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Introduction: Seroma formation following inguinal hernia surgery is a significant concern, causing considerable morbidity for patients. It can lead to prolonged hospital stays and, most devastatingly, mesh infection. Every effort should be made to reduce seroma formation, and newer techniques are being advocated to address this issue. Aim: To assess the role of pseudosac fixation during Totally Extraperitoneal (TEP) repair for direct inguinal hernia in relation to postoperative seroma formation. Materials and Methods: The present single-blinded randomised controlled study was conducted in the Department of Surgery, ABVIMS and Dr. Ram Manohar Lohia Hospital, New Delhi, India, from June 2019 to May 2021. A total of 60 patients (group A: 30 patients with pseudosac fixation; group B: 30 patients without pseudosac fixation) aged 18 years and above, presenting with direct inguinal hernia, were included. All patients underwent TEP repair. Seroma formation, postoperative pain and early recurrence were assessed in the postoperative period. Statistical analysis were performed using the Statistical Package for Social Sciences (SPSS) version 22.0. Fisher’s exact test and t-tests were employed, with a p-value of

Abstract The present study comprehensively investigated the fermentation process of fresh dates pulp to alcoholic beverage, analyzing various aspects including physicochemical properties, nutraceutical potential, amino acid composition, color properties, sensory evaluation, and microbial load. Over the fermentation period, the alcohol content of the beverage reached 8.79%, suggesting it is an off-dry wine. Total Soluble Solids (TSS) decreased from an initial 24.17°Brix to 5°Brix. The pH level dropped from 7 to 3.9, and the titratable acidity increased from 0.15 to 0.22%. The nutraceutical potential of the alcoholic beverage displayed dynamic transformations, with total phenolic content (TPC) decreasing from 23 to 9 mg GAE mL−1, while total flavonoid content (TFC) increased significantly (p 0.05) between the alcoholic beverage and juice in terms of color, but the alcoholic beverage scored higher in appearance, flavor, texture, taste, mouthfeel, and overall acceptability.Microbial load increased from an initial 5–6 log CFU mL−1 to 8–9 log CFU mL−1 after 5 days, indicating the occurrence of alcoholic fermentation. Kinetics study was also performed for different quality parameters. This is the first study provides a comprehensive understanding of the multifaceted changes occurring during the fermentation process, offering valuable insights for winemakers and researchers. Graphical Abstract

Abstract Freezing of gait (FOG) is a debilitating problem that markedly impairs the mobility and independence of 38-65% of people with Parkinson’s disease. During a FOG episode, patients report that their feet are suddenly and inexplicably “glued” to the floor. The lack of a widely applicable, objective FOG detection method obstructs research and treatment. To address this problem, we organized a 3-month machine-learning contest, inviting experts from around the world to develop wearable sensor-based FOG detection algorithms. 1,379 teams from 83 countries submitted 24,862 solutions. The winning solutions demonstrated high accuracy, high specificity, and good precision in FOG detection, with strong correlations to gold-standard references. When applied to continuous 24/7 data, the solutions revealed previously unobserved patterns in daily living FOG occurrences. This successful endeavor underscores the potential of machine learning contests to rapidly engage AI experts in addressing critical medical challenges and provides a promising means for objective FOG quantification.

This study examines the heat and mass transfer aspects of the natural convective flow of a nanofluid along a vertical flat surface, incorporating electrified nanoparticles and electric Reynolds number. While conventional nanofluid models like Buongiorno’s model overlook the nanoparticle electrification and electric Reynolds number mechanisms, this study addresses the nanoparticle electrification and electric Reynolds number mechanisms by justifying its relevance, particularly when tribo-electrification results from Brownian motion. This incorporation of the electric Reynold number and nanoparticle electrification mechanism is a unique aspect of this investigation. Using the similarity method and nondimensionalization, the governing partial differential equations of the flow are transformed into a set of locally similar equations. MATLAB's bvp4c solver is employed to solve this set of equations, along with the boundary conditions. The obtained results are validated by comparison with those from previously published works. Graphical representations are provided for the numerical outcomes of non-dimensional velocity, concentration and temperature concerning the nanoparticle electrification parameter and electric Reynolds number. The combined effects of the nanoparticle electrification parameter and the electric Reynolds number on non-dimensional heat and mass transfer coefficients are examined in tabular form. Furthermore, the impact of the nanoparticle electrification parameter on both heat and mass transfer for varying values of the Brownian motion parameter is explored graphically. The primary finding of this investigation indicates that the electrification mechanism of nanoparticles quickens the transfer of heat and mass from a flat surface to nanofluid, suggesting promising prospects for utilization in cooling systems and biomedical applications.

Abstract Cell stiffness is regulated by dynamic interaction between ras-related C3 botulinum toxin substrate 1 (Rac1) and p21 protein-activated kinase 1 (PAK1) proteins, besides other biochemical and molecular regulators. In this study, we investigated how the Placental Growth Factor (PlGF) changes endometrial mechanics by modifying the actin cytoskeleton at the maternal interface. We explored the global effects of PlGF in endometrial stromal cells (EnSCs) using the concerted approach of proteomics, atomic force microscopy (AFM), and electrical impedance spectroscopy (EIS). Proteomic analysis shows PlGF upregulated RhoGTPases activating proteins and extracellular matrix organization-associated proteins in EnSCs. Rac1 and PAK1 transcript levels, activity, and actin polymerization were significantly increased with PlGF treatment. AFM further revealed an increase in cell stiffness with PlGF treatment. The additive effect of PlGF on actin polymerization was suppressed with siRNA-mediated inhibition of Rac1, PAK1, and WAVE2. Interestingly, the increase in cell stiffness by PlGF treatment was pharmacologically reversed with pravastatin, resulting in improved trophoblast cell invasion. Taken together, aberrant PlGF levels in the endometrium can contribute to an altered pre-pregnancy maternal microenvironment and offer a unifying explanation for the pathological changes observed in conditions such as pre-eclampsia (PE).

ABSTRACT Respiratory tract infections are the most common triggers for heart failure in elderly people. The healthy respiratory commensal microbiota can prevent invasion by infectious pathogens and decrease the risk of respiratory tract infections. However, upper respiratory tract (URT) microbiome in the elderly is not well understood. To comprehend the profiles of URT microbiota in the elderly, and the link between the microbiome and heart failure, we investigated the oropharyngeal (OP) microbiome of these populations in Heilongjiang Province, located in the North-East of China, a high-latitude and cold area with a high prevalence of respiratory tract infection and heart failure. Taxonomy-based analysis showed that six dominant phyla were represented in the OP microbial profiles. Compared with young adults, the OP in the elderly exhibited a significantly different microbial community, mainly characterized by highly prevalent Streptococcus, unidentified_Saccharibacteria, Veillonella, unidentified_Pre votellaceae, and Neisseria. While unidentified_Prevotellaceae dominated in the young OP microbiome. There was competition for niche dominance between Streptococcus and member of Prevotellaceae in the OP. Correlation analysis revealed that the abundance of unidentified_Saccharibacteria was positive, while Streptococcus was negatively correlated to age among healthy elderly. The bacterial structure and abundance in the elderly with heart failure were much like healthy controls. Certain changes in microbial diversity indicated the potential OP microbial disorder in heart failure patients. These results presented here identify the respiratory tract core microbiota in high latitude and cold regions, and reveal the robustness of OP microbiome in the aged, supplying the basis for microbiome-targeted interventions.IMPORTANCETo date, we still lack available data on the oropharyngeal (OP) microbial communities in healthy populations, especially the elderly, in high latitude and cold regions. A better understanding of the significantly changed respiratory tract microbiota in aging can provide greater insight into characteristics of longevity and age-related diseases. In addition, determining the relationship between heart failure and OP microbiome may provide novel prevention and therapeutic strategies. Here, we compared OP microbiome in different age groups and elderly people with or without heart failure in northeastern China. We found that OP microbial communities are strongly linked to healthy aging. And the disease status of heart failure was not a powerful factor affecting OP microbiome. The findings may provide basic data to reveal respiratory bacterial signatures of individuals in a cold geographic region.

