bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pediatric patients undergoing hematopoietic stem cell transplantation can greatly benefit from a novel once‐daily intravenous busulfan dosing nomogram
Authors: Rhee Su‐jin , Lee Ji Won , Yu Kyung‐Sang , Hong Kyung Taek , Choi Jung Yoon , Hong Che Ry , Park Kyung Duk , Shin Hee Young , Song Sang Hoon , Kang Hyoung Jin , Lee Howard 
Published: March 2017

AbstractBusulfan, a bifunctional alkylating agent, has been used as a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this study was to derive a novel once‐daily intravenous (IV) busulfan dosing nomogram for pediatric patients undergoing HSCT using a population pharmacokinetic (PK) model. A population PK analysis was performed using 2183 busulfan concentrations in 137 pediatric patients (age: 0.6‐22.2 years), who received IV busulfan once‐daily for 4 days before undergoing HSCT. Based on the final population PK model, an optimal once‐daily IV busulfan dosing nomogram was derived. The percentage of simulated patients achieving the daily target area under the concentration‐time curve (AUC) by the new nomogram was compared with that by other busulfan dosing regimens including the FDA regimen, the EMA regimen, and the empirical once‐daily regimen without therapeutic drug monitoring (TDM). A one‐compartment open linear PK model incorporating patient's body surface area, age, dosing day, and aspartate aminotransferase as a significant covariate adequately described the concentration–time profiles of busulfan. An optimal dosing nomogram based on the PK model performed significantly better than the other dosing regimens, resulting in >60% of patients achieving the target AUC while the percentage of patients exceeding the toxic AUC level was kept <25% during the entire treatment period. A novel once‐daily busulfan dosing nomogram for pediatric patients undergoing HSCT is useful for clinicians, particularly in a setting where TDM service is not readily available or to optimize the dose on day 1.
Natural history of chronic myelomonocytic leukemia treated with hypomethylating agents
Authors: Alfonso Ana , Montalban‐Bravo Guillermo , Takahashi Koichi , Jabbour Elias J. , Kadia Tapan , Ravandi Farhad , Cortes Jorge , Estrov Zeev , Borthakur Gautam , Pemmaraju Naveen , Konopleva Marina , Bueso‐Ramos Carlos , Pierce Sherry , Kantarjian Hagop , Garcia‐Manero Guillermo 
Published: March 2017

AbstractHypomethylating agents (HMA) are the most commonly used therapeutic intervention in chronic myelomonocytic leukemia (CMML). Due to the lack of CMML‐specific clinical trials, the impact of these agents in the natural history of CMML is not fully understood. We present the largest retrospective series of CMML (n = 151) treated with HMA. Mean age at diagnosis was 69 years (range 50‐88). According to the CMML‐specific prognostic scoring system (CPSS): 17 (15%) were low‐risk, 45 (39%) intermediate‐1 risk, 42 (36%) intermediate‐2, and 12 (10%) high‐risk. 35 (23%) patients received single agent azacitidine, 73 (48%) single agent decitabine, and 43 (29%) combinations. With a median follow‐up of 17 months, overall response rate (ORR) was 75%, with 41% achieving complete response (CR). Median overall survival (OS) was 24 months (95%CI: 20‐28) and event‐free survival 14 months (95%CI: 11‐17). By multivariate analysis, age < 70 years, higher levels of hemoglobin, absence of blast in peripheral blood and lower CPSS cytogenetic risk predicted for better OS. CR was significantly higher in those patients treated with decitabine (58.3%) when compared with azacitidine (20.6%) (P < .001). 13 patients (9%) received allo‐SCT after a median of 4 cycles of HMA. 66 patients (50%) had HMA failure: 26 primary (34%) and 50 secondary (66%), including 35 (46%) that transformed to AML. Outcomes after HMA failure were poor with OS of 7 months (95%CI: 3‐12). In conclusion, HMA are effective in CMML but new agents and combinations are needed. This data could be a benchmark for further drug development in CMML.
Long term impact of hyperleukocytosis in newly diagnosed acute myeloid leukemia patients undergoing allogeneic stem cell transplantation: An analysis from the acute leukemia working party of the EBMT
Authors: Canaani Jonathan , Labopin Myriam , Socié Gerard , Nihtinen Anne , Huynh Anne , Cornelissen Jan , Deconinck Eric , Gedde‐Dahl Tobias , Forcade Edouard , Chevallier Patrice , Bourhis Jean H. , Blaise Didier , Mohty Mohamad , Nagler Arnon 
Published: March 2017

