Search

Cancer immunotherapies produce remarkable results in B cell malignancies; however, optimal cell surface targets for many solid cancers remain elusive. Here, we present an integrative proteomic, transcriptomic, and epigenomic analysis of tumor and normal tissues to identify biologically relevant cell surface immunotherapeutic targets for neuroblastoma, an often-fatal childhood cancer. Proteogenomic analyses reveal sixty high-confidence candidate immunotherapeutic targets, and we prioritize delta-like canonical notch ligand 1 (DLK1) for further study. High expression of DLK1 directly correlates with a super-enhancer. Immunofluorescence, flow cytometry, and immunohistochemistry show robust cell surface expression of DLK1. Short hairpin RNA mediated silencing of DLK1 in neuroblastoma cells results in increased cellular differentiation. ADCT-701, a DLK1-targeting antibody-drug conjugate (ADC), shows potent and specific cytotoxicity in DLK1-expressing neuroblastoma xenograft models. Since high DLK1 expression is found in several adult and pediatric cancers, our study demonstrates the utility of a proteogenomic approach and credentials DLK1 as an immunotherapeutic target., Competing Interests: Declaration of interests F. Zammarchi, K. Havenith, and P.H.v.B. are or were employed by ADC Therapeutics at the time the work was conducted and hold or previously held shares/stocks in ADC Therapeutics. The following patent is held: WO2018146199A1., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The broad-spectrum antibacterial capabilities of fatty acids (FAs) and their reduced propensity to promote resistance have rendered as a promising substitute for conventional antibiotics. The structural significance of fatty acid production with the other lipids is a major energy source, and signal transduction has drawn a great deal of research attention to these biomolecules. Saturated and monounsaturated fatty acids reduce virulence by preventing harmful opportunistic bacteria like Pseudomonas aeruginosa and Chromobacterium violaceum from activating their quorum sensing (QS) systems. In this finding, the fatty acids capric acid, caprylic acid, and monoelaidin were selected to evaluate their anti-QS activity against the C. violaceum and P. aeruginosa. At the minimum inhibitory concentration (MIC) and sub-MIC concentration of the three fatty acids, the virulence factor production of both the bacteria was quantified. The virulence factors like EPS, biofilm quantification and visualization, and motility assays were inhibited in the dose-dependent manner (MIC and sub-MIC) for both the organisms whereas this pattern was followed in the pyocyanin, pyoverdine, rhamnolipid, protease of P. aeruginosa and the violacein, and chitinase of C. violaceum. In all these biochemical assays, the capric acid could effectively reduce the production and further validated at gene expression level by RT-qPCR. The study on the gene expression for all these virulence factors reveals that the capric acid inhibited the growth of both the organisms in a higher fold than the caprylic and monoelaidin. The in silico approach of structural validation for the binding of ligands with the proteins in the QS circuit was studied by molecular docking in Schrodinger software. The Las I and Las R in P. aeruginosa and the CviR of C. violaceum protein structures were docked with the selected three fatty acids. The capric acid binds to the pocket with the highest binding score of all the proteins than the caprylic and monoelaidin fatty acids. Thus, capric acid proves to be the therapeutic biomolecule for the anti-QS activity of opportunistic bacteria., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Since double-stranded RNA (dsRNA) is effective for silencing a wide variety of genes, all genes are typically considered equivalent targets for such RNA interference (RNAi). Yet, loss of some regulators of RNAi in the nematode Caenorhabditis elegans can selectively impair the silencing of some genes. Here, we show that such selective requirements can be explained by an intersecting network of regulators acting on genes with differences in their RNA metabolism. In this network, the Maelstrom domain-containing protein RDE-10, the intrinsically disordered protein MUT-16, and the Argonaute protein NRDE-3 work together so that any two are required for silencing one somatic gene, but each is singly required for silencing another somatic gene, where only the requirement for NRDE-3 can be overcome by enhanced dsRNA processing. Quantitative models and their exploratory simulations led us to find that (1) changing cis -regulatory elements of the target gene can reduce the dependence on NRDE-3, (2) animals can recover from silencing in non-dividing cells, and (3) cleavage and tailing of mRNAs with UG dinucleotides, which makes them templates for amplifying small RNAs, are enriched within 'pUG zones' matching the dsRNA. Similar crosstalk between pathways and restricted amplification could result in apparently selective silencing by endogenous RNAs., Competing Interests: DK, PR, FE, LD, AJ No competing interests declared, (© 2024, Knudsen-Palmer et al.)

Cardiovascular diseases are the leading cause of death in middle-income countries such as Malaysia. There is a significant gap in knowledge between cardiovascular disease-related risk assessments and interventions in the Malaysian population. In this scoping review, we have determined the status of cardiovascular research in Malaysia by prioritising lifestyle-related risk assessments and interventions. We searched five electronic databases (Ovid MEDLINE, Cochrane Central Register of Controlled Trials, APA PsychINFO, Embase and Scopus) to identify relevant research articles that had been published. The Joanna Briggs Institute and the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews served as a guide for the scoping review. Study selection was made using the Covidence platform, screened, and extracted. Thirty-one studies were included in this review. Studies reviewed reported a significant positive association between physical inactivity, smoking, poor dietary patterns, working hours, clustering of lifestyle risk, and cardiovascular disease risk. Most interventions focused on physical activity and a multimodal lifestyle approach, significantly improving primary and secondary cardiovascular disease-related outcomes. The findings suggest improving lifestyle-related risk assessments and interventions to prevent cardiovascular diseases in this population. It is unclear if these outcomes can translate to higher effectiveness in preventing cardiovascular disease. Nevertheless, intervention using the multifaceted lifestyle approach can improve cardiovascular disease-related outcomes., (© 2024. The Author(s).)

Since double-stranded RNA (dsRNA) is effective for silencing a wide variety of genes, all genes are typically considered equivalent targets for such RNA interference (RNAi). Yet, loss of some regulators of RNAi in the nematode C. elegans can selectively impair the silencing of some genes. Here we show that such selective requirements can be explained by an intersecting network of regulators acting on genes with differences in their RNA metabolism. In this network, the Maelstrom domain-containing protein RDE-10, the intrinsically disordered protein MUT-16, and the Argonaute protein NRDE-3 work together so that any two are required for silencing one somatic gene, but each is singly required for silencing another somatic gene, where only the requirement for NRDE-3 can be overcome by enhanced dsRNA processing. Quantitative models and their exploratory simulations led us to find that (1) changing cis -regulatory elements of the target gene can reduce the dependence on NRDE-3, (2) animals can recover from silencing in non-dividing cells and (3) cleavage and tailing of mRNAs with UG dinucleotides, which makes them templates for amplifying small RNAs, is enriched within 'pUG zones' matching the dsRNA. Similar crosstalk between pathways and restricted amplification could result in apparently selective silencing by endogenous RNAs., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest.

Oral squamous cell carcinoma (OSCC) is indeed one of the most common types of oral cancer, typically affecting individuals over the age of 50. It primarily originates from the squamous epithelial cells lining the oral cavity. While it is relatively rare in individuals under 40 years old, it can still occur, albeit less frequently in that age group. Risk factors for developing OSCC include tobacco use (smoking or chewing), excessive alcohol consumption, chronic irritation (such as from poorly fitting dentures), human papillomavirus (HPV), infection, and certain dietary foods. Early detection and treatment are crucial for improving outcomes and reducing the mortality associated with this type of cancer. This report describes a case of OSCC, staged T2 N0 M0, involving the right buccal mucosa of a 51-year-old male patient. The patient reported intense pain in an ulcer on the right side of his cheek. This report focuses on the etiological factors and a brief literature review of squamous cell carcinoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Gayathri et al.)

Heritable gene silencing has been proposed to rely on DNA methylation, histone modifications, and/or non-coding RNAs in different organisms. Here we demonstrate that multiple RNA-mediated mechanisms with distinct and easily detectable molecular signatures can underlie heritable silencing of the same open-reading frame in the nematode C. elegans . Using two-gene operons, we reveal three cases of gene-selective silencing that provide support for the transmission of heritable epigenetic changes through different mechanisms of RNA silencing independent of changes in chromatin that would affect all genes of an operon equally. Different heritable epigenetic states of a gene were associated with distinct populations of stabilized mRNA fragments with untemplated poly-UG (pUG) tails, which are known intermediates of RNA silencing. These 'pUG signatures' provide a way to distinguish the multiple mechanisms that can drive heritable RNA silencing of a single gene., Competing Interests: Competing Interest Statement: The authors declare no conflict of interest.

