Recent advances in understanding the Planck scale have led to a new, straightforward method for quantizing the general theory of relativity. This results in a theory of gravity that predicts the same outcomes as general relativity with greater fundamental comprehension connected directly to the Planck scale.

Unquestionably the rapidly changing climate and, therefore, alterations in the associated bioclimate, constitute an alarming reality with implications in daily practice and natural capital management. In this research the present and projected bioclimate evolution over the phytogeographical regions of Greece is displayed. For this purpose, ultrahigh-resolution computation results on the spatial distribution of the Emberger index’s Q2 classes of bioclimatic characterisation are analysed and illustrated for the first time. The assessments are performed over the reference period (1970–2000) and two future time frames (2021–2040; 2041–2060) under the RCP4.5 and RCP8.5 emission scenarios. By 2060 and under the extreme RCP8.5, intense xerothermic trends are demonstrated owing to the resulting significant spatial evolution mainly of the Arid-Hot, Semi-Arid-Very Hot, Semi-Arid-Hot and Semi-Arid-Temperate Q2 classes, respectively, over the phytogeographical regions of Kiklades (up to 29% occupation), Kriti and Karpathos (up to 30%), West Aegean Islands (up to 26%), North East (up to 56%)–North Central (up to 31%). The RCP8.5 long-term period exhibits the strongest impacts over approximately the right half of the Greek territory the bioclimate of which appears as more dry-thermal in the future.

We report a case in which a 74-year-old man suffering from esophageal achalasia complicated with epiphrenic esophageal diverticulum was successfully treated with a simultaneous laparoscopic surgery. The gentleman was referred with symptoms suggestive of a passage disorder in lower esophagus from 5 years. Esophagogastroduodenoscopy demonstrated an epiphrenic diverticulum at the left wall of the lower esophagus, and esophagography led to the suspicion of a combined esophageal achalasia. A simultaneous laparoscopic surgery, with an abdominal approach was performed in which, following the opening of the esophageal hiatus, the diverticular wall was separated from the mediastinal organs and diverticulectomy was performed with linear staplers. After Heller’s myotomy, Dor’s fundoplication was subsequently performed in which both incisional line of muscle layer and the suturing line of diverticulectomy were wrapped by the fornix of stomach to make up for the wall strength and avoid the suture leakage. It was theoretically considered logical and effective to reinforce this vulnerable site with Dor’s fundoplication. He had an uneventful recovery and a rapid relief from symptoms following surgery.

(1) Background: We aim to construct a machine learning (ML) algorithm to predict the risk of distant metastasis (DM) of T1 and T2gallbladder cancer (GBC); (2) Demographic and clinical pathological data of T1 and T2 GBC patients were extracted from the National Institutes of Health (NIH)’s Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 to develop seven ML algorithm models. Models were evaluated based on accuracy, precision, recall rate, F1- score, and area under the receiver operating characteristic curve (AUC); (3) Results:A total of 4371 patients were included in the study, of whom 764 (17.4%) developed DM. Multivariate logistic regression showed that age, histology, tumor size, T and N stages were independent factors in GBC with DM. A novel nomogram was established to predict distant metastasis in early T stage GBC patients. Evaluation indicators of the best model Random Forest (RF) were as follows: accuracy (0.828), recall rate (0.862), precision (0.811), F1- score (0.836), and AUC value (0.913); (4) Con-clusions: The RF model constructed in this study could accurately predict distant metastasis in GBC patients, which may provide clinicians with more personalized clinical decision-making recom-mendations.

In my paper, a divisibility rule named the Queen function is de- scribed, which has been generalized for every integer and encompasses all pre- viously established divisibility rules. Subsequently, the paper discusses other areas where this function is instrumental. These include simplifying ratios, generating prime numbers, and more. Towards the end of the paper, a set of hypotheses is also presented. Among these, the most significant is the novel approach involving the application of the Queen function for prime number generation.

(3+1)D quantum mechanics is a four-dimensional quantum formalism, which is developed neither in a Minkowski spacetime, nor in a purely Hilbert space and not its metric is Lorentzian. This quantum mechanics also yields the quantum Einstein field equation in (3+1)D quantum spacetime. Every observable (3+1)D quantum spacetime can be found to contain internally hidden opposite spin quantum state, that results Supersymmetry. Closed continuous mappings of this hidden quantum state immediately yield more extra hidden dimensions including string. This string is found to be fundamentally eleven-dimensional (rather than lower dimensional) by nature within this quantum spacetime, which is necessarily a natural phenomenon of (3+1)D Quantum Mechanics.

Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) is a clinical entity characterized by the absence of significant coronary artery obstruction in epicardial arteries (< 50%) on coronary angiography in the setting of acute myocardial infarction (AMI). This article aims to provide a narrative review of the pathophysiological mechanisms, diagnostic challenges, and prognosis associated with MINOCA focusing only on cases associated with myocardial ischemia but of non-atherosclerotic origin. Etiological factors, including thromboembolism, coronary artery spasm, spontaneous coronary artery dissection, coronary microvascular disease, and supply-demand mismatch are addressed. Imaging modalities such as echocardiography, advances in coronary angiography like intravascular ultrasound (IVUS) and optical coherence tomography (OCT), cardiac magnetic resonance (CMR), and coronary computed tomography angiography (CCTA) are also analyzed. MINOCA patients have a better short-term prognosis compared to those with obstructive coronary artery disease but face significant long-term risks, underscoring the need for precise diagnosis and management strategies. Elevated inflammatory markers and specific genetic predispositions are also associated with adverse outcomes in MINOCA. This review focused on MINOCA from the pathophysiological perspective on ischemic, non-atherosclerotic causes, the diverse underlying mechanisms, the challenges in achieving accurate diagnosis, the importance of a tailored therapeutic approach and the necessity for further investigation of clinical outcomes.

Since its conception with the smallpox vaccination, worldwide-used vaccines have thwarted multiple pandemics including the recent COVID-19 outbreak. Insightful studies uncovered complexities of different functional networks of CD4 T cells [T helper 1 (Th1); Th2, Th17] and CD8 T cells (T cytotoxic; Tc) as well as B cells (BIgM, BIgG, BIgA and BIgE) subsets during response to vaccination. Both T and B cell subsets forge central, peripheral and tissue-resident subsets during vaccination. It also became apparent that each vaccination formed the network of T regulatory subsets, namely CD4+CD25+Foxp3+ T regulatory (Treg) cells and interleukin-10 (IL-10)-producing CD4+Foxp3− T regulatory 1 (Tr1) as well as many others, are shaping the quality/quantity of vaccine-specific IgM, IgG, and IgA antibody production. These components are especially critical for immunocompromised patients, such as older individuals and allograft recipients, as their vaccination may be ineffective or less effective. This review focuses on presenting how pre- and post-vaccination Treg/Tr1 levels influence the vaccination efficacy. Experimental and clinical work revealed that the Treg/Tr1 involvement evoked different immune mechanisms in diminishing vaccine-induced cellular/humoral responses. Alternative steps may be considered to improve the vaccination response by increasing a dose, changing the delivery route and/or repeated booster doses of vaccines. Vaccination may be combined with anti-CD25 (IL-2Ra chain) or anti-PD-1 (programmed cell death protein) monoclonal antibody (mAb) to decrease Tregs and boost the T/B cell immune response. All these data and strategies for immunizations are presented and discussed, aiming to improve the efficacy of vaccination in humans and especially in immunocompromised and older individuals as well as organ transplant patients.

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 < 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< р<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.

Precise classification of sarcomas is crucial to drive optimal clinical management. In this prospective, multicenter, observational study within the Hellenic Group of Sarcoma and Rare Cancers (HGSRC) we assessed the effect of expert pathology review, coupled with the application of molecular diagnostics, on diagnosis and management of sarcoma patients. Newly diagnosed sarcoma patients were addressed by their physicians to one of the two sarcoma pathologists of HGSRC for histopathological diagnostic assessment. RNA next-generation sequencing was per-formed to all samples, using a platform targeting 86 sarcoma gene fusions. Additional molecular methods were performed on the opinion of the expert pathologist. Therefore, the expert pathologist provided a final diagnosis based on the histopathological findings and, when necessary on molecular tests. In total, 128 specimens from 122 patients were assessed. Among the 119 cases in which there was a preliminary diagnosis by a non-sarcoma pathologist, there were 37 modifications in diagnosis (31.1%) by the sarcoma pathologist, resulting in 17 (14.2%) modifications in management. Among the 110 cases in which molecular tests were performed, there were 29 modifications in diagnosis (26.4%) through the genomic results, resulting in 12 (10.9%) modifications in management. Our study confirms that expert pathology review is of utmost importance for the optimal sarcoma diagnosis and management and should be assisted by molecular methods in selected cases.

In the digital age, Artificial Intelligence (AI) is emerging as a transformative force in various sectors, in-cluding medicine. This article explores the potential of AI, akin to the magical genie of Aladdin's lamp, particularly within thoracic surgery and lung cancer management. It examines AI applications like ma-chine learning and deep learning in achieving more precise diagnoses, preoperative risk assessment, and improved surgical outcomes. The challenges and advancements in AI integration, especially in computer vision and multi-modal models, are discussed alongside their impact on robotic surgery and operating room management. Despite its transformative potential, implementing AI in medicine faces challenges regarding data scarcity, interpretability issues, and ethical concerns. Collaboration between AI and medi-cal communities is essential to address these challenges and unlock the full potential of AI in revolution-izing clinical practice. This article underscores the importance of further research and interdisciplinary collaboration to ensure the safe and effective deployment of AI in real-world clinical settings.

This systematic review provides a comprehensive neuropsychological analysis of psychotic spectrum disorders, including schizophrenia, bipolar disorder, and depression. It explores cognitive impairments in memory, attention, and executive function, and the relation between brain abnormalities and these deficits. The paper emphasizes the use of neuropsychological tests in diagnosis and early psychosis management, while also discussing interventions, the impact of dementia on psychosis, and the neurobiological patterns associated with these conditions. Additionally, it underlines the importance of childhood trauma in the development of psychosis and examines the effects of substance abuse and brain injury. Neuropsychological evaluations and targeted therapies are highlighted as crucial for the understanding, diagnosis, and treatment of psychotic disorders. The research further includes evidence of neurocognitive dysfunction in individuals with a high risk of psychosis and emphasizes the advanced brain aging in schizophrenia and bipolar disorder. The necessity of comprehensive clinical evaluations and targeted therapies for cognitive impairments is underscored throughout the research. The potential effects of dementia on individuals with psychosis, neurobiological patterns, the role of childhood trauma, the impact of psychosis in dementia patients, and proposed treatments are also explored in depth. Overall, the paper underscores the integral role neuropsychological knowledge plays in understanding, diagnosing, managing, and treating psychotic spectrum disorders.

Background: Historically, a large gender-related disparity in vascular access (AV) has been demonstrated, with a lower prevalence of women with arteriovenous fistula (AVF) compared to men and worse maturity rates. The cause of this difference is not entirely clear, although several reasons that could contribute to it have been hypothesized. The emergence of new percutaneous FAV (pFAV) systems could be an alternative for reducing these differences. Objective: The study aims to determine if there is a gender difference in the creation of AVFs using the new percutaneous systems. Material and Methods: A systematic review of the literature was conducted by searching PubMed and Google Scholar using the following terms: "percutaneous arteriovenous fistula", "endovascular arteriovenous fistula", and "hemodialysis". All clinical trials, comparative studies, and descriptive studies involving patients who underwent a pAVF were included. Results: Finally, the review includes 19 studies, comprising 14 retrospective and 5 prospective studies. Of these, 6 studies are comparative, 5 of which compare pAVF with surgically created AVFs (sAVF), and 1 comparing pAVFs performed using different systems with each other. A total of 1,269 patients were included in the review. Of the total number of patients, only 414 were women, representing 32.62%. Conclusion: The number of women included in the various studies analyzing pAVF remains very low, representing less than one-third of all patients. Although the causes of this difference are not entirely clear, several reasons have been hypothesized such as socio-economic factors, anatomical factors, or even patients' preferences. Given these results, further studies are needed to try to clarify the reasons for this gender disparity and to establish different strategies to mitigate the barriers faced by women in accessing the creation of an AVF.

3D printing is a non-traditional additive manufacturing process. It is different from the traditional subtractive manufacturing process. It offers exceptional rapid prototyping capabilities and results that traditional subtractive manufacturing methods cannot attain, especially in applications involving curved or intricately shaped components. Despite its advantages, metal 3D printing will face porosity, warpage, and surface roughness issues. These issues will affect the future practical application of the parts indirectly, for example, the structural strength and the parts assembly ca-pability. Therefore, this study compares the qualities of the warpage, weight, and surface rough-ness after milling and grinding processes under the same materials (316L stainless steel) between general rolled steel and 3D additive steel. Experimental results show that 3D printing parts are approximately 13% to 14% lighter than the general rolled steel. The surface roughness performance of 3D printing steel is better than general rolled steel under the same material after milling or grinding processing. The hardness of the 3D printing steel is better than that of the gen-eral rolled steel. The research verifies that 3D additive manufacturing can use surface processing to optimize surface performance and achieve the functions of lightness and hardness.

