Late Stage Research Articles

H2S donor S-propargyl-cysteine for skin wound healing improvement via smart transdermal delivery.

Hydrogen sulfide for wound healing has drawn a lot of attention recently. In this research, the S-propargyl-cysteine (SPRC), an endogenous H2S donor, was loaded on carbomerhydrogel, and a copper sheet rat burn model was developed. Pathological changes in rat skin tissue were examined using hematoxylin-eosin (HE) and Masson staining. The immunohistochemistry (IHC) staining was performed to detect the expression of Collagen I (Col I) and Collagen III (Col III). The mRNA levels of interleukin (IL)-6, Col Iα2, Col IIIα1, tissue inhibitors of metalloproteinase (TIMP)-1, matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-β1 were examined by quantitative real-time chain polymerase reaction. The findings demonstrated that the collagen layer was thicker in the SPRC group during the proliferative phase, SPRC hydrogel promoted VEGF expression. In the late stage of wound healing, the expression of IL-6, TIMP-1, MMP-9, and TGF-β1 was inhibited, and the Col I content was closer to that of normal tissue. These results surface that SPRC hydrogel can promote wound healing and play a positive role in reducing scar formation. Our results imply that SPRC can facilitate wound healing and play a positive role in reducing scar formation.

Oxidative Stress and ROS Link Diabetes and Cancer

Type 2 diabetes mellitus (T2DM) accounts for one-sixth of deaths globally, whereas cancer is the second leading cause of death in the U.S. T2DM is a known risk factor for many cancers. Reactive oxygen species (ROS)-altered metabolic and signaling pathways link T2DM to cancer. These reprogrammed metabolic and signaling pathways contribute to diabetic complications, impact the redox balance (oxidative stress), and have differential roles in the early and late stages of cancer. A respiratory chain that is highly reduced (as under hyperglycemic conditions) or if reduced cofactors accumulate, ROS are greatly elevated. ROS may cause mutations in mitochondrial DNA (mtDNA) that result in further ROS elevations. The amplification of ROS results in the activation of PKC, an overarching signaling pathway that activates MAPK with a subsequent regulation in several factors that result in pathophysiological manifestations of T2DM and cancer. An upregulation in PKC leads to a deregulation in NF-kß, which regulates the PKB/P13/Akt pathway and orchestrates the cell survival, growth, proliferation, and glucose metabolism manifested in cancer. It also affects Insulin Receptor Substrate (IRS-1), decreasing insulin-stimulated glucose transport and glucose uptake, disrupting subsequent cell signaling pathways contributing to the development of T2DM. Dyslipidemia is a hallmark of T2DM and cancer. ROS-induced lipid peroxidation leads to systemic inflammation, producing inflammatory prostaglandins, cytokines, and chemokines that result in tumor proliferation, rapid tumor growth, and modulation of immunity. The dual role of ROS in the early and late stages of cancer makes antioxidant therapy precarious and may be responsible for controversial results. A system that delivers an antioxidant directly to mitochondria may be useful in inhibiting the formation of ROS early during the pre-diabetic stage, whereas antioxidant therapy must be halted in later stages to retard metastasis.

Shallow Thermal Anomalies and Their Role in the Breakup Evolution Along the Conjugate Margins of the Fram Strait (Svalbard and Eastern North Greenland), Indicated by Low‐Temperature Thermochronology

AbstractWe investigated highly mature sedimentary rocks exposed along both sides of the Fram Strait in the northern North Atlantic using apatite fission track and (U‐Th)/He thermochronology to obtain information on the thermal imprint of rifting and continental breakup processes along a sheared margin. Our data showed that the conjugate margins experienced several heating episodes, which we explain as resulting from heat transfer along segments of the De Geer Fracture Zone, a large continental transform system which connected magmatic centers north and south of the Fram Strait. Heating occurred prior to and during the Eurekan intraplate orogeny, which occupied the position of the present‐day Fram Strait during the Eocene. Heat transfer may have caused or contributed to lithospheric weak zones, which focussed deformation during intraplate orogeny. Movements along the transform fault system continued during the Oligocene, after the end of the Eurekan Orogeny, causing further structural weakening of pre‐existing fault zones. These were exploited during the final continental breakup leading to the opening of the Fram Strait. No unambiguous thermal signature associated with this latest stage of breakup was detected. Our data underline recent studies on the importance of structural inheritance and continental transform faults for the prolonged and complex processes of continental rifting and breakup.

