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The androgen receptor (AR) is the main driver in the development of castration‐resistant prostate cancer, where the emergence of AR splice variants leads to treatment‐resistant disease. Through detailed molecular studies of the marine alkaloid manzamine A (MA), we identified transcription factor E2F8 as a previously unknown regulator of AR transcription that prevents AR synthesis in prostate cancer cells. MA significantly inhibited the growth of various prostate cancer cell lines and was highly effective in inhibiting xenograft tumor growth in mice without any pathophysiological perturbations in major organs. MA suppressed the full‐length AR (AR‐FL), its spliced variant AR‐V7, and the AR‐regulated prostate‐specific antigen (PSA; also known as KLK3) and human kallikrein 2 (hK2; also known as KLK2) genes. RNA sequencing (RNA‐seq) analysis and protein modeling studies revealed E2F8 interactions with DNA as a potential novel target of MA, suppressing AR transcription and its synthesis. This novel mechanism of blocking AR biogenesis via E2F8 may provide an opportunity to control therapy‐resistant prostate cancer over the currently used AR antagonists designed to target different parts of the AR gene.

Abstract Recent studies have reported the involvement of peripheral nervous system (PNS) in association with MOG‐IgG, including isolated neuropathies. In this retrospective study we characterized the PNS involvement in MOG antibody associated disease (MOGAD). Six out of 215 MOGAD patients had PNS involvement (all polyradiculopathy) that occurred concurrently with a CNS demyelinating episode. We also demonstrated MOG expression in healthy human controls' proximal nerve root. Nine patients with true‐positive MOG‐IgG1 had PNS involvement temporally unrelated to a CNS demyelinating event. All these patients had an alternate etiology of PNS involvement. Isolated peripheral neuropathy is not a feature of MOGAD, but inflammatory nerve root involvement can occur concurrently with CNS demyelinating events.

ABSTRACT Context Meditation and related relaxation techniques are good means of alleviating stress and maintaining good health. Osho dynamic meditation decreases several psychopathological variables such as anxious‐depressive syndrome, aggressive behaviors, and depression which is practiced in Nepal and all over the world. Various studies have shown alteration in different hormone levels due to meditation by strengthening adaptive mechanisms. Aim The aim of this study was to evaluate the effect of Osho meditation on serum hormonal levels in pre‐ and postmeditation participants. Methods A pre–post study was conducted among 70 healthy volunteers (42 male and 28 female) where various types of Osho dynamic meditation techniques were incorporated together to understand their combined effects on serum hormone levels in participants attending the 7 days meditation camp. Serum hormones such as cortisol, estrogen, progesterone, free triiodothyronine (fT3), free thyroxine (fT4), thyroid‐stimulating hormone (TSH), testosterone, and growth hormone were measured by chemiluminescence immunoassay. Results Out of 70 participants, 68 participants (97%) had subjective opinion of Osho dynamic meditation being effective in alleviating stress, depression, and anger. Also, there was a significant decline in body weight and body mass index in both male and female populations after a strict vegetarian diet and meditation. Likewise, a significant rise in the level of estrogen (p < 0.001), progesterone (p < 0.001), growth hormone (p < 0.001), testosterone (p = 0.002), and fT3 (p = 0.049) in postmeditation male participants indicates the importance of Osho dynamic meditation on elevating sex hormones such as estrogen, progesterone, testosterone as well as fT3, and growth hormones among Osho meditation practicing participants. Conclusion Our findings suggest significant changes in the hormonal levels and improvement in stress and depression in participants undergoing Osho meditation.

Abstract Anomalously overturned thrust faults, lineaments and segmentation causing cross‐cutting basement structures characterize the tectonic setting of Sikkim Himalaya. However, its seismotectonics is poorly constrained along with the speculated northward extension of the Dhubri‐Chungthang Fault Zone (DCFZ) causing segmentation. Here, we utilize the precise location of newly acquired local earthquake data and fault plane solutions using full‐waveform moment tensor inversion to better constrain seismically active zones. Transtensional shearing along the Main Himalayan Thrust in central Sikkim is possibly incited by fluid‐rich upper‐crust. Cessation of the mapped 20 km wide mid‐crustal seismogenic zone of DCFZ at Chungthang and its northward discontinuation into the Higher Himalayas is confirmed by the striking variation in focal mechanisms. Earthquakes along imbricated segments in the lower‐crust originate possibly in response to crustal shortening. Extensional shearing along the Moho triggers seismicity to the northwest of Sikkim. Such complex tectonic dynamics instigating persistent seismicity indicates high potential for future great earthquakes in Sikkim Himalaya.