(1) Background: This study aims to investigate differences in the perspectives of exercise intensity for resistance exercise of healthcare professionals (HCPs) and adults living with spinal cord injury (SCI) in Asian countries. Also, it verifies the appropriateness of the conventional indicators for resistance exercise intensity in an Asian context; (2) Methods: 121 certified HCPs and 107 adults with SCI participated in a survey conducted in Indonesian, Japanese, Korean and Thai languages. The survey asked what principles are important for prescribing resistance exercise, and if ‘moderate’ and ‘vigorous’ were appropriate terms for indicating an intensity level. Perspective differences were examined between both groups and, further, between countries from a psychosocial perspective; (3) Results: Of the HCPs, 92% perceived that resistance exercise intensity was far more important than frequency, time or type of exercise while frequency (61%) followed by intensity (58%) was perceived as important by respondents with SCI. Only Japanese respondents with SCI agreed with HCP’s perception of intensity. Both HCPs and respondents with SCI showed unfavorable responses on the usage of ‘moderate’ and ‘vigorous’ for describing resistance exercise intensity, especially Japanese HCP and respondents with SCI from Indonesia; (4) Conclusion: Our findings suggest that non-HCPs must improve their perceptions of exercise intensity. Findings also suggest the need for more explicit and user-friendly terms or expressions indicating the level of intensity in a local (Asian) context.

The impact of systemic vascular resistance (SVR) in hypertrophic (HCM) and amyloid cardio-myopathies has been seldom investigated. We studied pressure-strain loop derived myocardial work (MW) indices and SVR in patients with either sarcomere HCM or wild type transthyretin cardiac amyloidosis (ATTR), presented with heart failure and preserved left ventricular ejection fraction (HFpEF) at the outpatient cardiology units at Messina and Catania University Hospitals (Italy). Patients were in sinus rhythm and needed to have good transthoracic ultrasound imaging quality to undergo transthoracic strain-echocardiography. Other than conventional parameters, SVR and GWI (global work index) were measured. Based on cross-tabulation (a way to assess the ventricular-arterial coupling), the patients were then classified in 4 classes according to the cut-off values suggested by previous studies of 1,440 dyne/s/cm-5 for SVR (Stefadouros et al., 1973) and 1576 mm Hg% for GWI (Olsen et al., 2022). Sixty patients, 30 in each group, aged 61±16 years, 78% males, were studied. HCM were younger than ATTR patients and in a better clinical status (23% HCM vs 77% ATTR were NYHA class 3, p<0.001). Overall, 51 patients (85%) showed high SVR, of whom 21 were HCM (70%) and 30 ATTR (100%) (p<0.005). Both, SVR and GWI were impaired (the poorest class C) in 43% HCM patients (with greater left ventricular concentric hypertrophy) vs 93% of ATTR patients (in advanced NYHA class) (p<0.001). In conclusion, assessing SVR and GWI in HFpEF patients with HCM or ATTR can help clinicians to interpret the pathophysiological and clinical features of such complex diseases.

Colorectal cancer (CRC) with KRAS mutation is prone to develop metachronous metastasis. However, effective measures for prediction and prevention of such clinical issue are currently unavailable. In this study, we confirmed that KRAS mutation is a risk factor for CRC metachronous metastasis through meta-analysis and public database analysis. Based on the ICGC-AGRO database, we have constructed a risk scoring model for predicting metachronous metastasis in KRAS-mutant CRC using machine learning, which was validated in public datasets. Furthermore, we discovered that KRAS inhibitors can effectively suppress the migration and invasion capabilities of high risk CRC cells by wound healing assay and transwell experiment, which was validated ex vivo and in vivo using organoids and splenic liver metastatic mouse model. Finally, RNA sequencing, RT-qPCR, and western blots have proven that KRAS inhibitors can suppress the epithelial-mesenchymal transition (EMT) and transforming growth factor beta (TGF-beta) signaling pathway in CRC. Collectively, our study suggests that KRAS inhibitors may inhibit the metastatic ability of CRC by suppressing EMT and the TGF-beta pathway, suggesting their potential for the prevention of metachronous metastasis in CRC with KRAS mutation.

The General equilibrium theory tries to show how and why all free markets tend toward equilibrium in the long run. However, what is meant by equilibrium in this paper is more from a thermodynamical point of view. In order to understand the actual situation, it is necessary to study open systems which are complex. In physics, such a behavior in a complex system can be explain by using Non Equilibrium Thermodynamics. A system is able to self-organize and sustain itself away from equilibrium. Economic systems may fluctuate around a particular point. To sustain it far from the equilibrium state, it needs to degrade more energy and materials. In this study, the energy consumption patterns of Sri Lanka and USA are discussed. The pattern concerning Sri Lanka is close to the model proposed here, whereas the energy consumption pattern of USA is more complicated due to external factors.

Background and Objectives: Recent studies have focused on the association between the risk of diabetic retinopathy (DR) and rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene, whereas their results remain inconclusive. Thus, a systematic review and meta-analysis was car-ried out to clarify the role of these polymorphisms in the development of DR. Materials and Methods: A systematic research of electronic databases (PubMed, Scopus, and Cochrane Library) was conducted until June 16, 2023, and a reference list of relevant articles was collected, which explored the association between rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene and the risk of DR. The pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated via random-effects model and the meta-analysis was implemented by using Review Manager 5.4. Results: In total, 6 out of 178 studies, with 1,888 cases (DR) and 2,285 controls (without DR), were included in the meta-analysis. A statistically significant association between rs1501299 poly-morphism and DR risk was recorded in G vs. T in the overall analysis (OR=0.84, 95% CI=0.72-0.99, p=

Introduction: Senescence-resembling alterations on lymphocytes of dialysis patients have been widely described. However, pathophysiology behind these phenomena has not been clarified. In this study, we examine the impact of dialysis prescription and residual renal function on T and B lymphocytes, in dialysis patients. Methods: T and B cell subsets were determined with flow cytometry in 36 hemodialysis and 26 hemodiafiltration patients, according to the expression of CD45RA, CCR7, CD31, CD28, CD57 and PD1 for T cells, and IgD and CD27 for B cells. Immune phenotype was associated with dialysis modality, hemofiltration volume, and mortality. Results: Compared to hemodialysis, hemodiafiltration patients had significantly decreased percentage of CD4+CD28-CD57- T cells [3.8(2.4-5.3) vs 2.1(1.3-3.3)%, respectively, P=0.002] and exhausted CD4+ T cells [14.1(8.9-19.4) vs 8.5(6.8-11.7)% , respectively, P=0.005]. Additionally, hemofiltration volume was negatively correlated to CD8+ EMRA T cells (r=-0.46, P=0.03). Finally, exhausted CD4+ T cells percentage could predict all-cause mortality in dialysis patients, independently of age. Conclusion: Hemodiafiltration, especially with high hemofiltration volume, may have beneficial effects on senescence-related immune phenotype. Immune phenotype may also be a predicting factor for mortality in dialysis patients.

Antler is the fastest growing tissue. Because is based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus its extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound testing direct effects in cells of different tumours: glioblastoma (GBM), colorectal and breast cancer, and leukaemia. DVA reduced viability of tumour but not healthy cells. Mobility decreased at least at the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight 66.3% and 61.4% respectively, and also spleen weight. In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related with tumour fighting and down-regulated those related with inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system.

The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting "nodes" in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being “shared” between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour, before considering future directions in the field.

Background: Accreditation is a qualitative assessment aimed at technical-professional quality, but above all, at organizational and measurable aspects through process and outcome checks. Method: There are few references in the literature relating to the accreditation and improvement of the quality and safety of care and treatment in the field of primary care. Clinical Governance must also be applied and certified in the field of primary care. Results: An accreditation system for general medicine is proposed based on a new dynamic model and implement that meets different requirements and assessed on the basis of indicators. Discussion: In the current Italian health system, accreditation of health structures is addressed only to public hospitals and private structures and to providers of services and services, however primary care. GPs / PLS do not have quality and safety guarantee systems or models or systems or public or private accreditation certifications with the SSR and SSN. Conclusion: Given the fundamental importance in the NHS of primary care of MG / PLS as the main and fundamental provider of services to the patient in all his socio-welfare and clinical needs, it is considered essential to think and implement an accreditation system extended to the territorial general practice as already present and in place for all affiliated and provider structures on behalf of the NHS.

This narrative review critically evaluates the multidimensional impacts of team sports on student wellness through the Wellness Wheel framework, encompassing physical, emotional, intellectual, social, spiritual, occupational, and environmental well-being. Methodologically, the review synthesizes empirical studies, systematic reviews, and meta-analyses from the last 20 years, extracted from databases such as PubMed, PsycINFO, Scopus, Web of Science, and Google Scholar, to construct a comprehensive understanding of how team sports contribute to holistic student development. Our findings highlight team sports as a vital component of educational and wellness programs, significantly enhancing not just physical health but also emotional stability, cognitive performance, social skills, spiritual enrichment, and environmental awareness. The review underscores the necessity of integrating team sports into educational curricula to promote a balanced and comprehensive approach to student well-being. It also identifies existing gaps in literature, particularly the need for further research on enhancing inclusivity and accessibility in team sports, ensuring that all students can benefit from their wide-ranging impacts. This study advocates for strategic initiatives to incorporate team sports in educational settings, emphasizing their essential role in cultivating a well-rounded, healthy, and inclusive student body.

Obesity results in hepatic fat accumulation, i.e., steatosis. Besides the fat overload, impaired fatty acid β-oxidation also promotes steatosis. Fatty acid β-oxidation takes place in mitochondria and peroxisomes. Usually very long chain and branched-chain fatty acids are first oxidized in peroxisomes, and the resultant short chain fatty acids are further oxidized in mitochondria. Peroxisome biogenesis is regulated by peroxin 16 (PEX16). In liver-specific PEX16 knockout (Pex16Alb-Cre) mice, hepatocyte peroxisomes were absent, but hepatocytes proliferated, and liver mass was enlarged. These results suggest that normal liver peroxisomes restrain hepatocyte proliferation and liver sizes. After high fat diet (HFD) feeding, body weights were increased in PEX16 floxed (Pex16fl/fl) mice and adipose-specific PEX16 knockout (Pex16AdipoQ-Cre) mice but not in the Pex16Alb-Cre mice, suggesting that the development of obesity is regulated by liver PEX16 but not by adipose PEX16. However, it was previously reported that HFD-induced obesity in the Pex16AdipoQ-Cre mice was more severe than in the wild type mice, which was not observed until 27 weeks of HFD feeding. Thus, liver initiates the development of obesity, which is enhanced by abnormal adipocytes. HFD increased liver mass in the Pex16fl/fl mice but somehow reduced the already enlarged liver mass in the Pex16Alb-Cre mice. Basal levels of serum triglyceride, free fatty acids and cholesterol were decreased whereas serum bile acids were increased in the Pex16Alb-Cre mice, and HFD-induced steatosis was not observed in the Pex16Alb-Cre mice. These results suggest that normal liver peroxisomes contribute to the development of liver steatosis and obesity.

Glycerol conversion to valuable biomolecules has been a research avenue that has attracted a significant interest in recent years due to its increasing over production, with possibilities for chemical transformation for eco-friendly processes and distinct compounds with biological activities. Also, in the current climate change in which a major emphasis is being placed on the design of green processes, solvents are key factors from both an economic and environmental point of view. In this context, due to its abundance and low-price, glycerol represents an innovative solvent coming from biomass and produce in high amount. On the other hand, Epichlorydrin, Glycidol and Solketal have become useful intermediates in chemical transformations when using glycerol as a raw material. This review focuses on glycerol as a green solvent in the synthesis of complex molecules, Epichlorydrin, Glycidol, Solketal and Tosyl solketal as an efficient recycling process for glycerol, as well as building blocks in the synthesis of glycerol derivatives, which are undeniable new source of potentials drugs.

Keywords: Oral health, diabetes, periodontal disease, caries, periodontitis.

Cancer cells can release EGF-like peptides, acquiring the capacity of autocrine stimulation via EGFR-mediated signaling. One of these peptides (HBEGF) was found to be released from a membrane-bound precursor protein, and is critically implicated in the proliferative potential of cancer cells. We observed that the increased lactate levels characterizing neoplastic tissues can induce the release of uPA, a prote-ase promoting HBEGF shedding. This effect led to EGFR activation and increased ERK1/2 phosphoryla-tion. Since EGFR-mediated signaling potentiates glycolytic metabolism, this phenomenon can induce a self-sustaining deleterious loop, favoring tumor growth. A well characterized HBEGF inhibitor is CRM197, a single-site variant of diphtheria toxin. We observed that when administered individually, CRM197 did not trigger evident antineoplastic effects. However, its association with a uPA inhibitor caused dampening of EGFR-mediated signaling and apoptosis induction. Overall, our study highlights that the increased glycolytic metabolism and lactate production can foster the activated state of EGFR receptor, and suggests that the inhibition of EGFR-mediated signaling can be attempted by means of CRM197 administered with an appropriate protease inhibitor. This attempt could help in overcoming the problem of the acquired resistance to the conventionally used EGFR inhibitors.

