bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased expression of bone morphogenetic protein-2 is correlated with biochemical recurrence in prostate cancer: Immunohistochemical analysis
Authors: Tae Bum Sik , Cho Seok , Kim Hyun Cheol , Kim Cheol Hwan , Kang Seok Ho , Lee Jeong Gu , Kim Je Jong , Park Hong Seok , Cheon Jun , Oh Mi Mi , Kang Sung Gu 
Published: July 2018

AbstractWe evaluated the prognostic value of BMP-2 expression in prostate cancer tissue via immunohistochemistry in prostate cancer patients. From July 2007 to August 2010, radical prostatectomy specimens from 90 patients with clinically localized prostate cancer (mean age, 62.7 years, mean follow-up 90.4 months) were assessed for BMP-2 expression using immunohistochemistry. We used stepwise multivariate Cox regression models stratified by study to assess the independent effects of the predictive factors and estimated hazard ratios (HRs). There were significant differences in the baseline characteristics of Gleason score (GS) and biochemical recurrence (BCR) between the groups with decreased and normal BMP-2 expression. Univariate analysis revealed GS, T stage (≥T3), and decreased BMP-2 expression as significant predictive determinants of BCR. In addition, GS (7: HR 2.836, p = 0.022; ≥8: HR 3.506, p = 0.048) and decreased BMP-2 expression (HR 2.007, p = 0.047) were significantly correlated with BCR in multivariate analysis. Overall five-year BCR-free survival rates in the group with decreased BMP-2 expression were worse than those in the group with normal expression. Therefore, decreased BMP-2 expression in prostate cancer tissue was correlated with the prognostic factors for BCR-free survival in patients with prostate cancer.
Blast-induced cochlear synaptopathy in chinchillas
Authors: Hickman T. T. , Smalt C. , Bobrow J. , Quatieri T. , Liberman M. C. 
Published: July 2018

AbstractWhen exposed to continuous high-level noise, cochlear neurons are more susceptible to damage than hair cells (HCs): exposures causing temporary threshold shifts (TTS) without permanent HC damage can destroy ribbon synapses, permanently silencing the cochlear neurons they formerly activated. While this “hidden hearing loss” has little effect on thresholds in quiet, the neural degeneration degrades hearing in noise and may be an important elicitor of tinnitus. Similar sensory pathologies are seen after blast injury, even if permanent threshold shift (PTS) is minimal. We hypothesized that, as for continuous-noise, blasts causing only TTS can also produce cochlear synaptopathy with minimal HC loss. To test this, we customized a shock tube design to generate explosive-like impulses, exposed anesthetized chinchillas to blasts with peak pressures from 160–175 dB SPL, and examined the resultant cochlear dysfunction and histopathology. We found exposures that cause large >40 dB TTS with minimal PTS or HC loss often cause synapse loss of 20–45%. While synaptopathic continuous-noise exposures can affect large areas of the cochlea, blast-induced synaptopathy was more focal, with localized damage foci in midcochlear and basal regions. These results clarify the pathology underlying blast-induced sensory dysfunction, and suggest possible links between blast injury, hidden hearing loss, and tinnitus.
FIB-FESEM and EMPA results on Antoninianus silver coins for manufacturing and corrosion processes
Authors: Doménech-Carbó María Teresa , Di Turo Francesca , Montoya Noemí , Catalli Fiorenzo , Doménech-Carbó Antonio , De Vito Caterina 
Published: July 2018

AbstractA set of ancient Antoninianus silver coins, dating back between 249 and 274 A.D. and minted in Rome, Galliae, Orient and Ticinum, have been characterized. We use, for the first time, a combination of nano-invasive (focused ion beam-field emission scanning electron microscopy-X-ray microanalysis (FIB-FESEM-EDX), voltammetry of microparticles (VIMP)) and destructive techniques (scanning electron microscopy (SEM-EDX) and electron microprobe analysis (EMPA)) along with non-invasive, i.e., micro-Raman spectroscopy. The results revealed that, contrary to the extended belief, a complex Ag-Cu-Pb-Sn alloy was used. The use of alloys was common in the flourishing years of the Roman Empire. In the prosperous periods, Romans produced Ag-Cu alloys with relatively high silver content for the manufacture of both the external layers and inner nucleus of coins. This study also revealed that, although surface silvering processes were applied in different periods of crisis under the reign of Antoninii, even during crisis, Romans produced Antoninianus of high quality. Moreover, a first attempt to improve the silvering procedure using Hg-Ag amalgam has been identified.
Outcome and prognostic factors in 593 non-metastatic rectal cancer patients: a mono-institutional survey
Authors: Langrand-Escure Julien , Diao Peng , Garcia Max-Adrien , Wang Guoping , Guy Jean-Baptiste , Espenel Sophie , Guillaume Elodie , Rehailia-Blanchard Amel , Pigné Grégoire , de Laroche Guy , Kaczmarek David , Muron Thierry , Porcheron Jack , Phelip Jean-Marc , Vallard Alexis , Magné Nicolas 
Published: July 2018

