julilili42/papers huggingface dataset:
Nuclear matrix protein‐22: a prospective evaluation in a population at risk for bladder cancer. Results from the UroScreen study
2012-02-07

Study Type – Diagnostic (non‐consecutive cohort without consistently applied reference standard) Level of Evidence 3b What's known on the subject? and What does the study add? The prognosis of bladder cancer significantly depends on tumour stage and time of diagnosis so early diagnosis is desirable to decrease mortality and treatment costs. The NMP22 test is approved for clinical application by the Food and Drug Administration (FDA) of the US. Previous studies have reported values of 47–100% for sensitivity and 58–91% for specificity with this test, but there is no new data on the predictive value of NMP22 for screening bladder cancer (BC). The most important risk factor for BC is the tobacco consumption but occupational exposure to carcinogenic substances, especially aromatic amines, is regarded as another risk factor. The UroScreen study is a prospective longitudinal study for the early detection of BC. To our knowledge, it is the largest prospective validation study conducted over the longest period of time. The study results led us to conclude that, based on the currently available data, NMP22 should not be regarded as an alternative to endoscopy, and we could not make a general recommendation for screening or follow‐up. The UroScreen results indicate that urine‐based molecular markers could be a suitable addition to urine cytology and the detection of microhaematuria. OBJECTIVE To evaluate the value of nuclear matrix protein‐22 (NMP22) in bladder cancer (BC) screening, and its effect on variables in a prospective study in a high‐risk population. PATIENTS AND METHODS A total of 1772 chemical workers (mean age 62 years) exposed to carcinogenic aromatic amines were enrolled in the study. In all, 7091 screening check‐ups in 1609 subjects were performed. Urine samples were collected for a quantitative NMP22 immunoassay, urine analysis and creatinine concentration assessment. Cystoscopy and subsequent transurethral resection were performed where there were suspicious findings. RESULTS Histopathological analysis found three papillary urothelial neoplasms of low malignant potential, five recurrent BCs and 13 primary BCs. Three tumours were at a muscle‐invasive stage (pT2, pT3a or pT3b). We found higher NMP22 concentrations (&gt;10 U/mL) in 224 patients, which correctly predicted BC in six cases (sensitivity 97.29%, specificity 28.57%; negative predictive value 99.04%, positive predictive value 12.24%). Gross haematuria affected NMP22 results (odd ratio [OR] 3.49, 95% confidence interval [CI] 1.81–6.73). Infection also affected NMP22 results (OR 4.13, 95% CI 2.31–7.35). NMP22 was more frequently positive in urine with creatinine concentration &gt;2.5 g/L (OR 1.61, 95% CI 0.91–2.86). CONCLUSIONS NMP22 outcomes are affected by haematuria, infection and concentrated urine. NMP22 alone cannot be recommended for primary screening in a high‐risk population nor as an alternative to cystoscopy during follow‐up. A NMP22 test might be a useful adjunct to urine cytology.
Serum‐ and glucocorticoid‐dependent kinase‐1‐induced cell migration is dependent on vinculin and regulated by the membrane androgen receptor
2012-02-07

The serum‐ and glucocorticoid‐dependent kinases 1–3 (SGK1–3) are downstream effectors of phosphatidylinositol 3‐kinases, implicated in various cell responses including colon cancer tumorigenesis in mice. Here, we investigated the role of SGK1 in the regulation of cell motility. Using Caco‐2 colon tumor and HEK293 embryonic kidney cells, we report that transfection with the constitutively active SGK1 mutant (SGK1‐SD) significantly enhanced cell motility. The cell‐adhesion protein vinculin was effectively dephosphorylated in SGK1‐SD‐transfected cells. Treatment of the cells with phosphatase inhibitors restored vinculin phosphorylation and inhibited cell migration, indicating a significant role for vinculin phosphorylation in SGK1‐induced motility. SGK1‐SD‐enhanced cell motility was inhibited by activation of membrane androgen‐binding sites (mAR) via testosterone‐conjugates in both cell lines, whereas intracellular androgen receptor (iAR)‐silencing and flutamide treatment revealed that these effects were clearly independent of the interaction of SGK1 with the classical androgen receptors (iAR). More importantly, mAR activation restored vinculin phosphorylation in SGK1‐SD‐transfected cells, whereas silencing of vinculin fully reversed the mAR‐induced inhibition of the migratory capacity, implying that this protein is directly involved in cell motility regulation by SGK1 and mAR. This study indicates for the first time that SGK1 regulates cell migration via vinculin dephosphorylation, a mechanism that is controlled by mAR function.
Nature of the scalar-isoscalar mesons in the uniformizing-variable method based on analyticity and unitarity
2012-02-07

