Substrate stress relaxation regulates neural stem cell fate commitment.

Adult neural stem cells (NSCs) reside in the dentate gyrus of the hippocampus, and their capacity to generate neurons and glia plays a role in learning and memory. In addition, neurodegenerative diseases are known to be caused by a loss of neurons and glial cells, resulting in a need to better understand stem cell fate commitment processes. We previously showed that NSC fate commitment toward a neuronal or glial lineage is strongly influenced by extracellular matrix stiffness, a property of elastic materials. However, tissues in vivo are not purely elastic and have varying degrees of viscous character. Relatively little is known about how the viscoelastic properties of the substrate impact NSC fate commitment. Here, we introduce a polyacrylamide-based cell culture platform that incorporates mismatched DNA oligonucleotide-based cross-links as well as covalent cross-links. This platform allows for tunable viscous stress relaxation properties via variation in the number of mismatched base pairs. We find that NSCs exhibit increased astrocytic differentiation as the degree of stress relaxation is increased. Furthermore, culturing NSCs on increasingly stress-relaxing substrates impacts cytoskeletal dynamics by decreasing intracellular actin flow rates and stimulating cyclic activation of the mechanosensitive protein RhoA. Additionally, inhibition of motor-clutch model components such as myosin II and focal adhesion kinase partially or completely reverts cells to lineage distributions observed on elastic substrates. Collectively, our results introduce a unique system for controlling matrix stress relaxation properties and offer insight into how NSCs integrate viscoelastic cues to direct fate commitment.

Exploring selection signatures in the divergence and evolution of lipid droplet (LD) associated genes in major oilseed crops.

BACKGROUND: Oil bodies or lipid droplets (LDs) in the cytosol are the subcellular storage compartments of seeds and the sites of lipid metabolism providing energy to the germinating seeds. Major LD-associated proteins are lipoxygenases, phospholipaseD, oleosins, TAG-lipases, steroleosins, caleosins and SEIPINs; involved in facilitating germination and enhancing peroxidation resulting in off-flavours. However, how natural selection is balancing contradictory processes in lipid-rich seeds remains evasive. The present study was aimed at the prediction of selection signatures among orthologous clades in major oilseeds and the correlation of selection effect with gene expression. RESULTS: The LD-associated genes from the major oil-bearing crops were analyzed to predict natural selection signatures in phylogenetically close-knit ortholog clusters to understand adaptive evolution. Positive selection was the major force driving the evolution and diversification of orthologs in a lineage-specific manner. Significant positive selection effects were found in 94 genes particularly in oleosin and TAG-lipases, purifying with excess of non-synonymous substitution in 44 genes while 35 genes were neutral to selection effects. No significant selection impact was noticed in Brassicaceae as against LOX genes of oil palm. A heavy load of deleterious mutations affecting selection signatures was detected in T-lineage oleosins and LOX genes of Arachis hypogaea. The T-lineage oleosin genes were involved in mainly anther, tapetum and anther wall morphogenesis. In Ricinus communis and Sesamum indicum > 85% of PLD genes were under selection whereas selection pressures were low in Brassica juncea and Helianthus annuus. Steroleosin, caleosin and SEIPINs with large roles in lipid droplet organization expressed mostly in seeds and were under considerable positive selection pressures. Expression divergence was evident among paralogs and homeologs with one gene attaining functional superiority compared to the other. The LOX gene Glyma.13g347500 associated with off-flavor was not expressed during germination, rather its paralog Glyma.13g347600 showed expression in Glycine max. PLD-α genes were expressed on all the tissues except the seed,δ genes in seed and meristem while ß and γ genes expressed in the leaf. CONCLUSIONS: The genes involved in seed germination and lipid metabolism were under strong positive selection, although species differences were discernable. The present study identifies suitable candidate genes enhancing seed oil content and germination wherein directional selection can become more fruitful.

Tracheostomy Complications Over 5 Years: Decannulation Analysis.

