julilili42/papers huggingface dataset:
Development of a new outcome prediction model in carcinoma invading the bladder based on preoperative serum C‐reactive protein and standard pathological risk factors: the TNR‐C score
2011-04-20

Study Type – Prognosis (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? There is increasing evidence for a prognostic significance of pretherapeutically elevated serum C‐reactive protein levels in various cancers. However, little is known about its significance in patients with invasive bladder cancer. This study shows that serum CRP is an independent predictor for cancer‐specific survival in bladder cancer, and its incorporation into a new outcome model (TNR‐C Score) encompassing major pathological determinants for survival, increases significantly its predictive accuracy. OBJECTIVE • To assess the predictive value of preoperative C‐reactive protein (CRP) in patients undergoing radical cystectomy (RC) for carcinoma invading the bladder in light of recent data showing it to be an independent indicator of adverse oncological outcome in other malignancies. PATIENTS AND METHODS • A contemporary, consecutive series of 246 patients undergoing RC and bilateral pelvic lymphadenectomy for bladder cancer between 1999 and 2009. • Elevated CRP was defined as &gt;0.5 mg/dL and was consistent during the study period. The median (range) follow‐up was 30 (6–116) months. • Kaplan–Meier analysis was used to estimate cancer‐specific survival (CSS) using a log‐rank test and Cox regression analysis for multivariate analysis of risk factors. • Based on regression estimates of significant parameters in multivariate analysis, a new CRP‐based scoring model was developed to predict cancer‐specific outcomes. The predictive accuracy of the model was evaluated using the concordance index. RESULTS • The 3‐year CSS was 74.0% in patients with normal and 44.0% with elevated CRP ( P &lt; 0.001). • In multivariate analysis, CRP ( P &lt; 0.001; used as a continuous variable), tumour stage ( P = 0.001), lymph‐node density ≥0.09 ( P = 0.02) and resection margin status ( P &lt; 0.001) were independent predictors of CSS. • The 3‐year CSS in patients with a score in the ranges 0–2, 3–6 and 7–10 was 80.5%, 44.9% and 7.1%, respectively ( P &lt; 0.001). Consideration of CRP in the final model increased its predictive accuracy by 4.9% with a concordance index of 0.788 ( P = 0.01). CONCLUSIONS • This is the largest, contemporary series to date indicating that preoperative serum CRP is an independent risk factor for CSS. • CRP may be a useful parameter to include in predictive bladder cancer nomograms.
First Hominoid from the Late Miocene of the Irrawaddy Formation (Myanmar)
2011-04-20

For over a century, a Neogene fossil mammal fauna has been known in the Irrawaddy Formation in central Myanmar. Unfortunately, the lack of accurately located fossiliferous sites and the absence of hominoid fossils have impeded paleontological studies. Here we describe the first hominoid found in Myanmar together with a Hipparion (s.l.) associated mammal fauna from Irrawaddy Formation deposits dated between 10.4 and 8.8 Ma by biochronology and magnetostratigraphy. This hominoid documents a new species of Khoratpithecus, increasing thereby the Miocene diversity of southern Asian hominoids. The composition of the associated fauna as well as stable isotope data on Hipparion (s.l.) indicate that it inhabited an evergreen forest in a C3-plant environment. Our results enlighten that late Miocene hominoids were more regionally diversified than other large mammals, pointing towards regionally-bounded evolution of the representatives of this group in Southeast Asia. The Irrawaddy Formation, with its extensive outcrops and long temporal range, has a great potential for improving our knowledge of hominoid evolution in Asia.
Sorting of droplets by migration on structured surfaces
2011-04-20

Background: Controlled transport of microdroplets is a topic of interest for various applications. It is well known that liquid droplets move towards areas of minimum contact angle if placed on a flat solid surface exhibiting a gradient of contact angle. This effect can be utilised for droplet manipulation. In this contribution we describe how controlled droplet movement can be achieved by a surface pattern consisting of cones and funnels whose length scales are comparable to the droplet diameter. Results: The surface energy of a droplet attached to a cone in a symmetry-preserving way can be smaller than the surface energy of a freely floating droplet. If the value of the contact angle is fixed and lies within a certain interval, then droplets sitting initially on a cone can gain energy by moving to adjacent cones. Conclusion: Surfaces covered with cone-shaped protrusions or cavities may be devised for constructing “band-conveyors” for droplets. In our approach, it is essentially the surface structure which is varied, not the contact angle. It may be speculated that suitably patterned surfaces are also utilised in biological surfaces where a large variety of ornamentations and surface structuring are often observed.
The obese brain: Association of body mass index and insulin sensitivity with resting state network functional connectivity
2011-04-21

