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Obesity is a chronic disease marked by the buildup of extra adipose tissue and a higher chance of developing concomitant illnesses such as heart disease, diabetes, high blood pressure, and some malignancies. Over the past few decades, there has been a global increase in the prevalence of obesity, which now affects around one-third of the world's population. According to recent studies, a variety of factors, including genetics and biology as well as environmental, physiological, and psychosocial factors, may have a role in the development of obesity. The prevalence of obesity is often higher among Hispanic American groups than among White people in the U.S. Obesity is a widespread condition with a high risk of morbidity and death, and it is well-recognized that the prevalence of comorbidities rises with rising levels of obesity or body mass index. To combat the rising prevalence of obesity in the USA, especially among Hispanics, one of the fastest-growing racial/ethnic groups in the country, there is an urgent need for obesity therapies. The exact cause of this disparity is unclear, but some responsible factors are a lack of education, high unemployment rates, high levels of food insecurity, an unhealthy diet, inadequate access to physical activity resources, a lack of health insurance, and constricted access to culturally adequate healthcare. Additionally, managing obesity and giving needed/timely support to obese people is a difficult responsibility for medical professionals and their loved ones. The need for caregivers is increasing with the increased number of individuals with obesity, particularly Hispanics. Our article summarizes the status of obesity, focusing on Hispanic populations, and we also highlight specific factors that contribute to obesity, including genetics, epigenetics, biological, physiological, and psychosocial factors, medication and disease, environment, and socio-demographics. This article also reviews caregiver duties and challenges associated with caring for people with obesity. [ABSTRACT FROM AUTHOR]

A double catalytic layer scheme is proposed and investigated for the low temperature growth of carbon nanotubes (CNTs) over Co (Cobalt), Al (Aluminum), and Ti (Titanium) catalysts on a silicon substrate. In this work, we demonstrate the growth of CNTs by a thermal chemical vapor deposition (TCVD) process at both 350 °C and 400 °C. Based on scanning electron microscopy (SEM) and Raman spectroscopy analyses, the good quality of the CNTs is demonstrated. This study contributes to the on-going research on integrating semiconductors into packaging and power-related applications, as demonstrated with the low resistance (~128 Ω) and high thermal conductivity (~29.8 Wm−1 K−1) of our developed CNTs. [ABSTRACT FROM AUTHOR]

Simple Summary: Circulating biomarkers for the identification of patients with "actionable" nodules may increase screening uptake and decrease false-positive rates associated with low-dose computed tomography (LDCT). Novel autoantibody biomarkers were identified utilizing a HuProt™ protein microarray. Luminex assays were developed for the targeted measurement of identified biomarkers within a large Biomarker Development Cohort (n = 841). Each individual biomarker's performance was assessed. The Biomarker Development Cohort was split into three separate cohorts: Training, Validation 1, and Validation 2. Utilizing a Training cohort, a random forest model for identifying patients with "actionable" nodules from those with "non-actionable" nodules was built. The random forest model performance characteristics were determined for both a Validation 1 and the Validation 2 cohort. From these steps we have developed a risk-stratification method that assesses circulating levels of a panel of novel autoantibody biomarkers to serve as a companion diagnostic method for lung cancer screening. Due to poor compliance and uptake of LDCT screening among high-risk populations, lung cancer is often diagnosed in advanced stages where treatment is rarely curative. Based upon the American College of Radiology's Lung Imaging and Reporting Data System (Lung-RADS) 80–90% of patients screened will have clinically "non-actionable" nodules (Lung-RADS 1 or 2), and those harboring larger, clinically "actionable" nodules (Lung-RADS 3 or 4) have a significantly greater risk of lung cancer. The development of a companion diagnostic method capable of identifying patients likely to have a clinically actionable nodule identified during LDCT is anticipated to improve accessibility and uptake of the paradigm and improve early detection rates. Using protein microarrays, we identified 501 circulating targets with differential immunoreactivities against cohorts characterized as possessing either actionable (n = 42) or non-actionable (n = 20) solid pulmonary nodules, per Lung-RADS guidelines. Quantitative assays were assembled on the Luminex platform for the 26 most promising targets. These assays were used to measure serum autoantibody levels in 841 patients, consisting of benign (BN; n = 101), early-stage non-small cell lung cancer (NSCLC; n = 245), other early-stage malignancies within the lung (n = 29), and individuals meeting United States Preventative Screening Task Force (USPSTF) screening inclusion criteria with both actionable (n = 87) and non-actionable radiologic findings (n = 379). These 841 patients were randomly split into three cohorts: Training, Validation 1, and Validation 2. Of the 26 candidate biomarkers tested, 17 differentiated patients with actionable nodules from those with non-actionable nodules. A random forest model consisting of six autoantibody (Annexin 2, DCD, MID1IP1, PNMA1, TAF10, ZNF696) biomarkers was developed to optimize our classification performance; it possessed a positive predictive value (PPV) of 61.4%/61.0% and negative predictive value (NPV) of 95.7%/83.9% against Validation cohorts 1 and 2, respectively. This panel may improve patient selection methods for lung cancer screening, serving to greatly reduce the futile screening rate while also improving accessibility to the paradigm for underserved populations. [ABSTRACT FROM AUTHOR]

In the 21st century, melanoma and non-melanoma skin cancers have become an epidemic outbreak worldwide. Therefore, the exploration of all potential preventative and therapeutic measures based on either physical or bio-chemical mechanisms is essential via understanding precise pathophysiological pathways (Mitogen-activated protein kinase, Phosphatidylinositol 3-kinase Pathway, and Notch signaling pathway) and other aspects of such skin malignancies. Nano-gel, a three-dimensional polymeric cross-linked porous hydrogel having a diameter of 20–200 nm, possesses dual properties of both hydrogel and nanoparticle. The capacity of high drug entrapment efficiency with greater thermodynamic stability, remarkable solubilization potential, and swelling behavior of nano-gel becomes a promising candidate as a targeted drug delivery system in the treatment of skin cancer. Nano-gel can be either synthetically or architectonically modified for responding to either internal or external stimuli, including radiation, ultrasound, enzyme, magnetic, pH, temperature, and oxidation-reduction to achieve controlled release of pharmaceuticals and several bio-active molecules such as proteins, peptides, genes via amplifying drug aggregation in the active targeted tissue and reducing adverse pharmacological effects. Several drugs, such as anti-neoplastic biomolecules having short biological half-lives and prompt enzyme degradability capacity, must be appropriate for administration employing either chemically bridged or physically constructed nano-gel frameworks. The comprehensive review summarizes the advancement in the preparation and characterization methods of targeted nano-gel with enhanced pharmacological potential and preserved intracellular safety limits for the mitigation of skin malignancies with a special emphasize on skin cancer inducing pathophysiological pathways and prospective research opportunities for skin malignancy targeted nano-gels. [ABSTRACT FROM AUTHOR]

T and B cell receptor signaling involves the activation of Akt, MAPKs, and PKC as well as an increase in intracellular Ca2+ and calmodulin activation. While these coordinate the rapid turnover of gap junctions, also implicated in this process is Src, which is not activated as part of T and B cell receptor signaling. An in vitro kinase screen identified that Bruton's tyrosine kinase (BTK) and interleukin-2-inducible T-cell kinase (ITK) phosphorylate Cx43. Mass spectroscopy revealed that BTK and ITK phosphorylate Cx43 residues Y247, Y265, and Y313, which are identical to the residues phosphorylated by Src. Overexpression of BTK or ITK in the HEK-293T cells led to increased Cx43 tyrosine phosphorylation as well as decreased gap junction intercellular communication (GJIC) and Cx43 membrane localization. In the lymphocytes, activation of the B cell receptor (Daudi cells) or T cell receptor (Jurkat cells) increased the BTK and ITK activity, respectively. While this led to increased tyrosine phosphorylation of Cx43 and decreased GJIC, the cellular localization of Cx43 changed little. We have previously identified that Pyk2 and Tyk2 also phosphorylate Cx43 at residues Y247, Y265, and Y313 with a similar cellular fate to that of Src. With phosphorylation critical to Cx43 assembly and turnover, and kinase expression varying between different cell types, there would be a need for different kinases to achieve the same regulation of Cx43. The work presented herein suggests that in the immune system, ITK and BTK have the capacity for the tyrosine phosphorylation of Cx43 to alter the gap junction function in a similar manner as Pyk2, Tyk2, and Src. [ABSTRACT FROM AUTHOR]

