Miracle-dz/UniFAR-FTUs huggingface dataset:
Abstract P3-10-36: Concordance of HER2 Central Assessment by Two International Central Laboratories: A Ring Study within the Framework of the Adjuvant HER2-Positive ALTTO Trial (BIG2-06/N063D/EGF106708)

In the Breast International Group (BIG) and North Central Cancer Treatment Group (NCCTG) co-led phase III adjuvant breast cancer trial, ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation), two central laboratories, the European Institute of Oncology (IEO; Milan, Italy) and Mayo Clinic (Rochester, MN), are responsible for confirming the human epidermal growth factor receptor-2 (HER2), estrogen receptor α(ER), and progesterone receptor status of the primary breast tumors for the Rest of World (excluding China, which conducts a separate central review) and North American patients, respectively, prior to patient study entry. As of December 2009, discordance in HER2 and ER testing between local and central laboratories was observed by both central laboratories. For IEO, 14.5% of 8,037 HER2 cases locally positive [by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)] were not able to be confirmed as centrally positive; whereas for Mayo, 5.8% of 412 HER2 cases locally positive were not able to be confirmed as centrally positive (Table 1). Central and local IHC ER discordance was 12.1% and 11.7% for 9,021 IEO screened cases and 419 Mayo screened cases, respectively (Table 2). In particular, IEO observed more false-positive (locally positive/centrally negative) HER2 findings than Mayo and Mayo observed more false-positive ER findings than IEO. Purpose: Motivated by the above findings, we launched a ring study to assess whether the central lab results of a subset of local/central discordant ALTTO cases could be confirmed in the other central lab. Methods: IEO and Mayo exchanged and retested a subset of FFPE breast tumors collected in ALTTO. IEO sent 20 HER2 false-positive, 5 ER false-positive, and 5 ER false-negative (locally negative/centrally positive) ALTTO breast tumors to Mayo. Mayo sent 5 HER2 false-positive, 20 ER false-positive, and 5 ER false-negative ALTTO breast tumors to IEO. IEO and Mayo performed IHC for ER according to their own methodology: DAKO cocktail of ER 1D5 and 2.123 monoclonal antibodies and monoclonal ER 1D5 antibody, respectively. The two laboratories performed IHC for HER2 according to the HercepTest® manufacturers’ instructions (Dako, Carpenteria, CA) and FISH for HER2 using the PathVysion HER2 DNA probe kit and the HER2/centromere 17 probe mixture (Abbott Molecular, Des Plaines, IL). Results: IEO and Mayo confirmed the central HER2-negative result in 100% of 25 cases. Analyses of ER are ongoing and ER results will be presented. Conclusions: In this subset of patients, enrollment ineligibility did not change when HER2 testing was performed by either IEO or Mayo Clinic central laboratories. Table 1. HER2 Local/Central Lab Results Table 2. ER Local/Central Lab Results Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-36.
Does Information on Blood Heavy Metals Improve Cardiovascular Mortality Prediction?

Background To evaluate whether blood markers of lead, cadmium, and mercury can improve prediction for cardiovascular disease (CVD) mortality when added individually, jointly, or as an integrative index/Environmental Risk Score (ERS), in a model with established risk factors. Methods and Results Our study sample comprised 16 028 adults aged ≥40 years who were enrolled in the National Health and Nutrition Examination Survey 1999–2012 and followed up through December 31, 2015. The study sample was randomly split into training for the ERS construction (n=8043) and testing for the evaluation of prediction performance (n=7985). ERS was computed using elastic‐net penalized Cox's model based on the selected metal predictors predicting CVD mortality. During median follow‐up of 7.2 years, 517 died from CVD. In the training set, linear terms of cadmium and mercury, squared terms of lead and mercury, and all 3 pairwise interactions were selected by elastic‐net for ERS construction. In the testing set, the C‐statistic increased from 0.845 when only established CVD risk factors were in the model to 0.854 when the ERS was additionally added to the model. Addition of all linear, squared, and pairwise interaction terms of blood metals to the Cox's models improved C‐statistic from 0.845 to 0.857. The improvement remained significant when it was assessed by net reclassification improvement and integrated discrimination improvement. Conclusions Our findings suggest that blood markers of toxic metals can improve CVD risk prediction over the established risk factors and highlight their potential utility for CVD risk assessment, prevention, and precision health.
Chlorhexidine gluconate transparent dressing does not decrease central line‐associated bloodstream infection in critically ill patients: A randomized controlled trial

