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Mountains composed of granite are generally regarded as stable geological formations. However, in Alpine and high-altitude mountains in the eastern part of the Tibetan Plateau, geological hazards such as collapses and landslides occur frequently due to the deterioration of granite mechanical properties caused by the freeze–thaw cycles. To investigate this phenomenon, a freeze–thaw cyclic mechanical test is conducted on granite from the Basu area, and the rock's damage trend during the freeze–thaw process is analyzed through wave velocity and nuclear magnetic resonance (NMR) tests. The results indicated that the internal damage of granite increases and its wave velocity decreases significantly with increasing the freeze–thaw cycles, implying a decline in the rock's integrity. Furthermore, the development pattern of the NMR T2 relaxation time distribution indicates that the crack size range of naturally weathered rock samples further increased after freeze–thaw cycles, whereas less-weathered rocks showed a more concentrated range of crack sizes. Triaxial compression tests conducted on rock samples after the freeze–thaw cycles showed that parameters such as the uniaxial compressive strength, elastic modulus, internal friction angle, and cohesion of the rock decreased with increasing freeze–thaw cycles, while a significant change of Poisson's ratio was not observed. Based on the test data and theoretical analysis, a freeze–thaw damage constitutive model of the Basu granite can be established to simulate and predict the overall variation in rock stress and strain under various confining pressures and freeze–thaw cycles. Hopefully, the present study will provide useful guidance for research on the hazard mechanism and hazard prevention of granite sand-sliding slopes in the Basu area. [ABSTRACT FROM AUTHOR]

Retinal degenerative diseases lead to irreversible vision loss due to photoreceptor cell death, driven by complex genetic and environmental factors. Ceramide, a sphingolipid metabolite, emerges as a critical mediator in the apoptotic cascade associated with retinal degeneration. Our previous work demonstrated L-Cycloserine's ability to protect photoreceptor-derived cells from oxidative stress by inhibiting the de novo ceramide pathway and thus prompting further investigation on its effect in the in vivo retina. This study investigates the potential of L-Cycloserine to protect albino BALB/c mice against light-induced retinal degeneration (LIRD). L-Cycloserine, in an optimal dose, administered systemically 30 min before LIRD, was found to prevent photoreceptor cell death significantly from light-induced degeneration. We further determined the retinal bioavailability and pharmacokinetic behavior of L-Cycloserine, its effect on sphingolipid profile, expression of sphingolipid biosynthetic, and cell death-promoting genes and proteins from the retina to understand the underlying mechanisms. This study lays the groundwork for further preclinical and clinical investigations into L-Cycloserine's potential as a novel therapeutic in treating retinal degenerative diseases. [ABSTRACT FROM AUTHOR]

Being considered a driver of economic growth as well as social participation and inclusion, skill development and vocational education and training (VET) policies constitute possible solutions to present challenges and ongoing problems. Therefore, VET has been the distinct subject of attempts toward development and improvement over time. For more than two decades, VET reforms have been a specific focus of Indian educational governance. However, in the subcontinent, reform initiatives have only partially succeeded in terms of their successful and sustainable implementation. This paper investigates promoting and inhibiting factors for vocational education and training policy implementation in Indian skill ecosystems. Taking the example of bottom-up policy implementation in the form of the Mahatma Gandhi National Fellowship (MGNF) programme, factors that affect the VET policy initiative are identified, based on a combination of quantitative and qualitative methods. Through a comprehensive questionnaire administered to a sample of 63 graduates of the programme, their perceptions on key implementation challenges regarding the local policy context, stakeholder cooperation, and institutional as well as implementer capacity were identified. The findings point to areas of further focus for policymakers for the effective implementation of VET initiatives while at the same time adding theoretical contributions to understanding and evaluating VET initiatives. [ABSTRACT FROM AUTHOR]

Disease prediction using computer-based methods is now an established area of research. The importance of technological intervention is necessary for the better management of disease, as well as to optimize use of limited resources. Various AI-based methods for disease prediction have been documented in the literature. Validated AI-based systems support diagnoses and decision making by doctors/medical practitioners. The resource-efficient dissemination of the symptoms identified and the diagnoses undertaken is the requirement of the present-day scenario to support paperless, yet seamless, information sharing. The representation of symptoms using grammar provides a novel way for the resource-efficient encoding of disease diagnoses. Initially, symptoms are represented as strings, and, in terms of grammar, this is called a sentence. Moreover, the conversion of the generated string containing the symptoms and the diagnostic outcome to a QR code post encryption makes it portable. The code can be stored in a mobile application, in a secure manner, and can be scanned wherever required, universally. The patient can carry the medical condition and the diagnosis in the form of the QR code for medical consultations. This research work presents a case study based on two diseases, influenza and coronavirus, to highlight the proposed methodology. Both diseases have some common and overlapping symptoms. The proposed system can be implemented for any kind of disease detection, including clinical and diagnostic imaging. [ABSTRACT FROM AUTHOR]

Muscles are very important parts of the human body. When there is an injury to a muscle that causes long-term dysfunctionality, sensors and artificial muscles can be used to help alleviate problems. Muscles have complex structures; thus, ultrasound and other types of scans may be needed to determine their parameters and model their shapes. Additionally, the measurement of chemicals in muscles plays a significant role in analyzing their performance and potential diseases in humans. All the above-mentioned components are needed for understanding the structure and function of muscles. The areas studied in this review include artificial muscles and exoskeletons, determining muscle parameters and modelling, assessing musculoskeletal functions, chemicals in muscles, and various applications, including those of wearable sensors. In future studies, we would like to understand the link between the brain and muscles and develop technologies that can assist in augmenting the motor skills of individuals affected by various debilitating conditions. [ABSTRACT FROM AUTHOR]

Background: Electronic and electrical waste (e-waste) production has emerged to be of global environmental public health concern. E-waste workers, who are frequently exposed to hazardous chemicals through occupational activities, face considerable health risks. Methods: To investigate the metabolic and exposomic changes in these workers, we analyzed whole blood samples from 100 male e-waste workers and 49 controls from the GEOHealth II project (2017–2018 in Accra, Ghana) using LC-MS/MS. A specialized computational workflow was established for exposomics data analysis, incorporating two curated reference libraries for metabolome and exposome profiling. Two feature detection algorithms, asari and centWave, were applied. Results: In comparison to centWave, asari showed better sensitivity in detecting MS features, particularly at trace levels. Principal component analysis demonstrated distinct metabolic profiles between e-waste workers and controls, revealing significant disruptions in key metabolic pathways, including steroid hormone biosynthesis, drug metabolism, bile acid biosynthesis, vitamin metabolism, and prostaglandin biosynthesis. Correlation analyses linked metal exposures to alterations in hundreds to thousands of metabolic features. Functional enrichment analysis highlighted significant perturbations in pathways related to liver function, vitamin metabolism, linoleate metabolism, and dynorphin signaling, with the latter being observed for the first time in e-waste workers. Conclusions: This study provides new insights into the biological impact of prolonged metal exposure in e-waste workers. [ABSTRACT FROM AUTHOR]

In analyzing the decoupling of emissions from economic growth, current literature foregoes the nonlinear complexities of macroeconomic systems, leading to ineffective energy transition policies, specifically for developing countries. This study focuses on the Indian energy–economy–emission nexus to establish a control system that internalizes inflation, trade openness, and fossil fuel imports with economic growth and macro-emissions to visualize the complex pathways of decoupling. Through long-term cointegration and vector error correction modeling, it was found that GDP and energy affect capital, inflation and energy imports, which are locked in a long-run negative feedback loop that ultimately increases emissions. Capital growth enables decoupling at 0.7% CO2 emissions reduction for every 1% capital growth, while 1% inflation growth inhibits decoupling by increasing CO2 emissions by 0.8%. A cybernetic fractional circuit of R-C elements and operational amplifiers was utilized to examine the delay of pulses from GDP to the loop elements, which revealed that capital is periodic with GDP pulses. However, inflation, being aperiodic with the clock pulses of GDP, causes the pulse-width of capital to decrease and fossil fuel imports to increase. Through the circuital model, it was possible to determine the exact policy intervention schedule in business cycle growth and recession phases that could build clean energy capital and limit inflation-induced recoupling. [ABSTRACT FROM AUTHOR]

