Miracle-dz/UniFAR-FTUs huggingface dataset:
A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk

Abstract Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression. We investigated the genetic variants of EGFR, ERBB2, VEGFR and their ligands, EGF and VEGF on glioma and glioblastoma risk. In addition, we evaluated the association of genetic variants of a newly discovered family of genes known to interact with EGFR: LRIG2 and LRIG3 with glioma and glioblastoma risk. Methods. We analyzed 191 tag single nucleotide polymorphisms (SNPs) capturing all common genetic variation of EGF, EGFR, ERBB2, LRIG2, LRIG3, VEGF and VEGFR2 genes. Material from four case-control studies with 725 glioma patients (329 of who were glioblastoma patients) and their 1 610 controls was used. Haplotype analyses were conducted using SAS/Genetics software. Results. Fourteen of the SNPs were significantly associated with glioma risk at p< 0.05, and 17 of the SNPs were significantly associated with glioblastoma risk at p< 0.05. In addition, we found that one EGFR haplotype was related to increased glioblastoma risk at p=0.009, Odds Ratio [OR] = 1.67 (95% confidence interval (CI): 1.14, 2.45). The Bonferroni correction made all p-values non-significant. One SNP, rs4947986 next to the intron/exon boundary of exon 7 in EGFR, was validated in an independent data set of 713 glioblastoma and 2 236 controls, [OR] = 1.42 (95% CI: 1.06,1.91). Discussion. Previous studies show that regulation of the EGFR pathway plays a role in glioma progression but the present study is the first to find that certain genotypes of the EGFR gene may be related to glioblastoma risk. Further studies are required to reinvestigate these findings and evaluate the functional significance.
Response to Trans‐2016‐0405.R1

Gavva and colleagues recommend platelet transfusions as first-line treatment for bleeding episodes in patients with Factor V (FV) deficiency irrespective of etiology. I have the following concerns about their recommendation. Solvent-detergent treated plasma (SD-plasma) is the treatment of choice for bleeding episodes in patients who have congenital FV deficiency in the absence of inhibitor. Ease of availability, viral safety, low batch-to-batch variation in FV levels, and absence of risk of transfusionrelated acute lung injury (TRALI) support this recommendation. Viral safety must remain of prime concern given the potential need for repeated treatments in the lifetime of the patient with a congenital bleeding disorder. Platelet FV/Va originates from megakaryocyte endocytosis of plasma FV followed by intracellular processing, resulting in a molecule with intrinsic procoagulant activity (FV/FVa) that is resistant to inactivation by activated protein C. Transfusion of fresh-frozen plasma (FFP) in a patient with undetectable FV resulted in the stable repletion of platelet FV/Va, reaching a peak at 24 hours and capable of conferring hemostatic competence 10 days after the transfusion of FFP (platelet FV/Va level, approximately 7%), long after plasma FV became undetectable. The high concentration of platelet FV/Va at sites of vascular injury enables effective site-specific hemostasis. Concerns about viral safety, TRALI, and alloimmunization argue against the use of platelet transfusions as first-line therapy in the treatment of patients with congenital FV deficiency. During 2005 through 2009, 48% of the confirmed transfusion-related deaths in the United States reported to the US Food and Drug Administration were secondary to TRALI. There had been no reported instances of TRALI associated with SD-plasma as of 2011, although more than 13 million units had been transfused. Considering the unique role of platelet FV in promoting site-specific hemostasis, the use of platelet concentrates may be a valuable therapeutic addition to transfusion of SD-plasma in patients who have FV deficiency with acute, severe bleeding or intracranial hemorrhage. FV deficiency secondary to inhibitors is extremely rare and is treated more effectively with platelet transfusions in addition to other measures, including immunosuppressive therapy.
The emerging neuropathology of essential tremor

Essential tremor (ET) is one of the most prevalent neurological disorders. At the same time, it is among the most poorly‐understood of these disorders. The underlying anatomical pathology of ET has been elusive until recently. Postmortem studies have begun to display some of the underlying brain changes in patients with this disease. These types of investigations are likely to lead the way to additional insights into the pathophysiology of ET and guide the development of therapies for this common movement disorder. © 2007 Movement Disorder Society
Group Report: Early Social Attachment and Its Consequences

