Assessing sigmoidal function on memristive maps.

Memristors offer a crucial element for constructing discrete maps that have garnered significant attention in complex dynamics and various potential applications. In this study, we have integrated memristive and sigmoidal function to propose innovative mapping techniques. Our research confirms that the amalgamation of memristor and sigmoidal functions represents a promising approach for creating both 2D and 3D maps. Particularly noteworthy are the chaotic maps featuring multiple sigmoidal functions and multiple memristors, as highlighted in our findings. Specifically focusing on the novel STMM1 map, we delve into its dynamics and assess its feasibility. Intriguingly, the introduction of sigmoidal functions leads to alterations in the quantity of fixed points and the symmetry of the map.

Secondary bile acids and the biliary epithelia: The good and the bad.

The biliary tract has been considered for several decades a passive system just leading the hepatic bile to the intestine. Nowadays several researches demonstrated an important role of biliary epithelia (i.e. cholangiocytes) in bile formation. The study of biliary processes therefore maintains a continuous interest since the possible important implications regarding chronic cholestatic human diseases, such as primary biliary cholangitis or primary sclerosing cholangitis. Bile acids (BAs), produced by the liver, are the most represented organic molecules in bile. The physiologic importance of BAs was initially attributed to their behavior as natural detergents but several studies now demonstrate they are also important signaling molecules. In this minireview the effect of BAs on the biliary epithelia are reported focusing in particular on secondary (deriving by bacterial manipulation of primary molecules) ones. This class of BAs is demonstrated to have relevant biological effects, ranging from toxic to therapeutic ones. In this family ursodeoxycholic and lithocholic acid present the most interesting features. The molecular mechanisms linking ursodeoxycholic acid to its beneficial effects on the biliary tract are discussed in details as well as data on the processes leading to lithocholic damage. These findings suggest that expansion of research in the field of BAs/cholangiocytes interaction may increase our understanding of cholestatic diseases and should be helpful in designing more effective therapies for biliary disorders.

Decline of Admission for Acute Coronary Syndromes and Acute Cardiovascular Conditions during COVID-19 Pandemic in Veneto Region.

Background: The present study aimed to examine longitudinal trends in hospitalizations for acute coronary syndrome (ACS) before and during the COVID-19 pandemic, by reviewing the data from 13 hospitals of the Veneto Region, in the north-east of Italy. Methods: We performed a multicenter, retrospective analysis including all the consecutive patients presenting with ACS and other acute cardiovascular (CV) conditions (defined as heart failure, arrhythmias, cardiac arrest and venous thromboembolism) hospitalized in 13 different hospitals of the Veneto Region covering a population of 2,554,818 inhabitants, during the first (between 15 March 2020 and 30 April 2020) and second (between 15 November 2020 and 30 December 2020) COVID-19 pandemic waves (the 2020 cohort). Data were compared with those obtained at the same time-windows of years 2018 and 2019 (the historical cohorts). Results: Compared to the historical cohorts, a significant decrease in the number of ACS cases was observed in 2020 (−27.3%, p = 0.01 and −32%, p < 0.001, comparing 2018 versus 2020 and 2019 and 2020, respectively). The proportion of patients hospitalized for acute CV conditions decreased during the first and second wave COVID-19 pandemic when compared to the historical cohorts (−36.5%, p < 0.001 and −40.6%, p < 0.001, comparing 2018 versus 2020 and 2019 and 2020, respectively). Pearson's correlation evidenced a significant inverse relationship between the number of COVID-19 cases and both ACS hospital admissions (r = −0.881, p = 0.005) and hospitalizations for acute CV conditions (r = −0.738, p = 0.01), respectively. Conclusions: The decrease in hospitalizations for ACS and other acute CV conditions will strongly affect future patients' management since undiagnosed nonfatal CV events represent a source of increased (and unknown) CV morbidity and mortality.

Takotsubo Syndrome during COVID-19 Pandemic in the Veneto Region, Italy.

