The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in a significant surge of critically ill patients and an unprecedented demand on intensive care services. The rapidly evolving understanding of pathogenesis, limited disease specific evidence and demand-resource imbalances have posed significant challenges for intensive care clinicians. COVID-19 is a complex multisystem inflammatory vasculopathy with a significant mortality implication for those admitted to intensive care. Institutional strategic preparation and meticulous intensive care support are essential to maximising outcomes during the pandemic. The significant mortality variation observed between institutions and internationally, despite a single aetiology and uniform presentation, highlights the potential influence of management strategies on outcome. Given that optimal organ support and adjunctive therapies for COVID-19 have not yet been well defined by trial-based outcomes, strategies are predicated on existing literature and experiential learning. This review outlines the relevant pathophysiology and management strategies for critically ill patients with COVID-19, and shares some of the collective learning accumulated in a high volume Severe Respiratory Failure centre in London.

The constant news about the corona virus is scary. It is not possible to separate treatment for Cancer due to COVID-19. An effective treatment comparison strategy is needed. We need to have a handy tool to understand cancer progression in this unprecedented scenario. Linking different events of cancer progression is the need of the hour. It is a methodological challenge. We provide the solutions to overcome the issue with interval between two consecutive events in motivating head and neck cancer (HNC) data.

New developments in broadcast technology, such as the ad hoc wireless network and the detection devices that work, enable daily connections to the Internet, commonly referred to as the Internet of Things (IoT). IoT saw this as a support for the development of creative and contextual services and applications. The service can respond to the user's environment and preferences. Finite state machines are recently making waves when the issue of self-controlling systems come into the picture of designs. This research focuses on the design of a fault tolerant system that controls random failures impressed on the network. The method comprises of diodes, Resistors, Optocouplers, ESP8266 WI-FI Module Webpage with button, and two Arduinos which in effect will determine iteratively who to handle a failure at hand modelled as when the button on the webpage is pressed. In this work, a Heartbeat Detection and Monitoring System will be made using Arduino that detect the electrical state using the Pulse Sensor and show the readings in Beats Per Minute on the LED connected a microcontroller. It sends the texts to the server using the Wi-Fi module ESP8266 to signals can be monitored from the monitoring zone via the internet. This is reflected by the declaration of a master state by either of two Arduinos whenever the push button is pressed as observed on the codes. The result obtained from the research shows apparently, the state of the fault tolerance system none power deny of heartbeat condition connected to the LED.

The use of high strength to weight ratio laminated composites is emerging in marine industry and applications as a very efficient solution for improving productivity. Nevertheless, delamination between the layers is a limiting factor for the wider application of laminated composites, as it reduces the stiffness and strengths of the structure. Interleaving nanofibrous mats between layers of composite laminates has been proved to be an effective method for improving composites delamination resistance. This paper aims to characterize the effect of interleaved nanofiber on mode I interlaminar properties and failure mechanisms when subjected to static and fatigue loadings. For this purpose, virgin and nanomodified woven laminates were subjected to Double Cantilever Beam (DCB) specimens. Static and fatigue tests were performed and the tests were monitored by acoustic emission technique. The mechanical results showed a 130% increase of delamination toughness for nanomodified specimens in the static loadings and more crack growth resistance in the fatigue loading. The AE results revealed that different type of failure mechanisms was the cause of these improvements for the modified specimens compared with the virgin ones.

More and more works are using machine learning techniques while adopting supervisory control and data acquisition (SCADA) system for wind turbine anomaly or failure detection. While parameter selection is important for modelling a wind turbine’s health condition, only a few papers have been published focusing on this issue and in those papers interconnections among sub-components in a wind turbine are used to address this problem. However, merely the interconnections for decision making sometimes is too general to provide a parameter list considering the differences of each SCADA dataset. In this paper, a method is proposed to provide more detailed suggestions on parameter selection based on mutual information. Moreover, after proving that Copula, a multivariate probability distribution for which the marginal probability distribution of each variable is uniform is capable of simplifying the estimation of mutual information, an empirical copula based mutual information estimation method (ECMI) is introduced for an application. After that, a real SCADA dataset is adopted to test the method, and the results show the effectiveness of the ECMI in providing parameter selection suggestions when physical knowledge is not accurate enough.

The production of lithium-ion battery cells is characterized by a high degree of complexit due to numerous cause-effect relationships between process characteristics. Knowledge about the multi-stage production is spread among several experts, rendering tasks such as failure analysis challenging. In this paper, a method is presented, which includes expert knowledge acquisition in production ramp-up by combining Failure Mode and Effects Analysis (FMEA) with a Bayesian Network. We show the effectiveness of this holistic method by building up a large scale, cross-process Bayesian Failure Network in lithium-ion battery production. Using this model, we are able to conduct root cause analyses as well as analyses of failure propagation. The former support operators in identifying root causes once a cell possesses a specific failure by calculating most-probable explanations matched to the individual battery cell data. The latter enable us to analyze propagation of failures and deviations in the production chain and thus provide support for placement of quality gates, leading to a significant reduction in scrap rate. Moreover, it gives an insight into which process steps are key drivers for which final product characteristics.

Over the past few decades, the landscape for multiple myeloma (MM) therapy has significantly advanced, largely due to the approval and introduction of new-generation proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs). Despite these advancements, MM remains incurable. In March 2021, the U.S. FDA approved the chimeric antigen receptor T-cell (CAR-T) therapy idecabtagene vicleucel (ide-cel) for relapsed/refractory multiple myeloma (R/R MM), heralding the advent of cellular therapies for R/R MM. However, due to factors such as the downregulation or loss of tumor antigen expression, T-cell exhaustion, and the influence of the tumor immune microenvironment, most R/R MM patients inevitably experience relapse following CAR-T cell therapy. Consequently, salvage therapy in the post-CAR-T setting has emerged as a critical area of research. This review discusses the potential factors leading to CAR-T therapy failure in R/R MM patients and discusses subsequent salvage therapeutic strategies, offering recommendations for addressing treatment failure in this context.

Diuretic resistance is a servomechanism involving superoxide that results from the use of escalating doses of diuretics in the treatment of heart failure. Without intervention this may lead to increased heart failure mortality. Recent heart failure studies involving the use of SGLT2 inhibitors and GLP-1 agonists have shown reductions in the need for loop diuretics along with reductions in hospitalizations for heart failure and cardiovascular mortality. Multiple mechanisms have been proposed to explain the benefits of both these drug classes but this paper is the first to explain and propose superoxide induced diuretic resistance as a therapeutic target for the treatment of heart failure.

Embryo’s Implantation is a question that we are not in the position to answer in full details. We know that it depends on embryo’s quality and uterine receptivity. It is possible to access uterine cavity before in vitro fertilisation by a variety of tools, however hysteroscopy is the gold standard in evaluation of uterine cavity and potential pathology. The frequencies of unrecognised uterine pathology revealed by hysteroscopy are 18-50% and 40-43% in patients undergoing in vitro fertilisation or after recurrent implantation failure respectively. Data is inconclusive regarding the role of hysteroscopy on pregnancy outcome after in vitro fertilisation. This review aims to evaluate the validity of office hysteroscopy in subfertile population before or after IVF treatment

Background: Despite tremendous advances in medicine, infective endocarditis (IE) continues to be a challenge for physicians due to increasing morbidity and unchanged high mortality. Objectives: Our aim was to evaluate clinical outcomes in patients with IE and to identify predictors of in-hospital mortality. Material and methods: The study was retrospective, single-centered, and included 270 patients diagnosed with IE, for the period 2005-2021 (median age 65 (51–74), man 177 (65.6%). Results: Native IE (NVIE) was found in 180 (66.7%), prosthetic IE (PVIE) in 88 (33.6%) and cardiac device-related IE (CDRIE) in 2 (0.7%), significantly more in the non-survivors group. Healthcare associated IE (HAIE) was 72 (26.7%), the most common pathogen were Staphylococci and the proportion of Gram-negative bacteria (GNB) non-HACEK were significantly higher in non-survivor’s vs survivors (11 (15%) vs 9 (4.5%), p=0.004). Overall, early surgery was performed in 54 (20%) patients, with a significant difference between deceased/alive (3 (4.5%) vs 51 (25.1%, p=0.000). The all-cause in-hospital mortality rate was 24.8% (67). The risk factors identified that increased the risk of death were septic shock (OR – 83 1; 95% CI (17.0-405.2), p=0.000) and acute heart failure (OR –24.6; 95% CI (9.2-65.0), p=0.000). Early surgery (OR – 0.03, 95% CI (0.01-0.16), p=0.000) and low Charlson comorbidity index (OR – 0.85, 95% CI (0.74-0.98, p=0.026) in turn reduce this risk. Conclusion: We found that acute heart failure and septic shock are independent predictors of in-hospital mortality. Low Charlson comorbidity index and early surgery increased survival. Knowing the predictors of death would change the therapeutic approach to a more aggressive one and improve the near and long-term prognosis of patients with IE.

Bioimpedance analysis (BIA) is a validated non-invasive technique already proven to be useful for the diagnosis, prognosis, and management of body fluids in subjects with heart failure (HF) and chronic kidney disease (CKD). Although BIA has been widely employed for research purposes, its clinical application is still not fully widespread. The aim of this review is to provide a comprehensive overview of the state of art of BIA utilization by analysing the clinical benefits, limitations, and the potential future developments in this clinically unexplored field.

The increasing frequency of urban flooding, driven by global climate change, poses significant threats to the safety and resilience of urban rail transit systems. This study systematically examines the cascading failure processes and resilience of these networks under flood conditions, with a specific focus on the Shanghai Metro. A comprehensive resilience evaluation model was developed by integrating geographic information, static network characteristics, and dynamic passenger flow indicators. This study employs an improved Coupled Map Lattice (CML) model to simulate cascading failures, considering the coupling effects of station centrality, geographic elevation, and passenger flow dynamics. Results indicate that stations with higher degree centrality are more likely to trigger rapid cascading failures across the network. However, incorporating dynamic passenger flow and geographic elevation data helps mitigate these effects, emphasizing the need for multi-dimensional resilience strategies. The findings provide valuable insights for urban transit management, offering a scientific foundation for developing targeted disaster response strategies to enhance network resilience against floods. This study advances the understanding of the vulnerability of urban rail transit systems and offers practical guidance for improving disaster preparedness in urban transportation infrastructure.

Heart failure (HF) is a global health concern with rising incidence and poor prognosis. While the essential role of nutritional and dietary strategies in HF patients is acknowledged in the existing scientific guidelines and clinical practice, there are no comprehensive nutritional recommendations for optimal dietary management of HF. In this review, we discuss results from recent studies on the obesity paradox and the effects of calorie restriction and weight loss, intermittent fasting, the Western diet, the Mediterranean diet, the ketogenic diet, and the DASH diet on HF progression. Many of these strategies remain under clinical and basic investigation for their safety and efficacy, and there is considerable heterogeneity in the observed response, presumably because of heterogeneity in the pathogenesis of different types of HF. In addition, while specific aspects of cardiac metabolism, such as changes in ketone body utilization, might underlie the effects of certain dietary strategies on the heart, there is a critical divide between supplement strategies (i.e. with ketones) and dietary strategies that impact ketogenesis. This review aims to highlight this gap by exploring emerging evidence supporting the importance of personalized dietary strategies to prevent progression and improve outcomes in the context of HF.

The development of Artificial Intelligence-based tools is having a big impact on industry. In this context, the maintenance operations of important assets and industrial resources are deeply changing both from a theoretical and a practical perspective, even in the field of ship propulsion systems. Namely, conventional preventive maintenance schedules audits and checks at fixed times by using statistics on component failures, but it can be improved by a predictive maintenance based on the real component health status, which is inspected by proper sensors. In this way, time and costs are saved. More in details, data-driven models, through Machine Learning (ML) algorithms, generate the expected values of monitored variables for comparison with real measurements coming from the asset, hence for a diagnosis based on the difference between expectations and observations. Then, a ML-based fault detection starts with the choice of the ML algorithm. This process is often not the consequence of an in-depth deep analysis of the different algorithms available in the literature. For that reason, the authors propose a simple procedure to support a first implementation stage of the so-called Condition Based Maintenance (CBM): a quick benchmarking of the most suitable ML algorithms useful for fault detection. The algorithms are compared by taking into account not only the algorithm output error, shown by the Mean Squared Error between predictions and data, but also the response time, which is a crucial variable for maintenance purpose.

