Genetic screening

The rise of multidrug-resistant bacteria underlines the need for innovative treatments, yet the introduction of new drugs has stagnated despite numerous antimicrobial discoveries. A major hurdle is a poor correlation between promising in vitro data and in vivo efficacy in animal models, which is essential for clinical development. Early in vivo testing is hindered by the expense and complexity of existing animal models. Therefore, there is a pressing need for cost-effective, rapid pre-clinical models with high translational value...

There is a need for point-of-care diagnostics for future mass casualty events involving radiation exposure. The development of radiation exposure and dose prediction algorithms for biodosimetry is needed for screening of large populations during these scenarios, and exploration of the potential effects which sex, age, genetic heterogeneity, and physiological comorbidities may have on the utility of biodosimetry diagnostics is needed. In the current study, proteomic profiling was used to examine sex-specific differences in age-matched C57BL6 mice on the blood proteome after radiation exposure, and the usefulness of development and application of biodosimetry algorithms using both male and female samples...

OBJECTIVE: To explore the genetic etiology of a fetus with cryptophthalmos detected by prenatal ultrasonography. METHODS: A fetus undergoing induced labor at 32nd gestational week due to absence of bilateral eye fissures detected by prenatal ultrasonography in January 2017 was selected as the study subject. Umbilical cord blood sample from the fetus and peripheral blood samples from its parents were collected for the extraction of genomic DNA. Pathogenic variants were screened through whole exome sequencing (WES) and verified by Sanger sequencing...

OBJECTIVE: To analyze the clinical phenotype and genetic basis of a Chinese pedigree affected with Otopalatodigital syndrome type 1 (OPD1). METHODS: A pedigree which was evaluated at the Department of Endocrinology, General Hospital of the Central Theater Command on December 3, 2020 was selected as the study subject. Clinical phenotype and genetic features of the proband were analyzed. Whole exome sequencing was employed to screen for genetic variants in the proband, and Sanger sequencing was used to verify the candidate variants in the proband's mother, uncle, maternal aunt, and paternal aunt...

OBJECTIVE: To analyze the types and distribution of pathogenic variants for neonatal genetic diseases in Huzhou, Zhejiang Province. METHODS: One thousand neonates (48 ~ 42 h after birth) born to Huzhou region were selected as the study subjects. Dry blood spot samples were collected from the newborns, and targeted capture high-throughput sequencing was carried out for pathogenic genes underlying 542 inherited diseases. Candidate variants were verified by Sanger sequencing...

Accurate prediction of the efficacy of immunotherapy for cancer patients through the characterization of both genetic and phenotypic heterogeneity in individual patient cells holds great promise in informing targeted treatments, and ultimately in improving care pathways and clinical outcomes. Here, we describe the nanoplatform for interrogating living cell host-gene and (micro-)environment (NICHE) relationships, that integrates micro- and nanofluidics to enable highly efficient capture of circulating tumor cells (CTCs) from blood samples...

The availability of an alternative and efficient genetic editing technology is critical for fundamental research and strain improvement engineering of Streptomyces species, which are prolific producers of complex secondary metabolites with significant pharmaceutical activities. The mobile group II introns are retrotransposons that employ activities of catalytic intron RNAs and intron-encoded reverse transcriptase to precisely insert into DNA target sites through a mechanism known as retrohoming. We here developed a group II intron-based gene editing tool to achieve precise chromosomal gene insertion in Streptomyces...

Ovarian cancer develops insidiously and is frequently diagnosed at advanced stages. Screening for ovarian cancer is an effective strategy for reducing mortality. This study aimed to investigate the molecular mechanisms underlying the development of ovarian cancer and identify novel tumor biomarkers for the diagnosis and prognosis of ovarian cancer. Three databases containing gene expression profiles specific to serous ovarian cancer (GSE18520, GSE12470, and GSE26712) were acquired. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were analyzed for the differentially expressed gene (DEGs)...

Differences in tumor biology and genetic predisposition have been suggested as factors influencing overall survival and increased mortality in Black breast and ovarian cancer patients. Therefore, it is key to evaluate genetic susceptibilities in Afro-Caribbean patients because the black population in the US is not homogeneous. Identifying a high incidence of hereditary breast and ovarian cancer (HBOC) in Afro-Caribbean countries can lead to understanding the pattern of inherited traits in US-Caribbean immigrants and their subsequent generations...

Polatuzumab Vedotin (Pola-V) is an antibody-drug conjugate directed to the CD79B subunit of the B cell receptor (BCR). When combined with conventional immunochemotherapy, Pola-V improves outcomes in DLBCL. To identify determinants of Pola-V sensitivity, we used CRISPR-Cas9 screening for genes that modulated Pola-V toxicity for lymphomas or the surface expression of its target, CD79B. Our results reveal the striking impact of CD79B glycosylation on Pola-V epitope availability on the lymphoma cell surface and on Pola-V toxicity...

