The dermatological manifestations of Long Covid (LC) have languished in the shadows of chronic fatigue and brain fog. Yet they are all linked by gut dysbiosis and the cytokine triad of TNF-α, IL-1β, and IL-6. The gut microbiome common not only to LC, psoriasis, AA, and vitiligo but also to neurodegenerative disease has been recently described. This gut microbiome induces an altered tryptophan metabolism linked to autoimmune disease. SARS CoV2 invades enterochromaffin cells rich in ACE2 receptors and curtails absorption of the essential amino acid tryptophan and subsequent synthesis of serotonin and melatonin. This review suggests that an etiologic prebiotic (d-mannose)/probiotic (lactobacilli, bifidobacteria)/postbiotic (butyrate) approach to autoimmune skin disease that improves intestinal barrier integrity and that suppresses the triad of TNF-α, IL-6, and IL-1β may enhance or even eliminate the traditional immunotherapy of targeted monoclonal antibodies, Janus kinase inhibitors, and steroids. Health benefits of this approach extend well beyond suppression of autoimmune skin disease.

Upon the outbreak of the COVID-19, countries worldwide developed policies with the goal to introduce restrictive measures geared towards mitigating the spread of the virus. Although these health initiatives were put in place through top-down public directives, they relied heavily on the cooperation of citizens who had to be willing to carry them out. As a consequence, we could observe differences in compliance with governmental restrictions within and between countries. Increasing policy stringency was the method adopted overall to promote people’s compliance. This article used survey data from 10308 participants in Brazil to examine whether there was a positive correlation between policy stringency and compliance with restrictive measures to reduce the spread of COVID-19. The results revealed, however, that there was no direct influence of policy stringency on people’s health behaviors. Accordingly, I hypothesized that individual differences in personality traits were one of the drivers behind policy compliance, as they would support self-interests such as the duty to support authorities as well as the perceived health risks of certain behaviors and ultimately motivate compliance. The findings’ implications for both compliance research and for authorities wanting to nurture voluntary compliance with public health orders are discussed and suggestions are provided.

This work introduces a novel facial image capture system that utilizes computer vision technology and artificial intelligence for real-time detecting, tracking, and capturing of human faces. The objective of this study is to address the challenges posed by poor-quality facial images in biometric authentication, especially in passport photo acquisition and recognition. By combining face-aware capture technology with AES encryption for secure image storage, we present a completely open-source hardware solution that consists of a Jetson processor, a 16MP autofocus RGB camera, a custom enclosure, and a touch sensor LCD for user interaction. Pilot data collection demonstrates the system's ability to capture high-quality images, achieving a 98.98% accuracy in storing images of acceptable quality. The integration of AES encryption ensures data security, making the proposed system suitable for real-time applications in other domains beyond identity verification in passport applications, such as security systems, video conferencing, etc

Albert Einstein, shortly after publishing his General Relativity Theory (GRT) applied it to the entire universe in a paper of 1917. Einstein assumed that such a universe was static in time and possessed a uniform distribution of matter on the largest scales, obtaining a static and finite universe of spherical spatial curvature of radius R. Although this model was refuted by Edwin Hubble's discovery of the expansion of the universe, it is still often studied as a theoretical framework for some problems, such as the twin paradox. This paper will show that Einstein's static universe model leads to a privileged frame of reference, so that any observer moving at the speed v will be able to measure speeds of light other than c depending on the direction of beam transmission. The above will refute the validity of the application to this closed and static universe of the Special Relativity Theory (SRT) proposed by Einstein in 1905 in his article . In addition, a new synchronization convention and new coordinate transformations will be deduced, the "generic" transformations, which will replace those of Lorentz. Finally, the twin paradox in this universe will be solved by making use of them.

Exosomes, a subset of extracellular vesicles, have emerged as pivotal mediators of intercellular communication, revolutionizing our comprehension of cellular interactions. Their diverse cargo, comprising proteins, nucleic acids, and bioactive molecules, plays a crucial role in various physiological and pathological processes. In the intricate landscape of adult neurogenesis, exosomes wield significant influence, actively participating in the generation of new neurons within the adult mammalian brain. Originating predominantly from non-niche cells, these vesicles contribute substantially to the regulation of neuroinflammation, thereby impacting neurogenesis and offering therapeutic promise for neurological disorders. In the specific context of Parkinson's disease (PD), exosomes assume a multifaceted role, prominently implicated in the propagation of α-synuclein oligomers and the orchestration of neuroinflammation. Stem cell-derived exosomes present themselves as promising therapeutic agents, capable of reshaping the microenvironment, repairing neuronal damage, and mitigating apoptosis. The ongoing exploration of exosomes continues to unravel intricate biological processes, paving the way for innovative medical interventions and treatments, particularly within the challenging landscape of neurodegenerative diseases such as PD. The comprehensive understanding of exosomal functions holds the potential to advance our therapeutic approaches, offering new avenues for intervention and treatment strategies in the realm of neurodegenerative disorders.

Among the number of hurdles that the vaccines based in modRNA platforms have been facing, there is now another critical one: immune imprinting which decreases even more the effectiveness of the modRNA Covid vaccines.

The initiation of micro-cracks in concrete is primarily due to its brittleness, which causes severe impacts on the overall behavior of the concrete. However, incorporating fibers in concrete could significantly improve its mechanical properties. The current study demonstrates the influence of two types of fibers on the mechanical properties of concrete. Nylon Fiber Threads (NFT) and Nylon Fiber Strands (NFS) at a fiber content of 2.5 kg/m³ were incorporated in the concrete mix. Concrete with a compressive strength of 30 MPa and a water-cement ratio of 0.4 was produced to investigate the fresh and mechanical properties of conventional and nylon-fiber reinforced concrete (NFRC). The concrete prims and cylinders were tested for compressive, splitting, and flexural strength using ASTM standards (ASTM C-39, C-496, and D-790, respectively). It was found that NFT-reinforced samples achieved higher mechanical properties of concrete (13.05%) compared to NFS-reinforced samples. Test results showed that incorporation of nylon fibers (NF) in concrete decreased the compressive strength of cylindrical and cubical specimens by 0–10% and 5–15%, respectively. However, it increased the splitting tensile and flexural strengths by 0-15%, and 5-15% respectively. Furthermore, the incorporation of NF in concrete significantly improved the ductility and delayed the crack initiation in concrete.

The Power Theory of Exchange and Money (PTEM) refines the economic neoclassical two-equation model of exchange. PTEM replaces the statistical average condition of exchange, which represents the equality of supply and demand for all transactions in the market, with a more specific equation of the equality of the generalized power of the parties in relation to their objects of exchange. The purpose of the article is to show the application of PTEM for the study of various social phenomena. Along with a brief summary of the main statements of this theory, its integration into the existing corpus of theories and ideas in economics and sociology is considered. The conclusions of power theory are then applied to consider the following topics: the objective motivation of exchange by the desire to increase power, the power nature of market equilibrium, the power nature of money, the accumulation of power through profit, the creation of money as a power act, the role of the state in the creation of money, the measure of power as a possible tool for social and political research.

In the domain of financial trading, where accuracy and swift response to data discrep- ancies are paramount for maintaining clienttrust, our research paper delves into the development of a real-time alert system utilizing SpringBoot, a framework renowned for its robustness and adaptability in enterprise applications. We embark on a comprehensive journey, beginning with addressing thefoundational challenges inherent in monitoring trade inquiries - the necessity for real-time processing, unwavering data accuracy,and ensuring unwavering system reliability. The study then methodically transitions to the architectural design, where we explore howSpringBoot’s capabilities are optimally utilized to meet these challenges. Following this, we delve into the im- -plementationphase, detailing the strategic selection of compatible technologies and methods for effective data management and discrepancydetection. The paper culminates in a thorough evalu- ation of the system, where we assess performance across various operationalscenarios, scrutinize the accuracy of the discrepancy detection mechanisms, and integrate real-world feedback from users in thetrading sector. This holistic approach not only highlights the versatility and efficiency of SpringBoot in creating reliable alert systems in the high-stakes world of financial trading but also serves as a detailed guide for similar endeavors in this field

Background. Myocardial involvement mediated by chronic obstructive pulmonary disease (COPD) is a common cause of morbidity and mortality. Conventional transthoracic echocardiography (TTE) parameters are poor in the detection of subclinical myocardial dysfunction. Aim.To investigate the contribution of strain in the early detection of cardiac damage in stable COPD patients Methods. Group A and B patients with COPD were enrolled in this study. The COPD assessment test, spirometry, 6-minute walk test, and both conventional TTE and strain were performed in these patients. Results. 80 COPD patients, with a mean age 65.6 ± 8.9 years, were included. The. Left ventricular ejection fraction (LVEF) was 60.7 ± 5.1%. Right atrium and right ventricle (RV) strain were 24.5 ± 6.6% and -19.9 ± 3.7%, respectively. Additionally, left ventricle global longitudinal strain (LV GLS) was -21.1 ± 2. Forty-eight patients had impaired RV strain. Compared to COPD patient with normal RV strain, those with RV reduced starin had a lower 6meter walk distance (6MWD) (p=0.001) and forced expiratory volume in the first second (FEV1) (p=0.012), and a higher CAT score (p=0.012). A reduced RV strain was correlated with a higher risk of hospitalizations for acute exacerbation in the post inclusion year (55% versus 25%; p=0.024). No deaths were recorded during the follow-up period. No significant factors causing neither RA starin alteration nor LV GLS reduction were revealed. Conclusion. Group A and B COPD patients having normal conventional TTE parameters, speckle tracking is a key parameter in the detection of subclinical myocardial dysfunction.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Colorectal cancer is the third most diagnosed cancer in males and in females, representing 8% of estimated new cases and the third cause of cancer-related death in both sexes, accounting for 9% of cancer deaths in men and 8% in women. About 20% of patients diagnosed with CRC present metastatic disease. Although lung metachronous or synchronous metastatic spread without other involved sites has been reported in only a small proportion of patients, considering that this tumor is frequently diagnosed, the clinical approach to CRC pulmonary metastases represents a major issue for thoracic surgeons and CRC oncologists. Among patients diagnosed with pulmonary metastases from CRC, about 9 – 12% are eligible for local treatments with radical intent, including surgical resection, SBRT and ablation therapy. Due to the lack of randomized controlled trials among different local strategies, there is no definitive evidence about the optimal approach, although surgical resection is considered the most effective therapeutic option in this clinical scenario. Oncological achievement of primary radical resection, the biology of primary tumor and metastatic sites, disease free interval and or progression free survival are independent prognostic factors which make it possible to define a cohort of patients which might significantly benefit from pulmonary metastasectomy.

Interstitial lung diseases (ILDs) constitute a group of more than 200 disorders, being idiopathic pulmonary fibrosis (IPF) one of the most frequent. Telomere length (TL) shortening causes loss of function of the lung parenchyma. However, little is known about its role as prognostic factor in ILD patients. With the aim of investigating the role of TL and telomerase activity in the prognosis of patients affected by ILDs, we analysed lung tissue samples from 61 patients. We measured relative TL and telomerase activity by conventional procedures. Both clinical and molecular parameters were associated with overall survival by the Kaplan-Meier method. Patients with IPF had poorer prognosis than patients with other ILDs (p = 0.034). When patients were classified according to TL, those with shortened telomeres reported lower overall survival (p = 0.085); differences reached statistical significance after excluding ILD patients who developed cancer (p = 0.021). In a Cox regression analysis, TL behaved as a risk-modifying variable for death associated with rheumatological disorders (RD) co-occurrence (p = 0.029). Also, in patients without cancer, ferritin was significantly increased in cases with RD and IPF co-occurrence (p = 0.032). In relation to telomerase activity, no significant differences were detected. In conclusion, TL in lung tissue emerges as a prognostic factor in ILD patients, Specifically, in cases with RD and IPF co-occurrence, TL can be considered as a risk-modifying variable for death.

Introduction and Aims: COVID-19-associated invasive pulmonary aspergillosis (CAPA) is common and is associated with poor outcomes in critically ill patients. This prospective observational study aimed to explore the association between CAPA development and the incidence and prognosis of cytomegalovirus (CMV) reactivation in critically ill COVID-19 patients. Materials and Methods: We included all consecutive critically ill adult patients with confirmed COVID-19 infection who were admitted to three COVID-19 intensive care units (ICUs) in an Italian hospital from February 25, 2020, to May 8, 2022. A standardized procedure was employed for early detection of CAPA. Risk factors associated with CAPA and CMV reactivation and the association between CMV recurrence and mortality were estimated using adjusted Cox proportional hazard regression models. Results: CAPA occurred in 96 patients (16,6%) of the 579 patients analyzed. Among the CAPA population 40 (41,7%) patients developed CMV blood reactivation with a median time of 18 days (IQR 7-27). The CAPA+CMV group did not exhibit a significantly higher 90-day mortality rate (62.5% vs. 48.2%) than the CAPA alone group (p=0.166). The CAPA+CMV group had a longer ICU stay, fewer ventilation-free days, and a higher rate of secondary bacterial infections than the control group of CAPA alone. In the CAPA population, prior immunosuppression was the only independent risk factor for CMV reactivation (HR 2.33, 95% C.I. 1.21-4.48, p=0.011). Conclusions: In critically ill COVID-19 patients, CMV reactivation is common in those with a previous CAPA diagnosis. Basal immunosuppression before COVID-19 appeared to be the primary independent variable affecting CMV reactivation in patients with CAPA. Furthermore, the association of CAPA+CMV versus CAPA alone appears to impact ICU length of stay and secondary bacterial infections but not mortality.

Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease characterized by progressive parenchymal fibrosis and respiratory failure. In a model of bleomycin-induced pulmonary fibrosis, the antifibrotic and anti-inflammatory activity of Longidaza (bovhyaluronidase azoxymer), which contains a conjugate of the hyaluronidase enzyme with a high molecular weight synthetic carrier azoxymer bromide, was investigated. Experiments were conducted in male C57BL/6 mice. Longidaza was administered at different doses by intranasal and intramuscular routes. Histology, hematology and enzyme-linked immunosorbent assay were used in the study. The use of Longidaza reduced pulmonary fibrosis as evidenced by an improvement in histopathologic damage to the lungs, a decrease in the area of connective tissue and the levels of profibrotic factors (TGF-β1, hydroxyproline, collagen I) in lung tissue. In addition, Longidaza inhibited the inflammatory response in pulmonary fibrosis, decreased the levels of IL-6, TNF-α, hyaluronic acid in lung tissue and the recruitment of inflammatory cells into lung tissue. The highest therapeutic efficacy was observed with the use of Longidaza at doses of 120 and 1200 U/kg intramuscularly, which was superior to that of the reference drug pirfenidone axunio. The data presented in this study suggest that Longidaza is a new and promising drug for the treatment of IPF that warrants further investigation in patients with fibrotic interstitial lung disease.

Pulmonary aspiration is a serious anaesthetic complication with morbidity and up to 9% of all anaesthesia-related mortality. Aspiration risk is especially focused on fastening time. We aimed to evaluate the prevalence of 'risky stomach' defined by ultrasound imagine of solid contents and/or calculated gastric fluid volume >1.25 mL/kg in elective surgery also comparing this definition with the 0-2 qualitative rating scale used for "empty/risky stomach". This prospective study has 97 patients aged 2-18. Ultrasonographic evaluations of the gastric antrum content is scaled with qualitative assessment in supine and right lateral decubitus (RLD) position. Gastric volume was calculated. In our study, stomach content and volume were evaluated by ultrasound in 97% of children and 5.2% had Grade 2 antrum. In RLD position, antral CSA was 2.36 cm², and the median gastric volume was 0.46 mL/kg. In patients with grade 0 antrum has moderate and positive correlation between antral CSA and BMI, and strong and positive correlation between antral CSA and age like grade 1 antrum. We showed that 0.1%-4.7% of elective children had gastric fluid volumes of >1.25 mL/kg as "risky stomach". Ultrasound for gastric contents could be used routine practice to determine pulmonary aspiration risk in emergency and elective procedures.

(1) Infective endocarditis is a severe inflammatory disease associated with substantial mortality and morbidity. Alkaline phosphatase (AP) levels have been shown to change significantly during sepsis additionally we previously found higher initial AP drop after cardiac surgery is associat-ed with unfavorable outcomes. Therefore, the course of AP after surgery for endocarditis is of special interest. (2) 314 patients with active isolated left-sided infective endocarditis at the De-partment of Cardiac Surgery (Medical University of Vienna, Austria) between 2009 and 2018 were enrolled in this retrospective analysis. Blood samples were analyzed at different time points (baseline, postoperative day 1-7, postoperative days 14, and 30). Patients were categorized ac-cording to relative alkaline phosphatase drop (≥30% vs. <30%). (3) The rate of postoperative renal replacement therapy with or without prior renal replacement therapy (7.4 vs. 21.8%; p=0.001 and 6.7 vs. 15.6%; p=0.015, respectively) and extracorporeal membrane oxygenation (2.2 vs. 19.0%; p=0.000) was observed after a higher initial alkaline phosphatase drop. Short-term (30-day mor-tality 3.0 vs. 10.6%; p=0.010) and long-term mortality (p=0.008) were significantly impaired after a higher initial alkaline phosphatase drop. (4) The higher initial alkaline phosphatase drop was accompanied by impaired short and long-term outcomes after cardiac surgery for endocarditis. Future risk assessment scores for cardiac surgery should consider alkaline phosphatase.

A 57-year-old male with a history of hyperlipidemia and mild pulmonary hypertension presented for a left inguinal hernia repair. Preoperative electrocardiogram showed severe right axis deviation at 177 degrees and abnormal repolarization. Right ventricular hypertrophy secondary to pulmonary hypertension was the primary differential but was quickly ruled out due to the patient being asymptomatic and having great exercise tolerance. Dextrocardia was also ruled out due to normal progression on the precordial leads. The simultaneous severe right axis deviations of P, R, and T waves raised suspicion for erroneous lead placement. The repeat electrocardiogram confirmed the diagnosis.

Pulmonary thromboembolism is a very common cardiovascular disease, with a still high mortality rate. Despite the clear guidelines, this disease still represents a great challenge both in diagnosis and treatment. Heterogeneous clinical picture, often without pathognomonic signs and symptoms, represents a huge differential diagnostic problem even for experienced doctors. The decision on the therapeutic regimen also represents a major dilemma in the group of patients who are hemodynamically stable at initial presentation and have signs of right ventricular (RV) dysfunction proven by echocardiography and positive biomarker values (pulmonary embolism of intermediate-high risk). Studies have shown conflicting results about the benefit of using fibrinolytic therapy in this group of patients until hemodynamic decompensation, due to the risk of major bleeding. The latest recommendations give preference to new oral anticoagulants (NOACs) compared to vitamin K antagonists (VKA), except for certain categories of patients (patients with antiphospholipid syndrome, mechanical valves, pregnancy). When using oral anticoagulant therapy, special attention should be paid to drug-drug interactions, which can lead to many complications, even to the death of the patient. Special population groups such as pregnant women, obese patients, patients with antiphospholipid syndrome and cancer represent a great therapeutic challenge in the application of anticoagulant therapy. In these patients, not only the effectiveness of the drugs must be taken into account, but great attention must be paid to their safety and possible side effects, which is why a multidisciplinary approach is emphasized in order to provide the best therapeutic option.

Cultural recovery of Mucorales from hyphae-laden tissue is poor, and the clinical implications of culture positivity are scarcely studied. Therefore, we compared clinical and histological characteristics of culture-positive and culture-negative histology-proven pulmonary mucormycosis cases among cancer patients. Histology specimens were blindly reviewed by a Thoracic Pathologist and graded on four histopathologic features: hyphal quantity, tissue necrosis, tissue invasion, and vascular invasion. Twenty cases with a corresponding fungal culture were identified; five were culture-positive, and 15 culture-negative. Although no statistically significant differences were found, culture-positive patients were more likely to exhibit a high burden of necrosis and have a high burden of hyphae but tended to have less vascular invasion than culture-negative patients. In terms of clinical characteristics, culture-positive patients were more likely to have acute myeloid leukemia (60% vs. 27%, p=0.19), a history of hematopoietic cell transplant (80% vs. 53%, p=0.31), severe lymphopenia (absolute lymphocyte count ≤500/µL, 100% vs. 73%, p=0.36), and monocytopenia (absolute monocyte count ≤100/µL, 60% vs. 20%, p=0.11). Forty-two-day all-cause mortality was comparable between culture-positive and culture-negative patients (60% and 53%, p=0.80). This pilot study represents the first comprehensive histopathological scoring method to examine the relationship between histopathologic features, culture positivity, and clinical features of pulmonary mucormycosis.

Hydrogels, hydrophilic polymeric compounds, have been recently put under investigation as regenerative medicine applications and delivery systems for antineoplastic drugs, particularly chemotherapeutics (anthracyclines, alkylating agents), target drugs (trastuzumab) and immunotherapies. Porosity, conductivity, biodegradability and physical states are some of the peculiarities that render hydrogels suitable for therapies implementation. Chemically-modifying agents and enzymes can be also coupled to hydrogels for pharmacokinetical parameters improvement and side effects avoidance. Cardiotoxicity is in fact one of the major issues for oncological patients after treatment efficacy. Heart failure, myocarditis and hypertension are causes of morbidity and mortality that can possibly be avoided. Specific reaching of the target tumor site has been achieved by several authors in preclinical in vivo studies but clinical studies are currently under design processes. Polydioxanone, a hydrogel-mimicking agent, is capable to interact with the elastic properties of pulmonary artery. An advantageous characteristic is that can be also reabsorbed within biological systems and can cause a remodeling process of the vessel wall. Hydrogels currently represent a strong topic of interest for researchers and probably will guide future clinical investigations and practice.

Pulmonary embolism (PE) is one of the leading causes of cardiovascular mortality, therefore new parameters regarding risk stratification are sought after. In patients admitted for acute PE we investigated associations between the initial coagulation impairment, expressed by prothrombin time international normalised ratio (INR), and parameters reflecting PE severity. Furthermore, in-hospital, 30-day and long-term mortality were also evaluated. The analysis included 848 patients who were divided into two groups: with normal INR≤1.2, and elevated INR>1.2 (252 patients, 29.7%). The group with elevated INR presented higher incidence of tachycardia and lower systolic blood pressure, higher CRP, d-dimer, and NT-proBNP. This group presented higher estimated systolic pulmonary artery pressure (49 IQR39-62mmHg vs 43 IQR32-53mmHg, p<0.001) and shorter pulmonary artery acceleration time (65 IQR55-85ms vs 81 IQR63-102ms; p<0.001). Patients with elevated INR had more often a sPESI of 1 or higher (78%vs60%, p=0.003). Cox regression model revealed that age, leukocyte level, SBP, neoplasm, and INR are associated with higher risk of death (p<0.001). Finally, elevated INR was associated with higher in-hospital (13%vs3%; p<0.001), 30-day (19%vs6%; p<0.001), and long-term mortality (p<0.001). Summing up, elevated INR on admission is frequent in patients with PE, reflects worse clinical condition and is related to PE severity and prognosis.

Background: The Corona Virus Disease 2019 (COVID-19) is spreading globally now. However, the clinical presentation that predict prognosis of the patients are still largely unknow. Methods: We enrolled 393 patients infected with COVID-19 and 30 patients with common pulmonary bulla and reviewed their clinical features to evaluate the potential prognostic value of pulmonary vesicles, especially in the patients with severe symptoms. One COVID-19 patient with vesicles was treated by bullectomy for last resort, and its characteristics of the patient’s perioperative laboratory tests was analyzed. The pathological findings of bullectomy were described and compared with those of common bulla cases. Results: Patients infected with COVID-19 showed more dependence on ventilator, occurrence of super resistant bacteria, and prone to vesicle formation than common bulla (p<0.05). Disease severity is associated with age, sex, and usage of ventilator, ECMO and antibiotics, super resistance bacteria and vesicle formation (p<0.05). The average mortality rate of COVID-19 patients was 4.10% (25.4% in severe patients, 0.00% in mild patients). Interestingly, the mortality rate further increased in severe patients with pulmonary vesicles than those without pulmonary vesicles (35.7% vs 22.4%, p=0.0442). One COVID-19 patient with vesicles underwent bullectomy and had a poor prognosis, who showed diffuse alveolar damage and extensive necrosis in bullectomy specimen. Conclusions: Patients infected with COVID-19 are more prone to form pulmonary vesicles showed on chest CT scans, as an important poor prognosis factor, especially in the severe patients.

Many lifestyle and occupational habits negatively impact on physical and mental health, increasing the risk of cardiovascular and other diseases. While larger institutions fulfill occupational health requirements to ensure their employees’ wellbeing at work, smaller business workers and entrepreneurs may neglect initial signs of stress or physical decline, putting themselves at increased risk. Early detection of compromised cardiopulmonary health or fitness has the potential to flag up indications for early interventions and reduce the risk of disease onset and progression. This case study highlights the usefulness of respiratory muscle training (RMT) in improving pulmonary and cardiovascular parameters as an early countermeasure to cardiopulmonary decline. We suggest RMT as an easily accessible, cost- and time effective opportunity to support a healthy lifestyle.

Introduction: The rising trend in allergic diseases has occurred in parallel with an increasing prevalence in obesity, and suggesting a possible association. The increased body mass has numerous health consequences, including an impairment function of the respiratory system. The associations between eating habits and hypersensitivity to allergens have not been clarified sufficiently. Aim: to evaluate pulmonary function, nutritional status, eating habits and risk factors of obesity in children and adolescents with allergic rhinitis. Material and Methods: The study was performed in 106 children with allergic rhinitis (mean age 12.1+/-3.4; M/F 60/46) from the Department of Allergology. 43 (40.6%) of children presented only allergic rhinitis and in 63 (59.4%) additionally diagnosed with asthma bronchiale. Clinical data, detailed interview about allergies, assessment of pulmonary function and nutritional status, allergy skin test (Allergopharma) and spirometry (Jaeger) were evaluated. Nutritional habits were assessed by a food frequency questionnaire. The statistical analysis was done using the program Statistica v 10.0. Results: In the study group the mean centile of BMI was 49.4; underweight presented 25.4% of children, 55.6 % normal BMI and 18.8 % presented overweight or obesity. Multiple regression analysis showed a significant (adjusted R-squared: 0.97; p<0.05) association between high BMI and snacking between meals and low physical activity. No statistical association between the severity of diseases and BMI or body composition was observed. Conclusions: 1. The prevalence of excess body mass in the study group reached 13.5%. Eating habits were incorrect, especially obese children significantly more frequently ate snacks between meals than children with normal body weight. 2. Among the studied group of children and adolescents with allergic rhinitis and asthma bronchiale, the significant risk factors of obesity were snacking and low physical activity.