Abstract Amid the escalating prevalence of eye diseases and the intricate nature of the eye as a crucial target organ for drug delivery, researchers face significant challenges in developing delivery systems tailored specifically for ocular complications. Addressing the gaps in the current conventional ocular drug delivery system (ODDS) is crucial and this can be achieved by incorporating polymers while designing newer ODDS. This review aims to offer a concise overview of the diverse polymers utilized in the development of ODDS, designed to address various eye conditions and disorders, enhance treatment outcomes, and ensure patient adherence. Introducing the anatomy of the eye and different ocular routes of administration, alongside the barriers encountered, this review presents polymer‐based ODDS, renowned for their unique properties facilitating the engineering of specialized devices for enhanced drug delivery. Further discussions delve into the applications of polymers in ophthalmology. Emphasis is placed on emerging polymer‐based technologies available in the market for treating ocular diseases, underscoring their potential for revolutionizing ocular healthcare. The review also addresses challenges in translating these advancements into clinical practice, while highlighting the versatility of polymers in treating diverse eye diseases and disorders through customizable properties and sustained drug delivery.

Abstract Ferroptosis and apoptosis are key cell‐death pathways implicated in several human diseases including cancer. Ferroptosis is driven by iron‐dependent lipid peroxidation and currently has no characteristic biomarkers or gene signatures. Here a continuous phenotypic gradient between ferroptosis and apoptosis coupled to transcriptomic and metabolomic landscapes is established. The gradual ferroptosis‐to‐apoptosis transcriptomic landscape is used to generate a unique, unbiased transcriptomic predictor, the Gradient Gene Set (GGS), which classified ferroptosis and apoptosis with high accuracy. Further GGS optimization using multiple ferroptotic and apoptotic datasets revealed highly specific ferroptosis biomarkers, which are robustly validated in vitro and in vivo. A subset of the GGS is associated with poor prognosis in breast cancer patients and PDXs and contains different ferroptosis repressors. Depletion of one representative, PDGFA‐assaociated protein 1(PDAP1), is found to suppress basal‐like breast tumor growth in a mouse model. Omics and mechanistic studies revealed that ferroptosis is associated with enhanced lysosomal function, glutaminolysis, and the tricarboxylic acid (TCA) cycle, while its transition into apoptosis is attributed to enhanced endoplasmic reticulum(ER)‐stress and phosphatidylethanolamine (PE)‐to‐phosphatidylcholine (PC) metabolic shift. Collectively, this study highlights molecular mechanisms underlying ferroptosis execution, identified a highly predictive ferroptosis gene signature with prognostic value, ferroptosis versus apoptosis biomarkers, and ferroptosis repressors for breast cancer therapy.

Abstract We are frequently exposed to potentially harmful microbes of various types on a daily basis. Our immune system is an amazing collection of unique organs and cells that defends us from hazardous germs as well as certain diseases. It plays a crucial role in protecting the body against external invaders, including bacteria, viruses, and parasites. Maintaining a healthy immune system requires consuming a balanced diet that provides a variety of macro‐ and micronutrients. By consuming sufficient amounts of water, minerals such as zinc and magnesium, micronutrients, herbs, and foods rich in vitamins C, D, and E, and adopting a healthy lifestyle, one can enhance their health and immunity, and prevent infections. This article provides a comprehensive review of the scientific literature on common foods known for their potential to boost human immunity. The review begins by discussing the various components of the immune system and their functions. It then delves into the current understanding of how nutrition can influence immune response, highlighting the importance of a well‐balanced diet in supporting optimal immune function. The article presents an extensive analysis of a range of common foods that have been studied for their immune‐boosting properties. These foods include fruits, vegetables, whole grains, and animal‐based foods. Each food category is explored in terms of its specific nutrients and bioactive compounds that contribute to immune support. Foods such as milk, eggs, fruits, leafy greens, and spices like onion, garlic, and turmeric contain beneficial compounds that can enhance the immune system's function, activate and inhibit immune cells, and interfere with multiple pathways that eventually lead to improved immune responses and defense. The available literature on the issue was accessed via online resources and evaluated thoroughly as a methodology for preparing this manuscript.