Abstract Background Central line‐associated blood stream infections are accompanied by increased mortality and health care costs. The application of different types of dressings in infection control has not been fully investigated to date. Aim To assess the effects of two different dressing types on central line‐associated bloodstream infections. Methods A randomized, nonblinded, controlled trial was conducted. Central lines were randomly allocated to intervention (chlorhexidine gluconate transparent dressing, n = 259) and control groups (standard dressing, n = 215). The central line‐associated bloodstream infection rate was assessed. Results A statistically nonsignificant difference was noted in the overall central line‐associated bloodstream infection rates between the two groups. The frequency of dressing changes in the patients with the chlorhexidine gluconate transparent dressing was significantly lower than that in the patients with a standard dressing. The predominant type of infectious microorganisms isolated from the central line‐associated bloodstream infection episodes was Gram‐negative bacteria (57.2%). Gram‐positive bacteria and fungi were noted at lower percentages (28.5% and 14.3%, respectively). Conclusion The use of a chlorhexidine gluconate transparent dressing does not decrease the central line‐associated bloodstream infection rate, although it decreases the frequency of dressing changes so may save nursing time.
Terpenoids from the South China Sea soft coral Sinularia multiflora

Abstract A rare sinulariane-type norcembranoid sinulariadiolide B (1) with a unique cyano group, and a eunicellin-based diterpenoid multifloralin (2), along with two known related analogues, sinulariadiolide (3) and sclerophytin E (4), were isolated from the extract of the South China Sea soft coral Sinularia multiflora. Their structures were elucidated on the basis of detailed spectroscopic analysis and by comparison with previously reported data. Compounds 2 and 4 showed potent antifouling activity against barnacle Balanus albicostatus. Graphical Abstract
Lopinavir-Ritonavir Impairs Adrenal Function in Infants.

BACKGROUND Perinatal treatment with lopinavir boosted by ritonavir (LPV/r) is associated with steroidogenic abnormalities. Long-term effects in infants have not been studied. METHODS Adrenal-hormone profiles were compared at weeks 6 and 26 between human immunodeficiency virus (HIV)-1-exposed but uninfected infants randomly assigned at 7 days of life to prophylaxis with LPV/r or lamivudine (3TC) to prevent transmission during breastfeeding. LPV/r in vitro effect on steroidogenesis was assessed in H295R cells. RESULTS At week 6, 159 frozen plasma samples from Burkina Faso and South Africa were assessed (LPV/r group: n = 92; 3TC group: n = 67) and at week 26, 95 samples from Burkina Faso (LPV/r group: n = 47; 3TC group: n = 48). At week 6, LPV/r-treated infants had a higher median dehydroepiandrosterone (DHEA) level than infants from the 3TC arm: 3.91 versus 1.48 ng/mL (P < .001). Higher DHEA levels (>5 ng/mL) at week 6 were associated with higher 17-OH-pregnenolone (7.78 vs 3.71 ng/mL, P = .0004) and lower testosterone (0.05 vs 1.34 ng/mL, P = .009) levels in LPV/r-exposed children. There was a significant correlation between the DHEA and LPV/r AUC levels (ρ = 0.40, P = .019) and Ctrough (ρ = 0.40, P = .017). At week 26, DHEA levels remained higher in the LPV/r arm: 0.45 versus 0.13 ng/mL (P = .002). Lopinavir, but not ritonavir, inhibited CYP17A1 and CYP21A2 activity in H295R cells. CONCLUSIONS Lopinavir was associated with dose-dependent adrenal dysfunction in infants. The impact of long-term exposure and potential clinical consequences require evaluation.Giving lopinavir to infants during their first year of life induces early, asymptomatic adrenal disruption compatible with the combined inhibition of CYP 21 and CYP 17 enzymes. The impact of prolonged treatment on the adrenal glands may require further attention.
Streptococcus pyogenes pbp2x Mutation Confers Reduced Susceptibility to β-lactam antibiotics.