This review article focuses on the role of Artificial Intelligence (AI) in transforming healthcare in Africa, specifically in combatting infectious diseases, neglected tropical diseases (NTDs), and antimicrobial resistance. We provide a comprehensive overview of the significance of AI in the healthcare industry, highlighting its urgency and importance in addressing these specific health challenges in Africa. We begin by discussing the role of AI in infectious disease surveillance and outbreak detection. We explore how AI technology can be employed for real-time tracking and prediction of outbreaks, providing examples of successful AI applications in infectious disease surveillance within the African context.Next, we examine the potential of AI-enabled diagnosis and treatment for faster and more accurate diagnoses of infectious diseases and NTDs. We highlight specific examples of AI applications in diagnosing and treating these diseases in Africa, showcasing the potential of AI to improve clinical outcomes and save lives.Furthermore, we focus on how AI-driven drug discovery and development can expedite the search for new treatments for infectious diseases and combat antimicrobial resistance. We present examples of AI applications in drug discovery within the African context, illustrating the potential for AI to revolutionize the development of effective therapeutics.In addition, we delve into how AI-powered public health interventions can enhance the design and implementation of targeted interventions. We explore how AI can optimize resource allocation and facilitate data-driven decision-making processes, providing examples of AI applications in public health in Africa.Finally, we address the challenges and limitations of implementing AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. We discuss potential barriers and ethical concerns surrounding AI applications in healthcare, aiming to encourage informed and responsible utilization of AI technologies.Overall, this review emphasizes the importance and potential of AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. It positions AI as a catalyst for revolutionizing healthcare in the region, leading to more effective disease surveillance, diagnosis, treatment, drug discovery, and public health interventions.

In this paper, I investigate Hyers-Ulam-Rassias stabilities of the general quintic functional equation and the general sextic functional equation.

This paper discovers that current variational principle and Noether theorem for different physics systems with (in)finite freedom systems have missed the double extremum processes of the general extremum functional that both is deduced by variational principle and is necessarily taken in deducing all the physics laws, but these have not been corrected for over a century since Noether's proposing her famous theorem, which result in the crisis deducing relevant mathematical laws and all physics laws. This paper discovers there is the hidden logic cycle that one assumes Euler-Lagrange equations, and then he finally deduces Euler-Lagrange equations via the equivalent relation in the whole processes in all relevant current references. This paper corrects the current key mistakes that when physics systems choose the variational extreme values, the appearing processes of the physics systems are real physics processes, otherwise, are virtual processes in all current articles, reviews and (text)books. The real physics should be after choosing the variational extreme values of physics systems, the general extremum functional of the physics systems needs to further choose the minimum absolute extremum zero of the general extremum functional, otherwise, the appearing processes of physics systems are still virtual processes. Using the double extremum processes of the general extremum functionals, the crisis and the hidden logic cycle in current variational principle and current Noether theorem are solved. Furthermore, the new mathematical and physical double extremum processes and their new mathematical pictures and physics for (in)finite freedom systems are discovered. This paper gives both general variational principle and general Noether theorem as well as their classical and quantum new physics, which would rewrite all relevant current different branches of science, as key tools of studying and processing them.

The carbohydrate antigen Sda is expressed on cells and secretions of the vast majority of Caucasians. The epitope is formed by a terminal GalNAc residue β4-linked to a α3-sialylated galactose. Different carbohydrate chains N- or O-linked to glycoproteins can be terminated by this epitope. The final step of Sda biosynthesis is catalyzed by the GalNAc transferase B4GALNT2. In this review, we will discuss the multifaceted aspects of B4GALNT2/Sda biology. In particular, we will see its implications in fertility and pregnancy, in susceptibility to infectious diseases, in chronic kidney diseases and in Duchene muscular dystrophy. In particular, we will show its regulation and prognostic implications in cancer.

In this paper, we introduce a way of representing a given mapping as the sum of odd and even mappings. Then, by using this representation, we investigate the stability of various forms for the general nonic functional equation.

Many experiments and collected data support general relativity as it explains spacetime as a smooth Riemannian manifold. However, general relativity does not explain the chaotic nature of spacetime on the quantum level, where determinism is almost impossible. This is one of the major problems in physics yet it requires a deeper theory to solve this incompatibility. In this research, a derivation made from Newton’s law of gravitation to better explain the behavior of spacetime in the quantum world with the assumption that spacetime is quantized with energy wave-particles and these wave-particles accumulate to form massive wave like particles (hence the standard model of particle physics). In the end, the derivation and the assumption together clearly illustrate general relativity and quantum theory.

The association between the choice of general anesthetic agents and the risk of acute kidney injury (AKI) and long-term renal function after nephrectomy has not yet been evaluated. We reviewed 1087 cases of partial or radical nephrectomy. The incidence of postoperative AKI, new-onset chronic kidney disease (CKD) stage 3a and CKD upstaging were compared between different general anesthetic agent groups: propofol, sevoflurane, and desflurane. Four different propensity score analyses were performed to minimize confounding for each pair of comparison (propofol vs sevoflurane; propofol vs desflurane; sevoflurane vs desflurane; propofol vs volatile agents). Study outcomes were compared before and after matching. Kaplan-Meier survival curve analysis was performed to compare renal survival determined by the development of CKD stage 3a between groups up to 36 months after nephrectomy before and after matching. Propofol was associated with a lower incidence of AKI, CKD upstaging and a higher three-year renal survival after nephrectomy compared to sevoflurane or desflurane group after matching (AKI: propofol 23.2% vs. sevoflurane 39.5%, P=0.004, vs. desflurane 34.3%, P=0.031; CKD upstaging: propofol 27.2% vs. sevoflurane 58.4%, P<0.001, vs. desflurane 48.6%, P=0.017; Log-rank test propofol vs. sevoflurane P<0.001, vs. desflurane P=0.015). Propofol was also associated with a lower incidence of new-onset CKD after nephrectomy compared to sevoflurane after matching (P<0.001). However, there were no significant differences between sevoflurane and desflurane. In conclusion, propofol, compared to volatile agents, may be the reasonable choice of general anesthetic agent for nephrectomy to attenuate postoperative renal dysfunction. Randomized prospective trials are warranted to test this hypothesis.

Background/Objectives: Infectious Endocarditis often requires surgical intervention, with postoperative acute kidney injury (AKI) posing a significant concern. This retrospective study aimed to investigate AKI incidence, its impact on short-term mortality, and identify modifiable factors in patients with endocarditis scheduled for valve surgery. Methods: This single center study enrolled 130 consecutive endocarditis patients from 2013 to 2021 undergoing valve surgery. Creatinine levels were monitored pre- and postoperatively, and AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patient demographics, comorbidities, procedural details, and complications were recorded. Primary outcomes included AKI incidence, the relevance of creatinine levels for AKI detection, and the association of AKI with 30-, 60- and 180-day mortality. Modifiable factors contributing to AKI were explored as secondary outcomes. Results: Postoperatively, 35.4% developed AKI. The highest creatinine elevation occurred on the 2nd postoperative day. Best predictive value for AKI was a creatinine level of 1.35 mg/dl on the 2nd day (AUC: 0.901; sensitivity: 0.89, specificity: 0.79). Elevated creatinine levels on the 2nd day were robust predictors for short-term mortality at 30, 60 and 180 days postoperatively (AUC ranging from 0.708 to 0.789). CK-MB levels at 24 hours postoperatively and minimum hemoglobin during surgery were identified as independent predictors for AKI in logistic regression. Conclusions: This study highlights the crucial role of creatinine levels in predicting short-term mortality in surgical endocarditis patients. A specific threshold (1.35 mg/dl) provides a practical marker for risk stratification, offering insights for refining perioperative strategies and optimizing outcomes in this challenging patient population.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is an extremely rare type of vasculitis characterized by inflammation within small blood vessels or tissues that may cause damage to the lungs, heart, kidneys, and other organs. Here, we present a rare case of EGPA with cardiac involvement that presented with acute heart failure. Clinical findings: A 44-year-old woman with a history of bronchial asthma and sinusitis pre-sented with fever, shortness of breath, fatigue, unintentional weight loss, and polyarthritis. Physical examination revealed a fine basal crepitation and mononeuritis multiplex. Diagnosis: The peripheral film revealed dimorphic features, an elevated eosinophil count, low hemoglobin (Hb), and abnormally high lactate dehydrogenase levels. The cardiac enzyme levels were elevated upon admission. Cardiac magnetic resonance imaging (CMR) revealed global hypokinesia and features suggestive of myocarditis. Echocardiography showed a low ejection fraction of 25%. Thus, the patient diagnosed with EPGA and myocarditis presented with acute heart failure. Interventions: The patient was administered high-dose corticosteroids (intravenous bolus methylprednisolone 500 mg for three days, followed by 1 mg/kg of prednisolone) and cyclo-phosphamide 750 mg intravenously. Outcome: After one months, the patient showed a marked improvement in clinical and labora-tory parameters. The ejection fraction improved to 30-40%, the eosinophil count returned to normal, and the hemolytic anemia resolved. The patient was sent home with mycophenolate mofetil 1 g twice a day as maintenance therapy. Conclusion: Patients with EGPA have a higher morbidity and mortality rate when they have cardiac in-volvement. The pathophysiological mechanism of cardiac involvement in EGPA warrants con-sideration of immunosuppressive therapy in addition to standard heart failure treatment.

The susceptible-infected-recovered-vaccinated-deceased (SIRVD) epidemic compartment model extends the SIR model to include the effects of vaccination campaigns and time-dependent fatality rates on epidemic outbreaks. It encompasses the SIR, SIRV, SIRD, and SI models as special cases, with individual time-dependent rates governing transitions between different fractions. We investigate a special class of exact solutions and accurate analytical approximations for the SIRVD and SIRD compartment models. While the SIRVD and SIRD equations pose complex integro-differential equations for the rate of new infections and the fractions as a function of time, a simpler approach considers determining equations for the sum of ratios for given variations. This approach enables us to derive fully exact analytical solutions for the SIRVD and SIRD models. For nonlinear models with a high-dimensional parameter space, such as the SIRVD and SIRD models, analytical solutions, exact or accurately approximative, are of high importance and interest: not only as suitable benchmarks for numerical codes, but especially as they allow us to understand the critical behavior of epidemic outbursts as well as the decisive role of certain parameters. In the second part of our study, we apply a recently developed analytical approximation for the SIR and SIRV models to the more general SIRVD model. This approximation offers accurate analytical expressions for epidemic quantities, such as the rate of new infections and the fraction of infected persons, particularly when the cumulative fraction of infections is small. The distinction between recovered and deceased individuals in the SIRVD model affects the calculation of the death rate, which is proportional to the infected fraction in the SIRVD/SIRD cases but often proportional to the rate of new infections in many SIR models using a posteriori approach. We demonstrate that the temporal dependence of the infected fraction and the rate of new infections differs when considering the effects of vaccinations and when the real-time dependence of fatality and recovery rates diverge. These differences are highlighted for stationary ratios and gradually decreasing fatality rates. \Revised{The case of stationary ratios allows one to construct a new powerful diagnostics method to extract analytically all SIRVD model parameters from measured COVID-19 data of a completed pandemic wave.

The healthcare situation in Africa is characterized by limited resources and a high burden of disease, presenting significant challenges to the healthcare systems in the region. The integration of Artificial Intelligence (AI) technologies in African healthcare holds immense potential for addressing these challenges and improving health outcomes. This paper aims to provide a comprehensive understanding of the current healthcare landscape in Africa and the urgent need for AI-driven solutions.In addition to discussing the potential applications of AI in African healthcare, such as disease diagnosis, treatment planning, and medical imaging analysis, this manuscript seeks to shed light on the specific challenges hindering the implementation of AI in the region. By providing detailed examples and case studies, we aim to offer insights into the obstacles that need to be overcome and potential solutions that can be pursued.By leveraging AI technologies, Africa has the opportunity to revolutionize its health systems, bridging the gap in access to quality healthcare across the continent. The objective of this review article is to not only highlight the potential benefits that AI can bring to African healthcare but also to emphasize the urgent need for action and collaboration in implementing and scaling up AI innovations in the region. By doing so, African countries can pave the way for improved health outcomes and ensure that their populations receive the healthcare services they deserve.

