Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic significance of proliferation activity and neuroendocrine differentiation to predict treatment failure after radical prostatectomy

Objectives. Neuroendocrine (NE) cells in prostate cancer may influence tumor cell proliferation in a paracrine fashion. The aims of this study were to clarify the prognostic value of tumor cell proliferation and NE tumor cell differentiation in prostate cancer after radical prostatectomy, and to compare these parameters with each other. Material and methods. Specimens were pooled from a total of 528 patients treated with radical prostatectomy without neoadjuvant hormonal therapy between 1996 and 2003. NE differentiation (NED) was determined by immunohistochemistry using antibodies directed against chromogranin A (CgA), and was scored as either NE-negative (0–1+) or -positive (2–3+). Tumor cell proliferation was assessed by means of the Ki-67 labeling index (Ki-67 LI). The mean post-surgical follow-up period was 49 months (range 10–116 months). Any subsequent rise in prostate-specific antigen (PSA) level was regarded as reflecting disease progression. The prognostic values of Ki-67 and CgA were comparatively analyzed using multivariate Cox regression. Results. NED was present in 6.1% of tumors. The mean Ki-67 LI was significantly higher in the CgA-positive group in comparison with CgA-negative specimens (6.6% vs 5.0%; p=0.029). The Ki-67 LI showed the highest correlations with Gleason score and pathological tumor stage (r=0.31 and r=0.3, respectively). NED was found to have the strongest association with pathological tumor stage (r=0.2). Multivariate analysis determined Gleason score ≥7 (4+3) [hazard ratio (HR) 3.04], NED (HR 1.89), lymph node metastases (HR 1.84), preoperative PSA level>20 ng/ml (HR 1.66), and Ki-67 LI≥5% (HR 1.62) to be significant predictors of biochemical progression. Conclusion. Our results identify Ki-67 LI and NED as additional prognostic markers after radical prostatectomy.
Trends in the early investigational drug development and areas for improvement

The continuous discovery of ‘druggable’ protein involved in different signal transduction pathways and aberrant tumorigenic processes, has led to rapid progress in drug development. Nowadays several agents interfering with intriguing pathways are in early- and late-phase clinical development. Alteration in the cyclin-dependent kinase–retinoblastoma protein pathway is frequent in various types of cancer. In breast cancer, CDK 4/6 inhibitors have shown robust anticancer potencies, both in in vitro and in vivo studies. Numerous PI3K inhibitors have been developed and are in varying stages of clinical testing involving different and complementary therapeutic strategies in an effort to circumvent multiple pathway redundancies and pathway crosstalk. The molecular chaperone heat shock protein 90 targeted inhibition could lead to the blockade of multiple oncogenic signaling pathways in tumor cells, making it an attractive opportunity in the treatment of human malignancies. The acquired resistance to EGFR-tyrosine kinase inhibitors stimulates the development of several new drugs. Finally, among promising molecules, Janus-associated kinase inhibitors have been found to play a crucial role in the pathophysiology of cancer in combination with traditional and/or experimental treatment. This editorial gives an overview on the state-of-art development of different strategies in the targeted therapies scenario.
A Hybrid Feature Based Mobile Forensics System

Due to the limited computing ability of current mobile computing platform, many intelligent applications are hard to be implemented, such as some complex pattern recognition algorithms. This paper proposes a kind of fast hybrid feature based progressive person recognition algorithm for forensics application which form the candidate set according to the biometric feature first and then conduct face recognition algorithm in the candidate set. A bionic pattern recognition based face recognition algorithm is also proposed. Experimental results show that the proposed algorithm has a satisfied recognition precision and low time complexity which could be conducted on mobile forensics devices with high efficiency.
Deletion of the chloride transporter Slc26a9 causes loss of tubulovesicles in parietal cells and impairs acid secretion in the stomach

