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Astroblastoma is an uncommon circumscribed glial tumor mostly involving the cerebral hemisphere. The characteristic molecular alteration is meningioma (disrupted in balanced translocation) 1 (MN1) rearrangement. No definite World Health Organization grade has been assigned as both low- and high-grade tumors are known to occur. Tumors in the spine are extremely rare; to date only three cases have been reported in the literature. A vigilant microscopy and ancillary testing aid in diagnosis when the tumors present in unusual locations, as in our case. The prompt differentiation of this tumor from its mimickers is a mandate as modalities of management are different and not clearly established.
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Neoplasias Neuroepiteliales , Humanos , Neoplasias Neuroepiteliales/patología , Neoplasias Neuroepiteliales/genética , Neoplasias Neuroepiteliales/diagnóstico por imagen , Preescolar , Proteínas Supresoras de Tumor/genética , Neoplasias de la Médula Espinal/patología , Neoplasias de la Médula Espinal/genética , Neoplasias de la Médula Espinal/diagnóstico por imagen , Masculino , Femenino , TransactivadoresRESUMEN
Ion channels are ion-permeable protein pores that are found in all cell lipid membranes. Distinct ion channels play multiple roles in biological processes. Proteomic data is fast accumulating as a result of the fast growth of mass spectrometry and giving us the chance to comprehensively explore ion channel classes along with their subclasses. This paper proposes an eXtreme Gradient Boosting (XGBoost)-based method to estimate the ion channel classes and their subclasses. Here, 12 feature vectors are applied to better characterize protein sequences like amino acid composition, pseudo-amino acid composition, normalized moreau-broto autocorrelation, amphiphilic pseudo-amino acid composition, dipeptide composition, Geary autocorrelation, tripeptide composition, sequence-order-coupling number, composition/transition/distribution, conjoint triad, moran autocorrelation, quasi-sequence-order descriptors. Here, a total of 9920 features are extracted from the protein sequence. The principal component analysis is applied to determine the optimal number of features to optimize the performance. In 10-fold cross-validation the proposed XGBoost based approach with optimal 50 features achieved accuracy of 100%, 98.70%, 98.77%, 97.26%, 87.40%, 97.39%, 98.03%, 96.42%, and F1-Score of 100%, 99%, 99%, 97%, 87%, 97%, 98%, 97%, for prediction of ion channel and nonion channel, voltage-gated and ligand-gated ion channels, subclasses of voltage-gated ion channels (VGICs), subclasses of ligand-gated ion channels (LGICs), subclasses of voltage-gated calcium channels (VGCCs), subclasses of voltage-gated potassium channels (VGKCs), subclasses of voltage-gated sodium channels (VGSCs), and subclasses of voltage-gated chloride channels, respectively. Here the proposed approach also compares with the other approaches such as support vector machine, k-nearest neighbor, Gaussian Naïve Bayes, and random forest and also compares with existing methods such as support vector machine (SVM) with maximum relevance maximum distance with an accuracy of 86.6%, 83.7%, and 85.1%, for ion channels, non-ion channels and overall respectively and SVM with radial basis function kernel-based method with an accuracy of 100%, 97% and 99.9% for ion channels, nonion channels, and overall accuracy, respectively.
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Algoritmos , Canales Iónicos Activados por Ligandos , Teorema de Bayes , Proteómica , Aprendizaje Automático , Canales de Calcio , Aminoácidos/químicaRESUMEN
Furukawa predicted that at late times, the domain growth in binary fluids scales as î (t) â¼ t2/3, and the growth is driven by fluid inertia. The inertial growth regime has been highly elusive in molecular dynamics (MD) simulations. We perform coarsening studies of the (d = 3) Stockmayer (SM) model comprising of magnetic dipoles that interact via long-range dipolar interactions as well as the usual Lennard-Jones (LJ) potential. This fascinating polar fluid exhibits a gas-liquid phase coexistence, and magnetic order even in the absence of an external field. From comprehensive MD simulations, we observe the inertial scaling [î (t) â¼ t2/3] in the SM fluid for an extended time window. Intriguingly, the fluid inertia is overwhelming from the outset - our simulations do not show the early diffusive regime [î (t) â¼ t1/3] and the intermediate viscous regime [î (t) â¼ t] prevalent in LJ fluids.
