Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential effects of heat‐inactivated, secretome‐deficient MSC and metabolically active MSC in sepsis and allogenic heart transplantation

Mesenchymal stem cells (MSCs) are used in various clinical and preclinical models for immunomodulation. However, it remains unclear how the immunomodulatory effect of MSC is communicated. MSC‐induced immunomodulation is known to be mediated through both MSC‐secreted cytokines and direct cell‐cell interactions. Recently, it has been demonstrated that metabolically inactive, heat‐inactivated MSCs (HI‐MSCs) have similar anti‐inflammatory capacities in LPS‐induced sepsis compared with viable MSC. To further investigate the immunomodulatory effects of MSC, we introduced MSC and HI‐MSC in two animal models with different immunological causes. In the first model, allogeneic hearts were transplanted from C57BL/6 mice to BALB/c recipients. MSC in combination with mycophenolate mofetil (MMF) significantly improved graft survival compared with MMF alone, whereas the application of HI‐MSC had no effect on graft survival. We revealed that control MSC dose‐dependently inhibited CD3+ and CD8+ T‐cell proliferation in vitro, whereas HI‐MSC had no effect. In the second model, sepsis was induced in mice via cecal ligation and puncture. HI‐MSC treatment significantly improved the overall survival, whereas control MSCs had no effect. in vitro studies demonstrated that HI‐MSCs are more effectively phagocytosed by monocytes than control MSCs and induced cell death in particular of activated CD16+ monocytes, which may explain the immune protective effect of HI‐MSC in the sepsis model. The results of our study demonstrate that MSC‐mediated immunomodulation in sepsis is dependent on a passive recognition of MSC by monocytes, whereas fully functional MSCs are required for inhibition of T‐cell‐mediated allograft rejection.
Transplacental Transmission of Theileria equi Is Not a Common Cause of Abortions and Infection of Foals in Israel

Simple Summary Theileria equi is a parasite of horses that is mainly transmitted by ticks but has also been reported to be transmitted from infected mares to their foals during pregnancy. This type of transmission may lead to abortion or to the birth of sick or infected foals. Little data are available regarding the magnitude of this type of transmission, although T. equi is considered to be a major cause of abortion in some areas. The aim of this study was to determine if T. equi is often transferred from mares to foals in an area where this parasite is abundant. We found that although the majority of aborting mares carried the parasite, none of the aborted fetuses were infected. Further, in a farm where all mares were infected, only one foal was infected by 6 months of age, and that infection was probably not from its dam. Although the number of inspected animals was small, our findings suggest that T. equi is not frequently transferred to foals during pregnancies of carrier mares. Abstract Although the main route of transmission of Theileria equi is through tick feeding, transplacental transmission is also possible and may lead to abortion, or to the birth of a sick or carrier foal. The aim of this study was to evaluate the role of T. equi as a cause of abortions in Israel and the risk of foals being infected at a young age. Eight aborting mares were serologically evaluated for exposure to T. equi via the immunofluorescence antibody test (IFAT) and their aborted fetuses were evaluated using PCR and qPCR. In addition, five mares and their foals (aged 4–6 months) from a highly endemic farm were tested for T. equi infection using IFAT, PCR and qPCR. Five of the eight aborting mares were seropositive for T. equi; however, none of the aborted fetuses was infected. All five mares from the endemic farm were subclinically infected with T. equi. Of their five foals, one was infected, with relatively high parasitemia and different parasite genotype than its dam’s, suggesting another source of infection. The results of this study suggest that transplacental transmission of T. equi is not common and does not appear to be a prominent cause of abortion in chronically infected mares.
Combined Aerobic and Resistance Exercise Training Reduces Circulating Apolipoprotein J Levels and Improves Insulin Resistance in Postmenopausal Diabetic Women