Background: Heart failure (HF) remains a challenging healthcare issue, necessitating innovative therapies like cardiac resynchronization-defibrillation therapy (CRT-D). However, defining CRT-D responders lacks uniformity, impeding effective clinical evaluation. This study explores diverse CRT-D responder definitions, encompassing functional, echocardiographic, and laboratory criteria. Materials & Methods: A single-center study involving 132 CRT-D patients scrutinized responder criteria, including NYHA stage, LVEF increase, and proBNP decrease. Statistical analyses, such as Kaplan–Meier curves and Cox hazard regression, were employed to evaluate responder characteristics and survival outcomes. Results: Responder rates varied across criteria, revealing nuanced patient profiles. CRT-D responders, defined by NYHA decrease, LVEF increase, or proBNP decrease, exhibit improved survival rates after 2 and 3 years (p < 0.050). Young age, absence of recent myocardial infarction, and normal right ventricular, echocardiographic parameters emerge as predictors for positive response. In part, drug-based HF therapy correlates with increased responder rates. Cox regression identified LVEF ≥ 5% and proBNP decrease ≥ 25% as independent predictors of extended survival. Conclusions: CRT-D responder definitions exhibit considerable variability, emphasizing the need for a nuanced, patient-centered approach. Factors like right ventricular function, drug therapy, atrial fibrillation, and renal function influence responses. The study enriches our understanding of CRT-D response, contributing to the foundation for personalized HF management.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome characterized by multiple risk factors and associated conditions. HFpEF prevalence is rising, and its prognosis remains poor after the first hospitalization. Using a two-hit HFpEF murine model, we aimed at studying cardiac reverse remodelling after stopping the causing stress (Angiotensin II [AngII]) and a high-fat diet [HFD]; MHS) and introducing voluntary exercise. We studied in young male and female C57Bl6/J mice fed or not with an HFD (60% calories from fat) the cardiac response to AngII (1.5 mg/kg/day for 28 days). Then, MHS was stopped, and VE was started for another four weeks (RR). We studied the effects of MHS and RR on the circulatory microRNA (miR) profile (miRNome) and the myocardial miRNome to characterize the cardiac and non-cardiac response of small RNAs. AngII alone and MHS but not the HFD caused cardiac hypertrophy (CH), left ventricular (LV) concentric remodelling and left atrial enlargement in male mice. HFD-induced CH and LV concentric remodelling only in female mice. Four weeks after RR, CH, LV concentric remodelling and atrial enlargement were reversed. We performed bulk circulatory and LV miR sequencing. We did not observe differences linked to biological sex. RR restored normality for circulatory miRNome, whereas LV miRNome remained relatively similar to the one after MHS. Among the 25 most abundant circulatory miRs, ten were modulated by MHS (9 upregulated). In the LV, 8 of the 25 most abundant miR were upregulated by MHS, and 10 were downregulated. MiRNomes from AngII, HFD or MHS shared many common modulated miRs (32), suggesting that the overall response of organs producing the bulk of circulatory small non-coding RNA was similar even for seemingly different stress.

Health care is currently showing a fall in heart failure (HF) prevalence and incidence particularly in developed countries, but with only a subset receiving appropriate therapy to protect the heart against maladaptive processes such as fibrosis and hypertrophy. Appropriate markers of advanced HF are still needed, which should help choosing the most suitable therapy and avoid major compliance problems. Speckle tracking echocardiography (STE) is a good choice, being a non-invasive imaging technique and is able to assess cardiac deformation in a variety of conditions. Several multicenter studies and meta-analyses have demonstrated its clinical applications and accuracy in early and late stages of HF, as well as its association with both left ventricular (LV) filling pressures and myocardial oxygen consumption, the two are important parameters in the evaluation of HF patients. Also, STE assists in assessing right ventricular free-wall longitudinal strain (RVFWLS) which is a solid predictor of right ventricle failure (RVF) following LV assist device (LVAD) implantation. Despite its limitations, STE plays an essential role in the clinical evaluation of patients with HF, early and advanced, in explaining symptoms and signs and also as an accurate prognosticator. The aim of this review is to examine the advantages of STE in early evaluation of myocardial dysfunction and their correlation with right heart catheterization (RHC) parameters, which should have a significant clinical relevance in the management of HF patients.

Elevated blood glucose levels, known as glycemia, play a significant role in sudden cardiac arrest, often resulting in sudden cardiac death, particularly among those with diabetes. Understanding the internal mechanisms has been a challenge for healthcare professionals, leading many research groups to investigate the relationship between blood glucose levels and cardiac electrical activity. Our hypothesis suggests that glucose-sensing biophysics mechanisms in cardiac tissue could clarify this connection. To explore this, we adapted a single-compartment, computational model of the human atrial node's action potential. We incorporated glucose-sensing mechanisms with voltage-gated sodium ion channels using ordinary differential equations. Parameters for the model were based on existing experimental studies to mimic the impact of glucose levels on atrial node action potential firing. Simulations using voltage clamp and current clamp techniques showed that elevated glucose levels decreased sodium ion channel currents, leading to a reduction in the sinoatrial node action potential frequency. In summary, our mathematical model provides a cellular-level understanding of how high glucose levels can lead to bradycardia and sudden cardiac death.

This study reveals the essential load-bearing characteristics of the steel-concrete composite floor system under fire conditions applying structural stressing state theory. Firstly, the strain data in the entire process of the fire test are modeled as state variables which can present the slab’s stressing state evolution characteristics; Then, the state variables are used to build the stressing state mode and the parameter characterizing the mode. Further, the Mann-Kendall criterion is adopted to detect the leap points in the evolution curves of the characteristic parameters during the entire fire exposure process. Also, the evolution curves of the stressing state modes are investigated to verify the leap profiles around the leap/characteristic points; Finally, the detected leap points are defined as the failure starting points and elastoplastic branching points, which is unseen in the past researches focusing on the failure endpoint defined at the ultimate load-bearing state of the composite floor system. The failure starting point and the elastoplastic branching point are the embodiment of natural law from quantitative change to quality change of a system rather than an empirical and statistical judgment. Hence, both characteristic points avoidably exist in the strain data of the composite floor system undergoing the fire process, which can be revealed through the proper modeling methods and update the existing theories and methods on structural analysis and design in fire.

Heart failure (HF) is a life-threatening disorder and is treated by drug therapies and surgical interventions such as heart transplantation and left ventricular assist device (LVAD). However, these treatments can lack effectiveness in the long term and are associated with issues such as donor shortage in heart transplantation, and infection, stroke, or gastrointestinal bleeding in LVADs. Therefore, alternative therapeutic strategies are still needed. In this respect, stem cell therapy has been introduced for the treatment of HF and numerous preclinical and clinical studies using various types of stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been shown to improve cardiac function and attenuate left ventricular remodeling. IPSCs, which have a capacity of unlimited proliferation and differentiation to cardiomyocytes, are a promising cell source for myocardial regeneration therapy. This review discusses the current status of cardiac regenerative therapy using iPSCs.

Cardiovascular diseases (CVDs) remain the leading cause of mortality. Traditional approaches to diagnosing and treating CVDs often involve interpretation, which can lead to errors. The emergence of Artificial Intelligence (AI) and Machine Learning aids the management of CVDs. AI examines amounts of data and identifies patterns offering solutions for disease detection, risk prediction, and patient care. The American Heart Association's 2023 Scientific Sessions (AHA23) showcased studies that highlight AIs potential to revolutionize cardiac healthcare. This article presents a review of these cutting-edge studies exploring how AI is applied in health, the outcomes of these applications, and their implications for clinical practice. The insights gained from this review will contribute to the discussion on AI's role in healthcare and its capacity to enhance outcomes.

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

Heart failure (HF) affects about 60 million people worldwide, making it one of the chronic conditions with the greatest health and economic impact. The primary objective was to assess the efficacy of lung ultrasound (LUS) in the management of HF in order to intervene early and reduce the rate of hospital readmissions. A systematic search was conducted on PubMed, Embase, Google Scholar, Web of Science, and Scopus, including clinical trials, meta-analysis, systematic reviews, and original articles from 2019/1/1-2023/12/31, about LUS for the assessment of HF, on an outpatient basis, for HF diagnosis or/and decompensation. There may be risk of bias because the effects are dependent on the persons delivering the intervention. The results were synthetized by PRISMA method. A total of 873 articles were identified of which 33 articles were selected: [n=19] focused on prognostic assessment of HF, [n=11] centred on multimodal diagnostic assessments, and [n=2] addressing therapeutic guidance for HF diagnosis. LUS exhibits advantages in the detection of sub-clinical congestion linked to prognostic significance in re-admission and mortality during out-patient follow-up, after hospital discharge, and in complex scenarios as the patients' homes or institutional long-term care facilities. However, there are considerable uncertainties in their interpretation and monitoring changes due to its lack of standardization. The need for an updated international consensus on the use of LUS seems obvious.

The ubiquitous deployment of Li-ion batteries (LIBs) in more demanding applications has reinforced the need to understand root-causes of thermal runaway. Herein we perform a forensic simulation of a real-case failure scenario, using localised heating of Li(Ni0.5Mn0.3Co0.2)O2 versus graphite 18650 cylindrical cells. This study determined the localised temperatures that would lead to venting and thermal runaway of these cells, as well as correlating the gases produced as a function of degradation pathway. Catastrophic failure, involving melting (with internal cell temperatures exceeding 1085°C), deformation and ejection of cell componentry, was induced by locally applying 200 °C and 250 °C to a fully charged cell. Conversely, catastrophic failure was not observed when the same temperatures were applied to the cells at lower state of charge (SOC). This work highlights the importance of SOC, chemistry and heat in driving the thermal failure mode of Ni-rich LIB cells, allowing for a better understanding of battery safety and associated design improvements.

Cirrhosis is a chronic disease with multiple etiologies, multiple manifestations, and multi-organ involvement. Affects about 200 million people worldwide. Its main complication is Portal hypertension (PHT). Cirrhotic cardiomyopathy is a consequence of PHT, with heart failure (HF) being the main manifestation. On the other hand, for people with cardiopathy due to other reasons beyond cirrhosis, the presence of the last could act as a trigger to acute HF. Finally, when HF and cirrhosis coexist, the renal system suffers the most, originating from type-5 cardio-renal syndrome, a complex entity with many challenges in diagnosis and treatment. This entity was recently defined and there is a lack of data on the epidemiology of this syndrome. A 77-year-old woman, with cardiovascular risk factors; heart failure with reduced ejection fraction (HFrEF), secondary ischemic and valvular cardiopathy, chronic Kidney disease (CKD), and stable decompensated cirrhosis, went to the emergency department after progressive abdominal perimeter augmentation, legs’ edema and hematochezia. It was assumed acute decompensated cirrhosis and acute decompensated chronic kidney disease, had triggered digestive bleeding and the patient stayed hospitalized. Intravenous diuretic therapy was started but, the ascites and kidney function got worse, the Nt pro-BNP grew until 1125000 pg/ml, and a transthoracic echocardiography showed important signs of congestion, isolated right ventricular dysfunction, with normal cardiac output. After teamwork’s discussion, a type-5 cardio-renal syndrome was assumed deciding not to act on tricuspid regurgitation due to the maladaptive RV remodeling. Hepatorenal syndrome treatment was begun (oral terlipressin and intravenous albumin), followed by decongestion therapy, resulting in a marked improvement in clinical presentation. The kidney, heart, and liver recovered to these basal states. With this clinical case, the authors want to show how multidisciplinary management is important to face tricuspid regurgitation and right ventricular dysfunction.

This paper aims to quantify the influence of hydrogen embrittlement on Wierzbicki and Xue (W-X) model parameters. This model has 4 parameters which have been obtained by tensile tests on smooth specimens, tensile notch specimens, single notch tensile specimens (SENT) and pure shear specimens. Hydrogen embrittlement has been obtained by electrolytic method. Application of the (W-X) model has been done to get the local resistance used to predict failure by the Volumetric Method (VM). An example is given for the case of an embedded pipe submitted to service pressure and lateral seismic displacement. The effect of this displacement is then assimilated to the shearing of the straight section of the pipe. The pipe shows a corrosion defect considered a semi-elliptical crack. The influence of hydrogen embrittlement on local strain resistance and safety factors is discussed.

Background: We aimed to evaluate whether baseline GLS and NT-proBNP and their changes after cardiac resynchronization therapy (CRT) can predict the long-term clinical outcomes and the echocardiographic-based response to CRT (defined by 15% relative reduction in left ventricular end-systolic volume). Methods: We enrolled 143 patients with stable, ischemic heart failure (HF) undergoing CRT-D implantation. NT-proBNP and echocardiogram were obtained before and 6 months after. The patients were followed-up (median: 58 months) for HF-related deaths and/or HF hospitalizations (primary endpoint) or HF-related deaths (secondary endpoint) Results: 84 patients achieved the primary and 53 the secondary endpoint, while 104 patients were considered as CRT-responders and 39 as non-responders. At baseline, event-free patients had higher absolute GLS values (p&lt;0.001) and lower NT-proBNP serum levels (p&lt;0001) than those achieving primary endpoint. A similar pattern was observed in favor of CRT-responders vs non-responders. In Cox regression analysis, lower baseline absolute GLS value (HR=0.77;95%CI, 0.51-1.91; p=0.002), higher baseline NT-proBNP levels (HR=1.55;95%CI, 1.43-2.01;p=0.002) and diabetes (HR=1.27;95%CI, 1.12-1.98;p=0.003) were associated with lower incidence of primary endpoint. Conclusions: In HF patients undergoing CRT-D, baseline GLS and NT-proBNP concentrations may serve as prognostic factors, while they may predict the echocardiographic-based response to CRT.