Artificial intelligence (AI) has emerged as a powerful tool for addressing the challenges posed by climate change and their impact on public health. By leveraging its capacity to analyze and predict climatic patterns, AI offers opportunities to enhance resource management and develop effective strategies for climate change mitigation. Moreover, AI can contribute to generating sustainable solutions that address the complex and interconnected nature of climate change. For example, AI can enable the optimization of energy consumption and facilitate the integration of renewable energy sources into existing systems. It can also support the development of climate models that provide timely and accurate predictions, enabling policymakers to implement proactive measures for disaster preparedness and response. Furthermore, AI-powered disease surveillance and mitigation techniques can improve public health outcomes by identifying patterns and trends in the spread of diseases in relation to climatic factors.However, the widespread adoption of AI-based solutions is not without challenges. Ethical concerns surrounding privacy and data ownership must be addressed, as the use of AI requires access to large datasets, raising potential privacy risks. Technical constraints, such as limited computational power and the need for sophisticated algorithms, also pose obstacles to the implementation of AI in climate change mitigation strategies. Furthermore, issues related to the accessibility and affordability of AI technologies must be resolved to ensure equitable distribution and maximize its potential impact on public health.To fully harness the power of AI in addressing climate change and improving public health outcomes, it is crucial to promote innovation, multidisciplinary collaboration, and open data science. Innovation can drive the development of new AI algorithms and technologies specifically tailored to address climate change challenges. Multidisciplinary approaches that bring together experts from diverse fields, including climate science, public health, and computer science, can foster a holistic understanding of complex systems and enable the design of comprehensive solutions. Finally, open data science practices, such as sharing data and algorithms, can facilitate collaboration and accelerate progress in mitigating climate change and its public health impacts.In conclusion, AI offers promising opportunities for effectively addressing climate change and its impact on public health. However, to fully realize its potential, it is essential to tackle ethical and privacy concerns, overcome technical constraints, and ensure accessibility and affordability. By promoting innovation, multidisciplinary collaboration, and open data science, we can unlock the transformative power of AI in mitigating climate change and improving public health outcomes.

Improving the quality and access to healthcare services in rural areas is fundamental to develop sustainable healthcare systems. This research aims to explore the motivations of healthcare professionals to work and settle in rural island areas of Greece with limited access to secondary and tertiary care. The study suggests practical ways to encourage self-motivation and attract more health workers in rural areas. An exploratory qualitative research approach was employed, involving semi-structured interviews with 16 healthcare professionals working in primary care units that lack direct hospital or hospital-health center access. The research was conducted specifically in the rural islands of Cyclades. Thematic analysis was conducted to identify common themes and unique insights from the participants. The analysis revealed three thematic categories. Τhe «attraction» thematic was influenced by personal factors, random selection, origin, accommodation factors, professional factors and obligatoriness. The «recruitment» thematic was associated with understaffing, special care issues, unstable working environment, educational and organizational aspects, and insular lifestyle. The thematic of «retention» highlighted personal issues, accommodation difficulties, economic and work-related issues, and unique challenges posed by an insular lifestyle. This research provides valuable insights into the motivations that drive healthcare professionals to settle, work, and remain in remote island units, as well as the challenges they encounter in making this decision. The study proposes strategies to motivate and attract more healthcare professionals to rural areas. These findings should be considered when formulating or reviewing primary healthcare empowerment policies to ensure equitable healthcare access for all individuals.

The increasing prevalence of Metabolic Syndrome (MetS), a serious condition associated with elevated risks of cardiovascular diseases, stroke, and type 2 diabetes, underscores the urgent need for effective diagnostic tools. This research carefully examines the effectiveness of 16 diverse machine learning (ML) models in predicting MetS, a multifaceted health condition linked to increased risks of heart disease and other serious health complications. Utilizing a comprehensive, unpublished dataset of imbalanced blood test results, spanning from 2017 to 2022, from the Laboratory Information System of the General Hospital of Amfissa, Greece, our study embarks on a novel approach to enhance MetS diagnosis. By harnessing the power of advanced ML techniques, we aim to predict MetS with greater accuracy using non-invasive blood test data, thereby reducing the reliance on more invasive diagnostic methods. Central to our methodology is the application of the Borda count method, an innovative technique employed to refine the dataset. This process prioritizes the most relevant variables, as determined by the performance of the leading ML models, ensuring a more focused and effective analysis. Our selection of models, encompassing a wide array of ML techniques, allows for a comprehensive comparison of their individual predictive capabilities in identifying MetS. This study not only illuminates the unique strengths of each ML model in predicting MetS but also reveals the expansive potential of these methods in the broader landscape of health diagnostics. The insights gleaned from our analysis are pivotal in shaping more efficient strategies for the management and prevention of Metabolic Syndrome, thereby addressing a significant concern in public health.

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes owing to COVID-19 include QT prolongation and ST-T changes; however, there have been no studies on ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases. All had abnormalities in ambulatory echocardiogram parameters detected by high-resolution 24-h electrocardiogram monitoring: positive late potentials (LPs) and T-wave alternans (TWA), abnormal heart rate variability (HRV), and heart rate turbulence (HRT). Case 1 involved a 78-year-old woman with a history of chronic kidney disease, Case 2 a 76-year-old man with hypertension and diabetes, and Case 3 a 67-year-old man with renal cancer, lung cancer, and diabetes. None of them had a prior history of significant structural heart disease. Although no significant consistent increases in clinical markers were observed, all three patients died, mainly because of respiratory failure with mild heart failure. LP, TWA, HRV, and HRT were all positive in three cases with no significant structural cardiac disease at the initial phase of admission. There is a possibility that LP, TWA, HRV, and HRT have the potential to be risk stratifiers of COVID-19 pneumonia in the early phase of admission. Further accumulation of data regarding ambulatory electrocardiographic markers in patients with COVID-19 is needed.

The gastrointestinal tract is colonized by trillions of different microorganisms, named the gut microbiota, which is key to degrade undigested food such as dietary fibers. The fermentation of these food components leads to the production of short-chain fatty acids (SCFA) acetate, propionate, and butyrate, which exploit several beneficial roles for the host’s health. Their production and absorption happen in different ways in the human intestine and depend on the type of dietary fiber reaching the gut and the microorganisms involved in the fermentation. The supplementation of SCFAs, mostly butyrate, in treating gastrointestinal, metabolic, cardiovascular, and gut-brain-related diseases has been reported in the medical literature. This review aims to give an overview of the production and absorption dynamics of acetate, propionate, and butyrate in the human gut, with a final focus on the role played by these SCFAs on gastrointestinal and metabolic health and the present therapeutic implications.

We introduce two symmetric concepts to physics: “distance” (space and time in one) and “wavematter” (electromagnetic wave packet and matter in one). We claim that physics has chosen the wrong concept of time: It is not aware that the time of a moving object flows in a direction other than my time. We provide 15 proofs for our claim by solving 15 mysteries of physics graphically! For example, we prove that length contraction and time dilation are actually geometrical effects in a 4D manifold that we call “Euclidean spacetime” (ES). We prove that the discrepancy in calculating the Hubble constant stems from a systematic error in the redshift measurement. We prove that what I deem wave, deems itself matter, which solves wave–particle duality. We even untangle quantum entanglement without the issue of non-locality. We finally understand why alternative theories of Euclidean relativity have failed: They are all based on four dimensions of space rather than distance. A huge amount of energy was injected into ES at a point that we take as origin. Ever since has this energy been moving radially away at the speed of light. We live in the 3D hypersurface of an expanding 4D hypersphere. Hyperspherical coordinates have the great advantage that they reduce all that is ever happening to just one formula. So, it is the Theory of Everything in these coordinates: “Energy is covering radial distance which, divided by Euclidean time, is equal to the speed of light.” Acceleration and force like gravitation emerge from a rotation of objects in ES and a subsequent projection to 3D space. Matching the symmetry simplifies physics.

Non-union is one of the severe complications of traumatic fracture and still no standard therapeutic recommendations currently. A total of eleven patients were treated on the lesions for non-union, after the failure of open reduction internal fixation (ORIF) or total hip replacement, by autologous conditioned serum (ACS) for one to three times monthly and followed up. Seven patients received ACS three times, three patients received it two times, and the only one who underwent total hip replacement received it once. Ten patients achieved union at the last follow-up visit, indicating the effectiveness of ACS on patients who suffered from non-union after ORIF. ACS has the potential as an alternative or adjective treatment for non-union and is worthy to be investigated further for the benefits of patients.

A new heterocyclic compound, 2-(2,6-diisopropylphenyl)-1-methylimidazo[1,5-a]quinolin-2-ium tetrafluoroborate 1 was obtained from its precursor, N-(2,6-diisopropylphenyl)-N-(quinolin-2-ylmethyl)acetamide 2, by POCl3-mediated cyclization. For the first time – the tertiary acetamide 2, precursor of 1, was synthesized by using commercially available starting materials. The structure of 1 was unquestionably confirmed by 1H-, 13C-, 2D-NMR-, IR- spectroscopy and mass-spectrometry. Its optical properties were also studied.

This paper presents a methodology based on deep learning models and metaheuristic algorithms for the optimization of airfoils for the design of aircraft wings with large endurance. The use of AZTLI-NN (a neural network with an architecture composed of a multilayer perceptron and a variational autoencoder) is implemented for the prediction of graphs of the aerodynamic coefficients of the airfoil as a function of the angle of attack. This neural network presents good predictions of the aerodynamic coefficients, similar to the coefficients obtained with computational fluid dynamics simulations. AZTLI-NN in combination of metaheuristic algorithms and the CST profile parameterization method show excellent performance in single-objective and multi-objective profile optimization tasks.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent world-wide. It progresses from simple steatosis to non-alcoholic steatohepatitis (NASH). Fibrosis is often present during NAFLD progression; however, factors determining which subjects develop NASH or fibrosis are unclear. Insulin-like growth factor binding proteins (IGFBP) is a family of secreted proteins involved in senescence and scarring mainly synthetized in the liver. Here we aimed to study the association of IGFBP and its induced senescence with the progression of NAFLD and liver fibrosis. Materials and Methods: 16 weeks old male C57BL/6 mice weighing 23 ± 3 g were fed either Methionine-Choline Deficient or control diet for 2, 8 or 12 weeks. Blood and liver samples were collected; histological assessment of NAFLD and fibrosis was performed. Fat contents were measured. Cellular senescence was evaluated in the liver. IGFBP levels were assessed in liver and serum. Data was expressed as Mean ± SD and analyzed by one-way ANOVA followed Tukey’s test. Lineal regression models were applied for NAFLD and fibrosis progression. p

Turkiye, located in the Mediterranean Basin, has started to experience the impacts of climate change, primarily manifesting in severe droughts that significantly affect agricultural output. Water stands as a crucial component in agricultural production. This study aims to propose water efficiency measures essential for climate change adaptation. By accessing pertinent data, partic-ularly in agriculturally reliant developing nations, this research endeavours to analyse yield losses in major crops within agricultural regions using the most suitable methodologies. Furthermore, it seeks to ascertain the financial ramifications of such losses. The methodological framework de-vised for this purpose was implemented in Türkiye's Iğdır Plain, selected as the study site. In 2022, the Iğdır province received 40% less precipitation than its usual levels. This study anticipates substantial losses in agricultural yield due to water scarcity resulting from prolonged drought conditions. Analysis reveals that among the crops cultivated in the region, clover belonging to the field crops category exhibits the highest water dependency, while apricot demonstrates the least reliance on water resources. In light of these considerations, the recommended crop rotation for the Iğdır Plain under water constraints comprises wheat, watermelon, maize, melon, apple, and apricot. Emphasizing enhanced water transmission and utilization efficiency, particularly in ir-rigation zones, prioritizing water stress-resistant crops within basin crop patterns, and favouring alternative crops over those demanding excessive water will foster sustainable water resource management. This approach encourages farmers to actively engage in the adaptation process to climate change and drought conditions while minimizing the agricultural sector's vulnerability to the impacts of climate change, which heavily relies on water consumption

Introduction: The Get Active Questionnaire (GAQ), developed by the Canadian Society for Ex-ercise Professionals (CSEP) was recently recommended for pre-participation screening for the general population in Singapore before increasing exercise levels. This review examines the evi-dence behind the GAQ and relevance to our tropical environment. Methods: Searches were done via Pubmed, MEDLINE and the Cochrane Central Register of Controlled Trials. Resources referenced by the CSEP were hand-searched. The CSEP was also contacted for further information. Evidence behind each GAQ question was compared to inter-national literature and guidelines, where applicable. Results: Out of 273 studies, 49 were suitable for analysis. Two GAQ studies commissioned by the CSEP showed a high negative predictive value but high false negative rate. Of the nine GAQ questions, those on dizziness, joint pains and chronic diseases appear justified. Those on heart disease/stroke, hypertension, breathlessness and concussion require modification. That on syncope can be amalgamated into the dizziness question. The remaining question may be deleted. No long-term studies were available to validate use of the GAQ. Heat disorders were not considered in the GAQ. Conclusions: Modification of the GAQ, including inclusion of environmental factors, may make it more suitable for the general population and should be considered.

Artificial intelligence (AI) is increasingly being used to improve the quality control of point-of-care diagnostics. This is caused by a number of factors, including the following: 1. AI can accelerate and improve testing accuracy. In comparison to humans, AI technology can review data more quickly and precisely, reducing errors and improving overall quality assurance. 2. When it comes to improving POC test findings on healthcare issues such as infectious diseases or medical crises such as heart attacks, AI can be used for sophisticated predictive analytics and modeling that aid in better decision-making. 3. Artificial intelligence facilitates process automation, increasing productivity and lowering labor costs in labor-intensive tasks such as testing and analyzing samples collected at point-of-care facilities. 4. The use of AI enables organizations implementing these solutions to gain insights from large volumes of raw diagnostic data generated faster and more accurately, allowing them to build solid frameworks around preventive care initiatives and significantly influence public health outcomes.5. Artificial intelligence (AI) has been demonstrated to be a useful tool for real-time monitoring systems that identify any problems with test results early so that they can be corrected before affected patients receive inaccurate diagnoses or treatment plans based on false information provided by diagnostic tests performed at points of care such as clinics or hospitals.Using these technologies would allow healthcare organizations to spend less on labor while still receiving exact diagnoses and rapid treatment delivery at a fraction of the cost that manual approaches required earlier.

