Pan-cancer analyses identify MIR210HG overexpression, epigenetic regulation and oncogenic role in human tumors and its interaction with the tumor microenvironment.

BACKGROUND: Molecular entities showing dysregulation in multiple cancers may hold great biomarker or therapeutic potential. There is accumulating evidence that highlights the dysregulation of a long non-coding RNA, MIR210HG, in various cancers and its oncogenic role. However, a comprehensive analysis of MIR210HG expression pattern, molecular mechanisms, diagnostic or prognostic significance or evaluation of its interaction with tumor microenvironment across various cancers remains unstudied. METHODS: A systematic pan-cancer analysis was done using multiple public databases and bioinformatic tools to study the molecular role and clinical significance of MIR210HG. We have analyzed expression patterns, genome alteration, transcriptional and epigenetic regulation, correlation with patient survival, immune infiltrates, co-expressed genes, interacting proteins, and pathways associated with MIR210HG. RESULTS: The Pan cancer expression analysis of MIR210HG through various tumor datasets demonstrated that MIR210HG is significantly upregulated in most cancers and increased with the tumor stage in a subset of them. Furthermore, prognostic analysis revealed high MIR210HG expression is associated with poor overall and disease-free survival in specific cancer types. Genetic alteration analysis showed minimal alterations in the MIR210HG locus, indicating that overexpression in cancers is not due to gene amplification. The exploration of SNPs on MIR210HG suggested possible structural changes that may affect its interactions with the miRNAs. The correlation of MIR210HG with promoter methylation was found to be significantly negative in nature in majority of cancers depicting the possible epigenetic regulation of expression of MIR210HG. Additionally, MIR210HG showed negative correlations with immune cells and thus may have strong impact on the tumor microenvironment. Functional analysis indicates its association with hypoxia, angiogenesis, metastasis, and DNA damage repair processes. MIR210HG was found to interact with several proteins and potentially regulate chromatin modifications and transcriptional regulation. CONCLUSIONS: A first pan-can cancer analysis of MIR210HG highlights its transcriptional and epigenetic deregulation and oncogenic role in the majority of cancers, its correlation with tumor microenvironment factors such as hypoxia and immune infiltration, and its potential as a prognostic biomarker and therapeutic target in several cancers.

Systematic review analyzing significance of endometrial cavity fluid during assisted reproductive techniques.

OBJECTIVE: The objective of our study is to estimate the prevalence of endometrial cavity fluid (ECF) in Assisted Reproductive Techniques (ART) cycles and analyze its effects on pregnancy outcome in such cycles. DATA SOURCES: PubMed, Cochrane Central, Scopus, and clinicaltrials.gov were searched for articles. The reference lists of relevant publications were explored for other studies. STUDY ELIGIBILITY CRITERIA: Studies that had assessed the pregnancy outcome in ART cycles and had commented on ECF accumulation were included. Pregnancy outcomes were assessed in all ART cycles where ECF was observed and were compared to the non-ECF cycles. RESULTS: A total of nine studies were included in the meta-analysis for a total of 28,210 cycles. Pooled analysis of the prevalence of ECF cycles out of total cycles in females undergoing ART using a fixed effect model showed that it was 14% (95% CI is 13% to 14%; I2 = 99%, p = < 0.01). The random effect model prevalence of ECF cycles was around 7% (95% CI: 4% to 10%). There was a statistically significant (25%) decrease in pregnancy rates per cycle transfer in the ECF cycle versus the non-ECF cycle group during ART [OR = 0.75, 95% CI = 0.67-0.84), p < 0.001; moderate quality evidence]. When ECF size was compared, there was a statistically significant increase in pregnancy rates if ECF size was less than 3.5 mm versus greater than or equal to 3.5 mm [OR = 13.67, 95% CI = 1.43-130.40), p = 0.02; high quality evidence]. Sub-group analysis revealed that the ECF present at the time of embryo transfer significantly decreased the pregnancy rates by 26% as compared to the group where the ECF was not present at the time of embryo transfer [OR = 0.74, 95% CI = 0.65-0.85), p < 0.001]. CONCLUSIONS: This meta-analysis proposes that the presence of ECF significantly decreases the implantation and pregnancy rates of ART cycles, and even more so if its size is greater than 3.5 mm. Interventions to decrease ECF formation or treat it have enhanced the pregnancy outcome in ART cycles. PROSPERO REGISTRATION: Date: 17th September 2020; Number: CRD42020182262.

