Miracle-dz/UniFAR-FTUs huggingface dataset:
Single Cell Transcriptomics and Solid Organ Transplantation.

Single cell RNA-sequencing (scRNA-seq) allows the measurement of transcriptomes from individual cells providing new insights into complex biological systems. scRNA-seq has enabled the identification of rare cell types, new cell states and intercellular communication networks that may be masked by traditional bulk transcriptional profiling. Researchers are increasingly using scRNA-seq to comprehensively characterize complex organs in health and disease. The diversity of immune cell types, some present at low frequency, in a transplanted organ undergoing rejection makes scRNA-seq ideally suited to characterize transplant pathologies because it can quantify subtle transcriptional differences between rare cell types. In this review we discuss single cell sequencing methods and their application in transplantation to date, current challenges and future directions. We believe that the remarkably rapid pace of technological development in this field makes it likely that single cell technologies such as scRNA-seq will have an impact in clinical transplantation within a decade.
Diagnostic Accuracy of Serum, Synovial, and Tissue Testing for Chronic Periprosthetic Joint Infection After Hip and Knee Replacements: A Systematic Review

Background: Chronic periprosthetic joint infection (PJI) is a devastating complication that can occur following total joint replacement. Patients with chronic PJI report a substantially lower quality of life and face a higher risk of short-term mortality. Establishing a diagnosis of chronic PJI is challenging because of conflicting guidelines, numerous tests, and limited evidence. Delays in diagnosing PJI are associated with poorer outcomes and morbid revision surgery. The purpose of this systematic review was to compare the diagnostic accuracy of serum, synovial, and tissue-based tests for chronic PJI. Methods: This review adheres to the Cochrane Collaboration’s diagnostic test accuracy methods for evidence searching and syntheses. A detailed search of MEDLINE, Embase, the Cochrane Library, and the grey literature was performed to identify studies involving the diagnosis of chronic PJI in patients with hip or knee replacement. Eligible studies were assessed for quality and bias using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Meta-analyses were performed on tests with sufficient data points. Summary estimates and hierarchical summary receiver operating characteristic (HSROC) curves were obtained using a bivariate model. Results: A total of 12,616 citations were identified, and 203 studies met the inclusion criteria. Of these 203 studies, 170 had a high risk of bias. Eighty-three unique PJI diagnostic tests were identified, and 17 underwent meta-analyses. Laboratory-based synovial alpha-defensin tests and leukocyte esterase reagent (LER) strips (2+) had the best performance, followed by white blood-cell (WBC) count, measurement of synovial C-reactive protein (CRP) level, measurement of the polymorphonuclear neutrophil percentage (PMN%), and the alpha-defensin lateral flow test kit (Youden index ranging from 0.78 to 0.94). Tissue-based tests and 3 serum tests (measurement of interleukin-6 [IL-6] level, CRP level, and erythrocyte sedimentation rate [ESR]) had a Youden index between 0.61 to 0.75 but exhibited poorer performance compared with the synovial tests mentioned above. Conclusions: The quality of the literature pertaining to chronic PJI diagnostic tests is heterogeneous, and the studies are at a high risk for bias. We believe that greater transparency and more complete reporting in studies of diagnostic test results should be mandated by peer-reviewed journals. The available literature suggests that several synovial fluid-based tests perform well for diagnosing chronic PJI and their use is recommended in the work-up of any suspected case of chronic PJI. Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Acute Kinematic Effects of Sprinting With Motorized Assistance