Abstract Obesity is a key risk factor for the development of insulin resistance, Type 2 diabetes and associated diseases; thus, it has become a major public health concern. In this context, a detailed understanding of brain networks regulating food intake, including hormonal modulation, is crucial. At present, little is known about potential alterations of cerebral networks regulating ingestive behavior. We used “resting state” functional magnetic resonance imaging to investigate the functional connectivity integrity of resting state networks (RSNs) related to food intake in lean and obese subjects using independent component analysis. Our results showed altered functional connectivity strength in obese compared to lean subjects in the default mode network (DMN) and temporal lobe network. In the DMN, obese subjects showed in the precuneus bilaterally increased and in the right anterior cingulate decreased functional connectivity strength. Furthermore, in the temporal lobe network, obese subjects showed decreased functional connectivity strength in the left insular cortex. The functional connectivity magnitude significantly correlated with body mass index (BMI). Two further RSNs, including brain regions associated with food and reward processing, did not show BMI, but insulin associated functional connectivity strength. Here, the left orbitofrontal cortex and right putamen functional connectivity strength was positively correlated with fasting insulin levels and negatively correlated with insulin sensitivity index. Taken together, these results complement and expand previous functional neuroimaging findings by demonstrating that obesity and insulin levels influence brain function during rest in networks supporting reward and food regulation. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
p53 Hypersensitivity Is the Predominant Mechanism of the Unique Responsiveness of Testicular Germ Cell Tumor (TGCT) Cells to Cisplatin
2011-04-21

Consistent with the excellent clinical results in testicular germ cell tumors (TGCT), most cell lines derived from this cancer show an exquisite sensitivity to Cisplatin. It is well accepted that the high susceptibility of TGCT cells to apoptosis plays a central role in this hypersensitive phenotype. The role of the tumor suppressor p53 in this response, however, remains controversial. Here we show that siRNA-mediated silencing of p53 is sufficient to completely abrogate hypersensitivity not only to Cisplatin but also to non-genotoxic inducers of p53 such as the Mdm2 antagonist Nutlin-3 and the proteasome inhibitor Bortezomib. The close relationship between p53 protein levels and induction of apoptosis is lost upon short-term differentiation, indicating that this predominant pro-apoptotic function of p53 is unique in pluripotent embryonal carcinoma (EC) cells. RNA interference experiments as well as microarray analysis demonstrated a central role of the pro-apoptotic p53 target gene NOXA in the p53-dependent apoptotic response of these cells. In conclusion, our data indicate that the hypersensitivity of TGCT cells is a result of their unique sensitivity to p53 activation. Furthermore, in the very specific cellular context of germ cell-derived pluripotent EC cells, p53 function appears to be limited to induction of apoptosis.
2‐(4‐(Biphenyl‐4‐ylamino)‐6‐chloropyrimidin‐2‐ylthio)octanoic acid (HZ52) – a novel type of 5‐lipoxygenase inhibitor with favourable molecular pharmacology and efficacyin vivo
2011-04-21

