bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment exceeds expectations with vemurafenib monotherapy in a patient with BRAFV600E-mutant metastatic melanoma
Authors: Yilmaz Mesut , Güven Meşe Şermin 
Published: March 2020

Introduction Patients with distant metastatic melanoma has a poor prognosis, with a reported median survival time of six to eight months. In modern era, survival has prolonged with the immunotherapy and targeted therapy options. Potent and selective BRAF inhibitors have been developed that specifically inhibit mutated BRAF over other RAF kinases. Vemurafenib was the first selective tyrosine kinase inhibitor developed to target the V600E allele of BRAF-mutant melanoma. Case Report In this report, we present a case of BRAFV600E-mutant metastatic melanoma, which is being treated with vemurafenib monotherapy with complete response for about seven years. Management and Outcome The patient is still being treated with vemurafenib and radiologic complete response is ongoing for about seven years. Discussion Patients treated with BRAF inhibitors monotherapy had promising response rates and improvement in the progression-free survival and overall survival, but melanoma cells became resistant very quickly, affecting the progression. In this case, we present a case that has permanent response to vemurafenib monotherapy.
Study of Indicators for Early and Rapid Diagnosis of Radiation Injury Is the Most Important in Patients With Cancer During Radiotherapy
Authors: Liu Gang , Niu Li-Mei , Wang Li-Qin , Li Ye , Wu Xiao-Qin , Liu Yin-Yin , Zhang Rong 
Published: March 2020

Objective: To establish a complete technical solution for the radiation biological dose estimation, to enable prediction of individuals’ response to radiotherapy (RT), and to control treatment dose for reduced irradiation injury and promote repair; and to evaluate the risk of radiation-induced late effects for patients undergoing external photon beam RT and provide the reliable dose–response relationships. Methods: Select 49 tumor patients using 60Co and linear accelerator for radiation therapy; initial radiation dose was 250 cGy. Chromosome aberration and blood count were analyzed before radiation therapy and 2 hours after the first day of RT. Results: Two hours after the first day of RT, peripheral blood cell count of lymphocytes of patients with cancer was significantly decreased ( P < .01). The frequency of chromosome aberration was higher ( P < .01). Conclusion: High-dose radiation of the radiation therapy makes significant injuries to peripheral blood lymphocytes.
Accuracy of combined quantitative diffusion-weighted MRI and routine contrast-enhanced MRI in discrimination of benign and malignant salivary gland tumors
Authors: Nada Ayman , Hady Dina , Youssef Ayda , Mahmoud Esmat , Assad Ramy Edward 
Published: March 2020

Background Preoperative imaging of salivary gland tumors is important for predicting and differentiating benign from malignant tumors, and for aiding management planning. We aimed to investigate the accuracy of combined quantitative diffusion-weighted magnetic resonance imaging (MRI) and routine contrast-enhanced MRI in the evaluation of salivary gland tumors and the differentiation of benign from malignant tumors. Results This study included 51 patients with a total of 16 benign and 35 malignant lesions that were detected by histopathological analysis. There was a statistically significant difference between the apparent diffusion coefficient values (ADC) of malignant and benign lesions (0.69 ± 0.22 × 10−3 mm2/s and 1.39 ± 0.52 × 10−3 mm2/s respectively). The optimal cut-off ADC value was 1.08 with 75% specificity and 97% sensitivity. The routine contrast-enhanced MRI had predicted benign and malignant tumors with 65% sensitivity and 44% specificity. The sensitivity and specificity were greatly increased when quantitative diffusion-weighted MRI was combined with routine contrast-enhanced MRI: 100%, and 88% respectively. A receiver operating curve was generated. The area under curve was 0.88 ( p < 0.001, 95% CI: 0.76–0.99). Conclusion Combined quantitative diffusion-weighted MRI with ADC measurements and routine contrast-enhanced magnetic resonance imaging are helpful tools for the evaluation of salivary gland tumors and help differentiate benign from malignant lesions.
Secondary prevention through comprehensive cardiovascular rehabilitation: From knowledge to implementation. 2020 update. A position paper from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology
Authors: Ambrosetti Marco , Abreu Ana , Corrà Ugo , Davos Constantinos H , Hansen Dominique , Frederix Ines , Iliou Marie C , Pedretti Roberto F E , Schmid Jean-Paul , Vigorito Carlo , Voller Heinz , Wilhelm Matthias , Piepoli Massimo F , Bjarnason-Wehrens Birna , Berger Thomas , Cohen-Solal Alain , Cornelissen Veronique , Dendale Paul , Doehner Wolfram , Gaita Dan , Gevaert Andreas B , Kemps Hareld , Kraenkel Nicolle , Laukkanen Jari , Mendes Miguel , Niebauer Josef , Simonenko Maria , Zwisler Ann-Dorthe Olsen 
Published: March 2020

