Plant cells' ability to withstand abiotic stress is strongly linked to modifications in their mechanical characteristics. Nevertheless, the lack of a workable method for consistently tracking plant cell mechanical properties severely restricts our comprehension of the mechanical alterations in plant cells under stress. With Polyethylene Glycol (PEG6000), we created a drought-like environment, and we used the Double Resonator Piezoelectric Cytometry (DRPC) method to dynamically and non-invasively track changes in the stress (ΔS) created and viscoelasticity (storage modulus G' and loss modulus G") of protoplasts and suspension cells of rice during drought stress. The findings demonstrate that, rice suspension cells and protoplasts react mechanically differently to 5%–15% PEG6000 stress, implying distinct resistance mechanisms. However, neither of them can withstand 25% PEG6000 stress, they respond mechanically similarly to 25% PEG6000 stress. The results of DRPC are further corroborated by the morphological alterations of rice cells and protoplasts observed under an optical microscope. To sum up, the DRPC technique functions as a precise cellular mechanical sensor and offers novel research tools for the evaluation of plant cell adversity and differentiating between the mechanical reactions of cells and protoplasts under abiotic stress.

The existences of the N→C dative bonds in the complexes between N-containing molecules and fullerenes have been verified both theoretically and experimentally. However, finding stable N→C dative bonds is still a highly challenging task. In this work, we investigated computationally the N→C dative bonds in the complexes formed by fullerene C60 with 1,2,5-chalcogenadiazoles, 2,1,3-benzochalcogenadiazoles and 1,2,4,5-chalcogenatriazoles, respectively. It was found that the N→C dative bonds are formed along with the formation of the N–Ch···C (Ch = S, Se, Te) chalcogen bonds. In the gas phase, from S-containing complexes through Se-containing complexes to Te-containing complexes, the intrinsic interaction energies become more and more negative, which indicates that the N–Ch···C chalcogen bonds can facilitate the formation of the N→C dative bonds. The intrinsic interaction energies are compensated by the large deformation energy of fullerene C60. The total interaction energies of Te-containing complexes are negative, while both of the total interaction energies of S-containing complexes and Se-containing complexes are positive. This means that the N→C dative bonds in the Te-containing complexes are more easily observed in experiments in comparison with those in the S-containing complexes and Se-containing complexes. This study provides a new theoretical perspective on the experimental observation of the N→C dative bonds in the complexes involving fullerenes. Further, the formation of stable N→C dative bonds in the complexes involving fullerenes can significantly change the properties of fullerenes, which will greatly simulate and expand the application range of fullerenes.

Proposed fundamental laws of biology and a model of health and disease underscore the importance of the lymphatic system. The lymphatics are responsible for two of the laws of biology and the fulcrum of health and disease balancing proliferation with regeneration through the immune system. It is responsible for protection from the environment and repair of senile and damaged tissue. Life is constantly bombarded by forces that increase entropy. Lymphatics provide negative entropy to maintain health. Lymphatics help maintain cellular homeostasis removing products of metabolism. Using these principles, the role of lymphatics is investigated in salt sensitivity hypertension, cardiorenal system, the new pillar of heart failure and kidney disease - Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors, and brain diseases. The realization of organ lymphatics in maintenance of health and disease opens the avenue to new therapeutics. This is the unrealized potential of lymphatic study.

This study provides a comprehensive analysis of the conformational dynamics of pseudo-endocannabinoid receptors (p-CBRs) CB₁ and CB₂ in response to ligand binding. The ligands studied include N-arachidonoyl dopamine (NADA), Cannabidiol (CBD), known agonists (FUB-MDMB and E3R), and inverse agonists (Taranabant and AM630). Using homology models based on crystal structures (PDB ID: 5U09 for CB₁ and 5ZTY for CB₂), molecular docking, and molecular dynamics (MD) simulations, the research validates the structural integrity and dynamic behaviours of these pseudo-receptors. Induced-fit docking revealed NADA as having the highest binding affinity for both receptors, with docking scores of −13.92 kcal/mol for CB₁ and −13.32 kcal/mol for CB₂, facilitated by key hydrogen bond interactions. MD simulations over 250 ns at ~298 K showed successful equilibration, indicating the most stable interaction for NADA, thereby further validating the models. CB₁ and CB₂ exhibited distinct conformational responses to ligands, with Cα RMSD and Cα RMSF analyses suggesting a more rigid binding pocket for CB₁ and a flexible binding pocket for CB₂. These findings highlight the significance of receptor behaviour and dynamics in the development of cannabinoid-based therapeutics, supporting the potential of CBD and NADA as modulators for CB₁ and CB₂, respectively.

We monitored the water quality and hydrological conditions of a horizontal subsurface constructed wetland (HSSF-CW) in Beijing, China, for 2 years. We simulated the area rate constant and the temperature coefficient with the first-order kinetic model. We examined the relationships between the nitrogen (N) removal rate, N load, seasonal variations in the N removal rate, and environmental factors, such as the area rate constant, temperature, and dissolved oxygen (DO). The effluent ammonia (NH₄⁺-N) and nitrate (NO₃⁻-N) concentrations were significantly lower than the influent concentrations (p<0.01, n=38). The NO₃⁻-N load was significantly correlated with the removal rate (R²=0.9566, p<0.01), but the NH^₄+-N load was not correlated with the removal rate (R²=0.0187, p>0.01). The area rate constants of NO₃⁻-N and NH₄⁺-N at 20 °C were 27.01±26.49 and 16.63±10.58 m∙yr⁻¹, respectively. The temperature coefficients for NO₃⁻-N and NH₄⁺-N were estimated at 1.0042 and 0.9604, respectively. The area rate constants for NO₃⁻-N and NH₄⁺-N were not correlated with temperature (p>0.01). The NO₃⁻-N area rate constant was correlated with the corresponding load (R²=0.9625, p<0.01). The NH₄⁺-N area rate was correlated with DO (R²=0.6922, p<0.01), suggesting that the factors that influenced the N removal rate in this wetland met Liebig's law of the minimum.

Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.

Background: Physical activity has been considered as a promising approach to slow down the disease process in Multiple Sclerosis (MS) patients. While the functional impairments of MS have been studied in detail, but there is limited evidence of the efficacy of exercise interventions on the Multiple Sclerosis functional composite (MSFC) score in these patients. The study aim was to in-vestigate the improvement in MSFC score by multi-function swing suspension training (MFSST) in the women with MS. Methods: The patients were divided into the intervention and control groups. A total of 47 MS patients completed the MSFC components at baseline and after the intervention. Z scores were created for each test based on control means. Results: The MSFC components showed a significant increment in comparison with the baseline levels in the four, six, and eight weeks following the first exercise session (all p<0.05). These dif-ferences in the control group were not significant. The improvement in the MSFC score and the component Z-scores in the intervention groups was found from the fourth week onwards. Conclusions: The study findings highlight that MFSST can be used as an effective treatment method in MS patients due to its positive effects on physical parameters, such as muscles strength, functional impairments, and cognitive problems.

1) Background: Several studies have shown the benefit of drawing when learning anatomy. Virtual Reality (VR) also appears to be useful to increase the understanding of the location of anatomical structures. This study aims to describe how students in an Operating Room Nursing (OR nursing) master study program perceive the benefit of active learning methods, including drawing and the use of VR. 2) Methods: We combined these two methods in a class of 29 students. 38 half-finished drawings of anatomical structures were made. The students were to complete these during lectures with guidance from the teacher. The students also attended a two-hour VR session where they were to find various anatomical structures. A paper questionnaire was applied to evaluate the teaching program. Data were analyzed statistically. 3) Results: The students highly appreciated these learning methods. They reported that drawing made them work more actively during lectures and increased their learning outcome. They also perceived that the use of VR technology increased their understanding of the location of anatomical structures. 4) Conclusion: The combination of drawing and VR technology may be of benefit to OR Nursing students when learning anatomy by both increasing student activity and learning outcomes.

Alzheimer’s disease (AD) and the therapies of AD with anti-amyloid1-42 (Aβ) monoclonal antibodies are associated with the vascular complications of brain edema, hemorrhage, and cerebral amyloid angiopathy (CAA) termed amyloid-related imaging abnormalities (ARIAs). The neuropathology of normal and AD brains demonstrates that monocyte/macrophages (MMs) are critical in successful brain clearance in healthy brain by up-loading, transporting, and degrading Aβ but fail degradation and clearance in AD patients by releasing Aβ into vessels at the blood-brain barrier, causing vasculitis and ARIAs. The naturally-formed epoxides (EpFAs) of polyunsaturated fatty acids (PUFA’s), including arachidonic, docosahexaenoic, and eicosapentaenoic fatty acids, may repair degradation of Aβ by regulating Aβ-degrading enzymes, inflammatory cytokines, and unfolded protein response (UPR) to endoplasmic reticulum stress in a homeostatic fashion. EpFAs are, however, degraded by the soluble epoxide hydrolase enzyme (sEH) but are protected by the sEH inhibitor (sEHI) TPPU. In the cultures of AD patients’ macrophages, TPPU with the epoxide EEQ, and the cGAS/STING inhibitor H-151 increased uptake of Aβ at 2 hours and degradation of Aβ at 24 hours. In conclusion, the soluble epoxide hydrolase inhibitor TPPU with omega-3 fatty acids and the cGAS/STING inhibitor H-151 increase Aβ uptake and degradation in macrophages of AD patients, and potentially enhancing Aβ clearance in the AD brain.

Cryptococcosis is one of the most serious opportunistic diseases in patients living with HIV. For this reason, it is important to have early diagnosis and appropriate treatment. Objectives. The aim of the study was to know the evolution of patients diagnosed with cryptococcosis by detection of Cryptococcus antigen in serum by lateral flow (CrAg LFA) without nervous system involvement and with treatment in accordance with the results. Materials and Methods. A retrospective, longitudinal, analytical study was performed. Seventy patients with cryptococcosis initially diagnosed by serum CrAg LFA without meningeal involvement between January 2019 and April 2022 were analyzed for medical records. The treatment regimen was adapted to the results of blood culture, respiratory material or pulmonary tomography imaging. Results. Seventy patients were included, 13 had probable pulmonary cryptococcosis, 4 had proven pulmonary cryptococcosis, 3 had fungemia and 50 had pre-emptive therapy without microbiological or imaging findings compatible with cryptococcosis. Among the 50 patients with pre-emptive therapy, none had meningeal involvement or cryptococcosis recurrences to date. Conclusion. Pre-emptive therapy avoided progression to meningitis in patients with CrAg LFA-positive patients. Pre-emptive therapy with dose adjustment of fluconazole in patients with the mentioned characteristics was useful despite the use of lower doses than recommended.

Assessing the economic supply of biomass in a geospatial context while accounting for risk from natural disasters was studied. Risk levels were estimated from a component of factors which included: population density, road density, federal ownership, U.S. Environmental Protection Agency ecoregions, and Presidential Disaster Declarations. The Presidential Disaster Declarations included risks due to: coastal storm, drought, fire, flood, freezing, hurricane, mud land slide, severe ices, severe storms, snow, tornado, and tropical storm. Presidential Disaster Declarations included summaries based on a short-term time period from 2000-2011, and on a long-term time period from 1964-2011. Risk categories were developed as a function of the number of disaster declarations, agricultural-to-forest land ratio, average road density, and average population density. A significant contribution of the research was the allocation of spatially explicit data using GIS technology at the 5-digit zip code tabulation area. The average area for 5-digit ZCTAs in the Eastern U.S. study region was approximately 169 kilometers². Long-term risk (1964-2011) from disaster declarations had a greater impact on the economic availability of biomass supply relative to short-term declarations (2000-2011). The greatest risk to biomass supply came from population density relative to the other risk factors studies. Of the 25,044 total ZCTAs, 12,256 ZCTAs were in locations that did not include population density ≥ 150/km², road density ≥ 14 km/km², federal ownership, and US Environmental Protection Agency Level III ecoregions. Of the remaining 12,256 ZCTAs, 26.8% were considered to be moderate-to-high risk based on short-term declarations (2000-2011) and 29.4% were considered to be moderate-to-high risk based on long-term declarations (1964-2011). Lower risk locations for procuring biomass supply for both short-term and long-term declarations, across all risk factors, were in southern Georgia, South Carolina, and Texas.

The objective of this study is to determine the relationship between body condition score (BCS) and body carcass fat (BCF) of ewes at two key stages of the production cycle. Data were collected from 88 Coopworth ewes including BCS measurements manually evaluated by the farm manager, BCF measurements determined by computerized tomography (CT) and body parameter measurements automatically determined by an image processing application. Artificial neural network (ANN) statistical analysis method was used to develop a relationship between the body parameters and the BCF with an r2=0.96 and RMSE=1.01 using all top and side variables.

1) Background- Coronary artery bypass grafting (CABG) is a common surgical intervention for patients with severe coronary artery disease. The Model for End-Stage Liver Disease (MELD) score has been widely used to predict mortality risk in patients with end-stage liver disease, but its utility in predicting postoperative outcomes in cardiac surgery patients is less well-established. 2) Methods-This retrospective study aims to investigate the association between preoperative MELD score and post-operative complications, length of hospital stay, and mortality in patients under-going coronary artery bypass grafting. This is a single-center, retrospective cohort study conducted at a tertiary care academic medical center. The study includes all adult patients who underwent elective coronary artery bypass grafting between January 2011 and December 2020. Preoperative MELD scores were calculated for each patient, and postoperative outcomes including major ad-verse cardiac events, length of hospital stay, and 30-day mortality was assessed. To ensure a homogeneous study cohort, we excluded patients who underwent emergent cardiac procedures or had incomplete data necessary for the calculation of MELD scores and assessment of postoperative outcomes. Data was extracted from the electronic medical records, including patient de-mographics, comorbidities, preoperative laboratory values, operative details, and postoperative outcomes. The study protocol was approved by the Institutional Review Board, and the require-ment for informed consent was waived due to the retrospective nature of the study.3) Results- This study reveals a statistical association between the MELD score calculated at admission and the length of hospital stay, duration in the ICU, patient age, and the duration of aortic clamping and extracorporeal circulation. Specifically, there is an exponential increase in the MELD score corre-lating with the rise in these factors, both collectively and individually, highlighting a significant relationship between the duration of extracorporeal circulation and aortic clamping time. 4) Conclusion-Patients with a high MELD score had an increased risk of postoperative complications and mortality compared to those with a low MELD score. Careful preoperative patient selection and optimization of the patient's clinical condition may improve outcomes in patients with advanced liver disease undergoing cardiac surgery.

