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"Gupta, Anuj"
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Unmanned aerial vehicles for Internet of Things (IoT) : concepts, techniques, and applications
\"The 15 chapters in this book explore the theoretical as well as a number of technical research outcomes on all aspects of UAVs. UAVs has widely differing applications such as disaster management, structural inspection, goods delivery, transportation, localization, mapping, pollution and radiation monitoring, search and rescue, farming, etc. The advantages of using UAVs are countless and have led the way for the full integration of UAVs, as intelligent objects into the IoT system. The book covers such subjects as: efficient energy management systems in UAV based IoT networks, IoE enabled UAVs, mind-controlled UAV using Brain-Computer Interface (BCI), the importance of AI in realizing autonomous and intelligent flying IoT, blockchain-based solutions for various security issues in UAV-enabled IoT, the challenges and threats of UAVs such as hijacking, privacy, cyber-security, and physical safety\"-- Provided by publisher.
Book
Retrotransposon LINE-1 bodies in the cytoplasm of piRNA-deficient mouse spermatocytes: Ribonucleoproteins overcoming the integrated stress response
Transposable elements (TE) are mobile DNA sequences whose excessive proliferation endangers the host. Although animals have evolved robust TE-targeting defenses, including Piwi-interacting (pi)RNAs, retrotransposon LINE-1 (L1) still thrives in humans and mice. To gain insights into L1 endurance, we characterized L1 Bodies (LBs) and ORF1p complexes in germ cells of piRNA-deficient Maelstrom null mice. We report that ORF1p interacts with TE RNAs, genic mRNAs, and stress granule proteins, consistent with earlier studies. We also show that ORF1p associates with the CCR4-NOT deadenylation complex and PRKRA, a Protein Kinase R factor. Despite ORF1p interactions with these negative regulators of RNA expression, the stability and translation of LB-localized mRNAs remain unchanged. To scrutinize these findings, we studied the effects of PRKRA on L1 in cultured cells and showed that it elevates ORF1p levels and L1 retrotransposition. These results suggest that ORF1p-driven condensates promote L1 propagation, without affecting the metabolism of endogenous RNAs.
Journal Article
Drug-eluting coronary stents: insights from preclinical and pathology studies
Implantation of drug-eluting stents (DES) is the dominant treatment strategy for patients with symptomatic coronary artery disease. However, the first-generation DES had substantial drawbacks, including delayed healing, local hypersensitivity reactions and neoatherosclerosis, which all led to a steady increase in major adverse cardiovascular events over time. Subsequently, newer-generation DES were introduced with thinner struts, different scaffold designs (to improve deliverability while maintaining radial strength), different durable and biodegradable polymers — and in some cases no polymer (to improve vascular biocompatibility) — and new antiproliferative drug types and doses. Currently, >30 different DES are commercially available in Europe, with fewer available in the USA but with many new entrants coming onto the US market in the next few years. Never before have cardiologists been faced with so many choices of stent, each with its own unique design. In this Review, we detail preclinical and pathology studies for each stent design, examining thromboresistance, speed of neointimal coverage and completeness of healing, including endothelialization. We conclude by discussing how these design characteristics might affect the potential for shortening the minimum duration of dual antiplatelet therapy needed after coronary intervention.
Journal Article
Stimulation of CRISPR-mediated homology-directed repair by an engineered RAD18 variant
Precise editing of genomic DNA can be achieved upon repair of CRISPR-induced DNA double-stranded breaks (DSBs) by homology-directed repair (HDR). However, the efficiency of this process is limited by DSB repair pathways competing with HDR, such as non-homologous end joining (NHEJ). Here we individually express in human cells 204 open reading frames involved in the DNA damage response (DDR) and determine their impact on CRISPR-mediated HDR. From these studies, we identify RAD18 as a stimulator of CRISPR-mediated HDR. By defining the RAD18 domains required to promote HDR, we derive an enhanced RAD18 variant (e18) that stimulates CRISPR-mediated HDR in multiple human cell types, including embryonic stem cells. Mechanistically, e18 induces HDR by suppressing the localization of the NHEJ-promoting factor 53BP1 to DSBs. Altogether, this study identifies e18 as an enhancer of CRISPR-mediated HDR and highlights the promise of engineering DDR factors to augment the efficiency of precision genome editing.