Clinical and Epidemiological Characteristics of a Contingent of Elderly Patients Treated in the Somatopsychiatric Department of a Multi-Field Hospital

Background: comorbidity of somatic and mental pathology is the most common reason that complicates the provision of medical care to the elderly even under the conditions of a specialized somatopsychiatric department (SPD) of a multi-field hospital, which dictates the need for further study of the clinical and epidemiological features of these patients population.The aim of the study was to investigate the clinical and epidemiological characteristics of a contingent of elderly patients treated over a year in SPD of a multi-field hospital in comparison with similar data from a psychiatric hospital. The objectives of the study were to analyze the demographic structure of this contingent, the distribution of various types (categories) of somatic and mental pathology, routes of admission, time and outcomes of treatment in SPD of a multidisciplinary hospital.Materials and methods: the research material was the medical documentation of a sample of patients treated during 2019 in the SPD of the City Clinical Hospital № 1 named after. N.I. Pirogov of the Moscow Department of Health Protection (the total number of patients treated was 3379 people, of which 1456 were aged 65 and older). To conduct a comparative analysis, we used data from an epidemiological study in a psychiatric hospital (City Psychiatric Hospital № 13 of the Moscow Department of Health Protection), conducted in the same 2019 year.Results: it was established that in the SPD of a multi-field hospital, care is provided to a heterogeneous (demographic and clinical-diagnostic) group of patients, predominantly of late age (65 years and older). The most common diagnosis is dementia of various origins, complicated by severe somatic pathology (acute or associated with decompensation of a chronic somatic disease).Conclusion: elderly and senile patients make up more than half of the contingent of patients treated in the SPD of a multidisciplinary hospital. Significant differences were revealed in the SPD diagnostic distribution of young-middle-aged and elderly patients. Special features of the gender and age distribution of patients in the indicated age groups were established. Data were obtained on a higher mortality rate for those aged 65 years and older. The presence of problems in providing care to patients of older age groups in SPD determines the need for its improvement. For this purpose, it is advisable to consider the issue of creating a model of SPD of geriatric profile in a multi-field hospital to provide emergency psychiatric and somatic care to elderly patients.

Sorghum Response to Supplementary Irrigation at Different Growth Stage in Rain-Fed Agriculture for Increasing Yield and Water Productivity at Raya Valley

In arid and semi-arid ecosystems, the efficient use of water becomes increasingly important because water is a crucial limiting factor for increased food and fibre production to supply an ever-growing number of people. A field experiment was conducted in three consecutive seasons three year in Mekhoni Agricultural Research Centre, Raya valley, to investigate with the objective of to evaluate the influence of supplemental irrigation applied at different growth stages on the yield, to prevent sorghum failure caused by less rain water and to maximize the water productivity of the sorghum. The experiment was laid out in a random complete block design (RCBD) consisting of eleven supplemental irrigation treatments (one supplemental irrigation during initial stage, one supplemental during development stage, one supplemental during mid-stage, one supplemental during Late stage, one supplemental during initial and development stage, one supplemental during initial and mid stage, one supplemental during initial and late stage, one supplemental during development and late stage, one supplemental during development and late stage and rain-fed (with no SI) as a control treatment with three replications. The result was showed a significant difference on plant height, panicle length, grain, biomass yield and water productivity sorghum. The highest grain yield was obtained from the treatment supplement one SI at development and mid stage and followed by one SI at mid stage and at late stage. Whereas, the lowest grain yield of sorghum was observed from treatment with rainfed (non-supplementary). It is concluded that in the study area the rain fed amount were very inadequate and supplementary irrigation will help to increase crop productivity, minimize crop failure due to the low rainfed. The experiment showed that supplementary irrigation offers a great potential for improving crop production in Raya valley.