Background and Objectives: ARNE score was developed for the prediction of difficult airway for both general and ENT surgery with a universal cut-off value. We tested the accuracy of this score in the case of laryngeal surgery and provided an insight of its combination with flexible laryngoscopy. Materials and Methods: This prospective pilot clinical study included 100 patients who were being scheduled for microscopic laryngeal surgery. We have calculated ARNE score for every patient and flexible laryngoscopy was provided preoperative. Difficult intubation was assessed according to intubation difficulty score (IDS). Results: A total of 33% patients had difficult intubation according to IDS. ARNE score showed to be accurate for prediction of difficult intubation in laryngology with P&lt;0.0001 and AUC 0.784. Flexible laryngoscopy showed to be an independent parameter with P&lt;0.0001 and AUC 0.766. We have defined a new cut-off value of 15.50 for laryngology, according to AUC curve. After the patients were divided in two groups, according to the new cut-off value and provided cut-off value, AUC improved to 0.707 from 0.619 respectively. Flexible laryngoscopy improved the prediction model of ARNE score to AUC 0.882 and of new cut-off value to AUC 0.833. Conclusions: It is recommended to use flexible laryngoscopy together with ARNE score in difficult airway prediction in patients with laryngeal pathology. Also, universally recommended cut-off value of 11 can not be effectively used in laryngology and a new cut-off value of 15.50 is recommended.

In this review, we outline our current understanding of the mechanisms involved in the absorption, storage, and transport of dietary vitamin A to the eye, the trafficking of rod opsin protein to the photoreceptor outer segments, which encompasses the logistical backbone required for visual function. Two key mechanisms of this process are emphasized in this manuscript: Ocular and systemic vitamin A membrane transporters, and rhodopsin transporters. Understanding the complementary mechanisms responsible for the generation and proper transport of the retinylidene opsin to the photoreceptor outer segment will eventually shed light on the importance of genes encoded by these proteins, and their relationship on normal visual function and in the pathophysiology of retinal degenerative diseases.

Security in the Internet of Things (IoT) is a critical concern due to the growing number of connected devices and the limited resources to implement robust security mechanisms in most of them. Adopting standard assessment frameworks, such as CVSS (Common Vulnerability Score System), allows for systematic vulnerability assessment. At the same time, CVE (Common Vulnerabilities and Exposures) records provide unique identifiers for known security issues, making it easier to share information. However, comparing security solutions is still challenging due to the diverse nature of IoT devices and the ever-evolving threat landscape, requiring continual innovation and collaboration between stakeholders. Furthermore, there still needs to be a simple way to compare technologies and solutions, taking into account the security provided by them. In this sense, in this article, we propose a tool for calculating a security score based on the CVSS index of each existing vulnerability in a given technology. We explain how the tool performs the calculation, discuss some challenges, and propose improvements for future work.

Mucosal healing (MH) is the main treatment target in ulcerative colitis and Crohn’s disease, and it is defined by a combination of complete endoscopic and histologic remission. Indeed, the complete resolution of mucosal inflammation should be confirmed at histology. Neutrophil infiltration represents the unique histological marker in discriminating the active vs quiescent phase of disease, also including crypt injuries (cryptitis and crypt abscesses), erosions and ulcerations. Basal plasmacytosis do not qualify by itself the remission in inflammatory bowel diseases (IBD), but it represents a diagnostic clue, mostly at onset. Several histological scoring systems have been developed to evaluate therapeutic efficacy, even though they often resulted tricky and subjective. Moreover, these scores listed a heterogeneous group of histological features as parameters. The recently proposed simplified histological score on MH was based on neutrophils and their distribution in the gut mucosa was also considered, aiming to provide a simple, time-sparing and reproducible tool to be applied to the routinary diagnostic practice. The artificial intelligence could be a promising tool both in evaluating and standardizing the histological assessment of disease activity in IBD. Moreover, novel molecules involved in the inflammatory dynamics in the gut could be employed in supporting the diagnostic practice in IBD.

This paper, based on the "Unified Theory of Forces," rigorously proves the formula of de Broglie's wave function. This helps us better understand the following important issues: 1) Theoretically prove and understand the essence of de Broglie's wave function; 2) Prove that when the particle's momentum P is determined, the greater the mass of the particle, the more concentrated its wave function distribution, and the weaker the interference effect; 3) Correct the spatial distribution of the wave function of free particles, proving that the wave function of free particles is strictly constrained within a finite spatial range, which is consistent with the facts we observe.

Using the h-index to assess individual researchers is not only unethical and unfair but also inaccurate and misleading. This index fails to offer a reliable measure of a researcher's impact based on their citation scores. Beyond statistical and conceptual considerations, authorship practices, especially in the case of multi-authored publications, give rise to significant problems that often go unnoticed. While some modifications of the h-index have been proposed to mitigate these weaknesses, the fundamental deficiencies persist. Most of these flaws have been effectively addressed by the c-score, a composite citation index. The c-score excludes self-citations, normalizes the number of citations by considering the number of authors in each paper, and takes into account first, single, and last authorship. This approach provides a more realistic measure of the impact of each individual researcher based on raw citations.

Background: Mechanical ventilation in preterm neonates aims for synchrony, preventing complications such as lung injury. Neurally Adjusted Ventilatory Assist (NAVA) stands out as a unique mode relying on diaphragmatic electrical signals for synchronization. We attempted to review studies that have explored the long-term consequence of using invasive NAVA in neonates with a specific focus on respiratory outcomes, namely bronchopulmonary dysplasia (BPD). Methods: A systematic review following PRISMA explored invasive NAVA in preterm neonates. Primary objectives compared NAVA to conventional ventilation, assessing BPD incidence, ventilation duration, length of stay, and adverse events. Secondary objectives analyzed ventilator parameters. Results: After screening 282 records, nine studies were included. NAVA showed reduced oxygen requirement at 28 days but no significant differences in oxygen need at 36 weeks postmenstrual age, total length of stay, or ventilator days. Adverse events such as air leak, mortality, patent ductus arteriosus, and intraventricular hemorrhage revealed no substantial variations. Ventilator variables favored NAVA, indicating decreased peak inspiratory pressure, tidal volume, work of breathing, and respiratory severity score. Conclusion: Despite short-term benefits, our study found no significant reduction in BPD with NAVA. Future large-scale trials are essential to comprehensively assess NAVA's impact on preterm infants' long-term outcomes.

Sepsis is a serious disease that can lead to mortality. The etiology of the disease is connected to how the body as a host reacts toward microbes such as bacteria, viruses, and fungi invasion. Current research shows that during sepsis, the reaction toward microbe attacks takes two main phases. The first is known as a cytokine storm, while the second is a vicious cycle of pro-inflammatory responses followed by a strict anti-inflammatory response led by CD4+ Tregs. Various immunomodulatory therapies have been proposed to break the cycle of pro- and anti-inflammatory reactions to sepsis. However, clinical trials did not show promising results, indicating further research into the mechanism that Treg uses to inhibit proinflammatory reactions. We used next-generation sequencing (NGS) analysis of bulk RNA-seq and single-cell RNA-seq data to examine the exact molecular pathways used by Treg to inhibit the immune response in sepsis. Our approach identified ACOD1 (Aconitate Decarboxylase 1) as a primary mediator of Treg suppression of immune cells. We identified and validated CD36 as a downstream target of ACOD1. CD36 is a known metabolite regulator in Tregs. Taken together, our results indicate that targeting ACOD1 could prove valuable in regulating Treg function during sepsis.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy that adversely affects maternal and offspring health. A variety of risk factors, such as BMI and age, have been associated with increased risks of gestational diabetes. However, in many cases gestational diabetes occurs in healthy nulliparous women with no obvious risk factors. Emerging data suggest that the tendency to develop gestational diabetes has genetic and environmental components. Here we develop a polygenic risk score for gestational diabetes. We further investigate relationships between the genetic architecture of GDM and genetically constructed risk factors and biomarkers. Our results show that genetics can be used as an early screening tool that identifies at-risk at higher risk of GDM before its onset to propose comprehensive monitoring and preventative programs to mitigate the risks.

Objectives: To assess the concordance of the preoperative application of the #Enzian classification (#ENZIANi) with the postoperative result (#ENZIANs) using surgical findings as the reference standard. Methods: This retrospective study included 282 consecutive patients with deep endometriosis undergoing surgical treatment. Preoperative assessment with transvaginal sonography and magnetic resonance imaging was compared with postoperative assessment. Concordance and diagnostic test evaluation were calculated. Results: The highest concordance was observed in the F (abdominal wall endometriosis) with k Cohen of 0.837, following the values for pelvic locations, with 0.795 for T left, 0.791 for T right, 0.776 for F (adenomyosis), 0.766 for C (rectum), and 0.75 and 0.72 for O right k and O left, respectively. The highest sensitivity was demonstrated for the P compartment *(98%), T compartment (both sides 97%), and A, B, C (94%- 96%), corresponding with deep endometriosis. Conclusions: Preoperative assessment using TVS/TAS+MRI with the ENZIANi score correlates well with the ENZIANs postoperative score and demonstrates good concordance in the detection and localization of deep endometriosis, thereby minimizing false negative results and ensuring accurate preoperative staging. The ENZIAN classification is well-suited to surgeons&#39; needs and benefits from continuous development. Future improvements, such as adding the expanded C module, may be considered in the next edition.

Removal of the proliferation component of gene expression by PCNA adjustment has been addressed in numerous survival prediction studies for breast cancer and all cancers in the TCGA. These studies indicate that widespread co-regulation of proliferation upwardly biases survival prediction when gene selection is performed on a genome-wide basis. In addition, removal of the correlative effects of proliferation does not reduce the random bias associated with survival prediction using random gene selection. Since most cancers become addicted to DNA repair as a result of forced cellular replication, increased oxidation, and repair deficiencies from oncogenic loss or genetic polymorphisms, we pursued an investigation to remove the proliferation component of expression in DNA repair genes to determine survival prediction. This translational hypothesis-driven focus on DNA repair genes is directly amenable to finding new sets of DNA repair genes that could potentially be studied for inhibition therapy. Overall survival (OS) prediction was evaluated in 18 cancers by using normalized RNA-Seq data for 126 DNA repair genes with expression available in TCGA. Transformations for normality and adjustments for age at diagnosis, stage, and PCNA metagene expression were performed for all DNA repair genes. We also analyzed genomic event rates (GER) for somatic mutations, deletions, and amplification in driver genes and DNA repair genes. After performing empirical p-value testing with use of randomly selected gene sets, it was observed that OS could be predicted significantly by sets of DNA repair genes for 61% (11/18) of the cancers. Interestingly, PARP1 was not a significant predictor of survival for any of the 11 cancers. Results from cluster analysis of GERs indicates that the most opportunistic cancers for inhibition therapy may be AML, colorectal, and renal papillary, because of potentially less confounding due to lower GERs for mutations, deletions, and amplifications in DNA repair genes. However, the most opportunistic cancer for inhibition therapy is likely to be AML, since it showed the lowest GERs for mutations, deletions, and amplifications in DNA repair genes. In conclusion, our hypothesis-driven focus to target DNA repair gene expression adjusted for the PCNA metagene as a means of predicting OS in various cancers resulted in statistically significant sets of genes.

In recent years, the need for safe and modern composite barrier for the prevention of groundwater contamination and the provision of Geo-environmental protection has been studied together with the need of designing low cost and effective liner for isolating landfill contents from the environment. In this study, various mix designs involving two natural adsorbents, the Na-Bentonite and the pH-adjusted sawdust were prepared for a series of Geo-environmental experiments to be carried out to determine the adsorption capacity, buffering capacity, pH changes, and COD changes among others, in the presence of Pb(NO3)2 contaminant concentrations. Generally, the results showed an increase in adsorption capacity in the acidic segment of the treatment. An increase of 58% of the adsorption efficiency of the Na-Bentonite in adsorbing the contaminant at the highest concentration was the most important achievement of the system while in the acidic segment.

The objective of this study aimed to develop biodegradable calcium alginate microspheres carrying doxorubicin (Dox) at the micrometer-scale for sustained-release and the capacity of pH regulatory for transarterial chemoembolization. Ultrasonic atomization and CaCl2 cross-linking technologies were used to prepare the microspheres. A 4 by 5 experiment was first designed to identify imperative parameters. The concentration of CaCl2 and the flow rate of the pump were found to be critical to generate microspheres with a constant volume median diameter (~ 39 m) across 5 groups with different alginate:NaHCO3 ratios using each corresponding flow rate. In each group, the encapsulation efficiency was positively correlated to the Dox-loaded efficiency. Fourier-transform infrared spectroscopy showed that NaHCO3 and Dox were step-by-step incorporated into the calcium alginate microspheres successfully. Microspheres containing alginate:NaHCO3 = 1 exhibited rough and porous surfaces, high Young’s modulus and hardness. In each group with the same alginate:NaHCO3 ratio, the swelling rates of microspheres were higher in PBS containing 10% FBS compared to those in PBS alone. Microspheres with relative high NaHCO3 concentrations in PBS containing 10% FBS maintained better physiological pH and higher accumulated Dox release ratios. In two distinct hepatocellular carcinoma-derived cell lines, treatments with microspheres carrying Dox demonstrated that the cell viabilities decreased in groups with relative high NaHCO3 ratios in time- and dose-dependent manners. Our results suggested that biodegradable alginate microspheres containing relative high NaHCO3 concentrations improved the cytotoxicity effects in vitro.

