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Abstract Aims Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there is no definitive evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis. Animal models of cardiovascular (CV), as well as neurological diseases, have demonstrated that cannabidiol has significant anti‐inflammatory properties and may represent a promising therapy in acute myocarditis. This efficacy has been shown in a murine model of autoimmune myocarditis as well as in in vitro and in vivo models of heart failure (HF). Methods and results We present the rationale and design of the ARCHER Trial, an international multicentre, double‐blind, randomized, placebo‐controlled, phase II study examining the safety and efficacy of a pharmaceutically produced cannabidiol formulation, in patients with mild to moderate acute myocarditis. Eligible patients are those with acute myocarditis, randomized within 10 days of the diagnostic cardiac MRI (CMR), which has met defined diagnostic criteria for myocarditis. Oral treatment (cannabidiol or placebo) is titrated from 2.5 mg/kg of body weight up to 10 mg/kg of body weight b.i.d. (or highest tolerated dose) and taken for 12 weeks in addition to standard of care therapy for HF. The primary endpoints are defined as changes in global longitudinal strain (GLS) and extra cellular volume (ECV), measured by CMR at 12 weeks. Assuming 80% power, a 5% alpha risk and 25% missing CMR follow‐up data at Week 12, 100 patients are required to demonstrate the desired treatment effect of 18%. The change in left ventricular ejection fraction (LVEF) from baseline to Week 12 was selected as the secondary endpoint. Additional exploratory endpoints include changes in hs‐troponin, NT‐proBNP, markers of inflammation and endothelial function during the 12‐week treatment period. The trial is ongoing but is now more than 50% recruited. As enrolment in the trial continues, no interim data are available for inclusion in this Design paper. Conclusions The ongoing ARCHER Trial is an international, multicentre, double‐blind, randomized, placebo‐controlled phase II study, designed to determine the effect of a pharmaceutically produced cannabidiol formulation on CMR parameters in patients presenting with acute myocarditis. Enrolment of 100 patients is expected to conclude in Q3 2024. Study results will be available in early 2025.

Inspired by the uses and gratifications theory, this study examines the role of closed women’s Facebook groups in mediating the relationship between various forms of loneliness and perceived gratification among Israeli women. We surveyed 521 female participants to explore the mediating effect of engagement on loneliness and perceived gratification. Our findings suggest that these closed Facebook groups serve as significant platforms for interaction and personal disclosure, thereby contributing to the perceived importance of these groups in members’ lives. However, the results also show that these groups may not effectively alleviate social-emotional loneliness, and increased engagement within these groups does not significantly influence the relationship between loneliness and perceived gratification. In contrast, these groups act as alternative support systems for women experiencing family loneliness, with a heightened sense of gratification correlating with active participation. Despite these findings, the study reveals the limitations of these groups in addressing all forms of loneliness, underscoring the vital role of offline interactions. Therefore, these results highlight the need to further explore the interplay between online and offline spaces in shaping women’s experiences of loneliness and perceived gratification. The study also suggests that additional research is necessary to examine the applicability of these findings across different cultural contexts and a broader range of online groups.

Background: Limited observational reports link elevated lipoprotein(a) (Lp[a]) levels to aortic stenosis (AS) or to disease progression. Data on large cohorts of verified severe AS patients are lacking. Objectives: The purpose of the study was to characterize Lp(a) levels of severe AS patients referred to transcatheter aortic valve implantation (TAVI) and compare them to a large cohort of Lp(a) samples derived from the general population. Methods: Lp(a) levels obtained from frozen serum samples of TAVI patients between 2012 and 2017 were compared to a control group for whom Lp(a) levels were obtained for any reason and stratified by gender. Multivariable binary logistic regression analyses were conducted to investigate associations between younger age at TAVI and an Lp(a) cutoff of 50 mg/dL. Results: Lp(a) levels of 503 TAVI were compared to 25,343 controls. Patients in the AS group had mildly higher median Lp(a) levels compared to controls (20.5 vs 18.7 mg/dL, P = 0.04). Lp(a) levels in males with severe AS were higher than controls (19.9 vs 16.6 mg/dL, P = 0.04). Females had a nonsignificant difference (22.1 vs 21.3 mg/dL, P = 0.87). In multivariable analysis, an Lp(a) cutoff of above 50 mg/dL was not associated with an earlier age at TAVI (beta: 1.04; 95% CI: 0.42-2.57; P = 0.94). Conclusions: Median Lp(a) levels were only mildly higher in severe AS patients undergoing TAVI in comparison to a large control group, mainly driven by higher Lp(a) levels in males. Higher Lp(a) levels were not associated with an earlier age at TAVI, rejecting its association with an accelerated disease progression.

