Miracle-dz/UniFAR-FTUs huggingface dataset:
Myocardial Strain and Cardiac Output are Preferable Measurements for Cardiac Dysfunction and Can Predict Mortality in Septic Mice

Background Sepsis is the overwhelming host response to infection leading to shock and multiple organ dysfunction. Cardiovascular complications greatly increase sepsis‐associated mortality. Although murine models are routinely used for preclinical studies, the benefit of using genetically engineered mice in sepsis is countered by discrepancies between human and mouse sepsis pathophysiology. Therefore, recent guidelines have called for standardization of preclinical methods to document organ dysfunction. We investigated the course of cardiac dysfunction and myocardial load in different mouse models of sepsis to identify the optimal measurements for early systolic and diastolic dysfunction. Methods and Results We performed speckle‐tracking echocardiography and assessed blood pressure, plasma inflammatory cytokines, lactate, B‐type natriuretic peptide, and survival in mouse models of endotoxemia or polymicrobial infection (cecal ligation and puncture, [CLP]) of moderate and high severity. We observed that myocardial strain and cardiac output were consistently impaired early in both sepsis models. Suppression of cardiac output was associated with systolic dysfunction in endotoxemia or combined systolic dysfunction and reduced preload in the CLP model. We found that cardiac output at 2 hours post‐CLP is a negative prognostic indicator with high sensitivity and specificity that predicts mortality at 48 hours. Using a known antibiotic (ertapenem) treatment, we confirmed that this approach can document recovery. Conclusions We propose a non‐invasive approach for assessment of cardiac function in sepsis and myocardial strain and strain rate as preferable measures for monitoring cardiovascular function in sepsis mouse models. We further show that the magnitude of cardiac output suppression 2 hours post‐CLP can be used to predict mortality.
Atlantic‐Pacific seesaw and its role in outgassing CO2 during Heinrich events

[1] Paleoproxy records indicate that a marked weakening of the Atlantic Meridional Overturning Circulation (AMOC) during Heinrich events was often accompanied by a notable atmospheric CO2 increase. However, previous modeling studies display conflicting atmospheric CO2 responses to an AMOC shutdown. Here we use model simulations combined with paleoproxy records to show that depending on the deep and bottom water transport in the Northern and Southern Pacific Ocean during an AMOC weakening, the ocean can act either as a sink or a source of carbon. Results from idealized meltwater experiments as well as from a transient experiment covering Heinrich stadial 4 suggest that a shutdown of the AMOC during Heinrich stadials 4 (HS4) and 1 (HS1) led to an enhancement of Antarctic Bottom Water (AABW) and North Pacific Deep Water (NPDW) transport. We show that enhanced deep and bottom water transport in the Pacific Ocean ventilates deep Pacific carbon through the Southern Ocean, thus contributing to a rise in atmospheric CO2. This mechanism yields a good agreement between paleoproxy records and modeling results, thus highlighting the possible establishment of an Atlantic-Pacific seesaw during Heinrich stadials. Enhanced AABW and NPDW transport could account for most of the observed atmospheric CO2 increase during HS4 and for about 30% of the atmospheric CO2 increase during HS1.
Selective internal radiation therapy using yttrium-90 resin microspheres in patients with unresectable hepatocellular carcinoma: a retrospective study.

Background Selective internal radiation therapy (SIRT) with yttrium-90 resin (Y-90 resin) microspheres has been used as a locoregional therapy for patients with unresectable hepatocellular carcinoma (HCC). We examined patient and disease characteristics that might affect survival after Y-90 resin, as well as treatment tolerability. Methods Data from patients with unresectable HCC treated with Y-90 resin at a single institution were reviewed retrospectively. Survival was assessed with Kaplan-Meier curves and log-rank tests. Response was evaluated with the response evaluation criteria in solid tumors (RECIST) criteria. Adverse events (AEs) were noted, and laboratory values were graded with CTCAE v3.0. Results Data from 111 patients were analyzed. AEs occurred in 23 patients at 1 week after treatment and in 46 at 3 months. At 6 months, 13 patients had a complete response and 13 had a partial response. Factors associated with longer overall survival (OS) included early-stage disease [27.8 months for patients with Barcelona-Clinic Liver Cancer (BCLC) A vs. 9.2 months for BCLC C]; treatment with other locoregional therapies (69.0 vs. 11.4 months); and lack of bilobar disease (23.5 vs. 9.4 months), portal vein thrombosis (16.2 vs. 8.6 months), ascites (16.6 vs. 10.3 months), and treatment with sorafenib (17.2 vs. 10.3 months). In six patients, Y-90 resin was used as a bridge to liver transplantation, which greatly improved survival (69.0 vs. 12.1 months). Conclusions Several characteristics may prove useful for selecting patients likely to respond well to Y-90 resin. These results should be confirmed in prospective studies.
Erythromycin-resistant Streptococcus pneumoniae: phenotypes, genotypes, transposons and pneumococcal vaccine coverage rates.