Slc26a9 is a recently identified anion transporter that is abundantly expressed in gastric epithelial cells. To study its role in stomach physiology, gene targeting was used to prepare mice lacking Slc26a9. Homozygous mutant (Slc26a9−/−) mice appeared healthy and displayed normal growth. Slc26a9 deletion resulted in the loss of gastric acid secretion and a moderate reduction in the number of parietal cells in mutant mice at 5 weeks of age. Immunofluorescence labeling detected the H-K-ATPase exclusively on the apical pole of gastric parietal cells in Slc26a9−/− mice, in contrast to the predominant cytoplasmic localization in Slc26a9+/+ mice. Light microscopy indicated that gastric glands were dilated, and electron micrographs displayed a distinct and striking absence of tubulovesicles in parietal cells and reductions in the numbers of parietal and zymogen cells in Slc26a9−/− stomach. Expression studies indicated that Slc26a9 can function as a chloride conductive pathway in oocytes as well as a Cl−/HCO3− exchanger in cultured cells, and localization studies in parietal cells detected its presence in tubulovesicles. We propose that Slc26a9 plays an essential role in gastric acid secretion via effects on the viability of tubulovesicles/secretory canaliculi and by regulating chloride secretion in parietal cells.
The effect of bias correction and climate model resolution on wheat simulations forced with a regional climate model ensemble

Regional climate model (RCM) simulations are often used with agricultural models to assess the impact of climate change on agriculture. This study assesses the suitability of climate data sets from an RCM ensemble for forcing simulations of wheat yields for New South Wales, Australia, performed using the Agricultural Production Systems sIMulator (APSIM). Differences in yields between APSIM simulations forced with RCM output for the 1990–2009 period and APSIM simulations forced with observations are examined, as are simulated changes in yields between 1990–2009 and 2060–2079. The RCM ensemble downscales four global climate models (GCMs) using three different RCMs, firstly to a horizontal resolution of approximately 50 km, and then to approximately 10 km. All of the RCM simulations, 50 and 10 km, are able to simulate the spatial pattern of yields across the study region. However, some simulations have biases in yields. The largest of these are due to biases in rainfall during the growing season inherited from the GCMs. If the RCM output is bias‐corrected, the largest positive yield biases are reduced because the underlying biases in growing season rainfall are reduced. Simulated future changes in yields are affected because there is a non‐linear relationship between simulated yields and growing season rainfall. Downscaling to 10 km, rather than 50 km, is only beneficial when bias correction is used. The bias‐correction technique used does not eliminate all biases in growing season rainfall and increases some of the smaller biases. Nonetheless, because of the potentially large effect of the rainfall biases on simulated future yield changes, this study supports the use of bias correction in assessments of the impacts of climate change that use RCM output to force APSIM. Indeed, our findings suggest that bias correction may be necessary to obtain reliable future changes in other outputs of other biophysical models that respond non‐linearly to climate inputs.
Ensuring Inclusion of Adolescent Key Populations at Higher Risk of HIV Exposure: Recommendations for Conducting Biological Behavioral Surveillance Surveys

Ending acquired immune deficiency syndrome (AIDS) depends on greater efforts to reduce new human immunodeficiency virus (HIV) infections and prevent AIDS-related deaths among key populations at highest HIV risk, including males who have sex with males, sex workers, and people who inject drugs. Although adolescent key populations (AKP) are disproportionately affected by HIV, they have been largely ignored in HIV biological behavioral surveillance survey (BBSS) activities to date. This paper reviews current ethical and sampling challenges and provides suggestions to ensure AKP are included in surveillance activities, with the aim being to enhance evidence-informed, strategic, and targeted funding allocations and programs toward ending AIDS among AKP. HIV BBSS, conducted every few years worldwide among adult key populations, provide information on HIV and other infections’ prevalence, HIV testing, risk behaviors, program coverage, and when at least three of these surveys are conducted, trend data with which to evaluate progress. We provide suggestions and recommendations on how to make the case to ethical review boards to involve AKP in surveillance while assuring that AKP are properly protected. We also describe two widely used probability sampling methods, time location sampling and respondent driven sampling, and offer considerations of feature modifications when sampling AKP. Effectively responding to AKP’s HIV and sexual risks requires the inclusion of AKP in HIV BBSS activities. The implementation of strategies to overcome barriers to including AKP in HIV BBSS will result in more effective and targeted prevention and intervention programs directly suited to the needs of AKP.
Event-Based Receding Horizon Control for Two-Stages Multi-Product Production Plants