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Background The Covid-19 pandemic and subsequent lockdown in India caused disruptions in cancer treatment due to the restriction on movement of patients. We aimed to maintain continuity in cancer treatment during the lockdown through teleconsultations. We tried to reach out to our patients using telephonic consultations by establishing a Teleconsult Centre facility run by a team of doctors and patient navigators. Methods We telephonically contacted all patients who had outpatient appointments from 23 March to 30 April 2020 at our centre through the Teleconsult Centre to understand their current circumstances, feasibility of follow-up, local resources and offered best possible alternatives to continue cancer treatment, if required. Results Of the 2686 patients scheduled for follow-up during this period, we could contact 1783 patients in 9 working days. Through teleconsultations, we could defer follow-ups of 1034 patients (57.99%, 95% confidence interval [CI] 55.6%-60.3%), thus reducing the need for patients to travel to the hospital. Change in systemic therapy was made in 75 patients (4.2%, 95% CI 3.3%-5.2%) as per the requirements and available resources. Symptoms suggestive of disease progression were picked up in 12 patients (0.67%, 95% CI 0.35%-1.17%), who were advised to meet local physicians. Conclusion Our study suggests that the majority of patients on follow-up can be managed with teleconsultation in times of crisis. Teleconsultation has the potential of being one of the standard methods of patient follow-up even during periods of normalcy.
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COVID-19 , Neoplasias , Telemedicina , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Centros de Atención Terciaria , Pandemias , Control de Enfermedades Transmisibles , India/epidemiología , Continuidad de la Atención al Paciente , Neoplasias/epidemiología , Neoplasias/terapiaRESUMEN
Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are an immunocompromised group who are likely to develop severe complications and mortality because of coronavirus disease 2019 (COVID-19). We report here a 61-year-old male patient of primary myelofibrosis who underwent an allo-HSCT 6 years earlier, had chronic graft-versus-host disease (cGVHD) involving the liver, lung, eyes, and skin, (with recurrent episodes of pulmonary infections) who developed severe COVID-19. The patient was treated with tocilizumab, and a combination of lopinavir/ritonavir, ribavirin, interferon-ß1b. He was discharged after 31 days with full recovery. Tocilizumab, a humanized monoclonal antibody against IL6, has been shown to benefit respiratory manifestations in severe COVID19. However, this is first report, to our knowledge, of its use and benefit in a post HSCT recipient.
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Tratamiento Farmacológico de COVID-19 , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Anticuerpos Monoclonales Humanizados , Antivirales/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Trasplante de Células Madre/efectos adversosRESUMEN
Mesenchymal stem cells-conditioned media (MSCs-CM) contains several growth factors and cytokines, thus may be used as a better alternative to stem cell therapy, which needs to be elucidated. The present study was conducted to evaluate the therapeutic potential of caprine, canine, and guinea pig bone marrow-derived MSCs-CM in excision wound healing in a guinea pig model. MSCs were obtained from bone marrow, expanded ex vivo and characterized as per ISCT criteria. CM was collected assayed by western blot to ascertain the presence of important secretory biomolecules. Quantitative estimation by enzyme-linked immunosorbent assay was done for a vascular epidermal growth factor (VEGF) and interleukin-6 (IL-6) in caprine MSCs-CM and optimum time for collection of CM was decided as 72 hr. CM from all the species was lyophilized by freeze-drying method. Full-thickness (2 × 2 cm2 ) excision skin wounds were created in guinea pigs (six animals in each group) and respective lyophilized CM mixed with laminin gel was applied topically at weekly interval. On Day 28, histopathological examinations of healed skin were done by hemotoxylin and eosin staining. MSCs were found to secrete important growth factors and cytokines (i.e., VEGF, transforming growth factor-ß1, fibroblast growth factor-2, insulin-like growth factor-1, stem cell factor, and IL-6) as demonstrated by immunohistochemistry and western blot assay. It was found that allogenic and xenogenic application of CM significantly improved quality wound healing with minimal scar formation. Thus, MSCs-CM can be used allogenically as well as xenogenically for quality wound healing.
