Browse Articles

3D echocardiography derived reference values and determinants of left ventricular twist and torsion from the population-based STAAB cohort study

Abstract Left ventricular (LV) rotational function parameters provide in-depth information about LV mechanical function as well as prognostic information. Using three-dimensional (3D) echocardiography, we identified determinants of LV “twist” and “torsion”, and established reference values using a large population-based cohort. 3D echocardiography images were recorded in n = 2803 subjects within the prospective STAAB cohort study investigating a representative age- and sex-stratified sample of residents of the city of Würzburg, aged 30–79 years, without history of heart failure. Valid 3D image analysis was performed in n = 1831 (65.3%) subjects (mean age 57 ± 11 years, 49.3% women). Using general linear models, we identified determinants of LV twist and torsion: there was a positive association between LV rotational parameters and age, female sex, and blood pressure but a negative association with body weight. From a subset of 479 apparently healthy individuals exhibiting no cardiovascular (CV) risk factors or CV disease (mean age 52 ± 10 years, 56.4% women), we derived reference percentiles for twist and torsion. LV rotation is determined by a complex interplay of sub-endocardial and sub-epicardial fibers which might be affected differentially by potential risk factors. We found a differential association with respective determinants as LV rotational parameters increased with age and with higher blood pressure but decreased with higher body weight. Further research is needed to elucidate these associations in more detail and to determine the additional information contributed by twist and torsion. To facilitate respective attempts and to set an individual’s results in relation to a population-based reference, we derived normal values for twist and torsion from a sub-collective of healthy individuals.

Author Correction: Hypothalamic S1P/S1PR1 axis controls energy homeostasis

Machine learning identifies the association between second primary malignancies and postoperative radiotherapy in young-onset breast cancer patients

Background A second primary malignant tumor is one of the most important factors affecting the long-term survival of young women with breast cancer (YWBC). As one of the main treatments for breast cancer YWBC patients, postoperative radiotherapy (PORT) may increase the risk of second primary malignancy (SPM). Methods Machine learning components, including ridge regression, XGBoost, k-nearest neighbor, light gradient boosting machine, logistic regression, support vector machine, neural network, and random forest, were used to construct a predictive model and identify the risk factors for SPMs with data from the Surveillance, Epidemiology and End Results. Multivariate logistic regression analysis was used to assess the risk of SPM associated with PORT. The cumulative incidence of SPMs was determined by competing risk regression analysis. Results Among the 44223 YWBC patients included in our study, 3017 developed SPMs. Among all the clinical characteristics, PORT was the most common SPM. YWBC patients receiving PORT had significantly greater risks of second primary solid malignancies (SPSMs, RR = 1.61), including breast cancer (RR = 1.89), lung cancer (RR = 2.12) and thyroid cancer (RR = 1.48), but not second primary hematologic malignancies (RR = 1.32; 0.94–1.88). SPSMs were more common in YWBC individuals who were black, had a lower median household income and had fewer lymph nodes examined. Additionally, we developed a prediction nomogram with an area under the curve of 0.75 to assess the likelihood of developing SPMs. Conclusion YWBC patients receiving PORT had a greater risk of developing SPSMs (thyroid, lung, and breast cancer), indicating the necessity of long-term surveillance of these patients. Standard adjuvant PORT should not be recommended for breast cancer patients with favorable histology and a low risk of relapse.

Childhood Obesity and GLP-1 Receptor Agonists — A Coming of Age?

Intelligence and obesity during the obesity epidemic

Spatially controlled multicellular differentiation of stem cells using triple factor-releasing metal–organic framework-coated nanoline arrays

Analysis of the kinematic pattern of free throw by wheelchair basketball athletes: a systematic review

Athletes are stratified into classes that range from 1.0 to 4.5 points subdivided at intervals of 0.5 points in the Wheelchair Basketball (WCB) modality. The discussion regarding the non-utilization of quantitative data based on functional classification (FC) in WCB has become considerably important for research due to its impact on athletes’ careers. The aim of this systematic review was to verify the kinematic patterns of the free throw performed by WCB athletes of distinct FC. After researching four online databases, only 7 out of 68 studies fulfilled the inclusion criteria. High-class players (classes 3.0 – 4.5) presented a throw pattern, with a greater angle on the shoulder joint, on the angular speed of the wrist, and the height of the ball throw; low-class athletes (classes 1.0 – 2.5) exhibited a pushing pattern, with greater speed and throw angles, greater angular speed at the shoulder and elbow joints. Thus, inter-individual differences allow for the stratification of players into distinct classes and serve as relevant tools for increasing accuracy and performance despite different disabilities. Further studies are necessary to explore the associated patterns for each FC.

