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Background: Coronavirus disease-2019 belonging to Corona virus family, was first reported in Wuhan, China in November 2019 which is an ongoing Pandemic. The apparent vulnerable group more susceptible to the symptomatic infection are the elderly population, tobacco and alcohol users and people having underlying comorbid conditions. Methods: An unmatched case-control study was conducted in March 2021 through purposive sampling amongst the Covid-19 infected population. The socio-demographic details, use of tobacco, alcohol and underlying comorbid conditions were studied to show the association with symptomatic Covid-19 infection, in the population more than 18 years of age in Mumbai City. Results: Out of the total 528 Covid-19 infected individuals, 38.8% were symptomatic and 61.2% were asymptomatic. The elderly population and the underlying comorbid conditions were not found to be associated with symptomatic Covid-19 infection. Alcohol consumption (OR 0.87 (95% CI -0.39, 1.92)), and both alcohol consumption and smoking (OR 0.94[95% CI 0.45, 1.97) association with symptomatic Covid-19 infection were found to be insignificant at 95% CI in the present study whereas significant negative association was observed in smoking (OR 0.21 (95% CI 0.08, 0.53)) with symptomatic covid-19 infection. Conclusions: Covid-19, addiction and the non-communicable diseases together is a major public health concern in India. Since no significant association was found, study on other unknown factors like the genetics, race, ongoing treatment for underlying comorbid disease and other should be conducted to understand the actual risk factors of the novel disease.

Disruption of KDM6A, a histone lysine demethylase, is one of the most common somatic alternations in bladder cancer. Insights into how KDM6A mutations affect the epigenetic landscape to promote carcinogenesis could help reveal potential new treatment approaches. Here, we demonstrated that KDM6A loss triggers an epigenetic switch that disrupts urothelial differentiation and induces a neoplastic state characterized by increased cell proliferation. In bladder cancer cells with intact KDM6A, FOXA1 interacted with KDM6A to activate genes instructing urothelial differentiation. KDM6A-deficient cells displayed simultaneous loss of FOXA1 target binding and genome-wide redistribution of the bZIP transcription factor ATF3, which in turn repressed FOXA1-target genes and activated cell-cycle progression genes. Importantly, ATF3 depletion reversed the cell proliferation phenotype induced by KDM6A deficiency. These data establish that KDM6A loss engenders an epigenetic state that drives tumor growth in an ATF3-dependent manner, creating a potentially targetable molecular vulnerability.Significance:A gain-of-function epigenetic switch that disrupts differentiation is triggered by inactivating KDM6A mutations in bladder cancer and can serve as a potential target for novel therapies.

Optimum procedural sedation is very essential for conducting non-operating room procedures such as endoscopic retrograde cholangiopancreatography (ERCP). The combination of ketamine and dexmedetomidine (KD) is expected to balance out the undesirable effects of either drug and provide smooth sedation. Together ketamine and propofol (KP) also provide synergistic sedation with stable hemodynamics. This prospective, single-blinded randomized study aimed to compare the effect of both the combinations during ERCP in terms of oxygen desaturation, respiratory depression, hemodynamic parameters, analgesia, recovery time, and ease with which the endoscopist could perform the endoscopy.This prospective, single-blinded randomized study (CTRI/2019/08/020625) was conducted on 84, ASA (American Society of Anesthesiologists) physical status I or II patients, of age 18-65 years presenting for ERCP in a tertiary care center. They were randomized to receive either KD (n=42) or KP (n=42) combination during ERCP. Mean SPOThe mean SpOThe combination of ketamine-dexmedetomidine for procedural sedation during ERCP is a safe alternative to ketamine-propofol with a better respiratory profile.CTRI/2019/08/020625 ( www.ctri.nic.in ).

