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AimsEpidemiological surveillance has raised safety concerns for mRNA SARS-CoV-2-vaccination-related myocarditis. We aimed to analyze epidemiological, clinical and imaging findings associated with clinical outcomes in these patients in an international multi-center registry (NCT05268458).Methods and resultsPatients with clinical and CMR diagnosis of acute myocarditis within 30 days after mRNA SARS-CoV-2—vaccination were included from five centers in Canada and Germany between 05/21 and 01/22. Clinical follow-up on persistent symptoms was collected. We enrolled 59 patients (80% males, mean age 29 years) with CMR-derived mild myocarditis (hs-Troponin-T 552 [249–1,193] ng/L, CRP 28 [13–51] mg/L; LVEF 57 ± 7%, LGE 3 [2–5] segments). Most common symptoms at baseline were chest pain (92%) and dyspnea (37%). Follow-up data from 50 patients showed overall symptomatic burden improvement. However, 12/50 patients (24%, 75% females, mean age 37 years) reported persisting symptoms (median interval 228 days) of chest pain (n = 8/12, 67%), dyspnea (n = 7/12, 58%), with increasing occurrence of fatigue (n = 5/12, 42%) and palpitations (n = 2/12, 17%). These patients had initial lower CRP, lower cardiac involvement in CMR, and fewer ECG changes. Significant predictors of persisting symptoms were female sex and dyspnea at initial presentation. Initial severity of myocarditis was not associated with persisting complaints.ConclusionA relevant proportion of patients with mRNA SARS-CoV-2-vaccination-related myocarditis report persisting complaints. While young males are usually affected, patients with persisting symptoms were predominantly females and older. The severity of the initial cardiac involvement not predicting these symptoms may suggest an extracardiac origin.

Introduction Dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) reduces major adverse cardiovascular events (MACE) and stent thrombosis. However, DAPT duration is a concern in high bleeding risk (HBR) patients. We evaluated the effect of short DAPT (1–3 months) compared to standard DAPT (6–12 months) on bleeding and ischemic events in HBR PCI. Methods We searched MEDLINE, Embase and CENTRAL up to August 18, 2022. Randomized controlled trials (RCTs) comparing short DAPT (1–3 months) versus standard DAPT in HBR PCI were included. We assessed risk of bias (RoB) using the Cochrane RoB2 tool, and certainty of evidence using GRADE criteria. Outcomes included MACE, all-cause death, stent thrombosis, major bleeding, and the composite of major or clinically-relevant non-major bleeding. We estimated risk ratios (RR) and 95% confidence intervals (CI) using a random-effects model. Results From 503 articles, we included five RCTs (n = 7,242) at overall low risk of bias with median follow-up of 12-months. Compared to standard DAPT, short DAPT did not increase MACE (RR 1.02, 95% CI 0.84–1.23), all-cause death (RR 0.92, 95% CI 0.71–1.20) or stent thrombosis (RR 1.47, 95% CI 0.73–2.93). Short DAPT reduced major bleeding (RR 0.34, 95% CI 0.13–0.90) and the composite of major or clinically-relevant non-major bleeding (RR 0.60, 95% CI 0.44–0.81), translating to 21 and 34 fewer events, respectively, per 1000 patients. Conclusions In HBR PCI, DAPT for 1–3 months compared to 6–12 months reduced clinically-relevant bleeding events without jeopardizing ischemic risk. Short DAPT should be considered in HBR patients receiving PCI.