ABSTRACT Two years after first patients approached the emergency rooms of hospitals in Wuhan becouse of respiratory distress,thousend of SARS-CoV-2 infected persons continue to die every day worldwide.SARS-CoV-2-infected patients undergo a process of dehydration and malnutrition before they develop respiratory problems and approach the emergency room of a hospital.This is,in many cases, the consequence of high fever which causes massive loss of fluids. In addition loss of appetite, is responsible for the deficit of protein intake.Most of the virus-infected patients admitted to the emergency room are therefore hypovolemic and hypoproteinemic and suffer of respiratory distress accompanied by ground grass opacities at CT-scan of the lungs.Critically ill patients are treated following the guidelines for treatment of septic shock but with „conservative“ fluid replacement and administration of diuretics to assure sufficient hourly urine production. The combination of conservative fluid administration with reduced protein content in the enterally administered diet, together with administration of diuretics, has severe hemodynamic consequenses in mostly aged,dehydrated,critically ill patients. Many of them will develop acute kidney injury in the next 24 hours.In most of the cases, patients continue to loose weight by loosing skeletal muscle mass. Ischemic damage in the lung capillaries is responsible for the acute respiratory distreass syndrome (ARDS) and for the hallmark of autoptic findings,diffuse alveolar damage (DAD) characterized by hyaline membrane formation,fluid invasion of the alveoli recruitment of some inflammatory cells and progressive arrest of blood flow in the pulmonary vessels.The consequence is progressive congestion , increase of lung weight and progressive hypoxia (progressive severity of ARDS).Sequestration of blood in the lungs worsen hypovolemia and ischemia in different organs.This is most probably responsible for recruitment of inflammatory cells and for persistance of elevated serum levels of positive acute-phase markers and of hypoalbuminemia. Autoptic studies have been performed mostly in patients who died in the ICU after SARS-CoV-2-infection because of progessive ARDS.In those patients, tubulus epithelium necrosis in the kidney is a frequent finding as it has been the case in the first SARS-CoV-1 pandemic.In the death certification charts, many times weeks after first symptoms have started ,cardiac arrest is the cause of death after respitatory insufficiency.Replacement therapy with sufficient amount of fluid and albumin should be part of the early individualized life-saving supportive measures avoiding mechanical ventilation.

Background: The burden of resistant fungal infection is rising in patients with pulmonary disease. Options for antifungal therapy are limited, and the only orally-available antifungals, the triazoles, demonstrate inter and intra-patient variability, non-linear kinetics, toxicity, drug interactions and increasing antifungal resistance. Therapeutic drug monitoring (TDM) of itraconazole, voriconazole and posaconazole has been necessary to ensure their safety and efficacy, but is considered unnecessary for the newest triazole isavuconazole, use of which is increasing. Aims: To characterise isavuconazole susceptibility of Aspergillus fumigatus isolates in a tertiary respiratory referral centre to understand prevalence of isavuconazole antimicrobial resistance. To retrospectively review experience of isavuconazole use in this setting, assessing tolerability and therapeutic drug monitoring. Methods: A retrospective observational analysis of adult patients with respiratory disease in a tertiary hospital setting between Sept 2016 and Aug 2021. Clinical cultures were collected and triazole Minimum inhibitory concentration (MIC) were recorded (based on Clinical &amp; Laboratory Standards Institute (CLSI method)). Isavuconazole trough drug levels were carried out as part of the standard of care. Clinical outcomes of treatment were evaluated, along with drug tolerance and TDM. Results: During the study period, isavuconazole susceptibility testing was performed on 26 Aspergillus spp isolates. 80.8% of Aspergillus fumigatus isolates were non-wild type and had isavuconazole MIC &gt; 1mg/L, and 73.0% had MIC above the EUCAST (European Committee on Antimicrobial Susceptibility Testing) epidemiological cut-off (ECOFF) of 2mg/L. There was good correlation between isavuconazole MIC and voriconazole MIC (r =0.7, p=0.0002). 54 patients had isavuconazole therapy over the study period with a median duration of 7.7 months (IQR 0.79 - 16.42). 67% of patients were able to tolerate isavuconazole, despite toxicity with prior azole treatment being the primary indication for use (in 61.8%). Increased age (r=0.29; p=0.03 (95%CI 0.02,0.52)) and gender (r for female sex=-0.31; p=0.027 (95%CI -0.52,0.036) were associated risk factors for development of adverse events (AEs). 127 Isavuconazole TDM levels were performed over the study period with 90% &gt;1mg/L and 72% &gt;2mg/L. Dose change from manufacturer’s dose recommendation, however, was required in 15% of patients to achieve a serum drug concentration above the EUCAST ECOFF or Area of technical uncertainty (ATU) value of 2mg/L. Conclusion: In our study, we show use of Isavuconazole as salvage therapy in chronic pulmonary fungal disease setting with high prevalence of azole resistance. Isavuconazole MICs demonstrated good correlation with voriconazole MICs suggesting the latter could be a useful surrogate marker for isavuconazole susceptibility. Although Isavuconazole achieved excellent serum drug concentrations at standard dose compared to other azole drugs, we highlight the importance of antifungal stewardship and TDM monitoring to optimise therapy in this setting.

This review paper delves into the multifaceted aspects of pineapple cultivation, focusing on morphology studies, harvesting challenges, and mechanization efforts. Pineapple, renowned for its commercial value and unique flavor, holds a prominent position in global agriculture, with India alone producing 19.64 lakh tonnes annually. However, the hilly terrains of regions like northeastern India pose significant hurdles to traditional harvesting methods, necessitating innovative solutions. Understanding the morphology of pineapple plants is crucial for optimizing cultivation practices and designing efficient harvesting equipment. Insights from various studies shed light on leaf structure, fruit maturity, and growth patterns, providing valuable information for engineering tailored solutions. Mechanization endeavors, including semi-mechanized harvesting machines and semi-manual harvesters, demonstrate promising results in improving efficiency and reducing labor-intensive practices. Despite challenges such as increased crop losses and operational costs, continued research and development in mechanization hold the key to sustainable pineapple cultivation. This paper underscores the importance of integrating morphology studies and mechanization efforts to address the unique challenges faced by pineapple farmers, particularly in hilly terrains, and highlights the need for ongoing innovation to ensure the long-term sustainability of pineapple cultivation.

This paper proposes an innovative postulate based on experimental observations, namely, that the speed of light can vary between two inertial reference systems. This postulate is defined as the principle of relative change in the speed of light, which refreshes the concept of absolute speed of light in traditional physics. By integrating the principle of the invariance of the speed of light with the principle of relativity in relativity theory, several important conclusions are derived: space and time must be capable of and proportionally expand and contract. Between two inertial reference systems with different relative speeds of light, objects have an energy difference of k^2 times, which induces a natural tendency for objects to move towards a state of lower energy. The acceleration is only related to the relative change rate of the speed of light in vacuum space and is independent of the mass of the object. The kinetic energy obtained by the object comes from the reduction of internal energy of the object, emphasizing the key role of energy conversion in this process. The paper provides a new theoretical perspective for explaining the physical mechanisms of universal gravitation and dark energy.

Introduction and importance: Congenital bicuspid aortic valve (BAV) is a common cardiac malformation predisposing individuals to aortic stenosis, regurgitation, and aortopathy. This risk persists even after aortic valve replacement (AVR). Case presentation: We report a case of a male in his 60s with a history of BAV who underwent bioprosthetic aortic valve replacement (BVR) and ascending aorta/root repair in 2014. The patient was noncompliant with follow-up and presented nine years later with severe bioprosthetic aortic stenosis and an 8.0 cm ascending aortic aneurysm with no symptoms. Emergent redo BVR and aneurysm repair were successful. Clinical discussion: It should be emphasized that successful outcomes for BAV patients require a lifelong commitment to surveillance, even after surgical intervention. Noncompliance can lead to life-threatening consequences like bioprosthetic valve deterioration or progressive aortic dilation. Conclusion: This case highlights the importance of early BAV diagnosis for ongoing monitoring, accessible follow-up care after complex cardiac procedures, and addressing patient barriers to treatment adherence.

This paper discusses the application and advantages of artificial intelligence technology in digital media interactive product design. Firstly, the development background of artificial intelligence technology and its promoting effect on design innovation is introduced, and the application of new technologies, such as generative adversarial networks in art creation and design personalization, is definitely analyzed. It then explores in detail the ability of AI to break traditional constraints in interactive design, innovate design, and optimize user experience, especially in digital media. Finally, the case study of Microsoft Cortana shows the method of classifying and processing user queries by machine learning system and its experimental results. The research of this paper provides the theoretical basis and empirical support for the application of artificial intelligence technology in the future interactive design of digital media and has important academic and practical significance.

The energy transition towards Net Zero Emission by 2060 hinges on the renewable energy power plants in Indonesia. Good practices in several countries suggest a peer-to-peer (P2P) energy trading system using blockchain technology, supported by renewable energy (solar panels), an innovation to provide equal access to sustainable electricity while reducing the impact of climate change. The P2P energy trading concept has a higher social potential than the conventional electricity buying and selling approach, such as that of PLN (the grid management concept), but does not have a sharing element. This model implements a solar-powered mini-grid system and produces a Smart Contract that facilitates electricity network users to buy, sell, and trade electricity in rural areas via smartphones. This study aims to analyze the stakeholders' perceptions of the peer-to-peer (P2P) energy trading model using blockchain technology in Gumelar District, Banyumas Regency, Central Java Province, Indonesia. The stakeholders include households, the Ministry of Energy and Mineral Resources (ESDM), the State Electricity Company (PLN), the Institute for Essential Services Reform (IESR), Awina Company, and IPB University. The strength factors of this model are the freedom to generate and sell electricity (0.1) and transparency in electricity usage and sales by disclosing the amount, duration, and price of electricity (0.1). Regarding weakness factors, this model is primarily suitable for the lower middle class residing in rural or remote areas (0.02). Additionally, the intermittent electricity production to meet the substantial demand is a weakness (0.03). The opportunity factor for the model is the increase in public awareness and cooperation in using environmentally friendly, pollution-free electricity (0.12). Furthermore, there is an opportunity for additional income (0.12) and new business investment (0.12). Regarding threat factors, the model faces significant threats from the implementation aspect involving multiple parties (0.04). There is a potential threat in the form of losses for state utilities such as PLN or individuals who have already established electricity infrastructure if this program is implemented on a large scale (0.04). This model is located at the coordinate point (-0.40; 0.31), placing it in quadrant II. This indicates that the model should apply the Stability Strategy and focus on the Selective Maintenance Strategy for improvement. The stability strategy goal is to maintain the current situation by leveraging opportunities and addressing weaknesses. For effectiveness and efficiency, the strategy emphasizes fostering collaboration with PLN, which holds the legal authority as the sole utility company in Indonesia with an extensive electricity network, as well as advocating for regulations that support the independent purchase and sale of solar-powered electricity, particularly in areas without PLN network coverage.

This paper presents a mathematically rigorous investigation into the incompleteness of Einstein-de Sitter spacetime. The incompleteness of the spacetime is proved using results regarding isometries between connected Semi-Riemannian manifolds following the computation of the Einstein tensor of the Einstein-de Sitter spacetime. Various properties of the Einstein-de Sitter spacetime apart from its incompleteness is also discussed based on its incompleteness with the help of various results of Semi-Riemannian manifolds. Also, few properties of spacetime which cannot be concluded from the incompleteness of the spacetime is also discussed.

Preoperative assessment is crucial in surgical care, traditionally relying on physical examinations and paper-based questionnaires. The emergence of digital tools like Pathpoint® ePOA represents a significant advancement, aiming to enhance the efficiency, accuracy, and standardisation of preoperative evaluations. Pathpoint® ePOA is a cloud-based platform designed to integrate seamlessly with Electronic Health Records (EHRs), providing a comprehensive, data-driven approach to preoperative assessments. It supports improved risk stratification, optimised resource allocation, and enhanced patient engagement through features such as customisable templates and real-time data integration.Current research highlights that digital preoperative tools like ePOA offer notable advantages, including increased clinical capacity, better complexity stratification, and improved patient follow-up. Despite these benefits, gaps remain in comparative studies, detailed clinical outcomes, and patient engagement strategies, indicating areas for further exploration. Pathpoint® ePOA adheres to rigorous safety standards and risk management protocols, ensuring reliability and data security while contributing to improved surgical outcomes. The benefit-risk ratio for ePOA is favourable, underscoring its potential to advance preoperative care by optimising clinical workflows and enhancing patient safety.

This study discusses the application of deep learning technology in network intrusion detection systems (IDS) and focuses on a new model named CNN-Focal. First, through the review of traditional IDS technology, it analyzes its limitations in dealing with complex network traffic. Then, the design principle of the CNN-Focal model is described in detail, which uses threshold convolution and SoftMax multi-class classification technology to effectively improve abnormal traffic detection's accuracy and efficiency. The experimental results show that CNN-Focal performs well on the open data set, demonstrating the potential and advantages of its application in the natural network environment and providing a new perspective and method for further research of deep learning in the field of network security in the future.

The theory says that number interacts with spaces based on the meaning of mathematics, in this way it is possible to obtain numerical knowledge. The theory shows the possibility of using spaces related to each other to explain the reasons why two even numbers form a pair, two odd numbers form a pair, an even number and an odd number form an odd number, three odd numbers form an odd number . three even numbers make an odd number. an even, an odd and two evens make an odd, two odd and an even make a pair. Furthermore, it is possible to extend the logic to larger numbers, but applying rules to make it work.