In the era of technological advancements in healthcare and medicine, monitoring of health status and treatment conditions has been made convenient by the development of various categories and forms of biomedical sensors. They have been incorporated within watches and mobile phones and can be worn as stand-alone based on user preference. However, the longevity, cost, and sustainable functionality have impeded its adoption within the population. In this review article, we have introduced a concept of bridging the textile industry and biomedical sensors to yield a self-powered biomedical system that operates on textile-based energy harvesters. Textile-based wearable systems have been compared to E-skin-based systems. The energy released by different actions in human motion has been quantified along with insights on its effective utilization in the form of energy harvesters in the subsequent sections. Information on designing such a textile-based system with schematics has been done. This review focuses on the development and connection of textile-based energy harvesters to existing models of biomedical sensors.

Supplementary Table 2

Figures S1 to S17

Hundreds of genes become aberrantly silenced in acute myeloid leukemia (AML), with most of these epigenetic changes being of unknown functional consequence. Here, we demonstrate how gene silencing can lead to an acquired dependency on the DNA repair machinery in AML. We make this observation by profiling the essentiality of the ubiquitination machinery in cancer cell lines using domain-focused CRISPR screening, which revealed Fanconi anemia (FA) proteins UBE2T and FANCL as unique dependencies in AML. We demonstrate that these dependencies are due to a synthetic lethal interaction between FA proteins and aldehyde dehydrogenase 2 (ALDH2), which function in parallel pathways to counteract the genotoxicity of endogenous aldehydes. We show DNA hypermethylation and silencing of ALDH2 occur in a recurrent manner in human AML, which is sufficient to confer FA pathway dependency. Our study suggests that targeting of the ubiquitination reaction catalyzed by FA proteins can eliminate ALDH2-deficient AML.Significance:Aberrant gene silencing is an epigenetic hallmark of human cancer, but the functional consequences of this process are largely unknown. In this study, we show how an epigenetic alteration leads to an actionable dependency on a DNA repair pathway through the disabling of genetic redundancy.This article is highlighted in the In This Issue feature, p. 2113

Supplementary Table 1

The E2/E3 sgRNA guide sequences.

An enhanced requirement for nutrients is a hallmark property of cancer cells. Here, we optimized an in vivo genetic screening strategy in acute myeloid leukemia (AML), which led to the identification of the myo-inositol transporter SLC5A3 as a dependency in this disease. We demonstrate that SLC5A3 is essential to support a myo-inositol auxotrophy in AML. The commonality among SLC5A3-dependent AML lines is the transcriptional silencing of ISYNA1, which encodes the rate-limiting enzyme for myo-inositol biosynthesis, inositol-3-phosphate synthase 1. We use gain- and loss-of-function experiments to reveal a synthetic lethal genetic interaction between ISYNA1 and SLC5A3 in AML, which function redundantly to sustain intracellular myo-inositol. Transcriptional silencing and DNA hypermethylation of ISYNA1 occur in a recurrent manner in human AML patient samples, in association with IDH1/IDH2 and CEBPA mutations. Our findings reveal myo-inositol as a nutrient dependency in AML caused by the aberrant silencing of a biosynthetic enzyme.Significance:We show how epigenetic silencing can provoke a nutrient dependency in AML by exploiting a synthetic lethality relationship between biosynthesis and transport of myo-inositol. Blocking the function of this solute carrier may have therapeutic potential in an epigenetically defined subset of AML.This article is highlighted in the In This Issue feature, p. 275

Supplementary Data from Inherited Germline Cancer Susceptibility Gene Variants in Individuals with Non–Muscle-Invasive Bladder Cancer

