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Abstract Epileptogenesis is the process by which a normal brain becomes hyperexcitable and capable of generating spontaneous recurrent seizures. The extensive dysregulation of gene expression associated with epileptogenesis is shaped, in part, by microRNAs (miRNAs) – short, non-coding RNAs that negatively regulate protein levels. Functional miRNA-mediated regulation can, however, be difficult to elucidate due to the complexity of miRNA-mRNA interactions. Here, we integrated miRNA and mRNA expression profiles sampled over multiple time-points during and after epileptogenesis in rats, and applied bi-clustering and Bayesian modelling to construct temporal miRNA-mRNA-mRNA interaction networks. Network analysis and enrichment of network inference with sequence- and human disease-specific information identified key regulatory miRNAs with the strongest influence on the mRNA landscape, and miRNA-mRNA interactions closely associated with epileptogenesis and subsequent epilepsy. Our findings underscore the complexity of miRNA-mRNA regulation, can be used to prioritise miRNA targets in specific systems, and offer insights into key regulatory processes in epileptogenesis with therapeutic potential for further investigation.

Aggression toward peers who are perceived as weaker or different is a widespread problem for middle school students including those attending Catholic middle schools. Middle school students' normative beliefs about the acceptability of various types of aggressive behavior influences their own potential involvement in bullying. Therefore, how middle schoolers decide to respond to situations of peer aggression may affect their standing as either victims, bystanders to bullies, or as bully-victims in school environments over time. This study looks at how middle schoolers (sixth, seventh, and eighth grade girls and boys) in Catholic schools think it best to respond to peer aggression by examining their decision-making preferences for how targeted peers (from a vulnerable group) should respond to physical, verbal, or cyber aggression situations. Although significant effects regarding gender, grade, and type of peer aggression were found for the decision-making of the middle schoolers, findings reveal that overall middle schoolers' preferences were well developed for resisting peer aggression. The study provides important insights for how to supplement commonly existing curricula on social emotional learning in Catholic Schools with decision-making training inputs for the design of future school-based bullying prevention programs. Preparing middle schoolers in Catholic schools to respond to stop peer aggression in a proactive way supports the mission of Catholic schools to create safe and caring school environments.

IntroductionCancer patients may have increased risk for adverse cardiac events, but our understanding of cardiovascular risk in thymic cancer patients is not clear. We sought to characterize baseline cardiometabolic risk factors before thymic cancer diagnosis and the potential association between cancer treatment and subsequent cardiac events.MethodsThis was a retrospective cohort study evaluating patients with thymic cancer from 2003 to 2020 compared to age- and sex-matched controls without cancer. Baseline cardiovascular risk factors, cancer characteristics, and incidence of cardiac events were collected from the health information exchange. Multivariable regression was used to examine the impact of cardiovascular risk factors and cancer therapies.ResultsWe compared 296 patients with pathology-confirmed thymic cancer to 2,960 noncancer controls. Prior to cancer diagnosis, thymic cancer patients (TCPs) had lower prevalence of hypertension, dyslipidemia, and diabetes mellitus and similar rates of obesity, tobacco use, and pre-existing cardiovascular disease (CVD) compared to controls. After diagnosis, high-risk TCPs (>2 cardiovascular risk factors or pre-existing CVD) had higher risk for cardiac events (HR 3.73, 95% CI 2.88–4.83, p

The population of patients with cancer is rapidly expanding, and the diagnosis and monitoring of cardiovascular complications greatly rely on imaging. Numerous advances in the field of cardio-oncology and imaging have occurred in recent years. This review presents updated and practical approaches for multimodality cardiovascular imaging in the cardio-oncology patient and provides recommendations for imaging to detect the myriad of adverse cardiovascular effects associated with antineoplastic therapy, such as cardiomyopathy, atherosclerosis, vascular toxicity, myocarditis, valve disease, and cardiac masses. Uniquely, we address the role of cardiovascular imaging in patients with pre-existing cardiomyopathy, pregnant patients, long-term survivors, and populations with limited resources. We also address future avenues of investigation and opportunities for artificial intelligence applications in cardio-oncology imaging. This review provides a uniform practical approach to cardiovascular imaging for patients with cancer.