In this paper, we present a receding horizon control approach for multi-product production plants. Two-stage multi-product plants are considered. In the first stage, a set of parallel production lines generates intermediate products from raw materials. In the second stage, intermediate products are assembled together into final products through an assembly line. A set of buffers for the intermediate products connects the production lines and the assembly line and allows a continuous production flow. We propose a systematic event-based and control-oriented approach to this class of problems. We employ receding horizon control (RHC) techniques to control the production line flow in order to satisfy the time-varying request from the assembly line and optimize a certain performance criterion which includes the minimization of the intermediate products storage and the reduction of the processing time. Experimental data show the benefits deriving from the application of the proposed approach, to a process of car engine manufacturing
A new chaotic feature for EEG classification based seizure diagnosis

Seeking effective measures to characterize the chaotic patterns of EEG signals for seizure diagnosis is a long-term endeavor in the literature. We propose to count the number of zero-crossing (ZC) points on Poincaré surface as a feature when the time series of interest is embedded into the reconstructed state space. The experiments show that Poincaré surface can act as a platform to observe the chaotic patterns of EEG signals and the ZC feature on Poincaré surface is a promising pattern descriptor to discriminate different categories of EEG signals. When used alone for EEG classification, the ZC feature achieves 100%, 99.27%, and 94.68% accuracy in 2-class, 3-class, and 5-class classification on a widely used benchmark.
Echocardiographic Assessment of the Right Ventricular Stress–Velocity Relationship Under Normal and Chronic Overload Conditions

The effects of chronic volume or pressure overload on the velocity of right ventricular ejection have not been previously well defined. We hypothesized that, as formerly shown for the left ventricle, there would be a direct relationship between the velocity of ejection and an estimate of systolic wall stress. Methods: Echocardiograms of asymptomatic patients, not on cardiac medications, with either an isolated secundum atrial septal defect ≥ 5 mm in diameter or isolated pulmonic stenosis with a peak instantaneous pressure gradient ≥ 20 mmHg, were reviewed. Forty‐one patients with an atrial septal defect and 34 with pulmonary stenosis met criteria, and were compared to age‐matched normal controls. Total subjects were 127 with ages ranging from 1 day to 54 years. Right ventricular monoplane ejection fraction, ejection time corrected for heart rate (ETc), mean normalized systolic ejection rate (MNSERc) and meridianal peak‐systolic wall stress (WSps) were measured. Results: Compared to controls, ejection fractions were not significantly different, but WSps averaged 81% and 110% higher, ETc 8% and 9% longer, and MNSERc 5% and 9% slower in the atrial septal defect and pulmonary stenosis groups, respectively. Among all subjects WSps had a significant linear correlation with ETc (r = 0.61, P < 0.01), MNSERc (r =−0.46, P < 0.01), and ejection fraction (r =−0.19, P < 0.05). Conclusions: Increases in WSps cause an incremental slowing of MNSERc in the right ventricle, with a relationship that is linear over a wide range of normal and abnormal loading conditions. (ECHOCARDIOGRAPHY, Volume 21, January 2004)
PI3 kinase/Akt activation mediates estrogen and IGF‐1 nigral DA neuronal neuroprotection against a unilateral rat model of Parkinson's disease

Recently, using the medial forebrain bundle (MFB) 6‐hydroxydopmaine (6‐OHDA) lesion rat model of Parkinson's disease (PD), we have demonstrated that blockade of central IGF‐1 receptors (IGF‐1R) attenuated estrogen neuroprotection of substantia nigra pars compacta (SNpc) DA neurons, but exacerbated 6‐OHDA lesions in IGF‐1 only treated rats (Quesada and Micevych [2004]: J Neurosci Res 75:107–116). This suggested that the IGF‐1 system is a central mechanism through which estrogen acts to protect the nigrostriatal DA system. Moreover, these results also suggest that IGF‐1R‐induced intracellular signaling pathways are involved in the estrogen mechanism that promotes neuronal survival. In vitro, two convergent intracellular signaling pathways used by estrogen and IGF‐1, the mitogen‐activated protein kinase (MAPK/ERK), and phosphatidyl‐inositol‐3‐kinase/Akt (PI3K/Akt), have been demonstrated to be neuroprotective. Continuous central infusions of MAPK/ERK and PI3K/Akt inhibitors were used to test the hypothesis that one or both of these signal transduction pathways mediates estrogen and/or IGF‐1 neuroprotection of SNpc DA neurons after a unilateral administration of 6‐OHDA into the MFB of rats. Motor behavior tests and tyrosine hydroxylase immunoreactivity revealed that the inhibitor of the PI3K/Akt pathway (LY294002) blocked the survival effects of both estrogen and IGF‐1, while an inhibitor of the MAPK/ERK signaling (PD98059) was ineffective. Western blot analyses showed that estrogen and IGF‐1 treatments increased PI3K/Akt activation in the SN; however, MAPK/ERK activation was decreased in the SN. Indeed, continuous infusions of inhibitors blocked phosphorylation of PI3K/Akt and MAPK/ERK. These findings indicate that estrogen and IGF‐1‐mediated SNpc DA neuronal protection is dependent on PI3K/Akt signaling, but not on the MAPK/ERK pathway. © 2008 Wiley Periodicals, Inc. Develop Neurobiol 2008
Cytotoxicity reactions during immunotherapy of melanoma with neuraminidase altered autologous tumor cells