Abstract Due to the exponential growth of interconnected devices and reduced cell coverage, beyond fifth‐generation networks will be dense. Thus, instead of wired backhaul, wireless backhaul will be cost‐effective and flexible. For security in multi‐transmitter systems, sub‐optimal and optimal transmitter selection schemes exist. However, including backhaul activity knowledge available (BKA) and backhaul activity knowledge unavailable (BKU) cases and transmitter selection schemes, there is no generalized secrecy analysis method. Moreover, evaluation of the ergodic secrecy rate (ESR) of the optimal selection schemes is impossible using existing solution approaches. To address these, two sub‐optimal and optimal transmitter selection schemes are proposed for a small‐cell multi‐transmitter system in BKU or BKA cases in the presence of multiple colluding eavesdroppers. The distribution of the ratio of the destination channel SNR and eavesdropping channel SNR is derived, thereby providing different secrecy performance metrics uniformly irrespective of selection schemes and BKU or BKA cases. Simplified asymptotic expressions are provided to elucidate the influence of the system parameters and of the backhaul reliability. It is observed that the secrecy performance improves when the knowledge of backhaul link activity is utilized, and the improvement is most noticeable when the backhaul is highly unreliable. It is also observed that while the secrecy performance degrades with an increasing number of eavesdroppers, neither the asymptotic saturation value of the secrecy outage probability nor the rate of improvement of the ESR with signal‐to‐noise‐ratio depends on the number of eavesdroppers.

Abstract Background Stiff person spectrum disorder (SPSD) is heterogeneous, and accurate diagnosis can be challenging. Methods Patients referred for diagnosis/suspicion of SPSD at the Mayo Autoimmune Neurology Clinic from July 01, 2016, to June 30, 2021, were retrospectively identified. SPSD diagnosis was defined as clinical SPSD manifestations confirmed by an autoimmune neurologist and seropositivity for high‐titer GAD65‐IgG (>20.0 nmol/L), glycine‐receptor‐IgG or amphiphysin‐IgG, and/or confirmatory electrodiagnostic studies (essential if seronegative). Clinical presentation, examination, and ancillary testing were compared to differentiate SPSD from non‐SPSD. Results Of 173 cases, 48 (28%) were diagnosed with SPSD and 125 (72%) with non‐SPSD. Most SPSD were seropositive (41/48: GAD65‐IgG 28/41, glycine‐receptor‐IgG 12/41, amphiphysin‐IgG 2/41). Pain syndromes or functional neurologic disorder were the most common non‐SPSD diagnoses (81/125, 65%). SPSD patients more commonly reported exaggerated startle (81% vs. 56%, p = 0.02), unexplained falls (76% vs. 46%, p = 0.001), and other associated autoimmunity (50% vs. 27%, p = 0.005). SPSD more often had hypertonia (60% vs. 24%, p

Knowledge about biological rhythms of diseases may not only help in understanding the pathophysiology of diseases but can also help health service policy makers and emergency department directors to allocate resources efficiently. Aneurysmal subarachnoid haemorrhage (SAH) has high rates of morbidity and mortality. The incidence of SAH has been attributed to patient-related factors such as characteristics of aneurysms, smoking, and hypertension. There are studies showing that the incidence of aneurysmal SAH appears to behave in periodic fashions over long time periods. However, there are inconsistencies in the literature regarding the impact of chronobiological factors such as circadian, seasonal, and lunar cycle factors on the occurrence of SAH. In this study, we focused on the analysis of a temporal pattern of SAH (infradian rhythms) with a novel approach using circular statistical methods. We aimed to see whether there is a circular pattern for the occurrence of SAH at all and if so, whether it can be related to known temporal patterns based on available literature. Our study did not support the notion that aneurysmal subarachnoid haemorrhages occur on any specific day in a cycle with specific lengths up to 365 days including specific weekdays, full moon, equinoxes, and solstices. Hence, we found no relationship between SAH incidence and timing. Study in larger populations using similar circular statistical methods is suggested.

Sperm traits are important in determining fertilisation success and are metabolically expensive to produce. There is little known about how energy acquisition and allocation affect sperm traits in avian taxa. This study assesses the impact of experimentally manipulated diet on long‐tailed finch sperm by comparing the length of sperm components (head, midpiece, flagellum and total sperm) between the treatment groups (homogenous diet and diverse diet) and across time points (before and after the experiment). Diet homogeneity was manipulated as this may impact diet quality in a species that is usually fed a diversity of seed species to thrive in captivity. Our results showed no impact of diet on the length of different sperm components. These results contrast with findings of a similar recent study of the zebra finch which found a significant level of diet‐affected plasticity in midpiece length. For both diet treatment groups in this study there was a slight but significant increase in head, flagellum and total sperm length over the treatment period. Despite this, all sperm components were highly repeatable, consistent with the finding from observational studies in passerine birds. The efficacy of our dietary manipulation was confirmed by a significant reduction in the saturation of bill colour in the long‐tailed finches as a result of the homogenous diet, and a difference in body mass across the treatment groups.