Background: During the COVID-19 pandemic, the risk of SARS-CoV-2 infection, the public health measures of social distancing, the freedom limitations, quarantine, and the enforced homeworking under the lockdown period, as well as medical causes including COVID-19 infection per se, may have caused major emotional distress, especially in the most vulnerable patients. We aimed to evaluate the variations in the number of admissions due to Takotsubo syndrome (TTS) during the COVID-19 pandemic in the Veneto region. Methods: We retrospectively reviewed and analyzed the number of admissions because of TTS in 13 Divisions of Cardiology located in the Veneto region, the northeastern area of Italy, covering a population of more than 2.5 million inhabitants, during the two major pandemic waves of COVID-19 (the first between 15 March and 30 April 2020 and the second between 15 November and 30 December 2020) that occurred in 2020. Results: In total, 807 acute coronary syndromes were admitted in the 13 enrolling hospitals. Among these, 3.9% had TTS. Compared to the corresponding 2018 and 2019 time periods, we observed a significant increase in the number of TTS cases (+15.6%, p = 0.03 and +12.5%, p = 0.04, comparing 2018 to 2020 and 2019 to 2020, respectively). Geographical distribution of the TTS cases reflected the broad spread of the SARS-CoV-2 infection with a significant direct relationship between TTS incidence and the number of COVID-19 infections according to Pearson's correlation (r = 0.798, p < 0.001). Conclusions: The higher incidence of TTS during the 2020 COVID-19 pandemic waves, especially in the areas that were hit hardest in terms of morbidity and mortality by the SARS-CoV-2 infection, suggest a strong direct and/or indirect role of COVID-19 in the pathogenesis of TTS.

The effect of the Caputo fractional difference operator on a new discrete COVID-19 model.

This study aims to generalize the discrete integer-order SEIR model to obtain the novel discrete fractional-order SEIR model of COVID-19 and study its dynamic characteristics. Here, we determine the equilibrium points of the model and discuss the stability analysis of these points in detail. Then, the non-linear dynamic behaviors of the suggested discrete fractional model for commensurate and incommensurate fractional orders are investigated through several numerical techniques, including maximum Lyapunov exponents, phase attractors, bifurcation diagrams and C 0 algorithm. Finally, we fitted the model with actual data to verify the accuracy of our mathematical study of the stability of the fractional discrete COVID-19 model.

Chaos in Cancer Tumor Growth Model with Commensurate and Incommensurate Fractional-Order Derivatives.

Analyzing the dynamics of tumor-immune systems can play an important role in the fight against cancer, since it can foster the development of more effective medical treatments. This paper was aimed at making a contribution to the study of tumor-immune dynamics by presenting a new model of cancer growth based on fractional-order differential equations. By investigating the system dynamics, the manuscript highlights the chaotic behaviors of the proposed cancer model for both the commensurate and the incommensurate cases. Bifurcation diagrams, the Lyapunov exponents, and phase plots confirm the effectiveness of the conceived approach. Finally, some considerations regarding the biological meaning of the obtained results are reported through the manuscript.

Chaotic dynamics in a novel COVID-19 pandemic model described by commensurate and incommensurate fractional-order derivatives.

Mathematical models based on fractional-order differential equations have recently gained interesting insights into epidemiological phenomena, by virtue of their memory effect and nonlocal nature. This paper investigates the nonlinear dynamic behavior of a novel COVID-19 pandemic model described by commensurate and incommensurate fractional-order derivatives. The model is based on the Caputo operator and takes into account the daily new cases, the daily additional severe cases, and the daily deaths. By analyzing the stability of the equilibrium points and by continuously varying the values of the fractional order, the paper shows that the conceived COVID-19 pandemic model exhibits chaotic behaviors. The system dynamics are investigated via bifurcation diagrams, Lyapunov exponents, time series, and phase portraits. A comparison between integer-order and fractional-order COVID-19 pandemic models highlights that the latter is more accurate in predicting the daily new cases. Simulation results, besides to confirming that the novel fractional model well fit the real pandemic data, also indicate that the numbers of new cases, severe cases, and deaths undertake chaotic behaviors without any useful attempt to control the disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s11071-021-06867-5.

A novel discrete-time COVID-19 epidemic model including the compartment of vaccinated individuals.

Referring tothe study of epidemic mathematical models, this manuscript presents a noveldiscrete-time COVID-19 model that includes the number of vaccinated individuals as an additional state variable in the system equations. The paper shows that the proposed compartment model, described by difference equations, has two fixed points, i.e., a disease-free fixed point and an epidemic fixed point. By considering both the forward difference system and the backward difference system, some stability analyses of the disease-free fixed point are carried out.In particular, for the backward difference system a novel theorem is proved, which gives a condition for the disappearance of the pandemic when an inequality involving some epidemic parameters is satisfied. Finally, simulation results of the conceived discrete model are carried out, along with comparisons regarding the performances of both the forward difference system and the backward difference system.

Chronic rejection after liver transplantation: Opening the Pandora's box.