Amivantamab plus Lazertinib in Previously Untreated <i>EGFR</i> -Mutated Advanced NSCLC

Generalizability of machine learning models for diabetes detection a study with nordic islet transplant and PIMA datasets

Neurovascularization inhibiting dual responsive hydrogel for alleviating the progression of osteoarthritis

Abstract Treating osteoarthritis (OA) associated pain is a challenge with the potential to significantly improve patients lives. Here, we report on a hydrogel for extracellular RNA scavenging and releasing bevacizumab to block neurovascularization at the osteochondral interface, thereby mitigating OA pain and disease progression. The hydrogel is formed by cross-linking aldehyde-phenylboronic acid-modified sodium alginate/polyethyleneimine-grafted protocatechuic acid (OSAP/PPCA) and bevacizumab sustained-release nanoparticles (BGN@Be), termed OSPPB. The dynamic Schiff base bonds and boronic ester bonds allow for injectability, self-healing, and pH/reactive oxygen species dual responsiveness. The OSPPB hydrogel can significantly inhibit angiogenesis and neurogenesis in vitro. In an in vivo OA model, intraarticular injection of OSPPB accelerates the healing process of condyles and alleviates chronic pain by inhibiting neurovascularization at the osteochondral interface. The injectable hydrogel represents a promising technique to treat OA and OA associated pain.

Assessment of contamination of natural waters with radionuclides and heavy metals the case of Karabulak creek at the Semipalatinsk Test Site

This paper presents research data on water contamination levels of artificial radionuclides and heavy metals in Karabulak Creek at the Semipalatinsk Test Site. The uranium isotopic composition has been studied (235U and 238U). Priority contaminants and the most ‘contaminated’ sections of the Karabulak creek were identified, and water quality-related indicators were also estimated. The environmental situation around Karabulak Creek at the «Degelen» site—at which underground nuclear tests have been conducted—was found to be unique and attributed to the combined effect of man-made radiation and natural factors and, in particular, to geochemical features of the region.

Lead Poisoning

FOPID controller design for pneumatic control valves with ultra-low overshoot, rapid response and enhanced robustness

A rare PRIMER cell state in plant immunity

Abstract Plants lack specialized and mobile immune cells. Consequently, any cell type that encounters pathogens must mount immune responses and communicate with surrounding cells for successful defence. However, the diversity, spatial organization and function of cellular immune states in pathogen-infected plants are poorly understood1. Here we infect Arabidopsis thaliana leaves with bacterial pathogens that trigger or supress immune responses and integrate time-resolved single-cell transcriptomic, epigenomic and spatial transcriptomic data to identify cell states. We describe cell-state-specific gene-regulatory logic that involves transcription factors, putative cis-regulatory elements and target genes associated with disease and immunity. We show that a rare cell population emerges at the nexus of immune-active hotspots, which we designate as primary immune responder (PRIMER) cells. PRIMER cells have non-canonical immune signatures, exemplified by the expression and genome accessibility of a previously uncharacterized transcription factor, GT-3A, which contributes to plant immunity against bacterial pathogens. PRIMER cells are surrounded by another cell state (bystander) that activates genes for long-distance cell-to-cell immune signalling. Together, our findings suggest that interactions between these cell states propagate immune responses across the leaf. Our molecularly defined single-cell spatiotemporal atlas provides functional and regulatory insights into immune cell states in plants.

