There is a new public health crisis threatening the world with the emergence and spread of novel coronavirus (SARS-CoV-2). The outbreak of coronavirus disease 2019 (COVID-19), which originated in Wuhan, China, in December 2019, has been declared a public health emergency of international concern by WHO. Most patients infected with SARS-CoV-2 exhibited symptoms of fever, cough, myalgia, fatigue and shortness of breath. Many infected people may be asymptomatic. It is generally believed that airway exposure to respiratory droplets from an infected patient is the main transmission route of this disease. However, apart from respiratory source, other source specimens like faecal matter and urine could be possible for COVID-19 infectivity. The spreading other routes of the virus has been alarming sign, both for public and health care professionals. Understanding the spreading routes of SARS-CoV-2 is crucial for patient management and defining biosafety strategies for public and health care workers.

The widespread availability of digital image processing softwares has given rise to various forms of image manipulation and forgery which can pose a significant challenge in different fields such as law enforcement, journalism etc,. it can also lead a privacy concern. We are proposing a privacy-preserving framework to encrypt images before processing them is vital to maintain the privacy and confidentiality of sensitive images, especially those used for purpose of Investigation. To address these challenges, we propose a novel solution that detects image forgeries while preserving the privacy of the images. Our method proposes a privacy-preserving framework that encrypts the images before processing them, making it difficult for unauthorized individuals to access them. The proposed method utilizes a compression quality analysis in the encrypted domain to detect the presence of forgeries in images if the forged portion (dummy image) has a compression quality different from the original image (featured image) in the encrypted domain. This approach effectively localizes the tampered portions of the image, even for small pixel blocks of size 10x10 in the encrypted domain. Furthermore, the method identifies the featured image's JPEG quality using the first minima in the energy graph.

Each year, the global population and agriculture suffer critical agricultural output losses as a result of severe drought devastation. Physiological drought occurs when plants are unable to extract water from the soil, even though it is available in the root zone. Apart from having a significant effect on plant physiology, drought stress has the effect of reducing crop yield. Drought stress influences plant metabolism both directly and indirectly. Drought stress alters the morpho-anatomical, physiological, and biochemical composition of plants, thereby decreasing transpiration water loss and increasing the efficiency with which plants use their water. Constant water loss through transpiration, combined with previously lost water, results in leaf water deficits. Nonetheless, drought stress has a wide variety of effects, ranging from lesions to confusion. Plant health is harmed when their ability to absorb water and nutrients, interact with their environment, and breathe is harmed. Apart from oxidative damage to plants, it may also result in cell death, which can occur under certain conditions when cells are exposed to their environment. Drought induces a plethora of physiological and molecular changes in plants, the majority of which assist them in adapting to the harsh environment. To mitigate drought's adverse effects, we must first gain a better understanding of how drought affects plant physiology. The purpose of this research is to better understand how drought affects plant development by examining the causes and effects of drought stress.

Over the years, Artificial Intelligence (AI) has seen a steady progress in development and evolution that can aid many sectors. Today, AI plays an essential role in the Fourth Industrial Revolution, and it is making its way into the military sector as well. Many countries are actively looking into AI military technology. Some of these innovations include image recognition, text analysis, Self-driving vehicles (SDV), gaming, robotic process automation (RPA) & Robotic and Autonomous Systems (RAS), and Autonomous Weapons Systems (AWS). In this research, we discuss the advantages of each innovation mentioned and analyze the many different cybersecurity threats that awaken due to military artificial intelligence systems. We then discuss the open research areas to better improve the current state of military artificial intelligence applications in terms of ethics, system security, proper strategy plan, accepted responsibility matrix, and introduction of relevant laws.

Hypertension is one of the most common primary cardiometabolic diseases and is a major contributor to cardiac mortality and morbidity. Furthermore, cardiac risk factors such as obesity and sedentary lifestyle are often seen in hypertensive patients. Regular exercise acts against these risk factors and improves the overall health of an individual. High-intensity interval training appears to do so in a more efficient way. We used a systematic literature review (SLR) approach to provide an overview of the present literature highlighting the cardiovascular advantages of HIIT in hypertensive individuals. We reviewed 4004 articles from reputable journals published between 2013 and August 14, 2023, focusing on 7 selected papers for in-depth analysis. This systematic review revealed the protective effects of HIIT against cardiac complications in hypertension. All the reviewed articles showed a decrease in blood pressure and many other risk variables of cardiovascular diseases. However, guidelines for this exercise are needed for maximum benefits. Therefore, further research on HIIT is necessary to fully harness its potential.

In this paper we compare using computational fluid dynamics the aerothermal performance of two candidate casing manifolds for supplying an impingement-actuated active tip clearance control system for an aero-engine high-pressure turbine. The two geometries are (a) single-entry: an annular manifold fed at one circumferential location; (b) multiple-entry: a casing manifold split into four annular sectors, each sector supplied separately from an annular ring main. Both the single-entry and multiple-entry systems analysed in this paper are idealised version of active clearance control systems in current production engines. Aerothermal performance is quantitatively assessed on the basis of the heat transfer coefficient distribution, driving temperature difference for heat transfer between the jet and casing wall, and total pressure loss within the high-pressure turbine active clearance control system. We predict that the mean heat transfer coefficient (defined with respect to the inlet temperature and local wall temperature) of the single-entry active clearance control system is 77% greater than the multiple-entry system; primarily because the coolant in the multiple-entry case picks up approximately 40 K of temperature from the ring main walls, and secondarily because the average jet Reynolds number of impingement holes in the single entry system is 1.2 times greater than in the multiple entry system. The multiple-entry system exhibits many local hot and cold spots, depending on the position of the transfer boxes, while the single-entry case has a more predictable aerothermal field across the system. The multiple-entry feed system uses an average of 20% of the total available pressure drop, while the feed system for the single-entry geometry uses only 2% of the total available pressure drop. From the aerothermal results of this computational study, and in consideration of holistic aero-engine design factors, we conclude that a single-entry system is closer to an optimal solution than a multiple-entry system.

