HO molecules. Two crystallographically independent dpds ligands, both adopting the bis-monodentate bridging mode, connect two Cu(II) ions to form a one-dimensional zigzag chain-like coordination polymer.

Future Goal Aspirations of Students With Extensive Support Needs: Findings From NLTS 2012.

This study used data from the National Longitudinal Transition Study 2012 (NLTS 2012) to explore the future goal aspirations of students with extensive support needs who participate in alternate assessments, compared to other students with extensive support needs and to students with other disabilities. We examined students' individualized education program (IEP)/transition planning meeting experiences and postschool goals in relation to their functional, communication, and self-advocacy skills, as well as their school/community support. Students with other disabilities held higher expectations than all students with extensive support needs for future participation in postsecondary education, employment, independent living, and financial independence.

A Web-Based Resilience-Enhancing Program to Improve Resilience, Physical Activity, and Well-being in Geriatric Population: Randomized Controlled Trial.

Background: Resilience is a protective factor in healthy aging, helping to maintain and recover physical and mental functions. The Resilience in Illness Model has proven effective in fostering resilience and well-being. Physical activity is crucial for older adults' independence and well-being, even as aging causes a progressive decline.

Identification of potential biomarkers of leprosy: A study based on GEO datasets.

Leprosy has a high rate of cripplehood and lacks available early effective diagnosis methods for prevention and treatment, thus novel effective molecule markers are urgently required. In this study, we conducted bioinformatics analysis with leprosy and normal samples acquired from the GEO database(GSE84893, GSE74481, GSE17763, GSE16844 and GSE443). Through WGCNA analysis, 85 hub genes were screened(GS > 0.

Structure-guided identification and characterization of potent inhibitors targeting PhoP and MtrA to combat mycobacteria.

Mycobacteria are causative agents of tuberculosis (TB), which is a global health concern. Drug-resistant TB strains are rapidly emerging, thereby necessitating the urgent development of new drugs. Two-component signal transduction systems (TCSs) are signaling pathways involved in the regulation of various bacterial behaviors and responses to environmental stimuli.

Discovery of a potent inhibitor, D-132, targeting AsfvPolX, via protein-DNA complex-guided pharmacophore screening and in vitro molecular characterizations.

The heightened transmissibility and capacity of African swine fever virus (ASFV) induce fatal diseases in domestic pigs and wild boars, posing significant economic repercussions and global threats. Despite extensive research efforts, the development of potent vaccines or treatments for ASFV remains a persistent challenge. Recently, inhibiting the AsfvPolX, a key DNA repair enzyme, emerges as a feasible strategy to disrupt viral replication and control ASFV infections.

Postschool Goal Expectations for Youth With Intellectual and Developmental Disabilities.

Using National Longitudinal Transition Study 2012 data, this study explored parent and youth expectations in the areas of postsecondary education, employment, independent living, and financial independence. Compared to youth with other disabilities, youth with intellectual and developmental disabilities and their parents had much lower expectations for the four postschool goals, and parent expectations were much lower than youth's own expectations. Also, youth's race, along with their daily living skills and functional abilities, were positively associated with parent and youth expectations in several future goal areas.

Effects of coach extraversion and educational environment on transformational leadership and athlete outcomes: A moderated mediation model.

The importance of coach leadership to athlete development and performance has been identified in the literature. We respond to the call to investigate antecedents of coach transformational leadership and their indirect effects on athlete outcomes. We propose that coach extraversion as an antecedent of coach transformational leadership can indirectly impact follower cohesion and satisfaction.

Physical Therapy for Adults with Heart Failure.

Heart failure (HF) is a complex clinical syndrome caused by structural and/or functional abnormalities that results in significant disease burdens not only to the patients and their families but also to the society. Common symptoms/signs of HF include dyspnea, fatigue, and exercise intolerance, which significantly reduce the quality of life of individuals. Since the coronavirus disease 2019 (COVID-19) pandemic in 2019, it has been found that individuals with cardiovascular disease are more vulnerable to COVID-19-related cardiac sequelae including HF.

Analysis of a Yp11.2 region deletion in a Chinese female with Turner syndrome: A case report.

In recent years, an increasing number of abnormal DNA genotypes caused by chromosomal abnormalities have been revealed in cases of individual identification and sex-typing analysis, especially analyses of the amelogenin and short tandem repeat (STR) loci on the sex chromosomes. Here, we report a 17-year-old female with Turner syndrome typed as male due to the presence of the amelogenin Y allele. The Y-STR haplotype showed allele dropout of three Y-STR loci (DYS549, DYS392 and DYS448).

Immunogenicity of a spike protein subunit-based COVID-19 vaccine with broad protection against various SARS-CoV-2 variants in animal studies.

SARS-CoV-2 pandemic has profound impacts on human life and global economy since the outbreak in 2019. With the new variants continue to emerge with greater immune escaping capability, the protectivity of the available vaccines is compromised. Therefore, development a vaccine that is capable of inducing immunity against variants including omicron strains is in urgent need.

Hydrogen Bond-Enabled High-ICE Anode for Lithium-Ion Battery Using Carbonized Citric Acid-Coated Silicon Flake in PAA Binder.

A silicon-based lithium-ion battery (LIB) anode is extensively studied because of silicon's abundance, high theoretical specific capacity (4200 mAh/g), and low operating potential versus lithium. Technical barriers to large-scale commercial applications include the low electrical conductivity and up to about 400% volume changes of silicon due to alloying with lithium. Maintaining the physical integrity of individual silicon particles and the anode structure is the top priority.

The effectiveness of mind-body approaches for enhancing resilience in older adults: A systematic review and network meta-analysis.

Background: Resilience in older adults is associated with good well-being and resilience training has been shown to be beneficial. Mind-body approaches (MBAs) combine physical and psychological training in age-appropriate exercise programs.This study aims to evaluate the comparative effectiveness of different modes of MBAs in enhancing resilience in older adults.

kHz-frequency electrical stimulation selectively activates small, unmyelinated vagus afferents.

Background: Vagal reflexes regulate homeostasis in visceral organs and systems through afferent and efferent neurons and nerve fibers. Small, unmyelinated, C-type afferents comprise over 80% of fibers in the vagus and form the sensory arc of autonomic reflexes of the gut, lungs, heart and vessels and the immune system. Selective bioelectronic activation of C-afferents could be used to mechanistically study and treat diseases of peripheral organs in which vagal reflexes are involved, but it has not been achieved.