Introduction: Tracheostomy is a life-saving surgical intervention commonly performed in patients requiring prolonged mechanical ventilation. However, the decannulation process is associated with various complications that can affect patient outcomes. This study aimed to assess complications and their management during decannulation in a cohort of tracheostomy patients at a tertiary care hospital, considering the complexities introduced by prior intubation. Materials and Methods: A retrospective cohort study was conducted involving 450 patients who underwent tracheostomy during a stipulated timeframe. Data regarding demographic characteristics, complications, and management strategies during decannulation were analysed. Special attention was given to distinguishing between complications directly related to the tracheostomy procedure and those potentially influenced by previous intubation. Results: Out of the 450 patients, 250 experienced minor complications such as localized bleeding, oxygen desaturation, and minor infections. Another 40 faced major complications including severe haemorrhage, tracheal damage, and stenosis. Increasing age and tracheostomy duration were identified as significant predictors of complications. Pharmacological treatments, surgical interventions, and respiratory therapy were among the management strategies employed. The differentiation between complications arising from tracheostomy and prior intubation highlighted the need for comprehensive patient evaluation. Conclusion: Complications associated with decannulation occur frequently with varying severity. Efficient recognition and management of these complications are vital for improving patient outcomes. The study provides important insights into the challenges experienced during the decannulation process and highlights the necessity of considering prior intubation history in the management of tracheostomy decannulation to refine patient care protocols.

The Cellular Genesis of Metabolic Syndrome and the Role of Anti-urate Drugs in Hyperuricemia Patients: A Systematic Review.

Hyperuricemia results due to the underexcretion of uric acid through kidneys or overproduction due to either intake of purine-rich foods, a high caloric diet, or a decreased activity of purine recycler hypoxanthine-guanine phosphoribosyl transferase (HGPRT). Increased xanthine oxidoreductase (XOR) enzyme activity may contribute to hyperuricemia. Literature provides growing evidence that an independent component that contributes to the development of metabolic syndrome (MetS) and associated comorbidities is hyperuricemia. Thus, precise cellular mechanisms involved during MetS and related comorbidities in hyperuricemia, and the role of anti-urate medicines in these mechanisms require further investigations. We searched online libraries PubMed and Google Scholar for data collection. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines for literature identification, selection, screening, and determining eligibility to produce unbiased meaningful outcomes. We applied quality assessment tools for the quality appraisal of the studies. And, outcomes were extracted from the selected studies, which revealed the relationship between hyperuricemia and MetS components by causing inflammation, endothelial dysfunction, oxidative stress, and endoplasmic reticulum stress. The selected studies reflected the role of xanthine oxide (XO) inhibitors beyond inhibition. This systematic review concluded that hyperuricemia independently causes inflammation, oxidative stress, endothelial damage, and endoplasmic reticulum stress in patients with hyperuricemia. These mechanisms provide a cellular basis for metabolic syndrome and related comorbidities. In this context, XO inhibitors and their beneficial effects go beyond XOR inhibition to ameliorate these pathological mechanisms.

Network pharmacology-based approach to investigate the molecular targets and molecular mechanisms of Rosmarinus officinalis L. for treating aging-related disorders.

Aging, a natural biological process, presents challenges in maintaining physiological well-being and is associated with increased vulnerability to diseases. Addressing aging mechanisms is crucial for developing effective preventive and therapeutic strategies against age-related ailments. Rosmarinus officinalis L. is a medicinal herb widely used in traditional medicine, containing diverse bioactive compounds that have been studied for their antioxidant and anti-inflammatory properties, which are associated with potential health benefits. Using network pharmacology, this study investigates the anti-aging function and underlying mechanisms of R. officinalis. Through network pharmacology analysis, the top 10 hub genes were identified, including TNF, CTNNB1, JUN, MTOR, SIRT1, and others associated with the anti-aging effects. This analysis revealed a comprehensive network of interactions, providing a holistic perspective on the multi-target mechanism underlying Rosemary's anti-aging properties. GO and KEGG pathway enrichment analysis revealed the relevant biological processes, molecular functions, and cellular components involved in treating aging-related conditions. KEGG pathway analysis shows that anti-aging targets of R. officinalis involved endocrine resistance, pathways in cancer, and relaxin signaling pathways, among others, indicating multifaceted mechanisms. Genes like MAPK1, MMP9, and JUN emerged as significant players. These findings enhance our understanding of R. officinalis's potential in mitigating aging-related disorders through multi-target effects on various biological processes and pathways. Such approaches may reduce the risk of failure in single-target and symptom-based drug discovery and therapy.