Abstract
Secondary prevention through comprehensive cardiac rehabilitation has been recognized as the most cost-effective intervention to ensure favourable outcomes across a wide spectrum of cardiovascular disease, reducing cardiovascular mortality, morbidity and disability, and to increase quality of life. The delivery of a comprehensive and ‘modern’ cardiac rehabilitation programme is mandatory both in the residential and the out-patient setting to ensure expected outcomes. The present position paper aims to update the practical recommendations on the core components and goals of cardiac rehabilitation intervention in different cardiovascular conditions, in order to assist the whole cardiac rehabilitation staff in the design and development of the programmes, and to support healthcare providers, insurers, policy makers and patients in the recognition of the positive nature of cardiac rehabilitation. Starting from the previous position paper published in 2010, this updated document maintains a disease-oriented approach, presenting both well-established and more controversial aspects. Particularly for implementation of the exercise programme, advances in different training modalities were added and new challenging populations were considered. A general table applicable to all cardiovascular conditions and specific tables for each clinical condition have been created for routine practice.
Extensor hallucis longus tendon is a new distal landmark for coronal tibial component alignment in total knee arthroplasty: A study of magnetic resonance imaging
Authors: Hino Manabu , Nakagawa Shuji , Arai Yuji , Inoue Hiroaki , Kan Hiroyuki , Fujii Yuta , Ikoma Kazuya , Kubo Toshikazu 
Published: March 2020

Purpose: In total knee arthroplasty (TKA), various landmarks are generally used to ensure correct osteotomy. In this study, we examined whether the tibialis anterior tendon (TAT) or the extensor hallucis longus tendon (EHLT) could be used as a landmark of the center of the ankle joint in patients with knee osteoarthrosis (OA), using magnetic resonance imaging (MRI). Methods: The subjects were 61 patients with OA in 79 knees (males: 8 with 9 knees and females: 53 with 70 knees). With the ankle joint secured in the intermediate position, MRI from the knee joint to the ankle joint was performed in the same foot position. We prepared individual lines connecting the center of the ankle joint with the TAT or EHLT to measure the angle difference (ΔA) from Akagi’s line in the knee joint. We analyzed whether the ΔA might be affected by deformity of the knee joint or foot region, and tibial torsion. Results: At the ankle joint level, the ΔA of EHLT was the smallest, with an average of 1.6 ± 3.4°. The ΔA for the femorotibial angle, hallux valgus angle, and varus–valgus angle showed no correlations with deformity of the knee joint and foot region, or tibial torsion. Conclusions: MRI findings showed that EHLT would be useful as a landmark of the ankle joint center in extramedullary tibial osteotomy in TKA for medial knee OA. It was also clarified that the landmark would not be affected by severe deformity of the knee joint, deformity of the foot region, or external torsion of the tibia.
Proximal Over-resection During Femoral Osteochondroplasty Negatively Affects The Distractive Stability Of The Hip Joint
Authors: Lazaro Lionel E. , Lim Daniel P. , Nelson Trevor , Eberlein Samuel , Banffy Michael B. , Metzger Melodie 
Published: March 2020

Objectives: Hip microinstability is an increasingly recognized source of hip pain and disability. Femoral osteochondroplasty is usually performed with direct visualization through an arthroscope, assisted with repeated fluoroscopic imaging. However, a two-dimensional representation of a three-dimensional structure is misleading and may compromise the precision of the planned osteochondroplasty. The resection can occasionally extend proximally into the Femoral Head diminishing the articular surface area available for suction seal. The purpose of this study was to determine whether proximal over-resection decreases the rotational and distractive stability of the hip joint. Methods: Six hemi-pelvises were repeatedly tested in the following conditions: (a) intact, (b) T-capsulotomy, (c) Osteochondroplasty to the physeal scar, followed by (d) 5mm and (e) 10mm proximal extension. The pelvis was secured to a metal plate and the femur was potted and attached to a multi-axial hip jig. Specimens were axially distracted with a load from 0-150N followed by 5Nm of internal and external torque at 0o, 15o, 30o, 60o, 90o of flexion. Displacement/rotation was recorded using a 3D motion tracking system. Repeated measures ANOVA was used with significance set at p<0.05. Results: Proximal extension of the resection by 5mm and 10mm increased axial instability at every angle of flexion tested, with the greatest increase observed at higher angles of flexion,p<0.05. T-capsulotomy alone increased both internal and external rotation at all angles of flexion, p<0.05. Subsequent resection and extension of the resection did not significantly increase rotational instability compared to the capsulotomy state. Conclusion: Extending the osteochondroplasty proximally into the femoral head compromises the distractive stability of the hip joint, but doesn’t not effect hip rotational stability. Clinically, this highlights the importance of accuracy when performing femoral osteochondroplasty to minimize proximal extension that may increase iatrogenic instability of the hip joint, leading to reduced post-operative outcomes.
An Update on Foot and Ankle Fellowship Website Content and Accessibility
Authors: Khwaja Ansab , Du Peter , Sherman Nathan , Truchan Lisa 
Published: March 2020