Purpose: Studies report conflicting findings regarding choroidal thickness changes in response to myopic defocus in humans. This study aimed to investigate the choroidal response to myopic defocus in children and adults using automated analysis., Methods: Participants (N = 46) were distance-corrected in both eyes and viewed a movie on a screen for 10 minutes. Two optical coherence tomography (OCT) radial scans were collected for each eye, then +3 diopters was added to one eye. Participants continued to watch the movie, OCT scans were repeated every 10 minutes for 50 minutes, and then recovery was assessed at 60 and 70 minutes. Defocus was interrupted for approximately two out of each 10 minutes for OCT imaging. OCT images were analyzed using an automated algorithm and trained neural network implemented in MATLAB to determine choroidal thickness at each time point. Repeated-measures ANOVA was used to assess changes with time in three age groups (6-17, 18-30, and 31-45 years) and by refractive error group (myopic and nonmyopic)., Results: Choroidal thickness was significantly associated with spherical equivalent refraction, with the myopic group having a thinner choroid than the nonmyopic group (P < 0.001). With imposed myopic defocus, there were no significant changes in choroidal thickness at any time point for any age group and for either refractive error group (P > 0.05 for all)., Conclusions: Findings demonstrate that, using the described protocol, the choroidal thickness of children and adults does not significantly change in response to short-term, full-field myopic defocus, in contrast to several previously published studies.

Background: Limited literature exists on structural racism measures on health outcomes for Asian Americans, Native Hawaiians, and Pacific Islanders (AAs and NH/PIs). AAs and NH/PIs make up approximately 6.2% of the U.S. population and consist of diverse ethnic subgroups with distinct languages, cultures, religions, socioeconomic statuses, and historical backgrounds. The lack of disaggregated data collection and contextualized measures hinders our understanding of how structural racism affects health outcomes in these populations., Methods: We conducted a scoping review to assess the extent to which measures of structural racism are used in research with AAs and NH/PIs. Databases, including CINAHL, EBSCO, PsychINFO, PubMed, Scopus, and Social Science Citation Index, were searched for peer-reviewed articles on the measures of and empirical impacts of structural racism on AA and NH/PI health. We identified 23 full-text articles from a pool of 11,660 screened articles. Four articles were included in the final analysis., Results: Among the selected studies, two studies identified an association between racial segregation and mental and behavioral health outcomes within AAs and NH/PIs. The other two studies found redlining on chronic health outcomes in these communities. These studies uncovered associations between government systems and policies and AA and NH/PI health outcomes., Discussion: Existing measures may not adequately capture the complex relationships between structural racism and health outcomes in AAs and NH/PIs. Future research should contextualize and operationalize the multifaceted manifestations of structural racism unique to AAs and NH/PIs to achieve health equity., (© 2024. W. Montague Cobb-NMA Health Institute.)

Neurodegenerative diseases (NDDs) comprise a large number of disorders that affect the structure and functions of the nervous system. The major cause of various neurodegenerative diseases includes protein aggregation, oxidative stress and inflammation. Over the last decade, there has been a gradual inclination of neurological research in order to find drugs that can prevent, slow down, or treat these diseases. The most common NDDs are Alzheimer's, Parkinson's, and Huntington's illnesses which claims the lives of 6.8 million people worldwide each year and it is expected to rise by 7.1%. The focus on alternative medicine, particularly plant-based products, has grown significantly in recent years. Plants are considered a good source of biologically active molecules and hence phytochemical screening of plants will pave the way for discovering new drugs. Neurodegeneration has long been linked to oxidative stress, either as a direct cause or as a side effect of other variables. Therefore, it has been proposed that the use of antioxidants to combat cellular oxidative stress within the nervous system may be a viable therapeutic strategy for neurological illnesses. In order to prevent and treat NDDs, this review article covers the therapeutic compounds/ metabolites from plants with the neuroprotective role. However, these exhibit other beneficial molecular functions in addition to antioxidant activity is the potential application in the management or prevention of neurodegenerative disorders. Further, it gives future researchers the significance of considering peptide-based therapeutics through various mechanisms in delaying or curing neurodegenerative diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cancer immunotherapies have produced remarkable results in B-cell malignancies; however, optimal cell surface targets for many solid cancers remain elusive. Here, we present an integrative proteomic, transcriptomic, and epigenomic analysis of tumor specimens along with normal tissues to identify biologically relevant cell surface proteins that can serve as immunotherapeutic targets for neuroblastoma, an often-fatal childhood cancer of the developing nervous system. We apply this approach to human-derived cell lines (N=9) and cell/patient-derived xenograft (N=12) models of neuroblastoma. Plasma membrane-enriched mass spectrometry identified 1,461 cell surface proteins in cell lines and 1,401 in xenograft models, respectively. Additional proteogenomic analyses revealed 60 high-confidence candidate immunotherapeutic targets and we prioritized Delta-like canonical notch ligand 1 (DLK1) for further study. High expression of DLK1 directly correlated with the presence of a super-enhancer spanning the DLK1 locus. Robust cell surface expression of DLK1 was validated by immunofluorescence, flow cytometry, and immunohistochemistry. Short hairpin RNA mediated silencing of DLK1 in neuroblastoma cells resulted in increased cellular differentiation. ADCT-701, a DLK1-targeting antibody-drug conjugate (ADC), showed potent and specific cytotoxicity in DLK1-expressing neuroblastoma xenograft models. Moreover, DLK1 is highly expressed in several adult cancer types, including adrenocortical carcinoma (ACC), pheochromocytoma/paraganglioma (PCPG), hepatoblastoma, and small cell lung cancer (SCLC), suggesting potential clinical benefit beyond neuroblastoma. Taken together, our study demonstrates the utility of comprehensive cancer surfaceome characterization and credentials DLK1 as an immunotherapeutic target., Highlights: Plasma membrane enriched proteomics defines surfaceome of neuroblastomaMulti-omic data integration prioritizes DLK1 as a candidate immunotherapeutic target in neuroblastoma and other cancersDLK1 expression is driven by a super-enhancer DLK1 silencing in neuroblastoma cells results in cellular differentiation ADCT-701, a DLK1-targeting antibody-drug conjugate, shows potent and specific cytotoxicity in DLK1-expressing neuroblastoma preclinical models.

Diabesity is showing rising prevalence. Current treatment modalities include pharmacological and non-pharmacological approaches, yet associated with various drawbacks. Recently, gut microbial dysbiosis is documented as a crucial factor in the pathogenesis of diabesity. Targeting gut microbiome using modulators shows promising therapeutic strategy for diabesity management. In this line, nanonutraceuticals represent new class of gut microbial modulators. The present article explores the potential of nanonutraceuticals including nanoprobiotics, nanoprebiotics, and plant-derived nanovesicles that are fabricated on the ecofriendly food based scaffold with gut microbial modulatory potential for diabesity management. A number of compelling evidences from different studies support Bifidobacterium, Enterococcus, and Bacteroides genera and Lactobacillus plantarum and Akkermansia muciniphila species significant in diabesity management. The probable mechanisms reported for gut microbial dysbiosis-induced diabesity are mentioned. The review findings suggest gut microbiome as significant therapeutic target for diabesity management. Moreover, ecofriendly nanonutraceuticals developed using natural products including food-grade materials are efficient modulators of gut microbiome and indicate next-generation diabesity therapeutics. Clinical studies are imperative as further exploration may provide new dimensions to the future research., (© 2023. Controlled Release Society.)

