bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Parkin on methamphetamine‐induced α‐synuclein degradation dysfunction in vitro and in vivo
Authors: Meng Yunle , Qiao Honghua , Ding Jiuyang , He Yitong , Fan Haoling , Li Chen , Qiu Pingming 
Published: February 2020

AbstractIntroductionMethamphetamine (METH) is a psychostimulant drug with complicated neurotoxicity, and abuse of METH is very common. Studies have shown that METH exposure causes alpha‐synuclein (α‐syn) accumulation. However, the mechanism of α‐syn accumulation has not been determined.MethodsIn this study, we established cell and animal models of METH intoxication to evaluate how METH affects α‐syn expression. In addition, to explore METH‐induced neurotoxicity, we measured the level of Parkin and the phosphorylation levels of α‐syn, Polo‐like kinase 2 (PLK2), the proteasome activity marker CD3δ, and the apoptosis‐related proteins Caspase‐3 and PARP. Parkin is a key enzyme in the ubiquitin–proteasome system. In addition, the effect of Parkin on METH‐induced neurotoxicity was investigated by overexpressing it in vitro and in vivo.ResultsMETH exposure increased polyubiquitin and α‐syn expression, as did MG132. Furthermore, the level of Parkin and the interaction between Parkin and α‐syn decreased after METH exposure. Importantly, the increases in α‐syn expression and neurotoxicity were relieved by Parkin overexpression.ConclusionsBy establishing stable cell lines and animal models that overexpress Parkin, we confirmed Parkin as an important factor in METH‐induced α‐syn degradation dysfunction in vitro and in vivo. Parkin may be a promising target for the treatment of METH‐induced neurotoxicity.
Does the Babinski sign predict functional outcome in acute ischemic stroke?
Authors: Qu Jian‐Feng , Chen Yang‐Kun , Luo Gen‐Pei , Qiu Dong‐Hai , Liu Yong‐Lin , Zhong Huo‐Hua , Wu Zhi‐Qiang 
Published: February 2020

AbstractObjectiveThe aim of this prospective cohort study was to determine the incidence and neuroimaging risk factors associated with Babinski sign following acute ischemic stroke, as well as its relationship with the functional outcome of patients.MethodsA total of 351 patients were enrolled in the study within 7 days of acute ischemic stroke. The Babinski sign along with other upper motor neuron signs were examined upon admission and between days 1 and 3 and days 5 and 7 after admission. Neuroimaging parameters included site and volume of infarction and white matter lesions. All patients were followed up at 3 months. Functional outcome was assessed with the Lawton Activities of Daily Living scale and modified Rankin Scale.ResultsBabinski sign was observed in 115 of 351 (32.8%) patients in the acute ischemic stroke. These patients had higher National Institutes of Health Stroke Scale (NIHSS) scores at admission and higher rates of atrial fibrillation and cardioembolism; higher frequencies of frontal, temporal, and limbic lobes and basal ganglia infarcts; and larger infarct volume. Higher NIHSS score and basal ganglia infarct were significant predictors of the presence of Babinski sign. After adjusting for confounds, the presence of Babinski sign did not predict poor functional outcome.ConclusionThe incidence of Babinski sign was 32.8% in the acute ischemic stroke. Severe infarction and basal ganglia infarct were independent predictors of Babinski sign. Although Babinski sign is common in acute ischemic stroke patients, it does not predict poor functional outcome 3 months later.
Straightforward method for calibration of mechanistic cation exchange chromatography models for industrial applications
Authors: Saleh David , Wang Gang , Müller Benedict , Rischawy Federico , Kluters Simon , Studts Joey , Hubbuch Jürgen 
Published: February 2020

