Unpacking the Mood States of Children and Youth in Saskatchewan, Canada, in the Context of the COVID-19 Pandemic: Insights from the "See Us, Hear Us 2.0" Study.

Background/objectives: The COVID-19 pandemic created a growing need for insights into the mental health of children and youth and their use of coping mechanisms during this period. We assessed mood symptoms and related factors among children and youth in Saskatchewan. We examined if coping abilities mediated the relationship between risk factors and mood states.

Clozapine, relapse, and adverse events: a 10-year electronic cohort study in Canada.

Background: Clozapine is the most effective medication for treatment-resistant psychoses, but the balance of benefits and risks is understudied in real-world settings.

Aims: To examine the relative re-hospitalisation rates for mental health relapse and adverse events associated with clozapine and other antipsychotics in adult and child/youth cohorts.

Method: Data were obtained from the Canadian Institute of Health Information for adults ( = 45 616) and children/youth ( = 1476) initially hospitalised for mental health conditions in British Columbia, Manitoba and Saskatchewan from 2008 to 2018.

See us, hear us! children, adolescents and families in Saskatchewan coping with mental health during the COVID-19 pandemic.

Purpose: To examine the lived experiences of children and adolescents coping with mental health issues and seeking mental health services in Saskatchewan during the COVID-19 pandemic.

Methods: In our descriptive phenomenological qualitative study, we interviewed forty-six individuals, including children aged 8-15 and their parents. Thematic analysis was applied to interpret the interview data.

Media coverage, fake news, and the diffusion of xenophobic violence: A fine-grained county-level analysis of the geographic and temporal patterns of arson attacks during the German refugee crisis 2015-2017.

Over the year of 2015, about 800.000 refugees arrived in Germany, a number which equals around one percent of the total population. This migration process was labelled the refugee crisis and was accompanied by a contested debate.

A functional sgRNA-CRISPR screening method for generating murine RET and NTRK1 rearranged oncogenes.

CRISPR/Cas9 gene editing represents a powerful tool for investigating fusion oncogenes in cancer biology. Successful experiments require that sgRNAs correctly associate with their target sequence and initiate double stranded breaks which are subsequently repaired by endogenous DNA repair systems yielding fusion chromosomes. Simple tests to ensure sgRNAs are functional are not generally available and often require single cell cloning to identify successful CRISPR-editing events.

Mental Health and Health-Related Quality of Life of Children and Youth during the First Year of the COVID-19 Pandemic: Results from a Cross-Sectional Survey in Saskatchewan, Canada.

For children and youth, the COVID-19 pandemic surfaced at a critical time in their development. Children have experienced extended disruptions to routines including in-person schooling, physical activities, and social interactions-things that bring meaning and structure to their daily lives. We estimated the prevalence of anxiety and depression symptoms of children and youth and their experiences of health-related quality of life (HRQoL), during the first year of the pandemic, and identified factors related to these outcomes.

Evaluation of KRAS inhibitor responses in novel murine KRAS lung cancer cell line models.

Introduction: The KRAS(G12C) mutation is the most common genetic mutation in North American lung adenocarcinoma patients. Recently, direct inhibitors of the KRAS protein have been developed and demonstrate clinical response rates of 37-43%. Importantly, these agents fail to generate durable therapeutic responses with median progression-free survival of ~6.

Durable responses to alectinib in murine models of EML4-ALK lung cancer requires adaptive immunity.

Lung cancers bearing oncogenic EML4-ALK fusions respond to targeted tyrosine kinase inhibitors (TKIs; e.g., alectinib), with variation in the degree of shrinkage and duration of treatment (DOT).

Novel EGFR-mutant mouse models of lung adenocarcinoma reveal adaptive immunity requirement for durable osimertinib response.

Lung cancers bearing oncogenically-mutated EGFR represent a significant fraction of lung adenocarcinomas (LUADs) for which EGFR-targeting tyrosine kinase inhibitors (TKIs) provide a highly effective therapeutic approach. However, these lung cancers eventually acquire resistance and undergo progression within a characteristically broad treatment duration range. Our previous study of EGFR mutant lung cancer patient biopsies highlighted the positive association of a TKI-induced interferon γ transcriptional response with increased time to treatment progression.

Intergenerational wealth transmission and homeownership in Europe-a comparative perspective.

The literature on social and wealth inequality has long acknowledged the importance of intergenerational wealth transmission (IWT) to inequality in homeownership tenure. However, it has paid insufficient attention to the institutional structures that moderate these inequalities. Therefore, in this study, we ask how institutional factors via differential housing finance systems and governmental housing policies, moderate the association between IWT and homeownership tenure.

Real-world effectiveness and safety of tildrakizumab in long-term treatment of plaque psoriasis: Results from the non-interventional, prospective, multicentre study TILOT.

Background: Plaque psoriasis is a chronic inflammatory disorder affecting the skin and impacting quality of life. Tildrakizumab (TIL) is an IL-23 inhibitor licensed for moderate-to-severe plaque psoriasis. Regulatory approval of medicinal products is based on safety and efficacy data from randomized controlled trials (RCTs) which impose stringent selection criteria.

Changes of Self-Rated Health Status, Overweight and Physical Activity During Childhood and Adolescence-The Ratchet Effect of High Parental Socioeconomic Status.