PURPOSE To assess the antibiotic resistance, transposon profiles, serotype distribution and vaccine coverage rates in 110 erythromycin-resistant S. pneumoniae clinical isolates. METHODOLOGY Erythromycin, clindamycin, tetracycline, chloramphenicol and kanamycin susceptibilities were assessed using the E-test/disc diffusion method. Inducible macrolide resistance was tested using the erythromycin-clindamycin double disc diffusion test. Serogrouping and serotyping were performed using latex particle agglutination and the Quellung reaction, respectively. Drug resistance genes and transposon-specific genes were investigated by PCR. RESULTS Of the isolates, 93 % were resistant to clindamycin; 81 % were resistant to tetracycline; 76 % were multi-drug-resistant, having resistance to both clindamycin and tetracycline; and 12 % had extended-drug resistance, being resistant to clindamycin, tetracycline, chloramphenicol and kanamycin. The majority of isolates (88.2 %) exhibited the cMLSB phenotype. The association between the cMLSB phenotype and tetracycline resistance was related to transposons Tn2010 (38.2 %), Tn6002 (21.8 %) and Tn3872 (18.2 %). M and iMLSB phenotypes were observed in 7 and 5 % of the isolates, respectively. The most frequent serotype was 19 F (40 %). Among the erythromycin-resistant pneumococci, vaccine coverage rates for the 13-valent pneumococcal conjugate vaccine (PCV-13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV-23) were 76.4 and 79.1 %, respectively, compared to 82.2 and 85.1 % transposon-carrying isolates. CONCLUSIONS Multi-drug resistance among erythromycin-resistant S. pneumoniae isolates mainly occurs due to the horizontal spread of the Tn916 family of transposons. The majority of the transposon-carrying isolates are covered by 13- and 23-valent pneumococcal vaccines. Since serotype distribution and transposons in S. pneumoniae isolates may change over time, close monitoring is essential.
Effects of Flaxseed Interventions on Circulating Inflammatory Biomarkers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There have been various clinical studies on the effect of flaxseed-derived products on circulating inflammatory biomarkers, but the findings from these are contradictory. The aim of the present study was to clarify any association. A comprehensive literature search was conducted from inception to May 2018. From the eligible trials, 32 articles describing studies conducted on adults aged 18-70 y were selected for the meta-analysis. Meta-analyses using the random-effects model were performed to investigate the data and results showed significant effects of flaxseed intake on circulating high-sensitivity CRP (hs-CRP) [weighted mean difference (WMD) = -0.75; 95% CI: -1.19, -0.30; P < 0.001] and TNFα (WMD = -0.38; 95% CI: -0.75,-0.01; P = 0.04). However, no significant changes were found in IL6 concentration (WMD = -0.24; 95% CI: -0.70, 0.21; P = 0.28) and C-reactive protein (CRP) (WMD = -0.34; 95% CI:-0.89, 0.20; P = 0.22). Moreover, by eliminating 1 of the studies from the sensitivity analysis, changes in IL6 concentration were significant (WMD = -0.44; 95% CI: -0.81, -0.08). The changes in inflammatory biomarkers were dependent on study design (parallel or crossover), supplement type (flaxseed, flaxseed oil, or lignan), study quality (high or low), and participants' age and BMI. According to this meta-analysis, flaxseed significantly reduced circulating concentrations of hs-CRP and TNFα, but did not affect IL6 and CRP. Further research is needed to examine the effect of different doses and long-term benefits of flaxseed and its derivatives on inflammatory factors.
Long-term cognitive disability after traumatic brain injury: Contribution of the DEX relative questionnaires

