Usefulness of regional right ventricular and right atrial strain for prediction of early and late right ventricular failure following a left ventricular assist device implant: A machine learning approach

Background: Identifying candidates for left ventricular assist device surgery at risk of right ventricular failure remains difficult. The aim was to identify the most accurate predictors of right ventricular failure among clinical, biological, and imaging markers, assessed by agreement of different supervised machine learning algorithms. Methods: Seventy-four patients, referred to HeartWare left ventricular assist device since 2010 in two Italian centers, were recruited. Biomarkers, right ventricular standard, and strain echocardiography, as well as cath-lab measures, were compared among patients who did not develop right ventricular failure (N = 56), those with acute–right ventricular failure (N = 8, 11%) or chronic–right ventricular failure (N = 10, 14%). Logistic regression, penalized logistic regression, linear support vector machines, and naïve Bayes algorithms with leave-one-out validation were used to evaluate the efficiency of any combination of three collected variables in an “all-subsets” approach. Results: Michigan risk score combined with central venous pressure assessed invasively and apical longitudinal systolic strain of the right ventricular–free wall were the most significant predictors of acute–right ventricular failure (maximum receiver operating characteristic–area under the curve = 0.95, 95% confidence interval = 0.91–1.00, by the naïve Bayes), while the right ventricular–free wall systolic strain of the middle segment, right atrial strain (QRS-synced), and tricuspid annular plane systolic excursion were the most significant predictors of Chronic-RVF (receiver operating characteristic–area under the curve = 0.97, 95% confidence interval = 0.91–1.00, according to naïve Bayes). Conclusion: Apical right ventricular strain as well as right atrial strain provides complementary information, both critical to predict acute–right ventricular failure and chronic–right ventricular failure, respectively

Dissociated Fear and Spatial Learning in Mice with Deficiency of Ataxin-2

Mouse models with physiological and behavioral differences attributable to differential plasticity of hippocampal and amygdalar neuronal networks are rare. We previously generated ataxin-2 (Atxn2) knockout mice and demonstrated that these animals lacked obvious anatomical abnormalities of the CNS, but showed marked obesity and reduced fertility. We now report on behavioral changes as a consequence of Atxn2-deficiency. Atxn2-deficiency was associated with impaired long-term potentiation (LTP) in the amygdala, but normal LTP in the hippocampus. Intact hippocampal plasticity was associated behaviorally with normal Morris Water maze testing. Impaired amygdala plasticity was associated with reduced cued and contextual fear conditioning. Conditioned taste aversion, however, was normal. In addition, knockout mice showed decreased innate fear in several tests and motor hyperactivity in open cage testing. Our results suggest that Atxn2-deficiency results in a specific set of behavioral and cellular disturbances that include motor hyperactivity and abnormal fear-related behaviors, but intact hippocampal function. This animal model may be useful for the study of anxiety disorders and should encourage studies of anxiety in patients with spinocerebellar ataxia type 2 (SCA2)

Why do Process Improvement Projects Fail in Organizations? A Review and Future Research Agenda

Purpose: The purpose of this article is to examine the Critical Failure Factors (CFFs) linked to various types of Process improvement (PI) projects such as Kaizen, Lean, Six Sigma, Lean Six Sigma and Agile. Proposing a mitigation framework accordingly is also an aim of this study. Design/ Methodology/ Approach: This research undertakes a systematic literature review of 49 articles that were relevant to the scope of our study and that were published in four prominent databases including Google Scholar, Scopus, Web of Science and EBSCO. Findings: Further analysis identifies 39 factors that contribute to the failure of PI projects. Among these factors, significant emphasis is placed on issues such as "resistance to cultural change," "insufficient support from top management," "inadequate training and education," "poor communication," and "lack of resources", as primary causes of PI project failures. To address and overcome the PI project failures, we propose a framework for failure mitigation based on change management models. We present future research directions that aim to enhance both the theoretical understanding and practical aspects of PI project failures. Practical Implications: Through this study researchers and project managers can benefit from well structured guidelines and invaluable insights that will help them identify and address potential failures, leading to successful implementation and sustainable improvements within organizations. Originality: This paper is the first study of its kind that examine the CFFs of five PI methodologies and introduces a novel approach derived from change management theory as a solution to minimize the risk associated with PI failure

