Miracle-dz/UniFAR-FTUs huggingface dataset:
Parallel FISH and Immunohistochemical Studies of ALK Status in 3244 Non–Small-Cell Lung Cancers Reveal Major Discordances

Introduction: Anaplastic lymphoma kinase (ALK) rearrangements occur in 1% to 7% of non–small-cell lung cancers (NSCLCs). Crizotinib, an ALK inhibitor, has been demonstrated to provide dramatic clinical benefits in ALK-positive advanced-stage NSCLC. Fluorescent in situ hybridization (FISH) has been established in clinical trials as the standard procedure method for detecting ALK rearrangements. Although the detection of ALK by immunohistochemistry (IHC) has been proposed for the screening of patients, large-scale studies are warranted to validate such a hierarchical approach. Methods: In this article, we report the largest series thus far of parallel FISH and IHC ALK testing in 3244 consecutive NSCLC cases analyzed at two independent French centers. Results: FISH-positive and/or IHC-positive results were demonstrated in 150 of 3244 cases (4.6%). An imbalanced sex ratio was detected, with women exhibiting a 2.2-fold relative risk for an alteration. Strikingly, only 80 of 150 specimens were classified as ALK positive by both techniques. The specimens with discordant FISH/IHC analyses were FISH-positive/IHC-negative (36), FISH-negative/IHC-positive (19), or FISH-noncontributive/IHC-positive (15). Thus, a single FISH or IHC analysis performed alone would have failed to detect approximately one-fourth of the ALK-positive cases with similar findings in our two centers. Conclusions: This study highlights the feasibility of systematic NSCLC testing by both FISH and IHC in routine practice. Many preanalytical factors may account for the apparent discrepancies between both methods, suggesting that hierarchical screening may underscore ALK-positive cases. This significant level of discrepancy supports the need of combined testing to optimize the detection of ALK-inhibitor–eligible patients given that some patients with discordant testing were found to respond to crizotinib.
Stigmergic Linking for Optimising and Reasoning Over Information Networks

This main contribution of this report will be to describe and evaluate a set of tests, used to measure the effectiveness of stigmergic linking with regard to query optimisation. It will be shown that the results of queries can be autonomously fed back through a network to allow it to self-optimise. The type of network that is being considered is a network of information sources, such as a 'knowledge network'. This is a construct that will self-organise distributed knowledge in a way that allows it to be efficiently retrieved and used. Key elements thereof are its lightweight, reference-based structure and its autonomous nature. The network may have permanent organisational structures based on semantics. However, the stigmergic links will add an extra dimension to the self-organisation and allow it to optimise the query process effectively. These links will in effect create temporary views that reflect the use of the system and complement any permanent organisation created through semantics. Some tests on reasoning over the stored information will also be provided and shows that higher levels of reasoning can also be obtained.
An Examination of Strategies for Gaining Convergent Validity in Natural Experiments

Widely disseminated programs often fail to include experimental or quasi-experimental evaluation designs to test effectiveness. This article presents several data-analyzing strategies that may help evaluators assess program effectiveness under the conditions of natural experiments. The suggested methodology is to perform multiple independent analyses to demonstrate the degree of convergence or divergence on outcomes of the D.A. R.E (Drug Abuse Resistance Education) prevention program. When used in combination, multiple analyses strengthen the estimate of program effect by minimizing potentially spurious results that may emerge due to a particular analytic strategy.
Experimental Pharmacology of Glucosamine Sulfate

Several clinical studies demonstrated that glucosamine sulfate (GS) is effective in controlling osteoarthritis (OA), showing a structure-modifying action. However, little is known about the molecular mechanism(s) by which GS exerts such action and about the effects of GS at a tissue level on osteoarthritic cartilage and other joint structures. Here we provide mechanistic evidence suggesting that in vitro GS attenuates NF-κB activation at concentrations in the range of those observed after GS administration to volunteers and patients, thus strengthening previous findings. Furthermore, we describe the effects of GS at a tissue level on the progression of the disease in a relevant model of spontaneous OA, the STR/ort mouse. In this model, the administration of GS at human corresponding doses was associated with a significant decrease of OA scores. Histomorphometry showed that the lesion surface was also significantly decreased, while the number of viable chondrocytes within the matrix was significantly increased. GS improved the course of OA in the STR/Ort mouse, by delaying cartilage breakdown as assessed histologically and histomorphometrically.
Prolonged survival after complete resection of disseminated melanoma and active immunotherapy with a therapeutic cancer vaccine.

