Somatics

In myeloid neoplasms, both fusion genes and gene mutations are well-established events identifying clinicopathological entities. In this study, we present a thus far undescribed t(X;21)(p11.4;q22.12) in five cases with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The translocation was isolated or accompanied by additional changes. It did not generate any fusion gene or gene deregulation by aberrant juxtaposition with regulatory sequences. Molecular analysis by targeted next-generation sequencing showed that the translocation was accompanied by at least one somatic mutation in TET2, EZH2, RUNX1, ASXL1, SRSF2, ZRSR2, DNMT3A, and NRAS genes...

Gamma radiation (60 Co)-induced mutagenesis offers an alternative to develop rice lines by accelerating the spontaneous mutation process and increasing the pool of allelic variants available for breeding. Ionizing radiation works by direct or indirect damage to DNA and subsequent mutations. The technique can take advantage of in vitro protocols to optimize resources and accelerate the development of traits. This is achieved by exposing mutants to a selection agent of interest in controlled conditions and evaluating large numbers of plants in reduced areas...

Transspinal (or transcutaneous spinal cord) stimulation is a non-invasive, cost-effective, easily applied method with great potential as a therapeutic modality for recovering somatic and non-somatic functions in upper motor neuron disorders. However, how transspinal stimulation affects motor neuron depolarization is poorly understood, limiting the development of effective transspinal stimulation protocols for rehabilitation. In this study, we characterized the responses of soleus α motor neurons to single pulse transspinal stimulation using single motor unit discharges as a proxy given the 1:1 discharge activation between the motor neuron and the motor unit...

OBJECTIVE: In the domain of competitive events, Latin dance athletes have always suffered competitive anxiety, which is a prevalent and prevailing psychological facet, in pre-, intra-, and post-competitive engagements. Usually, the implementation of systematic desensitization training is an efficacious approach to reduce competitive anxiety levels in routine sports to fortify psychological resilience of athletes (like swimming, volleyball, and basketball). This study focuses on the effect of systematic desensitization training on competition anxiety in the training of Latin dancers to establish good mental ability and promote the competitive ability of athletes...

The viral vector-based COVID-19 vaccine Ad26.COV2.S has been recommended by the WHO since 2021 and has been administered to over 200 million people. Prior studies have shown that Ad26.COV2.S induces durable neutralizing antibodies (NAbs) that increase in coverage of variants over time, even in the absence of boosting or infection. Here, we studied humoral responses following Ad26.COV2.S vaccination in individuals enrolled in the initial Phase 1/2a trial of Ad26.COV2.S in 2020. Through 8 months post vaccination, serum NAb responses increased to variants, including B...

CONTEXT: Genetic analysis of sporadic medullary thyroid carcinoma (MTC) has revealed somatic variants in RET , RAS , and occasionally other genes. However, around 20% of patients with sporadic MTC lack a known genetic driver. OBJECTIVE: To uncover potential new somatic or germline drivers, we analyze a distinct cohort of patients with sporadic, very early-onset, and aggressive MTC. METHODS: Germline and somatic DNA exome sequencing was performed in 19 patients, previously tested negative for germline RET variants...

RASopathies are syndromes caused by congenital defects in the Ras/mitogen-activated protein kinase (MAPK) pathway genes, with a population prevalence of 1 in 1,000. Patients are typically identified in childhood based on diverse characteristic features, including cryptorchidism (CR) in >50% of affected men. As CR predisposes to spermatogenic failure (SPGF; total sperm count per ejaculate 0-39 million), we hypothesized that men seeking infertility management include cases with undiagnosed RASopathies. Likely pathogenic or pathogenic (LP/P) variants in 22 RASopathy-linked genes were screened in 521 idiopathic SPGF patients (including 155 CR cases) and 323 normozoospermic controls using exome sequencing...

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by challenges in communication, social interaction, and repetitive behaviors. Children with ASD often experience comorbidities such as speech impairment and attention deficit, which can significantly impact their quality of life and ability to engage in daily activities. This case report aims to investigate the potential benefits of osteopathic manipulation in addressing speech impairment and attention deficit in a child diagnosed with ASD...

Lynch Syndrome (LS) is the most common hereditary cancer syndrome. Heterozygous loss-of-function variants in PMS2 are linked to LS. While these variants are not directly cancer causing, reduced PMS2 function results in the accumulation of somatic variants and increased cancer risk over time due to DNA mismatch repair dysfunction. It is reasonable that other types of genetic variation that impact the expression of PMS2 may also contribute to cancer risk. The Kozak sequence is a highly conserved translation initiation motif among higher eukaryotes and is defined as the nine basepairs upstream of the translation start codon through the first four bases of the translated sequence (5'-[GTT]GCATCCATGG-3'; human PMS2 NM_000535...

BACKGROUND: Hepatocellular carcinoma represents a significant global burden in terms of cancer-related mortality, posing a substantial risk to human health. Despite the availability of various treatment modalities, the overall survival rates for patients with hepatocellular carcinoma remain suboptimal. The objective of this study was to explore the potential of novel biomarkers and to establish a novel predictive signature utilizing multiple transcriptome profiles. METHODS: The GSE115469 and CNP0000650 cohorts were utilized for single cell analysis and gene identification...