Proteomics research has become one of the most important topics in the fields of life science and natural science. At present, research on protein–protein interaction networks (PPINs) mainly focuses on detecting protein complexes or function modules. However, existing approaches are either ineffective or incomplete. In this paper, we investigate function module detection mechanisms in PPIN, including open databases, existing detection algorithms and recent solutions. After that, we describe the proposed solution based on simplified swarm optimization (SSO) algorithm and gene ontology knowledge. The proposed solution implements SSO algorithm for clustering proteins with similar function, and imports biological gene ontology knowledge for further identifying function complexes and improving detection accuracy. Furthermore, we use four different categories of species dataset for experiment: Fruitfly, Mouse, Scere, and Human. The testing and analysis result show that the proposed solution is feasible, efficient and could achieve a higher accuracy of prediction than existing approaches.

Background: Vestibular Neuritis (VN) induces Acute Vestibular Syndrome (AVS). This study aimed to identify predictive factors of VN recovery by healing and/or compensation. Methods: In this longitudinal and prospective study, 40 patients were included. The first assessment (T0) included medical history taking (general and specific), for cardiovascular risk factors (CVRFs), a battery of diagnostic tests, bithermal caloric test (BCT), video Head Impulse Test (VHIT) and skull vibration induced nystagmus (SVIN). All patients also completed a Dizziness Handicap Inventory (DHI). All assessments were repeated 90±15 days (T3) later. Subjective criteria compensation were based on DHI total score and objective criteria compensation on the instrumental test results. Four groups of patients (A, B, C, D) were delineated by combining patients with normal vs abnormal vestibular tests and patients with normal vs abnormal DH. Results: CVRFs were associated with a poorer recovery of symptoms but not the age or BMI. Vestibular tests mainly BCT (canal paresis %), VHIT (lateral semicircular canal gain) and SVINT (nystagmus slow phase velocity) recovered within normal values in 20%, 20%, 26% of cases respectively at T3 for the 40-patient group. Conclusions: Vascular risk factors (hypercholesterolemia) are correlated with patients who do not recover their symptoms either by healing or compensation. The evolution did not show any significant difference between high or low frequency vestibular tests in patients recovering from their symptoms. However, some patients with objective recovery may continue to show persisting subjective symptoms.

The aim of this study was to investigate the physicochemical characterization and biological activities of chitosan (CH) based composite films with the incorporation of chestnut flower essential oil (CFEO). The composite films were prepared by casting method and characterized in terms of structural, morphological and mechanical properties via FT-IR, XRD, UV, SEM and TGA. The results proved the significantly increased water vapor permeability (WVP), heat resistance, antibacterial and antioxidant capabilities of CH-CFEO films. The incorporation of CH and CFEO enhanced the UV blocking, which made the film shield almost all UV light. Films with the tensile strength of 6.37 ± 0.41 MPa and elongation at break of 22.57 ± 0.35% were got with 6 mg mL-1 CFEO. Subsequently, the fruit preservation experiments also confirmed that the composite films could effectively extend the shelf life of bananas through their excellent water vapor and oxygen barrier. These desirable performances enable our newly developed composite films to be a remarkable packaging material to solve the fresh fruit preservation dilemma.

Treatment of HIV-associated lymphoma (HIV-Ly) with autologous stem cell transplantation (ASCT) has shown a surprisingly low relapse rate in several series. The aim of this study was to compare the clinical outcomes of HIV-Ly and lymphomas of the general population receiving ASCT. We compared two series of consecutive HIV-positive and HIV-negative patients, based on a 1:1 propensity score analysis, matching for age, sex, histology, disease status and prior therapies. We identified 44 patients in both groups. All HIV-positive patients received combination antiretroviral therapy (cART). With a median follow-up of 51 months, PFS was significantly higher in HIV-positive patients (4-years PFS 81% and 51%, in HIV-positive and HIV-negative patients, respectively, p=0.027). Four-year OS was 81% for HIV-positive and 67% in HIV-negative patients (p=0.15). The relapse rate was significantly higher in HIV-negative patients (36% vs 23%) (p=0.04). Our results clearly show that ASCT is an effective curative option for HIV-Ly, with better PFS and lower relapse rate compared to uninfected patients. A favourable effect of ASCT on HIV infection and immune system recovery, potential off-target effects of cART or other yet unknown factors may account for this observation.

Hematological malignancies refer to a heterogeneous group of neoplastic conditions of lymphoid and hematopoietic tissues classified in leukemias, Hodgkin and non-Hodgkin lymphomas and multiple myeloma, according to their presumed cell of origin, genetic abnormalities, and clinical features. Metabolic adaptation and immune escape, which influence various cellular functions including proliferation and survival of hematological malignant tumor cells, are major aspects of these malignancies that lead to therapeutic drug resistance. Targeting specific metabolic pathways is emerging as novel therapeutic strategy in hematopoietic neoplasms, particularly in acute myeloid leukemia and multiple myeloma. In this context, CD147, also known as Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) or Basigin, is one target-candidate involved in reprogramming metabolism in different cancer cells, including hematological malignant tumor cells. CD147 overexpression significantly contributes to the metabolic transformation of these cancer cells, by mediating signaling pathway, growth, metastasis and metabolic reprogramming, through its interaction, direct or not, with various membrane proteins related to metabolic, regulation including monocarboxylated transporters, integrins, P-glycoprotein and Glucose Transporter 1. This review explores the metabolic functions of CD147 and its impact on the tumor microenvironment, influencing the progression and neoplastic transformation in leukemias, myeloma and lymphomas. Furthermore, we highlight new opportunities for the development of targeted therapies against CD147, potentially improving the treatment of hematologic malignancies.

We introduce a full binary directed tree structure to represent the set of natural numbers, further categorizing them into three distinct subsets: pure odd numbers, pure even numbers, and mixed numbers. We adopt a binary string representation for natural numbers and elaborate on the composite methodology encompassing odd- and even-number functions. Our analysis focuses on examining the iteration sequence (or composition) of the Collatz function and its reduced variant, which serves as an analog to the inverse function, to scrutinize the validity of the Collatz conjecture. To substantiate this conjecture, we incorporate binary strings into an algebraic formula that captures the essence of the Collatz sequence. By this means, we transform discrete powers of 2 into continuous counterparts, ultimately culminating in the smallest natural number, 1. Consequently, the sequence generated through infinite iterations of the Collatz function emerges as an eventually periodic sequence, thereby validating an enduring 87-year-old conjecture.

The Mobius function is commonly used to define Euler's totient function and the Mangoldt function. Similarly, the summatory Mobius function (the Mertens function) can be used to define the summatory totient function and the summatory Mangoldt function (the second Chebyshev function).

Background: Molecular genetic events are among the numerous factors affecting the clinical course of papillary thyroid carcinoma (PTC). Recent studies have demonstrated that aberrant expression of miRNA, as well as different thyroid-related genes, correlate with the aggressive clinical course of PTC and unfavorable treatment outcome, which opens up new avenues for using them in personalization of the treatment strategy for patients with PTC. In the present work, our goal was to assess the applicability of molecular markers in preoperative diagnosis of aggressive variants of papillary thyroid cancer. Methods: The molecular genetic profile (expression levels of 34 different markers and BRAF mutation) was studied for 108 cytology specimens collected by fine-needle aspiration biopsy in patients with PTC having different clinical manifestations. Results: Statistically significant differences with adjustment for multiple comparisons (p &lt; 0.0015) for clinically aggressive variants of PTC were obtained for four markers: miRNA-146b, miRNA-221, FN1, and CDKN2A. Weak statistical correlation (0.0015&lt; р&lt;0.05) was observed for miRNA-31, -375, -551b, -148b, -125b, mtDNA, CITED1, TPO, HMGA2, CLU, NIS, SERPINA1, TFF3, and TMPRSS4. Conclusions: The recurrence risk of papillary thyroid carcinoma can be preoperatively predicted using miRNA-221, the fibronectin and cyclin-dependent kinase inhibitor 2A genes.

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) has gradually come to be regarded as an effective therapy, but the hospital mortality rate after ECPR is still high and unpredictable. The present study tested whether age-adjusted Charlson comorbidity index (ACCI) can be used as an objective selection criterion to ensure the most efficient utilization of medical resources. Methods: Adult patients (age ³ 18 years) receiving ECPR at our institution between 2006 and 2015 were included. Data regarding ECPR events and ACCI characteristics were collected immediately after extracorporeal membrane oxygenation (ECMO) setup. Adverse events during hospitalization were also prospectively collected. The primary endpoint was survival to hospital discharge. The second endpoint was short-term (2-year) follow-up outcome. Results: A total of 461 patients included in the study were grouped into low ACCI (ACCI 0–3) (240, 52.1%) and high ACCI (ACCI 4–13) (221, 47.9%) groups. The median ACCI was 2 (IQR: 1–3) and 5 (IQR: 4–7) for the low and high ACCI groups, respectively (P < 0.001). Cardiopulmonary resuscitation (CPR)-to-ECMO duration was comparable between the groups (42.1 ± 25.6 and 41.3 ± 20.7 min in the low and high ACCI groups, respectively; P = 0.754). Regarding hospital survival rate, 256 patients (55.5%) died on ECMO support. A total of 205 patients (44.5%) were successfully weaned off ECMO, but only 138 patients (29.9%) survived to hospital discharge (32.1% and 27.6% in low and high ACCI group, P = 0.291). Multivariate logistic regression analysis revealed CPR-to-ECMO duration and CPR cause of septic shock as significant risk factors for hospital survival after ECPR (P = 0.043 and 0.014, respectively), whereas age and ACCI were not (P = 0.334 and 0.164, respectively). The 2-year survival rate after hospital discharge for the 138 hospital survivors was 96% and 74% in the low and high ACCI groups, respectively (P = 0.002.)Conclusions: High ACCI before ECPR does not predict poor outcome of hospital survival. Therefore, ECPR should not be rejected solely due to high ACCI. However, high ACCI in hospital survivors is associated with a higher 2-year mortality rate than low ACCI, and patients with high ACCI should be closely followed up.

LCK, a member of the Scr kinase family, is a non-receptor tyrosine kinase involved in immune cell activation, antigen recognition, tumor growth, and cytotoxic response. The enzyme has usually been linked to T lymphocyte activation upon antigen recognition. Lck activation is central to CD4, CD8, and NK activation. However, recently, it has become clearer that activating the enzyme in CD8 cells can be independent of antigen presentation and enhance cytotoxic response. The role of Lck in NK cytotoxic function has been controversial in a similar fashion as the role of the enzyme in CAR T cells. Inhibition of Lck has been mainly to treat hematologic malignancies with a high rate of success. They may be useful in treating other tumor types, and they may be useful to prevent cell exhaustion. New, more selective inhibitors have been documented, and they have shown inter-esting activities not only in tumor growth but in the treatment of autoimmune diseases, asthma, and graft vs host disease. Drug repurposing and bioinformatics can aid in solving several unsolved is-sues on the role of Lck in cancer. In summary, the role of Lck in immune response and tumor growth is not a simple event and requires more research.

In surveying engineering tasks, close-range photogrammetry belongs to leading technology considering different aspects like the achievable accuracy, availability of hardware and software, accessibility to measured objects, or the economy. Hence, constant studies on photogrammetric data processing are desirable. Especially in industrial applications, the control points for close-range photogrammetry are usually measured using total stations. In the case of small objects, more precise positions of control points can be obtained by deploying and adjusting a three-dimensional linear network set up on the object. The article analyzes the accuracy of the proposed method, based on the measurement of the linear network using a tape with a precision of ±1 mm. The experiment shows that the adjusted positions of the network control points can be determined with high, one-millimeter accuracy. The photogrammetric 3D model derived referring to such control points and stereo-images captured with a non-metric camera is also characterized by the highest possible precision, which qualifies the presented method to accurate measurements used in surveying engineering. The authors prove that the distance between two randomly optional points derived from the 3D model of a dimensioned object is equal to the actual distance measured directly on it with one-millimeter accuracy.

Purpose: Inflammation and neutrophils play a central role in both Covid-19 disease and cancer. We aimed to assess the impact of pre-existing tumor-related inflammation on Covid-19 outcomes in patients with cancer and to elucidate the role of circulating neutrophil subpopulations. Methods: We conducted a multicenter retrospective analysis of 524 patients with cancer and SARS-CoV-2 infection, assessing the relationship between clinical outcomes and circulating inflammatory biomarkers collected before and during Covid-19 infection. Additionally, a unicenter prospective cohort provided data for an exploratory analysis, assessing the immunophenotype of circulating neutrophils and inflammatory cytokines. The primary endpoints were 30-day mortality and severity of Covid-19 disease. Results: Prior to Covid-19, 25% of patients with cancer exhibited elevated dNLR, which increase to 55% at the time of Covid-19 diagnosis. We developed the FLARE score, incorporating both tumor and infection-induced inflammation, which categorized patients into four prognostic groups. The poor prognostic group had a 30-day mortality rate of 68%, significantly higher than the 23% in the favorable group (p<0.0001). The score proved to be an independent predictor of early mortality. The prospective analysis revealed a shift towards immature forms of neutrophils and higher IL-6 levels in patients with cancer and severe Covid-19 infection. Conclusions: A pre-existing tumor-induced pro-inflammatory state significantly impacts Covid-19 outcomes in patients with cancer. The FLARE score serves as an easy-to-use and worldwide accessible effective tool to predict outcomes in this population, while circulating neutrophil subpopulations might provide additional information and could help refine outcome prediction.