Manipulating DNA repair pathways can be used to improve the outcomes of CRISPR-based genome editing. Here the authors derive an enhanced RAD18 variant that suppresses 53BP1 recruitment to DNA double-strand breaks to enhance homology-mediated repair.
Journal Article
Transcriptional profiling identifies novel regulators of macrophage polarization
Macrophages are key inflammatory immune cells that display dynamic phenotypes and functions in response to their local microenvironment. Major advances have occurred in understanding the transcriptional, epigenetic, and functional differences in various macrophage subsets by in vitro modeling and gene expression and epigenetic profiling for biomarker discovery. However, there is still no standardized protocol for macrophage polarization largely due to the lack of thorough validation of macrophage phenotypes following polarization. In addition, transcriptional regulation is recognized as a major mechanism governing differential macrophage polarization programs and as such, many genes have been identified to be associated with each macrophage subset. However, the functional role of many of these genes in macrophage polarization is still unknown. Moreover, the role of other regulatory mechanisms, such as DNA methylation, in macrophage polarization remains poorly understood. Here, we employed an optimized model of human M1 and M2 macrophage polarization which we used for large-scale transcriptional and DNA methylation profiling. We were unable to demonstrate a role for DNA methylation in macrophage polarization, as no significant changes were identified. However, we observed significant changes in the transcriptomes of M1 and M2 macrophages. Additionally, we identified numerous novel differentially regulated genes involved in macrophage polarization, including CYBB and DHCR7 which we show as important regulators of M1 and M2 macrophage polarization, respectively. Taken together, our improved in vitro human M1 and M2 macrophage model provides new understandings of the regulation of macrophage polarization and candidate macrophage biomarkers.
Journal Article
Childhood Depression: Breaking the Silence
Depression is one of the most important risk factors for suicide and therefore assessment of suicide risk is recommended to be done routinely in depressed children and adolescents. |4'61 One of the primary challenges is the stigma associated with mental health issues in our society. According to Indian Academy of Pediatrics (IAP) home environment, education/employment, eating, activities, drugs, sexuality, suicide/depression, and safety (HEEADSSS) history along with past and family history of psychiatric issues should be elicited.141 Other methods like pictorial instruments and depression rating scales can be used, which can be useful for better clinical understanding of mental state of children. Psychosocial management in childhood thus remains the mainstay. |4'51 There is a need to convey the parents that maltreatment of adolescents by parents or family members, alcohol use and smoking in family might be the factors for depression among adolescents and emphasis should be laid on sharing of problems of adolescents with family. |4'51 In severe cases or when specialized intervention is needed, Pediatricians need to refer patients to child psychologists, psychiatrists, or mental health clinics and thus play a critical role in coordinating care with these specialists.
Journal Article
Prospective observational study of peripheral intravenous cannula utilisation and frequency of intravenous fluid delivery in the emergency department—Convenience or necessity?
Peripheral Intravenous Cannulas (PIVCs) are frequently utilised in the Emergency Department (ED) for delivery of medication and phlebotomy. They are associated with complications and have an associated cost to departmental resources. A growing body of international research suggests many of the PIVCs inserted in the ED are unnecessary.
The objective of this study was to determine the rates of PIVC insertion and use. This was a prospective observational study conducted in one UK ED and one Italian ED. Adult ED patients with non-immediate triage categories were included over a period of three weeks in the UK ED in August 2016 and two weeks in the Italian ED in March and August 2017. Episodes of PIVC insertion and data on PIVC utilisation in adults were recorded. PIVC use was classified as necessary, unnecessary or unused. The proportion of unnecessary and unused PIVCs was calculated. PIVCs were defined as unnecessary if they were either used for phlebotomy only, or solely for IV fluids in patients that could have potentially been hydrated orally (determined against a priori defined criteria). PIVC classified as unused were not used for any purpose.
A total of 1,618 patients were included amongst which 977 PIVCs were inserted. Of the 977 PIVCs, 413 (42%) were necessary, 536 (55%) were unnecessary, and 28 (3%) were unused. Of the unnecessary PIVCs, 473 (48%) were used solely for phlebotomy and 63 (6%) were used for IV fluids in patients that could drink.