PURPOSE The curative effect of surgery in certain patients with metastatic melanoma suggests the presence of endogenous antitumor responses. Because melanoma is immunogenic, we investigated whether a therapeutic cancer vaccine called Canvaxin (CancerVax Corporation, Carlsbad, CA) could enhance antitumor immune responses and thereby prolong survival. PATIENTS AND METHODS Of 263 patients who underwent complete resection of American Joint Committee on Cancer stage IV melanoma, 150 received postoperative adjuvant vaccine therapy and 113 did not. The overall survival (OS) for the two groups was compared by Cox regression. Further survival analysis was performed by matched-pair analysis according to three prognostic variables: sex, metastatic site, and number of tumor-involved organ sites. RESULTS Five-year OS rates were 39% for vaccine and 19% for nonvaccine patients. On multivariate analysis, vaccine therapy was the most significant prognostic variable in this cohort (P =.0001). Analysis of 107 matched pairs of vaccine and nonvaccine patients revealed a significant OS advantage for vaccine therapy (P =.0009): 5-year OS was 39% for vaccine patients versus 20% for nonvaccine patients. There was a significant delayed-type hypersensitivity (DTH) response to adjuvant vaccine therapy (P =.0001), and OS was significantly correlated with DTH to vaccine (P =.0001) but not with DTH to purified protein derivative (PPD), a control antigen. CONCLUSION Prolonged survival was observed in patients who received postoperative active immunotherapy with Canvaxin therapeutic cancer vaccine. The correlation of survival with vaccine-DTH responses but not PPD-DTH indicates a treatment-specific effect. These findings suggest that adjuvant active specific immunotherapy should be considered after cytoreductive surgery for advanced melanoma.
Work values: Some demographic and cultural correlates

Employment-related values were recorded at two levels of scope: perceived importance of the work-role and of particular job characteristics. Associations with workers' sex, age, employment status, and education level were significant. Work values also differed among countries with a different cultural heritage - historically catholic, historically communist, or historically protestant. Implications for research into job content and reactions and for evaluative judgments in the operation of traits, motives, and attitudes were considered.
Potential Vorticity Evolution of a Protoplanetary Disk with an Embedded Protoplanet

We present two-dimensional inviscid hydrodynamic simulations of a protoplanetary disk with an embedded planet, emphasizing the evolution of potential vorticity (the ratio of vorticity to density) and its dependence on numerical resolutions. By analyzing the structure of spiral shocks made by the planet, we show that progressive changes of the potential vorticity caused by spiral shocks ultimately lead to the excitation of a secondary instability. We also demonstrate that very high numerical resolution is required to both follow the potential vorticity changes and identify the location where the secondary instability is first excited. Low-resolution results are shown to give the wrong location. We establish the robustness of a secondary instability and its impact on the planet's torque. After the saturation of the instability, the disk shows large-scale nonaxisymmetry, causing the torque on the planet to oscillate with large amplitude. The impact of the oscillating torque on the protoplanet's migration remains to be investigated.
Personal meanings of death: A content analysis of free-response narratives

Abstract Despite the proliferation of research on death attitudes, relatively little attention has been paid to idiosyncratic meanings of death, as opposed to the large volume of work on death anxiety using standardized measures. This study applied a reliable coding system to narrative descriptions of the meaning of death contributed by 504 respondents. Content analysis of these free-form responses suggested that constructions of death differed significantly depending on the subject's sex, health status, previous history of suicide attempts or ideation, and death fear or threat. Most importantly, respondents professing a coherent “personal philosophy of death” viewed death as more purposeful, expected, and involving some form of continued existence, whereas those without such a philosophy wrote narratives implying a negative evaluation, low acceptance, and low understanding of death. Modifications of the coding system for use with free-response data are suggested, along with applications of the method to .
The Anatomy of Subjective Well-Being

This paper contributes to the literature on subjective well-being (SWB) by taking into account different aspects of life, called domains, such as health, financial situation, job, leisure, housing, and environment. We postulate a two-layer model where individual total SWB depends on the different subjective domain satisfactions. A distinction is made between long-term and short-term effects. The individual domain satisfactions depend on objectively measurable variables, such as income. The model is estimated using a large German panel data set.
Designing and evaluating the acceptability of Realshare: An online support community for teenagers and young adults with cancer

A participatory action approach was used to design and evaluate the acceptability of the Realshare online community. Pre and post-intervention focus groups were conducted and participants were asked to test out Realshare during two intervention periods: when a facilitator was present and when one was not. Focus group data and forum messages were thematically analysed. The themes identified related to participants’ website design requirements, how they used the community and the evaluation of Realshare after having used it. Amendments were made to Realshare throughout the project. Realshare is available to young oncology patients in the South West of England.
Renal damage in systemic lupus erythematosus: a comparative analysis of different age groups