Water contamination is a global concern as a result of growing industrialization and urbanization. Dye waste produced by numerous industries pollutes the water, so dye-based wastewater is a major alarm for animals, human health, and the environment. The elimination of these dye contaminants from water supplies is currently critical and significant due to the dyes' toxicity on humans, livestock, and plants. To remove/degrade dyes, various methods have been investigated, including extraction, absorption, membrane separation, coagulation, adsorption, biological treatment, and advanced oxidation process (AOPs). Graphitic carbon nitride (g-C3N4), a captivating formed polymer, has been transformed as an intriguing issue in AOP science because of its metal-free advantages and its high sensitivity to light. Accordingly, when AOPs are joined with g-C3N4, superb dye degradation has occurred. This paper overviewed the g-C3N4-based AOPs are discussed for dye removal. The synergist effectiveness and mechanisms behind catalytic activity of g-C3N4-based catalysts are broadly discussed. In the meantime, the impacts of pH, water temperature, dissolved oxygen, initial dye concentration, catalyst dosage, and scavengers on the reaction carried out by g-C3N4-based catalysts are illustrated.

The present study endeavours to substantially contribute towards alleviating the global water scarcity problem. The task entailed designing a computational model of a renewable energy-based evaporator. Using ANSYS Fluent, the CFD simulations of a three-dimensional conventional continuous single slope, single basin solar still were carried out in summer at 23.79°N, 86.43°E coordinates. With the optimized inclination condensation angle of 29° and water depth at 1 cm, the solar still recorded the highest hourly drinking water, about 1.5 kg m−2, at 11:00 h. The continuous production resulted in a water collection rate of 8.6 kg m−2 day −1, encompassing the production of all previous models. Additionally, compared with the literature correlation for solar still simulated mass, the Power model calculation was the closest, with a 12.4% variation. Furthermore, the study showcases that CFD is an economical, efficient, and easily diagnosable technique for designing solar stills.

Sharing accurate and lossless images with higher quality through digital mediums is challenging, particularly, images shared on social media platforms can serve as good carriers for sending hidden data. However, social media platforms apply severe compression when transferring images end-to-end to serve efficient network transporting bandwidth and provide enough storage space to the users. Within the scope of this research, the proposed method introduces a novel approach by combining cryptographic and steganographic techniques, providing a robust solution to protect hidden data even when subjected to repeatedly compression. The method first encrypts the secret data to be hidden using the Advanced Encryption Standard Cipher Block Chaining (AES-CBC) technique. Then, data hiding is performed on the coefficients obtained by applying Discrete Cosine Transform (DCT) to repeatedly compressed JPEG images, coefficients that are minimally affected by compression or remain unaffected are specifically selected for data hiding. Therefore, secret data is extracted with high accuracy. Experimental results show that the proposed method outperforms the state-of-the-art in achieving robust and effective data hiding techniques based on bit error rate.

Background. Musculoskeletal diseases like osteoarthritis (OA) are widespread. OA affects the knees, makes the joints wear out and hurt, and makes it hard to move around. Body mass index (BMI) is a way to measure obesity, which is linked to a higher chance of getting OA and making it worse. The main aim of this cross-sectional study was to find out how body mass index (BMI) is related to how lousy knee osteoarthritis is. Methods. One hundred people at the Shri Guru Ram Rai Institute of Medical and Health Sciences in Dehradun met the study’s requirements and were enrolled. The Kellgren-Lawrence grading method was used to find the severity of knee osteoarthritis (OA), and standard measurements were used to calculate body mass index (BMI). A correlation study was done to examine the link between BMI and the severity of OA. Results. The sample included 100 participants on average of 60 years old. The typical knee OA symptoms lasted five years. A body mass index distribution analysis showed 35% obese, 40% overweight, and 25% underweight or average weight. Twenty percent of knee OA patients were mild, 35 percent intermediate, 30 percent severe, and 15 percent progressed. The association investigation revealed a significant positive correlation between BMI and knee osteoarthritis severity (r = 0.65, p < 0.001). Conclusion. Our results show that being overweight can worsen knee OA, proving that people with this problem need to watch their weight. If we treat obesity as a risk factor that can be changed, we might be able to improve the results of OA.

Introduction: Guselkumab is an interleukin 23p19 inhibitor, and the first in this group, to be approved by the US Food and Drug Administration (FDA) for the management of moderate to severe psoriasis. Apart from its utility in psoriasis, there are a number of other dermatologic conditions where guselkumab has demonstrated value. Objectives: The aim of this narrative review is to describe the utility of guselkumab in psoriasis as well as its implication in off-label dermatologic disorders. Methods: Pubmed, Google Scholar, Scopus and ResearchGate were searched for scholarly articles related to guselkumab and its utility in dermatology using the search terms “Guselkumab” AND “Psoriasis” AND “other dermatological disorders”. Results: Guselkumab is a valuable biologic agent for the management of psoriasis and psoriatic arthropathy. It has also been used successfully for other dermatologic disorders like hidradenitis suppurativa, lichen planus, pityriasis rubra pilaris and pyoderma gangrenosum. Recently, its utility in Stewart-Treves angiosarcoma (STA) has been exemplified. Conclusion: Guselkumab’s usage is not limited to psoriasis. Its benefit extends to many more dermatologic conditions. Its utility in STA could open an avenue for its application in the field of oncology. Furthermore, it has an acceptable safety profile.

Background Baseline anemia is associated with poor intracerebral hemorrhage (ICH) outcomes. However, underlying drivers for anemia and whether anemia development after ICH impacts clinical outcomes are unknown. We hypothesized that inflammation drives anemia development after ICH and assessed their relationship to outcomes. Methods and Results Patients with serial hemoglobin and iron biomarker concentrations from the HIDEF (High‐Dose Deferoxamine in Intracerebral Hemorrhage) trial were analyzed. Adjusted linear mixed models assessed laboratory changes over time. Of 42 patients, significant decrements in hemoglobin occurred with anemia increasing from 19% to 45% by day 5. Anemia of inflammation iron biomarker criteria was met in 88%. A separate cohort of 521 patients with ICH with more granular serial hemoglobin and long‐term neurological outcome data was also investigated. Separate regression models assessed whether (1) systemic inflammatory response syndrome (SIRS) scores related to hemoglobin changes over time and (2) hemoglobin changes related to poor 90‐day outcome. In this cohort, anemia prevalence increased from 30% to 71% within 2 days of admission yet persisted beyond this time. Elevated systemic inflammatory response syndrome was associated with greater hemoglobin decrements over time (adjusted parameter estimate: −0.27 [95% CI, −0.37 to −0.17]) and greater hemoglobin decrements were associated with poor outcomes (adjusted odds ratio per 1 g/dL increase, 0.76 [95% CI, 0.62–0.93]) independent to inflammation and ICH severity. Conclusions We identified novel findings that acute anemia development after ICH is common, rapid, and related to inflammation. Because anemia development is associated with poor outcomes, further work is required to clarify if anemia, or its underlying drivers, are modifiable treatment targets that can improve ICH outcomes. Registration https://www.clinicaltrials.gov Unique identifier: NCT01662895

Introduction: Indoor Air Pollution (IAP) is a serious problem, especially in enclosed environments where humans are present for a long period. Similar enclosed environments can be seen in educational Institutions, where employees and students spend much of their time. The objective of this research is to assess the Indoor Air Quality (IAQ) of engineering Institute's laboratories. Materials and methods: The sample of Indoor Air Pollutants (IAPs) such as Particulate Matters (PM1.0, PM2.5, PM10), Total Volatile Organic Compounds (TVOC), Formaldehyde (HCHO), and Carbon dioxide (CO2) were obtained by using a portable air quality meter from 12 different laboratories during July 2021 to September 2021 from 10:00 to 17:00. The statistical analysis was performed to interpret the outcomes. Results: As a result, the higher concentration of PM1.0, PM2.5, PM10, TVOC, HCHO, and CO2 was observed in ML11, ML2, ML12, ML5 and ML4. The correlation analysis shows that all laboratories, with the exception of ML4, ML5, ML9, and ML11, show good positive correlation for Particulate Matter (PM) of all sizes (R2>0.90). Additionally, ML6 and ML9 exhibited a strong positive association (R2 >0.78) for TVOC, ML4 and ML8 for HCHO (R2>0.68), and ML3 and ML10 for CO2(R2>0.66). In addition, cluster analysis was performed on the datasets to group them into similar source categories. As a result, 3, 2, 2, 4, 3, and 3 clusters for PM1.0, PM2.5, PM10, TVOC, HCHO, and CO2 are extracted. Conclusion: Overall, it appears that the presence of IAPs is caused by nearby outdoor activities, sweeping and dusting, wood furniture, paints, and poor ventilation in laboratories.