The Role of Intolerance of Uncertainty and Religiousness in Schizotypal Personality and Life Satisfaction: A Cross-Sectional Study.

Intolerance of uncertainty is an important trans-diagnostic determinant of mental disorders. It is related to psychotic symptoms and religiousness. Religiousness is related to schizotypal personality and wellbeing. Therefore, in a cross-sectional study, we studied the effects of intolerance of uncertainty and religiousness on schizotypal personality and the schizotypal personality-mediated effects of intolerance of uncertainty and religiousness on life satisfaction. On a sample of 734 college students (age, M = 20.3, SD = 3.48), intolerance of uncertainty, religiousness, life satisfaction, and schizotypal personality were measured through paper-pencil questionnaires. The results showed that intolerance of uncertainty had positive (direct) relationships with all schizotypal personality dimensions. However, intolerance of uncertainty had positive (mediated by ideas of reference and magical thinking) and negative (mediated by eccentric behavior) indirect effects on life satisfaction. Religiousness had direct as well as indirect (mediated by eccentric behavior) positive effects on life satisfaction. However, the behaving (mediated by ideas of reference) and belonging (mediated by magical thinking) sub-dimensions of religiousness had some indirect negative effects on life satisfaction. Thus, the present study shows that intolerance of uncertainty is an important contributor to psychotic proneness. Religiousness is largely health-enhancing. Moreover, there is a nuanced pattern of interactional relationship between intolerance of uncertainty, religiousness, schizotypal personality, and life satisfaction. We have discussed the theoretical and applied implications of the findings.

Sustainable Sensing with Paper Microfluidics: Applications in Health, Environment, and Food Safety.

This manuscript offers a concise overview of paper microfluidics, emphasizing its sustainable sensing applications in healthcare, environmental monitoring, and food safety. Researchers have developed innovative sensing platforms for detecting pathogens, pollutants, and contaminants by leveraging the paper's unique properties, such as biodegradability and affordability. These portable, low-cost sensors facilitate rapid diagnostics and on-site analysis, making them invaluable tools for resource-limited settings. This review discusses the fabrication techniques, principles, and applications of paper microfluidics, showcasing its potential to address pressing challenges and enhance human health and environmental sustainability.

Extracellular Vesicular miRNA in Pancreatic Cancer: From Lab to Therapy.

Pancreatic cancer is a prevalent lethal gastrointestinal cancer that generally does not show any symptoms until it reaches advanced stages, resulting in a high mortality rate. People at high risk, such as those with a family history or chronic pancreatitis, do not have a universally accepted screening protocol. Chemotherapy and radiotherapy demonstrate limited effectiveness in the management of pancreatic cancer, emphasizing the urgent need for innovative therapeutic strategies. Recent studies indicated that the complex interaction among pancreatic cancer cells within the dynamic microenvironment, comprising the extracellular matrix, cancer-associated cells, and diverse immune cells, intricately regulates the biological characteristics of the disease. Additionally, mounting evidence suggests that EVs play a crucial role as mediators in intercellular communication by the transportation of different biomolecules, such as miRNA, proteins, DNA, mRNA, and lipids, between heterogeneous cell subpopulations. This communication mediated by EVs significantly impacts multiple aspects of pancreatic cancer pathogenesis, including proliferation, angiogenesis, metastasis, and resistance to therapy. In this review, we delve into the pivotal role of EV-associated miRNAs in the progression, metastasis, and development of drug resistance in pancreatic cancer as well as their therapeutic potential as biomarkers and drug-delivery mechanisms for the management of pancreatic cancer.

Long-COVID-19 Impact in non-hospitalized patients: Sleep and quality of life 24 months after SARS-CoV-2 infection.