Edible oils are inevitable requisites in the human diet as they are enriched with essential fatty acids, vitamins, carotenoids, sterols, and other antioxidants. Due to their nutritive value and commercial significance, edible oils have been used for food preparation for many centuries. The use of global consumption of edible oils has dramatically increased throughout the world in the 21 st century owing to their incredible application in all kinds of food preparation. However, a variety of pollutants, such as pesticides, toxic chemicals, heavy metals, and environmental pollution, have contributed to the contamination of edible oils. Furthermore, the benzophenanthridine alkaloids, sanguinarine, dihydrosanguinarine, butter yellow, and other several agents are added intentionally, which are known to cause a number of human diseases. Apart from this, repeated heating and reusing of oils results in trans fats, and lipid peroxidation alters the fatty acid composition, which adversely affects the health of consumers and increases the risk of cardiovascular diseases. Moreover, the prevention of edible oil contamination in human health at various levels is inevitable to ensure consumer safety. Hence, the present review provides an overview of vegetable cooking oils and the health ailments that detection techniques are focused on., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ultraviolet B wavelength ray radiation (UVB) is an environmental stressor with detrimental effects to the aquatic and human systems but also enhances adverse effects when combined with several other environmental factors such as temperature and pollution. UV rays induce cellular oxidative damage and impair motility. This study aimed to examine the photo-protective activity of flavonoid luteolin against UV-B irradiation-induced oxidative stress and cellular damage using zebrafish. An in-vivo photoaging model was established using UV-B irradiation in zebrafish larvae exposed to 100 mJ/cm 2 . Data demonstrated that UV-B irradiation of swimming water enhanced production of ROS and superoxide anions as well as depleted total glutathione levels in zebrafish larvae. UV-B irradiation also triggered cellular damage and membrane rupture in zebra fish. Further, 100 mJ/cm 2 of UV-B radiation exposure to adult-wild type zebrafish co-exposed with intraperitoneally (ip) injected luteolin upregulated the local neuroendocrine axes by activating vascular endothelial growth factor (VEGF) and elevating levels of pro-inflammatory cytokines IL-1β and TNF-α. Histologically, UV-B irradiation induced skin lesions and locomotory defects with clumping and degeneration of brain glial cells. However, luteolin effectively inhibited the excess production of reactive oxygen species (ROS) and decreased superoxide anion levels induced by UV-B irradiation. Luteolin restored the depleted glutathione levels. In addition, luteolin blocked apoptosis and lipidperoxidation. Luteolin protected adult zebrafish by downregulating the pro-inflammatory cytokine protein expression levels and diminishing VEGF activation. Luteolin also alleviated locomotory defects by inhibiting activation of microglia and inflammatory responses by preventing accumulation of glial cells and vacuolation. Data demonstrate that luteolin may protect zebrafish from UV-B-induced photodamage through DNA-protective, antioxidant and anti-inflammatory responses.

Soil fertility and environmental factors play an important role in improving productivity and cropland quality in the agricultural sector. A new prediction and classification model for the potential of soil nutrients and hydrogen (pH) levels is proposed. The proposed model, Hybrid Whale Archimedes Optimization-based Multilayer Perceptron Neural Network (HWAO-MLPNN), is utilized for soil features classification of pH levels, and the soils are collected from the villages such as phosphorous (P), organic carbon (OC), boron (B), and potassium (K). The village-wise soil fertility prediction and classification model aims to improve soil health, reduce harmful fertilizer usage, enhance environmental quality, and achieve more profits. The proposed model combines the Multilayer Perceptron Neural Network (MLPNN) model and the Hybrid Whale Archimedes Optimization (HWAO) algorithm to enhance the classification performance on the validation data. The Marathwada dataset is selected to validate the soil nutrient prediction and classification model, and various measuring units such as cross-validation accuracy, Area Under Curve (AUC), accuracy, Mean Squared Error (MSE), G-mean, precision, specificity, and sensitivity are used for evaluation. The comparative study of this paper shows that the proposed HWAO-MLPNN achieved more classification accuracy of 98.1%, cross-validation accuracy of 98.3% for pH classification, and cross-validation accuracy of 97.9% for soil nutrient classification. The proposed model can be utilized to accurately classify soil nutrients and pH levels, which can have a significant impact on improving soil health, reducing harmful fertilizer usage, enhancing environmental quality, and ultimately increasing profitability in the agricultural sector., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Banana starch is explored for its use in food and pharmaceutical applications. In this study, in order to improve the techno-functional properties of native banana starch (NS), different chemical modifications namely acid thinning (AT), oxidation (OX), sodium-trimetaphosphate method (STMP), cross linking phosphorylation (CLP), hydroxypropylation (HYP) were employed. Among the modified starches, amylose content was higher in CLP starch and the least was observed in AT. Resistant starch (RS) of HYP (65.38 %) and CLP starches (62.76 %) were significantly higher than other modified starches. Lesser amylose, higher water solubility and lower swelling of AT starch resulted in inferior paste clarity and inability to make a firm gel. Non-Newtonian behaviour of starch gels were observed from static viscosity observations. The dynamic rheological behaviour of the starch gels affirmed the higher gel strength of STMP (0.46) and CLP (0.56) starches. Imperfection and exo-corrosion in starch morphology was observed through SEM and influence of chemicals on the starch structure was elucidated through FTIR and XRD analyses. Except AT starch, modified starches with higher RS resulted in lowering glycemic index (57-69 %). STMP starches recorded highest prebiotic activity score of 0.88. Chemical modifications enable to enhance the functionalities of banana starch and offers potential industrial uses., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Suresh Kumar Paramasivam reports financial support was provided by Indian Council of Agricultural Research., (Copyright © 2023 Elsevier B.V. All rights reserved.)

(1) Background: Understanding the physicians' knowledge, attitudes, and antimicrobial prescribing behavior is a crucial step towards designing strategies for the optimal use of these agents. (2) Methods: A cross-sectional online survey was conducted among clinicians across India between May and July 2022 using a self-administered questionnaire in English comprising 35 questions pertaining to demographic characteristics, knowledge, attitude, and practices domains. (3) Results: A total of 544 responses were received from 710 physicians contacted. Sixty percent of participants were males, with mean age of 34.7 years. Mean ± Standard Deviation scores for knowledge, attitude, and practices domains were 8 ± 1.6, 20.2 ± 3.5, and 15.3 ± 2.1, respectively. Higher scores were associated with basic [odds ratio (95% Confidence Interval), p value: 2.95 (1.21, 7.2), 0.02], medical and allied sciences [2.71 (1.09, 6.67), 0.03], and central zone [3.75 (1.39, 10.12), 0.009]. A substantial proportion of dissatisfactory responses were found regarding hospital antibiograms, antibiotics effective against anaerobes, WHO AWaRe (access, watch, and reserve) classification of antibiotics, and the role of infection prevention and control (IPC) measures in the containment of antimicrobial resistance (AMR). (4) Conclusions: There is a need to sensitize and educate clinicians on various issues related to antimicrobial use, such as antibiograms, double anaerobic cover, IPC practices, and guideline-based recommendations, to curb the AMR pandemic.

Background: Cancer immunotherapies including immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR) T-cell therapy have shown variable response rates in paediatric patients highlighting the need to establish robust biomarkers for patient selection. While the tumour microenvironment in adults has been widely studied to delineate determinants of immune response, the immune composition of paediatric solid tumours remains relatively uncharacterized calling for investigations to identify potential immune biomarkers., Methods: To inform immunotherapy approaches in paediatric cancers with embryonal origin, we performed an immunogenomic analysis of RNA-seq data from 925 treatment-naïve paediatric nervous system tumours (pedNST) spanning 12 cancer types from three publicly available data sets., Results: Within pedNST, we uncovered four broad immune clusters: Paediatric Inflamed (10%), Myeloid Predominant (30%), Immune Neutral (43%) and Immune Desert (17%). We validated these clusters using immunohistochemistry, methylation immune inference and segmentation analysis of tissue images. We report shared biology of these immune clusters within and across cancer types, and characterization of specific immune cell frequencies as well as T- and B-cell repertoires. We found no associations between immune infiltration levels and tumour mutational burden, although molecular cancer entities were enriched within specific immune clusters., Conclusions: Given the heterogeneity of immune infiltration within pedNST, our findings suggest personalized immunogenomic profiling is needed to guide selection of immunotherapeutic strategies., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Borassus flabellifer L., commonly known as Asian palmyra, is native to South and Southeast Asia. The endosperms of B. flabellifer (known as nungu in Dravidian culture) are widely consumed during the summer season. It is rich in various nutrients and helps in reducing weight, treating skin and digestive issues, lowering body temperature, and managing migraines and diabetes. This study focuses on identifying the small molecules and proteins from the two varieties of B. flabellifer tender fruit endosperms collected from districts around Chennai, Tamil Nadu, India. The collected free nuclear endosperm was subjected to direct extraction and the mesocarp and cellular endosperms were lyophilized and homogenized. Metabolites were extracted by hexane, methanol, and chloroform and investigated using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The compounds identified were from the classes of carboxylic acids, flavonoids, amino acids, alkaloids, fatty acids, oligopeptides, vitamins, and glycosides. High-performance liquid chromatography (HPLC) technique was employed to estimate the quantity of amino acids, wherein the total amino acid in the green variety was found to be higher than in the black variety. Proteins were identified after simulating with a gastrointestinal enzyme using liquid chromatography tandem mass spectrometry (LC-MS/MS)-based peptide mass fingerprinting. The different mineral oxides present in the tender fruit endosperm were identified using X-ray diffraction studies, which confirmed the presence of mineral oxides, such as Br 1.25 ClO 2.75 Pb 3.88 , calcium zirconium tantalum oxide, and barium fluoroniobate. This study validates the presence of bioactive metabolites in green and black varieties of B. flabellifer tender fruit endosperm with a range of activities, such as anti-inflammatory, antibacterial, anticancer, and anti-diabetic properties.