Growing up and reaching for the top: A longitudinal study on swim performance and its underlying characteristics in talented swimmers

ABSTRACT The present study strived to gain a more profound understanding of the distinctions in development between swimmers who are considered to be on track to the elite level at late junior age (males aged 16; females aged 15) compared to those who are not. In this effort, swimmers were followed during their pubertal years (males aged 13–15; females aged 12–14), which marks a period when performance development aligns with maturation. Longitudinal data of 90 talented sprint and middle-distance swimmers on season best times (SBT) and underlying performance characteristics (anthropometrics, maximal swimming velocity, stroke index [SI] and countermovement jump [CMJ]) were collected over three swimming seasons. Based on their SBT at late junior age (males aged 16; females aged 15), swimmers were classified as high-performing late juniors or lower-performing late juniors. Retrospectively studying these swimmers, we found that all but two high-performing late juniors were already on track to the elite level at early junior age (males aged 13; females aged 12), evidenced with faster SBT throughout puberty compared to their lower-performing peers (p < 0.05). Independent sample t-tests revealed that high-performing late juniors significantly outscored their lower-performing peers when they were early juniors on maximal swimming velocity (males aged 13–15 and females aged 12–14), SI (males aged 13 and 14; females aged 12), CMJ (females aged 14) and height (females aged 13 and 14, p < 0.05). Additionally, multilevel models showed faster rates of development for high-performing late juniors on maximal swimming velocity (males and females) and SI (males) compared to lower-performing peers throughout puberty (p < 0.05). Higher initial levels of SBT and underlying performance characteristics at early junior age as well as the faster rates of development on SBT, maximal swimming velocity and SI (males only) during the pubertal years, may be crucial factors in maintaining the trajectory towards the elite level after puberty.

Reliability model for key components of urban rail transit train based on improved hunter-prey optimization

The reliability of key components of urban rail transit (URT) plays an important role in the maintenance plans of URT. It is necessary to establish the reliability model of URT trains. In the current research, the reliability model has a limited scope of application and fails to accurately depict the reliability of key components in URT trains. To solve the above problem, a multi-peak type mixture Weibull distribution model is established using several three-parameter Weibull distributions based on fault modes of components sourced from historical lifetime data. Due to the complexity of this model, parameter estimation is challenging. For this purpose, an improved hunter-prey optimization (IHPO) was proposed to improve parameter estimation accuracy. Firstly, an improved Hénon chaos map was introduced to improve the distribution of the initial population. Secondly, the Lévy flight was introduced to increase the probability of the individual spreading to the whole range at the late stage. Lastly, a nonlinear balance factor was proposed to enhance the algorithm’s global search capability. The simulation experiment was carried out with examples of the balanced pressing wheel and the wheelset. The IHPO algorithm-based parameter estimation method shows the highest R-square with values of 0.996 and 0.999, respectively, and the lowest root mean square error with values of 0.019 and 0.008, respectively. The simulation results demonstrate that the stability and optimization of the HPO are improved, and the multi-peak mixture Weibull distribution model based on the IHPO can accurately depict URT trains’ reliability.

