An easy and simple access to 2,3-dihydrofuran derivatives from 1,3-dicarbonyl compounds and methyl cinnamate is reported here. The reaction was facilitated by the CAN mediated oxidative free radical ...cyclisation reaction. Moderate to good yields of products were obtained and preliminary studies of these showed potential medicinal activities. These compounds also find application in material chemistry and in dyes.
Blockchain Based Approach for tackling Deepfake videos Patil, Ujwal; Chouragade, Prof. P. M.
International Journal of Scientific Research in Computer Science, Engineering and Information Technology,
5/2021
Journal Article
Odprti dostop
The technological advancements and a qualitative improvement in the field of artificial intelligence and deep learning leads to the creation of realistic-looking but phoney digital content known as ...deepfakes .These manipulated videos can quickly be shared via social media to spread fake news or disinformation which not only impacts those who are deceived it also harms social media sites by diminishing faith.These deepfake videos cannot be checked since there are no regulatory mechanisms in place .As a result these untrustworthy outlets will post whatever they wish causing confusion in society in some ways.Current solutions are unable to provide digital media history tracing and authentication it is essential to develop successful methods for detecting deepfake video as a result it is necessary to determine the source or origin of such deepfake footage.That’s why we are implementing blockchain techniques to trace back and determine the origin of digital media blockchain techniques helps in the effective recognition of deepfake video and calculating the trust factor of user.
The voltage-dependent anion channel (VDAC) is the major pathway mediating the transfer of metabolites and ions across the mitochondrial outer membrane. Two hallmarks of the channel in the open state ...are high metabolite flux and anion selectivity, while the partially closed state blocks metabolites and is cation selective. Here we report the results from electrostatics calculations carried out on the recently determined high-resolution structure of murine VDAC1 (mVDAC1). Poisson–Boltzmann calculations show that the ion transfer free energy through the channel is favorable for anions, suggesting that mVDAC1 represents the open state. This claim is buttressed by Poisson–Nernst–Planck calculations that predict a high single-channel conductance indicative of the open state and an anion selectivity of 1.75—nearly a twofold selectivity for anions over cations. These calculations were repeated on mutant channels and gave selectivity changes in accord with experimental observations. We were then able to engineer an in silico mutant channel with three point mutations that converted mVDAC1 into a channel with a preference for cations. Finally, we investigated two proposals for how the channel gates between the open and the closed state. Both models involve the movement of the N-terminal helix, but neither motion produced the observed voltage sensitivity, nor did either model result in a cation-selective channel, which is observed experimentally. Thus, we were able to rule out certain models for channel gating, but the true motion has yet to be determined.
Zoonotic sporotrichosis is a neglected fungal disease, whereby outbreaks are primarily driven by Sporothrix brasiliensis and linked to cat-to-human transmission. To understand the emergence and ...spread of sporotrichosis in Brazil, the epicentre of the current epidemic in South America, we aimed to conduct whole-genome sequencing (WGS) to describe the genomic epidemiology.
In this genomic epidemiology study, we included Sporothrix spp isolates from sporotrichosis cases from Brazil, Colombia, and the USA. We conducted WGS using Illumina NovaSeq on isolates collected by three laboratories in Brazil from humans and cats with sporotrichosis between 2013 and 2022. All isolates that were confirmed to be Sporothrix genus by internal transcribed spacer or beta-tubulin PCR sequencing were included in this study. We downloaded eight Sporothrix genome sequences from the National Center for Biotechnology Information (six from Brazil, two from Colombia). Three Sporothrix spp genome sequences from the USA were generated by the US Centers for Disease Control and Prevention as part of this study. We did phylogenetic analyses and correlated geographical and temporal case distribution with genotypic features of Sporothrix spp isolates.
72 Sporothrix spp isolates from 55 human and 17 animal sporotrichosis cases were included: 67 (93%) were from Brazil, two (3%) from Colombia, and three (4%) from the USA. Cases spanned from 1999 to 2022. Most (61 85%) isolates were S brasiliensis, and all were reported from Brazil. Ten (14%) were Sporothrix schenckii and were reported from Brazil, USA, and Colombia. For S schenckii isolates, two distinct clades were observed wherein isolates clustered by geography. For S brasiliensis isolates, five clades separated by more than 100 000 single-nucleotide polymorphisms were observed. Among the five S brasiliensis clades, clades A and C contained isolates from both human and cat cases, and clade A contained isolates from six different states in Brazil. Compared with S brasiliensis isolates, larger genetic diversity was observed among S schenckii isolates from animal and human cases within a clade.