AbstractThis retrospective study was undertaken to provide more modern data of real-life management of non-metastatic rectal cancer, to compare therapeutic strategies, and to identify prognostic factors of overall survival (OS) in a large cohort of patients. Data on efficacy and on acute/late toxicity were retrospectively collected. Patients were diagnosed a non-metastatic rectal cancer between 2004 and 2015, and were treated at least with radiotherapy. OS was correlated with patient, tumor and treatment characteristics with univariate and multivariate analyses. Data of 593 consecutive non-metastatic rectal cancer patients were analyzed. Median follow-up was 41 months. Median OS was 9 years. Radiotherapy was delivered in pre-operative (n = 477, 80.5%), post-operative (n = 75, 12.6%) or exclusive (n = 41, 6.9%) setting. In the whole set of patients, age, nutritional condition, tumor stage, tumor differentiation, and surgery independently influenced OS. For patients experiencing surgery, OS was influenced by age, tumor differentiation and nodal status. Surgical resection is the cornerstone treatment for locally-advanced rectal cancer. Poor tumor differentiation and node involvement were identified as major predictive factor of poor OS. The research in treatment intensification and in identification of radioresistance biomarkers should therefore probably be focused on this particular subset of patients.
Structural dynamics of calmodulin-ryanodine receptor interactions: electron paramagnetic resonance using stereospecific spin labels
Authors: Her Cheng , Thompson Andrew R. , Karim Christine B. , Thomas David D. 
Published: July 2018

AbstractWe have used electron paramagnetic resonance, with rigid and stereospecific spin labels, to resolve structural states in calmodulin (CaM), as affected by binding of Ca and a CaM-binding peptide (RyRp) derived from the ryanodine receptor (RyR), the Ca channel that triggers muscle contraction. CaM mutants containing a pair of cysteines in the N-lobe and/or C-lobe were engineered and labeled with a stereospecifically bound bifunctional spin label (BSL). RyRp was synthesized with and without TOAC (a stereospecifically attached spin-labeled amino acid) substituted for a single amino acid near the N-terminus. Intramolecular DEER distance measurements of doubly-labeled BSL-CaM revealed that CaM exists in dynamic equilibrium among multiple states, consistent with open, closed, and compact structural models. Addition of RyRp shifted the equilibrium partially toward the compact state in the absence of Ca, and completely toward the compact state in the presence of Ca, supporting a conformational selection model. Inter-protein distance measurements show that Ca stabilizes the compact state primarily by inducing ordered binding of the CaM N-lobe to RyRp, while only slightly affecting the C-lobe. The results provide insight into the structural mechanism of CaM-mediated RyR regulation, while demonstrating the power of using two types of rigidly and stereospecifically bound spin labels.
Dentinogenic effects of extracted dentin matrix components digested with matrix metalloproteinases
Authors: Okamoto Motoki , Takahashi Yusuke , Komichi Shungo , Cooper Paul R. , Hayashi Mikako 
Published: July 2018

AbstractDentin is primarily composed of hydroxyapatite crystals within a rich organic matrix. The organic matrix comprises collagenous structural components, within which a variety of bioactive molecules are sequestered. During caries progression, dentin is degraded by acids and enzymes derived from various sources, which can release bioactive molecules with potential reparative activity towards the dentin-pulp complex. While these molecules’ repair activities in other tissues are already known, their biological effects are unclear in relation to degradation events during disease in the dentin-pulp complex. This study was undertaken to investigate the effects of dentin matrix components (DMCs) that are partially digested by matrix metalloproteinases (MMPs)in vitroandin vivoduring wound healing of the dentin-pulp complex. DMCs were initially isolated from healthy dentin and treated with recombinant MMPs. Subsequently, their effects on the behaviour of primary pulp cells were investigatedin vitroandin vivo. Digested DMCs modulated a range of pulp cell functionsin vitro. In addition, DMCs partially digested with MMP-20 stimulated tertiary dentin formationin vivo, which exhibited a more regular tubular structure than that induced by treatment with other MMPs. Our results indicate that MMP-20 may be especially effective in stimulating wound healing of the dentin-pulp complex.
Population authentication of the traditional medicinal plant Cassia tora L. based on ISSR markers and FTIR analysis
Authors: Kumar Vikas , Roy Bijoy Krishna 
Published: July 2018