Background and Aims: Sleep disruption and reduced quality of life are common long coronavirus disease (COVID) manifestations, affecting survivors irrespective of initial COVID-19 severity. Limited research investigates symptoms beyond 24 months post-infection. We aimed to address this gap by longitudinally studying sleep patterns and overall quality of life in non-hospitalized adults, 24 months after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Methods: This prospective observational study involved the enrolment of 337 adult non-hospitalized patients in a consecutive fashion. Individuals with past COVID-19 (from 15 April 2020 to 30 June 2021) were examined at two Government hospitals and completed a telephone interview between 1 May 2023 and 30 June 2023, located in Jharkhand, India. Participants were queried about their sleep patterns and quality of life, utilizing the DSM5 LEVEL 2 and EQ-ED-5L tool, respectively. Results: Among 337 non-hospitalized participants, 212 completed the survey. Within this group (59.4% men, mean age 38), 36 (17.0%) experienced sleep impairment. All five dimensions of quality of life (QoL) were adversely affected in long COVID patients. Advanced age, high income, residing in rural or semi-urban areas, and having comorbidities were associated with a higher likelihood of decreased quality of life across various domains. Conversely, participants who were married, employed in healthcare or government positions, and vaccinated exhibited a reduced likelihood of experiencing lower quality of life. Conclusion: Long COVID-19 affects sleep and quality of life, with various demographic and clinical factors influencing outcomes. This study provides insights into the extended consequences of long COVID-19 and aids healthcare systems in addressing the challenges posed by this condition.

Exploring the potential of Bacillus for crop productivity and sustainable solution for combating rice false smut disease.

Rice false smut, which is caused by the soil-borne fungal pathogen Ustilaginoidea virens (U. virens), is one of the most threatening diseases in most of the rice-growing countries including India that causes 0.5-75% yield loss, low seed germination, and a reduction in seed quality. The assessment of yield loss helps to understand the relevance of disease severity and facilitates the implementation of appropriate management strategies. This study aimed to mitigate biotic stress in rice by employing a rhizobacterial-based bioformulation, which possesses diverse capabilities as both a plant growth promoter and a biocontrol agent against U. virens. Rhizobacteria were isolated from the soil of the rice rhizospheres from the healthy plant of the false smut affected zone. Furthermore, they were identified as Bacillus strains: B. subtilis (BR_4), B. licheniformis (BU_7), B. licheniformis (BU_8), and B. vallismortis (KU_7) via sequencing. Isolates were screened for their biocontrol potential against U. virens under in vitro conditions. The antagonistic study revealed that B. vallismortis (KU_7) inhibited U. virens the most (44.6%), followed by B. subtilis BR_4 (41.4%), B. licheniformis BU_7 (39.8%), and B. licheniformis BU_8 (43.5%). Various biochemical and plant growth promoting attributes, such as phosphate and Zn solubilization, IAA, ammonium, siderophore, and chitinase production, were also investigated for all the selected isolates. Furthermore, the potential of the isolates was tested in both in vitro and field conditions by employing talc-based bioformulation through bio-priming and root treatment. The application of bioformulation revealed a 20% decrease in disease incidence in plants treated with B. vallismortis (KU_7), a 60.5% increase in the biological yield, and a 45% increase in the grain yield. This eco-friendly approach not only controlled the disease but also improved the grain quality and reduced the chaffiness.

Tumor-derived Hsp70-CD14 interaction enhances the antitumor potential of cytotoxic T cells by activating tumor-associated macrophages to express CC chemokines and CD40 costimulatory molecules.

Heat shock proteins are a widely distributed group of proteins. It is constitutively expressed in almost all organisms and shows little variation throughout evolution. Previously, HSPs, particularly Hsp70, were recognized as molecular chaperones that aid in the proper three-dimensional folding of newly synthesized polypeptides in cells. Recently, researchers have focused on the potential induction of immune cells, including macrophages, antigen-specific CD8+ cytotoxic T cells, and PBMCs. It induces the expression of CC chemokines such as MIP-1α and RANTES, which are responsible for the chemotactic movement and migration of immune cells at the site of infection to neutralize foreign particles in vivo and in vitro in several cell lines but their effect on tumor-associated macrophages is still not known. These cytokines are also known to influence the movement of several immune cells, including CD8+ cytotoxic T cells, toward inflammatory sites. Therefore, the effect of tumor-derived autologous Hsp70 on the expression of MIP-lα and RANTES in tumor-associated macrophages (TAMs) was investigated. Our results indicated that Hsp70 treatment-induced MIP-lα and RANTES expression was significantly greater in TAMs than in NMOs. According to the literature, the CC chemokine shares the same receptor, CCR5, as HIV does for their action, and therefore could provide better completion to the virus for ligand binding. Furthermore, Hsp70-preactivated TAMs induced increased IL-2 and IFN-γ expression in T cells during coculture for 48 h and upregulated the antitumor immune response of the host. Therefore, the outcome of our study could be useful for developing a better approach to restricting the growth and progression of tumors.

