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By comparing phenotypic clinical characteristics and cardiovascular magnetic resonance (CMR) findings in 14 patients with COVID-19 mRNA vaccine-associated myocarditis to 14 patients with acute myocarditis from other causes, we found that patients with COVID-19 vaccination- associated acute myocarditis have higher left ventricular ejection fraction, higher left ventricular global circumferential and radial strain, and less involvement of late gadolinium enhancement in the septal segments with less involvement of midmyocardial pattern of late gadolinium enhancement, compared to patients with acute myocarditis from other causes.

In the present study, non-equiatomic nanocrystalline high entropy alloys (Fe, Al, Cr, Mn, and Ni) powder was synthesized using a high-energy planetary ball mill. During milling, a small amount of powder was collected after a different interval of milling time (2 h, 5 h, 10 h, and 20 h). The milled powders after different milling times were characterized using X-ray diffraction (XRD), and Differential Scanning Calorimetry (DSC). The crystallite size of the milled powder was calculated by analyzing XRD results using the Williamson-Hall method. XRD analysis exhibits that the crystallite size of 20 h milled powder particles is in the nano regime. Besides, lattice parameter, micro-strain and dislocation density of the milled powders were calculated. The melting point of milled powder was analyzed using DSC. The characterization of milled powder suggests the successful formation of nanocrystalline high entropy alloys powder using high-energy ball milling.

Immune checkpoint inhibitor therapy has revolutionized the treatment of many different types of cancer. However, despite dramatic improvements in tumor oncologic response and patient outcomes, immune checkpoint blockade has been associated with multiple distinctive side-effects termed immune-related adverse events. These often have important clinical implications because these can vary in severity, sometimes even resulting in death. Therefore, it is important for both radiologists and clinicians to recognize and be aware of these reactions to help appropriately guide patient management. This article specifically highlights imaging manifestations of the most common cardiothoracic toxicities of these agents, including pneumonitis, sarcoid-like granulomatosis and lymphadenopathy, and myocarditis.

Background Despite its high sensitivity in diagnosing COVID-19 in a screening population, chest CT appearances of COVID 19 pneumonia are thought to be non-specific. Purpose To assess the performance of United States (U.S.) and Chinese radiologists in differentiating COVID-19 from viral pneumonia on chest CT. Methods A total of 219 patients with both positive COVID-19 by RT-PCR and abnormal chest CT findings were retrospectively identified from 7 Chinese hospitals in Hunan Providence, China from January 6 to February 20, 2020. A total of 205 patients with positive Respiratory Pathogen Panel for viral pneumonia and CT findings consistent with or highly suspicious for pneumonia by original radiology interpretation within 7 days of each other were identified from Rhode Island Hospital in Providence, RI. Three Chinese radiologists blindly reviewed all chest CTs (n=424) to differentiate COVID-19 from viral pneumonia. A sample of 58 age-matched cases was randomly selected and evaluated by 4 U.S. radiologists in a similar fashion. Different CT features were recorded and compared between the two groups. Results For all chest CTs, three Chinese radiologists correctly differentiated COVID-19 from non-COVID-19 pneumonia 83% (350/424), 80% (338/424), and 60% (255/424) of the time, respectively. The seven radiologists had sensitivities of 80%, 67%, 97%, 93%, 83%, 73% and 70% and specificities of 100%, 93%, 7%, 100%, 93%, 93%, 100%. Compared to non-COVID-19 pneumonia, COVID-19 pneumonia was more likely to have a peripheral distribution (80% vs. 57%, p

