Exploring racial disparities and inequalities among children and youth with acquired brain injury: a systematic review.

PURPOSE: Racial minoritized children and youth with acquired brain injury (ABI) often experience multiple forms of discrimination. The purpose of this systematic review was to understand the racial disparities in health care among children and youth with ABI and their caregivers. METHOD: Six international databases (Ovid Medline, Embase, Healthstar, Psychinfo, Scopus, and Web of Science) were systematically searched for peer-reviewed articles. Studies were screened by two researchers who also conducted the data extraction and quality appraisal. A narrative synthesis approach was used to analyze the data. RESULTS: Of the 8081 studies identified in the search, 34 met the inclusion criteria, which involved 838,052 children and youth with brain injuries (or caregivers representing them) across two countries. The following themes were noted in the studies in our review: (1) racial disparities in accessing care (i.e., diagnosis, hospital admission, length of stay, rehabilitation treatment); (2) racial disparities in ABI-related health outcomes (i.e., functional outcomes and mortality rates); and (3) factors affecting racial disparities (i.e., sources in injury, insurance and expenditures, and intersectionality). CONCLUSIONS: Our findings reveal the concerning racial disparities among children and youth with ABI. Further research should explore solutions for addressing such racial disparities and solutions to address them.

Racial minoritized youth with acquired brain injury experience many barriers and inequalities in accessing care and health care leaders should help to address such gaps and disparities in the health system.Clinicians should familiarize themselves with the common factors affecting racial disparities in acquired brain injury outcomes including sources of injury, types of insurance and cultural factors.Additional training in working with patients from racially diverse backgrounds and in providing culturally appropriate care among healthcare providers is needed.More efforts are needed to address racial disparities at the individual and structural levels that continue to exist in rehabilitation services for children and youth with acquired brain injury.

Family-based Interventions of Preventing Substance Use Among Immigrant Youth: A Scoping Review.

Introduction: Immigrant youth face heightened risks of substance use due to the stress associated with immigration and acculturation. While parental intervention can have a preventative impact on substance use, parents need to be well-informed about substance use and effective interventions that can prevent substance use among immigrant youth. Such interventions ought to be culturally sensitive, family-based, and targeted at the specific substances that are prevalent in a given context. Identifying and curating interventions that can empower parents in addressing substance use can help mitigate the risks that immigrant youth may face. Methods: This scoping review aimed to identify the types, characteristics, and effectiveness of family-based substance use intervention programs. Based on Arksay and O'Malley's guidelines, interventions included in the review must have met the following criteria: (a) was a family-based intervention aiming to prevent substance use; (b) targeted immigrant teens aged 12 to 17 years old; (c) was published in English; (d) originated from Australia, Canada, New Zealand, or the United States. The pinch table was used to synthesize included articles, after which studies were compared and categorized, and cross-cutting categories were identified. Results: After screening 4551 searched literature, 13 studies that utilized family-based interventions were included in the review. All interventions were face-to-face programs, and most interventions involved parents and youth as participants. Eco-developmental theory and active learning strategies were used by multiple interventions. Given immigrant families were target stakeholders, both deep structure and surface structure cultural adaptations were utilized. Interventions increased parents' knowledge and skills regarding substance use prevention and delayed substance use initiation among youth. Conclusion: From the review, it was evident that parents are an essential element in any program aiming to prevent or reduce children's substance use. Besides information about substance use prevention, the curriculum also involves parenting and communication skills for parents to understand the protective effects of family. Effective family-based interventions for immigrant youth require attention to parenting and immigration stress, while also considering cultural adaptation. Future directions and limitations are also discussed.

Covalent targeted radioligands potentiate radionuclide therapy.