The experimental data on the processes in the channel have been jointly analyzed to study the status and nature of the . The method of analysis is based on analyticity and unitarity and uses an uniformization procedure. Some spectroscopic implications from results of the analysis are discussed.
Prospective assessment of histological serial sectioning of pelvic lymph nodes in prostate cancer: a cost‐benefit analysis
2012-02-07

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Metastatic spread to the regional lymph nodes (LNs) is the single worst predictor of survival in prostate cancer. Knowledge of the LN status is crucial, as the treatment strategy is substantially altered in non‐organ‐confined disease. Current routine pathological protocols for evaluation of LN resection specimens do not demand a minimum of cross‐sections per LN to be examined. Depending on the LN size, usually one to two sections are examined. This might lead to underestimation of the true metastatic burden. The present study shows that additional examination of cross‐sections in pelvic LNs and applying prostate cancer‐specific cytokeratine immunostaining does not lead to significantly increased detection of prostate cancer metastases. However, the work‐load and the expenses were significantly higher compared with routine evaluation. OBJECTIVE To evaluate the diagnostic gain in the detection of lymph node (LN) metastases of prostate cancer and the additional expenses of histological step‐section analysis, including immunohistochemistry compared with routine histopathological evaluation. PATIENTS AND METHODS In a prospective study, 19 patients with prostate cancer at high risk of LN metastases (&gt;cT2c and/or PSA level of &gt;20 ng/mL and/or Gleason score &gt;8) underwent sentinel‐guided LN resection. All palpable LNs were submitted to step‐section analysis in 200‐μm sections and concomitant immunohistochemical staining for cytokeratine (AE1/AE3), in addition to routine histopathology of one or two haematoxylin and eosin‐stained sections per LN. The number of positive LNs and LN‐positive patients for each method was compared; additional expenses in labour time and material for the extended evaluation were estimated. RESULTS In all, 413 LNs were resected; 220 LNs were palpable and were included in the study. In seven of the 19 patients routine histopathological evaluation revealed LN metastases in 24 of 220 LNs (10.9%). Extended LN evaluation with step sectioning and cytokeratin immunohistochemistry did not reveal any additional patients with LN metastases. In one patient already diagnosed with LN metastases on routine histology, four additional LN metastases were detected upon extended LN evaluation. Three LNs of two patients, one of them pN0, contained disseminated tumour cells. Compared with conventional histological evaluation, serial‐section analysis and immunohistochemistry increased expenses in materials and labour time 18.7‐fold. CONCLUSIONS Serial‐section analysis seems to have only a minimal diagnostic gain; however, valid conclusions cannot be drawn, as not all LNs were submitted to extended evaluation. Considering the additional expenses, extensive LN evaluation in prostate cancer cannot generally be recommended.
Schistosomes Induce Regulatory Features in Human and Mouse CD1dhi B Cells: Inhibition of Allergic Inflammation by IL-10 and Regulatory T Cells
2012-02-08

Chronic helminth infections, such as schistosomes, are negatively associated with allergic disorders. Here, using B cell IL-10-deficient mice, Schistosoma mansoni-mediated protection against experimental ovalbumin-induced allergic airway inflammation (AAI) was shown to be specifically dependent on IL-10-producing B cells. To study the organs involved, we transferred B cells from lungs, mesenteric lymph nodes or spleen of OVA-infected mice to recipient OVA-sensitized mice, and showed that both lung and splenic B cells reduced AAI, but only splenic B cells in an IL-10-dependent manner. Although splenic B cell protection was accompanied by elevated levels of pulmonary FoxP3(+) regulatory T cells, in vivo ablation of FoxP3(+) T cells only moderately restored AAI, indicating an important role for the direct suppressory effect of regulatory B cells. Splenic marginal zone CD1d(+) B cells proved to be the responsible splenic B cell subset as they produced high levels of IL-10 and induced FoxP3(+) T cells in vitro. Indeed, transfer of CD1d(+) MZ-depleted splenic B cells from infected mice restored AAI. Markedly, we found a similarly elevated population of CD1d(hi) B cells in peripheral blood of Schistosoma haematobium-infected Gabonese children compared to uninfected children and these cells produced elevated levels of IL-10. Importantly, the number of IL-10-producing CD1d(hi) B cells was reduced after anti-schistosome treatment. This study points out that in both mice and men schistosomes have the capacity to drive the development of IL-10-producing regulatory CD1d(hi) B cells and furthermore, these are instrumental in reducing experimental allergic inflammation in mice.
Working Memory and Response Inhibition as One Integral Phenotype of Adult ADHD? A Behavioral and Imaging Correlational Investigation
2012-02-08