Background Circulating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in patients with type 2 diabetes mellitus. Methods Postmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE, n=30) or control (CON, n=15) group. Participants in the EXE group were enrolled in a 12-week program consisting of a combination of aerobic and resistance exercises. At baseline, 4, 8, and 12 weeks, body composition and metabolic parameters including homeostatic model assessment of insulin resistance (HOMA-IR) and serum ApoJ levels were assessed. Results In the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (P<0.05 and P<0.001, respectively). In the EXE group, 12 weeks of exercise resulted in significant decreases in body weight, percent body fat, and HOMA-IR indices. Concurrently, weight-adjusted appendicular skeletal muscle mass (ASM/wt) was increased in the EXE group compared with the CON group. Importantly, changes in the ApoJ level were significantly correlated with changes in ASM/wt. Conclusion Exercise training resulted in a significant decrease in the circulating ApoJ level, with changes in ApoJ associated with an improvement in some insulin resistance indices. These data suggest that circulating ApoJ may be a useful metabolic marker for assessing the effects of exercise on insulin resistance.
Ultrastructural localisation of the α4 nicotinic acetylcholine receptor subunit in rat nigro-striatal neurons

Within the mammalian central nervous system, pentameric nicotinic acetylcholine receptors (nAChR) are assembled from a portfolio of 11 subunits, (a2-7,9 & 10 and p 2-4), giving the potential for numerous nAChR subtypes with different pharmacological and functional properties. Presynaptic nAChRs that modulate neurotransmitter release are widespread in the CNS, and the nicotinic stimulation of dopamine release from striatal slices and synaptosomes has been well characterised (Wonnacott 1997, Wonnacott et al. 2000). Pharmacological evidence implicates the contribution of both a3p2* and a4p2* nAChR subtypes on dopamine terminals in the striatum (Kaiser et al. 1998, Sharpies et al. 2000). The aim of this study was to examine a4 nAChR subunit immunoreactivity in axonal boutons in the dorsal striatum to determine the distribution at dopaminergic terminals in light of the pharmacological data. Previous studies have only investigated the cell bodies of dopaminergic neurons to the ultrastructural level (Sorenson et al. 1998, Arroyo-Jimenez et al.1999). Using five available anti-a4 nAChR subunit antibodies, light and confocal microscopy studies revealed a4 nAChR subunit immunoreactivity in tyrosine hydroxylase (TH) positive (dopaminergic) perikarya and dendrites in the substantia nigra pars compacta (SNc). At this resolution there was no apparent labelling of the striatum, in agreement with previous studies (Sorenson et al. 1998, Arroyo-Jimenez et al. 1999). However, immunolabelling was observed in striatal synaptosome preparations, although this labelling appeared to be inconsistent between the antibodies used. Attempts at labelling tissue for ultrastructural analysis were restricted by the loss of antigenicity in glutaraldehyde fixed tissue. Investigation of several fixation regimes determined that paraformaldehyde-lysine-periodate (PLP) fixative provided good ultrastructural morphology and retained enough antigenicity to enable immunolabelling. The labelling seen at the ultrastructural level was weak compared to light level experiments, there again appeared to be inconsistencies between the antibody labelling patterns, raising questions about antibody specificity. In an attempt to determine which antibodies were specific, western blot and immunoprecipitation was performed for each antibody, on rat, wild type (WT) and
Ribosome and Translational Control in Stem Cells

Embryonic stem cells (ESCs) and adult stem cells (ASCs) possess the remarkable capacity to self-renew while remaining poised to differentiate into multiple progenies in the context of a rapidly developing embryo or in steady-state tissues, respectively. This ability is controlled by complex genetic programs, which are dynamically orchestrated at different steps of gene expression, including chromatin remodeling, mRNA transcription, processing, and stability. In addition to maintaining stem cell homeostasis, these molecular processes need to be rapidly rewired to coordinate complex physiological modifications required to redirect cell fate in response to environmental clues, such as differentiation signals or tissue injuries. Although chromatin remodeling and mRNA expression have been extensively studied in stem cells, accumulating evidence suggests that stem cell transcriptomes and proteomes are poorly correlated and that stem cell properties require finely tuned protein synthesis. In addition, many studies have shown that the biogenesis of the translation machinery, the ribosome, is decisive for sustaining ESC and ASC properties. Therefore, these observations emphasize the importance of translational control in stem cell homeostasis and fate decisions. In this review, we will provide the most recent literature describing how ribosome biogenesis and translational control regulate stem cell functions and are crucial for accommodating proteome remodeling in response to changes in stem cell fate.
Brain Tumor Analysis Empowered with Deep Learning: A Review, Taxonomy, and Future Challenges