Background Mutations to the co‐chaperone protein BAG3 (B‐cell lymphoma‐2–associated athanogene‐3) are a leading cause of dilated cardiomyopathy (DCM). These mutations often impact the C‐terminal BAG domain (residues 420–499), which regulates heat shock protein 70‐dependent protein turnover via autophagy. While mutations in other regions are less common, previous studies in patients with DCM found that co‐occurrence of 2 BAG3 variants (P63A, P380S) led to worse prognosis. However, the underlying mechanism for dysfunction is not fully understood. Methods and Results In this study, we used proteomics, Western blots, and myofilament functional assays on left ventricular tissue from patients with nonfailing, DCM, and DCM with BAG363/380 to determine how these mutations impact protein quality control and cardiomyocyte contractile function. We found dysregulated autophagy and increased protein ubiquitination in patients with BAG363/380 compared with nonfailing and DCM, suggesting impaired protein turnover. Expression and myofilament localization of BAG3‐binding proteins were also uniquely altered in the BAG3,63/380 including abolished localization of the small heat shock protein CRYAB (alpha‐crystallin B chain) to the sarcomere. To determine whether these variants impacted sarcomere function, we used cardiomyocyte force‐calcium assays and found reduced maximal calcium‐activated force in DCM and BAG363/380. Interestingly, myofilament calcium sensitivity was increased in DCM but not with BAG363/380, which was not explained by differences in troponin I phosphorylation. Conclusions Together, our data support that the disease‐enhancing mechanism for BAG3 variants outside of the BAG domain is through disrupted protein turnover leading to compromised sarcomere function. These findings suggest a shared mechanism of disease among pathogenic BAG3 variants, regardless of location.

Abstract Himalaya is experiencing frequent catastrophic mass movement events such as avalanches and landslides, causing loss of human lives and infrastructure. Millions of people reside in critical zones potentially exposed to such catastrophes. Despite this, a comprehensive assessment of mass movement exposure is lacking at a regional scale. Here, we developed a novel method of determining mass movement trajectories and applied it to the Himalayan Mountain ranges for the first time to quantify the exposure of infrastructure, waterways, roadways, and population in six mountain ranges, including Hindu Kush, Karakoram, western Himalaya, eastern Himalaya, central Himalaya, and Hengduan Shan. Our results reveal that the exposure of buildings and roadways to mass movements is highest in Karakoram, whereas central Himalaya has the highest exposed waterways. The hotspots of exposed roadways are concentrated in Nepal, the North Indian states of Uttarakhand, Himachal Pradesh, the Union Territory of Ladakh, and China's Sichuan Province. Our analysis shows that the population in the central Himalaya is currently at the highest exposure to mass movement impacts. Projected future populations based on Shared Socio‐economic and Representative Concentration Pathways suggest that changing settlement patterns and emission scenarios will significantly influence the potential impact of these events on the human population. Assessment of anticipated secondary hazards (glacial lake outburst floods) shows an increase in probable headward impacts of mass movements on glacial lakes in the future. Our findings will support researchers, policymakers, stakeholders, and local governments in identifying critical areas that require detailed investigation for risk reduction and mitigation.

Abstract Background The microRNAs (miRs) secreted by the trophectoderm (TE) cells have recently been implicated in the conceptus‐endometrial cross talk during implantation and placentation. These miRs modulate various cellular processes during conception and throughout the pregnancy by regulating the gene expression in the foetal and maternal tissues. Objectives This study was undertaken to elucidate the function of TE secreted miRNAs in the maternal‐foetal cross‐talk during implantation/placentation in buffalo. Methods The in vitro produced blastocysts were cultured on a cumulus feeder layer for 21 days. The relative expression profiles of a selected panel of miRs was generated using the spent media collected on Days 0, 7, 12, 16, and 21. A custom‐designed mirVana™ miRNA mimic was used to transfect the endometrial epithelial cells (EECs) in order to determine the role of miRNA exhibiting highest expression on Days 21 and 21. Results The expression of miR‐1246 (p < 0.001) and let‐7b (p < 0.01) was found to be significantly higher on Day 21 of TE culture in comparison to the control (Day 0). This elevated expression indicated the involvement of these miRs in the maternal‐foetal cross‐talk. Interestingly, after the transfection of EECs with miRNA mimic for miR‐1246 (a novel molecule vis‐à‐vis implantation), the expression of beta‐catenin and mucin1 in these cells was found to be significantly (p < 0.05) downregulated vis‐à‐vis the control, that is, the IFN‐τ primed EECs (before transfection). Conclusions The TE secreted miR‐1246 appeared to lower the expression of the endometrial receptivity genes (mucin1 and beta‐catenin) which apparently assists the endometrium in preparing for placentation.