Germplasm is a valuable natural resource in plant diversity that is crucial for its potential use. It provides knowledge about a species genetic composition. Germplasm protection strategies are not just planting hope threatened with extinction, they preserve medicinal and other essential plants on which survival rests. The successful use of genetic plant resources necessitates diligent collection, storage, analysis, documentation, and germplasm exchange. Slow growth cultures, cryopreservation, pollen and DNA banks, botanic gardens, genetic reserves and farmer’s fields are few conservation techniques. However, usage of an in vitro procedure with any chance of genetic instability leads to the destruction of the entire substance. Improved understanding of basic regeneration biology would, in turn, undoubtedly increase the capacity to regenerate plants from in vitro harvested explants, thus expanding selection possibilities. Germplasm conservation seeks to conserve endangered and vulnerable plant species worldwide for future proliferation and development; it is also the bedrock of agricultural production.

This project involves the development of Fire Suppression System (FSS) leveraging of Home automation system using Graphical System design (LabVIEW) software and Arduino microcontroller for real-time monitoring and control. The system integrates an Infrared (IR) flame sensor, an MQ2 gas sensor to detect and suppress fire hazards efficiently. The LabVIEW interface facilitates real-time monitoring of sensor data, allowing users to visualize and analyze the environmental conditions. Through this system, fires are automatically subdued, enhancing safety without requiring human intervention. This advances fire safety by swiftly containing threats and minimizing potential damage.

Urothelial cell carcinoma (UCC, bladder cancer) remains a difficult to treat malignancy with rising incidence worldwide. In the U.S., UCC is the sixth most incident neoplasm and ~90% of diagnoses are made in those >55 years of age, ~four times more commonly observed in men than women. The most important risk factor for developing bladder cancer is tobacco smoking, which accounts for ∼50% of cases followed by occupational exposure to aromatic amines and ionizing radiation. The standard of care for advanced UCC includes platinum-based chemotherapy and programmed cell death (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors, administered as frontline, second-line, or maintenance therapy. UCC is highly aggressive and remains generally incurable since these cancers are associated with intrinsic and acquired drug resistance. UCC is highly lethal in the metastatic state and characterized by genomic instability, high PD-L1 expression, DNA damage-response mutations, and high tumor mutational burden. Although immune checkpoint inhibitors (ICIs) achieve long-term durable responses in other cancers, their ability to achieve similar results with metastatic UCC (mUCC) is not as well-defined. Here, we discuss the novel therapies to improve the management of mUCC.

There are numerous hazards found on the farms. Most of them are ignored, which might cause the farmer to pay later in terms of his ill health, potential injuries or death. The current article discusses some of the common issues such as dust and air quality concerns; environmental (weather) stressors and psychological stressors; noise and hearing protection; and tractor safety and seatbelt use. And finally, the recommendations to overcome the hazards are discussed.

The plant-microbe-soil nexus is critical in maintaining biogeochemical balance of the biosphere. However, soil loss and land degradation are occurring at alarmingly high rates, with soil loss exceeding soil formation rates. This necessitates evaluating marginal soils for their capacity to support and sustain plant growth. In a greenhouse study, we evaluated the capacity of marginal incipient basaltic parent material to support native plant growth, and the associated variation in soil microbial community dynamics. Three plant species, native to the Southwestern Arizona-Sonora region were tested with three soil treatments including basaltic parent material, parent material amended with 20% compost, and potting soil. The parent material with and without compost supported germination and growth of all the plant species, though germination was lower than the potting soil. A 16S rRNA amplicon sequencing approach showed Proteobacteria to be the most abundant phyla in both parent material and potting soil, followed by Actinobacteria. Microbial community composition had strong correlations with soil characteristics but not plant attributes within a given soil material. Predictive functional potential capacity of the communities revealed chemoheterotrophy as the most abundant metabolism within the parent material, while photoheterotrophy and anoxygenic photoautotrophy were prevalent in the potting soil. These results show that marginal incipient basaltic soil has the ability to support native plant species growth, and non-linear associations may exist between plant-marginal soil-microbial interactions.

Polymeric hydrogels are promising polymeric functional materials that have been widely used in the biomedical field as an emerging carrier of various therapeutic agents. Polymeric hydrogels as a carrier of therapeutics can leverage therapeutically beneficial outcomes of drug delivery than systemic chemotherapy and can provide spatial and temporal control over the release of various therapeutic agents. Polymeric hydrogels are cross-linked three-dimensional networks constructed by hydrophilic polymers and they are capable of absorbing and re-taining a large amount of water. Polymeric hydrogels share many physiochemical features with natural tissues due to their water abundance, biomimetic microstructure, and intrinsic flexibility. Polymeric hydrogels have excellent biocompatibility, biodegradability, and lower toxicity. Polymeric hydrogels enhance the convenience and efficiency of drug delivery by assisting in situ gelation and controlling drug release by changing their volume and other properties when it encounters some stimuli (e.g., heat, pH, light, and ultrasound). This review aims to outline the overview of polymeric hydrogels, properties, types, advantage, disadvantages, characteri-zation, and their application with present status and future perspective used for the delivery of therapeutics in pharmaceutical and biomedical sciences.