Background: The content and accessibility of foot and ankle fellowship websites impact applicants and fellowship programs. This study aimed to evaluate the accessibility provided via the American Orthopaedic Foot & Ankle Society (AOFAS) websites and individual websites. Methods: The AOFAS website was used to identify existing foot and ankle fellowship programs. The database information was reviewed for links to fellowship program websites, which was corroborated through a Google search for accessibility. Information from fellowship program websites and the AOFAS was analyzed for the presence of recruitment and educational content, and this analysis was compared to previously reported metrics. Results: Forty-eight orthopedic foot and ankle fellowship programs were identified. The AOFAS database featured direct links to 19 (40%) fellowship websites with the Google search providing direct links to 35 (73%) websites. Foot and ankle fellowship information markedly improved in domains of Salary/Benefits (+233%), Rotations/Curriculum (+199%), and Faculty Listing (+67%), but there was a reduction in available content in the domains of Operative Experience (–79%), Office/Clinic information (–78%), and Didactics (–39%) compared with the lone existing study. Conclusion: There continues to be variability between foot and ankle fellowship websites and the AOFAS website regarding program content and descriptions. Some information is more readily available, but other domains have less information now than in previously reported research.
A murine photothrombotic stroke model with an increased fibrin content and improved responses to tPA-lytic treatment
Authors: Sun Yu-Yo , Kuo Yi-Min , Chen Hong-Ru , Short-Miller Jonah C. , Smucker Marchelle R. , Kuan Chia-Yi 
Published: March 2020

Abstract
The Rose Bengal (RB) dye-based photothrombotic stroke (PTS) model has many methodological advantages including consistent location and size of infarct, low mortality, and relatively simple surgical procedures. However, the standard PTS has the caveat of poor responses to tissue-type plasminogen activator (tPA)–mediated lytic treatment, likely as a result of the platelet-rich, fibrin-poor content of the blood clots. Here we tested whether the admixture of thrombin (80 U/kg) and RB dye (50 mg/kg) in the proximal middle cerebral artery (MCA)–targeted PTS will modify the clot composition and elevate the responsiveness to tPA-lytic treatment (Alteplase, 10 mg/kg). Indeed, intravital imaging, immunostaining, and immunoblot analyses showed less-compacted platelet aggregates with a higher fibrin content in the modified thrombin (T) plus RB photothrombotic stroke (T+RB-PTS) model compared with the standard RB-PTS-induced clots. Both RB-PTS and T+RB-PTS showed steady recovery of cerebral blood flow (CBF) in the ischemic border from 1 day after infarction, but without recanalization of the proximal MCA branch. Intravital imaging showed high potency of restoring the blood flow by tPA after single vessel-targeted T+RB-PTS. Further, although intravenous tPA failed to restore CBF or attenuate infarction in RB-PTS, it conferred 25% recovery of CBF and 55% reduction of the infarct size in T+RB-PTS (P &lt; .05) if tPA was administered within 2 hours postphotoactivation. These results suggest that T+RB-PTS produces mixed platelet:fibrin clots closer to the clinical thrombus composition and enhanced the sensitivity to tPA-lytic treatment. As such, the modified photothrombosis may be a useful tool to develop more effective thrombolytic therapies of cerebral ischemia.
Checkpoint inhibition before haploidentical transplantation with posttransplant cyclophosphamide in Hodgkin lymphoma
Authors: De Philippis Chiara , Legrand-Izadifar Faezeh , Bramanti Stefania , Giordano Laura , Montes de Oca Catalina , Duléry Rémy , Bouabdallah Reda , Granata Angela , Devillier Raynier , Mariotti Jacopo , Sarina Barbara , Harbi Samia , Maisano Valerio , Furst Sabine , Pagliardini Thomas , Weiller Pierre-Jean , Lemarie Claude , Calmels Boris , Chabannon Christian , Santoro Armando , Mohty Mohamad , Blaise Didier , Castagna Luca 
Published: March 2020