AbstractCassia torais a plant of medicinal importance. Medicinal plants from different localities are believed to differ in their therapeutic potency. In this study, six populations ofC. torawith different eco-geographical origins were investigated genotypically (ISSR) and phytochemically (FTIR) to establish an integrated approach for population discrimination and authentication of the origin of this medicinal herb.CHSgene expression analysis and determination of flavonoid content were carried out to substantiate the study. A total of 19 population-specific authentication bands were observed in 11 ISSR fingerprints. Authentication codes were generated using six highly polymorphic bands, including three authentication bands. FTIR spectra revealed that the peaks at wavenumber 1623 cm−1(carbonyl group) and 1034 cm−1(>CO- group) were powerful in separating the populations. These peaks are assigned to flavonoids and carbohydrates, respectively, were more intense for Ranchi (highland) population. Variation in the transcript level ofCHSgene was observed. The findings of FTIR and RT-PCR analyses were in agreement with the TFC analysis, where, the lowest amount of flavonoids observed for Lucknow (lowland) population. All the populations ofC. torahave been authenticated accurately by ISSR analyses and FTIR fingerprinting, and the Ranchi site was observed to be more suitable for the potential harvesting of therapeutic bioactive compounds.
Copper/iron co-catalyzed alkoxycarbonylation of unactivated alkyl bromides
Authors: Li Yahui , Wu Xiao-Feng 
Published: July 2018

AbstractCarbonylative transformations of alkyl bromides have been explored less than those of aryl halides, in part because of the high barrier to activation of aryl bromides. Additionally, alkyl-metal reagents formed in situ can tend to undergo β-hydride elimination. Here we describe a copper/iron co-catalyzed alkoxycarbonylation of unactivated alkyl bromides. In the presence of catalytic quantities of iron and copper catalysts, primary, secondary, and tertiary alkyl bromides are carbonylatively transformed into the corresponding aliphatic esters in good yields. A potential reaction mechanism is proposed based on control experiments.
The near-nucleus gas coma of comet 67P/Churyumov-Gerasimenko prior to the descent of the surface lander PHILAE
Authors: Zakharov V. V. , Crifo J.-F. , Rodionov A.V. , Rubin M. , Altwegg K. 
Published: July 2018

Context.The European Space Agency (ESA) Rosetta mission was the most comprehensive study of a comet ever performed. In particular, the Rosetta orbiter, which carried many instruments for monitoring the evolution of the dusty gas emitted by the cometary nucleus, returned an enormous volume of observational data collected from the close vicinity of the nucleus of comet 67P/Churyumov-Gerasimenko.Aims.Such data are expected to yield unique information on the physical processes of gas and dust emission, using current physical model fits to the data. We present such a model (the RZC model) and our procedure of adjustment of this model to the data.Methods.The RZC model consists of two components: (1) a numerical three-dimensional time-dependent code solving the Eulerian/Navier-Stokes equations governing the gas outflow, and a direct simulation Monte Carlo (DSMC) gaskinetic code with the same objective; and (2) an iterative procedure to adjust the assumed model parameters to best-fit the observational data at all times.Results.We demonstrate that our model is able to reproduce the overall features of the local neutral number density and composition measurements of Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA) Comet Pressure Sensor (COPS) and Double Focusing Mass Spectrometer (DFMS) instruments in the period August 1–November 30, 2014. The results of numerical simulations show that illumination conditions on the nucleus are the main driver for the gas activity of the comet. We present the distribution of surface inhomogeneity best-fitted to the ROSINA COPS and DFMS in situ measurements.
Diabetes Mellitus and Autoimmune Hepatitis: Demographical and Clinical Description of a Relatively Rare Phenotype
Authors: de Sousa Gideon , Prinz Nicole , Becker Marianne , Dürr Renate , Faller Uta , Meraner Dagmar , Heise Nicolai , Engelmann Illa , Bruckmayer Herbert , Wiemann Dagobert , Fritsch Maria , Stratmann Bernd , Holl Reinhard 
Published: July 2018