Targeted radionuclide therapy, in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation, has addressed unmet clinical needs and improved outcomes for patients with cancer1-4. A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue, which remains a major challenge5,6. A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution. Here we installed a sulfur (VI) fluoride exchange (SuFEx) chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance. When the engineered radiopharmaceutical binds to the tumour-specific protein, the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the 'click' SuFEx reaction. The application of this strategy to a fibroblast activation protein (FAP) inhibitor (FAPI) triggered more than 80% covalent binding to the protein and almost no dissociation for six days. In mice, SuFEx-engineered FAPI showed 257% greater tumour uptake than did the original FAPI, and increased tumour retention by 13-fold. The uptake in healthy tissues was rapidly cleared. In a pilot imaging study, this strategy identified more tumour lesions in patients with cancer than did other methods. SuFEx-engineered FAPI also successfully achieved targeted ß- and α-radionuclide therapy, causing nearly complete tumour regression in mice. Another SuFEx-engineered radioligand that targets prostate-specific membrane antigen (PSMA) also showed enhanced therapeutic efficacy. Considering the broad scope of proteins that can potentially be ligated to SuFEx warheads, it might be possible to adapt this strategy to other cancer targets.

An aldehyde-crosslinking mitochondrial probe for STED imaging in fixed cells.

Fluorescence labeling of chemically fixed specimens, especially immunolabeling, plays a vital role in super-resolution imaging as it offers a convenient way to visualize cellular structures like mitochondria or the distribution of biomolecules with high detail. Despite the development of various distinct probes that enable super-resolved stimulated emission depletion (STED) imaging of mitochondria in live cells, most of these membrane-potential-dependent fluorophores cannot be retained well in mitochondria after chemical fixation. This lack of suitable mitochondrial probes has limited STED imaging of mitochondria to live cell samples. In this study, we introduce a mitochondria-specific probe, PK Mito Orange FX (PKMO FX), which features a fixation-driven cross-linking motif and accumulates in the mitochondrial inner membrane. It exhibits high fluorescence retention after chemical fixation and efficient depletion at 775 nm, enabling nanoscopic imaging both before and after aldehyde fixation. We demonstrate the compatibility of this probe with conventional immunolabeling and other strategies commonly used for fluorescence labeling of fixed samples. Moreover, we show that PKMO FX facilitates correlative super-resolution light and electron microscopy, enabling the correlation of multicolor fluorescence images and transmission EM images via the characteristic mitochondrial pattern. Our probe further expands the mitochondrial toolkit for multimodal microscopy at nanometer resolutions.

Integrating visual factors in crash rate analysis at Intersections: An AutoML and SHAP approach towards cycling safety.

Cycling crashes constitute a significant and rising share of traffic accidents. Consequently, exploring factors affecting cycling safety has become a priority for both governmental bodies and scholars. However, most existing studies have neglected the vision factors capable of quantitatively describing the city-level cycling environment. Moreover, they have relied on limited models that lack interpretability and fail to capture the spatial variations in the contribution of factors. To address these gaps, this research proposed a framework that used origin-destination-based cycling flow and vision factors generated from Google Street View images to identify the leading factors. It also employed the comparative Automatic Machine Learning and interpretable SHAP value-based geospatial analysis to explain each factor's contribution to the cycling crash risk, with a particular focus on the spatial variations in the influence of vision factors. The effectiveness of this framework was validated by a case study in Manhattan, which examined the leading risk factors of cycling crash rates at intersections. The results showed that the LightGBM model, with selected subsets of factors, outperformed other models. Through SHAP explanations of global feature importance, the study identified the proportion of road barriers, the proportion of open sky, and the number of visible trucks as the leading visual risk factors. Additionally, using SHAP-based geospatial analysis, the study revealed the local variations in the effects of these three factors and identified eight areas with higher cycling crash rates. Based on these findings, the study provided practical measures for a safer cycling environment in Manhattan.

Identification, structural characterization, and molecular dynamic simulation of ACE inhibitory peptides in whey hydrolysates from Chinese Rushan cheese by-product.

To realize the high-value utilization of Rushan cheese by-product, Rushan cheese whey was used as a raw material to prepare angiotensin-Ⅰ-converting enzyme inhibitory peptides (ACEIPs). After enzymatic hydrolysisn and ultrafiltration, the sequences of peptides were identified by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Two novel ACE inhibitory peptides Phe-Asp-Arg-Pro-Phe-Leu (FDRPFL) and Lys-Trp-Glu-Lys-Pro-Phe (KWEKPF) were identified. Additionally, both of the peptides exhibited good water-solubility and no toxicity according to in-silico prediction. Fourier transform infrared spectroscopy results show that both FDRPFL and KWEKPF were enriched in ß-turn and ß-sheet structures. Lineweaver-Burk plots revealed that FDRPFL and KWEKPF exhibited non-competitive and mixed inhibition patterns, respectively. Molecular docking and MD simulation showed that hydrogen bonds and ionic bonds forces allowed FDRPFL and KWEKPF to form stable and compact complexes with ACE. In conclusion, enzymatic hydrolysis of Rushan cheese by-products yields bioactive peptides, increases the added value of whey and reduces environmental pollution.