IntroductionSolid organ transplantation in children is a lifesaving therapy, however, pediatric organ donation rates remain suboptimal.MethodsWe conducted a cross-sectional survey of Canadian organ donation organizations (ODOs) and pediatric transplant programs (TPs), aiming to describe policies and practices for pediatric organ allocation, acceptance, and utilization in Canada.ResultsResponse rates were 82% and 83% respectively for ODOs and transplant programs comprising 7 kidney, 3 heart, 2 lung, 2 liver and 1 intestine programs. All 9 ODOs reported offering pediatric organs following death by neurological criteria (DNC), while 8 reported offering organs following death by circulatory criteria (DCC) for some organs. Variability was found across ODOs and TPs. There was little agreement on both absolute and organ-specific donor exclusion criteria between ODOs. There was further disagreement in organ specific acceptance criteria between ODOs and TPs and between TPs themselves. Notably, despite the development of pediatric donation after DCC guidelines, organs from DCC donors are excluded by many ODOs and TPs.DiscussionFurther variability in pediatric specific training, policies, and allocation guidelines are also documented. Significant areas for improvement in standardization in organ acceptance, offering, and allocation in pediatric donation and transplantation across Canada were identified.

Enhancing electronic transport properties of thermoelectric oxides is of great technological importance. Oxides are promising candidates for waste heat harvesting at elevated temperatures as well as for electricity generation in low‐power applications. To this purpose, fundamental understanding of their electrical and thermal conduction mechanisms is essential. Herein, the conduction mechanism of CaMnO3 materials is focused on and how dopant identity and amount alter the kinetic properties of charge transport is investigated. Ca1−xRxMnO3 compounds with R = Y and La are synthesized, where 0 ≤ x ≤ 0.13, and the electrical conductivity and Seebeck coefficient for temperatures ranging from 300 to 1050 K, indicating that Y‐doped compounds are usually more conductive than their La‐doped counterparts, are measured. Analysis of both in terms of the small polaron hopping model reveals that Y doping reduces conduction activation energies, resulting in higher electrical conductivity and charge carrier mobility. Remarkably high values of thermoelectric power factor for the Ca0.97La0.03MnO3 compound, for example, 300 μWm−1 K−2 at 1050 K are observed; furthermore, these values are preserved for a wide temperature range, rendering this compound a good candidate for heat‐to‐electrical power generation at elevated temperatures.

Abstract Aims This study aimed to characterize the final diagnosis and prognosis of patients with grade 1 myocardial scintigraphy uptake, which is an unequivocal result for the diagnosis of transthyretin cardiac amyloidosis (ATTR‐CA) requiring further invasive investigation with tissue biopsy. Methods and results We retrospectively compared the clinical and imaging parameters of patients suspected for ATTR‐CA (based on clinical and echocardiographic parameters) with grade 1 vs. grades 2/3 technetium pyrophosphate uptake on cardiac scintigraphy. Prospectively, grade 1 patients underwent re‐evaluation for ATTR‐CA at long term. Of the 132 ATTR‐CA suspected patients, 89 (67%) were diagnosed as grade 1 and 43 (33%) as grades 2/3 uptake. Grade 1 vs. grades 2/3 patients were younger and female predominant with lower biomarker levels and left ventricular mass. Based on available imaging and pathology findings, only 6 out of the 89 patients with grade 1 uptake (7%) were finally diagnosed with light‐chain cardiac amyloidosis, whereas no patient was diagnosed with ATTR‐CA. At 2 [interquartile range (IQR) 0.75, 3.25] years of follow‐up, the survival of patients with grade 1 vs. grades 2/3 uptake was significantly better [hazard ratio 0.271 (95% confidence interval 0.130 to 0.563, P = 0.0005)]. Prospectively, 30 patients with grade 1 uptake were re‐evaluated at a median follow‐up of 3.2 (IQR 2.2, 3.9) years. Their New York Heart Association class, biomarker levels, and echocardiography findings remained stable. No patient (0/25) demonstrated grades 2/3 uptake at repeated long‐term scintigraphy. Conclusions Patients with suspected ATTR‐CA and a grade 1 scintigraphy uptake demonstrate a stable clinical, laboratory, imaging, and scintigraphy phenotype along with a benign survival profile at long‐term follow‐up. Larger studies should define the optimal evaluation strategy in this population.