Even despite rapid advances in colorectal surgery, morbidity and mortality rates in elective gastrointestinal surgery play a significant role. For decades, there have been tempestuous discussions on preventive measures to minimize the risk of anastomotic dehiscence. When mechanical bowel preparation before elective procedure, one of the key hypotheses, has been introduced into practice, it was assumed that it would decrease number of infectious complications and anastomotic dehiscence. The advancements in antibiotic treatment supported concomitant administration of oral antibiotics and mechanical bowel preparation. In the prospective study conducted at our clinic, we performed left-side colorectal procedures without the prior mechanical preparation. All patients enrolled in the study underwent the surgery and had been observed in the 3rd Surgical Clinic, Faculty of Medicine, Comenius University in Bratislava, Slovakia, from January 2019 to January 2020. As a control group we used similar group of patients with MBP. Our observed group included 87 patients with tumors in the left part of their large intestine (lineal flexure, descendent colon, sigmoid colon, and rectum). Dixon laparoscopic resection was performed in 26 patients. Sigmoid laparoscopic resection was performed in 27 patients. In 12 patients, the procedure was started laparoscopically but had to be converted due to adverse anatomical conditions. The conservative approaches mostly included Dixon resections (19 patients), sigmoid colon resection (5 patients) and left side hemicolectomy (6 patients), and Miles´ tumor resection with rectal amputation (4 patients). Our study highlighted the fact that MBP does not have the unequivocal benefit for patients with colorectal infection, which has an impact on development of anastomotic dehiscence.

In this article key results in general relativity are studied and the dynamics of quantum fields in curved spacetime is reviewed. It has been shown geometrically how dark energy breaks strong energy condition. We study tan-hyperbolic inflation for an open FRWL universe and show that over half and full period scalar field remains in it's initial state.

Characterization of cancer cells and neural stem cells indicates that tumorigenicity and pluripotency are coupled cell properties determined by neural stemness, and tumorigenesis represents a process of progressive loss of original cell identity and gain of neural stemness. This reminds of a most fundamental process required for the development of the nervous system and body axis during embryogenesis, i.e., embryonic neural induction. Neural induction is that, in response to extracellular signals that are secreted by the Spemann-Mangold organizer in amphibians or the node in mammals and inhibit epidermal fate in ectoderm, the ectodermal cells lose their epidermal fate and assume the neural default fate and consequently, turn into neuroectodermal cells. They further differentiate into the nervous system and also some non-neural cells via interaction with adjacent tissues. Failure in neural induction leads to failure of embryogenesis, and ectopic neural induction due to ectopic organizer or node activity or activation of embryonic neural genes causes a formation of secondary body axis or a conjoined twin. During tumorigenesis, cells progressively lose their original cell identity and gain of neural stemness, and consequently, gain of tumorigenicity and pluripotency, due to various intra-/extracellular insults in cells of a postnatal animal. Tumorigenic cells can be induced to differentiation into normal cells and integrate into normal embryonic development within an embryo. However, they form tumors and cannot integrate into animal tissues/organs in a postnatal animal because of lack of embryonic inducing signals. Combination of studies of developmental and cancer biology indicates that neural induction drives embryogenesis in gastrulating embryos but a similar process drives tumorigenesis in a postnatal animal. Tumorigenicity is the manifestation of aberrant occurrence of pluripotent state in a postnatal animal. Pluripotency and tumorigenicity are both but different manifestations of neural stemness in pre- and postnatal stage, respectively, of animal life. The unique property of neural stemness is derived from the evolutionary advantage of neural genes and the neural-biased state of the last common unicellular ancestors of metazoan. Based on these findings, I discuss about some confusion in cancer research, propose to distinguish the causality and associations and discriminate causal and supporting factors involved in tumorigenesis, and suggest revisiting the focus of cancer research.

Background: During the pandemic, Emergency departments were overcrowded with critically ill patients and confronted ethical dilemmas to assign respiratory support to them due to scarce resources. Quick tools to evaluate patients at admission were needed; many scores were used but inaccurate to predict outcomes. The Rox Index is an easy and fast score that reflects the respiratory status in acute respiratory failure patients, this score could predict the outcome of covid 19 patients. Hypothesis: The 24-hour difference in the Rox Index discriminate accurately the mortality and needs for mechanical ventilation of patients with covid-19. Methods: Study design: Prospective analytic study. Population: 204 Patients admitted to the emergency department from May to August 2020. Data were collected from the clinical records. The Rox Index was calculated at admission and 24h later, the difference was used to establish the outcome, a logistic regression model adjusting for age, sex, presence of comorbidities and disease severity to build and perform ROC analysis. Results: Difference in respiratory ROX Index between admission and 24h is a good predictor for death AUC 0.92 and for mechanic ventilation AUC: 0.75. Each decrease in one unit of the difference at 24h had an Odds Ratio for death risk: 1.48 (95%CI: 1.31-1.67) and for mechanic ventilation: 1.16 (95%IC: 1.1-1.23). Conclusion: The 24-hour variation of Rox Index has good predictive value and allows healthcare professionals to identify which patients will benefit from invasive treatment, especially in low resource settings where emergency physicians deal with survival.

Early detection of PDAC remains challenging due to the lack of early symptoms and absence of reliable biomarkers. The aim of the present project was to identify miRNA and proteomics sig-natures discriminating PDAC patients with DM from nondiabetic PDAC patients. Proteomics analysis and miRNA array were used for protein and miRNA screening. We used western blot-ting and Real-Time Quantitative Reverse Transcription polymerase chain reaction (qRT-PCR) for protein and miRNA validation. Comparisons between experimental groups with normal dis-tributions were performed using one-way ANOVA followed by Tukey’s post hoc test and pair-wise tests were performed using t tests. P≤0.05 was considered statistically significant. Protein cluster of differentiation 166 (CD166), glycoprotein CD63 (CD63), S100 calcium binding protein A13 (S100A13), and tumor necrosis factor-β (TNF-β) were detected in the proteomics screening. The miRNA assay revealed a differential miRNA 1285 regulation. Previously described in the literature target proteins of miR-1285 cadherin-1 (CDH-1), cellular Jun (c-Jun), p53, mothers against decapentaplegic homolog 4 (Smad4), human transglutaminase 2 (TGM2) and yes-associated protein (YAP), were validated via Western blotting. miR-1285-3p was successfully validated as differentially regulated in PDAC + DM via qRT-PCR. Overall, our data suggest miRNA1285-3p, TGM2, CDH-1, CD166 and S100A13 as potential meaningful biomarker candi-dates to characterize patients with PDAC + DM. Data are available via ProteomeXchange with identifier PXD053169.

Incisional hernias have a particular dynamic related both to the repair method and to the absence or presence of a prosthetic material. The incidence of incisional hernias is estimated at 9.8% after 21 months and increases to 18.7% after ten years. This study presents a surgical method for the repair of recurrent incisional hernias, through open surgery and the use of existing mesh. The selection criteria regarding the use of this method are: the prosthesis is well integrated, without granulomas, suppurations, defect appearing on the same prosthetic abdominal area. The analyzed factors were the location of the incisional hernias, the duration of the operation, the duration of hospitalization, identified complications, the size of the parietal defect. The retrospective study carried out focused on recurrences of incisional hernias from a group of 631 patients operated on for incisional hernias in a general surgery department of Dr. Constantin Andreoiu County Emergency Hospital, Ploiești, Romania, during January 2018 - December 2022. Of the total of 18.22% relapses, 13.6% were relapsed eventrations after prosthetic procedures. Following the application of the selection criteria, several 8 patients with recurrent eventrations were operated by the open method using the existing mesh. In the case of recurrences after prosthetic procedures of incisional hernias, the recurrence can be solved by open surgery using the existing well-integrated prosthesis, without tension, absence of suppuration in the wound, and the peritoneal cavity. For the presented case, the return to daily activities occurred after 22 hours of hospitalization.

We demonstrate that multiple well-known metrics, such as the Schwarzschild metric and the extremal solution of the Reissner-Nordstr ̈om metric, can be expressed in what we will call thermodynamic form. These formulations appear to be valid for all Rs = ct growing black holes and, therefore, also within the framework of Rh = ct growing black hole cosmology. However, the metrics can also be applied to non-black hole gravitational objects as long as one calculates the CMB and Hawking temperature of the hypothetical black hole from the gravitational mass.

Recent developments, begun by the ascending spiral of the anticipated endless prospects of ChatGPT, promote artificial intelligence (AI) as an indispensable tool and commodity whose time has come. Yet the sinister specter of a technology that has hidden and unmanageable attributes that might be harmful to society looms in the background. As well as the likelihood that it will never deliver on the purported promise of artificial general intelligence (AGI). Currently the prospects for the development of AI and AGI are more a matter of opinion than based on a consistent methodological approach. Thus the need to take a step back to develop a general framework from which to evaluate current AI efforts, which also permits the determination of the limits to its future prospects as AGI. To gain insight into the development of a general framework, a key question that needs resolution is, what is the connection between human intelligence and machine intelligence? This is the question that needs a response because humans are at the center of AI creation and realize that without an understanding of how we become what we become, we have no chance of finding a solution. This work proposes infoautopoiesis, the self-referential, recursive and interactive process of self-production of information, as the needed general framework. Infoautopoiesis shows how the key ingredient of information is fundamental to an insightful resolution to this crucial question and allows predictions as to the present and future of AGI.

Abstract: A new method for constructing exact solutions of the General Relativity equations for a dusty matter with fractal property is proposed. This method allows to find the solution of the GR-equations in terms of matter velocities : the connection coefficients and the Ricci tensor of space-time are expressed in terms of matter velocities; the metric tensor and the matter density are found as functions of velocity from the GR-equations. The connection coefficients and the Ricci tensor are invariant with respect to the discrete scaling transformation of velocity , where is constant. Therefore, the found solution can be used to simulate the fractal properties of the cosmic web in terms of matter velocities. This solution includes isotropic and anisotropic distributions of matter density. In an isotropic case, there is a class of exact solutions including both the well-known Friedmann’s solution and a solution with a periodic distribution of the matter density in space. This last solution may be used to simulate the quasi-periodic distribution of matter in the cosmic web. It is possible that, the cosmic web and its fractal properties are the space-time primary properties. These properties are described with a deformation tensor of the space-time.

In recent years, the prevalence of tobacco and electronic cigarette (e-cigarette) use among adolescents has raised significant public health concerns worldwide. This study aims to investigate respiratory symptoms among Polish adolescents. We conducted an online survey among Polish school students from all provinces, collecting data over two months in Spring 2021. Students voluntarily complete the anonymous survey, answering questions about respiratory symptoms, smoking habits (both traditional and electronic cigarettes), and demographic information. Analysis focused on four subgroups: non-tobacco users, traditional cigarette smokers, e-cigarette users, and dual users, totaling 10,388 pupils aged 12-18 years, predominantly attending secondary technical and comprehensive schools. A total of 10388 pupils participated in the study, 55.6 % (5778) of whom were girls and 44.4 % (4610) boys. Adolescents, who admitted using both e-cigarettes and traditional cigarettes experienced more frequent episodes of cough during the day (39.70%) and at night (18.40%) compared to their peers in other groups. Chest discomfort, including pain and pressure, was also reported more often by adolescents, who used e-cigarettes and traditional cigarettes concurrently (27.60%) compared to their peers in other groups. Chest pressure was experienced less commonly by non-smoking adolescents (14.40%) than by smokers (18.90%). Higher severity of cough during the day and at night was observed in the group of adolescents using traditional cigarettes and e-cigarettes concurrently compared to the other groups. The adolescents in the dual user group experienced more severe dyspnoea and wheezing compared to the other groups included in the comparison. The results of this study confirm the correlation between the occurrence of respiratory symptoms in adolescents who smoke cigarettes, use e-cigarettes and in dual users. The respiratory symptoms occur most frequently and are the most severe in the group of adolescents who use e-cigarettes and traditional cigarettes

The objective of this study is to investigate how different therapies modulating insulin resistance, either causally or consequently, affect metabolic parameters in treatment-naive subjects with T2DM. A total of 212 subjects were assigned to receive either a tight Japanese diet (n=65), pioglitazone at doses ranging from 15-30 mg/day (n=70), or canagliflozin at doses ranging from 50-100 mg/day (n=77) for a duration of three months. Correlations and changes (Δ) in metabolic parameters relative to insulin resistance were investigated. Across these distinct therapeutic interventions, ΔHOMA-R exhibited significant correlations with ΔFBG and ΔHOMA-B, while demonstrating a negative correlation with baseline HOMA-R. However, other parameters such as ΔHbA1c, ΔBMI, ΔTC, ΔTG, Δnon-HDL-C, or ΔUA displayed varying patterns depending on the treatment regimens. Participants were stratified into two groups based on the median value of ΔHOMA-R: the lower half (X) and upper half (Y). Group X consistently demonstrated more pronounced reductions in FBG compared to Group Y across all treatments, while other parameters including HbA1c, HOMA-B, TC, TG, HDL-C, non-HDL-C, TG/HDL-C ratio, or UA exhibited distinct regulatory responses depending on the treatment administered These findings suggest that 1) regression to the mean is observed in the changes of insulin resistance across these therapies. 2) modulation of insulin resistance with these therapies, either causally or consequentially, results in differential effects on glycemic parameters, beta-cell function, specific lipids, body weight or UA.

