VISUALIZING A FRAMEWORK FOR TANGIBILITY IN MULTIMEDIA LEARNING FOR PRESCHOOLERS

ABSTRAC

Comparative genetic architectures of schizophrenia in East Asian and European populations

Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Where do girls who aspired to mathematical careers in secondary school end up 20 years later? A longitudinal examination of women's and men's motivations, choices and pathways from adolescence to adulthood.

Gender representation in Science, Technology, Engineering and Mathematics (STEM) is a longstanding concern. Women have increased representation in life and health sciences but remain the minority in mathematical STEM which can have negative consequences for individuals, workplaces and societies. Through 3 publications, women’s choices away from mathematical STEM focus on 3 life milestones: tertiary education, starting a family and career entry. Studies utilise Study of Transitions and Educational Pathways data following adolescents into adulthood. Study 1 (N = 212; 115 women) examined how adolescent mathematics motivations predicted attainment of mathematical STEM or life science vs. non-STEM degrees, for women versus men. Mathematical interest was key to women, but not men, attaining a mathematical STEM degree. Study 2 (N = 300; 168 women) examined the relations of traditional gender role beliefs and starting a family on mathematical career trajectories from adolescent aspirations to actual adult careers. Women with no children showed an upward trajectory compared with women who had children, or men regardless of having children or not. Counter to hypothesis, traditional gender role beliefs did not explain these relationships, interpreted in light of these participants’ rather egalitarian values. Study 3 (N = 279; 153 women) examined how agentic and communal occupational goal combinations could affect mathematical career trajectories. Women were more likely than men to endorse a combination of high communal/low agentic goals, associated with a downward trajectory, unlike other goal combinations. Collectively, mathematical interest, motherhood, and occupational goals shaped mathematical career trajectories of women. Implications underscore promoting mathematical interest, family-friendly policies, and communal values in mathematical STEM at all career stages to sustain and improve women’s representation by addressing deterrents from their adolescent aspirations

A Nile Rat Transcriptomic Landscape Across 22 Organs by Ultra-Deep Sequencing and Comparative RNA-seq Pipeline (CRSP)

RNA sequencing (RNA-seq) has been a widely used high-throughput method to characterize transcriptomic dynamics spatiotemporally. However, RNA-seq data analysis pipelines typically depend on either a sequenced genome and/or corresponding reference transcripts. This limitation is a challenge for species lacking sequenced genomes and corresponding reference transcripts. The Nile rat (Arvicanthis niloticus) has two key features - it is daytime active, and it is prone to diet-induced diabetes, which makes it more similar to humans than regular laboratory rodents. However, at the time of this study, neither a Nile rat genome nor a reference transcript set were available, making it technically challenging to perform large-scale RNA-seq based transcriptomic studies. This genome-independent work progressed concurrently with our generation of a Nile rat genome. A well -annotated genome requires several iterations of manually reviewing curated transcripts and takes years to achieve. Here, we developed a Comparative RNA-Seq Pipeline (CRSP), integrating a comparative species strategy independent of a specific sequenced genome or species-matched reference transcripts. We performed bench -marking to validate that our CRSP tool can accurately quantify gene expression levels. In this study, we generated the first ultra-deep (2.3 billion x 2 paired-end) Nile rat RNA-seq data from 59 biopsy samples representing 22 major organs, providing a unique resource and spatial gene expression reference for Nile rat researchers. Importantly, CRSP is not limited to the Nile rat species and can be applied to any species without prior genomic knowledge. To facilitate a general use of CRSP, we also characterized the number of RNA-seq reads required for accurate estimation via simulation studies. CRSP and documents are available at: https://github.com/pjiang 1105/CRSP

Treatment preferences among Japanese patients and physicians for epidermal growth factor receptor‐mutant non‐small cell lung cancer

Abstract Introduction Evidence is limited on preferences of Japanese patients and physicians in treatment for epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC). Several oral or intravenous novel agents for EGFR exon 20 insertions are under development. The aim of our study was to investigate which attributes of novel treatments influenced selection of oral or intravenous agents among treated patients and treating physicians in Japan. Methods The study was designed by board‐certified oncologists, patient representatives, and analytics specialists. Eligible participants completed an online survey with a discrete choice experiment presenting two treatment profiles described by attributes: mode of administration (oral or intravenous); frequency of administration; overall response rate (ORR); average progression‐free survival (PFS); chance of experiencing severe side effects (SEs); mild–moderate gastrointestinal SEs; mild–moderate skin‐related SEs; and patient out‐of‐pocket costs. Results Fifty‐four patients (all self‐reported EGFR‐mutant) and 74 physicians participated from December 2021 to August 2022. All attributes being equal, there was greater preference for oral administration. However, there was greater preference for intravenous over oral, when ORR and PFS improved by 10% and 1 month, and severe SEs reduced by 10%. Physicians exhibited greater preference for PFS compared to patients (p < 0.01). Ranked order of attribute importance was as follows: (1) PFS; (2) ORR; (3) severe SEs, expressed by patients and physicians alike. Conclusions Our study revealed Japanese physician and patient preferences in treatment options for EGFR‐mutant NSCLC. Compared to the strong preference for a more efficacious drug, the preference of oral versus intravenous revealed a smaller impact

A chlamydial type III-secreted effector protein (Tarp) is predominantly recognized by antibodies from humans infected with Chlamydia trachomatis and induces protective immunity against upper genital tract pathologies in mice.

Chlamydia trachomatis genome is predicted to encode a type III secretion system consisting of more than 40 open reading frames (ORFs). To test whether these ORFs are expressed and immunogenic during chlamydial infection in humans, we expressed 55 chlamydial ORFs covering all putative type III secretion components plus control molecules as fusion proteins and measured the reactivity of these fusion proteins with antibodies from patients infected with C. trachomatis in the urogenital tract (24 antisera) or in the ocular tissue (8 antisera). Forty-five of the 55 proteins were recognized by at least 1 of the 32 human antisera, suggesting that these proteins are both expressed and immunogenic during chlamydial infection in humans. Tarp, a putative type III secretion effector protein, was identified as a novel immunodominant antigen due to its reactivity with the human antisera at high frequency and titer. The expression and immunogenicity of Tarp were confirmed in cell culture and mouse systems. Tarp was mainly associated with the infectious form of chlamydial organisms and became undetectable between 13 and 24 h during the infection cycle in cell culture. Mice intravaginally infected with C. muridarum developed Tarp-specific humoral and cellular immune responses. More importantly, immunization of mice with Tarp induced Th1-dominant immunity that significantly reduced the shedding of live organisms from the lower genital tract and attenuated inflammatory pathologies in the fallopian tube tissues. These observations have demonstrated that Tarp, an immunodominant antigen identified by human antisera, can induce protective immunity against chlamydial infection and pathology in mice