Epigenetic regulators MLL1 and Menin plays important role in cancer progression, metastasis, and relapse. Apart from the oncogenic translocations in leukemias, MLL1 forms a COMPASS complex with Menin and other binding partners to act as an H3K4 methyltransferase. Inhibition of COMPASS complex by blocking the Menin-MLL1 interaction is reported to be effective in different cancers. In this study, we found that a specific Menin-MLL1 inhibitor, MI-503 inhibits neuroblastoma cancer stem cells (NB CSCs; CD114+ cells) to inhibit overall neuroblastoma (NB) growth in both in vitro and in vivo NB tumor models. NB is an extracranial solid pediatric cancer that accounts for about 15% of all pediatric cancer-related deaths, with the long-term survival of relapsed NB patients being less than 10%. We found that MI-503 significantly and in a dose-dependent manner inhibits cell proliferation in nine NB cell lines tested including MYCN amplified (NGP, LAN-5, IMR-32), MYCN non-amplified (SH-SY5Y, SK-N-AS, CHLA-255), and primary patient-derived NB cell lines (COG-N-415, COG-N-269, COG-N-357), in contrast to control fibroblasts. Additionally, MI-503 significantly inhibits NB 3D spheroidal tumor growth and live cell counts compared to control treatments. Further, flow cytometry analysis revealed that MI-503 specifically induces apoptosis and blocks cell cycle progression at the S phase in the NB CSCs (CD114+ cells) in comparison to non-CSCs (CD114- cells) that leads to significant inhibition of overall NB CSC levels in different NB cell lines. By inhibiting the COMPASS complex, MI-503 significantly inhibits H3K4me3 levels as determined by the histone immunoblot assays. This leads to the inhibition of multiple cancer stemness-related genes expression such as OCT4, Nanog, HOXA, AF9, and MEIS1. Further, we determined the efficacy of MI-503 in NB xenograft mouse models and found that MI-503 significantly inhibits overall NB tumor growth (12.3 fold; p Citation Format: Rameswari Chilamakuri, Saurabh Agarwal. Epigenetic regulator Menin-MLL1 maintains cancer stem cells and promotes neuroblastoma growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB314.

COVID-19 is a pandemic that has affected the healthcare system and the global economy. The symptoms of COVID-19 and pneumonia are very similar, so it is a challenging task to differentiate between the two diseases. Available Test Methods such as Real-time Reverse Transcription-Polymerase Chain Reaction (RRT-PCR) and Rapid Diagnostic Tests (RDT) are costly, time-consuming, with high false detection rates and limited availability. Therefore, the research community should come forward with other alternative methods that can detect these diseases faster and prevent the spread of COVID-19 and hence, Chest X-ray (CXR) has emerged as a very popular solution as it is cheap and very easily available everywhere. This paper proposes an automated COVID-19 detection model based on chest X-rays. The proposed model developed a fusion of multiple pre-trained convolutional neural networks to extract deep and high-level features from CXR images. This model is tested for three different classes on two different data sets and ach

Highlights • AKT overexpression correlates with poor prognosis in neuroblastoma patients. • BX-795 inhibits PDK1 and abrogates the AKT signaling pathway activation. • BX-795 demonstrates strong efficacy in neuroblastoma spheroid tumor model. • Combination with BX-795 synergistically enhances doxorubicin antitumor activity. • BX-795 synergistically sensitized ALK mutated neuroblastoma cell lines to crizotinib., High-risk neuroblastoma (NB) represents a major clinical challenge in pediatric oncology due to relapse of metastatic, drug-resistant disease, and treatment-related toxicities. An analysis of 1235 primary NB patient dataset revealed significant increase in AKT1 and AKT2 gene expression with cancer stage progression. Additionally, Both AKT1 and AKT2 expression inversely correlate with poor overall survival of NB patients. AKT1 and AKT2 genes code for AKT that drive a major oncogenic cell signaling pathway known in many cancers, including NB. To inhibit AKT pathway, we repurposed an antiviral inhibitor BX-795 that inhibits PDK1, an upstream activator of AKT. BX-795 potently inhibits NB cell proliferation and colony growth in a dose-dependent manner. BX-795 significantly enhances apoptosis and blocks cell cycle progression at mitosis phase in NB. Additionally, BX-795 potently inhibits tumor formation and growth in a NB spheroid tumor model. We further tested dual therapeutic approaches by combining BX-795 with either doxorubicin or crizotinib and found synergistic and significant inhibition of NB growth, in contrast to either drug alone. Overall, our data demonstrate that BX-795 inhibits AKT pathway to inhibit NB growth, and combining BX-795 with current therapies is an effective and clinically tractable therapeutic approach for NB., Graphical abstract Image, graphical abstract

SARS-CoV-2–infected patients are reported to show immunocompromised behavior that gives rise to a wide variety of complications due to impaired innate immune response, cytokine storm, and thrombo-inflammation. Prolonged use of steroids, diabetes mellitus, and diabetic ketoacidosis (DKA) are some of the factors responsible for the growth of Mucorales in such immunocompromised patients and, thus, can lead to a life-threatening condition referred to as mucormycosis. Therefore, an early diagnosis and cell-based management cosis is the need of the hour to help affected patients overcome this severe condition. In addition, extended exposure to antifungal drugs/therapeutics is found to initiate hormonal and neurological complications. More recently, mesenchymal stem cells (MSCs) have been used to exhibit immunomodulatory function and proven to be beneficial in a clinical cell-based regenerative approach. The immunomodulation ability of MSCs in mucormycosis patient boosts the immunity by the release of chemotactic proteins. MSC-based therapy in mucormycosis along with the combination of short-term antifungal drugs can be utilized as a prospective approach for mucormycosis treatment with promising outcomes. However, preclinical and in mucormyIn mucormycosis, the hyphae of clinical trials are needed to establish the precise mechanism of MSCs in mucormycosis treatment.

