Identification of lncRNAs regulating seed traits in Brassica juncea and development of a comprehensive seed omics database.

Brassica juncea is a crucial oilseed crop, and its seeds possess high economic value as they are a source of edible oil. In order to understand the role of long non coding RNAs (lncRNAs) in the regulation of seed development, we carried out computational analysis using transcriptome data of developing seeds of two contrasting genotypes of B. juncea, Pusajaikisan (PJK) and Early Heera 2 (EH2). The seeds were sampled at three stages, 15, 30, and 45 days after pollination. We identified 1,539 lncRNAs, of which 809 were differentially expressed. We also carried out extensive characterization and functional analysis of seed lncRNAome. The expression patterns were analysed using k-means clustering, and the targets were analysed using pathway, transcription factor, and GO enrichment, as well as ortholog information. We shortlisted a total of 25 robust lncRNA candidates for seed size, oil content, and seed coat color. We also identified 4 lncRNAs as putative precursors of miRNAs regulating seed development. Moreover, a total of 28 miRNA-lncRNA-mRNA regulatory networks regulating seed traits were identified. We also developed a comprehensive database, (BrassIca juncea database or "BIJ" ( https://bij.cuh.ac.in/ ), which provides seed omics as well as other functional genomics and genetics data in an easily accessible form. These candidate lncRNAs are suitable for including in crop improvement programs through molecular breeding, as well as for future validations through genome editing. Together, the knowledge of these candidate lncRNAs and availability of BIJ database shall leverage the crop improvement efforts in B. juncea.

Expression of Programmed Death Ligand 1 [PD-L1] and Mismatch Repair Status in Squamous Cell Carcinomas of Cervix.

Background and Objectives: To assess mismatch repair (MMR) status and programmed death-ligand 1 (PD-L1) expression in squamous cell carcinomas of the cervix and their association with clinicopathologic parameters. Material and Methods: Expression of PD-L1 and MMR status (MSH2, MSH6, MLH1, and PMS2) was assessed on 50 cases of SCCs of the cervix by immunohistochemistry. Results: 80% of tumor cells and 84% of tumor-infiltrating lymphocytes showed PD-L1 expression. 80% of cases had a combined positive score (CPS) of > 1, whereas 20% had a CPS of < 1. 94% of cases showed pMMR proteins, while 6% showed dMMR. 94% of the SCCs were HPV associated, and 6% were HPV-independent. All HPV-independent SCCs of the cervix showed PD-L1 expression, and all HPV-associated SCCs showed MMR deficiency. Between PD-L1 expression in the tumor and the grade of the tumor, a statistically significant association was noted (p = 0.022). All MMR-deficient SCCs were HPV-independent. Conclusion: This research highlighted the HPV association in cervical SCCs in the Indian population. Most of the cervical SCCs were HPV-associated. Furthermore, most of the HPV-associated SCCs were MMR stable. This study found no significant association between MMR status and PD-L1 expression in cervical SCCs.

Superior hypogastric nerve plexus (SHNP) block for pain management after minimally invasive gynecology surgeries: A prospective randomized controlled trial.

OBJECTIVES: Our study aimed to evaluate the effect of superior hypogastric nerve plexus (SHNP) block in postoperative pain management in the first 24 h after minimally invasive gynecological (MIG) surgeries. METHODS: We conducted a double-blinded, randomized controlled trial in the Department of Obstetrics and Gynecology at a tertiary care centre from May 1, 2023 to September 30, 2023 in women undergoing major MIG surgeries. At the completion of the surgery, women were randomized to the intervention group who received SHNP block with ropivacaine 10 mL (0.75%) before port removal, whereas no intervention was taken in the control group. The extubation time was noted, and the pain score was assessed after 1, 2, 6, 12, and 24 h of extubation in the postoperative period using the visual analog scale (VAS). Statistical analysis was done, with a significance level of 0.05, to test the differences between the two groups. RESULTS: A total of 64 patients were randomly allocated to intervention and control groups. The median pain score was lower at 1 and 2 h post-extubation and comparable between the two groups at 6, 12, and 24 h. The surrogate markers that is need for additional analgesia and duration of stay did not differ significantly in the two groups, with P-values of 0.08 and 0.943, respectively. CONCLUSION: Although the SHNP group experienced considerably lower immediate postoperative pain levels in the initial hours following extubation, the impact of this benefit remains uncertain in the longer postoperative period. The effectiveness of this modality for pain control needs further study, particularly at later postoperative hours.