Industry 4.0 Benefits, Challenges, Critical Success Factors: Comparative analysis through the lens of Resource Dependence Theory across continents and economies

Purpose: As we enter a new era of digital transformation, Industry 4.0 promises to revolutionize the way we do business, providing unprecedented opportunities and challenges. This study aims to investigate empirically and comparatively analyse the benefits, challenges, and critical success factors of Industry 4.0 (I 4.0) across four continents and developing and developed economies. Methodology: This study employed an online survey to explore the benefits, challenges, and critical success factors of developed and developing economies. In order to ensure the validity of the survey, a pilot test was conducted with 10 respondents. A total of 149 participants with senior managerial, vice-presidential, and directorial positions from developed and developing economies spanning four continents were invited to take part in the survey. Findings: The study ranks benefits, challenges and CSFs across economies and continents. Further, the benefit of Industry 4.0 helping to achieve organizational efficiency and agility differed across the developing and developed economies. Further, the benefit improves customer satisfaction significantly differed across continents; in terms of challenges, Employee resistance to change had a higher proportion in developing economies. Future viability of Industry 4.0 also differed across the continents. Regarding CSFs, there was no difference across the developing and developed economies. Finally, change management and project management vary across the continents. Implications: This study contributes to a balanced understanding of Industry 4.0 by providing empirical evidence for a comparative analysis. Moreover, it extends the concept of Resource- Dependent Theory (RDT) to explain how organizations in developing economies and developed economies deploy resources to manage external condition uncertainties to implement Industry 4.0. Furthermore, this study provides a structural framework to understand the specific benefits, challenges, and critical success factors of implementing Industry 4.0, which can be utilized by policymakers to promote Industry 4.0 in their economies or continents. Originality of Value: As far as our knowledge goes, no studies have empirically demonstrated the comparative analysis of benefits, challenges and CSFs across economies and continents and distinguish an original contribution of our work

Building green innovation networks for people, planet, and profit: A multi-level, multi-value approach

In this conceptual paper we explore the problem of how firms balance profit considerations against their contribution to society and the environmental. We theorize how firms build networks that support green transition, enabling them to reconfigure processes that match sustainability goals and maintain profitable. We explore how building networks for green transition supports firms\u27 transition to more sustainable approaches that support the adoption of, and transition to, green strategies. We extend current theorization of how firms build multi-level B2B networks that support green transition that benefits society and the environment. We suggest three propositions that support the development of a multi-level, multi-value model for building green innovation networks. We identify four critical success factors - embedding technological diversity, developing knowledge sharing mechanisms, embracing open innovation strategies, overcoming resistance to change, − that support this process and help firms overcome value creation frictions and deliver multi-value benefits to society (people) and the environment (planet), whilst enabling firms to make a profit. Our conclusion outlines our contribution and highlights areas for future research

MicroRNA-30d and -483-3p for bi-ventricular remodelling and miR-126-3p for pulmonary hypertension in advanced heart failure

Aims: MicroRNAs play a role in pathogenic mechanisms leading to heart failure. We measured a panel of 754 miRNAs in the myocardial tissue and in the serum of patients with heart failure with reduced ejection fraction due to dilatative idiopathic cardiomyopathy (DCM, N = 10) or ischaemic cardiomyopathy (N = 3), referred to left ventricular assist device implant. We aim to identify circulating miRNAs with high tissue co-expression, significantly associated to echocardiographic and haemodynamic measures. Methods and results: We have measured a panel of 754 miRNAs in the myocardial tissue [left ventricular (LV) apex] and in the serum obtained at the same time in a well selected study population of end-stage heart failure with reduced ejection fraction due to either DCM or ischaemic cardiomyopathy, referred to continuous flow left ventricular assist device implant. We observed moderate agreement for miR-30d, miR-126-3p, and miR-483-3p. MiR-30d was correlated to LV systolic as well as diastolic volumes (r = 0.78, P = 0.001 and r = 0.80, P = 0.005, respectively), while miR-126-3p was associated to mPAP and PCWP (r = −0.79, P = 0.007 and r = −0.80, P = 0.005, respectively). Finally, serum miR-483-3p had an association with right ventricular end diastolic diameter (r = −0.73, P = 0.02) and central venous pressure (CVP) (r − 0.68 p 0.03). Conclusions: In patients with DCM, few miRNAs are co-expressed in serum and tissue: They are related to LV remodelling (miR-30d), post-capillary pulmonary artery pressure (miR-126-3p), and right ventricular remodelling/filling pressures (miR-483-3p). Further studies are needed to confirm their role in diagnosis, prognosis or as therapeutic targets in heart failure with reduced ejection fraction