Background: Non-alcoholic fatty liver disease (NAFLD) also referred as metabolic as metabolic (dysfunction) associated fatty liver disease. Type 2 diabetes mellitus (T2DM) is a major cause in progression of NAFLD and non-alcoholic steatohepatitis (NASH). The aim of the present study is to assess the activity of liver enzymes in T2DM in North Indian population. Method: This was a cross-sectional descriptive study clinic-based study in patients with T2DM. A total of 612 participants (226 healthy controls and 386 T2DM) were recruited. Body mass index (BMI), activity of liver enzymes including alanine and aspartate aminotransferase (ALT, AST) along with alkaline phosphatase (ALP) was measured. Fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) along with total protein (TP) and albumin were also measured. Quantitative variables were expressed as mean ± SD, while qualitative variables as frequencies (%). Pearson/Spearman correlation test, unpaired t-test, Chi-squared test was used to assess the correlation, association and significant differences between study groups respectively. A P-value of

Background: Femoral neck-shaft angle has its importance in describing biomechanics of hip. Measurement methods like plain radiography and CT scans have its limitations. The modied neck-shaft angle (mNSA) drawn on MRI scans is less susceptible to rotational effects and is more reliable for getting normal values. The present study was undertaken to assess the neck shaft angle on MRI and establish differences according to age and gender. Methods: Total 200 adults were recruited and equally distributed under four study cohorts according to age and gender. MRI of hip joint was analysed and mNSA was measured using pre-dened axial lines and landmarks. Results: The mean age of the participants was 49.76±18.184 years (18 to 87 years). The mean mNSA was 147.855o. Males had signicantly higher mean mNSA (149.93±6.61)o than females (145.78±5.71)o. Though the younger age group ( 60years) age group (147.3900±6.35), the difference was not statistically signicant. Conclusions: We conclude that gender-based variation exists in the population with the higher values of mNSAin males as compared to females in any age group. The age based difference is also present, but it is not signicant. Neck shaft angle calculated on the MRI has the advantage that it is unaffected by rotation of the hip and is radiation free. The orthopaedic surgeons can use the mNSAfor the diagnosis and planning surgeries around hip, for designing implants and prosthesis. It can also be of help for the forensic anthropologists and to the anatomists. Multicentric studies may be undertaken to include a larger population.

IntroductionThe orbital complications of sinusitis including cellulitis and abscess formation are well documented in both children and adults, but remain relatively uncommon. If left untreated, several complications such as orbital complications could progress rapidly, leading to optic neuritis, cavernous sinus thrombophlebitis or life-threatening intracranial complications and orbital cellulitis can manifest including blindness, meningitis, and even death.Material and MethodsA prospective and observational study of patients presented with orbital complication secondary to sinusitis in our Hospitals from January 2019 to December 2019.ResultsIn our study total 60 patients, male patients (63.3%) more common than women (36.6%) with a ratio of 1.7:1. Frequency of age groups of 1-20 years are 23 patients (38.3%) and least were more than 61 years old patients 5%. CT of orbits and sinuses was conducted in all patients, and sinusitis and preseptal cellulitis / orbital abscess was evident in all these cases. Maximum cases were Maxillary Sinusitis (n=41) and least were Sphenoid Sinusitis (n=3). In each of the patients with sinus disease, generally more than 1 ocular symptom were found. Proposes is the highest manifestation of ocular symptoms (n=30) due to diseases of the par nasal sinuses. Other ocular symptoms that least common were decrease visual acuity (n=3) and relative afferent pupillary defect present (n=4). All patients received intravenous antimicrobials, 7(11.6%) with amoxicillin/clavulanate alone, 2(3.33%) with ampicillin/ sulbactam alone, gentamicin in 12 (20%), and the other 39 (65%) with multiple antimicrobials.ConclusionOrbital complications, secondary to sinusitis, in the new millennium still pose a serious threat to patient’s vision and life; it can lead to irreversible damage if not treated aggressively. Medical treatment is efficient in early stages while surgical drainage (endoscopic or external) in preseptal, sub periosteal or orbital abscess.