Renal damage in systemic lupus erythematosus: a comparative analysis of different age groups A Mak, CC Mok, WP Chu, CH To, SN Wong and TC Au Please note that the following pdf is a corrected version of the article which appears in the printed version of Lupus 16/1. An Erratum will also appear in print in Lupus; 16(2). The corrected line can be found in the abstract. It was changed from: Patients were categorized into childhood (age ≥6 years), adult (between 16 and 50 years) or late onset (≥50 years) SLE. To: Patients were categorized into childhood (age 16 years), adult (between 16 and 50 years) or late onset (50 years) SLE.The objective of this study was to compare the frequency and severity of renal damage in systemic lupus erythematosus (SLE) with regard to the age of disease onset. Among 287 patients with new onset SLE diagnosed between 1991 and 2003 in our hospital, we identified those who fulfilled the American College of Rheumatology (ACR) criteria for renal involvement. Patients were categorized into childhood (age <6 years), adult (between 16 and 50 years) or late onset (≥50 years) SLE. Clinical presentation of renal disease and cumulative renal damage as assessed by the renal domain of the Systemic Lupus International Collaborating Clinics/ACR damage index (SDI) were compared. A linear regression model was constructed to study the effect of age on renal damage. One-hundred and forty-nine patients were studied (134 women and 15 men), including 28 childhood, 107 adult and 14 late onset SLE patients. The mean age of SLE onset was 29.7 ± 14 years. The prevalence of renal disease was 53% in childhood onset, 50% in adult onset and 58% in late onset SLE patients (P = 0.66). At renal disease presentation, late onset SLE patients had significantly lower creatinine clearance and were more likely to be hypertensive. Histological classes of nephritis and initial treatment response, however, did not differ significantly among the patients. After a mean observation of 80.3 months, 32 (21%) patients developed renal damage (renal SDI ≥ 1). Late onset SLE patients had accrued more renal damage than the others. In a multiple regression model, age was not a significant determinant of renal damage after adjustment for baseline renal parameters, duration of renal disease, use of cyclophosphamide and initial treatment response. We concluded that the prevalence of renal disease was similar among SLE patients of different ages of onset. Late onset SLE patients had accrued more renal damage but age did not correlate with renal damage after adjustment for various clinical parameters.
Prognostic significance of human pituitary tumor-transforming gene immunohistochemical expression in differentiated thyroid cancer.

CONTEXT Human securin pituitary tumor-transforming gene (hPTTG) is overexpressed in a variety of primary neoplasias, including differentiated thyroid cancer (DTC). OBJECTIVE The objective of this study was to examine the immunohistochemical expression of hPTTG in DTC and its association with known prognostic factors. DESIGN hPTTG expression was analyzed by immunostaining on paraffin-embedded tissues. Clinical data were used to determine any associations between the expression of hPTTG and prognostic variables of DTC. A median follow-up of 43 months allowed us to analyze the persistence of disease and the response to radioiodine therapy. SETTING The study was conducted at a tertiary university hospital. PATIENTS Ninety-five patients undergoing surgical resection for DTC (n = 60) or benign nodular thyroid disease (n = 35) were studied. MAIN OUTCOME MEASURE The main outcome measure was the association between hPTTG expression and prognostic factors in DTC. RESULTS Among DTC cases, 21 (35%) had low and 39 (65%) had high hPTTG immunostaining. Adjacent nonneoplastic thyroid tissue was largely unstained. Among benign nodular thyroid disease cases, immunostaining was detected focally in eight (22.8%). A significant association was found between hPTTG expression and the presence of nodal (P < 0.01) or distant metastases (P < 0.05). A significant association with TNM was also found, because 83.3% of advanced TNM stages showed elevated hPTTG (P < 0.05). The association between hPTTG overexpression and decreased radioiodine uptake during follow-up was also significant (P < 0.05). The expression levels of hPTTG were confirmed as an independent prognostic factor for persistent disease (relative risk, 3.0; 95% confidence interval, 1.1-8.7; P < 0.05). CONCLUSIONS Immunohistochemical analysis of hPTTG is of potential value in the determination of tumor aggressiveness in DTC.
Computer-aided detection output on 172 subtle findings on normal mammograms previously obtained in women with breast cancer detected at follow-up screening mammography.