Simple Summary: The majority of breast cancers express estrogen receptors (ER) and are treated with antiestrogens. However, many patients relapse and do not respond to further treatment. Therefore, an understanding of which molecules/pathways are affected in breast cancer is important. The Akt/mTOR (mechanistic target of rapamycin) pathway is often altered in breast cancers and is an important target for cancer therapy. The ribosomal S6 kinase 2 (S6K2) acts downstream of mTOR and has been associated with ER-positive breast cancers, but little is known about how S6K2 functions in these cancers. The aim of our present study was to identify potential downstream effectors of S6K2. We identified p21/CDKN1A as a novel downstream target of S6K2 in ER-positive breast cancer cells and showed that S6K2 acts via Akt and JNK signaling pathways to regulate p21 and an upregulation of p21 contributes to chemoresistance. Thus, targeting components of the S6K2/p21 signaling pathway could reverse chemoresistance. Background/Objectives: The ribosomal S6 kinase 2 (S6K2) acts downstream of the mechanistic target of rapamycin complex 1 and is a homolog of S6K1 but little is known about its downstream effectors. The objective of this study was to use an unbiased transcriptome profiling to uncover how S6K2 promotes breast cancer cell survival. Methods: RNA-Seq analysis was performed to identify novel S6K2 targets. Cells were transfected with siRNAs or plasmids containing genes of interest. Western blot analyses were performed to quantify total and phosphorylated proteins. Apoptosis was monitored by treating cells with different concentrations of doxorubicin. Results: Silencing of S6K2, but not S6K1, decreased p21 in MCF-7 and T47D breast cancer cells. Knockdown of Akt1 but not Akt2 decreased p21 in MCF-7 cells whereas both Akt1 and Akt2 knockdown attenuated p21 in T47D cells. While Akt1 overexpression enhanced p21 and partially reversed the effect of S6K2 deficiency on p21 downregulation in MCF-7 cells, it had little effect in T47D cells. S6K2 knockdown increased JUN mRNA and knockdown of cJun enhanced p21. Low concentrations of doxorubicin increased, and high concentrations decreased p21 levels in T47D cells. Silencing of S6K2 or p21 sensitized T47D cells to doxorubicin via c-Jun N-terminal kinase (JNK)-mediated downregulation of Mcl-1. Conclusions: S6K2 knockdown enhanced doxorubicin-induced apoptosis by downregulating the cell cycle inhibitor p21 and the anti-apoptotic protein Mcl-1 via Akt and/or JNK. [ABSTRACT FROM AUTHOR]

Our study examined how different titanium alloy Ti6Al4V (Ti64) and zirconia (ZrO2) surfaces, ranging from rough to very smooth, affect the expression of elastase (NE), matrix metalloproteinase (MMP)-8, MMP-9, and extracellular traps (NETs) by neutrophils. Discs of Ti64 and ZrO2, 10 mm in diameter and 1.5 mm thick, were created using diamond-impregnated polishing burs and paste to produce rough (Ra > 3 µm), smooth (Ra ≥ 1 to 1.5 µm), and very smooth (Ra < 0.1 µm) surfaces. Neutrophils from Wistar rats were cultured on these surfaces, and the culture supernatants were then examined for NE, MMP-8, and MMP-9 using ELISA. At the same time, NET formation was demonstrated immunohistochemically by staining neutrophils with CD16b and DNA with DAPI. Overall, the expressions of NE and MMP-8 were significantly higher from neutrophil culture on Ti64 and ZrO2 rough surfaces compared to the very smooth surface (R > S > VS) after 2 h and 4 h of culture. The expression of MMP-9 also increased with culture time; however, no significant surface effects on expression were observed. Similarly, rough Ti64 and ZrO2 surfaces (R & S) also showed significantly larger NET formation compared to the very smooth surface (VS) after 4 h and 8 h cultures. Our findings suggest that increasing surface roughness on Ti64 and ZrO2 triggers higher NE, MMP-8, and NET formation secretion. [ABSTRACT FROM AUTHOR]

Synthetic carbon-based compounds are a prevalent wastewater contaminant that can adversely impact water resources due to their potential carcinogenic and toxic effects on aquatic biota and human health. This research investigates the versatility of graphene oxide (GO) as an alternative to commonly used adsorbents (zeolite NaY (NaY) and granular activated carbon (GAC)) for removal of synthetic cationic dyes. Rhodamine B (RhB) and methylene blue (MB), were selected as the target contaminants to represent cationic synthetic dyes with differing molecular sizes and structural compositions. Batch experiments using GO, NaY, and GAC as adsorbents were used to assess both physicochemical interactions between adsorbent surfaces and contaminants, and removal efficiency. GO demonstrated the highest removal efficiency for both target contaminants—at 99% and 86%, respectively—while the lowest removal efficiency was observed for NaY. Langmuir, Freundlich, Temkin, and BET isotherm models were used to describe the adsorption isotherms. Overall, GO demonstrated a more robust and higher removal efficiency of cationic dyes compared with GAC and NaY, indicating the potential of graphene oxide for the removal of complex structured organic contaminants in wastewater treatment. [ABSTRACT FROM AUTHOR]

Using drone cells to optimize Radio Access Networks is an exemplary way to enhance the capabilities of terrestrial Radio Access Networks. Drones fitted with communication and relay modules can act as drone cells to provide an unobtrusive network connection. The multi-drone-cell placement problem is solved using adapted Dispersive Flies Optimization alongside other meta-heuristic algorithms such as Particle Swarm Optimization and differential evolution. A home-brewed simulator has been used to test the effectiveness of the different implemented algorithms. Specific environment respective parameter tuning has been explored to better highlight the possible advantages of one algorithm over the other in any particular environment. Algorithmic diversity has been explored, leading to several modifications and improvements in the implemented models. The results show that by using tuned parameters, there is a performance uplift in coverage probability when compared to the default meta-heuristic parameters while still remaining within the constraints implied by the problem's requirements and resource limitation. This paper concludes by offering a study and comparison between multiple meta-heuristic approaches, investigating the impact of parameter tuning as well as analyzing the impact of intermittent restarts for the algorithms' persistent diversity. [ABSTRACT FROM AUTHOR]

Chemotherapy treatment against pancreatic ductal adenocarcinoma (PDAC) is thwarted by tumoral activation of multiple therapy resistance pathways. The growth hormone (GH)–GH receptor (GHR) pair is a covert driver of multimodal therapy resistance in cancer and is overexpressed in PDAC tumors, yet the therapeutic potential of targeting the same has not been explored. Here, we report that GHR expression is a negative prognostic factor in patients with PDAC. Combinations of gemcitabine with different GHR antagonists (GHRAs) markedly improve therapeutic outcomes in nude mice xenografts. Employing cultured cells, mouse xenografts, and analyses of the human PDAC transcriptome, we identified that attenuation of the multidrug transporter and epithelial-to-mesenchymal transition programs in the tumors underlie the observed augmentation of chemotherapy efficacy by GHRAs. Moreover, in human PDAC patients, GHR expression strongly correlates with a gene signature of tumor promotion and immune evasion, which corroborate with that in syngeneic tumors in wild-type vs. GH transgenic mice. Overall, we found that GH action in PDAC promoted a therapy-refractory gene signature in vivo, which can be effectively attenuated by GHR antagonism. Our results collectively present a proof of concept toward considering GHR antagonists to improve chemotherapeutic outcomes in the highly chemoresistant PDAC. [ABSTRACT FROM AUTHOR]

Sterol biosynthesis requires the oxidative removal of two methyl groups from the C-4 position by sterol C-4-demethylase and one methyl group from the C-14 position by sterol C-14-demethylase. In Leishmania donovani, a CYP5122A1 (Cytochrome P450 family 5122A1) protein was recently identified as the bona fide sterol C-4 methyl oxidase catalyzing the initial steps of C-4-demethylation. Besides CYP5122A1, Leishmania parasites possess orthologs to ERG25 (ergosterol pathway gene 25), the canonical sterol C-4 methyl oxidase in Saccharomyces cerevisiae. To determine the contribution of CYP5122A1 and ERG25 in sterol biosynthesis, we assessed the essentiality of these genes in Leishmania major, which causes cutaneous leishmaniasis. Like in L. donovani, CYP5122A1 in L. major could only be deleted in the presence of a complementing episome. Even with strong negative selection, L. major chromosomal CYP5122A1-null mutants retained the complementing episome in both promastigote and amastigote stages, demonstrating its essentiality. In contrast, the L. major ERG25-null mutants were fully viable and replicative in culture and virulent in mice. Deletion and overexpression of ERG25 did not affect the sterol composition, indicating that ERG25 is not required for C-4-demethylation. These findings suggest that CYP5122A1 is the dominant and possibly only sterol C-4 methyl oxidase in Leishmania, and inhibitors of CYP5122A1 may have strong therapeutic potential against multiple Leishmania species. [ABSTRACT FROM AUTHOR]

