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Handwritten signatures in biometric authentication leverage unique individual characteristics for identification, offering high specificity through dynamic and static properties. However, this modality faces significant challenges from sophisticated forgery attempts, underscoring the need for enhanced security measures in common applications. To address forgery in signature-based biometric systems, integrating a forgery-resistant modality, namely, noninvasive electroencephalography (EEG), which captures unique brain activity patterns, can significantly enhance system robustness by leveraging multimodality's strengths. By combining EEG, a physiological modality, with handwritten signatures, a behavioral modality, our approach capitalizes on the strengths of both, significantly fortifying the robustness of biometric systems through this multimodal integration. In addition, EEG's resistance to replication offers a high-security level, making it a robust addition to user identification and verification. This study presents a new multimodal SignEEG v1.0 dataset based on EEG and hand-drawn signatures from 70 subjects. EEG signals and hand-drawn signatures have been collected with Emotiv Insight and Wacom One sensors, respectively. The multimodal data consists of three paradigms based on mental, & motor imagery, and physical execution: i) thinking of the signature's image, (ii) drawing the signature mentally, and (iii) drawing a signature physically. Extensive experiments have been conducted to establish a baseline with machine learning classifiers. The results demonstrate that multimodality in biometric systems significantly enhances robustness, achieving high reliability even with limited sample sizes. We release the raw, pre-processed data and easy-to-follow implementation details.
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Electroencefalografía , Humanos , Escritura Manual , Identificación Biométrica/métodos , BiometríaRESUMEN
Zinc-air batteries are promising energy storage devices owing to their high energy density, low cost, and environmental friendliness. However, the development of durable and efficient bifunctional electrocatalysts is a major concern for Zn-air batteries. In this review, we summarize the recent progress on transition metal dichalcogenides (TMDs) as bifunctional electrocatalysts for Zn-air batteries. We discuss the advantages of TMDs, such as high activity, good stability, and tunable electronic structure, as well as the challenges, such as low conductivity, poor durability, and limited active sites. We also highlight the strategies for fine-tuning the properties of TMDs, such as defect engineering, doping, hybridization, and structural engineering, to enhance their catalytic performance and stability. We provide a comprehensive and in-depth analysis of the applications of TMDs in Zn-air batteries, demonstrating their potential as low-cost, abundant, and environmentally friendly alternatives to noble metal catalysts. We also suggest future directions like exploring new TMDs materials and compositions, developing novel synthesis and modification techniques, investigating the interfacial interactions and charge transfer processes, and integrating TMDs with other functional materials. This review aims to illuminate the path forward for the development of efficient and durable Zn-air batteries, aligning with the broader objectives of sustainable energy solutions.
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The emergence of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses and their transmission to dairy cattle and animals, including humans, poses a major global public health threat. Therefore, the development of effective vaccines and therapeutics against H5N1 clade 2.3.4.4b virus is considered a public health priority. In the United States, three H5N1 vaccines derived from earlier strains of HPAI H5N1 (A/Vietnam, clade 1, and A/Indonesia, clade 2.1) virus, with (MF59 or AS03) or without adjuvants, are licensed and stockpiled for pre-pandemic preparedness, but whether they can elicit neutralizing antibodies against circulating H5N1 clade 2.3.4.4b viruses is unknown. In this study, we evaluated the binding, hemagglutination inhibition and neutralizing antibody response generated after vaccination of adults with the three licensed vaccines. Individuals vaccinated with the two adjuvanted licensed H5N1 vaccines generated cross-reactive binding and cross-neutralizing antibodies against the HPAI clade 2.3.4.4b A/Astrakhan/3212/2020 virus. Seroconversion rates of 60-95% against H5 clade 2.3.4.4b were observed after two doses of AS03-adjuvanted-A/Indonesia or three doses of MF59-adjuvanted-A/Vietnam vaccine. These findings suggest that the stockpiled US-licensed adjuvanted H5N1 vaccines generate cross-neutralizing antibodies against circulating HPAI H5N1 clade 2.3.4.4b in humans and may be useful as bridging vaccines until updated H5N1 vaccines become available.
