Subsequent Measurements Research Articles

Quantification of Rapid Cooling of Glycerol/Water Solutions Based on Photoluminescence from Thioflavin T.

Rapid cooling to a solid state allows intermediates in chemical and biomolecular processes that occur in solution near room temperature to be trapped for subsequent measurements by magnetic resonance spectroscopies, electron microscopy, or other techniques. In time-resolved solid state nuclear magnetic resonance and rapid freeze-quench electron paramagnetic resonance studies, solutions are typically frozen by spraying into a cold bath or onto a cold metal surface. Although simulations suggest freezing on millisecond or submillisecond time scales, direct experimental measurements of cooling rates have been elusive. Here, we describe a method for quantification of rapid cooling rates based on measurements of temperature-dependent photoluminescence from thioflavin T (ThT). In our experiments, a jet of ThT solution in glycerol/water, with 10.8 m/s jet velocity and 30 μm diameter, freezes on a cold, rotating copper surface. Images of ThT photoluminescence on the copper surface indicate that the cooling rate of the solution increases linearly with the surface velocity over the 0.45-6.2 m/s range. At surface velocities greater than 3.8 m/s, the time to cool from 300 to 260 K or from 300 to 230 K is less than 100 μs or less than 700 μs. The experimental results do not agree quantitatively with calculations in which a layer of glycerol/water cools by thermal conduction when suddenly brought in contact with a cold copper surface. Discrepancies between experimental results and simplistic calculations illustrate the importance of direct measurements of cooling rates.

Cut-offs for relapse detection in men with stage I testicular germ cell tumors during active surveillance within a prospective multicentre cohort study using either raw or housekeeper normalized miR-371a-3p serum levels

PurposeMiR-371a-3p represents a novel liquid biomarker that detects all histologies of germ-cell tumors (GCT) except teratoma. However, it is currently unclear whether miR-371a-3p results obtained directly from RT-PCR (raw Cq) or normalized for housekeeper genes and transformed into the relative quantity (RQ) value should be used and at what cut-off level. The purpose of this research was to evaluate, which values should be used, and a potential cut-off level for relapse-detection to inform subsequent studies. Materials and MethodsWe applied a CE-certified qRT-PCR test to measure miR-371a-3p at each follow-up visit during active surveillance in 34 men with stage I testicular GCT. MiR-371a-3p levels were calculated by the ΔΔ method. ResultsAbout 18 Patients had pure seminoma and 16 had mixed or nonseminomatous testicular GCT. Recurrences were detected in 10 patients and were correctly identified by both raw and housekeeper-normalized miR-371a-3p serum levels. The raw Cq, with a cut-off value of <28, resulted in only 1 false positive (3%), whereas RQ, with a cut-off value of >15, produced 6 false positive results (17%). Most of these false positive results normalized in subsequent measurements. The RQ approach detected recurrence in 1 patient 6 months earlier than the raw Cq approach. ConclusionOur preliminary data suggest that this CE-certified assay, using previously suggested cut-off values, is a promising method for detecting disease recurrence, provided a confirmatory second test is conducted to identify false positive results. To avoid unnecessary scans or overtreatment, we are currently validating this assay and cut-offs in a prospective cohort study.

Comparative evaluation of the upper pharyngeal airway among children with/without UCLP and with/without OSA.

To evaluate the volume and the most constricted cross-sectional area (lumen) sizes of the upper pharyngeal airway among children with/without unilateral cleft lip and palate (UCLP) and with/without obstructive sleep apnea (OSA). This prospective study was conducted on 66 Thai children aged 5 to 12 years, encompassing demographic information, polysomnographic data, and sex distribution: 34 with non-syndromic UCLP (16 with OSA; 18 without OSA) and 32 non-cleft children (16 with OSA; 16 without OSA). Subjects were divided into two age groups: preadolescent group (ages 10-12) and younger group (ages 5-9). Cone-beam computed tomography images were acquired with subjects in a supine position. Subsequent measurements were conducted using the Dolphin imaging program (version 11.7 premium) to investigate and compare the volumes and lumens of the nasopharyngeal, oropharyngeal, and hypopharyngeal airways. In the younger group, the UCLP with OSA group exhibited significantly smaller volumes and lumens in the oropharyngeal airway compared to the non-cleft group without OSA (volume: p = 0.044; lumen: p = 0.031, 95% CI). All upper pharyngeal airway parts had comparable volumes and lumens between age groups. However, preadolescence reported no significant differences. Statistically significant differences were observed only in the oropharyngeal airway measurements in the younger sample compared to the adolescent sample. This underscores the importance of considering oropharyngeal airway structure in diagnosing and preventing OSA in children. However, it is essential to note that while airway size is a fundamental factor, it may not be the sole determinant of OSA occurrence. Other factors likely contribute to the condition as well.