ABSTRACT Executive functions are high-level cognitive processes commonly impaired after severe traumatic brain injury (sTBI), which may be associated with persistent anosognosia. The dysexecutive questionnaire (DEX) was designed to assess different domains of executive functioning in daily life. Two versions of the DEX exist (DEX-S completed by the patient, DEX-O completed by a relative) to compare cognitive complaints and patient’s awareness. This work was aimed at studying the relevance of DEX-O for assessing daily-life limitations, the persistence of anosognosia and its association with global disability (GOSE) and magnetic resonance imaging (MRI) markers of brain alterations. Sixty-three patients (and relatives) were included within 63.4 months (±20.7) after sTBI. DEX-S and DEX-O scores were significantly positively correlated. We obtained significant correlations between DEX-S and episodic memory and phasic alert but not with executive assessment, GOSE and diffusion MRI markers. DEX-O was significantly correlated with executive function, episodic memory, attention (phasic alert sustained and divided attention), with the GOSE and the volume of the body of the corpus callosum (MRI marker). Anosognosia score (DEX-O minus DEX-S) correlated with mean diffusivity measure. These results highlight the clinical interest of DEX-O in assessing long-term disability.
Volumetry and topography of the human brain by magnetic resonance imaging

Software, termed Morph©, is described for the morphometric analysis of magnetic resonance images of the human brain. Algorithms for objective contrast border recognition, surface feature classification, and surface feature contour unfolding are evaluated. Intraoperator and interoperator variabilities and errors were determined to be less than 2% over a group of operators (n = 6) for the known volume of a cerebral hemisphere obtained at autopsy. Volumetric errors were measured to be ± 3% for simulated objects and less than 1% for images of phantoms. Contours of brains of normal elderly subjects (n = 6) and patients with probable Alzheimer's disease (n = 6), segmented into sulcal and gyral features to determine gyrification indices, showed concordance with literature values. Flat maps or topograms were obtained of the convoluted cortex by unfolding the segmented contours. The areas of surface features were readily obtained. The activation of the frontal eye fields (FEF) defined by functional magnetic resonance imaging (fMRI) with an oculomotor control task was mapped onto a topogram of the precentral sulcus. This software provides accurate volumetric analysis with additional topographical tools for characterizing convoluted cortical features and for presenting three‐dimensional fMRI activation patterns as two‐dimensional maps. © 2001 John Wiley & Sons, Inc. Int J Imaging Syst Technol 11, 198–208, 2000
The Relationship between Primary Gross Tumor Volume and Tumor Response of Locally Advanced Rectal Cancer: pGTV as a More Accurate Tumor Size Indicator

Abstract Purpose: To identify the clinical predictive factors of tumor response and to evaluate the significance of primary gross tumor volume (pGTV), obtained from radiotherapy planning, in predicting tumor response. Materials and Methods: We retrospectively analyzed data of consecutive locally advanced rectal cancer (LARC) patients who were treated with neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery at our institution between March 2009 and December 2017. We identify independent predictors of tumor response to nCRT by statistical analysis. Disease-free survival (DFS) starting from the time of surgery was calculated by the Kaplan–Meier method, and log-rank tests were performed to compare DFS between patients with superior and inferior tumor response. Results: Overall, 185 LARC patients received nCRT, of whom 89 (48.11%) achieved superior tumor response. Diminutive pGTV (p = 0.038) and distance from the anal verge (DAV) (p = 0.006) were independent predictive factors of superior tumor response. Meanwhile, pGTV can be regarded as an independent predictor of pathologic complete response (pCR) (p = 0.036). The log-rank test revealed that DFS was longer in the diminutive pGTV group than in the giant pGTV group (p = 0.001). Conclusions: pGTV, as a measure of tumor size, is not only an important prognostic indicator but also an independent predictive factor of tumor response, even pCR.
Pure Viral Sepsis Secondary to Community-Acquired Pneumonia in Adults: Risk and Prognostic Factors