BACKGROUND AND PURPOSE 5‐Lipoxygenase (5‐LO) is the key enzyme in the biosynthesis of pro‐inflammatory leukotrienes (LTs) representing a potential target for pharmacological intervention with inflammation and allergic disorders. Although many LT synthesis inhibitors are effective in simple in vitro test systems, they frequently fail in vivo due to lack of efficacy. Here, we attempted to assess the pharmacological potential of the previously identified 5‐LO inhibitor 2‐(4‐(biphenyl‐4‐ylamino)‐6‐chloropyrimidin‐2‐ylthio)octanoic acid (HZ52). EXPERIMENTAL APPROACH We evaluated the efficacy of HZ52 in vivo using carrageenan‐induced pleurisy in rats and platelet‐activating factor (PAF)‐induced lethal shock in mice. We also characterized 5‐LO inhibition by HZ52 at the cellular and molecular level in comparison with other types of 5‐LO inhibitor, that is, BWA4C, ZM230487 and hyperforin. KEY RESULTS HZ52, 1.5 mg·kg −1 i.p., prevented carrageenan‐induced pleurisy accompanied by reduced LTB 4 levels and protected mice (10 mg·kg −1 , i.p.) against PAF‐induced shock. Detailed analysis in cell‐based and cell‐free assays revealed that inhibition of 5‐LO by HZ52 (i) does not depend on radical scavenging properties and is reversible; (ii) is not impaired by an increased peroxide tone or by elevated substrate concentrations; and (iii) is little affected by the cell stimulus or by phospholipids, glycerides, membranes or Ca 2+ . CONCLUSIONS AND IMPLICATIONS HZ52 is a promising new type of 5‐LO inhibitor with efficacy in vivo and with a favourable pharmacological profile. It possesses a unique 5‐LO inhibitory mechanism different from classical 5‐LO inhibitors and seemingly lacks the typical disadvantages of former classes of LT synthesis blockers.
Evidence of Platelet Activation at Medically Used Hypothermia and Mechanistic Data Indicating ADP as a Key Mediator and Therapeutic Target
2011-04-22

Objective— Hypothermia is used in various clinical settings to inhibit ischemia-related organ damage. However, prothrombotic effects have been described as potential side effects. This study aimed to elucidate the mechanism of hypothermia-induced platelet activation and subsequent prothrombotic events and to develop preventative pharmacological strategies applicable during clinically used hypothermia. Methods and Results— Platelet function was investigated ex vivo and in vivo at clinically used hypothermia (28°C/18°C). Hypothermic mice demonstrated increased expression of platelet activation marker P-selectin, platelet-leukocyte aggregate formation, and thrombocytopenia. Intravital microscopy of FeCl 3 -injured murine mesenteric arteries revealed increased platelet thrombus formation with hypothermia. Ex vivo flow chamber experiments indicated increased platelet-fibrinogen adhesion under hypothermia. We show that hypothermia results in reduced ADP hydrolysis via reduction of CD39 (E-NTPDase1) activity, resulting in increased levels of ADP and subsequent augmented primary and secondary platelet activation. In vivo administration of ADP receptor P 2 Y 12 antagonists and recombinant soluble CD39 prevented hypothermia-induced thrombus formation and thrombocytopenia, respectively. Conclusion— The platelet agonist ADP plays a key role in hypothermia-induced platelet activation. Inhibition of receptor binding or hydrolysis of ADP has the potential to protect platelets against hypothermia-induced activation. Our findings provide a rational basis for further evaluation of novel antithrombotic strategies in clinically applied hypothermia.
Glycated Hemoglobin Predicts All-Cause, Cardiovascular, and Cancer Mortality in People Without a History of Diabetes Undergoing Coronary Angiography
2011-04-23

OBJECTIVE Glycated hemoglobin has been suggested to be superior to fasting glucose for the prediction of vascular disease and death from any cause. The aim of the present work was to analyze and compare the predictive value of glycated hemoglobin and fasting glucose on all-cause and cause-specific mortality in subjects who underwent coronary angiography. RESEARCH DESIGN AND METHODS We studied 2,686 participants of the Ludwigshafen Risk and Cardiovascular health study without a history of diabetes. The majority of this cohort had coronary artery disease. Glycated hemoglobin was measured at the baseline examination. The mean (± SD) duration of the follow-up for all-cause, cardiovascular, and cancer mortality was 7.54 ± 2.1 years. RESULTS A total of 508 deaths occurred during the follow-up. Of those, 299 were accounted for by cardiovascular diseases and 79 by cancer. Baseline glycated hemoglobin was predictive of all-cause, cardiovascular, and cancer mortality. The multivariable-adjusted hazard ratios (HR) (95% CI) for glycated hemoglobin values of &amp;lt;5.0, 5.0–5.4, 5.5–5.9, 6.0–6.4, 6.5–7.4, and ≥7.5% for all-cause mortality were 1.36 (0.85–2.18), 1.00 (0.76–1.32), 1.00 (reference), 1.11 (0.88–1.41), 1.39 (1.07–1.82), and 2.15 (1.32–3.53), respectively. Similar J-shaped relationships were found between glycated hemoglobin and cardiovascular and cancer mortality. The associations of glycated hemoglobin with all-cause and cardiovascular mortality remained significant after inclusion of fasting glucose as a covariate. However, fasting glucose was not significantly related to mortality when adjusting for glycated hemoglobin. CONCLUSIONS Glycated hemoglobin significantly and independently of fasting glucose predicts all-cause and cardiovascular mortality in whites at intermediate to high cardiovascular risk.
Novel simulation-based algorithms for optimal open-loop and closed-loop scheduling of deficit irrigation systems
2011-04-23