An Overview of The Risk Factors for Patients with Inguinal Hernia at Aloei Saboe Hospital in Gorontalo

Introduction: Hernias happen when an organ or tissue bulges through a weak point in the abdominal wall. Inguinal hernias are common and may need surgery. The present study report the overview of the risk to affect the inguinal hernia at Aloei Saboe Hospital.Method: The research focused on patients with inguinal hernias who underwent examinations at Aloei Saboe Hospital, in Gorontalo Province from January to December 2022. The study used the total sampling technique, with a sample size of 42 individuals. It was conducted in September and October 2023 at the same hospital.Results: The data indicates that a significant portion of patients in the range of age 56-65 years (28.6%), with a majority being male (85.7%). Additionally, the majority of patients who were not employed (19.0%) were also found to have this condition, as well as a vast majority of those with a primary diagnosis of inguinal hernia (88.1%).Conclusion: Most patients with inguinal hernia at Aloei Saboe Hospital are males in the late elderly age group who are no longer working. The main diagnosis for most patients is inguinal hernia. The study's findings suggest that the hospital can enhance its system, particularly in archiving medical records or electronic medical forms, to serve its patients better. Key words: Gorontalo, hernias, inguinal hernia

Wheel Replacing Pyramid: Better Paradigm Representing Totality of Evidence-Based Medicine.

Evidence-based medicine (EBM), as originally conceived, used all types of peer-reviewed evidence to guide medical practice and decision-making. During the SARS-CoV-2 Coronavirus disease (COVID-19) pandemic, the standard usage of EBM, modeled by the Evidence-Based Medicine Pyramid, undermined EBM by incorrectly using pyramid levels to assign relative quality. The resulting pyramid-based thinking is biased against reports both in levels beneath randomized control trials (RCTs) and those omitted from the pyramid entirely. Thus, much of the evidence was ignored. Our desire for a more encompassing and effective medical decision-making process to apply to repurposed drugs led us to develop an alternative to the EBM Pyramid for EBM. Herein, we propose the totality of evidence (T-EBM) wheel. To create an easily understood graphic that models EBM by incorporating all peer-reviewed evidence that applies to both new and repurposed medicines, and to demonstrate its potential utility using ivermectin as a case study. The graphics were produced using Microsoft Office Visio Professional 2003 except for part of the T-EBM wheel sunburst chart, which was produced using Microsoft 365 Excel. For the case study, PubMed® was used by searching for peer-reviewed reports containing "ivermectin" and either "covid" or "sars" in the title. Reports were filtered for those using ivermectin-based protocols in the treatment of COVID-19. The resulting 265 reports were evaluated for their study design types and treatment outcomes. The three-ringed graphical T-EBM wheel was composed of two inner rings showing all types of reports and an outer ring showing outcomes for each type. The T-EBM wheel avoids the biases of the EBM Pyramid and includes all types of reports in the pyramid along with reports such as population and mechanistic studies. In both early and late stages of medical emergencies, pyramid-based thinking may overlook indications of efficacy in regions of the T-EBM wheel beyond RCTs. This is especially true when searching for ways to prevent and treat a novel disease with repurposed therapeutics before RCTs, safety assessments, and mechanisms of action of novel therapeutics are established. As such, T-EBM Wheels should replace the EBM Pyramids in medical decision-making and education. T-EBM Wheels can be expanded upon by implementing multiple outer rings, one for each different kind of outcome (efficacy, safety, etc.). A T-EBM Wheel can be created for any proprietary or generic medicine. The ivermectin (IVM) T-EBM Wheel displays the efficacy of IVM-based treatments of COVID-19 in a color-coded graphic, visualizing each type of evidence and the proportions of each of their outcomes (positive, inconclusive, negative).

Characterization of Non-Ischemic Dilated Cardiomyopathy in a Native Tanzanian Cohort: MOYO Study.