Weakly-Supervised Hair SEM Microscope Image Segmentation Using a Priori Structure Information

The analysis of microscopic images of hair has a wide range of applications in the domains of cosmetics, healthcare and forensics. The segmentation of the hair represents the initial step of automatic large-scale quantitative analysis of microscopic images of hair. It ensures that subsequent quantitative measurements are performed in an appropriate area corresponding to the hair, avoiding artifacts near the boundaries. This process can be time-consuming, tedious and susceptible to subjective errors when conducted by a human operator. Deep learning methods represent a promising solution; however, obtaining pixel-level accurate masks is a costly process. This paper presents a novel weakly supervised pipeline for the segmentation of hair SEM (Scanning Electron Microscope) microscopic images, which requires only simple image-level annotations for training. The proposed method incorporates the Radon transform, the Sobel operator and a novel Boundary Discrimination Module (BD-module) for the estimation of the presence of boundaries. The proposed pipeline was evaluated on a recently collected hair SEM dataset (429 images). Furthermore, it is benchmarked with methods including Unet and Segment Anything Model (SAM). The results demonstrated a mean Hausdorff Distance improvement of over 30% and a standard deviation improvement of over 50% in comparison with the Unet and SAM. Moreover, we proposed additional refinement modules to address boundary nonlinear cases and conducted Grad-CAM analysis to enhance the interpretability of the BD-module. Additionally, we proposed a novel quality estimation metric based on gradient map for self-quality assessment. The SEM hair dataset is accessible to the research community in an open-source format.

Safety evaluation and modulatory effects on innate immune system of pyrazoline-derived compounds.

Pyrazolines are compounds that have been studied for their strong biological potential and structure diversity. Several studies demonstrated their biological effectiveness, highlighting their anti-inflammatory potential. This study aimed to evaluate the physicochemical profile, the safety, and the anti-inflammatory effects of four pyrazolines (PH0, PH3, PH4, and PH7). Initially, in silico analysis were performed on SwissADME and QSAR Toolbox platforms. The anti-inflammatory activity was assessed by in vitro and in vivo methodologies. Neutrophils collected from mice peritoneum and macrophages immortalized cell line (Raw 264.7) were stimulated with lipopolysaccharide (LPS), and subsequent measurement of nitric oxide (NO) and IL-1β, TNF, and IL-6 cytokines were performed by ELISA method. The effect on cell migration was evaluated by chemotaxis assay. The effect on efferocytosis was investigated using senescent neutrophils and macrophages from mice's bone marrow. The in silico results suggest suitable properties for a pharmacological prototype for oral administration, with no significant toxic effects. All compounds significantly reduced NO levels, as well as levels of IL-1β, TNF, and IL-6 cytokines. Also, they were able to reduce cell migration and increase efferocytosis. The in vivo air pouch model confirmed the effects of pyrazolines on cell kinetics and on the levels of cytokines (IL-1β and TNF) on the air pouch lavage. All of the pyrazolines evaluated showed to have positive effects on mechanisms that modulate the inflammatory response. Furthermore, the in silico analysis suggests that chemical changes in the structure can lead to improvement of the biological and pharmacokinetics proprieties.

Densely Populated Cell and Organelles Segmentation With Multi-Plane Deep Learning Pipeline.

Here we develop a robust machine vision pipeline for cell and organelle segmentation within vEM datasets. We collect neural network predictions along multiple planes, capturing 3D correlations using only 2D neural networks. We segment and analyze hundreds of platelets and report quantitative morphological measurements. We apply our segmentation pipeline to the CREMI neuron segmentation challenge data and provide state-of-the-art results. Our work paves the way for large-scale platelet studies and lends unique insight into platelet structure. We publish a lightweight Jupyter notebook for initializing and running the neural network. We also provide Amira Avizo protocols for converting neural network outputs to cell and organelle instances and subsequent morphological measurements.

