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Active targeting strategy is adopted in nanomedicine for cancer treatment. Personalizing the nanomedicine in accordance with patients' omics, under the precision medicine platform, is met with challenges in targeting ligand and matrix material selection at nanoformulation stage. The past 5-year literatures show that the nanoparticulate targeting ligand and matrix material are not selected based upon the cancer omics profiles of patients. The expression of cancer cellular target receptors and metabolizing enzymes is primarily influenced by age, gender, race/ethnic group and geographical origin of patients. The personalized perspective of a nanomedicine cannot be realised with premature digestion of matrix and targeting ligand by specific metabolizing enzymes that are overexpressed by the patients, and unmatched targeting ligand to the majority of cell surface receptors overexpressed in cancer. Omics analysis of individual metabolizing enzyme and cancer cell surface receptor expressed in cancer facilitates targeting ligand and matrix material selection in nanomedicine development.

Student absenteeism affects students’ engagement in school and academic and professional success. While research documents a significant association between school bullying/fighting and student absenteeism due to fear of being at school or getting to school, little research has examined the association of adolescent dating violence (ADV) victimization with this type of absenteeism. This study examined the relationship between physical and/or sexual ADV victimization in the past year (dichotomized as yes or no), and number of days of student absenteeism due to feeling unsafe at school or on the way to school in the past month (dichotomized as any vs. none). We analyzed cross-sectional data from the 2019 Youth Risk Behavior Survey (YRBS), a nationally representative survey of U.S. high school students ( n = 9507). We conducted crude and multivariate regression models for the total sample and stratified by sex to assess our hypothesized association of ADV victimization and absenteeism; sex, grade, race/ethnicity, and sexual identity were included as covariates in adjusted models. Findings demonstrate that students reporting past year ADV victimization had 3.69 times the odds of student absenteeism due to feeling unsafe, when compared to students who did not report ADV victimization (95% CI: 3.06–4.45, p < 0.001). Sex-stratified models reveal that this effect is significantly stronger for males than for females, as indicated by non-overlapping confidence intervals (male AOR: 5.67, 95% CI: 4.18–7.68; female AOR: 2.95, 95% CI: 2.32–3.74). The multivariate models also show that Black and Latinx compared with White students, and lesbian/gay/bisexual/unsure compared with heterosexual students, had higher odds of student absenteeism due to feeling unsafe. Findings indicate the need to address ADV victimization and student absenteeism with integrated and gender-tailored responses, and with consideration of greater vulnerabilities for queer students and students of color.

IntroductionKawasaki disease (KD) is an acute idiopathic systemic vasculitis with a self- limiting course that predominantly affects children under 5 years old, particularly in the East Asian countries. Nevertheless, to date, the data on KD in Malaysia are limited. This study aimed to evaluate the epidemiology, clinical features, treatment, and outcomes of KD among the pediatric patients admitted to Hospital Canselor Tunku Muhriz (HCTM), Kuala Lumpur, Malaysia.MethodA retrospective cohort study of 66,500 pediatric patients presented at HCTM from the year 2004 to 2021 was conducted.Results62 KD cases out of 66,500 pediatric admissions were reported, with a male-to-female ratio of 1.58 to 1. Majority of KD patients (95.0%) were younger than 5 years old. Prior infection was reported in 5 KD patients (8.1%). Apart from the classical features, manifestations of various organ systems including cardiovascular (16.1%), gastrointestinal (43.5%), neurological (1.61%), musculoskeletal (1.61%), and genitourinary (17.7%) systems were observed. There was a significant association between sterile pyuria and coronary artery aneurysm (CAA) (p p p DiscussionThe presence of family history, immunological disorder, and previous infection in our KD patients suggested that there is a possibility of genetic, immunological, and infectious roles in the pathophysiology of KD. IVIG resistance is more likely to occur in KD patients with hepatic dysfunction or incomplete KD presentation. These findings highlighted the significant contribution of laboratory parameters to the prognosis of KD, prompting more in-depth research on the KD scoring systems and their relevance in this country.

X-linked lymphoproliferative disease (XLP) is either caused by loss of the SLAM-associated protein (SAP; XLP-1) or the X-linked inhibitor of apoptosis (XIAP; XLP-2). In both instances, infection with the oncogenic human Epstein Barr virus (EBV) leads to pathology, but EBV-associated lymphomas only emerge in XLP-1 patients. Therefore, we investigated the role of XIAP during B cell transformation by EBV. Using humanized mice, IAP inhibition in EBV-infected mice led to a loss of B cells and a tendency to lower viral titers and lymphomagenesis. Loss of memory B cells was also observed in four newly described patients with XIAP deficiency. EBV was able to transform their B cells into lymphoblastoid cell lines (LCLs) with similar growth characteristics to patient mothers’ LCLs in vitro and in vivo. Gene expression analysis revealed modest elevated lytic EBV gene transcription as well as the expression of the tumor suppressor cell adhesion molecule 1 (CADM1). CADM1 expression on EBV-infected B cells might therefore inhibit EBV-associated lymphomagenesis in patients and result in the absence of EBV-associated malignancies in XLP-2 patients.