This review aims to examine the existence of Pseudomonas aeruginosa (P. aeruginosa) and their antibiotic resistance genes (ARGs) in aquatic settings and the alternative treatment ways. P. aeruginosa in a various aquatic environment have been identified as contaminants with impacts on human health and the environment. P. aeruginosa resistance to multiple antibiotics, such as sulfamethoxazole, ciprofloxacin, quinolone, trimethoprim, tetracycline, vancomycin, as well as specific antibiotic resistance genes including sul1, qnrs, blaVIM, blaTEM, blaCTX, blaAIM-1, tetA, ampC, blaVIM. The development of resistance can occur naturally, through mutations, or via horizontal gene transfer facilitated by sterilizing agents. In addition, an overview of the current knowledge on inactivation of Pseudomonas aeruginosa and ARG and the mechanisms of action of various disinfection processes in water and wastewater (UV chlorine processes, catalytic oxidation, Fenton reaction, and ozonation) is given. An overview of the effects of nanotechnology and the resulting wetlands is also given.

Purpose: The head and neck cancer (HNC) literature is rife with reports of differences in planned versus actual radiation doses to the parotid gland (PG) due to changes in anatomy during the course of radiation therapy. We prospectively studied and quantified changes in planned and delivered doses due to weight loss and changes in lateral neck dimensions. Methods and Materials: Sixty patients were enrolled in this prospective non-randomized observational study. The inclusion criterion was having a newly diagnosed, histologically proven squamous cell carcinoma of HNC. Weight loss (WL) and change in lateral neck dimensions (LND) were assessed weekly, and new hybrid plans were generated using interval replanning CT scans. Dose variations were monitored and extrapolated for replanning CT scans and correlated with WL and change in LND. Results: The Pearson correlation coefficients for WL and difference in Dmean of ipsilateral and contralateral PG was 0.3292 (P = .0124) and 0.4232 (P = .0010), respectively. There was significantly higher change in the Dmean of bilateral PG (Ipsilateral(I) > contralateral(C)) in patients who experienced WL of >5%. Change in LND correlated with difference in Dmean of ipsilateral PG at 0.4829 (P = .0001) and difference in D50 at 0.4146 (P < .0013). Contralateral PG correlated with difference in Dmean at 0.5952 (P < .0001). The difference in Dmean for ipsilateral PG was 1.8535 Gy for those showing reduction in LND of >1 cm compared with 0.8596 Gy (P = .0091) for those who had ≤1 cm reduction in LND. Conclusions: Either WL of >5% or reduction in LND of >1 cm can be used as an external parameter to help select patients who might benefit most from replanning and adaptive radiation therapy.

In today’s digital landscape, maintaining the integrity and ownership of digital content is crucial across various fields, including the critical domain of medical applications. However, existing watermarking techniques face significant challenges, such as vulnerability to attacks and limitations in capacity and robustness. To address these challenges, this work presents a novel hybrid reversible watermarking approach utilizing the Lucas number series (LNS), normalization, and squint ternary least significant bit (STLSB). Additionally, the method incorporates a lightweight encryption technique based on homomorphic binomial coefficients (LHBC) to encrypt watermark images. The encrypted image is then embedded into the cover image at the STLSB position, specifically three bits from the left-most significant bit, resulting in a watermarked image. The Present issues in watermarking medical data include ensuring the watermark’s robustness against attacks while maintaining data integrity and confidentiality, and balancing the need for traceability with the risk of compromising sensitive patient information. Experimental results show that the proposed method significantly improves embedding capacity by approximately 10% compared to existing techniques, achieving a PSNR of 52.0 dB, NCC of 1, SSIM of 0.9967, and consistently low BER, demonstrating enhanced robustness against various attacks, including JPEG compression, sharpening, resizing, and rotation. These findings highlight the method’s effectiveness for secure medical image watermarking applications, ensuring integrity and confidentiality, and extending to practical uses in digital asset management, copyright protection, and authentication systems across diverse industries.

With recent advances in technology protecting sensitive healthcare data is challenging. Particularly, one of the most serious issues with medical information security is protecting of medical content, such as the privacy of patients. As medical information becomes more widely available, security measures must be established to protect confidentiality, integrity, and availability. Image steganography was recently proposed as an extra data protection mechanism for medical records. This paper describes a data-hiding approach for DICOM medical pictures. To ensure secrecy, we use Adversarial Neural Cryptography with SHA-256 (ANC-SHA-256) to encrypt and conceal the RGB patient picture within the medical image’s Region of Non-Interest (RONI). To ensure anonymity, we use ANC-SHA-256 to encrypt the RGB patient image before embedding. We employ a secure hash method with 256bit (SHA-256) to produce a digital signature from the information linked to the DICOM file to validate the authenticity and integrity of medical pictures. Many tests were conducted to assess visual quality using diverse medical datasets, including MRI, CT, X-ray, and ultrasound cover pictures. The LFW dataset was chosen as a patient hidden picture. The proposed method performs well in visual quality measures including the PSNR average of 67.55, the NCC average of 0.9959, the SSIM average of 0.9887, the UQI average of 0.9859, and the APE average of 3.83. It outperforms the most current techniques in these visual quality measures (PSNR, MSE, and SSIM) across six medical assessment categories. Furthermore, the proposed method offers great visual quality while being resilient to physical adjustments, histogram analysis, and other geometrical threats such as cropping, rotation, and scaling. Finally, it is particularly efficient in telemedicine applications with high achieving security with a ratio of 99% during remote transmission of Electronic Patient Records (EPR) over the Internet, which safeguards the patient’s privacy and data integrity.

Rising urbanization necessitates robust air quality monitoring and prediction systems, particularly in developing nations like India, to mitigate adverse health impacts. Previous research primarily focused on machine learning algorithms for Air Quality Index (AQI) prediction and classification. We propose a novel MI-MMA-XGB which coupled features of multimodal imputer(MI) with the features of multi-modal autoencoder (MMA) and fed to an XGBoost(XGB) algorithm for AQI prediction and classification. Moreover, imputation approaches namely, KNN, MICE, and SVD were employed to address problems with null values and outliers. Furthermore, SMOTE is employed to balance the imputed data and then the model was trained on both balanced and unbalanced imputed data to extract predictive features. In this process, our model MI-MMA-XGB achieves significant accuracy, reaching 97.14% and 93.87% with and without SMOTE, respectively. Additionally, it attains an $R^{2}$ score of 0.9578 and an RMSE of 0.203 for AQI prediction in Indian cities. The proposed model outperforms baseline models in both classification and regression tasks across various evaluation metrics.