Abstract 4137672: Prevalence, Clinical Characteristics, and Outcomes in Heart Failure with Improved Ejection Fraction by Sex

Background: Heart failure with improved ejection fraction (HFimpEF) is a growing clinical entity. While males are more likely to present with HFrEF, there remains little understanding of how sex relates to the epidemiology, predictors, and progression of HFimpEF. Research Question: What are the differences in epidemiology, clinical characteristics, medical management, and outcomes in patients (pts) with HFimpEF based on sex. Methods: We identified adults age ≥18 years with incident HFrEF (EF ≤40%) between January 2013 and December 2018 within Kaiser Permanente Northern California, an integrated health system serving &gt;4.5 million members. HFimpEF was defined as subsequent EF measurement &gt;40% within the following 12 months. Sex was based on self-report. Among pts with HFimpEF, we examined guideline-directed medical therapy (GDMT) use at time of incident HFimpEF, and at 6- and 12-months post-HFimpEF, stratified by sex. The incidence of worsening HF (WHF) events and all-cause death was assessed in a landmark analysis at 12 months post-HFrEF. We compared event rates between patients with HFimpEF and persistent HFrEF using Cox proportional hazards models adjusted for baseline age and EF. Results: Among 12,639 patients with incident HFrEF (female: 36%), 33% experienced HFimpEF. Females were more likely to experience HFimpEF in the 12 months following HFrEF than males (34% vs. 32%, p&lt;0.01). Among pts with HFimpEF, treatment with GDMT was similar among males and females and declined after incident HFimpEF in both sexes (Figure, Panel A). Females had similar rates of WHF or all-cause death compared to males (adjusted [a]HR: 1.10, 95% CI: 0.96, 1.26, P=0.17). Compared with those with persistent HFrEF, pts with HFimpEF had lower rates of WHF or all-cause death, a finding which was consistent by sex (male: aHR: 0.55, 95% CI: 0.50 to 0.61, female: aHR: 0.54, 95% CI: 0.48 to 0.62; Pinteraction by sex=0.78; Figure, Panel B). Conclusions: HFimpEF is more common among females compared to males, but prognosis is similar. Despite similar medical therapy, GDMT discontinuation after EF improvement is prevalent. Improvement in EF is similarly associated with improved outcomes across sex. Further data are needed to elucidate the differential etiologies of HF by sex.

Measurement of Steam-Generator-Tube Vibration Damping Caused by Anti-Vibration-Bar Supports

Abstract In 2013, Atomic Energy of Canada Limited (now Canadian Nuclear Laboratories) experimentally measured the damping of a straight tube with a variety of tube supports to examine low-frequency damping. These tests were motivated by the discovery of severe tube damage caused by in-plane fluidelastic instability (FEI) in the U-bend regions of new replacement recirculating steam generators (SG). The measurements were intended to assess the applicability of existing design guidelines for estimating the support-related damping of a tube. In the tests, the damping ratios of a single steam generator tube were measured using both log-decrement and power-based methods. Noncontacting excitation and position-sensing techniques were employed to improve accuracy. Initial baseline tests explored configurations with no support and drilled-hole supports of different hole sizes, and these results were compared with previously published work. Subsequent tests were performed to measure damping of tube vibration parallel to flat-bar supports. Most of the tests were performed with the tube fully submerged in still water. The tests examined the effects of fluid (water or air), natural frequency, gap width, preload, and vibration normal to the bars. This paper describes the test apparatus, methods, and analysis techniques. A summary of the results is presented. The initial baseline results showed that the damping ratios measured without any supports and with a drilled-hole support were consistent with previously published data. However, the subsequent measurements showed that, contrary to a published design guideline, the anti-vibration bars resulted in no significant additional viscous or squeeze-film damping when the vibration was parallel to the bars. On the other hand, the results did show that anti-vibration bars could introduce significant in-plane Coulomb-type damping if there was sufficient tube-to-support preload or impacting.

