Miracle-dz/UniFAR-FTUs huggingface dataset:
Effective genetic markers for identifying the Escherichia coli F4ac receptor status of pigs

The F4ac receptor locus (F4acR), which encodes susceptibility or resistance to Escherichia coli diarrhoea, is inherited as an autosomal recessive monogenetic trait. F4acR is localized on pig chromosome 13 (SSC13q41-q44) near the MUC13 gene. Two flanking markers (CHCF1 and ALGA0106330) with a high linkage disequilibrium (LD) with F4acR were found to be effective for the genetic identification of F4ac-resistant pigs in the Swiss Large White breed (one recombinant out of 2034 genotyped pigs). Three recombinant boars, one each from the Duroc, Swiss Landrace and Piétrain breeds, were genotyped with seven different markers and phenotyped by means of a microscopic adhesion test. Only ALGA0072075, CHCF1 and CHCF3 indicated the correct phenotype. To test the effect of the resistance allele on production traits, 530 Large White pigs from the national test station were investigated. A significant difference existed among the F4acR locus genotypes in the intramuscular fat content of the longissimus dorsi muscle, whereas no other production traits were influenced by the resistance allele. The frequency of the CHCF1-C and ALGA0106330-A alleles associated with resistance in the Swiss Large White population was 60%, which is advantageous for implementing this trait in a breeding programme to select for E. coli F4ac-resistant animals. The selection of resistant pigs should start on the male side due to the inability of resistant sows to produce sufficient amounts of protecting antibodies in the colostrum. Selection of genetically F4ac-resistant pigs is a sustainable and suitable alternative to decreasing animal loss and antibiotic use due to diarrhoea.
Reliability and validity of the Canadian–French ecological adaptation of the weighted version of the Melbourne low-vision ADL Index

Abstract Background: The Mesure de l’impact de la déficience visuelle dans les activités quotidiennes (MIDVAQ) is the Canadian–French adaptation of the Melbourne Low-Vision ADL Index. It measures performance, personal importance and handicap situation in 16 instrumental activities requiring near vision (standardized material, part A) and in 9 self-care and domestic activities (self-report questionnaire, part B). This study aimed at measuring the MIDVAQ reliability and its relationship with measures of visual functions and functional vision. Methods: The MIDVAQ was administered twice to 100 visually impaired participants, at home, with their personal visual and non-visual aid. A second rater was present at T1. Two different versions of part A were used alternately at T1 and T2. Results: The total Handicap scale demonstrates good internal reliability (Cronbach’s alpha coefficient = 0.82) and very high inter-rater and test-retest reliability (ICCs = 1.00 and 0.86). Part A alternative versions are highly comparable. Vision function measures are significantly correlated with total Handicap score, for which 48% of the variance is explained by functional vision estimates, age, and education. Conclusions: The MIDVAQ is highly valid and reliable. It can be useful to measure the functional impact of the visual impairment, its progression, and the outcomes of low vision rehabilitation services. Implications for rehabilitation Even if administered at home in an ecological way, this measure of the impact of the visual impairment in daily activities is very reliable. Given its good metric properties, this tool can be confidently used to assess the functional impact of visual impairment, outcomes of the low vision rehabilitation services, etc. This measurement tool provides complementary information to those obtained from clinical measures of visual functions, by reflecting the interaction between the functional abilities with the requirements of the environment.
Antioxidants and Phase 2 Enzymes in Macrophages: Regulation by Nrf2 Signaling and Protection Against Oxidative and Electrophilic Stress