Background: For patients with resected stage III colon cancer, 6 months of adjuvant fluoropyrimidine-based chemotherapy has been the standard of care. The IDEA collaboration aimed to evaluate whether 3 months of adjuvant chemotherapy was noninferior to 6 months. Despite failing to meet its primary endpoint, the subgroup analyses demonstrated noninferiority based on regimen and treatment duration when a risk-stratified approach was used., Patients and Methods: To evaluate the impact of the results of the IDEA collaboration, we evaluated adjuvant chemotherapy prescribing practice patterns, including planned adjuvant treatment regimen and duration from January 1, 2016, to January 31, 2021. The time period was selected to evaluate chemotherapy prescribing patterns prior to the abstract presentation of the IDEA collaboration in June 2017 and after full manuscript publication in March 2018., Results: A total of 399 patients with stage III colon cancer who received adjuvant chemotherapy were included in the analysis. A significant increasing trend for use of 3 months of adjuvant chemotherapy was observed after presentation of the IDEA abstract (P<.001). A significant change in CAPOX (capecitabine/oxaliplatin) prescribing was also observed, increasing from 14% of patients prior to presentation of the IDEA abstract to 48% after presentation (P<.001). Comparing 3 months of CAPOX with 6 months of FOLFOX (fluorouracil/leucovorin/oxaliplatin), 3 months of CAPOX use also steadily increased over time (adjusted odds ratio [aOR], 1.28; 95% CI, 1.20-1.37; P<.001). Among subgroups of interest, no differences in adoption of CAPOX were observed. The adoption of 3 months of CAPOX was similar in patients with low-risk cancer (aOR, 1.27; 95% CI, 1.17-1.37) and those with high-risk cancer (aOR, 1.31; 95% CI, 1.16-1.47)., Conclusions: Despite the IDEA collaboration failing to demonstrate noninferiority of 3 months' duration of adjuvant therapy compared with 6 months, the findings have influenced practice prescribing patterns, favoring CAPOX and a shorter duration of planned adjuvant treatment.

Metabolic syndrome (MetS), characterized by hyperglycemia, obesity, and hyperlipidemia, can increase the risk of developing late-onset dementia. Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. The goal of the current study was to investigate the link between cognitive function, tau pathology, and O-GlcNAc signaling in an aging mouse model of MetS, agouti KKAy +/- . Male and female C57BL/6, non-agouti KKAy -/- , and agouti KKAy +/- mice were aged 12-18 months on standard chow diet. Body weight, blood glucose, total cholesterol, and triglyceride were measured to confirm the MetS phenotype. Cognition, sensorimotor function, and emotional reactivity were assessed for each genotype followed by plasma and brain tissue collection for biochemical and molecular analyses. Body weight, blood glucose, total cholesterol, and triglyceride levels were significantly elevated in agouti KKAy +/- mice versus C57BL/6 controls and non-agouti KKAy -/- . Behaviorally, agouti KKAy +/- revealed impairments in sensorimotor and cognitive function versus age-matched C57BL/6 and non-agouti KKAy -/- mice. Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy +/- versus C57BL/6 control mice. Together, these data demonstrate that impaired cognitive function and AD-related pathology are associated with reduced O-GlcNAc signaling in aging MetS KKAy +/- mice. Overall, our study suggests that interaction of tau pathology with O-GlcNAc signaling may contribute to MetS-induced cognitive dysfunction in aging., (© 2023 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Objective: To report a rare case of suprachoroidal hemorrhage during phacoemulsification in a patient with bilateral carotid-cavernous fistula., Method: Case report., Result: A 76-year-old woman with underlying hypertension presented left eye poor vision due to an underlying dense cataract. Her initial preoperative assessment was uneventful, and she underwent phacoemulsification. During epinucleus removal, there was sudden, unexpected anterior chamber shallowing, resulting in posterior capsule rupture. While the surgeon extended the wound to facilitate epinucleus removal, there was a further decrease of red reflex, followed by hardening of the globe, indicating a suprachoroidal hemorrhage. The corneal wound was opposed swiftly without an intraocular lens. Further evaluation after that revealed the patient had a chronic headache for several years, and ocular examination showed bilateral esophoria. A computed tomography demonstrated features suggestive of bilateral carotid-cavernous fistula, which was confirmed with computed tomography angiography later., Conclusion: Patients with carotid-cavernous fistula have elevated episcleral venous pressure and vortex venous pressure. Sudden decompression of the globe in these patients predisposes them to higher suprachoroidal hemorrhage risk, although this condition is generally rare in phacoemulsification.

Background Coronavirus disease 2019 (COVID-19) isolation protocols in India restricted family members of COVID-19 patients from visiting them in hospitals and in intensive care units, especially during the peak of the pandemic. This along with the elaborate personal protective equipment (PPE) created challenges for intensivists and nurses in COVID ICUs in effectively communicating with patients and patients' families, especially in shared decision-making processes. Methods This article is the outcome of a qualitative study using in-depth one-on-one interviews with 10 intensivists and four intensive care nurses in two teaching hospitals in Bengaluru, South India. Each participant, purposively selected till data saturation was reached, had spent extensive periods of time in a COVID ICU during both COVID-19 waves in 2020 and 2021. A framework of descriptive phenomenology led to the design of the study in which varied experiences and insights of participants were captured using an interview guide to understand their lived reality. The interviews were conducted online or in person between July 2021 and October 2021 and were audio recorded and transcribed verbatim. Coding of transcripts using the NVivo 12 (Burlington, MA: QSR International Pty Ltd) software helped with the thematic analysis. This was guided by interpretive phenomenological methods that derived meaning from participants' life experiences. Results Four themes involving challenges in effective communication in the COVID ICU emerged as follows: physical barriers, emotional and mental stressors, infrastructural challenges, and ethical and moral dilemmas. Sub-themes included personal protective equipment as a barrier, reduced energy levels, and isolation of family from patients under the domain of physical challenges; fears of the unknown, handling death of patients in isolation, and the frustrations of families were challenges under the emotional and mental domain. Infrastructural/systemic challenges included poor connectivity and insufficient mobile phones, and the absence of rules to handle interruptions. Privacy breaches, taking consent over the phone, end-of-life discussions, and medico-legal risks emerged as the subthemes under the domain of ethical and moral challenges. A mobile phone communication policy specifying usage times and operating methods, a mandatory communication and counseling training module for intensivists and intensive care nurses, and a set of protocols for highly restrictive, intensive care units in pandemic situations were recommendations and lessons learned. Conclusions The lack of face-to-face interactions was a serious barrier to communication between ICU staff and patients and their caregivers. It had a bearing on trust levels and had emotional and ethical consequences for healthcare teams to handle. Opportunities for self-care, venting of anxiety and distress, and opportunities to celebrate and reward special efforts and cooperation between consultants, residents, nurses, and technicians in stressful environments like a pandemic ICU were important to sustain empathy and keep care and communication humane., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Vaz et al.)

Background and Aims: Though the role of fasting preoperative gastric ultrasound has been validated in different patient populations, namely, obese, pregnant and diabetics, it has not been explored in patients with chronic kidney disease (CKD). This prospective, observational study compared the fasting sonological assessment of gastric contents in patients with CKD versus those with normal renal function scheduled for elective surgery., Methods: After ethical approval and trial registration were obtained, preoperative gastric ultrasound was done in 115 CKD patients and 115 with normal renal function. Qualitative and quantitative assessment of residual gastric volume was done. Also, the patients were administered the Porto Alegre Dyspeptic Symptoms Questionnaire (PADYQ) to evaluate gastroparesis objectively. The researcher was not blinded to the patient groups. Data analyses were done using the Statistical Package for Social Sciences (SPSS) for Windows software (version 22.0)., Results: Gastric volumes exceeding 1.5 ml/kg or particulate or solid contents were found in 57 patients with CKD and 36 patients with normal renal function ( P = 0.004). The PADYQ scores were 6.54 ± 8.49 for CKD and 2.15 ± 5.71 for normal renal function ( P < 0.0001) groups. CKD patients had a higher age ( P < 0.001), lower body mass index ( P = 0.005) and higher incidence of diabetes mellitus ( P < 0.001). There were no incidents of gastric aspiration., Conclusion: Renal dysfunction contributes to delayed gastric emptying. PADYQ can also help identify those at high risk of gastroparesis. Combining the questionnaire and preoperative gastric ultrasound must be considered in these patients to ensure optimum safety., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Anaesthesia.)

Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, the Children's Brain Tumor Network (CBTN) and Pacific Pediatric Neuro-Oncology Consortium (PNOC) created a systematic process for tumor biobanking, model generation, and sequencing with immediate access to harmonized data. We leverage these data to establish OpenPBTA, an open collaborative project with over 40 scalable analysis modules that genomically characterize 1,074 pediatric brain tumors. Transcriptomic classification reveals universal TP53 dysregulation in mismatch repair-deficient hypermutant high-grade gliomas and TP53 loss as a significant marker for poor overall survival in ependymomas and H3 K28-mutant diffuse midline gliomas. Already being actively applied to other pediatric cancers and PNOC molecular tumor board decision-making, OpenPBTA is an invaluable resource to the pediatric oncology community., Competing Interests: C.S.G.’s spouse was an employee of Alex’s Lemonade Stand Foundation, which was a sponsor of this research. J.A.S., C.L.S., C.J.B., S.J.S., and J.N.T. are or were employees of Alex’s Lemonade Stand Foundation, a sponsor of this research. A.J.W. is a member of the Scientific Advisory boards for Alexion and DayOne Biopharmaceuticals., (© 2023 The Author(s).)

Accumulating evidence highlights protein O-GlcNAcylation as a putative pathogenic contributor of diabetic vascular complications. We previously reported that elevated protein O-GlcNAcylation correlates with increased atherosclerotic lesion formation and VSMC proliferation in response to hyperglycemia. However, the role of O-GlcNAc transferase (OGT), regulator of O-GlcNAc signaling, in the evolution of diabetic atherosclerosis remains elusive. The goal of this study was to determine whether smooth muscle OGT (smOGT) plays a direct role in hyperglycemia-induced atherosclerotic lesion formation and SMC de-differentiation. Using tamoxifen-inducible Myh11-CreER T2 and Ogt fl/fl mice, we generated smOGT WT and smOGT KO mice, with and without ApoE-null backgrounds. Following STZ-induced hyperglycemia, smOGT WT and smOGT KO mice were kept on a standard laboratory diet for the study duration. In a parallel study, smOGT WT ApoE -/- and smOGT KO ApoE -/- were initiated on Western diet at 8-wks-age. Animals harvested at 14-16-wks-age were used for plasma and tissue collection. Loss of smOGT augmented SM contractile marker expression in aortic vessels of STZ-induced hyperglycemic smOGT KO mice. Consistently, smOGT deletion attenuated atherosclerotic lesion lipid burden (Oil red O), plaque area (H&E), leukocyte (CD45) and smooth muscle cell (ACTA2) abundance in Western diet-fed hyperglycemic smOGT KO ApoE -/- mice. This was accompanied by increased SM contractile markers and reduced inflammatory and proliferative marker expression. Further, smOGT deletion attenuated YY1 and SRF expression (transcriptional regulators of SM contractile genes) in hyperglycemic smOGT KO ApoE -/- and smOGT KO mice. These data uncover an athero-protective outcome of smOGT loss-of-function and suggest a direct regulatory role of OGT-mediated O-GlcNAcylation in VSMC de-differentiation in hyperglycemia.

Background: Soil nutrients play an important role in soil fertility and other environmental factors. Soil testing is an effective tool for evaluating soil nutrient levels and calculating the appropriate quantitative of soil nutrients based on fertility and crop requirements. Because traditional soil nutrient testing models are impractical for real-time applications, efficient soil nutrient and potential hydrogen (pH) prediction models are required to improve overall crop productivity. Soil testing is an effective method to evaluate the presence of nutrient status of soil and assists in determining appropriate nutrient quantity., Methods: Various machine learning (ML) models proposed, predict the soil nutrients, soil type, and soil moisture. To assess the significant soil nutrient content, this study develops an enhanced reptile search optimization with convolutional autoencoder (ERSOCAE-SNC) model for classifying and predicting the fertility indices. The model majorly focuses on the soil test reports. For classification, CAE model is applied which accurately determines the nutrient levels such as phosphorus (P), available potassium (K), organic carbon (OC), boron (B) and soil pH level. Since the trial-and-error method for hyperparameter tuning of CAE model is a tedious and erroneous process, the ERSO algorithm has been utilized which in turn enhances the classification performance. Besides, the ERSO algorithm is derived by incorporating the chaotic concepts into the RSO algorithm., Results: Finally, the influence of the ERSOCAE-SNC model is examined using a series of simulations. The ERSOCAE-SNC model reported best results over other approaches and produces an accuracy of 98.99% for soil nutrients and 99.12% for soil pH. The model developed for the ML decision systems will help the Tamil Nadu government to manage the problems in soil nutrient deficiency and improve the soil health and environmental quality. Also reduces the input expenditures of fertilizers and saves time of soil experts., Competing Interests: The authors declare that they have no competing interests., (© 2023 Raman and Chelliah.)

Biomarkers are biological molecules associated with physiological changes of the body and aids in the detecting the onset of disease in patients. There is an urgent need for self-monitoring and early detection of cardiovascular and other health complications. Several blood-based biomarkers have been well established in diagnosis and monitoring the onset of diseases. However, the detection level of biomarkers in bed-side analysis is difficult and complications arise due to the endothelial dysfunction. Currently single volatile organic compounds (VOCs) based sensors are available for the detection of human diseases and no dedicated nanosensor is available for the elderly. Moreover, accuracy of the sensors based on a single analyte is limited. Hence, breath analysis has received enormous attention in healthcare due to its relatively inexpensive, rapid, and noninvasive methods for detecting diseases. This review gives a detailed analysis of how biomarker imprinted nanosensor can be used as a noninvasive method for detecting VOC to health issues early using exhaled breath analysis.

