bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel humanized anti‐tumor necrosis factor‐related apoptosis‐inducing ligand‐R2 monoclonal antibody induces apoptotic and autophagic cell death
Authors: Chen Longfei , Qiu Yuhe , Hao Zhenliang , Cai Jiong , Zhang Shuyong , Liu Yanxin , Zheng Dexian 
Published: July 2017

AbstractIt is well known that the tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL/TNFSF10) is specifically expressed in various tumor cells, but less or no expression in most normal tissues and cells. While TRAIL engages with its native death receptors, TRAIL receptor 1 (TRAIL‐R1) or 2 (TRAIL‐R2), usually elicits the tumor cell death by apoptosis. In this study, we report that a novel humanized monoclonal antibody against TRAIL‐R2 (named as zaptuzumab) well remain the biological activity of the parental mouse antibody AD5‐10 inducing cell death in various cancer cells, but little effect on normal cells. Zaptuzumab also markedly inhibited the tumor growth in the mouse xenograft of NCI‐H460 without toxicity to the liver and kidney, and the efficacy of tumor suppression was increased significantly while it combined with cis‐dichlorodiamineplatinum. Especially, 131I‐labeled zaptuzumab injected into mouse tail vein specifically targeted to the xenograft of the lung cancer cells. Confocal analysis showed that zaptuzumab bound with TRAIL‐R2 on cell surface could be quickly internalized and transferred into the lysosome. Furthermore, zaptuzumab possessed a high level of antibody‐dependent cytotoxicity as well as complement‐dependent cytotoxicity. Study on the mechanisms of cell death induced by zaptuzumab showed that it efficiently induced both caspase‐dependent apoptosis and autophagic cell death. These data suggest that the humanized anti‐TRAIL‐R2 monoclonal antibody or the second generation of the antibody may have an important clinical usage for cancer immunotherapy. © 2017 IUBMB Life, 69(9):735–744, 2017
Ti6Al4V laser surface preparation and functionalization using hydroxyapatite for biomedical applications
Authors: Faria D. , Abreu C. S. , Buciumeanu M. , Dourado N. , Carvalho O. , Silva F. S. , Miranda G. 
Published: July 2017

AbstractThis work presents a novel texture design for implants surface functionalization, through the creation of line‐shaped textures on Ti6Al4V surfaces and subsequent sintering of hydroxyapatite (HAp) powder into the designated locations. HAp‐rich locations were designed to avoid HAp detachment during insertion, thus guaranteeing an effective osseointegration. This process starts by creating textured lines using a Nd:YAG laser, filling these lines with HAp powder and sintering HAp using a CO2 laser. The adhesion of HAp is known to be influenced by HAp sintering parameters, especially laser power and scanning speed and also by the textured lines manufacturing. Different laser parameters combinations were used to assess the sintering and adhesion of HAp to the textured lines. HAp adhesion was assessed by performing high energy ultrasonic cavitation tests and sliding tests mimicking an implant insertion, with Ti6Al4V/HAp specimens sliding against animal bone. The HAp content retained after these tests was measured and results showed that an excellent HAp sintering and adhesion was achieved when using a scan speed of 1 mm/s and laser power between 9 and 9.6 W. It is important to emphasize that results indicated that the HAp bioactivity was maintained when using these conditions, validating this functionalization process for the production of hip prosthesis with improved bioactivity. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1534–1545, 2018.
Single‐Center Evaluation of the Pharmacokinetics and Safety of the Angiotensin II Receptor Antagonist Azilsartan Medoxomil in Mild to Moderate Hepatic Impairment
Authors: Dudkowski Caroline , Karim Aziz , Zhao Zhen , Alonso Alberto B. , Garg Dyal , Preston Richard A. 
Published: July 2017