Background: There are important knowledge gaps in type 2 myocardial infarction (T2MI). Our primary objective was to compare the outcomes of patients with T2MI with those of patients with type 1 myocardial infarction (T1MI). Our secondary objective was to determine whether randomized controlled trials (RCTs) evaluating dual antiplatelets (DAPTs) have explicitly included patients with T2MI. Methods: We performed a meta-analysis comparing outcomes of patients with T2MI with patients with T1MI and a separate systematic review to evaluate the inclusion of T2MI in RCTs evaluating DAPT. There were 19 cohorts enrolling 48,829 patients (40,604 with T1MI and 5361 with T2MI) and 51 RCTs enrolling 188,132 patients with acute coronary syndrome. Results: Patients with T2MI had approximately 2-fold increases in unadjusted odds of long-term mortality compared with patients with T1MI (odds ratio, 2.47; 95% confidence interval, 2.06-2.96; P < 0.0001) and a 45% increase in adjusted odds of long-term mortality (odds ratio, 1.45; 95% confidence interval, 1.25-1.69; P < 0.0001, respectively). There was no published evaluation of efficacy, effectiveness, and safety of DAPT in patients with T2MI. Conclusion: Patients with T2MI are at increased risk of adjusted all-cause long-term mortality compared with patients with T1MI. The role of DAPT remains unclear in T2MI. Résumé: Contexte: Il existe d’importantes lacunes dans notre connaissance de l’infarctus du myocarde de type 2 (IMT2). Notre objectif principal était de comparer le devenir de patients ayant subi un IMT2 et celui de patients ayant subi un infarctus du myocarde de type 1 (IMT1). Notre objectif secondaire était de déterminer si des essais contrôlés randomisés (ECR) visant à évaluer des bithérapies antiplaquettaires (BA) avaient inclus explicitement des patients ayant subi un IMT2. Méthodologie: Nous avons réalisé une méta-analyse afin de comparer le devenir de patients ayant subi un IMT2 et celui de patients ayant subi un IMT1. Nous avons aussi effectué une revue systématique distincte des données pour évaluer l’inclusion de cas d’IMT2 dans les ECR visant à évaluer des BA. Il y avait 19 cohortes regroupant 48 829 patients (40 604 ayant subi un IMT1 et 5 361 ayant subi un IMT2) et 51 ECR regroupant 188 132 patients atteints d’un syndrome coronarien aigu. Résultats: Chez les patients ayant subi un IMT2, la probabilité non corrigée de mortalité à long terme était environ 2 fois plus élevée que chez les patients ayant subi un IMT1 (rapport de cotes : 2,47; intervalle de confiance à 95 % : 2,06-2,96; p < 0,0001), et la probabilité corrigée de mortalité à long terme était accrue de 45 % (rapport de cotes : 1,45; intervalle de confiance à 95 % : 1,25-1,69; p < 0,0001). Aucune évaluation de l’efficacité (potentielle ou réelle) et de l’innocuité des BA chez les patients ayant subi un IMT2 n’a été publiée. Conclusion: Le risque corrigé de mortalité à long terme toutes causes confondues est plus élevé chez les patients ayant subi un IMT2 que chez les patients ayant subi un IMT1. Le rôle des BA reste à élucider dans les cas d’IMT2.

Sub-Saharan Africa is often presented as the continent most vulnerable to climatic change with major repercussions for food systems. Coupled with high rates of population growth and existing nutritional deficiencies, the need to enhance food production across the continent is thus seen as a major global imperative. We argue here, however, that current models of agricultural development in Eastern Africa often marginalise critical small-holder knowledge from the process of future agricultural design due to a lack of a methodological tools for engagement. This paper addresses this by outlining a potential means to capture and share locally produced agronomic information on a large scale. We report on a ‘Citizen Science’ pilot study that worked with smallholder farmers in Elgeyo-Marakwet County, western Kenya, to co-design a mobile application using the well-developed Sapelli platform that easily allows farmers to identify, record and geolocate cropping patterns and challenges at multiple stages in the agricultural calendar using their own understandings. The pilot project demonstrated the technical and epistemological benefits of co-design, the abilities of smallholder farmers to co-design and use smartphone applications, and the potential for such technology to produce and share valuable agricultural and ecological knowledge in real time. Proof-of-concept data illustrates opportunities to spatially and temporally track and respond to challenges related to climate, crop disease and pests. Such work expounds how smallholder farmers are a source of largely untapped ecological and agronomic expert knowledge that can, and should, be harnessed to address issues of future agricultural resilience and food system sustainability.

