Anxiety and Depression in School-going children with Epilepsy

Background: This study was designed to find the prevalence of anxiety and depression in school-going children with epilepsy.Methods:All the patients with epilepsy presenting during the study period underwent detailed clinical and EEG evaluation. Hospital Anxiety and Depression score (HADS) was used to screen for anxiety and depression.Results:We identified 190 patients with epilepsy during the study period. Out of these 30 (15.8%) were diagnosed as having treatment resistance epilepsy. Anxiety was diagnosed in 114 (60%) and depression in 62 (32.6%). Patients with drug resistant epilepsy were found to have statistically significant markers in the form of higher scores for depression and anxiety, and lower IQ scores. Frequency of GTCS (Generaized Tonic Clonic Seizures) showed inverse correlation with IQ scores and direct correlation to the anxiety/depression scores.Conclusion:We conclude that anxiety and depression in school-going children with epilepsy is common and that it has a correlation with treatment resistance.

TNF-Alpha Inhibitors and Ustekinumab for the Treatment of Psoriasis: Therapeutic Utility in the Era of IL-17 and IL-23 Inhibitors

Psoriasis is a chronic inflammatory condition for which eleven FDA-approved biologic therapies are approved. Over the past decade, studies have documented the higher efficacy of IL-17 and IL-23 inhibitors for the treatment of psoriasis compared to the TNF-alpha inhibitors and ustekinumab, an IL-12/23 inhibitor. Despite this, there remains an important role for the use of TNF-alpha inhibitors and ustekinumab in the treatment of psoriasis. Here, we review how considerations of infection and malignancy risk, patient demographics, treatment resistance, and comorbidities may make certain TNF-alpha inhibitors or ustekinumab an excellent choice for therapy in particular patient subgroups.

Comprehensive Characterization of Tumor Purity and Its Clinical Implications in Gastric Cancer

Solid tumour tissues are composed of tumour and non-tumour cells, such as stromal cells and immune cells. These non-tumour cells constitute an essential part of the tumour microenvironment (TME), which decrease the tumour purity and play an important role in carcinogenesis, malignancy progression, treatment resistance and prognostic assessment. However, the implications of various purity levels in gastric cancer (GC) remain largely unknown. In the present study, we used an in-silico approach to infer the tumour purity of 2,259 GC samples obtained from our hospital and 12 public datasets based on the transcriptomic data. We systematically evaluated the association of tumour purity with clinical outcomes, biological features, TME characteristics and treatment response in GC. We found that tumour purity might be a patient-specific intrinsic characteristic of GC. Low tumour purity was independently correlated with shorter survival time and faster recurrence and significantly associated with mesenchymal, invasive and metastatic phenotypes. Integrating GC purity into a clinical prognostic nomogram significantly improved predictive validity and reliability. In addition, low tumour purity was strongly associated with immune and stromal cell functions. Fibroblasts, endothelial cells and monocytes were markedly enriched in low-purity tumours, serving as robust indicators of a poor prognosis. Moreover, patients with low GC purity may not benefit more from adjuvant chemotherapy. Our findings highlight that tumour purity confers important clinical, biological, microenvironmental and treatment implications for patients with GC. Therefore, a comprehensive evaluation of tumour purity in individual tumours can provide more insights into the molecular mechanisms of GC, facilitate precise classification and clinical prediction and help to develop more effective individualised treatment strategies.

Topographic mapping of the glioblastoma proteome reveals a triple-axis model of intra-tumoral heterogeneity

Glioblastoma is an aggressive form of brain cancer with well-established patterns of intra-tumoral heterogeneity implicated in treatment resistance and progression. While regional and single cell transcriptomic variations of glioblastoma have been recently resolved, downstream phenotype-level proteomic programs have yet to be assigned across glioblastoma’s hallmark histomorphologic niches. Here, we leverage mass spectrometry to spatially align abundance levels of 4,794 proteins to distinct histologic patterns across 20 patients and propose diverse molecular programs operational within these regional tumor compartments. Using machine learning, we overlay concordant transcriptional information, and define two distinct proteogenomic programs, MYC- and KRAS-axis hereon, that cooperate with hypoxia to produce a tri-dimensional model of intra-tumoral heterogeneity. Moreover, we highlight differential drug sensitivities and relative chemoresistance in glioblastoma cell lines with enhanced KRAS programs. Importantly, these pharmacological differences are less pronounced in transcriptional glioblastoma subgroups suggesting that this model may provide insights for targeting heterogeneity and overcoming therapy resistance.