BACKGROUND AND AIMS: Cardiovascular disease and colorectal cancer (CRC) are significant health problems and share some risk factors. The aim of our study was to develop and validate a predictive score for advanced colorectal neoplasia (CRN) based on risk factors for cardiovascular disease and CRC. MATERIALS AND METHODS: A cross-sectional study comprising a derivation cohort and an external validation cohort of 1049 and 308 patients respectively. A prediction score for advanced CRN (CRNAS: Colorectal Neoplasia Advanced Score) was developed from a logistic regression model, comprising sex, age, first-degree family history for CRC, systolic and diastolic blood pressure, total cholesterol, HDL-cholesterol, body mass index, diabetes, smoking, and antihypertensive treatment. Other cardiovascular risk scores (Framingham-Wilson, REGICOR, SCORE and FRESCO) were also used to predict the risk of advanced CRN. The discriminatory capacity of each score was evaluated using the area under the curve (AUC). RESULTS: CRN were found in 379 subjects from the derivation cohort (36%) including 228 patients (22%) with an advanced CRN. Male sex, age, diabetes, and smoking were identified as independent risk factors for advanced CRN. The newly created score (CRNAS), showed an AUC of 0.68 (95% CI: 0.64-0.73) for advanced CRN, which was better than cardiovascular risk scores (p

We propose a neural-network-based watermarking method that introduces the quantized activation function that approximates the quantization of JPEG compression. Many neural-network-based watermarking methods have been proposed. Conventional methods have acquired robustness against various attacks by introducing an attack simulation layer between the embedding network and the extraction network. The quantization process of JPEG compression was replaced by the noise addition process in the attack layer of the conventional methods. In this paper, we propose a quantized activation function that can simulate the JPEG quantization standard as it is in order to improve the robustness against the JPEG compression. Our quantized activation function consists of several hyperbolic tangent functions and is applied as an activation function for neural networks. Our network was introduced in the attack layer of ReDMark proposed by Ahmadi et al. to compare it with their method. That is, the embedding and extraction networks had the same structure. We compared the usual JPEG compressed images and the images applying the quantized activation function. The results showed that a network with quantized activation functions can approximate JPEG compression with high accuracy. We also compared the bit error rate (BER) of estimated watermarks generated by our network with those generated by ReDMark. We found that our network was able to produce estimated watermarks with lower BERs than those of ReDMark. Therefore, our network outperformed the conventional method with respect to image quality and BER.

Fortified human milk is the first choice for preterm infants. Although individualized fortification is recommended, the optimal method for this population remains uncertain. We conducted a comparative study assessing the growth effects of adjusted (AF) and targeted fortification (TF) in extremely low birth weight (ELBW) infants. This single-center, randomized, controlled clinical trial was conducted at a tertiary neonatal unit in Spain. Eligible participants were premature infants with a birthweight <1000g exclusively fed with human milk. A total of 38 patients were enrolled, 15 of them randomised to AF group and 23 to TF group. AF was based on BUN concentration and TF on human milk analysis. The primary outcome was weight gain velocity (g/kg/day).No significant differences were found in weight gain velocity at 28 days, at 36 weeks of postmenstrual age, at discharge nor during intervention. Protein intake was significantly higher in AF group (5.02 g/kg/day vs 4.48 g/kg/day, p= 0.001). No differences were found in lipids, carbohydrates and energy intake; neither in weight z score change between the different time points; nor in length and head circumference growth. Both AF and TF are comparable methods of fortification and provide appropriate growth rate in ELBW infants.

A crucial aspect in developing machine learning algorithms (or any type of predictive models) is the comparison of different algorithmic candidates based on evaluation criteria that measure their accuracy and practical value in terms of successfully capturing the complexity of the underlying problem and generalizing in a wide range of real-world scenarios. In the domain of diabetes mellitus machine learning techniques are widely employed in the prediction of future values of glucose concentration in the blood in order to assist the patient in avoiding deviations from the normo-glycemic value range and the consequences of hyper- and hypoglycemia. In the relative literature there is an apparent lack of a uniformly adopted evaluation metric which could combine the clarity and direct comparative nature of statistical mathematical formulas dealing with prediction error residuals (e.g., the RMSE) with the clinical insights and the visual-qualitative approach of clinical evaluation tools (e.g., Clarke's EGA). Mean Adjusted Exponent (MADEX) error metric, proposed in this paper, attempts to address this need by providing a validation tool based on an easy to implement mathematical formula, that incorporates adjustable parameters of clinical significance.

Cellulose nanocrystals (CNCs) are a kind of nano-inclusions that have experienced tremendous expansion in the material industry due to their outstanding mechanical qualities, sizable surface area, and capacity for functional tuning. Due to their vast potential, however, present practises fall short of fully using them. For example, employing CNCs in various matrices with various surface chemistries can be challenging; this problem tends to get worse if the focus is furthered on bio-based applications. This paper reviews the use of CNCs as fillers in natural and man-made polymers; we have explored in depth the production, characterisation, and of CNCs from various sources and their inclusion into various matrices. Surface alterations and the introduction of CNCs in biodegradable polymer can have a significant impact on several industrial behemoths such as tissue engineering and biomedical applications; therefore, pursue of current manuscript is extremely warranted. Throughout the manuscript various assembly techniques that involves alteration and adjustment of polymer network in building up a hydrogel with higher fracture energy and mechanical properties are also included. From rheological perspective the hydrogel processing is also discussed with some models routinely used in the literature to describe these hydrogels. Finally, bio-based hydrogels mechanically reinforced with CNCs such as Xanthan Gum, Alginate, protein, and polysaccharides were discussed.

To advance probiotic research, a comprehensive understanding of bacterial interactions with human physiology at the molecular and cellular levels is fundamental. Lacticaseibacillus rhamnosus LGG® is a bacterial strain that has long been recognized for its beneficial effects on human health. Probiotic effector molecules derived from LGG®, including secreted proteins, surface-anchored proteins, polysaccharides, and lipoteichoic acids, that interact with host physiological processes have been identified. In vitro and animal studies have revealed that specific LGG® effector molecules stimulate epithelial cell survival, preserve intestinal barrier integrity, reduce oxidative stress, mitigate excessive mucosal inflammation, enhance IgA secretion, and provide long-term protection through epigenetic imprinting. Pili on the cell surface of LGG® promote adhesion to the intestinal mucosa and ensure close contact to host cells. Extracellular vesicles produced by LGG® recapitulate many of these effects through their cargo of effector molecules. Collectively, the effector molecules of LGG® exert a significant influence on both the gut mucosa and immune system, that promotes intestinal homeostasis and immune tolerance.

This paper is devoted to the study of multi-dimensional integral transform with Fox H-function in the kernel in weighted spaces integrable functions in the domain R+n with positive coordinates. Mapping properties such as the boundedness, the range, the representations of the considered transformation are established.

In recent experimental studies, we reported the aggravating effects of Asian sand dust (ASD) on male reproductive function in mice. However, the effects of fetal ASD exposure on male reproductive function have not been investigated. The present study investigated the effects of fetal ASD exposure on reproductive function in male offspring. Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14 of gestation, and the reproductive function of male offspring was determined at 5, 10, and 15 weeks after birth. The secondary sex ratio was significantly lower in the fetal ASD-exposed mice than in the controls. Histologic examination showed partial vacuolation of seminiferous tubules in immature mice. Moreover, daily sperm production (DSP) was significantly less in the fetal ASD-exposed mice than in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less than the controls at both 5 and 10 weeks. However, both the histologic changes and the DSP decrease were reversed as the mice matured. These findings suggest that ASD exposure affects both the fetal development and the reproductive function of male offspring. In the future, it will be necessary to clarify the onset mechanisms of ASD-induced male fetus death and male reproductive disorders.

Chronic kidney disease patients treated by hemodialysis present a high cardio-vascular morbidity and mortality. There is an imperative need for novel biomarkers in identifying and to offer possible therapeutically intervention in these patients. We performed a prospective observational cohort study on 77 patients in the period October 2021 – October 2023. We measured serum plasma levels of Interleukin 1-Beta, Galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. Mean age was 61.02 (±11.81) years, 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54 %) and more than two thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-Beta correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle tele systolic diameter. Galectin 3 values negatively correlated with aortic valve fibrosis and mitral valve calcifications and human suppression tumorigenity factor 2 negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better asses the cardio-vascular disease in patients on maintenance hemodialysis.

Systemic AL amyloidosis is a challenging disease for which many patients are considered frail in daily clinical practice. However, no study has so far addressed frailty and its impact on the outcome of these patients. We built a simple score to predict mortality based on three frailty-associated variables: age, ECOG performance status (&lt;2 vs. 2) and NT-proBNP (&lt;8500 vs. 8500 ng/L). Four-hundred and sixteen consecutive newly diagnosed patients diagnosed at ten sites from the Spanish Myeloma Group were eligible for the study. The score was developed in a derivation cohort from a referral center, and it was externally validated in a multicenter cohort. On multivariate analysis the three variables were independent predictors of survival. The score was able to discriminate four groups of patients in terms of overall survival and early mortality in both cohorts. Comorbidity was also analyzed with the Charlson comorbidity index, but it did not reach statistical significance in the model. A nomogram was created to easily estimate the mortality risk of each patient at each time point. This score is a simple, robust, and efficient approach to dynamically assess frailty-dependent mortality both at diagnosis and throughout the follow-up. The optimal treatment for frail AL amyloidosis patients remains to be determined but we suggest that the estimation of frailty-associated risk could complement current staging systems, adding value in clinical decision-making in this complex scenario.

Although, central venous pressure (CVP) is among the most frequent estimated hemodynamic parameters in the critically ill setting, extremely little is known on how intensive care unit (ICU) nurses use this index in their decision-making process. The purpose of the study was to develop a new questionnaire for accessing how ICU nurses use CVP measurements to address patients’ he-modynamics investigating its validity and reliability. A cross-sectional study was conducted among 120 ICU nurses from four ICUs of Greece. Based on a comprehensive literature review and the evaluation of a five-experts panel a new questionnaire, named “CVP-Score”, was created having 8 items. The construct validity and the reliability of the questionnaire were examined. The half of the study participants’ (51.7%) was working at a specialized ICU, and they had a mean [±Standard Deviation (SD)] ICU experience of 13(±7.1) years. The estimated construct validity of the new-developed tool was acceptable, while the internal consistency reliability as measured by Cronbach alpha was excellent (0.901). CVP Score had acceptable test-retest reliability (r=0.996, p<0.001) and split-half reliability (0.855). CVP Score is a valid and reliable instrument for measuring how critical care nurses use CVP measurements in their decision-making process.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

A Challenging task in routine practice is finding distinction between benign and malignant paragangliomas and pheochromocytomas. The aim of this study is a comparative analysis of angiogenesis by assessing intratumoral microvascular density (MVD) with immunohistochemical (IHC) markers (CD31, CD34, CD105, ERG), and S100 immunoreactivity, Ki67 proliferative index, SDHB expressiveness, tumor size with one the most utilized score Pheochromocytoma of Adrenal Gland Scales Score (PASS), using tissue microarray (TMA) with 115 tumor samples, 61 benign (PASS&lt;4) and 54 potentially malignant (PASS ≥4). We found no notable difference between intratumoral MVD and potentially malignant behavior. Group of potentially malignant tumors are significantly larger in size, have lower intratumoral MVD, and decreased number of S100 labeled sustentacular cells. Both groups have low proliferative activity (mean Ki67 is 1,02 and 1,22 respectively). Most tumors maintains SDHB expression, only 6 cases (5,2%) showed a loss of expression (4 of them in PASS&lt;4 group and 2 in PASS≥4). PASS score is easy available for assessment, and complemented with markers of biological behavior completes risk stratification algorithm. Size is directly related with PASS score and malignancy. Intratumoral MVD is extensively developed but it is not crucial in evaluating the malignant potential.

The basic idea is to expand the completed zeta function $\xi(s)$ in MacLaurin series (infinite polynomial), which can be further expressed as infinite product (Hadamard product) by conjugate complex roots. Finally, the functional equation $\xi(s)=\xi(1-s)$ leads to $(s-\alpha_i)^2 = (1-s-\alpha_i)^2, i \in \mathbb{N}$ with solution $\alpha_i= \frac{1}{2}, i \in \mathbb{N}$, where $\alpha_i$ are the real parts of the zeros of $\xi(s)$, i.e., $s_i =\alpha_i\pm j\beta_i, i\in \mathbb{N}$. Therefore, a proof of the Riemann Hypothesis is achieved.

Selecting the optimal activation function for training deep neural networks has always been challenging because it significantly impacts the neural network’s performance and training speed. At this point, researchers are more likely to employ RELU than other well-known activation functions. After RELU, researchers have proposed many activation functions to improve RELU. None of them was capable of surpassing RELU as their most significant rival. SWISH outperformed RELU in several challenging experiments like classification, object detection, and tracking. Replacing RELU units with SWISH, which improves performance in many tasks. This paper proposed a new activation function surpassing Google’s brain’s SWISH function, Which we named AIF. Experiments indicate that our proposed activation function outperforms SWISH in various tasks.

The quiet-time solar wind electrons feature non-thermal characteristics when viewed from the perspective of their velocity distribution functions. They typically have an appearance of being composed of a denser thermal “core” population plus a tenuous energetic “halo” population. At first, such a feature was empirically fitted with the Kappa velocity space distribution function, but ever since the ground-breaking work by Tsallis, the space physics community has embraced the potential implication of the Kappa distribution as reflecting the non-extensive nature of the space plasma. From the viewpoint of microscopic plasma theory, the formation of non-thermal electron velocity distribution function can be interpreted in terms of the plasma being in a state of turbulent quasi equilibrium. Such a finding brings forth the possible existence of a profound inter-relationship between the non-extensive statistical state and the turbulent quasi-equilibrium state. The present paper further develops the idea of solar wind electrons being in the turbulent equilibrium, but unlike the previous model, which involves the electrostatic turbulence near the plasma oscillation frequency (i.e., Langmuir turbulence), the present paper considers the impact of transverse electromagnetic turbulence, particularly, the turbulence in the whistler-mode frequency range. It is found that the coupling of spontaneously-emitted thermal fluctuations and the background turbulence leads to the formation of non-thermal electron velocity distribution function of the type observed in the solar wind during quiet times. This demonstrates that the whistler-range turbulence represents an alternative mechanism for producing the Kappa-like non-thermal distribution, especially close to the Sun and in the near-Earth space environment.