Two near-identical clinical Streptococcus pyogenes isolates of emm subtype emm43.4 with a pbp2x missense mutation (T553K) were detected. Minimum inhibitory concentrations (MICs) for ampicillin and amoxicillin were 8-fold higher, and the MIC for cefotaxime was 3-fold higher than for near-isogenic control isolates, consistent with a first-step in developing β-lactam resistance.
The Contributions of Illness Stigma, Health Communication Difficulties, and Thwarted Belongingness to Depressive Symptoms in Youth with Inflammatory Bowel Disease.

OBJECTIVE Youth with inflammatory bowel disease (IBD) often experience difficulties communicating about their disease. It is suspected that the stigmatizing nature of IBD symptoms contributes to youths' health communication difficulties, leaving youth feeling disconnected from their social environment and potentially resulting in decreased social belongingness and poorer emotional functioning. In this study, we tested an illness stigma → health communication difficulties → thwarted belongingness → depressive symptoms serial mediation model. It was anticipated that youth illness stigma would confer a serial indirect effect on youth depressive symptoms through the sequential effects of stigma on health communication difficulties and thwarted social belongingness. METHODS Seventy-five youth with IBD between the ages of 10 and 18 completed measures of perceived illness stigma, health communication difficulties, thwarted belongingness, and depressive symptoms. RESULTS Results indicated a significant illness stigma → thwarted belongingness → depressive symptoms simple mediation path. Importantly, findings also revealed a significant serial mediation path for illness stigma → health communication difficulties → thwarted belongingness → depressive symptoms. CONCLUSIONS Youth who perceive greater IBD stigma appear to experience increased difficulty communicating about their IBD with others, which in turn is associated with feelings of thwarted social belongingness and ultimately elevated depressive symptoms. These findings suggest that difficulty communicating about IBD is one potential route by which illness stigma has a negative impact on youth adjustment outcomes. Results could also inform clinical interventions to address IBD stigma and health communication difficulties associated with the social and emotional challenges in youth with IBD.
Prevalence of Positive Family History of Colorectal Cancer in the Iranian General Population

Individuals with a positive family history of colorectal cancer have an increased risk of developing this type of cancer. The number of affected relatives and the age at diagnosis are two factors that increase the risk of colorectal cancer. The aim of this study was to assess the prevalence of a positive family history of colorectal cancer in a random sample among the Iranian general population. Methods: Five thousand five hundred (5500) subjects' aged≥20 years were randomly selected by cluster sampling and invited to participate in an interview about the occurrence of colorectal cancer in their first- or second-degree relatives. Results: Of all the responders, 162 (2.9%) subjects reported a positive family history of colorectal cancer; 71 (1.24%) reported having one first-degree relative with colorectal cancer diagnosed before the age of 50; or reported two or more first-degree relatives with colorectal cancer. In addition, 83 (1.51%) and 14 (0.25%) subjects reported having one and two or more second-degree relatives with colorectal cancer respectively. Conclusion: The prevalence of a positive family history of colorectal cancer in Iran is lower than the United States and European countries. Identifying high-risk population for colorectal cancer and encouraging them to participate in surveillance protocols is the first step in targeting preventive measures.
Immunohistochemistry for PRAME in the Distinction of Nodal Nevi From Metastatic Melanoma