Breast Cancer Tumor Microenvironment and Molecular Aberrations Hijack Tumoricidal Immunity

Breast cancer is the most common malignancy among females in western countries, where women have an overall lifetime risk of >10% for developing invasive breast carcinomas. It is not a single disease but is composed of distinct subtypes associated with different clinical outcomes and is highly heterogeneous in both the molecular and clinical aspects. Although tumor initiation is largely driven by acquired genetic alterations, recent data suggest microenvironment-mediated immune evasion may play an important role in neoplastic progression. Beyond surgical resection, radiation, and chemotherapy, additional therapeutic options include hormonal deactivation, targeted-signaling pathway treatment, DNA repair inhibition, and aberrant epigenetic reversion. Yet, the fatality rate of metastatic breast cancer remains unacceptably high, largely due to treatment resistance and metastases to brain, lung, or bone marrow where tumor bed penetration of therapeutic agents is limited. Recent studies indicate the development of immune-oncological therapy could potentially eradicate this devastating malignancy. Evidence suggests tumors express immunogenic neoantigens but the immunity towards these antigens is frequently muted. Established tumors exhibit immunological tolerance. This tolerance reflects a process of immune suppression elicited by the tumor, and it represents a critical obstacle towards successful antitumor immunotherapy. In general, immune evasive mechanisms adapted by breast cancer encompasses down-regulation of antigen presentations or recognition, lack of immune effector cells, obstruction of anti-tumor immune cell maturation, accumulation of immunosuppressive cells, production of inhibitory cytokines, chemokines or ligands/receptors, and up-regulation of immune checkpoint modulators. Together with altered metabolism and hypoxic conditions, they constitute a permissive tumor microenvironment. This article intends to discern representative incidents and to provide potential innovative therapeutic regimens to reinstate tumoricidal immunity.

The Prevalence of Impulse Control Disorders and Behavioral Addictions in Eating Disorders: A Systematic Review and Meta-Analysis

Aim: Individuals with eating disorders (EDs) may present with impulse control disorders (ICDs) and behavioral addictions (BAs), which may result in additional suffering and treatment resistance. However, the prevalence of ICDs and BAs in EDs has not been systematically examined. Therefore, this systematic review and meta-analysis aimed to assess the prevalence of ICDs and BAs in ED samples.Methods: A comprehensive electronic database search of the peer-reviewed literature was conducted in the following online databases: MEDLINE, PsycINFO, Embase, and CINAHL from their inception to May 2021. We restricted review eligibility to research studies reporting prevalence for ICDs or BAs in individuals with diagnosed EDs. The outcome for this review was the prevalence of ICDs or BAs in individuals with EDs. A series of random-effects meta-analyses were performed on eligible studies to estimate the pooled proportions and 95% confidence intervals (CIs).Results: Thirty-five studies met the inclusion criteria, including a total of 9,646 individuals identified as having an ED, 18 of these studies specifically examined ICDs/BAs in AN, BN, and BED. Random-effects pooled estimates demonstrated that the comorbid prevalence of any ICD was 22%. The prevalence of comorbid pathological/compulsive buying was highest (19%), followed by kleptomania (18%), pathological internet use (12%), intermittent explosive disorder (4%), trichotillomania (3%), and gambling disorder (2%). In addition, the prevalence of stealing/shoplifting behaviors was 30% in those with EDs.Conclusion: This is the first meta-analysis on the comorbid prevalence of EDs and ICDs/BAs. We found a moderate prevalence for these comorbid conditions, with approximately one out of five individuals with an ED also displaying a comorbid ICD/BA. Although causal inferences cannot be drawn, the numbers strongly suggest that clinical screening/monitoring of ICDs/BAs should be part of the clinical routine in cohorts with EDs. ED settings need either the capacity to manage these disorders or adequate access to relevant services. Further investigations are needed to reveal common underlying pathomechanisms.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier: CRD42020202044.

PARP1 Upregulation in Recurrent Oral Cancer and Treatment Resistance

First-line treatments for oral cancer typically include surgery, radiation, and in some cases, chemotherapy. Radiation and oral cancer chemotherapeutics confer cytotoxicity largely by inducing DNA damage, underscoring the importance of the cellular DNA damage repair and response pathways in cancer therapy. However, tumor recurrence and acquired resistance, following the initial response to treatment, remains as a major clinical challenge. By analyzing oral tumor cells derived from the primary and recurrent tumors of the same patient, our study revealed upregulated PARP1 expression in the recurrent tumor cells. Cisplatin and 5-fluorouracil treatment further augmented PARP1 expression in the recurrent, but not the primary, tumor cells. Post-treatment upregulation of PARP1 was dependent on the catalytic activities of PARP and CDK7. Consistent with the established function of PARP1 in DNA repair, we showed that overexpression of PARP1 rendered the primary tumor cells highly resistant to DNA damage treatment. Conversely, PARP inhibition partially reversed the treatment resistance in the recurrent tumor cells; combinatorial treatment using a PARP inhibitor and cisplatin/5-fluorouracil significantly sensitized the tumor response in vivo. Taken together, we reported here PARP1 upregulation as a clinically relevant mechanism involved in oral cancer recurrence, and suggested the clinical benefit of PARP inhibitors, currently approved for the treatment of several other types of cancer, in oral cancer.