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Introduction: Rheumatic heart disease (RHD) poses a substantial global health challenge, especially impacting resource-limited nations, with over 40.5 million cases reported in 2019. The crucial role of Benzathine penicillin G in both primary and secondary prevention, particularly the latter, emphasizes its significance. Method: Following PRISMA guidelines, our systematic review explored Medline, Scopus, Google Scholar, and Embase databases from 1990 to 2022. Registered with PROSPERO ), the review utilized quality appraisal tools, including the PRISMA checklist, Cochrane bias tool and Newcastle-Ottawa scale. The objective was to identify and stratify the impact of socio-economic factors on adherence to secondary prophylaxis in RHD. Results and discussion: The impact of education on adherence has been found to be significant. Socially disadvantaged environments significantly influenced adherence, shaped by education, socio-economic status, and geographical location and access to healthcare. Surprisingly, lower education levels were associated with better adherence in certain cases. Factors contributing to decreased adherence included forgetfulness, injection-related fears, and healthcare provider-related issues. Conversely, higher adherence correlated with younger age, latent disease onset, increased healthcare resources, and easy access. Conclusion: Patient education and awareness were crucial for improving adherence. Structured frameworks, community initiatives, and outreach healthcare programs were identified as essential in overcoming barriers to secondary prophylaxis. Taking active steps to address obstacles like long-distance commute, waiting time, injection fears, and financial issues has the potential to greatly improve adherence. This, in turn, can lead to a more effective prevention of complications associated with RHD.
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BACKGROUND: Recurrent somatic mutations in the JAK2, CALR, and the MPL genes are noted in BCR: ABL1 negative classic myeloproliferative neoplasms (MPN) that includes polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). MATERIALS AND METHODS: Mutation profile and clinical features of MPN cases diagnosed at a tertiary care center in North India are being described. JAK2V617F mutation was screened using ARMS PCR, and CALR mutation was screened using allele-specific PCR followed by fragment analysis. MPL and JAK2 Exon 12 mutations were screened by Sanger sequencing. Some of the samples were also screened using commercial kits based on single-plex RT PCR. RESULTS: A total of 378 cases (including 124 PV, 121 ET, and 133 PMF cases) were screened over 6.5 years. JAK2V617F mutation was noted in 90.3%, 61.1%, and 69.2% of cases of PV, ET, and PMF, respectively. In PV, JAK2V617F wild-type cases were associated with a significantly lower age (44 yrs vs 54 yrs; P = 0.001), lower TLC (6.3 vs 16.9; P = 0.001), and a lower platelet count (188 × 109/L vs 435 × 109/L; P = 0.009) as compared to the JAK2V617F mutated cases. CALR and MPL mutations were noted in 17.4% and 12% and 0.8% and 5.3% of ET and PMF cases, respectively. Type 1 CALR mutations were commoner in both ET and PMF. The triple negative cases constituted 20.7% and 13.5% cases of ET and PMF, respectively. In ET, the triple negative cases were found to have a significantly lower median age of presentation (42 yrs vs 52 yrs; P = 0.001), lower median TLC (10.2 × 109/L vs 13.2 × 109/L; P = 0.024), and a higher median platelet count (1238 × 109/L vs 906 × 109/L; P = 0.001) as compared to driver genes mutated cases. In PMF, the triple negative cases were found to have a significantly lower hemoglobin level (7.9 g/dl vs 11.0 gl/dl; P = 0.001) and a significant female preponderance (P = 0.05) as compared to the mutated cases. CALR mutations were found to have a significantly lower median age (43 yrs vs 56 yrs; P = 0.001) and lower hemoglobin (9.6 g/dl vs 11.3 g/dl) as compared to the JAK2 mutations. CONCLUSION: Our data on the driver gene mutational profile of BCR: ABL1 negative MPN is one of the largest patient cohorts. The prevalence and clinicopathological features corroborate with that of other Asian studies.