AbstractWe studied demographic, metabolic, and clinical characteristics of patients with diabetes and autoimmune hepatitis (AIH) from the German/Austrian DPV registry. A total of 139 patients with diabetes and AIH were analyzed and compared to 437 728 patients with diabetes without AIH. The prevalence of AIH in patients with T1DM (44.8/100 000) seems higher than in the general population, the prevalence of AIH in patients with T2DM (23.6/100 000) does not seem to be increased. Patients with T2DM and AIH had a shorter duration of diabetes (p=0.007) and a higher proportion of females (p<0.001) compared to T2DM without AIH. Patients with diabetes (T1DM or T2DM) and AIH required higher insulin doses (p<0.001 and p=0.03, respectively) and showed increased liver enzymes (aspartate transaminase, alanine transaminase, gamma-glutamyltransferase) compared to diabetes patients without (all p<0.001). We detected a lower percentage of patients treated with oral antidiabetic drugs (p=0.01) and a higher percentage of patients treated by insulin in patients with T2DM and AIH (p<0.001) compared to patients with T2DM alone. We observed a higher incidence of autoimmune thyroid disease (AIT) in patients with diabetes (T1DM or T2DM) and AIH (p<0.001) compared to diabetes patients without AIH. AIH seems more frequent in patients with T1DM. Patients with diabetes and AIH require intensification of antidiabetic therapy and seem to have a higher prevalence of AIT.
Increased Plasma Thrombin-Antithrombin III Complex Levels in Non-Insulin Dependent Diabetic Patients with Albuminuria Are Reduced by Ethyl Icosapentatenoate
Authors: Shimizu Hiroyuki , Ohtani Ken-Ichi , Tanaka Yoshito , Fukatsu Akira , Uehara Yutaka , Sato Noriyuki , Mori Masatomo 
Published: July 2018

SummaryHypercoagulability may increase the risk of cardiovascular disease (CVD) in diabetic patients with albuminuria. Plasma thrombin-antithrombin III complex (TAT) levels, representing a functional state of clotting system, were studied in one hundred and fifteen non-insulin- dependent diabetic (NIDDM) patients. The patients were divided into three groups according to the urine albumin index (UAI: mg/g Cr): Group A; UAI<30, Group B; 30<UAI<300, Group C; UAI>300. The effect of albuminuria on plasma TAT levels was significant (p<0.02). Ethyl icosapentatenoate (EPA: 1800 mg/day) for 4 weeks significantly (p<0.0005) decreased plasma TAT levels. These data indicate that the degree of diabetic albuminuria is related to plasma TAT levels in NIDDM patients and that treatment with EPA may reduce TAT levels and possibly therefore the rate of development of CVD in patients with NIDDM.
Recombinant Human Soluble Thrombomodulin Reduces Endotoxin-Induced Pulmonary Vascular Injury Via Protein C Activation in Rats
Authors: Uchiba Mitsuhiro , Okajima Kenji , Murakami Kazunori , Nawa Katsuhico , Okabe Hiroaki , Takatsuki Kiyoshi 
Published: July 2018

SummaryAdult respiratory distress syndrome (ARDS) is a serious complication of disseminated intravascular coagulation (DIC) or multiple organ failure. To determine whether recombinant soluble human thrombomodulin (rsTM) may be useful in treating ARDS due to sepsis, we investigated the effect of rsTM on lipopolysaccharide (LPS)-induced pulmonary vascular injury in rats. The intravenous administration of rsTM prevented the increase in pulmonary vascular permeability induced by LPS. Neither heparin plus antithrombin III (AT III) nor dan- syl Glu Gly Arg chloromcthyl ketone-treated factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, prevented LPS-induced vascular injury. The agents rsTM, heparin plus AT III, and DEGR-Xa all significantly inhibited the LPS-induced intravascular coagulation. Recombinant soluble TM pretreated with a monoclonal antibody (moAb) that inhibits protein C activation by rsTM did not prevent the LPS-induced vascular injury; in contrast, rsTM pretreated with a moAb that does not affect thrombin binding or protein C activation by rsTM prevented vascular injury. Administration of activated protein C (APC) also prevented vascular injury. LPS-induced pulmonary vascular injury was significantly reduced in rats with leukopenia induced by nitrogen mustard and by ONO-5046, a potent inhibitor of granulocyte elastase.Results suggest that rsTM prevents LPS-induced pulmonary vascular injury via protein C activation and that the APC-induced prevention of vascular injury is independent of its anticoagulant activity, but dependent on its ability to inhibit leukocyte activation.
Inhibition of Arterial Thrombus Formation in Two Canine Models: Comparison of Ancrod, a Fibrinogen-Depleting Agent, the Thrombin-Inhibitor r-Hirudin, and the Glycoprotein IIb/IIIa-Receptor Antagonist Ro 43-8857
Authors: Rübsamen K , Hornberger W , Kirchengast M 
Published: July 2018