Abstract We investigated the risk and prognostic factors of pure viral sepsis in adult patients with community-acquired pneumonia (CAP), using the Sepsis-3 definition. Pure viral sepsis was found in 3% of all patients (138 of 4028) admitted to the emergency department with a diagnosis of CAP, 19% of those with CAP (138 of 722) admitted to the intensive care unit, and 61% of those (138 of 225) with a diagnosis of viral CAP. Our data indicate that males and patients aged ≥65 years are at increased risk of viral sepsis.
WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs

Abstract WebGestalt is a popular tool for the interpretation of gene lists derived from large scale -omics studies. In the 2019 update, WebGestalt supports 12 organisms, 342 gene identifiers and 155 175 functional categories, as well as user-uploaded functional databases. To address the growing and unique need for phosphoproteomics data interpretation, we have implemented phosphosite set analysis to identify important kinases from phosphoproteomics data. We have completely redesigned result visualizations and user interfaces to improve user-friendliness and to provide multiple types of interactive and publication-ready figures. To facilitate comprehension of the enrichment results, we have implemented two methods to reduce redundancy between enriched gene sets. We introduced a web API for other applications to get data programmatically from the WebGestalt server or pass data to WebGestalt for analysis. We also wrapped the core computation into an R package called WebGestaltR for users to perform analysis locally or in third party workflows. WebGestalt can be freely accessed at http://www.webgestalt. org.
Causes and consequences of cardiac fibrosis in patients referred for surgical aortic valve replacement

Cardiac fibrosis is associated with left ventricular (LV) remodelling and contractile dysfunction in aortic stenosis (AS). The fibrotic process in this condition is still unclear. The aim of this study was to determine the role of both local and systemic inflammation as underlying mechanisms of LV fibrosis and contractile dysfunction. The diagnostic values of 2D‐strain echocardiography and serum biomarkers in the evaluation of cardiac fibrosis in this condition were assessed through correlation analyses.
Serum CD64 and ascitic fluid calprotectin and microRNA-155 as potential biomarkers of spontaneous bacterial peritonitis

Aim Patients with ascites are at a higher risk for associated of on top bacterial infections with subsequent life-threatening complications. We aimed to evaluate CD64, calprotectin, and microRNA-155 (miR-155) levels as diagnostic markers of spontaneous bacterial peritonitis (SBP) and the effect of using more than one use on the same spot over their diagnostic efficiency. Patients and methods An observational comparative study included 103 patients with ascites admitted to the Tropical Medicine Department, Mansoura University Hospital, Egypt, divided into two groups: case group (64 patients) with ascites with SBP and control group (39 patients) with decompensated cirrhotic non-SBP ascites. Twenty milliliters of ascetic fluid was obtained from all participants for bacterial culture, and assessment of calprotectin and miR-155, in addition to 2 ml blood for the CD64 marker expression assay by a flowcytometer. Results The sensitivity and specificity of CD64 expression assay were 95.3 and 92.3%, respectively, area under the curve (AUC)=0.93, whereas those of ascetic fluid calprotectin and miR-155 were 87.5 and 82.1%, AUC=0.90 and 95.3 and 97.4%, with AUC of 0.95. Combined blood CD64 and ascetic fluid calprotectin had a diagnostic accuracy of 0.988 for blood CD64 and ascetic fluid miR-155, AUC=0.991, and that for ascetic fluid calprotectin and miR-155 was 0.988. On using the three studied markers together, the diagnostic accuracy was the best recorded, AUC=0.994. P values were less than 0.001. Conclusion CD64, calprotectin, and miR-155 were good diagnostic markers of SBP and on using this combination, greater efficiency in diagnosis was achieved.
Augmin accumulation on long-lived microtubules drives amplification and kinetochore-directed growth

Vertebrate cells assemble mitotic spindles through multiple pathways. It is shown that Augmin-dependent, noncentrosomal nucleation generates the vast majority of microtubules in metaphase spindles. This results in a strong directional bias of microtubule growth toward individual kinetochores.
Incest Survivors’ Life-Narratives