Purpose:Identification of inherited germline variants can guide personalized cancer screening, prevention, and treatment. Pathogenic and likely pathogenic (P/LP) germline variants in cancer predisposition genes are frequent among patients with locally advanced or metastatic urothelial carcinoma, but their prevalence and significance in patients with non–muscle-invasive bladder cancer (NMIBC), the most common form of urothelial carcinoma, is understudied.Experimental Design:Germline analysis was conducted on paired tumor/normal sequencing results from two distinct cohorts of patients initially diagnosed with NMIBC. Associations between clinicopathologic features and clinical outcomes with the presence of P/LP germline variants in ≥76 hereditary cancer predisposition genes were analyzed.Results:A similar frequency of P/LP germline variants were seen in our two NMIBC cohorts [12% (12/99) vs. 8.7% (10/115), P = 0.4]. In the combined analysis, P/LP germline variants were found only in patients with high-grade NMIBC (22/163), but none of the 46 patients with low-grade NMIBC (13.5% vs. 0%, P = 0.005). Fifteen (9.2%) patients with high-grade NMIBC had P/LP variants in DNA damage response genes, most within the nucleotide excision repair (ERCC2/3) and homologous recombination repair (BRCA1, NBN, RAD50) pathways. Contrary to prior reports in patients with NMIBC not receiving Bacillus Calmette-Guerin (BCG), P/LP germline variants were not associated with worse recurrence-free or progression-free survival in patients treated with BCG or with risk of developing upper tract urothelial carcinoma.Conclusions:Our results support offering germline counseling and testing for all patients with high-grade bladder cancer, regardless of initial tumor stage. Therapeutic strategies that target impaired DNA repair may benefit patients with high-grade NMIBC.

Disruption of KDM6A, a histone lysine demethylase, is one of the most common somatic alternations in bladder cancer. Insights into how KDM6A mutations affect the epigenetic landscape to promote carcinogenesis could help reveal potential new treatment approaches. Here, we demonstrated that KDM6A loss triggers an epigenetic switch that disrupts urothelial differentiation and induces a neoplastic state characterized by increased cell proliferation. In bladder cancer cells with intact KDM6A, FOXA1 interacted with KDM6A to activate genes instructing urothelial differentiation. KDM6A-deficient cells displayed simultaneous loss of FOXA1 target binding and genome-wide redistribution of the bZIP transcription factor ATF3, which in turn repressed FOXA1-target genes and activated cell-cycle progression genes. Importantly, ATF3 depletion reversed the cell proliferation phenotype induced by KDM6A deficiency. These data establish that KDM6A loss engenders an epigenetic state that drives tumor growth in an ATF3-dependent manner, creating a potentially targetable molecular vulnerability.Significance:A gain-of-function epigenetic switch that disrupts differentiation is triggered by inactivating KDM6A mutations in bladder cancer and can serve as a potential target for novel therapies.

Supplementary Figure 3

ATF3 target genes downregulated in K2 that harbor FOXA1 peaks in RT4

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Supplementary Figure 7

Supplementary Table S1

Supplementary Figure 2

List of TCGA cases used in ATAC-seq analysis

Supplementary Figure 4

Supplementary Figure 1

Supplementary Figure 8

The current world encounters a huge application in additive manufacturing. One of the recent technologies branched from additive engineering is 4D printing technologies. The notion of 4D printing technology became a huge success because of its ability to change and reform. This ability helps to manipulate materials at micro and nano levels. This itself finds a lot of opportunities in the forefront industries like engineering, space technology, biomedical etc. Innovation of these novel materials and the modification of the manufacturing entities still pose a great challenge in the form of a blind wall. In this paper we have reviewed the smart materials like ceramics, hydrogels, smart metal alloys. This paper also incorporates the survey of smart materials and multi-materials along with its applications. We have also learned about the limitations of these materials which lead to the conclusion of the paper that includes information about the scope for exploration in this pitch.

We have combined two low-threshold detector technologies to develop a large-mass, low-threshold detector system that simultaneously measures the athermal phonons in a sapphire detector while an adjacent silicon high-voltage detector detects the scintillation light from the sapphire detector. This detector system could provide event-by-event discrimination between electron and nuclear events due to the difference in their scintillation light yield. While such systems with simultaneous phonon and light detection have been demonstrated earlier with smaller detectors, our system is designed to provide a large detector mass with high amplification for the limited scintillation light. Future work will focus on at least an order of magnitude improvement in the light collection efficiency by having a highly reflective detector housing and custom phonon mask design to maximize light collection by the silicon high-voltage detector., 6 pages, 12 figures