The Diaphorina citri Kuwayama (D. citri) is one of the major pests in the citrus industry, which spreads Citrus Huanglongbing disease. It has developed resistance to chemical insecticides. Therefore, searching for greener solutions for pest management is critically important. The main aim of this study was to evaluate the repellent and insecticidal efficacy of essential oils (EOs) from four species of Myrtaceae plants: Psidium guajava (PG), Eucalyptus robusta (ER), Eucalyptus tereticornis (ET), and Baeckea frutescens (BF) against D. citri and to analyze their chemical composition. GC-MS analysis was performed, and the results indicated that the EOs of PG, ER, ET, and BF were rich in terpenoids, ketones, esters, and alcohol compounds. The repellent rate of all four EOs showed that it decreased with exposure time but increased with concentrations of EOs. Repellent rates ranged from 80.50% to 100.00% after treating D. citri for 6 hours with four EOs at 100% concentration and decreased to 67.71% to 85.49% after 24 hours of exposure. Among the compounds from the EOs tested, eucalyptol had the strongest repellent activity, with a 24-hour repellency rate of 100%. The contact toxicity bioassay results showed that all EOs have insecticidal toxicity to D. citri; the LC50 for nymphs was 36.47-93.15 mL/L, and for adults, it was 60.72-111.00 mL/L. These results show that when PG is used as the reference material, both ER, ET, and BF EOs have strong biological activity against D. citri, which provides a scientific basis for the further development of plant-derived agrochemicals.

This study is based on the BP neural network regression model optimised by genetic algorithm and dedicated to predicting the amount of car purchase, this study is important for all parties in the automotive industry. By plotting the violins of six indicators, including gender, age, annual salary, credit card debt, net worth, and car purchase amount, we found that, except for gender, the other data showed a trend of dense in the middle gradually decreasing to the upper and lower sides, with an overall normal distribution. The correlation analysis shows that the amount of car purchase has a high positive correlation with age (0.63), followed by annual income (0.62), the correlation between net worth and the amount of car purchase is 0.49, while the correlation between credit card debt and the amount of car purchase is low (0.03). In the experimental part, we analyse the predicted-actual values of the training and test sets in comparison and find that the model predicted values are very close to the actual values. The RMSE of the training set is 11.559 and the RMSE of the test set is 11.4835, which is not much different from each other, indicating that the model has good generalisation ability. In addition, the R2 of both the training and test sets is 1, indicating that the model fits well. The MAE of the training set is 8.2512 and the MAE of the test set is 9.578; the MBE of the training set is -4.3035 and the MBE of the test set is -2.4547.These metrics indicate that the model performs well in predicting the amount of car purchase. In conclusion, this study provides an effective and reliable method to predict the amount of car purchase, creating a useful bridge between car manufacturers, dealers and consumers.

This study presents a groundbreaking approach in the field of gaming AI, focusing on the classic game” Pacman” through the lens of DRL integrated with advanced optimization techniques. The core of the research involves adapting DRL models for” Pacman”, utilizing the ESO for hyper- parameter tuning. These novel adaptations significantly enhance the AI agent’s performance, demonstrating a remarkable improvement in adaptability, responsiveness, and efficiency within the game environment. A pivotal aspect of this research is the innovative integration of metaheuristic optimization techniques into the DRL framework, a first in the domain of Atari gaming AI. This integration has proven essential in fine-tuning the DRL models, leading to a more effective and dynamic gaming experience. The study thoroughly evaluates and compares the performance of these algorithms, providing empirical support for their effectiveness and setting a new benchmark in AI-driven game development. The implications of this research extend beyond gaming AI, opening up possibilities for future exploration in several directions. Expanding DRL models to other complex gaming environments, continuous algorithmic enhancements, real-time learning adaptations, and applying these principles to robotics and autonomous vehicles are examples. The research also emphasizes ethical and responsible AI use in gaming to address fairness and addiction issues.

Ten new Schiff bases, including thiocarbohydrazone derivatives (1–10), were synthesized using an efficient, uncomplicated, and environmentally friendly approach using the reaction of alkyl-substituted aldehydes. The thiocarbohydrazones that were obtained were derived from o-phthalaldehyde. The chemical structures of the compounds were identified by the utilization of UV-Vis spectroscopy, Fourier transform infrared (FT-IR), ¹H nuclear magnetic resonance (¹H NMR), ¹³C nuclear magnetic resonance (¹³C NMR), and elemental analysis methods. The thermal stability of thiocarbohydrazones was examined using thermogravimetric analysis (TGA-DSC). Investigations were conducted on urease inhibition tests, pharmacokinetic property research, and molecular docking. The collection of samples with the urease enzyme revealed significant molecular docking findings, with MolDock scores ranging from -153 to -189. The compounds have the potential to be effective drug candidates for treating certain diseases, as indicated by the consistent results of molecular docking, urease inhibition tests, and pharmacokinetic characteristics investigations.

Verification of inclusivity of molecular detection methods gives indications on the reliability of viral infections diagnosis because of the tendency of viral pathogens to undergo sequence variation. This study was aimed to select inclusive probe based reverse transcription quantitative PCR (RT-qPCR) assays for the diagnosis of the most widespread and detrimental viruses infecting honeybees, namely the acute bee paralysis virus (ABPV), the black queen cell virus (BQCV), the chronic paralysis bee virus (CBPV), the deformed wing virus variants A (DWVA) and B (DWVB), and the sacbrood virus (SBV). Therefore, detection methods previously described were re-evaluated in silico for specificity and inclusivity. Based on this evaluation, selected methods were modified or new ones were designed and tested in duplex RT-qPCR reactions. The limits of detection (LODs), effect of multiplexing on sensitivity and viral RNA quantification potential in bees and hive debris were assessed. This study made available diagnostic assays able to detect an increased number of virus variants compared to previously described tests and two viral pathogens in a single PCR reaction.

Coal bottom ash (CBA) is a byproduct of coal-burning power plants. This material can be used as a fine aggregate replacement in concrete to reduce global natural material depletion. Concrete usage is increasing rapidly; subsequently, the industry’s carbon footprint is increasing. Using CBA in the construction industry will reduce the technical and economic problems associated with power plants by reducing solid waste. This project aimed to determine if adding new sustainable materials, such as CBA, to concrete will reduce natural raw material usage, energy consumption, and greenhouse gas emissions while improving performance. This study included two projects: comparing increased CBA content to the two-control project and determining the optimum content based on the compressive strength. The optimum CBA content is 50%, which reduces fine aggregate usage in a concrete mix by 50% while maintaining equivalent or better concrete strength than a pure Portland concrete mix without CBA. The air content of the concrete mix containing % CBA decreased with increased CBA content and compressive strength, possibly due to the spacing factor of the voids in the mix and CBA’s porous and fineness behavior. The CBA optimum content had a unit weight lower than the controls for both projects, which makes the CBA mix a lightweight concrete. Using this material can significantly reduce natural material usage and environmental harm by reducing CBA waste disposal and improving concrete performance.

Mesenchymal stem cells due to their multipotent ability are considered one of the best candidates to be used in regenerative medicine. The most used source of those stem cells long the last decades was the bone marrow, despite its limited cell resources and the painful and very invasive surgical treatment. Therefore, the scientific community investigated many alternative sources for the harvesting of these stem cell subpopulations. Adipose tissue attracted the biggest interest thanks to special features, such as great tissue abundance, easy availability, and in the end the large amount of positive mesenchymal stem cells. Once it was verified that these stem cell subpopulations possess the same bone marrow differentiation potential, it became evident that they would be the ideal candidate to be used in regenerative and tissue engineering applications. Even the regenerative use of these cells long become a sensitive point because not all the acquired phenotypes resulted in the best source for plastic procedures. As documented in the literature, the ideal fillers for regenerative is represented by stem cell population. Therefore, it became crucial to investigate any kind of biological mechanism on the differentiative ability of those mesenchymal stem cells, especially their regulative factors. One of the most studied and important regulators are the miRNAs. Indeed, miRNA play a crucial role in the differentiation process of adipose stem cell cultures isolated from patients or obtained by commercial cell lines toward osteocytes, chondrocytes, and adipocytes differentiated populations.

Given the increased provision of international exchange programmes in higher education, this paper examines students’ perceptions of their learning process in one Erasmus+ programme in Food Innovation and Product Design. Using evaluation model of international exchange programme and triple helix model as the analytical framework, students’ testimonials from 2015–2021 were analysed using a critical discourse analysis. EU and non-EU students had similar perceptions of learning outcomes related to knowledge of the food innovation industry, but non-EU students had a stronger sense of awareness of both the international context and multicultural interaction.

In this report we describe the case of a healthy, young, athletic woman who developed acute lymphoblastic leukaemia (ALL)/lymphoblastic lymphoma (LBL) after receiving the second dose of the Pfizer/BioNTech modified mRNA (modRNA) COVID-19 genetic vaccine (marketed as Comirnaty^®). The first dose of the genetic vaccine did not appear to illicit any noticeable side effects, but within 24 hours of the second dose the patient suffered widespread and intensifying bone pain, fever, vomiting, and general malaise. Due to the persistence of the symptoms, the patient underwent a series of tests and examinations including a full laboratory workup, a consult with a clinical immunologist and rheumatologist, a Positron Emission Tomography (PET) imaging, as well as an osteomedullary biopsy. These together led to a definitive diagnosis of ALL. A time interval of 16 weeks from the second vaccination to the diagnosis of cancer was noted. Several similar cases with identical pathology which developed after the modRNA COVID-19 vaccination, are described in case reports in the scientific literature. The massive and indiscriminate use of genetic vaccines to fight COVID-19 is raising serious concerns about their safety and about the technology platform as a whole for this purpose. Growing evidence is accumulating regarding the biodistribution and persistence of the modRNA which can reach, thanks to the lipid nanoparticles, a multitude of tissues and organs of the body, including the bone marrow and other blood-forming organs and tissues. Moreover, there is evidence that the modRNA vaccines display a particular tropism for the bone marrow, influencing the immune system at multiple levels and being able to trigger not only autoimmune-based pathologies, but also neoplastic mechanisms. The aim of this article is to assess, on the basis of the available scientific literature, the risk of developing haematopoietic cancers after modRNA vaccination, and to investigate the potential genetic mechanisms involved in the pathogenesis of disease.

Efficient triaging and referral assessment are critical in ensuring prompt medical intervention in the Community Health Care (CHC) system. However, the existing triaging systems in many Community Health Services are an intensive, time-consuming process and often lack accuracy, particularly for various symptoms that might represent heart failure or other health-threatening conditions. There is a noticeable limit of research papers describing AI technologies for triaging patients. This paper proposes a novel quantitative data-driven approach using machine learning (ML) modelling to improve the community clinical triaging process. Furthermore, this study aims to employ the feature selection process and machine learning power to reduce the triaging process’s waiting time and increase accuracy in clinical decision-making. The model was trained on medical records of “Heart Failure” patients’ dataset, which included demographics, past medical history, vital signs, medications, and clinical symptoms. A comparative study was conducted using the list of machine learning algorithms where XGBoost demonstrated the best performance among other ML models. The triage levels of 2,35,982 patients achieved an accuracy of 99.94%, precision of 0.9986, recall of 0.9958, and f1-score of 0.9972 within 0.059 seconds. The proposed diagnostic model can be implemented for the CHC decision system and be developed further for other medical conditions.

Organ-on-a-chip (OOC) is an emerging technology that simulates an artificial organ within a microfluidic cell culture chip. Current cell biology research focuses on in vitro cell culture due to various limitations of in vivo testing. Unfortunately, in vitro cell culture fails to provide an accurate microenvironment, and in vivo cell culture is expensive and has historically been a source of ethical controversy. OOC aims to overcome these shortcomings and provide the best of both in vivo and in vitro cell culture research. The key component of the OOC design is utilizing microfluidics to ensure a stable concentration gradient, dynamic mechanical stress modeling, and accurate reconstruction of a cellular microenvironment. OOC also has the advantage of complete observation and control of the system, which is impossible to recreate in in vivo research. Multiple throughputs, channels, membranes, and chambers are constructed in a polydimethylsiloxane (PDMS) array to simulate various organs on a chip. Various experiments can be performed utilizing OOC technology, including drug delivery research and toxicology. Current technological expansions involve multiple organ microenvironments on a single chip, allowing for studying inter-tissue interactions. Other developments in the OOC technology include finding a more suitable material as a replacement for PDMS and minimizing artefactual error and non-translatable differences.

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.

This study delves into the realm of potential therapeutics for breast cancer by conducting a comprehensive docking simulation and virtual screening analysis using Autodock Vina Algorithm. The focus based on the human epidermal growth factor receptor 2 (HER2), a key protein associated with various cancers, particularly in the context of breast cancer.The results reveal compelling insights into the binding interactions of several natural compounds and drugs with HER2. Notably, Acebilustat, Bemcentinib, and Amentoflavone exhibit outstanding binding energies, averaging around -10 kcal/mol, suggesting strong and favorable interactions with the HER2 target.These encouraging findings not only emphasize the potential biological significance of these compounds but also hint at their potential usefulness in fighting breast cancer.Their promising binding affinities with HER2 position them as potential candidates for further investigation and development as therapeutic agents against breast cancer.

This study investigates the potential antimicrobial utility of the natural substance Amentoflavone against four dangerous bacterial strains—Mycobacterium tuberculosis, Helicobacter pylori, Haemophilus influenzae, and Pseudomonas aeruginosa. Utilizing molecular docking studies, are assessed the binding interactions between Amentoflavone and key protein targets crucial for the viability of these bacteria. The findings suggest promising binding affinities, particularly in the active sites of Aminoglycoside 2'-N-acetyltransferase, Thioredoxin Reductase, N-acetylneuraminate Lyase, and Glucose-1-phosphate Thymidylyltransferase in the respective bacterial strains. While these in silico results provide initial insights, further in vitro and in vivo experiments are essential to validate the biological relevance and efficacy of Amentoflavone as a potential antimicrobial agent against these bacterial pathogens.