Developing a microbial chassis with efficient enzymes is key to the synthesis of products by metabolic engineering. The wide distribution of desired pathway enzymes across several species and categories is posing major challenges in screening and selection of the same for pathway reconstruction. One such key enzyme is isopropylmalate isomerase (IPMI) of leucine/isoleucine biosynthetic pathway. The enzymes reported earlier as citraconase and maleate hydratase in Arthrobacter sp. and Pseudomonas sp. respectively, were found to have the characteristics of IPMI. If a systematic study is undertaken to show that these orphan enzymes indeed are part of the aconitase family of enzymes, these reported ones will add to the repertoire of enzymes available for branch-chained amino acid pathway engineering. This work is focused on functional characterisation of the enzymes citraconase and maleate hydratase based on the properties of IPMI. The partially sequenced gene of maleate hydratase reported earlier served as a template to identify the respective genes in these organisms which is found to be that of IPMI with conserved regions in the active site. The native enzymes and the IPMI of A. globiformis and P. pseudoalcaligenes, expressed in E. coli acted upon all the substrates in the forward direction comprising of D-citramalate, citraconate & D-erythro-3-methylmalate. In the reverse direction all the enzymes converted citraconate to D-citramalate with high activity. The estimated equilibrium ratio was same for both the native enzyme and the over-expressed IPMI which is 96:1.5:2.5 for D-citramalate: citraconate: D-erythro-3-methylmalate. The iron requirement for both enzymes which is characteristic of IPMI is ascertained by chelation and reconstitution of the same. Therefore, this work elucidated the broad specificity and the reactions in equilibrium catalysed by these enzymes like that of IPMI, paving way for the integration of these two efficient candidates into aconitase family of enzymes facilitating pathway engineering., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Chloroquine (CQ) is mainly known for antimalarial activity but due to lower sensitivity, it has not been well explored in the microbial disease treatment. In the present investigation, we attempted to enhance the CQ sensitivity in Pseudomonas aeruginosa . Presence of efflux pump is well demonstrated in bacterial system which plays an important role in drug sensitivity and resistance in bacteria and also serves other functions. Taking the advantage of presence of efflux pump in Pseudomonas aeruginosa , we made an attempt to sensitize the Pseudomonas aeruginosa with various plant extracts and phytochemicals for the development of CQ sensitivity. Ten rationally selected plant extracts were screened for the development of chloroquine sensitivity in P. aeruginosa . The chloroquine susceptibility assay was demonstrated by combining CQ and verapamil (a known efflux pump inhibitor) as a standard in an in vitro assay system. Results were quite encouraging as methanolic extracts of Syzygium aromaticum, Zingiber officinale and Curcuma longa were able to enhance chloroquine sensitivity in P. aeruginosa by increasing the zone of inhibition in well-defined assay system. These plant extracts were finally analysed for the presence of various phytochemicals. The Syzygium aromaticum extract showed the presence of phytochemicals, such as quinones, phenol, triterpenoid, saponins, tannins, alkaloids and flavonoids. On the other hand, the methanolic extract of Zingiber officinale and Curcuma longa showed the presence of saponins, tannins, alkaloids and flavonoids in the extract. Towards the identification of active principle of selected plant extract for CQ sensitivity enhancement, thin-layer chromatography was performed and various phytocomponent bands were isolated. Flavonoid ( R f 0.44) in Syzygium aromaticum, alkaloid ( R f 0.43) in Zingiber officinale and phenol ( R f 0.62) in Curcuma longa were found responsible for the enhancement of CQ susceptibility in P. aeruginosa . This interesting finding confirmed the concept that a prior course or combination of plant extracts or phytochemicals with chloroquine can be effective against P. aeruginosa . Present investigation successfully presented the proof of concept for the enhancement of chloroquine sensitivity in bacterial system by modulating an efflux pump. Concept can be explored for repurposing chloroquine for new applications., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03382-1., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© King Abdulaziz City for Science and Technology 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Angiotensin-converting enzyme I (ACE I) is a zinc-containing metallopeptidase involved in the renin-angiotensin system (RAAS) that helps in the regulation of hypertension and maintains fluid balance otherwise, which results in cardiovascular diseases (CVDs). One of the leading reasons of global deaths is due to CVDs. RAAS also plays a central role in maintaining homeostasis of the CV system. The commercial drugs available to treat CVDs possess several fatal side effects. Hence, phytochemicals like peptides having plant-based origin should be explored and utilized as alternative therapies. Soybean is an important leguminous crop that simultaneously possesses medicinal properties. Soybean extracts are used in many drug formulations for treating diabetes and other disorders and ailments. Soy proteins and its edible products such as tofu have shown potential inhibitory activity against ACE. Thus, this review briefly describes various soy proteins and products that can be used to inhibit ACE thereby providing new scope for the identification of potential candidates that can help in the design of safer and natural treatments for CVDs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ramlal, Nautiyal, Baweja, Kumar, Mehta, Mahto, Tripathi, Shanmugam, Pujari Mallikarjuna, Raman, Lal, Raju and Rajendran.)

Introduction: Metabolic syndrome (MetS) amplifies the risks of atherosclerosis. Despite well-known sexual dimorphism in atherosclerosis, underlying mechanisms are poorly understood. Our previous findings highlight a proatherogenic protein, thrombospondin-1 (TSP-1), in hyperglycemia- or hyperleptinemia (mimicking obesity)-induced atherosclerosis. However, the role of TSP-1 in the development of atherosclerosis prompted by co-existing hyperglycemia and obesity, characteristic of MetS, is unknown. The goal of this study was to examine sex-specific differences in lesion progression in a model of combined MetS and atherosclerosis (KKAyApoE) and interrogate how these differences relate to TSP-1 expression., Methods: Male and female KKAy +/- ApoE -/- (with ectopic agouti gene expression) and age-matched non-agouti KKAy -/- ApoE -/- littermates were placed on a standard laboratory diet from 4 to 24 weeks age followed by blood and tissue harvests for biochemical, molecular, and aortic root morphometric studies., Results: Metabolic profiling confirmed MetS phenotype of KKAy +/- ApoE -/- ; however, only male genotypes were glucose intolerant with elevated VLDL-cholesterol and VLDL-triglyceride levels. Aortic root morphometry demonstrated profound lipid-filled lesions, increased plaque area, and augmented inflammatory and SMC abundance in MetS vs non-MetS males. This increase in lesion burden was accompanied with elevated TSP-1 and attenuated LMOD-1 (SM contractile marker) and SRF (transcriptional activator of SM differentiation) expression in male MetS aortic vessels. In contrast, while lipid burden, plaque area, and TSP-1 expression increased in MetS and non-MetS female mice, there was no significant difference between these genotypes. Increased collagen content was noted in MetS and non-MetS genotypes, specific to female mice. Measurement of plasma testosterone revealed a link between the atherogenic phenotype and abnormally high or low testosterone levels. To interrogate whether TSP-1 plays a direct role in SMC de-differentiation in MetS, we generated KKAy +/- mice with and without global TSP-1 deletion. Immunoblotting showed increased SM contractile markers in male KKAy +/- TSP-1 -/- aortic vessels vs male KKAy +/- TSP-1 +/ + . In contrast, TSP-1 deletion had no effect on SM contractile marker expression in female genotypes., Conclusion: Together, the current study implicates a role of plasma testosterone in sex-specific differences in atherosclerosis and TSP-1 expression in MetS vs non-MetS mice. Our data suggest a sex-dependent differential role of TSP-1 on SMC de-differentiation in MetS. Collectively, these findings underscore a fundamental link between TSP-1 and VSMC phenotypic transformation in MetS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gupta, Khanal, Bhavnani, Mathias, Lallo, Kiriakou, Ferrell and Raman.)

Oral Squamous Cell Carcinoma comprises nearly 90% of all Oral cancers. Recent studies on Oral Squamous Cell Carcinoma are done with a focus on identification of factors that affect the outcome of treatment, one of which is vitamin D levels. The aim of this study was to evaluate vitamin D3 levels in patients with Oral Squamous Cell Carcinoma and Normal Population with saliva as a biomarker. The study sample comprised of 40 subjects, of whom 20 were patients diagnosed with OSCC and 20 healthy subjects. The salivary samples obtained were assessed using Vitamin D3 ELISA kit. The mean salivary Vitamin D3 levels were 39.09 ng/dl among OSCC patients and 44.49 ng/dl among healthy subjects. Salivary Vitamin D levels in OSCC patients were found to be significantly less compared to the healthy controls. More than 90% of cancers of the oral cavity are Oral Squamous Cell Carcinoma (OSCC). Recent studies are done with a focus on identification of factors affecting the treatment of cancer, one of which is vitamin D levels. The aim of the study was to evaluate salivary vitamin D3 levels in patients with Oral Squamous Cell Carcinoma and in Normal Population. 40 patients were selected for the study. Salivary samples collected were assessed using Vitamin D3 ELISA Kit-EDI Total 25-OH Vitamin D EIA Kit to detect the salivary vitamin D levels. Mean Salivary Vitamin D3 levels were found to be 39.09 ng/dl in OSCC patients and 44.49 ng/dl in healthy subjects. A salivary Vitamin D level in OSCC patients was found to be significantly less compared to the healthy controls. Decreased Vitamin D3 levels in patients with OSCC indicate that Vitamin D3 deficiency increases the rate of cell proliferation, invasion, angiogenesis & metastasis in patients with OSCC. Vitamin D level is likely to reduce the severity of the disease and hence Vitamin D supplementation for OSCC patients in the early stages of treatment and after treatment can be done to enhance the prognosis., (© 2022 Biomedical Informatics.)

In this work, organic aerogels from spent ground coffee and apple pomace were prepared and characterized for the first time. Apple aerogel was found to be much lighter than that from coffee (0.19 vs. 0.016 g/cm 3 , whereas the specific surface areas are comparable (229 vs. 208 m 2 /g). Being intrinsically hydrophilic, these aerogels were silanized, both in liquid and gas phase, to increase stability in aqueous media. The latter modification method allowed chemical grafting of the silane to the aerogel surface (evidenced by FTIR and TGA) and resulted in certain hydrophobicity, as was evidenced via contact angle measurements: both aerogels possess a contact angle of ca. 100° after the gas hydrophobization, while for the pristine aerogels it was 50°. Furthermore, it was observed that the gas-phase silanization process is more applicable to apple aerogels.