AbstractUp to 20% of acute myeloid leukemia (AML) patients present initially with hyperleukocytosis, placing them at increased risk for early mortality during induction. Yet, it is unknown whether hyperleukocytosis still retains prognostic value for AML patients undergoing hematopoietic stem cell transplantation (HSCT). Furthermore, it is unknown whether hyperleukocytosis holds prognostic significance when modern molecular markers such as FLT3‐ITD and NPM1 are accounted for. To determine whether hyperleukocytosis is an independent prognostic factor influencing outcome in transplanted AML patients we performed a retrospective analysis using the registry of the acute leukemia working party of the European Society of Blood and Marrow Transplantation. A cohort of 357 patients with hyperleukocytosis (159 patients with white blood count [WBC] 50 K‐100 K, 198 patients with WBC ≥ 100 K) was compared to 918 patients without hyperleukocytosis. Patients with hyperleukocytosis were younger, had an increased rate of favorable risk cytogenetics, and more likely to be FLT3 and NPM1 mutated. In multivariate analysis, hyperleukocytosis was independently associated with increased relapse incidence (hazard ratio [HR] of 1.55, 95% confidence interval [CI], 1.14‐2.12; P = .004), decreased leukemia‐free survival (HR of 1.38, 95% CI, 1.07‐1.78; P = .013), and inferior overall survival (HR of 1.4, 95% CI, 1.07‐1.84; P = .013). Hyperleukocytosis retains a significant prognostic role for AML patients undergoing HSCT.
Renal outcomes in patients with AL amyloidosis: Prognostic factors, renal response and the impact of therapy
Authors: Kastritis Efstathios , Gavriatopoulou Maria , Roussou Maria , Migkou Magdalini , Fotiou Despina , Ziogas Dimitrios C , Kanellias Nikos , Eleutherakis‐Papaiakovou Evangelos , Panagiotidis Ioannis , Giannouli Stavroula , Psimenou Erasmia , Marinaki Smaragdi , Apostolou Theofanis , Gakiopoulou Hariklia , Tasidou Anna , Papassotiriou Ioannis , Terpos Evangelos , Dimopoulos Meletios A. 
Published: March 2017

AbstractA staging system for patients with renal AL amyloidosis, based on eGFR (<50 ml/min/1.73 m2) and proteinuria (≥5 g/day) at diagnosis, as well as criteria for renal progression (≥25% eGFR reduction) and response (≥30% reduction of proteinuria without renal progression) were recently proposed. We validated these criteria in a cohort of 125 patients with renal AL amyloidosis, mostly treated with bortezomib or lenalidomide. We confirmed the prognostic value of the renal staging system but also identified the limitations of renal progression criteria which are based only on eGFR reduction. We identified the ratio of 24h proteinuria to eGFR as a sensitive marker of renal risk which also accounts for changes in both proteinuria and eGFR: 24h proteinuria/eGFR ratio <30 (in mg/ml/min/1.73 m2) was associated with a 2‐year progression to dialysis rate of 0% compared to 9% for a ratio of 31‐99 and 35% for a ratio ≥100 (P < .001). In landmark analysis, patients who achieved a reduction of this ratio by at least 25% or ≤100 (if initially >100) at 3 months had a 2‐year progression to dialysis of 0% vs 24% for patients who either did not reduce to or still had a ratio >100 (P = .001); similar results were obtained by applying the same criteria at 6 months; thus, the evaluation of treatment effect on renal function may be identified early. Furthermore, primary bortezomib‐based therapy was more effective than lenalidomide‐based therapy, in terms of renal outcomes, especially in patients at intermediate renal risk, but without affecting overall survival.
The fat‐but‐fit paradigm within the context of cognitive function
Authors: Edwards Meghan K. , Loprinzi Paul D. 
Published: March 2017

