COVID-19 is causing major turmoil around the globe, and the clinical trial industry is likely to face unprecedented challenges to health and business sectors. In an effort to find a suitable treatment and prevention options for COVID-19, several COVID-19 clinical trials are being planned and initiated, while a large number of clinical trials for non- COVID-19 indications are suffering delays. With over more than 1000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrolment. This analysis deals with the specific impacts of the COVID-19 pandemic on the clinical trial and pharmaceutical industry. The objective of this study is to provide an updated information of the disrupted clinical trials and its impact on various therapeutic areas and different drugs. Among the severely affected clinical trials, oncology and CNS trials are the hardest hit therapy areas.This article will certainly emphasize the need for advanced and innovative approaches to maintain the health of the clinical trial ecosystem by continuing the existing trials and the start of the new studies. We have to take and follow necessary actions to guarantee that the initiatives will not be locked during the COVID-19 pandemic, both for the treatment of patients and for the researchers to conduct decision-relevant clinical trials.

This experimental study investigates the effect of scarf geometry in restoring the impact response of scarf patched 3 mm thick glass-fibre reinforced polymer (GFRP) matrix composite laminates. Traditional circular along with rounded rectangular scarf patch configurations considered as repair patches. Experimental measurements revealed that the temporal variations of force and energy response of the pristine specimen are close to that of circular repaired specimens. The predominant failure modes were witnessed only in repair patch which include the matrix cracking, fibre fracture, delamination and no discontinuity in adhesive interface was witnessed. When compared with the pristine samples, the top ply damage size of the of the circular repaired specimens is larger by 9.91 %, while that of the rounded rectangular repaired specimens is larger by 434.23 %. The results show that circular scarf repair is more suitable choice of repair approach under the condition of 37J low-velocity impact event even though the global force-time response is similar.

In this short paper we study some properties of the lines associated with van Aubel’s theorem in the special case when squares are replaced with equilateral triangles constructed on the sides of an arbitrary quadrilateral.

A locally-rotationally-symmetric Bianchi-I model filled with strange quark matter (SQM) is explored in f(R, T) gravity. We take f(R, T) = R + 2 f(T) = R + 2λT, where R is the Ricci scalar, T is the trace of energy-momentum tensor and λ is an arbitrary constant. Exact solutions are obtained by assuming that the expansion scalar is proportional to the shear scalar. This yields a constant value for the deceleration parameter, q = 2, which corresponds to the decelerated phase of the universe. The model is found to be physically viable for λ < −1. SQM during early evolution mimics ultra-relativistic radiation whereas at late times, it behaves as dust, quintessence or even the cosmological constant depending on the value of λ. The effective matter acts as a stiff fluid irrespective of the matter content and of the f(R, T) terms. The model is shear free at late times but remains anisotropic throughout the evolution. In the absence of the f(R, T) terms, SQM accelerates the universe. In the specific case when SQM vanishes at late times, the effect of f(R, T) is to accelerate the universe. The model admits the possibility that SQM could be an alternative to dark energy.

HIV-1 Nef is a multifunctional protein with well-known lethal properties. HIV infects various cells from the brain compartment and expressed nef is responsible for developing neuropathogenic potential. HIV-infected glial cells express nefvirotoxinand stimulate the cascade of various pathways to activate uninfected cells to release neurotoxic elements damaging cells themselves. A lot of genetic variabilities of this protein have been reported from patients with HIV-associated neurocognitive disorders. To determine the neurotoxic potential of subtype-specific nef plasmids and nef plasmids of clinical samples with and without HAND were transfected in normal human astrocytes (NHA) and monocyte-derived macrophages (MDM) using nef-pCMV-HA plasmid constructs. Supernatants from subtype-specific Nef plasmids indicated the upregulation of proinflammatory cytokines. The induced expression might be due to the nef genetic variability or variations in the transfection efficiency and expression levels of nef.The mRNA expression of IL-6, IP-10, and TNF-α indicated upregulation of 5.0-fold in NHA and 3-fold in MDM with respect to empty vector control transfection. Further, the kynurenine metabolites were also assessed from culture supernatants of NHA and MDM indicating the upregulation of IDO and KYNU in NHA by 3.0-fold and 3.2-fold in MDM.The expression levels of nef and cytokines at the translational level were confirmed by western blotting and bio-plex Pro cytokine estimation assay respectively along with controls expressing green fluorescent protein (GFP).The oxidative stress was also found to be elevated as compared to control cells as determined by the estimation of nitric oxide from the culture supernatant to confirm the neurotoxic potential of HIV nef plasmids. The downregulation in the levels of cytokines, as well as kynurenine metabolites, was observed in culture supernatants after blocking the expression of nef using HIV nef siRNA. Phylogenetic analysis of Nef sequences indicated subtype C predominance except one sequence showing the partial sequence of HIV-1 subtype B sequence forming BC recombinantThe upregulation in the cytokine and pathway-specific metabolites might be linked with the neurotoxic potential of HIV-1 Nef leading to neuropathogenesis. In conclusion, the variation in the transfection efficiency, nef expression levels, and the genetic variability of Nef might be responsible for upregulating the expression levels of cytokines and kynurenine metabolites in astrocytes and MDM.

The air pollutant NO2 is derived largely from transportation sources and is known to cause respiratory disease. A substantial reduction in transport and industrial processes around the globe from the novel SARS-CoV-2 coronavirus and subsequent pandemic resulted in sharp declines in emissions, including for NO2. Additionally, the COVID-19 disease that results from the coronavirus may present in its most severe form in those who have been exposed to high levels of air pollution. To explore these links, we compared ground-based NO2 sensor data from 11 US cities from a two-month window (March-April) over the previous five years versus the same window during 2020 shutdowns. NO2 declined roughly 12-41% in the 11 cities. This decreased coincided with a sharp drop in vehicular traffic from shutdown-related travel restrictions. To explore this link more closely, we gathered more detailed traffic count data in one city, Indianapolis, Indiana, and found a strong correlation between traffic counts/classification and vehicle miles travelled, and a moderate correlation between NO2 and traffic related data. This finding indicates that we can use such analysis in targeting reduction in pollutants like NO2 by examining and manipulating traffic patterns, thus potentially leading to more population-level health resilience in the future.

Plant breeding conventionally depends on genetic variability available in a species to improve a particular trait in the crop. However, epigenetic diversity may provide an additional tier of variation. The recent advent of epigenome technologies has elucidated the role of epigenetic variation in shaping phenotype. Further, the development of epigenetic recombinant inbred lines (epi-RILs) in the model species such as Arabidopsis has enabled accurate genetic analysis of epigenetic variation. Subsequently, mapping of epigenetic quantitative trait loci (epiQTL) allowed association between epialleles and phenotypic traits. Thus, quantitative epigenetics provides ample opportunities to dissect the role of epigenetic variation in trait regulation, which can be eventually utilized in crop improvement programs. Moreover, locus-specific manipulation of DNA methylation by epigenome-editing tools such as clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) can facilitate epigenetic based molecular breeding of important crop plants.

Pesticides are among the most widely used synthetic chemicals worldwide to protect crops, but besides being beneficial, they pose several environmental and health issues. The present study evaluates toxic effects of acetamiprid (ACMP) in rat liver and kidney tissues. Rats were exposed to ACMP (21.7 mg/kg b.wt; 1/10th LD50) for 21 days. Oxidative stress generation, apoptotic progression, and structural changes were evaluated via biochemical assays, semi-quantitative PCR, western blotting, and histopathology. ACMP exposure significantly decreased body weight and altered relative organ weight in hepato-renal tissues. Significant oxidative stress was evident by increased oxidative injuries to lipids and proteins and alterations of endogenous anti-oxidative enzymes. The administration of ACMP upregulated mRNA expression of Bax and caspase-3, while downregulated the mRNA expression of Bcl-2 and released cytochrome c into the cytosol of the liver and kidney tissues. Likewise, exposure to ACMP caused severe degenerative changes in the histo-architecture of hepato-renal tissues. The results of the present study confirmed the toxicity of ACMP in rats’ liver and kidney tissues and emphasized the need for strict regulation and more mechanistic understanding to delineate the toxicity of ACMP in mammals.

We investigate the Friedmann–Lemaitre–Robertson–Walker cosmological models within the framework of Rastall gravity incorporating particle creation. The modified field equations for Rastall gravity are derived and exact solutions are obtained under various choices of scale factors. The qualitative behaviour of our solutions depends on the Rastall coupling parameter ψ=kλ. Following the literature, we have restricted the Rastall coupling parameter ψ(k=1) to the range −0.0001 < ψ < 0.0007 at 68% CL from CMB+BAO data. Further, we have discussed the distinct physical behaviour of the derived models in detail.

This study explores the correlation between payment statistics and sector-wise Gross Value Added (GVA) in the Indian economy from 2011 to 2022, assessing the importance of payment and settlement systems. Through regression analysis, the impact of payment statistics on GVA across diverse sectors is assessed. The results indicate that, during the specified period, payment statistics exhibit a significant influence on sector-wise GVA. These findings underscore the pivotal role of payment and settlement systems in the Indian financial landscape.