Background: A common MRI reference space allows for easy communication of findings, and has led to high-impact discoveries in neuroscience. Brain MRI of neuro-oncology patients with mass lesions or surgical cavities can now be accurately transformed into reference space, allowing for a reliable comparison across patients. Despite this, it is currently seldom used in neuro-oncology, leaving analytic tools untapped. The aim of this study was to systematically review the neuro-oncology literature utilizing reference space. Methods: A systematic review of the neuro-oncology publications was conducted according to PRISMA statement guidelines. Studies specially reporting the use of the Montreal Neurological Institute (MNI) reference space were included. Studies were categorized according to their type of input data and their contributions to the field. A sub-analysis focusing on connectomics and transcriptomics was also included. Results: We identified only 101 articles that utilized the MNI brain in neuro-oncology research. Tumor locations (n = 77) and direct electrocortical stimulation (n = 19) were the most common source of data. A majority of studies (n = 51) provided insights on clinical factors such as tumor subtype, growth progression, and prognosis. A small group of studies (n = 21) have used the novel connectomic and transcriptomic tools. Conclusions: Brain MRI of neuro-oncology patients can be accurately transformed to MNI space. This has contributed to enhance our understanding of a wide variety of clinical questions ranging from tumor subtyping to symptom mapping. Many advanced tools such as connectomics and transcriptomics remain relatively untapped, thereby hindering our knowledge of neuro-oncology.

ObjectiveSubstance use disorder (SUD) is a significant public health issue with a high mortality rate. Deep brain stimulation (DBS) has shown promising results in treating SUD in certain cases. In this study, we conducted a meta-analysis to evaluate the efficacy of DBS in the treatment of SUD and reduction of relapse rates.MethodsWe performed a thorough and methodical search of the existing scientific literature, adhering to the PRISMA guidelines, to identify 16 original studies that fulfilled our inclusion criteria. We used the evidence levels recommended by the Oxford Centre for Evidence-Based Medicine to assess bias. The R version 4.2.3 software was utilized to calculate the mean effect size. We estimated study heterogeneity by employing tau2 and I2 indices and conducting Cochran’s Q test.ResultsThe results showed that DBS treatment resulted in a significant improvement in the clinical SUD scales of patients, with an average improvement of 59.6%. The observed relapse rate was 8%. The meta-analysis estimated a mean effect size of 55.9 [40.4; 71.4]. Heterogeneity analysis showed a large degree of heterogeneity among the included studies. Subgroup and meta-regression analysis based on age and SUD type suggested that DBS may be more effective for patients above 45 years of age, and for alcohol and opioid addiction compared to nicotine addiction.ConclusionThe current literature suggests that DBS has a moderate effect on SUD symptoms. However, the limited number of studies and small sample size indicate that more research is needed to better understand the factors that influence its effectiveness.

The Greater Bay Area (GBA) accounts for a high percentage of pollution due to the large number of internal combustion engines. In the past few decades, there has been a significant increase in internal combustion engines vehicles while electric vehicles have not taken off yet in GBA. To a certain extent, the acceptance of electric vehicles is still questionable from the industrial practitioners and local communities. As such, this research study aims to identify the challenges and opportunities of electric vehicles in GBA to address the future direction of electric vehicles in GBA. In this study, it identifies technology and economy as the main driving forces behind the development of electric vehicles. Furthermore, sustainability, safety, and the life of the batteries may induce the slow adoption of electric vehicles. As expected, the study develops a research agenda and contributes new knowledge in the field of electric vehicle.