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Tratamiento Basado en Trasplante de Células y Tejidos , Células Madre Mesenquimatosas/efectos de los fármacos , Trasplante de Células Madre , Cicatrización de Heridas/genética , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Diferenciación Celular/genética , Proliferación Celular/genética , Medios de Cultivo Condicionados/farmacología , Perros , Fibroblastos/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Cabras/genética , Cobayas , Humanos , Interleucina-6/genética , Células Madre Mesenquimatosas/citología , Factor A de Crecimiento Endotelial Vascular/genéticaAsunto(s)
Anemia Aplásica , Suero Antilinfocítico , Hemólisis , Inmunosupresores , Humanos , Suero Antilinfocítico/efectos adversos , Suero Antilinfocítico/uso terapéutico , Anemia Aplásica/tratamiento farmacológico , Anemia Aplásica/inducido químicamente , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Hemólisis/efectos de los fármacos , Niño , Masculino , FemeninoRESUMEN
The magnetic susceptibility (MS) measurements are used for rapid and cost-effective soil surveys and for accessing heavy metal contamination worldwide. In the sub-Himalayan plains of India, nearly 6.05 × 104 km2 area of most the fertile land occurs as interfluve of Late Quaternary age between the two major glacier-fed rivers (Ganga and Yamuna). The vast areal expanse of interfluve terminates at the rivers' confluence in Sangam (25°25'13â³N-81°53'22â³E), Allahabad. This is the first study of MS soil survey of the interfluve region at the confluence comprising 490 samples from 49 locations. The MS values are between 8.84 and 261.25 × 10-8 m3 kg-1 and the change is more pronounced (8.84-312.65 × 10-8 m3 kg-1) with increasing depth. A sudden increase in the MS between 12- (11.28-303.32 × 10-8 m3 kg-1) and 14-cm (11.21-238.45 × 10-8 m3 kg-1) depth is observed similar to observations worldwide. The high MS hotspots are aligned parallel to major traffic networks of the city suggesting a major contribution emanating from the anthropogenic load. A significant difference has been noted in the MS values of present-day mid-channel bar sediments of Ganga (25.24 × 10-8 m3 kg-1) and Yamuna (116.47 × 10-8 m3 kg-1) Rivers. The laser-induced breakdown spectroscopy (LIBS) data showed the presence of heavy (Fe, Ti, Cr, Cu, Cd, Zn, and Pb) and light (H, C, N, and O) elements supporting MS data. The concentration of toxic elements predicted by partial least squares regression (PLSR) approach concurs with magnetic measurements. The topsoil MS values increase up to a depth of ~ 6.25 cm suggesting the dominant role of anthropogenic source for the increased heavy metal concentration compared with basement contributions.
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Monitoreo del Ambiente/métodos , Metales Pesados/análisis , Ríos/química , Contaminantes del Suelo/análisis , Suelo/química , Urbanización , Ciudades , India , Magnetometría/métodos , Análisis Espectral/métodosRESUMEN
This study was conducted to know the impact of cryopreservation on caprine fetal adnexa derived mesenchymal stem cells (MSCs) on the basic stem cell characteristics. Gravid caprine uteri (2-3 months) were collected from local abattoir to derive (amniotic fluid [cAF], amniotic sac [cAS], Wharton's jelly [cWJ], and cord blood [cCB]) MSCs and expanded in vitro. Cells were cryopreserved at 3rd passage (P3) using 10% DMSO. Post-thaw viability and cellular properties were assessed. Cells were expanded to determine growth kinetics, tri-lineage differentiation, localization, and molecular expression of MSCs and pluripotency markers; thereafter, these cells were transplanted in the full-thickness (2 × 2cm2 ) rat skin wound to determine their wound healing potential. The post-thaw (pt) growth kinetics study suggested that cWJ MSCs expanded more rapidly with faster population doubling time (PDT) than that of other fetal adnexa MSCs. The relative mRNA expression of surface antigens (CD73, CD90, and CD 105) and pluripotency markers (Oct4, KLF, and cMyc) was higher in cWJ MSCs in comparison to cAS, cAF, and cCB MSCs post-thaw. The percent wound contraction on 7th day was more than 50% for all the MSC-treated groups (pre and post-thaw), against 39.55% in the control group. On day 28th, 99% and more wound contraction was observed in cAF, cAF-pt, cAS-pt, cWJ, cWJ-pt, and cCB, MSCs with better scores for epithelization, neovascularization, and collagen characteristics at a non-significant level. It is concluded that these MSCs could be successfully cryopreserved without altering their stemness and wound healing properties. J. Cell. Physiol. 232: 2186-2200, 2017. © 2016 Wiley Periodicals, Inc.