The distinction of metastatic melanoma from melanocytic nevi in lymph nodes can on occasion be difficult. As diffuse immunohistochemical (IHC) PRAME (PReferentially expressed Antigen in MElanoma) expression is detected in the majority of primary and metastatic melanomas, but rarely in nevi, we reasoned that PRAME could be a useful adjunct marker for the diagnosis of melanocytes in lymph nodes. In this study, we examined 45 nodal melanocytic deposits comprising 30 nodal nevi and 15 melanoma metastases. The latter were diagnostically not straightforward because they either coexisted with nodal nevi or were present in perinodal fibrous tissue. All nodal nevi (30/30) were negative for PRAME, whereas all melanoma metastases (15/15) were diffusely positive for PRAME IHC. We additionally report the novel use of a PRAME/Melan A dual-label immunostain. Our results show that PRAME IHC may be useful in the assessment of diagnostically challenging nodal melanocytic deposits, such as intraparenchymal nodal nevi, metastases confined to the capsular fibrous tissue, or in the setting of small metastases coexisting with a nodal nevus in the same lymph node.
The Processing of Linguistic Prominence

Prominence, the expression of informational weight within utterances, can be signaled by prosodic highlighting (head-prominence, as in English) or by position (as in Korean edge-prominence). Prominence confers processing advantages, even if conveyed only by discourse manipulations. Here we compared processing of prominence in English and Korean, using a task that indexes processing success, namely recognition memory. In each language, participants’ memory was tested for target words heard in sentences in which they were prominent due to prosody, position, both or neither. Prominence produced recall advantage, but the relative effects differed across language. For Korean listeners the positional advantage was greater, but for English listeners prosodic and syntactic prominence had equivalent and additive effects. In a further experiment semantic and phonological foils tested depth of processing of the recall targets. Both foil types were correctly rejected, suggesting that semantic processing had not reached the level at which word form was no longer available. Together the results suggest that prominence processing is primarily driven by universal effects of information structure; but language-specific differences in frequency of experience prompt different relative advantages of prominence signal types. Processing efficiency increases in each case, however, creating more accurate and more rapidly contactable memory representations.
Identification of Hepatocellular Carcinoma-Related Potential Genes and Pathways Through Bioinformatic-Based Analyses.

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent tumors worldwide. However, the key roles of most molecules associated with tumor proliferation, invasion, and metastasis in HCC remain unclear. It is therefore important to explore potential mechanisms underlying tumorigenesis and to screen genes and pathways identified from such research for their role in pathogenesis. Materials and Methods: We selected microarray data GSE62043 consisting of paired tissue samples from 100 HCC patients, then these data were analyzed to identify differentially expressed genes (DEGs). Next, the gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to elucidate the biological processes, molecular function, cellular component (CC), and KEGG signaling pathways for DEGs. We then constructed protein-protein interaction (PPI) networks, followed by a functional enrichment analysis, from which we obtained two significant gene modules. Finally, the gene expression data obtained from this test set were subjected to validation studies using an independent set of hepatocellular patient data archived in The Cancer Genome Atlas and Genotype-Tissue Expression (TCGA/GTEx) database. Results: A total of 425 DEGs were identified that met both of our criteria for significance: (1) a |log2-fold change (FC)| ≥ 1.2 and (2) an adjusted p value <0.01. From these data, two significant gene modules, containing 28 pathway-related hub genes, were identified. Conclusion: Through application of a test/validation algorithm using HCC datasets from two independent databases, we identified a number of genes that could serve as potential biomarkers for the molecular diagnosis and therapeutic intervention of HCC, including the known genes, IGF1, IGF2, NDC80, CDK1, CENPF, CDCA8, CCNB1, BIRC5, NCAPG, and CDCA5, and the novel genes, CENPU and SPC25, which are associated with cell cycle, mitotic cell cycle, and organelle organization.
Stem cell derived oligodendrocytes to study myelin diseases