AbstractMechanistic modeling of chromatography processes is one of the most promising techniques for the digitalization of biopharmaceutical process development. Possible applications of chromatography models range from in silico process optimization in early phase development to in silico root cause investigation during manufacturing. Nonetheless, the cumbersome and complex model calibration still decelerates the implementation of mechanistic modeling in industry. Therefore, the industry demands model calibration strategies that ensure adequate model certainty in a limited amount of time. This study introduces a directed and straightforward approach for the calibration of pH‐dependent, multicomponent steric mass action (SMA) isotherm models for industrial applications. In the case investigated, the method was applied to a monoclonal antibody (mAb) polishing step including four protein species. The developed strategy combined well‐established theories of preparative chromatography (e.g. Yamamoto method) and allowed a systematic reduction of unknown model parameters to 7 from initially 32. Model uncertainty was reduced by designing two representative calibration experiments for the inverse estimation of remaining model parameters. Dedicated experiments with aggregate‐enriched load material led to a significant reduction of model uncertainty for the estimates of this low‐concentrated product‐related impurity. The model was validated beyond the operating ranges of the final unit operation, enabling its application to late‐stage downstream process development. With the proposed model calibration strategy, a systematic experimental design is provided, calibration effort is strongly reduced, and local minima are avoided.
Integrative clinical and biopathology analyses to understand the clinical heterogeneity of infantile rhabdomyosarcoma: A report from the French MMT committee
Authors: Butel Thibault , Karanian Marie , Pierron Gaelle , Orbach Daniel , Ranchere Dominique , Cozic Nathalie , Galmiche Louise , Coulomb Aurore , Corradini Nadège , Lacour Brigitte , Proust Stéphanie , Guerin Florent , Boutroux Hélène , Rome Angélique , Mansuy Ludovic , Vérité Cécile , Defachelles Anne‐Sophie , Tirode Franck , Minard‐Colin Veronique 
Published: February 2020

AbstractBackgroundRhabdomyosarcoma (RMS) in infants is a particular entity with various clinical presentations and outcomes. To better understand the clinical heterogeneity of RMS in infants, an integrative clinical, histological, and molecular analysis was performed.MethodsFrom 1989 to 2015, 37 infants aged less than 6 months with a diagnosis of RMS and archival tumor materials were identified in France. Clinical data, central pathologic review, and molecular profile including RNA sequencing were analyzed.ResultsNineteen patients (51%) had embryonal RMS (ERMS) (including three highly differentiated ERMS with PTCH deletion), eight (22%) had spindle cell RMS (SRMS) (three VGLL2‐, one NTRK‐, and two (B)RAF‐fusions), six (16%) had alveolar RMS (ARMS) (all FOXO1‐ or PAX3‐fusion), two had unclassified RMS, and two poorly differentiated RMS were retrospectively diagnosed as rhabdoid tumors (RT) with loss of INI1 expression. The two RT patients died of rapid disease progression. Five‐year event‐free (EFS) and overall survival (OS) for RMS were 62% (95%CI, 47‐82) and 52% (95%CI, 37‐72). Eleven patients (31%) relapsed and four (11%) had primary refractory disease (all ERMS). In univariate analysis, EFS and OS were only associated with histology subtype, with 100% survival of known fusion‐positive SRMS. RNA cluster expression showed three main clusters: ARMS, ERMS, and “VGLL2‐fusion” cluster, consisting of SRMS and ERMS.ConclusionsBiopathology findings from this study support the different prognosis of infantile RMS. New fusion‐positive SRMS has a very good outcome which may allow more conservative treatment in the future.
Prognostic nomograms and Aggtrmmns scoring system for predicting overall survival and cancer‐specific survival of patients with kidney cancer
Authors: Zhou Yuan , Zhang Rentao , Ding Yinman , Wang Zhengquan , Yang Cheng , Tao Sha , Liang Chaozhao 
Published: February 2020

AbstractBackgroundCurrently, the prognosis of kidney cancer depends mainly on the pathological grade or tumor stage. Clinicians have few effective tools that can personalize and adequately evaluate the prognosis of kidney cancer patients.MethodsA total of 70 481 kidney cancer patients were selected from the Surveillance, Epidemiology, and End Results database, among which patients diagnosed in 2005‐2011 (n = 42 890) were used to establish nomograms for overall survival (OS) and cancer‐specific survival (CSS), and those diagnosed in 2012‐2015 (n = 24 591) were used for external validation. Univariate and multivariate Cox analyses were used to determine independent prognostic factors. Concordance index (C‐index), receiver operating characteristic curve, and calibration curve were used to evaluate the predictive capacity of the nomograms. We further reduced subgroup classification and used propensity score matching to balance clinical informations, and analyzed the effect of other variables on survival. We established a new kidney cancer prognostic score system based on the effect of all available variables on survival. Cox proportional hazard model and Kaplan‐Meier curves were used for survival comparison.ResultsAge, gender, marital status, surgery, grade, T stage, and M stage were included as independent risk factors in the nomograms. The favorable area under the curve (AUC) value (for OS, AUC = 0.812‐0.858; and for CSS, AUC = 0.890‐0.921), internal (for OS, C‐index = 0.776; and for CSS, C‐index = 0.856), and external (for OS, C‐index = 0.814‐0.841; and for CSS, C‐index = 0.894‐0.904) validation indicated that the proposed nomograms could accurately predict 1‐, 3‐, and 5‐year OS and CSS of kidney cancer patients. The Aggtrmmns prognostic scoring system based on age, gender, race, marital status, grade, TNM stage, and surgery of kidney cancer patients could stage patients more explicitly than the AJCC staging system.ConclusionThe nomogram and Aggtrmmns scoring system can predict OS and CSS in kidney cancer patients effectively, which may help clinicians personalize prognostic assessments and clinical decisions.
Regenerated Traumatic Bone Cyst With Platelet‐Rich Fibrin in the Mandible: A Case Report
Authors: Bernabeu‐Mira Juan Carlos , Soto‐Peñaloza David , Peñarrocha‐Oltra Sonia , Diago María Peñarrocha 
Published: February 2020