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Crop plants face complex tropospheric ozone (O3) stress, emphasizing the need for a food security-focused management strategy. While research extensively explores O3's harmful effects, this study delves into the combined impacts of O3 and CO2. This study investigates the contrasting responses of O3-sensitive (PBW-550) and O3-resistant (HUW-55) wheat cultivars, towards elevated ozone (eO3) and elevated carbon dioxide (eCO2), both individually and in combination. The output of the present study confirms the positive effect of eCO2 on wheat cultivars exposed to eO3 stress, with more prominent effects on O3-sensitive cultivar PBW-550, as compared to the O3-resistant HUW-55. The differential response of the two wheat cultivars can be attributed to the mechanistic variations in the enzyme activities of the Halliwell-Asada pathway (AsA-GSH cycle) and the ascorbate and glutathione pool. The results indicate that eCO2 was unable to uplift the regeneration of the glutathione pool in HUW-55, however, PBW-550 responded well, under similar eO3 conditions. The study's findings, highlighting mechanistic variations in antioxidants, show a more positive yield response in PBW-550 compared to HUW-55 under ECO treatment. This insight can inform agricultural strategies, emphasizing the use of O3-sensitive cultivars for sustained productivity in future conditions with high O3 and CO2 concentrations.
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Ácido Ascórbico , Dióxido de Carbono , Glutatión , Ozono , Triticum , Ozono/toxicidad , Ozono/farmacología , Triticum/efectos de los fármacos , Triticum/metabolismo , Dióxido de Carbono/metabolismo , Glutatión/metabolismo , Ácido Ascórbico/metabolismo , Contaminantes Atmosféricos/toxicidadRESUMEN
Less than 6% of rare illnesses have an appropriate treatment option. Repurposed medications for new indications are a cost-effective and time-saving strategy that results in excellent success rates, which may significantly lower the risk associated with therapeutic development for rare illnesses. It is becoming a realistic alternative to repurposing "conventional" medications to treat joint and rare diseases considering the significant failure rates, high expenses, and sluggish stride of innovative medication advancement. This is due to delisted compounds, cheaper research fees, and faster development time frames. Repurposed drug competitors have been developed using strategic decisions based on data analysis, interpretation, and investigational approaches, but technical and regulatory restrictions must also be considered. Combining experimental and computational methodologies generates innovative new medicinal applications. It is a one-of-a-kind strategy for repurposing human-safe pharmaceuticals to treat uncommon and difficult-to-treat ailments. It is a very effective method for discovering and creating novel medications. Several pharmaceutical firms have developed novel therapies by repositioning old medications. Repurposing drugs is practical, cost-effective, and speedy and generally involves lower risks when compared to developing a new drug from the beginning.
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Human immunoglobulin preparations contain a diverse range of polyclonal antibodies that reflect past immune responses against pathogens encountered by the blood donor population. In this study, we examined a panel of intravenous immunoglobulins (IGIVs) manufactured over the past two decades (1998-2020) for their capacity to neutralize or enhance Zika virus (ZIKV) infection in vitro. These IGIVs were selected specifically based on their production dates in relation to the occurrences of two flavivirus outbreaks in the U.S.: the West Nile virus (WNV) outbreak in 1999 and the ZIKV outbreak in 2015. As demonstrated by enzyme-linked immunosorbent assay (ELISA) experiments, IGIVs made before the ZIKV outbreak already harbored antibodies that bind to various peptides across the envelope protein of ZIKV because of the WNV outbreak. Using phage display, the most dominant binding site was mapped precisely to the P2 peptide between residues 211 and 230 within domain II, where BF1176-56, an anti-ZIKV monoclonal antibody, also binds. When tested in permissive Vero E6 cells for ZIKV neutralization, the IGIVs, even after undergoing rigorous enrichment for P2 binding specificity, failed, as did BF1176-56. Meanwhile, BF1176-56 enhanced ZIKV infection in both FcγRII-expressing K562 cells and human peripheral blood mononuclear cells. However, for enhancement by the IGIVs to be detected in these cells, a substantial increase in their P2 binding specificity was required, thus linking the P2 site with ZIKV enhancement in vitro. Our findings warrant further study of the significance of elevated levels of anti-WNV