Macrophages play important roles in immunity and other physiological processes. They are also target cells of various toxic agents, including oxidants and electrophiles. However, little is known regarding the molecular regulation and chemical inducibility of a spectrum of endogenous antioxidants and phase 2 enzymes in normal macrophages. Understanding the molecular pathway(s) controlling the coordinated expression of various macrophage antioxidants and phase 2 defenses is of importance for developing strategies to protect against macrophage injury induced by oxidants and electrophiles. Accordingly, this study was undertaken to determine the role of the nuclear factor E2-related factor 2 (Nrf2) in regulating both constitutive and chemoprotectant-inducible expression of various antioxidants and phase 2 enzymes in mouse macrophages. The constitutive expression of a series of antioxidants and phase 2 enzymes was significantly lower in macrophages derived from Nrf2-null (Nrf2−/−) mice than those from wild-type (Nrf2+/+) littermates. Incubation of wild-type macrophages with 3H-1,2-dithiole-3-thione (D3T) led to significant induction of various antioxidants and phase 2 enzymes, including catalase, glutathione, glutathione peroxidase (GPx), glutathione reductase, glutathione S-transferase, and NAD(P)H:quinone oxidoreductase 1. The inducibility of the above cellular defenses except for GPx by D3T was completely abolished in Nrf2−/− macrophages. As compared with wild-type cells, Nrf2− /− macrophages were much more susceptible to cell injury induced by reactive oxygen/nitrogen species, as well as two known macrophage toxins, acrolein and cadmium. Up-regulation of the antioxidants and phase 2 enzymes by D3T in wild-type macrophages resulted in increased resistance to the above oxidant-and electrophile-induced cell injury, whereas D3T treatment of Nrf2− /− macrophages provided only marginal or no cytoprotec-tion. This study demonstrates that Nrf2 is an indispensable factor in controlling both constitutive and inducible expression of a wide spectrum of antioxidants and phase 2 enzymes in macrophages as well as the susceptibility of these cells to oxidative and electrophilic stress.
MRI-Based Definition of a Stereotactic Two-Dimensional Template of the Human Insula

Objective: This study aimed to create a stereotactic two-dimensional description of the human insula based on accurate radiological morphometric studies. Methods: Seventy-five normal cerebral MRIs were selected and drawings of the insula then obtained from serial sagittal slices. These drawings were digitalized before superimposing the anterior (AC) and posterior (PC) commissures as references. This allowed us to quantify interindividual anatomical variations in a large cohort of subjects. Results: The morphometric analysis of the insula revealed a more complex shape than previously described. This structure is delimited by four peri-insular sulci (anterior, superior, posterior and inferior) instead of the three sulci classically mentioned. Males have a statistically larger surface area than females, according to a correlated index. Precise measurements of the different insular components allowed us to quantify their potential interindividual anatomical variations and to define their average shapes and stereotactic locations. Conclusion: These data create a two-dimensional template of the human insula, with regard to the classical AC-PC stereotactic reference system. They furthermore allow us to quantify the probability that a given element of this structure is located at a predefined position. This should be useful in functional neuroimaging studies and in insular surgery for diagnostic and therapeutic goals.
Note: This Copy Is for Your Personal Non-commercial Use Only. to Order Presentation-ready Copies for Distribution to Your Colleagues or Clients, Contact Us at Education Exhibits Postoperative Imaging in Liver Transplantation: What Radiologists Should Know Learning Objectives for Test 1

Liver transplantation is now frequently used in the treatment of end-stage liver disease. Therefore, it is important that radiologists be aware of common anastomotic techniques and expected postoperative imaging findings. Imaging is most useful in evaluating for posttransplantation complications, which are broadly classified into vascular, biliary, and other complications. Hepatic artery thrombosis is the most significant complication and is often associated with graft failure. Radiologists have multiple modalities at their disposal for optimal evaluation. Doppler ultrasonography (US) is the preliminary imaging modality for gross evaluation of the liver parenchyma, biliary tree, and vasculature for abnormalities. When US findings are indeterminate or there is persistent clinical suspicion for an abnormality, computed tomography (CT) is often performed. The major indications for CT are detection of bile leak, hemorrhage, and abscess, but CT is also useful in the assessment of the vasculature. T-tube cholangiography and magnetic resonance cholangio-pancreatography are the best noninvasive imaging tools for evaluating for biliary stricture. Some investigators would argue that endoscopic retrograde cholangiopancreatography (ERCP) is a better diagnostic imaging modality; however, ERCP is invasive. Hepatobiliary scintigraphy is optimal for the evaluation of biliary leakage. Early detection of post-transplantation complications will help lower morbidity rates and will likely allow graft salvage in selected cases. 1 Abbreviations: CBD = common bile duct, ERCP = endoscopic retrograde cholangiopancreatography, IVC = inferior vena cava After reading this article and taking the test, the reader will be able to: Describe the anas-■ tomotic techniques used in liver trans-plantation.
Enhancement of Carboplatin-Mediated Lung Cancer Cell Killing by Simultaneous Disruption of Glutathione and Thioredoxin Metabolism