Abstract Clark, K, Cahill, M, Korfist, C, and Whitacre, T. Acute kinematic effects of sprinting with motorized assistance. J Strength Cond Res 35(7): 1856–1864, 2021—Although assisted sprinting has become popular for training maximum velocity, the acute effects are not fully understood. To examine this modality, 14 developmental male sprinters (age: 18.0 ± 2.5 years, 100-m personal best: 10.80 ± 0.31 seconds) performed maximal trials, both unassisted and assisted with a motorized towing device using a load of 7 kg (9.9 ± 0.9% body mass). Significant increases in maximum velocity (+9.4%, p ≤ 0.001, d = 3.28) occurred due to very large increases in stride length (+8.7%, p ≤ 0.001, d = 2.04) but not stride rate (+0.7%, p = 0.36, d = 0.11). Stride length increased due to small changes in distance traveled by the center of mass during ground contact (+3.7%, p ≤ 0.001, d = 0.40) combined with very large changes in distance traveled by the center of mass during flight (+13.1%, p ≤ 0.001, d = 2.62). Although stride rate did not demonstrate significant between-condition differences, the combination of contact and flight time was different. Compared to unassisted sprinting, assisted sprinting caused small but significant decreases in contact time (−5.2%, p ≤ 0.001, d = 0.49) and small but significant increases in flight time (+3.4%, p < 0.05, d = 0.58). Sprinting with motorized assistance elicited supramaximal velocities with decreased contact times, which may represent a neuromuscular stimulus for athletes attempting to enhance sprinting performance. Future research is needed to investigate the effects of this modality across various assistive loads and athletic populations, and to determine the longitudinal efficacy as a training method for improving maximum-velocity sprinting performance.
Effect of Fe3O4 Nanoparticles on Mixed POPC/DPPC Monolayers at Air-Water Interface

Fe3O4 nanoparticles (NPs) as a commonly used carrier in targeted drug delivery are widely used to carry drugs for the treatment of diseases. However, the mechanism of action of between Fe3O4 NPs and biological membranes is still unclear. Therefore, this article reports the influence of hydrophilic and hydrophobic Fe3O4 NPs on mixed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) that were studied using the Langmuir-Blodgett (LB) film technique and an atomic force microscope (AFM). From surface pressure-area (π-A) isotherms, we have calculated the compression modulus. The results showed that hydrophobic Fe3O4 NPs enlarged the liquid-expanded (LE) and liquid-condensed (LC) phase of the mixed POPC/DPPC monolayers. The compressibility modulus of the mixed POPC/DPPC monolayer increases for hydrophilic Fe3O4 NPs, but the opposite happens for the hydrophobic Fe3O4 NPs. The adsorption of hydrophobic Fe3O4 NPs in mixed POPC/DPPC monolayers was much more than the hydrophilic Fe3O4 NPs. The interaction of hydrophilic Fe3O4 NPs with the head polar group of the mixed lipids increased the attraction force among the molecules, while the interaction of hydrophobic Fe3O4 NPs with the tail chain of the mixed lipids enhanced the repulsive force. The morphology of the monolayers was observed by AFM for validating the inferred results. This study is of great help for the application of Fe3O4 NPs in biological systems.
Role of elastin peptides and elastin receptor complex in metabolic and cardiovascular diseases

The Cardiovascular Continuum describes a sequence of events from cardiovascular risk factors to end‐stage heart disease. It includes conventional pathologies affecting cardiovascular functions such as hypertension, atherosclerosis or thrombosis and was traditionally considered from the metabolic point of view. This Cardiovascular Continuum, originally described by Dzau and Braunwald, was extended by O'Rourke to consider also the crucial role played by degradation of elastic fibers, occurring during aging, in the appearance of vascular stiffness, another deleterious risk factor of the continuum. However, the involvement of the elastin degradation products, named elastin‐derived peptides, to the Cardiovascular Continuum progression has not been considered before. Data from our laboratory and others clearly showed that these bioactive peptides are central regulators of this continuum, thereby amplifying appearance and evolution of cardiovascular risk factors such as diabetes or hypertension, of vascular alterations such as atherothrombosis and calcification, but also nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. The Elastin Receptor Complex has been shown to be a crucial actor in these processes. We propose here the participation of these elastin‐derived peptides and of the Elastin Receptor Complex in these events, and introduce a revisited Cardiovascular Continuum based on their involvement, for which elastin‐based pharmacological strategies could have a strong impact in the future.
Taiji: System-level identification of key transcription factors reveals transcriptional waves in mouse embryonic development