This study examines the dynamics of failure development in marginalized communities, investigating the interplay of socioeconomic, environmental, and community engagement factors. The research aims to uncover underlying causes, provide policy recommendations, and elucidate the challenges faced by these communities. However, limitations include a restricted focus on marginalized areas, data limitations, and an exclusive emphasis on socioeconomic factors. The analysis reveals gaps in addressing political influences, limited coverage of success stories, and potential biases in the methodology. The conclusion emphasizes the transformative power of community-led initiatives to address challenges, foster inclusivity, and create sustainable change. These initiatives prioritize capacity building, social cohesion, economic development, and access to education and healthcare. Implications for policy and practice underscore the need for comprehensive interventions, collaboration, empowerment, and sustainable development. Future research directions include exploring the long-term impact of historical failures, intersectionality, the role of technology, mental health implications, and comparative analysis.

When designing the battery of an electric vehicle, different parameters must be considered to obtain the safest arrangement of the battery/modules/cells from the mechanical and thermal point of view. In this study, the thermal runaway propagation mechanism of lithium-ion cells is analyzed as a function of their arrangement within a battery pack in case of a fire propagation of a battery pack in which a thermal runaway has occurred. The objective is to identify which cell/module arrangement is most critical within the battery pack by microscopic analysis of the structure and chemical composition of the most damaged cells, both horizontally and vertically, of a battery belonging to a burnt vehicle. And their final condition has been compared with the condition of new cells of the same type. In this way the structure and chemical composition of the anode, cathode and separator after Thermal Runaway has been compared. This research has been carried out to obtain information to understand the mechanical properties of lithium-ion cells and their behavior after thermal runaway heating leading to the propagation of a fire. Through the analysis carried out, it is concluded that cells placed in a vertical arrangement have worse behavior than cells in a horizontal arrangement. Regarding the safety of the battery, the results of this study will allow to determine which arrangement and structure of the cells within the battery pack is safer against thermal runaway due to thermal failure.

An analysis of the stiffness theory reveals that coal mass compression bumps occur only when both the failure criterion and the stiffness criterion are simultaneously satisfied. Then a new structural factor called uneven stiffness coal seam structure (USCS) is proposed, which consists of an uneven stiffness coal seam along with continuous roof and floor. The USCS serves the dual functions of pressure concentration and stiffness reduction. The former facilitates stress concentration from the low stiffness zone (LSZ) to the high stiffness zone (HSZ), thus raising the risk (rF) of failure. The latter reduces the stiffness of the surrounding rock of the HSZ, allowing the system to meet the stiffness criterion even with a hard roof, thereby reconciling the contradiction between the stiffness theory and engineering experience and raising the risk (rI) of instability. The HSZ of the USCS, including thinning zones, bifurcating areas, magmatic intrusion areas, and remnant pillar affected areas, is more susceptible to coal bump incidents than a conventional coal seam. Mechanical analysis and simple numerical simulations validate the pressure concentration and stiffness reduction functions of the USCS. The results demonstrate the following: 1) The normal stress of the HSZ positively correlates with ER, HR, KH, and SL, but negatively correlates with KL and SH; The stiffness of surrounding rock of the HSZ negatively correlates with HR, KH, SL, and SH, but positively correlates with ER and KL. 2) Failures within the HSZ of the USCS enables the roof strata to release bending deformation energy without undergoing fracturing. 3) The alignment between the HSZ of an existing USCS and the HSZ of an artificial USCS advancing with the working face intensifies stress concentration and reduces stiffness, thereby significantly increases the risk (rCB) of coal bump. By applying the stiffness theory and relevant USCS findings, new explanations can be provided for engineering phenomena such as the time-delayed coal bumps, the inefficient pressure relief in ultra thick coal seams, and the “microseism deficiency” observed prior to certain coal bumps.

Keywords: Mandra flash flood, soil erosion, slope failure, RES, mitigation measures, landslide susceptibility

Although the frequency of myocarditis in the general population is very difficult to accurately determine due to the large number of asymptomatic cases, the incidence of this disease is increasing significantly due to better defined criteria for diagnosis and the development of modern diagnostic method. The multitude of different etiological factors, the diversity of the clinical picture and the variability of the diagnostic findings make this disease often demanding both for the selection of the diagnostic modality and for the proper therapeutic approach. The previously known most common viral etiology of this disease is today overshadowed by new findings based on immune-mediated processes, associated diseases that in their natural course can lead to myocardial involvement, but also the iatrogenic cause of myocarditis due to use of immune checkpoint inhibitors in the treatment of cancer patients. Suspecting that a patient with polymorphic and non-specific clinical signs and symptoms, changes in ECG and echocardiography has myocarditis is the starting point in the diagnostic algorithm. Cardio magnetic resonance imaging is non-invasive diagnostic gold standard for diagnosis and clinical follow-up of thses patients. Endomyocardial biopsy as an invasive method is the diagnostic choice in life-threatening patients with suspicion of fulminant myocarditis where the diagnosis has not yet established or there is no adequate response to the applied therapeutic regimen. The treatment of myocarditis is increasingly demanding and includes conservative methods of treating heart failure, immunomodulatory and immunospressive therapy, methods of mechanical circulatory support and heart transplantation. The goal of developing new diagnostic and therapeutic methods is to reduce mortality from this complex disease, which is still high.

Background: Trans-septal endocardial left ventricle lead placement is an alternative technique used capture the left ventricular endocardially but it is use is limited due lack of evidence, practice uptake and clinical trials. we evaluated the efficiency of the procedure, post procedural complication rate, rate of thromboembolic events as well as changes in echocardiographic parameters, brain natriuretic peptide (BNP) level and the New York Heart Association (NYHA) class. Results: TSLV lead implant is safe, improves ejection fraction, LVEDV, LVESV, LVIDd. Significantly reduces NTproBNP levels and NYHA class. Stroke rate was reported only in one patient (9%), noticeably, this particular patient was on DOAC rather than anti-vitamin K antagonists. In this group, patients, who were on Warfarin , were not reported to have any thrombo-embolic events. Discussion: Trans-septal endocardial LV lead implant in patients with a failed CS approach remains a viable alternative however, there is a higher risk of stroke amongst these patients, as well as more procedure related risk of complications compared to conventional CRT. The data analysis demonstrates that patients undergoing a TSLV lead implant due to a failed trans-venous approach have more advanced heart failure, defined by their higher NYHA class compared to conventional trans-venous CRT implant groups. Their pre TSLV implant, echocardiographic parameters are also worse compared to trans-venous CRT implant group

The present paper describes a study case of the failure investigation of Duplex stainless steel (UNS S31803) on the tube and tube sheet section of a shell and tube heat exchanger BEM TEMA type with seawater as the cooling medium. Although UNS S31803 offers high strength, high resistance to chloride-induced SCC, and high resistance to pitting attack in chloride environments, in this study case, the heat exchanger experienced some material degradation; 26 tubes were leaked and plugged on both sides, and scales plugged 76 tubes. The examination in this study case revealed the formation of biofilm inside the tubes, XRD examination revealed that the film contained aragonite (CaCO3), and by using microstructural examination on the inner surface of the tube, the austenite grains were preferentially attacked by crevice corrosion. In this case, the failure was caused by crevice corrosion, and crevice corrosion was enhanced by microbiological-induced corrosion (MIC). Recommendations to avoid similar failures are also suggested in this paper.

Beyond plasma glucose-lowering in patients with type 2 diabetes, sodium- glucose cotransporter 2 inhibitors (SGLT2i) significantly reduced the hospitalization for heart failure (HF) and retarded the progression of chronic kidney disease (CKD). Endothelial dysfunction is not only involved in the development and progression of cardiovascular disease (CVD), and is also associated with the progression of CKD. In patients with type 2 diabetes, hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia induce the development of endothelial dysfunction. SGLT2i have shown an improvement in endothelial dysfunction, as assessed by flow-mediated vasodila-tion, in individuals at high risk for CVD. Along with an improvement of endothelial dysfunction, SGLT2i showed improvements in oxidative stress, inflammation, mitochondrial dysfunction, glucotoxicity such as advanced glycation end products signaling and nitric oxide bioavailability. The improvements in endothelial dysfunc-tion and such endothelium-derived factors may play an important role in preventing the development of coronary artery disease, coronary microvascular dysfunction and diabetic cardiomyopathy which cause HF and in retarding CKD. The suppression of the development of HF and the progression of CKD achieved by SGLT2i might have been largely induced by the improvement of vascular endothelial function by SGLT2i.

Background: Anthracyclines form the backbone of many systemic chemotherapy regimens but dose-limiting cardiotoxicity can also lead to reduction in cardiac function and an increased risk of heart failure. Methods: This review was conducted in accordance with PRISMA guidelines and registered on PROSPERO (CRD42022373496). Results: 26 studies met the eligibility criteria including a total of 910 patients. Overall reduction in pooled mean left ventricular ejection fraction (LVEF) post‐anthracyclines in the placebo arms of included randomised-controlled trials was 4.6% (95% CI, 2.7 to 6.6). The trend in LVEF showed a progressive decline until approximately 180 days after which there was no significant change. Those receiving a cumulative anthracycline dose 300 mg/m2 experienced a more profound reduction. The risk of a 10% absolute decline in LVEF from baseline or decline to an LVEF below 50%, the overall pooled risk was 16% (95% CI: 11 to 21; I2 = 77%). Sensitivity analyses by baseline LVEF and trastuzumab treatment status did not yield significant differences. Conclusion: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines are required.

Autonomic dysfunction is an increasingly recognised complication in chronic neurological conditions such as Parkinson’s disease , and other medical conditions, including diabetes mellitus, chronic fatigue syndrome, postural tachycardia syndrome with and without Ehlers-Danlos syndrome, fibromyalgia and recently Long Covid. Despite laboratory-based tests to evaluate normal and abnormal autonomic function, there are no home-based tests to record neuro-cardiovascular autonomic responses to common stimuli in daily life that are dependent on the normal functioning of the autonomic nervous system. We have developed an adapted blood pressure/heart Autonomic Profile (aAP) that can be used by an individual independently and repeatedly in a domiciliary setting to determine the physiological and symptomatic response to standing, food, and physical and mental (cognitive, emotional) activities. The aAP aids separating autonomic failure (often irreversible) from autonomic dysfunction. This helps the individual and attending healthcare professional understand the relationship between symptoms and common triggers in daily life and informs on self-management in debilitating conditions such as the postural tachycardia syndrome (PoTS) and Long Covid.

Background: Left ventricular noncompaction (LVNC) is a genetically determined cardiomyopathy, that occurs following a disruption of endomyocardial morphogenesis. The purpose of this study was to identify the clinical characteristics and genetic profile of children with LVNC. Methods: From February 2008 to July 2020, a total of 32 children (median 11.5 years) with LVNC were prospectively enrolled and followed up for the median of 4.02 years. Diagnosis was made based on characteristic features of LVNC in echocardiography and cardiovascular magnetic resonance (CMR). Patients’ clinical symptoms, family history, ECG, Holter ECG and genetic tests were also evaluated. Results: The most common presenting symptom was heart failure (31% of children). ECG abnormalities were noted in 56% of patients. The most prominent features were ventricular arrhythmias, sinus bradycardia and paroxysmal third-degree atrioventricular block. Most of the patients (94%) met the criteria for LVNC and CMR confirmed this diagnosis in 82% of cases. The molecular etiology was found in 53% of children. Conclusion: Although heart failure and arrhythmias were very frequent in our study group, thromboembolic events and genetic syndromes were rare. For accurate and reliable assessment of children with LVNC, it is necessary to get to know their family history and detailed clinical profile.

A newly identified novel coronavirus named as severe acute respiratory syndrome-related coronavirus2 (SARS‐CoV 2) has given rise to the global pandemic. SARS-CoV2 which causes coronavirus disease 2019 (COVID-19), is a positive-stranded RNA virus with nucleocapsid. It binds to host angiotensin-converting enzyme2 (ACE2) receptor through surface glycoprotein (S protein). These ACE 2 receptors are attached to the cell membranes of many organs. Thus, COVID-19 does not only result in acute respiratory distress syndrome but also affects multiple organ systems, requiring a multidisciplinary approach to manage this disease. COVID-19 can damage the myocardial cells and result in fulminant myocarditis, acute cardiac injury, cardiomyopathy, heart failure, cardiogenic shock, or arrhythmia. COVID-19 seeds harmful immune response through cytokine storm leading to indirect organ damage. In this literature review, the available data is comprehended regarding cardiovascular complications in COVID-19, and the correlation of biomarkers with the disease activity is discussed. This literature review also highlights the important treatment options and outcomes of the individual study.

Presepsin is a diagnostic and prognostic biomarker of sepsis; however, elevated presepsin levels have also been documented without sepsis. This study aims to retrospectively analyze the laboratory parameters and Sequential Organ Failure Assessment (SOFA) score affecting presepsin levels in 567 patients. Some patients with elevated presepsin levels exhibited renal dysfunction or elevation of biliary enzymes despite a low SOFA score. The univariate regression analysis revealed a close correlation between presepsin levels and SOFA score, serum creatinine (CRE), blood urea nitrogen, and biliary enzymes. In addition, a multivariate regression analysis revealed that SOFA score, alkaline phosphatase (ALP), and CRE independently affected presepsin levels significantly. The analysis of covariance (ANCOVA) revealed that presepsin levels were significantly higher in patients with hepatobiliary disease. Besides, we found that patients who presented with the dilatation of intra- or extrahepatic bile ducts and the elevation of ALP or total bilirubin exhibited remarkable high presepsin levels in the bile. Furthermore, the presepsin production in the liver’s Kupffer cells was established by immunostaining in patients who received surgical liver resection. Overall, this study elucidates that biliary enzymes’ elevation affects presepsin levels, presepsin exists in high concentrations in the bile, and is positive in Kupffer cells.