The inception of microfluidic devices marks a confluence of diverse scientific domains, including physics, biology, chemistry, and fluid mechanics. These multidisciplinary roots have catalyzed the evolution of microfluidic devices, which serve as versatile platforms for various chemical and biological processes. Notably, microfluidic devices have garnered attention as efficient reactors, offering distinct benefits such as minimized spatial requirements for reactions, reduced equipment costs, and accelerated residence times. These advantages, among others, have ignited a compelling interest in harnessing microfluidic technology for the conception, refinement, and production of various nanomaterials and nanocomposites, pivotal within both industrial and medicinal sectors. This comprehensive exposition delves into multifaceted aspects of nanomaterial synthesis, underscoring the transformative role of microfluidic methodologies as a departure from conventional techniques. The discourse navigates through intricate considerations surrounding the preparation of nanomaterials, elucidating how the microfluidic paradigm has emerged as a promising alternative. This paper serves as an illuminating exploration of the juncture between microfluidic innovation and nanomaterial synthesis. It traverses the transformative potential of microfluidics in revolutionizing traditional approaches, heralding a new era of precision engineering for advanced materials with applications spanning industrial to medicinal domains. [ABSTRACT FROM AUTHOR]

Vesicular stomatitis virus (VSV) is a prototype RNA virus that has been instrumental in advancing our understanding of viral molecular biology and has applications in vaccine development, cancer therapy, antiviral screening, and more. Current VSV genome plasmids for purchase or contract virus services provide limited options for modification, restricted to predefined cloning sites and insert locations. Improved methods and tools to engineer VSV will unlock further insights into long-standing virology questions and new opportunities for innovative therapies. Here, we report the design and construction of a full-length VSV genome. The 11,161 base pair synthetic VSV (synVSV) was assembled from four modularized DNA fragments. Following rescue and titration, phenotypic analysis showed no significant differences between natural and synthetic viruses. To demonstrate the utility of a synthetic virology platform, we then engineered VSV with a foreign glycoprotein, a common use case for studying viral entry and developing anti-virals. To show the freedom of design afforded by this platform, we then modified the genome of VSV by rearranging the gene order, switching the positions of VSV-P and VSV-M genes. This work represents a significant technical advance, providing a flexible, cost-efficient platform for the rapid construction of VSV genomes, facilitating the development of innovative therapies. [ABSTRACT FROM AUTHOR]

Inflammation contributes to the pathogenesis of type 2 diabetes (T2DM). This study sought to document how the systemic biomarkers of inflammation varied based on food choices among patients with T2DM. This cross-sectional study enrolled ambulatory patients with T2DM. Demographic and clinical information was collected. Five drops of fingerstick blood were collected using an absorbent paper device (HemaSpot HFR). C-reactive protein (CRP), serum amyloid A protein (SAA), and fibrinogen were measured using a Luminex assay. Patient-generated 7-day food diaries were analyzed using a validated food processor software. Data were analyzed by Pearson's correlation tests, linear regression and logistic regression with the significance level set at 0.05. Among the 71 participants, 43 (60.6%) were females. The average age and duration of T2DM were 64.1 ± 10.3 and 15.8 ± 9.1 years, respectively. In a simple linear regression run with selected micronutrients, iron [F (1, 53) = 5.319, p < 0.05, adj. R2 = 0.074] significantly predicted plasma CRP. This significance was lost with multiple linear regressions including age, gender, BMI, T2DM duration, T2DM complications, glycohemoglobin A1c (HbA1c) and other micronutrients. The average intake of most micronutrients by the participants was below the recommended daily intake. A higher intake of iron-rich foods was associated with higher levels of systemic inflammation in a simple linear regression model, but the association was not present after adjusting for patient factors like age, gender, BMI and T2DM-related variables. This relationship needs to be explored further given the key role of inflammation in the pathogenesis of T2DM and its associated complications. [ABSTRACT FROM AUTHOR]

Dengue is a viral infection caused by the dengue virus (DENV), transmitted to humans through the bite of infected Aedes mosquitoes. About half of the world's population is now at risk of dengue, which represents a global public health concern, especially in tropical and subtropical countries. Early detection of the viral infection is crucial to manage the disease; hence, effective rapid diagnostic tests are essential. In this study, we evaluated the performance between the new Fujifilm Dengue non-structural antigen diagnosis kit (FF NS1 kit) and the SD Bioline NS1 antigen test kit (SD NS1 kit) against the quantitative real-time polymerase chain reaction (qRT-PCR) assays. The 140 acute serum samples collected from the Yangon General Hospital and Yangon Children's Hospital, Myanmar, from 2017 to 2019 were characterised by the three assays. With the qRT-PCR as the standard, the FF NS1 kit and the SD NS1 kit exhibited sensitivity of 94.3% and 88.6%, respectively, and specificity of 100% in both kits. Moreover, the positivity rates of the FF NS1 kit and the SD NS1 kit were 97.5% and 95% in primary infection and 90% and 80% in secondary infection, respectively. Our overall results suggest that the FF NS1 kit is reliable and accurate for detecting DENV infection. [ABSTRACT FROM AUTHOR]

For developing nations to achieve net-zero targets, macroeconomic linkages impacting the decoupling of emissions from economic growth must account for non-linear business cycles and economic shocks. This study aims to delineate decarbonization policy pathways for the Indian electricity sector in the aftermath of COVID-19 by analysing the long-term evolution of the economy–electricity–emissions (3E) nexus during the 2008 financial crisis and during COVID-19, covering the period of 1996Q2 to 2020Q3. Upon testing multiple theoretical 3E systems, it was found that a model internalizing trade, inflation, and stochasticity was able to minimize the reproduction errors from growth to recession phases, as well as predict the rebound effect from an economic crisis. This was revealed to be due to more information within the coefficients in a trade stochastic model. Our results confirm the existence of electricity-associated emission decoupling with capital formation in the long-run, post-crisis, while economic growth and inflation increase CO2 emissions. The main finding highlights the negative feedback loop of inflation->trade->emissions, which shows that GDP and emissions are not directly causal. This long-run macroeconomic dynamic death spiral causes decoupling to be inhibited, where fossil fuel imports should not be subsidized for economic shock rebound, and the risk hedging of energy transition investments should occur in the post-COVID-19 era. [ABSTRACT FROM AUTHOR]

Liver X receptors (LXRs) are members of the nuclear receptor superfamily of ligand-dependent transcription factors. LXRα is predominantly expressed in metabolic tissues, whereas LXRβ is ubiquitously expressed. Upon ligand binding, they regulate the expression of target genes involved in lipid metabolism, cholesterol homeostasis, and immune responses, including those which function in pathways that are commonly reprogrammed during carcinogenesis. Known LXR ligands include oxysterols and natural and synthetic agonists which upregulate LXR transcriptional activity and target gene expression. Synthetic inverse agonists have also been identified that inhibit LXR activity. While both types of ligands have been shown to inhibit cancer cells and tumor growth either directly or indirectly by modulating the activities of stromal cells within the tumor microenvironment, they appear to target different aspects of cancer metabolism and other cancer hallmarks, including immune evasion. This review summarizes the characterization of LXRs and their ligands and their mechanisms of action in cancer models and discusses the future directions for translating these discoveries into novel cancer therapeutics. [ABSTRACT FROM AUTHOR]