A novel method for identifying genes with global importance leads to the discovery of transcriptional waves during embryogenesis. Transcriptional regulation is pivotal to the specification of distinct cell types during embryonic development. However, it still lacks a systematic way to identify key transcription factors (TFs) orchestrating the temporal and tissue specificity of gene expression. Here, we integrated epigenomic and transcriptomic data to reveal key regulators from two cells to postnatal day 0 in mouse embryogenesis. We predicted three-dimensional chromatin interactions in 12 tissues across eight developmental stages, which facilitates linking TFs to their target genes for constructing transcriptional regulatory networks. To identify driver TFs, we developed a new algorithm, dubbed Taiji, to assess the global influence of each TF and systematically uncovered TFs critical for lineage-specific and stage-dependent tissue specification. We have also identified TF combinations that function in spatiotemporal order to form transcriptional waves regulating developmental progress. Furthermore, lacking stage-specific TF combinations suggests a distributed timing strategy to orchestrate the coordination between tissues during embryonic development.
Goblet cells and mucus layer in the gut of young pigs: Response to dietary contents of threonine and non-essential amino acids.

Mucins secreted by goblet cells (GC) are the major components of mucus layer coating and protecting gut epithelium. The study aimed at determining the effect of non-essential amino acids (NEAA) and threonine (Thr) levels on GC number and mucus layer thickness measured in different parts of the gut. A two-factorial experiment was conducted on 72 pigs (initial BW 12.5 kg) using as factors: Thr level (5.1, 5.7, 6.3 and 6.9 g standardized ileal digestible [SID] Thr/kg) and wheat gluten (WG) level used as a source of NEAA (20.4, 40.4 and 60.4 g WG protein in WG20, WG40 and WG60 diets respectively). All diets covered the requirement for essential AA, except for Thr, and they were fed to six pigs for 20 days. Thr level affected only the count of GC containing acidic mucins in the proximal colon, which was higher in pigs fed a diet with 5.1 g SID Thr/kg in comparison with diet containing 6.3 g SID Thr/kg. In the villi, WG40 and/or WG60 increased the GC number containing acidic mucins and lowered that with neutral mucins in the middle jejunum. In the crypts, higher WG levels decreased the GC number with acidic mucins in the duodenum, ileum and proximal colon and increased that with neutral and mixed mucins in the duodenum and ileum. The mucus layer was thicker in the proximal and middle jejunum in WG20 pigs, whereas in the proximal colon it was thicker in WG60 pigs. The lowest GC count was found in the middle jejunum and the highest in the duodenum and proximal colon. The mucus layer was the thinnest in the proximal and middle jejunum and the thickest in the ileum. The results did not show the negative effect of a moderate Thr deficiency and the positive effect of non-essential AA supplementation on GC functions.
Entrustable professional activities in health care education: a scoping review

The shift in medical education from time‐based learning to outcome‐based learning has drawn much attention to entrustable professional activities (EPAs) as an ideal assessment framework to translate competencies into clinical practice. Given the relative novelty of EPAs, this review aims to highlight research gaps and explore and consolidate available evidence pertaining to the development and implementation of EPAs in health care.
Inquiry into the correlation between burnout and depression.

The extent to which burnout refers to anything other than a depressive condition remains an object of controversy among occupational health specialists. In three studies conducted in two different countries and two different languages, we investigated the discriminant validity of burnout scales by evaluating the magnitude of the correlation between (latent) burnout and (latent) depression. In Study 1 (N = 911), burnout was assessed with the Maslach Burnout Inventory-General Survey's Exhaustion subscale and depression with the depression module of the Patient Health Questionnaire (PHQ). In Study 2 (N = 1,386), the Shirom-Melamed Burnout Measure was used to assess burnout and the PHQ, depression. In Study 3 (N = 734), burnout was assessed with the Maslach Burnout Inventory-Educators Survey and depression, with the PHQ and the Center for Epidemiological Studies Depression scale; additionally, anxiety was measured with the Generalized Anxiety Disorder scale. In each study, we examined the burnout-depression association based on confirmatory factor analysis (CFA), controlling for item-level content overlap. In the three studies, latent exhaustion, the core of burnout, and latent depression were highly correlated (correlations ranging from .83 to .88). In Studies 2 and 3, second-order CFAs indicated that depressive (and anxiety) symptoms and the exhaustion and depersonalization components of burnout are reflective of the same second-order distress/dysphoria factor. Our findings, with their replication across samples, languages, and measures, together with meta-analytic findings, cast serious doubt on the discriminant validity of the burnout construct. The implications of burnout's problematic discriminant validity are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
The links of hepcidin and erythropoietin in the interplay of inflammation and iron deficiency in a large observational study of rheumatoid arthritis