Types and factors affecting and impact of ableism among Asian children and youth with disabilities and their caregivers: a systematic review of quantitative studies.

PURPOSE: Asian children and youth with disabilities often experience multiple barriers and discrimination in education, healthcare, and social settings, which influence their well-being, especially the transition to adulthood. This review aims to explore the types, factors affecting and impact of ableism on Asian children and youth with disabilities and their caregivers. METHODS: We conducted a systematic review and a narrative synthesis whereby we searched the literature from six international databases, including Healthstar, Ovid Medline, Embase, PsycInfo, Scopus, and Web of Science. RESULTS: Twenty-nine studies were included in the review, and three themes were identified that related to ableism: (1) types and rates of ableism (i.e., stigma, bullying and victimization, and discrimination and inequalities); (2) factors affecting ableism (i.e. sociodemographic factors, familial factors, and societal factors); and (3) impacts of ableism (i.e. mental health, family impacts, and societal impacts). CONCLUSIONS: Our review highlights that ableism has various types and can be influenced by multiple factors, influencing social and health outcomes of Asian families with children and youth with disabilities. This review also emphasizes the importance of increasing the public's awareness regarding disabilities to reduce ableism among Asian families with children with disabilities.

Asian children and youth with disabilities often experience bullying and victimization, therefore it is necessary to develop educational materials to raise awareness of disabilities.Healthcare providers should consider developing more educational programs for caregivers to reduce self-stigma and affiliate stigma and promote mental health.  Healthcare service providers should consider creating and implementing more inclusive programs to reduce health disparities and the influence of socio-demographic factors.

Accessible independent housing for people with disabilities: A scoping review of promising practices, policies and interventions.

BACKGROUND: Accessible housing is imperative to enabling independent living for many people with disabilities; yet, research consistently shows how people with disabilities often lack appropriate accessible housing and are more likely to experience unaffordable, insecure, and/or poor quality housing. Therefore, the aim of this study was to understand promising practices, policies and interventions regarding accessible independent housing for people with disabilities. METHODS: We conducted a scoping review that involved searching seven international literature databases that identified 4831 studies, 60 of which met our inclusion criteria. RESULTS: The reviewed studies involved 18 countries over a 20-year period. Our review highlighted the following key trends: (1) removing barriers to obtaining accessible housing (e.g., advocacy, builders enhancing housing supply, subsidies and financial incentives); (2) policies influencing accessible housing; (3) interventions to enhance accessible housing (i.e., home modifications, smart homes, mobile applications and other experimental devices); and (4) the impact of accessible independent housing on health and wellbeing. CONCLUSIONS: Our findings emphasize the importance of accessible housing for people with disabilities and the urgent need to advance accessible housing options.

Carbazole and tetrahydro-carboline derivatives as dopamine D3 receptor antagonists with the multiple antipsychotic-like properties.

Dopamine D3 receptor (D3R) is implicated in multiple psychotic symptoms. Increasing the D3R selectivity over dopamine D2 receptor (D2R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D3R selective ligands. Through a structure-based virtual screen, ZLG-25 (D3R Ki = 685 nmol/L; D2R Ki > 10,000 nmol/L) was identified as a novel D3R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D3R-selective analogs with tetrahydro-ß-carboline or tetrahydro-γ-carboline core. Further functional studies showed that most derivatives acted as hD3R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.

CDKL5 deficiency in adult glutamatergic neurons alters synaptic activity and causes spontaneous seizures via TrkB signaling.