Introduction The propensity of nucleotide bases to form pairs, causes folding and the formation of secondary structure in the RNA. Therefore, purine (R): pyrimidine (Y) base-pairing is vital to maintain uniform lateral dimension in RNA secondary structure. Transversions or base substitutions between R and Y bases, are more detrimental to the stability of RNA secondary structure, than transitions derived from substitutions between A and G or C and T. The study of transversion and transition base substitutions is important to understand evolutionary mechanisms of RNA secondary structure in the 5′ and 3′ untranslated (UTR) regions of SARS-CoV-2. In this work, we carried out comparative analysis of transition and transversion base substitutions in the stem and loop regions of RNA secondary structure of SARS-CoV-2. Methods We have considered the experimentally determined and well documented stem and loop regions of 5′ and 3′ UTR regions of SARS-CoV-2 for base substitution analysis. The secondary structure comprising of stem and loop regions were visualized using the RNAfold web server. The GISAID repository was used to extract base sequence alignment of the UTR regions. Python scripts were developed for comparative analysis of transversion and transition frequencies in the stem and the loop regions. Results The results of base substitution analysis revealed a higher transition (ti) to transversion (tv) ratio (ti/tv) in the stem region of UTR of RNA secondary structure of SARS-CoV-2 reported during the early stage of the pandemic. The higher ti/tv ratio in the stem region suggested the influence of secondary structure in selecting the pattern of base substitutions. This differential pattern of ti/tv values between stem and loop regions was not observed among the Delta and Omicron variants that dominated the later stage of the pandemic. It is noteworthy that the ti/tv values in the stem and loop regions were similar among the later dominant Delta and Omicron variant strains which is to be investigated to understand the rapid evolution and global adaptation of SARS-CoV-2. Conclusion Our findings implicate the lower frequency of transversions than the transitions in the stem regions of UTRs of SARS-CoV-2. The RNA secondary structures are associated with replication, translation, and packaging, further investigations are needed to understand these base substitutions across different variants of SARS-CoV-2.

The discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) technology has revolutionized field of cancer treatment. This review explores usage of CRISPR/Cas9 for editing and investigating genes involved in human carcinogenesis. It provides insights into the development of CRISPR as a genetic tool. Also, it explores recent developments and tools available in designing CRISPR/Cas9 systems for targeting oncogenic genes for cancer treatment. Further, we delve into an overview of cancer biology, highlighting key genetic alterations and signaling pathways whose deletion prevents malignancies. This fundamental knowledge enables a deeper understanding of how CRISPR/Cas9 can be tailored to address specific genetic aberrations and offer personalized therapeutic approaches. In this review, we showcase studies and preclinical trials that show the utility of CRISPR/Cas9 in disrupting oncogenic targets, modulating tumor microenvironment and increasing the efficiency of available anti treatments. It also provides insight into the use of CRISPR high throughput screens for cancer biomarker identifications and CRISPR based screening for drug discovery. In conclusion, this review offers an overview of exciting developments in engineering CRISPR/Cas9 therapeutics for cancer treatment and highlights the transformative potential of CRISPR for innovation and effective cancer treatments.

Objective: This article presents a study comparing the responses of two AI chatbots, ChatGPT and ChatSonic, regarding inquiries about epilepsy. Overall, ChatGPT and ChatSonic are very similar in terms of their capabilities and limitations and they are the most widely used AI software. However, there are some key differences, such as their training data, supported languages, and pricing model. The study aims to assess the potential application of AI in patient counseling and decision-making regarding epilepsy treatment. Methods: The study categorized the inquiries of patients about epilepsy into two groups: patient counseling and judgment. Ten questions were formulated within these categories. Two specialized doctors evaluated the reliability and accuracy of the chatbot replies using the Global Quality Scale (GQS) and a modified version of the DISCERN score. Results: The median value for GQS of 4.5 was given by Evaluator JC, and a median value for GQS of 4.0 was given by Evaluator VV. Furthermore, a median for RS of 5.0 was given by Evaluator JC, and a median for RS of 4.0 was given by Evaluator VV. The GQS data from Evaluators JC and VV have a Spearman correlation coefficient of -0.531, indicating an inversely proportional association, and a p-value of 0.016, indicating a statistically significant relationship between the variables. However, the correlation coefficient of RS between data by Evaluator JC and Evaluator VV is 0.368 which indicates the correlation is a directly proportional relationship, with a p-value of 0.110 which is not statistically significant, does not establish a relation between the variables. Weighted Kappa was used to study the agreement between the data. With a weighted kappa value of -0.318 and a 95 %CI of -0.570, -0.065 was obtained for GQS. This can help reject the null hypothesis indicating that the values by the Evaluator JC and Evaluator VV are statistically significant and has a negative agreement. However, a weighted kappa value of 0.1327 with a 95 %CI of -0.093, 0.359 obtained for RS, fails to reject the null hypothesis indicating that the values by the Evaluator JC and Evaluator VV are not significant and no agreement exists between the Evaluators. The results of this study suggest that both ChatGPT and ChatSonic have the potential to be valuable tools for epilepsy patients and their healthcare providers. However, it is important to note that the two evaluators had better agreement on the GQS scores than on the RS scores, suggesting that the GQS may be a more reliable measure of the quality of chatbot responses. Conclusion: The findings underscore the importance of collaboration among policymakers, healthcare professionals, and AI designers to ensure appropriate and safe utilization of AI chatbots in the healthcare domain. While AI chatbots can provide valuable information, it is crucial to acknowledge their limitations, including reliance on the training data and occasional factual errors. The study highlights the need for further testing and validation of AI language models in the management of epilepsy as it concludes.

In the digital age, where information is a cornerstone for decision-making, social media's not-so-regulated environment has intensified the prevalence of fake news, with significant implications for both individuals and societies. This study employs a bibliometric analysis of a large corpus of 9678 publications spanning 2013–2022 to scrutinize the evolution of fake news research, identifying leading authors, institutions, and nations. Three thematic clusters emerge: Disinformation in social media, COVID-19-induced infodemics, and techno-scientific advancements in auto-detection. This work introduces three novel contributions: 1) a pioneering mapping of fake news research to Sustainable Development Goals (SDGs), indicating its influence on areas like health (SDG 3), peace (SDG 16), and industry (SDG 9); 2) the utilization of Prominence percentile metrics to discern critical and economically prioritized research areas, such as misinformation and object detection in deep learning; and 3) an evaluation of generative AI's role in the propagation and realism of fake news, raising pressing ethical concerns. These contributions collectively provide a comprehensive overview of the current state and future trajectories of fake news research, offering valuable insights for academia, policymakers, and industry.

Background: Peyronie’s disease (PD) is a localized fibrosis of tunica albuginea, which causes the anatomical and functional changes to the penis. Corporoplasty with grafting is indicated in severe (>60°) and complex curvature. Buccal mucosa is the most favored autologous graft material nowadays. The ventrolateral aspect of lingual mucosa has similar histological features to the rest of the oral cavity. Methods: This study aimed to test the efficacy, safety, durability, and reproducibility of corporoplasty with lingual mucosal graft (LMG) in the surgical treatment of PD in terms of surgical outcome, sexual function, and donor site complications. This prospective study included 19 patients of PD with severe and complex curvature, who underwent corporoplasty with LMG. Surgical and functional outcomes were assessed at follow-up planned at 2 weeks, 3 months, 6 months, 1 year, and 2 years. Results: The mean operative time was 126.31 ± 21.45 min. Additional Nesbit’s plication to correct the residual deformity was required in 26% (5 / 19) of patients. Straightening of the penis (curvature 1 cm) postoperatively was achieved in 63% (12 / 19) of patients and a shortening of penis occurred in 5% (1 / 19) of patients. Newer onset erectile dysfunction developed in 11% (2 / 19) of patients, and patient and partner satisfaction rates were 89% (17 / 19) and 84% (16 / 19), respectively, in a mean follow-up of 20.66 ± 5.37 months. Donor site complications were minimal and no patient had any salivary changes or speech disturbances. Conclusion: LMG provided excellent short-term results in terms of deformity correction, improved sexual function, and minimal donor site morbidity. The method is simple and reproducible, and multicenter studies with larger number of cases with longer follow-up are required to confirm these favorable results.