Non-ischemic dilated cardiomyopathy (NIDCM) is a common cause of heart failure with progressive tendency. The disease occurs in one in every 2,500 individuals in the developed world, with high morbidity and mortality. However, detailed data on the role of NIDCM in heart failure in Tanzania is lacking. To characterize NIDCM in a Tanzanian cohort with respect to demographics, clinical profile, imaging findings and management. Characterization of non-ischemic dilated cardioMyOpathY in a native Tanzanian cOhort (MOYO) is a prospective cohort study of NIDCM patients seen at the Jakaya Kikwete Cardiac Institute. Patients aged ≥18 years with a clinical diagnosis of heart failure, an ejection fraction of ≤45% on echocardiography and no evidence of ischemia were enrolled. Clinical data, echocardiography, electrocardiography (ECG), coronary angiography and stress ECG information were collected from February 2020 to March 2022. Of 402 patients, n = 220 (54.7%) were males with a median (IQR) age of 55.0 (41.0, 66.0) years. Causes of NIDCM were presumably hypertensive n = 218 (54.2%), idiopathic n = 116 (28.9%), PPCM n = 45 (11.2%), alcoholic n = 10 (2.5%) and other causes n = 13 (3.2%). The most common presenting symptoms were dyspnea n = 342 (85.1%), with the majority of patients presenting with New York Heart Association (NYHA) Class III n = 195 (48.5%). The mean (SD) left ventricular ejection fraction (LVEF) was 29.4% (±7.7), and severe systolic dysfunction (LVEF <30%) was common n = 208 (51.7%). Compared with other forms of DCM, idiopathic DCM patients were significantly younger, had more advanced NYHA class (p < 0.001) and presented more often with left bundle branch block on ECG (p = 0.0042). There was suboptimal use of novel guidelines recommended medications ARNI n = 10 (2.5%) and SGLT2 2-inhibitors n = 2 (0.5%). In our Tanzanian cohort, the majority of patients with NIDCM have an identified underlying cause, and they present at late stages of the disease. Patients with idiopathic DCM are younger with more severe disease compared to other forms of NIDCM.

A Bleeding Edge Web Application for Early Detection of Cyanobacterial Blooms

Harmful Algal and Cyanobacterial Bloom (HACB) threaten aquatic ecosystems, human health, and the economy. Many factors influence these dynamic events, which are often difficult to detect until the late stages of growth. The inclusion of an Early Warning System (EWS) can be instrumental in identifying hazards and preventing or at least minimizing their impact. Traditional monitoring approaches often fail to provide the real-time, high-resolution data needed for effective early warnings. The integration of Internet of Things (IoT) technologies offers a promising avenue to address these limitations by creating a network of interconnected sensors capable of continuously collecting and transmitting data from various aquatic environments. In this paper, we present DEVS-BLOOM-WebUI, an advanced web application that extends the capabilities of the DEVS-BLOOM framework, providing a user-friendly interface that supports different user roles. The application includes an interface to manage users and permissions, dashboards to inspect data (from sensors, Unmanned Surface Vehicles (USVs), weather stations, etc.), train AI models, explore their predictions, and facilitate decision-making through notification of early warnings. A key feature of DEVS-BLOOM-WebUI is the Scenario Configuration Editor (SCE). This interactive tool allows for users to design and configure the deployment of monitoring infrastructure within a water body, enhancing the system’s adaptability to user-defined simulation scenarios. This paper also investigates the practical implementation of an IoT-based EWS, discussing design considerations, sensor technologies, and communication protocols essential for seamless data integration and effective operation of the EWS.

Phenalenyl-Based Photocatalyst for Bioinspired Oxidative Dehydrogenation of N-Heterocycles and Benzyl Alcohols.

The environmental benefits of molecular oxygen as the oxidizing agent in oxidation reactions that synthesize fine chemicals cannot be overstated. Increased interest in developing robust photocatalysts is stimulated by the fact that the current photocatalytic transformation boom has made previously inaccessible synthetic approaches possible. Motivated by enzymatic catalysis, employing a reusable phenalenyl-based photocatalyst, we have successfully developed oxidative dehydrogenation utilizing molecular oxygen as a greener oxidant. Under photoinduced oxidative dehydrogenation conditions, different types of saturated N-heterocycles and alcohols were successfully dehydrogenated. The versatility of this bioinspired protocol is demonstrated by the fact that a wide variety of N-heteroaromatics, such as quinoline, carbazole, quinoxaline, acridine, and indole derivatives, as well as aldehydes and ketones, were successfully synthesized. Detailed mechanistic studies validate the proposed mechanism. Fluorescence lifetime and CV experiments revealed the crucial role of water on the efficiency of the reaction. The present protocol also provides chemoselectivity and scalability, leading to superior results and allowing for the functionalization of bioactive molecules at a late stage in a sustainable manner.