Structure-based virtual screening methods for the identification of novel phytochemical inhibitors targeting furin protease for the management of COVID-19.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is a highly contagious respiratory disease with widespread societal impact. The symptoms range from cough, fever, and pneumonia to complications affecting various organs, including the heart, kidneys, and nervous system. Despite various ongoing efforts, no effective drug has been developed to stop the spread of the virus. Although various types of medications used to treat bacterial and viral diseases have previously been employed to treat COVID-19 patients, their side effects have also been observed. The way SARS-CoV-2 infects the human body is very specific, as its spike protein plays an important role. The S subunit of virus spike protein cleaved by human proteases, such as furin protein, is an initial and important step for its internalization into a human host. Keeping this context, we attempted to inhibit the furin using phytochemicals that could produce minimal side effects. For this, we screened 408 natural phytochemicals from various plants having antiviral properties, against furin protein, and molecular docking and dynamics simulations were performed. Based on the binding score, the top three compounds (robustaflavone, withanolide, and amentoflavone) were selected for further validation. MM/GBSA energy calculations revealed that withanolide has the lowest binding energy of -57.2 kcal/mol followed by robustaflavone and amentoflavone with a binding energy of -45.2 kcal/mol and -39.68 kcal/mol, respectively. Additionally, ADME analysis showed drug-like properties for these three lead compounds. Hence, these natural compounds robustaflavone, withanolide, and amentoflavone, may have therapeutic potential for the management of SARS-CoV-2 by targeting furin.

Temporal Bone Fractures after Trauma: A Prospective Analysis of Presentation, Management, and Outcomes.

To comprehensively understand the manifestation, treatments, and resultant consequences of temporal bone fractures, given their substantial impact on auditory and balance systems and the overall quality of life. A prospective study, adhering to the STROBE guidelines, spanning five years (2011-2015) was conducted on 83 male patients aged between 20 and 54 years, diagnosed with temporal bone fractures primarily caused by road traffic accidents. Evaluations comprised symptom presentation, otologic manifestations, radiological classifications, and management strategies, including both conservative and surgical interventions. Our study found that patients commonly presented with symptoms such as Oto-haematorrhoea, hearing impairment, and vertigo. Specifically, longitudinal fractures were the most frequent radiological finding, occurring in 63 cases (p < 0.001 for road traffic accidents). In terms of treatment outcomes, there was a notable improvement in the average hearing threshold, decreasing from 50 dB to 25 dB post-treatment (p < 0.001), and the air-bone gap reduced from 30 dB to 10 dB (p < 0.001). Audiometric outcomes varied significantly with fracture type, showing severe hearing loss was more common in transverse fractures (50%, p < 0.001) compared to longitudinal and mixed fractures. Additionally, the study revealed a significant reduction in the incidence of post-trauma vertigo over eight weeks (p < 0.001), underscoring the importance of early and appropriate intervention in managing temporal bone fractures. Efficient early detection and tailored interventions for temporal bone fractures lead to optimistic results. This research underscores the imperative for healthcare practitioners to adopt a comprehensive approach, from initial diagnosis to ongoing monitoring, to achieve optimal patient care. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04519-9.

Evaluation of Nasal Conditions on Sleep: Integrating Wearable Tech in Surgical Outcomes.