Anaemia affects quality of life and radiographic outcome in rheumatoid arthritis (RA). In a cross‐sectional study with 779 patients, we assessed the prognostic potential of the major haematopoietic regulators, hepcidin and erythropoietin, comparing their serum concentrations with respect to different anaemia types, inflammatory activity, anti‐cytokine‐specific treatment effects and iron deficiency (ID) indices. The results showed that clinical disease activity was more closely associated with haemoglobin levels than with anti‐tumour necrosis factor‐alpha or interleukin 6 receptor effects. In ID, hepcidin was suppressed, independently of inflammation. Erythropoietin levels were inappropriately low in relation to the degree of anaemia, but, in contrast to low haemoglobin, not directly associated with joint damage progression. Hepcidin and erythropoietin levels are intimately connected with inflammation and ID. Interventional studies on these important targets are already in progress.
Evaluating the impact of social-media on sales forecasting: a quantitative study of world's biggest brands using Twitter, Facebook and Google Trends

In the world of digital communication, data from online sources such as social networks might provide additional information about changing consumer interest and significantly improve the accuracy of forecasting models. In this thesis I investigate whether information from Twitter, Facebook and Google Trends have the ability to improve daily sales forecasts for companies with respect to the forecasts from transactional sales data only. My original contribution to this domain, exposed in the present thesis, consists in the following main steps: 1. Data collection. I collected Twitter, Facebook and Google Trends data for the period May 2013 May 2015 for 75 brands. Historical transactional sales data was supplied by Certona Corporation. 2. Sentiment analysis. I introduced a new sentiment classification approach based on combining the two standard techniques (lexicon-based and machine learning based). The proposed method outperforms the state-of-the-art approach by 7% in F-score. 3. Identification and classification of events. I proposed a framework for events detection and a robust method for clustering Twitter events into different types based on the shape of the Twitter volume and sentiment peaks. This approach allows to capture the varying dynamics of information propagation through the social network. I provide empirical evidence that it is possible to identify types of Twitter events that have significant power to predict spikes in sales. 4. Forecasting next day sales. I explored linear, non-linear and cointegrating relationships between sales and social-media variables for 18 brands and showed that social-media variables can improve daily sales forecasts for the majority of brands by capturing factors, such as consumer sentiment and brand perception. Moreover, I identified that social-media data without sales information, can be used to predict sales direction with the accuracy of 63%. The experts from the industry consider the results obtained in this thesis to be valuable and useful for decision making and for making strategic planning for the future.
Suboptimal T-cell Therapy Drives a Tumor Cell Mutator Phenotype That Promotes Escape from First-Line Treatment