Our results suggest that the ongoing epidemic driven by S brasiliensis in Brazil represents several, independent emergence events followed by animal-to-animal and animal-to human transmission within and between Brazilian states. These results describe how S brasiliensis can emerge and spread within a country.
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil; the São Paulo Research Foundation; Productivity in Research fellowships by the National Council for Scientific and Technological Development, and Ministry of Science and Technology of Brazil.
Background: Diabetes mellitus, a chronic noncommunicable disease, is associated with long-term damage of multiple organ system with its long-term complications and significantly impacts upon the ...quality of life (QoL) of affected patients. Methods: A survey was carried out on 245 patients during thirty sessions of diabetes outpatient department at multispecialty hospitals, among which 228 patients agreed for the participation. A final survey was carried on 200 patients, whereas 28 patients did not fit into the criteria. Further evaluation was carried out using the World Health Organization QoL-BREF questionnaire in Hindi, English, and Marathi versions. The mean score and total score of domains were calculated to check the QoL of the patients. Results: Almost 72% of the participants mentioned good QoL in physical domain with 18% mentioning average QoL. Around 35% mentioned excellent QoL in psychological domain with 46% mentioning good QoL. Around 55% mentioned good QoL in social domain. Majority of participants mentioned good (23%) to excellent (71%) QoL in environmental domain. The physical domain demonstrated a mean score of 66.6 ± 9.303 (min 44, max 94). The psychological domain demonstrated the mean score of 70.9, ±15.558, (min 5, max 94). The social domain demonstrated the mean score of 75.96, ±15.245, (min 31, max 100). The environmental domain demonstrated the mean score of 82.19, ±13.211, (min 31, max 100). Conclusion: Overall patients mentioned average-to-good QoL in physical, psychological, and social domain, and a majority of patients had good QoL in environmental domain.
Thrombectomy with aspiration catheters has shown to be effective for treatment of intracranial large vessel occlusion (LVO). We present preclinical evaluation of the safety and efficacy of React68 ...and React71 (Medtronic PLC, Irvine, CA) catheters in animal models of LVO.
In vivo evaluation of catheter safety was performed in superficial cervical, internal maxillary, and renal arteries in a porcine model with or without clot (LVO). Animals were survived for 3 days and 30 days. Angiographic outcomes, usability, and histological parameters were compared for treatment with React68, React71, and ACE68 (Penumbra, Alameda, CA) catheters.
The in vivo angiographic analysis in a porcine thrombectomy LVO model demonstrated that there was no statistically significant difference in the rate of Thrombolysis in Cerebral Infarction scale 2b/3 recanalization between React68, React71, and ACE68 catheters. There were no physical or neurologic deficits in any of the treated animals throughout the survival period. Histologic analysis showed statistically non-inferior safety profile of React68 and React71 catheters relative to ACE68 catheters, with minimal but similar mild internal elastic lamina disruption and smooth muscle loss, but a lack of inflammation, fibrin deposits, and changes in the adventitia at both time points examined.
React68 and React71 aspiration catheters have an excellent safety, efficacy, and usability profile in animal models of LVO.
Infections due to drug-resistant herpes simplex viruses (HSV) represent an important clinical concern, especially in immunocompromised patients. The present study was aimed at detecting acyclovir ...(ACV) susceptibility in HSV clinical samples.
A total of 13 HSV-positive clinical samples (5 HSV-1 and 8 HSV-2) recovered from patients (1 immunocompromised and 12 of unknown immune status) were included in the study. The genotypic analysis involved an initial UL23 (thymidine kinase) gene sequencing, followed by a confirmatory phenotypic assay using plaque reduction technique.
Two novel amino acid changes, A37V and H283N, were detected in HSV-1 positive clinical samples, which were found to be susceptible to acyclovir (half maximal effective concentration = 1.5 µM) by plaque reduction assay.
These two novel amino acid changes could be therefore considered as natural polymorphisms, a phenomenon widely associated with the HSV-UL23 gene.
Critically ill solid organ malignancy patients admitted to intensive care unit (ICU) as unplanned medical admissions behave differently from other subsets of cancer patients (hematolymphoid ...malignancies and cancer patients admitted for postoperative care). These patients if appropriately selected may benefit from the ICU care. There is paucity of data on critically ill unplanned admissions of solid organ malignancies from South Asia. We analyzed data of patients with solid tumors with unplanned admissions to the ICU to determine the clinical, epidemiological characteristics, and predictors of hospital mortality in an Indian ICU.
This prospective, observational study was done in our 14-bedded mixed medical-surgical ICU from July 2014 to November 2015. We included all consecutive adult unplanned admissions with solid organ malignancies having ICU stay of >24 hours. Surgical admissions, hematolymphoid malignancies, advanced malignancy with no treatment options, and those cured of cancer >5 years were excluded.