Online product reviews play a critical role for consumers to make a decision of product purchasing, and become an important data source for vendors to build recommendation systems. Some consumers won’t even buy a product without reading online reviews first, and some vendors invite reviewers to write product reviews before a product is released to the market. However, the review quality could greatly impact the use of the reviews for supporting the purchase decision and recommendation. In order to produce enough high-quality reviews, it is a common practice that vendors provide incentives for writing product reviews. Current research is divided. Some research showed that incentive reviews could be more biased compared to organic reviews, but other scholars showed incentive reviews contain more useful information. Furthermore, other academic publications showed very different results regarding the differences between the incentivized and organic reviews. One of the reasons explaining the observation differences could be due to the quality of the reviewers and reviews. Therefore, it is necessary to control the quality of the reviewers and their reviews for a more objective comparison. In this research, we first discuss an approach for ensuring the quality of the data collection and processing to ensure the quality of the comparison study. Then, we explore the differences between incentivized reviews and organic reviews collected from a website that provides reviews for enterprise software systems. Several parameters of the reviews, such as the overall score, sentiment, and subjectivity of the reviews, were analyzed and compared. Our results could provide a reference for appropriately using reviews and managing the reviewing process.

Abstract Significant weight loss can modify the progression of Nonalcoholic fatty liver disease (NAFLD) with the most convincing evidence coming from bariatric surgery cohorts. Effective ways to non-invasively characterise NAFLD in these patients has been lacking, with high Fibroscan failure rates reported. We prospectively evaluated the utility of Fibroscan using XL-probe over a two-year period. 190 consecutive patients undergoing bariatric surgery were followed as part of their routine care. All patients had Fibroscan performed on the day of surgery and at follow-up a mean of 13 months (± 6.3) later. The majority of patients were female (82%) with mean age of 42. Fibroscan was successful in 167 (88%) at baseline and 100% at follow up. Patients with a failed Fibroscan had higher body mass index (BMI) and alanine transaminase (ALT), but no difference in FIB-4/NAFLD score. Mean baseline Liver stiffness measurement was 5.1 kPa, with 87% of patients classified as no fibrosis and 4% as advanced fibrosis. Mean baseline controlled attenuation parameter was 291, with 78% having significant steatosis, 56% of which was moderate-severe. Significant fibrosis was associated with higher BMI and HbA1c. Significant steatosis was associated with higher BMI, ALT, triglycerides and insulin resistance. Mean follow up time was 12 months with weight loss of 25.7% and BMI reduction of 10.4 kg/m2. Seventy patients had repeat fibroscan with reductions in steatosis seen in 90% and fibrosis in 67%. Sixty-four percent had complete resolution of steatosis. Fibroscan can be performed reliably in bariatric cohorts and is useful at baseline and follow-up. Significant steatosis, but not fibrosis was seen in this cohort with substantial improvements post-surgery.

AimsTo perform a systematic review assessing the clinical manifestations and outcomes of cardiorenal syndrome or the presence of both cardiac and renal complications in the 2019 coronavirus disease (COVID-19) patients.MethodsAll relevant studies about cardiorenal syndrome or both cardiac and renal complications in COVID-19 patients were retrieved on PUBMED, MEDLINE, and EMBASE from December 1, 2019 to February 20, 2022.ResultsOur search identified 15 studies including 637 patients with a diagnosis of cardiorenal syndrome or evidence of both cardiac and renal complications followingSARS-CoV-2 infection. They were male predominant (66.2%, 422/637), with a mean age of 58 years old. Cardiac complications included myocardial injury (13 studies), heart failure (7 studies), arrhythmias (5 studies), or myocarditis and cardiomyopathy (2 studies). Renal complications manifested as acute kidney injury with or without oliguria. Patients with cardiorenal injury were often associated with significantly elevated levels of inflammatory markers (CRP, PCT, IL-6). Patients with a diagnosis of cardiorenal syndrome or evidence of both cardiac and renal complications had more severe disease and poorer prognosis (9 studies).ConclusionThe presence of either cardiorenal syndrome or concurrent cardiac and renal complications had a significant impact on the severity of the disease and the mortality rate among patients with COVID-19 infection. Therefore, careful assessment and management of potential cardiac and renal complications in patients with COVID-19 infection are important to improve their outcomes.