Flow cytometry enables quantitative measurements of fluorescence in single cells. The technique was widely used for immunology to identify populations with different surface protein markers. More recently, the usage of flow cytometry has been extended to additional readouts, including intracellular proteins and fluorescent protein transgenes, and is widely utilized to study developmental biology, systems biology, microbiology, and many other fields. A common file format (FCS format, defined by the International Society for Advancement of Cytometry (ISAC)) has been universally adopted, facilitating data exchange between different machines. A diverse spectrum of software packages has been developed for the analysis of flow cytometry data. However, those are either 1) costly proprietary softwares, 2) open source packages with prerequisite installation of R or Python and sometimes require users to have experience in coding, or 3) online tools that are limiting for analysis of large data sets. Here, we present EasyFlow, an open-source flow cytometry analysis graphic user interface (GUI) based on Matlab or Python, that can be installed and run locally across platforms (Windows, MacOS, and Linux) without requiring previous coding knowledge. The Python version (EasyFlowQ) is also developed on a popular plotting framework (Matplotlib) and modern user interface toolkit (Qt), allowing more advanced users to customize and keep contributing to the software, as well as its tutorials. Overall, EasyFlow serves as a simple-to-use tool for inexperienced users with little coding experience to use locally, as well as a platform for advanced users to further customize for their own needs.

Indoor Localization is gaining increased importance due to numerous location-based services in healthcare, logistics, and security, to name few, that are expected to be provided by next-generation wireless networks. Such services are characterized by stringent accuracy requirements, short response time, and lower cost which makes the localization problem more challenging and deserving of attention. A key element of the localization process is distance estimation (also known as ranging). In this paper, we design and analyze an efficient decimeter-level two-way ranging scheme for ubiquitous WiFi networks in the 5 GHz frequency band whose accuracy approaches ideal one-way ranging with no phase mismatches. We investigate the idea of channel frequency response (CFR) stitching across non-contiguous WiFi channels and how two-way CFR measurements help in achieving the CFR coherency necessary for accurate ranging. In addition, we quantify the decrease in ranging accuracy of two-way compared to one-way ranging due to SNR degradation, Line-of-Sight (LoS) component shrinkage, and doubling the multipath delay spread. Furthermore, We design a novel scheme to bridge the performance gap between two-way ranging and ideal one-way ranging which operates in three main steps: square-root of the two-way CFR, followed by phase unwrapping, and finally deep fade detection and phase errors correction. Our proposed scheme achieves significant performance gains over two-way ranging with only a slight performance gap from ideal one-way ranging. Moreover, our proposed scheme enjoys robustness as it preserves the ranging accuracy gains in various WiFi communication scenarios when operating at different SNR levels, different multipath channel models, and different CFR bandwidths, as well as operating under system impairments such as Sample Timing Offset (STO). The accuracy gains achieved by the proposed schemes are demonstrated using both simulations and an in-house WiFi testbed. Finally, we quantify the added complexity of our proposed scheme and show it to be insignificant compared to that of the MUSIC super-resolution ranging steps which confirms the practical viability of our proposed scheme.

Background Various hemodynamic changes occur following transcatheter aortic valve implantation (TAVI) that may impact therapeutic decisions. NICaS is a noninvasive bioimpedance monitoring system aimed at hemodynamic assessment. We used the NICaS system in patients with severe aortic stenosis (AS) to evaluate short‐term hemodynamic changes after TAVI. Methods and Results We performed hemodynamic analysis using NICaS on 97 patients with severe AS who underwent TAVI using either self‐expandable (68%) or balloon‐expandable (32%) valves. Patients were more often women (54%) and had multiple comorbidities including hypertension (83%), coronary artery disease (46%), and diabetes (37%). NICaS was performed at several time points—before TAVI, soon after TAVI, at hospital discharge, and during follow‐up. Compared with baseline NICaS measurements, we observed a significant increase in systolic blood pressure and total peripheral resistance (systolic blood pressure 132±21 mm Hg at baseline versus 147±23 mm Hg after TAVI, P