Introduction: This study is done to evaluate the role of different clinical factors in hematoma enlargement, especially severe hypertension during the early phase of spontaneous ICH. Materials and Methods: All patients with spontaneous intracranial hematoma who were of > 18 years in age, presented within 24 hour of onset, were enrolled for this study. Repeat CT scan was done within 24 - 48 hours after 1st scan. Results: 88 patients were enrolled and among them, 11 (12.5%) had >20% enlargement in the size of the hematoma on the second CT. The Mean increase in the size of hematoma was 19.8 11.4 ml (47.3 27.2 %). Progression of symptom after onset and after admission, lower GCS ( from onset to CT the enlargement of the hematoma. Mean systolic BP at admission > 200 mm Hg was present in a higher proportion of patients with hematoma enlargement. Conclusion: The present study showed that patients of spontaneous ICH presenting within 6 hours with higher NIHSS, low GCS (GCS hematoma enlargement. SBP >200 mm of Hg at admission may be a potential risk factor. ( Hematoma enlargement, NIHSS =National Institute Health Stroke Scale score, GCS =Glasgow Coma Scale, MAP=mean arterial pressure) Keywords: ute Health SHematoma enlargement, National Instittroke Scale score, Glasgow Coma Scale

Background: Leprosy is a leading cause of permanent physical disability. Approx 60% of global burden of leprosy is represented by India. Histopathological examination is still considered gold standard for accurate categorization of leprosy so that timely treatment can be started. Objectives: To categorize and correlate types of leprosy clinically and histomorphologically in Kumaon region. Methods: The present cross-sectional study of 62 cases was conducted in the Department of Pathology & Skin and V.D in a tertiary care centre of Kumaon region from August 2016 to April 2018. The cases were clinically examined and categorized according to Ridley-Jopling classification. Skin Biopsy and Slit-Skin Smear (SSS) were taken for accurate histomorphogical categorization of leprosy and assessment of bacterial index, followed by clinico-histomorphological correlation. Statistical analysis was done in term of chi-square test. Kappa test was used as agreement test for clinical versus histological classification of different type of leprosy. Results: A total of 62 clinically diagnosed leprosy cases evaluated histopathologically. Clinically, lepromatous leprosy (LL) was the most common type of leprosy (38.70%), followed by borderline tuberculoid (30.64%). On histopathological examination, indeterminate leprosy (IL) (21 cases; 33.90%) was the most common followed by lepromatous leprosy (16 cases; 25.80%). Overall clinico-histopathological correlation was seen in 36 cases (58. 06%) with maximum correlation seen in indeterminate leprosy (100%) and tuberculoid leprosy (TT) (100%). Conclusion: This study concludes that correlation of clinical and histopathological features along with bacterial index is more useful for accurate typing of leprosy than considering any of the single parameter alone so that early and appropriate treatment could be started.

Depression is a common problem worldwide since the ages. Mostly it is treated with Selective serotonin reuptake inhibitors (SSRI) but they are not effective in each and every patient. Hence other methods for better effective ways to treat depression are needed. This study was divided as acute and chronic study. Each containing five groups control, escitalopram (standard),omega -3 fatty acid (FA),escitalopram + omega -3 FA (2 doses).A 15 min pretest was done followed 24h later by a 5 min test.Various models of depression were used and biochemical analysis was done. In acute study there was no significant potentiation effect seen .In chronic study there was significant potentiation effect of omega 3 FA. Based on the results we conclude omega 3 fatty acid can be considered as a part of therapeutic use along with escitalopram. Further clinical studies may be required to validate the results of this study.