The origins and consequences of early social attachments are longstanding interests of developmental scientists that have been enlivened through the integrative contributions of psychobiological research. Among the issues to emerge in this integrative work are: • A better understanding of the behavioral and biological prerequisites for forming first attachments in infancy, and how these are reorganized when first attachments must develop later than is species-typical, or under atypical conditions. • A better understanding of how attachment develops in different cultural settings within the context of the biologically adaptive requirements of inclusive fitness. • A clearer conceptualization of the interaction between behavioral experience and psychobiological development with respect to how early caregiving shapes infant regulatory capacities, and how these influences become progressively updated through new caregiving experiences. • Greater theoretical clarification of how attachment continues to develop beyond infancy, and the representations associated with this developmental process, in concert with the development of new measures and methods for assessing attachment at later ages. • More systematic inquiry into the internal and external processes mediating continuity and change in attachment relationships over time, and what are the expectable consequences of early attachment relationships for both behavioral and psychobiological organization. • The integration of biological and behavioral insights into the most compelling question of all: How does early experience influence later behavior?
Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism

Background Cornelia de Lange syndrome (CdLS) is a multisystem disorder with distinctive facial appearance, intellectual disability and growth failure as prominent features. Most individuals with typical CdLS have de novo heterozygous loss-of-function mutations in NIPBL with mosaic individuals representing a significant proportion. Mutations in other cohesin components, SMC1A, SMC3, HDAC8 and RAD21 cause less typical CdLS. Methods We screened 163 affected individuals for coding region mutations in the known genes, 90 for genomic rearrangements, 19 for deep intronic variants in NIPBL and 5 had whole-exome sequencing. Results Pathogenic mutations [including mosaic changes] were identified in: NIPBL 46 [3] (28.2%); SMC1A 5 [1] (3.1%); SMC3 5 [1] (3.1%); HDAC8 6 [0] (3.6%) and RAD21 1 [0] (0.6%). One individual had a de novo 1.3 Mb deletion of 1p36.3. Another had a 520 kb duplication of 12q13.13 encompassing ESPL1, encoding separase, an enzyme that cleaves the cohesin ring. Three de novo mutations were identified in ANKRD11 demonstrating a phenotypic overlap with KBG syndrome. To estimate the number of undetected mosaic cases we used recursive partitioning to identify discriminating features in the NIPBL-positive subgroup. Filtering of the mutation-negative group on these features classified at least 18% as ‘NIPBL-like’. A computer composition of the average face of this NIPBL-like subgroup was also more typical in appearance than that of all others in the mutation-negative group supporting the existence of undetected mosaic cases. Conclusions Future diagnostic testing in ‘mutation-negative’ CdLS thus merits deeper sequencing of multiple DNA samples derived from different tissues.
Mitosis count and number of cancer cells in cases of primary pulmonary adenocarcinoma: Correlations among phosphorylated histone 3, number of cancer cells, nuclear grade, pathologic features and prognosis

Immunohistochemistry findings for the phosphorylated form of histone 3 (pHH3) have been shown to be a reliable mitosis‐specific marker. We evaluated the correlation between pHH3‐stained mitotic figures (PHMFs) and clinical outcome, and compared the results with findings for numbers of PHMFs and cancer cells. The primary tumor was obtained from 113 patients with pulmonary adenocarcinomas (≤2 cm maximum dimension). All specimens were stained with pHH3, then the number of cancer cells in each was determined. Cases with a cancer‐cell index ≥1000 showed worse recurrence‐free survival as compared to those with a value <1000 (P < 0.001). Also, cases with a pHH3 index ≥0.27 showed worse recurrence‐free survival as compared to <0.27 (P = 0.001) and cases with a pHH3/cancer‐cell index ≥0.001 showed worse recurrence‐free survival as compared to <0.001 (P = 0.002). Multivariate analysis demonstrated that pHH3/cancer‐cell index was significantly correlated with prognosis, but not Ki‐67 index. The number of cancer cells was also strongly correlated with progression of Noguchi's classification and WHO pathologic type. pHH3/cancer‐cell index was correlated with prognosis, and those were useful for prognostic evaluation of pulmonary adenocarcinoma patients. Furthermore, cancer cell number was correlated with Noguchi's classification and WHO pathologic type.
Role of Monocytes and Intestinal Macrophages in Crohn's Disease and Ulcerative Colitis