CDKL5 deficiency disorder (CDD) is a severe epileptic encephalopathy resulting from pathological mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene. Despite significant progress in understanding the neuronal function of CDKL5, the molecular mechanisms underlying CDD-associated epileptogenesis are unknown. Here, we report that acute ablation of CDKL5 from adult forebrain glutamatergic neurons leads to elevated neural network activity in the dentate gyrus and the occurrence of early-onset spontaneous seizures via tropomyosin-related kinase B (TrkB) signaling. We observe increased expression of brain-derived neurotrophic factor (BDNF) and enhanced activation of its receptor TrkB in the hippocampus of Cdkl5-deficient mice prior to the onset of behavioral seizures. Moreover, reducing TrkB signaling in these mice rescues the altered synaptic activity and suppresses recurrent seizures. These results suggest that TrkB signaling mediates epileptogenesis in a mouse model of CDD and that targeting this pathway might be effective for treating epilepsy in patients affected by CDKL5 mutations.

Exploring the experiences of ableism among Asian children and youth with disabilities and their families: a systematic review of qualitative studies.

PURPOSE: Asian children and youth with disabilities often experience multiple barriers, stigmas and discrimination within and outside their families; yet less is understood about their lived experiences. This systematic review explored the experiences of ableism among Asian children and youth with disabilities and their families. METHODS: We conducted a systematic review of qualitative studies and a qualitative meta-synthesis. We searched six databases including Ovid Medline, Embase, PsychInfo, Healthstar, Web of Science, and Scopus. RESULTS: Forty-two articles met our inclusion criteria involving 17 countries and regions over a 22-year period. The findings were synthesized into four themes: (1) individual- and family-level ableism (i.e., stigma, fears, concerns, stress and anxieties, physical abuse, bullying, reduced engagement in community activities); (2) institutional-level ableism (i.e., barriers to accessing and navigating supports, ableist attitudes among service providers, unavailable services); (3) societal-level ableism (i.e., cultural and religious stigma, social rejection, discrimination, environmental and policy barriers); and (4) coping strategies (i.e., self-care activities, supports from family, friends and people with similar conditions, religious beliefs). CONCLUSIONS: Our results highlight the ableist experiences that Asian children and youth with disabilities and their caregivers often encounter and the strong need for further supports to address ableism using culturally responsive strategies.

Asian children and youth with disabilities encounter multiple forms of ableism at the individual, family and institutional levels.It is important for healthcare providers to customize resources that are culturally appropriate and aligned with the cultural and language backgrounds of the clients they serve.Clinicians and service providers should engage in culturally sensitive training and education to understand the barriers faced by the clients they serve.Clinicians and service providers should continue to advocate for marginalized and equity-deserving groups.

Barriers and facilitators to obtaining accessible housing among children, youth and young adults with disabilities and their families: a scoping review.

PURPOSE: Accessible housing is a fundamental human right and yet many children and youth with disabilities live in inaccessible, insecure, unaffordable and poor quality housing. The aim of our study was to understand the barriers and facilitators to obtaining accessible housing among children, youth and young adults with disabilities and their families. METHODS: We conducted a scoping review involving seven international literature databases from 2000 to 2022 that identified 38 studies meeting our inclusion criteria. RESULTS: The reviewed studies involved 10 countries over a 22-year period. Our review emphasized the following key trends: (1) barriers to obtaining accessible homes (i.e. common types of accessibility barriers, rates of inaccessible housing, factors affecting home accessibility), and negative impacts of inaccessible housing; and (2) rates and facilitators to obtaining accessible housing (i.e., common types of home modifications, enablers of home modifications) and positive impacts of accessible housing. CONCLUSIONS: Our findings highlight the barriers and enablers of obtaining accessible housing among children, youth and young adults with disabilities and their families and the critical need to support them in securing appropriate housing.

Evidence suggests that clinicians and community service providers should support youth with disabilities and their parents to make home modifications and secure accessible housing.Clinicians should consider advocating for accessible housing and help to remove barriers for children with disabilities and their families with particular attention to marginalized and equity-deserving groups.Clinicians and service providers should involve families in the process of making accessible home modifications and help them to connect with relevant housing stakeholders.

Characteristics of Hepatitis B virus integration and mechanism of inducing chromosome translocation.