PURPOSE To evaluate, by using a computer-aided detection (CAD) program, the nonspecific findings on normal screening mammograms obtained in women in whom breast cancer was later detected at follow-up screening mammography. MATERIALS AND METHODS Four hundred ninety-three mammogram pairs-an initial negative screening mammogram and a subsequently obtained screening mammogram showing cancer-were collected. The mean interval between examinations was 14.6 months. In 169 cases, in which 172 cancers were later depicted, findings on the initial mammogram were subtle enough that either none or only one or two of five blinded radiologists recommended screening recall. On the initial negative mammograms, of the 172 areas where cancer later developed, 137 (80%) had subtle nonspecific findings and were retrospectively judged as having a benign or normal appearance. The mammograms with these subtle findings were evaluated with a commercially available CAD program, and the numbers of CAD marks on these nonspecific findings were analyzed. RESULTS Of the 172 cancers, 129 (75%) were invasive and 43 (25%) were ductal carcinoma in situ. The CAD program marked 72 (42%) of the 172 findings that subsequently developed into cancer: 24 (29%) of 82 findings recalled by none, 25 (49%) of 51 findings recalled by one, and 23 (59%) of 39 findings recalled by two of the five radiologists. Among the 137 areas with nonspecific normal or benign findings, 41 (30%) areas where cancer subsequently developed were marked by the CAD program. CONCLUSION A subset of cancers have perceptible but nonspecific mammographic findings that may be marked by a CAD program, even when the findings do not warrant recall as judged at blinded and unblinded radiologist review. The authors believe failure to act on such nonspecific but CAD-marked findings prospectively does not constitute interpretation below a reasonable standard of care.
The girl child and the family.

The appalling conditions of the Hindu, Muslim, Christian, and Sikh female children in India are emphasized. There is systematic neglect and exploitation of girls from birth through death. Dowries are still expected at the time of marriage and for years to come, regardless of the illegality. Within marriage, there is cruelty and insult, and even bride killing, known as dowry death. Parents can be accomplices in permitting the injury to begin or continue with impunity. Patience and tolerance is expected of daughters; the husband is the commanding presence. Spinsterhood is shameful. Suicide is a viable option for widowhood. Over the 40 years of freedom from British rule, antiquated norms and superstitions persist. Fundamentalism in increasing. A daughter is pitied at birth and a mother is blamed. Mothers-in-law are notorious for the blaming. These beliefs occur in spite of scientific evidence that it is the male who carries the chromosome in the sperm for sex determination. A modern practice helps to perpetuate female infanticide: amniocentesis and abortion. When food shortages occur, the pecking order favors males over pregnant women and children. Illiteracy is high among girls, who are kept home and given household chores. Better education is given to males even in middle class homes. Peer pressure and societal attitudes maintain the subservience of females. Orphanages are filled with unwanted female babies. The rape of a girl is considered shameful for life, while the rape of a boy is disregarded as unfortunate and forgotten. Expectations are that boys will be decision makers and girls can cope with domestic matters. The brainwashing to inferiority continues until the son marries and is then perpetuated.
The Freezing and Unfreezing of Impressional Primacy

Three constructive replications were executed to test the hypotheses that primary effects in impression formation are more pronounced when the individual feels (1) high versus low need for cognitive structure and (2) low versus high fear of invalidity. The experiments differed partially among themselves in the particular operational definitions of the structure and validity needs. In the first experiment need for structure was manipulated via demands for unidimensional (hence, global and undifferentiated) versus multidimensional judgments; and the fear of invalidity, via potential costs to the target person of subject's judgmental mistake. In the second experiment fear of invalidity was manipulated as in the first experiment and need for structure, via degrees of time pressure. In the third experiment need for structure was manipulated as in the first experiment and fear of invalidity, via degrees of evaluation apprehension. The research hypotheses were strongly confirmed in all three experiments. These results crossvalidate the findings of Kruglanski and Freund (1983) in which need for structure was operationalized via time pressure, and fear of invalidity, via evaluation apprehension.
Activation of intestinal CFTR Cl‐ channel by heat‐stable enterotoxin and guanylin via cAMP‐dependent protein kinase.

Heat‐stable enterotoxins (STa) produced by pathogenic bacteria induce profound salt and water secretion in the gut, leading to diarrhea. Recently, guanylin, an endogenous peptide with properties similar to STa, was identified. While STa and guanylin bind to the same receptor guanylyl cyclase and raise cell cGMP, the signaling mechanism distal to cGMP remains controversial. Here we show that STa, guanylin and cGMP each activate intestinal Cl‐ secretion, and that this is abolished by inhibitors of cAMP‐dependent protein kinase (PKA), suggesting that PKA is a major mediator of this effect. These agents induce Cl‐ secretion only in cells expressing the wild‐type CFTR, indicating that this molecule is the final common effector of the signaling pathway. The involvement of CFTR suggests a possible cystic fibrosis heterozygote advantage against STa‐induced diarrhea.
Contextualizing Gender and Migration: Galician Immigration to Switzerland

Focusing on two main aspects of the Spanish-Galician migration experience, this article attempts to analyze how migrants’ actions and discourses are shaped by notions of gender. First, the discourse of returning will question notions of family and how differently men and women define their positions as members of a family. While men seem to link their social identity to immovable goods of prestige back in Galicia, women are able to redefine their social identity as they base it on social relations. The second aspect deals with the fact that cleaning is defined as women's work, but at the same time it is – under certain conditions – performed by men.