Two hundred and thirty-five consecutive patients were included in this cohort. ICU and hospital mortalities were 36.6 and 40%, respectively. On multivariate analysis, cancer status odds ratio (OR): 3.204; 95% confidence interval (CI): 1.271-8.078, invasive mechanical ventilation (OR: 5.940; 95% CI: 2.632-13.408), and sequential organ failure assessment (SOFA) score on the day of ICU admission (OR: 1.199; 95% CI: 1.042-1.379) were independent predictors of hospital mortality.
Acute respiratory failure and septic shock are the common reasons of unplanned ICU admission for patients with solid organ malignancies. With good patient selection, more than half of such patients are likely to be discharged alive from the hospital.
Siddiqui SS, Narkhede AM, Chaudhari HK, Ravisankar NP, Dhundi U, Sarode S, et al. Clinico-demographic and Outcome Predictors in Solid Tumor Patients with Unplanned Intensive Care Unit Admissions: An Observational Study. Indian J Crit Care Med 2021;25(12):1421-1426.
Integral membrane proteins remain a challenge to proteomics because they contain domains with physicochemical properties poorly suited to today's bottom-up protocols. These transmembrane regions may ...potentially contain post-translational modifications of functional significance, and thus development of protocols for improved coverage in these domains is important. One way to achieve this goal is by using top-down mass spectrometry whereby the intact protein is subjected to mass spectrometry and dissociation. Here we describe top-down high resolution Fourier transform mass spectrometry with collisionally activated dissociation to study post-translationally modified integral membrane proteins with polyhelix bundle and transmembrane porin motifs and molecular masses up to 35 kDa. On-line LC-MS analysis of the bacteriorhodopsin holoprotein yielded b- and y-ions that covered the full sequence of the protein and cleaved 79 of 247 peptide bonds (32%). The experiment proved that the mature sequence consists of residues 14–261, confirming N-terminal propeptide cleavage and conversion of N-terminal Gln-14 to pyrrolidone carboxylic acid (−17.02 Da) and C-terminal removal of Asp-262. Collisionally activated dissociation fragments localized the N6-(retinylidene) modification (266.20 Da) between residues 225–248 at Lys-229, the sole available amine in this stretch. Off-line nanospray of all eight subunits of the cytochrome b6f complex from the cyanobacterium Nostoc PCC 7120 defined various post-translational modifications, including covalently attached c-hemes (615.17 Da) on cytochromes f and b. Analysis of murine mitochondrial voltage-dependent anion channel established the amenability of the transmembrane β-barrel to top-down MS and localized a modification site of the inhibitor Ro 68-3400 at Cys-232. Where neutral loss of the modification is a factor, only product ions that carry the modification should be used to assign its position. Although bond cleavage in some transmembrane α-helical domains was efficient, other regions were refractory such that their primary structure could only be inferred from the coincidence of genomic translation with precursor and product ions that spanned them.
Chikungunya disease (CHIKD) is a threat to global health, as it impairs the quality of life of an infected individual ranging from months to years. A systematic evaluation of the serological, ...virological, and immunological aspects of the circulating viruses and their impact on the host response is imperative for better understanding of the evolving disease dynamics.
Serum samples were collected from 196 acute CHIKD patients from ten tertiary care hospitals across India during 2016–2021. Out of 196 patients, paired convalescent samples were collected from 51 patients (one-month post-onset of symptoms). The serum samples were profiled for cytokines and neutralisation capacity. Further, chikungunya virus (CHIKV) was isolated from the acute sera and the replication kinetics of the clinical isolates was evaluated.
Serological analysis indicated that neutralisation could be correlated to seroconversion in the convalescent phase but not found significant in acute phase. In the acute phase samples, there was a correlation between elevated serum levels of IFN-γ, IP-10, MCP-1 and MIG and disease severity. During convalescent phase, pro-inflammatory markers such as IL-6, IL-1β, IL-9 and IP-10 were found to be elevated with a corresponding decline in the secretion of anti-inflammatory cytokines such as IL-4 and IL-10, which correlated with persistent arthralgia. Analysis of replication of the clinical isolates revealed that 68.4% of viruses were fast-growing in the Vero cells (cytopathic effect CPE observed within 24 h post-infection), and their corresponding acute serum samples showed an elevated secretion of IFN-α, IL-1RA, IL-17F, IL-9, MCP-1 and MIP-1α.
This study provides an important overview of neutralisation capabilities and cytokine responses along with virus pathogenesis associated with CHIKV infections in India.
Biotechnology Industry Research Assistance Council (BIRAC).
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