Objective: It is an open question whether working memory (WM) and response inhibition (RI) constitute one integral phenotype in attention deficit hyperactivity disorder (ADHD). Method: The authors investigated 45 adult ADHD patients and 41 controls comparable for age, gender, intelligence, and education during a letter n-back and a stop-signal task, and measured prefrontal oxygenation by means of functional near-infrared spectroscopy. Results: The authors replicated behavioral and cortical activation deficits in patients compared with controls for both tasks and also for performance in both control conditions. In the patient group, 2-back performance was correlated with stop-signal reaction time. This correlation did not seem to be specific for WM and RI as 1-back performance was correlated with go reaction time. No significant correlations of prefrontal oxygenation between WM and RI were found. Conclusion: The authors’ findings do not support the hypothesis of WM and RI representing one integral phenotype of ADHD mediated by the prefrontal cortex.
Functional and total IGFBP3 for the assessment of disorders of the GH/IGF1 axis in children with chronic kidney disease, GH deficiency, or short stature after SGA status at birth
2012-02-08

Pediatric CKD patients displayed elevated serum concentrations of t-IGFBP3 but not f-IGFBP3, supporting the hypothesis that IGFBP3 fragments not binding IGF1 accumulate during uremia. f-IGFBP3 is an indicator of IGFBP3 fragmentation and seems to reflect IGF1 binding in CKD better than t-IGFBP3. However, the role of f-IGFBP3 for the diagnosis of disturbances of the GH/IGF hormonal axis appears to be limited.
Double Beta Decay, Nuclear Structure and Physics beyond the Standard Model
2012-02-08

Neutrinoless Double Beta Decay ( ) is presently the only known experiment to distinguisch between Dirac neutrinos, different from their antiparticles, and Majorana neutrinos, identical with their antiparticles. In addition allows to determine the absolute scale of the neutrino masses. This is not possible with neutrino oscillations. To determine the neutrino masses one must assume, that the light Majorana neutrino exchange is the leading mechanism for and that the matrix element of this transition can ba calculated reliably. The experimental transition amplitude in this mechanism is a product of the light left handed effective Majorana neutrino mass and of this transition matrix element. The different methods, Quasi-particle Random Phase Approximation (QRPA), Shell Model (SM), Projected Hartree-Fock-Bogoliubov (PHFB) and Interacting Boson Model (IBM2) used in the literature and the reliability of the matrix elements in these approaches are reviewed. In the second part it is investigated how one can determine the leading mechanism or mechanisms from the data of the decay in different nuclei. Explicite expressions are given for the transition matrix elements. is shown, that possible interference terms allow to test CP (Charge and Parity conjugation) violation.
Effects of polypharmacy on outcome in patients with schizophrenia in routine psychiatric treatment
2012-02-09

Längle G, Steinert T, Weiser P, Schepp W, Jaeger S, Pfiffner C, Frasch K, Eschweiler GW, Messer T, Croissant D, Becker T, Kilian R. Effects of polypharmacy on outcome in patients with schizophrenia in routine psychiatric treatment. Objective: Evaluating the effects of different types of psychotropic polypharmacy on clinical outcomes and quality of life (QOL) in 374 patients with schizophrenia and schizoaffective disorder in routine care. Method: Psychotropic regimen, clinical outcomes, and QOL were assessed before discharge and after 6, 12, 18, and 24 months. Data were analyzed by mixed‐effects regression models for longitudinal data controlling for selection bias by means of propensity scores. Results: At baseline 22% of participants received antipsychotic monotherapy (APM) (quetiapine, olanzapine, or risperidone), 20% more than one antipsychotic drug, 16% received antipsychotics combined with antidepressants, 16% antipsychotics plus benzodiazepines, 11.5% had antipsychotics and mood stabilizers, and 16% psychotropic drugs from three or more subclasses. Patients receiving APM had better clinical characteristics and QOL at baseline. Patients receiving i) antipsychotics plus benzodiazepines or ii) antipsychotics plus drugs from at least two additional psychotropic drug categories improved less than patients with APM. Conclusion: Combinations of antipsychotics with other psychotropic drugs seem to be effective in special indications. Nevertheless, combinations with benzodiazepines and with compounds from multiple drug classes should be critically reviewed. It is unclear whether poorer outcomes in patients with such treatment are its result or its cause.
Cytotoxicity of new duplex drugs linking 3′‐C‐ethynylcytidine and 5‐fluor‐2′‐deoxyuridine against human melanoma cells
2012-02-09