This study investigated the development of novel probiotic formulations specifically designed for rainbow trout aquaculture. The project evaluated the effects of two formulations containing potential probiotic strains isolated from rainbow trout itself. These effects were assessed on various parameters including growth performance, immune response, liver enzyme activity, gene expression related to immunity, and the composition of the bacterial gut microbiota in rainbow trout (Oncorhynchus mykiss). In a completely randomized experimental design, a total of 450 rainbow trout were randomly divided into 70-liter fiberglass tank. The study included six treatments of three replicates (n=18 tanks). Six dietary treatments were included (A) and (B) containing three strains of Pediococcus sp P15, Lactococcus lactis ml3, Weissella cibaria ml6 at two dosages (300 and 500 mg/kg), treatments (C) and (D) containing five strains of P. sp P15, L. lactis ml3, W. cibaria ml6, Enterococcus faecium E10 and Lactobacillus curvatus 13A at two dosages (300 and 500 mg/kg), a commercial probiotic (E) at 300 mg/kg, and a control group (F) without probiotics. Treatments of (A), (B) and (E) resulted in the highest final weights in compared to control group. Fish fed treatments (A) and (B) had the lowest FCR than other groups. Treatments (A) and (D) showed a significant increase in immunoglobulin M (IgM) concentration compared to other groups. The expression of tumor necrosis factor (TNF) was significantly lower in group (A) than the control. In contrast, the expression of interleukin 6 (IL6) and immunoglobulin T (IgT) was increased 4.4-fold and 41-fold, respectively, in group (A) compared to control group. Among the probiotic fed treatments, group (A) showed a significant higher number of lactic acid bacteria compared to other groups during the experiment. This study highlights the significant role of treatment (A) containing three strains of P. sp P15, L. lactis ml3, and W. cibaria ml6 at a dosage of 300 mg/kg as a potential probiotic product for the rainbow trout industry.

Two distinct measures of information, connected respectively to the amplitude and phase of the wave function of a particle, are proposed. There are relations between the time derivatives of these two measures and their gradients on the configuration space, which are equivalent to the wave equation. The information related to the amplitude measures the strength of the potential coupling of the particle (which is itself aspatial) with each volume of its configuration space, i.e. its tendency to participate in an interaction localized in a region of ordinary physical space corresponding to that volume. The information connected to the phase is that required to obtain the time evolution of the particle as a persistent entity starting from a random succession of bits. It can be considered as the information provided by conservation principles. The meaning of the so-called "quantum potential" in this context is briefly discussed.

In order to solve the problem of feature extraction of underwater acoustic signals in complex ocean environment, a new method for feature extraction from ship radiated noise is presented based on empirical mode decomposition theory and permutation entropy. It analyzes the separability for permutation entropies of the intrinsic mode functions of three types of ship radiated noise signals, and discusses the permutation entropy of the intrinsic mode function with the highest energy. In this study, ship radiated noise signals measured from three types of ships are decomposed into a set of intrinsic mode functions with empirical mode decomposition method. Then, the permutation entropies of all intrinsic mode functions are calculated with appropriate parameters. The permutation entropies are obviously different in the intrinsic mode functions with the highest energy, thus, the permutation entropy of the intrinsic mode function with the highest energy is regarded as a new characteristic parameter to extract the feature of ship radiated noise. After that, the characteristic parameters, namely, the energy difference between high and low frequency, permutation entropy, and multi-scale permutation entropy, are compared with the permutation entropy of the intrinsic mode function with the highest energy. It is discovered that the four characteristic parameters are at the same level for similar ships, however, there are differences in the parameters for different types of ships. The results demonstrate that the permutation entropy of the intrinsic mode function with the highest energy is better in separability as the characteristic parameter than the other three parameters by comparing their fluctuation ranges and the average values of the four characteristic parameters. Hence, the feature of ship radiated noise can be extracted efficiently with the method.

This study presents a novel approach for automating the body condition scoring of dairy cows, leveraging advancements in 3D imaging technology and deep neural networks. The primary objective was to design and implement a system capable of accurately and efficiently assessing the body condition of dairy cows, a critical metric in livestock management for optimizing health and productivity. To achieve this, a 3D camera was employed to capture detailed point cloud data, reconstructing the three-dimensional morphology of individual cows. The obtained data were then fed into a deep neural network, specifically tailored for the task of ranking body condition. The neural network was trained on a diverse dataset of annotated body condition score representing varying degrees of body condition, ensuring robust performance across different physiological states. The results demonstrate the efficacy of the proposed system in automatically and objectively scoring the body condition of dairy cows. The automated process not only expedites the assessment but also reduces the subjectivity associated with manual scoring methods. This innovative approach holds promise for improving the efficiency of dairy farm management by providing timely and accurate body condition assessments. The integration of 3D imaging and deep learning techniques paves the way for future advancements in precision livestock farming, contributing to enhanced animal welfare, optimized production, and sustainable agriculture practices.

Background and Objectives:: Hip osteoarthritis is the main cause physical disability, also has a serious impact on the efficiency and independence of older people. The aim of the study was to analyze the relationship between hip osteoarthritis and the risk of sarcopenia. Our main hypothesis was whether the risk of sarcopenia, as measured by the SARC F questionnaire , is related to the physical fitness of older people with hip osteoarthritis. Materials and Methods: The study was conducted with the participation of 177 people of aged 65 or more, diagnosed hip osteoarthritis. The subjects were assessed using the SARC F questionnaire, the Short Physical Performance Battery (SPPB) and Timed Up and Go (TUG) test. The subjects were divided into two groups depending on the result they obtained in the SARC F questionnaire (group 1- SARC F &lt;4, group 2 - SARC F ≥ 4). Results: There was a significant correlation between the results in the SARC F and the results of the TUG (p&lt;0.001) and the SPPB test, both the SPPB total score (p&lt;0.001)and its elements: SBBP chair stand test (p&lt;0.001), SPPB balance test (p&lt;0.001), SPPB gait speed test (p&lt;0.001). Logistic regression of the SPPB and TUG predictors showed that in SARC F more than 4 predicted worse SPPB and TUG outcomes. In the SARC group, F above 4 increases the odds of poorer scores in SPPB OR=1.097; CI 95% 1.053-1.146 and TUG, OR=1.096; CI 95% 1.104-1.266. Conclusion: The study showed that the results obtained in the SARC F questionnaire correlate with the possibilities of physical functioning in patients with hip osteoarthritis SARC F is an inexpensive method that can be used to assess the risk of sarcopenia. Healthcare professionals, especially in primary care, should consider assessing the risk of sarcopenia especially in people with hip osteoarthritis.

One of the major challenges in the post-genomic era is elucidating the genetic basis of human diseases. In recent years, studies have shown that polygenic risk scores (PRS), based on aggregated information from millions of variants across the human genome, can estimate individual risk for common diseases. In practice, the current medical practice still predominantly relies on physiological and clinical indicators to assess personal disease risk. For example, caregivers mark individuals with high body mass index (BMI) as having an increased risk to develop type 2 diabetes (T2D). An important question is whether combining PRS with clinical metrics can increase the power of disease prediction in particular from early life. In this work we examined this question, focusing on T2D. We show that an integrated approach combining adult BMI and PRS achieves considerably better prediction than each of the measures on unrelated Caucasians in the UK Biobank (UKB, n=290,584). Likewise, integrating PRS with self-reports on birth weight (n=172,239) and comparative body size at age ten (n=287,203) also substantially enhance prediction as compared to each of its components. While the integration of PRS with BMI achieved better results as compared to the other measurements, the latter are early-life measurements that can be integrated already at childhood, to allow preemptive intervention for those at high risk to develop T2D. Our integrated approach can be easily generalized to other diseases, with the relevant early-life measurements.

Vascular impairment, muscle atrophy, and cognitive decline are important age-related conditions that have a significant impact on health. Vascular impairment directly disrupts the flow of blood, leading to the decline of muscle mass associated with aging (sarcopenia) and the decline of neuronal functions (neurodegeneration). Our inadequate understanding of the complex relationships between these conditions impedes precise diagnosis and effective treatment. This review analyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sarcopenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, inflammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can enhance therapeutic strategies and lead to better outcomes for patients. Here, we highlight the intricate relationship among vascular dysfunction, degenerative muscle, and cognitive decline, underscoring the need for multidisciplinary approaches to treatment. Progress in this field can result in improved diagnosis, more potent therapeutic options, and enhanced preventative measures, all of which can contribute to an improved quality of life for the aging population.

Methylmercury (MeHg) intoxication is a global health concern. Although MeHg neurotoxicity is well-recognized, less is known about MeHg's effects on metabolism. In this study, we evaluated MeHg intoxication (20mg/L in drinking water for 20 days) effects on liver and epididymal white fat (EWF) in young ApoE knockout (ko) and wild-type mice. The former is well-known to show spontaneous dyslipidemia. Hg levels in hair, liver, and EWF were measured to assess the degree of MeHg exposure. We also evaluated body weight gain, plasma triglycerides, total cholesterol levels, and liver injury by assessing steatosis score, AST, ALT, SOD, and TBAR levels. To evaluate EWF, we analyzed mean wet weight and adipocyte diameter, plasma leptin levels and metabolomics. Hg levels were markedly higher among intoxicated mice. ApoE ko mice showed higher Hg in the hair but lower levels in the liver and EWF than wild-type controls. Among wild-type mice, MeHg compromised weight gain and increased liver TBAR levels compared to non-challenged controls. Among non-intoxicated mice, ApoE deficiency significantly increased triglyceride, total cholesterol, and liver transaminases with reduced EWF wet weight, hepatic SOD, and plasma leptin levels. MeHg accumulation together with ApoE deficiency elevated total cholesterol, triglycerides, hepatic transaminases, and TBARS. We found distinct EWF metabolite activity in different scenarios of ApoE deficiency and MeHg intoxication, highlighting increased cardiovascular risk especially when both challenges occur. Further studies are required to elucidate the underlying mechanisms involved in these effects and the target nutritional interventions in most need to ameliorate them.

The accurate forecasting of solar power output is essential for ensuring the stable and efficient operation of grid-connected photovoltaic (PV) systems, especially when faced with variable weather patterns. This research focuses on the integration of Machine Learning (ML) methodologies and climatic parameters to predict solar panel energy generation, with a specific emphasis on addressing consumption-production imbalances. Leveraging a dataset sourced from the Kaggle platform, the study is conducted in the context of Estonia, aiming to optimize solar energy utilization in this geographic region. The dataset, obtained from Kaggle, encompasses comprehensive information on climatic variables, including sunlight intensity, temperature, and humidity, alongside corresponding solar panel energy output. Leveraging machine learning algorithms, including XGBoost regression and neural networks, our model aims to identify complex patterns and relationships within the datasets. By tailoring the model to Estonia's climatic nuances, we seek to enhance the accuracy of energy production forecasts and, consequently, better manage the challenges associated with consumption-production imbalances. Furthermore, the research investigates the adaptability of the proposed model to diverse climatic conditions, ensuring its applicability for similar endeavors in other geographical locations. The performance of the forecasting model will be evaluated using error metrics like mean absolute error (MAE) and root mean squared error (RMSE). This study leverages a comprehensive dataset from Kaggle and utilizes advanced machine learning techniques to generate valuable insights. These insights can inform the development of sustainable energy policies and practices, ultimately leading to a more efficient and reliable renewable energy infrastructure.

The uncertainty in the secondary path of an Active Noise Control (ANC) headphone affects the waterbed effect and stability of the feedback system. This study focuses on the uncertainty of the secondary path when real users wear headphones, and proposes a new uncertainty constraint based on the measured results of the secondary path transfer function under different wearing conditions of dummy head and limited subjects. This constraint and a cascaded second-order infinite impulse response filter with fixed coefficients are used to formulate a control strategic function, which is optimized by the Improved Grey Wolf Optimizer (IGWO) algorithm to obtain the optimal controller with better noise reduction performance. The proposed method and simulation model are validated based on the experimental test results. The results demonstrate that the safety factor and waterbed suppressing factor contained in the proposed uncertainty constraint ensures more stable noise reduction and effective suppression of the waterbed effect for new subjects without a priori data.

Although a growing number of evidence emphasizes superior of VATS over conventional thoracotomy, still is little known about early postoperative diaphragm muscle function after lobectomy via these two approahces. To fill the gap in existing literature, we conducted comparative study between VATS and conventional thoracotomy in terms of postoperative diaphragm muscle function, assessing its contractility, strength, magnitude of effort and potential risk of dysfunction such as: atrophy and paralysis. A total of 59 patients (30 after VATS), who underwent anatomical pulmonary resection at our institution, were enrolled into this study. The control group was consisted of 28 health subjects without medical condition could contribute to diaphragm dysfunction. Diaphragm muscle was assessed before and after surgery using ultrasonography. We found that both surgical approaches were associated with postoperative impairment of diaphragm muscle function - compared to baseline data. Postoperative reduction of diaphragm contraction was demonstrated in all of 59 patients. In case of control group, the differences between measurements were no observed. We noted that lobectomy via thoracotomy was linked with greater percentage of patients with diaphragm paralysis or/and atrophy that VATS. Similar findings were observed in refer to diaphragm magnitude effort, as well as, diaphragm contraction strength, where minimal invasive surgery was associated with better diaphragm function parameters - in comparison to thoracotomy. Disturbance of diaphragm work was reported both at operated and non-operated side. Upper right and left lobectomy was connected with greater diaphragm function impairment than other segments. In conclusion, VATS technique seems to be less invasive than conventional thoracotomy providing a better postoperative function of a main respiratory muscle.

The relationship of Amyotrophic Lateral Sclerosis, Parkinson Disease and other age-related neurodegenerative diseases associated with mitochondrial dysfunction has led to study of the mitochondrial fission gene Drp1 in Drosophila. Drp1 can interact with mitochondrial proteins including parkin and the Drosophila Bcl-2 proteins. Mutations in Drp1 can lead to mitochondrial dysfunction and neuronal loss. Ddc-Gal4 was exploited to direct the expression of Drp1 and the inhibition of Drp1 in neurons. Here, the inhibition of Drp1 seems to compromise locomotor function throughout life but does not alter longevity. The consequences of Drp1 overexpression can be suppressed through overexpression of pro-survival Bcl-2 gene Buffy or by inhibition of the pro-cell death Bcl-2 homologue Debcl. The expression of Buffy suppresses the poor climbing induced by loss of Drp1 function. Interestingly, the loss of parkin function is rescued by the directed inhibition of Drp1. Alteration of the expression of Drp1 acts to phenocopy neurodegenerative disease phenotypes in Drosophila, while overexpression of Buffy can counteract these phenotypes to improve overall health. The pro-survival effect of Buffy can rescue the phenotypic effect due to the Drp1-induced apoptosis. The diminished health due to either overexpression or inhibition of Drp1 has produced a novel model to investigate mechanisms underlying neurodegenerative disease.