An H-bond involves the sharing of a hydrogen atom between an electronegative atom to which it is covalently bound (the donor) and another electronegative atom serving as an acceptor. Such bonds represent a critically important geometrical force in biological macromolecules and, as such, have been characterized extensively. H-bond formation invariably leads to a weakening within the acceptor moiety due to the pulling exerted by the donor hydrogen. This phenomenon can be compared to a spring connecting two masses; pulling one mass stretches the spring, similarly affecting the bond between the two masses. Herein, we describe the opposite phenomenon when investigating the energetics of the C–H···O=C bond. This bond underpins the most prevalent protein transmembrane dimerization motif (GxxxG) in which a glycine Cα-H on one helix forms a hydrogen bond with a carbonyl in a nearby helix. We use isotope-edited FT-IR spectroscopy and corroborating computational approaches to demonstrate a surprising strengthening of the acceptor C=O bond upon binding with the glycine Cα-H. We show that electronic factors associated with the Cα-H bond strengthen the C=O oscillator by increasing the s-character of the σ-bond, lowering the hyperconjugative disruption of the π-bond. In addition, a reduction of the acceptor C=O bond's polarity is observed upon the formation of the C–H···O=C bond. Our findings challenge the conventional understanding of H-bond dynamics and provide new insights into the structural stability of inter-helical protein interactions. [ABSTRACT FROM AUTHOR]

Supramolecular chemistry is a relatively new field of study that utilizes conventional chemical knowledge to produce new edges of smart materials. One such material use of supramolecular chemistry is the development of sensing platforms. Biologically relevant molecules need frequent assessment both qualitatively and quantitatively to explore several biological processes. In this review, we have discussed supramolecular sensing techniques with key examples of sensing several kinds of bio-analytes and tried to cast light on how molecular design can help in making smart materials. Moreover, how these smart materials have been finally used as sensing platforms has been discussed as well. Several useful spectroscopic, microscopic, visible, and electronic outcomes of sensor materials have been discussed, with a special emphasis on device-based applications. This kind of comprehensive discussion is necessary to widen the scope of sensing technology. [ABSTRACT FROM AUTHOR]

Simple Summary: Oxidative stress generates harmful oxygen radicals that activate biomolecules in the lungs of asthmatics. The effects of these mediators are not directly targeted by first-line therapeutics. Using a clinically relevant murine model of allergic asthma, this study reveals that immuno-pharmacological neutralization of oxidized phospholipids in the lung can ameliorate inflammation and asthma symptoms. This suggests that specifically targeting mediators generated by oxidative stress could offer new therapeutic options for asthma to complement conventional therapies. Oxidative stress is associated with asthma pathobiology. We reported that oxidized phosphatidylcholines (OxPCs) are mediators of oxidative stress and accumulate in the lung in response to allergen challenge. The current study begins to unravel mechanisms for OxPC accumulation in the lung, providing the first insights about how OxPCs underpin allergic airway pathophysiology, and pre-clinical testing of selective neutralization of OxPCs in a murine model of allergic asthma. We hypothesized that intranasal delivery of E06, a natural IgM antibody that neutralizes the biological activity of OxPCs, can ameliorate allergen-induced airway inflammation and airway hyperresponsiveness. Adult BALB/c mice were intranasally (i.n.) challenged with house dust mite (HDM) (25 μg/mouse, 2 weeks). Some animals also received E06 monoclonal antibody (mAb) (10 µg) i.n. 1 hr before each HDM challenge. HDM challenge reduced mRNA for anti-oxidant genes (SOD1, SOD2, HO-1, and NFE2L2) in the lung by several orders of magnitude (p < 0.05). Concomitantly, total immune cell number in bronchoalveolar lavage fluid (BALF) increased significantly (p < 0.001). E06 mAb treatment prevented allergen-induced BALF immune cell number by 43% (p < 0.01). This included a significant blockade of eosinophils (by 48%, p < 0.001), neutrophils (by 80%, p < 0.001), macrophages (by 80%, p < 0.05), and CD4 (by 30%, p < 0.05) and CD8 (by 42%, p < 0.01) lymphocytes. E06 effects correlated with a significant reduction in TNF (by 64%, p < 0.001) and IL-1β (by 75%, p < 0.05) and a trend to diminish accumulation of other cytokines (e.g., IL-4, -10, and -33, and IFN-γ). E06 mAb treatment also inhibited HDM exposure-induced increases in total respiratory resistance and small airway resistance by 24% and 26%, respectively. In conclusion, prophylactic treatment with an OxPC-neutralizing antibody significantly limits allergen-induced airway inflammation and airway hyperresponsiveness, suggesting that OxPCs are important mediators of oxidative stress-associated allergic lung pathophysiology. [ABSTRACT FROM AUTHOR]

Simple Summary: Melanoma, a severe type of skin cancer, often becomes resistant to chemotherapy, making it difficult to treat. This research investigates a novel mechanism by which growth hormone (GH) contributes to chemotherapy resistance. We examined small particles, called exosomes, which are released from melanoma cells treated with GH and found to carry proteins that increase drug resistance and cancer cell movement. The effects were more pronounced when GH was combined with the chemotherapy drug, doxorubicin. We also found that blocking the GH action with a drug called pegvisomant reduced the expression of these exosomal proteins, ultimately making the cancer cells more responsive to chemotherapy and less likely to migrate. Our findings provide new insights into how GH action promotes melanoma chemoresistance via exosomes, suggesting that targeting/inhibiting GH action could improve melanoma treatment. Drug resistance in melanoma is a major hindrance in cancer therapy. Growth hormone (GH) plays a pivotal role in contributing to the resistance to chemotherapy. Knocking down or blocking the GH receptor has been shown to sensitize the tumor cells to chemotherapy. Extensive studies have demonstrated that exosomes, a subset of extracellular vesicles, play an important role in drug resistance by transferring key factors to sensitize cancer cells to chemotherapy. In this study, we explore how GH modulates exosomal cargoes from melanoma cells and their role in drug resistance. We treated the melanoma cells with GH, doxorubicin, and the GHR antagonist, pegvisomant, and analyzed the exosomes released. Additionally, we administered these exosomes to the recipient cells. The GH-treated melanoma cells released exosomes with elevated levels of ABC transporters (ABCC1 and ABCB1), N-cadherin, and MMP2, enhancing drug resistance and migration in the recipient cells. GHR antagonism reduced these exosomal levels, restoring drug sensitivity and attenuating migration. Overall, our findings highlight a novel role of GH in modulating exosomal cargoes that drive chemoresistance and metastasis in melanoma. This understanding provides insights into the mechanisms of GH in melanoma chemoresistance and suggests GHR antagonism as a potential therapy to overcome chemoresistance in melanoma treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Parathyroid glands are four in number and usually located adjacent to the thyroid gland, however, variations in location and number can exist. Parathyroid glands produce and release parathyroid hormone (PTH) important for maintaining blood calcium levels. In primary hyperparathyroidism (PHPT), there is increased secretion of PTH with resultant elevated blood calcium levels due to causes within the parathyroid gland, such as a single or multiple tumours which could be benign or malignant. The role of imaging is to locate abnormal parathyroid gland including its presence in unusual location if any, localise tumour within the parathyroid gland and plan surgical approach. Additional role of imaging in a suspected case of parathyroid malignancy is to look for any distant spread. There is emerging evidence to suggest that incidental detection of enlarged parathyroid glands on routine CT by the radiologist, can lead to early diagnosis of PHPT before obvious symptoms and signs develop. In this article, we have described the various imaging modalites available for evaluation of various types of parathyroid tumours, along with their imaging appearances and advantages and disadvantages. In addition, we have prepared a flowchart for guiding management decisions for parathyroid tumours. Parathyroid pathologies are suspected based on the biochemical alterations and clinical manifestations, and the predominant roles of imaging in primary hyperparathyroidism are localisation of tumour within parathyroid glands, surgical planning, and to look for any ectopic parathyroid tissue in the setting of recurrent disease. This article provides a comprehensive review of embryology and anatomical variations of parathyroid glands and their clinical relevance, surgical anatomy of parathyroid glands, differentiation between multiglandular parathyroid disease, solitary adenoma, atypical parathyroid tumour, and parathyroid carcinoma. The roles, advantages and limitations of ultrasound, four-dimensional computed tomography (4DCT), radiolabelled technetium-99 (99mTc) sestamibi or dual tracer 99mTc pertechnetate and 99mTc-sestamibi with or without single photon emission computed tomography (SPECT) or SPECT/CT, dynamic enhanced magnetic resonance imaging (4DMRI), and fluoro-choline positron emission tomography (18F-FCH PET) or [11C] Methionine (11C -MET) PET in the management of parathyroid lesions have been extensively discussed in this article. The role of fluorodeoxyglucose PET (FDG-PET) has also been elucidated in this article. Management guidelines for parathyroid carcinoma proposed by the American Society of Clinical Oncology (ASCO) have also been described. An algorithm for management of parathyroid lesions has been provided at the end to serve as a quick reference guide for radiologists, clinicians and surgeons. [ABSTRACT FROM AUTHOR]