Background: Children had been affected less by COVID-19 than adults. But as the pandemic progressed more cases of severe pediatric COVID infection were reported. Aim of this study is to describe the clinical characteristics, laboratory parameters, treatments, and predictors of pediatric intensive care unit (PICU) admission among hospitalized children with SARS-CoV-2 infection. Subjects and Methods: This was a retrospective, observational study performed in a tertiary care COVID referral hospital among hospitalized children aged from 1 month to 12 years, from May 2020 to March 2021. Children treated in the pediatric ward were compared with those admitted in the PICU to assess predictors of intensive care admission. Results: Out of 447 hospitalized patients with confirmed COVID-19 infection, 92 (20.58%) required admission in the PICU. Mean age of the study population was 44.58 (16.77–72.39) months. Thirty-eight patients (8.50%) fulfilled multisystem inflammatory syndrome in children (MIS-C) diagnostic criteria. Invasive mechanical ventilation and inotropic support were needed for 28.26% and 36.96% of PICU-admitted patients, respectively. The mortality rate was 1.57%. Independent risk factors for PICU admission were infant age group, longer duration of fever (>5 days), shortness of breath, presence of shock, underlying comorbidities and higher pediatric early warning score (PEWS ≥5), poor Glasgow coma scale (GCS 50 mg/L), neutrophil–lymphocyte ratio (NLR ≥4.5), and hypoalbuminemia (

We report the results of a DREAM challenge designed to predict relative genetic essentialities based on a novel dataset testing 98,000 shRNAs against 149 molecularly characterized cancer cell lines. We analyzed the results of over 3,000 submissions over a period of 4 months. We found that algorithms combining essentiality data across multiple genes demonstrated increased accuracy; gene expression was the most informative molecular data type; the identity of the gene being predicted was far more important than the modeling strategy; well-predicted genes and selected molecular features showed enrichment in functional categories; and frequently selected expression features correlated with survival in primary tumors. This study establishes benchmarks for gene essentiality prediction, presents a community resource for future comparison with this benchmark, and provides insights into factors influencing the ability to predict gene essentiality from functional genetic screens. This study also demonstrates the value of releasing pre-publication data publicly to engage the community in an open research collaboration.

Histone phosphorylation is a ubiquitous post-translational modification. Here the authors present a programmable chromatin kinase, dCas9-dMSK1, that enables controlled histone phosphorylation and specific gene activation.

To plan for retirement, it is important to understand how needs and purchases may change. We use data from a survey of elderly Australians to see how needs and purchases changed in different categories of goods and services. We looked especially at those who had experienced financial or health shocks. Our analysis shows variation in people's experiences, particularly for health costs, which increase with age. Having private health insurance appears to increase the level and volatility of health costs – presumably as a result of out‐of‐pocket costs. This information can be useful for financial advisors and superannuation trustees. [ABSTRACT FROM AUTHOR]

Several biologic agents have been approved for use in dermatology and other disciplines of medicine. However, based on the mechanism of action and a track record of the response, these agents are being increasingly used for off-label purposes to garner control of more remote and difficult disease processes. Herein, we present three difficult to treat patients where innovative uses of biologics beyond their approved indications have yielded good responses. Our first patient was a case of bullous pemphigoid, who showed excellent response to omalizumab. The second case was a patient of lepromatous leprosy with tenosynovitis and erythema nodosum leprosum, who was treated effectively with infliximab. Our third case was a treatment-resistant pyoderma gangrenosum, where infliximab showed a very good response. In the present study, we report the cases to highlight the usefulness of biologics that can expand much beyond the routine FDA approved indications.