Photoperiodic physiology of summer breeding birds and a search for the role of eye.

Photoperiod regulation of gonadal cycles is well studied and documented in both birds and mammals. Change in photoperiod is considered as the most effective and important cue to time the initiation of the annual physiological cycles in birds. Approaching of long days (as observed in summer months), signal long-day breeding birds to initiation reproduction and other related functions. Birds and other non-mammalian vertebrates use the extraocular photoreceptors which may be present in the mediobasal hypothalamus (MBH) or associated regions to measure the photoperiodic time and so are different from mammals where only the eyes are lone photoreceptive organs. The downstream signaling involves thyroid responsive genes playing a crucial role in mediating photoperiodic signals in both birds and mammals. Role of eyes in the avian seasonal cycle has been a questionable issue with evidences both favoring and negating any role. We propose that morphological as well as physiological data argue that retinal photoreceptors can participate in gonadal cycle, at least in the quail and duck. The present review details the studies of photoneuroendocrine control of gonadal axis in birds and review evidences to decipher the role eyes in photoperiodic mediated physiologies in birds.

Upfront debulking surgery or delayed surgery after neoadjuvant chemotherapy for advanced-stage epithelial ovarian cancer: Comparison of survival from a noncancer center in India.

BACKGROUND: In advanced-stage epithelial ovarian cancer (EOC) standard of care is upfront debulking surgery (UDS) followed by adjuvant chemotherapy. Interval debulking surgery after neoadjuvant chemotherapy(NACT-IDS) is a reasonable alternative. METHODS: This study was a retrospective review of patients of Stage III/IV EOC treated either by UDS or NACT-IDS between January 2016 and December 2018 to report the comparison of progression-free survival(PFS) and overall survival(OS) of patients with advanced-stage EOC treated with either UDS or NACT-IDS. RESULTS: Out of 50 patients, 19 (38%) underwent UDS, and 31 (62%) received NACT. The mean follow-up duration was 27.7 months. No gross residual disease was achieved in 52.6% of the UDS group and in 70.4% of the NACT-IDS group. The median PFS of 20 and 30 months was observed in the UDS and NACT-IDS groups, respectively (log-rank P = 0.054). The median OS was 36 months in the NACT-IDS group and could not be reached in the UDS group (log-rank P = 0.329). Only residual disease was significantly associated with survival (hazards ratio 3.03, 95% confidence interval: 1.19-7.74) on multivariate Cox regression analysis. CONCLUSIONS: In advanced-stage EOC, the survival outcomes of NACT-IDS are comparable with those of UDS. Apart from the patient-specific parameters, the decision for UDS or NACT-IDS should take in account the expertise of the surgeon and the institutional capacity as a whole.

Tranexamic Acid, a Trivial in Preventing Postpartum Blood Loss in Vaginal Delivery- a Double Blinded, Randomized Controlled Trial.

OBJECTIVE: To assess the effect of intravenous tranexamic acid (1 g) in reducing blood loss during the 3rd and 4th stages of labor following vaginal delivery, in addition to active management of the third stage of labor. METHODS: This double-blinded randomized controlled trial included 650 women with singleton pregnancies of ≥ 34 weeks gestation undergoing vaginal delivery. Eligible women were randomly assigned to receive 1 g of tranexamic acid or placebo intravenously in addition to active management of the third stage of labor. Calibrated blood collection bags were used to measure postpartum blood loss during the 3rd and 4th stages of labor. RESULTS: Out of 886 expectant women who were approached, 650 instances that met the study's inclusion criteria were enrolled and a total of 320 women in group A and 321 in group B were analyzed. Maternal characteristics did not differ between the two groups. Mean blood loss did not differ significantly among the intervention and placebo groups (378.5±261.2 ml vs. 383±258.9 ml; p = 0.93). The incidence of primary postpartum hemorrhage was comparable in both groups (Group A: 15.9%, Group B: 15.3%, p = 0.814). The median fall in haemoglobin within 12-24 hours following delivery in both groups was comparable (group A: 0.60 g% with interquartile range (IQR) 0.4-0.9 g %; group B: 0.6 g% with IQR 0.4-0.8 g %; p = 0.95). The most common adverse effect reported was dizziness. No thromboembolic events were reported at the follow-up of three months in both groups. CONCLUSION: Prophylactic use of tranexamic acid in addition to active management of the third stage of labor does not help further reduce postpartum blood loss following vaginal delivery.