The flood hazard risks and vulnerability in the urban areas alongside major rivers of India have been gradually increasing due to extreme climatic events. The present study is intended to assess flood hazard vulnerability and potential risk areas and aims to ascertain the management strategies in Nabadwip Municipality, a statutory urban area of West Bengal. The multi-criteria decision making (MCDM) of selected criteria and geospatial techniques have been employed to determine the urban flood vulnerability in the study area. The study has been conducted using secondary datasets including relevant remotely sensed data and participant observation. The potential flood-affected zones have been determined using the normalized difference flood index (NDFI) and flood vulnerability index (FVI). The analysis of the standardized precipitation index (SPI) of 20 years of monthly precipitation shows the variability of seasonal rainfall distribution in the study area. Furthermore, the spatial distribution of the composite Ibrahim index of socio-economic development accents that the urban development of the study area was uneven. The municipal wards situated in the central and northeastern portions of Nabadwip Municipality were extremely vulnerable, whereas the western and southwestern wards were less vulnerable. It is also revealed from the strengths–weaknesses–opportunities–challenges (SWOC) of the principal management strategies of the flood situation analysis that the unplanned sewerage system is one of the most effective weaknesses in the area. All-embracing and integrative flood management strategies need to be implemented in the study area considering the intra-regional vulnerability and development for the resilient and sustainable development of the study area. [ABSTRACT FROM AUTHOR]

Climate change has amplified the severity of droughts with potentially adverse impacts on agriculture in western Canada. This study assessed meteorological and agricultural drought in the Southern Saskatchewan River Basin (SSRB) using an array of drought indices, including the Standardized Precipitation Index (SPI), the Standardized Precipitation-Evapotranspiration Index (SPEI), the Self-Calibrated Palmer Drought Severity Index (scPDSI), the Soil Moisture Deficit Index (SMDI), and the Evapotranspiration Deficit Index (ETDI). These indices were evaluated using multiple regional climate model (RCM) projections assuming 1.5, 2.0, and 3.0 °C thresholds of global warming. A modified Soil and Water Assessment Tool (SWAT-M) was used to simulate the soil water content (SWC), actual evapotranspiration (AET), and potential evapotranspiration. The results of a sensitivity analysis using the SUFI-2 method in SWAT-CUP showed that the model performed well with BIAS lower than 10% and NSE and R higher than 0.7, and the range of SWC output closely matched the observed SWC. According to the RCM projections, the annual precipitation increases for all three global temperature thresholds while the annual mean temperature increases at a greater rate than the rise in global mean temperature. The projected PDSI and the SPEI suggest that drought duration and severity will exceed historical values while SPI will remain largely unchanged. Furthermore, severe drought conditions (SMDI < 2.0) are more frequent under the 3.0 °C global temperature scenario. The mean ETDI was historically 0.58 while the projected value is 0.2, 0.1, and −0.2 for the first to third scenarios, respectively. Simulated values, spatial maps, and heat maps of SMDI and ETDI illustrated that Canesm2.CRCM5 projects the driest conditions among all the RCMs. Agricultural drought indices, which incorporate SWC data, show more significant effects than meteorological drought indices. The increasing dryness will potentially impact agricultural crop production, particularly under the third scenario (3 °C) in the SSRB. [ABSTRACT FROM AUTHOR]

Global energy demand has unquestionably increased significantly in recent years. Nowadays, industries are very aware of global warming, and to save the environment, they produce green products with energy consumption. Day by day, energy use is increasing due to population, end-use markets of construction, transportation, industry, etc. But the energy limit is finite, whereas the daily use is rising, so the price is increasing. In this study, two situations have been shown in two models with renewable energy consumption. Model 1 analyzes the manufacturer and retailer's optimal green quality and sales price in two-echelon supply chain systems with centralized and decentralized cases. In this case, the retailer sells their products through three different channels: online, offline, and buy-online-pickup-in store, with three different selling prices. In Model 2, Manufacturer 1 and Manufacturer 2 produce green and regular products with renewable energy consumption. In this case, both manufacturers sell their products through three different channels: online, offline, and buy-online-pickup-in store, with three different selling prices. There is competition between substitutable products with respect to green quality and the selling price of the products. A hybrid channel policy is studied here to maximize the total profit with considering corporate social responsibility under renewable energy consumption. The study has been analyzed mathematically. The classical optimization approach and game theory are applied here to find the optimal values of procurement cost, selling price, and green quality development cost. A numerical study shows that the centralized system gives a better result to the manufacturer than the decentralized system. When the demand is a power function of the selling price, the manufacturer producing eco-friendly products gains 0.99 % more profit than the conventional product. This result shows that manufacturers creating eco-friendly products motivate other manufacturers to make eco-friendly products. [ABSTRACT FROM AUTHOR]

Simple Summary: Human papilloma virus–negative (HPV(−)) oral cavity squamous cell carcinoma (OCSCC) is the leading cause of mortality amongst head and neck cancers. Radiation resistance remains a prime cause of treatment failure in OCSCC. Overall, failure to cure locally advanced OCSCC remains a formidable challenge. The aim of our study was to exploit the hyperactive CDK4/6 axis in HPV(−) OCSCC by targeting it with the p16 mimetic palbociclib and to assess the resulting effect on susceptibility to radiation. Our study demonstrates that both homologous recombination (HR) and Non-homologous end joining pathway (NHEJ), two critical DNA damage repair pathways, are compromised after palbociclib-induced senescence in OCSCC cells, leading to enhance radiation sensitivity. Our findings provide important insight towards a promising treatment paradigm in OCSCC. Purpose: HPV(−) OCSCC resists radiation treatment. The CDKN2A gene, encoding p16INK4A, is commonly disrupted in OCSCC. p16 inhibits CDK4/CDK6, leading to cell cycle arrest, but the biological sequelae of CDK4/6 inhibition in OCSCC remains understudied. This study examines whether inhibition of CDK4/6 enhances radiation response in OCSCC. Methods: MTT assays were performed in OCSCC cell lines HN5 and CAL27 following treatment with palbociclib. Clonogenic survival and synergy were analyzed after radiation (RT-2 or 4Gy), palbociclib (P) (0.5 µM or 1 µM), or concurrent combination treatment (P+RT). DNA damage/repair and senescence were examined. CDK4/6 were targeted via siRNA to corroborate P+RT effects. Three-dimensional immortalized spheroids and organoids derived from patient tumors (conditionally reprogrammed OCSCC CR-06 and CR-18) were established to further examine and validate responses to P+RT. Results: P+RT demonstrated reduced viability and synergy, increased β-gal expression (~95%), and ~two-fold higher γH2AX. Rad51 and Ku80 were reduced after P+RT, indicating impairment of both HR and NHEJ. siCDK4/6 increased senescence with radiation. Spheroids showed reduced proliferation and size with P+RT. CR-06 and CR-18 further demonstrated three-fold reduced proliferation and organoids size with P+RT. Conclusion: Targeting CDK4/6 can lead to improved efficacy when combined with radiation in OCSCC by inducing senescence and inhibiting DNA damage repair. [ABSTRACT FROM AUTHOR]