Neurodegenerative diseases like Alzheimer's diseases are irreversible, progressive, and refractory in nature and managed very poorly. AD is manifested with the aggregation of unfolded proteins, synaptic pathology and dementia and poses challenges to the health care system globally. Only very few treatments with minimal effect are available to the patients and their caregivers. Despite numerous clinical trials which were launched for AD, unfortunately, most of them failed in satisfying the pharmacological criteria. At cellular levels, many signaling pathways have been proposed for the sterile / refractory behavior of degenerating neurons. Among those, Mitogen activated protein kinases (MAPKs) are the critical cellular networks which are involved in the development of Alzheimer’s disease. Several studies have demonstrated a favorable impact of MAPK inhibition on inflammatory programming, synaptic plasticity, and memory problems in mouse models of AD. In view of this, various clinical trials were launched with several MAPK inhibitors (with good safety profile and less side-effects) have yielded positive results in AD patients suggesting that MAPK targeting may be effective for reducing the pathogenesis of AD, but due to selectivity, dosing and patient stratification, this aspect still need development. In view of selectivity and off-target effects, only a few MAPK inhibitors have been employed in clinical trials against AD indicating a scope of development in this area. Therefore, this study focuses on MAPK based interventions as an upcoming and innovative approach for alleviating AD with special emphasis on clinical studies.

This study introduces a multilayer perceptron (MLP) error compensation method for real-time camera orientation estimation, leveraging a single vanishing point and road lane lines within a steady-state framework. The research emphasizes cameras with a roll angle of 0°, predominant in autonomous vehicle contexts. The methodology estimates pitch and yaw angles using a single image and integrates two Kalman filter models with inputs from image points (u, v) and derived angles (pitch, yaw). Performance metrics, including AE, MINE, MAXE, SSE, and STDEV, were utilized, testing the system in both simulator and real-vehicle environments. The outcomes indicate that our method notably enhances the accuracy of camera orientation estimations, consistently outpacing competing techniques across varied scenarios. This method’s potency is evident in its adaptability and precision, holding promise for advanced vehicle systems and real-world applications.

Recent evidences support a role of menthol, a TRPM8 agonist, in enhanced energy expenditure, thermogenesis and BAT-like activity in classical WAT depots in TRPM8 dependent and independent manner. The present study was designed to analyze whether oral and topical administration of menthol is bioavailable at subcutaneous adipose tissue and is sufficient to induce desired energy expenditure effects directly. GC-FID was performed to study menthol bioavailability in serum and subcutaneous white adipose tissue following oral and topical administration. Further, 3T3L1 adipocytes were treated with bioavailable menthol doses and different parameters (lipid accumulation, “browning/brite” and energy expenditure gene expression, metal analysis, mitochondrial complex’s gene expression) were studied. No difference was observed in serum levels but significant difference was seen in the menthol concentration on subcutaneous adipose tissues after oral and topical application. Menthol administration at bioavailable doses significantly increased “browning/brite” and energy expenditure phenotype, enhanced mitochondrial activity related gene expression, increased metal concentration but didn’t alter the lipid accumulation. Further, we used pharmacological antagonism based approach to study the TRPM8 involvement in menthol effect. In conclusion, the present study provides an evidence that bioavailable menthol after single oral and topical administration is sufficient to induce “brite” phenotype in subcutaneous adipose tissue.

The study proposes laser shock peening without a coating of high strength ultrafine bainitic steel to mitigating the fatigue failures for automotive and structural engineering applications. Laser pulse density of 2500 pulses/cm2 (75% overlapping) was optimised based on the induced residual stresses for employing the wide range of characterisations. The roughness and topographic results showed that surface roughening was controlled by tuning the laser pulse density. The High-Resolution X-ray Diffraction analysis confirmed the lattice misorientation resulting peak shift and the trend towards martensite phase transformations. The electron microscopic micro/nanostructure analyses revealed the grain refinement features such as nano-twins, micro shear bands and shear cells. The work hardening depth and nanomechanical properties were significantly enhanced. A fully reversed (R= -1) high-cycle fatigue tests extended the lifespan by an average of fifteen times than the untreated. Also, it has potential to repair the structural components effectively.

Terrestrial vegetation dynamics are closely influenced by a multitude of factors. This study investigated the relationships between vegetation patterns and their main influencing factors. The joint entropy method was employed to evaluate the dependence between normalized difference vegetation index (NDVI) and coupled variables in the middle reaches of Hei River basin. Based on the spatial distribution of mutual information, the whole study area was divided into five sub-regions. In each sub-region, nested statistical models were applied to model the NDVI on the grid and regional scales, respectively. Results showed that the annual average NDVI increased with a rate of 0.005/a in recent 11 years. In the desert regions, the NDVI increased significantly with an increase in precipitation and temperature, and high accuracy of retrieving NDVI model was obtained by coupling precipitation and temperature, especially in sub-region I. In the oasis regions, groundwater was also an important factor driving vegetation growth, and the rise of groundwater level contributed to the growth of vegetation. However, the relationship was weaker in artificial oasis regions (sub-region III and sub-region V) due to the influence of human activities, such as irrigation. The overall correlation coefficient between the observed NDVI and modeled NDVI was observed to be 0.97. Outcomes of this study are suitable for ecosystem monitoring, especially under the realm of climate change. Further studies are necessary and should consider more factors, such as runoff and irrigation.

Taiwan is highly susceptible to global warming, experiencing a 1.4°C increase in air temperatures from 1911-2005, which is twice the average for the Northern Hemisphere. This has led to higher rates of respiratory and cardiovascular mortality. Accurately predicting maximum temperatures during the summer season is crucial, but numerical weather models become less accurate and more uncertain beyond five days. To improve forecast reliability, statistical post-processing is needed to address systematic errors. In September 2020, NOAA NCEP implemented the Global Ensemble Forecast System version 12 (GEFSv12) to help manage climate risks. This study developed a Hybrid statistical post-processing method that combines Artificial Neural Networks (ANN) and Quantile mapping (QQ) approaches to predict daily maximum temperatures and extremes in Taiwan during the summer season. The Hybrid technique, utilizing deep learning techniques, was applied to the GEFSv12 reforecast data and evaluated against ERA5 reanalysis. The Hybrid technique was the most effective among the three techniques tested. It had the lowest bias, RMSE, and highest correlation coefficient. It successfully reduced the warm bias and overestimation of Tmax extreme days. This led to improved prediction skills for all forecast lead times. Compared to ANN and QQ, the Hybrid method was more effective in predicting summer daily Tmax and its extremes on an extended-range time scale deterministic and ensemble probabilistic forecasts over Taiwan.

The GAI‐RGA ‐ and ‐SCR (GRAS) proteins belong to the plant-specific transcription factor gene family and involved in several developmental processes, phytohormone and phytochrome signaling, symbiosis, stress responses etc. GRAS proteins have a conserved GRAS domain at C-terminal and hypervariable N-terminal. The C-terminal conserved domain directly affects the function of the GRAS proteins. For instance, in Arabidopsis, mutations in this domain in Slender rice 1 (SLR1) and Repressor of GA (RGA) proteins cause significant phenotypic changes. GRAS proteins have been reported in more than 30 plant species and till now it has been divided into 17 subfamilies. This review highlighted GRAS protein's importance during several biological processes in plants, structural features of GRAS proteins, their expansion and diversification in the plants, GRAS-interacting proteins complexes and their role in biological processes. We also summarized available recent research that utilized CRISPR-Cas9 technology to manipulate GRAS genes in a plant for different traits. Further, the exploitation of GRAS genes in crop improvement programs has also been discussed

Water quality retrieval for small urban waterbodies by remote sensing get used to be difficult due to coarse spatial resolution of the remote sensing imagery. The recently launched Sentinel-2 produces imagery with a spatial resolution of 10 m. It provides an opportunity to solve the problem of retrieving water quality for small waterbodies. Additionally, many water management issues also require fine resolution of imagery, e.g. illegal discharge to an urban waterbody. Since illegal discharges are an important issue for urban water management, chemical oxygen demand (COD), total phosphorous (TP), and total nitrogen (TN) were chosen as the target parameters for water quality retrieval in this study. COD, TP and TN, however, are non-optically active parameters. There were limited studies in the past to retrieve these parameters in comparison with optically active parameters, e.g. Chlorophyll-A etc. This study compared three machine learning models, namely Random Forest (RF), Support Vector Regression (SVR), and Neural Networks (NN), to investigate the opportunity to retrieve the above non-optically active parameters. Results showed that R² of TP, TN, and COD by NN, RF and SVR were 0.94, 0.88, and 0.86, respectively. The performances of water quality retrieval for these non-optically active parameters were significantly improved by the optimized machine learning models. These models hence solved the problem to use remote sensing data to retrieve these non-optically active water quality parameters and provided a new monitoring strategy for small waterbodies. Water quality mapping obtained by Sentinel-2 imagery provided a full spatial coverage of the water quality characterization for the entire water surface. Compared with water samples collecting and testing, it greatly reduced labor cost, reagents cost, and waste treatment cost. It also may help identify illegal discharges to urban waterbodies. The method developed in this research provides a new practical and efficient water quality monitoring strategy in managing water with consideration of environmental sustainability.

Neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyloidal lateral sclerosis (ALS), and Huntington disease (HD) are the most concerned disorders due to the lack of effective therapeutics and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, yet they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and ER-stress, which combats with stress conditions, but the overwhelming cellular stress response induces cell damage. Small molecules such as flavonoids could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the mechanistic ways of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders.

Metallic substrates and polymer adhesive in composite-metal joints have a relatively large coefficient of thermal expansion (CTE) mismatch, which is a barrier in the growing market of electric vehicles and their battery structures. It is reported that adding carbon nanotubes (CNTs) to the adhesive reduces the CTE of the CNT enhanced polymer adhesive multi-material system, therefore when used in adhesively bonded joints it would, theoretically, result in low CTE mismatch in the joint system. The current article presents the influence of two specific mass ratios of CNTs on the CTE of the enhanced polymer. It was observed that the addition of 1.0 wt% and 2.68 wt% of multi-walled CNTs (MWCNTs) decreased the CTE of the polymer adhesive from 7.5e-5 1/C (pristine level) to 5.87e-5 1/C and 4.43e-5 1/C, respectively by 22% and 41% reduction. The reduction in the CTE was predicted, theoretically, which showed that CTE should have been reduced to 3.6e-5 1/C (52% reduction) and 1.4e-5 1/C (81% reduction). This may be due to the fact that, Raman spectroscopy of the MWCNTs identified defects in the raw material, and scanning electron microscopy (SEM) identified agglomeration of MWCNTs on the surface and cross-section of the modified polymers.

The encapsulation of proteins into core-shell structures is a widely utilised strategy for controlling protein stability, delivery and release. Despite the recognised utility of these microstructures, however, core-shell fabrication routes are often too costly or poorly scalable to allow for industrial translation. Furthermore, many scalable routes rely upon emulsion-techniques implicating denaturing or environmentally harmful organic solvents. Herein, we investigate core-shell protein encapsulation through single-feed, aqueous spray drying: a cheap, industrially ubiquitous particle-formation technology in the absence of organic solvents. We show that an excipient’s preference for the surface of the spray dried particle is well-predicted by its hydrodynamic diameter (Dh) under relevant feed buffer conditions (pH and ionic strength) and that the predictive power of Dh is improved when measured at the spray dryer outlet temperature compared to room temperature (R2 = 0.64 vs. 0.59). Lastly, we leverage these findings to propose an adaptable design framework for fabricating core-shell protein encapsulates by single-feed aqueous spray drying.

We confirm that energy dissipation weighting provides the most accurate approach to determining the effective hydraulic conductivity (Keff) of a binary K grid. A deep learning algorithm (UNET) can infer Keff with extremely high accuracy (R2 > 0.99). The UNET architecture could be trained to infer the energy dissipation weighting pattern from an image of the K distribution with high fidelity, although it was less accurate for cases with highly localized structures that controlled flow. Furthermore, the UNET architecture learned to infer the energy dissipation weighting even if it was not trained on this information directly. However, the weights were represented within the UNET in a way that was not immediately interpretable by a human user. This reiterates the idea that even if ML/DL algorithms are trained to make some hydrologic predictions accurately, they must be designed and trained to provide each user-required output if their results are to be used to improve our understanding of hydrologic systems most effectively.

Attack on health has become a significant concern for non-belligerents of war, including healthcare personnel and facilities as witnessed in the ongoing Sudan conflict. About 1.5 billion people living in fragile and conflict-affected settings (FCAS) have a heightened need for essential health services. Conflicts often lead to the disruption of building blocks of health systems, lack of access to health facilities, failure of essential medical supply chains, the collapse of political, social and economic systems, migration of health care workers, and upsurges in illness. While health indicators often decline in conflict, health can also bring peace and harmony among communities. Investment in health systems and health diplomacy is a neutral starting point for bringing peace and mitigating conflicts. The international commitment towards Sustainable Development Goals (SDGs) provides the impetus to emphasize the relationship between health and peace with the amalgamation of SDG 3, SDG 16, and SDG 17. The inspection of how health should be used as a ‘tool for peace’ and not as leverage during the war must be reiterated by international institutions.

Bread wheat (Triticum aestivum L.) is one of the world's most important staple food crop providing 20% global energy and dietary proteins. It is widely grown in sub-tropical and tropical areas and as such exposed to heat-stress especially at grain filling period (GFP). Global warming has further affected its production and productivity in these heat-stressed environments. We examined the effect of heat-stress on 18 morpho-physiological and yield-related traits in 96 bread wheat accessions. Heat susceptibility index (HSI <0.60) and yield stability (i <0.55) used as criteria for selecting the tolerant accessions. Heat-stress, imposed by delayed sowing, decreased crop growth and GFP, and as a result reduced morphological and yield-related traits, namely days to 50% anthesis, plant height, peduncle length, flag-leaf area, spike length, spikelets per spike, grain length and width, thousand grain weight (TGW), harvest index and yield. The reduction in the trait values was severe in susceptible accessions (48.2% yield reduction in IC277741) than the tolerant. Physiological traits like chlorophyll content, canopy temperature depression (CTD), normalized difference vegetation index (NDVI), plant waxiness and leaf rolling showed higher expression in the tolerant accessions under heat-stress. Scanning electron microscopy of matured wheat grains revealed ultrastructural changes in endosperm and aleurone cells caused due to heat-stress. The reduction of size and density of large starch granules is the major cause of yield and TGW decrease in the heat-stress susceptible lines. The most stable and high-yielding accessions namely IC566223, IC128454, IC335792, EC576707, IC535176, IC529207, IC446713 and IC416019 were identified as the climate-smart germplasm lines. Germplasm lines possessing desirable traits were selected as po-tential parents for the development of bi-parental and multi-parental populations.

Chronic hepatitis B (CHB) infection and the Hepatitis B virus X protein (HBx) are major risk factors associated with hepatocellular carcinoma (HCC). In CHB infection, HBx induces mitochondrial dysfunction, exhaustion and impaired function in hepatocytes. Restoring hepatocyte health along with reduction in virus replication could be an ideal treatment for CHB. Thiourea derivatives are well known for their antiviral property though their effect on mitochondrial and/ or hepatocyte health remains obscure. This study focus on the repurposing of thiourea derivatives (DSA-00, DSA-02, and DSA-09) on hepatocyte replenishment. HepG2.2.15 cells were treated with thiourea derivatives, alongside Entecavir (ETV). The proteomics analysis showed both DSA-00 and ETV were enriched with proteins associated with antiviral responses. In addition, DSA-00 additionally showed increase in proteins linked to mitochondrial response. Whereas DSA-02 exhibited association with innate immune system and citric acid cycle and DSA-09 displayed pathways similar to DSA-00 and ETV. Treated groups exhibited enhanced bio-energetic and antiviral response as compared to the untreated group. FACS analysis revealed the restoration of exhausted hepatocytes by thiourea derivatives through targeting mitochondria. Our findings suggest that thiourea derivatives hold potential as a novel therapeutic agent that seems to restore mitochondrial health along with anti-viral response in CHB.

Accumulation of extra fats in the body results in disturbance in homeostasis causing obesity. The pathophysiology of obesity has been associated with various genetic, epigenetic factors and the disturbed lifestyles of an individual. One of the outcomes is disturbance in the sleep cycle which leads to sleep disorders. The evolutionary significance of sleep lies in the fact that it saves energy and is crucial for adjustment of an individual to ecological and environmental factors, and thus maintains homeostasis. Sleep has an anabolic function and replenishes the wakefulness-associated loss of glycogen stores. However, the modern lifestyle is well known to disrupt sleep behavior and patterns affecting human health negatively. Alteration in homeostasis leads to several acute and chronic pathophysiological conditions like obesity and related metabolic morbidities being one amongst them. Shorter sleep duration and poor sleep quality are important risk factors associated with the development of obesity and have more adverse effects on energy homeostasis. Consequently, it is crucial to comprehend the obesity and sleep relationship and its therapeutic strategies, given that strong crosstalk exists between energy balance that favors obesity and sleep apnea. It is therefore highly recommended to the people with a high risk of obesity to maintain sleep discipline and good sleep hygiene in our daily life. Interventions are required to improve both sleep quality and quantity, and associated obesity. More focused research is needed for uncovering the pieces of evidence that determine whether such interventions can improve obesity-related health consequences. The present review discusses the important findings on the therapeutic and neuroendocrine mechanisms regulating sleep and obesity.