Chronic rejection (CR) of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation. Although its prevalence has declined steadily with the introduction of potent immunosuppressive therapy, CR still represents an important cause of graft injury, which might be irreversible, leading to graft loss requiring re-transplantation. To date, we still do not fully appreciate the mechanisms underlying this process. In addition to T cell-mediated CR, which was initially the only recognized type of CR, recently a new form of liver allograft CR, antibody-mediated CR, has been identified. This has indeed opened an era of thriving research and renewed interest in the field. Liver biopsy is needed for a definitive diagnosis of CR, but current research is aiming to identify new non-invasive tools for predicting patients at risk for CR after liver transplantation. Moreover, the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury, which should not be disregarded. Therapies for CR may only be effective in the "early" phases, and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver damage. Herein, we provide an overview of the current knowledge and research on CR, focusing on early detection, identification of non-invasive biomarkers, immunosuppressive management, re-transplantation and future perspectives of CR.

Remote mentoring in laparotomic and laparoscopic cancer surgery during Covid-19 pandemic: an experimental setup based on mixed reality.

In this paper, Mixed Reality (MR) has been exploited in the operating rooms to perform laparoscopic and open surgery with the aim of providing remote mentoring to the medical doctors under training during the Covid-19 pandemic. The employed architecture, which has put together MR smartglasses, a Digital Imaging Player, and a Mixed Reality Toolkit, has been used for cancer surgery at the IRCCS Hospital 'Giovanni Paolo II' in southern Italy. The feasibility of using the conceived platform for real-time remote mentoring has been assessed on the basis of surveys distributed to the trainees after each surgery.

Current Strategies to Minimize Ischemia-Reperfusion Injury in Liver Transplantation: A Systematic Review.

BACKGROUND: Hepatic Ischemia Reperfusion Injury (IRI) is a serious threat that characterizes the liver but also other transplantable organs. The worst effect of long-term IRI on an impaired graft could lead to irreversible damage and organ failure. Several events characterize the cascade that ultimately leads to organ failure. Among all, multiple strategies have been attempted to identify early phenomena of IRI with divergent results, and biomarkers might represent a novel approach to early detect ischemic damage. METHODS: A literature review of the current state-of-the-art on IRI was conducted in the present manuscript. Information was collected from worldwide clinical trials conducted in highly specialized institutions. Experiments conducted on IRI animal models and clinical studies were screened. The final outcomes were analyzed and reported in the present review. RESULTS: Matrix Metalloproteinases (MMPs) represent an interesting example of the early detector of neutrophil invasion after acute and chronic hepatic IRI. Neutrophil Gelatinase-associated Lipocalin (NGAL) is another biomarker which seems more predictable of the IRI gravity phase. Mitochondrial flavin mononucleotide (FMN) was recently discovered and might become a reliable biomarker of hepatic IRI during Hypothermic Oxygenation Machine Perfusion (HOPE). CONCLUSION: The available strategies to avoid IRI, despite constantly improving, are still lacking a gold standard method. Further studies are still needed to explore new options in the IRI diagnosis and treatment, and to this purpose, regenerative medicine and tissue engineering surely can play a pivotal role in the transplantation field.

Gastrointestinal endoscopy in cirrhotic patient: Issues on the table.

Patients with liver cirrhosis are fragile and present specific clinical hallmarks. When undergoing to gastrointestinal (GI) endoscopy, these subjects require an individual pre evaluation, taking into account: Level of haemostasis impairment, the individual risk of infection, the impact of sedation on hepatic encephalopathy and other factors. The overall assessment of liver function, employing common scoring systems, should be also assessed in the preprocedural phase. Beside some common general problems, regarding GI endoscopy in cirrhotic subjects, also specific issues are present for some frequent indications or procedures. For instance, despite an increased incidence of adenomas in cirrhosis, colon cancer screening remains suboptimal in subjects with this disease. Several studies in fact demonstrated liver cirrhosis as a negative factor for an adequate colon cleansing before colonoscopy. On the other hand, also the routine assessment of gastroesophageal varices during upper GI endoscopy presents some concern, since important inter-observer variability or incomplete description of endoscopic findings has been reported in some studies. In this review we discussed in details the most relevant issues that may be considered while performing general GI endoscopic practice, in patient with cirrhosis. For most of these issues there are no guidelines or clear indications. Moreover until now, few studies focused on these aspects. We believe that targeting these issues with corrective measures may be helpful to develop a tailored endoscopic approach for cirrhosis, in the future.