Neuroblastoma (NB) is the most common extracranial solid tumor in early childhood. Despite intensive multimodal therapy, nearly half of children with high-risk disease will relapse with therapy-resistant tumors. Dysregulation of MAPK pathway has been implicated in the pathogenesis of relapsed and refractory NB patients, which underscores the possibility of targeting MAPK signaling cascade as a novel therapeutic strategy. In this study, we found that high expressions of RAF family kinases correlated with advanced tumor stage, high-risk disease, tumor progression, and poor overall survival. Targeted inhibition of RAF family kinases with the novel small molecule inhibitor agerafenib abrogated the activation of ERK MAPK pathway in NB cells. Agerafenib significantly inhibited the cell proliferation and colony formation ability of NB cells in vitro, and its combination with traditional chemotherapy showed a synergistic pro-apoptotic effect. More importantly, agerafenib exhibited a favorable toxicity profile, potently suppressed tumor growth, and prolonged survival in NB mouse models. In conclusion, our preclinical data suggest that agerafenib might be an effective therapeutic agent for NB treatment, both as a single-agent and in combination with chemotherapy.

Neuroblastoma (NB) is a pediatric tumor of the peripheral nervous system. Approximately 80% of relapsed NB show RAS-MAPK pathway mutations that activate ERK, resulting in the promotion of cell proliferation and drug resistance. Ulixertinib, a first-in-class ERK-specific inhibitor, has shown promising antitumor activity in phase 1 clinical trials for advanced solid tumors. Here, we show that ulixertinib significantly and dose-dependently inhibits cell proliferation and colony formation in different NB cell lines, including PDX cells. Transcriptomic analysis revealed that ulixertinib extensively inhibits different oncogenic and neuronal developmental pathways, including EGFR, VEGF, WNT, MAPK, NGF, and NTRK1. The proteomic analysis further revealed that ulixertinib inhibits the cell cycle and promotes apoptosis in NB cells. Additionally, ulixertinib treatment significantly sensitized NB cells to the conventional chemotherapeutic agent doxorubicin. Furthermore, ulixertinib potently inhibited NB tumor growth and prolonged the overall survival of the treated mice in two different NB mice models. Our preclinical study demonstrates that ulixertinib, either as a single agent or in combination with current therapies, is a novel and practical therapeutic approach for NB.

Malignant pleural mesothelioma (MPM) is a rare cancer of lungs' pleural cavity, with minimally effective therapies available. Thus, there exists a necessity for drug repurposing which is an attractive strategy for drug development in MPM. Repurposing of an old FDA-approved anti-leprotic drug, Clofazimine (CFZ), presents an outstanding opportunity to explore its efficacy in treating MPM.Cytotoxicity, scratch assay, and clonogenic assays were employed to determine CFZ's ability to inhibit cell viability, cell migration, and colony growth. 3D Spheroid cell culture studies were performed to identify tumor growth inhibition potential of CFZ in MSTO-211H cell line. Gene expression analysis was performed using RT-qPCR assays to determine the CFZ's effect of key genes. Western blot studies were performed to determine CFZ's ability to induce apoptosis its effect to induce autophagy marker.CFZ showed significant cytotoxicity against both immortalized and primary patient-derived cell lines with ICIt can be concluded that CFZ could be a promising molecule to repurpose for MPM treatment which needs numerous efforts from further studies.

India has an estimated 12 million visually impaired people and is home to the world’s largest number in any country. Smart walking stick devices use various technologies including machine vision and different sensors for improving the safe movement of visually impaired persons. In machine vision, accurately recognizing an object that is near to them is still a challenging task. This paper provides a system to enable safe navigation and guidance for visually impaired people by implementing an object recognition module in the smart walking stick that uses a local feature extraction method to recognize an object under different image transformations. To provide stability and robustness, the Weighted Guided Harris Corner Feature Detector (WGHCFD) method is proposed to extract feature points from the image. WGHCFD discriminates image features competently and is suitable for different real-world conditions. The WGHCFD method evaluates the most popular Oxford benchmark datasets, and it achieves greater repeatability and matching score than existing feature detectors. In addition, the proposed WGHCFD method is tested with a smart stick and achieves 99.8% recognition rate under different transformation conditions for the safe navigation of visually impaired people.

Agriculture not only supplies food but is also a source of income for a vast population of the world. Paddy plants usually produce a brown-coloured husk on the top and their seed, after de-husking and processing, yields edible rice which is a major cereal food crop and staple food, and therefore, becomes the cornerstone of the food security for half the world’s people. However, with the increase in climate change and global warming, the quality and its production are highly degraded by the common diseases posed in rice plants due to bacteria and fungi (such as sheath rot, leaf blast, leaf smut, brown spot, and bacterial blight). Therefore, to accurately identify these diseases at an early stage, recently, recognition and classification of crop diseases is in burning demand. Hence, the present work proposes an automatic system in the form of a smartphone application (E-crop doctor) to detect diseases from paddy leaves which can also suggest pesticides to farmers. The application also has a chatbot named “docCrop” which provides 24 × 7 support to the farmers. The efficiency of the two most popular object detection algorithms (YOLOv3 tiny and YOLOv4 tiny) for smartphone applications was analysed for the detection of three diseases—brown spot, leaf blast, and hispa. The results reveal that YOLOv4 tiny achieved a mAP of 97.36% which is significantly higher by a margin of 17.59% than YOLOv3 tiny. Hence, YOLOv4 tiny is deployed for the development of the mobile application for use.