This article analyzes the narratives of survivors of father−daughter incest using 20 in-depth interviews with women, each asked to choose a title for her life-story and reflect on its meaning. Three narratives emerged: “Surviving” tells of a struggle for personal achievement in an independent life alongside intensely traumatic experiences and negative feelings, “Fighting Back/Seeking Vengeance” tells of aspiring to strength by acting on their will to fight back and desire for revenge, and “Growing” reflects the wish to fight and win a place in the world through a “rebuilding” process. The conceptualization of incest survivors’ life-narratives is based on the dialectical perspective.
Immunohistochemical Expression of Epithelial-Mesenchymal Transition Markers in Early Gastric Cancer: Cancer Tissue versus Noncancer Tissue

Background/Aims Epithelial-mesenchymal transition (EMT) is a developmental process, wherein the epithelial cells show reduced intercellular adhesions and acquire migratory fibroblastic properties. EMT is associated with downregulation in epithelial marker expression, abnormal translocation of E-cadherin, and upregulation in mesenchymal marker expression. Here, we investigated the immunohistochemical (IHC) expression of EMT markers in early gastric cancer (EGC) between cancer and noncancer tissues. Methods Tissue samples were prospectively obtained from 19 patients with EGC that underwent endoscopic submucosal dissection (ESD). We compared the expression level of transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF), E-cadherin, α-smooth muscle actin (α-SMA), and vimentin between cancer and noncancer tissues using IHC. Among the 19 patients, 15 patients had follow-up biopsy at 3 months after ESD for EGC. Results Cancer tissues presented higher values of EMT mesenchymal markers (α-SMA/vimentin/TGF-β/VEGF) than the noncancerous tissues (p<0.05) that were significantly low after ESD (p<0.05). No significant correlation was reported for tumor location and initial Helicobacter pylori infection. Conclusions The mesenchymal expression of EMT markers was higher in the cancerous tissues than in the noncancer tissues.
A glycan shield on chimpanzee CD4 protects against infection by primate lentiviruses (HIV/SIV)

Significance HIV-1 arose following the cross-species transmission of a simian immunodeficiency virus of chimpanzees (SIVcpz) to humans. In this study, we looked at genetic diversity in chimpanzee CD4, which encodes the main receptor for both HIV and SIVcpz. We identified multiple CD4 alleles circulating in chimpanzee populations, some of which impede cellular entry of HIV-1 and SIVcpz. We demonstrate that some chimpanzees would be significantly protected from virus infection because their CD4 protein is modified by the addition of glycans to the virus binding surface. These glycans create a shield that protects the receptor from being engaged by viruses, demonstrating a powerful form of host resistance against deadly primate lentiviruses. Pandemic HIV-1 (group M) emerged following the cross-species transmission of a simian immunodeficiency virus from chimpanzees (SIVcpz) to humans. Primate lentiviruses (HIV/SIV) require the T cell receptor CD4 to enter into target cells. By surveying the sequence and function of CD4 in 50 chimpanzee individuals, we find that all chimpanzee CD4 alleles encode a fixed, chimpanzee-specific substitution (34T) that creates a glycosylation site on the virus binding surface of the CD4 receptor. Additionally, a single nucleotide polymorphism (SNP) has arisen in chimpanzee CD4 (68T) that creates a second glycosylation site on the same virus-binding interface. This substitution is not yet fixed, but instead alleles containing this SNP are still circulating within chimpanzee populations. Thus, all allelic versions of chimpanzee CD4 are singly glycosylated at the virus binding surface, and some allelic versions are doubly glycosylated. Doubly glycosylated forms of chimpanzee CD4 reduce HIV-1 and SIVcpz infection by as much as two orders of magnitude. Full restoration of virus infection in cells bearing chimpanzee CD4 requires reversion of both threonines at sites 34 and 68, destroying both of the glycosylation sites, suggesting that the effects of the glycans are additive. Differentially glycosylated CD4 receptors were biochemically purified and used in neutralization assays and microscale thermophoresis to show that the glycans on chimpanzee CD4 reduce binding affinity with the lentiviral surface glycoprotein, Env. These glycans create a shield that protects CD4 from being engaged by viruses, demonstrating a powerful form of host resistance against deadly primate lentiviruses.