Hepatitis B virus (HBV) integration is closely associated with the onset and progression of tumors. This study utilized the DNA of 27 liver cancer samples for high-throughput Viral Integration Detection (HIVID), with the overarching goal of detecting HBV integration. KEGG pathway analysis of breakpoints was performed using the ClusterProfiler software. The breakpoints were annotated using the latest ANNOVAR software. We identified 775 integration sites and detected two new hotspot genes for virus integration, N4BP1 and WASHP, along with 331 new genes. Furthermore, we conducted a comprehensive analysis to determine the critical impact pathways of virus integration by combining our findings with the results of three major global studies on HBV integration. Meanwhile, we found common characteristics of virus integration hotspots among different ethnic groups. To specify the direct impact of virus integration on genomic instability, we explained the causes of inversion and the frequent occurrence of translocation due to HBV integration. This study detected a series of hotspot integration genes and specified common characteristics of critical hotspot integration genes. These hotspot genes are universal across different ethnic groups, providing an effective target for better research on the pathogenic mechanism. We also demonstrated more comprehensive key pathways affected by HBV integration and elucidated the mechanism for inversion and frequent translocation events due to virus integration. Apart from the great significance of the rule of HBV integration, the current study also provides valuable insights into the mechanism of virus integration.

Association between walking speed and calcaneus stiffness index in older adults.

INTRODUCTION: The aim here is to examine the association between objectively measured usual walking speed (UWS) and bone status in community-dwelling older Chinese. MATERIALS AND METHODS: This is a cross-sectional study of a population of 1528 adults (817 females, mean age 68.5 ± 5.3; 711 males, mean age 69.1 ± 5.2) aged 60-79, living in communities in Shanghai. Walking speed was assessed using a 4-m walk test at a usual-pace walking speed a walking speed at which the subject felt relaxed-and bone status measured by quantitative ultrasound (QUS). The health-related characteristics of participants include family background, physical activity level, chronic disease, smoking and alcohol consumption, frequency of falls, vitamin intake, and hormone therapy. RESULTS: Multiple linear regression is used to analyses any association between UWS and bone status, adjusting for confounding factors showing a significant association between faster UWS and a higher calcaneal stiffness index (SI) (p < 0.01). Comparing the lowest quartile of the data set with the highest at UWS, a high SI is achieved with 5.34 (95% CI = 3.22, 7.46) (p < 0.01), after adjusting for confounders. An increase of 1 dm/s was associated with a 0.91 (95% CI = 0.53, 1.29) increase in SI. This relationship for most subgroups is consistent. CONCLUSION: Our findings suggest that UWS can be a sensitive indicator of calcaneal bone loss among an older population.

Addressing health care inequities in Canadian critical care through inclusive science: a pilot tool for standardized data collection.

PURPOSE: Sociodemographic risks contributing to health inequities are often inadequately captured and reported in critical care studies. To address the lack of standardized terms and definitions, we sought to develop a practical and convenient resource of questions and response options for collecting sociodemographic variables for critical care research. SOURCE: To identify domains and variables that impact health equity, we searched: 1) PubMed for critical care randomized trials (2010 to 2021); 2) high-impact critical care and general medicine journals for special issues relating to equity; and 3) governmental and nongovernmental resources. PRINCIPAL FINDINGS: We identified 23 domains associated with health equity, including pronouns, age, sex, gender identity, sexual orientation, race and ethnicity, visible minorities, language, household income, marital/relationship status, education, disabilities, immigrant and refugee status, employment, primary care access, expanded health insurance, internet access, housing security, food security, dependents, religion, and postal code. For each domain we provided standardized questions and response options; for 13/23 domains, we included more than one version of the question and response categories. CONCLUSION: We developed a standardized, practical, and convenient demographic data collection tool for critical care research studies. Questions and response options can be adapted by researchers for inclusion in individual study questionnaires or case report forms.