The article touches upon current problems of speech genres functioning on the Internet and fits into the context of modern research in the field of virtual genre studies. The article discusses the speech genre of the movie announcement and describes the means of its language embodiment. The research is focused on the analysis of clichéd constructions and is based on 250 Indian film announcements written in Russian and posted on Indiankino.net. The author offers a descriptive model of the movie announcement speech genre which includes the following parameters: the communicative goal and type of speech genre, the image of the author and the addressee, the image of the future and the image of the past, the composition of movie announcement, the type of dictum content, means of its linguistic embodiment, non-verbal means. There is a special focus on the use of clichéd constructions in all compositional parts of the analyzed texts (name of the film, exposition, plot of the film, denouement). The research has shown that clichés function in every compositional element. The author singles out the main functions of clichéd constructions in the speech genre of the movie announcement: persuading function, advertising function, as well as text-building and genre-forming functions.

Background Gastrointestinal route is considered for feeding in subjects who are unable to swallow, either as a temporary or permanent option. Percutaneous endoscopic gastrostomy (PEG) is the preferred mode for long-term enteral nutrition. The aim was to study the outcome of protocol-based PEG placement in a tertiary medical center. Materials and Methods All the patients who underwent PEG placement between January 2017 and December 2019 were included in the retrospective study. Study variables were entered into a uniform structured proforma. The procedure was done by two people using Ponsky-Gauderer pull-technique. Fluoroscopy guidance was considered for placement in special situations. Post-procedure, all the patients were regularly followed as per protocol to evaluate for adverse events. Results One hundred and eighteen patients with placement of PEG were included in the study. The mean age of the patients was 49.6 ± 7 years with 67.8% males. The most common indication of PEG was inability to swallow associated with head injury (43, 36.4%), followed by carcinoma esophagus (35, 29.8%) and stroke (24, 20.3%). Fluoroscopy was useful in 38 (32%) for PEG site identification. Tube dislodgement (16, 13.5%) and aspiration pneumonia (20, 16.9%) were the common adverse events. Age more than 60 years and dysphagia in neurologic disorders accounted for more than 60% of adverse events. Forty-nine (42%) of the PEG patients expired due to either primary illness or due to sepsis after a median time of 139 days (range: 32–288 days). There was no difference in the survival in patients with or without PEG-related complications (p = 0. 74). Conclusions Fluoroscopy assistance helps in accurate PEG placement in one third. Age > 60 years and dysphagia in neurologic disorders were independent risk factors associated with PEG tube complications.

Goal directed behavior requires the sequential retrieval and evaluation of the multiple choices for action and their deterministic outcomes. Here, the authors report sequential, decodable probabilistic outcome representations in magnetoencephalography (MEG) signals during a risky foraging task.

Background: In the recent years, the frequency, severity, clinical characteristics, treatment response, and relapse rate of dermatophytosis have dramatically changed in India. Given the surge in dermatophytosis, we had undertaken a study to isolate and identify the common species causing dermatophyte infection and to know the in vitro efficacy of the common antifungals against them. Materials and Methods: total of 103 new cases that were not on any treatment for the past 3 months were included. Skin scrapings were collected for direct microscopic examination and for fungal culture in Sabouraud 4% dextrose agar (SDA) with chloramphenicol and cycloheximide slant tubes, and dermatophyte test media. Fungi were identified on the basis of their macroscopic and microscopic features with the help of lactophenol cotton blue staining and urease test. Also, the drug sensitivity of the dermatophytes was tested with the common antifungals. Results: Of the 55 cases (53.4%) that were positive for dermatophytes in the culture, 29 showed possible contamination. Trichophyton was the predominant organism (49 cases) with T. verrucosum being the commonest species (26 cases), followed by T. rubrum (15 patients), and T. mentagrophytes(8 cases). All species of Trichophyton were found to be most sensitive to itraconazole amongst systemic antifungals and luliconazole amongst topical antifungals. Conclusion: This study concluded that the causative agent for the dermatophytosis was changing in India and in our subset, T. verrucosum caused the maximum number of infections. Itraconazole and luliconazole had the highest sensitivity amongst systemic and topical antifungals, respectively. It also showed that terbinafine had comparatively less sensitivity to most organisms.