JAK2 V617F is a somatic mutation associated with myeloproliferative neoplasm (MPN): polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). In MPNs this mutation is associated with the germline GGCC (46/1) haplotype. Most studies consider the association of the JAK2 haplotypeGGCC_46/1 with some MPNs clinical parameters but no one analyzed the association between JAK2 haplotypeGGCC_46/1 and the onset of onco-drug resistance. Thus, we assessed for JAK2 46/1 haplotype correlation with therapy response in JAK2 V617F positive patients. Patients with MPN, selected by the Hematology Laboratory of “V. Fazzi” Hospital (LE), were analyzed with RLFP-PCR assay with rs10974944 SNP. Most of them had PV (63%) or PMF (61%). Among patients that developed onco-drug resistance, 58% had C/G genotype and only 11% had the G/G allele. No correlation between onco-drug resistance and JAK2 haplotype 46/1 variants emerged. Nevertheless, we observed that G/G allele seems to be related to MPNs evolution to myelofibrosis and to the development of onco-drug resistance clinical parameters (p-value= 0.002449; odd ratio of 3.701209). Thus, although other analyses are required, due to the narrow cardinality of sample, our findings suggest how the G/G allele could be useful for MPNs diagnosis and for the prediction of the disease outcome.

The objective of this study was to analyze the epidemiological links of HIV, HCV and HIV-HCV coinfections to less studied types of transmission in certain populations. We performed an observational, prospective study on 903 patients aged between 15-87 years who took part in the Open Test Project. They were divided into two subgroups: general population and individuals from prisons, and questioned about multiple risk factors. Chi-Square Independence Test was used to establish correlations between the risk factors and the results of the screening tests. Logistic regression was used to calculate the probability of a reactive screening test based on each independent risk factor and age. HIV was very strongly associated with unprotected sexual intercourse with HIV-positive partners (the strongest association), unprotected sexual intercourse with sex workers, newly diagnosed sexually transmitted diseases (STDs), intravenous drug use (IDUs) and sharing injecting materials. In the case of HCV reactive tests, very strong associations have been established with injecting drug use (the strongest association), unprotected sexual intercourse with IDUs and sharing injecting materials. Our study indicates the need for implementing targeted public health programs, tailored to the local epidemiology that can ultimately lead to micro-elimination of hepatitis and HIV infections in this area.

Background: Study to assess glucose levels of people with type 1 diabetes (T1D) overnight based on insulin type and timing. Methods: Real-world, retrospective study in T1D using multiple daily insulin injections. Contin-uous glucose monitoring and insulin injections data were collected for ten hours after dinner us-ing the Insulclock® connected cap. Meal events were identified using ROC detection methodology. The timing of rapid insulin, second injections, and the type of insulin analogs used were evaluat-ed. Results: Nocturnal profiles (n=775, 49 subjects) were analyzed. Higher glucose AUC over 180mg/dL was observed in delayed injections (number; %; mg/dL x h): -45-15min (n=136; 17.5%, 175.9 ±271.0); -15-0min (n= 231; 29.8%, 164.0 ±237.1); 0+45min (n= 408; 52.6%, 203.6 ±260.9), (p 0.049). The use of ultrarapid (FiAsp®) (URI) vs rapid insulin analogs (RI) was associated with less hypoglycemia events (7.1 vs 13.6%; p 0.005) and TBR70 (1.7 +6.9 vs 4.6 +13.9%; p 0.003). Us-ers of glargine U300 vs degludec had higher TIR (70.7 vs 58.5 %) (Adjusted R-squared: 0.22, p < 0.001). The use of a correction injection (n= 144, 18.6%) was associated with higher hypoglycemia events (18.1 vs 9.5%; p 0.003), TBR70 (5.5 +14.2 vs 3.0 +11.1%; p 0.003), glucose AUC over 180 mg/dL (226.1 +257.8 vs 178.0 +255.3 mg/dL x h; p 0.001), and lower TIR (56.0 +27.4 vs 62.7 +29.6 mg/dL x h; p 0.004). Conclusions: Dinner rapid insulin timing, insulin types and correction injections affect nocturnal glucose profile in T1D.

Parasomnias are a group of sleep disorders characterized by abnormal and unpleasant motor, verbal or behavioral events that occur during sleep or during transitions between wake and sleep states. They disrupt sleep and can have a detrimental impact on the individual experiencing them. Our goal was to identify types of parasomnias and their prevalence in the post-secondary student population and to explore students' coping strategies for parasomnias they found distressing. Seventy-seven post-secondary students completed the 21-item Munich Parasomnia Screening (MUPS) frequency scale. They also rated, on a 10-point scale, how disturbing each parasomnia was. Not only did 92% percent of students report at least one parasomnia, but our results also indicate that the vast majority of students experienced more than one parasomnia. This led us to investigate the likelihood of the co-occurrence of different parasomnias. With respect to the level of subjectively experienced distress, the most prevalent parasomnias were not always the more disturbing ones. Coded open-ended responses about what students do about the disturbing parasomnias indicate that grounding strategies and physical manipulation of one’s body were the most common, although most participants indicated that in spite of distress, they do nothing to cope. In conclusion, our study found a strikingly high prevalence of parasomnias in this sample of young adults and a lack of knowledge about effective means of dealing with these.

Anti-interferon (IFN)-γ autoantibodies are linked to varicella-zoster virus (VZV) infection. Given the elevated risks of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKi), we aimed to examine the relationship between anti-IFN-γ autoantibodies with HZ development in JAKi-treated patients. In twenty-four RA patients with new-onset HZ and forty-two without HZ, serum titers of anti-IFN-γ autoantibodies, plasma levels of IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IFN-γ inducible protein-10 (IP-10) were measured by ELISA. Significantly lower MCP-1 levels were observed in patients with HZ compared to those without (median, 98.21pg/ml, interquartile range (IQR) 77.63-150.30pg/ml versus 142.3pg/ml, IQR 106.7-175.6pg/ml, p&lt;0.05). There was no significant difference in anti-IFN-γ titers, IFN-γ levels, or IP-10 levels between patients with and without HZ. Three of 24 patients with HZ had severe HZ with multi-dermatomal involvement. Anti-IFN-γ titers were significantly higher in patients with severe HZ than in those with non-severe HZ (median 24.8ng/ml, IQR 21.0-38.2ng/ml versus 10.5ng/ml, IQR 9.9-15.0ng/ml, p&lt;0.005). In conclusion, patients with HZ had significantly lower MCP-1 levels than those without HZ, and patients with severe HZ had significantly higher titers of anti-IFN-γ than those with non-severe HZ. Given small sample size, our results need further validation in future studies.

VSM is a recently introduced method for entering and displaying any type of knowledge, in a form that is both semantically precise for computation and intuitive for human understanding. VSM is the combination of a new semantic model, and the design for a dedicated user interface to support it. Here we present the implementation of this user interface, as a sophisticated HTML-element, <vsm-box>, that can be embedded in any web-based curation app. We show how developers can use it for biocuration projects, customize it to particular end-user needs, and contribute to its growth. Vsm-box is open-source at https://github.com/vsmjs/vsm-box under the AGPL license, as a JavaScript (ES6) Vue.js web-component that runs in all modern web browsers. It is the capstone of the Vsmjs organization at https://github.com/vsmjs that groups its supporting modules. Extensive supplementary material on VSM and vsm-box is available at https://vsmjs.github.io.

In this short review paper we have assembled the main characteristics of partial oxidation reactions (oxidative dehydrogenation and selective oxidation to olefins or oxygenates, as aldehydes and carboxylic acids and nitriles), as well as total oxidation, particularly for depollution, environmental issues and wastewater treatments. Both gas-solid and liquid-solid media have been considered with recent and representative examples within these fields. We have also discussed about their potential and prospective industrial applications. Particular attention has been brought to new raw materials stemming from biomass and to liquid-solid catalysts cases. This review paper also summarizes the progresses made in the use of unconventional activation methods for performing oxidation reactions, highlighting the synergy of these technologies with heterogeneous catalysis. Focus has been centered on usual catalysts activation methods but also on less usual ones, such as the use of ultrasounds, microwaves, grinding (mechanochemistry) and photo-activated processes, as well as their combined use.

The fact that real dissipative (entropy producing) processes may be detected by non–comoving observers (tilted), in systems that appear to be isentropic for comoving observers, in general relativity, is explained in terms of the information theory, in analogy with the explanation of the Maxwell's demon paradox.

Art therapy fosters emotional healing and growth. This process can offer healthcare professionals (HCPs) novel insights into patients’ medication experiences. We developed a Metaverse Art Gal-lery of Image Chronicles (MAGIC), which depicted patients’ medication experiences symbolically as hero-villain portrayals. This gallery aimed to enhance healthcare students’ learning through re-latable insights into patients’ medication therapies. A character sheet was used to craft patients’ personifications of their medication experiences. ChatGPT, NightCafe, Canva, HeyGen and Cam-tasia were used to generate hero-villain portraits based on the character traits and mounted in MAGIC, which consisted of three virtual realms, each with a unique theme. Alpha-testing among sixteen Generation Z healthcare learners indicated that the content in MAGIC enabled them to understand the concepts of medication adherence (93.7%), art therapy (87.5%) and how patients related to their medications (81.3%). Perceived playfulness (rs=0.925, p

Background: Microscopic examination of acid-fast stained sputum smears for detecting mycobacterial acid-fast bacilli (AFB) remains the most economical and readily available method for laboratory diagnosis of tuberculosis (TB). However, this conventional approach has limitations, including low sensitivity and labor-intensive procedures. Methods: An automated microscopy system incorporating artificial intelligence (AI) and machine learning for AFB identification was evaluated. The study was conducted at an Infectious Disease Hospital in Jiangsu Province, China, utilizing an intelligent microscope system (TB-Scan, Wellgen Medical, Kaohsiung). A total of 1,000 sputum smears were included in the analysis, with the system capturing digital microscopic images and employing an image recognition model to automatically identify and classify AFB. Referee technicians provided the gold standard for discrepant results. Results: The automated system demonstrated an overall accuracy of 95.00% (950/1,000), sensitivity of 91.24% (177/194), and specificity of 95.91% (773/806). Notably, the system identified 21 smears as positive that were previously reported as negative, with referee technicians confirming 17 of these as true positive and retracting the test results accordingly. Recalculating the performance, the accuracy increased to 96.70% (967/1,000), sensitivity to 91.94% (194/211), and specificity to 97.97% (773/789), with a false negative rate of 8.06% (17/211) and a false positive rate of 2.03% (16/789). Conclusions: The incorporation of AI and machine learning into an automated microscopy system demonstrated the potential to enhance the sensitivity and efficiency of AFB detection in sputum smears compared to conventional manual microscopy. This approach holds promise for widespread application in TB diagnostics and potentially other fields requiring labor-intensive microscopic examination.

M-polynomial of different molecular structures helps to calculate many topological indices. A topological index of graph G is a numerical parameter related to G which characterizes its molecular topology and is usually graph invariant. In the field of quantitative structure-activity (QSAR) quantitative structure-activity structure-property (QSPR) research, theoretical properties of the chemical compounds and their molecular topological indices such as the Zagreb indices, Randic index, Symmetric division index, Harmonic index, Inverse sum index, Augmented Zagreb index, multiple Zagreb indices etc. are correlated. In this report, we compute closed forms of M-polynomial, first Zagreb polynomial and second Zagreb polynomial of Octagonal network. From the M-polynomial we recover some degree-based topological indices for Octagonal network. Moreover, we give a graphical representation of our results.

Resistance to the existing drugs and increasing numbers of diseases result in identifying new drug candidates with new forms of activity. Marine sources of alkylglycerols such as the liver oil Shark (SLO) mixture of certain species or rat fish (elasmobranch fishes) contain high levels of these compounds as a mixture of few species varying by length and unsaturation or saturation of the alkyl chain. They have multiple biological activities such as hematopoiesis stimulation, lowering radiotherapy-induced injuries, reducing tumor growth and improving vaccination efficiency. The synthesis of two Alkylglycerols (AKGs) containing at least one alkyne moiety in the alkyl chain has been reported. In this work, we describe the synthesis of others unknown AKGs based alkyne 1-O-(hexadec-11’-ynyl)-sn-glycerol 4 and 1-O-(octadec-9’-ynyl)-sn-glycerol 5 as analogues of bioactive ether lipids found in the SLO mixture.