Objectives. Invasive fungal spondylodiscitis (IFSD) is rare and could be lethal in certain circumstances. Previous literature revealed limited data concerning the outcomes. This study aimed to establish a risk-scoring system. Methods. A total of 53 patients were included in the study from a multi-centered database in Taiwan. All the clinicopathological and laboratory data were retrospectively analyzed. Variables strongly related to 1-year mortality were identified using a multivariate Cox proportional hazards model. A receiver operating characteristic curve was used to express the performance of our IFSD scoring model. Results. Five strong predictors were included in the IFSD score: predisposing immunocompromised state, the initial presentation of either radiculopathy or myelopathy, initial laboratory findings of WBC > 12.0 or < 0.4 103/uL, hemoglobin < 8 g/dL, and evidence of candidemia. 1-year mortality rates for patients with IFSD Scores of 0, 1, 2, 3, and 4 were 0%, 16.7%, 56.3%, 72.7%, and 100%, respectively. The area under the curve of the receiver operating characteristic curve was 0.823. Conclusions. We developed a practical scoring model with easily obtained demographic, clinical, and laboratory parameters to predict the probability of 1-year mortality in patients with IFSD. However, more large-scale and international validations would be necessary before this scoring model is commonly used.

This longitudinal study examined the development of executive function and calibration accuracy in pre-adolescents. Two hundred sixty two students(127 females) from grades 4 (n = 91), 5 (n = 89) and 6 (n = 82) took measures of executive function and performance calibration in a sport task, three times within a period of 20 months. A latent growth curve modeling analysis showed a significant relation between the rates of change of executive function and calibration. Further, the results showed a dynamic interplay in the development of executive function and calibration. There were significant inter-individual differences in the estimated population means both in executive function and calibration and in the rate of change of executive function, but not in the rate of change for calibration. The age of the participants had a positive effect only on the estimated population mean of executive function.

The unified Mittag-Leffler (ML) function is important factor in formulation of compact form of fractional integrals. In this paper estimations of integral operators, with the unified ML function as kernel are given. The Hadamard inequality in the form of fractional integrals is proved by considering refinement of convexities. These estimations provide various inequalities as refinements of recently published results.

Cardiovascular disease (CVD) is considered to be one of the leading health issues in Thailand. CVD not only contributes to an increase in the number of hospital admissions year on year but also impacts on the rising health care expenditure for the treatment and long-term care of CVD patients. Therefore, this study is aimed at examining the impacts of risk reduction strategies on the number of CVD hospital admissions, Disability-Adjusted Life Years (DALYs) and the costs of hospitalisation. To estimate such impacts a CVD cost-offset model wasapplied using a Microsoft Excel spreadsheet. The number of the mid-year population was classified by age, gender and the CVD risk factor profiles from the recent Thai National Health Examination Survey (NHES) IV. This survey was chosen as the baseline population. The CVD risk factor profiles included age, gender, systolic blood pressure, total cholesterol, and smoking status. The Asia-Pacific Collaborative Cohort Study (APCCS) equation was applied to predict the probability of developing CVD over the next eight-year period. Estimates on the following were obtained from the model: (1.) the CVD events both fatal and non-fatal; (2.) the difference between the projected number of deaths and the actual number of deaths in that population; (3.) the number of patients who are expected to live with CVD; (4.) the DALYs from the estimated number of fatal and non-fatal events; (5.) the cost of hospital admissions. Four CVD risk strategy scenarios were investigated as follows: (1.) the do nothing scenario; (2.) the optimistic scenario; (3.) achieve the UN millennium development goal; and (4.) the worst-case scenario. The findings showed that over the next eight years there are likely to be 3,297,428 recorded cases of CVD; 5,870,049 cases of DALYs; and, approximately ฿57,000 million, ($1.9 billion), is projected as the total cost of hospital admissions. However, if the current health policy can reduce the levels of risk factors as defined in the optimistic scenario or such policy meets the specifications of the UN millennium development goal,there would be a significant reduction in the number of hospital admissions. These are estimated to be a reduction of 522,179 male and 515,416 female cases. With these results it is expected that health care costs would save approximately ฿9,000 million, ($298.3 million), for CVD and 900,000 million of DALYs over the next eight years. However, if there is an upward trend in the risk factors as predicted in the worst-case scenario, then there will be an increase of 428,220 CVD cases; consequently, DALYs cases may rise by 766,029 while the hospitalisation costs may increase by approximately ฿7,000 million, ($232.1 million). Based on our findings, reducing the levels of CVD risk factors in the population will drastically reduce: (1.) the number of CVD cases; (2.) DALYs cases; and (3.) health care costs. Therefore it is recommended that the health policy should enhance the primary prevention programs which would be targeted at reducing the CVD risk factors in the population.

Background/Objectives: Community-acquired pneumonia (CAP) is a common emergency presentation in Australia, with the choice of admitting specialty unit often influenced by pneumonia severity and comorbidities. However, it remains unclear whether there are between-specialty differences in patient characteristics and outcomes. We sought to address this issue by investigating the characteristics and outcomes of CAP patients admitted to General Medicine (GM) versus Respiratory units.Methods: This retrospective observational study utilised data from the two largest metropolitan hospitals in South Australia, encompassing all non-COVID-19-related CAP admissions throughout 2021 to 2023. Hospital length of stay (LOS), in-patient and 30-day mortality, and 30-day readmission rates were assessed by propensity-score-matching (PSM) with using 14 variables.Results: Of the 3,004 cases of non-COVID-19 CAP admitted across the two hospitals during the study period, 2,673 (71.8%) were admitted under GM units and 331 (9.1%) under Respiratory units. GM patients were, on average, a decade older, presented with a significantly higher burden of comorbidities, exhibited a greater prevalence of frailty and had higher pneumonia severity compared to those admitted under a Respiratory unit, (P

Prior work has suggested that discrimination and immigration-related stress may impede mental health care seeking and utilization among Latinx populations. These effects may be more nuanced as both discrimination and immigration-related stress may increase symptomology, particularly posttraumatic stress disorder (PTSD) and depression. Both symptoms may in turn prompt attempts to seek care. The current study examined the direct effects of discrimination and immigration-related stress on care access, as well as potentially indirect effects with PTSD and depression symptoms as mediators. Interviews and online surveys were completed with 234 Latinx residents of the Midwest assessing everyday discrimination, discrimination in healthcare, PTSD symptoms, depression symptoms, current mental health utilization, and previous unsuccessful attempts to seek care. Direct effects of discrimination and immigration-related stress were largely unrelated to care access variables. Discrimination in healthcare settings predicted both unsuccessful attempts to seek care and current use, but this effect was positive. The indirect effect was largely supported, but only for PTSD symptoms and not depression. Results indicate further investigation is necessary to understand the direct effects of discrimination on care access. Further, discrimination and immigration-related stress may indirectly prompt attempts to seek mental health care.

This study aimed to translate and psychometrically validate the Neck Outcome Score (NOOS) in the Polish population according to the recommendations of American Academy of Orthopedic Surgeons (AAOS) for the Cross-Cultural Adaptation of Health Status Measures. Participants completed the NOOS, Neck Disability Index (NDI), and Visual Analogue Scale (VAS) for pain assessment. The questionnaires were completed by 57 women and 32 men with cervical spine ailments. A retest was performed in all patients after 48 hours. The analysis confirmed the high internal consistency (Cronbach's alpha of 0.95) of the Polish NOOS. No floor / ceiling effects were observed. The Polish NOOS showed a significant correlation with NDI (0.87; p<0.001) and VAS (0.79; p<0.001). The intraclass correlation coefficient (ICC) for the test-retest was found to be high (0.97). The Polish version of NOOS can be used for clinical and research purposes as an equivalent to the original English version. This study contributes to the area of patient-reported outcome measures available in the Polish language.

Background: Idiopathic normal pressure hydrocephalus is a syndrome with neuroradiological findings and clinical pattern characteristic but not specific for the pathology. Since the prevalence is growing due to the rapidly aging society, standardized and validated protocol for diagnosis is needed, also because this condition may mimic other disorders among elderly such as Parkinson's and Alzheimer's disease. Material and methods: We analysed data from 44 patients with suspect diagnosis of idiopathic normal pressure hydrocephalus with age > 60 years, clinical triad and neuroradiological pattern examined in our ward from November 2018 to November 2022. Neu-ropsychological assessment includes Mini Mental State Examination and Mental Deterioration Battery. Motor scores were collected from gait and balance tests. The evaluation was performed before and after an extended lumbar drainage last 48h. Patients who has scores improvement after the extended lumbar drainage, undergo ventriculoperitoneal shunt with a programmable valve. Results: All patients undergo neuropsychological assessment and motor tests, only 2 patients were unable to perform motor tests because bedridden. 16 patients showed no benefit from the tests, in 2 cases even a worsening of cognitive performance. 28 patients showed an improvement in their performances, but in most cases the improvement involved only the neuropsychological as-sessment. All patients underwent ventriculoperitoneal shunt have had a typical answers pattern in Mental Deterioration Battery test. We performed 9 ventriculoperitoneal shunt and 1 ventricu-lo-atrial shunt. Conclusions: Qualitative neurocognitive tests come out to be more sensitive compared to quantitative neurocognitive tests in identifying patients with suspected idiopathic normal pressure hydrocephalus benefiting from extended lumbar drainage test and then un-derwent surgical treatment. This could be considered a valid screening in elderly patients with suspected idiopathic normal pressure hydrocephalus in order to minimize the number of invasive procedures. More studies are necessary to validate this tool.

A robust bank industry is a major player in the stability of an economy. The operational efficiency and stability of banks are therefore paramount. By way of financial ratios and Z-score, this study analysed UT Bank’s financial performance prior to the 2017 bank sector reforms in Ghana. Annual financials over a ten year period (2007-2016) were used. Debt management practices of UT Bank per the results obtained were quite on the hind side and unimpressive. This was reflected in the poor leverage and risk management variables. UT Bank would have been unable to meet creditors’ claims considering the mean average values of debt-to-assets and debt-to equity ratios of 0.76 and 0.90 respectively. The entire bank sector will benefit if credit management practices of individual banks are refreshed and worked on. The bank industry regulator should tighten its supervisory and monitoring role over banks to help detect early signs of non-performing banks. The study further recommends that statutory lending limits of banks be re-enforced to uphold the threshold of 10 percent for unsecured loans and 25 percentage for secured loans of net owned funds of the bank.

Objective: We determined, in stable ambulatory heart failure with preserved ejection fraction (HFpEF) subjects and matched controls, the capability of a novel blood based cardiac-specific cBIN1 Score (CS) to diagnose heart failure and prognosticate future hospitalization. Background: Heart failure (HF) poses a costly health care burden worldwide with rising prevalence. Abnormal calcium signaling is intrinsic to HF pathophysiology and correlates with reduced expression of a cardiac membrane scaffolding protein, cardiac bridging integrator 1 (cBIN1). We hypothesize that CS, a numerical score derived from plasma cBIN1 concentration, is a diagnostic and prognostic biomarker of HF. Methods: Plasma cBIN1 is quantified by an ELISA test, and CS is calculated as the natural log of the normalized reciprocal of plasma cBIN1 concentration. We determined CS among 52 clinically stable individuals with HFpEF (LVEF ≥ 50%) (mean age 57 ± 15 years old, 63% men) and 104 age and sex matched volunteers with no known history of HF. We obtained plasma concentrations of NT-proBNP, a marker of volume status, as comparison. Baseline co-morbidities and one year longitudinal clinical information were obtained through electronic medical records. Results: Median CS is 0 (IQR -0.4 – 0.6) in the control cohort and is increased to 1.8 in the HFpEF cohort (IQR 1.5 – 2.3, p < 0.0001). For HFpEF diagnosis, CS has a receiver operating characteristic (ROC) area under the curve (AUC) of 0.94 (95% CI 0.95 – 0.99) and NT-proBNP of 0.89 (95% CI 0.83 – 0.95). Kaplan-Meier analysis of one year cardiovascular hospitalizations reveals that HFpEF patients with CS ≥ 1.8 have a hazard ratio (HR) of 4.0 (95% CI 1.4 – 11.2, p=0.009). Combining CS ≥ 1.8 with NT-proBNP ≥ 300 pg/mL, increases HR to 21.4 (95% CI 2.7 – 171.6, p=0.004). Conclusions: In a cohort of stable ambulatory HF patients with cardiomyopathies of multiple etiologies and preserved ejection fraction, a positive CS correlates with worsening myocardial health and predicts future hospitalization. CS, a marker of cardiac muscle health, provides a novel index to informing the management of stable ambulatory HF patients.