Background: Extension of dual antiplatelet therapy (DAPT) beyond 1 year after acute coronary syndrome is associated with a reduction in ischemic events but also increased bleeding. The DAPT score identifies individuals likely to derive overall benefit or harm from DAPT extension. We sought to evaluate the impact of providing the DAPT score to treating physicians on the decision to extend DAPT beyond 1 year after non–ST-segment elevation myocardial infarction. Methods: Moderate to high-risk non–ST-segment elevation myocardial infarction patients were enrolled from July 2016 to May 2018 in 13 Canadian hospitals by 52 cardiologists. Participating cardiologists were randomly assigned 1:1 to receive their individual patients’ DAPT scores before the 1-year follow-up visit vs not receiving their patients’ DAPT scores. Rates of DAPT extension were compared among the randomized groups. Results: At 1 year, 370 of the 585 (63.2%) patients discharged on DAPT were receiving DAPT. Among patients on DAPT at 1 year, the median (25th, 75th percentile) DAPT score was 2 (1,3). DAPT was extended beyond 1 year in 36.2% randomly assigned to provision of DAPT score vs 35.7% in the control group (P = 0.93). In the subgroup of patients with DAPT score ≥ 2, DAPT extension was 49.5% in the DAPT score provision arm vs 40.4% in the control arm (P = 0.22); among patients with DAPT score < 2, DAPT termination was 78.6% in the DAPT score provision arm vs 70.6% in the control arm (P = 0.26) (P value for interaction = 0.1). Conclusions: In this exploratory randomized trial, provision of the DAPT score to treating physicians had no impact on the duration of DAPT treatment beyond 1 year. Résumé: Introduction: La prolongation de la bithérapie antiplaquettaire au-delà d'un an après un syndrome coronarien aigu est associée à la réduction des accidents ischémiques, mais aussi à l’augmentation des hémorragies. Le score de bithérapie antiplaquettaire permet de déterminer les individus susceptibles d’obtenir des avantages globaux ou des inconvénients de la prolongation de la bithérapie antiplaquettaire. Nous avons cherché à évaluer les répercussions de l’obtention du score de bithérapie antiplaquettaire par les médecins traitants sur la décision quant à la prolongation de la bithérapie antiplaquettaire au-delà d'un an après l'infarctus du myocarde sans élévation du segment ST. Méthodes: De juillet 2016 à mai 2018, 52 cardiologues de 13 hôpitaux du Canada ont inscrit des patients exposés à un risque modéré à élevé d’infarctus du myocarde sans élévation du segment ST. Nous avons réparti de façon aléatoire selon un rapport 1:1 les cardiologues participants qui recevaient les scores de bithérapie antiplaquettaire individuels de leurs patients avant la consultation de suivi après un an vs ceux qui ne recevaient pas les scores de bithérapie antiplaquettaire de leurs patients. Nous avons comparé les taux de prolongation de la bithérapie antiplaquettaire des groupes répartis de façon aléatoire. Résultats: Après un an, 370 (63,2 %) patients sur 585 qui avaient eu à la sortie de l’hôpital une bithérapie antiplaquettaire recevaient la bithérapie antiplaquettaire. Parmi les patients qui prenaient la bithérapie antiplaquettaire après un an, le score médian de bithérapie antiplaquettaire (25e, 75e percentiles) était de 2 (1, 3). La bithérapie antiplaquettaire était prolongée au-delà d'un an chez 36,2 % des patients répartis de façon aléatoire qui avaient un score de bithérapie antiplaquettaire vs 35,7 % dans le groupe témoin (P = 0,93). Dans le sous-groupe de patients qui avaient un score de bithérapie antiplaquettaire ≥ 2, la prolongation de la bithérapie antiplaquettaire était de 49,5 % dans le bras qui avait un score de bithérapie antiplaquettaire vs 40,4 % dans le bras témoin (P = 0,22); parmi les patients qui avaient un score de bithérapie antiplaquettaire < 2, la cessation de la bithérapie antiplaquettaire était de 78,6 % dans le bras qui avait un score de bithérapie antiplaquettaire vs 70,6 % dans le bras témoin (P = 0,26) (valeur P pour l’interaction = 0,1). Conclusions: Dans cet essai exploratoire à répartition aléatoire, l’obtention du score de la bithérapie antiplaquettaire par les médecins traitants n’a pas engendré de répercussions sur la durée de la bithérapie antiplaquettaire au-delà d'un an.

Objective Inflammation is associated with atherogenesis. Although a higher neutrophil count is associated with the plaque burden, the role of neutrophil activation is unclear. Human neutrophil peptides 1–3 (HNP1–3) are a risk factor for atherogenesis in bench models and are elevated in human atheromas. This study aimed to examine the association between skin HNP1–3 deposition and the severity of coronary artery disease (CAD), including long-term outcomes. Methods HNP1–3 levels were immunohistochemically quantified in skin biopsies, which were prospectively taken from 599 consecutive patients before clinically indicated coronary angiography. Established cardiovascular risk factors and blood markers for atheroinflammation were obtained. CAD severity and the incidence of repeat revascularization and mortality at 48 months of follow-up were assessed in relation to HNP1–3 levels. Results The risk of CAD was independently associated with age and HNP1–3 in the entire cohort (F = 0.71 and F = 7.4, respectively). Additionally, HNP1–3 levels were significantly associated with myocardial necrosis (R = 0.26). At the follow-up, high HNP1–3 levels negatively affected mortality (19.54%) and recurrent revascularization (8.05%). Conclusion HNP1–3 tissue deposition is positively associated with the severity of CAD, myonecrosis, and long-term sequelae. HNP1–3 levels may be suppressed using colchicine.