The scarcity of water compared with the abundance of land constitutes the main drawback within agricultural production. Besides the improvement of irrigation techniques a task of primary importance is solving the problem of intra-seasonal irrigation scheduling under limited seasonal water supply. An efficient scheduling algorithm has to take into account the crops' response to water stress at different stages throughout the growing season. Furthermore, for large-scale planning tools compact presentations of the relationship between irrigation practices and grain yield, such as crop water production functions, are often used which also rely on an optimal scheduling of the considered irrigation systems. In this study, two new optimization algorithms for single-crop intra-seasonal scheduling of deficit irrigation systems are introduced which are able to operate with general crop growth simulation models. First, a tailored evolutionary optimization technique (EA) searches for optimal schedules over a whole growing season within an open-loop optimization framework. Second, a neuro-dynamic programming technique (NDP) is used for determining optimal irrigation policy. In this paper, different management schemes are considered and crop-yield functions generated with both the EA and the NDP optimization algorithms compared.
Accuracy of serum LDH elevation for the diagnosis of Pneumocystis jiroveci pneumonia
2011-04-25

In 328 immunocompromised patients, 105 with and 193 without Pneumocystis jiroveci pneumonia (PCP), serum lactate dehydrogenase (LDH) was analysed retrospectively, taking into consideration the time interval from the onset of symptoms to the start of specific therapy. 97 of the 105 PCP patients were negative for human immunodeficiency virus (HIV). Eight were positive. Of the 193 patients without PCP 134 were HIV-negative and 59 were HIV-positive. In HIV-negative patients the sensitivity of LDH elevation was 63% and specificity 43%. In HIV-positive patients sensitivity was 100% and specificity 47%. The overall accuracy of LDH for the diagnosis of PCP was 52%, 51% in HIV-negative and 58% in HIV-positive patients. Except for its sensitivity in HIV-positive patients, the value of LDH for the diagnosis of PCP should not be overestimated.
Hypofrontality in schizophrenic patients and its relevance for the choice of antipsychotic medication: An event-related potential study
2011-04-26

The NGA might be a useful tool in developing individualized treatment strategies based on pathophysiological aspects of schizophrenic illnesses that can be easily determined in clinical routine settings.
Three processes underlying the carry effect in addition – Evidence from eye tracking
2011-04-27

Recent research indicated that processes of unit‐decade integration pose particular difficulty on multi‐digit addition. In fact, longer response latencies as well as higher error rates have been observed for addition problems involving a carry operation (e.g., 18 +27) compared to problems not requiring a carry (e.g., 13 +32). However, the cognitive instantiation of this carry effect remained unknown. In the current study, this question was pursued by recording participants’ eye fixation behaviour during addition problem verification. Analyses of the eye fixation data suggested a prominent role of the unit digits of the summands. The need for a carry seems to be recognized very early during the encoding of the problem after initial unit sum calculation has established the basis for the no carry / carry detection . Additionally, processes related to the actual carry execution seemed to be associated with the processing of the decade digit of the solution probe but were less unambiguous. Taken together, our findings indicate that unit‐based calculations and the associated recognition that a carry is needed as well as its completion determine the difficulty of carry addition problems. On a more general level, this study shows how the nature of numerical‐cognitive processes can be further differentiated by the evaluation of eye movement measures.
Synthesizing and databasing fossil calibrations: divergence dating and beyond
2011-04-27