SummaryInhibition of arterial thrombus formation by ancrod, a fibrinogen depleting agent isolated from a snake venom, r-hirudin, an inhibitor of thrombin-mediated fibrinogen cleavage, or the glycoprotein (GP)IIb/IIIa-receptor antagonist Ro 43-8857 interfering with fibrinogen binding to platelets, was evaluated in two canine models. As a marker of platelet-dependent thrombus formation, cyclic blood flow reductions (CFR) were induced in the left coronary artery (LAD) of mongrel dogs by mechanical injury of the endothelium combined with critical stenosis. In the second model CFRs were induced by thrombolysis of a copper coil-induced thrombus in the carotid artery. Blood flow rate during the reocclusion phase was used as an additional parameter of efficacy.The frequency of CFRs used as indicator of platelet aggregation and adhesion was significantly diminished by all treatments in both the carotid artery- and the LAD-model. In the LAD-model, following ancrod treatment, CFRs were correlated with plasma fibrinogen concentrations. Carotid artery blood flow after reperfusion, used as indicator of occlusive thrombus formation, rapidly declined to zero in the control group but remained at a high level after treatment with ancrod or r-hirudin. Ro 43-8857 at the selected dose improved blood flow rate only to a minor degree but prolonged the bleeding time from a mean value of 87.2 ± 10.9 s (n = 24) to values >300 s in 50% of the animals.Our results indicate that CFRs as indicator of platelet aggregation and adhesion are inhibited by either treatments. Blood flow as indicator of occlusive thrombus formation, however, is effectively improved by ancrod and r-hirudin only. Inhibition of fibrinogen binding to platelet GPIIb/IIIa receptors alone was found to be a less potent antithrombotic principle in this model.
Haemophilia A: Mutation Type Determines Risk of Inhibitor Formation
Authors: Schwaab R , Brackmann H-H , Meyer C , Seehafer J , Kirchgesser M , Haack A , Olek K , Tuddenham E G D , Oldenburg J 
Published: July 2018

SummaryThe formation of factor VIII antibodies is a major problem for replacement therapy of haemophilia A patients. Antibodies occur in 5-30% of patients with severe haemophilia A. The reason for antibody formation is still unknown. In this study we correlate for the first time different factor VIII gene mutations, stop- and missense mutations, large and small deletions and intrachromosomal intron 22 recombinations to antibody formation. A total of 364 patients with known inhibitor status of our institute, of the database, and of 3 studies representing intron-22-inversion data are included. The results show that the risk for developing factor VIII antibodies is strongly related to stop mutations, large deletions and intrachromosomal recombinations. A probable explanation could be the complete lack of endogenous circulating factor VIII protein in these cases. Other factors that might be important for the pathogenesis of inhibitor formation, e. g. the antenatal period, as well as possible therapeutic effects, are discussed.
Changes in Haemostatic Factors and Activation Products after Exercise in Healthy Subjects with Different Ages
Authors: van den Burg P J M , Hospers J E H , van Vliet M , Mosterd W L , Bouma B N , Huisveld I A 
Published: July 2018

SummaryWe studied exercise-induced changes in coagulation and fibrinolytic factors and activation products in different age categories. Thirty-eight sedentary males, divided in three age categories (cats I-III; 20-30, 35-45 and 50-60 y) were subjected to a standardized exercise test.Pre-exercise levels (cats I-III resp) of FVII:c (105 ± 5, 121 ±6 and 123 ± 7% NP), fibrinogen (2.35 ± 0.12, 2.55 ± 0.10 and 2.66 ± 0.09 mg/ml), prothrombin activation fragment F1+2 (0.80 ± 0.10,0.80 ± 0.11 and 1.22 ±0.16 nM), t-PA (5,2 ± 0.6, 9.2 ± 1.0, 8.6 ± 1.2 ng/ml) and PAI-1 (42.8 ± 7.5, 67.6 ± 7.6, 62.2 ± 10.9 ng/ml) showed differences that seemed related to age. Regression analysis revealed associations with anthropometry (FVII:c, fibrinogen, F1+2, t-PA, PAI-1) rather than with age.Exercise-induced changes in coagulation (increase in von Wille-brand factor and FVIII:c and a shortening of APTT) and fibrinolytic potential (increase in t-PA and u-PA) were of comparable magnitude for the three age categories. Hardly any change in F1+2 (6%) was observed, while thrombin-antithrombin complexes (93%), plasmin-antiplasmin complexes (79%) and D-dimer (77%) almost doubled during maximal exercise.We conclude that anthropometric differences play a more significant role than age on constitutive levels of haemostatic factors in participants up to 60 years of age. The magnitude of exercise-induced changes is comparable in the age categories under study, and simply superimposed on constitutive (pre-exercise) levels. Clear evidence for prothrombin activation is lacking, but plasmin formation is enhanced during exercise.