Oligodendroglial pathology is central to de‐ and dysmyelinating, but also contributes to neurodegenerative and psychiatric diseases as well as brain injury. The understanding of oligodendroglial biology in health and disease has been significantly increased during recent years by experimental in vitro and in vivo preclinical studies as well as histological analyses of human tissue samples. However, for many of these diseases the underlying pathology is still not fully understood and treatment options are frequently lacking. This is at least partly caused by the limited access to human oligodendrocytes from patients to perform functional studies and drug screens. The induced pluripotent stem cell technology (iPSC) represents a possibility to circumvent this obstacle and paves new ways to study human disease and to develop new treatment options for so far incurable central nervous system (CNS) diseases. In this review, we summarize the differences between human and rodent oligodendrocytes, provide an overview of the different techniques to generate oligodendrocytes from human progenitor or stem cells and describe the results from studies using iPSC derived oligodendroglial lineage cells. Furthermore, we discuss future perspectives and challenges of the iPSC technology with respect to disease modeling, drug screen, and cell transplantation approaches.
COPD_A_210759 2273..2281

Department of Radiation Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea; Division of Pulmonary andCritical CareMedicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Radiation Oncology, Samsung Medical Center, Seoul, South Korea; Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, SungkyunkwanUniversity School of Medicine, Seoul, South Korea; Statistics and Data Center, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea
The Nsp12-coding region of type 2 PRRSV is required for viral subgenomic mRNA synthesis

ABSTRACT As one of many nonstructural proteins of porcine reproductive and respiratory syndrome virus (PRRSV), nonstructural protein 12 (Nsp12) has received relatively little attention, and its role in virus replication, if any, is essentially unknown. By the application of reverse genetic manipulation of an infectious PRRSV clone, the current study is the first to demonstrate that Nsp12 is a key component of PRRSV replication. In addition, the biochemical properties of Nsp12 were evaluated, revealing that Nsp12 forms dimers when exposed to oxidative conditions. Furthermore, we systemically analyzed the function of Nsp12 in PRRSV RNA synthesis using a strand-specific PCR method. To our surprise, Nsp12 was not found to be involved in minus-strand genomic RNA (-gRNA) synthesis; importantly, our results indicate that Nsp12 is involved in the synthesis of both plus- and minus-strand subgenomic mRNAs (+sgmRNA and -sgmRNA). Finally, we found that the combination of cysteine 35 and cysteine 79 in Nsp12 is required for sgmRNA synthesis. To our knowledge, we are the first to report the biological role of Nsp12 in the PRRSV lifecycle, and we conclude that Nsp12 is involved in the synthesis of both + sgRNA and -sgRNA.
Adult and Continuing Education: Theory and Practice

The first edition of Adult and Continuing Education established itself as one of the most widely used and respected introductory texts on this important area of education. For this second edition, Peter Jarvis has made extensive revisions and has included substantial additional material to take account of the many changes which have occurred in the field of adult education. outlines a rationale for the provision of education for adults analyses contemporary theory offers practical advice on curriculum development and the teaching of adults.
Animal-assisted therapy and equine-assisted therapy/learning in Canada : surveying the current state of the field, its practitioners, and its practices

Supervisory Committee Dr. Timothy G. Black, Department of Educational Psychology and Leadership Studies Supervisor Dr. John O. Anderson, Department of Educational Psychology and Leadership Studies Departmental Member Animal-assisted therapy (AAT) and equine-assisted therapy/learning (EAT/L) are innovative techniques in counselling, psychotherapy, mental health, coaching, and other personal growth interventions. Although this field has experienced tremendous growth in the United States, very little is known about its Canadian equivalent. The purpose of this study was therefore to examine the current state of AAT and EAT/L in Canada, by conducting a national, bilingual (English and French) survey of helping professionals who involve animals in their practices. A total of 131 questionnaires were retained for analysis. The results of this study suggest that the field is very diverse, with a multitude of confusing terms and expressions, varying levels of education and training, and disagreement on how different practices are defined, resulting in a fragmented, confusing and inconsistent appearance. Recommendations for the evolution of the field and suggestions for future research are provided.
Blood : textbook of hematology

This edition of the benchmark text is more a complete revitalization than a revision: over 75 per cent of the text and 80 per cent of the references are new. Clearly written and abundantly illustrated, it presents the pathogenesis, clinical manifestations, and management of all hematologic disorders. It follows a logical organization from definition to treatment, and descriptions are written in language common to both clinical and basic science, making it as accessible to the general internist as to the specialist