RéSUMé: OBJECTIF: Les risques sociodémographiques qui contribuent aux inégalités en matière de santé sont souvent mal saisis et rapportés dans les études de soins intensifs. Pour remédier au manque de termes et de définitions normalisés, nous avons cherché à élaborer une ressource à la fois pratique et utile de questions et d'options de réponse pour le recueil des variables sociodémographiques pour la recherche en soins intensifs. SOURCES: Pour identifier les domaines et les variables qui ont une incidence sur l'équité en santé, nous avons effectué des recherches dans : 1) PubMed, pour en extraire les études randomisées en soins intensifs (2010 à 2021); 2) des revues de soins intensifs et de médecine générale à impact élevé pour identifier les numéros spéciaux liés à l'équité; et 3) les ressources gouvernementales et non gouvernementales. CONSTATATIONS PRINCIPALES: Nous avons identifié 23 domaines associés à l'équité en santé, y compris les pronoms, l'âge, le sexe, l'identité de genre, l'orientation sexuelle, la race et l'origine ethnique, les minorités visibles, la langue, le revenu du ménage, l'état matrimonial / relationnel, l'éducation, les handicaps, le statut d'immigrant·e et de réfugié·e, l'emploi, l'accès aux soins primaires, l'assurance maladie élargie, l'accès à l'internet, la sécurité du logement, la sécurité alimentaire, les personnes à charge, la religion et le code postal. Pour chaque domaine, nous avons fourni des questions et des options de réponse normalisées; pour 13/23 domaines, nous avons inclus plus d'une version des catégories de questions et réponses. CONCLUSION: Nous avons mis au point un outil de collecte de données démographiques normalisé, pratique et utile pour la recherche en soins intensifs. Les options de questions et de réponses peuvent être adaptées par les chercheuses et chercheurs pour être incluses dans des questionnaires d'étude individuels ou des formulaires de présentation de cas.

Identification, characterization and in vitro activity of hypoglycemic peptides in whey hydrolysates from rubing cheese by-product.

The by-product of Chinese rubing cheese is rich in whey protein. Whey hydrolysates exhibit good hypoglycemic activity, but which specific peptide components are responsible for this effect have not yet been investigated. Herein, the α-glucosidase inhibitory activity of the ultrafiltered fraction (<3 kDa) of rubing cheese whey hydrolysates was evaluated with the inhibition rate of 37.89 %. In addition, peptide identification was conducted using LC-MS/MS, and three peptides YPVEPF, VPYPQ, and LPYPY were identified. Among these, YPVEPF had higher α-glucosidase inhibitory activity (IC50 = 3.52 mg/mL) and interacted with α-glucosidase via hydrogen bonding and hydrophobic forces. YPVEPF was characterized as an amphipathic peptide rich in antiparallel (50.50 %) and random coil (35.20 %) structures, as well as showed good tolerance to gastrointestinal digestion and incubation under the temperature range of 20-80 °C. Notably, YPVEPF activity increased in the presence of Al3+ and Fe3+, as well as within the pH range of 2.0-6.0. Furthermore, YPVEPF had negligible hemolytic activity at a concentration of 1.0 mg/mL, no toxicity at concentrations below 0.5 mg/mL, and significantly promoted glucose consumption in HepG2 cells (p < 0.0001). Collectively, these findings indicate the potential of YPVEPF to be used as a novel hypoglycemic peptide in functional foods.

The structure-based optimization of 3-substituted indolin-2-one derivatives as potent and isoform-selective c-Jun N-terminal kinase 3 (JNK3) inhibitors and biological evaluation.

An indolin-2-(4-thiazolidinone) scaffold was previously shown to be a novel chemotype for JNK3 inhibition. However, more in vivo applications were limited due to the unconfirmed configuration and poor physicochemical properties. Here, the indolin-2-(4-thiazolidinone) scaffold validated the absolute configuration; substituents on the scaffold were optimized. Extensive structure activity relationship (SAR) studies were performed using kinase activity assays, thus leading to potent and highly selective JNK3 inhibitors with neuroprotective activity and good oral bioavailability. One lead compound, A53, was a potent and selective JNK3 inhibitor (IC50 = 78 nM) that had significant inhibition (>80% at 1 µM) to only JNK3 in a 398-kinase panel. A53 had low inhibition against JNK3 and high stability (t1/2(α) = 0.98 h, t1/2(ß) = 2.74 h) during oral administration. A modeling study of A53 in human JNK3 showed that the indolin-2-(4-thiazolidinone)-based JNK3 inhibitor with a 5-position-substituted hydrophilic group offered improved kinase inhibition.

Multiple HPV integration mode in the cell lines based on long-reads sequencing.