PURPOSE: Glioblastoma is a malignant brain tumor with a poor prognosis. Genetic mutations associated with this disease are complex are not fully understood and require further elucidation for the development of new treatments. The purpose of this study was to comprehensively analyze genetic mutations in glioblastomas and evaluate the usefulness of RNA sequencing. PATIENTS AND METHODS: We analyzed 42 glioblastoma specimens that were resected in routine clinical practice and found wild-type variants of the IDH1 and IDH2 genes...

INTRODUCTION: The effects of dipeptidyl peptidase-4 inhibitors (DPP-4is) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) on quality of life (QOL) and treatment satisfaction have not been directly compared. This sub-analysis of a randomized-controlled trial with an SGLT2i, luseogliflozin, and DPP-4is compared their effects on QOL and treatment satisfaction of patients. METHODS: This study recruited 623 patients with type 2 diabetes mellitus who were drug-naïve or treated with antidiabetic agents other than SGLT2is and DPP-4is...

Programmed death-1 (PD-1) inhibitors are approved for therapy of gynecologic cancers with DNA mismatch repair deficiency (dMMR), although predictors of response remain elusive. We conducted a single-arm phase 2 study of nivolumab in 35 patients with dMMR uterine or ovarian cancers. Co-primary endpoints included objective response rate (ORR) and progression-free survival at 24 weeks (PFS24). Secondary endpoints included overall survival (OS), disease control rate (DCR), duration of response (DOR) and safety...

BACKGROUND: Systematic doping programs like in the GDR were applied in adolescent competitive athletes to induce supramaximal athletic performance. The substances had adverse somatic and psychological effects. The psychological development of the young athletes was impaired and they suffered in adulthood from long-term effects and secondary diseases even years after the doping period. METHOD: The study compared three groups: competitive athletes with doping (I), competitive athletes without doping (II) and persons with no sports activities (III)...

Heatwaves are increasingly prevalent and can constrain investment into important life-history traits. In addition to heatwaves, animals regularly encounter threats from other organisms in their environments, such as predators. The combination of these two environmental factors introduces a decision-making conflict-heat exposure requires more food intake to fuel investment into fitness-related traits, but foraging in the presence of predators increases the threat of mortality. Thus, we used female variable field crickets ( Gryllus lineaticeps ) to investigate the effects of heatwaves in conjunction with predation risk (exposed food and water sources, and exposure to scent from black widow spiders, Latrodectus hesperus ) on resource acquisition (food intake) and allocation (investment into ovarian and somatic tissues)...

Porokeratosis is a clonal keratinization disorder characterized by solitary, linearly arranged, or generally distributed multiple skin lesions. Previous studies showed that genetic alterations in MVK, PMVK, MVD, or FDPS-genes in the mevalonate pathway-cause hereditary porokeratosis, with skin lesions harboring germline and lesion-specific somatic variants on opposite alleles. Here, we identified non-hereditary porokeratosis associated with epigenetic silencing of FDFT1, another gene in the mevalonate pathway...

BACKGROUND: There is currently limited literature assessing the real-world treatment patterns and clinical outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) mutations. METHODS: Medical charts were abstracted for mCRPC patients with ≥ 1 of 12 HRR somatic gene alterations treated at US oncology centers participating in the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange...

Persons with severe mental ill-health die early from preventable physical ill-health. Registered nurses in psychiatric outpatient care play a key role in improving persons' physical health, and it is important to examine how they view their responsibility, their experiences of care, and the obstacles they meet in providing person-centred care. The purpose of this study was to explore registered nurses' experiences of caring for persons with mental ill-health and somatic comorbidity in psychiatric outpatient care, using qualitative content analysis to analyze data from semi-structured interviews...

OBJECTIVES: The reported prevalence of mental health conditions (MHCs) in people with systemic lupus erythematosus (SLE) ranges widely. Whether MHCs are associated with increased risk of SLE or the outcomes of the disease is unclear. This paper aimed to conduct an umbrella and updated meta-analysis of MHCs in people with SLE and to identify whether MHCs are associated with the risk of SLE or patient outcomes. METHODS: We comprehensively searched PubMed, Web of Science, and Embase databases to identify relevant studies published before June 2023...

IMPORTANCE: Pathogenic or likely pathogenic (P/LP) germline CDH1 variants are associated with risk for diffuse gastric cancer and lobular breast cancer (LBC) in the so-called hereditary diffuse gastric cancer (HDGC) syndrome. However, in some circumstances, LBC can be the first manifestation of this syndrome in the absence of diffuse gastric cancer manifestation. OBJECTIVES: To evaluate the frequency of germline CDH1 variants in women with the hereditary LBC (HLBC) phenotype, somatic CDH1 gene inactivation in germline CDH1 variant carriers' tumor samples, and the association of genetic profiles with clinical-pathological data and survival...