Abstract Melanoma is an increasingly common and potentially fatal malignancy of the skin and some mucous membranes. As no cure exists for metastatic disease, there is an urgent need for novel drugs. 2′‐Deoxy‐5‐fluorouridylyl‐(3′‐5′)‐3′‐C‐ethynylcytidine [5‐FdU(3′‐5′)ECyd] and 3′‐C‐ethynylcytidinylyl‐(5′→1‐O)‐2‐O‐octadecyl‐sn‐glycerylyl‐(3‐O→5′)‐2′‐deoxy‐5‐fluorouridine [ECyd‐lipid‐5‐FdU] represent cytostatic active duplex drugs, which can be metabolized into various active antimetabolites. We evaluated the cytotoxicity of these heterodinucleoside phosphate analogs, their corresponding monomers ECyd and 5‐FdU and combinations thereof on six metastatic melanoma cell lines and six ex vivo patient‐derived melanoma cells in comparison to current standard cytostatic agents and the BRAF V600E inhibitor Vemurafenib. In vitro (real‐time)‐proliferation assays demonstrated that 5‐FdU(3′‐5′)ECyd and ECyd‐lipid‐5‐FdU had a high cytotoxic efficacy causing 75% melanoma cell death at concentrations in the nanomolar and micromolar range. Cytotoxicity was conducted by induction of DNA cleavage indicating apoptotic cells. Chicken embryotoxicity demonstrated that the duplex drugs were less toxic than 5‐FdU at 0.01 μM. In vivo the duplex drug 5‐FdU(3′‐5′)ECyd was efficacious in the murine LOX IMVI melanoma xenograph model on administration of 11.2 mg/kg/injection every fourth day. Both duplex drugs are promising novel cytostatic agents for the treatment of malignant melanoma meriting clinical evaluation.
Interventions for erosive lichen planus affecting mucosal sites
2012-02-10

This review suggests that there is only weak evidence for the effectiveness of any of the treatments for oral ELP, whilst no evidence was found for genital ELP. More RCTs on a larger scale are needed in the oral and genital ELP populations. We suggest that future studies should have standardised outcome variables that are clinically important to affected individuals. We recommend the measurement of a clinical severity score and a participant-rated symptom score using agreed and validated severity scoring tools. We also recommend the development of a validated combined severity scoring tool for both oral and genital populations.
The Composition of Family Background: The Influence of the Economic and Cultural Resources of both Parents on the Offspring's Educational Attainment in the Netherlands between 1939 and 1991
2012-02-10

This article studies the effect of parental background on the educational attainment of the offspring. In particular, it compares the effects of parental occupation and education and investigates whether the relative importance of these resources have shifted over time. In addition, this article studies, which parent has the strongest effect on the offspring's education. Using data for the Netherlands, this article finds that occupational status has the same effect regardless of who contributed it, while for the effect of parental education, it matters whether the parent is the highest, same, or lowest educated parent. No evidence was found that the relative sizes of these effects have changed over cohorts.
Dietary Fiber Intake Modulates the Association Between Variants in TCF7L2 and Weight Loss During a Lifestyle Intervention
2012-02-10

Single nucleotide polymorphisms (SNPs) within the transcription factor 7-like 2 ( TCF7L2 ) gene are well known risk variants for type 2 diabetes (1). The best studied SNP is rs7903146, which is additionally associated with insulin secretion (2) and BMI (3). We furthermore reported that this variant influenced weight loss during the Tubingen Lifestyle Intervention Program (TULIP) such that carriers of the nonrisk CC alleles lost more weight than carriers of XT alleles (4). The TULIP program consists of exercise and diet intervention with decreased intake of fat and increased intake of fibers (participants were instructed to eat at least 15 g fiber per 1,000 kcal). However, a recent report (1) from the Diabetes Prevention Program (DPP) failed to replicate the association of TCF7L2 SNP rs7903146 with successful weight loss during lifestyle intervention. The authors speculated that ...
Associating the magnitude of relative afferent pupillary defect (RAPD) with visual field indices in glaucoma patients
2012-02-10