Lymphocyte cytotoxicity, serum cytotoxicity, and the ability of the serum to inhibit lymphocyte cytotoxicity (blocking effect) were studied in a melanoma patient treated with six monthly injections of her own (autologous) tumor cells incubated with neuraminidase to increase their antigenicity. The same tumor cells grown in tissue culture were used as target cells for the cytotoxicity test. Large fluctuations of blocking effect in the serum were found, which correlated with the clinical course of tumor removal, recurrence, and regression. After the fifth injection of autologous tumor cells, the blocking effect disappeared from the serum (unblocking). In general, changes in serum cytotoxicity corresponded with changes in the amount of blocking effect produced by the serum. The results suggest that active immunotherapy may play a role in the prevention of metastases and, that when used within the autologous system, the cytotoxicity test is valuable in studying response to this type of therapy.
Single-Tunnel Double-Bundle Anterior Cruciate Ligament Reconstruction with Anatomical Placement of Hamstring Tendon Graft

Background Anatomical reconstruction techniques that can restore normal joint kinematics without increasing surgical complications could potentially improve clinical outcomes and help manage anterior cruciate ligament injuries more efficiently. Hypothesis Single-tunnel double-bundle anterior cruciate ligament reconstruction with anatomical placement of hamstring tendon graft can more closely restore normal knee anterior-posterior, medial-lateral, and internal-external kinematics than can conventional single-bundle anterior cruciate ligament reconstruction. Study Design Controlled laboratory study. Methods Kinematic responses after single-bundle anterior cruciate ligament reconstruction and single-tunnel double-bundle anterior cruciate ligament reconstruction with anatomical placement of hamstring tendon graft were compared with the intact knee in 9 fresh-frozen human cadaveric knee specimens using a robotic testing system. Kinematics of each knee were determined under an anterior tibial load (134 N), a simulated quadriceps load (400 N), and combined torques (10 N·m valgus and 5 N·m internal tibial torques) at 0°, 15°, 30°, 60°, and 90° of flexion. Results Anterior tibial translations were more closely restored to the intact knee level after single-tunnel double-bundle reconstruction with anatomical placement of hamstring tendon graft than with a single-bundle reconstruction under the 3 external loading conditions. Under simulated quadriceps load, the mean internal tibial rotations after both reconstructions were lower than that of the anterior cruciate ligament—intact knee with no significant differences between these 3 knee conditions at 0° and 30° of flexion (P > .05). The increased medial tibial shifts of the anterior cruciate ligament—deficient knees were restored to the intact level by both reconstruction techniques under the 3 external loading conditions. Conclusion Single-tunnel double-bundle anterior cruciate ligament reconstruction with anatomical placement of hamstring tendon graft can better restore the anterior knee stability compared with a conventional single-bundle reconstruction. Both reconstruction techniques are efficient in restoring the normal medial-lateral stability but overcorrect the internal tibial rotations. Clinical Relevance Single-tunnel double-bundle anterior cruciate ligament reconstruction with anatomical placement of hamstring tendon graft could provide improved clinical outcomes over a conventional single-bundle reconstruction.
Interaction between lymphocytes and cultured high endothelial cells: an in vitro model of lymphocyte migration across high endothelial venule endothelium