Purpose: There is limited research on the reasons behind startup failure, and none of the available studies use a competency approach. In this study we applied Spencer’s competency model to identify the competencies in startups which, according to their CEOs, contributed to failure. Methodology: Three coders analyzed the stories of 50 startup failures published online using modified Critical Incident Technique. Findings: Two salient competencies were identified playing a fundamental role in startup failures if missing: Information seeking and Customer service orientation. A network pattern of 9 more prevalent competency deficits was created: Technical/professional/managerial expertise, Analytical thinking, Flexibility, Self-control, Concern for order, quality and accuracy, Interpersonal understanding, Self-confidence, Team leadership and Teamwork and cooperation. Besides startup-specific behavior descriptions were added to Spencer’s competencies. Research implications: Competency approach and Critical Incident Technique method proved to be feasible to identify competency deficits in failed startups. Practical implications: The identified competency deficits offer relevant focus areas for the assessment and development of startup teams. Originality: The study provided research evidence to describe the competency deficits of startup teams that are connected to their failure.

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

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

Background/Objectives: Heart failure (HF) is a chronic disease with a steadily increasing prevalence, high mortality, social and economic costs. Furthermore, every hospitalisation for acute HF is associated with worsening prognosis and reduced life expectancy. In order to prevent hospitalisations, it would be useful to have instruments that can predict them well in advance. Methods: We performed a review on remote monitoring of heart failure through implantable devices.; Results: Precise multi-parameter algorithms, available for ICD and CRT-D patients, have been created, which also use artificial intelligence and are able to predict a new heart failure event more than 30 days in advance. There are also implantable pulmonary artery devices that can predict hospitalisations and reduce the impact of heart failure. proper organisation of transmission and alerts management is crucial for clinical success in using these tools. Conclusions: The full implementation of remote monitoring of implantable devices and in particular the use of new algorithms for the prediction of acute heart failure episodes represents a huge challenge but also a huge opportunity.

Heart failure (HF) is a syndrome characterized by signs and symptoms resulting from structural or functional cardiac abnormalities, confirmed by elevated natriuretic peptides or evidence of congestion. HF patients are classified according to left ventricular ejection fraction (LVEF). Worsening HF (WHF) is associated with increased short- and long-term mortality, re-hospitalization, and healthcare costs. Standard treatment of HF includes angioten-sin-converting enzyme inhibitors, angiotensin receptor-neprilysin inhibitors, mineralocorti-coid-receptor antagonists, beta-blockers, and sodium-glucose co-transporter 2 inhibitors. To manage systolic HF by reducing mortality and hospitalizations in patients experiencing WHF, treatment with vericiguat, a direct stimulator of soluble guanylate cyclase (sGC), is indicated. This drug acts by stimulating sGC enzymes, part of the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway, regulating the cardiovascular system by catalyzing cGMP synthesis in response to NO. cGMP acts as a second messenger, triggering various cellular effects. Deficiencies in cGMP production, often due to low NO availability, are implicated in cardiovascular diseases. Vericiguat stimulates sGC directly, bypassing the need for a functional NO-sGC-cGMP axis, thus preventing myocardial and vascular dysfunction associated with de-creased sGC activity in heart failure. Approved by the FDA in 2021, vericiguat administration should be considered, in addition to the four pillars of HFrEF therapy, in symptomatic patients with LVEF < 45% following a worsening event. Cardiac rehabilitation represents an ideal setting where there is more time to implement therapy with vericiguat and incorporate a greater num-ber of medications for the management of these patients. This review covers vericiguat's metab-olism, molecular mechanisms, and drug-drug interactions.

In this paper, a continuous power management for a decentralized DC microgrid (DCMG) is proposed to achieve voltage regulation and power balance even under system uncertainty and voltage sensor failure. The DCMG system achieves a continuous power management through only the primary controller to reduce the computational burden of each power agent. To enhance the reliability and resilience of the DCMG system under voltage sensor failure, a DC bus voltage (DCV) sensor fault detection algorithm is proposed. In this algorithm, the DCV sensor failure is detected by comparing the measured DCV with the estimated DCV. When the power agent identifies the DCV sensor failure, it changes the operation properly according to the proposed control mode decision algorithm to maintain the stability of the DCMG system. When uncertain conditions such as the power variation of the distributed generations, sudden grid disconnection, DCV sensor failure, electricity price change, and critical battery status occur, the DCMG system is changed to transitional operation modes. These transitional operation modes are employed to transmit the power agent information to other agents without digital communication links (DCLs) and to accomplish power sharing even under such uncertain conditions. In the transitional operation modes of the DCMG system, the DCV levels are temporarily shifted to an appropriate level, enabling each power agent to detect the uncertainty conditions, and subsequently to determine its operation modes based on the DCV levels. Simulation and experimental results under different test conditions confirm the reliability and effectiveness of the proposed control scheme.

The majority of contemporary total hip arthroplasty (THA) implants are constructed from Ti-alloys, which are generally believed to generate fewer adverse local tissue reactions (ALTR) compared to CoCr-alloys. This study presents a case of unusual primary THA failure where a substantial release of Ti-alloy debris was observed. A 52-year-old active male underwent THA after posttraumatic aseptic necrosis of the femoral head in 2006. Seventeen years after the procedure, the patient presented with groin pain and restricted range of motion. X-rays revealed protrusion of the alumina ceramic head through the Ti6Al4V acetabular cup. Trace element analysis indicated significantly elevated levels of serum Ti, Al and V. CT and MRI confirmed Ti-alloy cup failure and severe ALTR. During revision surgery, the worn-out ceramic head was in direct contact with the acetabular cup, having protruded through the central hole it created over time. Histological analysis of tissue samples showed wear-induced synovitis with areas of multinucleated foreign-body giant cells and accumulation of numerous metal particles but no acute inflammatory response. Six months after the revision THA, the patient has experienced favourable outcomes. This case provides an instructive illustration for studying the consequences of substantial release of Ti-alloy debris from orthopaedic implants.

Existing reinforced concrete buildings with seismically-deficient column details affect the overall behavior depending on the failure type of column. The purpose of this study is to develop and validate a machine learning-based prediction model for the column failure modes (shear, flexure-shear and flexure failure modes). For this purpose, artificial neural network (ANN), K-nearest neighbor (KNN), decision tree (DT), and random forest (RF) models were used considering previously-collected experimental data. Using four machine learning methodologies, we developed a classification learning model that can predict the column failure modes in terms of the input variables using concrete compressive strength, steel yield strength, axial load ratio, height-to-dept aspect ratio, longitudinal reinforcement ratio, and transverse reinforcement ratio. The performance of each machine learning model was compared and verified by calculating accuracy, precision, recall, F1-Score, and ROC. Based on the performance measurements of the classification model, the RF model represents the highest average value of the classification model performance measurements among the considered learning methods, and it can conservatively predict the shear failure mode. Thus, the RF model can rapidly predict the column failure modes with the simple column details. Additionally, it was demonstrated that the predicted failure modes from the selected model were exactly same as the failure mode determined from a code-defined equation (traditional method)

Background: Catheter ablation (CA) benefits atrial fibrillation (AF) patients with heart failure (HF). Brain natriuretic peptide (BNP), a marker of left-ventricular pressure load, may serve as a potential surrogate for predicting quality of life (QOL) in broader range of patients. Methods: Within the multicenter KiCS-AF registry, 491 AF patients underwent CA without clinical HF (e.g. documented history of HF, left ventricular ejection fraction ≤40%, or BNP levels ≥100 pg/mL). Participants, aged 61±10 years, were categorized by baseline BNP quartiles. Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire assessments were assessed at baseline and 1 year. Results: Lower baseline BNP correlated with reduced AFEQT scores. Post-CA, all groups showed significant AFEQT score improvements. Lower BNP group displayed notable enhancements (18.2±1.2, 15.0±1.1, 12.6±1.2, 13.6±1.2, p<0.005), especially in symptom and treatment concern areas. Even those with normal BNP levels (≤18.4 pg/ml) exhibited significant QOL improvements. Comparing PAF and non-PAF groups, the PAF group, especially with higher BNP levels, showed greater AFEQT score improvements. Conclusion: This study establishes BNP as a predictive marker for QOL enhancement in non-HF patients undergoing CA for AF. BNP levels represent AF stages, with individuals in earlier stages, especially within normal BNP levels, experiencing greater QOL improvement.

Despite significant strides in prevention, diagnosis, and treatment, cardiovascular diseases remain the number one cause of mortality in the United States, with rates climbing at an alarming rate in the developing world. Targeted delivery of therapeutics to the heart has been a lofty goal to achieve with strategies ranging from direct intra-cardiac or intra-pericardial delivery, intra-coronary infusion, to adeno-associated viral vectors which have preference, if not complete cardio-selectivity, for cardiac tissue. Cell penetrating peptides (CPP) are 5-30 amino acid long peptides that are able to breach cell membrane barriers while carrying cargoes up to several times their size, in an intact functional form. Identified nearly three decades ago, the first of these CPPs came from the HIV coat protein transactivator of transcription. Although a highly efficient CPP, its clinical utility is limited by its robust ability to cross any cell membrane barrier, including crossing the blood-brain barrier and transducing neuronal tissue non-specifically. Several strategies have been utilized to identify cell or tissue specific CPPs, one of which is phage display. Using this latter technique, we identified a cardiomyocyte targeting peptide (CTP) more than a decade ago, a finding that has been corroborated by several independent labs across the world that have utilized CTP for myriad different purposes in pre-clinical animal models. The goal of this publication is to provide a comprehensive review of the identification, validation, and application of CTP, and outlining its potential in diagnostic and therapeutic applications especially in the field of targeted RNA interference.

Traffic congestion is a persistent and challenging problem in urban areas, leading to increased travel times, fuel consumption, and environmental pollution. Signalized intersections play a pivotal role in regulating traffic flow, and their efficiency has a direct impact on the overall traffic performance of a city. This study investigates the effect of traffic signal in managing traffic volume and reducing congestion and delays at signalized intersections through a comprehensive analysis of existing research, data collection, and simulations.The research begins by analyzing the traffic characteristics by an installed LiDAR sensor at E Cold Spring Ln – Hillen Rd intersection in Baltimore City, MD. When the signal at this intersection stopped working for some hours during a working day in September 2023, the LiDAR recorded vehicle and pedestrian counts, vehicle-vehicle and vehicle-pedestrian conflicts, and jaywalking events conflicts. The research aims to assess the impact of traffic signal failures on traffic flow, congestion, safety (V2V and V2P conflicts), and the frequency of jaywalking events before, during, and after improper performance of the traffic signal. Furthermore, this study explores the factors influencing traffic signal performance, including traffic demand, geometric layout, pedestrian interactions, and the integration of emerging technologies. The analysis results highlighted the importance of signal control systems existence at this intersection that can adjust signal timing in response to changing the real-time traffic conditions.Reduced congestion, minimized delays, and enhanced traffic flow are observed outcomes, contributing to a more sustainable and efficient urban transportation system. However, it is crucial to consider the trade-offs and challenges associated with traffic signal optimization, such as the potential for increased travel times for certain modes of transportation and the need for ongoing maintenance and updates. In conclusion, this study underscores the pivotal role of traffic signals in managing traffic volume and reducing congestion and delays at signalized intersections. Through evidence-based analysis and innovative signal control strategies, urban planners and transportation authorities can work towards creating more efficient, sustainable, and less congested transportation networks. The insights derived from this research can inform policy decisions and guide the development of future traffic management solutions, ultimately leading to improved quality of life in urban areas.

The fatigue crack growth rate (FCGR) of aluminium alloys under the combined influence of temperature and humidity remains a relatively unexplored area, receiving limited attention due to its intricate nature and challenges in predicting the combined impact of these factors. The challenge was to investigate and address the specific mechanisms and interactions between temperature and humidity, as in coastal environment conditions, on the FCGR of aluminium alloy. The present study conducts a comprehensive investigation on the combined influence of temperature and humidity on the FCGR of Al6082 alloy. The fatigue pre-cracked compact tension specimens were corroded for 7 days and then subjected to various temperature and humidity conditions in a thermal chamber for 3 days to simulate coastal environments. The obtained data were analysed to determine the influence of temperature and humidity on the FCGR of Al6082 alloy. An empirical model was also established to predict fatigue life cycle values under these environmental conditions precisely. The correlation between FCGR and fracture toughness models was also examined. The Al6082 alloy exhibits a 34% increase in the Paris constant C, indicating reduced FCGR resistance due to elevated temperature and humidity levels. At the same time, fatigue, corrosion, moisture-assisted crack propagation, and hydrogen embrittlement lead to a 27% decrease in threshold fracture toughness. The developed model exhibited accurate predictions for fatigue life cycles, and the correlation between fracture toughness and FCGR showed less than 10% error, indicating a strong relationship between these parameters.

