Neuropsychological functions in a pediatric case of partial agenesis of the corpus callosum: Clinical implications.

The corpus callosum (CC) is involved in several cognitive processes and the interhemispheric transfer of information. The current case study investigated neurocognitive and emotional processes in a 7-year-old female with partial agenesis of the corpus callosum, with an absent splenium and posterior body, with comorbid autism and ADHD. We measured cognitive functions, such as response inhibition, error monitoring, attentional disengagement, and attention capture by irrelevant emotional stimuli. We found that response inhibition was intact in the case. When happy faces were used as stop-signals, it interfered with response inhibition compared to angry-face-stop-signals. Similarly, happy faces (relative to angry faces) interfered with error monitoring; irrelevant angry faces captured attention more than happy faces. Attentional disengagement functions were impaired in the case compared to healthy controls. The findings give an insight into the interaction between cognition and emotion in pediatric partial agenesis of the CC, and have important clinical and theoretical implications.

The Role of UBI in Mitigating the Effects of Psychosocial Stressors: A Review and Proposal.

Psychosocial stressors and social disadvantages contribute to inequalities in opportunities and outcomes. In the current paper, we use an epidemiological perspective and highlight the role stress plays on individuals by reviewing the outcomes of major stressors such as poverty and unemployment. We further analyzed the psychological and physical cost of these stressors and their long-term impact. We examined the role of universal basic income and closely looked at income experiments that were implemented in the past, in terms of their effectiveness in enhancing the community as well as individual outcomes and propose the UBI as a tool for alleviating the impact of these stressors. At a time when a major pandemic (e.g., COVID-19) threatens economic stability and health globally, we believe the UBI is relevant now, more than ever.

StrandAdvantage test for early-line and advanced-stage treatment decisions in solid tumors.

Comprehensive genetic profiling of tumors using next-generation sequencing (NGS) is gaining acceptance for guiding treatment decisions in cancer care. We designed a cancer profiling test combining both deep sequencing and immunohistochemistry (IHC) of relevant cancer targets to aid therapy choices in both standard-of-care (SOC) and advanced-stage treatments for solid tumors. The SOC report is provided in a short turnaround time for four tumors, namely lung, breast, colon, and melanoma, followed by an investigational report. For other tumor types, an investigational report is provided. The NGS assay reports single-nucleotide variants (SNVs), copy number variations (CNVs), and translocations in 152 cancer-related genes. The tissue-specific IHC tests include routine and less common markers associated with drugs used in SOC settings. We describe the standardization, validation, and clinical utility of the StrandAdvantage test (SA test) using more than 250 solid tumor formalin-fixed paraffin-embedded (FFPE) samples and control cell line samples. The NGS test showed high reproducibility and accuracy of >99%. The test provided relevant clinical information for SOC treatment as well as more information related to investigational options and clinical trials for >95% of advanced-stage patients. In conclusion, the SA test comprising a robust and accurate NGS assay combined with clinically relevant IHC tests can detect somatic changes of clinical significance for strategic cancer management in all the stages.

Identification of Novel Mutations in ABCA4 Gene: Clinical and Genetic Analysis of Indian Patients with Stargardt Disease.

Stargardt disease (STGD) is the leading cause of juvenile macular degeneration associated with progressive central vision loss, photophobia, and colour vision abnormalities. In this study, we have described the clinical and genetic features of Stargardt patients from an Indian cohort. The next generation sequencing was carried out in five clinically confirmed unrelated patients and their family members using a gene panel comprising 184 retinal specific genes. Sequencing results were analyzed by read mapping and variant calling in genes of interest, followed by their verification and interpretation. Genetic analysis revealed ABCA4 mutations in all of the five unrelated patients. Among these, four patients were found with compound heterozygous mutations and another one had homozygous mutation. All the affected individuals showed signs and symptoms consistent with the disease phenotype. We report two novel ABCA4 mutations in Indian patients with STGD disease, which expands the existing spectrum of disease-causing variants and the understanding of phenotypic and genotypic correlations. Screening for causative mutations in patients with STGD using panel of targeted gene sequencing by NGS would be a cost effective tool, might be helpful in confirming the precise diagnosis, and contributes towards the genetic counselling of asymptomatic carriers and isolated patients.

Molecular alterations in epidermal growth factor receptors as potential predictors of invasion in complete hydatidiform moles (CHM).

Molecular alterations in Epidermal growth factor receptor (EGFR) were investigated for the first time in molar placenta using protein expression, activation status, differential amplification status and mutational analysis. Invasive lesions showed upregulation of internal domain and downregulation of external domain with concomitantly high gene amplification and phosphorylation. Mutations distributed across different exons in non-invasive cases in contrast to single mutations restricted to exons 4 and 6 in invasive cases displayed a strong correlation to overexpression and phosphorylation status suggesting that higher copies of EGFR gene and mutations in exon 4&6 influence the invasive capacity of trophoblasts and can be used as a biomarker of invasion.

Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship.

BACKGROUND & AIMS: Identifying shared and disease-specific susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC) would help define the biologic relationship between the inflammatory bowel diseases. More than 30 CD susceptibility loci have been identified. These represent important candidate susceptibility loci for UC. Loci discovered by the index genome scans in CD have previously been tested for association with UC, but those identified in the recent meta-analysis await such investigation. Furthermore, the recently identified UC locus at ECM1 requires formal testing for association with CD. METHODS: We analyzed 45 single nucleotide polymorphisms, tagging 29 of the loci recently associated with CD in 2527 UC cases and 4070 population controls. We also genotyped the UC-associated ECM1 variant rs11205387 in 1560 CD patients and 3028 controls. RESULTS: Nine regions showed association with UC at a threshold corrected for the 29 loci tested (P < .0017). The strongest association (P = 4.13 x 10(-8); odds ratio = 1.27) was identified with a 170-kilobase region on chromosome 1q32 that contains 3 genes. We also found association with JAK2 and replicated a recently reported association with STAT3, further implicating the role of this signaling pathway in inflammatory bowel disease. Additional novel UC susceptibility genes were LYRM4 and CDKAL1. Twenty of the loci were not associated with UC, and several appear to be specific to CD. ECM1 variation was not associated with CD. CONCLUSIONS: Collectively, these data help define the genetic relationship between CD and UC and characterize common, as well as disease-specific mechanisms of pathogenesis.