Abstract Background Toxoplasma gondii is a widespread zoonotic protozoan parasite capable of infecting all warm‐blooded animals. Although the genotypes of T. gondii in pigs have been reported worldwide, there is no information on the genotypes and diversity of T. gondii in pigs in Grenada, West Indies. Objectives The aims of the present study were to isolate, genotype and determine the diversity of T. gondii genotypes in pigs. Methods We carried out a modified agglutination test (MAT) on blood from 149 pig hearts collected from a local meat market. Myocardial tissue homogenate from pigs that tested positive for T. gondii was homogenized and inoculated into mice for isolation of the parasite. We collected mouse tissues and extracted DNA for genotyping based on 11 polymerase chain reaction‐restriction fragment length polymorphism markers (SAG1, SAG2, alt. SAG2, SAG 3, BTUB, GRA6, L358, PK1, C22‐8, C 29‐2 and Apico). Results Out of the 149 pig hearts, 31 (20.8%) tested positive for T. gondii on MAT. Bioassays in mice yielded 12 isolates designated TgpgGr1 to TgpgGr12. Molecular characterisation of T. gondii revealed four genotypes as follows: ToxoDB #2‐clonal type III (seven isolates); ToxoDB #7 (three isolates); ToxoDB #13 (one isolate); ToxoDB #30 (1 isolate). Overall, ToxoDB #2 was the most common (58%). Toxo database (DB) # 13, which causes interstitial pneumonia in affected mice, has also been reported. Conclusion The genetic diversity of T. gondii in pigs in Grenada is lower than that in other surrounding Caribbean areas.

Abstract Purpose Cancer stem cells (CSCs) constitute a distinctive subpopulation of cancer cells that are competent in tumor initiation, invasion, recurrence, and resistance to chemoradiotherapy. CD44, a hyaluronic acid (HA) receptor has been considered as a potential CSC marker in head and neck cancer. The purpose of this study is to evaluate the correlation between CD44 and clinicopathological parameters, treatment response, survival, and recurrence. Methods The CD44 expression was examined by immunohistochemistry (IHC) in 90 samples of head and neck squamous cell carcinoma (HNSCC) confirmed patients. The expression of CD44 and its association with clinicopathological parameters, treatment response, and survival was determined. Results In all HNSCC patient samples, CD44 was expressed consistently at different intensities. Tumor size (p

Abstract Over the course of the last several decades, nanotechnology has garnered a growing amount of attention as a potentially valuable technology that has significantly impacted the food industry. Nanotechnology helps in enhancing the properties of materials and structures that are used in various fields such as agriculture, food, pharmacy, and so on. Applications of nanotechnology in the food market have included the encapsulation and distribution of materials to specific locations, the improvement of flavor, the introduction of antibacterial nanoparticles into food, the betterment of prolonged storage, the detection of pollutants, enhanced storage facilities, locating, identifying, as well as consumer awareness. Labeling food goods with nano barcodes helps ensure their security and may also be used to track their distribution. This review article presents a discussion about current advances in nanotechnology along with its applications in the field of food‐tech, food packaging, food security, enhancing life of food products, etc. A detailed description is provided about various synthesis routes of nanomaterials, that is, chemical, physical, and biological methods. Nanotechnology is a rapidly improving the field of food packaging and the future holds great opportunities for more enhancement via the development of new nanomaterials and nanosensors.

Abstract Improving the reliability of power distribution systems is critically important for both utilities and customers. This calls for an efficient service restoration module within a distribution management system to support the implementation of self‐healing smart grid networks. Although the emerging smart grid technologies, including distributed generators (DGs) and remote‐controlled switches, enhance the self‐healing capability and allow faster recovery, they still pose additional complexity to the service restoration problem, especially under cold load pickup (CLPU) conditions. Herein, a novel two‐stage restoration framework is proposed to generate a restoration solutions with a sequence of control actions. The first stage generates a restoration plan that supports both the traditional service restoration using feeder reconfiguration and the grid‐forming DG‐assisted intentional islanding methods. The second stage generates an optimal sequence of switching operations to bring the outaged system quickly to the final restored configuration. The problem is formulated as a mixed‐integer linear program that incorporates system connectivity, operating constraints, and the CLPU models. It is demonstrated that on using a multi‐feeder test case, the proposed framework is effective in utilizing all available resources to quickly restore the service and generate an optimal sequence of switching actions to be used by the operator to reach the desired optimal configuration.