AbstractObjectiveTo evaluate the association of the Fat‐but‐Fit paradigm with cognitive function in an older adult population.MethodsData from the 1999–2002 National Health and Nutrition Examination Survey were used (N = 2,336 adults 60–85 yrs). Physical activity was assessed via open‐ended questions asking about participation in 48 leisure‐time activities over the previous 30 days. Using Metabolic Equivalent of Task calculations for each activity, participants were classified as either active or inactive. Participants were then classified into one of six groups (Normal BMI and Inactive [referent], Overweight BMI and Inactive, Obese BMI and Inactive, Normal BMI and Active, Overweight BMI and Active, Obese BMI and Active), based on their activity status and body mass index (BMI). The Digit Symbol Substitution Test (DSST) was employed to assess cognitive function.ResultsCompared to those who had a normal BMI and were inactive (referent), those who had a normal BMI and were active had a 4‐unit higher DSST score (β = 4.0; 95% CI: 1.0–6.9; P = 0.009); those with an overweight BMI and active had a 4.5‐unit higher DSST score (β = 4.5; 95% CI: 1.3–7.6; P = 0.008); and those who had an obese BMI and active had a 3.7‐unit higher DSST score (β = 3.7; 95% CI: 0.96–6.4; P = 0.01).ConclusionBeing active, regardless of weight classification (normal, overweight, or obese) was positively associated with cognitive function in this sample of older adults. This suggests that perhaps the best strategy to promote cognitive health in this population may be to encourage adequate levels of physical activity.
2D:4D digit ratio is associated with cognitive decline but not frailty in community‐dwelling older adults
Authors: Gonçalves Celina , Coelho Tiago , Machado Sérgio , Rocha Nuno Barbosa 
Published: March 2017

AbstractObjectivesTo understand the relation between 2D:4D ratio, frailty, and cognitive decline in community‐dwelling elderly people.MethodsA total of 175 community‐dwelling elderly people were included. To determine frailty, participants completed the Tilburg Frailty Indicator (TFI) and the Survey of Health, Ageing and Retirement in Europe (SHARE‐FI). Cognitive functioning was determined using the Mini‐Mental State Examination (MMSE). 2D and 4D finger lengths of each hand were measured using a scanner. Barthel Index, Lawton, and Brody scale were also completed for each participant to determine the level of daily living functioning.ResultsWe did not find any correlations between 2D:4D ratio and frailty measures. We found a significant correlation between 2D:4D ratio and MMSE scores in the women sampled.ConclusionsWe cannot ascertain any contribution of prenatal exposure to androgens to the frailty status of community‐dwelling elderly people. We found that reduced prenatal exposure to testosterone in women may contribute to the prevention of cognitive decline in elderly women.
A Two‐Stage Dissociation System for Multilayer Imaging of Cancer Biomarker‐Synergic Networks in Single Cells
Authors: Qian Ruo‐Can , Cao Yue , Zhao Li‐Jun , Gu Zhen , Long Yi‐Tao 
Published: March 2017

AbstractThe monitoring of cancer biomarkers is crucial to the early detection of cancer. However, a limiting factor in biomarker analysis is the ability to obtain the multilayered information of various biomarker molecules located at different parts of cells from the plasma membrane to the cytoplasm. A two‐stage dissociation nanoparticle system based on multifunctionalized polydopamine‐coated gold nanoparticles (Au@PDA NPs) is reported, which allows for the two‐stage imaging of cancer biomarkers in single cells. We demonstrate the feasibility of this strategy on sialic acids (SAs), p53 protein, and microRNA‐21 (miRNA‐21) in MCF‐7 breast cancer cells by two custom‐built probes. Furthermore, the multicolor fluorescence information extracted is used for the monitoring of biomarker expression changes under different drug combinations, which allows us to investigate the complex interactions between various cancer biomarkers and to describe the cancer biomarker‐synergic networks in single cells.
The Lightest Element Phosphoranylidene: NHC‐Supported Cyclic Borylidene–Phosphorane with Significant B=P Character
Authors: Rosas‐Sánchez Alfredo , Alvarado‐Beltran Isabel , Baceiredo Antoine , Hashizume Daisuke , Saffon‐Merceron Nathalie , Branchadell Vicenç , Kato Tsuyoshi 
Published: March 2017

AbstractA borylidene–phosphorane, the lightest phosphoranylidene, which is stabilized by an N‐heterocyclic carbene ligand, was synthesized and fully characterized. Experimental electron density analysis and DFT calculations indicate an enhanced ylene character (rather than an ylide character) with an exceptionally strong B→P π‐back bonding related to the less electronegative boron compared to phosphorus.
A Biomimetic Phosphatidylcholine‐Terminated Monolayer Greatly Improves the In Vivo Performance of Electrochemical Aptamer‐Based Sensors
Authors: Li Hui , Dauphin‐Ducharme Philippe , Arroyo‐Currás Netzahualcóyotl , Tran Claire H. , Vieira Philip A. , Li Shaoguang , Shin Christina , Somerson Jacob , Kippin Tod E. , Plaxco Kevin W. 
Published: March 2017