Suboptimal antitumor immunotherapy increases genomic instability in tumor cells by inducing APOBEC3. Resulting mutations can promote tumor cell escape from co-applied therapies. Immunotherapies should be optimized early to prevent a direct enhancement of tumor cell escape. Antitumor T-cell responses raised by first-line therapies such as chemotherapy, radiation, tumor cell vaccines, and viroimmunotherapy tend to be weak, both quantitatively (low frequency) and qualitatively (low affinity). We show here that T cells that recognize tumor-associated antigens can directly kill tumor cells if used at high effector-to-target ratios. However, when these tumor-reactive T cells were present at suboptimal ratios, direct T-cell–mediated tumor cell killing was reduced and the ability of tumor cells to evolve away from a coapplied therapy (oncolytic or suicide gene therapy) was promoted. This T-cell–mediated increase in therapeutic resistance was associated with C to T transition mutations that are characteristic of APOBEC3 cytosine deaminase activity and was induced through a TNFα and protein kinase C–dependent pathway. Short hairpin RNA inhibition of endogenous APOBEC3 reduced rates of tumor escape from oncolytic virus or suicide gene therapy to those seen in the absence of antitumor T-cell coculture. Conversely, overexpression of human APOBEC3B in tumor cells enhanced escape from suicide gene therapy and oncolytic virus therapy both in vitro and in vivo. Our data suggest that weak affinity or low frequency T-cell responses against tumor antigens may contribute to the ability of tumor cells to evolve away from first-line therapies. We conclude that immunotherapies need to be optimized as early as possible so that, if they do not kill the tumor completely, they do not promote treatment resistance.
The Kronos Early Estrogen Prevention Study (KEEPS): what have we learned?

Abstract Objective: The Kronos Early Estrogen Prevention Study (KEEPS) was designed to address gaps in understanding the effects of timely menopausal hormone treatments (HT) on cardiovascular health and other effects of menopause after the premature termination of the Women's Health Initiative. Method: The KEEPS was a randomized, double-blinded, placebo-controlled trial to test the hypothesis that initiation of HT (oral conjugated equine estrogens [o-CEE] or transdermal 17β-estradiol [t-E2]) in healthy, recently postmenopausal women (n = 727) would slow the progression of atherosclerosis as measured by changes in carotid artery intima-media thickness (CIMT). Results: After 4 years, neither HT affected the rate of increase in CIMT. There was a trend for reduced accumulation of coronary artery calcium with o-CEE. There were no severe adverse effects, including venous thrombosis. Several ancillary studies demonstrated a positive effect on mood with o-CEE, and reduced hot flashes, improved sleep, and maintenance of bone mineral density with both treatments. Sexual function improved with t-E2. There were no significant effects of either treatment on cognition, breast pain, or skin wrinkling. Variants of genes associated with estrogen metabolism influenced the age of menopause and variability in effects of the HT on CIMT. Platelet activation associated with the development of white matter hyperintensities in the brain. Conclusions: KEEPS and its ancillary studies have supported the value and safety of the use of HT in recently postmenopausal women and provide a perspective for future research to optimize HT and health of postmenopausal women. The KEEPS continuation study continues to pursue these issues.
Radioactive seed localization and wire guided localization in breast cancer: A systematic review and meta-analysis.

PURPOSE Classically, wire-guided localization (WGL) is used for the localization of non palpable breast lesions. On the other hand, many studies report a newer technique called radioactive seed localization (RSL). The purpose of our study was a systematic review and meta analysis of the two techniques regarding the rate of positive margins and the quantity of excised tissue. METHODS Our study searched publications up to March 24th 2018 in Medline, Embase and Cochrane Library regarding studies comparing the two techniques of localization of subclinical lesions with WGL or RSL using technetium 99m as radioactive agent. The primary target was the rate of positive margins and the second was the rate of second surgery for reexcision. Revman5.3 and STATE12.0 were used for the statistics. RESULTS Five randomized controlled trials (RCTs) and 13 cohort studies comprising 3879 breast cancer patients were included. RSL was significantly superior than WGL both in better margin status (RR=0.72, 95% CI 0.56-0.92, p=0.01) and reduced reoperation rate (RR=0.68, 95% CI 0.52-0.88, p=0.004). Subgroup analysis of RCTs showed no different ability of both techniques in terms of free margin status (RR=0.85, 95% CI 0.55-1.31, p=0.46) and reoperation rate (RR=0.80, 95% CI 0.48-1.32, p=0.38). Further subgroup analysis excluding three studies with different ductal carcinoma in situ (DCIS) proportion exhibited same efficacy in margin negativity (RR=0.83, 95% CI 0.69-1.01, p=0.07) and further operation rate (RR=0.85, 95% CI 0.71-1.01, p=0.07).