Centromeric histones (CenH3s) are essential for chromosome inheritance during cell division in most eukaryotes. CenH3 genes have rapidly evolved and undergone repeated gene duplications and diversification in many plant and animal species. In Caenorhabditis species, two independent duplications of CenH3 (named hcp-3 for HoloCentric chromosome-binding Protein 3) were previously identified in C. elegans and C. remanei. Using phylogenomic analyses in 32 Caenorhabditis species, we find strict retention of the ancestral hcp-3 gene and 10 independent duplications. Most hcp-3L (hcp-3-like) paralogs are only found in 1-2 species, are expressed in both males and females/hermaphrodites, and encode histone fold domains with 69-100% identity to ancestral hcp-3. We identified novel N-terminal protein motifs, including putative kinetochore protein-interacting motifs and a potential separase cleavage site, which are well conserved across Caenorhabditis HCP-3 proteins. Other N-terminal motifs vary in their retention across paralogs or species, revealing potential subfunctionalization or functional loss following duplication. An N-terminal extension in the hcp-3L gene of C. afra revealed an unprecedented protein fusion, where hcp-3L fused to duplicated segments from hcp-4 (nematode CENP-C). By extending our analyses beyond CenH3, we found gene duplications of six inner and outer kinetochore genes in Caenorhabditis, which appear to have been retained independent of hcp-3 duplications. Our findings suggest that centromeric protein duplications occur frequently in Caenorhabditis nematodes, are selectively retained for short evolutionary periods, then degenerate or are lost entirely. We hypothesize that unique challenges associated with holocentricity in Caenorhabditis may lead to this rapid "revolving door" of kinetochore protein paralogs., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

The effects of different incubation periods on the contents of amino acids, proteins, glycosylated proteins and metabolites in germinated and ungerminated mung bean seeds were investigated in this study. The study employs soaking of mung bean seeds in water under laboratory conditions at 28 °C for 3, 6, and 9 h, followed by germination for 12, 24, 36, and 48 h. Seeds collected from different period of imbibition and germination were subjected to total protein extraction for phytochemical analysis. Germination of the seeds was found to be most successful after 6 h of soaking (rather than 9 h of incubation). Hence, seeds imbibed for 6 h were further investigated for germination at 28 °C for 12, 24, 36, and 48 h. Total protein was extracted from both imbibed and germinated seeds, followed by trypsin digestion. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based peptide mass fingerprinting revealed 38 proteins in 6 h water-imbibed seeds and 50 proteins in 24 h germinated seeds. Among these, 16 were identified as glycosylated proteins and the maximum number of glycosylated proteins were detected in 6 h water-imbibed seeds and 24 h germinated seeds. Moreover, High Performance Liquid Chromatography (HPLC) was used to quantify amino acids from the extracted proteins. A total of 15 amino acids were detected, of which eight were essential and the remaining were non-essential; amino acid concentrations increased following 3, 6, and 9 h of imbibition when compared to the control. It was concluded from the study that seeds with 6 h of imbibition and 24 h of germination can be used as potential nutritional source of different amino acids, proteins, glycosylated proteins, and other bioactive metabolites in human diet., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) pandemic poses a tremendous threat as a rapidly spreading disease, and has significant consequences on the global public health in particular to the psychological aspect of the survivors. The lived experiences require urgent documentation to tailor-make psychiatric assessments and long-term follow-ups., Aim: To explore adolescents' self-reported perspectives and lived experiences during their COVID-19 illness which was voluntarily shared through media and social media platforms during the nationwide lockdown in India., Methods: Being a preliminary study, the sample size was calculated as 20 based on similar studies in the literature. Voluntarily shared data of COVID-19 survivors were extracted from media and social media. Based on the data, an assessment sheet was prepared, pre-tested and shared with three observers via convenient sampling., Results: Male predominance was noted. The mean age was found to be 39.5 years. English was the most commonly uploaded language to communicate suffering. Instagram and YouTube were the most prevalent social media sites for self-reported experiences. The most prevalent physical symptom was fever and cough. Stress, anxiety and stigmatization were more commonly reported. Statistical significance was obtained between fear and end of life, depression and suicide, pain and isolation and worried with insomnia., Conclusion: COVID-19 not only affects physical health but also takes a toll on the mental health of the patients. There is a high prevalence rate of psychological distress among COVID-19 survivors, and we recommend a formal psychiatric assessment and long-term follow-up to understand the unique challenges faced by the COVID-19 survivors, with effective communication and empathy towards them., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Background and Aims: Cardiovascular diseases are the leading causes of morbidity and mortality in chronic kidney disease (CKD) patients. Our aim was to derive predictors of cardiac morbidity, mortality, cardiac complications and to develop/validate a scoring tool in patients with CKD undergoing non-cardiac surgery., Methods: A prospective observational multicentre study was done on 770 patients with CKD. The primary outcome ("Event") was one or more than one of sudden cardiac death, pulmonary oedema, acute coronary syndrome, arrhythmia and 30-day mortality. Secondary outcome was hypertension and hypotension. Predictors of cardiac risk were identified. A scoring tool was developed on the 2018 dataset and was validated on the 2019 dataset., Results: The overall incidence of cardiac events was 290 (37.66%) whereas the incidence of major adverse cardiac and cerebrovascular events was 15.04%. Mortality due to cardiac cause was 13 (1.68%). On multivariate regression analysis, seven perioperative variables had significant association with increased risk of events: age > 65 years ( P = 0.004), metabolic equivalents (METS) ≤4 ( P ≤0.032), emergency surgery ( P =0.032), mean arterial pressure >119 ( P = 0.001), echocardiographic scoring ( P = 0.054), type of anaesthesia ( P ≤ 0.0001) and type of surgery ( P = 0.056). Using these variables, a risk stratification tool was developed. C statistics showed favourable predictive accuracy (0.714) and the model showed good calibration., Conclusion: This risk scoring tool based on preoperative variables will help to predict the risk of events in high-risk CKD patients undergoing non-cardiac surgery. This will help in better counselling and optimisation., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Anaesthesia.)

Tongue acts as a mirror of our body. Diagnosis of tongue lesions is challenging to primary physicians as they might be the first sign or may be a part of underlying systemic diseases. Knowledge on the lesions of tongue is necessary for oral and overall health planning and education. Hence, this article illustrates a clinical case series of tongue lesions among a rural population in south Chennai, thus imparting a higher awareness of the specific tongue pathology-related etiology and management to increase the awareness on thorough oral screening including detailed assessment of tongue and provide a holistic care to patients to improve the Oral health related and Overall quality of life of patients (OHRQOL/QOL)., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Background: Availability of cardiopulmonary resuscitation (CPR) data from India is limited in published literature and data on patients with renal disease even more so. Documented survival-to-discharge rates worldwide range from 8 to 15% in renal disease as compared to 25% in the general population., Methods: An institution-wide format for collection of cardiac arrest data was introduced in late 2015. We have analyzed all adult onsite cardiac arrests from January 2016 to December 2019. Patient characteristics and CPR parameters were both studied in detail. Primary endpoint was defined as survival to discharge. Association between patient and treatment characteristics and survival to discharge was studied., Results: Successful CPR resulting in patient discharge occurred in 28 (31.4%) out of 89 patients. A very strong association was found between mortality and prolonged CPR ( p <0.00001). Events occurring out of hours ( p = 0.0029), patients admitted in the intensive care unit (ICU) ( p = 0.03), initiated on inotropes ( p = 0.003), and patients already on a ventilator ( p = 0.0018) had poorer outcomes. Sepsis as the etiology emerged as the most significant association with mortality ( p = 0.0007). Patient characteristics such as age, sex, presence or absence of chronic kidney disease, type of dialysis treatment, and vintage were found to be insignificant., Conclusion: Analysis revealed survival to discharge of 31.4%. Sepsis in association with renal disease has been found to be consistent with higher risk for mortality. Other factors such as an out of hours event, admission to ICU, early intubation and inotrope initiation were associated with worse outcomes., How to Cite This Article: Sharma S, Raman P, Sinha M, Deo AS. Factors Affecting Outcomes of Cardiopulmonary Resuscitation in a Nephro-Urology Unit: A Retrospective Analysis. Indian J Crit Care Med 2022;26(3):322-326., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2022; Jaypee Brothers Medical Publishers (P) Ltd.)