Deep Learning (DL) algorithms enabled computational models consist of multiple processing layers that represent data with multiple levels of abstraction. In recent years, usage of deep learning is rapidly proliferating in almost every domain, especially in medical image processing, medical image analysis, and bioinformatics. Consequently, deep learning has dramatically changed and improved the means of recognition, prediction, and diagnosis effectively in numerous areas of healthcare such as pathology, brain tumor, lung cancer, abdomen, cardiac, and retina. Considering the wide range of applications of deep learning, the objective of this article is to review major deep learning concepts pertinent to brain tumor analysis (e.g., segmentation, classification, prediction, evaluation.). A review conducted by summarizing a large number of scientific contributions to the field (i.e., deep learning in brain tumor analysis) is presented in this study. A coherent taxonomy of research landscape from the literature has also been mapped, and the major aspects of this emerging field have been discussed and analyzed. A critical discussion section to show the limitations of deep learning techniques has been included at the end to elaborate open research challenges and directions for future work in this emergent area.
Human Activity Sensing with Wireless Signals: A Survey

Wireless networks have been widely deployed with a high demand for wireless data traffic. The ubiquitous availability of wireless signals brings new opportunities for non-intrusive human activity sensing. To enhance a thorough understanding of existing wireless sensing techniques and provide insights for future directions, this survey conducts a review of the existing research on human activity sensing with wireless signals. We review and compare existing research of wireless human activity sensing from seven perspectives, including the types of wireless signals, theoretical models, signal preprocessing techniques, activity segmentation, feature extraction, classification, and application. With the development and deployment of new wireless technology, there will be more sensing opportunities in human activities. Based on the analysis of existing research, the survey points out seven challenges on wireless human activity sensing research: robustness, non-coexistence of sensing and communications, privacy, multiple user activity sensing, limited sensing range, complex deep learning, and lack of standard datasets. Finally, this survey presents four possible future research trends, including new theoretical models, the coexistence of sensing and communications, awareness of sensing on receivers, and constructing open datasets to enable new wireless sensing opportunities on human activities.
The brave new world of genetic testing in the management of the dyslipidaemias.

PURPOSE OF REVIEW With the exception of familial hypercholesterolaemia, the value of genetic testing for managing dyslipidaemias is not established. We review the genetics of major dyslipidaemias in context of clinical practice. RECENT FINDINGS Genetic testing for familial hypercholesterolaemia is valuable to enhance diagnostic precision, cascade testing, risk prediction and the use of new medications. Hypertriglyceridaemia may be caused by rare recessive monogenic, or by polygenic, gene variants; genetic testing may be useful in the former, for which antisense therapy targeting apoC-III has been approved. Familial high-density lipoprotein deficiency is caused by specific genetic mutations, but there is no effective therapy. Familial combined hyperlipidaemia (FCHL) is caused by polygenic variants for which there is no specific gene testing panel. Familial dysbetalipoproteinaemia is less frequent and commonly caused by APOE ε2ε2 homozygosity; as with FCHL, it is responsive to lifestyle modifications and statins or/and fibrates. Elevated lipoprotein(a) is a quantitative genetic trait whose value in risk prediction over-rides genetic testing; treatment relies on RNA therapeutics. SUMMARY Genetic testing is not at present commonly available for managing dyslipidaemias. Rapidly advancing technology may presage wider use, but its worth will require demonstration of cost-effectiveness and a healthcare workforce trained in genomic medicine.
Correction

EVOLUTION Correction for “Biological evidence supports an early and complex emergence of the Isthmus of Panama,” by Christine D. Bacon, Daniele Silvestro, Carlos Jaramillo, Brian Tilston Smith, Prosanta Chakrabarty, and Alexandre Antonelli, which appeared in issue 19, May 12, 2015, of Proc Natl Acad Sci USA (112:6110–6115; first published April 27, 2015; 10.1073/pnas.1423853112). The authors note that the following statement should be added to the Acknowledgments: “Financial support was also provided by National Science Foundation Grant DEB-0841729 (to R. T. Brumfield). ”
Phase Ib/II Clinical Trial of Pembrolizumab With Bevacizumab for Metastatic Renal Cell Carcinoma: BTCRC-GU14-003

