Overview of European patents in Germany, France and Spain, with a potential application to the development of electric vehicles

Within the Green Deal’s ‘Accelerating the shift to sustainable and smart mobility’, vehicles with alternative propulsion systems will play a significant role, as the transport sector is responsible for one-fifth of the European Union’s CO2 emissions. Therefore, more and more governments are supporting the purchase and production of electric vehicles, as it can be one of the main tools for locally reducing fossil fuel consumption as well as reducing CO2 emissions. The analysis highlights that the three most important vehicle-producing countries (based on 2019 OICA data) from the European Union are Germany, France, and Spain. The development trajectory of these countries in the field of electromobility is presented using descriptive statistics. Sustainable development goals can be achieved by creating an innovative environment and overcoming barriers to innovation, which can be indicated, for example, by the number of patents in a given country. Therefore, a long-term time series based on patents related to electric vehicles will be explored using the database of the European Patent Office. The study describes the vehicle manufacturers with the most patents, and the main patent areas in the three countries analysed

Új mechanizmusok azonosítása az oxidatív stressz indukálta mitokondrium-függő nekrotikus sejthalálban = Identification of novel mechanisms in the oxidative stress induced mitochondria-related necrotic cell death

Oxidatív stress körülményei között kimutattuk, hogy a PARP enzim gátlása növeli az MKP-1 expresszióját (ez a foszfatáz felelős elsődlegesen a JNK és p38 MAPK inaktivációjáért), ezért szerepet játszhat a PARP gátlás mediálta mitokondriális védelem folyamatában. LPS indukálta szeptikus shock modell rendszeren vizsgáltuk az Akt kináz mitokondriális targetjeit. Normál állatokban nem, míg a szeptikus shockban az MPT (mitochondrial permeability transition) előfordul, így azonosítani tudtuk a folyamatban részt vevő fehérjéket. Először írtuk le, hogy az Akt foszforilálni tudja a ciklofillin D-t, ezzel csökkentve az MPT folyamatát. Különböző technikákkal igazoltuk, hogy a PARP-1 direkt módon (ADP-ribozilálva) képes befolyásolni transzkripciós faktorokat, melyek az MKP-1, 2 illetve 3 expresszió szabályozásában vesznek részt. | In oxidative stress, we provided evidence that PARP inhibition increase the oxidative stress dependent expression of MKP-1 which is the main phosphatase responsible for the inactivation of JNK and p38 MAP kinase, and so it can play a role in the PARP inhibition mediated mitochondrial protection. Using control mouse liver and liver from LPS induced secptic shock models we isolated mitochondria, and isolated proteins by anti-Akt substrate antibodies. That way we could isolate mitochondrial targets of Akt kinase, and comparing the data we could detect which proteins are phosphorylated in septic shock. Since septic shock model animals mitochondrial permeability transition is taking place while in normal liver it is not, therefore these data may show which protein phosphorylation can contribute to mitochondrial permeability transition. Our data firstly indicated that Akt can phosphorylate cyclophilin D and thereby can prevent cyclophilin D dependent mitochondrial permeability transition. We identified the mechanism by which PARP-1 directly modulated (poly-ADP-ribosylates) nuclear transcription factors involved in the regulation of MKP-1, 2 & 3 expression

Baseline clinical characteristics of heart failure patients with reduced ejection fraction enrolled in the BUDAPEST-CRT Upgrade trial

The BUDAPEST-CRT Upgrade study is the first prospective, randomized, multicentre clinical trial investigating the outcomes after cardiac resynchronization therapy (CRT) upgrade in heart failure (HF) patients with intermittent or permanent right ventricular pacing (RVP) with wide paced QRS. This report describes the baseline clinical characteristics of the enrolled patients and compares them to cohorts from previous milestone CRT studies.This international multicentre randomized controlled trial investigates 360 patients having a pacemaker (PM) or implantable cardioverter defibrillator (ICD) device for at least six months prior to enrollment, reduced left ventricular ejection fraction (LVEF≤35%), HF symptoms (New York Heart Association functional class II-IVa), wide paced QRS (>150 ms), and ≥20% of RVP burden without having a native left bundle branch block. At enrollment, the mean age of the patients was 73±8 years; 89% were male, 97% of the patients were in NYHA II/III functional class, and 56% had atrial fibrillation. Enrolled patients predominantly had conventional PM devices, with a mean RVP burden of 86%. Thus, this is a patient cohort with advanced HF, low baseline LVEF (25%±7%), high N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels [2231 pg/mL (25th - 75th percentile 1254/4309 pg/mL)], and frequent HF hospitalizations during the preceding 12 months (50%).When compared with prior CRT trial cohorts, the BUDAPEST-CRT Upgrade study includes older patients with a strong male predominance and a high burden of atrial fibrillation and other comorbidities. Moreover, this cohort represents an advanced HF population with low LVEFs, high NT-proBNPs, and frequent previous HF events

Phenogrouping and risk stratification of patients undergoing cardiac resynchronization therapy upgrade using topological data analysis

Choosing the optimal device during cardiac resynchronization therapy (CRT) upgrade can be challenging. Therefore, we sought to provide a solution for identifying patients in whom upgrading to a CRT-defibrillator (CRT-D) is associated with better long-term survival than upgrading to a CRT-pacemaker (CRT-P). To this end, we first applied topological data analysis to create a patient similarity network using 16 clinical features of 326 patients without prior ventricular arrhythmias who underwent CRT upgrade. Then, in the generated circular network, we delineated three phenogroups exhibiting significant differences in clinical characteristics and risk of all-cause mortality. Importantly, only in the high-risk phenogroup was upgrading to a CRT-D associated with better survival than upgrading to a CRT-P (hazard ratio: 0.454 (0.228–0.907), p = 0.025). Finally, we assigned each patient to one of the three phenogroups based on their location in the network and used this labeled data to train multi-class classifiers to enable the risk stratification of new patients. During internal validation, an ensemble of 5 multi-layer perceptrons exhibited the best performance with a balanced accuracy of 0.898 (0.854–0.942) and a micro-averaged area under the receiver operating characteristic curve of 0.983 (0.980–0.986). To allow further validation, we made the proposed model publicly available ( https://github.com/tokmarton/crt-upgrade-risk-stratification )