Background. The type-2 sodium-glucose cotransporters inhibitors (SGLT2i) are a new relevant therapeutic option for patients affected by chronic heart failure with reduced ejection fraction (HFrEF). The aim of this study was to evaluate, in a real-world population from a single center, the feasibility of introducing SGLT2i and their interaction with other recommended drug classes. Methods. We evaluated the consecutive patients affected by chronic heart failure (CHF) since January 2022. At baseline clinical visit the therapy taken by the patients as well as that prescribed were accurately collected. During a 6-12 month follow-up the the changes in concomitant therapy were analyzed. Results. At baseline, among 350 patients evaluated, only 17 (5%) were already taking SGLT2i, 13 with HFrEF, 2 with CHF with mild reduced (HFmrEF) and 2 with preserved ejection fraction (HFpEF). After baseline evaluation, SGLT2i were prescribed to 220 (63%) of all the patients enrolled, among whom 178 (84%) of HFrEF patients, 25 (42%) of HFmrEF and 17 (22%) of HFpEF. After follow-up, SGLT2i therapy was highly tolerated and it was associated with a significant increased prescription of sacubitril/valsartan and a reduced use of diuretics. Finally, a significant improvement in functional status and left ventricular systolic function after SGLT2i therapy was observed. Conclusions. In this single center “real world” study, SGLT2i were prescribed in HFrEF patients most of all already in therapy with the other classes of drugs currently recommended for their treatment. Moreover, a further optimization in prescribed ther-apy was observed during a short term follow-up. These data further support the use of this thera-peutic approach in routine clinical practice.

The technology of left ventricular assist devices (LVADs) requires developing and implementing an intelligent control systems to optimize pump speed to achieve a physiological metabolic demands for heart failure (HF) patients. This work aimed to present an advanced control algorithm to drive an LVAD under different physiological conditions. Pole placement method in conjunction with of sliding mode control approach (PP-SMC) was utilized to design and construct the proposed control method. In this design, the method was adopted to use neural networks to eliminate system uncertainties of disturbances. An elastance function was also developed and used as an input signal to mimic the physiological perfusion of HF patients. Two scenarios ranging from rest to exercise were introduced to evaluate the proposed technique. In this technique, a lumped parameter model of cardiovascular system (CVS) was used for this evaluation. The results demonstrated that the designed controller was robustly tracking the input signal in the presence of the system parameter variations of CVS. In both scenarios, the proposed method shows that the controller automatically drive the LVAD with a minimum flow of 1.7 L/min to prevent suction and 5.7 L/min to prevent over-perfusion.

(1) Background: Heart failure (HF) is the final stage of multiple cardiac diseases, which has now become a severe public health problem worldwide. β-Adrenergic receptor (β-AR) overactivation is a major pathological factor associated with multiple cardiac diseases and mediates cardiac fibrosis and inflammation. Previous study has demonstrated that Bruton's tyrosine kinase (BTK) mediated cardiac fibrosis by TGF-β related signal pathways, indicating that BTK was a potential drug target for cardiac fibrosis. Zanubrutinib, a second-generation BTK inhibitor, has shown anti-fibrosis effects in previous research. However, it is unclear whether Zanubrutinib can alleviate cardiac fibrosis induced by β-AR overactivation;(2) Methods: In vivo: Male C57BL/6J mice were treated with or without the β-AR agonist isoproterenol (ISO) to establish cardiac fibrosis animal model. Here, results showed that BTK inhibitor Zanubrutinib (ZB) had a great effect on cardiac fibrosis and inflammation induced by β-AR. In vitro: Results showed that ZB alleviated β-AR-induced cardiac fibroblast activation and macrophage proinflammatory cytokine production. Further mechanism studies demonstrated that ZB inhibited β-AR-induced cardiac fibrosis and inflammation by BTK、STAT3、NF-κB and PI3K/Akt signal pathways both in vivo and in vitro; (4) Conclusions: our research provides evidence that ZB ameliorates β-AR-induced cardiac fibrosis and inflammation.

Aerobic exercise training (AET) has been used in the management of heart disease. AET may, totally or partially, restore the activity and/or expression of proteins that regulate calcium (Ca2+) handling, optimize intracellular Ca2+ flow, and attenuate cardiac functional impairment in failing hearts. However, the literature presents conflicting data regarding the effects of AET on Ca2+ transit and cardiac function in rats with heart failure resulting from aortic stenosis. The objective of this study was to evaluate the effects of AET on calcium handling and cardiac function in rats with heart failure due to aortic stenosis. Wistar rats were distributed into two groups: control (Sham; n= 61) and aortic stenosis (AoS; n= 44). After 18 weeks, the groups were redistributed into: non-exposed to exercise training (Sham, n = 28 and AoS, n = 22) and trained (Sham-ET, n = 33 and AoS-ET, n = 22) for 10 weeks. Treadmill exercise training was performed with a velocity equivalent to the lactate threshold. Echocardiogram, isolated papillary muscle, and isolated cardiomyocyte analyzed cardiac function. During isolated papillary muscle assay and isolated cardimyocyte was evaluated Ca2+. The expression of regulatory proteins of diastolic Ca2+ was analyzed via Western Blot. AET attenuated the diastolic dysfunction and benefited the systolic function. AoS-ET animals presented better response to post-rest contraction, and SERCA2a and L-type Ca2+ channels blocked than the AoS. Furthermore, AET was able to improve aspects of the mechanical function and the responsiveness of the myofilaments to the Ca2+ of the AoS-ET animals. AoS animals presented alteration in the protein expression of the SERCA2a and NCX, and AET restored SERCA2a and NCX levels near normal values. Therefore, AET increased SERCA2a activity, improved the cellular Ca2+ influx mechanism, and increased myofilament responsiveness to Ca2+, attenuating cardiac dysfunction at cellular, tissue, and chamber levels in animals with aortic stenosis and heart failure.

Abstract Objective: To review the relevant literature on the use of atrioventricular node ablation and pacing in patients with heart failure and atrial fibrillation. Methods: A PubMed/MEDLINE and SCOPUS search was performed in order to assess the clinical outcomes of atrioventricular node ablation and pacemaker implantation, as well as the complications that may occur. Results: Several clinical trials, observational analyses and meta-analyses have shown that “pace and ablate” strategy not only improves symptoms but also can enhance cardiac performance in patients with heart failure and atrial fibrillation. Although this procedure is effective and safe, some complications may occur including worsening of heart failure, permanent fibrillation, arrhythmias and sudden death. Regarding the implantation of pacemaker, cardiac resynchronization therapy is shown to be the optimal choice compared to right ventricle apical pacing. His bundle pacing is a promising alternative to cardiac resynchronization therapy and has shown beneficial effects, while left bundle brunch pacing is an innovative modality. Conclusions: Atrioventricular node ablation and implantation of pacemaker is shown to have beneficial effects on clinical outcomes of patients with atrial fibrillation ± heart failure who do not respond or are intolerant to medical treatment. Cardiac resynchronization therapy is the treatment of choice and His bundle pacing seems to be an effective alternative way of pacing in these patients.

Until 2021, in the Kyrgyz Republic, tuberculosis(TB) was diagnosed and treated only in the public sector. With funding support of the STOP-TB partnership, the private providers in four regions of the country and Bishkek city were mapped, trained and incentivized to screen for, identify presumptive TB patients, and refer them to the public facilities for diagnosis and treatment. In this study, we describe the cascade of care of such patients. This was a cohort study involving secondary analysis of routine data. Of 79,352 patients screened during February 2021-March 2022, 2,511(3%) had presumptive TB, of whom, 903(36%) were not tested for TB [pre-diagnostic loss-to-follow-up]. A total of 323(13%) patients were diagnosed as TB, of whom, 42(13%) were not started on treatment [pre-treatment loss-to-follow-up]. Among 257 patients eligible for outcome assessment, 197(77%) had treatment success, 29(11%) were lost-to-follow-up, 13(5%) died, 4(2%) had treatment failure and 14(5%) were not evaluated. While this donor-funded, pioneering initiative was successful in engaging the private sector, we recommend the national TB programme to scale-up the initiative nationally with dedicated budgets, activities and plans to monitor the progress. Qualitative research is urgently needed to understand the reasons for the gaps in the care cascade.

Urban trees are often more sun- and wind-exposed than their forest-grown counterparts. These environmental differences can impact how many species grow – impacting trunk taper, crown spread, branch architecture, and other aspects of tree form. Given these differences, windthrow models derived from traditional forest production data sources may not be appropriate for urban forest management. Additionally, visual abnormalities historically labeled as “defects” in timber production may not have a significant impact on tree failure potential. In this study, we look at urban tree failures associated with Hurricane Irma in Tampa, Florida, USA. We used spatial analysis to determine if patterns of failure existed among our inventoried trees. We also looked at risk assessment data to determine which visual defects were the most common and the most likely to be associated with branch or whole-tree failure. Results indicate that there was no spatial pattern associated with the observed tree failures – trees failed or withstood the storm as individuals. While some defects like decay and dead wood were associated with increased tree failure, other defects like weak branch unions and poor branch architecture were less problematic.

Artificial Intelligence are creating a paradigm shift in health care, being phenotyping patients through clustering techniques one of the areas of interest. Objective: To develop a predictive model to classify heart failure (HF) patients according to their left ventricular ejection fraction (LVEF), by using available data in Electronic Health Records (EHR). Subjects and methods: 2854 subjects more than 25 years old with diagnose of HF and LVEF measured by echocardiography were selected to develop an algorithm to predict patients with reduced EF using supervised analysis. Performance of the algorithm developed were tested in heart failure patients from Primary Care. To select the most influencing variables, LASSO algorithm setting was used and to tackle the issue of one class exceed the other one by a large proportion we used the Synthetic Minority Oversampling Technique (SMOTE). Finally, Random Forest (RF) and XGBoost models were constructed. Results: Full XGBoost model obtained the maximized accuracy, a high negative predictive value and the highest positive predictive value. Gender, age, unstable angina, atrial fibrillation and acute myocardial infarct are the variables that most influence FE value. Applied in the EHR data set with a total 25594 patients with an ICD-code of HF and no regular follow-up in Cardiology clinics, 6170 (21.1%) were identified as those pertaining to the reduced EF group. Conclusion: The algorithm obtained is able to rescue a number of HF patients with reduced ejection fraction that can be take benefit for a protocol with strong recommendation to succeed. Furthermore, the methodology can be used for studies with data extracted from the Electronic Health Records.

This paper aims to provide an overall review of degradation, damage evolution and fatigue models in the literature of various engineering materials, mostly metals, and composites.

Fatigue in any material is a result of continuous irreversible degradation process. Traditionally, fatigue life is predicted by extrapolating experimentally curve fitted empirical models. In the current study, unified mechanics theory is used to predict fatigue life of Ti-6Al-4V under monotonic tensile, compressive and cyclic load conditions. The unified mechanics theory is used to derive constitutive model for fatigue life prediction using a three-dimensional computational model. The proposed analytical and computational models have been used to predict the low cycle fatigue life of Ti-6Al-4V alloys. It is shown that the unified mechanics theory can be used to predict fatigue life of Ti-6Al-4V alloys by using simple predictive models that are based on fundamental equation of the material, which is based on thermodynamics associated with degradation of materials.

Globally 30% of landslides occur in the northeastern part of India [1]. One of the major earthquake events in Sikkim, India occurred on 18th September 2011 (Mw 6.9) led to over 300 landslides and 122 human deaths [2]. These landslides not only controlled by natural disasters but initiated due to human activities. The present study considered Lungchok landslide occurred in south district of Sikkim due to 2011 seismic event. The study focused on the failure mechanism of the landslide based on finite element analysis by adopting eight different cases. The deformation characteristic was investigated for dry and saturated slope conditions under static and dynamic behavior considering vehicle loads using GeoStudio software. The FEM analysis has been carried out using load deformation and linear elastic. The analysis shows that the failure of the slope was not sudden due to the 2011 earthquake event, but progressive failure was observed with time and construction activity. The paper demonstrates that, an increase in infrastructure development including construction by hill cutting increased the initiation of landslide with soil erosion. The cracks developed after 2011 earthquake event led to further deformations during future disasters required effective stabilization measures.

Objective: This study aims to construct an early risk warning model to predict the risk of treatment failure in patients undergoing sequential High-Flow Nasal Cannula (HFNC) oxygen therapy following mechanical ventilation weaning. Methods: A retrospective analysis was conducted on clinical data from 145 patients who received HFNC treatment in the Emergency Intensive Care Unit of the Third People's Hospital of Bengbu City from June 2018 to June 2023. A wide range of indicators including general information, comorbidities, laboratory test results, vital signs, disease-related scores, and oxygenation data were collected. Data analysis was performed using R software, starting with the Lasso regression to filter features related to treatment outcomes. Patients were divided into a training set (70%) and a validation set (30%) using random grouping software. The Random Forest algorithm was then employed to evaluate and rank the important features related to outcome indicators. The predictive efficiency and stability of the model were assessed through the Receiver Operating Characteristic (ROC) curve, calibration curve, and decision curve analysis, culminating in the construction of an early risk warning nomogram. Results: The study found that the Random Forest model exhibited high predictive accuracy in the training set (AUC=0.98) and good stability in the validation set (AUC=0.84). Key feature variables identified by the model, such as APACHE II score, BNP, NLR, mROX, and SOFA, were found to significantly impact the prediction of HFNC treatment failure. Based on these variables, an early warning nomogram was further developed, providing clinicians with a convenient and effective risk assessment tool. Conclusion: This study has constructed an early risk warning model based on the Random Forest algorithm, capable of effectively predicting the risk of HFNC treatment failure. The model's high predictive efficiency and stability offer strong support for clinical decision-making, contributing to personalized treatment and improved patient outcomes. Future research should aim to expand the sample size, perform multicenter validation, and explore the integration of the model into Clinical Decision Support Systems for real-time risk assessment and intervention.