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Proliferación Celular/efectos de los fármacos , Trasplante de Células Madre de Sangre del Cordón Umbilical , Criopreservación , Crioprotectores/farmacología , Dimetilsulfóxido/farmacología , Células Madre Fetales/efectos de los fármacos , Células Madre Fetales/trasplante , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/efectos de los fármacos , Herida Quirúrgica/cirugía , Cicatrización de Heridas , Líquido Amniótico/citología , Animales , Biomarcadores/metabolismo , Diferenciación Celular , Linaje de la Célula , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Sangre Fetal/citología , Células Madre Fetales/metabolismo , Cabras , Xenoinjertos , Cinética , Masculino , Células Madre Mesenquimatosas/metabolismo , Fenotipo , Embarazo , Ratas Wistar , Herida Quirúrgica/metabolismo , Herida Quirúrgica/patología , Gelatina de Wharton/citologíaRESUMEN
New forms of interaction made possible by developments in special educational technologies can now help students with dyscalculia. Artificial intelligence (AI) has emerged as a promising tool in recent decades, particularly between 2001 and 2010, offering avenues to enhance the quality of education for individuals with dyscalculia. Therefore, the implementation of AI becomes crucial in addressing the needs of students with dyscalculia. Content analysis techniques were used to examine the literature covering the influence of AI on dyscalculia and its potential to assist instructors in promoting education for individuals with dyscalculia. The study sought to create a foundation for a more inclusive dyscalculia education in the future through in-depth studies. AI integration has had a big impact on educational institutions as well as people who struggle with dyscalculia. This paper highlights the importance of AI in improving the educational outcomes of students affected by dyscalculia.
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Inflammatory bowel disease (IBD) is a chronic gut disorder that also elevates the risk of colorectal cancer (CRC). The global incidence and severity of IBD are rising, yet existing therapies often lead to severe side effects. Curcumin offers potent anti-inflammatory and chemotherapeutic properties. However, its clinical translation is hindered by rapid metabolism, as well as poor water solubility and stability, which limits its bioavailability. To address these challenges, we developed OC-S, a water-soluble and colon-targeted curcumin formulation that protects against colitis in mice. The current study advances OC-S as a dietary supplement by establishing its stability and compatibility with various commercial dietary products. Further, OC-S exhibited specific binding to inflamed colon tissue, potentially aiding in targeted drug retention at the inflammation site in colitis with diarrhea symptoms. We further investigated its efficacy in vivo and in vitro using a murine model of colitis and tumoroids from APCmin mice. OC-S significantly reduced colitis severity and pro-inflammatory cytokine expression compared with curcumin, even at very low doses (5 mg/kg/day). It also demonstrated higher anti-proliferative activity in CRC cells and colon cancer tumoroids vs. curcumin. Overall, this study demonstrated that OC-S effectively targets and retains water-soluble curcumin at the inflamed colon sites, while showing promise in addressing both colitis and colorectal cancer, which potentially paves the way for OC-S to advance into clinical development as a dietary product for both IBD and CRC.