AnnexinV has been shown to bind phosphatidylserine expressed by chemotherapy-induced apoptotic cells increasing their immunogeneicity. Here, the authors demonstrate in a preclinical tumor model that fusing tumor-antigen peptide to Annexin V enhances its efficacy when administered after chemotherapy and with other immune checkpoint inhibitors.

Abstract The tumor microenvironment exists in a state of dynamic equilibrium, in which a balance of agonist and antagonist signals govern the anti-tumor immune responses. Previous studies have shown that chemotherapy could shift this balance in favor of agonistic signals for the anti-tumor immune responses mounted by CD8+ cytotoxic T lymphocytes (CTL), providing sufficiently high antigen density within the tumor. We undertook the current study to characterize the anti-tumor immune response following chemotherapy and its underlying mechanisms. We show that this ‘adjuvant effect’ of chemotherapy is, at least partially, mediated by the release of tumor DNA and acts through the Toll-like receptor 9 (TLR9) pathway. We found that tumor-released DNA causes accumulation, antigen uptake, and maturation of dendritic cells (DCs) in the tumor in a TLR9-dependent manner. These DCs subsequently migrate into the draining lymph nodes and prime tumor-specific CTLs. Our study provides novel insights to the molecular and cellular mechanisms by which chemotherapy converts the tumor microenvironment into a site permissive for the activation of a potent tumor-specific adaptive immune response.

The author examines the inscription from Montepulciano, outskirts of Clusium (today Chiusi) (cippus Bucellius), where the Greek Dorian term was mentioned, which means a military colonist. Taking in consideration previous researches, the author tries to prove prescription of cippus Bucellius as a boundary; explain earlier date of the inscription (earlier 3rd, not 2nd centuries BC); represent own explanation of discussion terms, namely, ser is considered as reduction of the praenomen servei; hilar is determined as a plot of land; claruχieś is seen as a genitive case of term which means a military colonist-mercenary, created like the personal Etruscan names.

We face the problem to determine whether an algebraic polynomial is nonnegative in an interval the Yau Number Theoretic Conjecture and Yau Geometric Conjecture is proved. In this paper, we propose a new theorem to determine if an algebraic polynomial is nonnegative in an interval. It improves Wang-Yau Lemma for wider applications in light of Sturm’s Theorem. Many polynomials can use the new theorem but cannot use Sturm’s Theorem and Wang-Yau Lemma to judge whether they are nonnegative in an interval. New Theorem also performs better than Sturm’s Theorem when the number of terms and degree of polynomials increase. Main Theorem can be used for polynomials whose coefficients are parameters and to any interval we use. It helps us to find the roots of complicated polynomials. The problem of constructing nonnegative trigonometric polynomials in an interval is a classical, important problem and crucial to many research areas. We can convert a given trigonometric polynomial to an algebraic polynomial. Hence, our proposed new theorem affords a new way to solve this classical, important problem.

Dendritic cell (DC)-based vaccines are recognized as a promising immunotherapeutic strategy against cancer. Various adjuvants are often incorporated to enhance the modest immunogenicity of DC vaccines. More specifically, many of the commonly used adjuvants are derived from bacteria. In the current study, we evaluate the use of apoptosis inhibitor 5 (API5), a damage-associated molecular pattern expressed by many human cancer cells, as a novel DC vaccine adjuvant. We showed that API5 can prompt activation and maturation of DCs and activate NFkB by stimulating the Toll-like receptor signaling pathway. We also demonstrated that vaccination with API5-treated DCs pulsed with OVA, E7, or AH1-A5 peptides led to the generation of OVA, E7, or AH1-A5-specific CD8 + T cells and memory T cells, which is associated with long term tumor protection and antitumor effects in mice, against EG.7, TC-1, and CT26 tumors. Additionally, we determined that API5-mediated DC activation and immune stimulation are dependent on TLR4. Lastly, we showed that the API5 protein sequence fragment that is proximal to its leucine zipper motif is responsible for the adjuvant effects exerted by API5. Our data provide evidence that support the use of API5 as a promising adjuvant for DC-based therapies, which can be applied in combination with other cancer therapies. Most notably, our results further support the continued investigation of human-based adjuvants.