IntroductionTraumatic bone cyst is a pseudocyst which is characterized as an asymptomatic unilocular single lesion with an empty cavity without epithelial lining. Its etiology is still debated, it is more frequent among young people and it is often localized in the posterior mandible zone. A case report is described about diagnosis and conservative treatment of a traumatic bone cyst in anterior zone of lower mandible.Case PresentationThe report describes a 22‐year‐old female with a traumatic bone cyst in anterior mandible as accidental discovery from a routine orthopantomography. A conservative approach was conducted to treat the lesion through a submarginal incision, an osteotomy with ultrasound, a filling of the cavity with advanced platelet‐rich fibrin membranes, and repositioning of the cortical bone. The radiological follow‐up to 6 months confirmed the healing of the lesion.ConclusionThe conservative approach through submarginal incision, osteotomy with ultrasound, filling with A‐PRF+ membranes and repositioning of cortical bone ensures optimal bone healing and avoids gingival recessions at six months follow‐up, showing to be a good alternative for satisfactory defect resolution in similar clinical cases.
Predictors of left ventricular reverse remodeling after percutaneous therapy for mitral regurgitation with the MitraClip system
Authors: Nita Nicoleta , Scharnbeck Dominik , Schneider Leonhard‐Moritz , Seeger Julia , Wöhrle Jochen , Rottbauer Wolfgang , Keßler Mirjam , Markovic Sinisa 
Published: February 2020

AbstractObjectivesTo investigate the predictors and clinical impact of left ventricular reverse remodeling (LVRR) after MitraClip (MC) therapy for degenerative (DMR) and functional mitral regurgitation (FMR).BackgroundMC therapy induces LVRR in patients with mitral regurgitation (MR) at high‐risk for surgery. However, specific data on predictors of LVRR therapy are limited.MethodsThis study included 164 patients treated by MC implantation with complete clinical and echocardiographic evaluation at baseline, 6 months, and 12 months. LVRR was defined as a decrease of ≥10% of the left ventricular end‐diastolic diameter after 12 months and was found in 49% of the patients.ResultsLVRR was associated with significantly reduced event rate 2 years after MC procedure. In the total cohort, multivariate regression analysis determined severe recurrent/residual MR after 12 months (p = .010, odds ratio [OR] = 0.26), male gender (p = .050, OR = 0.49) and left ventricular ejection fraction (LVEF) <20% (p = .046, OR = 0.24) as predictors of absence of LVRR. In the subgroup analysis according to etiology of MR, multivariate regression analysis revealed severe recurrent/residual MR after 12 months (p = .04, OR = 0.184) to inversely predict LVRR only in the DMR subgroup. In FMR, residual severe tricuspid regurgitation (TR) inversely predicts LVRR (p = .032, OR = 0.361).ConclusionsLVRR occurs in half of the patients after MC and is associated with reduced MACCE rates at follow‐up. Combined information on residual/recurrent MR, baseline LVEF and gender predict LVRR after MC procedure. While residual/recurrent MR is the independent predictor for the absence of LVRR in DMR, in FMR only severe residual TR independently predict LVRR.
Combined and independent impact of coronary artery calcification and inflammation on risk for adverse cardiovascular events after percutaneous coronary intervention: Results from a large single‐center registry
Authors: Aoi Shunsuke , Baber Usman , Kovacic Jason C. , Mehran Roxana , Aquino Melissa , Dangas George , Sweeny Joseph , Vijay Pooja , Shah Srushti , Barman Nitin , Moreno Pedro , Kini Annapoorna S. , Sharma Samin K. 
Published: February 2020