PURPOSE We hypothesized that bevacizumab will potentiate activity of pembrolizumab. We conducted a phase Ib/II, single-arm, multisite clinical trial of the combination in metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS Patients with metastatic clear cell RCC who experienced progression after at least one systemic therapy (phase Ib) or were treatment naïve (phase II) were enrolled. In phase Ib, pembrolizumab (200 mg) and bevacizumab (10 or 15 mg/kg) were given intravenously every 3 weeks. The primary end point for phase II was overall response rate (ORR). With an 80% statistical power and a type I error probability of 0.1, 48 patients were to be accrued to detect an ORR of 42%. RESULTS Thirteen patients (ages 33-68 years; median, 55 years) were enrolled in the phase Ib study. No dose-limiting toxicities were reported. Pembrolizumab 200 mg and bevacizumab 15 mg/kg were chosen for phase II. Forty-eight patients (ages 42-84 years; median age, 61 years; 33 males) were accrued for the phase II study. The primary end point was met, with the ORR reaching 60.9% (95% CI, 45.4% to 74.9%), consisting of 1 complete response (CR), 2 CRs in target lesions, 25 partial responses, 18 responses of stable disease, 2 unevaluable responses. Median progression-free survival was 20.7 months (95% CI, 11.3 to 27.4 months). Median overall survival was not reached at the median follow-up of 28.3 months. The most common treatment-related grade 3 toxicities were hypertension and proteinuria. There were two grade 4 toxicities: duodenal ulcer and hyponatremia. Presence of tumor-infiltrating T cells, but not programmed death-ligand 1 expression, in tumor tissue correlated with response. CONCLUSION The combination of 200 mg of pembrolizumab and a 15 mg/kg dose of bevacizumab given every 3 weeks is safe and active in metastatic RCC.
Interim estimates of 2019/20 vaccine effectiveness during early-season co-circulation of influenza A and B viruses, Canada, February 2020

Interim results from Canada's Sentinel Practitioner Surveillance Network show that during a season characterised by early co-circulation of influenza A and B viruses, the 2019/20 influenza vaccine has provided substantial protection against medically-attended influenza illness. Adjusted VE overall was 58% (95% confidence interval (CI): 47 to 66): 44% (95% CI: 26 to 58) for A(H1N1)pdm09, 62% (95% CI: 37 to 77) for A(H3N2) and 69% (95% CI: 57 to 77) for influenza B viruses, predominantly B/Victoria lineage.
Circular RNA TUBD1 Acts as the miR-146a-5p Sponge to Affect the Viability and Pro-Inflammatory Cytokine Production of LX-2 Cells through the TLR4 Pathway

The functions and molecular mechanism of circRNAs in the development of radiation-induced liver disease (RILD) remain largely unknown. The goal of this study was to explore the expression and potential role of a new circular RNA, named circTUBD1, in irradiated and lipopolysaccharide (LPS)-stimulated human hepatic stellate cell (HSC) line LX-2 cells. The expression of circTUBD1 was significantly upregulated in irradiated and LPS-stimulated LX-2 cells compared to non-treated LX-2 cells. To explore the functions of circTUBD1, small interfering RNAs targeting circTUBD1 were designed. Silencing circTUBD1 inhibited proliferation, promoted apoptosis of LX-2 cells, and significantly decreased the expression level of pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α in irradiated and LPS-stimulated LX-2 cells. Mechanistic analysis suggested that circTUBD1 acted as the miR-146a-5p sponge to affect pro-inflammatory cytokine production through regulating expression of Toll-like receptor 4 (TLR4), interleukin receptor-associated kinase 1 (IRAK1), tumor necrosis factor receptor-associated factor-6 (TRAF6), and phosphorylation of nuclear factor-kappa B (pNF-κB) in irradiated and LPS-stimulated LX-2 cells. To our knowledge, this is the first study to show that circTUBD1 acts as a miR-146a-5p sponge to affect the viability and pro-inflammatory cytokine production of LX-2 cells through the TLR4 pathway, suggesting that circTUBD1 is a potential target for RILD therapy.
The Impact of Varenicline on Alcohol Consumption in Subjects With Alcohol Use Disorders: Systematic Review and Meta-Analyses.