Objective: We determined, in stable ambulatory heart failure with reduced ejection fraction (HFrEF) subjects and matched controls, the capability of a novel blood based cardiac-specific cBIN1 Score (CS), which assesses the health of cardiac muscle, to identify patients with known heart failure (HF) and to prognosticate future hospitalization. Background: Limited clinical tools are available in assessing cardiac muscle health in stable ambulatory patients. Cardiac bridging integrator 1 (cBIN1) is a cardiomyocyte t-tubule membrane scaffolding protein which regulates calcium signaling in cardiomyocytes, decreases in failing muscle, and is present in plasma in levels that correlate with cardiac content. We hypothesize that CS, a normalized index of plasma cBIN1 concentration, can function as a diagnostic and prognostic biomarker of HF. Methods: Plasma cBIN1 concentration is measured by an ELISA test, and CS is calculated as the natural log of the ratio of a constant population mean cBIN1 to measured cBIN1 concentration. We determined CS among 125 clinically stable individuals with HFrEF (LVEF ≤ 40%) (mean age 56 ± 10 years old, 79% men) and 125 age, sex matched volunteers with no known history of HF. We obtained plasma concentrations of NT-proBNP, a marker of volume status, as comparison. Baseline co-morbidities and 18-month longitudinal clinical information were obtained through electronic medical records. Results: CS follows a normal distribution with a median of 0 in the control population and median is significantly increased among HFrEF patients to 1.8 (IQR 1.4 – 2.1, p < 0.0001). CS diagnosed HFrEF with a receiver operating characteristic (ROC) area under the curve (AUC) of 0.93 (AUC is 0.98 for NT-proBNP, and combined CS and NT-proBNP AUC is 0.99). Unlike NT-proBNP, CS does not correlate with body mass index (BMI) in either the control or HFrEF population (Pearson’s r = -0.15, p = 0.12; Pearson’s r = 0.003, p = 0.97, respectively). NT-proBNP significantly correlates with renal function (Pearson’s r = -0.37, p = 0.001), while CS also has no correlation (Pearson’s r = 0.03, p = 0.71). During an 18-month follow-up, a high CS ≥ 1.8 at the initial visit predicted future cardiovascular hospitalizations (38% vs. 21%, p = 0.04, hazard ratio 2.0). NT-proBNP did not predict future cardiovascular hospitalizations. Conclusions: Plasma cBIN1 based CS is insensitive to BMI and renal function and differentiates myocardial health between patients with HFrEF versus matched controls. An abnormally high CS reflected poor intrinsic myocardial health and can predict future 18-month cardiac hospitalization in stable ambulatory patients.

Increased norepinephrine (NE) release from the sympathetic nerves during pregnancy in women or animal models, as occurs during stress, modifies the fetal environment and increases flow of NE to the fetus, programing the progeny and affecting its cardiovascular and metabolic function in adulthood. In the present work, gestating rats were exposed to stress during gestation and the female progeny was analyzed for heart and metabolic function. Pregnant Sprague–Dawley rats were exposed to cold stress (4 °C/3 h/day); rats’ female progeny were euthanized at 4, 20 and 60 days old and their hearts evaluated to determine the β-adrenergic receptor (βAR) mRNA, abundance and affinity to agonists and NE concentration. The in vivo response to glucose overload and the arterial pressure response to isoproterenol (ISO, 125 µg/kg weight/day/10 days) were monitored. Results: At 20 and 60 days old, stressed female progeny presented an increase in ventricular weight and no changes in the cardiac NE as compared with their age-matched controls. The β1AR mRNA in control rats decreased between 4 and 20 days of age, but stressed rats maintained 50% higher levels of mRNA as compared with their age-matched controls. This difference was also found in the protein abundance of β1AR. No differences were found at 60 days old. The β2AR mRNA levels were higher than in controls at both 4 and 20 days old, but not expressed in the amount of protein. An increase in the ratio of β1/β2 receptors was found at 20 days old but not at 60 days old. The displacement of 3H-dihydroalprenolol (DHA) from a membrane fraction with propranolol (β antagonist) showed decreased affinity (at 60 days old) but no changes in the βAR number. In vivo exposure to ISO induced a β-adrenergic overload and provoked death in 40% of stressed females by day 3 of ISO treatment. Regarding metabolic function, we found that stressed rats presented insulin resistance when adults. These data suggest permanent changes to the heart’s adrenergic response and metabolic function after rat progeny were stressed in the uterus.

Prostate cancer is the second most frequent malignancy (after lung cancer) in men worldwide. Prostate tissue biopsies are usually graded using scores according to the Gleason grading system. This Gleason score is the most popular prognostic marker that reveals the potential aggressiveness of the disease. However, inter-observer variability in rating by human assessors is a major limiting factor. Such variability could lead to missing a severe case or suggesting unnecessary treatments. This study explores the discriminative ability of artificial intelligence (deep learning models) for Gleason score assessment. The study was designed to use whole-slide images of digitized H&E-stained biopsies of prostate tissues to automate the grading process and provide a remotely accessible clinical decision support system. Custom convolutional neural network architectures were trained on 10,616 images of prostate tissues. Gaussian filters were applied to pre-process the images and improve model performance. Transfer learning was applied to train eight machine learning architectures namely: Xception, VGG16 & 19, ResNet101, MobileNet, DenseNet121, EfficientNetB5 & B7. Efficient NetB7 had the best performance 85.2% compared with ground-truth classification by experts. Performance improves as more data is available. The model was deployed and hosted as a web application API on Google cloud service to ensure remote access. Tissue biopsy images can be uploaded and the corresponding Gleason score recovered immediately. This system reduces diagnostics turnaround time, increase throughput, and compensate for limited skills, especially in low resource settings.

Ribosome profiling and mass spectroscopy have identified canonical and noncanonical translation initiation codons (TICs) that are upstream of the main translation initiation site and used to translate oncogenic proteins. Here, we use a Kozak Similarity Score algorithm to find that nearly all of these TICs have flanking nucleotides closely matching the Kozak sequence. Remarkably, the nucleotides flanking alternative noncanonical TICs are frequently closer to the Kozak sequence than the nucleotides flanking TICs used to translate the gene’s main protein. Of note, the 5’ untranslated region (5‘UTR) of cancer-associated genes with an upstream TIC tend to be significantly longer than the same region in genes not associated with cancer. The presence of a longer than typical 5’UTR increases the likelihood of ribosome binding to upstream noncanonical TICs, and may be a distinguishing feature of a number of genes overexpressed in cancer. Noncanonical TICs that are located in the 5’UTR, although thought disadvantageous and suppressed by evolution, may translate oncogenic proteins because of their flanking nucleotides

Objective: The Acute Cystitis Symptom Score (ACSS) was developed and validated as a self-reporting questionnaire for diagnosing and monitoring acute, uncomplicated cystitis (AC) in female patients. The study aims at the translation of the ACSS into Greek from original Russian as a source and American English as a new master version and at its linguistic validation. Material and Methods: Three independent professional native Greek translators, two of them experts in Russian and one in English, translated the ACSS from Russian and American English into Greek. The second group of three translators translated each of the three versions back into the original language to detect or correct any important discrepancies. These three Greek versions were then used for linguistic validation. Results: The English to Greek translation reflected more the spoken language, the two Russian to Greek translations more the written, formal language. A total of 60 randomly selected females and 30 healthcare professionals was asked about their preferences and to comment on each of the three translations. Considering all comments the scientific committee (SC) developed the Greek consensus version. For cognitive assessment additional 30 healthcare professionals and 30 females were asked to comment on the intelligibility of all items. Considering their comments the linguistically validated Greek study version was established by the SC. Conclusion: The linguistically validated Greek version of the ACSS can now be used for the clinical validation study.

Background To develop and validate the American-English version of the self-reporting Acute Cystitis Symptom Score (ACSS), a suitable tool for diagnosis and patient-reported outcome in female patients with acute uncomplicated cystitis (UC). Methods After certified translation into American-English and cognitive assessment, the clinical validation of the ACSS was performed as an embedded study in a US phase II trial (ClinicalTrials.gov Identifier: NCT03129295). Results A total of 167 female patients with typical symptoms of UC were included in the study following FDA guidance. At Day 1 (diagnosis) the mean(SD) sum score of the six ACSS typical symptoms reached 10.60(2.51). Of 100 patients followed-up last time on Day 5 or 6 (End-of-treatment, EoT), 91 patients showed clinical success according to the favoured ACSS criteria (sum score of typical symptoms 0.98(1.94)). There was no correlation between the severity of symptoms on Day 1 or between clinical success rate at EoT and level of bacteriuria on Day 1. Conclusion The American-English ACSS showed high predictive ability and responsiveness, and excellent levels of reliability and validity. It can now be recommended as the new master version in clinical and epidemiological studies, in clinical practice or for self-diagnosis of women with symptoms of UC.

A recent study claimed that genome-wide polygenic scores (GPSs) for five common diseases could identify individuals with risk equivalent to monogenic mutations. Receiver operator curve analyses were reported to have areas under the curve (AUCs) ranging from 0.63 for inflammatory bowel disease up to 0.81 for coronary artery disease (CAD) but these models also included age and sex, themselves strong predictors of risk. The GPS for CAD identified 8% of the population at threefold increased risk, which it was claimed was comparable to the excess risk from monogenic mutations. In the present study attempts were made to model the distribution of the GPS for CAD to match the information provided. These models were based on the reported distribution of prevalence by centile of GPS and on the distribution of GPS in controls and cases and were fitted to the reported results using linear approximations to the distributions and using simulations of a liability-threshold model. It was impossible to produce a compatible model in which the GPS produced an AUC as high as 0.81 and the most plausible estimate was that the true AUC was only 0.65. The reported distributions of the GPS in cases and controls overlap so much that they are not compatible with an AUC of 0.7 or higher. The AUC of the GPS for these diseases is modest. Furthermore, the literature robustly demonstrates that true CAD risk associated with monogenic mutations is much higher than the threefold increase which is predicted by the GPS. Together, these findings cast doubt on the clinical utility of the GPS.

It is already well known that infants and children infected with COVID-19 develop mild to mod-erate forms of the disease, with fever and oropharyngeal congestion being the most common symptoms. Nevertheless, there are cases in which the patients accuse respiratory symptoms. These cases need lung evaluation, which can be done using lung ultrasound (LUS), because it is a non-irradiating and repeatable imaging technique. 19 children with COVID-19 pneumonia were eval-uated using LUS. The LUS score (LUSS) for each patient varied between 1 to 8 points from a max-imum of 36 points. The arithmetic mean was 4.47 ± 2.36 (S.D), while 95% CI for the Arithmetic mean was 3.33 to 5.61. The lung changes were correlated with their biomarkers, specifically in-flammatory markers. The correlation between LUSS and LDH, D-dimers and IL-6 was a strong positive one with r=0.66 (p=0.01, 95% CI 0.147 to 0.896) between the LUSS and LDH level at symptomatic infants and children (with cough present) and r=0.66 (p=0.01, 95% CI 0.140 to 0.895) between LUSS and D-dimers level at symptomatic infants and children (with cough pre-sent). The results suggest that LUS could be a good imaging technique that can be used both in ini-tial evaluation of children with respiratory diseases, and, also in their follow-up, correlated with symptoms and biomarkers.

This longitudinal study aimed to analyze the effects of a team rowing-based training program on physical fitness and anthropometric parameters in female breast cancer survivors (n=40; 56.78±6.38 years). Participants were divided into two groups: one rowed in fixed seat rowing (FSR) boats (n=20; 56.35±4.89 years) and the other in sliding seat rowing (SSR) boats (n=20; 57.20±7.7 years). Both groups engaged in two 75-minute sessions per week for 24 weeks. Significant improvements were observed in both groups in resting heart rate (FSR: -10.65 bpm; SSR: -8.45 bpm), heart rate at the beginning of the 6-minute walk test (6MWT) (FSR: -10.7 bpm; SSR: -11.25 bpm), and heart rate at the end of the test (FSR: -13.85 bpm; SSR: -20.35 bpm). Blood pressure improved significantly in both diastolic blood pressure (FSR: -12.35 mmHg; SSR: -19.25 mmHg) and systolic blood pressure (FSR: -13 mmHg; SSR: -16.95 mmHg). Additionally, both groups increased the distance covered in the 6MWT (FSR: +63.05 m; SSR: +93.65 m). These results suggest that a rowing training program is a viable and safe activity for female breast cancer survivors, improving cardiac function, blood pressure, and cardiorespiratory capacity, particularly in sliding seat boats.

Stimulation of the alpha 7 nicotinic acetylcholine receptor (α7nAChR) has shown beneficial effects in several acute inflammatory disease models. This study aims to examine whether treatment with the selective α7nAChR agonist PHA 568487 can dampen inflammation and thereby improve cardiac function after myocardial infarction in mice. The possible anti-inflammatory properties of α7nAChR agonist PHA 568487 were tested in vivo using the air pouch model and in a permanent occlusion model of acute myocardial infarction in mice. Hematology parameters and cytokine levels were determined. Infarct size and cardiac function were assessed via echocardiography 24 h and one week after the infarction. Treatment with α7nAChR agonist PHA 568487 decreased 12 (CCL27, CXCL5, IL6, CXCL10, CXCL11, CXCL1, CCL2, MIP1a, MIP2, CXCL16, CXCL12 and CCL25) out of 33 cytokines in the air pouch model of acute inflammation. However, α7nAChR agonist PHA 568487 did not alter infarct size, ejection fraction, cardiac output or stroke volume at 24 h nor at 7 days after the myocardial infarction compared with control mice. In conclusion, despite promising immunomodulatory effects in the acute inflammatory air pouch model, α7nAChR agonist PHA 568487 did not affect infarct size or cardiac function after a permanent occlusion model of acute myocardial infarction in mice. Consequently, this study does not strengthen the hypothesis that stimulation of the α7nAChR is a future treatment strategy for acute myocardial infarction when reperfusion is lacking. However, whether other agonists of the α7nAChR can have different effects remains to be investigated.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

: Greenhouse plants are usually grown in containers filled with growing media. Peat is the main component of the growing media used in greenhouses. However, peat substrate is made from peat from drained peatlands, which is a limited resource. Wood fiber can be an alternative to use as a growing media for controlled-climate crops. The chemical properties of the growing media interact and change continuously due to the small volume of the growing media, which is limited by the vegetative container. Therefore, this study aims to gain new knowledge on the impact of nutrient changes in the microbial degradation of carbon compounds in wood fiber and mixtures with peat substrate on the content and uptake of nutrients required by plants. Cucumbers (Cucumis sativus L.) were cultivated in growing media of peat substrate and wood fiber: (1) peat substrate (PS); (2) wood fiber (WF); (3) wood fiber and peat substrate 50/50 v/v (WF/PS 50/50); (4) wood fiber and peat substrate 25/75 v/v (WF/PS 25/75). The rates of fertilization were the following: (1) conventional fertilization (CF); (2) N13; (3) N23; (4) N30. Fertilization of cucumbers with different rates of nitrogen influenced the nutrient uptake. Plants grown in WF/PS 50/50 and WF/PS 25/75 growing media had the best Cu uptake when fertilized with N23. When the plants grown in the wood fiber media and the 50/50 media were fertilized with N13, N23, and N30, the Mn content in the growing media at the end of the growing season was significantly lower than the Mn content in the media with conventional fertilization. Thus, nitrogen improved the uptake of Mn by plants grown not only in the wood fiber but also in combinations with peat substrate. Growing plants in wood fiber and fertilizing them with N13 can result in optimum uptake of micronutrients. The number and mass of cucumber fruits per plant were influenced by the amount of wood fiber in the growing media and the application of nitrogen fertilizer. The highest number of fruits and mass of fruits per plant was obtained significantly higher when cucumbers were grown on WF/PS 50/50 growing media with additional N13 fertilization.