IntroductionVaccination-associated myocarditis was reported following COVID-19 vaccine initially among persons aged 16 or older and recently among adolescents aged 12–15.ObjectivesTo describe the clinical and cardiac magnetic resonance (CMR) characteristics of adolescents aged 12–15 with myocarditis following the administration of the BNT162b2 mRNA COVID-19 vaccine.MethodsCMR of adolescents (age 12–15) with a clinical diagnosis of myocarditis within 42 days following the first COVID-19 vaccine were analyzed.ResultsA total of 182,605 adolescent were vaccinated, out of which 9 were diagnosed with clinically adjudicated myocarditis while CMR was performed in 5/9 patients (56%). Median age was 15 years (range 13–15), 4/5 (80%) males. All the patients we previously healthy. The ECG upon presentation was abnormal in 3/5 (60%) of patients. All cases were classified as clinically mild and no patient required inotropes or mechanical circulatory support treatment. The median follow-up time, for the 5-included patients, was 206 (IQR 192–229, range 179–233) days. During the follow-up, no re-admissions, deaths, or any other cardiac events have occurred.The median time between the diagnosis to the CMR was 104 days (range 27–149). The median left ventricular ejection fraction was within normal range 65% (range 62–69). Native T1 was available in four patients, the local T1 value was increased in three of them. T2 values were available in two patients and were all within normal range. The median late gadolinium enhancement (LGE) was 2% (range 0–6%) with inferolateral wall being the most common location (3/5). The patterns of the LGE were as following: (i) mid-wall in 3 patients; (ii) epicardial in 1-patient. LGE in the pericardium was present in 2/5 patients with pericardial effusion present in 4/5 patients with a median diameter of 4 mm (range 3–5 mm) at end-systole.ConclusionsCMR findings and clinical course of adolescents with COVID-19 vaccination associated myocarditis, are similar to those of older patients, being relatively mild and potentially implying favorable outcomes.

BackgroundMyocarditis has been reported following the first two doses of Pfizer-BNT162b2 messenger RNA (mRNA) COVID-19 vaccination. Administration of a third dose (booster) of the vaccine was initiated recently in Israel.ObjectiveThe aim of this study was to describe the characteristics of patients referred for cardiac magnetic resonance (CMR) imaging with myocarditis following the booster.MethodsPatients referred for CMR imaging with a clinical diagnosis of myocarditis within 21 days following the booster, between July 13 and November 11, 2021, were analyzed.ResultsOverall, 4 patients were included, 3/4 (75%) were men, and the mean age was 27 ± 10 years. The time from booster administration to the onset of symptoms was 5.75 ± 4.8 days (range 2–14). Obstructive coronary artery disease was excluded in 3 of the patients (75%). CMR was performed 34 ± 15 days (range 8-47 days) following the 3rd vaccination. The mean left ventricular ejection fraction was 61 ± 7% (range 53–71%), and regional wall motion abnormalities were present in one of the patients. Global T1 was increased in one of the patients, while focal T1 values were increased in 3 of the patients. Global T2 was increased in one of the patients, while focal T2 values were increased in all the patients. Global ECV was increased in 3 of the patients, while focal ECV was increased in all the patients. Median late gadolinium enhancement (LGE) was 4 ± 3% (range 1–9%), with the inferolateral segment as the most common location (3 of the 4 patients). All the patients met the Updated Lake Louise Criteria.ConclusionsPatient characteristics and CMR imaging findings of myocarditis following the administration of the booster vaccine are relatively mild and consistent with those observed with the first two doses. Although larger-scale prospective studies are necessary, these initial findings are somewhat reassuring.

BACKGROUND: For procedural education, the shift from the traditional apprenticeship model to simulation-based mastery has become increasingly accepted as the gold standard and has underscored the importance of high-fidelity, cost-effective training options. However, cost-effective pleural procedure simulators providing both realistic haptic feedback and ultrasound compatibility are lacking. OBJECTIVE: We aimed to create a pleural procedure simulator with characteristics of human tissue, at low cost and with ultrasound compatibility. METHODS: This work used design-based research principles and a collaborative rapid iteration approach in collaboration with the University of California, San Francisco, Makers Lab and design-based researchers at the University of California, Berkeley, which led to the creation of a three-dimensionally printed pleural procedure simulator. RESULTS: The needs assessment indicated significant discomfort with pleural procedures and a request for more accessible simulation opportunities. Iterative prototyping resulted in a three-dimensionally printed rib cage and a series of innovations in the fluid pocket and skin layers to provide realistic tactile feedback and ultrasound imaging compatibility. The final model costs significantly less than commercial simulators, with durable components and replaceable parts that can be reused multiple times. CONCLUSION: The development of a low-cost, high-fidelity pleural procedure simulator addresses the current limitations of commercially available pleural simulators. By integrating three-dimensional printing technology and easily accessible materials, we were able to produce a simulator that closely replicates the feel of human tissue, allows ultrasound use, and is adaptable for different patient anatomies and clinical scenarios. This novel simulator is a scalable solution to elevate the standard of procedural education and ultimately positively affect patient care.