Purpose: Cancer cells (relative to normal cells) show increased steady-state levels of hydroperoxides that are compensated by increased glucose and hydroperoxide metabolism. The current study determined whether inhibitors of glucose and hydroperoxide metabolism could induce chemoradiosensitization by enhancing oxidative stress in lung cancer cells. Experimental Design: A549 and NCI-H292 human lung carcinoma cells were treated with 2-deoxy-d-glucose (2DG) combined with carboplatin + ionizing radiation (IR). Lung cancer cells were further sensitized with inhibitors of glutathione (GSH)- and thioredoxin (Trx)-dependent metabolism [buthionine sulfoximine (BSO) and auranofin, respectively] in vitro and in vivo. Results: When 2DG was combined with carboplatin + IR, clonogenic cell killing was enhanced in A549 and NCI-H292 cells, and this combination was more effective than paclitaxel + carboplatin + IR. The thiol antioxidant (N-acetylcysteine, NAC) was capable of protecting cancer cells from 2DG + carboplatin -induced cell killing. Simultaneous treatment of cancer cells with BSO and auranofin, at doses that were not toxic as single agents, also enhanced lung cancer cell killing and sensitivity to 2DG + carboplatin. This treatment combination also increased oxidation of both GSH and Trx, which were inhibited by NAC. Mice treated with auranofin + BSO showed no alterations in circulating leukocytes or red blood cells. Xenograft lung tumor growth in mice was more effectively inhibited by treatment with auranofin + BSO + carboplatin than animals treated with carboplatin or auranofin + BSO alone. Conclusions: These results show in vitro and in vivo that simultaneous inhibition of GSH and Trx metabolism can effectively inhibit lung cancer cell growth and induce chemosensitization by a mechanism that involves thiol-mediated oxidative stress. Clin Cancer Res; 17(19); 6206–17. ©2011 AACR.
Severity of Analgesic Dependence and Medication-overuse Headache

Background and Aims: Medication-overuse headache (MOH) is a common chronic headache caused by overuse of headache analgesics. It has similarities with substance dependence disorders. The treatment of choice for MOH is withdrawal of the offending analgesics. Behavioral brief intervention treatment using methods adapted from substance misuse settings is effective. Here we investigate the severity of analgesics dependence in MOH using the Severity of Dependence Scale (SDS), validate the SDS score against formal substance dependence diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and examine whether the SDS predicts successful withdrawal. Methods: Representative recruitment from the general population; 60 MOH patients, 15 chronic headache patients without medication overuse and 25 population controls. Headaches were diagnosed using the International Classification of Headache Disorders, medication use was assessed and substance dependence classified according to the DSM-IV. The SDS was scored by interviewers blinded to patient group. Descriptive statistics were used and validity of the SDS score assessed against a substance dependence diagnosis using ROC analysis. Results: Sixty-two percent of MOH patients overused simple analgesics, 38% centrally acting analgesics (codeine, opiates, triptans). Fifty percent of MOH patients were classified as DSM-IV substance dependent. Centrally active medication and high SDS scores were associated with higher proportions of dependence. ROC analysis showed SDS scores accurately identified dependence (area under curve 88%). Lower SDS scores were associated with successful withdrawal (P = 0.004). Conclusions: MOH has characteristics of substance dependence which should be taken into account when choosing treatment strategy. Trial registration: Based on data collected in previously reported randomized BIMOH trial (Kristoffersen et al., 2012; Kristoffersen et al., 2015 in the present manuscript, Clinical trials registration number: NCT01314768). The present part, however, represents observational data and is not a treatment trial.
A new marker based on risk stratification of human papillomavirus DNA and tumor size to predict survival of locally advanced cervical cancer