Controlling epigenetic factors such as histone methyltransferases and demethylases has recently emerged as an attractive therapeutic approach for different cancers. KMT2 family protein KMT2A or MLL1 is a H3K4 methyltransferase, which is known to play an essential role in cancer development. MLL1 forms a COMPASS complex to function as an epigenetic regulator and Menin is one of the specific and required binding partner for the activation and function of this epigenetic enzyme. Menin acts as a tumor suppressor protein, and inhibition of Menin-MLL1 interaction has been shown to destabilize the MLL1 epigenetic complex, inhibits H3K4 methyltransferase activity, and hinder the oncogenic potential of various cancers. High-risk neuroblastoma (NB) is the most common extracranial solid pediatric tumor and accounts for almost 15% of all pediatric cancer-related deaths. Recent reports indicate that aberrant activation of epigenetic regulators may drive NB progression and relapse. Therefore, in the present study, we used a specific small-molecule inhibitor, MI-503 to disrupt Menin-MLL1 interaction, and to further understand the role of Menin in pediatric NB. We used different NB cell lines including MYCN-non-amplified (SH-SY5Y, SK-N-AS, CHLA-255) and MYCN-amplified (NGP, LAN-5, IMR-32), and performed cytotoxicity and Colonogenic assays to determine the effect of Menin inhibition on NB proliferation. Results showed that MI-503 significantly inhibits NB proliferation and colony formation capacity in a dose-dependent manner in contrast to controls. Further, we performed apoptosis and cell cycle assays and observed that MI-503 significantly induces apoptosis as detected by the increase of Annexin-V positive early apoptotic cells, and blocks cell cycle progression at the S phase in all NB cell lines tested. Additionally, Western blot assays demonstrated an overall inhibition of H3K3me3 levels in NB cells in response to MI-503. To further determine the effects of Menin inhibition on NB tumor growth, we developed a NB 3D spheroid tumor model that recapitulate in vivo tumor growth for solid tumors. Treatment with MI-503 significantly inhibits spheroidal tumor growth by inducing tumor cell death in a dose-dependent manner. Overall, these data highlight the role of epigenetic regulation, MLL1 complex, and of Menin in NB growth and tumorigenicity. In our future efforts, we will further elucidate the effects of MI-503 and the role of Menin in NB by using in vivo tumor models. Epigenetic inhibitor such as MI-503 holds significant potential for further clinical development and as a novel therapeutic approach for NB. Citation Format: Rameswari Chilamakuri, Saurabh Agarwal. Inhibition of epigenetic regulator menin is a novel therapeutic approach for high-risk neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2957.

Transcriptional enhancers enable exquisite spatiotemporal control of gene expression in metazoans. Enrichment of monomethylation of histone H3 lysine 4 (H3K4me1) is a major chromatin signature of transcriptional enhancers. Lysine (K)-specific demethylase 1A (KDM1A, also known as LSD1), an H3K4me2/me1 demethylase, inactivates stem-cell enhancers during the differentiation of mouse embryonic stem cells (mESCs). However, its role in undifferentiated mESCs remains obscure. Here, we show that KDM1A actively maintains the optimal enhancer status in both undifferentiated and lineage-committed cells. KDM1A occupies a majority of enhancers in undifferentiated mESCs. KDM1A levels at enhancers exhibit clear positive correlations with its substrate H3K4me2, H3K27ac, and transcription at enhancers. In Kdm1a-deficient mESCs, a large fraction of these enhancers gains additional H3K4 methylation, which is accompanied by increases in H3K27 acetylation and increased expression of both enhancer RNAs (eRNAs) and target genes. In postmitotic neurons, loss of KDM1A leads to premature activation of neuronal activity-dependent enhancers and genes. Taken together, these results suggest that KDM1A is a versatile regulator of enhancers and acts as a rheostat to maintain optimal enhancer activity by counterbalancing H3K4 methylation at enhancers.