Expression of Programmed Cell Death Ligand-1 and Mismatch Repair Status in Endometrial Carcinomas.

Background and Aims: Programmed death ligand-1 (PD-L1) is a co-regulatory molecule that suppresses local immunity, and mismatch repair (MMR) deficiency (dMMR) is reported to influence the response to anti-PD-L1-targeted therapy. This study was conducted to find the PD-L1 status, the occurrence of dMMR in endometrial carcinomas, and the association between them. Materials and Methods: The study included 35 resected specimens of endometrial carcinomas represented on formalin-fixed paraffin-embedded sections from January 2016 to July 2020. The clinicopathologic information including patient age, tumor histologic type, grade, stage, lymphovascular invasion, the extent of myometrial invasion, and the percentage of tumor-infiltrating lymphocytes (TILs) were obtained in all cases. The expression of PD-L1 and MMR antibodies including mutS homolog 2 (MSH-2), MSH-6, mutL homolog 1 (MLH-1) and MLH-3, and postmeiotic segregation 2 were assessed using immunohistochemistry. The statistical analysis was done using the Statistical Package for the Social Sciences (SPSS) version 26. Results: PD-L1 expression was noted in 48.6% of the cases in tumor cells and 65.7% of the cases in TILs and MMR was deficient in 28.6% of endometrial carcinomas. A statistically significant relation was noted between dMMR and TILs, PD-L1 expression in tumor cells and TILs, PD-L1 expression in tumor cells, and extent of myometrial invasion. Although there was no statistically significant association between MMR status and PD-L1 expression in tumor cells or TILs, 60% of patients with dMMR were PD-L1 positive. Conclusion: Sixty percent of dMMR cases showed PD-L1 expression in tumor cells. We conclude, ECs that are MMR deficient might get better response to anti-PD-L1 therapy. This study also revealed the prognostic use of TILs in PD-L1-expressed tumors.

To Try or Not to Try: A Questionnaire Study among Women with Previous Lower Segment Cesarean Section.

Background: The recent increase in the cesarean section (CS) rate worldwide has led to global concerns and vaginal birth after CS (VBAC) as an effective way to reduce the CS rate. In this study, our main aim was to know about various factors that help women make their preferred mode of delivery following a previous CS. Material and Method: This was a questionnaire-based study conducted in the Department of Obstetrics and Gynecology, All India Institute of Medical Sciences (AIIMS), Jodhpur, among 200 women with previous one lower segment CS (LSCS). Results: Elective repeat cesarean delivery (ERCD) was found to be more among uneducated women and those who had complications in their previous babies. The most common reason for opting for ERCD was fear of labor pains. Women who were counseled by senior doctors were more likely to opt for a trial of labor after cesarean section (TOLAC). Conclusion: Improving the education levels of mothers, counseling about advantages associated with vaginal birth, counseling by senior obstetrician, and information regarding labor analgesia can decrease CS rates.

Examining Risk Factors for Suicidality in Adolescents and Adults Experiencing Their First Episode of Psychosis.

This narrative review aimed to identify the risk factors associated with suicidality in adolescents and adults with first-episode psychosis. The review included studies that examined various factors such as psychiatric, familial, and social factors, as well as previous self-harm, suicidal ideation, and comorbid mental health disorders. A comprehensive literature search was conducted across three publicly available databases (Embase, American Psychological Association PsycINFO, and PubMed) using specific search terms related to first-episode psychosis, suicide, self-harm, and children/adolescents and adults. The inclusion criteria included original articles focusing on prospective and retrospective cohort trials, with substantial data on first-episode psychosis and self-harm, measuring both suicidal intent and outcome. Non-original studies, case reports, case series, non-English-language publications, and studies examining violence and self-harm related to substance-induced psychosis were excluded. After manual screening and removing duplicate articles, 13 articles met the established criteria for inclusion in this review. Included studies adhered to similar inclusion and exclusion criteria, had long-term follow-up, and assessed outcomes at least twice. The findings suggest that depressive symptoms, substance use disorders, previous self-harm or suicidal ideation, and longer duration of untreated psychosis are associated with an increased risk of suicidality. However, insights into psychosis and premorbid intellectual functioning did not show a direct association with suicidality.