PRAKTIK JUAL BELI BIBIT LELE DENGAN SISTEM TAKARAN PERSPEKTIF HUKUM ISLAM DAN HUKUM POSITIF

The growing public interest in catfish farming has resulted in an increased demand for catfish fingerlings. This trend has led many individuals to engage in the trade of catfish fingerlings, either as a primary source of income through the establishment of fisheries groups or as a supplementary means of generating additional revenue. This study aims to investigate the implementation of the catfish fingerling trading system based on volume measurement from the perspectives of Islamic law and positive law. Utilizing a qualitative research approach, primary data were collected through interviews and documentation. The primary data sources include informants from fisheries business groups and individuals involved in the trade of catfish fingerlings using the volume-based measurement system. The findings reveal that the volume measurement system is employed to simplify the calculation process, although the initial reference measurement is not consistently aligned with subsequent measurements. Nonetheless, both parties agree to add an additional volume as compensation for potential mortality of the fingerlings. From the perspective of Islamic law, the catfish fingerling trading practices in Gunung Sembung Village, Pegaden Subdistrict, Subang Regency, fulfill the essential elements and conditions required for lawful transactions under Islamic law and are deemed valid according to positive law, as they conform to existing legal regulations.

Evaluation of early cardiotoxicity in HER2-positive breast cancer patients receiving radiotherapy and concurrent trastuzumab.

Overexpression of human epidermal growth factor receptor 2 (HER-2) is associated with aggressive disease in breast cancer. Trastuzumab and radiotherapy are standard treatments for patients with HER-2 + breast cancer, but they may increase the risk of cardiotoxicity. This study aimed to assess early cardiotoxicity in patients receiving radiotherapy (RT) and concurrent trastuzumab. The study included 116 patients with HER-2 + breast cancer who received concurrent treatment with trastuzumab and RT (52 right-side; 64 left-side). Five left ventricular ejection fraction (LVEF) measurements were performed: one before treatment and four subsequent measurements taken at three-month intervals. LVEF was also assessed before (preRT-EF) and after (postRT-EF) radiotherapy. The baseline LVEF was 62.27 ± 5.5%, while the 12-month LVEF was 59.8 ± 5.8% (p < 0.05). In subgroups, post-RT LVEF values ​​were significantly lower than pre-RT LVEF values (p < 0.05). No significant difference was found between the reduction in LVEF for patients receiving 50Gy and 60Gy doses. Moreover, the contribution of regional lymph node irradiation to the decrease in LVEF could not be demonstrated. A positive correlation was found between the total trastuzumab dose and the decrease in LVEF from preRT to postRT. Additionally, a positive correlation was observed between the total taxane dose and the reduction in LVEF from baseline to 9months, both in the overall group and in the left breast cancer group. In our study,it was found that not only trastuzumab but also taxane-based agents could be cardiotoxic. However, no connection was found between RT doses and the decrease in LVEF.

Specific loss of GIPR signaling in GABAergic neurons enhances GLP-1R agonist-induced body weight loss

ObjectivesDual incretin agonists are among the most effective pharmaceutical treatments for obesity and type 2 diabetes to date. Such therapeutics can target two receptors, such as the glucagon-like peptide-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor in the case of tirzepatide, to improve glycemia and reduce body weight. Regarding body weight effects, GIPR signaling is thought to involve at least two relevant mechanisms: the enhancement of food intake reduction and the attenuation of aversive effects caused by GLP-1R agonists. Although it is known that dual GLP-1R-GIPR agonism produces greater weight loss than GLP-1R agonism alone, the precise mechanism is unknown. MethodsTo address this question, we used mice lacking GIPR in the whole body, GABAergic neurons, or glutamatergic neurons. These mice were given various combinations of GLP-1R and GIPR agonist drugs with subsequent food intake and conditioned taste aversion measurements. ResultsA GIPR knockout in either the whole body or selectively in inhibitory GABAergic neurons protects against diet-induced obesity, whereas a knockout in excitatory glutamatergic neurons had a negligible effect. Furthermore, we found that GIPR in GABAergic neurons is essential for the enhanced weight loss efficacy of dual incretin agonism, yet, surprisingly, its removal enhances the effect of GLP-1R agonism alone. Finally, GIPR knockout in GABAergic neurons prevents the anti-aversive effects of GIPR agonism. ConclusionsOur findings are consistent with GIPR research at large in that both enhancement and removal of GIPR signaling are metabolically beneficial. Notably, however, our findings suggest that future obesity therapies designed to modulate GIPR signaling, whether by agonism or antagonism, would be best targeted towards GABAergic neurons.