Abstract
We report on 59 Hodgkin lymphoma patients undergoing haploidentical stem cell transplantation (SCT; haplo-SCT) with posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis, comparing outcomes based on pretransplant exposure to checkpoint inhibitors (CPIs). Considering pretransplant characteristics, the 2 cohorts (CPI = 29 patients vs no-CPI = 30 patients) were similar, except for the number of prior lines of therapy (6 vs 4; P &lt; .001). With a median follow-up of 26 months (range, 7.5-55 months), by univariate analysis, the 100-day cumulative incidence of grade 2-4 acute GVHD was 41% in the CPI group vs 33% in the no-CPI group (P = .456), whereas the 1-year cumulative incidence of moderate to severe chronic GVHD was 7% vs 8%, respectively (P = .673). In the CPI cohort, the 2-year cumulative incidence of relapse appeared lower compared with the no-CPI cohort (0 vs 20%; P = .054). No differences were observed in terms of overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM) (at 2 years, 77% vs 71% [P = .599], 78% vs 53% [P = .066], and 15% vs 21% [P = .578], respectively). By multivariable analysis, CPI before SCT was an independent protective factor for PFS (hazard ratio [HR], 0.32; P = .037). Stable disease (SD)/progressive disease (PD) was an independent negative prognostic factor for both OS and PFS (HR, 14.3; P &lt; .001 and HR, 14.1; P &lt; .001, respectively) . In conclusion, CPI as a bridge to haplo-SCT seems to improve PFS, with no impact on toxicity profile.
Late infectious complications in hematopoietic cell transplantation survivors: a population-based study
Authors: Foord Aimee M. , Cushing-Haugen Kara L. , Boeckh Michael J. , Carpenter Paul A. , Flowers Mary E. D. , Lee Stephanie J. , Leisenring Wendy M. , Mueller Beth A. , Hill Joshua A. , Chow Eric J. 
Published: March 2020

Abstract
Few studies have compared the incidence of infections occurring ≥2 years after hematopoietic cell transplant (HCT) with other cancer patients and the general population. In this study, ≥2-year HCT survivors who were Washington residents treated from 1992 through 2009 (n = 1792; median age, 46 years; 52% allogeneic; 90% hematologic malignancies) were matched to individuals from the state cancer registry (n = 5455, non-HCT) and driver’s license files (n = 16 340; Department of Licensing [DOL]). Based on hospital and death registry codes, incidence rate ratios (IRRs; 95% confidence interval [CI]) of infections by organism type and organ system were estimated using Poisson regression. With 7-year median follow-up, the incidence rate (per 1000 person-years) of all infections was 65.4 for HCT survivors vs 39.6 for the non-HCT group (IRR, 1.6; 95% CI, 1.3-1.9) and 7.2 for DOL (IRR, 10.0; 95% CI, 8.3-12.1). Bacterial and fungal infections were each 70% more common in HCT vs non-HCT cancer survivors (IRR, 1.7; P &lt; .01), whereas the risk for viral infection was lower (IRR, 1.4; P = .07). Among potentially vaccine-preventable organisms, the IRR was 3.0 (95% CI, 2.1-4.3) vs the non-HCT group. Although the incidences of all infections decreased with time, the relative risk in almost all categories remained significantly increased in ≥5-year HCT survivors vs other groups. Risk factors for late infection included history of relapse and for some infections, history of chronic graft-versus-host disease. Providers caring for HCT survivors should maintain vigilance for infections and ensure adherence to antimicrobial prophylaxis and vaccination guidelines.
Designing Aptamer-Gold Nanoparticle-Loaded pH-Sensitive Liposomes Encapsulate Morin for Treating Cancer
Authors: Ding Xiaoyuan , Yin Chenyang , Zhang Weiwei , Sun Yu , Zhang Zhenzhen , Yang Endong , Sun Dongdong , Wang Weiyun 
Published: March 2020