Cardiovascular disease (CVD) is a major global health concern. The number of people with CVD is expected to rise due to aging populations and increasing risk factors such as obesity and diabetes. Identifying new molecular markers is crucial for early diagnosis and treatment. Among these, plasma levels of some miRNAs specifically expressed in cardiac and skeletal muscle known as myomiRs, has gained attention for their roles in cardiovascular health. This study analyzed the plasma levels of myomiR-133a, -133b, and -206 in the pathogenesis of cardiovascular diseases. Exploiting of a case-control study design with patients recruited from several nursing homes form Calabria (Southern Italy) characterized by different types of CVD compared to non-CVD controls, we found downregulation of miR-133a in heart failure and miR-133b in stroke, along with the overall decreased expression of miR-133b and miR-206 in CVD patients. In silico functional characterization of their targets and signaling pathways revealed their involvement in critical cardiovascular processes. Although further research is necessary to fully elucidate their mechanisms and clinical utility, the results here reported support the idea that myomiRs could serve not only as biomarkers but also as therapeutic targets, offering new avenues for managing and potentially preventing CVD progression.

The chronic high fat dysbiosis diet (HFD) instigates cardiac remodeling, dysfunction and chronic heart failure (CHF). The therapeutic approaches focusing oxidative stress, inflammation and hyperlipidemia have not yielded significant positive clinical outcomes. Recent studies report that although mitochondrial ATP citrate lyase (ACLY) supports cardiac function, however, decreases more in human HFpEF than HFrEF. Interestingly, the ACLY synthesizes lipids and creates hyperlipidemia. Epigenetically, ACLY acetylates histone. The mechanism(s) are unknown. One hypothesis is that the HFD induces epigenetic folate 1-carbon metabolism (FOCM), heperhomocysteinemia (HHcy, a cause of abrogation of sleep-time dipping in blood pressure and hypertension) and heart failure. Interestingly, the probiotics utilizes the fat/lipids post-biotically, and increases the mitochondrial bioenergetics and attenuates the HFD induced heart failure. We suggest a novel and paradigm-shift epigenetic mitochondrial sulfur transsulfuration pathways that selectively target HFD-induced CHF. The HFD via transport and metabolomic pathways instigates cardiac remodeling and dyfunction. Previous studies from our laboratory, using a single cell analysis, revealed increase in transporter (SLC25A) of s-adenosine-methionine (SAM) during elevated levels of homocysteine (Hcy, i.e., hyperhomocysteinemia, HHcy), a consequence of impaired epigenetic recycling of Hcy back to methionine by increase in FOCM methylation of H3K4, K9, H4K20 and gene writer (DNMT) and decrease in eraser (TET/FTO). The Hcy transported to mitochondria by SLC7A for clearance via sulfur metabolomic transsulfuration by 3-mercaptopyruvate sulfur transferase (3MST). Interestingly, the HHcy decreases ATP, OCR, H₂S, PGC1α, TFAM, and increase in fission/fusion ratio, causing mitochondria dysfunction. We suggest that gut dysbiosis by HFD disrupts rhythmic epigenetic memory via FOCM and increase in DNMT1 and creates HHcy, leading to decrease mitochondrial transsulfuration and bioenergetics. The treatment with a probiotic, lactobacillus will eat the fat/lipids post-biotically and bi-directionally will produce folic acid and lactone-ketone body that will mitigate the HFD-induced mitochondrial remodeling and heart failure.

Fatigue performance and self-repairing activity of asphalt binders are two properties that highly influence the fatigue cracking response of asphalt pavement. There are still numerous gaps of knowledge to fill linked with these two characteristics. For instance, current parameters fail to fully accommodate these two bitumen phenomena. This study aims to propose a new procedure to address this issue utilizing the linear amplitude sweep (LAS) test, LAS with rest period (RP) (LASH) test, and simplified viscoelastic continuum damage (S-VECD) model. This research work used four different types of asphalt binders: neat asphalt (NA), self-healing thermoplastic polyurethane (STPU)-modified bitumen (STPB), self-healing poly (dimethyl siloxane) crosslinked with urea bond (IPA1w)-modified bitumen (IPAB), and styrene–butadiene–styrene (SBS)-modified bitumen (SBSB). Before the testing process, all the materials were subjected to short-term and long-term aging. The new procedure showed a superior capacity to analyze and accommodate all bitumen fatigue performances and self-repairing activities compared to the current method. Another finding proved that asphalt binders with higher self-restoration behavior failed to show better fatigue performance. A breakthrough finding demonstrated that asphalt binder fatigue response augmented when the RP was applied at a higher damage intensity (S) value. STPBs and IPABs reached their highest increments of fatigue response, containing 1.0% of STPU and 0.5% of IPA1w, respectively. Those augmentations were 207.54% and 232.64%, respectively.

Prostate cancer is the most common non-cutaneous malignancy in men, with the majority of newly diagnosed patients eligible for active surveillance. Despite definitive treatment, a considerable percentage of men will experience biochemical recurrence and even regional and distant metastatic recurrence after radiation therapy or radical prostatectomy. Salvage prostatectomy, while oncologically effective, poses significant morbidity with poor functional outcomes. Salvage cryotherapy has emerged as a promising alternative for localized recurrence, demonstrating safety and efficacy. This review examines the oncologic and functional outcomes of whole-gland and focal salvage cryotherapy, including disease-free survival, cancer-specific survival, and overall survival. The crucial role of multiparametric prostate MRI and evolving role of next-generation PSMA-targeted PET imaging is also examined. Comparison of outcomes of cryotherapy to other salvage ablation modalities, such as high-intensity focused ultrasound (HIFU) is also explored.

Introduction: Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common condition associated with high morbidity and mortality. Although patients with heart failure (HF) are known to have an increased risk of PE, there is limited evidence regarding its specific impact on patients with acute PE, both in presentation and outcomes, and its relationship with left ventricular ejection fraction (LVEF). Material and Methods: A prospective observational study was conducted at two tertiary hospitals, including patients with symptomatic acute PE between January 2012 and December 2022. The primary objective of the study was the development of a composite outcome (mortality, major bleeding, and recurrence) within the first 30 days. The secondary objective was the development of early complications in patients with HF and reduced LVEF. Results: Out of 1991 patients included with symptomatic acute PE, 7.13% had a history of HF. Patients with HF were older and had more comorbidities. The HF group showed higher mortality (11.27% vs. 4.33%, p<0.001) and major bleeding (9.86% vs. 4.54%, p=0.005). In multivariate analysis, HF was an independent risk factor for the development of the composite outcome (HR 1.93; 95% CI: 1.35-2.76). Reduced LVEF was independently associated with a higher risk of bleeding (HR 3.44; 95% CI: 1.34-8.81). Conclusion: In patients with symptomatic acute pulmonary embolism, heart failure is independently associated with a higher risk of early complications. Additionally, heart failure with reduced LVEF is an independent risk factor for major bleeding.

The entry and exit method is a simple and practical method to determine the critical slip surface of slope. However, it has the drawback of sacrificing computational efficiency to improve search accuracy. To solve this problem, this paper proposes an improved entry and exit method to search for the critical slip surface. Based on the random fields generated by using Karhunen–Loève expansion method, the simplified Bishop’s method combined with the improved entry and exit method is used to determine the critical slip surface and its corresponding minimum factor of safety. Then, the failure probability is calculated by conducting Monte Carlo simulation. Two examples are reanalyzed to verify the accuracy and efficiency of the proposed method. Meaningful comparisons are made to demonstrate the calculating accuracy and calculating efficiency of the improved entry and exit method in searching for the minimum safety factor of slope, based on which the effect of the reduced searching range on slope reliability was explored. The results indicate that the proposed method provides a practical tool for evaluating the reliability of slopes in spatially variable soils. It can greatly improve the computational efficiency in relatively high-computational accuracy of slope reliability analysis.

The early failure of glaucoma surgery is mainly caused by an overly fibrosis at the subconjunctival space causing obliteration of the filtration bleb. Because fibrosis has a suspected basis of genetic predisposition, we have undertaken a prospective study to identify upregulated profibrotic genes in a population of glaucoma patients with signs of conjunctival fibrosis and early postoperative surgical failure. Clinical data of re-operated fibrosis patients, hyperfibrosis patients re-operated more than once in a short time, and control patients with no fibrosis were recorded and analyzed at each follow-up visit. Conjunctival-Tenon surgical specimens were obtained intraoperatively to evaluate the local expression of a panel of genes potentially associated with fibrosis. In order to correlate gene expression signature with protein levels, we quantified secreted proteins in primary cultures of fibroblasts from patients. Expression of VEGF-A, IL-8, C-MYC, and CDKN1A was induced in the conjunctiva of hyperfibrosis patients. VEGF-A and IL-8 protein levels were also increased in fibroblast supernatants. We propose that these proteins may act as biomarkers of conjunctival fibrosis in glaucoma patients undergoing filtering surgery. Molecular markers could be crucial for early detection of patients at high risk of failure of filtration surgery leading to more optimal and personalized treatments.

Because of the rapid advancement in the use of photovoltaic (PV) energy systems, it has become critical to look for ways to improve the energy generated by them. The extracted power from the PV modules is proportional to the output voltage. The relationship between output power and array voltage has only one peak under uniform irradiance, whereas it has multiple peaks under partial shade circumstances (PSC). There is only one global peak (GP) and many local peaks (LPs), where the typical maximum power point trackers (MPPT) may become locked in one of the LPs, significantly reducing the PV system's generated power and efficiency. The metaheuristic optimization algorithms (MOAs) solved this problem, albeit at the expense of the convergence time, which is one of these algorithms' key shortcomings. Most MOAs attempt to lower the convergence time at the cost of the failure rate and the accuracy of the findings because these two factors are interdependent. To address these issues, this work introduces the dandelion optimization algorithm (DOA), a novel optimization algorithm. The DOA's convergence time and failure rate are compared to other modern MOAs in critical scenarios of partial shade PV systems to demonstrate the DOA's superiority. The results obtained from this study showed substantial performance improvement compared to other MOAs, where the convergence time is reduced to 0.4 s with zero failure rate compared to 0.9 s, 1.25 s, and 0.43 s for other MOAs under study. The optimal number of search agents in the swarm, optimal initialization of search agents, and optimal design of the dc-dc converter is introduced for optimal MPPT performance.

Technology-enabled maintenance via sensors and the internet of things (IoT) technologies is seen as the “new maintenance strategy”. The aim is to use these technologies to focus on unnecessary breakdowns and increase levels of asset availability where the existing of a dedicated team to maintain or data on asset condition is limited, useless or full of noise. This paper presents the integration of various sensing nodes within an automated laser cutting machine for monitoring of critical components’ conditions. The integrated system provides a centralised platform for data collection from various sensors and provides early failure detection mechanism based on specified set points with alert mechanisms utilising a custom dashboard for data visualisation. The research highlights the required stages for the identification of the appropriate components and sensory devices for the development of efficient monitoring environment.

: The ichthyofauna of Lake Tanganyika consists of 12 families of fish of which five belong to Siluriformes (catfishes). Studies on siluriforms and their parasites in this lake are very fragmentary. The present study was carried out to help fill the knowledge gap on the monogeneans parasitizing the siluriform fishes of Lake Tanganyika in general and more particularly Clarias gariepinus. The gills of a specimen of Clarias gariepinus (Clariidae) were examined for ectoparasites. We identified the monogenean Gyrodactylus transvaalensis (Gyrodactylidae). This is the first time this parasite was found infecting gills. We are the first to observe a large spine in the male copulatory organ of this species, and to provide measurements of its genital spines; this completes the description of the male copulatory organ which is important in standard monogenean identification. This is the first monogenean species reported on C. gariepinus at Lake Tanganyika and the third known species on a representative of Siluriformes of this lake. It brings the total number of species of Gyrodactylus recorded in Lake Tanganyika to four. Knowing that other locations where this species has been reported are geographically remote from Lake Tanganyika, we propose a “failure to diverge” phenomenon for G. transvaalensis.