LPMSAEF: Lightweight process mining-based software architecture evaluation framework for security and performance analysis

The article discusses the need for a lightweight software architecture evaluation framework that can address practitioners' concerns. Specifically, the proposed framework uses process mining and Petri nets to analyze security and performance in software development's early and late stages. Moreover, the framework has been implemented in six case studies, and the results show that it is a feasible and effective solution that can detect security and performance issues in complex and heterogeneous architecture with less time and effort. Furthermore, the article provides a detailed explanation of the framework's features, factors, and evaluation criteria. Additionally, this article discusses the challenges associated with traditional software architecture documentation methods using Unified Modeling Language diagrams and the limitations of code alone for creating comprehensive Software Architecture models. Various methods have been developed to extract implicit Software Architecture from code artifacts, but they tend to produce code-oriented diagrams instead of Software Architecture diagrams. Therefore, to bridge the model-code gap, the article proposes a framework that considers existing Software Architecture in the source code as architectural components and focuses on Software Architecture behaviors for analyzing performance and security. The proposed framework also suggests comparing Software Architecture extracted by different Process Mining algorithms to achieve consensus on architecture descriptions, using visualizations to understand differences and similarities. Finally, the article suggests that analyzing the previous version of a system's Software Architecture can lead to improvements and deviations from planned Software Architecture can be detected using traceability approaches to aid software architects in detecting inconsistencies.

A contribution to the understanding of the origin of the Ginebra Gold District mineralizations, Colombia

Ginebra´s gold mineralization is hosted by the Ginebra Ophiolitic Massif and the Buga Batholith, in the western flank of the Central Cordillera of Colombia. Gold occurs as disseminations, quartz-carbonate stockwork veinlets and quartz lodes with a strong structural control and are composed by small amounts of sulfides, mostly pyrite, with galena, sphalerite and chalcopyrite in at least two different deposition events and related to strong sericite-chlorite-epidote haloes, indicative of near-neutral and reduced fluids. Petrography and Raman spectroscopy allowed to identify two main fluid inclusions assemblages primary to pseudo-secondary in origin, both of them aqueous and CO2-rich, with variable N2. Microthermometric analysis indicates the hydrothermal fluids associated with the gold were low saline (0.75-6.22 wt% NaCl equiv.) and presented a minimum trapping temperature ranging from 237.4 to 301.6°C. Petrography and microthermometric results suggest an isothermal fluid mixing and/or H2S loss as the main mechanisms related to gold bi-sulfide/thio-sulfide complexes destabilization and precipitation. Sulfur isotopes indicates a close to zero range (-8.2-+4.8‰), suggesting a restricted fluid circulation through the magmatic rocks of the Buga Batholith and the Ginebra Ophiolitic Massif. Besides, the oxygen and deuterium isotopes from hydrothermal sericite and chlorite accompanying to gold events, indicates a metamorphic origin for the hydrothermal fluids. 40Ar-39Ar dating of the hydrothermal alteration haloes, from El Retiro and La Esperanza, indicates a late Cretaceous-Paleocene age, between 67 and 65 Ma, contemporaneous with a regional strong dextral transpressive deformation related to subduction to obduction and exotic terrane accretion against the north-western part of the South American Plate. Although the hydrothermal fluid characteristics of the Ginebra Gold Disctrict are compatible with both the Intrusion-Related and Orogenic Gold deposit types, the metamorphic nature of the hydrothermal fluids and the tectonic regime at the time of mineralization event, allow us to propose they are compatible with an Orogenic Gold deposit.