Impaired sustained attention and executive dysfunction:bipolar disorder versus depression-specific markers of affective disorders

Objective - To identify neurocognitive measures that could be used as objective markers of bipolar disorder. Methods - We examined executive function, sustained attention and short-term memory as neurocognitive domains in 18 participants with bipolar disorder in euthymic state (Beuth), 14 in depressed state (Bdep), 20 with unipolar depression (Udep) and 28 healthy control participants (HC). We conducted four-group comparisons followed by relevant post hoc analyses. Results - Udep and Bdep, but not Beuth showed impaired executive function (p = 0.045 and p = 0.046, respectively). Both Bdep and Beuth, but not Udep, showed impaired sustained attention (p = 0.001 and p = 0.045, respectively). The four groups did not differ significantly on short-term memory. Impaired sustained attention and executive dysfunction were not associated with depression severity, duration of illness and age of illness onset. Only a small number of abnormal neurocognitive measures were associated with medication in Bdep and Beuth. Conclusion - Impaired sustained attention appears specific to bipolar disorder and present in both Beuth and Bdep; it may represent an objective marker of bipolar disorder. Executive dysfunction by contrast, appears to be present in Udep and Bdep and likely represents a marker of depression

Sex-specific Gene Expression in Flupirtine-Treated Cln3Δex7/8 Mouse Brain

Gene expression is a powerful tool to understand structure-function relationships in the nervous system. This study reports global gene expression changes induced by flupirtine in brain of male and female Cln3Δex7/8 mice, exposing potential flupirtine targets at the molecular level. Gene expression analysis of male and female Cln3Δex7/8 mouse brain was determined following oral administration of flupirtine for 14 weeks, using Mouse Genome 430 2.0 array Chips and an Affymetrix platform. Fifty-six genes in males and 79 in females were differentially expressed in flupirtine- versus vehicle-treated Cln3Δex7/8 mouse brain. Flupirtine altered several pathways in Cln3Δex7/8 mouse brain: apoptosis, the complement cascade, NF-kB, and p38α MAPK signaling pathways. Gene-gene network analysis highlighted networks and processes functionally pertinent to flupirtine treatment. These encompassed neurodegeneration, neuro-inflammation, and implicated neurological disorders such as Alzheimer and Parkinson disease. Flupirtine mediates its action in males and females through distinctive actionable targets in the same pathways. This work consolidates the groundwork for considering flupirtine as a treatment option in human CLN3 disease

Exogenous Flupirtine as Potential Treatment for CLN3 Disease

CLN3 disease is a fatal neurodegenerative disorder affecting children. Hallmarks include brain atrophy, accelerated neuronal apoptosis, and ceramide elevation. Treatment regimens are supportive, highlighting the importance of novel, disease-modifying drugs. Flupirtine and its new allyl carbamate derivative (compound 6) confer neuroprotective effects in CLN3-deficient cells. This study lays the groundwork for investigating beneficial effects in Cln3Δex7/8 mice. WT/Cln3Δex7/8 mice received flupirtine/compound 6/vehicle for 14 weeks. Short-term effect of flupirtine or compound 6 was tested using a battery of behavioral testing. For flupirtine, gene expression profiles, astrogliosis, and neuronal cell counts were determined. Flupirtine improved neurobehavioral parameters in open field, pole climbing, and Morris water maze tests in Cln3Δex7/8 mice. Several anti-apoptotic markers and ceramide synthesis/degradation enzymes expression was dysregulated in Cln3Δex7/8 mice. Flupirtine reduced astrogliosis in hippocampus and motor cortex of male and female Cln3Δex7/8 mice. Flupirtine increased neuronal cell counts in male mice. The newly synthesized compound 6 showed promising results in open field and pole climbing. In conclusion, flupirtine improved behavioral, neuropathological and biochemical parameters in Cln3Δex7/8 mice, paving the way for potential therapies for CLN3 disease