Aims: Heart failure (HF) is frequently accompanied by atrial fibrillation (AF), a combination that worsens the outcomes of both diseases. Despite advances in the treatment of AF, it remains a serious and unsolved problem for clinicians and researchers. The aim of this study was to examine risk factors for incidents of paroxysmal and persistent AF in patients having heart failure with mid-range ejection fraction (HFmrEF). Methods. Overall, 71 patients with HFmrEF and non-valvular AF, including paroxysmal and persistent types, were enrolled in this study. As a control group, 42 HFmrEF patients without AF were also enrolled. All patients underwent detailed physical examination, including resting electrocardiography, echocardiography, and 24-hour ambulatory Holter monitoring. Levels of the inflammation markers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) and the fibrotic marker transforming growth factor-β1 (TGF-β1) were measured by ELISA and expressed as odds ratios. Results: We show that paroxysmal AF was associated with higher diastolic blood pressure, whereas both paroxysmal and persistent forms of AF were associated with more frequent occurrence of hypertensive crisis episodes and greater body mass index. Progression from paroxysmal to persistent AF was associated with significant ventricular remodeling. Persistent and paroxysmal AF were associated with higher levels of inflammatory markers when compared to HFmrEF patients having no AF. In addition, TGF-1 was significantly increased in HFmrEF patients having persistent but not paroxysmal AF. Conclusions: Occurrence of AF, first paroxysmal and then persistent, in HFmrEF patients is associated with left ventricular remodeling and the appearance of systemic inflammatory and fibrotic markers. Changes in those parameters may be indicators by which to identify patients at increased risk of atrial fibrillation. Further studies are needed to determine the prognostic validity of these markers.

With global warming and accelerated degradation of permafrost, the engineering problems caused by the formation of weak zones between the shallow and permafrost layers of soil–rock mixture (S-RM) slopes in permafrost regions have become increasingly prominent. To explore the influence of rock content on the shear strength of the S-RM freezing–thawing interface, the variation in the shear strength for different rock content is studied herein using direct shear tests. In addition, a 3D laser scanner is used for obtaining the topography of the shear failure surface. Combined with the analysis results of the shear band-particle calculation model, the influence of the rock content on the shear strength of the interface is explored. It was found that the impact threshold of the rock content on the interface strength and failure mode is approximately 30%, when the rock content (R) is &gt; 30% and that the shear strength increases rapidly with increasing rock content. When R ≤ 30%, the actual shear plane is similar to waves; when R &gt; 30%, the shear plane appears as gnawing failure. The shear strength of S-RM freezing–thawing interface mainly comes from the bite force and friction between particles. The main reason for the increase in shear strength with increasing rock content is the increase in bite force between particles, which makes the ratio of bite force to friction force approximately 1:1.

Phosphodiesterases (PDEs) are the principal superfamily of enzymes responsible for degrading the secondary messengers 3’,5’-cyclic nucleotides cAMP and cGMP. Their refined subcellular localization and substrate specificity contribute to finely regulate cAMP/cGMP gradients in various cellular microdomains. Redistribution of multiple signal compartmentalization components is often perceived under pathological conditions. Thereby PDEs have long been pursued as therapeutic targets in diverse disease conditions including neurological, metabolic, cancer and autoimmune disorders in addition to numerous cardiovascular diseases. PDE2 is a unique member of the broad family of PDEs. In addition to its capability to hydrolyze both cAMP and cGMP, PDE2 is the sole isoform that may be allosterically activated by cGMP increasing its cAMP hydrolyzing activity. Within the cardiovascular system, PDE2 serves as an integral regulator for the crosstalk between cAMP/cGMP pathways and thereby may couple chronically adverse augmented cAMP signalling with cardioprotective cGMP signalling. This review provides a comprehensive overview of PDE2 regulatory functions in multiple cellular components within the cardiovascular system and also within various subcellular microdomains. Implications for PDE2 mediated crosstalk mechanisms in diverse cardiovascular pathologies are discussed highlighting the prospective use of PDE2 as a potential therapeutic target in cardiovascular disorders.

The failure to acknowledge and account for environmental externalities or spillovers in climate change adaptation policy, advocacy and programming spaces exercabates the risk of ecological degradation, more so, degradation of land. In particular use of unsuitable water sources for irrigation may increase salinisation risks. However, little if any policy assessments and research effort has been directed at investigating how farmer perceptions mediate spillovers from the ubiquitous irrigation adaptation strategy. In this study cognitive failure and/or bias construct is examined and proposed as an analytical lens in research, policy and learning and the convergence of disaster risk reduction and climate change adaptation discourses. The findings from small-scale farmers, Machakos and Kakamega counties, Kenya, suggest multifaceted biases and failures about the existence and importance of externalities in adaptation planning discourses. Among other dimensions, cognitive failure which encompasses fragmented approaches among institutions for use and management of resources, inadequate policy and information support, as well as, poor integration of actors in adaptation planning accounts for adaptation failure. The failures in such Human-Environment system interactions have the potential to exercabate existing vulnerability of farmer production systems in the long run. The findings further suggest that in absence of risk message information dissemination, education level, farming experience and information accumulation, as integral elements to human capital, do not seem to have significant effect on behaviour about mitigation of environmental spillovers. Implicitly, reversing the inherent adaptation failures calls for system approaches that enhance coordinated adaptation planning, prioritises proactive mitigation of slow onset disaster risks and broadens decision support systems, such as, risk information dissemination integration into the existing adaptation policy discourses and practice.

Comorbidities can have a cumulative effect on hospital outcomes of care, such as the length of stay (LOS), and hospital mortality. This study examines patients hospitalized with Congestive Heart Failure (CHF), a life-threatening condition, which, when it coexists with a burdened disease profile, the risk for negative hospital outcomes increases. Since coexisting conditions co-interact, with a variable effect on outcomes, clinicians should be able to recognize these joint effects. In order to study CHF comorbidities, we used medical claims data from CMS. After extracting the most frequent cluster of CHF comorbidities, we: (i) Calculated, step-by-step, the conditional probabilities for each disease combination inside this cluster (ii) Estimated the cumulative effect of each comorbidity combination on the LOS and hospital mortality (iii) Constructed (a) Bayesian, scenario-based graphs and (b) Bayes-networks to visualize results. Results show that, for CHF patients, different comorbidity constructs have variable effect on the LOS and hospital mortality. Therefore, dynamic comorbidity risk assessment methods should be implemented for informed clinical decision making in any ongoing effort for quality of care improvements.

The formability and failure behavior of TRIP steel blanks were investigated through various stress states. The forming limit diagram (FLD) at fracture is constructed both experimentally and numerically. Numerical studies are performed to evaluate the applicability of different damage criteria in predicting the FLD as well as complex cross-die deep drawing process. The fracture surface and numerical results revealed that the material failed in a different mode for different strain path. Therefore, Tresca model which is based on shear stress accurately predicted the conditions where shear had the profound effect on the damage initiation, whereas Situ localized necking criterion was able to calculate the conditions which localization was dominant.

This article addresses the question why initiatives in the field of green business and sustainable development often fail. Therefore, it dismantles some typical patterns of failure and shows – as a case study – how these patterns can be challenged through an innovative educational concept: the green business and sustainable development school. The applied methodology is a real-life project that is designed through blended, interdisciplinary elements from business model canvas, Theory U, participation and design thinking. The results of the school initiative are discussed and evaluated by four distinctive stakeholder groups and outline the school’s supporting potential to overcome typical patterns of failure by the younger generation in the future. This article concludes with ideas to enhance the school concept reaching out to even more stakeholder-groups to increase its reliability and viability.

Myxomatous mitral valve disease (MMVD) is a leading cause of cardiac morbidity and mortality in dogs, requiring targeted intervention at various stages of disease progression. MMVD is characterized by thickening of the mitral valve leaflets, leading to mitral regurgitation and cardiac remodeling. This progressive disease impairs valve function, causing volume overload in the left atrium and ventricle, which can eventually lead to congestive heart failure. MMVD involves complex mechanisms, including genetic predisposition, neurohormonal activation, and mechanical stress on the valve. Thickened valve leaflets fail to seal properly during systole, resulting in mitral regurgitation and increased left atrial pressure. This triggers compensatory mechanisms like activation of the renin-angiotensin-aldosterone system (RAAS), contributing to further cardiac remodeling. Chronic RAAS activation results in fluid retention, vasoconstriction, and fibrosis, all of which can worsen heart failure. This mini-review provides an overview of current therapeutic strategies for the management of MMVD and discusses preliminary findings from our consortium regarding the preclinical and clinical efficacy of the sodium-glucose co-transporter type-2 (SGLT-2) inhibitor, dapagliflozin, in dogs.

In the presented work, on the example of thin-walled specimens made by selective laser melting technology from AlSi10Mg subjected to preliminary heat treatment, it is shown that there is a critical point of transition from the elastic-plastic region of the engineering stress-strain diagram to the yield and fracture stresses. It was found that the critical point has a strong statistically significant correlation (0.83 by Spearman and 0.93 by Pearson) with the strain hardening coeffi-cient calculated in the section from yield strength to fracture strength. A regression equation linking the critical transition point to the strain hardening coefficient was obtained. It is shown that with increasing plasticity of thin-walled samples obtained by selective laser melting of AlSi10Mg leads to a change in the type of stress distribution in the elastic-plastic region (the Weibull distribution changes to a normal distribution) and the contribution of the probability density of stress distribution described by the Cauchy distribution with a mode near the fracture stress to the full probability density of fracture increases.

Background/Objectives: Bacterial infections (BI) are a major cause of mortality in patients with alcohol-associated hepatitis (AH); however, only a few studies have investigated BI in AH in the last decade. Therefore, we aimed to assess the features and outcomes of BI in patients with AH. Methods: This observational descriptive study included patients with AH admitted to a tertiary academic hospital between 2016–2021. Clinical and complete microbiological data were recorded and complications, including acute-on-chronic liver failure (ACLF), and mortality over 90-days were compared between infected and non-infected patients. Results: Overall, 115 patients with AH were recruited and 75 had severe AH; among them, 66 started corticosteroid treatment. We identified 69 cases of BI in 44 patients; the incidence of BI at hospital discharge was 32.2%, which reached 38.2% at 90 days. The predominant infection site was the chest (35%). Among the identified bacteria (52.1%), half were gram-positive and half gram-negative. A low rate of multidrug-resistant bacteria (14%) was also noted. Infected patients during hospitalization (n=37) exhibited higher rates of hepatic decompensation and ACLF p=0.001) and lower survival (81.8% vs. 95.8%, p=0.015) than did non-infected patients (n=78). In-hospital infected patients (n=22) exhibited worse survival (72.7%) than did those infected upon admission (93.3%) or non-infected patients (94.9%) (p=0.009). Corticosteroid-treated patients displayed a nonsignificant increase in the total number of BI; however, without greater mortality. Conclusions: BI were common in our cohort of patients with AH. Patients with in-hospital infections commonly experienced serious complications, including high ACLF and death rates. Infections diagnosed upon admission were treated without affecting survival.

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

Rock materials failures are accompanied by the co-existence of various failure mechanisms, in-cluding rock fracturing, shearing, and compaction yield. These mechanisms manifest macro-scopically as multiple failure modes and nonlinear strength characteristics related to stress levels. Considering the limitations of current rock mechanics strength theories, which are primarily derived from single failure mechanisms, this study evaluates the applicability of alternative strength theories. Based on the extensional-strain criterion and the PMC (Paul-Mohr-Coulomb) model, a piecewise linear strength model was proposed that is suitable for analyzing multiple failure mechanisms in rocks and revealing the intrinsic mechanisms of multi-mechanism rock material failure. A multiple failure mechanism strength model in the form of inequalities was proposed, using the generalized shear stress, mean stress, and stress Lode angle as parameters. Strength tests conducted on sandstone and granite rock material samples under different stress conditions revealed distinct piecewise linear strength characteristics for both rock types, vali-dating the rationality and applicability of the multiple failure mechanism model. The findings construct a multi-mechanism failure model for rocks, providing enhanced predictive capabilities and aiding in the prevention of rock structural failures.

Background: Liver failure profoundly affects the immune system, leading to dysregulation of innate and adaptive immune responses. Body: This review explores the intricate relationship between liver function and immune homeostasis. The role of the liver as a central hub in immune response initiation is elucidated, emphasizing its involvement in hepatic inflammation induction and subsequent systemic inflammation. Cytokines, chemokines, growth factors, and lipid mediators orchestrate these immune processes, serving as both prognostic biomarkers and potential therapeutic targets in liver failure-associated immune dysregulation. Furthermore, the review delves into the mechanisms underlying immunosuppression in liver failure, encompassing alterations in innate immune cell functions such as neutrophils, macrophages, and natural killer cells (NK cells), as well as perturbations in adaptive immune responses mediated by B and T cells. Conclusion: Understanding the immunological consequences of liver failure is crucial for developing targeted therapeutic interventions and improving patient outcomes in liver disease management.

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. In particular, the modRNA-based COVID-19 vaccines have proven that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options. MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and improves cardiac dysfunction. However, it remains elusive whether the early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. To obtain acute CCN5 expression, we used modRNA-mediated gene transfer in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: 1) preventive intervention and 2) therapeutic intervention. Cardiac function and structural changes were measured by echocardiography and magnetic resonance imaging. Finally, fibrosis and the underlying molecular pathway were analyzed by western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. The modRNA-CCN5 gene transfer successfully ameliorated CF and enhanced cardiac function in both preventive and therapeutic interventions without LV rupture or any adverse cardiac remodeling. Conclusively, early intervention in CF by modRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure without adverse structural remodeling.