Background and Objectives: Cardiovascular events are the leading cause of morbidity and mortal-ity in hemodialysis (HD) patients. Identifying risk factors can help in the effort to reduce cardi-ovascular risk and improve life expectancy. The purpose of this study was to evaluate the ability of CHA2DS2-VASc score [risk index of stroke in atrial fibrillation (AF)] in patients with end stage kidney disease, to predict stroke, major cardiovascular events and mortality. Materials and Meth-ods: CHA2DS2-VASc and HAS-BLED (bleeding risk from use of anticoagulation in AF) scores were calculated in 237 HD patients, [99 women, median age 76 (15) years], at time they com-menced on HD. The scores’ ability to predict long term cardiovascular morbidity and mortality was estimated, both in those with and without AF. Results: CHA2DS2-VASc score was signifi-cantly increased in AF (n=69) compared to non-AF (n=168) patients, 5 (2.5) versus 4 (2), p<0.0001, respectively. Increased CHA2DS2-VASc score was associated with heart failure (p=0.007, p=0.024), stroke (p<0.0001, p<0.0001) and risk of all-cause mortality (p<0.0001, p<0.0001), in both groups, respectively. C statistics indicated that CHA2DS2-VASc score performed modest discrimination in this HD population with and without AF for heart failure, stroke, and all-cause mortality, but for cardiovascular mortality in AF group only. Conclusions: Increased CHA2DS2-VASc score at time starting on HD, can predict stroke, heart failure and all-cause mortality in HD patients in-dependent of the presence of AF. Risk of cardiovascular mortality could be predicted only on patients with AF.

This study assessed the potential of back extensor strength as an alternative marker of frailty. A total of 560 farmers were included. Computed tomography scans measured fat and muscle mass volumes at the mid-L4 vertebral level. Back extensor strength was measured in a seated posture. Multivariate linear regression analyzed the associations between back extensor strength and trunk muscle/fat compositions. The participants were divided into two groups based on back extensor strength. Propensity score matching, multivariate logistic regression, and Extreme Gradient Boosting (XGBoost) were employed to evaluate the relationship between Fried's frailty criteria and back extensor strength. Back extensor strength exhibited positive associations with abdominal muscle volume (r = 1.12) as well as back muscle volume (r = 0.89) (p < 0.05). Lower back extensor strength was linked to more frail status, such as reduced grip strength, walking speed, and fre-quent self-reported exhaustion. Multivariate logistic regression indicated a significant association between lower back extensor strength and higher Fried frailty score (OR, 0.990; p<0.05). XGBoost analysis identified back extensor strength as the most important predictor (gain = 0.502) for frailty, surpassing the significance of age (gain = 0.325). These findings suggested the potential of back extensor strength as an alternative frailty marker.

Papillary thyroid cancer (PTC) is commonly characterized by multifocality, which is associated with aggressive features and a less favorable prognosis. The current study aimed to compare the clinicopathologic characteristics and long-term oncological outcomes of bilateral and unilateral multifocal PTC. The medical records of 1745 patients with multifocal PTC who underwent thyroid surgery at Seoul St. Mary’s Hospital were retrospectively reviewed. The clinicopathological characteristics and recurrence rates were compared based on cancer laterality. Further, 357 patients who underwent total thyroidectomy were matched to investigate the recurrence risk and disease-free survival (DFS). Before propensity score matching (PSM), there was no significant difference in the recurrence rate between the bilateral and unilateral multifocal PTC groups. Cancer laterality was not a predictor of DFS based on the Cox regression analyses. However, after PSM, unilateral multifocality was associated with a significantly high risk of recurrence. Similarly, unilateral multifocality was associated with a significantly poor DFS based on the Kaplan–Meier analysis. Compared with bilateral PTC, unilateral multifocal PTC was associated with a poor DFS. A comprehensive preoperative examination should be performed to detect multifocality before the initial surgical intervention for optimal treatment. Postoperative short-term follow-up is recommended for unilateral multifocal PTC for recurrence surveillance.

(1) Background: Ulcerative colitis (UC) is characterized by immune system dysregulation with frequent extraintestinal manifestations, including airways involvement. Reduction in CO diffusing capacity and functional alterations in small airways have been described. The extended analysis of Fractional Exhaled Nitric Oxide (FeNO), may distinguish the sites of production and the presence of small airways inflammation being a useful, non-invasive marker for these patient’s follow up. The aim of our study was to compare PFTs, FeNO and CANO values of UC patients with different clinical disease activity and healthy subjects to reveal lung function abnormalities and the presence of subclinical airway inflammation. (2) Methods: We enrolled 42 adult outpatients with different clinical activity stages of UC (mean age 39±13 years) and a healthy control group of 41 subjects (mean age 29±3 years). C-reactive protein (CRP) and FeNO values at different flows (50,100 and 200 ml/sec) were collected. All patients performed pulmonary function tests (PFT’s) with static volumes and diffusing capacity (DLCO). (3) Results: FENO, CANO and CRP values were significantly increased in UC patients when compared with controls (p=0.02 and p&lt;0.0001, respectively) and proportionally to the disease activity (FeNO class 3: 27.1 ppb vs class 1-2: 6.2 ppb; CANO values class 3: 8.1 ppb vs class 1-2: 2.0 ppb (p &lt; 0.0001). TLC and DLCO were significantly reduced in UC patients compared to controls (p=0.011 and p&lt;0.0001, respectively). (4) The results of this study show significant lung functional abnormalities in UC patients and suggest the presence of airway inflammation directly correlated with the disease activity suggesting an integrated approach in routine assessment.

In this article, we set up some adequate conditions for analytic functions associated with cosine hyperbolic function. We determine conditions on α such that 1+α (ϰ^(2+P(j-1) ) g^' (ϰ))/(Pg^j (ϰ)),for each j=0,1,2,3 are subordinated by Janowski function, then (g(ϰ))/ϰ^P <cosℏ⁡(ϰ),(ϰ∈C). By choosing specific values of functions g we get some adequate conditions for multivalent starlike function related with cosine hyperbolic.

Leishmanial skin lesions are characterized by inflammatory hypoxia alongside the activation of hypoxia inducible factors, HIF-1a and HIF-2a, and subsequent expression of the HIF-a target VEGF-A during Leishmania major infection. However, the factors responsible for HIF-a activation are not known. We hypothesize hypoxia and pro-inflammatory stimuli contribute to HIF-a activation during infection. RNASeq on leishmanial lesions found transcripts associated with HIF-1a signaling are induced. To determine whether hypoxia contributes to HIF-a activation, we followed the fate of myeloid cells infiltrating from the blood and into hypoxic lesions. Recruited myeloid cells experience hypoxia when they enter inflamed lesions, and the length of time in lesions increases their hypoxic signature. To determine whether pro-inflammatory stimuli in the inflamed tissue can also influence HIF-a activation, we subjected macrophages to various pro-inflammatory stimuli and measured VEGF-A. While parasites alone did not induce VEGF-A, and pro-inflammatory stimuli only modestly induce VEGF-A, HIF- stabilization increases VEGF-A during infection. HIF-a stabilization does not impact parasite entry, growth or killing. Alternatively, the absence of ARNT/HIF- signaling enhances parasite internalization. Altogether, these findings suggest HIF-a is active during infection, and while macrophage HIF-a activation promotes lymphatic remodeling through VEGF-A production, HIF-a activation does not impact parasite internalization or control.

In the paper, the authors generalize the notion "k-Mittag-Leffler function'', establish some integral transforms of the generalized k-Mittag-Leffler function, and derive several special and known conclusions in terms of the generalized Wright function and the generalized k-Wright function.

Introduction: There are unique technical and management challenges associated with living donor liver transplantation (LDLT) for Budd-Chiari Syndrome (BCS). The outcomes of LDLT for BCS in comparison to other indications remains unclear and warrants elucidation. Methods: Data of 24 BCS patients who underwent LDLT between January 2012 and June 2019 were analyzed. There were 20 adults and 4 children. The early and long-term outcomes of adult LDLT BCS patients were compared to a control group of LDLT patients for other indications and matched using propensity scoring methodology. Results: Primary BCS was observed in 22(91.7%) patients. Caval replacement was performed in 7(29.1%) patients. Early and late hepatic venous outflow tract (HVOT) complications were seen in 1(5.5%) and 3(16.7%) patients. Preoperative acute kidney injury was identified as a risk factor for mortality in the BCS cohort (p =0.013). On comparison, BCS recipients were younger with fewer comorbidities, more large volume ascites and higher rates of PVT. They also had longer cold ischemia time, increased blood loss and transfusion requirements, increased hospital stay, and higher late outflow complications. The 1-year and 3-year survivals were similar to non-BCS cohort (84.2% vs 94% and 70% vs 91.9%, respectively, log rank test p=0.09). Conclusion: LDLT is remains a good option for symptomatic BCS who have failed non-transplant interventions. The clinical and risk factor profile of BCS recipients is distinct from non-BCS recipients. By following an algorithmic management protocol, we show on propensity-score matched analysis that outcomes of LDLT for BCS are similar to non-BCS indications.

Primary ciliary dyskinesia (PCD) is caused by pathologic variants in over 50 different genes that affect the structure and function of motile cilia. Low nasal NO (nNO) is a biomarker for diagnosis in patients with features of PCD; but the reason why it is low is unclear. At the cellular level, a characteristic feature shared by most PCD patients is that antigens and other particles are not cleared from the epithelial surface. Poor antigen clearance results in pro-oxidant pathway activation and airway epithelial damage and may predispose PCD patients to DUOX1- and IL33- mediated asthma. Secondary ciliary dysfunction, such as that caused by viruses or by smoking, can also contribute to asthma development. Variants in genes underlying the function of cilia, can be associated with poor lung function, even in the absence of PCD. Single nucleotide polymorphisms in PCD – related genes can be associated with increased asthma severity. The role of cilia and antigen stasis is the pathophysiology of asthma is an important area for research, because specific airway clearance techniques and other therapeutic interventions, such as antioxidants, could be of value in preventing the development of asthma and asthma-like symptoms.

In mammals, the oviduct (or the Fallopian tube in humans) can be divided into the infundibulum (responsible for oocyte pick-up), ampulla (site of fertilization), isthmus (where preimplantation embryos develop), and uterotubal junction (where embryos transit to the uterus). The oviductal fluid, as well as extracellular vesicles produced from the oviductal epithelial cells, referred to as oEVs, have been shown to improve the fertilization process, prevent polyspermy, and aid in embryo development. oEVs contain molecular cargos (such as miRNAs, mRNAs, proteins, and lipids) that can be delivered and fuse to recipient cells. oEVs produced from the ampulla appear to be functionally distinct from those produced from the isthmus. In multiple species including mice, cats, dogs, pigs, and cows, oEVs can be incorporated into the oocytes, sperm, and embryos. In this review, we show the positive impact of oEVs on gamete function as well as blastocyst development and how they may improve embryo quality in in vitro conditions in an assisted reproductive technology setting for rodents, domestic animals, farm animals, and humans.

In this study, a commercial sodium butyrate protected by a new buffer salt solution (NSB) was tested to determine whether it can be used as an antibiotic alternative in broiler production. 192 1-day-old broilers were randomly allocated to three dietary treatments: soybean meal diet (CON), antibiotic diet (ANT, basal diet + 100 mg/kg aureomycin), and NSB (basal diet + 800 mg/kg NSB). The growth performance, serum anti-inflammatory cytokines, intestinal morphology, gut barrier function, antioxidative parameters, SCFAs content, and cecal microbiota were analyzed. The result showed that NSB significantly improved ADFI, ADG (p < 0.01), and decreased FCR (p < 0.01). Serum anti-inflammatory cytokine IL-10 was up-regulated (p < 0.01), and pro-inflammatory TNF-α was down-regulated (p < 0.05) by NSB supplementation. H&E results showed that VH and VH: CD ratio significantly increased (p < 0.05) in the jejunum and ileum in the NSB group. Furthermore, ZO-1 (p < 0.01), claudin-1 (p < 0.01), and occludin (p < 0.05) in the jejunum and claudin-1 (p < 0.01) and mucin-2 (p < 0.05) in the ileum significantly up-regulated in the NSB group, respectively. Additionally, SOD (p < 0.05) and T-AOC/MDA ratio (p < 0.01) in the jejunum and SOD in the ileum were significantly increased (p < 0.05) in the NSB group. The MDA level also significantly increased (p < 0.01) in the ANT group in the jejunum. Propionic acid (p < 0.05) and butyric acid (p < 0.01) content significantly increased in the NSB group in the jejunum and ileum segments. The 16S rRNA sequencing results showed no significant difference (p > 0.05) in alpha and beta diversity among the groups. LEFSe analysis also indicated that Peptostreptococcaceae, Colidextribacter, Firmicutes, Oscillospira, and Erysipelatoclostridiaceae, which promote SCFA production (p < 0.05), were identified as dominant taxon-enriched bacterial genera in the NSB group. The Spearman correlation analysis revealed that Colidextribacter with ADFI, ADG, VH, claudin-1 (p < 0.05), and unclassified_f__Peptostreptococcaceae with ADFI, IL-10, and ZO-1 were positively correlated (p < 0.05). Furthermore, ADFI and ADG with IL-10, claudin-1, SOD, T-AOC, and butyric acid (p < 0.05), and similarly, ADG with VH (p < 0.05) showed a positive correlation. In conclusion, NSB enhanced the growth performance by improving jejunum and ileum morphology, serum anti-inflammatory cytokines, regulating intestinal barrier function and antioxidant capacity, SCFAs content, and cecum microbiota, showing its potential use as an alternative to antibiotics in poultry nutrition.