Histones and their posttranslational modifications facilitate diverse chromatin functions in eukaryotes. Core histones (H2A, H2B, H3, and H4) package genomes after DNA replication. In contrast, variant histones promote specialized chromatin functions, including DNA repair, genome stability, and epigenetic inheritance. Previous studies have identified only a few H2B variants in animals; their roles and evolutionary origins remain largely unknown. Here, using phylogenomic analyses, we reveal the presence of five H2B variants broadly present in mammalian genomes. Three of these variants have been previously described: H2B.1, H2B.L (also called subH2B), and H2B.W. In addition, we identify and describe two new variants: H2B.K and H2B.N. Four of these variants originated in mammals, whereas H2B.K arose prior to the last common ancestor of bony vertebrates. We find that though H2B variants are subject to high gene turnover, most are broadly retained in mammals, including humans. Despite an overall signature of purifying selection, H2B variants evolve more rapidly than core H2B with considerable divergence in sequence and length. All five H2B variants are expressed in the germline. H2B.K and H2B.N are predominantly expressed in oocytes, an atypical expression site for mammalian histone variants. Our findings suggest that H2B variants likely encode potentially redundant but vital functions via unusual chromatin packaging or nonchromatin functions in mammalian germline cells. Our discovery of novel histone variants highlights the advantages of comprehensive phylogenomic analyses and provides unique opportunities to study how innovations in chromatin function evolve., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Purpose: The purpose of this study was to report a case of infective necrotizing scleritis following XEN Gel Stent with mitomycin-C., Methods: Case report. This is a case report of a 68-year-old woman., Results: XEN Gel Stent glaucoma surgery enhanced with mitomycin-C 0.04% and combined with cataract surgery was performed at a regional center to manage the patient's primary open-angle glaucoma. Past medical history was significant for rheumatoid arthritis requiring treatment with methotrexate and adalimumab. Periocular pain and swelling developed 14 months after the initial operation, followed by a rapid deterioration of visual acuity to 20/60, intraocular pressure of 4 mm Hg, and worsening pain 5 months later. On initial presentation to Sydney Eye Hospital, 180 degrees of scleral necrosis was evident with a moderate anterior segment inflammatory reaction and a large temporal choroidal effusion due to hypotony. Empirical hourly topical ofloxacin and cephalothin 5% drops, with oral moxifloxacin, were initiated. Conjunctival swab grew Staphylococcus aureus and Staphylococcus lugdunensis. Significant clinical improvement occurred, but the XEN Gel Stent became exposed after 9 days of treatment with worsening hypotony. Urgent surgical revision was performed to remove the XEN Gel Stent and apply a tutoplast plug with overlying amniotic membrane graft. Intraocular pressure gradually improved over 6 weeks to 15 mm Hg with reversal of hypotonous changes, and visual acuity stabilized at 20/40., Conclusions: To our knowledge, this is the first reported case of necrotizing scleritis following XEN Gel Stent insertion. It is a reminder that infection should always be the primary differential diagnosis in patients with surgical-induced necrotizing scleritis., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The purpose of this study was to identify the genes and pathways associated with IP, with progression to carcinoma-in-situ and invasive carcinoma., Methods: To determine genes and molecular pathways that may indicate progression and correlate with histologic changes, we analyzed six IP without dysplasia, five IP with carcinoma-in-situ, and 13 squamous cell carcinoma ex-IP by targeted sequencing. The HTG EdgeSeq Oncology Biomarker Panel coupled with next-generation sequencing was used to evaluate 2560 transcripts associated with solid tumors., Results: Progressive upregulation of 11 genes were observed (CALD1, COL1A1, COL3A1, COL4A2, COL5A2, FN1, ITGA5, LGALS1, MMP11, SERPINH1, SPARC) in the order of invasive carcinoma > carcinoma-in-situ > IP without dysplasia. When compared with IP without dysplasia, more genes are differentially expressed in invasive carcinoma than carcinoma-in-situ samples (341 downregulated/333 upregulated vs. 195 downregulated/156 upregulated). Gene set enrichment analysis determined three gene sets in common between the cohorts (epithelial mesenchymal transition, extracellular matrix organization, and coagulation)., Conclusions: Progressive upregulation of genes specific to IP malignant degeneration has significant clinical implications. This panel of 11 genes will improve concordance of histologic classification, which can directly impact treatment and patient outcomes. Additionally, future studies on larger tumor sets may observe upregulation in the gene panel that preceded histologic changes, which may be useful for further risk stratification., (© 2021 ARS-AAOA, LLC.)

The degree of metastatic disease varies widely among patients with cancer and affects clinical outcomes. However, the biological and functional differences that drive the extent of metastasis are poorly understood. We analyzed primary tumors and paired metastases using a multifluorescent lineage-labeled mouse model of pancreatic ductal adenocarcinoma (PDAC)-a tumor type in which most patients present with metastases. Genomic and transcriptomic analysis revealed an association between metastatic burden and gene amplification or transcriptional upregulation of MYC and its downstream targets. Functional experiments showed that MYC promotes metastasis by recruiting tumor-associated macrophages, leading to greater bloodstream intravasation. Consistent with these findings, metastatic progression in human PDAC was associated with activation of MYC signaling pathways and enrichment for MYC amplifications specifically in metastatic patients. Collectively, these results implicate MYC activity as a major determinant of metastatic burden in advanced PDAC. SIGNIFICANCE: Here, we investigate metastatic variation seen clinically in patients with PDAC and murine PDAC tumors and identify MYC as a major driver of this heterogeneity. This article is highlighted in the In This Issue feature, p. 275 ., (©2021 The Authors; Published by the American Association for Cancer Research.)

Background: Plasma-based circulating cell-free tumor DNA (ctDNA) genomic profiling by next-generation sequencing (NGS)is an emerging diagnostic tool for pancreatic cancer (PC). The impact of detected genomic alterations and variant allele fraction (VAF) in tumor response to systemic treatments and outcomes is under investigation., Methods: Patients with advanced PC who had ctDNA profiled at time of initial diagnosis were retrospectively evaluated. We considered the somatic alteration with the highest VAF as the dominant clone allele frequency (DCAF). ctDNA NGS results were related to clinical demographics, progression-free survival (PFS) and overall survival (OS)., Results: A total of 104 patients were evaluated. Somatic alterations were detected in 84.6% of the patients. Patients with ≥ 2 detectable genomic alterations had worse median PFS (p < 0.001) and worse median OS (p = 0.001). KRAS was associated with disease progression to systemic treatments (80.4% vs 19.6%, p = 0.006), worse median PFS (p < 0.001) and worse median OS (p = 0.002). TP53 was associated with worse median PFS (p = 0.02) and worse median OS (p = 0.001). The median DCAF was 0.45% (range 0-55%). DCAF >0.45% was associated with worse median PFS (p<0.0001) and median OS (p=0.0003). Patients that achieved clearance of KRAS had better PFS (p=0.047), while patients that achieved clearance of TP53 had better PFS (p=0.0056) and OS (p=0.037)., Conclusions: Initial detection of ctDNA in advanced PC can identify somatic alterations that may help predict clinical outcomes. The dynamics of ctDNA are prognostic of outcomes and should be evaluated in prospective studies., Competing Interests: Authors YF, LD and HD were employed by company Guardant Health, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Botrus, Uson Junior, Raman, Kaufman, Kosiorek, Yin, Fu, Majeed, Sonbol, Ahn, Chang, Drusbosky, Dada, Starr, Borad, Mody and Bekaii-Saab.)

Biologically active plant peptides, consisting of secondary metabolites, are compounds (amino acids) utilized by plants in their defense arsenal. Enzymatic processes and metabolic pathways secrete these plant peptides. They are also known for their medicinal value and have been incorporated in therapeutics of major human diseases. Nevertheless, its limitations (low bioavailability, high cytotoxicity, poor absorption, low abundance, improper metabolism, etc.) have demanded a need to explore further and discover other new plant compounds that overcome these limitations. Keeping this in mind, therapeutic plant proteins can be excellent remedial substitutes for bodily affliction. A multitude of these peptides demonstrates anti-carcinogenic, anti-microbial, anti-HIV, and neuro-regulating properties. This article's main aim is to list out and report the status of various therapeutic plant peptides and their prospective status as peptide-based drugs for multiple diseases (infectious and non-infectious). The feasibility of these compounds in the imminent future has also been discussed., Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare that are relevant to the content of this article., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022.)

Intraoral soft tissue injuries occur due to physical, chemical, or thermal agents, which may present as ulcerations, burns, desquamation, and gingival recession. Camphor is one such substance easily available in many Indian households and is not a very well-recognized potentially fatal toxic compound. Here, we report the first case of an intraoral soft-tissue burn in a geriatric female, as a result of direct injury to tissues due to the application of crushed camphor powder to manage tooth pain at home, which was successfully treated with 2% Curcuma longa. Health care professionals must be aware of the presentation and extent of injury that can be caused by camphor when placed on intraoral soft tissues. Awareness among the public and professionals must be created in order to avoid any potential mortality. The diagnostician must consider the possibility of a chemical agent, such as camphor, as a potential source of the oral mucosal injury., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Raman et al.)