Pathophysiological mechanisms of post-myocardial infarction depression: a narrative review.

Myocardial infarction (MI) can have significant physical and mental consequences. Depression is a prevalent psychiatric condition after MI which can reduce the quality of life and increase the mortality rates of patients. However, the connection between MI and depression has remained under-appreciated. This review examines the potential connection between depression and MI by overviewing the possible pathophysiologic mechanisms including dysregulation of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, coagulation system dysfunction, inflammation, environmental factors, as well as, genetic factors. Furthermore, depression can be an adverse event of medications used for MI treatment including beta-blockers, statins, or anti-platelet agents. The need for early detection and management of depression in patients with MI is, therefore, crucial for improving their overall prognosis. Adherence to treatments and regular follow-up visits can ensure the best response to treatment.

Managing Multiple Schwannomatosis of Vagus and Hypoglossal Nerves: The Unanticipated Complications.

Schwannomas are rare benign tumours of the nerve sheath. Extracranial schwannomas are usually found solitary, in the absence of other features of neurofibromatosis. The non NF1/2 multiple schwannomas are collectively described as the clinical scenario called schwannomatosis. We present a rare case of two extracranial schwannomas involving vagus and hypoglossal nerves in a 22-year-old female along with an unusual surgical complication of CSF leak presenting as post-op neck mass and a review of previously reported similar cases. A thorough literature search using the MeSH terms-'schwannomatosis' or 'Multiple Schwannoma' and 'Vagal Schwannoma' and 'Hypoglossal Schwannoma', was conducted using online databases and augmentated by hand search. A total of 13 reported cases were found and reviewed. Of the 14 cases described from review of literature and our case, 50% had involvement of vagus nerve as one of the components. 12.5% had hypoglossal and cervical sympathetic plexus involvement each. All patients underwent surgical excision. Half of the patients suffered intraoperative nerve sacrifice with resultant severe functional deficits like vocal cord paralysis, Horners syndrome, hypoglossal palsy, facial palsy and eleventh nerve palsy. In our case, there was un-unusual complication of CSF leak presenting as a cervical neck mass. Multiple extracranial head and neck schwannomas are rare and their management is fraught with several complications. Decision to operate is often perplexing. However, early planned surgical excision and preservation of nerve of origin minimizes the impact on quality of life postoperatively.

Role of Psychosomatic Symptoms in COVID-19 Vaccine Hesitancy.

Vaccination against COVID-19 is one of the highly effective preventative strategies to reduce morbidity and mortality associated with COVID-19 infection. The rapid approval of COVID-19 vaccination due to the raging pandemic, media coverage, anti-vaccination groups, and concerns about adverse effects associated with vaccination has given rise to COVID-19 vaccine hesitancy. Current evidence suggests that psychosomatic and nocebo-related adverse effects account for a significant proportion of common adverse effects following COVID-19 vaccination. The most common adverse effects are headache, fatigue, and myalgia, which are highly prone to nocebo effects. In our review article, we discuss the role of psychosomatic and nocebo effects in COVID-19 vaccination-related hesitancy, predictors of such effects, and strategies to reduce vaccine hesitancy. General education regarding psychosomatic and nocebo effects and specialized education for at-risk populations may reduce psychosomatic and nocebo-related adverse effects following COVID-19 vaccination, ultimately reducing hesitancy.

Artificial intelligence in intestinal polyp and colorectal cancer prediction.

Artificial intelligence (AI) algorithms and their application to disease detection and decision support for healthcare professions have greatly evolved in the recent decade. AI has been widely applied and explored in gastroenterology for endoscopic analysis to diagnose intestinal cancers, premalignant polyps, gastrointestinal inflammatory lesions, and bleeding. Patients' responses to treatments and prognoses have both been predicted using AI by combining multiple algorithms. In this review, we explored the recent applications of AI algorithms in the identification and characterization of intestinal polyps and colorectal cancer predictions. AI-based prediction models have the potential to help medical practitioners diagnose, establish prognoses, and find accurate conclusions for the treatment of patients. With the understanding that rigorous validation of AI approaches using randomized controlled studies is solicited before widespread clinical use by health authorities, the article also discusses the limitations and challenges associated with deploying AI systems to diagnose intestinal malignancies and premalignant lesions.