Significant progress has been achieved in enhancing early outcomes for individuals with maple syrup urine disease (MSUD), a rare metabolic disorder that leads to the accumulation of branched-chain amino acids leucine, isoleucine, and valine, where leucine is known as the primary neurotoxic metabolite. Newborn screening is helpful in early diagnosis and implementation of dietary treatment, thus reducing neurological deterioration and complications in young children. However, patients face the life-long challenge of maintaining metabolic control through adherence to a strict low-leucine diet to avoid long-term consequences of chronic hyperleucinemia, which include cognitive deficits, mood disorders, and movement disorders...

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant cancer predisposition syndrome characterized by cutaneous leiomyomas, uterine leiomyomas, and aggressive renal cancer. Germline variants in the fumarate hydratase (FH) gene predispose to HLRCC. Identifying germline pathogenic FH variants enables lifetime renal cancer screening and genetic testing for family members. In this report, we present a FH missense variant (c.1039T>C (p.S347P)), initially classified as a variant of uncertain significance...

This paper motivates institutional epistemic trust as an important ethical consideration informing the responsible development and implementation of artificial intelligence (AI) technologies (or AI-inclusivity) in healthcare. Drawing on recent literature on epistemic trust and public trust in science, we start by examining the conditions under which we can have institutional epistemic trust in AI-inclusive healthcare systems and their members as providers of medical information and advice. In particular, we discuss that institutional epistemic trust in AI-inclusive healthcare depends, in part, on the reliability of AI-inclusive medical practices and programs, its knowledge and understanding among different stakeholders involved, its effect on epistemic and communicative duties and burdens on medical professionals and, finally, its interaction and alignment with the public's ethical values and interests as well as background sociopolitical conditions against which AI-inclusive healthcare systems are embedded...

Coilia nasus , a migratory fish species found in the middle and lower reaches of the Yangtze River and along offshore areas of China, possesses considerable aquacultural and economic potential. However, the species faces challenges due to significant variation in the gonadal development rate among females, resulting in inconsistent ovarian maturation times at the population level, an extended reproductive period, and limitations on fish growth rate due to ovarian prematurity. In the present study, we combined genome-wide association study (GWAS) and comparative transcriptome analysis to investigate the potential single nucleotide polymorphisms (SNPs) and candidate genes associated with population-asynchronous ovarian development in C...

Lurasidone is an atypical anti-psychotic approved by the US Food and Drug Administration. It is mainly used to treat schizophrenia in adults through its antagonistic action on dopamine and 5-hydroxytryptamine receptors. The present study systematically assessed the efficacy and safety of lurasidone in the treatment of schizophrenia. Clinical, double-blind, parallel, randomized controlled trials (RCTs) of lurasidone in the treatment of schizophrenia were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and related clinical trial registration websites up to May 2023...

BACKGROUND: Individuals with genetic neurodevelopmental disorders (GNDs) or intellectual disability (ID) are often affected by complex neuropsychiatric comorbidities. Targeted treatments are increasingly available, but due to the heterogeneity of these patient populations, choosing a key outcome and corresponding outcome measurement instrument remains challenging. OBJECTIVES: The aim of this scoping review was to describe the research on outcomes and instruments used in clinical trials in GNDs and ID...

Genetic screens are valuable for identifying novel genes involved in the regulation of developmental processes. To identify genes associated with cell growth regulation in Drosophila melanogaster , a mutagenesis screen was performed. Undergraduate students participating in Fly-CURE phenotypically characterized the E.4.1 mutant which is associated with rough eyes and antennae overgrowth. Following complementation analysis and subsequent genomic sequencing, E.4.1 was identified as a novel mutant allele of GstE14 , a gene involved in ecdysone biosynthesis important for the timing of developmental events...

BACKGROUND: Studies have reported that metabolic disturbance exhibits in patients with Alzheimer's disease (AD). Still, the presence of definitive evidence concerning the genetic effect of metabolites on AD risk remains insufficient. A systematic exploration of the genetic association between blood metabolites and AD would contribute to the identification of new targets for AD screening and prevention. METHODS: We conducted an exploratory two-sample Mendelian randomization (MR) study aiming to preliminarily identify the potential metabolites involved in AD development...

BACKGROUND AND OBJECTIVES: Congenital ataxias are rare hereditary disorders characterized by hypotonia and developmental motor delay in the first few months of life, followed by cerebellar ataxia in early childhood. The course of the disease is predominantly nonprogressive, and many patients are incorrectly diagnosed with cerebral palsy. Despite significant advancements in next-generation sequencing in the past few decades, a specific genetic diagnosis is seldom obtained in cases of congenital ataxia...

BACKGROUND: Malignant tumors of the ureteric bud are not common, and cervical involvement is even rarer. So far, there have been no such cases in the literature. CASE SUMMARY: A 50-year-old woman developed intermittent light bleeding in the past 7 months and lower abdominal pain in the past 2 months. The human papillomavirus 16 (HPV) DNA, P16 chemical staining, thinPrep cytology test (TCT), and cervical and cervical canal tissue biopsy were all negative...