UPF3B is a constituent of the classical nonsense-mediated mRNA decay (NMD) pathway that degrades both the aberrant transcripts and a set of physiological transcripts. In higher eukaryotes, UPF3B have significant biochemical functions in diverse cellular processes including NMD and translation. UPF3B plays a crucial role in neuronal development and differentiation. Next-generation sequencing technologies identified several loss-of-function mutations in the UPF3B gene that results in neuro-developmental disorders in humans. To uncover the mechanistic role of UPF3B in neuronal functions, we have generated the UPF3B-knockout mammalian cell line model system using CRISPR-Cas9 gene editing method. RNA-Sequencing Analysis of cellular transcriptome from UPF3B-KO cells identified specific genes involved in cell growth and neuronal functions. Altered expression of genes related to the axon guidance pathway delineated the UPF3B function to regulate the neuron-specific genes. Functional enrichment analysis identified the genes involved in the disorders related to mental health and intellectual disability. Our study has the potential to identify the direct players of intellectual disability and will have broader implications.

Climate change has had a significant impact on many ecosystems worldwide, prompting native population species to adapt to the current weather patterns eventually. Pre-existing genetic variation in populations explains part of this adaptation. Still, recent studies have shown that new stable phenotypes can be generated through epigenetic modifications in just a few generations, thereby contributing to the stability and survival of plants in their natural habitat as they eventually adjust to the surrounding impacts. The state of chromatin inside plant cells varies, allowing cells to fine-tune their transcriptional profiles to better adapt to stimuli from the external environment. Within a cell, chromatin state changes such as post-transcriptional histone modifications and variations, DNA methylation, and non-coding RNA activity are all examples of chromatin state alterations that may epigenetically dictate certain transcriptional outputs. Recent advances in the field of ‘Omics’ in major crops has made it easier to identify epigenetic changes and their impact on plant responses to environmental stresses. These epigenetic mechanisms thus play an important role in improving crop adaptation and resilience to changing environments. This variation that has emerged can thus be exploited in crop breeding, ultimately leading to the generation of stable climate-resilient genotypes.

Zero-dose children, or children who have not received any routine vaccination, are a priority population for global health policy makers as these children are at high risk of mortality from vaccine-preventable illnesses. We conducted a narrative review to identify potential interventions, both within and outside of the health sector, to reach zero-dose children. We reviewed peer-reviewed and grey literature and identified 59 relevant resources. Additionally, we interviewed six key informants to enhance synthesis of our findings. Data were organized into three priority settings: (1) urban slums, (2) remote or rural communities, and (3) conflict settings. We found that zero-dose children in the three-priority settings face differing barriers to vaccina-tion and, therefore, require context-specific interventions, such as leveraging slum health commit-tees for urban slums or integrating with existing humanitarian response services for conflict set-tings. Three predominant themes emerged for grouping the various interventions: (1) community engagement, (2) health systems strengthening and integration, and (3) technological innovations. The barriers to reaching zero-dose children are multifaceted and nuanced to each setting, there-fore, no one intervention is enough. Technological interventions especially must be coupled with community engagement and health systems strengthening efforts. Evaluations of the suggested interventions are needed to guide scale up, as the evidence-base around these interventions is rel-atively small.

Abstract: Background: Bangladesh has achieved remarkable progress in reducing maternal mortality, yet postpartum deaths remain a significant issue. Emphasis on quality postnatal care (qPNC) is crucial, as increased coverage alone has not sufficiently reduced maternal morbidity and mortality. Methods: This study included data from the Bangladesh Maternal Mortality Survey of 32,106 mothers who delivered within three years prior to the survey. Descriptive statistics were used to report coverage and components of postnatal care stratified by covariates. Log-linear regression models were used to assess the determinants of quality postnatal care among facility and home births. Results: From 2010 to 2016, postnatal care coverage within 48 hours of delivery by a qualified provider rose from 23% to 47%. 94% of facility births received timely PNC, contrasted with only 6% for home births. Despite the increased coverage, quality of care remained as low as 1% for home births and 13% for facility births. Key factors affecting qPNC utilization included socio-demographic factors, pregnancy complications, delivery method, financial readiness, and mobile ownership. Conclusion: Importantly, deliveries assisted by skilled birth attendants correlated with higher quality postnatal care. The study reveals a significant gap between the coverage and quality of postnatal care in rural Bangladesh, especially for home births. It underscores the need for targeted interventions to enhance qPNC.

This paper presents a multi-year research study conducted at the University of Toledo, aimed at improving human-machine teaming (HMT) methods and technologies. With the incorporation of artificial intelligence (AI) into 21st-century machines, collaboration between humans and machines has become highly complicated for real-time applications. The penetration of intelligent and synthetic assistants (IA/SA) in virtually every field has opened a path for the new area of HMT. When it comes to crucial tasks such as patient treatment and care, defense, and industrial production, the use of non-standardized HMT technologies may pose a risk to human lives as well as up to billions of taxpayer dollars. A thorough literature survey revealed that there are not many established standards or benchmarks for HMT. In this paper, we aim to address the lack of HMT design and development standards. We propose a method to design an HMT based on a generalized architecture. This design includes the development of an intelligent collaborative system and human team. Followed by processes and metrics to test and validate the proposed model, we present a novel human-in-the-loop (HIL) simulation method using two controlled HMT scenarios; first, emergency care provider (ECP) training, and second, patient treatment by an experienced medic. Both scenarios include humans processing visual data and performing actions that represent real-world applications while responding to a Voice-Based Synthetic Assistant (VBSA) as a collaborator that keeps track of actions. As part of these HMT simulation studies, the impact of each parameter related to machines, humans, and HMT (such as errors made by humans and by the VBSA) is presented from the perspective of performance, rules, roles, and operation limitations. In addition, based on the analysis of results from two case studies, we presented guidelines for designing future HMT. Our conclusions indicate that the proposed HIL can be used to perform standardization studies in the pursuit of developing techniques for benchmarking HMT that can be used in critical situations.