Elevated blood glucose levels, known as glycemia, play a significant role in sudden cardiac arrest, often resulting in sudden cardiac death, particularly among those with diabetes. Understanding this link has been a challenge for healthcare professionals, leading many research groups to investigate the relationship between blood glucose levels and cardiac electrical activity. Our hypothesis suggests that glucose-sensing mechanisms in cardiac tissue could clarify this connection. To explore this, we adapted a single-compartment, in-silico model of the human atrial node's action potential. We incorporated glucose-sensing mechanisms with voltage-gated sodium ion channels using ordinary differential equations. Parameters for the model were based on existing experimental studies to mimic the impact of glucose levels on atrial node action potential firing. Simulations using voltage clamp and current clamp techniques showed that elevated glucose levels decreased sodium ion channel currents, leading to a reduction in the sinoatrial node action potential frequency. In summary, our model provides a cellular-level understanding of how high glucose levels can lead to bradycardia and sudden cardiac death.

Heart failure is associated with a significant mortality rate, and an elevated prevalence of this condition has been noted among hypertensive patients. The identification of predictive factors for heart failure progression in hypertensive individuals is crucial for early intervention and improved patient outcomes. In this study, we aimed to identify these predictive factors utilizing medical history data for hypertension patients. Specifically, we focused solely on utilizing medical data preceding the diagnosis of hypertension to enable patients to anticipate the onset of potential heart failure at the time of hypertension diagnosis. Age-specific and ICD system-specific predictive factors were identified utilizing the MIMIC-IV database through the application of two analytical approaches: chi-square tests and XGBoost modeling. Our findings reveal 21 overall predictive factors, encompassing conditions such as atrial fibrillation, the use of anticoagulants, kidney failure, obstructive pulmonary disease, and anemia. These factors were assessed through a comprehensive review of the existing literature. We anticipate that the results will offer valuable insights for the risk assessment of heart failure in hypertensive patients.

Non-neural Machine Learning (ML) and Deep Learning (DL) are used to predict system failures in industrial maintenance. However, only a few studies have assessed the effect of varying the amount of past data used to make a prediction and the extension in the future of the forecast. This study evaluates the impact of the size of the reading window and of the prediction window on the performances of models trained to forecast failures in three data sets of (1) an industrial wrapping machine working in discrete sessions, (2) an industrial blood refrigerator working continuously and (3) a nitrogen generator working continuously. A binary classification task assigns the positive label to the prediction window based on the probability of a failure to occur in such an interval. Six algorithms (logistic regression, random forest, support vector machine, LSTM, ConvLSTM and Transformers) are compared using multivariate time series. The dimension of the prediction windows plays a crucial role and the results highlight the effectiveness of DL approaches in classifying data with diverse time-dependent patterns preceding a failure and the effectiveness of ML approaches in classifying similar and repetitive patterns preceding a failure.

Aim: To analyze a single center's experience with Short Bowel Syndrome/ Chronic Intestinal Failure (SBS/CIF) in adult patients treated with Home Parenteral Nutrition (HPN). Materials and methods: In the last thirty years, 13 patients with SBS/CIF were included in an HPN program. Results: Between 1992 and 2023, 13 patients were included in an HPN program. The primary underlying pathology was acute mesenteric ischemia. The median age of the starting HPN was 44 years old. Most are submitted to several surgeries of extensive intestinal resection with posterior intestinal reconstruction. Five of the 13 patients have died while on HPN for a median of 42 months. The causes of death HPN-related were catheter sepsis, endocarditis with cardiac failure, or hepatic failure. One patient died due to underlying pathology: pelvic abscesses and bleeding related to radiotherapy. Eight patients remain alive with a median time of HPN of 173 months. During the HPN support, the most frequent complications were venous catheter infection and venous territory thrombosis. None of the eight patients alive have hepatic failure. Two patients recently started teduglutide, with good tolerance, and need reduction of HPN support. All these eight patients have a satisfactory quality of life (parenteral support needs range between five to two nutrition bags per week). Conclusion: HPN remains the gold standard of SBS/CIF treatment, although Teduglutide may reduce HPN needs and HPN complications and provide a better quality of life. An HPN multidisciplinary healthcare group support is essential to ensure these patients' survival and quality of life. Keywords Short bowel Syndrome, Chronic Intestinal failure, Home Parenteral Nutrition, Teduglutide, Complications of Parenteral Support.

Background: Heart failure is a major cause of morbidity and mortality worldwide; left ventricular diastolic dysfunction plays a leading role in this clinical context. Diastolic dysfunction may be predisposed by increased abdominal fat and, consequently, increased pericardial and epicardial adiposity. This study aimed to determine whether pericardial and epicardial fat are associated with left ventricular diastolic function. Methods: 82 patients had their abdominal circumference measured and underwent transthoracic echocardiography to measure the thickness of pericardial and epicardial fat and assess the left ventricular diastolic function. Two groups were created based on mean pericardial fat thickness (4.644 mm) and were related to abdominal circumference and echocardiographic parameters. Results: Subjects in the PF High group showed a significant decrease in septal e' (p&lt;0.0001), lateral e' (p&lt;0.0001) and E/A ratio (p=0.003) and a significant increase in E/e' ratio (p&lt;0. 0001), E wave deceleration time (p=0. 013), left atrial volume (p&lt;0.0001), LV mass (p=0.003), tricuspid regurgitant jet velocity (p&lt;0.0001) and LV diameter (p=0.014) compared to the PF Low group. Conclusions: Measurement of abdominal circumference, pericardial and epicardial fat is an early indicator of diastolic changes with transthoracic echocardiography being the gold standard exam.

The review aims to examine how well numerical indicators of business bankruptcy can predict outcomes. The paper examines ten critical studies that concentrate on statistical models for bankruptcy predictions utilizing PRISMA criteria. The findings highlight the usefulness of numerical indicators in indicating financial hardship, particularly cash flow ratios. In order to connect theoretical knowledge with real-world corporate strategy applications, the study ends by reaffirming the importance of these indicators in strategic decision-making.

Introduction: Digitalis use in patients with severe heart failure is controversial. We assessed the effects of digitalis therapy on mortality in a large, observational study in recipients of cardiac resynchronization therapy (CRT). Methods: Consecutive patients receiving a CRT-defibrillator in three European tertiary referral centers were enrolled and followed for a median of 28 months. Digitalis use was assessed at the time of CRT implantation. Multivariate Cox-regression model and propensity score matching was used to determine all-cause mortality as primary endpoint. CRT-response (defined as improvement of ≥1 NYHA class), echocardiographic improvement (defined as improvement of LVEF of ≥ 5%), and ICD shocks were assessed as secondary endpoints. Results: The study comprised 552 CRT recipients with standard indications, including 219 patients (40%) treated with digitalis. Compared to patients without digitalis, they had more often atrial fibrillation, poorer LVEF and higher NYHA class (all p ≤ 0.002). Crude analysis of all-cause mortality demonstrated a similar relative risk of death for patients with and without digitalis (HR=1.14; 95% CI 0.88-1.5; p=0.40). After adjustment for independent predictors of mortality, digitalis therapy did not alter the risk for death (adjusted HR=1.04; 95% CI 0.75-1.45; p=0.82). Also, in comparison to 286 propensity score matched patients, mortality was not affected by digitalis intake (propensity adjusted HR=1.11; 95% CI 0.72-1.70; p=0.64). CRT response was predominant in digitalis non-users concerning both improvement of HF symptoms and LVEF (NYHA p<0.01; LVEF p<0.01) while patients on digitalis had more often ventricular tachyarrhythmias requiring ICD shock (p=0.01). Conclusions: Digitalis therapy had no effect on mortality but did negatively affect CRT response and susceptibility to ventricular arrhythmias requiring ICD shock treatment.

Background. There are scant data about the effectiveness of high flow nasal cannula (HFNC) oxygen therapy in patients hospitalized with severe acute respiratory failure (ARF) in non-intensive medical wards, particularly regarding the effect on arterial oxygenation compared to conventional oxygen therapy (COT) and non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP). Methods. In a retrospective observational study, oxygenation parameters were measured before and immediately after HFNC initiation in 37 consecutive patients hospitalized in a geriatric ward in 2017. Results. HFNC was used as escalation therapy for untreatable hypoxia after failure of NIV/CPAP (n=18) or COT (n=19). Twenty-two patients died, 2 were transferred to the intensive care unit, while 13 were discharged alive. A “do not intubate” status was identified in 17 of the 22 deceased patients. Partial pressure of oxygen (pO2, p< 0.0001), oxygen saturation (SO2, p< 0.0001), pO2/fraction of inspired oxygen ratio (p=0.004) and peripheral SO2 measured by pulse oximetry (p< 0.0001) significantly increased soon after HFNC application. Oxygenation improvements were greater after escalation from NIV/CPAP and in patients discharged alive. Conclusion. HFNC significantly improved oxygenation in severe ARF after failure of COT or NIV/CPAP and may be particularly suitable for older patients hospitalized in non-intensive medical wards.

Cardiogenic shock (CS) is part of a clinical syndrome consisting of acute left ventricular failure causing severe hypotension leading to inadequate organ and tissue perfusion. The most com-monly used devices to support patients affected by CS are Intra-Aortic Balloon Pump (IABP), Impella 2.5 pump and Extracorporeal Membrane Oxygenation. The aim of this study is the com-parison between Impella and IABP using CARDIOSIM© software simulator of the cardiovascular system. The results of the simulations included baseline conditions from a virtual patient in CS followed by IABP assistance in synchronized mode with different driving and vacuum pressures. Subsequently, the same baseline conditions were supported by the Impella 2.5 with different ro-tational speeds. The percentage variation with respect to baseline conditions was calculated for hemodynamic and energetic variables during IABP and Impella assistance. Impella pump driven with a rotational speed of 50000 rpm increased the total flow by 4.36% with a reduction in left ventricular end diastolic volume (LVEDV) by ≅15% to ≅30%. A reduction in left ventricular end systolic volume (LVESV) by ≅10% to ≅18% (≅12% to ≅33%) was observed with IABP (Impella) as-sistance. Taking into account the limitations of a simulation setting, this study highlights that assistance with the Impella device leads to higher reduction in LVESV, LVEDV, left ventricular external work and left atrial pressure-volume loop area compared to IABP support.

In the development of the safety-critical systems, it is important to perform Failure Modes and Effects Analysis (FMEA) process to identify potential failures. However, traditional FMEA activities tend to be considered difficult and time-consuming tasks. To compensate for the difficulty of the FMEA task, various types of tools are used to increase the quality and the effectiveness of the FMEA reports. This paper explains an Automatic FMEA tool which integrates the Model-based Design (MBD), FMEA, and Simulated Fault Injection techniques in a single environment. The Automatic FMEA tool has the following advantages compared to the existing FMEA analysis tool. First, the Automatic FMEA tool automatically generates FMEA reports compared to the traditional spreadsheet-based FMEA tools. Second, the Automatic FMEA tool analyzes the causality between the failure modes and the failure effects by performing model-based fault injection simulation. In order to demonstrate the applicability of the Automatic FMEA, we used the electronic fuel injection system (EFI) Simulink model. The results of the Automatic FMEA were compared to that of the legacy FMEA.

The risk related to embankment dam breaches needs to be evaluated in order to prepare emergency action plans. The physical and hydrodynamic parameters of the flood wave generated from dam-failure event correspond to various breach parameters such as width, slope and formation time. This study aimed to simulate dam-breach failure scenario of Yabous dam (NE Algeria) and analyze its influence on areas (urban and natural environments) downstream the dam. The simulation was completed using the sensitivity analysis method in order to assess the impact of breach parameters on the dam-break scenario. The propagation of flood wave associated to dam-break was simulated using the one-dimensional HEC-RAS hydraulic model. This study ap-plied a sensitivity analysis of three breach parameters (slope, width, and formation time) in five sites selected downstream the embankment dam. The simulation showed that the maximum flow of the flood wave recorded at the level of the breach was 8768 m3/s, which gradually attenuated along the river course to reach 1579.2m3/s at about 8.5km downstream the dam. This study estab-lished the map of flood-prone areas that illustrated zones threatened with the flooding wave trig-gered by the dam failure due to extreme rainfall events. The sensitivity analysis showed that flood wave flow, height and width revealed positive and similar changes for the increase in adjustments (±25% and ±50%) of breach width and slope in the 5 sites. However, flood wave parameters of breach formation time showed significant trends that changed in the opposite direction compared to breach slope and width.

(1) Background: New sensor technologies in wearables and other consumer health devices open up promising opportunities to collect real-world data. As cardiovascular diseases remain reason number one for disease and mortality worldwide, cardiology offers potent monitoring use-cases with patients in their out-of-hospital daily routine. Therefore, the aim of this systematic review is to investigate the status quo of studies monitoring patients with cardiovascular risks and patients suffering from cardiovascular diseases in a telemedical setting using not only a smartphone-based app, but also consumer health devices such as wearables and other sensor-based devices. (2) Methods: A literature search was conducted across five databases and the results were examined according to the study protocols, technical approaches and qualitative and quantitative parameters measured. (3) Results: Out of 166 articles, 8 studies were included in this systematic review. These cover interventional and observational monitoring approaches in the area of cardiovascular diseases, heart failure and atrial fibrillation using various app, wearable and health device combination. (4) Conclusions: Depending on the researcher’s motivation a fusion of apps, patient reported outcome measures and non-invasive sensors can be orchestrated in a meaningful way adding major contributions to monitoring concepts for both, individual patients and larger cohorts.