AbstractPurposeOur study investigated the impact of coronary artery calcification (CAC) and systemic inflammation on risks for major adverse cardiovascular events (MACE) following percutaneous coronary intervention (PCI).BackgroundCAC and systemic inflammation are known to be associated with an increased risk of cardiovascular events.MethodsA total of 17,711 consecutive patients who underwent PCI in our hospital between January 1, 2009 and December 31, 2015 were categorized according to the degree of CAC (moderate/severe vs. none/mild) and high‐sensitivity C‐reactive protein (hsCRP) level (≥2 vs. <2 mg/L). MACE was defined as death, myocardial infarction (MI), or target vessel revascularization (TVR) occurring over 1 year.ResultsWithin the four groups, patients with both moderate/severe CAC and elevated hsCRP (n = 1,814 [10.2%]) were older with more comorbid risk factors compared to those with moderate/severe CAC alone (n = 1,687 [9.5%]), elevated hsCRP alone (n = 7,597 [42.9%]) or neither abnormality (n = 6,613 [37.3%]). The analogous 1‐year MACE rates were 21.2, 14.9, 11.5, and 7.8%, respectively (p‐trend < .001). Results were unchanged after multivariable adjustment, suggesting synergistic adverse effects in patients with both CAC and elevated hsCRP.ConclusionsThe presence of both moderate/severe CAC and systemic inflammation confers a synergistic effect on risk for MACE following PCI, indicating the need for novel or more intense therapeutic interventions to mitigate risk in such patients.
Electrochemical Characterization of Current‐Producing Human Oral Pathogens by Whole‐Cell Electrochemistry
Authors: Naradasu Divya , Guionet Alexis , Okinaga Toshinori , Nishihara Tatsuji , Okamoto Akihiro 
Published: February 2020

AbstractExtracellular electron transfer (EET) via cell‐bound redox enzymes and/or redox shuttles is extensively studied in environmental bacteria. Meanwhile, EET capable pathogens have been identified in the human gut. However, other EET‐capable bacterial niches where possible biofilm infections are prominent have scarcely been explored. Herein, we electrochemically characterized human oral biofilm pathogens, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, to examine their EET capability. Both strains showed current production with the electrode poised at +0.4 V vs. a standard hydrogen electrode, which was associated with a decrease in electron‐donor concentration, coupled with the appearance of oxidative peaks in differential pulse (DP) and cyclic voltammograms (CV). Addition of antibiotics that suppress the biosynthesis of membrane or protein showed a significant current decrease, demonstrating that current production reflects the cellular activity in these pathogens. DPV‐ and CV‐based kinetic analyses supported by transmission electron microscopy of the cells stained for transition metals suggest a potential EET mechanism associated with the presence of redox enzymes on the cell membrane. These results could be the basis to reevaluate human oral pathogens from an electroactive point of view. The identified electrochemical activity of the two strains can be an effective test for assessing the impact of antibacterial compounds on the pathogen cellular activity on an electrode.
Portable Microalgal Biosensor for Herbicide Monitoring
Authors: Boron Ignacio , Juárez Angela , Battaglini Fernando 
Published: February 2020

AbstractThe need for in‐situ and real‐time tools to monitor the fate of pesticides in extensive areas is of great concern to preserve the environment in countries where agroindustry represents an essential part of its economy. In this work, we present the construction of a portable system based on the reversible photosynthesis inhibition produced by herbicides on microalgae, using atrazine as a model compound. The decrease in oxygen production due to the photosynthesis inhibition is electrochemically detected using an automated flow system. The system presented here involves the immobilization of microalgae in a polyelectrolyte‐surfactant‐carbon nanotube self‐assembled material cast on a screen‐printed graphite electrode; these components contribute to the stability and sensitivity of the whole device. The system presents a limit of detection of 0.11 μM, showing an excellent performance in river samples. The sensor maintains its integrity after five months immersed in a freshwater algae medium at room temperature. These features are key to install this system along the course of a river at a low cost, allowing early detection of polluted areas and long term environmental studies.
Bright Luminescent Platinum(II)‐Biaryl Emitters Synthesized Without Air‐Sensitive Reagents
Authors: Wakasugi Chuei , Yoshida Masaki , Sameera W. M. C. , Shigeta Yasuhiro , Kobayashi Atsushi , Kato Masako 
Published: February 2020