The prevalence of RAPD in glaucoma patients is comparatively small (25%). The magnitude of RAPD in glaucoma subjects is associated most closely with the LVOL within 30° eccentricity (which is the maximum visual field region tested in this study) and most loosely with central DLS, underscoring the impact of the entire (30°) visual field area on the afferent pupillary system.
4-(4-Fluorophenyl)-1-(4-nitrophenyl)-3-(pyridin-4-yl)-1H-pyrazol-5-amine
2012-02-10

In the crystal structure of the title compound, C(20)H(14)FN(5)O(2), the pyrazole ring forms dihedral angles of 59.3 (2), 25.6 (2) and 46.0 (2)° with the directly attached 4-fluoro-phenyl, pyridine and nitro-phenyl rings, respectively. The crystal packing is characterized by inter-molecular N-H⋯N and N-H⋯O hydrogen bonds.
4-(4-Fluorophenyl)-1-phenyl-3-(pyridin-4-yl)-1H-pyrazol-5-amine
2012-02-10

In the title compound, C(20)H(15)FN(4), the pyrazole ring forms dihedral angles of 43.51 (6), 39.95 (6) and 32.23 (6)° with the directly attached 4-fluoro-phenyl, pyridine and phenyl rings, respectively. The crystal packing is stabilized by inter-molecular N-H⋯N and N-H⋯F hydrogen bonds.
Association of high cytoplasmic expression of p27 Kip1 on cancer-specific survival in clear cell renal cell carcinoma.
2012-02-10

418 Background: p27Kip1 is considered to contribute to the progression of ccRCC and is targeted by next generation dual-therapies. Cytoplasmic and nuclear differences of p27 Kip1 expression and localization in benign and clear cell renal cell carcinoma (ccRCC) were analyzed with regard to overall survival (OS) and cancer-specific survival (CSS). Methods: In 140 patients, ccRCC and corresponding benign kidney tissue were analyzed for nuclear and cytoplasmic staining of p27Kip1 by immunohistochemistry using a tissue microarray technique. Staining intensity and percentage of positive stained cells are given as expression scores. p27Kip1 expression was categorized as high if ccRCC tissue stained stronger than the respective level of the corresponding benign tissue and categorized as low if ccRCC tissue stained less than or equal to the corresponding benign tissue. Differences in OS and CSS were analyzed by log-rank analysis and expression levels were correlated with tumour and patient characteristics using Fisher’s exact test. Results: Cytoplasmatic (mean [SD]: 13.8% [1.2%] vs 10.7% [1.7%]; P = 0.04) and nuclear (mean [SD]: 75.6% [2.7%] vs 13.6% [2.1%]; P &lt; 0.001) staining of p27Kip1 were significantly stronger in ccRCC tissues compared to benign tissue. High cytoplasmic p27Kip1 expression was significantly associated with a higher T and N stage, Fuhrman grade and the presence of metastatic disease (P &lt; 0.001). The median follow-up time was 38.2 months. There was no difference in OS between the low and high expression groups, although CSS was significantly lower in patients with high cytoplasmic p27Kip1 (P &lt; 0.001) and CSS heavily tended to be lower in the nuclear low expression group (P = 0.069). Conclusions: High cytoplasmic p27Kip1 levels in renal cancer tissues are associated with advanced disease and reduced cancer specific survival, whereas low nuclear expression levels appear to be beneficial. The present study corroborates the consideration of cytoplasmic p27Kip1 for future diagnostic and targeted therapeutic approaches in RCC establishing a potential protective shift of p27Kip1 from the cytoplasm to the nucleus.
Right Portal Vein Ligation Combined With In Situ Splitting Induces Rapid Left Lateral Liver Lobe Hypertrophy Enabling 2-Staged Extended Right Hepatic Resection in Small-for-Size Settings
2012-02-11

Two-step hepatic resection performing surgical exploration, PVL, and ISS results in a marked and rapid hypertrophy of functional liver tissue and enables curative resection of marginally resectable liver tumors or metastases in patients that might otherwise be regarded as palliative.