Physical exercise is the greatest stress on the cardiovascular system, not only in humans but also in all vertebrates. Consequently, the cardiovascular response cannot be thought of as having only one "anthropocentric" interpretation. The modulation of cardiac output (Q) in response to exercise in the five major groups of vertebrates exhibits considerable variability. Moreover, the response of the heart rate (HR) and the stroke volume (SV), the fundamental factors that cause the rise in Q, is also highly variable. The difference in the range of HR is difficult to determine in many vertebrates, both at rest and at maximal effort. Additionally, the increase in SV varies among vertebrates. For example, while rainbow trout and leopards increase their SV by increasing end diastolic volume (EDV), humans do so at the expense of both increasing EDV and reducing end systolic volume (ESV). The variation in arterial pressure that arises during exercise varies notably among vertebrates, such as amphibians, whose blood pressure values do not increase as significantly as in mammals. Such differences in cardiovascular response among vertebrates may be linked to their habitat or living environment. This review aims to analyze the cardiovascular response of vertebrates to physical exercise as the most common stressor.

Resistance to therapy and disease progression are the main causes of mortality in most cancers. In particular, the development of resistance is an important limitation affecting the efficacy of therapeutic alternatives for cancer, including chemotherapy, radiotherapy, and immunotherapy. Signaling pathways are largely responsible for the mechanisms of resistance to cancer treatment and progression, and multiple myeloma is no exception. p38 mitogen-activated protein kinase (p38) is downstream of several signaling pathways specific to treatment resistance and progression. Therefore, in recent years, developing therapeutic alternatives directed at p38 MAPK has been of great interest, in order to reverse chemotherapy resistance and prevent progression. In this review, we discuss recent findings on the role of p38, including recent advances in our understanding of its expression and activity as well as its isoforms, and its possible clinical role based on the mechanisms of resistance and progression in multiple myeloma.

This paper explores the interactions of dynamic dark energy with other components of the cosmos, such as dark matter and baryonic matter, and its wide-ranging implications in cosmology. By investigating the interplay between dynamic dark energy and the universe's large-scale structure, we aim to provide a deeper understanding of cosmic evolution and the behavior of dark energy in different cosmological epochs. We also examine the potential of dynamic dark energy to offer novel insights into long-standing cosmological puzzles and their impact on the formation and evolution of cosmic structures.

Chinese calligraphy, revered globally for its therapeutic and mindfulness benefits, encompasses styles such as Regular (Kai Shu), Running (Xing Shu), Official (Li Shu), and Cursive (Cao Shu) scripts. Beginners often start with Regular script, advancing to more intricate styles like Cursive. Each style, marked by unique historical calligraphers' contributions, requires learners to discern distinct nuances. The integration of AI in calligraphy analysis, collection, recognition, and classification are pivotal. This study introduces an innovative Convolutional Neural Network (CNN) architecture, pioneering the application of CNN in the classification of Chinese calligraphy. Focusing on the four principal calligraphers' styles from the Tang dynasty (690-907 A.D), this research spotlights the era when the traditional regular script font (Kai Shu) was refined. A comprehensive dataset of 8282 samples from these calligraphers, representing the zenith of regular style, was compiled for CNN training and testing. The model distinguishes personal styles for classification, showing superior performance over existing networks. Achieving 89.5-96.2% accuracy in calligraphy classification, our approach underscores the significance of CNN in both font and artistic style categorization. This research paves the way for advanced studies in Chinese calligraphy and its cultural implications.

Chronological frameworks based on artefact typologies are essential for interpreting the archaeological record, but they inadvertently treat transitions between phases as abrupt events and disregard the temporality of transformation processes within and between individual phases. This study presents an absolute chronological investigation of a dynamic material culture from Early Iron Age urnfields in Denmark. The chronological framework of Early Iron Age in Southern Scandinavia is largely unconstrained by absolute dating, primarily due to it coinciding with the so-called ‘Hallstatt calibration plateau’ (c.750 to 400 cal BC), and it is difficult to correlate it with Central European chronologies due to a lack of imported artefacts. This study applies recent methodological advances in radiocarbon dating and Bayesian chronological modelling, specifically a statistical model for wood-age offsets in cremated bone and presents the first large-scale radiocarbon investigation of regional material culture from Early Iron Age in Southern Jutland, Denmark. Dated material is primarily cremated bone from 111 cremation burials from three urnfields. The study presents absolute date ranges for 16 types of pottery and 15 types of metalwork, which include most of the recognised metalwork types from the period. This provides new insights into gradual change in material culture, when certain artefact types were in production and primary use, how quickly types were taken up and later abandoned, and distinguishing periods of faster and slower change. The study also provides the first absolute chronology for the period, enabling correlation with chronologies from other regions. Urnfields were introduced at the Bronze-Iron Age transformation, which is often assumed to have occurred c.530-500 BC. We demonstrate that this transformation took place in the 7^th century BC, however, which revives the discussion of whether the final Bronze Age period VI should be interpreted as a transitional phase to the Iron Age.

Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing in-creased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play im-portant roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB de-pendence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima-media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter en-dothelial function or the contractile response to phenylephrine in these arteries. In contrast, CIH exposure increased the systemic arterial pressure, and enhanced the contractile response to phenylephrine while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta, without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH.

Heat exchangers play a vital role in numerous sectors like power generation and automotive manufacturing. Enhancing the energy efficiency of these exchangers stands as a significant hurdle. Utilizing nanofluids emerges as an optimal solution to augment heat transfer rates, leveraging their superior thermal conductivity while addressing economic constraints linked with traditional heat exchanger technologies. The motivation for this study is to consider the comprehensive synergistic features of MWCNTs, SiO₂, and hybrid MWCNTs–SiO₂ EG-based nanofluids in plate heat exchangers. This was achieved by simulating a plate heat exchanger using CFD (Fluent and Gambit softwares) considering the comparison of two SiO₂, MWCNTs, and their hybrid forms at different mass concentrations. The Reynolds-Averaged Navier-Stokes (RANS) method was employed to model turbulent flows, and the nanoparticles were compared in both single-phase and two-phase states, with their properties derived from experimental studies. Moreover, Nusselt number, convective heat transfer coefficient, and pressure drop variations were computed at different Reynolds numbers. The findings indicated an increase in the Nusselt number with the incorporation of the hybrid nanofluid, achieving a maximum enhancement of 11.19% in comparison to EG at a Reynolds number of 240 and a concentration of 0.86 wt.%. Noticeably, the pressure drop remained negligible at lower Reynolds numbers, exhibiting marginal variations up to 0.3% at higher Reynolds numbers. At a concentration of 0.86 wt.% and a Reynolds number of 480, the introduction of MWCNTs, hybrid, and SiO₂ nano-additives resulted in respective increases in the heat transfer coefficient by 21.02%, 10.76%, and 2.16% and corresponding alterations in pressure drop of 0.11%, 0.04%, and 0.02%.

Artificial intelligence (AI) driven language models have seen a rapid rise in development, deployment, and adoption over the last few years. This surge has sparked many discussions about their societal and political impact, including political bias. Bias is a crucial topic in the context of large models due to its far-reaching consequences on technology, politics, and society. It significantly influences public perception, decision-making, political discourse, and AI policy governance and ethics. This study investigates political bias through a comparative analysis of four prominent AI models: ChatGPT-4, Perplexity, Google Gemini, and Claude.Through a comprehensive analysis by systematically and categorically evaluating their responses to politically and ideologically charged tests and prompts, utilizing the Pew Research Center’s Political Typology Quiz, the Political Compass assessment, and ISideWith political party quiz, this study identifies significant ideological leanings and the nature of political bias within these models. The findings revealed that ChatGPT-4 and Claude exhibit a liberal bias, Perplexity is more conservative, while Google Gemini adopts more centrist stances. The presence of such biases underscores the critical need for transparency in AI development and the incorporation of diverse training datasets, regular audits, and user education to mitigate these biases. This analysis also advocates for more robust practices and comprehensive frameworks to assess and reduce political bias in AI, ensuring these technologies contribute positively to society and support informed, balanced, and inclusive public discourse, which will point towards neutrality.The results of this study add to the ongoing discourse about the ethical implications and development of AI models, highlighting the critical need to build trust and integrity in AI models. Additionally, future research directions have been outlined to explore and address the complex issue of bias in AI.

Grass pea (Lathyrus sativus L.) is a protein-rich crop that is resilient to various abiotic stresses, including drought. However, it is not cultivated widely for human consumption due to the neurotoxin β-N-oxalyl-L-α, β-diaminopropionic acid (β-ODAP), and its association with neurolathyrism. Though some varieties with low β-ODAP have been developed through classical breeding, the β-ODAP content is increasing due to genotype x environment interactions. This review covers grass pea nutritional quality, β-ODAP biosynthesis, mechanism of paralysis, traditional ways to reduce β-ODAP, candidate genes for boosting sulfur-containing amino acids, and the potential and targets of gene editing to reduce β-ODAP content. Recently, two key enzymes (β-ODAP synthase and β-cyanoalanine synthase) have been identified in the biosynthetic pathway of β-ODAP. We proposed four strategies through which the genes encoding these enzymes can be targeted and suppressed using CRISPR/Cas9 gene editing. Compared to its homology in Medicago truncatula, the grass pea β-ODAP synthase gene sequence and β-cyanoalanine synthase showed 62.9% and 95% similarity, respectively. The β-ODAP synthase converts the final intermediate L-DAPA into toxic β-ODAP whist β-cyanoalanine synthase converts O-Acetylserine into β-isoxazolin-5-on-2-yl-alanine. Since grass pea is low in methionine and cysteine amino acids, improvement of these amino acids is also needed to boost its protein content.

Present experimental study assesses the mechanical properties of glass/carbon/glass hybrid composite laminates after exposure to moisture and elevated temperatures for extended periods. The top and bottom layers of the hybrid laminates are glass fiber reinforced and the middle layer is carbon fiber reinforced with the matrix specified as a polymer material. The hybrid laminates were manufactured using the resin transfer molding method and their compressive and tensile properties were determined using a tensile testing machine. The material parameters such as the storage modulus, the loss modulus, and the damping factors of the laminates were identified using dynamic mechanical analysis as a function of the temperature and the vibration frequency. The experimental results on compressive and tensile properties revealed slight variations when the hybrid laminates were kept at low temperatures for extended periods. This might occur due to the increasing molecular cross-linking of the polymer network. As the temperature increased, compressive, tensile, storage modules, loss modulus, and damping factors decreased. This might occur due to the increasing mobility of the binder material. Particularly, the highest stiffness parameters were obtained on -80°C/GCG (Glass/Carbon/Glass) laminates due to the presence of beta transition on the glassy region. The relationships between the glass transitions and the targeted frequencies were characterized. The values of the glass transition shift towards higher temperatures as the frequency increases. This might occur due to a reduction in the gaps between the crosslinking of the epoxy network when the frequency increases. The accuracy of the storage modulus results was compared with the empirical models. The model based on the Arrhenius law provided the closest correlation. Meanwhile, another model was observed that was not accurate enough to predict when gamma and beta relaxations occur under a glassy state.

This paper presents a comparative study of fundamental similarity functions for Siamese networks in semantic textual similarity (STS) tasks. We evaluate various similarity functions using the STS Benchmark dataset, analyzing their performance and stability. Additionally, we introduce a multi-objective approach for optimal threshold selection. Our findings provide insights into the effectiveness of different similarity functions and offer a straightforward method for threshold selection optimization, contributing to the advancement of Siamese network architectures in STS applications.

Human papillomavirus (HPV), a DNA virus, causes one the most common sexually transmitted infections (STI), spreading through direct sexual contact to the anogenital and oropharyngeal regions. Although most infected individuals may be asymptomatic and naturally undergo viral clearance, in some individuals HPV causes carcinogenesis of the infected epithelia. HPV now accounts for over 70% of oropharyngeal carcinomas (OPC). More than 90% of these OPC are associated with HPV 16, one of the 14 high-risk subtypes. In recent years, HPV positive (HPV+) OPC has been one of the most rapidly rising cancers, by new cancer incidence rates, especially among men. The HPV driven OPCs present some unique infection driven cellular and molecular features, constituting distinct preventive, therapeutic and prognostic strategies, in contrast to HPV negative (HPV-) OPC. In this manuscript, we drive through the role of HPV, from a sexually transmitted infection to malignancy transformation landscape, while parsing through the significant immune response environment. In this comprehensive review we collate key literature around transmission and epidemiology of HPV, while addressing the current state of clinical management, diagnosis, prevention and screening strategies, that can help shed light on this critical area.

Dark pigmentation can be observed in various parts of the plant, ranging from foliage to petals to berries. The molecular basis of black pigmentation appears to vary among species, with anthocyanins playing a significant role, although specific anthocyanin types and their mechanisms differ. These findings suggest that the development of phenotypes is species-specific or varies between larger taxonomic groups; this is further supported by the polyphyletic nature of dark pigmentation. Additionally, several different regulatory mechanisms have been described for the occurrence of dark pigmentation. Firstly, the repression or knockout of the competing flavone biosynthesis has been shown to lead to darker pigmentation while another mechanism is based on the activation and upregulation of the anthocyanin biosynthesis genes in the presence of MYB transcription factors. Potential ecological functions of dark pigmentation were identified as the protection of the photosynthesis apparatus, camouflage against herbivores, and the attraction of pollinators. Promising industrial applications include microbial factories for the production of natural food colourants, induction of novel phenotypes for the ornamental plant industry and lastly the increase of anthocyanins within agriculturally relevant crops.