Abstract Background Dexamethasone is a potent corticosteroid when comes to effectively preventing postoperative nausea and vomiting (PONV). However, some studies have documented its association with hyperglycemia. In our study, we compared the effect of single-dose dexamethasone (8 mg) on blood glucose concentrations among diabetics and non-diabetic patients who received spinal anesthesia for elective lower abdominal and lower limb surgeries. Results We recruited 80 patients and divided them into two groups of 40 patients each. After dexamethasone administration, diabetic patients had an early peak rise of blood glucose levels at 3 h, (157.85 ± 12.19) compared to 6 h, (125.30 ± 14.95) in non-diabetics. In diabetic patients, blood glucose levels remained consistently over the baseline and maximum rise was seen at 12 h (188.25 ± 41.33), which obviated the need or administration of injection insulin. Hyperglycemia can lead to a variety of physiological derangements. Conclusions Although dexamethasone is a useful means of successful prevention and treatment of PONV, the clinician should use his clinical judgment before administering dexamethasone. Trial registration CTRI, CTRI/2020/06/025765, Registered 02 June 2020, prospectively registered, http://ctri.nic.in/Clinicaltrials/login.php .

The use of nanotechnology in the field of construction emerged as the utilization of nanomaterials to improve the mechanical properties of concrete. In this study, a novel form of stiffening scheme was suggested, named a catty-cornered propped concrete-filled steel tube (CFST) column. The performance of the suggested stiffened CFST column was analyzed under axial compression. The steel tube of CFST specimens was filled with normal and nanomaterial-based concrete. The three kinds of nanomaterials were utilized viz., nano-silica (NS), carbon nanotubes (CNT), and nano-titanium dioxide (NT). The results of the investigation were collected in terms of ultimate capacity, load vs strain behavior, and load vs deformation response. The ductility index (DI), secant stiffness, composite interaction, and confining effect variation were also discussed further. It was observed that the suggested stiffening scheme was able to increase the ultimate capacity of unstiffened CFST by approximately 14%. The use of nanomaterials in CFST infill concrete also resulted in an approximately 7% increase in load capacity. Further increasing the number of stiffening bars improved the ductility and stiffness of the column section. On the other hand, the inclusion of nanomaterials resulted in a decrease in the ductility index and improved the stiffness of the section. The proposed stiffening scheme resulted in better composite interaction and increased confinement. It was also concluded that the utilization of nanomaterial-based concrete as an infill in the stiffened CFST column could enhance its performance under axial compression loading.

ABSTRACTEscherichia coli is a highly versatile microorganism with a unique ability to survive and persist in varied niches of the human and animal hosts and the environment. While commensal strains of E. coli play a crucial role in preserving and maintaining the balance and function of their community within the gut microflora, pathogenic strains are often implicated in a wide range of infections and outbreaks, posing a serious threat to public health systems. With the increasing burden of highly virulent and antimicrobial-resistant E. coli infections, it is imperative to understand the host-defense mechanisms of bacteria from all possible dimensions. Mobile genetic elements (MGE)-mediated acquisition of genetic material, chromosomal reduction, and genome optimization are three important events that play a significant role in bacterial evolution and enable them to survive in diverse environmental niches. Toxin-antitoxin (TA) systems are genetic elements that help in the maintenance of MGEs and are often associated with stress response phenotypes, including antimicrobial resistance. In this study, large-scale comparative genomics of 950 genomes spanning 19 different sequence types (STs) (eight phylogroups) revealed ST-wide prevalence patterns of TA systems with a median of 23 toxin groups per strain. Our analyses revealed significant genomic reduction in the members of phylogroup B2 (ST131, ST95, ST73, ST12, and ST127) and phylogroup C (ST410) as evident from a diminished toxin repertoire amidst abundant orphan antitoxins. Moreover, our observations also enabled crucial insights into the copy number of toxin groups, the genetic organization of TA operons, and their association with other genetic coordinates (antimicrobial resistance encoding genes/virulence genes/mobile genetic elements). By unraveling the association of the genetic coordinates/STs with the toxin groups, this study significantly boosts our understanding of the functional implications of TA systems in different evolutionary contexts entailing pathogenic Escherichia.IMPORTANCELarge-scale genomic studies of E. coli provide an invaluable opportunity to understand how genomic fine-tuning contributes to the transition of bacterial lifestyle from being commensals to mutualists or pathogens. Within this context, through machine learning-based studies, it appears that TA systems play an important role in the classification of high-risk clonal lineages and could be attributed to their epidemiological success. Due to these profound indications and assumptions, we attempted to provide unique insights into the ordered world of TA systems at the population level by investigating the diversity and evolutionary patterns of TA genes across 19 different STs of E. coli. Further in-depth analysis of ST-specific TA structures and associated genetic coordinates holds the potential to elucidate the functional implications of TA systems in bacterial cell survival and persistence, by and large.

Scrub typhus is a vector-borne infectious disease caused by Orientia tsutsugamushi and it is reportedly associated with up to 20 % of hospitalized cases of febrile illnesses. The major challenge of vaccine development is the lack of identified antigens that can induce both heterotypic and homotypic immunity including the production of antibodies, cytotoxic T lymphocyte, and helper T lymphocytes. We employed a comprehensive immunoinformatic prediction algorithm to identify immunogenic epitopes of the 56-kDa type-specific cell membrane surface antigen and surface cell antigen A of O. tsutsugamushi to select potential candidates for developing vaccines and diagnostic assays. We identified 35 linear and 29 continuous immunogenic B-cell epitopes and 51 and 27 strong-binding T-cell epitopes of major histocompatibility complex class I and class II molecules, respectively, in the conserved and variable regions of the 56-kDa type-specific surface antigen. The predicted B- and T-cell epitopes were used to develop immunogenic multi-epitope candidate vaccines and showed to elicit a broad-range of immune protection. A stable interactions between the multi-epitope vaccines and the host fibronectin protein were observed using docking and simulation methods. Molecular dynamics simulation studies demonstrated that the multi-epitope vaccine constructs and fibronectin docked models were stable during simulation time. Furthermore, the multi-epitope vaccine exhibited properties such as antigenicity, non-allergenicity and ability to induce interferon gamma production and had strong associations with their respective human leukocyte antigen alleles of world-wide population coverage. A correlation of immune simulations and the in-silico predicted immunogenic potential of multi-epitope vaccines implicate for further investigations to accelerate designing of epitope-based vaccine candidates and chimeric antigens for development of serological diagnostic assays for scrub typhus.