AbstractThe real‐time monitoring of specific analytes in situ in the living body would greatly advance our understanding of physiology and the development of personalized medicine. Because they are continuous (wash‐free and reagentless) and are able to work in complex media (e.g., undiluted serum), electrochemical aptamer‐based (E‐AB) sensors are promising candidates to fill this role. E‐AB sensors suffer, however, from often‐severe baseline drift when deployed in undiluted whole blood either in vitro or in vivo. We demonstrate that cell‐membrane‐mimicking phosphatidylcholine (PC)‐terminated monolayers improve the performance of E‐AB sensors, reducing the baseline drift from around 70 % to just a few percent after several hours in flowing whole blood in vitro. With this improvement comes the ability to deploy E‐AB sensors directly in situ in the veins of live animals, achieving micromolar precision over many hours without the use of physical barriers or active drift‐correction algorithms.
A Reversible Fluorescent Probe for Real‐Time Quantitative Monitoring of Cellular Glutathione
Authors: Liu Zhixue , Zhou Xin , Miao Yu , Hu Ying , Kwon Nahyun , Wu Xue , Yoon Juyoung 
Published: March 2017

AbstractThe ability to monitor and quantify glutathione (GSH) in live cells is essential in order to gain a detailed understanding of GSH‐related pathological events. However, owing to their irreversible response mechanisms, most existing fluorescent GSH probes are not suitable for this purpose. We have developed a ratiometric fluorescent probe (QG‐1) for quantitatively monitoring cellular GSH. The probe responds specifically and reversibility to GSH with an ideal dissociation constant (Kd) of 2.59 mm and a fast response time (t1/2=5.82 s). We also demonstrate that QG‐1 detection of GSH is feasible in a model protein system. QG‐1 was found to have extremely low cytotoxicity and was applied to determine the GSH concentration in live HeLa cells (5.40±0.87 mm).
A bicistronic vector with destabilized mRNA secondary structure yields scalable higher titer expression of human neurturin in E. coli
Authors: Roy Varnika , Roth Robert , Berge Mark , Chitta Rajesh , Vajrala Sucheta , Kuntumalla Srilatha , E. Schmelzer Albert , Schoner Ron 
Published: March 2017

ABSTRACTHuman neurturin (NTN) is a cystine knot growth factor with potential therapeutic use in diseases such as Parkinson's and diabetes. Scalable high titer production of native NTN is particularly challenging because of the cystine knot structure which consists of an embedded ring comprised of at least three disulfide bonds. We sought to pursue enhanced scalable production of NTN in Escherichia coli. Our initial efforts focused on codon optimization of the first two codons following AUG, but these studies resulted in only a marginal increase in NTN expression. Therefore, we pursued an alternative strategy of using a bicistronic vector for NTN expression designed to reduce mRNA secondary structure to achieve increased ribosome binding and re‐initiation. The first cistron was designed to prevent sequestration of the translation initiation region in a secondary conformation. The second cistron, which contained the NTN coding sequence itself, was engineered to disrupt double bonded base pairs and destabilize the secondary structure for ribosome re‐initiation. The ensemble approach of reducing NTN's mRNA secondary structure and using the bicistronic vector had an additive effect resulting in significantly increased NTN expression. Our strain selection studies were conducted in a miniaturized bioreactor. An optimized strain was selected and scaled up to a 100 L fermentor, which yielded an inclusion body titer of 2 g/L. The inclusion bodies were refolded to yield active NTN. We believe that our strategy is applicable to other candidate proteins that are difficult‐to‐express due to stable mRNA secondary structures. Biotechnol. Bioeng. 2017;114: 1753–1761. © 2017 Wiley Periodicals, Inc.
European Pension Funds and Sustainable Development: Trade‐Offs between Finance and Responsibility
Authors: Sievänen Riikka , Rita Hannu , Scholtens Bert 
Published: March 2017