Background: Currently, normal values of the cardiac chambers' volumes are adjusted only for gender and body surface area (BSA). We aim to investigate the association between the heart rate and the volume of each of the four cardiac chambers using cardiac-gated computed tomography angiography (CCTA). Methods: A total of 350 consecutive patients without known cardiac diseases or significant (>50%) stenosis undergoing CCTA between January 2009 and June 2014 for suspected coronary artery disease were included. Cardiac chamber volumes adjusted to BSA were calculated using automated model-based segmentation analysis software of the CCTA data and correlated with patients' mean heart rate during the scan. Results: There were 240 men and 110 women, median interquartile range age was 55 years (47?61). Women were older 59.0 years (53.7?64) versus 52.0 years (45.0?59.0), had higher prevalence of hyperlipidemia, diabetes mellitus, anemia, and hypothyroidism, and higher median heart rates 64.0 (59.7?66.0) versus 60.0 (55.0?65.0) (p?0.001). Men had a negative correlation between the volume of each cardiac chamber and the heart rate [rage_adj?=?(?0.4)?(?0.27), p?

Abstract Background Chemotherapy induced cardio-toxicity has been recognized as a serious side effect since the first introduction to anthracyclines (ANT). Cardio-toxicity among patients with breast cancer is well studied but the impact on patients with sarcoma is limited, even though they are exposed to higher ANT doses. The commonly used term for cardio-toxicity is cancer therapeutics related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction (LVEF) reduction of > 10%, to a value below 53%. The aim of our study was to estimate the prevalence of CTRCD in patients diagnosed with sarcoma and to describe the baseline risk factors and echocardiography parameters among that population. Methods Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), enrolling all patients evaluated in the cardio-oncology clinic at our institution. The registry was approved by the local ethics committee and is registered in clinicaltrials.gov (Identifier: NCT02818517). All sarcoma patients were enrolled and divided into two groups - CTRCD group vs. non-CTRCD group. Results Among 43 consecutive patients, 6 (14%) developed CTRCD. Baseline cardiac risk factors were more frequent among the non-CTRCD group. Elevated left ventricular end systolic diameter and reduced Global Longitudinal Strain were observed among the CTRCD group. During follow-up, 2 (33%) patients died in the CTRCD group vs. 3 (8.1%) patients in the non-CTRCD group. Conclusions CTRCD is an important concern among patients with sarcoma, regardless of baseline risk factors. Echocardiography parameters may provide an early diagnosis of cardio-toxicity.

This paper reports on the physico-chemical removal of NH4+ from the supernatant line in municipal wastewater treatment plants (WWTPs), using zinc-hexa-cyano-ferrate (ZnHCF) beads. The work is divided into three parts: First, the characteristics of three (Zn-, Co-, Ni-) types of HCF beads were determined, with a finding that ZnHCF was the most suitable for the purpose of this work. Second, synthetic and actual supernatant wastewater was passed through a ZnHCF column for many cycles until apparent steady-state results were attained. Due to the very high affinity of the beads toward NH4+ and the much lower affinity toward competing cations, the same regeneration solution could be used for many cycles (20 cycles in this work) without affecting the following adsorption breakthrough curve efficiency and the operational capacity, which was >88% at the end of all adsorption steps. Finally, a cost analysis was performed, revealing that the cost of removing ~500 mg/L of ammonia from the supernatant line is ~$0.02 per m3 of raw wastewater flowing into the plant if the ammonia is recaptured and sold as NH4Cl. This may be cost-effective when the WWTP receives a higher-than-planned load, and an incentive exists for alleviating the ammonia load on the oxidation reactor.