Objective To assess the prognostic value of human papillomavirus (HPV) viral load in locally advanced cervical carcinoma treated with radical concurrent chemoradiotherapy. Methods From January 2012 to October 2013, a total of 246 locally advanced cervical carcinoma patients were included in this retrospective study. HPV DNA status was tested by Hybrid Capture 2 assay. Tumor size was measured on T2WI. All the patients in the study received concurrent cisplatin-based chemoradiotherapy with intensity-modulated radiotherapy and three-dimensional brachytherapy. Survival rate was calculated by the Kaplan-Meier method, and a log-rank test was used to compare the survival. Multivariate analysis employed the Cox regression model. Results The median follow-up time was 52 months. The median value of HPV DNA was 163.13 relative light unit/cut-off (RLU/CO) (range 1.65–2162.62 RLU/CO). The 5-year overall survival, distant metastasis-free survival of patients in the low HPV DNA group (HPV DNA ≤ 163.13 RLU/CO) and the high HPV DNA group (HPV DNA > 163.13 RLU/CO) were 46.3 % vs 58.5 % (p = 0.009) and 65.9 % vs 75.6% (p = 0.003), respectively. Multivariate analysis showed that the HPV DNA, tumor size, and International Federation of Gynecology and Obstetrics (FIGO) stage were independent prognostic factors for overall survival and distant metastasis-free survival. We choose the tumor size and HPV DNA as the risk stratification factors to build a new prediction marker which can better predict overall survival for locally advanced cervical cancer than can the FIGO stage. Conclusions HPV DNA may be a useful biomarker for locally advanced cervical cancer. Low HPV load predicts a worse survival. The new marker based on risk stratification by combining HPV DNA and tumor size is better associated with overall survival of locally advanced cervical cancer treated with concurrent chemoradiotherapy.
Proteomics in Pathology: The Special Issue

Methods and technologies for high-throughput analysis of proteins became necessary for a wide range of applications in life sciences. Proteomic profiling provides panoramic pictures of the final molecular actors of biological contexts of interest. Mass spectrometry (MS) at large has entered a new era in the past few years with potential applications for routine pathological diagnostics. [1,2] One year ago, we offered our point of view regarding the most promising proteomic workflows for future applications in tissue-based diagnostics and the prerequisites for a successful translational implementation. [3] Today, four approaches appear as possible future cornerstones for histoproteomic diagnostics in institutes of pathology: MALDI profiling and imaging, liquid chromatography-tandem mass spectrometry (LCMS/MS), and laser microdissection–based microproteomics. [3] MALDI profiling was recently demonstrated as a reliable approach for rapid diagnosis with the evaluation of isocitrate dehydrogenase mutational status in diffuse gliomas. [4] MALDI imaging allows for close correlation between histological structures and mass spectrometric measurements. [5] The analysis of tissue microarrays combined with classification algorithms holds great promise regarding disease diagnosis based on in situ proteomic signatures. [6] LC-MS/MS-based shotgun proteomic methods allow for the secure identification of tens of thousands of peptides corresponding to up to thousands of proteins in a single analytical run. [7] This approach has a high potential for tissue classification as a high number of biomarkers are identified. [8] Microproteomic workflows also represent future valuable methods for molecular pathology. Since tissues are a very heterogeneous mixture of different cell types, laser microdissection has to be performed in order to obtain pure cell populations. Today, it is possible to retrieve thousands of protein identifications from laser-microdissected, formalin-fixed and paraffinembedded (FFPE) tissue pieces bearing less than 3000 cells. [9,10] Hence, it may be expected that high spatial resolution will meet in-depth proteomic information in the near future. Recent advances in sample processing of tissues for shotgun proteomics
Signal peptide peptidase‐like 2c impairs vesicular transport and cleaves SNARE proteins

Members of the GxGD‐type intramembrane aspartyl proteases have emerged as key players not only in fundamental cellular processes such as B‐cell development or protein glycosylation, but also in development of pathologies, such as Alzheimer's disease or hepatitis virus infections. However, one member of this protease family, signal peptide peptidase‐like 2c (SPPL2c), remains orphan and its capability of proteolysis as well as its physiological function is still enigmatic. Here, we demonstrate that SPPL2c is catalytically active and identify a variety of SPPL2c candidate substrates using proteomics. The majority of the SPPL2c candidate substrates cluster to the biological process of vesicular trafficking. Analysis of selected SNARE proteins reveals proteolytic processing by SPPL2c that impairs vesicular transport and causes retention of cargo proteins in the endoplasmic reticulum. As a consequence, the integrity of subcellular compartments, in particular the Golgi, is disturbed. Together with a strikingly high physiological SPPL2c expression in testis, our data suggest involvement of SPPL2c in acrosome formation during spermatogenesis.
Higher Peripheral TREM2 mRNA Levels Relate to Cognitive Deficits and Hippocampal Atrophy in Alzheimer's Disease and Amnestic Mild Cognitive Impairment.