antibodies in IGIVs, considering that various mechanisms operating in vivo may modulate ZIKV infection outcomes.IMPORTANCEWe investigated the capacity of intravenous immunoglobulins manufactured previously over two decades (1998-2020) to neutralize or enhance Zika virus infection in vitro. West Nile virus antibodies in IGIVs could not neutralize Zika virus initially; however, once the IGIVs were concentrated further, they enhanced its infection. These findings lay the groundwork for exploring how preexisting WNV antibodies in IGIVs could impact Zika infection, both in vitro and in vivo. Our observations are historically significant, since we tested a panel of IGIV lots that were carefully selected based on their production dates which covered two major flavivirus outbreaks in the U.S.: the WNV outbreak in 1999 and the ZIKV outbreak in 2015. These findings will facilitate our understanding of the interplay among closely related viral pathogens, particularly from a historical perspective regarding large blood donor populations. They should remain relevant for future outbreaks of emerging flaviviruses that may potentially affect vulnerable populations.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Fiebre del Nilo Occidental , Virus del Nilo Occidental , Infección por el Virus Zika , Virus Zika , Humanos , Virus Zika/inmunología , Virus del Nilo Occidental/inmunología , Anticuerpos Antivirales/inmunología , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/virología , Animales , Chlorocebus aethiops , Células Vero , Fiebre del Nilo Occidental/inmunología , Fiebre del Nilo Occidental/virología , Anticuerpos Neutralizantes/inmunología , Sitios de Unión , Inmunoglobulinas Intravenosas/inmunología , Proteínas del Envoltorio Viral/inmunología , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
BACKGROUND: Tourniquets are commonly used in elective extremity orthopaedic surgery to reduce blood loss, improve visualization in the surgical field, and to potentially reduce surgical time. There is a lack of consensus in existing guidelines regarding the optimal tourniquet pressure, placement site, and duration of use. There is a paucity of data on the relationship between the site of a tourniquet and postoperative pain in foot and ankle surgery. AIM: To explore the relationship between tourniquet site and intensity of post-operative pain scores in patients undergoing elective foot and ankle surgery. METHODS: Retrospective analysis of prospectively collected data on 201 patients who underwent foot and ankle surgery in a single institution was undertaken. Intraoperative tourniquet duration, tourniquet pressure and site, and postoperative pain scores using Visual Analogue Score were collected in immediate recovery, at six hours and at 24 h post-op. Scatter plots were used to analyse the data and to assess for the statistical correlation between tourniquet pressure, duration, site, and pain scores using Pearson correlation coefficient. RESULTS: All patients who underwent foot and ankle surgery had tourniquet pressure of 250 mmHg for ankle tourniquet and 300 mmHg for thigh. There was no correlation between the site of the tourniquet and pain scores in recovery, at six hours and after 24 h. There was a weak correlation between tourniquet time and Visual Analogue Score immediately post-op (r = 0.14, P = 0.04) but not at six or 24 h post-operatively. CONCLUSION: This study shows that there was no statistically significant correlation between tourniquet pressure, site and post-op pain in patients undergoing foot and ankle surgery. The choice of using a tourniquet is based on the surgeon's preference, with the goal of minimizing the duration of its application at the operative site.
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Metal-air batteries can play a crucial role in curbing air pollution due to carbon emission. Here, we report the hydrothermally synthesized bimetal oxides (NiFe2O4 and CoFe2O4) and their hybrid nanostructures with MoSe2 as potential electrocatalysts for electrically rechargeable Zn-air batteries. The NiFe2O4-MoSe2 hybrid nanostructure exhibits the best electrocatalytic activity (overpotential η10 ≈ 218 mV and Tafel slope ≈ 37 mV dec-1) for the OER study among prepared electrocatalysts in 1 M KOH electrolyte. Among the designed rechargeable Zn-air batteries, hybrid nanostructure-based batteries show superior performance, with the NiFe2O4-MoSe2 based device showing the best performance, having a high open-circuit voltage of â¼1.43 V, a peak power density of â¼176 mW cm-2, a specific capacity of â¼1025 mAh gZn-1, and an energy density of â¼1205 Wh kgZn-1. The superior performance of the hybrid nanostructures is due to the synergistic effect between MoSe2 and bimetal oxides, which enhances the conductivity, oxygen mobility, and active sites of the catalysts.