Inducer of C-Repeat Binding Factor (CBF) expression (ICE), a well-known MYC-type bHLH transcription factor, plays a crucial role in the ICE-CBF-cold regulated (COR) cold signaling pathway. Brassica rapa (B. rapa), an important oilseed and vegetable crop, exhibits strong chilling and freezing tolerance. However, the exact molecular mechanisms by which ICE1 functions in B. rapa remain unclear. Here, 41 ICE1 homologous genes were identified from six widely cultivated Brassica species using a bioinformatics approach. These genes exhibit high conservation but reveal evolutionary complexity between diploid and allotetraploid species. Low-temperature stress induced ICE1 homolog expression, with patterns differing between strong and weak cold-tolerant varieties. Two novel ICE1 paralogs, BrICE1 and BrICE2, were cloned from Longyou 6. They positively regulate cold tolerance in B. rapa via a CBF-dependent pathway, contributing to reactive oxygen species (ROS) scavenfging and osmotic adjustment. Immunoblot analysis revealed that low temperatures induce BrICE1 and BrICE2 degradation via the 26S-proteasome pathway. In summary, ICE1 exhibits complex evolutionary relationships in Brassica species. BrICE1 and BrICE2 positively regulate cold tolerance via the CBF-dependent pathway and ROS scavenging mechanism and are also responsible for balancing the development and cold defense of B. rapa.

In the global carbon cycle, atmospheric carbon emissions, both ‘natural’ and anthropogenic, are balanced by carbon uptake (i.e. sequestration) that mostly occurs via photosynthesis, plus a much smaller proportion via geological processes. Since the formation of the Earth about 4.54 billion years ago the ratio between emitted and sequestered carbon has varied considerably with atmospheric CO₂ levels ranging from 100,000 ppm to a mere 100 ppm. Over this time, a huge amount of carbon has been sequestered due to photosynthesis and essentially removed from the cycle, being buried as fossil deposits of coal, oil and gas. Relatively low atmospheric CO₂ levels were the norm for the past 10 million years, and during the past million years they averaged about 220 ppm. More recently, the Holocene epoch, starting ~11,700 years ago, has been a period of unusual climatic stability with relatively warm, moist conditions and low atmospheric CO₂ levels of between 260 and 280 ppm. During the Holocene, stable conditions facilitated a social revolution with domestication of crops and livestock leading to urbanisation and development of complex technologies. As part of the latter process, immense quantities of sequestered fossil carbon have recently been used as energy sources, resulting in a particularly rapid increase in CO₂ emissions after 1950 CE to the current value of 424 ppm, with further rises to >800 ppm predicted by 2100. This is already perturbing the previously stable Holocene climate and threatening future food production and social stability. Today, the global carbon cycle has been shifted such that carbon sequestration is no longer keeping up with recent anthropogenic emissions. In order to address this imbalance it is important to understand the roles of high-capacity carbon sequestration systems, such as natural forests and tropical croplands, and to devise strategies to facilitate net CO₂ uptake.

Infrared thermography is a contactless imaging technique, useful to measure surface temperature at distance which has been widely applied in animal production. The possible applications within the pig husbandry include sow heat detection, reduction of the incidence of neonatal mortality, recognition of febrile state caused by pathogens, study of metabolic efficiency, evaluation of stress caused by heat, by constraints, or by aggressive interaction and meat quality prediction. Even if this technique could be easily influenced by environmental factors, the continuous improvement in the procedures and the decrease in the cost of the equipment will allow in the next future new and more applications in swine farming.

The energy transition is a challenge that affects all sectors, from transport to civil structures and industry. With reference to the industrial sector, the greatest need is the decarbonisation of industries energy-intensive, such as producers of iron and steel, aluminium, cement, petrochemicals, paper, etc. In particular, the steel industry is a hard to abate high-emissivity industry which due to chemical processes and high thermal demands (often above 500 °C) contributed to 7.4% of global CO₂ in the year 2021. This paper has explored the potential applications of hydrogen in the hard-to-abate sectors, highlighting its versatility and significance in decarbonization efforts. It provides an overview of hydrogen production methods, emphasizing the importance of sustainable and green hydrogen production. It reviews hydrogen production methods, storage, and potential in blended combustion. In the final part of the article, some considerations are introduced on the possible role of hydrogen in the steel sector (both as a supplementary fuel and as a reducing agent in innovative processes), showing how although there is potential for its inclusion as an element for the decarbonization, it is necessary to evaluate the energy balances of the various processes and the methods of hydrogen production very carefully, in order not to risk obtaining a marginal effect.

This paper examines the transformative journey of Artificial Intelligence (AI) agents from copilots to integral coworkers within diverse sectors. Beginning with a foundational overview, we delve into the historical evolution of AI agents, highlighting key technological milestones and the shift from simple automated tools to sophisticated decision-making systems capable of learning and adapting over time. We explore the capabilities of AI agents, including problem-solving, predictive analytics, and automation, and their applications across healthcare, business, and education, showcasing their role in diagnostics, customer service, and personalized learning, among other areas. We also address the integration of AI agents in the workplace, presenting strategies for collaboration between humans and AI, and outline the challenges and ethical considerations that accompany the development and deployment of AI technologies. A comprehensive tutorial provides insight into the development process of AI agents, emphasizing goal definition, data handling, algorithm selection, and ethical guidelines. We also consider the pathway towards Artificial General Intelligence (AGI) and the societal and ethical implications of widespread AI integration, proposing strategies for equitable and ethical AI use.

Based on our recent thermodynamic formulation of the Friedmann equation, we demon- strate how the age of the universe must be approximately 14.6 billion years. This is about 800 million years older than predicted by the Λ-CDM model and therefore greatly alleviates the early galaxy formation problem.

The importance of detecting and diagnosing the imminence of aneurysm rupture before it occurs cannot be overstated. However, this process is often time-consuming and challenging, with variability in conclusions not uncommon among experts. Furthermore, current state-of-the-art models in medical image segmentation suffer from limited availability of large annotated datasets for training, exacerbated by an immense data imbalance. In most segmentation tasks, 3D segmentation is preferred due to its capacity to leverage more contextual information. However, these models require more data, which is constrained by the aforementioned issues. In the realm of current diagnosis models, those lacking geographic context are notably ineffective. To address these issues, the aim is to develop a model pipeline to accurately detect cerebral intracranial aneurysms and diagnose rupture imminence through 3D magnetic resonance angiography (MRA) and tabular input, augmented with the implementation of neuro-symbolic ai. The utilization of data fusion to tackle the lack of context in tabular models is proposed, leveraging extracted geographical features from a segmentation model. To enhance segmentation results and tackle the data imbalance in aneurysm segmentation, a two-stage model pipeline that extracts contextual geographic features before aneurysm segmentation is suggested. Segmentation results are additionally improved through ensemble techniques and novel preprocessing techniques. Finally, a neuro-symbolic aspect is introduced to enhance model diagnosis, interpretability and performance. The multi-step Integrated Neuro-Symbolic Analysis Pipeline for Cerebral Aneurysm Rupture Diagnosis is introduced.

Friction stir welding (FSW) is a solid state welding process for joining metallic alloys and dissimilar metals. It has emerged as an alternative technology for welding high strength alloys that are difficult to join with conventional techniques. FSW is used to produce products with better mechanical properties. Now a days aluminum alloys have been widely used in several industrial applications such as aerospace, marine, automobile and commercial applications due to their light weight structure, better mechanical properties and high corrosion resistance.In this work, three welding parameters such as spindle speed, welding speed and plunge depth were considered for friction stir welding. FSW was carried out between dissimilar aluminum alloy plates (AA6061 and AA 8011) to produce butt joint.A Box-Behnken design with three factors and three levels was chosen to minimize the number of experimental conditions .The tensile strength and hardness of the welded regions were evaluated. The optimum level settings and the major parameters that influence the joint strength were obtained by Box-Behnken design.

This study explores the potential of natural compounds, including Daidzin, Luteolin, and Silibinin, as inhibitors of human monoamine oxidase B (MAO-B) for the treatment of Parkinson's disease. Docking simulations were performed using Autodock Vina with Pyrx program to evaluate the binding affinities of these compounds with MAO-B. Results indicate that Daidzin, Luteolin, and Silibinin exhibit promising binding affinities with MAO-B, with Daidzin demonstrating the highest affinity. Toxicity parameters were further predicted using the PkCSM Server, confirming the low toxicity of these compounds. Overall, the findings suggest that Daidzin, Luteolin, and Silibinin have the potential to be effective and safe treatments for Parkinson's disease through their inhibition of MAO-B. Further experimental validation is warranted to support their therapeutic efficacy in clinical settings.

“All diseases originate in the gut.” Hippocrates (400 BC) A healthy gut microbiome via the gut-brain-axis (GBA) elevates heart rate variability (HRV), a general measure of health and well-being. A dysbiotic gut microbiome, low in biodiversity and butyrate producers, alters tryptophan metabolism with release of proinflammatory cytokines, predominantly TNF-α, IL-6, and IL-1β. These also characterize chronic inflammation, oxidative stress, and a multitude of diseases, all exhibiting low HRV. Gut dysbiosis upregulates IFN-γ and with it IDO (indoleamine 2,3 dioxygenase). Tryptophan pivots from serotonin synthesis to that of IDO induced kynurenine, increasing the kynurenine to tryptophan ratio (KTR). An elevated KTR is positively linked to neurodegenerative and autoimmune diseases and negatively linked to HRV. Elevated IDO activity is not only enzymatic but also an intracellular signal transducer potentiated by TGF-β. This cytokine is the primary determinant of the TME. Also proposed is the gut-lung dysbiosis concept and consequent degradation of ACE2 (richest in lungs and gut). Leaky gut induced autoantibodies related to G-protein coupled receptors (GPCRs) in combination with increased Ang II further potentiate oxidative stress. Aldosterone and paroxysmal orthostatic tachycardia syndrome (POTS) paradoxes are highlighted in the context of GPCR and gut dysbiosis, and the role of Candida is explored. The triple play of a prebiotic (d-mannose), probiotic (bifidobacteria and lactobacilli), and postbiotic (butyrate) might improve intestinal barrier integrity, oppose entry of GPCR antigens, suppress the inflammatory cytokine triad, balance IFN-γ and TGF-β, suppress oxidative stress, depress KTR, elevate HRV, and extend lifespan and its quality.

With continued scaling of semiconductor devices , the value of predictive analysis through 1 accurate quantum transport modeling is exponentially increasing. Quantum transmitting Boundary 2 method (QTBM) has been a well-known method of choice to model quantum transport in simple 1-D 3 devices. Here, we present an extension of the QTBM to the 2-D domain and apply it for more realistic 4 devices for accurate performance analysis.

The necessity for effective intrusion detection systems (IDS) in big data environments has grown critical due to the rising prevalence of big data systems and the rising amount of security threats. Applying conventional intrusion detection methods to the enormous and intricate data produced by big data ecosystems presents difficulties. Deep learning, has proven to be exceptionally adept at deciphering complex, large-scale data. This study proposes a Deep Learning-based Intrusion Detection System (IDS) created specifically for the Big Data environment. Traditional intrusion detection systems struggle to efficiently identify and prevent cyber threats due to the ever-increasing volume and complexity of data in current networks. We suggest an IDS that makes use of Deep Learning (CNN, LSTM, GAN, etc.), to address this problem. These cutting-edge neural network topologies give the system the ability to process and analyze massive amounts of data for precise intrusion detection. Data collection, data preprocessing, feature engineering, DL model training, intrusion detection, warning generation, and reaction are some of the crucial parts of the suggested IDS. The data collection module mines the Big Data environment for network traffic, system logs, and security event information. To make sure the data is suitable for analysis, it is preprocessed. To improve the detection abilities of the DL models, important features are extracted from the data using feature engineering approaches.

There is a great need to develop research-based models for supporting collaboration between educational institutions. Collaboration models are needed, for example, to assist the transition from lower educational level to higher education or from higher education to work life. In this research, collaboration was conducted through a joint upper-secondary school and university course that addressed global challenges by using a project-based learning approach. There is a shortage of research exploring students’ perceptions of collaboration. Therefore, the main purpose of this qualitative case study is to explore the relevance of the joint course for students and university students. The research was guided by the following research question: What kind of relevance did the students experience in the joint project-based learning course? The data was gathered using questionnaires, interviews, and reflective study reports. The data was analyzed via theory-based content analysis where research-oriented relevance model was used as the analysis framework. The analysis framework enabled categorizing experienced relevance on individual, vocational and societal dimensions. Altogether, the analysis produced 7 relevance categories for upper-secondary students and 9 for university students. According to the analysis, upper-secondary school students felt that the course offered the most on an individual relevance dimension whereas university students experienced the vocational relevance dimension most diverse. As the main conclusion, this research produced new insights on the experienced relevance of upper-secondary level and higher education cooperation from the students’ point of view. The acquired knowledge can be useful for everyone developing new cross-institutional cooperation models.

This cross-sectional study investigates the impact of Virtual Private Networks (VPNs) on Nigerians during the 2021 Twitter ban, prompted by the Nigerian government's suspension of Twitter operations following the deletion of a tweet by the President. The study aims to analyze the frequency and awareness of VPN and Twitter usage among Nigerians during the ban, addressing specific objectives. Employing a survey research method, data was collected from 400 respondents through online and offline questionnaires. Descriptive statistical tools were used for data analysis, revealing significant findings. Results indicate a substantial decrease in Twitter usage during the ban, with IPVanish emerging as the preferred VPN brand. The study also highlights an increase in VPN awareness post-ban, emphasizing the need for educational initiatives. The demographic analysis reveals a dominant age group of 21 to 25 among social media users. Overall, the research underscores the complex interplay between social media dynamics, VPN adoption, and demographic factors, emphasizing the importance of nuanced regulatory approaches and ongoing user education in Nigeria's online landscape.