Cancer cells are adept at reprogramming energy metabolism and the precise manifestation of this metabolic reprogramming exhibits heterogeneity across individuals (and from cell to cell). In this study, we analyzed the metabolic differences between interpersonal heterogeneous cancer phenotypes. We used divergence analysis on gene expression data of 1156 breast normal and tumor samples from The Cancer Genome Atlas (TCGA) and integrated this information with a genome-scale reconstruction of human metabolism to generate personalized, context-specific metabolic networks. Using this approach, we classified the samples into four distinct groups based on their metabolic profiles. Enrichment analysis of the subsystems indicated that amino acid metabolism, fatty acid oxidation, citric acid cycle, androgen and estrogen metabolism and ROS detoxification distinguished these four groups. Additionally, we developed a workflow to identify potential drugs that can selectively target genes associated with the reactions of interest. MG-132 (a proteasome inhibitor) and OSU-03012 (a celecoxib derivative) were the top-ranking drugs identified from our analysis and known to have anti-tumor activity. Our approach has the potential to provide mechanistic insights into cancer-specific metabolic dependencies, ultimately enabling the identification of potential drug targets for each patient independently, contributing to a rational personalized medicine approach.

Flowering time is a critical stage for crop development as it regulates the ability of plants to adapt to an environment. To understand the genetic control of flowering time, a genome wide association study (GWAS) was conducted to identify the genomic regions associated with the control of this trait in durum wheat (Triticum durum Desf.). A total of 96 landraces and 288 modern lines were evaluated for days to heading, growing degree days, and accumulated day length at flowering across 13 environments spread across Morocco, Lebanon, Mauritania, and Senegal. These environments were grouped into four pheno-environments based on temperatures, day length and other climatic variables. Genotyping with 35K Axiom array generated 7,652 polymorphic SNPs in addition to 3 KASP markers associated to known flowering genes. In total, 34 significant QTLs were identified in both landraces and modern lines. Some QTLs had strong association with already known regulatory photoperiod genes, Ppd-A and Ppd-B and vernalization genes Vrn-A1, and Vrn3. However, these loci explained only 5 to 20% of variance for days to heading. Seven QTLs overlapped between the two germplasm groups in which Q.ICD.Eps-03 and Q.ICD.Vrn-17 consistently affected flowering time in all the pheno-environments, while Q.ICD.Eps-11 and Q.ICD.Ppd-12 were significant only in two pheno-environments and the combined analysis across all environments. These results help clarify the genetic mechanism controlling flowering time in durum wheat and show some clear distinctions to what is known for common wheat (Triticum aestivum L.)

Thermal Non-destructive Testing and Evaluation (NDT&E) is crucial in ensuring the quality and safety of industrial materials, components, and structures. It serves as a key tool for assessing their operational reliability, thus enhancing safety in a wide range of industries. There is a growing demand for dependable, swift, remote, and secure inspection and assessment techniques to detect hidden flaws, especially for sustainable solutions prompts adjustments in design and manufacturing standards. Hidden defects often emerge during the service life of these materials and structures due to various stress factors, potentially resulting in catastrophic failures. This study delves into the optimal and dependable experimental method for conducting fast, remote, and secure inspections and assessments of carbon fiber reinforced polymer materials using Infrared Imaging (IRI) as part of Thermal Non-Destructive Testing and Evaluation (TNDT&E). Additionally, it examines the post-processing approach associated with this technique. This perspective also sheds light on the current state-of-the-art infrared imaging methods employed in TNDT&E, emphasizing their strengths and weaknesses about their ability to detect subsurface defects present within the material Most of the methods discussed in previous research primarily focus on the thermal differences in specific areas of a sample using processed thermal images, even though these images come from analyzing a series of images captured over time. This study highlights the latest research in thermal/infrared non-destructive testing and evaluation, along with the related post-processing techniques. It aims to not only show hidden subsurface defects through thermal differences also provides information about how these defects change over time.

Infection by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) results in the novel coronavirus disease COVID-19, which has posed a serious threat globally. Infection of SARS-CoV-2 during pregnancy is associated with complications like preterm labor and premature rupture of membranes; a proportion of neonates born to the infected mothers are also positive for the virus. During pregnancy, the placental barrier protects the fetus from pathogens and ensures healthy development. However, whether or not SARS-CoV-2 can infect the placenta is unknown. Herein, utilizing single-cell RNA-seq data, we report that the SARS-CoV-2 binding receptor ACE2 and the S protein priming protease TMPRSS2 are co-expressed by a subset of syncytiotrophoblasts (STB) in the first trimester and extra villous trophoblasts (EVT) in the second trimester human placenta. The ACE2- and TMPRSS2-positive (ACE2+TMPRSS2+) placental subsets express mRNA for proteins involved in viral budding and replication. These cells also express mRNA for proteins that interact with SARS-CoV-2 structural and non-structural proteins in the host cells. We also discovered unique signatures of genes in ACE2+TMPRSS2+ STBs and EVTs. The ACE2+TMPRSS2+ STBs are highly differentiated cells and express genes involved mitochondrial metabolism and glucose transport. The second trimester ACE2+TMPRSS2+ EVTs are enriched for markers of endovascular trophoblasts. Further, both these subtypes abundantly expressed genes in Toll like receptor pathway, the second trimester EVTs (but not first trimester STBs) are also enriched for component of the JAK-STAT pathway that drive inflammation. To conclude, herein we uncovered the cellular targets for SARS-CoV-2 entry and show that these cells can potentially drive viremia in the developing human placenta. Our results provide a basic framework towards understanding the paraphernalia involved in SARS-CoV-2 infections in pregnancy.