Huntington disease (HD) is an autosomal dominantly inherited fatal neurodegenerative disease. It affects motor, cognitive and psychiatric functions, and ultimately leads to death. The pathology of the disease is due to an expansion of CAG repeats in exon 1 of the huntingtin gene on chromosome 4, which produces a mutant huntingtin protein (mhtt). HD patients manifest a typical phenotype of sporadic, rapid, involuntary control of limb movement, stiffness of limbs, impaired cognition and severe psychiatric disturbances. A variety of symptomatic treatments (which target excitotoxicity, the dopamine pathway, caspases, aggregation, mitochondrial dysfunction, transcriptional dysregulation, mHtt, nucleic acid, neurodegeneration, fetal neural transplants, etc.) are currently available, and new symptomatic and potentially disease-modifying therapies are being actively developed. Recent advances in novel therapeutic strategies, including targeting mutant huntingtin (mhtt) and the htt gene, promise another wave of disease-modifying trials in the near future. A better appreciation of heterogeneous clinical phenomenology and immediate tractable treatment goals coupled with advances in new therapeutics heralds a golden age of HD treatment that will positively impact the quality of life and longevity of HD patients and inform advances in other inherited and neurodegenerative neurological disorders. In the present review literature, our aims to address the latest research on promising therapeutics based on influencing the hypothesized pathological mechanisms associated with HD.

Bisphenols are widely used in the synthesis of polycarbonate plastics, epoxy resins and thermal paper, which are used in manufacturing items of daily use. Packaged foods and drinks are the main sources of exposure to bisphenols. These chemicals affect humans and animals by disrupting the estrogen, androgen, progesterone, thyroid, and aryl hydrocarbon receptor functions. Bisphenols exert numerous harmful effects because of their interaction with receptors, ROS formation, lipid peroxidation, mitochondrial dysfunction, and cell signal alterations. Both cohort and case-control studies have determined an association between bisphenol exposure and increased risk of cardiovascular diseases, neurological disorders, reproductive abnormalities, obesity, and diabetes. Prenatal exposure to bisphenol results in developmental disorders in animals. These chemicals also affect the immune cells and play a significant role in initiating the inflammatory response. Exposure to bisphenols exhibit age, gender, and dose-dependent effects. Even at low concentrations, bisphenols exert toxicity, and hence deserve a critical assessment for their uses. Since bisphenols have a global influence on human health, the need to discover the underlying pathways involved in all disease conditions is essential. Furthermore, it is important to promote the use of alternatives for bisphenols, thereby restricting their uses.

The aim of this work is to broaden the theory of computation by making use of fuzzy sets and multisets, which are generalization of ordinary sets. We study fuzzy multiset finite automata (FMFA), which are characterized by the incorporation of vagueness when it comes to the choice of the next state and multiple occurrences of the same input symbol. The resulting automaton is a genaralization of both classical automata and fuzzy automata. We discuss the algebraic characteristics of FMFA sub-automata—separatedness, strongly connectedness, cyclic, directable, and triangular FMFA in terms of equivalence classes induced by an equivalence relation defined on state set of FMFA. Intrestingly, for a given FMFA, a new FMFA can be constructed that is a homomorphic image of the original FMFA. We define different posets structures that can be associated with a given FMFA and show that some of them are upper semilattices and discuss the inter-relationship of a given poset, a finite upper semilattice (FUSL), a FMFA and a posets/FUSL associated with a given FMFA. Finally, we introduce the concept of decomposition of a FMFA in two different ways and characterize the strongly connected, triangular and directable FMFA.

Respiratory tract infections (RTIs) are one of the main causes of hospitalization and mortality causing substantial economic burden to healthcare systems globally. As opposed to the previous belief that respiratory infections are caused by a single pathogen, studies have shown that most RTIs are a result of a combination of bacterial and/or viral pathogens infecting the host. The clinical manifestation of RTIs is very similar (i.e., syndrome), often showing Influenza-like illness (ILI) symptoms. While COVID-19 has dominated ILI over the past few years, there are many other pathogens that are responsible for ILI. In addition, it is not uncommon to have coinfections with multiple pathogens in patients presenting with ILI and that such coinfections can even exacerbate the disease severity of RTIs. Therefore, an insight into coinfections can help with accurate disease prognosis, patient care management and outcomes. The goal of this study was to identify the different organisms in symptomatic patients presenting with ILI.

An HPLC method for indicating stability was developed, created, and confirmed for the quantification measurement of recombinant human erythropoietin in large quantities as well as dosage forms. An isocratic separation was accomplished using a Thermo Biobasic C18 (250 mm 4.6 mm i.d., 300Ao, 5 m) column with a flow rate of 1.0 mL min-1 as well as a UV detector to monitor the eluate at 278 nm. Acetonitrile, 0.05 mM potassium dihydrogen phosphate (80:20 v/v), and orthophosphoric acid adjusted to 4.0 made up the mobile phase. The drug was exposed to oxidative stress, hydrolysis, and photodegradation to simulate stress conditionsRecombinant Human Erythropoietin, the parent compound, was eluted at roughly 6.675 minutes, as well as all byproducts have been entirely disconnected inside an overall analytical run time of about 15 minutes. To identify quantification limits of 0.05 and 0.2 g mL-1, respectively, the method was linear over a concentration range of 1-6 g mL-1 (r = 0.9989). Recombinant Human Erythropoietin can be measured accurately, selectively, sensitively, and precisely using this method both in dosage form and in bulk. Stress-induced degradation products did not interact with the identification of Recombinant Human Erythropoietin, indicating that the assay is stable.

Background: Cervical laminoplasty is a useful for treatment of cervical myelopathy. However, this procedure has limitations for kyphotic cervical alignments. We used the finite element (FE) analysis and investigated the biomechanical changes in an intact and laminoplasty models with lordosis, straight, and kyphosis cervical alignments. Methods: A three-dimensional FE model of the cervical spine (C2-C7) with ligaments was created from computed tomography. The model was modified with the following cobb angles and the C3-C6 laminoplasty was conducted; a) laminoplasty-lordotic model (LM-L; C2-C7 angle: -10°), b) laminoplasty-straight model (LM-S; C2-C7 angle: 0°), and c) laminoplasty-kyphotic model (LM-K; C2-C7 angle: 10°). A pure moment with a compressive follower load of 100N to represent the weight of the head/cranium and cervical muscle stabilization was applied to these models. The range of motion (ROM), annular stress, nucleus stress and facet forces were analyzed. Results: ROM of LM-K increased when compared to the other models except for flexion. The LM-K had the highest mobility with 49% increase in ROM observed under extension, compared to the intact model. In all motion except for flexion, LM-L models’ ROM decreased by more than 10%, and LM-S and LM-K models’ ROM increased by more than 10% at C2-C7 compared to the intact model. The annular stresses and nucleus stresses in LM-K were higher compared to the other models. The maximum increase in annular stresses was about 194% in LM-K compared to the intact model, observed at the C3-C4 segment. The facet contact forces were lowest in the LM-K, compared to the other models.Conclusions: Patients with a cervical kyphosis alignment are at a disadvantage of increased kyphosis compared to cases with lordosis or straight alignment and should be treated with caution.

Fusarium Head Blight (FHB) is a destructive disease affecting the grain yield and quality of wheat, barley, rye and triticale. Developing varieties with genetic resistance is integral to successfully managing FHB. However, significant knowledge gap exists in the genetic diversity present in triticale for FHB resistance. This information is critical for breeding new varieties of triticale as its production continues to increase. In the present study, a set of 298 winter triticale accessions from a worldwide collection were screened for their type-2 FHB resistance in an artificially inoculated misted nursery with high levels of inoculum density. Most of the triticale accessions were susceptible to FHB, and only 8% of accessions showed resistance in the field nursery screening. The resistant accessions identified in the nursery screening were selected and further screened for three years in greenhouse conditions. Seven accessions were found to show robust FHB resistance over the three years of greenhouse testing. Thirteen accessions showed significantly lower levels of Deoxynivalenol accumulation when compared to the susceptible triticale control. The accessions identified in the study will be useful in triticale and wheat breeding programs for enhancing FHB resistance and reducing DON accumulation.

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.

A Friedmann-Lemaitre-Robertson-Walker space-time model with all curvatures k=0,±1 is explored in f(R,T) gravity. The solutions are obtained via the parametrization of the scale factor that leads to a model transiting from a decelerated universe to an accelerating one. The physical features of the model are discussed and analysed.

The Yang-Mills conjecture addresses the fundamental nature of the strong force, one of the four fundamental forces in nature, responsible for binding quarks together to form protons, neutrons, and other hadrons. It was proposed in the early 1950s, the Yang-Mills suggests a mathematical framework for describing the behaviours of gauge fields, which are the carriers of fundamental forces. In particular, it focuses on non-abelian gauge theories, where the gauge fields themselves interact with each other. The non-abelian aspect refers to the fact that the order of operations matters when combining these gauge transformations, leading to a more intricate structure compared to abelian theories. This conjecture posits the existence and significance of certain mathematical structures, known as Yang-Mills fields, which play a crucial role in the formulation of the Standard Model of particle physics. The Standard Model describes the electromagnetic, weak, and strong nuclear forces, as well as the elementary particles that constitute matter. Despite its foundational importance, proving the Yang-Mills conjecture has proven to be a formidable challenge. The conjecture is intimately connected to the concept of mass gap, which refers to the idea that the particles involved in the strong force interactions exhibit mass, in contrast to the photon in electromagnetism, which is massless. The successful resolution of the Yang-Mills conjecture is expected to deepen our understanding of the nature of particle physics and may provide insights into the unification of fundamental forces. In this regard we hereby provide solutions to solve Yang-Mills conjecture using the method of Self Information Entanglement and Quantum Information Transport Equations to elucidate the origin of Universe from Unperceivable Information called “Avyaktham” through the emergence of perceivable information “Vyaktham”. For the first time in the world we provided an empirically verifiable solution to the origin of emergence and existence of Universe based on the methods to predict the emergence using working model of clinical Ayurveda. It is computed that the value of mass gap mentioned in Yang-Mills conjecture is around mYM = mbit ≈ 1.06×10⁻⁴¹kg.