Abstract:Monocytes and macrophages are part of the body's first line of defence, eliminating pathogens by phagocytosis or by releasing a broad array of inflammatory mediators, such as cytokines, chemokines, and proteases. In humans, 3 subsets of monocytes are described in blood with seemingly different functions, the classical (CD14++CD16−) monocytes, the intermediate (CD14++CD16+) monocytes, and the nonclassical (CD14+CD16++) monocytes. In the intestine, macrophages can be divided into resident and inflammatory macrophages that are distinguished by low and high expression of CD14, respectively. However, the roles and function of the 3 monocyte subsets in health and disease are not fully understood. In this review, we describe what is known about the origin of human intestinal macrophages and their blood monocytic counterparts and many of their numerous distinct mechanisms influencing the intestinal immune system.
Canadian Treatment Guidelines on Psychosocial Treatment of Schizophrenia in Children and Youth

Objective: A panel of experts, including researchers, clinicians and people with lived experience, was brought together to develop the new Canadian schizophrenia guidelines for the psychosocial treatment of children and youth with schizophrenia or psychotic disorders. Method: The ADAPTE process, which relies on adapting existing high-quality guidelines, was used. Existing guidelines for children and youth (mostly from the National Institute for Health and Care Excellence [NICE]), as well as CPA adult guidelines, were reviewed and discussed in terms of their adaptability to the Canadian context and their level of recommendation for children and youth. New treatments were also considered when recent meta-analyses suggested their usefulness. Results: The children and youth psychosocial guidelines include many cross-sectional recommendations in terms of clinical and interpersonal skills needed to work with this clientele, setting and collaboration issues and needed adaptations for specific subpopulations. In terms of specific treatments, the treatments most strongly recommended are family intervention and cognitive behavior therapy. Also recommended, although with different degrees of support, are supported employment/supported education programs, patient education, cognitive remediation, and social skills training. Novel and upcoming psychosocial treatments are also briefly discussed. Conclusion: These novel Canadian guidelines for the psychosocial treatment of children and youth with schizophrenia or psychotic disorders report evidence-based treatments as well as important considerations for providers who work with this clientele. More studies with children and youth with schizophrenia and psychotic disorders are warranted. If followed, these guidelines should facilitate the recovery of children and youth with schizophrenia or psychotic disorders as well as the recovery of their families.
Tuberculosis contact investigation and DNA fingerprint surveillance in The Netherlands: 6 years' experience with nation-wide cluster feedback and cluster monitoring.

SETTING The Netherlands, 1995-2000. OBJECTIVES To describe the contribution of 6 years of nationwide DNA fingerprint surveillance to tuberculosis control in general and to conventional contact investigations in particular. DESIGN All Mycobacterium tuberculosis cultures are subjected to standardised IS6110-based RFLP typing, and clustered cases are systematically reported to the regional TB services involved (cluster feedback). Standardised questionnaires are used to collect information on contact investigations and epidemiological links (epi links) at regional level. Revision of the questionnaires for the period 1997-2000 allows comparison of epi linking before and after cluster feedback. RESULTS Among 2206 clustered cases, 462 (21%) epi links were expected before the RFLP result, whereas an additional 540 (24%) epi links were established after cluster feedback. Epi links based on documented exposure increased by 35%, from 357 to 550 (P < 0.001). Only 1% of contact investigations were extended, however, and relatively few additional persons with active or latent tuberculosis were diagnosed. Reasons for the limited impact on contact investigation outcome were 1) contact took place 1-7 years previously (51%), 2) documented contact involved a subsequent case in the cluster (21%), 3) casual contact (15.5%) and 4) different region (9%). Five per cent of epi links established by contact investigation were contradicted by RFLP data. Epi links were more frequently documented in Dutch (41%) than non-Dutch cases (19%, OR 3.0; 95%CI 1.41-1.91). Cluster monitoring permitted: 1) identification of transmission chains that could not be detected by contact investigations, 2) development and evaluation of targeted interventions, and 3) identification of professional failures and poor programme performance. CONCLUSIONS RFLP surveillance forms the bridge between conventional contact investigation and other forms of targeted active case finding. Combining both complementary strategies in a comprehensive approach to systematic outbreak monitoring and management allows countries in the elimination phase of the disease to better target and evaluate TB control interventions.
Regulation of Rab5 isoforms by transcriptional and post‐transcriptional mechanisms in yeast