In 2022, the European Commission updated its recommendation on cancer screening, inviting the Member States (MSs) to explore the feasibility of stepwise implementation of population-based screening for prostate cancer (PCa). In line with this recommendation, the PRAISE-U (Prostate Cancer Awareness and Initiative for Screening in the European Union (EU)) project was initiated. As part of the PRAISE-U, we aim to understand the current practice towards early detection in the EU MSs, the barriers to implementing or planning population-based screening programmes, and potential solutions to overcome these barriers. Methods: We adapted the Barriers to Effective Screening Tool (BEST) survey to the PCa context. However, it has not been validated in this context. We translated it into all spoken languages in the EU27 and disseminated it to different stakeholders across the EU using a snowballing approach. Results: We received 410 responses from 55 countries, of which 301 (73%) were from the 27 EU MSs. The most represented stakeholder group was urologists (218 (54%)), followed by general practitioners (GPs) (83 (21%)), patient representatives (35 (9%)), policy stakeholders (27 (7%)), researchers (23 (6%)), oncologists, pathologists, radiologists, nurses, and others (16 (4%)) and one industry representative. Among all respondents, 286 (69%) reported the absence of a population-based screening programme, mainly attributed to resource limitations and a lack of political and medical society support. Out of these 286 respondents, 196 (69%) indicated that opportunistic screening is being applied in their country, and 199 (70%) expressed their support for population-based screening programmes (which was highest amongst patient representatives and urologists and lowest amongst GPs and policy stakeholders). The highest scored barriers were lack of political support, insufficient operational resources, and inadequate participation. Suggested solutions to overcome these included awareness campaigns, consensus meetings, political lobbying and European guidelines (to overcome political support barriers), compatible IT systems (to overcome operational barriers), and easy access (to overcome participation barriers). Conclusions: Participants have noted the presence of opportunistic screening, and particularly urologists and patient representatives expressed their support for the establishment of a population-based PCa screening programme. Nevertheless, successful implementation of population-based screening programmes is complex; it requires political and medical society support, operational resources and capacity, awareness campaigns, as well as the development of protocols, guidelines, and legal frameworks. [ABSTRACT FROM AUTHOR]

The inhibition of soluble epoxide hydrolase (sEH) can reduce the level of dihydroxyeicosatrienoic acids (DHETs) effectively maintaining endogenous epoxyeicosatrienoic acids (EETs) levels, resulting in the amelioration of inflammation and pain. Consequently, the development of sEH inhibitors has been a prominent research area for over two decades. In the present study, we synthesized and evaluated sulfonyl urea derivatives for their potential to inhibit sEH. These compounds underwent extensive in vitro investigation, revealing their potency against human and mouse sEH, with 4f showing the most promising sEH inhibitory potential. When subjected to lipopolysaccharide (LPS)-induced acute lung injury (ALI) in studies in mice, compound 4f manifested promising antiinflammatory efficacy. We investigated the analgesic efficacy of sEH inhibitor 4f in a murine pain model of tail-flick reflex. These results validate the role of sEH inhibition in inflammatory diseases and pave the way for the rational design and optimization of sEH inhibitors based on a sulfonyl urea template. [ABSTRACT FROM AUTHOR]

High-sensitivity C-reactive protein (hs-CRP) is a widely used clinical biomarker of systemic inflammation, implicated in many chronic conditions, including type 1 diabetes (T1D). Despite the increasing emphasis on dietary intake as a modifiable risk factor for systemic inflammation, the association of hs-CRP with fruit and vegetable consumption is relatively underexplored in T1D. To address this gap, we investigated the longitudinal associations of dietary pattern-derived fruit and vegetable scores with hs-CRP in adults with and without T1D. Additionally, we examined the impact of berry consumption as a distinct food group. Data were collected in the Coronary Artery Calcification in Type 1 Diabetes study over two visits that were three years apart. At each visit, participants completed a food frequency questionnaire, and hs-CRP was measured using a particle-enhanced immunonephelometric assay. Mixed effect models were used to examine the three-year association of fruit and vegetable scores with hs-CRP. Adjusted models found a significant inverse association between blueberry intake and hs-CRP in the nondiabetic (non-DM) group. Dietary Approaches to Stop Hypertension- and Alternative Healthy Eating Index-derived vegetable scores were also inversely associated with hs-CRP in the non-DM group (all p-values ≤ 0.05). Conversely, no significant associations were observed in the T1D group. In conclusion, dietary pattern-derived vegetable scores are inversely associated with hs-CRP in non-DM adults. Nonetheless, in T1D, chronic hyperglycemia and related metabolic abnormalities may override the cardioprotective features of these food groups at habitually consumed servings. [ABSTRACT FROM AUTHOR]

Human corneal fibrosis can lead to opacity and ultimately partial or complete vision loss. Currently, corneal transplantation is the only treatment for severe corneal fibrosis and comes with the risk of rejection and donor shortages. Sphingolipids (SPLs) are known to modulate fibrosis in various tissues and organs, including the cornea. We previously reported that SPLs are tightly related to both, transforming growth factor beta (TGF-β) signaling and corneal fibrogenesis. The aim of this study was to investigate the effects of sphingosine-1-phosphate (S1P) and S1P inhibition on specific TGF-β and SPL family members in corneal fibrosis. Healthy human corneal fibroblasts (HCFs) were isolated and cultured in EMEM + FBS + VitC (construct medium) on 3D transwells for 4 weeks. The following treatments were prepared in a construct medium: 0.1 ng/mL TGF-β1 (β1), 1 μM sphingosine-1-phosphate (S1P), and 5 μM Sphingosine kinase inhibitor 2 (I2). Five groups were tested: (1) control (no treatment); rescue groups; (2) β1/S1P; (3) β1/I2; prevention groups; (4) S1P/β1; and (5) I2/β1. Each treatment was administered for 2 weeks with one treatment and switched to another for 2 weeks. Using Western blot analysis, the 3D constructs were examined for the expression of fibrotic markers, SPL, and TGF-β signaling pathway members. Scratch assays from 2D cultures were also utilized to evaluate cell migration We observed reduced fibrotic expression and inactivation of latent TGF-β binding proteins (LTBPs), TGF-β receptors, Suppressor of Mothers Against Decapentaplegic homologs (SMADs), and SPL signaling following treatment with I2 prevention and rescue compared to S1P prevention and rescue, respectively. Furthermore, we observed increased cell migration following stimulation with I2 prevention and rescue groups, with decreased cell migration following stimulation with S1P prevention and rescue groups after 12 h and 18 h post-scratch. We have demonstrated that I2 treatment reduced fibrosis and modulated the inactivation of LTBPs, TGF-β receptors, SPLs, and the canonical downstream SMAD pathway. Further investigations are warranted in order to fully uncover the potential of utilizing SphK I2 as a novel therapy for corneal fibrosis. [ABSTRACT FROM AUTHOR]

The carbohydrate ganglioside GD2/GD3 cancer vaccine adjuvanted by β-glucan stimulates anti-GD2 IgG1 antibodies that strongly correlate with improved progression-free survival (PFS) and overall survival (OS) among patients with high-risk neuroblastoma. Thirty-two patients who relapsed on the vaccine (first enrollment) were re-treated on the same vaccine protocol (re-enrollment). Titers during the first enrollment peaked by week 32 at 751 ± 270 ng/mL, which plateaued despite vaccine boosts at 1.2–4.5 month intervals. After a median wash-out interval of 16.1 months from the last vaccine dose during the first enrollment to the first vaccine dose during re-enrollment, the anti-GD2 IgG1 antibody rose to a peak of 4066 ± 813 ng/mL by week 3 following re-enrollment (p < 0.0001 by the Wilcoxon matched-pairs signed-rank test). Yet, these peaks dropped sharply and continually despite repeated boosts at 1.2–4.5 month intervals, before leveling off by week 20 to the first enrollment peak levels. Despite higher antibody titers, patients experienced no pain or neuropathic side effects, which were typically associated with immunotherapy using monoclonal anti-GD2 antibodies. By the Kaplan–Meier method, PFS was estimated to be 51%, and OS was 81%. The association between IgG1 titer during re-enrollment and β-glucan receptor dectin-1 SNP rs3901533 was significant (p = 0.01). A longer prime–boost interval could significantly improve antibody responses in patients treated with ganglioside conjugate cancer vaccines. [ABSTRACT FROM AUTHOR]