For the first time in the world, we provided a phenomenologically verifiable proof for the validation of origin of universe and perceivable reality from the unperceivable information based on Ayurveda. We also provided the axiomatic definitions for the terminologies used to deliver the theoretical framework for the same based on Bharatheeya Knowledge Systems. The presented manuscript provides a corelation between quantum information transport and emergence of gunam “Laghu” and gunam “Guru”. We identified that this point of emergence can be considered as the origin point in the continuous process of generation of Perceivable Reality “Vyaktham” from Unperceivable Information “Avyaktham”. In this context we can consider the unperceivable information in “Avyaktham” as dark matter. So, we must develop methods like gunascopy or informationscopy to understand the types of information imbibed in the quantum matter of a dravyam to understand its original physico-chemical-biological and information state of the constituent matter. This is possible through the assessment of Dravya Guna aspects and panchabhootha tatwas of the dravyas. For the first time in the world, we have developed the method to derive all the gunas from “guru” and “Laghu” and calculated the mass of the finitie components of Nava Dravyas including Mann, Aatma, Kaal, Disha, Aakash, Vaayu, Agni, Jal and Prithvi from the quantum information emergence equation. We strongly believe that this work will open up new avenues to explore the frontiers of reality and universe through natural cognition. The solutions to the Yang-Mill conjecture is achieved by our team using the Quantum Information Emergence and Transport Equations. We proved that the information bounded in the quantum states of the constituent quantum matter of quantum particles will provide them positive masses, even though they travel at the speed of light. Based on the phenomenologically verifiable axioms proposed in this work, we proved that the space on the topologically invarient 2D Poincare Sphere which is equivalent to a 2D space without boundaries can facilitate the never-ending loop of continuous quantum information transport between “Avyaktham” and “Vyaktham”. So the information availabe in the constituent quantum states of “Avyaktham” is equal to the postiive mass of quantum systems travelling at the speed of light. In such condition all the mass of the quantum particles will be converted in to information bounded in the corresponding quantum states of the quantum matter. This complete conversion of mass of the quantumparticles into information will happen only at maximum entropy. Thus at maximum entropy the information which is self information entangled with its own quantum states in “Avyaktham” will have a positive mass equal to the mass gap proposed in the Yang-Mill conjecture.

Ruxolitinib has been approved by FDA for the treatment of myeloproliferative neoplasms such as polycythemia vera and idiopathic myelofibrosis. Although ruxolitinib has been in the clinic for more than ten years, surprisingly, no JAK2 drug resistant mutations have been identified in patients. At the moment, it is not clear whether the absence of JAK2 mutations in MPN patients is due to a lack of JAK2 addiction or residues that mediate the drug resistance compromising the JAK2 function. To find out this, we established a Ba/F3 cell-based screening strategy to predict mutations in JAK2-V617F that cause resistance towards ruxolitinib. In this study, we have recovered seven residues in the kinase domain of JAK2 that affect ruxolitinib sensitivity. All these mutations confer cross-resistance across the panel of JAK2 kinase inhibitors except JAK2-L983F. JAK2-L983F reduces the sensitivity towards ruxolitinib. However, it is sensitive towards fedratinib indicating that our screen identifies the drug-specific resistance profiles. All the ruxolitinib resistant JAK2 variants displayed sensitivity towards Type II JAK2 inhibitor CHZ-868. Finally, our study also shows that HSP90 inhibitors are potent against ruxolitinib resistant variants through the JAK2 degradation and provides the rationale for clinical evaluation of potent HSP90 inhibitors in genetic resistance driven by JAK2 inhibitors.

The development of potent antiviral agents is of utmost importance to combat the global burden of viral infections. Traditional antiviral drug development involves targeting specific viral proteins, which may lead to the emergence of resistant strains. To explore alternative strategies, we investigated the antiviral potential of antimicrobial peptidomimetic compounds. In this study, we evaluated the antiviral potential of short anthranilamide-based peptidomimetic compounds 1-17 against two viruses: Murine Hepatitis Virus 1 (MHV-1-single stranded RNA virus) which is a surrogate of human coronaviruses and Herpes Simplex Virus 1 (HSV-1-double stranded DNA virus). The half-maximal inhibitory concentration (IC50) values of these compounds were determined in vitro to assess their potency as antiviral agents. Compounds 11 and 14 displayed the most potent inhibitory effect with IC50 values of 2.38μM, and 6.3μM against MHV-1 while compounds 9 and 14 showed IC50 values of 14.8μM and 13μM, against HSV-1. Multiple antiviral assessments and microscopic images obtained through transmission electron microscopy (TEM) collectively demonstrated that these compounds exert a direct influence on the viral envelope. Based on this outcome, it can be concluded that peptidomimetic compounds could offer a new approach for the development of potent antiviral agents.

Topological indices are invariant numerical fields of a graph that give facts about the structure of graphs and are found to be very helpful in predicting the physical properties of aluminophosphates. The characteristics of the aluminophosphates are similar to those of zeolites. Two examples of current applications are natural gas dehydration and humidity sensor. New frameworks are being synthesised by researchers in chemistry and materials science. There are many layers and holes in these substances. In this study, Vertex version of distance-based topological indices, the entropy of topological indices and their numerical analysis are explained.

Ionizing radiation exposure is known to induce molecular and cellular injury, inflicting a cascade of potentially catastrophic events leading to tissue and organ damage. Metabolomic analysis allows for the identification and quantification of small molecules downstream of genomic changes induced by radiation exposure. We aimed to characterize metabolomic changes that underscore the prefinal stage of lethally irradiated rhesus nonhuman primates (NHPs). Peripheral blood was drawn at baseline, post-exposure as well as at the preterminal stage of NHPs (immediately prior to death in moribund NHPs), which did not survive exposure with 7.2 Gy total-body radiation (LD70/60). Herein, we analyzed global metabolomic changes using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS) in plasma samples of NHPs collected at various timepoints in relation to irradiation. The overall goal was to identify metabolic shifts present immediately prior to death. Our findings, for the first time, show that radiation induced significant time dependent metabolic perturbations when compared to pre-irradiation samples, particularly in the glycerophospholipid metabolism and steroid hormone biosynthesis and metabolism pathways. These findings provide valuable insights for identifying biomarkers for lethality, which may be helpful for triage during a mass casualty scenario.

The utilisation of the industrial residual products to develop new value-added materials and to reduce footprint is one of the critical challenges of science and industry. Development of the new multifunctional and bio-based composites materials is an excellent opportunity for the effective utilisation of industrial residual products. Keeping the different issues in mind, in this work, we describe the manufacturing and characterisation of the three-phases bio-based composites. The key components are bio-based binder made of peat, devulcanised crumb rubber (DCR) from used tires and part of the fly ash, i.e. the cenosphere (CS). The three-phase composite prepared in the form of a block were investigated for their mechanical properties and density. The three-phase composite was prepared in the form a) of a block were investigated for their mechanical properties, and density and b) a form of granules for determination of the water and oil products sorption were investigated. We have also investigated the dependence of the properties on the DCR and CS fraction. It has been found, that maximum compression strength (in block form) observed for composition without CS and DCR addition was- 79.3 MPa, while the second-highest value of compression strength is 11.2 MPa for composition with 27.3 wt% of CS. For compositions with bio binder content from 17.4 to 55.8 wt% and with DCR contents in range from 11.0 to 62.0 wt%, the compression strength is in the range from 1.1 to 2.0 MPa. Liquid sorption analysis (water and diesel) showed that the maximum saturation of liquids in both cases is set after 35 minutes and ranges from 1.05 to 1.4 g·g -1 for water and 0.77 to 1.25 g·g-1 for diesel. It was noted that 90% of the maximum saturation with diesel fuel comes after 10 minutes and for water after 35 minutes.

Stereotactic radiosurgery (SRS) has become increasingly important in the management of brain metastases due to improving systemic disease control and rising incidence. Initial trials demonstrated SRS with whole brain radiotherapy (WBRT) improved local control rates versus WBRT alone. Concerns with WBRT associated neurocognitive toxicity have contributed to greater use of SRS alone, including for patients with multiple metastases and following surgical resection. Molecular information, targeted agents and immunotherapy have also altered the landscape for the management of brain metastases. This review summarises current and emerging data on the role of SRS in the management of brain metastases.