Category: Midfoot/Forefoot; Other Introduction/Purpose: The first tarsometatarsal (TMT) joint plays a crucial role in maintaining the stability of the midfoot and medial column. Disorders of this joint are associated with hallux valgus, hallux rigidus, flatfoot, Lisfranc injury and arthritis, and many others. It has been proven that there is a high variability in the morphology of the joint which may be related to joint stability thereby leading to certain deformities. Understanding the morphology of the articular surfaces comprising the joint is necessary. While prior studies have used XR and CT to analyze the joint[1], we present our work using 3D surface mapping to evaluate the cartilaginous articulation of the1st TMT joint. Methods: 22 fresh-frozen cadaveric feet without trauma nor surgery or significant deformities were dissected to expose the medial cuneiform (MeC) and 1st metatarsal (MT) bones, and the articular surfaces of the 1st TMT joint. Surface mapping of the articular surfaces and the two bones was completed using an Artec Space Spider 3D scanner and Mmics. Further digital analysis was completed using GeoMagic Studio 10. Results: Means and Standard Deviations (SDs) of the articular surface and the bone length were summarized in Table 1. The average articular area of the 1st TMT joint was 337.26 (±63.43) mm 2 on MeC, and 337.94 (±66.16) mm 2 on the 1st MT, with the length of the bones measured 25.50 (±2.56) mm for MeC and 63.93 (±4.22) mm for the 1st MT. There were statistically significant linear correlation between the articular-area and the length of the bone on both sides. 1 mm bone length increase was correlated with 11.48 mm 2 articular-area increase on MeC; and 10.33 mm 2 articular-area increase on 1st MT. (Figure 1,2) There were three types of morphologies of the 1st TMT joint (Type 1, with 2 facets linked to each other; Type 2, with 2 facets separated; Type 3, 1 large dorsal facet and two separate smaller facets inferiorly). The facet pattern is more obvious on the 1st MT than the MeC side. (Figure 3) Conclusion: Previous studies of the 1st TMT morphology were done using either direct manual measurements with descriptive reporting which does not reflect the exact contour of the joint, or XR/WBCT which cannot demonstrate the cartilaginous articulation. This study used a novel technique of surface mapping which overcame the above issues. The remodeled cartilaginous articular surfaces provide foundations for further comparison study, as well as integration of 3D surface mapping with weight- bearing CT analysis, which is currently under investigation by our research group. This will provide important information for diagnosis, surgical planning, and follow-up treatment for relevant disorders.

Category: Hindfoot; Ankle Introduction/Purpose: Recent studies have highlighted the important role of peritalar joint congruence in maintaining the alignment of the hindfoot. Peritalar subluxation is associated with a variety of pathological deformities including flatfoot, cavovarus foot, clubfoot, as well as foot and ankle stress fractures. To date, studies of peritalar joint congruence have all been performed using either XR, WBCT based direct measurements, or 3D segmentation and analysis. However, none of these techniques can demonstrate the cartilage location nor disruption, nor the exact location of the articulation on the bone surface. Data bias caused by the limitations of these study methodologies is therefore inevitable. This study used 3D surface mapping to assess morphometrics of the cartilage surfaces of the peritalar joints. Methods: 11 fresh-frozen cadaveric feet without trauma nor surgery or significant deformities were dissected to expose the calcaneus, cuboid, talus, and navicular bones, and the articular surfaces. Surface mapping of the articular surfaces and the two bones was completed using an Artec Space Spider 3D scanner and Mmics. Further digital analysis was completed using GeoMagic Studio 10. T-test was used for statistical comparisons, with p< 0.05 as statistically significantly different. Results: Detailed information of the articular surfaces is summarized in Table 1. The average articular area on both sides of the joint matched each other well in the posterior facet of the subtalar joint (4% difference), and calcaneocuboid joint (3% difference) without significant statistical difference, but not in the anterior & middle facets of the subtalar joint, nor the talonavicular joint. In the anterior & middle facets of the subtalar joint, the cartilage articular area on the talar side was 124% of that on the calcaneus (p < 0.05), and in the talonavicular joint the cartilage articular area on the navicular was 138% of that on the talus (p < 0.05). Conclusion: The cartilage articular surfaces in certain peritalar joints do not match its opposing surface in size. In the talonavicular joint, it is easy to understand since area of the socket must be much smaller than that of the ball in order for the joint to glide and rotate. There must be functional reasons for this phenomenon to happen in the anterior and middle facets of the subtalar joint, which need further investigation. This study shows that the extent of subluxation of the peritalar joints may be physiological and should not necessarily be considered as pathological.

Ehrlichia is Gram negative obligate intracellular bacterium that cause human monocytotropic ehrlichiosis (HME). HME is characterized by acute liver damage and inflammation that may progress to fatal toxic shock. We previously showed that fatal ehrlichiosis is due to deleterious activation of inflammasome pathways, which causes excessive inflammation and liver injury. Mammalian cells have developed mechanisms to control oxidative stress via regulation of nuclear factor erythroid 2 related 2 (NRF2) signaling. However, the contribution of NRF2 signaling to Ehrlichia-induced inflammasome activation and liver damage remains elusive. In this study, we investigated the contribution of NRF2 signaling in hepatocytes (HCs) to the pathogenesis of Ehrlichia-induced liver injury following infection with virulent Ixodes ovatus Ehrlichia (IOE, AKA E. japonica). Employing murine model of fatal ehrlichiosis, we found that virulent IOE inhibited NRF2 signaling in liver tissue of infected mice and in HCs as evidenced by downregulation of NRF2 expression, and downstream target GPX4, as well as decreased NRF2 nuclear translocation, a key step in NRF2 activation. This was associated with activation of non-canonical inflammasomes pathway marked by activation of caspase 11, accumulation of reactive oxygen species (ROS), mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. Mechanistically, treatment of IOE-infected HCs with the antioxidant 3H-1,2-Dithiole-3-Thione (D3T), that induces NRF2 activation, attenuated oxidative stress and caspase 11 activation, as well as restored cell viability. Importantly, treatment of IOE-infected mice with D3T resulted in attenuated liver pathology, decreased inflammation, enhanced bacterial clearance, prolonged survival, and resistance to fatal ehrlichiosis. Our study reveals, for the first time, that targeting anti-oxidative signaling pathway is a key approach in the treatment of severe and potential Ehrlichia-induced acute liver injury and sepsis.

Hepatocytes play a crucial role in host response to infection. Ehrlichia is an obligate intracellular bacterium that causes potentially life-threatening human monocytic ehrlichiosis (HME) characterized by an initial liver injury followed by sepsis and multi-organ failure. We previously showed that infection with highly virulent Ehrlichia japonica (E. japonica) induces liver damage and fatal ehrlichiosis in mice via deleterious MyD88-dependent activation of CASP11 and inhibition of autophagy in macrophage. While macrophages are major target cells for Ehrlichia, the role of hepatocytes (HCs) in ehrlichiosis remains unclear. We investigated here the role of MyD88 signaling in HCs during infection with E. japonica using primary cells from wild-type (WT) and MyD88-/- mice, along with pharmacologic inhibitors of MyD88 in a murine HC cell line. Similar to macrophages, MyD88 signaling in infected HCs led to deleterious CASP11 activation, cleavage of Gasdermin D, secretion of high mobility group box 1, IL-6 production, and inflammatory cell death, while controlling bacterial replication. Unlike macrophages, MyD88 signaling in Ehrlichia-infected HCs attenuated CASP1 activation but activated CASP3. Mechanistically, active CASP1/canonical inflammasome pathway negatively regulated the activation of CASP3 in infected MyD88-/- HCs. Further, MyD88 promoted autophagy induction in HCs, which was surprisingly associated with the activation of the mammalian target of rapamycin complex 1 (mTORC1), a known negative regulator of autophagy. Pharmacologic blocking mTORC1 activation in E. japonica-infected WT, but not infected MyD88-/- HCs, resulted in significant induction of autophagy, suggesting that MyD88 promotes autophagy during Ehrlichia infection not only in an mTORC1-indpenedent manner, but also abrogates mTORC1-mediated inhibition of autophagy in HCs. In conclusion, this study demonstrates that hepatocyte-specific regulation of autophagy and inflammasome pathway via MyD88 is distinct than MyD88 signaling in macrophages during fatal ehrlichiosis. Understanding hepatocyte-specific signaling is critical for the development of new therapeutics against liver-targeting pathogens such as Ehrlichia.

Zoonotic diseases, also referred to as zoonoses, are diseases that are transmitted from animals to humans [...]