AbstractPension funds try to account for sustainable development in their operations. This mainly translates in responsible investing. We investigate how this interacts with the financial objectives. We use a survey of more than 250 pension funds based in 15 European countries. Multinomial logistic regression is used to find out how pension funds trade off sustainable development and financial objectives. Our findings suggest that pension funds that have not included responsibility in their strategy and investments have a clear priority regarding their financial performance. Pension funds who integrate sustainable development in their strategy can bring balance between finance and responsibility. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Examining the effect of managing GHG emissions on business performance
Authors: Capece G , Di Pillo F , Gastaldi M , Levialdi N , Miliacca M 
Published: March 2017

AbstractUnprecedented climate changes menace not only the planetary ecosystem, but also the stability of the global economy. The European Union has for years promoted the transition of the economy towards a model of sustainable development, stimulating companies to adopt a strategic approach based on quality and environmental efficiency, rather than on quantity and reduction of costs.The aim of this study is to analyze how greater attention to the environmental effects of a company's activities (environmental management) and monitoring and reduction of CO2 emissions (emission management) can improve the company's economic performance. We analyze the financial data and greenhouse gas (GHG) emission figures for a sample of large Italian companies, searching for potential relations between increasing returns on capital invested and the reduction of pollutants. The results show that the companies examined are ever more attentive to environmental policies, and that those with a green vision achieve better operating performance. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Design and evaluation of reduced marker layouts for hand motion capture
Authors: Schröder Matthias , Waltemate Thomas , Maycock Jonathan , Röhlig Tobias , Ritter Helge , Botsch Mario 
Published: March 2017

AbstractWe present a method for automatically generating reduced marker layouts for marker‐based optical motion capture of human hands. The employed motion reconstruction method is based on subspace‐constrained inverse kinematics, which allows for the recovery of realistic hand movements even from sparse input data. We additionally present a user‐specific hand model calibration procedure that fits an articulated hand model to point cloud data of the user's hand. Our marker layout optimization is sensitive to the kinematic structure and the subspace representations of hand articulations utilized in the reconstruction method, in order to generate sparse marker configurations that are optimal for solving the constrained inverse kinematics problem. We propose specific quality criteria for reduced marker sets that combine numerical stability with geometric feasibility of the resulting layout. These criteria are combined in an objective function that is minimized using a specialized surface‐constrained particle swarm optimization scheme, which generates marker layouts bound to the surface of an animated hand model. Our method provides a principled way for determining reduced marker layouts based on subspace representations of hand articulations. We demonstrate the effectiveness of our motion reconstruction and model calibration methods in a thorough evaluation.
Use of four‐factor prothrombin complex concentrate for the mitigation of rivaroxaban‐induced bleeding in an emergent coronary artery bypass graft
Authors: Liu Michael , Aguele Cliff , Darr Umer 
Published: March 2017

Key Clinical MessageWe presented the first case of four‐factor prothrombin complex concentrate (4F‐PCC) for the alleviation of bleeding for emergent on‐pump coronary artery bypass graft (CABG) with the patient discharged by postoperative day (POD) 9 with no sequelae. Until direct antidotes are available, 4F‐PCC may play a role in the management of mitigating rivaroxaban‐induced bleeding in surgical procedure.
Odontogenic cutaneous fistula mimicking malignancy
Authors: Baba Akira , Okuyama Yumi , Shibui Takeo , Ojiri Hiroya 
Published: March 2017

Key Clinical MessageIt is important for the dentists to make accurate diagnosis and appropriate treatment of odontogenic cutaneous fistula. Although large facial skin lesions may bring up malignancy on top of the differential list, careful evaluation including physical observation, imaging, and pathology can rule out malignancies.
A Multi‐Stream Microchip for Process Intensification of Liquid‐Liquid Extraction
Authors: Kriel Frederik H. , Binder Claudia , Priest Craig 
Published: March 2017

AbstractSolvent extraction is a critical step in many industrial mineral‐processing circuits and is affected by chemical (e.g., metal ions, extractant, pH, reaction rate) and physical (e.g., interfacial phenomena, mass transport, temperature) factors. Here, a new type of microfluidic contactor is presented that enables higher volumetric throughputs and straightforward counter‐current operation compared with Y‐Y chips. A single chip design can handle a wide range of organic/aqueous phase ratios, thereby enabling stable operation for non‐ideal solutions and fluctuating flow. An expression defining this widened operational window has been derived based on the relative stream geometries and liquid viscosities. A two‐stage counter‐current circuit is demonstrated for the extraction of platinum(IV) chloride.