Abstract Background Context Pelvic ring fractures are becoming more common in the aging population and can prove to be fatal, having mortality rates between 10% and 16%. Stabilization of these fractures is challenging and often require immediate internal fixation. Therefore, it is necessary to have a biomechanical understanding of the different fixation techniques for pelvic ring fractures. Methods A previously validated three-dimensional finite element model of the lumbar spine, pelvis, and femur was used for this study. A unilateral pelvic ring fracture was simulated by resecting the left side of the sacrum and pelvis. Five different fixation techniques were used to stabilize the fracture. A compressive follower load and pure moment was applied to compare different biomechanical parameters including range of motion (contralateral sacroiliac joint, L1-S1 segment, L5-S1 segment), and stresses (L5-S1 nucleus stresses, instrument stresses) between different fixation techniques. Results Transiliac -trans sacral screw fixation at S1 and S2 showed the highest stabilization for horizontal and vertical displacement at the sacral fracture site and reduction of contralateral sacroiliac joint for bending and flexion range of motion by 165% and 121%, respectively. DTSF (Double transiliac rod and screw fixation) model showed highest stabilization in horizontal displacement at the pubic rami fracture site, while the L5_PF_W_CC (L5-Ilium posterior screw fixation with cross connectors) and L5_PF_WO_CC ( L5-Ilium posterior screw fixation without cross connectors) showed higher rod stresses, reduced L1-S1 (approximately 28%), and L5-S1 (approximately 90%) range of motion. Conclusions Longer sacral screw fixations were superior in stabilizing sacral and contralateral sacroiliac joint range of motion. Lumbopelvic fixations displayed a higher degree of stabilization in the horizontal displacement compared to vertical displacement of pubic rami fracture, while also indicating the highest rod stresses. When determining the surgical approach for pelvic ring fractures, patient-specific factors should be accounted for to weigh the advantages and disadvantages for each technique.

Abstract: (1) Background: We hypothesized measuring the extent of brain overwork can extrapolate the burden of mental distress. This study aimed to develop a scale that measures mental distress and validate it in the general population. (2) Methods: In this population-based cross-sectional study, we recruited a total of 739 adults aged 16-65 years from 64 sampling centers of a clinical cohort across Mongolia to validate a 10-item self-report questionnaire. Internal consistency was measured using the McDonald’s ω. Test-retest reliability was analyzed using intraclass correlation coefficients. Construct and convergent validities were examined using the principal component analysis (PCA) and confirmatory factor analysis (CFA). Hospital Anxiety and Depression Scale (HADS) and the abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF) were used to evaluate the criterion validity. (3) Results: Among the participants, 70.9% were women, 22% held a bachelor's degree or higher, 38.8% were employed, and 66% were married. The overall McDonald’s ω coefficient was 0.861 demonstrating evidence of excellent internal consistency. The total intraclass correlation coefficient of the test-retest analysis was 0.75, indicating moderate external reliability. PCA and CFA established a three-domain structure that provided an excellent fit to the data (RMSEA=0.033, TLI=0.984, CFI=0.989, χ2=58, p=0.003). This 10-item scale, the Brain Overwork Scale (BOS-10), determines mental distress in three dimensions: Excessive Thinking, Hypersensitivity, and Restless Behavior. All items had higher item-total correlations with their corresponding domain than the other domains, and correlations between the domain scores ranged from 0.547–0.615. The BOS-10 correlated with the HADS, whereas it was inversely correlated with the WHOQOL-BREF. (4) Conclusions: The results suggest that the BOS-10 is a valid and reliable instrument for assessing mental distress in the general population. The current findings also demonstrate that the BOS-10 is quantitative, simple, and applicable for large-group testing.

The widespread use of epoxy resin (ER) in industry, owing to its excellent properties, aligns with the global shift toward greener resources and energy-efficient solutions, where utilizing metal oxides in 3D printed polymer parts can offer extended functionalities across various industries. ZnO concentrations in polyurethane acrylate composites impacted adhesion and thickness of DLP samples, with 1 wt.% achieving a thickness of 3.99±0.16 mm, closest to the target thickness of 4 mm, while 0.5 wt.% ZnO samples exhibited the lowest deviation in average thickness (±0.03 mm). Tensile strength in digital light processed (DLP) composites with ZnO remained consistent, ranging from 23.29 MPa (1 wt.%) to 25.93 MPa (0.5 wt.%), with an increase in ZnO concentration causing a reduction in tensile strength to 24.04 MPa and a decrease in the elastic modulus to 2001 MPa at 2 wt.% ZnO. The produced DLP samples, with their good corrosion resistance in alkaline environments, are well-suited for applications as protective coatings on tank walls. Customized DLP techniques can enable their effective use as structural or functional elements, such as in Portland cement concrete walls, floors and ceilings for enhanced durability and performance.

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.

Maize (Zea mays subsp. mays) is the staple food crop in the world. In this study, multi-layer perceptron (MLP), support vector machine (SVM), genetic algorithm-based multi-layer perceptron (MLP-GA), and genetic algorithm-based support vector machine (SVM-GA) hybrid artificial intelligence algorithms were used for the prediction of drought tolerance and stress tolerance indices in teosinte maize lines. Correspondingly, the gamma test technique was applied to determine efficient input and output vectors. The potential of developed models was evaluated based on statistical indices and graphical representation. Results of gamma test based on the least value of gamma and standard error indices show that day of anthesis (DOA), day of silking (DOS), yield index (YI), and gross yield per plant (GYP) information vector arrangements were determined as efficient information vector combination for drought-tolerant index (DTI) as well as the stress-tolerant index (STI). The results of MLP, SVM, MLP-GA, and SVM-GA algorithms were compared based on statistical indices and visual interpretation that have satisfactory for prediction of the drought-tolerant index and stress-tolerant index in maize crop. It has also seemed that genetic algorithm-based hybrid models (MLP-GA and SVM-GA) were found a better prediction of the drought-tolerant index and stress-tolerant index in maize crop. Similarly, the SVM-GA model has the highest potential to forecast the DTI and STI in maize crops as compared to MLP, SVM, MLP-GA models.

Different therapeutic strategies have been investigated to target and eliminate HIV-1-infected cells by using armed antibodies specific to viral proteins, with varying degrees of success. Herein, we propose a new strategy by combining photodynamic therapy (PDT) with HIV Env-targeted immunotherapy, and refer to it as HIV photoimmunotherapy (PIT). A human anti-gp41 antibody (7B2) was conjugated to two photosensitizers with different charges through different linking strategies; “Click” conjugation by using an azide-bearing porphyrin attached via a disulfide bridge linker with a drug-to-antibody ratio (DAR) of exactly 4, and “Lysine” conjugation by using phthalocyanine IRDye 700DX dye with average DARs of 2.1, 3.0 and 4.4. These photo-immunoconjugates (PICs) were compared via biochemical and immunological characterizations regarding the dosimetry, solubility, and cell targeting. Photo-induced cytotoxicity of the PICs were compared using assays for apoptosis, reactive oxygen species (ROS), photo-cytotoxicity, and confocal microscopy. Targeted phototoxicity seems to be primarily dependent on the binding of PS-antibody to the HIV antigen on the cell membrane, whilst being independent of the PS type. This is the first report of the application of PIT for HIV immunotherapy by killing HIV Env-expressing cells.

Protein Kinase C delta (PKCδ) has emerged as a key protective molecule against systemic lupus erythematosus (SLE or lupus), an autoimmune disease characterized by anti-double stranded (ds) DNA IgGs. Although PKCδ deficient mice and lupus patients with mutated PRKCD genes clearly demonstrate the requirement of PKCδ for preventing lupus autoimmunity, this critical tolerance mechanism remains poorly understood. We recently reported that PKCδ selectively deletes anti-dsDNA B cells in the germinal center (GC), disclosing a key B cell tolerance mechanism that prevents lupus autoimmunity. PKCδ’s tolerance function is activated by sphingomyelin synthase 2 (SMS2), a lipid enzyme whose expression is generally reduced in B cells from lupus patients. Moreover, pharmacologic strengthening of the SMS2/PKCδ tolerance pathway alleviated lupus pathogenesis in mice. Here, we review relevant publications in order to provide mechanistic insights into PKCδ’s tolerance activity, and discuss the potential significance of therapeutically targeting PKCδ’s tolerance activity in the GC for selectively inhibiting lupus autoimmunity.

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and as such provides a semi-selective barrier between the blood and the interstitial space. Compromise of the lung EC barrier due to inflammatory or toxic events may results in pulmonary edema, which is a cardinal feature of acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS). The EC functions are controlled, at least in part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent the largest group of HDACs and are activated by Zn2+. Members of this HDAC group are involved in the epigenetic regulation primarily via modifying the structure of chromatin upon removal of acetyl groups from histones. In addition, they can deacetylate many non-histone histone proteins, including those located in extra nuclear compartments. Recently, the therapeutic potential of inhibiting zinc-dependent HDACs for EC barrier preservation has gained momentum. However, the role of specific HDAC subtypes in EC barrier regulation remains largely unknown. This review aims to provide an update on the role of zinc-dependent HDACs in endothelial dysfunction and its related diseases. We will broadly focus on biological contributions, signaling pathways and transcriptional roles of HDACs in endothelial pathobiology associated mainly with lung diseases and we will discuss the potential of their inhibitors for lung injury prevention.