AbstractAzilsartan medoxomil (AZL‐M) is a potent angiotensin II receptor blocker that decreases blood pressure in a dose‐dependent manner. It is a prodrug that is not detected in blood after its oral administration because of its rapid hydrolysis to the active moiety, azilsartan (AZL). AZL undergoes further metabolism to the major metabolite, M‐II, and minor metabolites. The objective of this study was to determine the effect of mild to moderate hepatic impairment on the pharmacokinetics of AZL and its major metabolite. This was a single‐center, open‐label, phase 1 parallel‐group study that examined the single‐dose (day 1) and multiple‐dose (days 4–8) — 40 mg — pharmacokinetics of AZL and M‐II in 16 subjects with mild and moderate hepatic impairment by Child‐Pugh classification (n = 8 per group) and subjects (n = 16) matched based on age, sex, race, weight, and smoking status. Mild or moderate hepatic impairment did not cause clinically meaningful increases in exposure to AZL and M‐II. Mild or moderate hepatic impairment had no clinically meaningful effect on the plasma protein binding of AZL and M‐II. Single and multiple doses of AZL‐M 40 mg were well tolerated in all subject groups. Based on the pharmacokinetic and tolerability findings, no dose adjustment of AZL‐M is required for subjects with mild and moderate hepatic impairment.
Developing better practices at the institutional level leads to better outcomes after pancreaticoduodenectomy in 3,378 patients: domestic audit of the Japanese Society of Pancreatic Surgery
Authors: Satoi Sohei , Yamamoto Tomohisa , Yoshitomi Hideyuki , Motoi Fuyuhiko , Kawai Manabu , Fujii Tsutomu , Wada Keita , Arimitsu Hidehito , Sho Masayuki , Matsumoto Ippei , Hirano Satoshi , Yanagimoto Hiroaki , Ohtsuka Masayuki , Unno Michiaki , Yamaue Hiroki , Kon Masanori 
Published: July 2017

AbstractBackgroundThe aim of the present study was to assess recent trends in pancreaticoduodenectomy (PD) and the role of institutional standardization on the development of postoperative complications in 3,378 patients who underwent PD in Japan.MethodsData were collected from 3,378 patients who underwent PD in 2006, 2010 and 2014 at 53 institutions. A standardized institution (SI) was defined as one that implements ≥7 of 13 quality initiatives according to departmental policy. There were 1,223 patients in the SI group and 2,155 in the non‐SI group. Clinical parameters were compared over time, and between groups. Risk factors for morbidity and mortality were assessed by logistic regression analysis with a mixed‐effects model.ResultsThe number of patients who underwent PD in SIs increased from 16.5% in 2006 to 46.4% in 2014. The SI group experienced an improved process of care and a lower frequency of severe complications vs. the non‐SI group (P < 0.001). Multivariate analysis revealed that the SI group was associated with a lower incidence of delayed gastric emptying (odds ratio −0.499, P = 0.008) and incisional surgical site infection (odds ratio −0.999, P < 0.001).ConclusionStandardization of care in PD may be important in reducing post‐PD complications, and is a critical element for improving clinical outcomes.
Performance evaluation of a collapsed cone dose calculation algorithm forHDRIr‐192 ofAPBItreatments
Authors: Terribilini Dario , Vitzthum Veronika , Volken Werner , Frei Daniel , Loessl Kristina , van Veelen Bob , Manser Peter , Fix Michael K. 
Published: July 2017

PurposeMost dose calculations forHDRbrachytherapy treatments are based on theAAPM‐TG43 formalism. Because patient's anatomy, heterogeneities, and applicator shielding are not considered, the dose calculation based on this formalism is inaccurate in some cases. Alternatively, collapsed cone (CC) methods as well as Monte Carlo (MC) algorithms belong to the model‐based dose calculation algorithms, which are expected to improve the accuracy of calculated dose distributions. In this work, the performance of aCCalgorithm,ACEin Oncentra Brachy 4.5 (ACE4.5), has been investigated by comparing the calculated dose distributions to theAAPM‐TG43 andMCcalculations for 10HDRbrachytherapy accelerated partial breast irradiation treatments (APBI). Comparisons were also performed with a corrected version ofACE4.5 (ACE4.5/corr).MethodsThe brachytherapy source microSelectronmHDR‐v2 (Elekta Brachytherapy) has been implemented in aMCenvironment and validated by comparingMCdose distributions simulated in a water phantom of 80 cm in diameter with dose distributions calculated with theAAPM‐TG43 algorithm. Dose distributions calculated withACE4.5,ACE4.5/corr,AAPM‐TG43 formalism, andMCfor 10APBIpatients plans have then been computed and compared usingHUscaled densities. In addition, individual dose components have been computed usingACE4.5,ACE4.5/corr, andMC, and compared individually.ResultsLocal differences betweenMCandAAPM‐TG43 calculated dose distributions in a large water phantom are < 1%. When usingHUs scaled densities for the breast cancer patients, both accuracy levels ofACE4.5 overestimate theMCcalculated dose distributions for all analyzed dosimetric parameters. In the planning target volume (PTV),ACE4.5 (ACE4.5/corr) overestimates on average V100%,PTVby 3% ± 1% (1% ± 1%) and D50,PTVby 3% ± 1% (1% ± 1%) and in the organs at risk D1cc, skinby 4% ± 2% (1% ± 1%), D0.5cc, ribsby 4% ± 2% (0% ± 1%), and D1cc, heartby 8% ± 2% (3% ± 1%) compared toMC. Comparisons of the individual dose components reveals an agreement for the primary component of < 2% local differences for bothACE4.5 andACE4.5/corr. Local differences of about 40% (20%) for the first and residual scatter components where observed when usingACE4.5 (ACE4.5/corr). Using uniform densities for one case shows a better agreement betweenACE4.5 andMCfor all dosimetric parameters considered in this work.ConclusionsIn general, on the 10APBIpatients theACE4.5/corr algorithm results in similar dose distributions as the commonly usedAAPM‐TG43 within thePTV. However, the accuracy of theACE4.5/corr calculated dose distribution is closer toMCthan toAAPM‐TG43. The differences between commercial versionACE4.5 andMCdose distributions are mainly located in the first and residual scatter components. InACE4.5/corr, the changes done in the algorithm for the scatter components substantially reduce these differences.
Visualization of macrophage recruitment in head and neck carcinoma model using fluorine‐19 magnetic resonance imaging
Authors: Khurana Aman , Chapelin Fanny , Xu Hongyan , Acevedo Joseph R. , Molinolo Alfred , Nguyen Quyen , Ahrens Eric T. 
Published: July 2017