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Colitis , Neoplasias Colorrectales , Curcumina , Animales , Curcumina/farmacología , Curcumina/uso terapéutico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/tratamiento farmacológico , Colitis/tratamiento farmacológico , Colitis/patología , Colitis/inducido químicamente , Ratones , Humanos , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Proliferación Celular/efectos de los fármacos , Suplementos Dietéticos , Masculino , Sustancias Protectoras/farmacologíaRESUMEN
We study self-assembly in a colloidal suspension of magnetic particles by performing comprehensive molecular dynamics simulations of the Stockmayer (SM) model, which comprises spherical particles decorated by a magnetic moment. The SM potential incorporates dipole-dipole interactions along with the usual Lennard-Jones interaction and exhibits a gas-liquid phase coexistence observed experimentally in magnetic fluids. When this system is quenched from the high-temperature homogeneous phase to the coexistence region, the nonequilibrium evolution to the condensed phase proceeds with the development of spatial as well as magnetic order. We observe density-dependent coarsening mechanisms-a diffusive growth law â(t)â¼t^{1/3} in the nucleation regime and hydrodynamics-driven inertial growth law â(t)â¼t^{2/3} in the spinodal regimes. [â(t) is the average size of the condensate at time t after the quench.] While the spatial growth is governed by the expected conserved order parameter dynamics, the growth of magnetic order in the spinodal regime exhibits unexpected nonconserved dynamics. The asymptotic morphologies have density-dependent shapes which typically include the isotropic sphere and spherical bubble morphologies in the nucleation region, and the anisotropic cylinder, planar slab, cylindrical bubble morphologies in the spinodal region. The structures are robust and nonvolatile, and exhibit characteristic magnetic properties. For example, the oppositely magnetized hemispheres in the spherical morphology impart the characteristics of a Janus particle to it. The observed structures have versatile applications in catalysis, drug delivery systems, memory devices, and magnetic photonic crystals, to name a few.
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BACKGROUND: Medical certification of cause of death (MCCD) provides valuable data regarding disease burden in a community and for formulating health policy. Inaccurate MCCDs can significantly impair the precision of national health information. OBJECTIVE: To evaluate the accuracy of cause of death certificates prepared at two tertiary cancer care hospitals in Northern India during the study period (May 2018 to December 2020). METHOD: A retrospective observational study at two tertiary cancer care hospitals in Varanasi, India, over a period of two and a half years. Medical records and cause of death certificates of all decedents were examined. Demographic characteristics, administrative details and cause of death data were collected using the WHO recommended death certificates. Accuracy of death certification was validated by electronic medical records and errors were graded. RESULTS: A total of 778 deaths occurred in the two centres during the study period. Of these, only 30 (3.9%) certificates were error-free; 591 (75.9%) certificates had an inappropriate immediate cause of death; 231 (29.7%) certificates had incorrectly labelled modes of death as the immediate cause of death; and 585 (75.2%) certificates had an incorrect underlying cause of death. The majority of certificates were prepared by junior doctors and were significantly associated with higher certification errors. CONCLUSION: A high rate of errors was identified in death certification at the cancer care hospitals during the study period. Inaccurate MCCDs related to cancers can potentially influence cancer statistics and thereby affect policy making for cancer control. IMPLICATIONS: This study has identified the pressing need for appropriate interventions to improve quality of certification through training of doctors.
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A convenient synthesis of natural and synthetic pterocarpans was achieved in three steps. Optical resolution of the respective enantiomers was accomplished by analytical and semi-preparative HPLC on a chiral stationary phase. For medicarpin and its synthetic derivative 9-demethoxymedicarpin, the absolute configuration was confirmed by a combination of experimental LC-ECD coupling and quantum-chemical ECD calculations. (-)-Medicarpin and (-)-9-demethoxymedicarpin are both 6aR,11aR-configured, and consequently the corresponding enantiomers, (+)-medicarpin and (+)-9-demethoxymedicarpin, possess the 6aS,11aS-configuration. A comparative mechanism study for osteogenic (bone forming) activity of medicarpin (racemic versus enantiomerically pure material) revealed that (+)-(6aS,11aS)-medicarpin (6a) significantly increased the bone morphogenetic protein-2 (BMP2) expression and the level of the bone-specific transcription factor Runx-2 mRNA, while the effect was opposite for the other enantiomer, (-)-(6aR,11aR)-medicarpin (6a), and for the racemate, (±)-medicarpin, the combined effect of both the enantiomers on transcription levels was observed.