Mahanadi is one of the major inter-state east flowing perennial rivers in peninsular India. Hamp watershed of Seonath Sub-basin of upper Mahanadi basin was considered for the study to estimate the sediment yield and nutrient loss-based identification of critical agricultural sub-watershed and its critical Hydrological Response Unit (HRU) using Soil and Water Assessment Tool (SWAT) in-terfaced with GIS i.e., ArcSWAT. The study area was divided into 14 sub-watersheds considering topographical parameters derived from DEM and drainage network. The land cover, soil layers, and DEM were used to generate 207 HRUs for analysis of annual runoff, sediment yield and nu-trient loss for 2004-2008 (calibration period) and 2010-2013 (validation period). The sediment yield, runoff estimation and nutrient loss matched consistently well with the monthly and seasonal measured values. On the basis of average annual sediment yield (18.18 t/ha), runoff (245.97 mm) and nutrient loss NO3-N (1.62 kg/ha), respectively, sub-watershed WS4 was categorized under high priority for critical are identification. The sub watershed WS4 comprises of 15 HRUs (No. 36 - 50) with four kharif crops viz rice, soybean, maize and sugarcane. Results showed that the crops soy-bean, maize and sugarcane reduced the average annual runoff by 18.1, 31.4 and 18.0 per cent, respectively whereas the sediment yield was increased drastically by 104.5, 37.5 and 5.7 per cent, respectively as compared to rice. Soybean and maize crops HRU generate significant amount of soil and nutrient loss and were found to be as the critical HRUs for the upper Mahanadi River basin

HIV-associated cognitive dysfunction during combination antiretroviral therapy (cART) involves mitochondrial dysfunction, but the impact of contemporary cART on chronic metabolic changes in the brain and in latent HIV infection is unclear. We interrogated mitochondrial function in a human microglia (hμglia) cell line harboring inducible HIV provirus, and in SH-SY5Y cells, after exposure to individual antiretroviral drugs or cART, using the MitoStress assay. cART-induced changes in protein expression, reactive oxygen species (ROS) production, mitochondrial DNA copy number, and cellular iron were also explored. Finally, we evaluated the ability of ROS scavengers or plasmid-mediated overexpression of the antioxidant iron-binding protein, Fth1, to reverse mitochondrial defects. Contemporary antiretroviral drugs, particularly bictegravir, depressed multiple facets of mitochondrial function by 20-30%, with most pronounced effects in latently infected-HIV+ hμglia and SH-SY5Y cells. Latently HIV-infected hμglia exhibited upregulated glycolysis. Increases in total and/or mitochondrial ROS, mitochondrial DNA copy number, and cellular iron accompanied mitochondrial defects in hμglia and SH-SY5Y cells. In SH-SY5Y cells, cART reduced mitochondrial iron-sulfur-cluster-containing supercomplex and subunit expression and increased Nox2 expression. Fth1 overexpression or pre-treatment with N-acetylcysteine prevented cART-induced mitochondrial dysfunction. Contemporary cART impairs mitochondrial bioenergetics in hμglia and SH-SY5Y cells, partly through cellular iron accumulation; some effects differ by HIV latency.

Background: Macrophage inflammatory protein-1 alpha (MIP-1α) and C-reactive protein (CRP) are pro-inflammatory biomarkers that quantify clinical and subclinical inflammation in cardiac ischemia in cardiac inflammation and disease. Adiponectin is an anti-inflammatory marker associated with good health. The susceptibility of periodontitis patients to cardiovascular events needs to be evaluated. Objective: This study aims to assess the levels of biomarkers in periodontitis patients with and without acute myocardial infarction (AMI) compared to controls. Material and methods: Pro-inflammatory and anti-inflammatory analytes were examined by collecting unstimulated saliva from three groups (n = 20/each): healthy individuals, individuals with stage III periodontitis, and post-myocardial infarction patients with stage III periodontitis. The samples were collected within 48 hours of AMI. Results: Adiponectin levels were significantly lower in patients with periodontitis with and without AMI compared to controls, while CRP and MIP-1α were significantly higher in patients with periodontitis with and without AMI compared to controls. The highest titers for MIP-1α and CRP were detected among patients with periodontitis with and AMI. Conclusion: Our study provides evidence of the association between periodontitis and salivary analytes that occur in tandem with cardiovascular disease. The lower levels of Adiponectin and higher levels of CRP and MIP-1α in patients with periodontitis indicate that this condition is a potential risk factor for cardiovascular disease. The findings emphasize the importance of early detection and intervention for periodontitis patients to prevent cardiovascular events.

In the recent past, there has been a rise in Prostate Cancer (PCa) in Asia, particularly India. Although systematic reviews on PCa have dealt on the genetics, genomics and the environmental influence in causal of PCa, no predictive analytics in comparing the PCa from Caucasian, American to Asian population was attempted. In this review article, we have attempted to elaborate this aspect of PCa and deliberated on challenges related to next generation sequencing methods of PCa’s manifestation when compared to the west.

The study explored the correlation between serum biomarkers and hepatocellular carcinoma detection in various fishing groups, utilizing a descriptive and experimental approach in Bangladesh. The study identified fishers often consume tobacco, polluted drinking water, and lack sufficient sunlight, all of which are extremely detrimental to their health. Fishermen who mostly fish at night and spend little time on the water during the daytime hours do not get enough sunlight, nor do they get enough vitamin D. An increased risk of liver cancer was found to be directly and strongly correlated with insufficient serum levels of vitamin D. In addition, a negligent lifestyle, a lack of awareness about hepatitis, and inadequate nutritional assistance have significantly increased their risk. Our results contribute to the information on HCC assessment and evaluation by clarifying the relevance of serum vitamin D, alpha-fetoprotein (AFP), creatinine (Cr), and hemoglobin A1C (HbA1c) in distinguishing between categories and sexes. According to the study, the combination of AFP, Vitamin-D, and Cr (AFP+Vit-D+Cr) has a high predictive value, which improves diagnosis and offers a reliable instrument for identifying liver cancer.

Aim: This analytical cross-sectional study aimed to examine whether there is a correlation between tumor differentiation and certain biomarkers in patients with hepatocellular carcinoma (HCC). Methods: Poorly differentiated (n=443), moderately differentiated (n=379), and well-differentiated (n=272) tumors were separated from the research population, along with a control group (n=364). Biopsies were used to establish the presence of HCC, and biomarker levels were analyzed using chemiluminescence immunoassays in both infected and uninfected individuals. Results: The correlation between age and tumor size was shown to be statistically significant (p0.05) across all subgroups using both descriptive and inferential statistics. Patients with hepatitis C virus and non-A, non-B hepatitis had more advanced tumors than those with other types of poorly differentiated liver cancer. Similarly, individuals with HBsAg and moderate differentiation had bigger tumors, although there was no correlation between hepatitis C and non-A, non-B. Patients with HBsAg or hepatitis C had bigger tumors in the well-differentiated group, albeit the hepatitis C connection was not statistically significant. In addition, the study stressed that tumor size increases with age and that farmers were the most commonly diagnosed profession category. Conclusions: It is clear that early detection in infected populations is crucial for improving HCC outcomes and that chemiluminescence immunoassay has the potential to be a helpful platform for biomarker research. However, the study is limited by its small sample size and its emphasis on only three tumor markers, indicating that more biomarker research is required to improve the accuracy of HCC diagnosis and prognosis.

: Alluvial soils naturally possess abundant soil nutrients. Nevertheless, excessive nitrogen addition and inappropriate use of nitrogen fertilizers lead to conditions where soil nutrients become immo-bilized, ultimately reducing productivity. This study investigates the potential of natural nano-material zeolite which is important land resources to improve nutrient utilization efficiency and mitigate the harmful effects of excessive fertilizer application. Specifically, the research ex-plores the incorporation of clinoptilolite zeolite and processed sewage sludge blends, alongside reduced recommended nitrogen fertilizer doses, to evaluate their impact on soil quality and plant growth. A greenhouse experiment was conducted (three-year study), comprising eight treatments with varying proportions of zeolite and sewage sludge. The efficacy of these treatments in en-hancing soil carbon pools, nutrient indices, and plant growth responses was assessed. Results in-dicate that a combination of 50% recommended fertilizer dose, 4-6% zeolite, and 5-10% sewage sludge significantly improved multiple aspects of plant growth, including leaves, tillers, culms, and panicles, leading to increased straw and grain yields. The addition of 6% zeolite in conjunc-tion with sewage sludge positively influenced plant tillering capacity. Certain treatment combina-tions exhibited a greater impact on plant height at different growth stages. For example, the treatment with 75% recommended fertilizer dose, 4% zeolite, and 5% sewage sludge significantly affected plant height at 40 and 55 days after treatment. Additionally, the combination of 50% recommended fertilizer dose, 6% zeolite, and 10% sewage sludge promoted plant height, carbon levels, and various yield parameters in later stages. Principal component analysis effectively dis-tinguished treatments incorporating zeolite and sewage sludge based on plant responses. The combination of 6% zeolite and 10% sewage sludge, along with a 50% recommended fertilizer dose, positively influenced soil carbon fractions, nutrient levels, and the growth response of rice plants.