Objective: The primary objective of this study was to explore and identify the impacts of nasal septum deviation and turbinate hypertrophy on respiratory function, sleep quality, and overall well-being. Additionally, the study aimed to establish the therapeutic efficacy of surgical intervention and comprehensively analyse the additional advantages of wearable sleep trackers when combined with established diagnostic techniques. Methods: A prospective cohort of 150 participants (75 with nasal septum deviation and 75 with turbinate hypertrophy) underwent surgical intervention. The NOSE scale, PSQI, SF-36, and wearable sleep tracker data were employed for pre- and post-surgical evaluations. Objective measurements, such as nasal airflow and acoustic rhinometry, were also used. Multivariate regression was utilised to identify potential predictors of post-surgical outcomes. Results: The cohort had a mean age of 41 years with evenly balanced gender distribution. Both conditions showed post-surgical improvements in respiratory function, sleep quality, and quality-of-life. Wearable sleep tracker data provided insights into REM sleep duration and interruptions during sleep. The results indicated significant disturbances in sleep patterns in individuals with nasal septum deviation before undergoing surgery. Duration of the nasal condition was found to be a significant factor in predicting outcomes. Conclusion: Nasal septum deviation and turbinate hypertrophy had a significant impact on sleep patterns, overall well-being, and respiratory function. Surgical interventions provided significant relief, and wearable sleep tracker integration provides deeper insights into sleep disorders. The study highlights the importance of early intervention and the benefit of modern technologies in clinical evaluations. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04524-y.

Echoes Beyond Hearing: Psycho-Social Impacts of OAE Outcomes on Families of Neonates: An Indian Perspective.

The main aim of this study was to explore the psycho-social impacts of Otoacoustic Emissions (OAE) screenings on families. This involved understanding the initial responses of parents to test results, identifying any resulting concerns, and acknowledging the coping mechanisms utilized to handle these unexpectedly encountered difficulties. This retrospective observational study was conducted from January 2021 to December 2022 at a tertiary care facility. An extensive assessment was carried out on 1100 newborns that had undergone the OAE screening. Parental emotional reactions, worries regarding their child's prospects, and employed coping mechanisms were determined using structured questionnaires and interviews. The study aimed to explore the link between socio-economic status and varying levels of post-test anxiety and to study the effect of immediate post-screening counselling. A notable emotional reaction was observed, with 85% of parents, whose neonates were advised for subsequent tests, showing signs of shock and denial. Apprehensions related to the child's growth and societal acceptance were dominant, with 70% parents concerned about potential hurdles. There was a marked correlation between a lower socio-economic status and elevated post-test anxiety. Prompt counselling post-screening resulted in a substantial reduction in parental stress and anxiety levels. While the relevance of OAE testing concerning neonatal health is unequivocal, the psycho-social repercussions it imposes on families are significant. The findings underscore the need for holistic healthcare approaches that not only focus on physiological outcomes but also prioritize the mental well-being of families. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04486-1.

Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks.

Aging is a complex and time-dependent decline in physiological function that affects most organisms, leading to increased risk of age-related diseases. Investigating the molecular underpinnings of aging is crucial to identify geroprotectors, precisely quantify biological age, and propose healthy longevity approaches. This review explores pathways that are currently being investigated as intervention targets and aging biomarkers spanning molecular, cellular, and systemic dimensions. Interventions that target these hallmarks may ameliorate the aging process, with some progressing to clinical trials. Biomarkers of these hallmarks are used to estimate biological aging and risk of aging-associated disease. Utilizing aging biomarkers, biological aging clocks can be constructed that predict a state of abnormal aging, age-related diseases, and increased mortality. Biological age estimation can therefore provide the basis for a fine-grained risk stratification by predicting all-cause mortality well ahead of the onset of specific diseases, thus offering a window for intervention. Yet, despite technological advancements, challenges persist due to individual variability and the dynamic nature of these biomarkers. Addressing this requires longitudinal studies for robust biomarker identification. Overall, utilizing the hallmarks of aging to discover new drug targets and develop new biomarkers opens new frontiers in medicine. Prospects involve multi-omics integration, machine learning, and personalized approaches for targeted interventions, promising a healthier aging population.

Process Standardization of Functionally Enriched Millet-Based Nutri-Cereal Mix Using D-Optimal Design Approach for Enhancing Food and Nutritional Security.