PurposeTo evaluate the role of infiltrating macrophages in murine models of single and double mutation head and neck tumors using a novel fluorine‐19 (19F) MRI technology.MethodsTumor cell lines single‐hit/SCC4 or double‐hit/Cal27, with mutations of TP53 and TP53 & FHIT, respectively, were injected bilaterally into the flanks of (n = 10) female mice. With tumors established, perfluorocarbon nanoemulsion was injected intravenously, which labels in situ predominantly monocytes and macrophages. Longitudinal spin density–weighted 19F MRI data enabled quantification of the macrophage burden in tumor and surrounding tissue.ResultsThe average number of 19F atoms within the tumors was twice as high in the Cal27 group compared with SCC4 (3.9 × 1019 and 2.0 × 1019 19F/tumor, respectively; P = 0.0034) two days after contrast injection, signifying increased tumor‐associated macrophages in double‐hit tumors. The difference was still significant 10 days after injection. Histology stains correlated with in vivo results, exhibiting numerous perfluorocarbon‐labeled macrophages in double‐hit tumors and to a lesser extent in single‐hit tumors.ConclusionsThis study helps to establish 19F MRI as a method for quantifying immune cells in the tumor microenvironment, allowing distinction between double and single‐hit head and neck tumors. This technique would be extremely valuable in the clinic for pretreatment planning, prognostics, and post‐treatment surveillance. Magn Reson Med 79:1972–1980, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Reliable assessment of the incidence of childhood autoimmune hemolytic anemia
Authors: Aladjidi Nathalie , Jutand Marthe‐Aline , Beaubois Cyrielle , Fernandes Helder , Jeanpetit Julien , Coureau Gaelle , Gilleron Véronique , Kostrzewa Aude , Lauroua Pierre , Jeanne Michel , Thiébaut Rodolphe , Leblanc Thierry , Leverger Guy , Perel Yves 
Published: July 2017

AbstractBackgroundChildhood autoimmune hemolytic anemia (AIHA) is a rare and severe disease characterized by hemolysis and positive direct antiglobulin test (DAT). Few epidemiologic indicators are available for the pediatric population. The objective of our study was to reliably estimate the number of AIHA cases in the French Aquitaine region and the incidence of AIHA in patients under 18 years old.ProcedureIn this retrospective study, the capture–recapture method and log‐linear model were used for the period 2000–2008 in the Aquitaine region from the following three data sources for the diagnosis of AIHA: the OBS'CEREVANCE database cohort, positive DAT collected from the regional blood bank database, and the French medico‐economic information system.ResultsA list of 281 different patients was obtained after cross‐matching the three databases; 44 AIHA cases were identified in the period 2000–2008; and the total number of cases was estimated to be 48 (95% confidence interval [CI]: 45–55). The calculated incidence of the disease was 0.81/100,000 children under 18 years old per year (95% CI 0.76–0.92).ConclusionAccurate methods are required for estimating the incidence of AIHA in children. Capture–recapture analysis corrects underreporting and provides optimal completeness. This study highlights a possible under diagnosis of this potentially severe disease in various pediatric settings. AIHA incidence may now be compared with the incidences of other hematological diseases and used for clinical or research purposes.
Management of chemotherapy‐induced febrile neutropenia in pediatric oncology patients: A North American survey of pediatric hematology/oncology and pediatric infectious disease physicians
Authors: Maxwell Rochelle R. , Egan‐Sherry Dana , Gill Jonathan B. , Roth Michael E. 
Published: July 2017