Uncertain price movement in staple food commodities puts agrarian economies at risk if not monitored and managed consistently. Hence, an attempt has been made to analyze the price behavior and integration across major wholesale and retail markets for rice and wheat in India. Monthly data (July 2000 to June 2022) on prices viz., wholesale and retail were sourced from the Food and Agriculture Organization and analyzed using growth rate, instability index, seasonal price index, Johansen’s test on cointegration, Granger causality test, and impulse response function. Findings indicated strong evidence of price dynamics in the selected markets in terms of spatial and temporal variation, clear-cut seasonality linking to production, and price divergence between wholesale and retail markets. Johansen’s test indicated a strong integration between wholesale and retail markets exhibiting unidirectional-, bidirectional- and no-causality. Impulse response analysis revealed that the selected wheat and rice markets are efficient in terms of ‘price discovery’ which takes place initially in the wholesale market, and then transmitted to the retail market. The study advocates decision-making information to the producers, traders, and consumers who have a potential interest in getting advantage of the price movement. It is concluded that strengthening market intelligence and reducing the distortion in markets will improve the existing overall performance.

In this work we study the energy consumption by various modern secured hash functions (MD2, MD5, SHA-1, and SHA-2) and modern symmetric key encryption protocols (Blowfish, DES, 3DES, and AES) from the algorithmic perspective. We identify various parameters that moderate energy consumption of these hashes and protocols. Our work is directed towards redesigning or modifying these algorithms to make them consume lesser energy. As a first step, we try to determine the applicability of the asymptotic energy complexity model by Roy et. al. on these hashes and protocols. Specifically, we try to observe whether parallelizing the access of blocks of data in these algorithms reduces their energy consumption based on the energy model. Our results confirm the applicability of the energy model on these hashes and protocols. Our work is motivated by the relevance and importance of cryptographic hashes and symmetric key protocols for modern ICT (Information and Communication Technology), and ICT enabled industry to keep them protected from dynamically changing threat scenarios. Hence the design of more energy efficient hashes and protocols will definitely contribute in reducing the ICT energy consumption that is continuously increasing.

The triple-negative breast cancer (TNBC) subtype is one of the most aggressive forms of breast cancer that has poor clinical outcome and still remains as an unmet clinical challenge. Accumulating evidence suggests that intratumoral heterogeneity or the presence of phenotypically heterogeneous cell populations within a tumor plays a crucial role in chemoresistance, tumor progression and metastasis. Increased understanding of the molecular regulators of intratumoral heterogeneity will enable the development of effective therapeutic strategies in TNBC. We have identified a molecular mediator involved in intratumoral heterogeneity in breast cancer using an unbiased approach. We isolated two heterogeneous tumor cell populations from the 4T1 TNBC tumor model and phenotypic characterization revealed that the cells are distinct in terms of their morphology, proliferation and self-renewal ability in vitro; as well as primary tumor formation and metastatic potential in vivo. Further, RNA sequencing on both cell populations was performed to identify the molecular mediators underlying this heterogeneity. Bioinformatic analysis performed on the differentially expressed genes along with the Kaplan-Meier survival analysis in TNBC patients identified Metastasis associated colon cancer 1 (Macc1) as the top candidate gene mediating the aggressive phenotype. The role of Macc1 in regulating the proliferative phenotype was validated using siRNA mediated gene knockdown. The role of Macc1 in the aggressive cancer cell phenotypes and disease progression is being studied further using a small molecule transcriptional inhibitor of Macc1 in cell line and animal models, thus increasing our understanding of the molecular underpinnings of intratumoral heterogeneity in breast cancer that is critical to the improvement in the treatment of women currently living with the highly aggressive TNBC subtype.

In recent years, the emergence of cancer drug resistance is one of the crucial tumor hallmarks which is supported by the level of genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression of ABC transporters and stemness are among the several key contributing molecular and cellular response mechanisms. Topo-active drugs, e.g., doxorubicin and topotecan, are clinically active and are utilized extensively against a wide variety of human tumors and often results in the development of resistance and failure to therapy. Thus, there is an urgent need for an incremental and comprehensive understanding of mechanisms of cancer drug resistance specifically in the context of topo-active drugs. This review delves into the intricate mechanistic aspects of these intracellular and extracellular topo-active drug resistance mechanisms and explores use of potential combinatorial approaches by utilizing various topo-active drugs and inhibitors of pathways involved in drug resistance. We believe that this review will help guide basic scientists, pre-clinicians, clinicians, and policymakers toward holistic and interdisciplinary strategies that transcend resistance, renewing optimism in the ongoing battle against cancer.