Purpose: Mucosal immunization is suggested to be crucial for controlling tumors in the mucosal region; however, therapeutic DNA vaccination with electroporation in various mucosal sites has yet to become clinically adaptable. Since tumor-draining lymph nodes (tdLNs) have been suggested as immune-educated sites that can be utilized to mount a potent antitumor immune response, we examined whether intramuscular DNA vaccination with electroporation at sites that target the mucosal tdLNs could elicit mucosal immune response to restrict tumor growth. Experimental Design: The efficacy and mechanism of intramuscular administration of a therapeutic DNA vaccine with electroporation at different sites was examined by lymphocyte analysis, tumor growth, mouse survival, as well as integrin expression, in mice bearing orthotopic HPV16 E6/E7+ syngeneic TC-1 tumors in various mucosal areas. Results: While provoking comparable systemic CD8+ T cell responses, intramuscular hind leg vaccination generated stronger responses in cervicovaginal-draining LNs to control cervicovaginal tumors, whereas intramuscular front leg vaccination generated stronger responses in oral-draining LNs to control buccal tumors. Surgical removal of tdLNs abolished the antitumor effects of therapeutic vaccination. Mucosal-tdLN-targeted intramuscular vaccination induced the expression of mucosal-homing integrins LPAM-1 and CD49a by tumor-specific CD8+ T cells in the tdLNs. Inhibition of these integrins abolished the therapeutic effects of vaccination and the infiltration of tumor-specific CD8+ T cells into mucosal tumors. Conclusions: Our findings demonstrate that tumor draining lymph nodes targeted intramuscular immunization can effectively control mucosal tumors, which represents a readily adaptable strategy for treating mucosal cancers in humans.

Having examined the frescoes from Tarquinia: the Tomb of Augurs, the Tomb of the Pulcinella, and the Tomb of the Olympiads dated back to the sixth century BCE that depict scenes with a personage Phersu, the author deals with Etruscan inscriptions, data of the Antique tradition about origin of scenic and gladiatorial games, as well as a number of interpretations of these scenes to prove that the Etruscan ritual ‘game Phersu’ is a prototype of the Roman gladiatorial games and ‘venatio’. Being a part of Etruscan funeral rite, the ritual game was a substitutive sacrifice that symbolised a fight of a human being against the demon of death Calu – an abductor of souls from the world of the living. The fight was supposed to be guided by an invisible and disguised power, being personified in the image of Phersu.

To test, whether 10 genes, diagnostic of renal allograft rejection in blood, are able to diagnose and predict cardiac allograft rejection, we analyzed 250 blood samples from heart transplant recipients with and without acute rejection (AR) and with cytomegalovirus (CMV) infection by QPCR. A QPCR-based logistic regression model was built on 5 of these 10 genes (AR threshold composite score >37% = AR) and tested for AR prediction in an independent set of 109 samples, where it correctly diagnosed AR with 89% accuracy, with no misclassifications for AR ISHLT grade 1b. CMV infection did not confound the AR score. The genes correctly diagnosed AR in a blood sample within 6 months prior to biopsy diagnosis with 80% sensitivity and untreated grade 1b AR episodes had persistently elevated scores until 6 months after biopsy diagnosis. The gene score was also correlated with presence or absence of cardiac allograft vasculopathy (CAV) irrespective of rejection grade. In conclusion, there is a common transcriptional axis of immunological trafficking in peripheral blood in both renal and cardiac organ transplant rejection, across a diverse recipient age range. A common gene signature, initially identified in the setting of renal transplant rejection, can be utilized serially after cardiac transplantation, to diagnose and predict biopsy confirmed acute heart transplant rejection.