Temporal Gene Expression Profiles From Pollination to Seed Maturity in Sorghum Provide Core Candidates for Engineering Seed Traits.

Sorghum (Sorghum bicolor (L.) Moench) is a highly nutritional multipurpose millet crop. However, the genetic and molecular regulatory mechanisms governing sorghum grain development and the associated agronomic traits remain unexplored. In this study, we performed a comprehensive transcriptomic analysis of pistils collected 1-2 days before pollination, and developing seeds collected -2, 10, 20 and 30 days after pollination of S. bicolor variety M35-1. Out of 31 337 genes expressed in these stages, 12 804 were differentially expressed in the consecutive stages of seed development. These exhibited 10 dominant expression patterns correlated with the distinct pathways and gene functions. Functional analysis, based on the pathway mapping, transcription factor enrichment and orthology, delineated the key patterns associated with pollination, fertilization, early seed development, grain filling and seed maturation. Furthermore, colocalization with previously reported quantitative trait loci (QTLs) for grain weight/size revealed 48 differentially expressed genes mapping to these QTL regions. Comprehensive literature mining integrated with QTL mapping and expression data shortlisted 25, 17 and 8 core candidates for engineering grain size, starch and protein content, respectively.

Tranexamic acid in preventing postpartum blood loss in vaginal delivery: a double-blinded randomized controlled trial.

BACKGROUND: Postpartum hemorrhage (PPH) is an obstetrical emergency that occurs in 1% to 10% of all deliveries and contributes to nearly one-quarter of all maternal deaths worldwide. Tranexamic acid has been established as an adjunct in the treatment of PPH but its role in its prevention of PPH following vaginal delivery has not been widely studied. OBJECTIVE: This study aimed to assess the effect of prophylactic tranexamic acid (1 g) along with active management of the third stage of labor in reducing postpartum blood loss and the incidence of postpartum hemorrhage after vaginal delivery. STUDY DESIGN: In this randomized controlled trial, 650 women with singleton pregnancies at ≥34 weeks of gestation who were undergoing vaginal delivery were included. Eligible women were randomly assigned to receive either 1 g of tranexamic acid or placebo intravenously along with active management of the third stage of labor. Calibrated blood collection bags were used to measure postpartum blood loss during the third and fourth stages of labor. RESULTS: Of 886 women approached for the study, 650 who met the inclusion criteria were enrolled, and 320 in group A and 321 in group B were analyzed. The maternal characteristics were similar between the groups. The mean blood loss did not differ significantly between the intervention and placebo groups (378.5±261.2 mL vs 383.0±258.9 mL; P=.93). The incidence of primary postpartum hemorrhage was comparable in both groups (15.9% in group A and 15.3% in group B; P=.814). The median quantitative decreases in hemoglobin levels within 12 to 24 hours after delivery were 0.60 g% (interquartile range, 0.40-0.90) in group A and 0.60 g% (interquartile range, 0.40-0.80) in group B, which were comparable in both groups (P=.95). The most common adverse effect reported was dizziness, and there was no thromboembolic event at 3 months follow-up in either group. CONCLUSION: The use of tranexamic acid as a prophylactic measure along with active management of the third stage of labor does not provide additional benefit in reducing the postpartum blood loss and incidence of postpartum hemorrhage after vaginal delivery. El resumen está disponible en Español al final del artículo.

A novel interplay between PRC2 and miR-3189 regulates epithelial-mesenchymal transition (EMT) via modulating COL6A2 in glioblastoma.

Recent studies have shed light on disrupted collagen signaling in Gliomas, yet the regulatory landscape remains largely unexplored. This study enquired into the role of polycomb repressive complex-2 (PRC2)-mediated H3K27me3 modification, a key epigenetic factor in glioma. Using in-house data, we identified miRNAs downregulated in glioblastoma (GBM) with the potential to regulate Collagen VI family genes. Notably, miR-3189 emerged as a prime PRC2 target. Its expression was significantly downregulated in Indian GBM patients as well as other glioma cohorts. Mechanistic insights, involving Luciferase assays, mutagenesis, and Western blot analysis, confirmed direct targeting of Collagen VI member COL6A2 by miR-3189-3p. Functional assays demonstrated that miR-3189-3p restrained GBM malignancy by inhibiting proliferation, migration, and epithelial-mesenchymal transition (EMT). Conversely, COL6A2 overexpressed in GBM patients, countered miR-3189, and promoted the malignant phenotype. Gene set enrichment analysis highlighted EMT enrichment in GBM patients with elevated COL6A2 expression, carrying prognostic implications. This study uncovers intricate interactions between two epigenetic regulators-H3K27me3 and miR-3189-working synergistically to modulate Collagen VI gene; thus, influencing the malignancy of GBM. Targeting this H3K27me3|miR-3189-3p|COL6A2 axis presents a potential therapeutic avenue against GBM.