Background: Polymorphous light eruption (PLE) is the most common idiopathic photodermatoses, with a wide range of clinical presentations that tends to mimic a number of dermatoses. Objective: The aim was to study the clinicopathological profile in patients diagnosed with PLE. Materials and Methods: This was a cross-sectional, descriptive study of seventy clinically diagnosed cases of PLE over a period of 1 year, wherein following patient enrolment, they underwent a thorough clinical evaluation, followed by a skin biopsy that was studied categorically. Results: A male preponderance (62.8%) was observed. Majority of patients were in the 21-30 years' age group (28.6%). Pruritus was witnessed in 98.5% of patients. The most common morphological type encountered was plaque PLE (35.7%), followed by lichen nitidus type (11.4%). Commonest site of involvement was sides and back of neck (75.7%), followed by dorsolateral aspect of both arms (31.4%). Hyperkeratosis was identified in 82.8%, spongiosis in 87.1%, liquefactive degeneration of basal cell layer in 82.8%, atrophy in 24.2%, and moderate-to-severe lymphocytic dermal infiltrates in 90% of our cohorts. Conclusion: PLE is a disorder with diverse clinical presentations, manifesting usually in the third decade of life that closely mimics a variety of other cutaneous disorders. Histological examination with certain specific criteria enables the clinician to arrive at a concrete conclusion in those cases where clinical findings alone pose diagnostic difficulties.

Abstract Archaea are a vast and unexplored cellular domain that thrive in a high diversity of environments, having central roles in processes mediating global carbon and nutrient fluxes. For these organisms to balance their metabolism, the appropriate regulation of their gene expression is essential. A key momentum in regulating genes responsible for the life maintenance of archaea is when transcription factor proteins bind to the promoter element. This DNA segment is conserved, which enables its exploration by machine learning techniques. Here, we trained and tested a support vector machine with 3935 known archaeal promoter sequences. All promoter sequences were coded into DNA Duplex Stability. After, we performed a model interpretation task to map the decision pattern of the classification procedure. We also used a dataset of known-promoter sequences for validation. Our results showed that an AT rich region around position − 27 upstream (relative to the start TSS) is the most conserved in the analyzed organisms. In addition, we were able to identify the BRE element (− 33), the PPE (at − 10) and a position at + 3, that provides a more understandable picture of how promoters are organized in all the archaeal organisms. Finally, we used the interpreted model to identify potential promoter sequences of 135 unannotated organisms, delivering regulatory regions annotation of archaea in a scale never accomplished before ( https://pcyt.unam.mx/gene-regulation/ ). We consider that this approach will be useful to understand how gene regulation is achieved in other organisms apart from the already established transcription factor binding sites.

Recent decades have seen dramatic development and adoption of digital technology. This technological advancement generates a large amount of critical data that must be safeguarded. The security of confidential data is one of the primary concerns in fog computing. As a result, achieving a reliable level of security in the fog computing environment is crucial. In this context, 3D point and mesh fog data are becoming increasingly popular among the various types of data stored in the fog. Data encryption using chaotic behavior is one of the preferred research areas due to its unique properties, such as randomness, determinism, sensitivity to initial conditions, and ergodicity. In this paper, we have taken advantage of this chaotic behavior to achieve higher security. This study presents a novel approach for protecting the privacy of 3D point and mesh fog data. Initially, the fog data coordinates are transformed using the sequence generated by the chaotic behavior. Then, bifurcation analysis is used to depict the enhanced scope of the proposed map. The quality of the proposed chaotic system is assessed using metrics such as the Lyapunov exponent and approximate entropy. Results show that the proposed encryption framework performs superior when subjected to brute-force and statistical attacks. Further, the designed framework produces better results than the prior literature.

This paper investigated the structural, optical, electronic and thermal characteristics of SrSnO3 perovskites that were calculated using the density functional theory. Software called WEIN2K is used to perform the calculation. According to our calculations, the band gap energy of the SrSnO3 is roughly 4.00 eV and it adopts a distorted cubic shape in the space group Pm3-m. The band structure and partial density of state reflects the major contribution of O 2p in the valence band while 5s orbital from Sn in the conduction band. The electron density plot significantly shows the contribution different clusters SrO12 and SnO6 that plays crucial role in electronic and optical properties. The creation of covalent bonds between the atoms of Sn and O as well as the ionic interaction between the atoms of Sr and O are both demonstrated by the electron density graphs and SCF calculation. The refractive index and extinction coefficient directly correlated with the real and imaginary part of complex dielectric function. Real part of dielectric function shows higher values at two major point of energy 3.54 eV and 9.78 eV associated with the absorption and optical activity of SrSnO3. Negative part of imaginary dielectric function part suggests metallic behavior also supported by -grep lapw method. Thermoelectric and thermal conductivity properties suggest the power factor need to be improved for the device application.

Abstract A novel local binary pattern‐based reversible data hiding (LBP‐RDH) technique has been suggested to maintain a fair symmetry between the perceptual transparency and hiding capacity. During embedding, the image is divided into various 3×3 blocks. Then, using the LBP‐based image descriptor, the LBP codes for each block are computed. Next, the obtained LBP codes are XORed with the embedding bits and are concealed in the respective blocks using the proposed pixel readjustment process. Further, each cover image (CI) pixel produces two different stego‐image pixels. Likewise, during extraction, the CI pixels are restored without the loss of a single bit of information. The outcome of the proposed technique with respect to perceptual transparency measures, such as peak signal‐to‐noise ratio and structural similarity index, is found to be superior to that of some of the recent and state‐of‐the‐art techniques. In addition, the proposed technique has shown excellent resilience to various stego‐attacks, such as pixel difference histogram as well as regular and singular analysis. Besides, the out‐off boundary pixel problem, which endures in most of the contemporary data hiding techniques, has been successfully addressed.

Renewable energy has gained enormous popularity in recent years. Both independent and grid-connected renewable energy generating capacity has increased. The potential to create green energy that is both ecologically benign and financially operative is the primary argument. To reduce the cost of maintaining a hybrid microgrid, this study provides a novel control algorithm as well as a suitable energy management system. The energy storage technologies are used in the hybrid microgrid system which consist of photovoltaic cell, fuel cell and supercapacitor. The optimal power flow in the hybrid microgrid component is developed using energy management system which consents control system to batteries, load and economic analysis with the input of electric grid. In this paper supercapacitor is which is directly connected to DC and provide fast response to load changing. DC voltage, current and hybrid microgrid is managed using the local control system. The power change in photovoltaic system is solved using energy storage system. The purpose of control method in hybrid microgrid is used to enhance the hybrid microgrid flexibility and generation of renewable resources and stored it in grid. The effectiveness and the flexibility of the proposed controller in energy management of hybrid microgrid system is simulated. The proposed energy management system provides high performance related to the existing energy management system.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have the potential to become powerful tools for disease modeling, drug testing, and transplantation; however, their immaturity limits their applications. Transcription factor (TF) overexpression can improve hPSC-CM maturity, but identifying these TFs has been elusive. Toward this, we establish here an experimental framework for systematic identification of maturation enhancing factors. Specifically, we performed temporal transcriptome RNAseq analyses of progressively matured hPSC-derived cardiomyocytes across 2D and 3D differentiation systems and further compared these bioengineered tissues to native fetal and adult-derived tissues. These analyses revealed 22 TFs whose expression did not increase in 2D differentiation systems but progressively increased in 3D culture systems and adult mature cell types. Individually overexpressing each of these TFs in immature hPSC-CMs identified five TFs (KLF15, ZBTB20, ESRRA, HOPX, and CAMTA2) as regulators of calcium handling, metabolic function, and hypertrophy. Notably, the combinatorial overexpression of KLF15, ESRRA, and HOPX improved all three maturation parameters simultaneously. Taken together, we introduce a new TF cocktail that can be used in solo or in conjunction with other strategies to improve hPSC-CM maturation and anticipate that our generalizable methodology can also be implemented to identify maturation-associated TFs for other stem cell progenies.