Pre-COVID and COVID experience of objective structured clinical examination as a learning tool for post-graduate residents in Obstetrics & Gynecology-a quality improvement study.

OBJECTIVE: Due to its comprehensive, reliable, and valid format, the objective structured clinical examination (OSCE) is the gold standard for assessing the clinical competency of medical students. In the present study, we evaluated the importance of the OSCE as a learning tool for postgraduate (PG) residents assessing their junior undergraduate students. We further aimed to analyze quality improvement during the pre-coronavirus disease (COVID) and COVID periods. METHODS: This quality-improvement interventional study was conducted at the Department of Obstetrics and Gynecology. The PG residents were trained to conduct the OSCE. A formal feedback form was distributed to 22 participants, and their responses were analyzed using a five-point Likert scale. Fishbone analysis was performed, and the 'plan-do-study-act' (PDSA) cycle was implemented to improve the OSCE. RESULTS: Most of the residents (95%) believed that this examination system was extremely fair and covered a wide range of clinical skills and knowledge. Further, 4.5% believed it was more labor- and resource intensive and time-consuming. Eighteen (81.8%) residents stated that they had learned all three domains: communication skills, time management skills, and a stepwise approach to clinical scenarios. The PDSA cycle was run eight times, resulting in a dramatic improvement (from 30% to 70%) in the knowledge and clinical skills of PGs and the standard of OSCE. CONCLUSION: The OSCE can be used as a learning tool for young assessors who are receptive to novel tools. The involvement of PGs in the OSCE improved their communication skills and helped overcome human resource limitations while manning various OSCE stations.

Unlocking the microbial studies through computational approaches: how far have we reached?

The metagenomics approach accelerated the study of genetic information from uncultured microbes and complex microbial communities. In silico research also facilitated an understanding of protein-DNA interactions, protein-protein interactions, docking between proteins and phyto/biochemicals for drug design, and modeling of the 3D structure of proteins. These in silico approaches provided insight into analyzing pathogenic and nonpathogenic strains that helped in the identification of probable genes for vaccines and antimicrobial agents and comparing whole-genome sequences to microbial evolution. Artificial intelligence, more precisely machine learning (ML) and deep learning (DL), has proven to be a promising approach in the field of microbiology to handle, analyze, and utilize large data that are generated through nucleic acid sequencing and proteomics. This enabled the understanding of the functional and taxonomic diversity of microorganisms. ML and DL have been used in the prediction and forecasting of diseases and applied to trace environmental contaminants and environmental quality. This review presents an in-depth analysis of the recent application of silico approaches in microbial genomics, proteomics, functional diversity, vaccine development, and drug design.

Comparison of GATA-3, Mammaglobin and GCDFP-15 Expression in Primary, Metastatic and Triple Negative Breast Carcinomas: An Indian Scenario.

BACKGROUND AND OBJECTIVE: Mammaglobin and GCDFP-15 are traditional immunohistochemistry (IHC) markers utilized to recognize metastasis of breast carcinoma in an unknown primary. GATA-3 is increasingly being used as a marker of primary breast origin. This study was done to evaluate and compare GATA-3 with GCDFP-15 and Mammaglobin in invasive primary including metastatic and triple negative breast carcinomas. METHODS: Immunohistochemistry for GATA-3, GCDFP-15 and Mammaglobin was applied on 100 cases of primary breast carcinomas, including 20 triple negative cases and 30 cases of metastatic breast carcinomas. Staining scores were given for each marker by multiplying the percentage of positive tumor cells by the intensity of staining (1+, 2+ or 3+), with scores ranging from 0 to 300. Staining score of 1 or more was considered positive. RESULTS: GATA-3 was expressed in 92% of primary, 80% of metastatic and 60% of triple negative breast carcinomas, with an average staining score of 270. Mammaglobin was expressed in 68% of primary, 56.6% of metastatic and 25% of triple negative breast carcinomas, with an average staining score of 180. GCDFP-15 was expressed in 48% of primary, 26.6% of metastatic and 05% of breast carcinomas, with an average staining score of 60. GATA-3 demonstrated to have higher staining score (average of 270) than other two markers in maximum number of cases. CONCLUSION: GATA-3 has a higher sensitivity and increased staining scores in primary breast carcinomas, metastatic breast carcinomas as well as in triple negative breast carcinomas.