Spectrum of Heart Disease in Pregnancy and its Effects on the Fetomaternal Outcome: A Retrospective Study from Western Rajasthan.

Background: Heart disease is the important cause of maternal morbidity and mortality during the antepartum and postpartum period. The prevalence of heart disease during pregnancy varies from 0.3 to 3.5% (2). We aimed to know the spectrum of heart disease in pregnancy and its impact on the maternal and fetal outcome. Methodology: The study was conducted in the Department of Obstetrics and Gynecology of the tertiary care referral Centre of Western Rajasthan, India. Data from November 2019 to October 2021 were collected from the labour room and obstetric ward records. Results:Forty-eight pregnant women were diagnosed with heart disease over a period of two years. The prevalence of heart disease in pregnancy was 1.3%. Rheumatic heart disease was the main cardiac lesion (85.42%), with mitral stenosis being the most commonly seen (31.25%). Previous cardiac surgery was found in 14.58% of patients. Half of women gave birth by spontaneous vaginal delivery (50%), 43.75% of subjects by cesarean section and 6.25% of participants underwent instrumental delivery. Admissions to intensive care unit (ICU) were noted in 16.67% of cases, and those to neonatal intensive care unit (NICU) in nine newborns (18.75%). There were only two maternal deaths and no baby born with congenital heart disease. Conclusion:Heart disease in pregnancy is a high-risk condition and significantly impacts the mother and fetal outcome. By proper antenatal, intrapartum and postnatal supervision under a multidisciplinary team, maternal and fetal mortality and morbidity can be reduced.

Psychiatric Comorbidities of Incarceration in a Patient With Gender Dysphoria: A Case Report and Literature Review.

ABSTRACT: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition defines gender identity disorder (GID) as a strong and persistent identification with the opposite sex and the distress that may accompany the incongruence between one's experienced or expressed gender and one's assigned gender. The onset of GID commonly begins early in childhood. Gender dysphoria has a higher prevalence of other comorbid psychiatric illnesses, such as mood, anxiety, and adjustment disorders, with increased suicide incidence and self-harming behaviors than the general population. Studies show that some temperamental, environmental, genetic, and psychological factors play a role in developing GID. Approximately 16% of transgender people and 21% of transgender women get incarcerated compared with the general US population. During incarceration, they face many issues, such as victimization, severe verbal harassment, purposeful humiliation, unwanted sexual advances, physical assault, forcible sex, and unwanted strip searches. There is a need for a better understanding of the issues and needs of this population to promote positive outcomes.

Unraveling the Inferno: An Arson Case Series.

Firesetting behaviors present multifaceted challenges that intersect the realms of mental health, law, and societal welfare. While distinct in nature, firesetting, arson, and pyromania collectively embody a spectrum of behaviors that cause harm with profound implications for mental health and legal system. Firesetting is a behavior, arson is a criminal offense, and pyromania is a classified psychiatric diagnosis. Nevertheless, the underlying motivations for these behaviors in the context of psychiatric symptomatoloty remain poorly understood. Arson alone exacts a staggering financial toll in the United States, emphasizing the urgent need to understand the reason behind these acts. Within legal contexts, mental health professionals frequently encounter individuals exhibiting firesetting behaviors while consulting on legal cases. The strong correlation between firesetting behavior and mental disorders shows a dire need for extensive and detailed collaboration between psychiatric experts, legal practitioners, and fire services. Here, we describe a series of firesetting cases and their ties to the mental health and legal systems underscoring the imperative for integrated, multifaceted approaches to address this pressing societal concern.

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.

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.

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.

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.

WITHDRAWN: Tranexamic acid to reduce postpartum blood loss after a vaginal delivery: a double-blinded, randomized controlled trial.

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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.