The Corona Virus Disease 2019 (COVID-19) pandemic has presented an unprecedented challenge globally. It is much bigger than a bio-medical concern now with the multitudes of socio-economic, socio-political, socio-cultural, and psycho-social impact, which are likely to outlast the pandemic itself by far and long. The pandemic and the resulting challenges across societies highlighted the existing social injustices in a neoliberal world for historically marginalized populations like homeless persons with mental illness (HPMI). The nationwide lockdown in India to resist the spread of the virus posed a unique challenge to this vulnerable population. The present study thus attempts to understand the experience of HPMI during the COVID-19 induced lockdown through the theoretical framework of social justice vis-à-vis injustice. Semi-structured interviews have been conducted on seven HPMI rehabilitated in the community through an NGO situated in Kolkata, India. Seven stakeholders have also been interviewed to understand their experience in providing services to the HPMI during the COVID-19 induced lockdown. Analyses of the narratives have been done using initial coding, focused coding and axial coding through the process of constant comparison of constructivist grounded theory (CGT) methodology. Critical insights from the study bring out experiences of HPMI during COVID-19 as a victim of structural violence, highlighting their exclusion and victimization due to the existing marginalized status, living closer to the edge as a consequence of the lockdown, lack of awareness of the gravity of the pandemic situation. The experiences of the stakeholders, on the other hand, pointed out the role of community members and social workers in partially mitigating the challenges. This study indicates that to mitigate the aftermaths, stakeholders, including community members, need to work together for rebuilding and enhancing the strength and resilience of the marginalized populations like HPMI, who are historically victims of social injustice in the neoliberal pandemic era.

Background and Aims: Pecs block and its variations provides perioperative analgesia, reduce PONV and other opioid related side effects. We hypothesized that COMIBPES block in addition to general anaesthesia will provide better postoperative analgesia when compared to general anaesthesia alone in breast cancer surgery patients. Methods: After obtaining permission from the institutional review board and registering the trial with Clinical Trials Registry of India (CTRI), we conducted a double blinded randomized controlled trial of 100 patients posted for elective breast surgery with axillary dissection. Patients were divided into two groups, P (Pecs block) and C (control). Intraoperative analgesia, postoperative analgesia, postoperative nausea vomiting (PONV) and shoulder mobility on first postoperative day (POD1) were noted. Primary outcomes were the pain scores measured by visual analog scale (VAS) and cumulative intravenous morphine consumption from patient controlled analgesia (PCA) pump at measurement intervals of 0, 1, 4, 8, 12 and 24 hours postoperatively. Results: Intraoperatively, Group P patients did not require any additional analgesia, whereas all the patients in Group C required additional intraoperative morphine (mean, SD: 5.12, 2.63 mg, compared to nil in group P, P< 0.01). COMBIPECS block group had lower pain scores and PCA morphine requirements, less PONV and better shoulder mobility on POD1. Conclusion: COMBIPECS block is a valuable addition to general anaesthesia for breast cancer surgery as it reduces pain and PONV while allowing better postoperative shoulder mobility.