Childhood and adolescence are important life periods for the development of health status and physical activity (PA) behaviours. This study analyses the stability and potential changes of self-rated health status, overweight and PA behaviour over time, specifically focusing on the age and the socioeconomic status of children and adolescents. We employ representative longitudinal data for German children and adolescents from the Motorik-Modul Study and the German Health Interview and Examination Survey.

Adversarial text-to-image synthesis: A review.

With the advent of generative adversarial networks, synthesizing images from text descriptions has recently become an active research area. It is a flexible and intuitive way for conditional image generation with significant progress in the last years regarding visual realism, diversity, and semantic alignment. However, the field still faces several challenges that require further research efforts such as enabling the generation of high-resolution images with multiple objects, and developing suitable and reliable evaluation metrics that correlate with human judgement.

Sports participation of children and adolescents in Germany: disentangling the influence of parental socioeconomic status.

Background: Participation in sports and physical activity (PA) is a critical resource for children's health and social development. This study analyzes how the parental socioeconomic status (SES) of children and adolescents affects their PA in sports clubs (organized sports) and outside of sports clubs (unorganized sports) and tests whether the potential impact of parental SES is mediated by the opportunity structure of their residential area (walkability, infrastructure, etc.) and by family and peer support for PA.

TP53 Null Mutations Identify Lung Cancer Cell Lines with Highest Sensitivity to the Nontaxane Microtubule Inhibitor Eribulin.

The nontaxane microtubule inhibitor eribulin is an approved therapeutic for metastatic breast cancer and liposarcoma. Eribulin was previously tested in unselected patients with lung cancer and yielded a modest objective response rate of ∼5%-12%. Because lung cancers represent diverse histologies and driving oncogenic mutations, we postulated that eribulin may exhibit properties of a precision oncology agent with a previously undefined specificity for a molecularly distinct subset of lung cancers.

A tyrosine kinase inhibitor-induced interferon response positively associates with clinical response in EGFR-mutant lung cancer.

Tyrosine kinase inhibitors (TKIs) targeting EGFR-mutant lung cancers promote a range of tumor regression responses to yield variable residual disease, a likely incubator for acquired resistance. Herein, rapid transcriptional responses induced by TKIs early in treatment that associate with the range of patient responses were explored. RNAseq was performed on EGFR mutant cell lines treated in vitro with osimertinib and on tumor biopsies of eight EGFR mutant lung cancer patients before and after 2 weeks of TKI treatment.

Role of epidermal growth factor receptor inhibitor-induced interferon pathway signaling in the head and neck squamous cell carcinoma therapeutic response.

Background: Epidermal growth factor receptor (EGFR) is frequently amplified or overexpressed in head and neck squamous cell carcinoma (HNSCC) and is a clinically validated target for the therapeutic antibody, cetuximab, in the management of this cancer. The degree of response to EGFR inhibitors measured by tumor shrinkage varies widely among HNSCC patients, and the biological mechanisms that underlie therapeutic heterogeneity amongst HNSCC patients remain ill-defined.

Methods: EGFR-dependent human and murine HNSCC cell lines were treated with the EGFR/ERBB inhibitors, gefitinib and AZD8931, and submitted to RNAseq, GSEA, and qRT-PCR.

Crossmodal Language Grounding in an Embodied Neurocognitive Model.

Human infants are able to acquire natural language seemingly easily at an early age. Their language learning seems to occur simultaneously with learning other cognitive functions as well as with playful interactions with the environment and caregivers. From a neuroscientific perspective, natural language is embodied, grounded in most, if not all, sensory and sensorimotor modalities, and acquired by means of crossmodal integration.

[Therapeutic vaccination for tumors and neurodegenerative diseases].

Therapeutic vaccines are intended for the treatment of established diseases by harnessing the patient's own immune system. In this article we discuss therapeutic areas that are of relevance for therapeutic vaccination, i.e.

Semantic Object Accuracy for Generative Text-to-Image Synthesis.

Generative adversarial networks conditioned on textual image descriptions are capable of generating realistic-looking images. However, current methods still struggle to generate images based on complex image captions from a heterogeneous domain. Furthermore, quantitatively evaluating these text-to-image models is challenging, as most evaluation metrics only judge image quality but not the conformity between the image and its caption.

Bootstrapping Knowledge Graphs From Images and Text.

The problem of generating structured Knowledge Graphs (KGs) is difficult and open but relevant to a range of tasks related to decision making and information augmentation. A promising approach is to study generating KGs as a relational representation of inputs (e.g.

RNA-Based Adjuvants: Immunoenhancing Effect on Antiviral Vaccines and Regulatory Considerations.

During the last decade, a wide variety of cellular RNA sensors and structural characteristics of their agonists have been identified. On the basis of this knowledge, RNA formulations were developed as innovative adjuvant candidates. In contrast to DNA, RNA does not have genotoxic potential and is rapidly degraded.

Functional RNAi Screens Define Distinct Protein Kinase Vulnerabilities in EGFR-Dependent HNSCC Cell Lines.

The inhibitory epidermal growth factor receptor (EGFR) antibody, cetuximab, is an approved therapy for head and neck squamous cell carcinoma (HNSCC). Despite tumor response observed in some HNSCC patients, cetuximab alone or combined with radio- or chemotherapy fails to yield long-term control or cures. We hypothesize that a flexible receptor tyrosine kinase coactivation signaling network supports HNSCC survival in the setting of EGFR blockade, and that drugs disrupting this network will provide superior tumor control when combined with EGFR inhibitors.