This research aims to find out whether the synthetic 1, 2, 4-triazine and its derivatives have antifungal effects and can protect humans from infection with Candida albicans. Molecular docking and molecular dynamic simulation are widely used in modern drug design to target a We are interested in using molecular docking and molecular dynamics modelling to investigate the interaction between the derivatives of 1, 2, 4-triazine and the resulting lanosterol 14 - demethylase (CYP51) of Candida albicans The inhibition of Candida albicans CYP51 is the main goal of our research. The 1, 2, 4-triazine and its derivatives have been docked to the CYP51 enzyme, which is involved in Candida albicans Multidrug Drug Resistance (MDR). Autodock tools were used to identifying the binding affinities of molecules against the target proteins. Compared to conventional fluconazole, the molecular docking results indicated that each drug has a high binding affinity for CYP51 proteins and forms unbound interactions and hydrogen bonds with their active residues and surrounding allosteric residues. The docking contacts were made using a 10 ns MD simulation with nine molecules. RMSD, RMSF, hydrogen bonds, and the Rg all confirm these conclusions. In addition, these compounds were expected to have a favorable pharmacological profile and low toxicity. The compounds are being offered as scaffolds for the development of new antifungal drugs and as candidates for future in vitro testing.

A novel, rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the evaluation of OTS167 pharmacokinetics in mouse serum. SN-38 was optimized to be selected as the internal standard. Chromatographic separation was performed on a BDS Hypersil C18 column (100 x 2.1 mm, 5 µm) using gradient elution with mobile phase solvent A as water containing 0.1% formic acid and solvent B as acetonitrile containing 0.1% formic acid. The analysis was carried out using multiple reaction monitoring (MRM) with a triple-quadrupole mass spectrometer operated in the positive electrospray ionization mode. Mass transitions of 487.2 > 348.0 and 393.2 > 349.2 were monitored for OTS167 and SN-38 respectively. The standard calibration curve demonstrated high linearity at a range of 5-1000 ng/mL, with a coefficient of determination (r2) ≥ 0.996. The accuracy for OTS167 ranged from 92.3% to 102.2% and the precision was ≤ 12.7%. Recovery was consistent at about 83% to 89%. No significant matrix effect was observed. This method was successfully applied to monitor the pharmacokinetic profiles in mice over 24 h after ingestion of 5 mg/kg of OTS167. Maximum serum concentrations (3197 ng/mL) of OTS167 was observed at 1.67 hour after OTS167 ingestion via garage at 5 mg/kg and area under the curve (AUC) was 28579 h*ng/mL, suggesting that OTS167 can be quickly absorbed after oral administration.

In this review we look at the developments in the field of artificial intelligence (A.I) and their current impact as well as future implications in the field of cardiology, we as physicians and cardiologists have tried to put our perspective on the rapidly evolving field, In light of the fact that many of the healthcare workers and professionals across the world still find the concept of A.I quite complicated, elusive and somewhat paradoxical, we have tried to simplify the concept of artificial intelligence and make it easy for everyone to understand from all walks of life. The Databases utilized for our review are PubMed, PubMed Central, Google Scholar. The Keywords used for our Data Search are “Artificial Intelligence”, “A.I Cardiology”, “A.I in Cardiovascular Medicine”, “Machine Learning in Cardiology”. We screened all relevant since inception till March 25th and included 44 relevant articles after careful consideration into our paper. We have discussed the implementation of and scope of artificial intelligence across a broad spectrum of applications including cardiovascular imaging and diagnostics like electrocardiograms, echocardiograms, cardiac CT/MRIs to novel cardiac monitoring devices, CRISPR gene editing in cardiology and implementation of artificial intelligence in the field of Cardiovascular Bioprinting. This is the initial review in a series of reviews regarding A.I in Cardiology.

Network effects, economies of scale, and lock-in-effects increasingly lead to a concentration of digital resources and capabilities, hindering the free and equitable development of digital entrepreneurship (SDG9), new skills, and jobs (SDG8), especially in small communities (SDG11) and their small and medium-sized enterprises (“SMEs”). To ensure the affordability and accessibility of technologies, promote digital entrepreneurship and community well-being (SDG3), and protect digital rights, we propose data cooperatives [1,2] as a vehicle for secure, trusted, and sovereign data exchange [3,4]. In post-pandemic times, community/SME-led cooperatives can play a vital role by ensuring that supply chains to support digital commons are uninterrupted, resilient, and decentralized [5]. Digital commons and data sovereignty provide communities with affordable and easy access to information and the ability to collectively negotiate data-related decisions. Moreover, cooperative commons (a) provide access to the infrastructure that underpins the modern economy, (b) preserve property rights, and (c) ensure that privatization and monopolization do not further erode self-determination, especially in a world increasingly mediated by AI. Thus, governance plays a significant role in accelerating communities’/SMEs’ digital transformation and addressing their challenges. Cooperatives thrive on digital governance and standards such as open trusted Application Programming Interfaces (APIs) that increase the efficiency, technological capabilities, and capacities of participants and, most importantly, integrate, enable, and accelerate the digital transformation of SMEs in the overall process. This policy paper presents and discusses several transformative use cases for cooperative data governance. The use cases demonstrate how platform/data-cooperatives, and their novel value creation can be leveraged to take digital commons and value chains to a new level of collaboration while addressing the most pressing community issues. The proposed framework for a digital federated and sovereign reference architecture will create a blueprint for sustainable development both in the Global South and North.

Endovascular therapy (EVT) has revolutionized the management of acute ischaemic strokes with large vessel occlusion, with emerging evidence suggesting its benefit also in large infarct core volume strokes. In the last 2 years, 4 randomised controlled trials have been published on this topic - RES-CUE-Japan-LIMIT, ANGEL-ASPECT, SELECT2 and TENSION, with overall results showing that EVT improves functional and neurological outcomes compared to medical management alone. This review seeks to summarise the recent evidence presented by these 4 trials and highlight some of the limitations of our current understanding on this topic.

Initial evaluations of the System of Rice Intensification in India and elsewhere have mainly fo-cused on its impact on yield and income and have usually covered just one or two seasons. Re-searchers at the ICAR-Indian Institute of Rice Research conducted a more comprehensive evalua-tion of SRI methods over six years (six wet and six dry seasons), comparing these methods with three other rice crop management systems: modified, partially mechanized SRI (MSRI); direct-seeded rice (DSR); and normal transplanting with inundated fields (NTP). SRI grain yield was found to be about 50% higher than with NTP (6.35 t ha-1 vs 4.27 t ha-1), while the MSRI yield was essentially the same (6.34 t ha-1) and 16% higher than with DSR (5.45 t ha-1). Compared to NTP, SRI methods significantly enhanced soil microbial populations over time, bacteria by 12%, fungi by 8%, and actinomycetes by 20%. Indicators of biological activity in the rhizosphere were also higher, dehydrogenase by 8.5% and FDA enzymes by 16%. Glucosidase activity, an indicator of soil organic matter, was 78% higher. Relative to normal transplanting methods, SRI reduced GHG emissions by 21%, while DSR reduced them by 23% and MSRI by 13%, which indicated pos-itive effects of the alternate and improved methods over normal transplanting. Economic analy-sis showed that both gross and net economic returns to be higher with SRI than with MSRI and the other management systems evaluated. While the six-year study documented many ad-vantages of SRI crop management, the MSRI version evaluated is a promising adaptation that provide similar benefits but with lower labor requirements.

Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.

The search for improved therapeutic approaches to breast cancer are still on going. Breast tumor kinase (BRK, also known as PTK6) is one of the targets, it is highly expressed in breast carcinomas while displaying low or no expression in the normal mammary gland, which hints at the oncogenic role of this enzyme in breast cancer. In these twenty years, an increasing number of studies have focused on understanding the cellular roles of BRK in breast cancers. This review outlines the advances made towards understanding the cellular and physiological role of BRK, the molecular and chemical inhibitors and its therapeutic significance in breast cancer.

The G-NUMEN array is the future gamma spectrometer of the NUMEN experiment (Nuclear Matrix Element for the Neutrinoless double beta decay), to be installed around the object point of the MAGNEX magnetic spectrometer at the INFN-LNS laboratory.. This project aims at exploring Double Charge Exchange (DCE) reactions in order to obtain crucial information about the neutrinoless double beta decay (0νββ). The primary objective of the G-NUMEN array is to detect the gamma rays emitted from the de-excitation of the excited states populated via DCE reactions with good energy resolution and detection efficiency, amidst a background composed of transitions from competingreaction channels with far higher cross-sections. To achieve this, the G-NUMEN signalswill be processed in coincidence with those generated by the detection of the reaction ejectiles in the MAGNEX Focal Plane Detector(FPD). Under the expected experimental conditions, G-NUMEN detectors will operate at high counting rates, of the order of hundreds of kHz per detector, while maintaining excellent energy and timing resolutions. The complete array will consist of over 100 LaBr3(Ce) scintillators. Initial tests have been conducted on the first detectors of the array, allowing for the determination of their performance at high rates.