This study employs molecular docking experiments to investigate the binding interactions of Hypericin with key proteins implicated in Alzheimer's disease (AD). Hypericin demonstrated a significant binding energy of -10.1 kcal/mol with ABAD (3-hydroxyacyl-CoA dehydrogenase type II). The analysis revealed multiple binding interactions, including hydrogen bonds with arginine 6, serine 7, and glutamic acid 140, as well as hydrophobic bonds involving leucine 11, aspartic acid 142, and aspartic acid 86. These findings illuminate the intricate molecular interactions between Hypericin and ABAD, suggesting its potential as a lead compound for further therapeutic development in the context of Alzheimer's disease. Additionally, a parallel docking investigation was conducted for Beta-secretase 1 (BACE1), a protein pivotal in the generation of beta-amyloid peptides—a hallmark of Alzheimer's disease. Inhibiting BACE1 activity is considered a promising therapeutic strategy for AD. Computational analyses suggest that Hypericin may serve as a potential inhibitor of BACE1. Molecular Docking results reveal a robust binding affinity between Hypericin and BACE1, supported by a significant binding energy score of -10.3 kcal/mol. Notably, both ABAD and BACE1 exhibit high binding affinity with Hypericin. This theoretical exploration provides an initial understanding of the intricate molecular pathways involved in Alzheimer's disease and proposes Hypericin as a potential therapeutic compound for mitigating its progression.

This study aimed to overcome the difficulty of conducting the horizontal-well cavity leaching test in the field and to investigate the long-term stability of the horizontal-well salt-cavity natural gas storage. The simulation test design is combined with the similarity theory to study the cavity expansion characteristics and the influence law of cavity leaching parameters. Through the design of a rubber hose connection, an integrated closed test system for multi-stage horizontal-well cavity leaching and brine drainage was built. The test system also realises the repeatable backward movement of the injection well during the test. A similarity simulation of the test design was carried out, and the test platform was constructed to carry out multi-stage horizontal-well leaching tests with a nitrogen cushion. In the horizontal-well leaching tests with a nitrogen cushion, the influence laws of the well spacing, flow rate and liquid level position on cavity expansion were investigated. Based on the morphological characteristics of the horizontal-well cavity, a numerical model of the horizontal-well salt cavity was developed, which reflects the real cavity morphology leached in the test. The long-term stability of the horizontal-well salt-cavity natural gas storage under different internal pressures was investigated through numerical simulation.

Energy communities are key actors in the energy transition since they optimally interconnect renewable energy capacities with the consumers. Despite versatile objectives, they usually aim at improving the self-consumption of renewable electricity within low voltage grids to maximize revenues. In addition, energy communities are an excellent opportunity to supply renewable electricity to regional and national energy systems. However, effective price signals have to be designed to coordinate the needs of the energy infrastructure with the interests of these local stakeholders. The aim of this paper is to demonstrate the integration of energy communities at the national level with a bottom-up approach. District energy systems with a building scale resolution are modelled in a mixed integer linear programming problem. The Dantzig-Wolfe decomposition is applied to reduce the computational time. The methodology lies within the framework of renewable energy hub, characterized by a high share of photovoltaic capacities. Both investments into equipment and its operation are considered. The model is applied on a set of five typical districts and weather locations representative of the Swiss building stock. The extrapolation to the national scale revealed a heterogeneous photovoltaic potential throughout the country. Present electricity tariffs promote a maximal investment into photovoltaic panels in every region, reaching an installed capacity of 67.2 GW and generating 80 TWh per year. Since the national PV capacity needed is forecast at 15.4 GW peak, coordinated investments between local and national actors are needed to prevent dispensable expenses. An uncoordinated design is expected to increase the total costs for residential energy systems by 43.2% and curtails 48.2% of local renewable electricity.

Physical properties like shape, volume and size affect the dynamics of biological systems. Along these lines, we focus on the topological properties of biological fluids and their biochemical and physiological outcomes. We take as a paradigmatic example the salivary fluid and describe how its topological features may affect the physiopathology of the oral cavity. Topological approaches assess the general properties of saliva, ignoring small-scale physical details such as density, flow rate, stiffness, viscosity. Specifically, the mucin aggregates scattered in the salivary fluid can be tackled in terms of topological holes, i.e., vortical clusters that modify the direction, flow, impulse, local rate-of-change and velocity of saliva. While the current methodological approaches are inclined to remove the effects of impurities assessing systems as homogeneous structures, we argue that the occurrence of mucins breaks up the salivary fluid’s homogeneity, leading to unexpected biophysical modifications. We suggest that every collected salivary sample is not reliable for accurate clinical and experimental investigation, since it displays highly local as well as variable chemical, physical and biological features, not reflecting the current physiological state of the oral cavity. Therefore, the assessment of a single salivary sample is not fully reproducible and cannot provide information about the biophysical, enzymatic and microbiological content of the whole saliva. In sum, the very topological features of the saliva - such as volume, shape, antipodal cells, vortex area, whirling fluid mass, segmentation, discretization, triangulation, node numbering - produce unnoticed biological consequences and network connectivity features with intriguing operational implications.

A paddle wheel aerator is developed in this research, which includes a wireless sensor network for measuring the water quality in the aquaculture of marine shrimp ponds. It can also move to the desired position to fill oxygen and measure water quality. A basic requirement is good standard water quality to prevent shrimp from epidemics and improve production. The water quality paddle wheel aerator applies a microcontroller and sensors to measure eight parameters of water quality. These water quality parameters are observed on the web application via an IoT module. The movement system of the water-quality paddle wheel aerator consists of a LiDAR, GPS, and remote RF signal. Each item of data is recorded immediately on the cloud server while the water-quality paddle wheel moves in the marine shrimp farm. The controlled paddle wheel aerator is harnessed automatically to enhance precisely the spatial monitoring resolution of the measurement system installed, which is needless for a multiple measurement system with high cost of investment. Also, farmers can access real data through the Line application. Hence, they are able to plan and control a good environment for aquaculture, preventing the occurrence of various epidemics and decomposing organic matter in the pond.

This study investigates the effects of home-based Kakao health care breathing exercises and stretching on respiratory function and fatigue in COVID-19 cured patients. A total of 35 participants performed four movements of home-based breathing exercise and five respiratory muscle stretching exercises four times a week for four weeks. Respiratory function was measured using FVC, FEV1, FEV1/FVC, and PEF. Fatigue was assessed using the Fatigue Severity Scale (FSS). Data analysis was performed using Independent Samples and Paired Samples T-tests in SPSS 24, with a significance level set at p &lt; 0.05. After four weeks of Home based Kakao health care Breathing Exercise, there were significant increases in respiratory FVC, FEV1, FEV1/FVC, and PEF function values observed in the training group (T.G.) after the exercise intervention (p &lt; 0.05). Such an increase was observed when comparing these values with the pre-exercise measurements. In contrast, there was no statistically significant difference in respiratory function outcomes before and after exercise in the control group (C.G.) (p &gt; 0.05). The FSS scores were statistically significant within the training group (T.G.). (p &gt;0.05). The 4-week Kakao health care Breathing Exercise was found to be capable of improving some respiratory functions in COVID-19-recovered patients, but it showed no significant improvement in fatigue levels.

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

Pulmonary sarcoidosis is a multisystem granulomatous interstitial lung disease (ILD) with a variable presentation and prognosis. Early accurate detection of pulmonary sarcoidosis may prevent progression to pulmonary fibrosis, a serious and potentially life-threatening form of the disease. However, the lack of a gold-standard diagnostic test and specific radiographic findings pose challenges in diagnosing pulmonary sarcoidosis. Chest computed tomography (CT) imaging is commonly used but requires expert, chest-trained radiologists to differentiate pulmonary sarcoidosis from lung malignancies, infections, and other ILDs. In this work, we developed a multichannel, CT and radiomics-guided ensemble network (RadCT-CNNViT) with visual explainability for pulmonary sarcoidosis vs. lung cancer (LCa) classification using chest CT images. We leverage CT and hand-crafted radiomics features as input channels, and a 3D convolutional neural network (CNN) and vision transformer (ViT) ensemble network for feature extraction and fusion before a classification head. The 3D CNN sub-network captures localized spatial information of lesions, while the ViT sub-network captures long-range, global dependencies between features. Through multichannel input and feature fusion, our model achieved the highest performance with accuracy, sensitivity, specificity, and combined AUC of 0.93±0.04, 0.94±0.04, 0.93±0.08 and 0.97 respectively in a 5-fold cross-validation study with pulmonary sarcoidosis (n=126) and LCa (n=93) cases. The model offers promising potential for improving the diagnosis of pulmonary sarcoidosis. A detailed ablation study showing the impact of CNN+ViT compared to CNN or ViT alone, and CT+radiomics input, compared to CT or radiomics alone, is also presented in this work.

Objective: to retrospectively evaluate the incidence rate (IR) of echocardiographic signs suspected for pulmonary hypertension (PH) in Systemic sclerosis (SSc) patients after the introduction of a combination therapy with bosentan and sildenafil for treatment or prevention of digital ulcers. Methods: patients attending the Scleroderma Unit of the Universital Hospital of Careggi from July 2010 to July 2023 were enrolled. Patients older than 18 years old, with an history of digital ulcers, treated with bosentan and sildenafil in combination for at least 12 months were included. Patients with a diagnosis of PH preceding the introduction of the therapy were excluded. Demographical data, disease duration, laboratoristic and instrumental data (pulmonary function tests, echocardiographic estimation of pulmonary artery pressure (PAPs) and ultrasonographic value of renal resistive index) were collected. The IR of echocardiographic signs suspected for pulmonary hypertension and their 95% confidence interval were calculated in events/1000 patients-years.Results: forty-seven patients were enrolled; mean disease duration was 12,14 years (SD 5,87). Mean duration of the combination treatment was 78.33 (SD 41.37) months and total at-risk time was 3525 months. Two patients (4,2%) presented echocardiographic signs of PH (sPAP 50 mmHg and 40 mmHg); the IR was calculated to be 6.8/1000 patients-years (95% CI 6,02-7,7). In one of the 2 patients RHC excluded PAH, while the other patient refused to undergo to RHC and PAH could not be confirmed/excluded. A stability of PFTs and echocardiografic PAPs was observed during the observation time. Conclusions: the results of this retrospective study suggest that combination therapy with endothelin receptor antagonist and Phosphodiesterase-5 (PDE5) inhibitors could help in preventing PAH in SSc; prospective case-control studies on larger population are needed to improve knowledge in this field.

Recurrent respiratory papillomatosis (RRP) is a non- malignant disease, characterized by the production of wart-like growths in respiratory tract, affecting both young and adults (Juvenile-Onset Recurrent Respiratory Papillomatosis, JORRP and Adult-Onset Recurrent Respiratory Papillomatosis, AORRP, respectively). Infection caused by Human Papillomavirus (HPV) is known as the main factors involved in RRP development. Complications of RRP may rarely occur, including lung involvement and malignant transformation. The present systematic review was aimed to evaluate the prevalence of severe complications, as lung involvement and lung tumor in JORRP and AORRP patients, following the guideline for reporting systematic reviews and meta-analysis (PRISMA Statement). Among the 378 studies were found on PubMed and Scopus using the following MESH terms “recurrent respiratory papillomatosis and lung tumor” and “pulmonary tumor and recurrent respiratory papillomatosis”. Basing on inclusion and exclusion criteria, a total of 11 studies were included in the systematic review. We found a pooled prevalence of 8% (95% CI:4%-14%; I2: 87.5%) for lung involvement in RRP patients. In addition, we found a pooled risk difference of 5% in lung involvement between JORRP and AORRP (95% CI: -7%-18%; I2 :85.6%, p-value: 0.41). Among patients with lung involvement, we observed a pooled prevalence of lung tumor of 4% (95% CI:1%- 7%; I2: 67.1%), and a pooled prevalence mortality for this group of 4% (95% CI:2%-6%; I2: 0%). Overall, the positivity rate for HPV-6 and -11 in patients with RRP was 91%. Considering only cases with pulmonary involvement, the pooled prevalence for HPV 11 was 21% (95% CI: 5%-45%; I2: 77.2%). Our results evidenced a low/middle risk of pulmonary involvement and lung tumor in JORRP and AORRP patients, with an increased risk for HPV-11 positive patients. Further studies should be performed to improve knowledge and adopt preventive measures to contrast the progression to severe diseases in RRP patients.

Pulmonary tuberculosis (PTB) is one of the leading causes of death in developing countries. This global health burden is worsened by the emergence of multi-drug resistance, which calls for new interventions to address the pandemic and medicinal plants remain a source for the new interventions. This study aimed to investigate the in vitro immunomodulatory effects of three plants used traditionally for the treatment of PTB in the Eastern Cape Province of South Africa. Eradication of Mycobacterium. tuberculosis in the lung tissue, requires the pro-inflammatory M1 phenotype. Thus, a plant extract with a high potential for anti-tuberculosis effects is expected to produce a high concentration of nitric oxide (NO) as the indicator for the pro-inflammatory M1 phenotype. To test this effect, lipopolysaccharide-activated RAW 264.7 macrophages were cultured and treated with the ethanolic crude extracts of three plants: Anthrixia philycoides, Lippia javaniva, and Sanicula elata at concentrations of 50µg/ml, 100µg/ml, and 200 µg/ml. After 24h, 50µl Griess reagent was added to the plates and absorbance was measure at 540nm. A standard curve of sodium nitrite dissolved in culture media was used to determine the concentration of NO in each sample. The results showed Anthrixia philycoides, and Lippia javanica, as anti-inflammatory when compared with the positive control, while Sanicula elata pro-inflammatory, producing a high amount of NO, compared with the positive control. Our results revealed the polarizing activity of Sanicula elata on macrophages towards M1 phenotype, with evidence of the nitric oxide production, warranting further in-vivo investigations of medicinal plant for anti-TB activity.