Background and Aims: Use of ultrasound (US) during internal jugular vein (IJV) cannulation reduces the risk of associated complications in children under general anaesthesia. We studied the effect of two varieties of supraglottic airway device (SGAD), the Ambu AuraOnce™ LMA (Ambu LMA), and i-gel™ on the anatomical relationship between IJV and common carotid artery (CCA). Both these SGAD are known to have similar safety profile in paediatric age group. Methods: A total of 62 children were randomly allocated into 2 groups. In group L: Ambu AuraOnce™ LMA (Ambu LMA) and in group I: i-gel™ was inserted. After induction of GA, US images were taken with head in neutral and 30 degrees rotated to the opposite side both before and after insertion of SGAD. The relationship between IJV and CCA was noted as lateral, anterolateral, and anterior. Degree of overlap between the two vessels was also noted. Results: Lateral rotation of the head significantly alters the relationship between the IJV and CCA and also increases the degree of overlap between them. Though these changes were noted to be similar with both varieties of SGAD, but between the two varieties of SGAD, these changes were significantly higher in group I. Conclusion: Higher oesophageal sealing pressure exerted by i-gel™ as compared to other SGAD might cause increased distortion of the surrounding soft tissue leading to altered anatomical relationship between IJV and CCA, which makes the CCA vulnerable to puncture during IJV cannulation using landmark technique.

Ultrasound-guided serratus anterior plane (SAP) block has been described to provide complete anaesthesia and analgesia to the lateral thoracic wall. Its use has been recently reported in breast reconstruction surgeries. We present a series of 11 patients where ultrasound-guided SAP block was used as part of multimodal analgesia in breast reconstruction surgery using latissimus dorsi (LD) myocutaneous flap after mastectomies. This resulted in excellent analgesia in the perioperative period and minimal use of intravenous analgesics. The SAP block technique described here is safe and also provides effective analgesia in breast reconstruction surgery with LD flap.

Abstract MicroRNAs (miRNAs) are non‐coding small RNAs that regulate gene expression at transcriptional and post‐transcriptional levels. The role of miRNAs in seed development and seed size/weight determination is poorly understood in legumes. In this study, we profiled miRNAs at seven successive stages of seed development in a small‐seeded and a large‐seeded chickpea cultivar via small RNA sequencing. In total, 113 known and 243 novel miRNAs were identified. Gene ontology analysis revealed the enrichment of seed/reproductive/post‐embryonic development and signaling pathways processes among the miRNA target genes. A large fraction of the target genes exhibited antagonistic correlation with miRNA expression. The sets of co‐expressed miRNAs showing differential expression between the two cultivars were recognized. Known transcription factor (TF) encoding genes involved in seed size/weight determination, including SPL, GRF, MYB, ARF, HAIKU1, SHB1, KLUH/CYP78A5, and E2Fb along with novel genes were found to be targeted by the predicted miRNAs. Differential expression analysis revealed higher transcript levels of members of SPL and REVOLUTA TF families and lower expression of their corresponding miRNAs in the large‐seeded cultivar. At least 19 miRNAs known to be involved in seed development or differentially expressed between small‐seeded and large‐seeded cultivars at late‐embryogenesis and/or mid‐maturation stages were located within known quantitative trait loci (QTLs) associated with seed size/weight determination. Moreover, 41 target genes of these miRNAs were also located within these QTLs. Altogether, we revealed important roles of miRNAs in seed development and identified candidate miRNAs and their target genes that have functional relevance in determining seed size/weight in chickpea.

Previous studies have reported that imitative responses may be modulated by top-down social factors such as self-focus. However, growing evidence suggests that such social factors may actually modulate domain-general processes such as spatially compatible responding, rather than specifically social processes such as imitation. In this study, we aimed to identify the cognitive processes being modulated under conditions of heightened or diminished self-focus. Participants performed a stimulus-response compatibility task which independently measures both spatial and imitative response tendencies, under two conditions: heightened self-focus, where the task was performed in the presence of two mirrors; and diminished self-focus, where the mirrors were covered. While participants were faster to respond to compatible trials than to incompatible trials, both imitatively and spatially, there was no significant modulation of either spatial or imitative compatibility by self-focus; although the magnitude of the modulation of spatial compatibility was numerically similar to the effect of self-focus on imitation found in previous studies. These results provide no evidence for an effect of self-focus on either social-specific, or domain-general, processes.