Neighborhood Social and Physical Environments and Sedentary Behaviors: Importance of Early Childhood in Shaping Health Behaviors.

This study aims to investigate the persistence of sedentary behaviors from early childhood to adolescence and the longitudinal association between neighborhood social and physical environments and childhood sedentary behaviors. Using the Future of Families & Child Wellbeing Study (N = 2716), we conducted a cross-lagged path analysis to examine the longitudinal association between neighborhood social and physical environments (neighborhood socioeconomic status, observed physical disorder, and crime rates) and sedentary behaviors at subsequent measurement points, after controlling for demographic factors and family socioeconomic status. We observed the continuity of sedentary behaviors in early childhood, extending throughout adolescence. Neighborhood socioeconomic status was significantly associated with sedentary behaviors at subsequent measurement points from early childhood to adolescence. Observation-based physical disorder and crime rates were associated with engagement in greater sedentary behaviors in adolescence but not in early and middle childhood. We also observed a partial mediation effect of neighborhood physical disorder and crime rates in the association between neighborhood socioeconomic status and sedentary behaviors in adolescence. Our results demonstrated the importance of early childhood in shaping healthy behaviors and highlighted the contribution of unfavorable environments to sedentary behaviors. These findings call for the need to support disadvantaged neighborhoods, particularly by addressing safety concerns and physical disorder, for promoting physical activity and reducing sedentary behaviors among adolescents.

The relationship between sense of coherence and self-efficacy with well-being and mental health-the situation of students at a typical German university during the COVID-19 pandemic and 1 year after the lifting of social restrictions.

The present study aims to evaluate the role of sense of coherence and self-efficacy in relation to mental health and well-being, with and without social restrictions due to the COVID-19 pandemic. Additionally, this study seeks to investigate the differences in sense of coherence, self-efficacy, mental health and well-being depending on the manner in which the pandemic is being handled. A total of 27,162 students at Heidelberg University were surveyed via email at two measurement points, once with and once without social restrictions. The survey assessed sense of coherence, self-efficacy, mental health and well-being. To this end, the questionnaires Sense of Coherence Scale, Patient Health Questionnaire, WHO-Well-being-Index and the General Self-Efficacy Scale were employed. A total of 2,398 individuals participated in the initial measurement, while 701 individuals participated in the subsequent measurement. The lifting of social restrictions has been associated with a notable improvement in well-being and mental health, particularly in the context of depressive syndromes. Further analysis demonstrated a positive correlation between the sense of coherence and self-efficacy at both measurement points, as well as between these two constructs and mental health and well-being. Furthermore, the sense of coherence and self-efficacy were found to account for a notable proportion of the observed variability in mental health and well-being values. Self-efficacy exhibited a significantly higher mean value at the initial measurement time point compared to the subsequent time point. In contrast, no significant difference was observed in the sense of coherence between the two measurement points. The findings presented here illustrate the significance of social interaction, sense of coherence and self-efficacy for mental health and well-being.