OBJECTIVE Varenicline has been shown to be safe and effective in improving abstinence in smokers. However, results from randomized, placebo-controlled trials using varenicline for alcohol use disorders (AUDs) are inconsistent. The present systematic review and meta-analyses aimed to ascertain whether varenicline improves drinking-related outcomes in subjects with AUDs. DATA SOURCES Ovid, Embase, and Scopus databases were queried using the search terms varenicline, alcoholism, alcohol-related disorders, and drinking behavior for English-language publications until August 29, 2019, of randomized, placebo-controlled trials in humans. STUDY SELECTION A total of 197 articles were identified by the literature search. Studies of subjects with heavy drinking or alcohol dependence/AUD that reported alcohol use-related outcomes were examined. DATA EXTRACTION Weighted mean difference (WMD), standardized mean difference (SMD), and 95% CIs were calculated. The primary outcome of interest was percentage of heavy drinking days. Secondary outcomes included the number of drinks per drinking day, percentage of days abstinent, and change in alcohol craving. RESULTS Ten studies (n = 731, 66.6% male, 55.1% smokers) were included in the systematic review. In meta-analyses, no significant differences in percentage of heavy drinking days (n = 597; WMD = -1.09; 95% CI, -4.86 to 2.69; I² = 22%), number of drinks per drinking day (n = 570; WMD = -0.71; 95% CI, -1.44 to 0.03; I² = 0%), or percentage of days abstinent (n = 439; WMD = 3.89; 95% CI, -1.25 to 9.02; I² = 0%) were noted with varenicline use. Overall risk of bias was low. A statistically significant decrease in craving was observed (n = 436; SMD = -0.63; 95% CI, -1.18 to -0.08; I² = 84%). CONCLUSIONS In the present systematic review and meta-analyses, varenicline was shown to reduce alcohol craving but not improve drinking-related outcomes in subjects with AUDs.
Development and Validation of a Nomogram to Preoperatively Estimate Post-hepatectomy Liver Dysfunction Risk and Long-term Survival in Patients With Hepatocellular Carcinoma

Supplemental Digital Content is available in the text Objective: To develop a nomogram to estimate the risk of SPLD (International Study Group of Liver Surgery definition grade B or C) and long-term survival in patients with HCC before hepatectomy. Background: SPLD is the leading cause of post-hepatectomy mortality. The decision to refer an HCC patient for hepatectomy is mainly based on the survival benefit and SPLD risk. Prediction of SPLD risk before hepatectomy is of great significance. Methods: A total of 2071 consecutive patients undergoing hepatectomy for HCC were recruited and randomly divided into the development cohort (n = 1036) and internal validation cohort (n = 1035). Five hundred ninety patients from another center were enrolled as the external validation cohort. A nomogram was developed based on independent preoperative predictors of SPLD determined in multivariable logistic regression analysis. Results: The SPLD incidences in the development, internal, and external validation cohorts were 10.1%, 9.5%, and 8.6%, respectively. Multivariable analysis identified total bilirubin, albumin, gamma-glutamyl transpeptidase, prothrombin time, clinically significant portal hypertension, and major resection as independent predictors for SPLD. Incorporating these variables, the nomogram showed good concordance statistics of 0.883, 0.851, and 0.856, respectively in predicting SPLD in the 3 cohorts. Its predictive performance in SPLD, 90-day mortality, and overall survival (OS) outperformed Child-Pugh, model for end-stage liver disease, albumin-bilirubin, and European Association for the Study of the Liver recommended algorithm. With a nomogram score of 137, patients were stratified into low and high risk of SPLD. High-risk patients also had decreased OS. Conclusions: The nomogram showed good performance in predicting both SPLD and OS. It could help surgeons select suitable HCC patients for hepatectomy.