Rab5 GTPases are master regulators of early endosome biogenesis and transport. The genome of Saccharomyces cerevisiae encodes three Rab5 proteins: Vps21, the major isoform, Ypt52 and Ypt53. Here, we show that Vps21 is the most abundant Rab5 protein and Ypt53 is the least abundant. In stressed cells, Ypt53 levels increase but never exceed that of Vps21. Its induction requires the transcription factors Crz1 and Gis1. In growing cells, the expression of Ypt53 is suppressed by post‐transcriptional mechanisms mediated by the untranslated regions of the YPT53 mRNA. Based on genetic experiments, these sequences appear to stimulate deadenylation, Pat1‐activated decapping and Xrn1‐mediated mRNA degradation. Once this regulation is bypassed, Ypt53 protein levels surpass Vps21, and Ypt53 is sufficient to maintain endosomal function and cell growth.
A Large-Scale Multi-Hop Localization Algorithm Based on Regularized Extreme Learning for Wireless Networks

A novel large-scale multi-hop localization algorithm based on regularized extreme learning is proposed in this paper. The large-scale multi-hop localization problem is formulated as a learning problem. Unlike other similar localization algorithms, the proposed algorithm overcomes the shortcoming of the traditional algorithms which are only applicable to an isotropic network, therefore has a strong adaptability to the complex deployment environment. The proposed algorithm is composed of three stages: data acquisition, modeling and location estimation. In data acquisition stage, the training information between nodes of the given network is collected. In modeling stage, the model among the hop-counts and the physical distances between nodes is constructed using regularized extreme learning. In location estimation stage, each node finds its specific location in a distributed manner. Theoretical analysis and several experiments show that the proposed algorithm can adapt to the different topological environments with low computational cost. Furthermore, high accuracy can be achieved by this method without setting complex parameters.
A triad of telomerase, androgen receptor and early growth response 1 in prostate cancer cells

ABSTRACT Telomerase activation is one of the key mechanisms that allow cells to bypass replicative senescence. Telomerase activity is primarily regulated at the level of transcription of its catalytic unit- hTERT. Prostate cancer (PCa), akin to other cancers, is characterized by high telomerase activity. Existing data suggest that hTERT expression and telomerase activity are positively regulated by androgenic stimuli in androgen-dependent prostate cancer (ADPC) cells. A part of the present study reaffirmed this by demonstrating a decline in the hTERT expression and telomerase activity on “loss of AR” in ADPC cells. The study further addressed 2 unresolved queries, i) whether AR-mediated signaling is of any relevance to hTERT expression in castration-resistant prostate cancer (CRPC) and ii) whether this signaling involves EGR1. Our data suggest that AR-mediated signaling negatively regulates hTERT expression in CRPC cells. Incidental support for the possibility of EGR1 being a regulator of hTERT expression in PCa was provided by i) immunolocalization of hTERT and EGR1 proteins in the same cell type (secretory epithelium) of PCa and BPH tissues; ii) significantly (p< 0.001) higher levels of both these proteins in CRPC (PC3 and DU145), compared with ADPC (LNCaP) cells. A direct evidence for the role of EGR1 in hTERT expression was evident by a significant (p<0.0001) decrease in the hTERT transcript levels in the EGR1-silenced CRPC cells. Further, “gain of AR” led to a significant reduction in the levels of hTERT and EGR1 in CRPC cells. However, restoration of EGR1 levels prevented the decline in the hTERT transcript levels in these cells. Taken together, our data indicate that AR regulates the expression of EGR1, which in turn acts as a positive regulator of hTERT expression in CRPC cells. Thus, AR exerts an inhibitory effect on hTERT expression and telomerase activity by modulating EGR1 levels in CRPC cells.
Sodium chloride supplementation of all plant protein broiler diets.