More than half of PIVCs placed in the ED were unnecessary in this study. This suggests that clinical decision making about the benefits and risks of PIVC insertion is not being performed on an individual basis.
Journal Article
Performance evaluation of Python and MATLAB for CGH generation using layer-based approach
In the field of computational holography, creating intricate holographic patterns is a fundamental yet computationally intensive endeavor, posing substantial challenges in obtaining large space-bandwidth product. The computational burden for calculating computer generated hologram (CGH) is notably affected by various factors, with object and CGH sizes being the prominent ones. As such, the task of optimizing CGH generation algorithms for larger matrix dimensions is paramount, especially in practical applications such as holographic dynamic displays. This work presents a comprehensive comparative analysis of two widely used programming languages, Python and MATLAB, for CGH calculation. The study tends to provide valuable insights to predict the suitability of these languages for CGH calculation in terms of efficiency and performance. The large matrix dimensions up to 8192 × 8192 are used as test cases to ensure the relevance and practicality of the findings. Our findings reveal that MATLAB and Python perform comparably in terms of the quality of reconstruction objects and also the execution time disparity diminishes, particularly for higher matrix dimensions. As a result, users can choose either language based on their requirement and personal comfort with the programming environment.
Journal Article
Androgen receptor activity in prostate cancer dictates efficacy of bipolar androgen therapy through MYC
Testosterone is the canonical growth factor of prostate cancer but can paradoxically suppress its growth when present at supraphysiological levels. We have previously demonstrated that the cyclical administration of supraphysiological androgen (SPA), termed bipolar androgen therapy (BAT), can result in tumor regression and clinical benefit for patients with castration-resistant prostate cancer. However, predictors and mechanisms of response and resistance have been ill defined. Here, we show that growth inhibition of prostate cancer models by SPA required high androgen receptor (AR) activity and were driven in part by downregulation of MYC. Using matched sequential patient biopsies, we show that high pretreatment AR activity predicted downregulation of MYC, improved clinical response, and prolonged progression-free and overall survival for patients on BAT. BAT induced strong downregulation of AR in all patients, which is shown to be a primary mechanism of acquired resistance to SPA. Acquired resistance was overcome by alternating SPA with the AR inhibitor enzalutamide, which induced adaptive upregulation of AR and resensitized prostate cancer to SPA. This work identifies high AR activity as a predictive biomarker of response to BAT and supports a treatment paradigm for prostate cancer involving alternating between AR inhibition and activation.
Journal Article
Evaluating the clinico-pathological features including the immunohistochemical and molecular landscape of synovial sarcoma cases from a tertiary care cancer referral centre in India
Background
Synovial sarcoma (SS) is a malignant mesenchymal neoplasm with variable epithelial differentiation, with a propensity to occur in young adults. The pathognomonic t(X;18) chromosomal translocation and subsequent development of the SS18:SSX fusion oncogenes are the driver of the distinct genomic features.
Aim
To study the Clinicopathological, immunohistochemical and molecular features of SS occurring in all the organ systems.
Method
A retrospective observational study was conducted over a period of 4 years at a tertiary cancer centre.
Result
One hundred eight patients were included in the study based on exclusion and inclusion criteria. The median age of patients was 30.5 years and mean tumor diameter was 10.5 cm. Most common site was lower limb followed by lung, and arm. 50 patients underwent surgery and 49 patients received adjuvant chemotherapy or radiotherapy. 87 patients (81%) presented with monophasic subtype and 21 (19%) with biphasic subtype.
The most helpful immunohistochemical markers for diagnosis and exclusion of close differentials were TLE1, EMA, Pancytokeratin, S-100, BCL2, and CD99. Molecular diagnostic confirmation was attained in 10 out of 15 patients. On median follow-up of 7.58 months, mean 4-year overall survival of the patients was 91.39%.
Conclusion
Meticulous pathologic evaluation and awareness of the typical and atypical histology of SS along with the apt application of immunohistochemical marker such as TLE1 and/or cytogenetics (SYT translocation) assist in precise recognition of this not so common entity. The main therapeutic modality is surgical excision with negative margins, with the addition of radiotherapy and/or chemotherapy based on patient and tumour characteristics.
Journal Article