Background: The integration of human papillomavirus (HPV) is closely related to the occurrence of cervical cancer. However, little is known about the complete state of HPV integration into the host genome. Methods: In this study, three HPV-positive cell lines, HeLa, SiHa, and CaSki, were subjected to NANOPORE long-read sequencing to detect HPV integration. Analysis of viral integration patterns using independently developed software (HPV-TSD) yielded multiple complete integration patterns for the three HPV cell lines. Results: We found distinct differences between the integration patterns of HPV18 and HPV16. Furthermore, the integration characteristics of the viruses were significantly different, even though they all belonged to HPV16 integration. The HPV integration in the CaSki cells was relatively complex. The HPV18 integration status in HeLa cells was the dominant, whereas the percentage of integrated HPV 16 in SiHa and CaSki cells was significantly lower. In addition, the virus sequences in the HeLa cells were incomplete and existed in an integrated state. We also identified a large number of tandem repeats in HPV16 and HPV18 integration. Our study not only clarified the feasibility of high-throughput long-read sequencing in the study of HPV integration, but also explored a variety of HPV integration models, and confirmed that viral integration is an important form of HPV in cell lines. Conclusion: Elucidating HPV integration patterns will provide critical guidance for developing a detection algorithm for HPV integration, as well as the application of virus integration in clinical practice and drug research and development.

Exploring arts-based interventions for youth substance use prevention: a scoping review of literature.

INTRODUCTION: There is a rise in problematic substance use among Canadian youth, which is precipitating a public health crisis. Interventions are needed to empower youth to mitigate substance use risks. Active youth involvement in substance use prevention is urgently needed to increase uptake and ownership of the process and outcome of the intervention. Arts-based interventions are ideal participatory action approaches that can empower young people to be active agents in substance use prevention. These approaches can help promote health, reduce harm, and change behaviours. Scoping reviews are a vital tool that can help the research team identify relevant interventions that can be adapted to a community. METHODS: This scoping review explores various arts-based substance use prevention interventions for youth. The scoping review used the iterative stages of Arksey and O'Malley to search Portal ERIC, Ovid MEDLINE, C.I.N.A.H.L., E.M.B.A.S.E., Web of Science, and A.P.A. PsycInfo and grey literature from Canadian Centre on Substance Use and Addiction and websites suggested by the Canadian Agency for Drugs and Technologies in Health. Inclusion criteria are a) articles utilizing arts-based intervention on substance use prevention; b) studies with a clearly defined intervention; c) intervention targeting the youth (age 12-17) and d) publications written in English. Thematic analysis was used to identify the main themes from the included articles. RESULTS AND DISCUSSION: Themes identified in a thematic synthesis of these studies included a) the intent of the intervention; b) intervention characteristics; and c) the perceived effectiveness of interventions. Art-based interventions increased knowledge and changed attitudes and practices on substance use among youth. Making the interventions aesthetically appealing and engaging, active youth involvement in the development of the intervention and developing youth-centred interventions which attended to the realities they faced were central to the success of these interventions.

Food insecurity among postsecondary international students: a scoping review protocol.

INTRODUCTION: International students make significant contributions to their host institutions and countries. Yet research shows that not all international students have the financial means to fend for themselves and meet their financial obligations for the entire study programme. Such students are at significant risk of food insecurity. The objective of this scoping review is to synthesise available information on the factors related to food insecurity among international students studying at postsecondary educational institutions and identify the types of food insecurity interventions that have been implemented to address this issue. METHODS AND ANALYSIS: The Joanna Briggs Institute scoping review methodology will be used to guide this scoping review, and we will search the following databases: MEDLINE (through Ovid), CINAHL (EBSCO), PubMed, ERIC (via Ovid), PROSPERO and ProQuest. The titles, abstracts, and subsequently full texts of the selected papers will then be screened against the inclusion criteria. Data from articles included in the review will be extracted using a data charting form and will be summarised in a tabular form. Thematic analysis will be used to identify common themes that thread through the selected studies and will be guided by the steps developed by Terry et al. ETHICS AND DISSEMINATION: Since this project entails a review of available literature, ethical approval is not required. The findings will be presented at academic conferences and published in a peer-reviewed journal. To make the findings more accessible, they will also be distributed via digital communication platforms.