Death in the high mountains: Evidence of interpersonal violence during Late Chalcolithic and Early Bronze Age at Roc de les Orenetes (Eastern Pyrenees, Spain).

To test a hypothesis on interpersonal violence events during the transition between Chalcolithic and Bronze Age in the Eastern Pyrenees, to contextualize it in Western Europe during that period, and to assess if these marks can be differentiated from secondary funerary treatment. Metric and non-metric methods were used to estimate the age-at-death and sex of the skeletal remains. Perimortem injuries were observed and analyzed with stereomicroscopy and confocal microscopy. Among the minimum of 51 individuals documented, at least six people showed evidence of perimortem trauma. All age groups and both sexes are represented in the skeletal sample, but those with violent injuries are predominantly males. Twenty-six bones had 49 injuries, 48 of which involved sharp force trauma on postcranial elements, and one example of blunt force trauma on a cranium. The wounds were mostly located on the upper extremities and ribs, anterior and posterior. Several antemortem lesions were also documented in the assemblage. The perimortem lesions, together with direct dating, suggest that more than one episode of interpersonal violence took place between the Late Chalcolithic and the Early Bronze Age in northeastern Spain. The features of the sharp force trauma indicate that different weapons were used, including sharp metal objects and lithic projectiles. The Roc de les Orenetes assemblage represents a scenario of recurrent lethal confrontation in a high mountain geographic context, representing the evidence of inferred interpersonal violence located at the highest altitude settings in the Pyrenees, at 1836 meters above sea level.

Identification of potential immunotherapeutic targets and prognostic biomarkers in Graves' disease using weighted gene co-expression network analysis

Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism resulting from autoantibody-induced stimulation of the thyroid gland. Despite recent advancements in understanding GD's pathogenesis, the molecular processes driving disease progression and treatment response remain poorly understood. In this study, we aimed to identify crucial immunogenic factors associated with GD prognosis and immunotherapeutic response. To achieve this, we implemented a comprehensive screening strategy that combined computational immunogenicity-potential scoring with multi-parametric cluster analysis to assess the immunomodulatory genes in GD-related subtypes involving stromal and immune cells. Utilizing weighted gene co-expression network analysis (WGCNA), we identified co-expressed gene modules linked to cellular senescence and immune infiltration in CD4+ and CD8+ GD samples. Additionally, gene set enrichment analysis enabled the identification of hallmark pathways distinguishing high- and low-immune subtypes. Our WGCNA analysis revealed 21 gene co-expression modules comprising 1,541 genes associated with immune infiltration components in various stages of GD, including T cells, M1 and M2 macrophages, NK cells, and Tregs. These genes primarily participated in T cell proliferation through purinergic signaling pathways, particularly neuroactive ligand-receptor interactions, and DNA binding transcription factor activity. Three genes, namely PRSS1, HCRTR1, and P2RY4, exhibited robustness in GD patients across multiple stages and were involved in immune cell infiltration during the late stage of GD (p < 0.05). Importantly, HCRTR1 and P2RY4 emerged as potential prognostic signatures for predicting overall survival in high-immunocore GD patients (p < 0.05). Overall, our study provides novel insights into the molecular mechanisms driving GD progression and highlights potential key immunogens for further investigation. These findings underscore the significance of immune infiltration-related cellular senescence in GD therapy and present promising targets for the development of new immunotherapeutic strategies.