Background: Lynch syndrome is an autosomal dominant condition that leads to an increased risk of many neoplasms. In the United Kingdom, NICE recommends that patients with colorectal and endometrial cancer should be tested for Lynch syndrome. There is conflicting evidence in the literature on the link between breast cancer and Lynch syndrome. Case presentation: A 54-year-old woman presented with a lump in her right breast with a background of locally advanced colorectal cancer and Lynch syndrome due to a MLH1 gene mutation. A core biopsy showed a grade 3, invasive, triple-negative NST carcinoma. The tumour was triple-negative with patchy positivity for CK14 and CK5/6. Simultaneously, a cystic skin lesion in the contralateral breast was noted, which comprised lesional cells with a proliferation of clear cells and bland basaloid cells. The lesion had evidence of sebaceous differentiation with AR, podoplanin and p63 positivity. MSH1 and PMS2 deficiency was found in the breast and skin lesions. Conclusions: In Lynch syndrome, it is vital to be aware of the increased risk of various types of cancer. This case adds to the body of evidence of the spectrum of malignancies that can be encountered in patients with Lynch syndrome. [ABSTRACT FROM AUTHOR]

Ionizing radiation induces many different types of DNA lesions. But one of its characteristics is to produce complex DNA damage, of which tandem DNA damage has received much attention, owing to its promise of distinctive biological properties. Oxidative stresses in response to inflammation in tissues and metal-catalyzed reactions that result in generation of radicals also form these DNA lesions. In this minireview, we have summarized the formation of the tandem lesions as well as the replication and repair studies carried out on them after site-specific synthesis. Many of these lesions are resistant to the traditional base excision repair, so that they can only be repaired by the nucleotide excision repair pathway. They also block DNA replication and, when lesion bypass occurs, it may be significantly error-prone. Some of these tandem DNA lesions may contribute to ageing, neurological diseases, and cancer. [ABSTRACT FROM AUTHOR]

This paper analyses sexual crimes within the Metaverse to develop an effective legal framework. The aim is to enhance safety in virtual realities, ensuring the Metaverse remains a secure, respectful, and liberating environment for all users. As the Metaverse continues to evolve, merging augmented physical reality with digital existence, it introduces new opportunities for socialisation, commerce, education, and entertainment. However, this digital realm also faces significant challenges, particularly the increase in sexual violence. This article evaluates the development of the Metaverse and its impact on sexual offences. It provides an overview of the Metaverse, followed by an in-depth exploration of the nature of sexual violence in this virtual space, its effects on victims, and the resulting legal and ethical issues. Additionally, this article examines the complexities of combating sexual violence within the Metaverse, reviewing the legal frameworks in various jurisdictions, including the United States, the European Union, the United Kingdom, and South Korea. These examinations reveal a range of legal viewpoints and possible solutions. This article outlines a proposed legal framework, highlighting key strategic areas for mitigating sexual violence in the Metaverse. The primary objective is to enrich the discourse on the Metaverse, pushing for strong, flexible, and holistic legal measures. Through this research, we aim to contribute to the creation of protective mechanisms against sexual violence in these emerging virtual landscapes. [ABSTRACT FROM AUTHOR]

Radio observations from normal pulsars indicate that the coherent radio emission is excited by curvature radiation from charge bunches. In this review, we provide a systematic description of the various observational constraints on the radio emission mechanism. We have discussed the presence of highly polarized time samples where the polarization position angle follow two orthogonal well-defined tracks across the profile that closely match the rotating vector model in an identical manner. The observations also show the presence of circular polarization, with both the right and left handed circular polarization seen across the profile. Other constraints on the emission mechanism are provided by the detailed measurements of the spectral index variation across the profile window, where the central part of the profile, corresponding to the core component, has a steeper spectrum than the surrounding cones. Finally, the detailed measurements of the subpulse drifting behaviour can be explained by considering the presence of non-dipolar field on the stellar surface and the formation of the partially screened gap (PSG) above the polar cap region. The PSG gives rise to a non-stationary plasma flow that has a multi-component nature, consisting of highly energetic primary particles, secondary pair plasma, and iron ions discharged from the surface, with large fragmentation resulting in dense plasma clouds and lower-density inter-cloud regions. The physical properties of the outflowing plasma and the observational constraints lead us to consider coherent curvature radiation as the most viable explanation for the emission mechanism in normal pulsars, where propagation effects due to adiabatic walking and refraction are largely inconsequential. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) contain at least one oxygen atom and one or more unpaired electrons and include singlet oxygen, superoxide anion radical, hydroxyl radical, hydroperoxyl radical, and free nitrogen radicals. Intracellular ROS can be formed as a consequence of several factors, including ultra-violet (UV) radiation, electron leakage during aerobic respiration, inflammatory responses mediated by macrophages, and other external stimuli or stress. The enhanced production of ROS is termed oxidative stress and this leads to cellular damage, such as protein carbonylation, lipid peroxidation, deoxyribonucleic acid (DNA) damage, and base modifications. This damage may manifest in various pathological states, including ageing, cancer, neurological diseases, and metabolic disorders like diabetes. On the other hand, the optimum levels of ROS have been implicated in the regulation of many important physiological processes. For example, the ROS generated in the mitochondria (mitochondrial ROS or mt-ROS), as a byproduct of the electron transport chain (ETC), participate in a plethora of physiological functions, which include ageing, cell growth, cell proliferation, and immune response and regulation. In this current review, we will focus on the mechanisms by which mt-ROS regulate different pathways of host immune responses in the context of infection by bacteria, protozoan parasites, viruses, and fungi. We will also discuss how these pathogens, in turn, modulate mt-ROS to evade host immunity. We will conclude by briefly giving an overview of the potential therapeutic approaches involving mt-ROS in infectious diseases. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) poses a significant threat to global health, infecting approximately 390 million people annually. This virus comprises four serotypes capable of causing severe disease. Genetic analyses are crucial for understanding the epidemiology, evolution, and spread of DENV. Although previous studies have focused on the envelope protein-coding (E) gene, only a few primers can efficiently detect and amplify the viral genes from multiple endemic countries simultaneously. In this study, we designed degenerate primer pairs for each DENV serotype to amplify and sequence the entire E gene, using globally representative sequences for each serotype. These primers were validated using DENV isolates from various Asian countries and demonstrated broad-spectrum detection capabilities and high-quality sequences. The primers provide effective tools for genetic analysis in the regions affected by dengue, aiding strain identification and epidemiological studies during outbreaks. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) consists of Crohn's disease (CD) and Ulcerative colitis (UC). The main goal of treatment is to obtain mucosal healing via endoscopy. More recently, intestinal ultrasounds, along with biochemical markers, have been increasingly popular as point-of-care testing to monitor treatment response. This systemic review and meta-analysis aimed to assess the diagnostic test performance of ultrasonography and biochemical markers (C-reactive protein and fecal calprotectin) compared with endoscopy for detecting inflammation in IBD. Methods: A comprehensive literature search was conducted using PubMed Medline, EMBASE, ScienceDirect, and CINAHL from 1 January 2018 to 1 January 2024. The included studies were prospective and retrospective observational studies, clinical trials, and cross-sectional studies investigating the diagnostic sensitivity and specificity of ultrasonography, biochemical markers, and endoscopy. Studies were selected based on the Preferred Reporting Items for Systematic Review and Meta-analysis Statement (PRISMA). Results: Of the 1035 studies retrieved, 16 met the inclusion criteria, and most of the included studies were prospective observational studies. Diagnostic test accuracy was conducted, and the pooled sensitivity and specificity of all the studies revealed that ultrasonography has the highest pooled sensitivity, at 85% (95% CI, 78 to 91%), and specificity, at 92% (95% CI, 86 to 96%), as compared with biochemical markers and endoscopy. More specifically, biochemical markers had a pooled sensitivity and specificity of 85% (95% CI, 81 to 87%) and 61% (95% CI, 58 to 64%), respectively, and endoscopy had 60% (95% CI, 52 to 68%) and 82% (95% CI, 76 to 87%), respectively. However, the results also show substantial heterogeneity in the studies because of various populations, protocols, and outcomes in the studies included. This was especially noted in the assessment of biochemical markers, in which a metaregression was performed showing a nonsignificant p-value of 0.8856 for the coefficient. Conclusions: IUS was found to have the highest pooled sensitivity and specificity of all the included studies for diagnosing inflammation in patients with CD and UC, and this, coupled with biochemical markers, can improve diagnostic utility. [ABSTRACT FROM AUTHOR]