Divergence dating studies, which combine temporal data from the fossil record with branch length data from molecular phylogenetic trees, represent a rapidly expanding approach to understanding the history of life. National Evolutionary Synthesis Center hosted the first Fossil Calibrations Working Group (3–6 March, 2011, Durham, NC, USA), bringing together palaeontologists, molecular evolutionists and bioinformatics experts to present perspectives from disciplines that generate, model and use fossil calibration data. Presentations and discussions focused on channels for interdisciplinary collaboration, best practices for justifying, reporting and using fossil calibrations and roadblocks to synthesis of palaeontological and molecular data. Bioinformatics solutions were proposed, with the primary objective being a new database for vetted fossil calibrations with linkages to existing resources, targeted for a 2012 launch.
Functional and Dysfunctional Brain Circuits Underlying Emotional Processing of Music in Autism Spectrum Disorders
2011-04-28

Despite intersubject variability, dramatic impairments of socio-communicative skills are core features of autistic spectrum disorder (ASD). A deficit in the ability to express and understand emotions has often been hypothesized to be an important correlate of such impairments. Little is known about individuals with ASD's ability to sense emotions conveyed by nonsocial stimuli such as music. Music has been found to be capable of evoking and conveying strong and consistent positive and negative emotions in healthy subjects. The ability to process perceptual and emotional aspects of music seems to be maintained in ASD. Individuals with ASD and neurotypical (NT) controls underwent a single functional magnetic resonance imaging (fMRI) session while processing happy and sad music excerpts. Overall, fMRI results indicated that while listening to both happy and sad music, individuals with ASD activated cortical and subcortical brain regions known to be involved in emotion processing and reward. A comparison of ASD participants with NT individuals demonstrated decreased brain activity in the premotor area and in the left anterior insula, especially in response to happy music excerpts. Our findings shed new light on the neurobiological correlates of preserved and altered emotional processing in ASD.
Phagocytosis of dying tumor cells by human peritoneal mesothelial cells
2011-04-28

Peritoneal carcinomatosis is an advanced form of metastatic disease characterized by cancer cell dissemination onto the peritoneum. It is commonly observed in ovarian and colorectal cancers and is associated with poor patient survival. Novel therapies consist of cytoreductive surgery in combination with intraperitoneal chemotherapy, aiming at tumor cell death induction. The resulting dying tumor cells are considered to be eliminated by professional as well as semi-professional phagocytes. In the present study, we have identified a hitherto unknown type of ‘amateur’ phagocyte in this environment: human peritoneal mesothelial cells (HMCs). We demonstrate that HMCs engulf corpses of dying ovarian and colorectal cancer cells, as well as other types of apoptotic cells. Flow cytometric, confocal and electron microscopical analyses revealed that HMCs ingest dying cell fragments in a dose- and time-dependent manner and the internalized material subsequently traffics into late phagolysosomes. Regarding the mechanisms of prey cell recognition, our results show that HMCs engulf apoptotic corpses in a serum-dependent and -independent fashion and quantitative real-time PCR (qRT-PCR) analyses revealed that diverse opsonin receptor systems orchestrating dying cell clearance are expressed in HMCs at high levels. Our data strongly suggest that HMCs contribute to dying cell removal in the peritoneum, and future studies will elucidate in what manner this influences tumor cell dissemination and the antitumor immune response.
Effects of Subthalamic Nucleus Stimulation on Emotional Prosody Comprehension in Parkinson's Disease
2011-04-28

In sum, presented results suggest that the processing of emotional speech is indeed modulated by STN-DBS. Observed alterations might, on the one hand, reflect a more efficient processing of highly conflicting stimulus material following DBS. However, on the other hand, given the lack of an improvement in accuracy, increased impulsivity associated with STN stimulation needs to be taken into consideration.
Increased Cyclosporine Concentrations in the Absence of Cyclosporine Administration
2011-04-28

CONSIDER1. Has the CsA therapy really been discontinued?2. Can delayed drug elimination explain the continued increased CsA concentrations?3. What tests could be done to identify any potential analytical interference?