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Conservadores de la Densidad Ósea/síntesis química , Técnicas de Química Sintética/métodos , Pterocarpanos/síntesis química , Animales , Animales Recién Nacidos , Conservadores de la Densidad Ósea/química , Conservadores de la Densidad Ósea/farmacología , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Proteína Morfogenética Ósea 2/biosíntesis , Conformación de Carbohidratos , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Subunidad alfa 1 del Factor de Unión al Sitio Principal/biosíntesis , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Pterocarpanos/química , Pterocarpanos/farmacología , Ratas , Ratas Sprague-Dawley , EstereoisomerismoRESUMEN
Classical federated learning approaches incur significant performance degradation in the presence of non-independent and identically distributed (non-IID) client data. A possible direction to address this issue is forming clusters of clients with roughly IID data. Most solutions following this direction are iterative and relatively slow, also prone to convergence issues in discovering underlying cluster formations. We introduce federated learning with taskonomy (FLT) that generalizes this direction by learning the task relatedness between clients for more efficient federated aggregation of heterogeneous data. In a one-off process, the server provides the clients with a pretrained (and fine-tunable) encoder to compress their data into a latent representation and transmit the signature of their data back to the server. The server then learns the task relatedness among clients via manifold learning and performs a generalization of federated averaging. FLT can flexibly handle a generic client relatedness graph, when there are no explicit clusters of clients, as well as efficiently decompose it into (disjoint) clusters for clustered federated learning. We demonstrate that FLT not only outperforms the existing state-of-the-art baselines in non-IID scenarios but also offers improved fairness across clients. Our codebase can be found at: https://github.com/hjraad/FLT/.
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Background: Non-communicable disease (NCD) is the leading cause of death, accounting for 70% of total death globally, and posing a major public health challenge. In India, nearly 5.8 million people (WHO report, 2015) die from NCDs every year. The basic element of NCD prevention is the identification of the associated risk factors and risk modification. The objective of the current study was conducted to assess the prevalence of risk factors for NCDs among healthcare staff of the two units of a Tertiary Cancer Hospital in Varanasi, India, using WHO STEPS approach. Methods: This cross sectional study was conducted among 528 participants who were willing to participate in the study, from among 967 healthcare staffs of the two units of the Tertiary Cancer Hospital. The participants were interviewed and the anthropometric and biochemical parameters were measured. Results: The prevalence of risk factors, associated with NCD, tobacco use, alcohol use, extra salt in diet, less than 5 servings of fruits/vegetables, physical inactivity and self-perceived high stress score was found in 34 (6.43%), 90 (17.04%), 461 (87.3%), 412 (78.03%), 409 (77.4%) and 159 (30.11%) respondents, respectively. Multiple logistic regression revealed that Diabetes was significantly associated with male sex, high BMI and physical inactivity. Hypertension was found significantly associated with male sex, increasing age, tobacco and or alcohol consumption, high BMI and high stress. Dyslipidemia was also found significantly associated with high BMI, male sex, physical inactivity and high stress levels. Conclusion: A high prevalence of risk factors for NCDs was found among the healthcare staff and it is the need of the hour to take preventive measures to reduce the prevailing burden of NCD.