AbstractTransition‐metal complexes bearing biaryl‐2,2′‐diyl ligands tend to show intense luminescence. However, difficulties in synthesis have prevented their further functionalization and practical applications. Herein, a series of platinum(II) complexes bearing biaryl‐2,2′‐diyl ligands, which have never been prepared in air, were synthesized through transmetalation and successive cyclometalation of biarylboronic acids. This approach does not require any air‐ or moisture‐sensitive reagents and features a simple synthesis even in air. The resulting (Et4N)2[Pt(m,n‐F2bph)(CN)2] (m,n‐F2bph=m,n‐difluorobiphenyl‐2,2′‐diyl) complexes exhibit intense green emissions with high quantum efficiencies of up to 0.80 at 298 K. The emission spectral fitting and variable‐temperature emission lifetime measurements indicate that the high quantum efficiency was achieved because of the tight packing structure and strong σ‐donating ability of bph.
Thermorheological properties of asphalt binders
Authors: Gunay Taylan , Tomkovic Tanja , Hatzikiriakos Savvas G. 
Published: February 2020

AbstractThe rheological properties of different types of asphalt binders were studied and compared considering their constituents and physical characteristics. The saturate, aromatic, resin, and asphaltene (SARA) analysis and differential scanning calorimetry (DSC) have shown their individual constituents and two distinct glass transition temperatures, indicating the phase changes of the two main components of the asphalt binders, namely asphaltenes and maltenes. Rheological characterization was performed over a wide range of temperatures (−10°C‐60°C) showing that these materials may exhibit viscoelastic solid to viscous liquid behaviour. Master curves of complex viscosity, storage modulus, and loss modulus were constructed by applying the time‐temperature superposition principle, which was found applicable over the temperature range considered. Stress relaxation and steady‐shear test were applied to the samples in order to determine their rheological behaviour in the nonlinear viscoelastic regime (viscosity and nonlinear relaxation modulus). The rheological results were modelled and revealed that the Kaye‐Bernstein‐Kearsley‐Zappas (K‐BKZ) constitutive equation is suitable in representing the rheological behaviour of asphalts. The SARA analysis and rheological measurements were found to be compatible.
Strain pattern and T‐wave alterations are predictors of mortality and poor neurologic outcome following stroke
Authors: Braga Gabriel P. , Gonçalves Renato S. , Minicucci Marcos F. , Bazan Rodrigo , Zornoff Leonardo A. M. 
Published: February 2020

AbstractBackgroundStroke is associated with electrocardiogram (ECG) abnormalities. However, the role of strain pattern as predictor of poor neurologic outcome and mortality after stroke has not yet been demonstrated.HypothesisECG abnormalities, with a particular focus on ST‐segment changes, are predictors of mortality and neurologic disability 90 days after stroke.MethodsPatients with up to 24 hours of stroke were prospectively recruited. An ECG was taken at the time of admission. The patients' clinical evolution was evaluated during hospitalization and after discharge by means of a prescheduled return in 90 days. The degree of disability was measured by the modified Rankin scale (mRs). In relation to the mRs, patients were divided into those with scores from 0 to 2 and those with scores equal to or greater than 3 at the end of the observation period.ResultsOf the 112 patients studied, 29 (25.8%) died during the study period. Patients who died presented higher National Institute of Health Stroke Scale and mRs scores on admission, elevated biomarkers of myocardial necrosis, and abnormalities on the ECG. The prevalence of ECG abnormalities was 63%. A logistic regression model showed that strain pattern and T‐wave alterations were predictors of mortality (odds ratio [OR]: 12.970, 95% confidence interval [CI]: 1.519‐110.723, P = .019; OR: 3.873, 95% CI: 1.135‐13.215, P = .031, respectively) and mRs at 90 days (OR: 12.557, 95% CI: 1.671‐94.374, P = .014; OR: 15.970, 95% CI: 3.671‐69.479, P < .001, respectively) after stroke, adjusted by sex, age, stroke subtype, entrance NIH, previous mRs score, and stroke thrombolysis.ConclusionStrain pattern and T‐wave alterations were predictors of mortality and poor neurologic outcome 90 days after stroke.