Circulating Angiopoietin-2 (Angpt2) levels predict diagnosis of Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Abstract Background Vascular remodeling following incomplete thrombus resolution is considered to be a key factor in the progression to chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE). Recent data demonstrated that Angpt2, which controls signaling via the Tie2 receptor, could interfere with the normal process of thrombus resolution. Our prior findings have shown that patients presenting with acute PE and having plasma levels of Angt-2 ≥5.5 ng/ml at admission are at a significantly increased risk (93 times higher) of being diagnosed with CTEPH in subsequent assessments. Purpose To externally validate the prognostic performance of Angpt2 for the development of CTEPH. Methods In a prospective cohort study of unselected consecutive all-comers with PE, survivors of the index acute event underwent 3-, 12- and 24-month follow-up with venous blood sampling for subsequent biomarker measurements. Angpt2 was measured on admission using specific enzyme linked immunosorbent assays (ELISA) detecting both the endogenous and the recombinant protein, according to the manufacturer (R&amp;D Systems). Results Overall, 319 patients with acute PE (median age: 62 [IQR, 50-73]; females: 55.2%) were included in the analysis with a median Angpt2 plasma level of 2.6 ng/ml (IQR, 1.8-3.7) (Figure 1). Patients with PE and Angpt-2 plasma levels above the median had more often comorbidities, such as chronic heart failure (24.2% and 11.0.%; p=0.045), chronic kidney disease (33.3% vs 14.0%; p=0.010), or diabetes (27.3% vs. 12.9%; p=0.032). Angpt2 plasma levels correlated with haemodynamic status and parameters indicating severe PE (right ventricle dysfunction, r=0.129 [p=0.021) and troponin, r=0.246 [p&amp;lt;0.001]). In total, post-PE impairment (PPEI) was diagnosed in 33 (10.3%) and CTEPH in four (1.3%) patients during follow-up. Angpt2 plasma levels were higher on admission in patients developing PPEI or CTEPH during follow-up compared to patients without PPEI or CTEPH (PPEI vs non-PPEI: median, 3.2 [2.3-4.1] ng/ml vs. 2.5 [1-3.4] ng/ml, p=0.035; CTEPH vs. non-CTEPH: median, 5.1 [2.9-10.5] ng/ml vs. 2.5 [1.7-3.6] ng/ml, p=0.055). Regarding the diagnosis of CTEPH during follow-up, ROC analysis illustrated an AUC for Angpt2 (0.779 [95% CI 0.56–0.99]; p=0.055]) (Figure 2). By using univariate logistic regression analysis, the calculated predefined Angpt2 cut-off value of ≥5.5 ng/ml was associated with a 9.2-fold increased risk (1.3–67.4, p=0.030) for a diagnosis of CTEPH during follow-up. Conclusion We were able to validate in a different patient cohort the usefulness of Angpt2 as a novel biomarker to identify patients at risk for CTEPH.

Neutron skins: A perspective from dispersive optical models

An overview of neutron skin predictions obtained using an empirical nonlocal dispersive optical model (DOM) is presented. The DOM links both scattering and bound-state experimental data through a subtracted dispersion relation which allows for fully consistent, data-informed predictions for nuclei where such data exist. Large skins were predicted for both 48Ca (Rskin48=0.25±0.023 fm in 2017) and 208Pb (Rskin208=0.25±0.05 fm in 2020). Whereas the DOM prediction in 208Pb is within 1σ of the subsequent PREX-2 measurement, the DOM prediction in 48Ca is over 2σ larger than the thin neutron skin resulting from CREX. From the moment it was revealed, the thin skin in 48Ca has puzzled the nuclear-physics community as no adequate theories simultaneously predict both a large skin in 208Pb and a small skin in 48Ca. The DOM is unique in its ability to treat both structure and reaction data on the same footing, providing a unique perspective on this Rskin puzzle. It appears vital that more neutron data be measured in both the scattering and bound-state domain for 48Ca to clarify the situation.

Defibrillator shocks and their effect on objective asian patient outcomes: results of the painfree SST clinical trial

