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Abstract In baseball pitchers the elbow is exposed to high and repetitive loads (i.e. external valgus torque), caused by pitching a high number of balls in a practice session or game. This can result in overuse injuries like the ulnar collateral ligament (UCL) injury. To understand injury mechanisms, the effect of repetitive pitching on the elbow load magnitude and variability was investigated. In addition, we explored whether repetitive pitching affects elbow muscle activation during pitching. Fifteen pitchers threw each 60 to 110 balls. The external valgus torque and electromyography of three elbow muscles were quantified during each pitch. Linear mixed model analyses were performed to investigate the effect of repetitive pitching. On a group level, the linear mixed models showed no significant associations of repetitive pitching with valgus torque magnitude and variability and elbow muscle activity. Significant differences exist between pitchers in their individual trajectories in elbow valgus torque and muscle activity with repetitive pitching. This shows the importance of individuality in relation to repetitive pitching. In order to achieve effective elbow injury prevention in baseball pitching, individual characteristics of changes in elbow load and muscle activity in relation to the development of UCL injuries should be investigated.

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental condition with onset in early childhood, still diagnosed only through clinical observation due to the lack of laboratory biomarkers. Early detection strategies would be especially useful in screening high-risk newborn siblings of children already diagnosed with ASD. We performed RNA sequencing on peripheral blood, comparing 27 pairs of ASD children vs their sex- and age-matched unaffected siblings. Differential gene expression profiling, performed applying an unpaired model found two immune genes, EGR1 and IGKV3D-15, significantly upregulated in ASD patients (both p adj = 0.037). Weighted gene correlation network analysis identified 18 co-expressed modules. One of these modules was downregulated among autistic individuals (p = 0.035) and a ROC curve using its eigengene values yielded an AUC of 0.62. Genes in this module are primarily involved in transcriptional control and its hub gene, RACK1, encodes for a signaling protein critical for neurodevelopment and innate immunity, whose expression is influenced by various hormones and known "endocrine disruptors". These results indicate that transcriptomic biomarkers can contribute to the sensitivity of an intra-familial multimarker panel for ASD and provide further evidence that neurodevelopment, innate immunity and transcriptional regulation are key to ASD pathogenesis.

Abstract The student population has been highly vulnerable to the risk of mental health deterioration during the coronavirus disease (COVID-19) pandemic. This study aimed to reveal the prevalence and predictors of mental health among students in Poland, Slovenia, Czechia, Ukraine, Russia, Germany, Turkey, Israel, and Colombia in a socioeconomic context during the COVID-19 pandemic. The study was conducted among 2349 students (69% women) from May–July 2020. Data were collected by means of the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-8), Perceived Stress Scale (PSS-10), Gender Inequality Index (GII), Standard & Poor's Global Ratings, the Oxford COVID-19 Government Response Tracker (OxCGRT), and a sociodemographic survey. Descriptive statistics and Bayesian multilevel skew-normal regression analyses were conducted. The prevalence of high stress, depression, and generalized anxiety symptoms in the total sample was 61.30%, 40.3%, and 30%, respectively. The multilevel Bayesian model showed that female sex was a credible predictor of PSS-10, GAD-7, and PHQ-8 scores. In addition, place of residence (town) and educational level (first-cycle studies) were risk factors for the PHQ-8. This study showed that mental health issues are alarming in the student population. Regular psychological support should be provided to students by universities.

Abstract During the various stages of shock loading, many transient modes of deformation can activate and deactivate to affect the final state of a material. In order to fundamentally understand and optimize a shock response, researchers seek the ability to probe these modes in real-time and measure the microstructural evolutions with nanoscale resolution. Neither post-mortem analysis on recovered samples nor continuum-based methods during shock testing meet both requirements. High-speed diffraction offers a solution, but the interpretation of diffractograms suffers numerous debates and uncertainties. By atomistically simulating the shock, X-ray diffraction, and electron diffraction of three representative BCC and FCC metallic systems, we systematically isolated the characteristic fingerprints of salient deformation modes, such as dislocation slip (stacking faults), deformation twinning, and phase transformation as observed in experimental diffractograms. This study demonstrates how to use simulated diffractograms to connect the contributions from concurrent deformation modes to the evolutions of both 1D line profiles and 2D patterns for diffractograms from single crystals. Harnessing these fingerprints alongside information on local pressures and plasticity contributions facilitate the interpretation of shock experiments with cutting-edge resolution in both space and time.