Background: The cost of heart failure hospitalizations in the US alone is over USD 10 billion per year. Over 4 million Americans are hospitalized every year due to heart failure (HF), with a median length of stay of 4 days and an in-hospital mortality rate that exceeds 5%. Hospitalizations of patients with HF can be prevented by early detection of lung congestion. Our study assessed a new contact-free optical medical device used for the early detection of lung congestion. Methods: The Gili system is an FDA-cleared device used for measuring chest motion vibration data. Lung congestion in the study was assessed clinically and verified via two cardiologists. An algorithm was developed using machine learning techniques, and cross-validation of the findings was performed to estimate the accuracy of the algorithm. Results: A total of 227 patients were recruited (101 cases vs. 126 controls). The sensitivity and specificity for the device in our study were 0.91 (95% CI: 0.86–0.93) and 0.91 (95% CI: 0.87–0.94), respectively. In all instances, the observed estimates of PPVs and NPVs were at least 0.82 and 0.90, respectively. The accuracy of the algorithm was not affected by different covariates (including respiratory or valvular conditions). Conclusions: This study demonstrates the efficacy of a contact-free optical device for detecting lung congestion. Further validation of the study results across a larger and precise scale is warranted.

Immune checkpoint inhibitor (ICI) and coronavirus disease 2019 (COVID-19) vaccine-induced myocarditis possibly share common mechanisms secondary to overactivation of the immune system. We aimed to compare the presenting characteristics of ICIs and COVID-19 vaccine-induced myocarditis. We performed a retrospective analysis of characteristics of patients diagnosed with either ICIs or COVID-19 vaccine-induced myocarditis and compared the results to a control group of patients diagnosed with acute viral myocarditis. Eighteen patients diagnosed with ICIs (ICI group) or COVID-19 vaccine (COVID-19 vaccine group)-induced myocarditis, and 20 patients with acute viral myocarditis (Viral group) were included. The ICI group presented mainly with dyspnea vs. chest pain and fever among the COVID-19 vaccine and Viral groups. Peak median high sensitivity Troponin I was markedly lower in the ICI group (median 619 vs. 15,527 and 7388 ng/L, p = 0.004). While the median left ventricular (LV) ejection fraction was 60% among all groups, the ICI group had a lower absolute mean LV global longitudinal strain (13%) and left atrial conduit strain (17%), compared to the COVID-19 vaccine (17% and 30%) and Viral groups (18% and 37%), p = 0.016 and p = 0.001, respectively. Despite a probable similar mechanism, ICI-induced myocarditis’s presenting characteristics differed from COVID-19 vaccine-induced myocarditis.

Cyanobacteria frequently constitute integral components of microbial communities known as phototrophic biofilms, which are widespread in various environments. Moreover, assemblages of these organisms, which serve as an expression platform, simplify harvesting the biomass, thereby holding significant industrial relevance. Previous studies of the model cyanobacterium Synechococcus elongatus PCC 7942 revealed that its planktonic growth habit results from a biofilm-suppression mechanism that depends on an extracellular inhibitor, an observation that opens the door to investigating cyanobacterial intercellular communication. Here, we demonstrate that the RNA polymerase sigma factor SigF1, is required for this biofilm-suppression mechanism whereas the S. elongatus paralog SigF2 is not involved in biofilm regulation. Comprehensive transcriptome analyses identified distinct regulons under the control of each of these sigma factors. sigF1 inactivation substantially lowers transcription of genes that code for the primary pilus subunit and consequently prevents pilus assembly. Moreover, additional data demonstrate absence of the biofilm inhibitor from conditioned medium of the sigF1 mutant, further validating involvement of the pilus assembly complex in secretion of the biofilm inhibitor. Consequently, expression is significantly upregulated for the ebfG-operon that encodes matrix components and the genes that encode the corresponding secretion system, which are repressed by the biofilm inhibitor in the wild type. Thus, this study uncovers a basic regulatory component of cyanobacterial intercellular communication, a field that is in its infancy. Elevated expression of biofilm-promoting genes in a sigF1 mutant supports an additional layer of regulation by SigF1 that operates via an intracellular mechanism.

Background: Transcatheter aortic valve replacement (TAVR), although associated with an increased risk for acute kidney injury (AKI), may also result in improvement in renal function. Objective: The aim of this study is to evaluate the magnitude of kidney function improvement (KFI) after TAVR and to assess its significance on long-term mortality. Design: This is a prospective single center study. Setting: The study was conducted in cardiology department, interventional unit, in a tertiary hospital. Patients: The cohort included 1321 patients who underwent TAVR. Measurements: Serum creatinine level was measured at baseline, before the procedure, and over the next 7 days or until discharge. Methods: Kidney function improvement was defined as the mirror image of AKI, a reduction in pre-procedural to post-procedural minimal creatinine of more than 0.3 mg/dL, or a ratio of post-procedural minimal creatinine to pre-procedural creatinine of less than 0.66, up to 7 days after the procedure. Patients were categorized and compared for clinical endpoints according to post-procedural renal function change into 3 groups: KFI, AKI, or preserved kidney function (PKF). The primary endpoint was long-term all-cause mortality. Results: The incidence of KFI was 5%. In 55 out of 66 patients patients, the improvement in kidney function was minor and of unclear clinical significance. Acute kidney injury occurred in 19.1%. Estimated glomerular filtration rate (eGFR)