Digitization of tissues allows examination of tissue morphologies in new ways enabling patient stratification for effective treatments. Current slide-scanning techniques capture the visible details of the tissue as whole-slide images and digitally record them in the form of spatial and color relationships. Specialized experimental techniques like Dielectric spectroscopy can also be used to investigate a tissue’s response to an applied electric field. This study used the dielectric spectroscopy method to collect the complex permittivity of healthy and abnormal biopsy tissues excised during gastroenterology procedures. A single pole Cole-Cole model is fitted to the measurements dataset to extract the parameters which are used as features in machine learning binary classification models. The models achieved high accuracy, demonstrating the feasibility of using microwave-based spectroscopy measurements to create a digital dielectric fingerprint for tissues under investigation.

In this paper, we consider a class of bilevel programming problems (abbreviated as, BLPP). Exploiting the generalized approximate convexity assumptions, we investigate the relations among the solutions of approximate Minty (respectively, Stampacchia) type variational inequalities (abbreviated as, AMTVI (respectively, ASTVI)), and the local ϵ-quasi solutions of the BLPP. Moreover, by employing the generalized Knaster–Kuratowski–Mazurkiewicz (abbreviated as, KKM)-Fan’s lemma, we derive some existence results for the solutions of approximate variational inequalities (abbreviated as, AVI), namely, AMTVI and ASTVI. A non-trivial example is given to highlight the importance of the established results. To the best of our knowledge, there is no research paper available in the literature that establishes relationships between the AVI and the BLPP under the assumptions of generalized approximate convexity in terms of limiting subdifferentials.

Despite the recent launch of Tolvaptan, the search for safer polycystic kidney disease (PKD) drugs continues. Ciclopirox, as the free acid (CPX) and its olamine salt (CPX-O) , are contained in number of commercially available topical antifungal agents. CPX is reported in the literature to possess anticancer activity in number of solid tumor cancers and hematological malignancy by several proposed mechanisms of action including chelation of iron and inhibition of iron dependent enzymes. Here, we show that CPX-O inhibited in vitro cystogenesis of primary human cyst epithelial cells cultured in 3D collagen matrix. To determine if CPX-O inhibits PKD progression, we treated PKD mice with a low dose of 10 mg/kg CPX-O by daily intraperitoneal injections from day 21 to day 49 post- partum. CPX-O reduced the kidney to body weight ratio of the PKD mice. This was associated with decreased cell proliferation decrease cystic area and improved renal function. We found that ferritin levels were significantly elevated in cystic kidneys of PKD mice, and that CPX-O treatment reduced renal ferritin levels and increased ferritinophagy marker, NCOA4. Our data suggest that CPX-O dose dependently induces ferritin degradation via ferritinophagy which is associated with decreased cyst growth and disease progression in PKD mice. Most importantly these data indicate that CPX-O, a drug used to treat skin infections and currently in clinical trials for cancer, has the potential to treat ADPKD.

With enhanced life expectancy and ageing global populations, the prevalence of multimorbidity continues to increase. However, there is a dearth of evidence linked to multimorbidity diagnoses, treatments and health outcomes which remains a concern for future proofing optimal healthcare services. Generating evidence is critical to managing multimorbidity, promoting public health and minimizing health inequalities via effective healthcare policies that improve quality of life for vulnerable populations. This study assessed meta-epidemiology of multimorbidity to report the gaps in scientific knowledge and clinical practice. A systematic methodology was designed and published in PROSPERO (CRD42022347308) to report meta-epidemiology analyses using databases including PubMed, Web of Science, ScienceDirect, EMBASE, The Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials and MEDLINE for studies published between the 1^st of January 1980 - 31^st December 2022. A random-effects model was used to estimate the pooled proportion of multimorbidity in adults. Forest plots, pooled odds ratios and statistical heterogeneity metrics were used to assess the association between multimorbidity and investigated factors. Funnel plots and Egger’s regression were used to detect and correct for publication bias. Our findings identified women to be 0.32 times more likely to have multimorbidity in comparison to males. In regard to ethnicity, white people were 0.47 times less likely to develop comorbidities than black people. People who identified as a drinker or unmarried were more likely to develop comorbidities than those who are non-drinkers or married, respectively. Regardless of smoking status, people were equally likely to have comorbidity. In terms of environmental influences, people in rural areas were found to be 0.2 times less likely to have comorbidity in comparison to those living in urban areas. Interestingly, people with a higher education level were 0.57 times more likely to develop comorbidities than those with only a high school education. It is evident that multimorbidity has a significant burden globally and impacts the provision of care necessitated across populations given its association with several social determinants of health. Robust research and healthcare policies are required to better manage multimorbidity in patients. An example of such intervention includes employing prevention programs to reduce risk and incidence of multimorbidity within at-risk populations.

The risk of 'zoonotic spillovers,' or the transmission of viruses from animals to humans, has been raised by climate change and the devastation of nature, as infectious disease experts have long warned. Even as the world works to stop the spread of the currently unfolding pandemic of coronavirus disease 2019 (COVID-19) and the breakout of monkeypox virus (MPXV), a new animal virus, the Langya henipavirus (LayV), has been discovered in humans in Eastern China. The scientists say there is little danger of the virus spreading among humans, but it shares genetic material with Hendra virus and Nipah virus, two other henipaviruses that infect humans and cause life-threatening respiratory diseases. Humans infected with LayV can expect to experience high body temperature, cough, weariness, poor appetite, muscle discomfort, myalgia, nausea and vomiting. It is likely that the virus will spread from animals to humans. Currently, the health authorities of Taiwan and other health organizations are tracking the progress of the ailment to ensure it does not reach humans. Researchers have examined 25 species of small wild animals for presence of the virus, and so far, shrews are the only ones that have tested positive for the virus's RNA. Based on these results, shrews are a possible candidate for the virus's natural reservoir. Too far, no therapies or vaccines have been developed and licensed for henipaviruses like the LayV. When other therapies fail to alleviate viral infections, ribavirin may be the next best thing. The need for novel vaccinations against the LayV infection and the timely delivery of these vaccines to areas at high epidemiological risk is real. To lessen the likelihood of a health calamity being caused by this newly developing virus, it is crucial to conduct active surveillance in a transparent and globally collaborative manner. The questions that have not been answered yet require additional study.