In the intricate dance between viruses and host cells, RNA-binding proteins (RBPs) serve as crucial orchestrators of gene expression and cellular processes. We will delve into the riveting realm of viral hijacking, where viruses deftly exploit host RBPs to manipulate cellular machinery for their replication and pathogenesis. Through a masterstroke of molecular subterfuge, viruses co-opt RBPs involved in various facets of RNA metabolism - from transcription to degradation - to promote viral gene expression and evade host immune defenses. This manipulation leads to global alterations in cellular RNA metabolism, impacting essential host genes vital for immune responses and homeostasis.Unveiling this clandestine alliance between viruses and RBPs is not just a scientific pursuit, but a critical imperative for devising innovative antiviral strategies to disrupt these interactions. By unraveling the intricate interplay between viral proteins and host RBPs throughout the viral life cycle - from entry to assembly - researchers aim to identify vulnerabilities that can be targeted for therapeutic intervention. Strategies such as disrupting viral protein-RBP interactions hold promise for inhibiting viral replication and curbing pathogenesis, offering a beacon of hope in the battle against viral infections.Our manuscript elucidates the indispensable roles played by RBPs in viral replication, translation, and pathogenesis, shedding light on the molecular mechanisms driving viral success. Delving deeper, it explores how viruses intricately entwine with host RBPs, manipulating cellular signaling pathways to create a hospitable environment for viral spread. By dissecting these manipulative tactics, researchers uncover new targets for antiviral therapy, envisioning a future where tailored interventions disrupt viral-host RBP interactions with precision and efficacy.As the narrative unfolds, the therapeutic implications of targeting RBPs or their interactions with viral proteins emerge as a promising frontier in the fight against viral infections. From small molecule inhibitors to RNA-based therapeutics, innovative approaches are on the horizon, offering new avenues for combatting viral diseases. We set the stage for future research, beckoning researchers to delve deeper into the molecular intricacies of viral hijacking of RBPs and charting a course towards novel therapeutic interventions that promise to reshape the landscape of antiviral therapy.\Ultimately, it beckons the scientific community to embark on a voyage of discovery, unraveling the secrets of viral hijacking of RBPs and paving the way for transformative advances in antiviral therapeutics. The stage is set for a new chapter in the battle against viral infections, where knowledge becomes the sword and innovation the shield against the pernicious machinations of viral pathogens.

Abstract: Background and objective: Iliopsoas abscess (IPA) is a rare condition with varied symptomology and etiology. Less than one-third of patients with IPA present on the emergency department (ED) admission with the traditional triad of fever, back pain, and restricted hip motion (or limp), leading to delays in diagnosis and management. This case report aims to bring awareness among healthcare professionals regarding the atypical presentation and introduce a potential differential diagnosis when evaluating patients with fever and back pain. The intention is to provide insights into the signs and symptoms that may indicate the presence of an iliopsoas abscess and prompt additional investigations. Case report: Here, we describe a case of primary iliopsoas abscess associated with drug-induced acute liver failure in our ED. The patient complained of pain in the left lumbar region and fatigue that started two weeks before this presentation, claiming that, during the previous night, the pain suddenly worsened. She had a fever, pain at palpation in the right hypochondriac and left lumbar regions, accompanied by fever and vomiting, jaundiced skin, and sclera at the examination in ED. On abdominal ultrasonography, the diagnosis of acute cholangitis was suspected. The laboratory test shows leukocytosis with neutrophilia, thrombocytosis, hepatocytolysis syndrome, and hyperbilirubinemia with the predominance of indirect bilirubin. We performed then abdominal and pelvic computed tomography, which confirmed the diagnosis of cholelithiasis observed with the diameter of the bile duct within normal limits but also showed an abscess-like collection fused to the interfibrillar level of the left iliopsoas muscle; a diagnosis we most likely would have been missed. After that, the patient was hospitalized in the General Surgery Department, and surgery drainage of the abscess was performed. The patient's evolution was excellent; she was discharged after 11 days. Conclusions: The case presented here exemplifies how iliopsoas abscess, a rare cause of back pain, can quickly go unrecognized, especially in the emergency department. Our experiences will raise awareness among doctors in emergency departments about this uncommon but essential diagnosis. With advancements in diagnostic tools and techniques, we aspire that more cases of iliopsoas abscess will be accurately diagnosed.

In this paper, two types of the general fractional derivatives of distributed order as well as a corresponding fractional integral of distributed type are defined and their basic properties are investigated. The general fractional derivatives of distributed order are constructed for a special class of the one-parametric Sonin kernels with a power law singularities at the origin. The conventional fractional derivatives of distributed order based on the Riemann-Liouville and the Caputo fractional derivatives are particular cases of the general fractional derivatives of distributed order introduced in this paper.

Establishing an effective evaluation model to analyze the actual environmental level of the multi-indicator systems is an urgent challenge. However, due to the complexity of the environmental system, the factors that determine the practical system are usually interrelated. To solve this problem, many methods have been proposed and verified. However, the disadvantage of unreasonable weight determination and only single-indicator assessment limits the practical application of these analysis methods. Here, we established an optimized entropy weight model and integrate it with the fuzzy comprehensive evaluation (FCE) method to quantify the complex environmental system. By introducing the linear programming method into the entropy weight solution, we can obtain high accuracy weight values and strong resistance to extreme data. Theoretical and simulation results demonstrate that our method can enhance the precision of weight calculation and evaluation results for multi-factor systems. Our work develops an effective method to quantify the complex environment system comprehensively and is significant to real applications of evaluation method.

We study the problem of matching interior and exterior solutions of Einstein’s equations along a particular hypersuface. We present the main aspects of the C3 matching approach that involves third-order derivatives of the corresponding metric tensors in contrast to the standard matching procedures known in general relativity, which impose conditions on the second-order derivatives only. The C3 alternative approach does not depend on coordinates and allows us to determine the matching surface by using the invariant properties of the eigenvalues of the curvature tensor.

We show how it is possible to define and study black holes of arbitrary shapes in the framework of Newtonian mechanics.

This article describes the transition of an undirected active network, used for numerical and logical analysis, and made up of communicating operators and nodes, and being self-extensible, into a network of semantic structures, and the extensions necessary to handle language. The network, called Active Structure, was infused with knowledge in the form of tens of thousands of definitions taken from a human-readable dictionary. Where the dictionary fell short, from circularity, lack of a hierarchical form for its senses and sub senses, or inadequate detail around verbs, the entries were extensively curated. The result is a machine which has access to every meaning of every word in its vocabulary, and needs to manage the right meaning for every use of a word, a task that our unconscious minds now handle. To demonstrate that such a network can aspire to human-level tasks, we have begun loading an Anti-Money Laundering Act so that the machine can devise and test strategies against money launderers. There is a higher goal being aimed at, the breaking of the Four Pieces Limit. That is, the network is not intended to save money on human cognitive labor, but to raise an absurdly low limit on it.

Intermolecular interactions are the fabrics underlying almost all processes in living organisms, where two cornerstone concepts, intermolecular binding affinity (K d ) and binding energy (ΔG), have long been established to physically describe the strengths of biomolecular interactions, e.g., drug-target K d and ΔG to describe the strength of drug-target interaction. The past two-three years saw a big step forward in the use of artificial intelligence (AI) in structural biology (e.g., AlphaFold for protein structure prediction) and drug discovery & design. In light of the roles of K d and ΔG in drug discovery & design, the speed of this AI progress raises a question of what’s next for its practical application in the pharmaceutical industry, in addition to a system-wide account of biomolecular structures and motions. Last August, the concept of a general intermolecular binding affinity calculator (GIBAC) was for the first time coined and proposed in an MDPI-published preprint. Here, this article puts forward an updated conceptual and practical framework of GIBAC, including its inception, definition, construction, practical applications, technical challenges and limitations, and future directions. Moreover, this article argues that the time is now ripe for the construction of such an accurate, precise and efficient GIBAC to be on the agenda of the entire drug discovery & design community, to ensure its applicability & reliability, and to enhance its value in drug R&D in future.

Particle swarm optimization (PSO) is an effective algorithm to solve the optimization problem in case that derivative of target function is inexistent or difficult to be determined. Because PSO has many parameters and variants, I propose a general framework of PSO called GPSO which aggregates important parameters and generalizes important variants so that researchers can customize PSO easily. Moreover, two main properties of PSO are exploration and exploitation. The exploration property aims to avoid premature converging so as to reach global optimal solution whereas the exploitation property aims to motivate PSO to converge as fast as possible. These two aspects are equally important. Therefore, GPSO also aims to balance the exploration and the exploitation. It is expected that GPSO supports users to tune parameters for not only solving premature problem but also fast convergence.

Considerable efforts have been devoted to modifying gravity, which aim to elucidate the possible existence or nature of dark matter and energy, describe observational data more effectively, and formulate quantum gravity. In addition, despite the immense success of the quantum field theory, the framework requires renormalization techniques and breaks down at high energies. Recently, the Planck legacy 2018 release has confirmed the existence of an enhanced lensing amplitude in the cosmic microwave background power spectra, which prefers a positively curved early Universe with a confidence level higher than 99%. This study considers the implied curvature of the early Universe as the curvature of “the background or 4D conformal bulk as a manifestation of vacuum energy” and distinguishes it from the localized curvature that is induced in the bulk by the presence of celestial objects that are regarded as ”4D relativistic cloud-worlds.” Analogously, because gravity appears to emerge owing to spacetime curvature and does not exhibit critical characteristics shared by other fields, it has been incorporated as the local curvature of the bulk affecting the embedded quantum fields that are regarded as propagating “4D relativistic quantum clouds.” To consider the effects of the bulk on embedded clouds, this paper presents interaction field equations in terms of brane-world modified gravity and the perspective of geometrization of the quantum mechanics wherein gravity is manifested by the curvature of 4D conformal bulk as an indicator of the field strength of vacuum energy on the embedded 4D relativistic clouds in addition to the boundary interactions, which could remove the singularities and satisfy a conformal invariance theory. A visualization of the evolution of the 4D relativistic cloud-worlds over the conformal spacetime of the 4D bulk is presented, whereas the standard said theories can be recovered from the interaction field equations.

The chain ladder method is a popular technique to estimate the future reserves needed to handle claims that are not fully settled. Since the predictions of the aggregate portfolio (consisting of different subportfolios) in general differ from the sum of the predictions of the subportfolios, a general multivariate chain ladder (GMCL) method has already been proposed. However, the GMCL method is based on the seemingly unrelated regression (SUR) technique which makes it very sensitive to outliers. To address this issue a robust alternative is introduced which estimates the SUR parameters in a more outlier resistant way. With the robust methodology it is possible to detect which claims have an abnormally large influence on the reserve estimates. We introduce a simulation design to generate artificial multivariate run-off triangles based on the GMCL model and illustrate the importance of taking into account contemporaneous correlations and structural connections between the run-off triangles. By adding contamination to these artificial datasets, the sensitivity of the traditional GMCL method and the good performance of the robust GMCL method is shown. From the analysis of a portfolio from practice it is clear that the robust GMCL method can provide better insight in the structure of the data.

Background P53 gene mutation is a very common event in human neoplasia, and genetic mutations in the P53 gene in a single allele are responsible for a hereditary cancer susceptibility syndrome (Li Fraumeni). These variants encode distinct isoforms of the p53 protein, which may disrupt its transcriptional activity. These point mutant proteins are more stable than the normal protein and the mutant product accumulates at a high level that allows obtaining important information about p53 gene expression in malignant cells, especially in Chronic Lymphocytic Leukemia, (CLL). By Enzyme Linked Immune-Absorbent Assay method, (ELISA), was analyzed the frequency of p53 protein expression to 20 eligible patients diagnosed with CLL for to investigate the relationship of this protein in the stages of the disease and the impact on treatment response and survival. In ELISA technique was used the specific antibodies for isoform p53 protein, PAb 240 antibodies. These antibodies bind specifically to denatured p-53 protein. Species reactivity is for human in conformity with the prospect from Manual, Catalog No. LS-F174, Bio-Rad. Results The average concentrations of p53 proteins in 17 of 20 cases were found 16.76 μg / dl, with CV = 0.5% and the probability index p = 0.034. Very high pathological values in the 3 cases of isoform p53 protein were calculated in 2 men, (PM) in the value of 60 µg / dL, respectively at 40 µg / dL and in the case of females, (PW), in 40 µg / dL value, with the transformation into Diffuse Large Lymphoma, (DLL). Conclusion This ELISA method has proven to be a useful prognostic tool for the application of personalized treatment of on-immune therapy, in cases diagnosed with the type B-CLL.

In this study, the separation conditions of UHPLC-QTOF-MS and the extraction conditions of QuEChERS were optimized. The analytical process for determining Broflanilide residues in different soil types was successfully established and applied to its adsorption, desorption and leaching in soil. Broflanilide was extracted from soil with acetonitrile as extraction solvent, and purified with 50 mg PSA + 150 mg MgSO4. The modified UHPLC-QTOF-MS method was used for determination. In different types of soil, the average recovery of Broflanilide was 87.7% -94.38%, and the RSD was lower than 7.6%. In the analysis and determination of the adsorption, desorption and leaching properties in four soils, the RSD was less than 9.2%, showing good stability and can be applied to the analysis and determination of the residue of Broflanilide in different soils.