Cold deformation behavior and microstructure evolution of biomedical Cu-containing L605 alloy

The effect of copper (Cu) addition on the microstructure evolution and deformation mechanism of L605 (Co-20Cr-15 W-10Ni) alloy during cold deformation was investigated by using transmission electron microscopy (TEM), X-Ray diffraction (XRD) and electron backscatter diffraction (EBSD) analysis. The results indicated that the addition of Cu slightly decreased the yield strength and ultimate tensile strength, while it significantly increased the elongation. EBSD results revealed that hexagonal close-packed (HCP) martensite was generated during cold deformation and increased with increasing cold deformation level. The deformation microstructure of both alloys at different cold deformation levels shows that the stacking faulting was the primary deformation mechanism at early stage of cold deformation, in contrast, dislocation planar-slip and face-centered cubic (FCC) to HCP martensitic transformation were prevailed at both medium and late cold deformation level. Cu addition significantly suppressed the dislocation and stacking fault multiplication at early deformation stage and delayed the martensitic transformation at medium and late deformation stage, which could be ascribed to the relatively high stacking faulting energy by Cu addition, resulting in the low strain hardening behavior in the entire deformation process. These cumulative results and analyses could provide a solid foundation for the further development of this novel type of biomedical Cu-containing cobalt-based alloy.

Thorium anomaly on the lunar surface and its indicative meaning

The Moon has been divided into three terranes: Procellarum KREEP Terrane (PKT), Feldspathic Highland Terrane (FHT), and South Pole-Aitken Terrane (SPAT), using globally measured Th and FeO. Many lunar evolution models have predicted that a lunar magma ocean will produce a residual layer enriched in incompatible elements such as K, REE, and P (i.e., KREEP) in the late age of crystallization; and that the distribution of thorium can be used as a proxy for determining the global distribution of KREEP. The thorium distribution in these three terranes is inhomogeneous. The highest concentration of thorium is in PKT, the medium concentration of thorium is in SPAT, and almost none in FHT. Then what is the specific distribution in each of the terrane and what enlightenment can it tell us? Here we present and describe the detailed thorium distribution in PKT, SPAT, and FHT and provide some information for the origin of asymmetries on the lunar surface.

Health-Related Quality of Life of Prostate Cancer Patients Receiving Care in Tertiary Hospitals in Ogun State

Prostate cancer is the commonest malignancy among males in Nigeria. Most prostate cancer cases in sub-Saharan Africa get diagnosed in its late stages – which is associated with poorer health-related quality of life (HRQoL). Meanwhile, HRQoL has been shown to be a strong predictor of survivorship; therefore, this study was conducted to examine the HRQoL among prostate cancer patients receiving care in tertiary hospitals in Ogun state. With the cross-sectional research design and sample size of 387 prostate cancer patients selected using purposive sampling technique, the FACT-P instrument was used in data collection. Descriptive statistics analysis was used to assess participants' HRQoL levels. Findings showed that prostate cancer patients in this region have an average health-related quality of life level; the physical wellbeing domain of participants health-related quality of life was most affected by prostate cancer, with physical wellbeing having the lowest mean score (M=14.66), followed by emotional wellbeing (M=15.57), functional wellbeing (M=17.7), and social wellbeing being the least affected (M=18.33). Tertiary hospitals should ensure the inclusion of psycho-oncology counselling and psychotherapy, into the treatment plan of all patients after a prostate cancer diagnosis to improve the emotional and psychological wellbeing of prostate cancer patients. Similarly, access to physical rehabilitation and physiotherapy should be made easily accessible to improve physical wellbeing among prostate cancer patients.

Evaluation of fendiline treatment in VP40 system with nucleation-elongation process: a computational model of Ebola virus matrix protein assembly.

Ebola virus (EBOV) infection can cause deadly hemorrhagic fever, which has a mortality rate of ~50%-90% without treatment. The recent outbreaks in Uganda and the Democratic Republic of the Congo illustrate its threat to human health. Though two antibody-based treatments were approved, mortality rates in the last outbreak were still higher than 30%. This can partly be due to the requirement of advanced medical facilities for current treatments. As a result, it is very important to develop and evaluate new therapies for EBOV infection, especially those that can be easily applied in the developing world. The significance of our research is that we evaluate the potential of lipid-targeted treatments in reducing EBOV assembly and egress. We achieved this goal using the VP40 system combined with a computational approach, which both saves time and lowers cost compared to traditional experimental studies and provides innovative new tools to study viral protein dynamics.