The Prognostic Value of Anemia in Patients with Preserved, Mildly Reduced and Recovered Ejection Fraction

Data on the relevance of anemia in heart failure (HF) patients with an ejection fraction (EF) > 40% by subgroup—preserved (HFpEF), mildly reduced (HFmrEF) and the newly defined recovered EF (HFrecEF)—are scarce. Patients with HF symptoms, elevated NT-proBNP, EF ≥ 40% and structural abnormalities were registered in the HFpEF-HFmrEF database. We described the outcome of our HFpEF-HFmrEF cohort by the presence of anemia. Additionally, HFrecEF patients were also selected from HFrEF patients who underwent resynchronization and, as responders, reached 40% EF. Using propensity score matching (PSM), 75 pairs from the HFpEF-HFmrEF and HFrecEF groups were matched by their clinical features. After PMS, we compared the survival of the HFpEF-HFmrEF and HFrecEF groups. Log-rank, uni-and multivariate regression analyses were performed. From 375 HFpEF-HFmrEF patients, 42 (11%) died during the median follow-up time of 1.4 years. Anemia (HR 2.77; 95%CI 1.47–5.23; p < 0.01) was one of the strongest mortality predictors, which was also confirmed by the multivariate analysis (aHR 2.33; 95%CI 1.21–4.52; p = 0.01). Through PSM, the outcomes for HFpEF-HFmrEF and HFrecEF patients with anemia were poor, exhibiting no significant difference. In HFpEF-HFmrEF, anemia was an independent mortality predictor. Its presence multiplied the mortality risk in those with EF ≥ 40%, regardless of HF etiology

Baseline clinical characteristics of heart failure patients with reduced ejection fraction enrolled in the BUDAPEST-CRT Upgrade trial

The BUDAPEST-CRT Upgrade study is the first prospective, randomized, multicentre clinical trial investigating the outcomes after cardiac resynchronization therapy (CRT) upgrade in heart failure (HF) patients with intermittent or permanent right ventricular pacing (RVP) with wide paced QRS. This report describes the baseline clinical characteristics of the enrolled patients and compares them to cohorts from previous milestone CRT studies.This international multicentre randomized controlled trial investigates 360 patients having a pacemaker (PM) or implantable cardioverter defibrillator (ICD) device for at least six months prior to enrollment, reduced left ventricular ejection fraction (LVEF≤35%), HF symptoms (New York Heart Association functional class II-IVa), wide paced QRS (>150 ms), and ≥20% of RVP burden without having a native left bundle branch block. At enrollment, the mean age of the patients was 73±8 years; 89% were male, 97% of the patients were in NYHA II/III functional class, and 56% had atrial fibrillation. Enrolled patients predominantly had conventional PM devices, with a mean RVP burden of 86%. Thus, this is a patient cohort with advanced HF, low baseline LVEF (25%±7%), high N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels [2231 pg/mL (25th - 75th percentile 1254/4309 pg/mL)], and frequent HF hospitalizations during the preceding 12 months (50%).When compared with prior CRT trial cohorts, the BUDAPEST-CRT Upgrade study includes older patients with a strong male predominance and a high burden of atrial fibrillation and other comorbidities. Moreover, this cohort represents an advanced HF population with low LVEFs, high NT-proBNPs, and frequent previous HF events

Topological data analysis to identify cardiac resynchronization therapy patients exhibiting benefit from an implantable cardioverter-defibrillator

Background: Current guidelines recommend considering multiple factors while deciding between cardiac resynchronization therapy with a defbrillator (CRT-D) or a pacemaker (CRT-P). Nevertheless, it is still challenging to pinpoint those candidates who will beneft from choosing a CRT-D device in terms of survival. Objective: We aimed to use topological data analysis (TDA) to identify phenogroups of CRT patients in whom CRT-D is associated with better survival than CRT-P. Methods: We included 2603 patients who underwent CRT-D (54%) or CRT-P (46%) implantation at Semmelweis University between 2000 and 2018. The primary endpoint was all-cause mortality. We applied TDA to create a patient similarity network using 25 clinical features. Then, we identifed multiple phenogroups in the generated network and compared the groups’ clinical characteristics and survival. Results: Five- and 10-year mortality were 43 (40–46)% and 71 (67–74)% in patients with CRT-D and 48 (45–50)% and 71 (68–74)% in those with CRT-P, respectively. TDA created a circular network in which we could delineate fve phenogroups showing distinct patterns of clinical characteristics and outcomes. Three phenogroups (1, 2, and 3) included almost exclusively patients with non-ischemic etiology, whereas the other two phenogroups (4 and 5) predominantly comprised ischemic patients. Interestingly, only in phenogroups 2 and 5 were CRT-D associated with better survival than CRT-P (adjusted hazard ratio 0.61 [0.47–0.80], p<0.001 and adjusted hazard ratio 0.84 [0.71–0.99], p=0.033, respectively). Conclusions: By simultaneously evaluating various clinical features, TDA may identify patients with either ischemic or nonischemic etiology who will most likely beneft from the implantation of a CRT-D instead of a CRT-P