ABSTRACTBackgroundChemotherapy‐induced febrile neutropenia (FN) is traditionally managed with hospital admission for parenteral antibiotics until neutropenia resolves. Recent studies have explored risk stratification and the safety of managing “low‐risk” patients as outpatients. Few studies have directly assessed pediatric provider preferences for managing FN.ProcedureWe conducted a survey of practicing US and Canadian pediatric hematology/oncology (PHO) and pediatric infectious disease (PID) physicians to assess their FN management preferences using case scenarios with varying risk profiles.ResultsTwenty‐one percent (n = 186) of PHO and 32% (n = 123) of PID physicians completed the survey. Overall, both groups of providers agreed regarding which patients with FN could be managed outpatient. For a child with acute lymphoblastic leukemia receiving maintenance chemotherapy with an absolute neutrophil count (ANC) of 400 cells/μl, 35% (n = 66) of PHO and 49% (n = 60) of PID physicians would consider outpatient management (P = 0.02). Of those physicians selecting inpatient management, 41% (n = 49) of PHO and 52% (n = 33) of PID physicians would be willing to discharge the patient without an increase in ANC, if afebrile with a negative blood culture (P = 0.16). For a similar patient with an ANC of 100 cells/μl, only 23% (n = 35) of PHO and 42% (n = 39) of PID physicians would consider discharge without an increase in ANC (P = 0.002).ConclusionsDespite the lack of established guidelines for low‐risk pediatric FN, a significant proportion of North American physicians report willingness to modify traditional management. This reinforces the need for evidence‐based low‐risk criteria and outpatient management guidelines to optimize consistency of care for these patients.
Outcomes of matched sibling donor bone marrow transplantation in children using single‐agent calcineurin inhibitors as prophylaxis for graft versus host disease
Authors: Elgarten Caitlin W. , Arnold Danielle E. , Bunin Nancy J. , Seif Alix E. 
Published: July 2017

AbstractBackgroundOptimal graft versus host disease (GVHD) prophylaxis prevents severe manifestations without excess immunosuppression. Standard prophylaxis includes a calcineurin inhibitor (CNI) with low‐dose methotrexate. However, single‐agent CNI may be sufficient prophylaxis for a defined group of patients. Single‐agent CNI has been used for GVHD prophylaxis for human leukocyte antigen (HLA)‐matched sibling donor (MSD) bone marrow transplants (BMTs) in young patients at the Children's Hospital of Philadelphia for over 20 years. Here, we describe outcomes using this prophylactic strategy in a recent cohort.ProcedureWe performed a single‐institution chart review and retrospective analysis of consecutive children undergoing MSD BMT who received single‐agent CNI for GVHD prophylaxis between January 2002 and December 2014.ResultsFifty‐two children with a median age of 6.1 years (interquartile range [IQR] 2.5–8.3) and donor age of 6 years (IQR 3–10), with malignant and nonmalignant diseases (n = 35 and 17, respectively) were evaluated. Forty‐three (82.6%) received oral prophylaxis with single‐agent tacrolimus after initial intravenous therapy. Rates of GVHD were consistent with reported rates on dual prophylaxis: the overall incidence of grades 2–4 acute GVHD was 25.5%, grades 3–4 GVHD 9.8%, and chronic GVHD 10.4%. The cumulative incidence of relapse among children with malignancy was 20% at a median of 237 days (IQR 194–318) post‐transplant. Two‐year overall survival was 82.7% (95% confidence interval [CI]: 69.4–90.6%) and event‐free survival was 78.9% (95% CI: 65.1–87.7%). No patient experienced graft failure.ConclusionsSingle‐agent CNI is a safe, effective approach to GVHD prophylaxis in young patients undergoing HLA‐identical sibling BMT. Additionally, single‐agent oral tacrolimus is a reasonable alternative to cyclosporine in this population.
Communication in pediatric oncology: State of the field and research agenda
Authors: Sisk Bryan A. , Mack Jennifer W. , Ashworth Rachel , DuBois James 
Published: July 2017