Male broiler chicks were fed all plant protein diets with soybean meal or a mixture of soybean and canola meals as the source of supplementary protein from 0 to 4 weeks of age. Supplementation of the diets with . 25% sodium chloride did not meet the requirements of the chicks for maximum growth. Growth was accelerated when the dietary sodium chloride concentration was increased to . 50 and 1.00%.
Inhomogeneity Based Characterization of Distribution Patterns on the Plasma Membrane

Cell surface protein and lipid molecules are organized in various patterns: randomly, along gradients, or clustered when segregated into discrete micro- and nano-domains. Their distribution is tightly coupled to events such as polarization, endocytosis, and intracellular signaling, but challenging to quantify using traditional techniques. Here we present a novel approach to quantify the distribution of plasma membrane proteins and lipids. This approach describes spatial patterns in degrees of inhomogeneity and incorporates an intensity-based correction to analyze images with a wide range of resolutions; we have termed it Quantitative Analysis of the Spatial distributions in Images using Mosaic segmentation and Dual parameter Optimization in Histograms (QuASIMoDOH). We tested its applicability using simulated microscopy images and images acquired by widefield microscopy, total internal reflection microscopy, structured illumination microscopy, and photoactivated localization microscopy. We validated QuASIMoDOH, successfully quantifying the distribution of protein and lipid molecules detected with several labeling techniques, in different cell model systems. We also used this method to characterize the reorganization of cell surface lipids in response to disrupted endosomal trafficking and to detect dynamic changes in the global and local organization of epidermal growth factor receptors across the cell surface. Our findings demonstrate that QuASIMoDOH can be used to assess protein and lipid patterns, quantifying distribution changes and spatial reorganization at the cell surface. An ImageJ/Fiji plugin of this analysis tool is provided.
Recent HIV Testing Prevalence, Determinants, and Disparities Among US Older Adult Respondents to the Behavioral Risk Factor Surveillance System

Background Although routine human immune deficiency virus (HIV) testing during health care visits is recommended for most adults, many older adults (i.e., ages 50–64 years) do not receive it. This study identified factors associated with HIV testing in the past 12 months (i.e., recent HIV testing) among US adults in the 3 categories of older adulthood (50–54, 55–59, and 60–64 years) for which routine HIV testing is recommended. Method This was a cross-sectional analysis of data from US older adult respondents to the 2010 Behavioral Risk Factor Surveillance System. We calculated prevalence (proportions) of HIV testing by age category and race/ethnicity. Using multiple logistic regression, we identified predisposing, enabling, and need factors associated with recent HIV testing within and across age categories, by race/ethnicity and controlling for covariates. Results HIV testing prevalence was low (<5%), varied by race/ethnicity, and decreased with age. Within and across age categories, the odds of testing were highest among blacks (odds ratio [OR], 3.47; 95% confidence interval [CI], 2.82–4.25) and higher among Latinos (OR, 2.06; 95% CI, 1.50–2.84) and the oldest and youngest categories of American Indians/Alaska Natives (OR, 2.48; 95% CI, 1.11–5.55; OR, 2.98; 95% CI, 1.49–5.95) than among whites. Those reporting a recent doctor visit (OR, 2.32; 95% CI, 1.92–2.74) or HIV risk behaviors (OR, 3.50; 95% CI, 2.67–4.59) had higher odds of HIV testing. Conclusion Regardless of risk, the oldest older adults, whites, and older women may forego HIV testing. Doctor visits may facilitate HIV testing. Additional research is needed to understand why eligible older adults seen by providers may not be screened for HIV infection.