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Cutaneous leishmaniasis is a parasitic skin disease prevalent in many parts of the world. Zinc has been investigated for its potential role in the immune response against Leishmania parasites. This study aimed to systematically review the literature and conduct meta-analyses to evaluate the serum zinc level and efficacy of zinc therapy in cutaneous leishmaniasis. A comprehensive search of electronic databases was performed to find studies reporting serum zinc levels and the efficacy of zinc therapy in cutaneous leishmaniasis. Meta-analyses were conducted using RevMan software (version 5.4), calculating the mean difference for serum zinc levels and risk ratio for the efficacy of zinc therapy. A total of 11 studies with 1009 participants were evaluated. Five of these studies, comprising 637 participants, examined serum zinc levels; the remaining six, involving 372 individuals, examined the effectiveness of zinc therapy in treating cutaneous leishmaniasis. The results showed that the serum zinc level was significantly lower in cutaneous leishmaniasis patients compared to controls (MD: - 26.65; 95% CI: [- 42.74, - 10.57]; p = 0.001). However, zinc therapy did not demonstrate a significant clinical improvement compared to standard treatment (RR: 0.96; 95% CI: [0.74, 1.23], p = 0.73).
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Leishmaniasis Cutánea , Zinc , Humanos , Zinc/uso terapéutico , Leishmaniasis Cutánea/tratamiento farmacológicoRESUMEN
Context: Previous research has shown the vast benefits associated with BhP. However, the dynamics of cortical activity in connection with Bhramari sound have not been investigated yet. Aim: To investigate the cortical activity in connection with Bhramari sound. Settings and Design: Humming sound was analyzed with a custom-made nasal device consisting of MAX4466 sensor time synchronized with the EEG setup. We anticipated that the modulation of cortical activity with the humming sound (either of long or short durations) leaves its effects after the Pranayama, which helps to understand the positive impacts of BhP. Methods and Material: 30 participants were instructed to perform the BhP for a period of 90 seconds. We proposed to investigate the cortical correlates before, during, and after the BhP through EEG. A custom-made nasal device consisting of MAX4466 sensor time synchronized with the EEG setup was used for analyzing the humming sound. Statistical Analysis Used: A paired t-test (P < 0.05) with a Bonferroni correction is carried out to explore the statistically significant difference in power spectral density (PSD) values. Results: Results show that the relative spectral power in theta band for short humming durations (less than or equal to 9 seconds) was similar on the frontal cortex during and after the Pranayama practice (P > 0.05) in most of the subjects. Conclusions: In conclusion, for the immediate positive effects of BhP, the humming duration should be kept less than or equal to 9 seconds. A wearable sound recording system can be developed in the future as a feedback system that provides biofeedback to the user so that a constant humming duration can be maintained.
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The focus of this paper revolves around the examination of flow of ternary hybrid nanofluid, specifically the Al2O3-Cu-CNT/water mixture, with buoyancy effect, across three distinct geometries: a wedge, a flat plate, and a cone. The study takes into account the presence of quadratic thermal radiation and heat source/sink of non-uniform nature. To develop the model, the Cattaneo-Christov theory is utilized. The equations governing the flow are solved by applying similarity transformations and employing the "bvp4c function in MATLAB" for numerical analysis and solution. Conventional methods for conducting parametric studies often face challenges in producing significant conclusions owing to the inherent complex form of the model and the method involved. To address the aforementioned issue, this paper explores the potential of machine learning methods to foresee the conduct of the flow characterized by multiple interconnected parameters. By utilizing simulated data, an artificial neural network is trained using the Levenberg-Marquardt algorithm to learn and comprehend the underlying patterns. Subsequently, the trained neural network is employed to estimate the Nusselt number on the surfaces of all three geometries. This approach offers a promising alternative to traditional parametric studies, enabling more precise predictions and insights into the behavior of complex systems. The Nusselt number is highest for THNF flow over the cone. The mean squared error (MSE) values for the ANN algorithm, across all analyzed cases, range from 0 to 0.03972. The findings contribute to an improved understanding of the characteristics and dynamics of ternary hybrid nanofluid flow in various geometries, assisting in the design and optimization of heat transfer systems involving such fluids.