Corneal opacification or scarring is one of the leading causes of blindness worldwide. Human limbus-derived stromal/mesenchymal stem cells (hLMSCs) have the potential of clearing corneal scarring. In the current preclinical studies, we aimed to determine their ability to heal the scarred corneas, in a murine model of corneal scar, and examined their ocular and systemic toxicity after topical administration to rabbit eyes. The hLMSCs were derived from human donor corneas and were cultivated in a clean room facility in compliance with the current good manufacturing practices (cGMP). Before the administration, the hLMSCs were analyzed for their characteristic properties including immunostaining, and were further subjected to sterility and stability analysis. The corneas (right eye) of C57BL/6 mice (n = 56) were stripped of their central epithelium and superficial anterior stroma using a rotary burr (Alger Brush® II). Few mice were left untreated (n = 8), while few (n = 24) were treated immediately with hLMSCs after debridement (prophylaxis group). The rest (n = 24, scar group) were allowed to develop corneal scarring for 2 weeks and then treated with hLMSCs. In both groups, the treatment modalities included encapsulated (En+) and non-encapsulated (En−) hLMSCs and sham (vehicle) treatment. The follow-up (4 weeks) after the treatment or debridement included clinical photography, fluorescein staining, and optical coherence tomography at regular intervals. All the images and scans were analyzed using ImageJ software to assess the changes in corneal haze, scar area, and the reflectivity ratio of the epithelium to the stroma. The scar area and the scar intensity were found to be decreased in the groups that received hLMSCs. The reflectivity of the stroma was found to be normalized to the baseline levels before the debridement in the eyes that were treated with hLMSCs, relative to the untreated. In the safety study, the central corneas of the left eye of 18 New Zealand rabbits were scraped with a needle and then treated with En+ hLMSCs, En− hLMSCs, and the sham (n = 6 each). Rabbits were then followed up for 4 weeks, during which blood and tear samples were collected at regular intervals. These rabbits were then assessed for changes in the quantities of inflammatory markers (TNF-α, IL-6, and IgE) in the sera and tears, changes in the ocular surface observations such as intraocular pressure (IOP), and the hematological and clinical chemistry parameters. Four weeks later, the rabbits were euthanized and examined histopathologically. No significant changes in conjunctival congestion, corneal clarity, or IOP were noticed during the ophthalmic examination. The level of inflammatory molecules (TNF-α and IL-6 TNF-α) and the hematological parameters were similar in all groups without any significant changes. Histological examination of the internal organs and ocular tissues did not reveal any abnormalities. The results of these studies summarize that the En+ and En− hLMSCs are not harmful to the recipient and potentially restore the transparency of debrided or scarred corneas, indicating that hLMSCs can be assessed for clinical use in humans. [ABSTRACT FROM AUTHOR]

Polypyrrole (PPy) nanoparticles are reliable conducting polymers with many industrial applications. Nevertheless, owing to disadvantages in structure and morphology, producing PPy with high electrical conductivity is challenging. In this study, a chemical oxidative polymerization-assisted ultra-sonication method was used to synthesize PPy with high conductivity. The influence of critical sonication parameters such as time and power on the structure, morphology, and electrical properties was examined using response surface methodology. Various analyses such as SEM, FTIR, DSC, and TGA were performed on the PPy. An R2 value of 0.8699 from the regression analysis suggested a fine correlation between the observed and predicted values of PPy conductivity. Using response surface plots and contour line diagrams, the optimum sonication time and sonication power were found to be 17 min and 24 W, respectively, generating a maximum conductivity of 2.334 S/cm. Meanwhile, the model predicted 2.249 S/cm conductivity, indicating successful alignment with the experimental data and incurring marginal error. SEM results demonstrated that the morphology of the particles was almost spherical, whereas the FTIR spectra indicated the presence of certain functional groups in the PPy. The obtained PPy with high conductivity can be a promising conducting material with various applications, such as in supercapacitors, sensors, and other smart electronic devices. [ABSTRACT FROM AUTHOR]

It is important to isolate exosomes (<150 nm) from biofluid for diagnosis or prognosis purposes, followed by sensing of exosomal proteins. In the present work, exosomes are isolated from human serum by immobilizing on a Screen-Printed Electrode (SPE) followed by electric field lysis and electrochemical impedance spectroscopy (EIS)-based sensing of relevant exosomal proteins (HSP70 and HER2). Upon immobilization of exosomes on the surface, the role of different electrical signals (sinusoidal and square wave) in the lysis of exosomes was studied by varying the frequency and voltage. HSP70 was used for EIS to determine the optimal voltage and frequency for lysing the exosomes. It was observed that the low frequencies and, specifically, sinusoidal signals are ideal for lysing exosomes as compared to square signals. The relative quantity of HSP70 obtained by lysing with different voltages (sinusoidal waveform) was compared using Western blotting. After electric field lysis of the exosome with an optimized signal, HER2, a breast cancer biomarker, was detected successfully from serum by EIS. In the proposed technique, 3.5 × 108 exosomes/mL were isolated from serum. With the limit of detection of 10 pg, the designed cell showed a linear detection of HER2 from 0.1 ng to 1 µg. It was observed from the results that the electric field lysis of exosomes not only plays a significant role in releasing the cargo protein but also improves the sensing of surface proteins associated with exosomes. [ABSTRACT FROM AUTHOR]

It is important to understand the features of an integrated renewable energy power system, especially for deregulated systems. The greatest obstacle to assimilating renewable energy generators with the existing electrical system is their unpredictability. Because wind energy is inconsistent, incorporating it into an established power system necessitates more planning. The effects of wind farm (WF) incorporation with fuel cells and a unified power flow controller (UPFC) on electric losses, voltage profile, generating price, and the economics of the system in a deregulated power market are examined in this paper. An impact analysis of integrating wind farms into controlled and uncontrolled situations is conducted. At two randomly selected locations in India, the real-time statistics of the actual wind speed (AWS) and forecasted wind speed (FWS) were merged for this study. The surplus charge rate and deficit charge rate are intended to evaluate the imbalance cost which is arising from the difference between anticipated and true wind speeds to determine the economics of the system. Customers are always trying to find electricity that is reliable, inexpensive, and efficient due to the reconfiguration of the power system. As a consequence, the security limitations of the system may be surpassed or might function beyond the safety limit, which is undesirable. In the last section, heuristic algorithms, such as sequential quadratic programming (SQP), artificial bee colony algorithms (ABC), and moth-flame optimization algorithms (MFO), are employed to analyze economic risk. In the real-time energy market, it also covers how the fuel cells and UPFC are utilized to rectify the WF integration's deviation. Economic risk evaluation approaches include value-at-risk (VaR) and conditional value-at-risk (CVaR). A modified IEEE 30-bus test system is used throughout the whole project. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer (OVCA) is a fatal gynecological disease for which there is no early detection test. Glucose-regulated protein 78 (GRP78), a protein marker of stress, increases during chronic stress. Chronic stress has been suggested as a hallmark of cancer development. This study examined whether expression of GRP78 is associated with development of OVCA and whether GRP78 can predict OVCA at early stage. This study found GRP78 expression and its secretion in blood increased during OVCA development and progression. This study also developed a GRP78-targeted ultrasound scanning agent that detected ovarian tumors at early stages. Thus, a woman with high levels of GRP78 in her blood may be referred to have targeted-ultrasound scanning for confirming if she has ovarian tumors. These results will be a foundation for a clinical study to examine the feasibility of GRP78 as a potential marker of blood and ultrasound scanning for early detection of OVCA. Background: Understanding malignant transformation associated with ovarian cancer (OVCA) is important to establish early detection tests. This study examined whether expression of glucose-regulated protein 78 (GRP78, marker of cellular stress) increases during OVCA development, and whether GRP78 can be detected by targeted-transvaginal ultrasound (TVUS) imaging. Methods: Normal ovaries (n = 10), benign (n = 10) and malignant ovarian tumors at early (n = 8) and late stages (n = 16), hens with and without ovarian tumors at early and late stages (n = 10, each) were examined for GRP78 expression during OVCA development by immunohistochemistry, immunoblotting, gene expression and immunoassay. Feasibility of GRP78-targeted TVUS imaging in detecting early OVCA was examined. Results: Compared with normal ovaries and benign tumors, intensity of GRP78 expression was higher (p < 0.0001) in OVCA patients. Compared with normal (9007.76 ± 816.54 pg/mL), serum GRP78 levels were significantly higher (p < 0.05) in patients with early (12,730.59 ± 817.35 pg/mL) and late-stage OVCA (13,930.12 ± 202.35) (p < 0.01). Compared with normal (222.62 ± 181.69 pg/mL), serum GRP78 levels increased (p < 0.05) in hens with early (590.19 ± 198.18 pg/mL) and late-stage OVCA (1261.38 ± 372.85) (p < 0.01). Compared with non-targeted, GRP78-targeted imaging enhanced signal intensity of TVUS (p < 0.0001). Conclusions: Tissue and serum levels of GRP78 increase in association with OVCA. GRP78 offers a potential serum and imaging marker for early OVCA detection. [ABSTRACT FROM AUTHOR]