Abstract The pathophysiology behind thrombus formation in paroxysmal atrial fibrillation (AF) patients is very complex. This can be due to left atrial (LA) flow changes, remodeling, or both. We investigated differences for cardiovascular magnetic resonance (CMR)-derived LA 4D flow and remodeling characteristics between paroxysmal AF patients and patients without cardiac disease. In this proof-of-concept study, the 4D flow data were acquired in 10 patients with paroxysmal AF (age = 61 ± 8 years) and 5 age/gender matched controls (age = 56 ± 1 years) during sinus rhythm. The following LA and LA appendage flow parameters were obtained: flow velocity (mean, peak), stasis defined as the relative volume with velocities

The efficacy of an implantable cardioverter-defibrillator (ICD) in patients with a non-ischaemic cardiomyopathy for primary prevention of sudden cardiac death is increasingly debated. We developed a multimodal deep learning model for arrhythmic risk prediction that integrated late gadolinium enhanced (LGE) cardiac magnetic resonance imaging (MRI), electrocardiography (ECG) and clinical data. Short-axis LGE-MRI scans and 12-lead ECGs were retrospectively collected from a cohort of 289 patients prior to ICD implantation, across two tertiary hospitals. A residual variational autoencoder was developed to extract physiological features from LGE-MRI and ECG, and used as inputs for a machine learning model (DEEP RISK) to predict malignant ventricular arrhythmia onset. In the validation cohort, the multimodal DEEP RISK model predicted malignant ventricular arrhythmias with an area under the receiver operating characteristic curve (AUROC) of 0.84 (95% confidence interval (CI) 0.71–0.96), a sensitivity of 0.98 (95% CI 0.75–1.00) and a specificity of 0.73 (95% CI 0.58–0.97). The models trained on individual modalities exhibited lower AUROC values compared to DEEP RISK [MRI branch: 0.80 (95% CI 0.65–0.94), ECG branch: 0.54 (95% CI 0.26–0.82), Clinical branch: 0.64 (95% CI 0.39–0.87)]. These results suggest that a multimodal model achieves high prognostic accuracy in predicting ventricular arrhythmias in a cohort of patients with non-ischaemic systolic heart failure, using data collected prior to ICD implantation. [ABSTRACT FROM AUTHOR]

Abstract Carbonate concretions are known to contain well-preserved fossils and soft tissues. Recently, biomolecules (e.g. cholesterol) and molecular fossils (biomarkers) were also discovered in a 380 million-year-old concretion, revealing their importance in exceptional preservation of biosignatures. Here, we used a range of microanalytical techniques, biomarkers and compound specific isotope analyses to report the presence of red and white blood cell-like structures as well as platelet-like structures, collagen and cholesterol in an ichthyosaur bone encapsulated in a carbonate concretion from the Early Jurassic (~182.7 Ma). The red blood cell-like structures are four to five times smaller than those identified in modern organisms. Transmission electron microscopy (TEM) analysis revealed that the red blood cell-like structures are organic in composition. We propose that the small size of the blood cell-like structures results from an evolutionary adaptation to the prolonged low oxygen atmospheric levels prevailing during the 70 Ma when ichthyosaurs thrived. The δ13C of the ichthyosaur bone cholesterol indicates that it largely derives from a higher level in the food chain and is consistent with a fish and cephalopod diet. The combined findings above demonstrate that carbonate concretions create isolated environments that promote exceptional preservation of fragile tissues and biomolecules.

Abstract Selection of microorganisms in marine sediment is shaped by energy-yielding electron acceptors for respiration that are depleted in vertical succession. However, some taxa have been reported to reflect past depositional conditions suggesting they have experienced weak selection after burial. In sediments underlying the Arabian Sea oxygen minimum zone (OMZ), we performed the first metagenomic profiling of sedimentary DNA at centennial-scale resolution in the context of a multi-proxy paleoclimate reconstruction. While vertical distributions of sulfate reducing bacteria and methanogens indicate energy-based selection typical of anoxic marine sediments, 5–15% of taxa per sample exhibit depth-independent stratigraphies indicative of paleoenvironmental selection over relatively short geological timescales. Despite being vertically separated, indicator taxa deposited under OMZ conditions were more similar to one another than those deposited in bioturbated intervals under intervening higher oxygen. The genomic potential for denitrification also correlated with palaeo-OMZ proxies, independent of sediment depth and available nitrate and nitrite. However, metagenomes revealed mixed acid and Entner-Dourdoroff fermentation pathways encoded by many of the same denitrifier groups. Fermentation thus may explain the subsistence of these facultatively anaerobic microbes whose stratigraphy follows changing paleoceanographic conditions. At least for certain taxa, our analysis provides evidence of their paleoenvironmental selection over the last glacial-interglacial cycle.