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Surface-enhanced Raman scattering (SERS) has attracted extensive attention for its rapid, ultra-sensitive, non-destructive and label-free fingerprint detection of trace molecules. Recently, two-dimensional transition metal dichalcogenides have been investigated as SERS substrates owing to their low cost, simple synthesis, excellent optical behavior, tunable bandgap, high carrier mobility and good biocompatibility. Here, we have synthesized 2H-MoS2 nanostructures of different morphologies (vertically and horizontally oriented) via the chemical vapor deposition (CVD) method on different substrates (FTO-coated glass, Si and SiO2-Si) and utilized them as SERS substrates for the detection of bilirubin and vitamin B12 biomolecules. The strong vibronic coupling within the charge transfer (CT) process leads to photo-induced charge transfer (PICT) resonance, showing enhanced SERS activity. This CT mechanism is further confirmed by observing quenching of the room temperature PL spectra and enhanced SERS signals of biomolecules over SERS substrates. To the best of our knowledge, the detection limit in this work (10-11 M for bilirubin and 10-8 M for vitamin B12) is considerably higher than previously reported values. The improved efficiency of the PICT process can be achieved at low temperature, and this is confirmed when performing low temperature-dependent photoluminescence (PL) studies on SERS substrates. Furthermore, we also demonstrated enhanced SERS activity at low temperature on CVD-grown pristine MoS2 films over different substrates for biomolecule detection for the first time, attributing this activity to the enhanced PICT process at low temperature.
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Intestinal malrotation is primarily a surgical condition of neonates due to abnormal intestinal rotation during fetal development. Usually, the presentation is immediately after birth. Adult midgut malrotation is rare and primarily detected at laparotomy or incidental radiological imaging for various conditions. We report a sporadic case of a 35-year-old male who presented to the surgical outpatient department (OPD) complaining of dull aching abdominal pain after taking meals for two months. He was able to tolerate a liquid diet only and able to carry out his routine work comfortably. In imaging studies, it was found to be a case of midgut malrotation with volvulus and superior mesenteric artery (SMA) thrombosis with collaterals without features of intestinal obstruction. The patient underwent diagnostic laparoscopy, and a midgut volvulus was identified with Ladd's bands. He underwent exploratory laparotomy with Ladd's procedure. Postoperatively symptoms were resolved, and the patient was discharged in stable condition. If intestinal malrotation presents in adults, it is challenging to diagnose it as it presents with atypical symptoms like chronic vague abdominal pain and weight loss. Often radiological correlation is essential to diagnose such patients. For surgical intervention, a laparoscopic approach is considered better in expert hands. Even though the disease has a chronic course, a high index of suspicion should arise when treating such cases of intestinal malrotation in an adult male. Timely surgery can do miracles and prevent catastrophic complications.