Simple Summary: The hyaluronan receptor CD44 plays a vital role in tumor cell growth and chemotherapy resistance. The tumor suppressor p53 binds to the CD44 promoter via a non-canonical p53 consensus sequence and suppresses CD44 expression, promoting apoptosis. Conversely, the apoptotic function of p53 is negatively regulated through its interactions with iASPP, a specific inhibitor of p53-induced apoptosis in both normal and cancer cells. CD44, p53, and iASPP are co-expressed in a wide array of human cancers; however, the precise role of CD44 in p53-mediated apoptosis is not known. We discovered that the standard isoform of CD44 physically bound to iASPP and dictated the sub-cellular localization of iASPP-p53 complexes. The iASPP-CD44 complex affected fibroblast adhesion, migration, growth, and p53-mediated apoptosis. In the present study, we show that the inhibitor of the apoptosis-stimulating protein of p53 (iASPP) physically interacts with the hyaluronan receptor CD44 in normal and transformed cells. We noticed that the CD44 standard isoform (CD44s), but not the variant isoform (CD44v), bound to iASPP via the ankyrin-binding domain in CD44s. The formation of iASPP-CD44s complexes was promoted by hyaluronan stimulation in fibroblasts but not in epithelial cells. The cellular level of p53 affected the amount of the iASPP-CD44 complex. iASPP was required for hyaluronan-induced CD44-dependent migration and adhesion of fibroblasts. Of note, CD44 altered the sub-cellular localization of the iASPP-p53 complex; thus, ablation of CD44 promoted translocation of iASPP from the nucleus to the cytoplasm, resulting in increased formation of a cytoplasmic iASPP-p53 complex in fibroblasts. Overexpression of iASPP decreased, but CD44 increased the level of intracellular reactive oxygen species (ROS). Knock-down of CD44s, in the presence of p53, led to increased cell growth and cell density of fibroblasts by suppression of p27 and p53. Our observations suggest that the balance of iASPP-CD44 and iASPP-p53 complexes affect the survival and migration of fibroblasts. [ABSTRACT FROM AUTHOR]

Contamination of barley by deoxynivalenol (DON), a mycotoxin produced by Fusarium graminearum, causes considerable financial loss to the grain and malting industries. In this study, two atmospheric cold plasma (ACP) reactors were used to produce plasma-activated water (PAW) bubbles. The potential of PAW bubbles for the steeping of naturally infected barley (NIB) during the malting process was investigated. The PAW bubbles produced by treating water for 30 min using a bubble spark discharge (BSD) at low temperature resulted in the greatest concentration of oxygen-nitrogen reactive species (RONS). This treatment resulted in 57.3% DON degradation compared with 36.9% in the control sample; however, the same treatment reduced germination significantly (p < 0.05). Direct BSD ACP treatment for 20 min at low temperature and indirect treatment for 30 min increased the percentage of germinated rootlets of the seedlings compared with the control. Considering both the DON reduction and germination improvement of barley seeds, continuous jet ACP treatment for 30 min performed better than the other treatments used in this study. At higher temperature of PAW bubbles, the concentration of RONS was significantly (p < 0.05) reduced. Based on quantitative polymerase chain reaction (qPCR) analysis and fungal culture tests, the PAW bubble treatment did not significantly reduce infection of NIB. Nonetheless, this study provides useful information for the malting industry for PAW treatment optimization and its use in barley steeping for DON reduction and germination improvement. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer (OVCA), a fatal malignancy of women, disseminates locally. Although NK cells mount immune responses against OVCA, tumors inhibit NK cells, and the mechanism is not well understood. Cytokines stimulate NK cells; however, chronic stimulation exhausts them and induces expression of cytokine-inducible SH2-containing protein (CISH). Tumors produce anti-inflammatory cytokine interleukin (IL)-10 which may induce NK cell exhaustion. The goal of this study was to examine if CISH expression in NK cells increases during OVCA development and to determine the mechanism(s) of OVCA-induced CISH expression in NK cells. Normal ovaries (n = 7) were used for CISH, IL-10 and GRP78 expression. In tumor ovaries, CISH was examined in early and late stages (n = 14 each, all subtypes) while IL-10 and GRP78 expression were examined in early and late stage HGSC (n = 5 each). Compared to normal, the population of CISH-expressing NK cells increased and the intensity of IL-10 and GRP78 expression was significantly higher in OVCA (p < 0.05). CISH expression was positively correlated with IL-10 expression (r = 0.52, r = 0.65, p < 0.05 at early and late stages, respectively) while IL-10 expression was positively correlated with GRP78 expression (r = 0.43, r = 0.52, p < 0.05, respectively). These results suggest that OVCA development and progression are associated with increased CISH expression by NK cells which is correlated with tumor-induced persistent cellular stress. [ABSTRACT FROM AUTHOR]

Liver X receptors (LXRs) are members of the nuclear receptor family of ligand-dependent transcription factors which regulate the expression of lipid and cholesterol metabolism genes. Moreover, LXRs and their ligands have been shown to inhibit tumor growth in a variety of cancers. We have previously identified the small molecule compound GAC0001E5 (1E5) as an LXR inverse agonist and a potent inhibitor of pancreatic cancer cells. Transcriptomic and metabolomic studies showed that 1E5 disrupts glutamine metabolism, an essential metabolic pathway commonly reprogrammed during malignant transformation, including in breast cancers. To determine the role of LXRs and potential application of 1E5 in breast cancer, we examined LXR expression in publicly available clinical samples, and found that LXR expression is elevated in breast tumors as compared to normal tissues. In luminal A, endocrine therapy-resistant, and triple-negative breast cancer cells, 1E5 exhibited LXR inverse agonist and "degrader" activity and strongly inhibited cell proliferation and colony formation. Treatments with 1E5 downregulated the transcription of key glutaminolysis genes, and, correspondingly, biochemical assays indicated that 1E5 lowered intracellular glutamate and glutathione levels and increased reactive oxygen species. These results indicate that novel LXR ligand 1E5 is an inhibitor of glutamine metabolism and redox homeostasis in breast cancers and suggest that modulating LXR activity and expression in tumor cells is a promising strategy for targeting metabolic reprogramming in breast cancer therapeutics. [ABSTRACT FROM AUTHOR]

Exosomes, whose mean diameter ranges from 20 nm to 200 nm, are cell-secreted vesicles and are abundant in most biological fluids, such as blood, urine, tears, sweat, breast milk, etc. Exosomal size variations and their composition can be attributed to several factors, such as age, gender and disease conditions of the individual. Existing techniques, such as ultracentrifugation and density gradient ultracentrifugation, for exosome isolation are instrument-dependent, time-consuming and lack specificity. In the present work, a gold-nanoparticle (GNP)-coated silicon (Si) wafer, functionalized with polyethylene glycol (PEG) was used for conjugation with anti-CD63 antibody via EDC NHS chemistry and incubated with serum to immobilize the exosomes on the Si surface. The surface-immobilized exosomes were eluted and quantified by a nanoparticle tracking analyzer (NTA). It was observed that an increase in GNP density on the Si wafer increases the size range and total number of exosomes that are being isolated. Western blotting performed for proteins such as HSP 70 and calnexin confirmed the immobilization and elution of exosomes. The proposed technique can be used as an alternative to existing techniques, as it has several benefits such as reusability of the Si surface for several isolations, minimal instrumental requirement, isolation of exosomes in two hours and compatibility with the microfluidic platform, making the technique suitable for real-time application. The proposed method could be useful in isolating a specific subrange of exosomes by altering the size of the GNP used for coating the Si wafer. [ABSTRACT FROM AUTHOR]