This essay uses Freudian–Lacanian psychoanalytic theory to interpret Hassan Blasim's short story "The Nightmares of Carlos Fuentes". Blasim's story depicts the psychological struggles of an Iraqi emigrant relating to his embattled sense of belonging in a Dutch society due to the recurrent nightmares of his "traumatic" past. It challenges his assimilationist fantasies. I develop Lacan's idea of ontological lack as a structural susceptibility that is exacerbated by actual experiences of trauma to underline how racialized refugees from the war-torn global South are doubly vulnerable to experiencing subjective dehiscence between their efforts to forget past war traumas and the challenges of assimilating into (white) host nations. This essay uses Blasim's story to illustrate a serious psychological issue experienced by racialized minority subjects in white/European host countries. [ABSTRACT FROM AUTHOR]

Background: As mortality declined significantly during the fourth and fifth waves compared to previous waves, the question of the future role of COVID-19 vaccination arose among both experts and the public in South Africa. Turning attention away from the general public, now considered to be at very low risk of severe COVID-19 disease, a commonly held view was that the vaccination campaign should focus only on those who remain highly vulnerable to severe disease and death from COVID-19. Primary amongst this group are patients with common chronic diseases attending hospital outpatient departments. We hypothesized that providing COVID-19 vaccinations on-site at a central hospital will increase uptake for the patients with co-morbid chronic conditions who need them most in the Omicron phase of the pandemic. Aim: Evaluate the acceptability, need, and uptake of a hospital-based vaccination site for patients attending the medical hospital outpatient departments. Objectives: To assess vaccination uptake, coverage, and hesitancy in people attending a central hospital, to determine factors associated with and influencing vaccination uptake, and to document implementation and assess acceptability of the vaccination project among staff and persons attending the hospital. Methods: Mixed-methods study using quantitative and qualitative methods. Results: Of the 317 participants enrolled in the study, 229 (72%) had already received at least one dose of the COVID-19 vaccine. A total of 296 participants were eligible for a first vaccination, additional vaccination, or booster vaccination according to the South African Department of Health guidelines. Of those previously vaccinated, 65% opted for an additional dose on the day it was offered (same day). Only 13 previously unvaccinated participants (15% of vaccine naïve participants) opted for vaccination, increasing vaccine coverage with at least one dose from 72% to 76%. Approximately 24% (n = 75) of all participants refused vaccination (vaccine hesitant). Variables tested for an association with vaccination status demonstrated that age reached statistical significance. Emerging themes in the qualitative analysis included perceptions of vulnerability, vaccine safety and efficacy concerns, information gaps regarding vaccinations, the value of convenience in the decision to vaccinate, and the role of health promoters. Conclusions: This study has shown that it is logistically acceptable to provide a vaccination site at a large hospital targeting patients attending outpatient services for chronic medical conditions. This service also benefits accompanying persons and hospital staff. Access and convenience of the vaccination site influence decision-making, increasing the opportunity to vaccinate. However, vaccine hesitancy is widespread with just under one-quarter of all those offered vaccinations remaining unvaccinated. Strengthening health education and patient–clinician engagement about the benefits of vaccination is essential to reach highly vulnerable populations routinely attending hospital outpatient departments with an appropriate vaccination program. [ABSTRACT FROM AUTHOR]

Pumps-as-Turbines (PATs) are increasingly used in micro-hydropower applications due to their cost competitiveness that is brought about by lower acquisition, design, operation, and maintenance costs. Despite these, limited research exists that investigates PAT failures. Notably, there is a literature gap concerning cavitation in PATs. As such, this study proposes an improvement to the deviation from the normal distribution (DND) technique to facilitate application in PAT cavitation detection. Probability density functions of vibration signals collected during operation at design speed and various cavitation states are developed and the DND computed using two approaches, i.e., the use of baseline data and the original method, for comparison purposes. Normal probability plots are presented to depict suitability of the two approaches in quantifying the DND. Results show higher deviation when using baseline data, hence, improved detection capabilities with amplification of the slope of the trend line under cavitating conditions when using the proposed DND approach. The proposed method also allows for establishing clear alarm limits for the condition monitoring of PATs in practice. Moreover, the proposed method is validated by application at various PAT operating speeds and cavitation states. The proposed method is found to be responsive, reliable, and independent from operating speed. [ABSTRACT FROM AUTHOR]

Thyroid cancer is the most common head and neck cancer (HNC) in the world. In this article, we comprehensively cover baseline, posttreatment, and follow-up imaging recommendations for thyroid carcinomas along with the eighth edition of the tumor, node, metastasis (TNM) staging system proposed by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC). We include characterization and risk stratification of thyroid nodules on ultrasound (US) proposed by various international bodies. Management guidelines (depending upon the type of thyroid carcinoma) based on the international consensus recommendations (mainly by the American Thyroid Association) are also extensively covered in this article, including the role of a radioiodine scan. The management of recurrent disease is also briefly elucidated in this article. In addition, we cover the risk factors and etiopathogenesis of thyroid carcinoma along with the non-imaging diagnostic workup essential for thyroid carcinoma management, including the significance of genetic mutations. US is the diagnostic imaging modality of choice, with US-guided fine needle aspiration (FNA) being the procedure of choice for tissue diagnosis. The roles of computed tomography (CT), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) in thyroid carcinoma staging are also specified. Through this article, we aim to provide a comprehensive reference guide for the radiologists and the clinicians in the pursuit of optimal care for patients with thyroid carcinoma. [ABSTRACT FROM AUTHOR]

An hourglass-shaped magnetic field pattern arises naturally from the gravitational collapse of a star-forming gas cloud. Most studies have focused on the prestellar collapse phase, when the structure has a smooth and monotonic radial profile. However, most observations target dense clouds that already contain a central protostar, and possibly a circumstellar disk. We utilize an analytic treatment of the magnetic field along with insights gained from simulations to develop a more realistic magnetic field model for the protostellar phase. Key elements of the model are a strong radial magnetic field in the region of rapid collapse, an off-center peak in the magnetic field strength (a consequence of magnetic field dissipation in the circumstellar disk), and a strong toroidal field that is generated in the region of rapid collapse and outflow generation. A model with a highly pinched and twisted magnetic field pattern in the inner collapse zone facilitates the interpretation of magnetic field patterns observed in protostellar clouds. [ABSTRACT FROM AUTHOR]

The increased decentralization of renewable energy has increased curtailment rates in stagnating demand zones, increasing the levelized cost of energy (LCOE). The geographically dynamic nature of gravity energy storage (GES) is emerging in the field of mechanical energy storage, over pumped hydro. However, GES costs vary geospatially, specifically in decentralized suburban areas, due to the impact of urban socioeconomics. This study aims to find a mathematical approximation of a cost-optimized location for suburban Solar–GES hybrid systems in curtailment-prone areas. A multi-parameterization model mathematically programmed land, transmission, supply chain and excavation costs into geospatial matrix approximations for suburban areas of 2500 km2 in Fukuoka and Ibaraki in Japan. It was found that SPV-GES location-dependent costs were mainly affected by distance from the city's economic center and flat plains in suburbs, and supply chain and transmission costs optimized the location-dependent cost for GES at a specific point. It was also found that flat terrains were more economical than mountainous terrains due to high GES supply chain costs. With GES found to be cost-competitive compared to other storage technologies in Japan, this study reveals that GES introduction benefits the LCOE of suburban, decentralized SPV when curtailment is >50% irrespective of terrain. [ABSTRACT FROM AUTHOR]