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Introduction: Acute Myocardial injury defined by increased troponin I level is associated with poor in-hospital outcomes and cardiovascular complications in patients with COVID-19. The current study was designed to determine the implications and clinical outcome of myocardial injury in COVID-19. Methods: This retrospective study included hospitalized COVID-19 patients. Myocardial injury was defined by high sensitivity Troponin I (hs-TNI)≥26ng/l. Cardiac biomarkers, inflammatory markers and clinical data were systemically collected and analyzed. Hazard ratio for in-hospital mortality and logistic regression for predictors of acute myocardial injury were analyzed. Results: Of the 1821 total patients with COVID-19, 293(16.09%) patients died and 1528 (83.91%) patients survived. Patients who died had significantly higher association with presence of cardiovascular risk factors, severe CTSS ( CT severity score ) and myocardial injury as compared to survived group. 628 (34.5%) patients had evidence of myocardial injury and they had statistically significant association with cardiovascular risk factors, in-hospital mortality, procalcitonin; higher hospital, and ICCU stay. We found significant hazard ratio of diabetes (HR=2.66, (CI:1.65-4.29)), Severe CT score (HR=2.81, (CI:1.74-4.52)), hs-TNI≥26 ng/l (HR=4.68, (CI:3.81-5.76)) for mortality. Severe CTSS score (OR=1.95, CI: 1.18-3.23, P=0.01) and prior CVD history (OR=1.65, CI:1.00-2.73, P=0.05) were found significant predictors of myocardial injury in regression analysis. Conclusion: Almost one third of hospitalized patients had evidence of acute myocardial injury during hospitalization. Acute myocardial injury is associated with higher hospital and ICCU stay, mortality, higher in-hospital infection which indicates more severe disease and the poor in-hospital outcomes.
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The effect of interleukin-6 (IL-6) supplementation during the different phases of in vitro embryo culturing (IVC) on embryo development and embryonic gene expression was studied in ovine. IL-6 was added to IVC medium during the late phases (72-192â¯h; 5, 10, and 25â¯ng/ml IL-6) or entire period (0-192â¯h; 10â¯ng/ml IL-6) of IVC to determine its effect on embryo development. Further, the effect of IL-6 (10â¯ng/ml) supplementation at the 72â¯h of IVC on gene expressions associated with JAK/STAT signalling and pluripotency in 8-16 cell embryos (1â¯h post-supplementation) and compact morulae (48â¯h post-supplementation), and apoptosis and primitive endoderm (PrE) development in compact morulae was investigated. The supplementation of 10â¯ng/ml IL-6 during the late phases of IVC significantly (Pâ¯<â¯0.05) increased blastocyst formation (35.2⯱â¯1.52%) compared to the control (21.1⯱â¯1.11%), and 5â¯ng/ml (25.9⯱â¯2.98%) or 25â¯ng/ml (16.5⯱â¯0.73%) IL-6 groups. Conversely, IL-6 (10â¯ng/ml) treatment throughout the IVC period significantly (Pâ¯<â¯0.05) decreased the rate of cleavage (55.4⯱â¯1.57%) and blastocyst formation (14.5⯱â¯1.28%) compared to the control group (65.8⯱â¯1.35% and 21.5⯱â¯0.97%, respectively). In 8-16 cell embryos and compact morulae, the IL-6 treatment significantly (Pâ¯<â¯0.05) affected the expression of genes associated with JAK/STAT signalling and pluripotency. Further, the treatment significantly (Pâ¯<â¯0.05) downregulated BAX and CASP3, and upregulated GATA6 expression in compact morulae. In conclusion, IL-6 supplementation affected the in vitro development of ovine embryos in a dose- and time-dependent manner. The beneficial effect of IL-6 on the development of late-stage embryos was mediated through the changes in gene expressions associated with JAK/STAT signalling, pluripotency, apoptosis and PrE development.