Background: Six diverse Demographic Development and Environmental Surveillance System (DDESS) sites were established in urban slum, urban resettlement, peri-urban, rural, and tribal areas located in Northern, North-East, Eastern, and Southern regions of India from June 2020 to March 2022. Understanding the community dynamics and engaging people in the community is critically important in the process of establishing DDESS. We ascertained the barriers, challenges, and facilitators during the establishment of multiple DDESS sites across India. Methods: This was a cross-sectional descriptive mixed-methods study. Results: Multiple barriers and challenges encountered were reported in the process of community engagement (CE), such as geographical inaccessibility, language barriers, adverse weather, non-responsiveness due to perceived lack of individual benefit or financial gain, fear of contracting COVID-19, COVID-19 vaccine hesitancy, etc. Facilitators in the CE process were pre-existing links with the community, constitution of community advisory boards, community need assessment, concomitant delivery of outreach health services, and skill-building facilities. Conclusion: Most community barriers in the development of DDESS sites in resource-limited settings can be overcome through a multipronged approach, including effective community engagement by focusing on demonstrating trust at the local level, enlisting community mobilization and support, utilizing pre-existing community linkages, initiating community diagnosis, and meeting perceived community health needs. [ABSTRACT FROM AUTHOR]

The knowledge regarding male out-migration due to climate change and large-scale, rapid-onset disasters and their impacts on the left-behind families is well known. However, research on the adaptation strategies for the families left behind due to disaster-induced male-out seasonal migration is rarely carried out. Thus, this study attempts to explore the coping and adaptation strategies adopted by the left-behind families in the salinity-induced male out-migration context. Analyzing the factors affecting the adaptation behaviors is also a major objective of this study. The study was carried out in Shyamnagar sub-district of coastal Bangladesh, where male-out seasonal migration for both rapid and slow-onset disasters is evidenced. The data regarding the adaptation measures were explored through different participatory rural appraisal techniques. Primary data were collected from 213 women from the left-behind families through a semi-structured questionnaire. Descriptive statistics as well as multiple linear regression for analyzing the factors affecting adaptation behaviors were applied. The results revealed that the left-behind families, especially the women and children, adopted a total of 35 coping and adaptation strategies in five different aspects, such as economic adaptation, social adaptation measures, environmental measures, educational measures, and health-related measures. Migrant husbands' age and their education, the household's alternative income sources' availability, receiving loans, disaster history, and migration history variables contributed most significantly to the adaptation behavior. This study provides a new perspective on seasonal male out-migration and the adaptation strategies of the left-behind families, which could be helpful for disaster-induced human migration management and enhancing the resilience of vulnerable communities. [ABSTRACT FROM AUTHOR]

Obesity is a growing health concern in today's society. Current estimates indicate that obesity occurs in both adults and young people. Recent research also found that the Hispanic population in the U.S. is 1.9 times more likely to be overweight as compared to their non-Hispanic population. Obesity is a multifactorial disease that has a variety of causes. All current treatment options incorporate dietary changes aimed at establishing a negative energy balance. According to current scientific research, multiple factors are involved with the development of obesity, including genetic, biochemical, psychological, environmental, behavioral, and socio-demographic factors. The people who suffer from obesity are far more likely to suffer serious health problems, such as stroke, diabetes, lung disease, bone and joint disease, cancer, heart disease, neurological disorders, and poor mental health. Studies indicate that multiple cellular changes are implicated in the progression of obesity, mitochondrial dysfunction, deregulated microRNAs, inflammatory changes, hormonal deregulation, and others. This article highlights the role that oxidative stress plays in obesity and current obesity-prevention techniques with an emphasis on the impact of catechins to prevent and treat obesity. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer (OVCA) is one of the most fatal gynecologic malignancies with most cases detected in late stages. High mortality rates are due, in part, to the lack of an effective early detection test. Tumor development and progression are associated with an increase in the expression of tissue proteins and/or their release into circulation. These proteins may offer potential markers for the early detection of OVCA. Nucleolin, a nuclear protein, is one such marker. This pilot study examined whether the tissue expression of nucleolin and its serum levels change in association with OVCA development and progression by using archived clinical samples and the laying hen model of spontaneous OVCA. Nucleolin was found to be highly expressed in ovaries and fimbriae with tumors and in serum levels compared to those without OVCA. This study also found that tumor-associated serum levels of nucleolin increase even before the tumor forms a detectable solid mass in the ovary or fimbria, suggesting that nucleolin may be involved in malignant transformation. A smaller sample size is a limitation of this study; however, it will lay the foundation for clinical studies with larger cohorts to examine the efficacy of nucleolin as a potential serum marker for the early detection of OVCA. Objective: Ovarian high-grade serous carcinoma (HGSC) is a fatal malignancy of women. Alterations in the expression of nuclear proteins are early steps in malignant transformation; nucleolin is one such protein. Changes in nucleolin expression and circulatory levels during ovarian HGSC development are unknown. The study goal was to determine if tissue and circulatory levels of nucleolin change in response to malignant transformation leading to ovarian HGSC. Methods: Sera, ovaries, and BRCA+ fimbria from healthy subjects, and sera and tumor tissues from patients (n = 10 each), and healthy hens and hens with HGSC were examined in exploratory and prospective studies for nucleolin expression by immunohistochemistry, immunoblotting, gene expression, and immunoassay, and analyzed by analysis of variance (ANOVA). Results: Compared with normal, nucleolin expression was higher in patients and hens with ovarian HGSC and in women with a risk of HGSC (P < 0.05). Compared with normal (1400 + 105 pg/mL, n = 8), serum nucleolin levels were 1.5 and 1.7-fold higher in patients with early- (n = 5) and late-stage (n = 5) HGSC, respectively. Additionally, serum nucleolin levels increased significantly (P < 0.05) prior to the formation of detectable masses. Conclusion: This pilot study concluded that tissue and serum levels of nucleolin increase in association with malignant changes in ovaries and fimbriae leading to ovarian HGSC. [ABSTRACT FROM AUTHOR]

Dietary strawberries have been shown to improve cardiometabolic risks in multiple clinical trials. However, no studies have reported effects on serum metabolomic profiles that may identify the target pathways affected by strawberries as underlying mechanisms. We conducted a 14-week randomized, controlled crossover study in which participants with features of metabolic syndrome were assigned to one of the three arms for four weeks separated by a one-week washout period: control powder, 1 serving (low dose: 13 g strawberry powder/day), or 2.5 servings (high dose: 32 g strawberry powder/day). Blood samples, anthropometric measures, blood pressure, and dietary and physical activity data were collected at baseline and at the end of each four-week phase of intervention. Serum samples were analyzed for primary metabolites and complex lipids using different mass spectrometry methods. Mixed-model ANOVA was used to examine differences in the targeted metabolites between treatment phases, and LASSO logistic regression was used to examine differences in the untargeted metabolites at end of the strawberry intervention vs. the baseline. The findings revealed significant differences in the serum branched-chain amino acids valine and leucine following strawberry intervention (high dose) compared with the low-dose and control phases. Untargeted metabolomic profiles revealed several metabolites, including serum phosphate, benzoic acid, and hydroxyphenyl propionic acid, that represented improved energy-metabolism pathways, compliance measures, and microbial metabolism of strawberry polyphenols, respectively. Thus, dietary supplementation of strawberries significantly improves the serum metabolic profiles of cardiometabolic risks in adults. [ABSTRACT FROM AUTHOR]

The broad aim of this introduction to a Special Issue on "Susceptibilities: Toward a Cultural Politics of Consent under Erasure" is to broach key questions and research directions that illuminate contemporary public debates about the conditions and limits of conscious intention (and consent as a byproduct thereof), which is typically treated as a "property" that can be "underdeveloped", "given", or "taken away". In keeping with Jacques Derrida's repudiation of the metaphysics of presence, the perspective animating this essay is that the psychoanalytic standpoint of the unconscious deconstructs the epistemological privilege of determinacy, consistency, and wholeness in treatments of intentional consciousness. Given Jean Laplanche's attention to the residues of coherent ego fetishism in Sigmund Freud's oeuvre, the former's critique of self-sovereignty as evinced in his theorization of the "enigmatic signifier", "primal repression", and "afterwardsness" assumes a pivotal role in the analysis of how writers as represented here by Sarah Polley in Run Towards the Danger narrate the vicissitudes of their traumatic memories of sexual assault. Ultimately, then, the implications of this analysis will carry over to brief discussions of this Special Issue's seven contributions by Melissa Wright, Karen McFadyen, J. Asher Godley, Madeleine Reddon, Gautam Basu Thakur, Robert Hughes, and Rebecca Saunders. [ABSTRACT FROM AUTHOR]