COVID-19 in normal, diseased and transplanted liver.

Starting from December 2019 the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has extended in the entire world giving origin to a pandemic. Although the respiratory system is the main apparatus involved by the infection, several other organs may suffer coronavirus disease 2019 (COVID-19)-related injuries. The human tissues expressing angiotensin-converting enzyme 2 (ACE2) are all possible targets of viral damage. In fact myocarditis, meningo-encephalitis, acute kidney injury and other complications have been described with regard to SARS-CoV-2 infection. The liver has a central role in the body homeostasis contributing to detoxification, catabolism and also synthesis of important factor such as plasma proteins. ACE2 is significantly expressed just by cholangiocytes within the liver, however transaminases are increased in more than one third of COVID-19 patients, at hospital admission. The reasons for liver impairment in the course of this infection are not completely clear at present and multiple factors such as: Direct viral effect, release of cytokines, ischemic damage, use of hepatotoxic drugs, sepsis, and others, may contribute to damage. While COVID-19 seems to elicit just a transient alteration of liver function tests in subjects with normal hepatic function, of concern, more severe sequelae are frequently observed in patients with a reduced hepatic reserve. In this review we report data regarding SARS-CoV-2 infection in subjects with normal or diseased liver. In addition the risks of COVID-19 in immunosuppressed patients (either transplanted or suffering for autoimmune liver diseases) are also described.

Generating Multidirectional Variable Hidden Attractors via Newly Commensurate and Incommensurate Non-Equilibrium Fractional-Order Chaotic Systems.

This article investigates a non-equilibrium chaotic system in view of commensurate and incommensurate fractional orders and with only one signum function. By varying some values of the fractional-order derivative together with some parameter values of the proposed system, different dynamical behaviors of the system are explored and discussed via several numerical simulations. This system displays complex hidden dynamics such as inversion property, chaotic bursting oscillation, multistabilty, and coexisting attractors. Besides, by means of adapting certain controlled constants, it is shown that this system possesses a three-variable offset boosting system. In conformity with the performed simulations, it also turns out that the resultant hidden attractors can be distributively ordered in a grid of three dimensions, a lattice of two dimensions, a line of one dimension, and even arbitrariness in the phase space. Through considering the Caputo fractional-order operator in all performed simulations, phase portraits in two- and three-dimensional projections, Lyapunov exponents, and the bifurcation diagrams are numerically reported in this work as beneficial exit results.

Moving forward in the treatment of cholangiocarcinoma.

Despite being the second most frequent primary liver tumor in humans, early diagnosis and treatment of cholangiocarcinoma (CCA) are still unsatisfactory. In fact, survival after 5 years is expected in less than one fourth of patients diagnosed with this disease. Rare incidence, late appearance of symptoms and heterogeneous biology are all factors contributing to our limited knowledge of this cancer and determining its poor prognosis in the clinical setting. Several efforts have been made in the last decades in order to achieve an improved classification/understanding with regard to the diverse CCA forms. Location within the biliary tree has helped to distinguish between intrahepatic, perihilar and distal CCA types. Sequence analysis contributed to identifying several characteristic genetic aberrations in CCA that may also serve as possible targets for therapy. Novel findings are expected to significantly improve the management of this malignancy in the near future. In this changing scenario our review focuses on the current and future strategies for CCA treatment. Both systemic and surgical treatments are discussed in detail. The results of the main studies in this field are reported, together with the ongoing trials. The current findings suggest that an integrated multidisciplinary approach to this malignancy would be helpful to improve its outcome.

Natremia and liver transplantation: The right amount of salt for a good recipe.

An adequate balance between electrolytes and clear water is of paramount importance to maintaining physiologic homeostasis. Natremia imbalance and, in particular, hyponatremia is the most frequent electrolyte abnormality observed in hospitalized subjects, involving approximately one-fourth of them. Pathological changes occurring during liver cirrhosis predispose patients to an increased risk of sodium imbalance, and hypervolemic hyponatremia has been reported in nearly 50% of subjects with severe liver disease and ascites. Splanchnic vasodilatation, portal-systemic collaterals' opening and increased excretion of vasoactive modulators are all factors impairing clear water handling during liver cirrhosis. Of concern, sodium imbalance has been consistently reported to be associated with increased risk of complications and reduced survival in liver disease patients. In the last decades clinical interest in sodium levels has been also extended in the field of liver transplantation. Evidence that [Na+] in blood is an independent risk factor for in-list mortality led to the incorporation of sodium value in prognostic scores employed for transplant priority, such as model for end-stage liver disease-Na and UKELD. On the other hand, severe hyponatremic cirrhotic patients are frequently delisted by transplant centers due to the elevated risk of mortality after grafting. In this review, we describe in detail the relationship between sodium imbalance and liver cirrhosis, focusing on its impact on peritransplant phases. The possible therapeutic approaches, in order to improve transplant outcome, are also discussed.