A community-level nutrition intervention was implemented among tribal children (3 to 6 years) in Telangana, India. The one-year intervention involved six nutrient-rich formulations of millet-pulse-groundnut based products, suited to local taste preferences. Anthropometric measurements of height, weight and Mid-Upper-Arm -Circumference (MUAC) along with haemoglobin (Hb) levels were monitored at baseline and endline. The treatment group showed considerable gain in height (3.2 cm), weight (1.68 kg) and MUAC (0.33 cm), over the control group. Paired t-test indicated significant differences (p<.01) between pre- and post-intervention anthropometric measurements. Positive shifts were observed in wasting (WHZ; -1.2 ±1.3 to -0.9± 1), stunting (HAZ; -1.8±1.6 to -0.3±1.3) and underweight (WAZ; -1.9±1.2 to -0.7±1) among treatment group. Hb levels in the treatment group also improved significantly from 9.70 ± 0.14 g/dl (moderately-anaemic) to 11.08 ± 0.13 g/dl (non-anaemic). Post-intervention Focus Group Discussions (FGDs) involving mothers and teachers confirmed the positive impact. Thus, nutritional intervention formulated using climate resilient millets, pulses and groundnut, promotes dietary diversity and improves the nutrition & health status of children.

Breast cancer (BC) is the most common type of cancer in both men and women alike, but it is more prevalent in women. Natural compounds that can modulate the oncogenic process can be considered a significant anti-cancer agent for treating BC. These natural compounds are more effective than synthetic drugs, which have profound side effects on the normal cell and resistance to cancer cells. Genistein is a type of dietary phytoestrogen included in the flavonoid group with a similar structure of estrogen that might provide a strong alternative and complementary medicine to existing chemotherapeutics drugs. Several research studies demonstrated that it can target the estrogen receptor (ER), Human epidermal growth factor receptor-2 (HER2), and Breast cancer gene-1 (BRCA-1) in multiple BC cell lines, as well as sensitize cancer cell lines to this compound when used at an optimal inhibitory concentration. Genistein effectively showed anti-cancer activities through apoptosis induction, arresting cell cycle, inhibiting angiogenesis with metastasis, reducing inflammation, mammosphere formation, tumor growth, up-regulating tumor suppressor gene, and downregulating oncogene in suppressing cancer progression in vitro and animal model study. In addition, research studies have also suggested that these phytochemicals synergistically reverse the resistance mechanism of chemotherapeutic drugs, increasing the efficacy of some chemoinformatics drugs. Our review article aims to unbox and validate the molecular pharmacology in breast tissue, cell-specific anti-cancer mechanism with synergistic activity, and possible pharmacokinetic parameters of Genistein as a potential alternative therapeutic option for the treatment of BC.

Drought stress at the reproductive stage in rice is one of the most important cause for yield reduction, affecting both productivity and quality. All Basmati rice varieties, including the popular cultivar ‘Pusa Basmati 1 (PB1)’ is highly sensitive to reproductive stage drought stress (RSDS). We report for the first time, improvement of a Basmati cultivar for RSDS tolerance, with the introgression of a major quantitative trait locus (QTL), ‘qDTY1.1’ into PB1. The QTL donor was sourced from an aus variety, Nagina 22 (N22). A QTL linked microsatellite (SSR) marker ‘RM 431’ was employed for foreground selection for qDTY1.1 in the marker assisted backcross breeding process. A set of 113 SSR markers polymorphic between N22 and PB1 were utilized for background selection to ensure higher genome recovery. After three backcrosses followed by five generations of selfing, eighteen near isogenic lines (NILs) were developed, through combinatory selection for agro-morphological, grain and cooking superiority traits. The NILs were evaluated for three consecutive Kharif seasons, 2017, 2018 and 2019 under well-watered and drought stress conditions. RSDS tolerance and yield stability indicated that NIL3, NIL5, NIL6, NIL7, NIL12, NIL15 and NIL17 were best in terms of overall agronomic and grain quality under RSDS. Additionally, NILs exhibited high yield potential under normal condition as well. The RSDS tolerant Basmati NILs with high resilience to water stress, is a valuable resource for sustaining Basmati rice production under water limiting production environments.