Background: Oscillation and pulmonary expansion (OPE) therapy can decrease postoperative pulmonary complications in a general surgical population, but its effect after cardiac surgery has not been reported, to our knowledge. We hypothesized that using an OPE device after cardiac surgery before extubation would decrease pulmonary complications. Methods: This retrospective cohort study included adults undergoing elective open cardiac surgery at our institution from January 2018 through January 2019, who had an American Society of Anesthesiologists score of 3 or greater. For mechanically ventilated patients after cardiac surgery, a new OPE protocol was adopted July 1, 2019, comprising an initial 10-minute OPE treatment administered in-line with the ventilator circuit, then continued treatments for 48 hours after extubation. Severe postoperative respiratory complications (primary outcome measure) included need for antibiotics, increased supplemental oxygen use, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcomes data were compared for patients before (usual care with postextubation hyperinflation) and after protocol implementation (OPE). Results: Of 104 patients, 54 patients received usual care, and 50 received OPE. Usual-care recipients had more men (74% vs 62%; P=.19) and were older (median, 70 vs 67 years; P=.009) than OPE recipients. The OPE group had a significantly shorter hospital LOS than the usual-care group (mean, 6.2 vs 7.4 days; P=.04). Other measures improved with OPE but did not reach significance: shorter ventilator duration (mean, 0.6 vs 1.1 days with usual care; P=.06) and shorter LOS in the intensive care unit (mean, 2.7 vs 3.4 days; P=.06). On multivariate analysis, intensive care unit LOS was significantly shorter for the OPE group (mean difference, 0.85 days; 95% CI, 1.65 to 0.06; P=.04). The OPE group had a lower percentage of postoperative complications (10% vs 20%). Conclusion: OPE therapy after cardiac surgery is associated with decreased ICU and hospital LOS.

COVID-19 generated a scenario for global health with multiple systemic impairments. This retrospective study evaluated the clinical, radiological, and pulmonary functional evolution in 302 post-COVID-19 patients. Regarding post-COVID-19 pulmonary symptoms, dry cough, dyspnea, and chest pain were the most frequent. Of the associated comorbidities, asthma was more frequent (23.5%). Chest Tomography (CT) initially showed a mean pulmonary involvement of 69.7%, and the evaluation in the subsequent months showed an improvement in the evolutionary image, and with less than six months post-pathology, there was a commitment of 37 .7%, from six to twelve months, 20% and after 12 months, 9.9%. And as for most of the sample, 50.3% of the patients presented CT normalization in less than six months after infection, 23% normalized between six and twelve months, and 5.2% normalized the images after twelve months, with one remaining. Percentage of 17.3% who maintained post-COVID-19 pulmonary residual sequelae. Regarding spirometry, in less than six months after the pathology, 59.3% of the patients already showed a regular exam; 12.3% normalized their function within six to twelve months, and 6.3% concluded a normal exam after twelve months of post-pathology evaluation. Only 3.6% of the patients still showed some alteration in this period.

Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher exercise frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients.

(1) Background: This retrospective study aimed to compare the efficacy and safety of one-stage computed tomography (OSCT)- to that of two-stage computed tomography (TSCT)-guided localization for the surgical removal of small lung nodules. (2) Methods: We collected data from patients with ipsilateral pulmonary nodules who underwent localization before surgical removal at Veteran General Hospital Kaohsiung between October 2017 and January 2022. The patients were divided into the OSCT and TSCT groups. (3) Results: We found that OSCT significantly reduced the localization time and risky time compared to TSCT, and the success rate of localization and incidence of pneumothorax were similar in both groups. However, the time spent under general anesthesia was longer in the OSCT group than in the TSCT group. (4) Conclusions: The OSCT-guided approach to localize pulmonary nodules in hybrid operation room is a safe and effective technique for the surgical removal of small lung nodules.

Background: This study presents the experience gained in the Newborn Intensive Care Unit (NICU) at “M. S. Curie” Emergency Clinical Hospital for Children in Bucharest after performing a series of bedside surgery interventions on newborns with congenital diaphragmatic hernia (CDH). We evaluate the advantages, complications, immediate and long-term outcome as well as the morbidity. Methods: We conducted a retrospective analysis of the data for all patients operated on-site be-tween 2011 and 2020, in terms of pre- and post-operative stability, procedures performed, com-plications and outcomes. Results: Our study is based on data from ten cases of newborns, term or small for gestation age with birthweights ranging from 2300 to 3300 grams, operated, on average, on the fifth day of life. The main reasons for operating on-site were the hemodynamical instability and the need to ad-minister inhaled Nitic Oxide (iNO) and HFOV ventilation. There were no unforeseen events dur-ing surgery, no immediate postoperative complications and no surgery related mortality. One noticed drawback was the unfamiliarity of the surgery team with the new operating environment. Conclusions: Our experience indicates that bedside surgery improves the likelihood of survival for critically ill neonates suffering from CDH. No immediate complications could be associated with this practice. Keywords: congenital diaphragmatic hernia, severe pulmonary hypertension, bedside surgery, NICU infrastructure

Coronavirus disease 2019 (COVID-19) can lead to systemic coagulation activation and thrombotic complications. We investigated the incidence of objectively confirmed venous thromboembolism (VTE) in 198 hospitalized patients with COVID-19 in a single-center cohort study. Seventy-four patients (37%) were admitted to the intensive care unit (ICU). At time of data collection, 58 (29%) were still hospitalized and 14% had died. During a median follow-up of 5 days (IQR, 3-9), 33 patients (17%) were diagnosed with VTE of whom 22 (11%) had symptomatic VTE, despite routine thrombosis prophylaxis. The cumulative incidences of VTE at 7 and 14 days were 15% (95% CI, 9.3-22) and 34% (95% CI, 23-46), respectively. For symptomatic VTE, these were 11% (95% CI, 5.8-17) and 23% (95% CI, 14-33). VTE appeared to be associated with death (adjusted HR, 2.9; 95% CI, 1.02-8.0). The cumulative incidence of VTE was higher in the ICU (25% at 7 days 95% CI, 15-36, and 48% at 14 days, 95% CI, 33-61) than on the wards (any VTE and symptomatic VTE 6.5 % at 7 days (95% CI, 1.5-17) and 10% at 14 days (95% CI, 2.9-24)).The observed risk for VTE in COVID-19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE. Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

The value of QuantiFERON in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment is unclear. The aims of this study were to evaluate the accuracy of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment in patients with active pulmonary tuberculosis (PTB). Between January 2013 and December 2015, 128 cases with active PTB and 128 controls with no mycobacterial infection, matched by age (within 3 years) and by the week that they visited Tainan Chest Hospital, were enrolled in the study. Serial testing by QFT-GIT at baseline and after 2 and 6 months of treatment was performed. At these time points, a comparison of the performance of QFT-GIT with that of sputum culture status among study subjects was conducted. Compared to baseline, 116 (87.2%) cases showed a decreased response, whereas 17 (12.8%) showed persistent or stronger interferon-gamma (IFN-γ) responses at 2 months. Their IFN-γ responses declined significantly from baseline to 2 months (median, 6.32 vs. 4.12; P < 0.005). The sensitivity values of the QFT-GIT test for the detection of pulmonary tuberculosis at cut-off points of 0.35 IU/ml, 0.20 IU/ml, and 0.10 IU/ml were 74.4%, 78.2%, and 80.5%, respectively. The specificity values at cut-off points of 0.35 IU/ml, 0.20 IU/ml, and 0.10 IU/ml were 66.2%, 63.9%, and 57.1%, respectively. Our results support the QFT-GIT assay as a potential tool for diagnosing tuberculosis and for monitoring the efficacy of anti-tuberculosis treatment.

The rapid emergence of Decentralized Finance (DeFi), driven by blockchain technology and smart contracts, is transforming the landscape of the financial industry by enabling peer-to-peer financial services without traditional intermediaries. This paper examines the impact of DeFi on traditional banking systems, focusing on the opportunities, challenges, and future directions of this revolutionary financial model. We explore how DeFi disrupts traditional financial intermediation by offering faster, cheaper, and more transparent financial services, potentially reducing the dominance of conventional banks. The study addresses critical issues such as regulatory challenges, including compliance with Anti-Money Laundering (AML) and Know Your Customer (KYC) requirements, and the importance of consumer protection in a decentralized environment. We also investigate collaboration opportunities between traditional banks and DeFi platforms, which could lead to innovative financial products and services. To provide a comprehensive analysis, the paper employs a mixed-method approach, combining a review of recent literature, empirical data, case studies, and expert interviews. The findings highlight significant gaps in current regulatory frameworks and emphasize the need for a balanced approach that fosters innovation while ensuring financial stability and consumer safety. This study concludes by offering recommendations for policymakers, financial institutions, and DeFi developers to harness the potential of DeFi while addressing its inherent risks, paving the way for the sustainable growth of decentralized finance in the broader financial ecosystem.

In this preliminary investigation, a concise molecular docking study using the Pyrx program screened thousands of compounds against the active site of HIV-1 reverse transcriptase. The Virtual Screening library was employed to assess binding energetics scores, focusing on identifying candidates with high Vina Scores. Eight compounds, including Tetrophan, Imatinib, Amentoflavone, Alprazolam, Bilobetin, Bafetinib, Nilotinib, and Ginketin, emerged as promising candidates with significant binding energies.Recognizing compounds that strongly bind to HIV-1 reverse transcriptase holds potential for antiretroviral drug development in the fight against HIV infection. Subsequently, the study evaluated the toxicity properties of these candidates using pKCSM. Amentoflavone, a natural biflavonoid found in Ginkgo biloba and Nilotinib, a tyrosine kinase inhibitor, demonstrated lower overall toxicity profiles compared to other candidates. Further toxicity analysis using Pro-Tox-II revealed Amentoflavone's higher predictive LD50, lower toxicity class, and reduced probabilities of hepatotoxicity, carcinogenicity, mutagenicity, and moderate immunotoxicity compared to Nilotinib. While Nilotinib, a pharmaceutical drug, exhibited higher probabilities of adverse effects in these categories. In summary, Amentoflavone and Nilotinib present as promising candidates with lower toxicity concerns. Amentoflavone, as a natural substance, showcases a more favorable toxicity profile than Nilotinib, offering valuable insights for potential therapeutic applications.

There are many features of homeostasis worth investigating such as how it works (information pathways, set point processing), where its command and control processors are located in the cell, the language used and how homeostasis interacts with all aspects of an organism's functional maintenance and development. All are necessary and valid inquiries, but this paper examines the implications of ignoring it as a factor of disease causation. Alternatively when properly understood the homeostasis profile becomes a rational explanation for any individual’s range of health; where some areas are very resistant to disease (resilient) and other areas of homeostasis are dysfunctional leading to minor, moderate or very susceptible tendencies to disease (lack of resilience in homeostasis). An understanding of this phenomenon, its interactions with gene expression (epigenetics) is necessary in order to evaluate the solutions for acute and chronic diseases. By this method diseases can be defined more precisely as specific susceptibilities in homeostasis, leading to a method to restore specific homeostasis functions.

Traditional urban design often overlooks the synchronisation of human and ecological connectivities, typically favouring corridors for ecological continuity. Our study challenges this convention by introducing a computational design approach, Meta-Connectivity, leveraging the deep generative models performing cross-domain translation to integrate human-wildlife landscape connectivity in urban morphology amidst the planetary urbanisation. Utilising chained Pix2Pix models, our research illustrates a novel meta-connectivity design reasoning framework, combining landscape connectivity modelling with conditional reasoning based on deep generative models. This framework enables the adjustment of both human and wildlife landscape connectivities based on their correlative patterns in one single design process, guiding the re-materialisation of urban landscapes without the need for explicit prior ecological or urban data. Our empirical study in East London demonstrated the framework's efficacy in suggesting wildlife connectivity adjustments based on human connectivity metrics. The results demonstrate the feasibility of creating an innovative urban form in which the land cover guided by the connectivity gradients replaces the corridors based on simple geometries. This research thus presents a methodology shift in urban design, proposing a symbiotic approach to integrating disparate yet interrelated landscape connectivities within urban contexts.

This paper deals with the design and kinematic analysis of a novel mechanism for the elbow joint of an upper-limb exoskeleton, with the aim of helping operators, in terms of effort and physical resistance, in carrying out heavy operations. In particular, the proposed eight-bar el-bow joint exoskeleton mechanism consists of a motorized Watt I six-bar linkage and a suitable RP dyad, which connects mechanically the external parts of the human arm with the corre-sponding forearm by hook and loop velcro and thus, helping their closing relative motion for lifting objects during repetitive and heavy operations. This relative motion is not a pure rotation and thus, the upper part of the exoskeleton is fastened to the arm, while the lower part is not rigidly connected to the forearm, but through a prismatic pair which allows both rotation and sliding along the forearm axis. Instead, the human arm is sketched by means of a crossed four-bar linkage, which coupler link is considered as attached to the glyph of the prismatic pair, that is fastened to the forearm. Therefore, the kinematic analysis of the whole ten-bar mecha-nism, which is obtained by joining the Watt I six-bar linkage and the RP dyad to the crossed four-bar linkage, is formulated to investigate the main kinematic performance and for design purposes. The proposed algorithm has given several numerical and graphical results. Finally, a double-parallelogram linkage, as particular case of the Watt I six-bar linkage, was considered in combination with the RP dyad and the crossed four-bar linkage, by giving a first mechanical de-sign and a 3D printed prototype.