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BACKGROUND: Since January 2020, India has faced two waves of COVID-19; preparation for the upcoming waves is the primary challenge for public health sectors and governments. Therefore, it is important to forecast future cumulative confirmed cases to plan and implement control measures effectively. METHODS: This study proposed a hybrid autoregressive integrated moving average (ARIMA) and Prophet model to predict daily confirmed and cumulative confirmed cases. The built-in auto.arima function was first used to select the optimal hyperparameter values of the ARIMA model. Then, the modified ARIMA model was used to find the best fit between the test and forecast data to find the best model parameter combinations. Articles, blog posts, and news stories from virologists, scientists, and health experts related to the third wave of COVID-19 were gathered using the Python web scraping package Beautiful Soup. Their opinions (sentiments) toward the potential third wave were analyzed using natural language processing (NLP) libraries. RESULTS: A spike in daily confirmed and cumulative confirmed cases was predicted in India in the next 180 days based on past time series data. The results were validated using various analytical tools and evaluation metrics, producing a root mean square error (RMSE) of 0.14 and a mean absolute percentage error (MAPE) of 0.06. The NLP processing results revealed negative sentiments in most articles and blogs, with few exceptions. CONCLUSION: The findings of this study suggest that there will be more active cases in the upcoming days. The proposed models can forecast future daily confirmed and cumulative confirmed cases. This study will help the country and states plan appropriate public health measures for the upcoming waves of COVID-19.
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COVID-19 , COVID-19/epidemiología , Humanos , India/epidemiología , Aprendizaje Automático , Modelos Estadísticos , Análisis de Sentimientos , Factores de TiempoRESUMEN
An efficient one step synthesis of new 2-hydroxymethylisoflavone is reported. A series of deoxybenzoin was subjected to cyclization with glyoxal in the presence of basic condition (KOH/EtOH) to afford the 2-hydroxymethyl isoflavone. The structures of compounds 5a-g were confirmed by NMR experiments including (1)H, (13)C, HMBC, HSQC and COSY. These compounds were assessed for stimulation of osteoblast function using primary culture of rat calvarial osteoblasts in vitro. Compounds 5a, 5d, 5f and 5g were potent in stimulating differentiation of osteoblasts as assessed by measuring alkaline phosphatase (ALP) activity. Besides, effect of these analogs was also seen on the transcript levels of osteogenic genes like Runx-2, osteocalcin and Bone morphogenetic protein-2 (BMP-2), involved in osteoblast differentiation and mineralization. Based on quantitative PCR data, compound 5f was found to be the potent followed by 5d. Compound 5f robustly increased the mRNA levels of Runx-2 (8.0 fold), BMP-2 (â¼2 fold) and osteocalcin (â¼2.0 fold) in osteoblasts. Collectively, we demonstrate osteogenic activity of the novel 2-hydroxymethyl isoflavones with 5f having the most potent activity.
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Isoflavonas/síntesis química , Osteogénesis/efectos de los fármacos , Animales , Células Cultivadas , Técnicas In Vitro , Isoflavonas/farmacología , Espectroscopía de Resonancia Magnética , Osteoblastos/citología , Osteoblastos/metabolismo , RatasRESUMEN
BACKGROUND: Highest incidence of oral cancer is reported in India with reduced survival rate in the advanced stages due to lack of effective biomarkers. Therefore, it is essential to develop novel biomarkers for the better management of this disease. In the current study, TNFAIP8/TIPE protein family comprising of four proteins is explored for its role in oral cancer. METHODS: IHC analysis of oral cancer TMA and Western blot analysis of tobacco treated oral cancer cells were performed to determine the differential expression of TIPE proteins in oral cancer. Further, CRISPR/Cas9-mediated gene editing was done to generate TIPE proteins' knockouts and MTT, colony formation, wound healing, cell cycle and Western blot analysis were performed to determine the effect of gene knockouts on various cancer hallmarks and the associated molecular targets of TIPE proteins. RESULTS AND DISCUSSION: IHC results revealed that expression of TIPE, TIPE2 and TIPE3 were upregulated and TIPE1 was downregulated in oral cancer tissues compared to normal tissues. Similar results were observed upon treating oral cancer cells with tobacco carcinogens. Furthermore, knockout of TIPE or TIPE2 or TIPE3 significantly reduced the survival, proliferation, colony formation and migration of oral cancer cells whereas knockout of TIPE1 had an opposite effect. Further, TIPE, TIPE2 and TIPE3 knockout-mediated inhibition of proliferation was associated with inhibition of cell cycle progression at S or G2/M phases, and downregulation of proteins involved in cancer progression. We found that TIPE, TIPE1 and TIPE2 proteins regulate oral cancer progression through modulation of Akt/mTOR signaling cascade, whereas TIPE3 acts through an Akt-independent mTOR/STAT3 pathway. CONCLUSION: Collectively, the TIPE proteins were proved to play significant roles in the progression of oral cancer thus warranting research and clinic attention for their therapeutic and prognostic values and raising the importance of specific targeting of TIPE proteins in cancer treatment.