Hydrological modelling to address the problem of flood risk corresponding to climate change can play an important role in water resources management. This paper describes the potential impact of climate change on an urban river catchment using a physically based hydrological model called Soil Water Assessment Tool (SWAT). The study area considered is the Dodder River basin located in the southern part of Dublin, the capital city of Ireland. Climate projections from three regional climate models and two representative concentration pathways (RPC 4.5 and RCP 8.5) were used to evaluate the impact of flooding corresponding to different climate change scenarios. Annual maximum flow (AMF) is generated by combining the bias-corrected climate projections with the calibrated and validated SWAT model to understand the projected changes in flood patterns for the year 2021–2100. The expected changes in flood quantiles were estimated using a generalised extreme value distribution. The results predicted up to 12% and 16% increase in flood quantiles corresponding to 50 years and 100 years return periods. Based on the flood quantiles, flood inundation maps were developed for the study area. [ABSTRACT FROM AUTHOR]

This article aims to analyse the performance of green roof in runoff reduction. A case study has been conducted through a deployed green roof at the custom house quay building in Dublin, Ireland. Modular green roofs have been deployed which have IoT scales associated to it for measuring the effective reduction in runoff. Hydro-meteorological variables such as rainfall, temperature, relative humidity and wind speed values were corresponded to the amount of runoff reduction by means of a regression-based relationship. Comparison of the observed runoff reduction from a modular green roof and that estimated based on the developed regression relationship yielded a R2 value of 0.874. Through this research, a pattern was identified which established that longer records and better weather variables data have the potential to improve the performance of the regression model in predicting the amount of runoff reduction corresponding to different rainfall and weather patterns. In general, performance of green roof was found to be highly positively correlated to the amount of rainfall received; however, low correlation between rainfall and the percentage of runoff reduction indicate that saturated soil in green roofs considerably deteriorates the performance in runoff reduction. Overall, this study can help in identification of locations where installation of green roofs can help mitigate floods at a city scale. [ABSTRACT FROM AUTHOR]

Metamaterial absorbers are used in the terahertz frequency regime as photo-detectors, as sensing elements, in imaging applications, etc. Narrowband absorbers, on account of their ultra-slender bandwidth within the terahertz frequency spectrum, show a significant shift in the absorption peak when an extrinsic entity relative to the absorber, like refractive index or temperature of the encircling medium, is altered. This property paves the path for the narrowband absorbers to be used as potential sensors to detect any alterations in the encircling medium. In this paper, a novel design of a terahertz metamaterial (MTM) absorber is proposed, which can sense the variations in the refractive index (RI) of the surrounding medium. The effective permeability of the structure is negative, while its permittivity is positive; thus, it is a μ-negative metamaterial. The layout involves a swastika-shaped design made of gold on top of a dielectric gallium arsenide (GaAs) substrate. The proposed absorber achieved a nearly perfect absorption of 99.65% at 2.905 terahertz (THz), resulting in a quality factor (Q-factor) of 145.25. The proposed design has a sensitivity of 2.12 THz/RIU over a range of varied refractive index from n = 1.00 to n = 1.05 with a step size of 0.005, thereby achieving a Figure of Merit (FoM) of 106. Furthermore, the sensor was found to have a polarization-insensitive characteristic. Considering its high sensitivity (S), the proposed sensor was further tested for gas sensing applications of harmful gases. As a case study, the sensor was used to detect chloroform. The proposed work can be the foundation for developing highly sensitive gas sensors. [ABSTRACT FROM AUTHOR]

Simple Summary: Oligometastases carries a better prognosis. Even though standard treatment for distant metastases is systemic therapy, those with oligometastases have a better survival rate if they receive surgery or stereotactic body radiotherapy (SBRT). The advantage of SBRT over surgery is its minimal toxicity and the induction of program death ligand 1 (PD-L1) formation. Thus, SBRT may increase the tumor response to immunotherapy with checkpoint inhibitors (CPI). We propose a protocol using SBRT upfront for oligometastases, followed four to six weeks later by CPI for older cancer patients as they may not tolerate conventional chemotherapy. This hypothesis should be tested in future prospective clinical trials. The standard of care for metastatic disease is systemic therapy. A unique subset of patients with limited metastatic disease defined as distant involvement of five anatomic sites or less (oligometastases) have a better chance of remission or improved survival and may benefit from local treatments such as surgery or stereotactic body radiotherapy (SBRT). However, to prevent further spread of disease, systemic treatment such as chemotherapy, targeted therapy, and hormonal therapy may be required. Older patients (70 years old or above) or physiologically frail younger patients with multiple co-morbidities may not be able to tolerate the conventional chemotherapy due to its toxicity. In addition, those with a good performance status may not receive optimal chemotherapy due to concern about toxicity. Recently, immunotherapy with checkpoint inhibitors (CPI) has become a promising approach only in the management of program death ligand 1 (PD-L1)-positive tumors. Thus, a treatment method that elicits induction of PD-L1 production by tumor cells may allow all patients with oligometastases to benefit from immunotherapy. In vitro studies have demonstrated that high dose of radiotherapy may induce formation of PD-L1 in various tumors as a defense mechanism against inflammatory T cells. Clinical studies also corroborated those observations. Thus, SBRT, with its high precision to minimize damage to normal organs, may be a potential treatment of choice for older patients with oligometastases due to its synergy with immunotherapy. We propose a protocol combining SBRT to achieve a minimum radiobiologic equivalent dose around 59.5 Gy to all tumor sites if feasible, followed four to six weeks later by CPI for those cancer patients with oligometastases. All patients will be screened with frailty screening questionnaires to identify individuals at high risk for toxicity. The patients will be managed with an interdisciplinary team which includes oncologists, geriatricians, nurses, nutritionists, patient navigators, and social workers to manage all aspects of geriatric patient care. The use of telemedicine by the team may facilitate patient monitoring during treatment and follow-up. Preliminary data on toxicity, local control, survival, and progression-free survival may be obtained and serve as a template for future prospective studies. [ABSTRACT FROM AUTHOR]

Studying a renewable energy integrated power system's features is essential, especially for deregulated systems. The unpredictability of renewable sources is the main barrier to integrating renewable energy-producing units with the current electrical grid. Due to its unpredictable nature, integrating wind power into an existing power system requires significant consideration. In a deregulated electricity market, this paper examines the implications of wind farm (WF) integration with CAES on electric losses, voltage profile, generation costs, and system economics. Comparative research was done to determine the impact of wind farm integration on regulated and deregulated environments. Four randomly chosen locations in India were chosen for this investigation, together with real-time information on each location's real wind speed (RWS) and predicted wind speed (PWS). Surplus charge rates and deficit charge rates were created to assess the imbalance cost arising from the discrepancy between predicted and real wind speeds to calculate the system economics. When the effect of imbalance cost is considered, the daily system profit shows a variation of about 1.9% for the locations under study. Customers are always seeking electricity that is dependable, affordable, and efficient due to the reorganization of the power system. As a result, the system security limit could be exceeded or the system might function dangerously. The final section of this paper presents an economic risk analysis using heuristic algorithms such as sequential quadratic programming (SQP), artificial bee colony algorithms (ABC), and moth flame optimization algorithms (MFO). It also discusses how the CAES is used to correct the deviation of WF integration in the real-time electricity market. Economic risk analysis tools include value-at-risk (VaR) and conditional value-at-risk (CVaR). The entire piece of work was validated using a modified IEEE 30-bus test system. This works shows that with a three-fold increase in wind generation, the risk coefficient values improves by 1%. [ABSTRACT FROM AUTHOR]

We performed a fully differential experimental and theoretical study on ionization of He in intermediate-energy collisions with protons for a small projectile coherence length. Data were taken for an ejected electron energy corresponding to a speed close to the projectile speed (velocity matching). In the fully differential angular electron distributions, a pronounced double-peak structure, observed previously for a coherence length much larger than the atomic size, is much less pronounced in the current data. This observation is interpreted in terms of interference between first-and higher-order transition amplitudes. Although there is large quantitative disagreement between experiment and theory, the qualitative agreement supports this interpretation. [ABSTRACT FROM AUTHOR]