AbstractThis study proposes the synthesis of a type of anticancer nanoparticle, aptamers and Au nanoparticle (Apt-Au)-modified Morin pH-sensitive liposome (MSL), which exhibits targeting properties. Tumors are difficult to cure because their microenvironment varies from that of normal tissue; its pH is lower than that of normal tissue, which generally impedes the effectiveness of drugs. Thus, pH-responsive drugs have attracted extensive attention. Gold nanoparticles (AuNPs) show potential as drug carriers because of their small size, good biocompatibility, easy surface modification, and strong cell penetration. Apt-Au@MSL exhibits excellent monodispersity and tumor-targeting properties and can be released in partly acidic environment via dialysis. We screened our model cancer cell by MTT assay and found that SGC-7901 cells can effectively suppress proliferation. In vivo results demonstrate that the administration of Apt-Au@MSL could inhibit tumor growth in xenograft mouse models. H&E staining and TUNEL assay further confirmed that Apt-Au@MSL can promote tumor apoptosis. Apt-Au@MSL may induce apoptosis by triggering overproduction of reactive oxygen species (ROS) and regulating multiple signal crosstalk. Both blood biochemistry tests and H&E staining suggested that these materials exhibit negligible acute toxicity and good biocompatibility in vivo. With its powerful function, Apt-Au@MSL can be used as a target-based anticancer material for future clinical cancer treatment.
OsVPE3 Mediates GA-induced Programmed Cell Death in Rice Aleurone Layers via Interacting with Actin Microfilaments
Authors: Zhang Heting , Xiao Yu , Deng Xiaojiang , Feng Hongyu , Li Zhe , Zhang Lulu , Chen Huiping 
Published: March 2020

Abstract
Background
Vacuolar processing enzymes (VPEs) have been identified as the enzymes that regulate vacuole-mediated programmed cell death (PCD) in plants. The mechanism that VPE regulates the PCD in rice aleurone layers remains unknown.

Results
The aleurone layers treated with distilled water exerted caspase-1 and VPE activity, both of which were inhibited by the caspase-1 specific inhibitor Ac-YVAD-CMK but not by the caspase-3 specific inhibitor Ac-DEVD-CHO. However, the caspase-1 and caspase-3 inhibitors weakened the activity of caspase-3. Combined with the effects of endogenous gibberellin (GA) on the induction of OsVPEs, we suggest that the OsVPE3 in the aleurone layers, which exhibits caspase-1-like activity, is a key molecule in GA-induced PCD via regulating the protease with caspase-3-like activity. Many studies have confirmed that vacuolar fusion is an important feature of vacuole-mediated PCD in plants. In this experiment, the process of vacuole fusion was accompanied by changes in the structure of actin filaments (AFs), specifically, their depolymerization and polymerization. The process of vacuolar fusion was accelerated or delayed by the promotion or inhibition of the depolymerization of AFs, respectively. Here, the inhibition of OsVPE3 blocked the depolymerization of AFs and delayed the fusion of vacuoles, indicating that OsVPE3 can regulate the fusion of vacuoles in rice aleurone layers via mediating AFs. Furthermore, the depolymerization of AFs contributed to the up-regulation of OsVPE3 gene expression and VPE activity, resulting in accelerated PCD in rice aleurone layers. However, the inhibitor of VPE reversed the effects of AF depolymerization on the activity of VPE, then postponing the process of PCD, implying that AF can involve in GA-induced PCD of rice aleurone layers by mediating OsVPE3.

Conclusions
Together, activation of OsVPE3 and depolymerization of AFs shortened the process of vacuolation and PCD in rice aleurone layers, and OsVPE3 interacted with AFs during regulation.
Bacterial chemotaxis: a way forward to aromatic compounds biodegradation
Authors: Ahmad Fiaz , Zhu Daochen , Sun Jianzhong 
Published: March 2020

AbstractWorldwide industrial development has released hazardous polycyclic aromatic compounds into the environment. These pollutants need to be removed to improve the quality of the environment. Chemotaxis mechanism has increased the bioavailability of these hydrophobic compounds to microorganisms. The mechanism, however, is poorly understood at the ligand and chemoreceptor interface. Literature is unable to furnish a compiled review of already published data on up-to-date research on molecular aspects of chemotaxis mechanism, ligand and receptor-binding mechanism, and downstream signaling machinery. Moreover, chemotaxis-linked biodegradation of aromatic compounds is required to understand the chemotaxis role in biodegradation better. To fill this knowledge gap, the current review is an attempt to cover PAHs occurrence, chemical composition, and potential posed risks to humankind. The review will cover the aspects of microbial signaling mechanism, the structural diversity of methyl-accepting chemotaxis proteins at the molecular level, discuss chemotaxis mechanism role in biodegradation of aromatic compounds in model bacterial genera, and finally conclude with the potential of bacterial chemotaxis for aromatics biodegradation.