The goal is the optimal synthesis of the parameters of the control law for a nonlinear satellite attitude control system under constraints related to the saturation effect of reaction wheels. The maximum stability degree of the control system is considered as a criterion for the optimality of the parameters of the control law, and the absolute values of the control torques and angular velocities of the reaction wheels, achievable within the limits of the physical characteristics of the drives, are considered as constraints. The solution to the optimal synthesis problem is based on the transformation of the nonlinear control system model into a linear model, within the framework of the problem of global asymptotic stability of the control system is also guaranteed. The problem is decomposed into a subproblems of obtaining the optimal transient process shape in the control system and considering the constraints. A method of synthesizing the optimal transient process shape based on the criterion of maximum stability degree had been developed. An analytical method of determining the optimal values of the control law parameters, based on decomposing the normalized characteristic polynomial in the linear model into three identical factors had been proposed. A method with regards to the constraints of the control torque and angular speed of the reaction wheels, based on transitioning from relative to real time is developed. An algorithm for calculation of the transition scale from relative to real time, ensuring the fulfillment of all constraints in the optimal synthesis problem, is proposed. An example demonstrating the efficiency and simplicity of the proposed methods and algorithm for targeted selection of technical characteristics of the control system, considering the maximum absolute values of angular speeds and control torques of the reaction wheels, is provided.

The human gastrointestinal gut contains about 100 trillion of microorganisms including up to 5000 different types of bacteria called the "gut microbiome". Alterations in the composition of gut microorganisms (dysbiosis) can cause threatening for life diseases. This present seeks to evaluate if finally diet and more specifically functional foods affect the intestinal microbiome, and if obesity and the metabolic syndrome (Mets) are associated with the intestinal microbiome. This systematic review was accomplished according to PRISMA guidelines mostly using the key words functional foods, microbiome, obesity, Mets, Mediterranean diet. The search was carried out of recent scien-tific articles from the databases Pubmed, Scopus, and Google Scholar. The most studies discussed in this review showed a potential therapeutic effect of the Mediterranean diet rich in beneficial nutrients, on body weight, fat deposition, in correlation with modulation of the synthesis of gut microbiome. This literature review demonstrates a possible relationship between the metabolites of the microflora, the endotoxemia, obesity and Mets. The role of probiotics, prebiotics, and polyphe-nols in the prevention of obesity and Mets is of high importance in promoting healthy aging. The future challenge is to understand how different dietary patterns can regulate the composition of the gut microflora and whether these changes could be long-term.

Opossums, native to the Americas, are unique marsupials with over 100 species. The Common Opossum and Virginia Opossum are notable species. They are nocturnal, omnivorous, and adapt to various habitats. Their reproduction involves a short gestation and marsupial pouch development. Despite their ecological benefits like seed dispersal and insect control, their proximity to human habitats exposes them to pathogens, posing public health risks. These include protozoa, helminths, and arthropods that can spread zoonotic parasites and vector-borne diseases. The marsupial immune system, including opossums, is complex, rivaling eutherian mammals. Key immune genes were identified in the grey short-tailed opossum genome. CD1 protein and VpreB surrogate light chain were also found. Marsupials are proposed as ideal models for studying developmental immunology. A West Indian opossum (Didelphis marsupialis) was found and examined. Blood tests revealed abnormalities, including a low white blood cell count and signs of anemia. The results contribute to understanding the species’ health and adaptability in the wild.

Idiopathic granulomatous mastitis (IGM) is a rare condition characterised by chronic inflammation and granuloma formation in the breast. The aetiology of IGM is unclear. By focusing on the protein-coding regions of the genome, where most disease-related mutations often occur, whole-exome sequencing (WES) is a powerful approach for investigating rare and complex conditions, like IGM. We report WES results on paired blood and tissue samples from eight IGM patients. Samples were processed using standard genomic protocols. Somatic variants were called with two analytical pipelines: nf-core/sarek with Strelka2 and GATK4 with Mutect2. Our WES study of eight patients did not find evidence supporting a clear genetic component. The discrepancies between variant calling algorithms, along with the considerable genetic heterogeneity observed amongst the eight IGM cases, indicate that common genetic drivers are not readily identifiable. With only three genes, CHIT1, CEP170, and CTR9, recurrently altered in multiple cases, the genetic basis of IGM remains uncertain. The absence of validation for somatic variants by Sanger sequencing raises further questions about the role of genetic mutations in the disease. These observations suggest that IGM may be influenced by non-genetic factors, such as environmental triggers or immune system dysregulation, rather than being primarily a genetic disorder.

This study introduces an advanced dual-mode composite attitude control framework for reusable launch vehicles (RLVs), underpinned by an enhanced particle swarm optimization (PSO) algorithm. This innovative strategy is tailored to meet the stringent demands for precision and robust anti-interference capabilities across the entire flight envelope of RLVs. The research commences with the formulation of a comprehensive attitude dynamics model and diverse heterogeneous actuator representations, meticulously crafted to reflect the distinct phases of RLV flight. Building upon this foundation, a synergistic control paradigm is engineered, integrating PID and fuzzy PID controllers, complemented by a refined fitness evaluation function. The crux of the study is the application of an upgraded PSO algorithm to fine-tune the controllers' weighting coefficients, culminating in an optimized dual-mode composite attitude control system. A series of comparative simulation analyses are meticulously executed to appraise the system's responsiveness, stability, precision, and resilience to interference. The findings unequivocally substantiate the superior performance of the proposed control system, affirming its substantial contribution to the advancement of RLV attitude control.

We propose a novel framework for understanding quantum phenomena through the lens of a modified electromagnetic spacetime governed by Einstein field equations. By assuming the existence of an electromagnetic spacetime that adheres to these modified geodesic and Einstein field equations, provided the field equations satisfy the Coulomb force law in weak-field approximations, we explore the derivation of Maxwell’s equations and highlight the necessity of incorporating spin to validate these equations. We derive the wave equation for the normalized transverse metric and establish its equivalence with the de Broglie wave proposition, suggesting a relationship between this metric and the particle's wavefunction. This approach offers a classical explanation for several quantum phenomena, including the double-slit experiment, entanglement, tunneling, non-locality, and wavefunction collapse. Additionally, it posits a method to visualize atomic orbital structures in line with quantum mechanical predictions. These findings suggest that the foundational principles of quantum mechanics can be interpreted as linearized approximations of general relativity applied to electromagnetic spacetime. While this theory does not yet extend to the correlations between general relativity, quantum electrodynamics (QED), and quantum chromodynamics (QCD), it provides a valuable visualization tool for physicists and advances our understanding of the unresolved challenges linking quantum mechanics with general relativity.

Van Wyk Grumbach syndrome refers to the development of peripheral precocious puberty, long-standing hypothyroidism, and gonadal masses; when not diagnosed, an unnecessary gonadectomy may be done; Here we present a case of a 10-year-old girl with Down syndrome, short stature, and vitiligo presented with vaginal bleeding, and a pelvic mass, in whom bilateral gonadectomy was performed. Most cases of Van Wyk Grumbach syndrome present in women, and classic hypothyroidism symptoms always precede the diagnosis; 11% of patients have Down Syndrome, sometimes tumor markers get elevated, and some develop severe symptoms (myopathy, short stature, mental delay, ascites, pericardial effusion, Cullen sign, pituitary hyperplasia, and severe anemia), that respond to levothyroxine treatment; Conclusions: Children with peripheral precocious puberty and gonadal masses, must be studied for hypothyroidism before any radical decision is made. Keywords: Puberty, Precocious; Ovarian Cysts, gonadectomy, Van Wyk Grumbach Syndrome

Background: Factors that could predict which patients will benefit from Immune Checkpoint Inhibitors (ICIs) are not fully understood. This study aimed to investigate the prognostic value of KRAS biomarker in patients with advanced non-small cell lung cancer (NSCLC) in relation to clinical characteristics, treatment response and PDL1 expression. Patients and methods: The study included 100 patients with NSCLC who received immunotherapy with or without chemotherapy as 1st line treatment. In biopsy samples, the PDL1 biomarker expression rate and somatic mutations of KRAS gene were determined. Results: The mean age of the patients was 67 ± 8 years. Patients were all male and 66% were found with adenocarcinoma whereas 34% with squamous cell carcinoma. The KRAS G12C mutation was found with the highest percentage (73%). In the Kaplan-Meier survival analysis, patients with PDL1&gt;49% in combination with a negative KRAS result had a median survival of 40 months compared to patients with a positive KRAS result (9 months, p&lt;0.05). In addition, patients diagnosed with adenocarcinoma, PDL1&lt;49% and negative KRAS result had a median survival of 39 months compared to patients with a positive result (28 months, p&lt;0.05). Conclusions: Our study suggests that the presence of KRAS mutations in advanced NSCLC patients has a poor prognostic value, regardless of their PDL1 expression values, after receiving immunotherapy as first-line treatment.

Strain L. fermentum U-21 secretes chaperones into the medium and it is considered as the candidate for the development of drugs, so-called disaggregases, for Parkinson’s disease therapy. This study is devoted to characterization of secreted protein encoded by C0965_000195 locus. Analysis of sequence and predicted structure of the protein encoded by C0965_000195 allows us to attribute it to the ClpL, homologs of which are known to be chaperones. The chaperone activity of ClpL L. fermentum U-21 was evaluated in vivo by refolding of differing in thermostability luciferases from Aliivibrio fischeri and Photorhabdus luminescens in Escherichia coli cells. It was observed that clpL from L. fermentum U-21 can compensate for the deficiency in the clpB gene and enhance the ability to refold thermodenatured proteins in clpB- cells. In vitro experiments have demonstrated the ability of a spent culture medium containing proteins secreted by L. fermentum U-21 cells, including ClpL, to prevent thermodenaturation of luciferases partially.We suggest that the ClpL protein from L. fermentum U-21 strain, which exhibits disaggregase properties against aggregating proteins, may be one of the clue components that play a role in the pharmabiotic properties of this strain.

Contrast-Induced Acute Kidney Injury (CI-AKI) remains a frequent iatrogenic condition since radiological procedures using intra-vascular iodinated contrast media (CM) are being widely administered for diagnostic and therapeutic purposes. Despite the improvement of the medical healthcare system worldwide, CI-AKI is still associated with direct short-term and indirect long-term outcomes including increased morbidity and mortality, specially, in patients under-lying pre-existing renal function impairment, cardiovascular disease or diabetes that could rap-idly progress into Chronic Kidney Disease. Although the RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease), AKIN (Acute Kidney Injury Network) and KDIGO (Kidney Disease Improving Global Outcomes) clinical criteria and recommendation guidelines are based on tra-ditional “gold standard” biomarkers known as serum creatinine, glomerular filtration rate and urinary output, new reliable serum and urinary biomarkers are still needed for an effective uni-fied diagnostic strategy for AKI. Starting from previous and recent publications on the benefits and limitations of validated biomarkers responding to kidney injury, glomerular filtration and inflammation among others, this review unravels the role of new emerging biomarkers used alone or in combination, as reliable tools for early diagnosis and prognosis of CI-AKI, taking into account patients and procedures-risk factors towards a new clinical perspective.

ATP is an essential molecule in many biocatalytic processes. The industrial implementation of these processes is hampered by the fact that they require stoichiometric quantities of this expen-sive co-factor. To avoid this problem, recycling systems are needed. This study characterizes a putative polyphosphate kinase enzyme from Burkholderia cenocepacia that can regenerate ATP from AMP. Sequence analysis shows that BcPPK2-III exhibits the characteristic structural motifs of known PPK2 enzymes, including conserved motifs Walker A and B, and the subclass-specific res-idue E137. Molecular docking simulations showed ADP had the highest binding affinity (-7.340 kcal/mol), followed by AMP (-7.284 kcal/mol), with ATP having the lowest affinity (-6.464 kcal/mol). The enzyme was overexpressed in E. coli. Protein expression and purification were monitored by SDS-PAGE and quantified by densitometric analysis. Enzymatic activity assays re-vealed that BcPPK2-III converts 70% ATP with a TTN of 334,000 after 24 hours and remains sta-ble over a pH range of 6-9 and temperatures up to 70°C. BcPPK2-III shows significant potential for industrial ATP regeneration and offers high conversion rates and stability. The enzyme's high conversion rate and stability make BcPPK2-III a promising candidate for the improvement of bio-catalytic processes that rely on ATP at industrial level.

Self-administered pre-participation screening for physical activity (PA) requires an instrument that should be easily used and identify individuals at high risk. The Physical Activity Readiness Questionnaire (PAR-Q+) has been used for many years. Its ease of use and ability to identify those not fit to undergo PA has not been assessed. This study was to determine the rates of the PAR-Q+ in identifying adults who may not be fit for moderate or intense PA and obtain feedback on the use of this tool. A public on-line voluntary survey on the PAR-Q+ was carried out obtaining participants’ bio-characteristics, them completing the PAR-Q+ form and providing feedback. With 1019 participants, about 57.8% engaged in at least 150 minutes of PA weekly. This decreased with increasing number of co-morbidities. Increasing age was associated with more co-morbidities. About 33.1% of the participants using the PARQ+ would have required further medical evaluation. Only 3 of the 7 main PAR-Q+ questions were easily understood. Difficulties were encountered with 39 of the 44 follow-up questions, especially amongst those with co-morbidities. The large number of technical terms was also a source of concern. The PAR-Q+ would need extensive simplification before it may be recommended for use.