Mycobacterium tuberculosis, the causative agent of tuberculosis, has evolved over time into a multidrug resistance strain that poses a serious global pandemic health threat. The ability to survive and remain dormant within the host macrophage relies on multiple transcription factors contributing to virulence. To date, very limited structural insights from crystallographic and NMR studies are available for TFs and TF–DNA binding events. Understanding the role of DNA structure in TF binding is critical to deciphering MTB pathogenicity and has yet to be resolved at the genome scale. In this work, we analyzed the compositional and conformational preference of 21 mycobacterial TFs, evident at their DNA binding sites, in local and global scales. Results suggest that most TFs prefer binding to genomic regions characterized by unique DNA structural signatures, namely, high electrostatic potential, narrow minor grooves, high propeller twist, helical twist, intrinsic curvature, and DNA rigidity compared to the flanking sequences. Additionally, preference for specific trinucleotide motifs, with clear periodic signals of tetranucleotide motifs, are observed in the vicinity of the TF–DNA interactions. Altogether, our study reports nuanced DNA shape and structural preferences of 21 TFs.

Pollutants are big threat for the environment. Their imperil nature have disturbed the balance in the ecosystem and have also endangered the existence of the life on the earth. Advanced oxidation process is one of the emerging approach for the treatment of recalcitrant pollutants in nature. The process mainly involves the generation of a strong oxidant, which can easily degrade the pollutants produced from different sources. This review manifests the need of advanced oxidation process, and gives an outline of the different types of advanced oxidation process. It discusses the mechanism, advantages and disadvantages of the various forms of advanced oxidation process. Parameters for a sustainable technology such as technical and economical feasibility of the process, toxicity level and degradation effectiveness of the medium have also been discussed in detail to profess the sustainability of the process. It has potential and efficacy in removal of organic, toxic and non-biodegradable pollutants with minimum harmful effects. The future perspectives provide the room for modification and development and motivates us to overcome the present challenges and achieve better outcomes in future.

Cyclic-di-AMP (c-di-AMP) is an important secondary messenger molecule that plays a critical role in monitoring several important cellular processes, especially in several Gram-positive bacteria. In this study, we seek to unravel the physiological significance of the molecule c-di-AMP in Mycobacterium smegmatis under different conditions, using strains with altered c-di-AMP levels: c-di-AMP null mutant (ΔdisA) and a c-di-AMP over-expression mutant (Δpde). Our thorough analysis of the mutants revealed that the intracellular concentration of c-di-AMP could determine many basic phenotypes such as colony architecture, cell shape, cell size, membrane permeability etc. Additionally, it was shown to play a significant role in multiple stress adaptation pathways in the case of different DNA and membrane stresses. Our study also revealed how the biofilm phenotypes of M. smegmatis cells are altered with high intracellular c-di-AMP concentration. Next, we checked how c-di-AMP contributes to antibiotic resistance or susceptibility characteristics of M. smegmatis, which was followed by a detailed transcriptome profile analysis to reveal key genes and pathways such as translation, arginine biosynthesis, cell wall and plasma membrane are regulated by c-di-AMP in mycobacteria.

Galactic spinning compact objects (COs) with nonzero ellipticity are expected to be sources of continuous gravitational waves (CGWs). Certain classes of hypothetical COs, such as neutron stars with quark cores (hybrid stars) and quark stars, are thought to be capable of sustaining large ellipticities from theoretical considerations. Such exotic COs (eCOs) with large ellipticities and spins should produce CGWs detectable by the current LIGO-Virgo-KAGRA GW detector network. Since no detections for CGWs from searches in LIGO-Virgo data have so far been reported, we place constraints on the abundance of highly elliptical, rapidly spinning eCOs in our Galaxy. We formulate a Bayesian framework to place upper limits on the number count N _tot of highly deformed Galactic eCOs. We divide our constraints into two classes: an “agnostic” set of upper limits on N _tot evaluated on a CGW frequency and ellipticity grid that depend only on the choice of spatial distribution of COs; and a model-dependent set that additionally assumes prior information on the distribution of frequencies. We find that COs with ellipticities ϵ ≳ 10 ^−5 have abundance upper limits at 90% confidence, of ${N}_{{\rm{tot}}}^{90{\rm{ \% }}}\lesssim 100$ , and those with ϵ ≳ 10 ^−6 have ${N}_{{\rm{tot}}}^{90{\rm{ \% }}}\lesssim {10}^{4}$ . We additionally place upper limits on the ellipticity of Galactic COs informed by our choices of spatial distributions, given different abundances N _tot .

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global health challenge, further compounded by the issue of antimicrobial resistance (AMR). AMR is a result of several system-level molecular rearrangements enabling bacteria to evolve with better survival capacities: metabolic rewiring is one of them. In this review, we present a detailed analysis of the metabolic rewiring of Mtb in response to anti-TB drugs and elucidate the dynamic mechanisms of bacterial metabolism contributing to drug efficacy and resistance. We have discussed the current state of AMR, its role in the prevalence of the disease, and the limitations of current anti-TB drug regimens. Further, the concept of metabolic rewiring is defined, underscoring its relevance in understanding drug resistance and the biotransformation of drugs by Mtb. The review proceeds to discuss the metabolic adaptations of Mtb to drug treatment, and the pleiotropic effects of anti-TB drugs on Mtb metabolism. Next, the association between metabolic changes and antimycobacterial resistance, including intrinsic and acquired drug resistance, is discussed. The review concludes by summarizing the challenges of anti-TB treatment from a metabolic viewpoint, justifying the need for this discussion in the context of novel drug discovery, repositioning, and repurposing to control AMR in TB.

Activating inflammatory caspases and releasing pro-inflammatory mediators are two essential functions of inflammasomes which are triggered in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). The canonical inflammasome pathway involves the activation of inflammasome and its downstream pathway via the adaptor ASC protein, which causes caspase 1 activation and, eventually, the cleavage of pro-IL-1b and pro-IL-18. The non-canonical inflammasome pathway is induced upon detecting cytosolic lipopolysaccharide (LPS) by NLRP3 inflammasome in Gram-negative bacteria. The activation of NLRP3 triggers the cleavage of murine caspase 11 (human caspase 4 or caspase 5), which results in the formation of pores (via gasdermin) to cause pyroptosis. Ehrlichia is an obligately intracellular bacterium which is responsible for causing human monocytic ehrlichiosis (HME), a potentially lethal disease similar to toxic shock syndrome and septic shock syndrome. Several studies have indicated that canonical and non-canonical inflammasome activation is a crucial pathogenic mechanism that induces dysregulated inflammation and host cellular death in the pathophysiology of HME. Mechanistically, the activation of canonical and non-canonical inflammasome pathways affected by virulent Ehrlichia infection is due to a block in autophagy. This review aims to explore the significance of non-canonical inflammasomes in ehrlichiosis, and how the pathways involving caspases (with the exception of caspase 1) contribute to the pathophysiology of severe and fatal ehrlichiosis. Improving our understanding of the non-canonical inflammatory pathway that cause cell death and inflammation in ehrlichiosis will help the advancement of innovative therapeutic, preventative, and diagnostic approaches to the treatment of ehrlichiosis.

Abstract In this study, we probe the role of secondary messenger c-di-AMP in drug tolerance, which includes both persister and resistant mutant characterization of Mycobacterium smegmatis. Specifically, with the use of c-di-AMP null and overproducing mutants, we showed how c-di-AMP plays a significant role in resistance mutagenesis against antibiotics with different mechanisms of action. We elucidated the specific molecular mechanism linking the elevated intracellular c-di-AMP level and high mutant generation and highlighted the significance of non-homology-based DNA repair. Further investigation enabled us to identify the unique mutational landscape of target and non-target mutation categories linked to intracellular c-di-AMP levels. Overall fitness cost of unique target mutations was estimated in different strain backgrounds, and then we showed the critical role of c-di-AMP in driving epistatic interactions between resistance genes, resulting in the evolution of multi-drug tolerance. Finally, we identified the role of c-di-AMP in persister cells regrowth and mutant enrichment upon cessation of antibiotic treatment.