BackgroundPublished literature documents tremendous gender inequities in the social, economic and health effects of the COVID-19 pandemic, but less evidence has come from low- and middle-income countries (LMICs) and even less from LMIC-based authors. We examine whether a) COVID-19 burden and b) LMIC-based authorship were associated with academic publications related to COVID-19 and women's well-being in LMICs.MethodsWe reviewed academic articles on COVID-19 and women's well-being in LMICs published between February 2020 and May 2021 (n=1076 articles), using six electronic databases (PubMed, Web of Science, PsycInfo, EconLit, RePeC, NBER). Multilevel, mixed effects linear regressions assessed the relationships between each of our independent variables - a) COVID-19 burden (cases/100 population, deaths/100 population, deaths/cases) and b) author's country of primary affiliation, with publications related to COVID-19 and women's well-being, both overall and stratified by country income group.FindingsEight-eight percent of articles had lead and/or senior authors affiliated with in-country institutions. Linear mixed effect models indicate that COVID-19 cases and case fatality ratios in a country were significantly and positively associated with the number of publications related to COVID-19 and women's well-being, though these relationships were significant only in upper-middle income group countries in stratified analyses. LMIC lead and senior authorship were also significantly and positively associated with our outcome, after adjusting for COVID-19 burden.InterpretationWhile the majority of COVID-19 research examining women's well-being in LMICs in the first year and a half of the pandemic included country-affiliated author leadership, there were important gaps in representation. Findings highlight the importance of LMIC-based scholars to build local and gendered research in crises.FundingBill and Melinda Gates Foundation (INV-018007).

Cranial radiation is important for treating both primary brain tumors and brain metastases. A potential delayed side effect of cranial radiation is neurocognitive function decline. Early detection of CNS injury might prevent further neuronal damage. Extracellular vesicles (EVs) have emerged as a potential diagnostic tool because of their unique membranous characteristics and cargos. We investigated whether EVs can be an early indicator of CNS injury by giving C57BJ/6 mice 10 Gy cranial IR. EVs were isolated from sera to quantify: 1) number of EVs using nanoparticle tracking analysis (NTA); 2) Glial fibrillary acidic protein (GFAP), an astrocyte marker; and 3) protein-bound 4-hydroxy-2-nonenal (HNE) adducts, an oxidative damage marker. Brain tissues were prepared for immunohistochemistry staining and protein immunoblotting. The results demonstrate: 1) increased GFAP levels (p 0.05) in EVs, but not brain tissue, in the IR group; and 2) increased HNE-bound protein adduction levels (p 0.05). The results support using EVs as an early indicator of cancer therapy-induced neuronal injury.

A case study of real-time networked gameplay by whole-body controller developed from a value-aligned design process within a hackathon format.

Asian populations are currently underrepresented in human genetics research. Here we present whole-genome sequencing data of 4,810 Singaporeans from three diverse ethnic groups: 2,780 Chinese, 903 Malays, and 1,127 Indians. Despite a medium depth of 13.7×, we achieved essentially perfect (>99.8%) sensitivity and accuracy for detecting common variants and good sensitivity (>89%) for detecting extremely rare variants with 0.01) that were absent in the existing public databases, highlighting the importance of local population reference for genetic diagnosis. We describe fine-scale genetic structure of Singapore populations and their relationship to worldwide populations from the 1000 Genomes Project. In addition to revealing noticeable amounts of admixture among three Singapore populations and a Malay-related novel ancestry component that has not been captured by the 1000 Genomes Project, our analysis also identified some fine-scale features of genetic structure consistent with two waves of prehistoric migration from south China to Southeast Asia. Finally, we demonstrate that our data can substantially improve genotype imputation not only for Singapore populations, but also for populations across Asia and Oceania. These results highlight the genetic diversity in Singapore and the potential impacts of our data as a resource to empower human genetics discovery in a broad geographic region.

There is compelling evidence suggesting that the immune-modulating effects of many conventional chemotherapeutics, including platinum-based agents, play a crucial role in achieving clinical response. One way in which chemotherapeutics can engage a tumor-specific immune response is by triggering an immunogenic mode of tumor cell death (ICD), which then acts as an "anticancer vaccine". In spite of being a mainstay of chemotherapy, there has not been a systematic attempt to screen both existing and upcoming Pt agents for their ICD ability. A library of chemotherapeutically active Pt agents was evaluated in an in vitro phagocytosis assay, and no correlation between cytotoxicity and phagocytosis was observed. A Pt(II) N-heterocyclic carbene complex was found to display the characteristic hallmarks of a type II ICD inducer, namely focused oxidative endoplasmic reticulum (ER) stress, calreticulin exposure, and both HMGB1 and ATP release, and thus identified as the first small-molecule immuno-chemotherapeutic agent.