AbstractFrom the time of diagnosis through either survivorship or end of life, communication between healthcare providers and patients or parents can serve several core functions, including fostering healing relationships, exchanging information, responding to emotions, managing uncertainty, making decisions, and enabling patient/family self‐management. We systematically reviewed all studies that focused on communication between clinicians and patients or parents in pediatric oncology, categorizing studies based on which core functions of communication they addressed. After identifying gaps in the literature, we propose a research agenda to further the field.
VIncristine, irinotecan, and temozolomide in children and adolescents with relapsed rhabdomyosarcoma
Authors: Setty Bhuvana A. , Stanek Joseph R. , Mascarenhas Leo , Miller Alexandra , Bagatell Rochelle , Okcu Fatih , Nicholls Lauren , Lysecki David , Gupta Abha A. 
Published: July 2017

AbstractBackgroundThe combination of vincristine, irinotecan, and temozolomide (VIT) is often used to treat children and adolescents with relapsed rhabdomyosarcoma (RMS); however, the outcome of these patients has not been previously described.ProceduresWe sought to determine the response rate (RR) and progression‐free survival (PFS) for patients with relapsed RMS treated with VIT by retrospective review of patients treated at five tertiary care hospitals. Prior treatment with irinotecan was permitted.ResultsAmong 19 patients with a median age of 8 years (range 2–17 years), 12 (63%) were males and 12 (63%) had embryonal histology. Median time to relapse from initial diagnosis was 16 months (range 2.8‐45 months). VIT was used as first, second, third, or fourth line of therapy in four (21%), seven (37%), six (32%), and two (10%) patients, respectively. Four patients received VIT as adjuvant therapy following radiation and/or surgery. Therefore, among 15 evaluable patients, the best response to VIT was 0 (complete response, CR), 0 (partial response, PR), 4 (stable disease, SD), and 11 (progressive disease, PD) for an overall clinical benefit rate (CR + PR + SD) of 26.7% (95% CI: 7.8–55.1%). After a median follow‐up of 8 months, 2 (10%) patients were alive without disease, 3 (16%) were alive with disease, and 14 (74%) patients died of PD. PFS at 3 months was 23% (95% CI: 5.7–46.7%).ConclusionsVIT therapy in combination with adequate local control is associated with some disease control in patients with first relapse RMS and may be another reasonable option to offer patients as salvage therapy.
Transverse myelitis as an unexpected complication following treatment with dinutuximab in pediatric patients with high‐risk neuroblastoma: A case series
Authors: Ding Yang‐Yang , Panzer Jessica , Maris John M , Castañeda Alicia , Gomez‐Chiari Marta , Mora Jaume 
Published: July 2017

AbstractImmunotherapy with the anti‐GD2 monoclonal antibody ch14.18, or dinutuximab, represents an important therapeutic advance in the treatment of pediatric high‐risk neuroblastoma and is now considered part of standard of care in this patient population. To date, transverse myelitis as a result of dinutuximab therapy has not been reported in clinical trials or in the published literature. We describe three patients with clinical symptoms of transverse myelitis, confirmed via magnetic resonance imaging, shortly following initiation of dinutuximab. All patients were discontinued from dinutuximab treatment and received urgent treatment, with rapid improvement in symptoms and resultant functional recovery.
Identification of a dimeric KDG aldolase from Agrobacterium tumefaciens
Authors: Soares da Costa Tatiana P. , Patel Madhvi , Desbois Sebastien , Gupta Ruchi , Faou Pierre , Perugini Matthew A. 
Published: July 2017

AbstractAgrobacterium tumefaciens is a Gram‐negative bacterium and causative agent of Crown Gall disease that infects a variety of economically important plants. The annotated A. tumefaciens genome contains 10 putative dapA genes, which code for dihydrodipicolinate synthase (DHDPS). However, we have recently demonstrated that only one of these genes (dapA7) encodes a functional DHDPS. The function of the other nine putative dapA genes is yet to be determined. Here, we demonstrate using bioinformatics that the product of the dapA5 gene (DapA5) possesses all the catalytic residues canonical to 2‐keto‐3‐deoxygluconate (KDG) aldolase, which is a class I aldolase involved in glucose metabolism. We therefore expressed, purified, and characterized recombinant DapA5 using mass spectrometry, circular dichroism spectroscopy, analytical ultracentrifugation, and enzyme kinetics. The results show that DapA5 (1) adopts an α/β structure consistent with the TIM‐barrel fold of KDG aldolases, (2) possesses KDG aldolase enzyme activity, and (3) exists as a tight dimer in solution. This study shows for the first time that dapA5 from A. tumefaciens encodes a functional dimeric KDG aldolase.