Millets are currently employed in a variety of ways, including direct consumption and usage in the manufacture of certain cuisines or snacks. The present investigation was aimed at optimizing functionally enriched millet-based nutri-cereal mix comprising chicken and vegetable for a nutrition-deficient population. A total of 16 experiments were carried out by using optimal (custom) design model of mixture design with 60% major ingredients, including malted sorghum flour (20-30%), malted green gram flour (15-25%), and boiled chicken powder (5-15%). To make 100% of the total nutri-cereal mixture, other ingredients such as malted pearl millet (10%), finger millet flour (10%), beetroot powder (2.5%), pumpkin powder (7.5%), skimmed milk powder (9.5%), and stevia powder (0.5%) were added. Numerical optimization was done using Design Expert software, version 13. The optimized ratio was 30% malted sorghum flour, 15% malted green gram flour, and 15% chicken powder. The predicted values of responses 5.101%, 3.616%, 1.963%, 11.165%, 28.005%, 50.149%, 330.282 kcal, and 0.373 were in accordance with experimental values 6.426%, 3.455%, 1.714%, 11.432%, 29.12%, 47.853%, 323.318 kcal, and 0.385 for moisture, ash, fat, fiber, protein, carbohydrates, energy, and water activity, respectively, with a small error percentage. The results of mineral content, phenolic content, and amino acid profiling revealed that the optimized Nutri-cereal mix have higher amounts of these components. The results also suggested that the optimized Nutri-cereal mix of these malted millet flours can potentially enhance the nutritional deficiency as well as improve food and nutritional security.

Classification of white blood cells (leucocytes) from blood smear imagery using machine and deep learning models: A global scoping review.

Machine learning (ML) and deep learning (DL) models are being increasingly employed for medical imagery analyses, with both approaches used to enhance the accuracy of classification/prediction in the diagnoses of various cancers, tumors and bloodborne diseases. To date however, no review of these techniques and their application(s) within the domain of white blood cell (WBC) classification in blood smear images has been undertaken, representing a notable knowledge gap with respect to model selection and comparison. Accordingly, the current study sought to comprehensively identify, explore and contrast ML and DL methods for classifying WBCs. Following development and implementation of a formalized review protocol, a cohort of 136 primary studies published between January 2006 and May 2023 were identified from the global literature, with the most widely used techniques and best-performing WBC classification methods subsequently ascertained. Studies derived from 26 countries, with highest numbers from high-income countries including the United States (n = 32) and The Netherlands (n = 26). While WBC classification was originally rooted in conventional ML, there has been a notable shift toward the use of DL, and particularly convolutional neural networks (CNN), with 54.4% of identified studies (n = 74) including the use of CNNs, and particularly in concurrence with larger datasets and bespoke features e.g., parallel data pre-processing, feature selection, and extraction. While some conventional ML models achieved up to 99% accuracy, accuracy was shown to decrease in concurrence with decreasing dataset size. Deep learning models exhibited improved performance for more extensive datasets and exhibited higher levels of accuracy in concurrence with increasingly large datasets. Availability of appropriate datasets remains a primary challenge, potentially resolvable using data augmentation techniques. Moreover, medical training of computer science researchers is recommended to improve current understanding of leucocyte structure and subsequent selection of appropriate classification models. Likewise, it is critical that future health professionals be made aware of the power, efficacy, precision and applicability of computer science, soft computing and artificial intelligence contributions to medicine, and particularly in areas like medical imaging.

The Alzheimer's disease-linked protease BACE2 cleaves VEGFR3 and modulates its signaling.

The ß-secretase BACE1 is a central drug target for Alzheimer's disease. Clinically tested, BACE1-directed inhibitors also block the homologous protease BACE2. Yet, little is known about physiological BACE2 substrates and functions in vivo. Here, we identify BACE2 as the protease shedding the lymphangiogenic vascular endothelial growth factor receptor 3 (VEGFR3). Inactivation of BACE2, but not BACE1, inhibited shedding of VEGFR3 from primary human lymphatic endothelial cells (LECs) and reduced release of the shed, soluble VEGFR3 (sVEGFR3) ectodomain into the blood of mice, non-human primates and humans. Functionally, BACE2 inactivation increased full-length VEGFR3 and enhanced VEGFR3 signaling in LECs and also in vivo in zebrafish, where enhanced migration of LECs was observed. Thus, this study identifies BACE2 as a modulator of lymphangiogenic VEGFR3 signaling and demonstrates the utility of sVEGFR3 as a pharmacodynamic plasma marker for BACE2 activity in vivo, a prerequisite for developing BACE1-selective inhibitors for a safer prevention of Alzheimer's disease.