Dynamical Analysis of a New Chaotic Fractional Discrete-Time System and Its Control.

This article proposes a new fractional-order discrete-time chaotic system, without equilibria, included two quadratic nonlinearities terms. The dynamics of this system were experimentally investigated via bifurcation diagrams and largest Lyapunov exponent. Besides, some chaotic tests such as the 0-1 test and approximate entropy (ApEn) were included to detect the performance of our numerical results. Furthermore, a valid control method of stabilization is introduced to regulate the proposed system in such a way as to force all its states to adaptively tend toward the equilibrium point at zero. All theoretical findings in this work have been verified numerically using MATLAB software package.

Hepatitis B virus recurrence after liver transplantation: An old tale or a clear and present danger?

Hepatitis B virus (HBV) recurrence after liver transplantation (LT) has been described more than 50 years ago. Similarly, to other clinical conditions, in which impairment of host immune defense favors viral replication, early reports described in details recurrence and reactivation of HBV in liver transplant recipients. The evidence of a possible, severe, clinical evolution of HBV reappearance in a significant percentage of these patients, allowed to consider, for some years, HBV positivity a contraindication for LT. Moving from the old to the new millennium this picture has changed dramatically. Several studies contributed to establish efficient prophylactic protocols for HBV recurrence and with the advent of more potent anti-viral drugs an increased control of infection was achieved in transplanted patients as well as in the general immune-competent HBV population. Success obtained in the last decade led some authors to the conclusion that HBV is now to consider just as a "mere nuisance". However, with regard to HBV and LT, outstanding issues are still on the table: (1) A standard HBV prophylaxis protocol after transplant has not yet been clearly defined; (2) The evidence of HBV resistant strains to the most potent antiviral agents is claiming for a new generation of drugs; and (3) The possibility of prophylaxis withdrawal in some patients has been demonstrated, but reliable methods for their selection are still lacking. The evolution of LT for HBV is examined in detail in this review together with the description of the strategies adopted to prevent HBV recurrence and their pros and cons.

Pro-inflammatory signalling and gut-liver axis in non-alcoholic and alcoholic steatohepatitis: Differences and similarities along the path.

Non-alcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD) represent a spectrum of injury, ranging from simple steatosis to steatohepatitis and cirrhosis. In humans, in fact, fatty changes in the liver, possibly leading to end-stage disease, were observed after chronic alcohol intake or in conditions of metabolic impairment. In this article, we examined the features and the pro-inflammatory pathways leading to non-alcoholic and alcoholic steatohepatitis. The involvement of several events (hits) and multiple inter-related pathways in the pathogenesis of these diseases suggest that a single therapeutic agent is unlikely to be an effective treatment strategy. Hence, a combination treatment towards multiple pro-inflammatory targets would eventually be required. Gut-liver crosstalk is involved not only in the impairment of lipid and glucose homoeostasis leading to steatogenesis, but also in the initiation of inflammation and fibrogenesis in both NAFLD and ALD. Modulation of the gut-liver axis has been suggested as a possible therapeutic approach since gut-derived components are likely to be involved in both the onset and the progression of liver damage. This review summarizes the translational mechanisms underlying pro-inflammatory signalling and gut-liver axis in non-alcoholic and alcoholic steatohepatitis. With a multitude of people being affected by liver diseases, identification of possible treatments and the elucidation of pathogenic mechanisms are elements of paramount importance.

The Co-existence of Different Synchronization Types in Fractional-order Discrete-time Chaotic Systems with Non-identical Dimensions and Orders.

This paper is concerned with the co-existence of different synchronization types for fractional-order discrete-time chaotic systems with different dimensions. In particular, we show that through appropriate nonlinear control, projective synchronization (PS), full state hybrid projective synchronization (FSHPS), and generalized synchronization (GS) can be achieved simultaneously. A second nonlinear control scheme is developed whereby inverse full state hybrid projective synchronization (IFSHPS) and inverse generalized synchronization (IGS) are shown to co-exist. Numerical examples are presented to confirm the findings.