In recent decades, "environmental xenobiotic-mediated endocrine disruption", especially by xeno-estrogens, has gained a lot of interest from toxicologists and environmental researchers. These estrogen-mimicking chemicals are known to cause various human disorders. Pesticides are the most heavily used harmful xenobiotic chemicals around the world. The estrogen-mimicking potential of the most widely used organochlorine pesticides is well established. However, their effect is not as clearly understood among the plethora of effects these persistent xenobiotics are known to pose on our physiological system. Estrogens are one of the principal risk modifiers of various disorders, including cancer, not only in women but in men as well. Despite the ban on these xenobiotics in some parts of the world, humans are still at apparent risk of exposure to these harmful chemicals as they are still widely persistent and likely to stay in our environment for a long time owing to their high chemical stability. The present work intends to understand how these harmful chemicals may affect the risk of the development of estrogen-mediated human cancer. [ABSTRACT FROM AUTHOR]

Anisotropic gold nanostructures have fascinated with their exceptional electronic properties, henceforth exploited for the fabrication of electrochemical sensors. However, their synthesis approaches are tedious and often require a growth template. Modern lifestyle has caused an upsurge in the risk of heart attack and requires urgent medical attention. Cardiac troponin I can serve as a biomarker in identification of suspected myocardial infection (heart attack). Hence the present work demonstrates the fabrication of a sensing platform developed by assimilating anisotropic gold nanoclusters (AuNCs) with anti cTnI antibody (acTnI) for the detection of cardiac troponin I (cTnI). The uniqueness and ease of synthesis by a template-free approach provides an extra edge for the fabrication of AuNC coated electrodes. The template-free growth of anisotropic AuNCs onto the indium tin oxide (ITO) glass substrates offers high sensitivity (2.2 × 10−4 A ng−1 mL cm−2) to the developed sensor. The immunosensor was validated by spiking different concentrations of cTnI in artificial serum with negligible interference under optimized conditions. The sensor shows a wide range of detection from 0.06–100 ng/mL with an ultralow detection limit. Thus, it suggests that the template-free immunosensor can potentially be used to screen the traces of cTnI present in blood serum samples, and the AuNCs based platform holds great promise as a transduction matrix, hence it can be exploited for broader sensing applications. [ABSTRACT FROM AUTHOR]

Studying the property of the combination of renewable energy sources in the existing power systems is of great importance, and especially in the case of deregulated systems. The uncertainty of renewable sources is the largest barrier to integrating renewable-energy-producing units into the existing electrical infrastructure. Due to its uncertainty, integrating wind power into an existing power system requires extra consideration. In this work, the impacts of wind farm (WF) integration and a pumped hydroelectric storage system (PHES) on the electric losses, voltage profiles, generation costs, and system economy in a deregulated power market were studied. A comparative study was performed to determine the impact of wind farm integration on regulated and deregulated environments. Four locations in India were chosen at random for this work, and we used the real-time statistics for the actual wind speeds (AWSs) and forecasted wind speeds (FWSs) for each chosen location. To determine the system economy, surplus charge rates and deficit charge rates were developed to evaluate the imbalance cost resulting from the mismatch between the predicted and actual wind speeds. Considering the effect of the imbalance cost, the system profit/day varies by an average of 1.6% for the locations studied. Because of the reorganization of the power system, consumers constantly look for reliable and affordable power that is also efficient. As a result, the system security limit may be breached, or the system may run in a dangerous state. Lastly, in this paper, an economic risk analysis is presented with the help of heuristic algorithms (i.e., artificial bee colony algorithm (ABC) and moth–flame optimization algorithm (MFO)), along with sequential quadratic programming (SQP), and the way in which the PHES is used to compensate for the deviation in the WF integration in the real-time electricity market is also presented. The value at risk (VaR) and conditional value at risk (CVaR) were used as the economic risk analysis tools. According to the work, with the increase in the wind generation, the system risk improves. The results show that, as the wind generation increases by three times, there is an improvement in the risk coefficient values by 1%. A modified IEEE 14-bus test system was used for the validation of the entire work. [ABSTRACT FROM AUTHOR]

Domain-driven design is one of the most used approaches for identifying microservice architectures, which should be built around business capabilities. There are a number of documentation with principles and patterns for its application. However, despite its increasing use there is still a lack of systematic approaches for creating the context maps that will be used to design the microservices. This article presents BPM2DDD, a systematic approach for identification of bounded contexts and their relationships based on the analysis of business processes models, which provide a business view of an organisation. We present an example of its application in a real business process, which has also be used to perform a comparative application with external analysts. The technique has been applied to a real project in the department of transport of a Brazilian state capital, and has been incorporated into the software development process employed by them to develop their new system. [ABSTRACT FROM AUTHOR]

Aspergillus fumigatus is a pathogenic microorganism that causes aspergillosis due to the presence of its allergenic proteins. During the last two years, a few clinical cases have been reported where allergic bronchopulmonary aspergillosis (ABPA) has been detected in COVID-19 patients. The administration of antifungal medicine did not provide satisfactory results. It is a challenging job for medical scientists to protect mankind by designing an epitope-based vaccine against the rare disease aspergillosis. Other than twenty-three allergenic proteins, this microorganism contains an extra-cellular cellulase CelA expansin protein (Afu5g08030), which is allergenic. To design a peptide vaccine against aspergillosis, the identification of B cell and T cell epitopes is state-of-the-art technology. In our latest research, probable T cell and B cell epitopes are predicted. Molecular docking analysis of these predicted epitopes with their receptors is performed. Here, the primary sequence of the expansin protein is extracted and analyzed. Then, its secondary and tertiary structures are predicted using a homology modeling method and validated. Considering the physicochemical properties of this antigenic protein, two short stretches of peptides, namely 80KPQADEDPNASSSSSSS96 and 286DGGKTWQGTTRTS298, are predicted as linear B cell epitopes. Similarly, based on its contacts with the highest number of alleles, the peptide sequence 221LDLFQNAFTQLADVS235 is chosen as the most possible T cell epitope for the protein present in Aspergillus fumigatus with the highest binding energy for MHC II allele HLA-DRB1* 01: 01. Considering the binding energy of the B cell epitope with IgE, the second epitope 286DGGKTWQGTTRTS298 is designated as the most potential epitope of B cells for this protein. Docking studies were performed with the T cell epitope with the human ternary complex of T cell receptor, CD4 receptor, and peptide-MHC II molecule (PDB ID 3T0E) with a binding energy of −192 Kcal/mole. For peptide-based vaccines, the proposed B cell and T cell epitopes may be used against aspergillosis after further experimental analysis. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy with checkpoint inhibitors (CPI) is well tolerated in older cancer patients due to its safety profile. In selected patients with a high program death-ligand 1 (PD-L1) tumor expression defined as 50% or above, the response rate and survival are significantly better than those for conventional chemotherapy. Modern radiotherapy techniques, such as intensity-modulated image-guided radiotherapy (IM-IGRT), volumetric modulated arc therapy (VMAT) or proton therapy, enhance the tumor's response to CPI while sparing the normal organs from excessive irradiation. Thus, the combination of IM-IGRT and CPI should work well in older head and neck cancer patients with a high PD-L1 expression who are not candidates for cisplatin-based chemotherapy due to pre-existing comorbidities. This hypothesis should be tested in future prospective clinical trials. The standard of care for locally advanced head and neck cancer is concurrent chemoradiation or postoperative irradiation with or without chemotherapy. Surgery may not be an option for older patients (70 years old or above) due to multiple co-morbidities and frailty. Additionally, the standard chemotherapy of cisplatin may not be ideal for those patients due to oto- and nephrotoxicity. Though carboplatin is a reasonable alternative for cisplatin in patients with a pre-existing hearing deficit or renal dysfunction, its efficacy may be inferior to cisplatin for head and neck cancer. In addition, concurrent chemoradiation is frequently associated with grade 3–4 mucositis and hematologic toxicity leading to poor tolerance among older cancer patients. Thus, a new algorithm needs to be developed to provide optimal local control while minimizing toxicity for this vulnerable group of patients. Recently, immunotherapy with check point inhibitors (CPI) has attracted much attention due to the high prevalence of program death-ligand 1 (PD-L1) in head and neck cancer. In patients with recurrent or metastatic head and neck cancer refractory to cisplatin-based chemotherapy, CPI has proven to be superior to conventional chemotherapy for salvage. Those with a high PD-L1 expression defined as 50% or above or a high tumor proportion score (TPS) may have an excellent response to CPI. This selected group of patients may be candidates for CPI combined with modern radiotherapy techniques, such as intensity-modulated image-guided radiotherapy (IM-IGRT), volumetric arc therapy (VMAT) or proton therapy if available, which allow for the sparing of critical structures, such as the salivary glands, oral cavity, cochlea, larynx and pharyngeal muscles, to improve the patients' quality of life. In addition, normal organs that are frequently sensitive to immunotherapy, such as the thyroid and lungs, are spared with modern radiotherapy techniques. In fit or carefully selected frail patients, a hypofractionated schedule may be considered to reduce the need for daily transportation. We propose a protocol combining CPI and modern radiotherapy techniques for older patients with locally advanced head and neck cancer who are not eligible for cisplatin-based chemotherapy and have a high TPS. Prospective studies should be performed to verify this hypothesis. [ABSTRACT FROM AUTHOR]