Hybrid universality classes of systemic cascades

Emergency care utilization by refugee children compared to controls: A statewide database analysis

Background Refugees face barriers to accessing healthcare despite provision of short-term services after arrival. Limited access to sustained primary care may lead to increased emergency department (ED) utilization and little is known regarding how refugee children access emergency care. Objective To compare the proportion of ED claims and median level of service (LOS) between refugee children and general population controls in a statewide claims database. Methods We conducted a retrospective cohort study of medical claims for patients aged 0 to 18 years old in a statewide claims database from 2014–2019. Refugee claims were identified using deterministic linkage of children with known refugee status. Procedure and diagnosis ICD9/10, Healthcare Common Procedure Coding System, and Current Procedural Terminology codes were obtained from the statewide database to indicate type of claim (ED vs outpatient) and LOS. Demographics were extracted from a data warehouse. Primary outcome was the number of ED claims per 1000 combined ED and outpatient claims. LOS was measured as a proxy for ED visit complexity. We compared demographics, frequency of claims, and median LOS using chi-square. Results There were 5,590,808 total claims with 1,235,476 ED claims. Median number of ED claims per individual patient was the same between groups, however the proportion of claims related to an ED visit was significantly higher in the refugee population than the general population controls (244 vs 221, p = 0.001). Median LOS for ED claims was Level 3 (99283) and there was no difference between groups. Conclusion Proportion of ED claims was higher in a refugee population compared to controls with no differences in LOS, indicating higher ED utilization among refugees for all acuity levels. Further study is needed to determine if healthcare disparities account for this difference and if population specific services may support the care of the refugee children.

Traveling Companions

Public health implications of multidrug-resistant and methicillin-resistant Staphylococcus aureus in retail oysters

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is a major challenge for food safety and public health. This study aimed to investigate the potential role of oysters sold in Egypt as a source for Staphylococcus aureus (S. aureus), MRSA, and multidrug-resistant methicillin-resistant Staphylococcus aureus (MDR-MRSA). It also examined the occurrence of tsst-1 virulence gene and assessed the associated zoonotic risks. Thirty-three pooled fresh oyster samples were acquired from different retail fish markets in Egypt. S. aureus was identified by conventional culture-based and molecular methods. Antimicrobial resistance was performed by the disk-diffusion method, and the multiple antibiotic resistance index (MARI) was calculated. Antimicrobial resistance (mecA and mecC) and virulence (tsst-1) genes were screened using polymerase chain reaction. The clustering of virulent MDR-MRSA isolates was performed using R with the pheatmap package. The prevalence of S. aureus was 39.4% (13 /33), and 77% of them (10/13) were classified as MDR with MARI values greater than 0.2. Notably, 46.2% (6 /13) of isolates were identified as MRSA and all MRSA isolates displayed MDR. Of the MDR-MRSA isolates, 66.7% (4 /6) possessed the mecA gene, while 16.7% (1 /6) tested positive for the mecC gene. Additionally, the tsst-1 gene was identified in one isolate (16.7%). Interestingly, two MDR-MRSA isolates exhibited a clustered pattern. The study sheds light on the emergence of virulent MDR-MRSA isolates in Egyptian oysters. It highlights oysters as a potential source for spreading these isolates within aquatic ecosystems, posing a threat to food safety and public health.

Topology controls flow patterns in active double emulsions

Nutraceutical COMP-4 confers protection against endothelial dysfunction through the eNOS/iNOS-NO-cGMP pathway

The nutraceutical COMP-4 –consisting of L-citrulline, ginger extract, and herbal components Paullinia cupana and muira puama–has been shown previously to stimulate the production of nitric oxide (NO) in a variety of tissue types. We hypothesized that COMP-4 may have a protective, stimulatory effect on the vascular endothelial cell. Human umbilical arterial endothelial cells were incubated for 24 hours with or without COMP-4 and, to replicate impairment of endothelial function, co-incubated with or without H2O2. NO intracellular content, nitrite formation and cGMP content in culture media, nitric oxide synthase (NOS) isoforms and mRNA content, pro-inflammatory cytokines, and PAI-1 expression and activity were measured. COMP-4 increased endothelial cell production of NO and cGMP and the expression of both endothelial NOS (eNOS) and inducible NOS (iNOS), in tandem with a reduction in cytokine expression and activity of PAI-1. Co-incubation of COMP-4 with H2O2 reversed detrimental effects of H2O2 on endothelial function, evidenced by improvement in NO availability and abrogation of the pro-inflammatory milieu. These results suggest that COMP-4 exerts a stimulatory effect on endothelial cell eNOS and iNOS to increase NO bioavailability, leading to a reduction in pro-inflammatory cytokines, particularly the prothrombotic PAI-1.