The mechanisms involved in immune responses to cancer have been extensively studied for several decades and, considerable attention has been paid to harnessing the immune system's therapeutic potential. Cancer immunotherapy has established itself as a promising new treatment option for a variety of cancer types. Various strategies including cancer vaccines, monoclonal antibodies (mAbs), adoptive T-cell-cancer therapy and immune test therapy have gained prominence through immunotherapy. However, it remains to be accomplished the full potential of cancer immunotherapy. In spite of having startling aspects, the cancer immunotherapies have some difficulties including the inability to effectively targeting the cancer antigens and the abnormalities in patient response. With the advancement of technology, this system has changed the genome-based immunotherapy process in the human body including generation of engineered T cells. Due to its high specificity, CRISPR-Cas9 has become a simple and flexible genome-editing tool to target nearly any genomic locus. Recently, the CD19-mediated CAR-T cell (chimeric antigen receptor T cell) therapy has opened a new avenue for the treatment of human cancer, though low efficiency is a major drawback of this process. Thus, increasing the efficiency of the CAR-T cell (engineered T cells that induce the chimeric antigen receptor) by using CRISPR-Cas9 technology could be a better weapon to fight against the cancer. In this review, we have broadly focused on the use of CRISPR-Cas9 technology for the modification of the T-cell, which can specifically recognize cancer cells and be used as immune therapeutics against cancer. We have also demonstrated the other potential strategies for the treatment of cancer.

Background: Colorectal cancer is considered the third most fetal among all type of cancer. Spleen tyrosine kinase (SYK) is a non-receptor type tyrosine-protein that plays crucial role in signaling mediated via immune receptor. We adopted an onco-informatics analysis to evaluate the SYK expression and prognostic value of SYK in colorectal cancer, and identification of potential phytochemicals which may inhibit overexpression of SYK protein as well as minimized colorectal cancer. Materials & Methods: Differential expression of SYK gene was analyzed using the several transcriptomic databases including Oncomine, UALCAN, GENT2 and GEPIA2. The server, cBioPortal was used to analyze mutation and copy number alterations whereas GENT2, GEPIA, OncoLnc and PrognoScan were employed to examine the survival rate. A protein-protein interaction network of SYK and co-expressed genes of SYK was conducted via GeneMANIA. Considering SYK gene encoding protein as drug target, selected phytochemicals were assessed by molecular docking using PyRx 0.8 packages. YASARA molecular dynamics simulators were applied for the post validation of the molecular docking data. Results: We have observed significant overexpression of mRNA expression levels of SYK gene colorectal adenocarcinoma (COAD) samples compared with normal tissues. Significant methylation level and various genetic alterations are assembled in SYK gene which can lead to the development of colorectal cancer. As a result, lower level of SYK expression was related to the more chances of patients’ survival by which all the outcomes from the multiple bioinformatics platforms and web resources have demonstrated the significant evidences that the SYK kinsase can possess as a potential biomarker for the treatment of colorectal cancer. Here, aromatic phytochemicals namely, Kaempferol and Glabridin targeting SYK showed more stability compared to controls and may be useful for the treatment of colorectal cancer. Conclusion: Our study showed dysregulated expression of SYK in colorectal cancer and potentiality to act as a biomarker for the prognosis of CRC. Moreover, we have shown phytochemicals (Kaempferol and Glabridin) target SYK as potential treatment strategies and drug repositioning potentiality in colorectal cancer.

Purpose: Hormone Replacement Therapy (HRT), an FDA-approved treatment for menopausal conditions was found to be associated with increased risk of endometrial cancer and reduced oestrogen. Studies showing benefits of HRT in preventing chronic diseases lead to development of clinical guidelines by American College of Physicians. This study aims to assess effectiveness of HRT treatments across cardiometabolic measures including Triglycerides (TG), Follicle-Stimulating Hormone, LDL cholesterol, HDL cholesterol, and Estradiol in menopausal women. It reports gaps in scientific knowledge and clinical practice to enhance current guidelines and policies.Methods: A systematic methodology designed and published in PROSPERO (CRD42022346057) to report network meta-epidemiology analysis was utilised. We used databases by PubMed, Web of Science, ScienceDirect, EMBASE and MEDLINE for studies published between 30th of April 1980-2022. Effects of HRT treatments were explored using a mixed treatment comparison (MTC) model. Fixed and random-effects models were used to address heterogeneity in published studies. Publication bias was assessed and corrected using funnel plots and Egger’s test.Results: Of 45 eligible studies, our findings indicate a significant statistical heterogeneity between HRTs and reduction of TG, SFH, LDL-C alongside increase of HDL-C and Estradiol among menopausal women. The analysis suggests a lack of direct evidence to support their efficacy in reducing TG, SFH and LDL-C levels or to substantiate HRT’s effectiveness in increasing HDL-C and Estradiol. The results showed no significant publication bias in the meta-analysis of included studies.Conclusion: Our findings demonstrate that use of HRT interventions among menopausal women may reduce TG, FSH and LDL-C levels and increase levels of HDL-C and estradiol via oral and oral + transdermal administration. Our study reaffirms efficacy of HRT in supporting favourable lipid profile in menopausal women whilst highlighting the need for robust and inclusive epidemiology studies and clinical trials to further develop clinical guidelines and policies.

Indian tobacco farm laborers are primarily women and children working for very low wages. The aim of this study was to explore occupational and reproductive health challenges faced by women tobacco farm labors in Mysore District, India. We conducted interview and six focus group discussions among 41 women tobacco farm laborers. Codes and themes were generated based on deductive and inductive approaches using the socio-ecological model. Participants reported symptoms of green tobacco sickness including headaches, back pain, gastric problems, weakness, and allergies during menstruation, pre-natal, and post-natal periods. Participants had poor awareness about the health effects of tobacco farming and there were gender inequalities in wages and use of personal protective equipment. Participants received support from family and commu-nity health workers during their pregnancy and post-natal period. Women reported wanting ma-ternity benefits from the tobacco board, monetary support, and nutritional supplements. There is a need for health education about the environmental dangers of tobacco among farm laborers, and more supportive policies for women farmworkers during pregnancy and post-natal periods.