Simple Summary: Metabolic reprogramming in HER2-positive breast cancer is associated with acquired resistance to targeted therapies. Thus, targeting dysregulated metabolic pathways in cancers is highly beneficial. In this study, we examined the anti-tumor effects of an LXR inverse agonist GAC0001E5 (1E5) in HER2-positive breast cancer in vitro. Strikingly, we observed disruption of two major pathways, glutaminolysis and de novo lipogenesis, leading to oxidative stress and cell death. Additionally, we discovered the indirect effects of 1E5 in downregulating HER2 expression through fatty acid synthase (FASN). Moreover, in combinatory treatments of 1E5 and lapatinib, 1E5 potentiates lapatinib's effects. These findings indicate the importance of 1E5 as a metabolic disruptor in HER2-positive breast cancer. The HER2-positive subtype accounts for approximately one-fifth of all breast cancers. Insensitivity and development of acquired resistance to targeted therapies in some patients contribute to their poor prognosis. HER2 overexpression is associated with metabolic reprogramming, facilitating cancer cell growth and survival. Novel liver X receptor (LXR) ligand GAC0001E5 (1E5) has been shown to inhibit cancer cell proliferation by disrupting glutaminolysis and inducing oxidative stress. In this study, HER2-positive breast cancer cells were treated with 1E5 to determine their potential inhibitory effects and mechanisms of action in HER2-positive breast cancers. Similar to previous observations in other cancer types, 1E5 treatments inhibited LXR activity, expression, and cancer cell proliferation. Expression of fatty acid synthesis genes, including fatty acid synthase (FASN), was downregulated following 1E5 treatment, and results from co-treatment experiments with an FASN inhibitor suggest that the same pathway is targeted by 1E5. Treatments with 1E5 disrupted glutaminolysis and resulted in increased oxidative stress. Strikingly, HER2 transcript and protein levels were both significantly downregulated by 1E5. Taken together, these findings indicate the therapeutic potential of targeting HER2 overexpression and associated metabolic reprogramming via the modulation of LXR in HER2-positive breast cancers. [ABSTRACT FROM AUTHOR]

Tropical cyclones, one of the most extreme and destructive meteorological incidents, cause extensive damage to lives and livelihoods worldwide. This study utilized remotely sensed data along with multi-criteria decision-making, geospatial techniques, and major cyclonic events Aila, Amphan, and Yaas to identify the changes in the vulnerability of cyclone-induced floods in the 19 community development blocks of Indian Sundarbans in the years 2009–2010, 2020–2021, and 2021–2022 (the post-cyclonic timespan). The Sundarbans are a distinctive bioclimatic region located in a characteristic geographical setting along the West Bengal and Bangladesh coasts. In this area, several cyclonic storms had an impact between 2009 and 2022. Using the variables NDVI, MNDWI, NDMI, NDBI, BSI, and NDTI, Landsat 8 Operational Land Imager, Thermal Infrared Sensor, Resourcesat LISS-III, and AWiFS data were primarily utilized to map the cyclonic flood-effective zones in the research area. The findings indicated that the coastline, which was most impacted by tropical storms, has significant physical susceptibility to floods, as determined by the AHP-weighted overlay analysis. Significant positive relationships (p < 0.05, n = 19 administrative units) were observed between mangrove damage, NDFI, and physical flood susceptibility indicators. Mangrove damage increased with an increase in the flood index, and vice versa. To mitigate the consequences and impacts of the vulnerability of cyclonic events, subsequent flood occurrences, and mangrove damage in the Sundarbans, a ground-level implementation of disaster management plans proposed by the associated state government, integrated measures of cyclone forecasting, mangrove plantation, coastal conservation, flood preparedness, mitigation, and management by the Sundarban Development Board are appreciably recommended. [ABSTRACT FROM AUTHOR]

In a concrete beam, cracking is generated on the tension side under the effect of flexure, shear, and torsional loadings. Accordingly, these weak concrete members require repair and/or strengthening to increase or restore their internal load capacity. In the current experimental and numerical investigations on concrete beams, the impact of using notches with different width to depth ratios on the ultimate flexural load under a three-point test was considered. Further, the flexural behavior performance of a notched concrete beam repaired using the three repair materials—cement mortar, bacterial mortar, and adhesive—was also examined. Consequently, a comparative study was implemented between the experimental and numerical results. A concrete damage plasticity (CDP) model was used for the finite element numerical analysis of the beams. The differences in numerical and experimental measured results ranged from 0.65 to 22.20% for the ultimate load carrying capacity. As the notch size increased, the ultimate load carrying capacity of the beam reduced. Additionally, a linear regression model was used to predict the ultimate load values at a notch width interval of 5 mm up to a maximum notch width of 100 mm. It was observed that the ultimate load capacity for a repaired beam increased as compared to the notched beam for all three repair materials under consideration. And the maximum ultimate load increased in the case of notched beams repaired using adhesive. Furthermore, in comparison to the cement mortar, the performance of the bacterial mortar in terms of the ultimate load was more. The bacterial mortar was found to be more sustainable and more durable as a repair material for concrete structures. [ABSTRACT FROM AUTHOR]

An effect of Cu powder dispersion and morphology on the surface structure and the physical–chemical and catalytic properties of Cu–CeO2 catalysts prepared by mechanochemical synthesis was studied in the preferential CO oxidation in a H2-rich stream (CO-PROX). Two catalysts, produced by 30 min ball-milling from CeO2 and 8 mass% of copper powders and with particle sizes of several tens (dendrite-like Cu) and 50–200 nm (spherical Cu obtained with levitation-jet method), respectively, were characterized by X-ray diffraction and electron microscopy methods, a temperature-programmed reduction with CO and H2, and with Fourier-transform infrared spectroscopy. The catalyst synthesized from the "large-scale" dendrite-like Cu powder, whose surface consisted of CuxO (Cu+) agglomerates located directly on the surface of facetted CeO2 crystals with a CeO2(111) and CeO2(100) crystal planes exposition, was approximately two times less active at 120–160 °C than the catalyst synthesized from the fine Cu powder, whose surface consisted of CuxO (Cu2+) clusters of 4–6 nm in size located on the steps of facetted CeO2 nanocrystals. Although a large part of CO2 reacted with a ceria surface to give carbonate-like species, no blockage of CO-activating centers was observed due to the surface architecture. The surface structure formed by the use of highly dispersed Cu powder is found to be a key factor responsible for the catalytic activity. [ABSTRACT FROM AUTHOR]

India has increased its wheat production phenomenally in the last two decades and it now has a buffer stock of 9.7 million tonnes. However, despite the release of several wheat cultivars, the end-use quality traits of Indian wheat varieties have not been explored in-depth to determine the increasing demand of the domestic processing industry as well as export. In this study, 55 wheat genotypes including 47 released varieties, and 8 genetic stocks were grown along with 10 Australian varieties grown during cropping seasons: 2019–2020 and 2020–2021 and diversity in different physiochemical and rheological traits was evaluated. They showed considerable diversity in all the quality traits studied. However, very few genotypes could be found suitable for any one end-use. Five genotypes were found to possess four to five traits for superior bread-making quality. Two varieties and three advanced breeding lines had up to four good chapati quality traits. None of the released varieties investigated had suitable traits for biscuit making; however, two breeding lines possessed requisite quality traits suitable for biscuit making. It is, therefore, concluded that systematic breeding efforts are required to develop genotypes that bring together the most important quality traits in a single genotype to be suitable for domestic industry as well as for export. [ABSTRACT FROM AUTHOR]

Specimens of 316 L stainless steel were printed using laser powder bed fusion (LPBF), a popular metal additive manufacturing (AM) technique, with varying island sizes. Not many researchers have considered the impact of spatter while optimizing LPBF printing parameters. In this research, the influence of spatter was considered while also investigating the effect of varied island size on the microstructure, surface roughness, microhardness, and corrosion resistance of LPBF-316 L. No correlation was observed between surface roughness or microhardness and minor variations in island size. However, a correlation was drawn between varied island sizes and porosity in LPBF-316 L. The specimens associated with larger island sizes showed significantly enhanced corrosion resistance due to fewer manufacturing defects and reduced porosity, attributed to the minimal influence of the spatter. Based on analysis, the LPBF parameters were revised, which lead to superior corrosion resistance of LPBF-316 L, attributed to high density and reduced porosity. [ABSTRACT FROM AUTHOR]