BACKGROUND Variants in triggering receptor expressed on myeloid cells 2 (TREM2) are associated with increased Alzheimer's disease (AD) risk. Recent studies have reported inconsistent peripheral TREM2 mRNA expression levels and relationship with cognitive scores in AD and mild cognitive impairment (MCI). Additionally, no study has examined the association of peripheral TREM2 levels with neuroimaging measures in AD and MCI. OBJECTIVE To determine peripheral TREM2 mRNA levels in AD, amnestic MCI (aMCI) and healthy controls, and the association with cognitive performance and brain structural changes. METHODS We measured peripheral TREM2 mRNA levels in 80 AD, 30 aMCI, and 86 healthy controls using real time polymerase chain reaction. TREM2 levels were correlated with various cognitive performance and brain volumes, correcting for APOE4 status. RESULTS TREM2 mRNA levels were significantly higher in AD compared to controls and aMCI. Levels did not differ between aMCI and controls. Corrected for APOE4, higher TREM2 levels correlated with lower Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA) and episodic memory scores, and lower total grey matter and right hippocampal volumes. Whole-brain voxel-based morphometry analysis found negative association between TREM2 mRNA levels and grey matter volumes in temporal, parietal and frontal regions. AD subjects with MoCA scores ≤20 had higher TREM2 levels correlating with smaller total grey matter, left hippocampal and right hippocampal volumes. CONCLUSION Peripheral TREM2 mRNA levels are higher in AD and are associated with AD-related cognitive deficits and hippocampal atrophy. Our findings suggest that TREM2 may be a potential non-invasive peripheral biomarker for AD diagnosis.
Characterization and expression analysis of KIT and MITF‐M genes in llamas and their relation to white coat color

The llama (Lama glama) is a fiber-producing species that presents a wide range of coat colors, among which white is one of the most important for the textile industry. However, there is little information about the molecular mechanisms that control the white phenotype in this species. In domestic mammals, a white coat is usually produced by mutations in the KIT proto-oncogene receptor tyrosine kinase (KIT) and microphthalmia-associated transcription factor (MITF) genes. In this work we have sequenced and described the coding regions of KIT and MITF-M, the melanocyte-specific isoform, and the two transcriptional variants MITF-M(-) and MITF-M(+). Moreover, we studied the expression of these genes in the skin of white and colored llamas. Although no variants were revealed to be associated with white coat color, significant differences between phenotypes were observed in the expression levels of KIT and MITF-M. Interestingly, white llamas expressed less MITF-M(+) than did colored ones, which is consistent with a consequent reduction in the synthesis of melanin. Even though our results indicate that downregulation of KIT and MITF-M expression is involved in white phenotype production in llamas, the causative gene of white coat color remains unknown.
Lactic Acid Bacteria from Andean Grain Amaranth: A Source of Vitamins and Functional Value Enzymes

Amaranth is a rediscovered pseudocereal with high nutritional properties. Lactic acid fermentation can increase the functional and nutritional value of foods. The aims of this study were to isolate and evaluate the functionality of lactic acid bacteria (LAB) from amaranth. LAB strains (n = 29) isolated from amaranth sourdough and grains included Lactobacillus (L.) plantarum (n = 8), L. rhamnosus (n = 6), Enterococcus (E.) mundtii (n = 4), E. hermanniensis (n = 3), E. durans (n = 1), Enterococcus sp. (n = 1), Leuconostoc (Lc.) mesenteroides (n = 3), and Lc. mesenteroides subsp. mesenteroides (n = 3). Only 21% of the strains showed the ability to synthesize capsular exopolysaccharides or display ropiness and only 8 strains showed amylolytic activity. L. plantarum CRL 2106 and E. durans CRL 2122 showed the highest phytase activity, which is of importance for mineral bioavailability. L. plantarum CRL 2106 and CRL 2107 and Lc. mesenteroides subsp. mesenteroides CRL 2131 synthesized the highest concentrations of B2 and B9 vitamin (140-250 ng/mL). This study demonstrates the potential of LAB to improve the nutritional and functional values of pseudocereal-derived foods.