Asunto(s)
Proteínas Reguladoras de la Apoptosis/biosíntesis , Carcinogénesis/metabolismo , Neoplasias de la Boca/metabolismo , Proteínas Proto-Oncogénicas c-akt/biosíntesis , Factor de Transcripción STAT3/biosíntesis , Serina-Treonina Quinasas TOR/biosíntesis , Proteínas Reguladoras de la Apoptosis/genética , Carcinogénesis/inducido químicamente , Carcinogénesis/genética , Carcinógenos/toxicidad , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/fisiología , Técnicas de Inactivación de Genes/métodos , Humanos , Péptidos y Proteínas de Señalización Intracelular/biosíntesis , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias de la Boca/genética , Proteínas Proto-Oncogénicas c-akt/genética , Factor de Transcripción STAT3/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/genética , Nicotiana/toxicidadRESUMEN
BACKGROUND: There is paucity of data regarding clinical characteristics, laboratory parameters and outcomes of coronavirus disease (COVID-19) in cancer versus non-cancer patients, particularly from India. MATERIALS AND METHODS: This was an observational, single-centre, retrospective analysis of patients with laboratory-confirmed COVID-19 hospitalised in our institution between 22 May 2020 and 1 December 2020. We compared baseline clinical characteristics, laboratory parameters and outcomes of COVID-19 (overall mortality, time to discharge) between cancer and non-cancer patients. RESULTS: A total of 200 COVID-19 infection episodes were analysed of which 109 (54.5%) were patients with cancer and 91 (45.5%) were patients without cancer. The median age was 43 (interquartile range [IQR]:32-57), 51 (IQR: 33-62) and 38 (IQR: 31.5-49.3) years; of whole cohort, cancer and non-cancer patients, respectively. Comparison of outcomes showed that oxygen requirement (31.2% [95% CI: 22.6-40.7] vs. 17.6% [95% CI: 10.4-26.9]; p = 0.03), median time to discharge (11 days [IQR: 6.75-16] vs. 6 days [IQR: 3-9.75]; p < 0.001) and mortality (10.0% [95% CI: 5.2-17.3] vs. 1.1% [95% CI: 0.03-5.9]; p = 0.017) were significantly higher in patients with cancer. In univariable analysis, factors associated with higher mortality in the whole cohort included diagnosis of cancer (10.1% vs. 1.1%; p = 0.027; odds ratio [OR]: 7.04), age ≥60 (17.4% vs. 2.6%; p = 0.001; OR: 7.38), oxygen requirement (22% vs. 0.6%; p < 0.001; OR: 29.01), chest infiltrates (19.2% vs. 1.4%; p < 0.001; OR: 22.65), baseline absolute lymphocyte count <1 × 109 /L (10.8% vs. 1.9%; p = 0.023; OR:5.1), C-reactive protein >1 mg% (12.8% vs. 0%; p = 0.027; OR: 24.69), serum procalcitonin >0.05 ng/ml (22.65% vs. 0%; p = 0.004; OR: 4.49) and interleukin-6 >6 pg/ml (10.8% vs. 1.3%; p = 0.036; OR: 3.08). In multivariable logistic regression, factors significantly associated with mortality were oxygen requirement (p = 0.005; OR: 13.11) and high baseline procalcitonin level (p = 0.014; OR: 37.6). CONCLUSION: Cancer patients with COVID-19 have higher mortality and require longer hospital stay. High procalcitonin levels and oxygen requirement during admission are other factors that affect outcomes adversely.