Sediments from Tibetan lakes in NW China are potentially sensitive recorders of climate change and its impact on ecosystem function. However, the important plankton members in many Tibetan Lakes do not make and leave microscopically diagnostic features in the sedimentary record. Here we established a taxon-specific molecular approach to specifically identify and quantify sedimentary ancient DNA (sedaDNA) of non-fossilized planktonic organisms preserved in a 5-m sediment core from Kusai Lake spanning the last 3100 years. The reliability of the approach was validated with multiple independent genetic markers. Parallel analyses of the geochemistry of the core and paleo-climate proxies revealed that Monsoon strength-driven changes in nutrient availability, temperature, and salinity as well as orbitally-driven changes in light intensity were all responsible for the observed temporal changes in the abundance of two dominant phytoplankton groups in the lake, Synechococcus (cyanobacteria) and Isochrysis (haptophyte algae). Collectively our data show that global and regional climatic events exhibited a strong influence on the paleoecology of phototrophic plankton in Kusai Lake. [ABSTRACT FROM AUTHOR]

Compton imaging represents a promising technique for range verification in proton therapy treatments. In this work, we report on the advantageous aspects of the i-TED detector for proton-range monitoring, based on the results of the first Monte Carlo study of its applicability to this field. i-TED is an array of Compton cameras, that have been specifically designed for neutron-capture nuclear physics experiments, which are characterized by [Formula: see text]-ray energies spanning up to 5-6 MeV, rather low [Formula: see text]-ray emission yields and very intense neutron induced [Formula: see text]-ray backgrounds. Our developments to cope with these three aspects are concomitant with those required in the field of hadron therapy, especially in terms of high efficiency for real-time monitoring, low sensitivity to neutron backgrounds and reliable performance at the high [Formula: see text]-ray energies. We find that signal-to-background ratios can be appreciably improved with i-TED thanks to its light-weight design and the low neutron-capture cross sections of its LaCl[Formula: see text] crystals, when compared to other similar systems based on LYSO, CdZnTe or LaBr[Formula: see text]. Its high time-resolution (CRT [Formula: see text] 500 ps) represents an additional advantage for background suppression when operated in pulsed HT mode. Each i-TED Compton module features two detection planes of very large LaCl[Formula: see text] monolithic crystals, thereby achieving a high efficiency in coincidence of 0.2% for a point-like 1 MeV [Formula: see text]-ray source at 5 cm distance. This leads to sufficient statistics for reliable image reconstruction with an array of four i-TED detectors assuming clinical intensities of 10[Formula: see text] protons per treatment point. The use of a two-plane design instead of three-planes has been preferred owing to the higher attainable efficiency for double time-coincidences than for threefold events. The loss of full-energy events for high energy [Formula: see text]-rays is compensated by means of machine-learning based algorithms, which allow one to enhance the signal-to-total ratio up to a factor of 2., (© 2022. The Author(s).)

The early treatment and rapid closure of acute or chronic wounds is essential for normal healing and prevention of hypertrophic scarring. The use of split thickness autografts is often limited by the availability of a suitable area of healthy donor skin to harvest. Cellular and non-cellular biological skin-equivalents are commonly used as an alternative treatment option for these patients, however these treatments usually involve multiple surgical procedures and associated with high costs of production and repeated wound treatment. Here we describe a novel design and a proof-of-concept validation of a mobile skin bioprinting system that provides rapid on-site management of extensive wounds. Integrated imaging technology facilitated the precise delivery of either autologous or allogeneic dermal fibroblasts and epidermal keratinocytes directly into an injured area, replicating the layered skin structure. Excisional wounds bioprinted with layered autologous dermal fibroblasts and epidermal keratinocytes in a hydrogel carrier showed rapid wound closure, reduced contraction and accelerated re-epithelialization. These regenerated tissues had a dermal structure and composition similar to healthy skin, with extensive collagen deposition arranged in large, organized fibers, extensive mature vascular formation and proliferating keratinocytes.