The interaction between lymphocytes and cultured high endothelial venule endothelium has been studied using light and electron microscopy. High endothelial cells (HEC) in monolayer culture bound lymphocytes 15‐200‐fold more efficiently than aortic endothelium, aortic fibroblasts or serum‐coated glass. Light microscopy of lymphocytes bound to HEC showed two populations. Type I lymphocytes were phase‐light, round and revealed no intracellular detail. Type II lymphocytes were phase‐dark and flattened. The nucleus and cytoplasm of type II cells were clearly visible under high power light microscopy. The relative positions of these two populations were determined by electron microscopy. Type I lymphocytes were attached to the surface of HEC and type I1 lymphocytes were flattened underneath. The transition from type I to type II was accompanied by a loss of surface microvilli and a redistribution of intracellular organelles. This suggested that lymphocytes actively migrated across the HEC layer in this assay.
Time-variant partial directed coherence for analysing connectivity: a methodological study

For the past decade, the detection and quantification of interactions within and between physiological networks has become a priority-in-common between the fields of biomedicine and computer science. Prominent examples are the interaction analysis of brain networks and of the cardiovascular–respiratory system. The aim of the study is to show how and to what extent results from time-variant partial directed coherence analysis are influenced by some basic estimator and data parameters. The impacts of the Kalman filter settings, the order of the autoregressive (AR) model, signal-to-noise ratios, filter procedures and volume conduction were investigated. These systematic investigations are based on data derived from simulated connectivity networks and were performed using a Kalman filter approach for the estimation of the time-variant multivariate AR model. Additionally, the influence of electrooculogram artefact rejection on the significance and dynamics of interactions in 29 channel electroencephalography recordings, derived from a photic driving experiment, is demonstrated. For artefact rejection, independent component analysis was used. The study provides rules to correctly apply particular methods that will aid users to achieve more reliable interpretations of the results.
The capitalization of coupled and decoupled CAP payments into land rental rates

This article explores the extent to which payments under the Common Agricultural Policy (CAP) are capitalized into land rents in Ireland with implications for the transfer efficiency of such payments, since subsidies may not benefit targeted recipients if they are capitalized into input prices. Capitalization in the years preceding and following the "decoupling" of agricultural support payments from agricultural production is explored. In the period prior to decoupling, direct support (Pillar 1) payments were highly capitalized into Irish agricultural rents (67–90 cents per euro of subsidies), while in the post-decoupling period capitalization appears to have declined somewhat.
Neutrophil Gelatinase-Associated Lipocalin Is Up-Regulated in Human Epithelial Cells by IL-1β, but Not by TNF-α 1

Synthesis of the antimicrobial protein neutrophil gelatinase-associated lipocalin (NGAL) increases dramatically in bronchial epithelial cells and alveolear type II pneumocytes during lung inflammation. IL-1β induces a >10-fold up-regulation of NGAL expression in the type II pneumocyte-derived cell line A549 cells, whereas TNF-α, IL-6, and LPS had no effect. Similar IL-1β selectivity was demonstrated in primary bronchial epithelial cells and epidermal keratinocytes and for an NGAL promoter fragment transfected into A549 cells. By deletion and substitution analysis of the NGAL promoter, a 40-bp region containing an NF-κB consensus site was found to control the IL-1β-specific up-regulation. Involvement of the NF-κB site was demonstrated by site-directed mutagenesis, by transfection with a dominant-negative inhibitor of the NF-κB pathway, and by EMSA. TNF-α activation of NF-κB, in contrast, did not increase NGAL synthesis, even though induced binding of NF-κB to the NGAL promoter was observed in vitro. IL-1β specificity was not contained within the NF-κB site of the NGAL promoter, as determined by exchanging the NGAL promoter′s NF-κB-binding sequence with that of the IL-8 promoter or with the NF-κB consensus sequence and by testing the NF-κB-binding sequence of the NGAL promoter against the heterologous SV40 promoter. Selectivity for the IL-1 pathway was substantiated by demonstrating that NGAL promoter activity could be induced by LPS stimulation of A549 cells transiently expressing Toll-like receptor 4, which use the same intracellular signaling pathway as the IL-1R. Together, this demonstrates a selective up-regulation of NGAL by the IL-1 pathway.