Abstract Background The implantable cardioverter defibrillator (ICD) reduces mortality in patients at risk of sudden cardiac death. However, the effect of ICD shock on device-measured activity is unknown. The aim of this analysis was to analyze the acute and long-term effects of ICD shock on objective behavioral data. Methods The PainFree SST study was a prospective, multicenter, global study that enrolled 2770 patients including 225 from from Asia (181 from Japan, 25 from India, and 19 from Malaysia). Patient physical activity was determined from the device built-in accelerometer. The device translates the accelerometer output into a count of active minutes, which is stored as a daily total value in device memory for a rolling window of 425 days. Obviously, activity is measured only after device implantation. Early after implant, activity is reduced due to the procedure and thus not representative. Therefore, no baseline can be reported for activity. The follow-up activity data was analyzed with a linear mixed model, with a random effect for patient and an auto-regressive correlation matrix for subsequent measurements of individual patients. Results Figure 1 shows average daily activity between 90 days before and 90 days after a shock. The dashed vertical line indicates the day of shock. Both patients from Asia and from other countries show a drop in activity after a shock with recovery in the subsequent 30-60 days. The curve for Asian patients is more variable than the curve for other countries due to the lower number of patients (there were 33 Asian patients with shocks contributing data). Figure 2 shows average daily activity before and after ATP therapy. Any post shock measurement is excluded. Contrary to the temporary reduction in activity around a shock (Figure 1), ATP therapies do not seem to have an impact on activity. In patients from the other countries, activity is significantly reduced when patients are hospitalized (-66.3 minutes/day, p&amp;lt;0.0001), but not in Asian patients (-5.1 minutes/day, p=0.71). Both in Asian and other countries, activity is significantly reduced after an ICD shock (Asian: -47.5 minutes/day, p=0.0002; Other countries: -21.5 minutes/day, p&amp;lt;0.0001). The effect of shock for Asian is greater than the other countries (p=0.054). In the month after the shock there is a significant recovery, +34.8 minutes/day in Asian patients (p=0.0077) and +7.7 minutes/day in patients from other countries (p=0.031). The recovery is trended to be bigger in Asian patients (p=0.058). Conclusions ICD shocks have a lasting adverse impact on objective, device-measured physical activity, particularly among Asian individuals. Successful management of patients with an ICD necessitates specific attention to clinically relevant behavioral outcomes, aiming to expedite recovery and facilitate a return to activities of daily living, with a particular focus on the Asian population.

Overcoming fixation and permeabilization challenges in flow cytometry by optical barcoding and multi-pass acquisition.

The fixation and permeabilization of cells are essential for labeling intracellular biomarkers in flow cytometry. However, these chemical treatments often alter fragile targets, such as cell surface and fluorescent proteins (FPs), and can destroy chemically-sensitive fluorescent labels. This reduces measurement accuracy and introduces compromises into sample workflows, leading to losses in data quality. Here, we demonstrate a novel multi-pass flow cytometry approach to address this long-standing problem. Our technique utilizes individual cell barcoding with laser particles, enabling sequential analysis of the same cells with single-cell resolution maintained. Chemically-fragile protein markers and their fluorochrome conjugates are measured prior to destructive sample processing and adjoined to subsequent measurements of intracellular markers after fixation and permeabilization. We demonstrate the effectiveness of our technique in accurately measuring intracellular FPs and methanol-sensitive antigens and fluorophores, along with various surface and intracellular markers. This approach significantly enhances assay flexibility, enabling accurate and comprehensive cellular analysis without the constraints of conventional one-time measurement flow cytometry. This innovation paves new avenues in flow cytometry for a wide range of applications in immuno-oncology, stem cell research, and cell biology.

Beating the clock: the impact of heart failure duration on CRT efficacy

Abstract Background Cardiac Resynchronization Therapy (CRT) stands as an established intervention for selected patients with heart failure (HF) presenting with a wide QRS complex. The optimal timing for CRT implantation remains uncertain. Current evidence suggests superior outcomes post-CRT in patients who have not been previously hospitalised for HF and those receiving the implant during their initial hospitalisation for HF.1 Purpose The primary objective of this study is to investigate the long-term clinical outcomes following CRT implantation relative to the duration of HF previous to the implant. It was analysed in a cohort of consecutive patients from a HF Unit who met the criteria for CRT as recommended by the ESC guidelines (QRS duration ≥150ms, left bundle branch block morphology, and left ventricular ejection fraction (LVEF) ≤35% despite optimal medical therapy). Methods We evaluated all patients who received CRT from January 2011 through September 2022. Follow-up ended in September 2023. Patients with CRT indicated for ventricular pacing due to high-degree atrioventricular block were excluded. Patients were categorized into two groups based on the duration of HF progression prior to CRT implantation: more than 3 years and 3 years or less. The primary outcome was all-cause mortality (ACM). Secondary outcomes included a composite of ACM and HF hospitalisation and the proportion of patients who demonstrated a significant improvement in LVEF (defined as an increase of ≥10% from baseline and a subsequent measurement of LVEF ≥40%). Results The cohort consisted of 127 patients, mean age 65.8±10.7 years, 23.6% were women, mean LVEF was 28.4±8.6% and 36.2% had ischaemic aetiology (Table 1). 62 patients either died or were hospitalized for HF. Mean follow-up was 4.9±2.7 years. After adjusting for age, sex and baseline LVEF, patients with HF for more than three years before CRT implantation had a worse prognosis: HRs of 2.31 for ACM (p=0.016) and 2.13 for the combined endpoint of ACM+HFH (p=0.010) (Figure 1). The proportion of patients with improved LVEF after CRT was significantly higher in the group with shorter HF duration (68.25%) compared to the group with longer HF duration (25%), p &amp;lt;0.001. Conclusions Our findings reveal that patients with a shorter history of HF (less than three years) prior to CRT implantation exhibit significantly better clinical outcomes. These results highlight the role of early intervention with CRT in patients with HF, suggesting that shorter HF duration prior to CRT may lead to more favourable long-term outcomes.