Digital images are becoming the backbone of the social platform. To day of life of the people, the high impact of the images has raised the concern of its authenticity. Image forensics need to be done to assure the authenticity. In this paper, a novel technique is proposed for digital image forensics. The proposed technique is applied for detection of median, averaging and Gaussian filtering in the images. In the proposed method, a first image is normalized using optimal range to obtain a better statistical information. Further, difference arrays are calculated on the normalized array and a proposed thresholding is applied on the normalized arrays. In the last, co-occurrence features are extracted from the thresholding difference arrays. In experimental analysis, significant performance gain is achieved. The detection capability of the proposed method remains upstanding on small size images even with low quality JPEG compression.

Novel coronavirus (COVID-19 or 2019-nCoV or SARS-CoV-2), which suddenly emerged in December 2019 is still haunting the entire human race and has affected not only the healthcare system but also the global socioeconomic balances. COVID-19 was quickly designated as a global pandemic by the World Health Organization as there have been about 98.0 million confirmed cases and about 2.0 million confirmed deaths, as of January 2021. Although, our understanding of COVID-19 has significantly increased since its outbreak, and multiple treatment approaches and pharmacological interventions have been tested or are currently under development to mitigate its risk-factors. Recently, some vaccine candidates showed around 95% clinical efficacy, and now receiving emergency use approvals in different countries. US FDA recently approved BNT162 and mRNA-1273 vaccines developed by Pfizer/BioNTech and Moderna Inc. for emergency use and vaccination in the USA. In this review, we present a succinct overview of the SARS-CoV-2 virus structure, molecular mechanisms of infection, COVID-19 epidemiology, diagnosis, and clinical manifestations. We also systematize different treatment strategies and clinical trials initiated after the pandemic outbreak, based on viral infection and replication mechanisms. Additionally, we reviewed the novel pharmacological intervention approaches and vaccine development strategies against COVID-19. We speculate that the current pandemic emergency will trigger detailed studies of coronaviruses, their mechanism of infection, development of systematic drug repurposing approaches, and novel drug discoveries for current and future pandemic outbreaks.

Acute aortic Intramural hematomas (IMH) and penetrating atherosclerotic (or aortic) ulcers (PAU) are potentially life-threatening lesions that demand timely diagnosis for appropriate triage and management. Diagnosis in turn relies heavily on imaging, with computed tomography (CT) serving as the standard first-line diagnostic imaging modality and magnetic resonance imaging (MRI) and echocardiography commonly invoked for problem solving or follow-up. This chapter focuses on CT and MRI protocols, lesion characteristics, and diagnostic challenges for both IMH and PAU.

The surgical management of paediatric femur fractures has evolved over the last few decades. Intramedullary stabilization with titanium elastic nail (TENS) is the preferred surgical management for length stable and mid diaphyseal femur fractures in children between 5-11 years of age. However, TENS is not preferred in length unstable fractures and in proximal or distal metaphyseal femur fractures due to higher incidence of angulation and shortening at fracture site. In such scenarios, submuscular plating has come up as an alternative surgical treatment modality which avoids these complications and provide good functional outcome. Many authors have suggested different surgical variations in techniques of submuscular plating for paediatric femur fracture. We have devised a technique of submuscular plating with help of external fixator (FAST) in paediatric femur fractures which minimises the surgical time and simplifies the procedure.

Digital images are prevalent medium for information representation. The wide acceptability of images also leads to some problems. Few people spread forged images for their own interests. This type of practice questions the credibility of images. To ensure the credibility, forensic investigation is carried out to ensure the genuineness of images. Detection of median filtering is one of the important forensic analyses. Median filtering has several uses in antiforensics. It is applied to hide the impression of image forgery due to its nonlinear nature. Some techniques are evolved to countering these antiforensics i.e., median filtering. These techniques can classify median filter operated and non-median filter operated images. In this paper, we compare three techniques that are based on Markov process. We find that performance of these techniques varies according to the size of database.