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Apoptosis , Interleucina-6 , Humanos , Ovinos , Animales , Desarrollo Embrionario , Transducción de SeñalRESUMEN
BACKGROUND: Breast cancer is one of the most common types of cancer among women worldwide, and its metastasis is a significant cause of mortality. Therefore, identifying potential inhibitors of proteins involved in breast cancer metastasis is crucial for developing effective therapies. BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is a key regulator of mitotic checkpoint control, which ensures the proper segregation of chromosomes during cell division. Dysregulation of BUB1B has been linked to a variety of human diseases, including breast cancer. Overexpression of BUB1B has been observed in various cancer types, and its inhibition has been shown to induce cancer cell death. Additionally, BUB1B inhibition has been suggested as a potential strategy for overcoming resistance to chemotherapy and radiation therapy. Given the importance of BUB1B in regulating cell division and its potential as a therapeutic target, the development of BUB1B inhibitors has been the focus of intense research efforts. Despite these efforts, few small molecule inhibitors of BUB1B have been identified, highlighting the need for further research in this area. In this study, the authors aimed to identify potential inhibitors of BUB1B from mushroom bioactive compounds using computational methods, which could ultimately lead to the development of new treatments for breast cancer metastasis. METHODS: This study has incorporated 70 bioactive compounds (handpicked through literature mining) of distinct mushrooms that were considered and explored to identify a suitable drug candidate. Their absorption, distribution, metabolism and excretion (ADME) properties were obtained to predict the drug-likeness of these 70 mushroom compounds based on Lipinski's rule of 5 (RO5). Screening these bioactive compounds and subsequent molecular docking against BUB1B provided compounds with the best conformation-based binding affinity. The best two complexes, i.e., BUB1B-lepitaprocerin D and BUB1B-peptidoglycan, were subjected to molecular dynamic simulations. Both complexes were assessed for their affinity, stability, and flexibility in protein-ligand complex systems. RESULTS: The molecular dynamic (MD) simulation studies revealed that lepitaprocerin D has an energetically favorable binding affinity with BUB1B. Results showed that the formation of a hydrogen bond between residues ASN123 and SER157, and lepitaprocerin D had strengthened the affinity of lepitaprocerin D with BUB1B. CONCLUSIONS: This study identified lepitaprocerin D as a potential and novel inhibitor for BUB1B that could be a plausible drug candidate for identifying and controlling the spread of breast cancer metastasis.
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Thermal transport and exciton dynamics of semiconducting transition metal dichalcogenides (TMDCs) play an immense role in next-generation electronic, photonic, and thermoelectric devices. In this work, we synthesize distinct morphologies (snow-like and hexagonal) of a trilayer MoSe2 film over the SiO2/Si substrate via the chemical vapor deposition (CVD) method and investigated their morphological dependent exciton dynamics and thermal transport behaviour for the first time to the best of our knowledge. Firstly, we studied the role of spin-orbit and interlayer couplings both theoretically as well as experimentally via first-principles density functional theory and photoluminescence study, respectively. Further, we demonstrate morphological dependent thermal sensitive exciton response at low temperatures (93-300 K), showing more dominant defect-bound excitons (EL) in snow-like MoSe2 compared to hexagonal morphology. We also examined the morphological-dependent phonon confinement and thermal transport behaviour using the optothermal Raman spectroscopy technique. To provide insights into the nonlinear temperature-dependent phonon anharmonicity, a semi-quantitative model comprising volume and temperature effects was used, divulging the dominance of three-phonon (four-phonon) scattering processes for thermal transport in hexagonal (snow-like) MoSe2. The morphological impact on thermal conductivity (ks) of MoSe2 has also been examined here by performing the optothermal Raman spectroscopy, showing ks â¼ 36 ± 6 W m-1 K-1 for snow-like and â¼41 ± 7 W m-1 K-1 for hexagonal MoSe2. Our research will contribute to the understanding of thermal transport behaviour in different morphologies of semiconducting MoSe2, finding suitability for next-generation optoelectronic devices.
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Cancer is one of the deadliest diseases developed through tumorigenesis and could be fatal if it reaches the metastatic phase. The novelty of the present investigation is to explore the prognostic biomarkers in hepatocellular carcinoma (HCC) that could develop glioblastoma multiforme (GBM) due to metastasis. The analysis was conducted using RNA-seq datasets for both HCC (PRJNA494560 and PRJNA347513) and GBM (PRJNA494560 and PRJNA414787) from Gene Expression Omnibus (GEO). This study identified 13 hub genes found to be overexpressed in both GBM and HCC. A promoter methylation study showed these genes to be hypomethylated. Validation through genetic alteration and missense mutations resulted in chromosomal instability, leading to improper chromosome segregation, causing aneuploidy. A 13-gene predictive model was obtained and validated using a KM plot. These hub genes could be prognostic biomarkers and potential therapeutic targets, inhibition of which could suppress tumorigenesis and metastasis.