The process of corneal wound healing is complex and induces scar formation. Corneal scarring is a leading cause of blindness worldwide. The fibrotic healing of a major ocular wound disrupts the highly organized fibrillar collagen arrangement of the corneal stroma, rendering it opaque. The process of regaining this organized extracellular matrix (ECM) arrangement of the stromal layer to restore corneal transparency is complicated. The surface retention capacity of ocular drugs is poor, and there is a large gap between suitable corneal donors and clinical requirements. Therefore, a more efficient way of treating corneal scarring is needed. The eight major classes of interventions targeted as therapeutic tools for healing scarred corneas include those based on exosomes, targeted gene therapy, microRNAs, recombinant viral vectors, histone deacetylase inhibitors, bioactive molecules, growth factors, and nanotechnology. This review highlights the recent advancements in molecular therapeutics to restore a cornea without scarring. It also provides a scope to overcome the limitations of present studies and perform robust clinical research using these strategies. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor-γ (PPAR-γ) has emerged as one of the most extensively studied transcription factors since its discovery in 1990, highlighting its importance in the etiology and treatment of numerous diseases involving various types of cancer, type 2 diabetes mellitus, autoimmune, dermatological and cardiovascular disorders. Ligands are regarded as the key determinant for the tissue-specific activation of PPAR-γ. However, the mechanism governing this process is merely a contradictory debate which is yet to be systematically researched. Either these receptors get weakly activated by endogenous or natural ligands or leads to a direct over-activation process by synthetic ligands, serving as complete full agonists. Therefore, fine-tuning on the action of PPAR-γ and more subtle modulation can be a rewarding approach which might open new avenues for the treatment of several diseases. In the recent era, researchers have sought to develop safer partial PPAR-γ agonists in order to dodge the toxicity induced by full agonists, akin to a balanced activation. With a particular reference to cancer, this review concentrates on the therapeutic role of partial agonists, especially in cancer treatment. Additionally, a timely examination of their efficacy on various other disease-fate decisions has been also discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: The extraction of quantitative data from standard-of-care imaging modalities offers opportunities to improve the relevance and salience of imaging biomarkers used in drug development. This review aims to identify the challenges and opportunities for discovering new imaging-based biomarkers based on radiomic and volumetric assessment in the single-site solid tumor sites: breast cancer, rectal cancer, lung cancer and glioblastoma. Developing approaches to harmonize three essential areas: segmentation, validation and data sharing may expedite regulatory approval and adoption of novel cancer imaging biomarkers. Clinical trials for oncology drug development have long relied on surrogate outcome biomarkers that assess changes in tumor burden to accelerate drug registration (i.e., Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria). Drug-induced reduction in tumor size represents an imperfect surrogate marker for drug activity and yet a radiologically determined objective response rate is a widely used endpoint for Phase 2 trials. With the addition of therapies targeting complex biological systems such as immune system and DNA damage repair pathways, incorporation of integrative response and outcome biomarkers may add more predictive value. We performed a review of the relevant literature in four representative tumor types (breast cancer, rectal cancer, lung cancer and glioblastoma) to assess the preparedness of volumetric and radiomics metrics as clinical trial endpoints. We identified three key areas—segmentation, validation and data sharing strategies—where concerted efforts are required to enable progress of volumetric- and radiomics-based clinical trial endpoints for wider clinical implementation. [ABSTRACT FROM AUTHOR]

Recent research has highlighted that a large section of druggable protein targets in the Human interactome remains unexplored for various diseases. It might lead to the drug repurposing study and help in the in-silico prediction of new drug-human protein target interactions. The same applies to the current pandemic of COVID-19 disease in global health issues. It is highly desirable to identify potential human drug targets for COVID-19 using a machine learning approach since it saves time and labor compared to traditional experimental methods. Structure-based drug discovery where druggability is determined by molecular docking is only appropriate for the protein whose three-dimensional structures are available. With machine learning algorithms, differentiating relevant features for predicting targets and non-targets can be used for the proteins whose 3-D structures are unavailable. In this research, a Machine Learning-based Drug Target Discovery (ML-DTD) approach is proposed where a machine learning model is initially built up and tested on the curated dataset consisting of COVID-19 human drug targets and non-targets formed by using the Therapeutic Target Database (TTD) and human interactome using several classifiers like XGBBoost Classifier, AdaBoost Classifier, Logistic Regression, Support Vector Classification, Decision Tree Classifier, Random Forest Classifier, Naive Bayes Classifier, and K-Nearest Neighbour Classifier (KNN). In this method, protein features include Gene Set Enrichment Analysis (GSEA) ranking, properties derived from the protein sequence, and encoded protein network centrality-based measures. Among all these, XGBBoost, KNN, and Random Forest models are satisfactory and consistent. This model is further used to predict novel COVID-19 human drug targets, which are further validated by target pathway analysis, the emergence of allied repurposed drugs, and their subsequent docking study. [ABSTRACT FROM AUTHOR]

Liberation is a psychological attribute that primarily aims towards peace of mind followed by emancipation from fetters. Every individual covets liberation through their actions and expects a conducive milieu to experience the same. However, for oppressed people, the journey to liberation is convoluted as it involves escape from many elements. In a hierarchical society like India, liberation means liberation from the whole structure in which religious affiliation plays an important role. The marginalized section of the population seldom has the liberty to choose for their lives and they continue to remain subordinated under age-old power relations, which are garbed in the names of destiny and ordinance. For them, liberation is a quest to make an identity and reinstate the value of self-worth. Christianity, with the Church as its mission partner, seeks to liberate these caged souls from their precarious standings. This study will try to show how the Canadian Baptist Mission, with a primary objective to evangelize, left a trail of aspiration among the tribal Savaras of Ganjam to undertake the pursuit of liberation and fight oppression on their own. [ABSTRACT FROM AUTHOR]

The recent increase in publicly available metagenomic datasets with geospatial metadata has made it possible to determine location-specific, microbial fingerprints from around the world. Such fingerprints can be useful for comparing microbial niches for environmental research, as well as for applications within forensic science and public health. To determine the regional specificity for environmental metagenomes, we examined 4305 shotgun-sequenced samples from the MetaSUB Consortium dataset—the most extensive public collection of urban microbiomes, spanning 60 different cities, 30 countries, and 6 continents. We were able to identify city-specific microbial fingerprints using supervised machine learning (SML) on the taxonomic classifications, and we also compared the performance of ten SML classifiers. We then further evaluated the five algorithms with the highest accuracy, with the city and continental accuracy ranging from 85–89% to 90–94%, respectively. Thereafter, we used these results to develop Cassandra, a random-forest-based classifier that identifies bioindicator species to aid in fingerprinting and can infer higher-order microbial interactions at each site. We further tested the Cassandra algorithm on the Tara Oceans dataset, the largest collection of marine-based microbial genomes, where it classified the oceanic sample locations with 83% accuracy. These results and code show the utility of SML methods and Cassandra to identify bioindicator species across both oceanic and urban environments, which can help guide ongoing efforts in biotracing, environmental monitoring, and microbial forensics (MF). [ABSTRACT FROM AUTHOR]