Pulmonary arterial hypertension (PAH) remains life-limiting despite numerous approved vasodilator therapies. Right ventricular (RV) function determines outcome in PAH but no treatments directly target RV adaptation. PAH is more common in women, yet women have better RV function and survival as compared to men with PAH. Lower levels of the adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate ester are associated with more severe pulmonary vascular disease, worse RV function, and mortality independent of other sex hormones in men and women with PAH. DHEA has direct effects on nitric oxide (NO) and endothelin-1 (ET-1) synthesis and signaling, direct antihypertrophic effects on cardiomyocytes, and mitigates oxidative stress. Effects of Dehydroepiandrosterone in Pulmonary Hypertension (EDIPHY) is an on-going randomized double-blind placebo-controlled crossover trial of DHEA in men ( n = 13) and pre- and post-menopausal women ( n = 13) with Group 1 PAH funded by the National Heart, Lung and Blood Institute. We will determine whether orally administered DHEA 50 mg daily for 18 weeks affects RV longitudinal strain measured by cardiac magnetic resonance imaging, markers of RV remodeling and oxidative stress, NO and ET-1 signaling, sex hormone levels, other PAH intermediate end points, side effects, and safety. The crossover design will elucidate sex-based phenotypes in PAH and whether active treatment with DHEA impacts NO and ET-1 biosynthesis. EDIPHY is the first clinical trial of an endogenous sex hormone in PAH. Herein we present the study’s rationale and experimental design.

Objective: It has been explored that Vitamin D play role in various non-skeletal disorders including Diabetes Mellitus. The present study was designed with the aim to assess association among control, pre-diabetic and diabetic with vitamin D and association between lipid profile and vitamin D. Materials and Methods: A total of 109 subjects were recruited for the cross-sectional study including 37 as control, 41 pre-diabetic and 31 diabetic. A clinical examination was done for all the groups including fasting samples (12hrs) for lipid parameters, serum 25 (OH) vitamin D level and (HbA1/C). Results: It was found that in control subjects 37.9% have the sufficient vitamin D3 level whereas 17.1% subjects in pre-diabetic, 16.6% in diabetic with good glycemic control and no subject was found to have sufficient vitamin D3 level in diabetic with poor glycemic control. The mean vitamin D3 levels was highest in control i.e. -26.53±11.99 ng/ml followed by 20.23±4.12ng/ml in prediabetics,19.07±8.01ng/ml in diabetics with good glycemic control and 12.92±6.77ng/ml in diabetics with poor glycemic control. HBA1/c and serum vitamin D3level share a significant association (P-value< 0.01).Total cholesterol (P-value< 0.0), serum triglyceride (P-value< 0.01), serum LDL cholesterol (P-value< 0.01) and serum VLDL (P-value< 0.01) had inverse association with vitamin D levels. HDL cholesterol has no effect with vitamin D. Conclusion: The present study showed vitamin D3 deficiency as a risk factor for worsening glycemic control and dyslipidemia.

Management of fractures of neck of femur in the elderly is largely joint sacrificing, with hemiarthroplasties being the most common entity used. Cemented and uncemented, both the techniques, are universally accepted; however, the former has been more time tested, despite its theoretical disadvantage in the form of cement embolism leading to intra-operative complications. Uncemented stems have been ever evolving with newer designs to increase incorporation, stability and durability. They have their own reported sets of disadvantages like subsidence and fractures. However, overall there is no established gold standard out of the two. The present systematic review and meta-analysis of current literature was conducted, so as to determine the superiority of one technique over the other by comparing the primary outcomes like hip function, residual pain, local and general complications and mortality. Additionally secondary outcomes like duration of surgery, blood loss and re-operations were analysed as well. Three databases of PubMed, EMBASE and SCOPUS were searched for relevant articles of last 10 years that directly compare uncemented and cemented hemiarthroplasties, and based on our inclusion and exclusion criteria, article selection was done. We analysed a total of six randomised controlled studies dated from 2008 to 2017. There was a significant difference in post-operative ability to ambulate at 1 year, between 2 groups with odds ratio 0.45 (95% CI 0.29–0.67, p = 0.0001) favouring cemented hemiarthroplasty. Prosthesis-related complications like fractures and subsidence and general complications like lung complications were more in uncemented group. Mortality at 1 year was more in cemented group. Mean surgical time was lesser in uncemented cases. There was no difference in blood loss and re-operation rates. Cementing techniques are here to stay, until a better, durable and more stable uncemented stem evolves, that could lessen the complications related to uncemented surgeries and match the cemented implants in pain relief and ambulation.

Excessive dependence on digital images has raised the need for its forensic analysis. Median filtering, due to its nonlinear nature, is extensively used in image antiforensics to hide the evidence ...