Assessment of a new index of myocardial strain for the diagnosis of cardiac sarcoidosis

Abstract Background The diagnosis of cardiac involvement in sarcoidosis is challenging and often expensive. Purpose The aim of this study is to assess whether a new strain index proposed by the authors has incremental value in the evaluation of cardiac involvement, compared to the use of left ventricular (LV) global longitudinal strain (GLS). Methods This is a single-center, non-blinded, pilot cross-sectional study. Patients of both genders, &amp;gt;18 years old, with confirmed diagnosis of cardiac sarcoidosis according to the Heart Rhythm Society criteria, and controls consisting of individuals diagnosed with systemic sarcoidosis without cardiac involvement, were included. Patients with obesity grade 2 or higher , moderate or severe primary heart valve disease, myocardial diseases of other etiologies, established coronary artery disease, and inadequate acoustic window were excluded. All patients underwent transthoracic echocardiography, with subsequent measurements performed on a workstation. The following LV indexes were evaluated: GLS and the new proposed index, calculated by the ratio between LVEF and the sum of the two segments with the lowest absolute strain values. ROC curves were calculated for both parameters using an online dedicated software, with determination of the optimal cutoff point for both variables, corresponding to the point of highest sensitivity and specificity. Confidence intervals were established by the DeLong method, and curves were compared using the Bonferroni method. A two-tailed p value of 0.05 was considered significant. Results Twenty patients with cardiac involvement and twenty patients without cardiac involvement were evaluated. The results of the variables are presented in table 1. Conclusions The new index showed a larger area under the curve compared to isolated GLS, as well as higher sensitivity and specificity for the identified cutoff point, although without statistical significance, possibly due to the small sample size. Further studies are needed for subsequent validation of this innovative index.

Operando Surface X‐Ray Diffraction Studies of Epitaxial Co3O4 and CoOOH Thin Films During Oxygen Evolution: pH Dependence

AbstractTransition metal oxides, especially cobalt oxides and hydroxides, are of great interest as precious metal free electrode materials for the oxygen evolution reaction (OER) in electrochemical and photoelectrochemical water splitting. Here, we present detailed studies of the potential‐ and pH‐dependent structure and structural stability of Co3O4 and CoOOH in neutral to alkaline electrolytes (pH 7 to 13), using operando surface X‐ray diffraction, atomic force microscopy, and electrochemical measurements. The experiments cover the pre‐OER and OER range and were performed on epitaxial Co3O4(111) and CoOOH(001) films electrodeposited on Au(111) single crystal electrodes. The CoOOH films were structurally perfectly stable under all experimental conditions, whereas Co3O4 films exhibit at all pH values reversible potential‐dependent structural transformations of a sub‐nanometer thick skin layer region at the oxide surface, as reported previously for pH 13 (F. Reikowski et al., ACS Catal. 2019, 9, 3811). The intrinsic OER activity at 1.65 V versus the reversible hydrogen electrode decreases strongly with decreasing pH, indicating a reaction order of 0.2 with respect to [OH−]. While the Co3O4 spinel is stable at pH 13, intermittent exposure to electrolytes with pH≤10 results in dissolution as well as gradual degradation of its OER activity in subsequent measurements at pH 13.