This paper describes and analyzes three cases to show the impact that curiosity-driven (CD) discourse based on self-video can have on the professional awareness and noticing skills of mathematics teachers and instructors of mathematics teachers. The findings indicate that CD discourse raises awareness of heretofore unnoticed events in the lesson, and improves the mathematical and pedagogical knowledge, teaching skills, and efficacy of teachers and instructors. This study combines pedagogical content knowledge (PCK) of teachers with Mason's "levels of awareness" model in studying, from an epistemological point of view, the contribution that CD discourse makes to growth of professional awareness in mathematics teachers and instructors. Thus, this study contributes to the theoretical and practical understanding of the growth of mathematics teachers as teachers and as teacher instructors, in their professional awareness, noticing skills, and attention shifting.

The association between anthracycline (ANT) and left ventricle (LV) dysfunction is well known; however, data regarding its direct effect on cardiac valve function is limited. We aimed to evaluate how ANT therapy affected valvular function in patients diagnosed with breast cancer. Data were prospectively collected as part of the Israel Cardio-Oncology Registry (ICOR). Patients underwent echocardiography exams at baseline (T1), during ANT therapy (T2), and after completion within 3 months (T3) and 6 months (T4). A total of 141 female patients were included, with a mean age of 51 ± 12 years. From T1 to T4, we observed a significant deterioration in LV ejection fraction (60.2 ± 1.5 to 59.2 ± 2.7%, p = 0.0004) and LV global longitudinal strain (−21.6 (−20.0–−23.0) to −20.0 (−19.1–−21.1)%, p < 0.0001)), and an increase in LV end-systolic diameter (25 (22–27) to 27 (24–30) mm, p < 0.0001). We observed a significant increase in the incidence of new mitral regurgitation (MR) development (4 to 19%, p < 0.0001), worsening with concomitant trastuzumab therapy (6% to 31%, p = 0.003), and a trend for tricuspid regurgitation development (4% to 8%, p = 0.19). ANT therapy is associated with the development of a new valvular disease, mainly MR, which may imply the need for a valvular focus in the monitoring of cancer patients.

Mapping neuronal networks is a central focus in neuroscience. While volume electron microscopy (vEM) can reveal the fine structure of neuronal networks (connectomics), it does not provide molecular information to identify cell types or functions. We developed an approach that uses fluorescent single-chain variable fragments (scFvs) to perform multiplexed detergent-free immunolabeling and volumetric-correlated-light-and-electron-microscopy on the same sample. We generated eight fluorescent scFvs targeting brain markers. Six fluorescent probes were imaged in the cerebellum of a female mouse, using confocal microscopy with spectral unmixing, followed by vEM of the same sample. The results provide excellent ultrastructure superimposed with multiple fluorescence channels. Using this approach, we documented a poorly described cell type, two types of mossy fiber terminals, and the subcellular localization of one type of ion channel. Because scFvs can be derived from existing monoclonal antibodies, hundreds of such probes can be generated to enable molecular overlays for connectomic studies.

Congenital diarrheas and enteropathies (CODE) are a group of rare, heterogenous, monogenic disorders that lead to chronic diarrhea in infancy. Definitive treatment is rarely available, and supportive treatment is the mainstay. Nutritional management in the form of either specialized formulas, restrictive diet, or parenteral nutrition support in CODE with poor enteral tolerance is the cornerstone of CODE treatment and long-term growth. The evidence to support the use of specific diet regimens and nutritional approaches in most CODE disorders is limited due to the rarity of these diseases and the scant published clinical experience. The goal of this review was to create a comprehensive guide for nutritional management in CODE, based on the currently available literature, disease mechanism, and the PediCODE group experience. Enteral diet management in CODE can be divided into 3 distinct conceptual frameworks: nutrient elimination, nutrient supplementation, and generalized nutrient restriction. Response to nutrient elimination or supplementation can lead to resolution or significant improvement in the chronic diarrhea of CODE and resumption of normal growth. This pattern can be seen in CODE due to carbohydrate malabsorption, defects in fat absorption, and occasionally in electrolyte transport defects. In contrast, general diet restriction is mainly supportive. However, occasionally it allows parenteral nutrition weaning or reduction over time, mainly in enteroendocrine defects and rarely in epithelial trafficking and polarity defects. Further research is required to better elucidate the role of diet in the treatment of CODE and the appropriate diet management for each disease.

BACKGROUND: Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described. METHODS: In this controlled case-ascertained household transmission study, we recruited asymptomatic children