bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost‐Effectiveness Analysis of Second‐Line Chemotherapy Agents for Advanced Gastric Cancer
Authors: Lam Simon W. , Wai Maya , Lau Jessica E. , McNamara Michael , Earl Marc , Udeh Belinda 
Published: November 2016

Study ObjectiveGastric cancer is the fifth most common malignancy and second leading cause of cancer‐related mortality. Chemotherapy options for patients who fail first‐line treatment are limited. Thus the objective of this study was to assess the cost‐effectiveness of second‐line treatment options for patients with advanced or metastatic gastric cancer.DesignCost‐effectiveness analysis using a Markov model to compare the cost‐effectiveness of six possible second‐line treatment options for patients with advanced gastric cancer who have failed previous chemotherapy: irinotecan, docetaxel, paclitaxel, ramucirumab, paclitaxel plus ramucirumab, and palliative care.Measurements and Main ResultsThe model was performed from a third‐party payer's perspective to compare lifetime costs and health benefits associated with studied second‐line therapies. Costs included only relevant direct medical costs. The model assumed chemotherapy cycle lengths of 30 days and a maximum number of 24 cycles. Systematic review of literature was performed to identify clinical data sources and utility and cost data. Quality‐adjusted life years (QALYs) and incremental cost‐effectiveness ratios (ICERs) were calculated. The primary outcome measure for this analysis was the ICER between different therapies, where the incremental cost was divided by the number of QALYs saved. The ICER was compared with a willingness‐to‐pay (WTP) threshold that was set at $50,000/QALY gained, and an exploratory analysis using $160,000/QALY gained was also used. The model's robustness was tested by using 1‐way sensitivity analyses and a 10,000 Monte Carlo simulation probabilistic sensitivity analysis (PSA). Irinotecan had the lowest lifetime cost and was associated with a QALY gain of 0.35 year. Docetaxel, ramucirumab alone, and palliative care were dominated strategies. Paclitaxel and the combination of paclitaxel plus ramucirumab led to higher QALYs gained, at an incremental cost of $86,815 and $1,056,125 per QALY gained, respectively. Based on our prespecified WTP threshold, our base case analysis demonstrated that irinotecan alone is the most cost‐effective regimen, and both paclitaxel alone and the combination of paclitaxel and ramucirumab were not cost‐effective (ICER more than $50,000). Both 1‐way sensitivity analyses and PSA demonstrated the model's robustness. PSA illustrated that paclitaxel plus ramucirumab was extremely unlikely to be cost‐effective at a WTP threshold less than $400,000/QALY gained.ConclusionIrinotecan alone appears to be the most cost‐effective second‐line regimen for patients with gastric cancer. Paclitaxel may be cost‐effective if the WTP threshold was set at $160,000/QALY gained.
Preparation of polypropylene microspheres for selective laser sintering via thermal‐induced phase separation: Roles of liquid–liquid phase separation and crystallization
Authors: Wang Shao‐Jie , Liu Jian‐Ye , Chu Li‐Qiu , Zou Hao , Zhang Shi‐Jun , Wu Chang‐Jiang 
Published: November 2016

ABSTRACTAlthough selective laser sintering (SLS) has been widely applied in many fields, more research work is needed to develop proper polymer microspheres for SLS. Thermal‐induced phase separation (TIPS) is a facile way but rarely reported to prepare the polymer microspheres. The roles of liquid–liquid phase separation (LLPS) and crystallization in the TIPS process are not clear. In this study, proper polypropylene (PP) microspheres for SLS are successfully prepared via TIPS with xylene. The diameters and morphologies of these PP microspheres can be regulated easily by changing the PP concentration and the quench temperature. The large undercooling drives the solution into the metastable LLPS region and produces PP microspheres with smooth surfaces. The PP crystallization occurs both on the LLPS interface and inside the polymer‐rich phase when the solution is quenched to a temperature near the binodal line, and the tiny bent lamellae are formed on the microsphere surface. At higher temperature only PP crystallization occurs, which results in the formation of PP particles consisting of packed lamellae. The PP microspheres prepared here are suitable for SLS and promote the development of SLS potentially. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 320–329
Interaction network of the ribosome assembly machinery from a eukaryotic thermophile
Authors: Baßler Jochen , Ahmed Yasar Luqman , Kallas Martina , Kornprobst Markus , Calviño Fabiola R. , Gnädig Marén , Thoms Matthias , Stier Gunter , Ismail Sherif , Kharde Satyavati , Castillo Nestor , Griesel Sabine , Bastuck Sonja , Bradatsch Bettina , Thomson Emma , Flemming Dirk , Sinning Irmgard , Hurt Ed 
Published: November 2016

AbstractRibosome biogenesis in eukaryotic cells is a highly dynamic and complex process innately linked to cell proliferation. The assembly of ribosomes is driven by a myriad of biogenesis factors that shape pre‐ribosomal particles by processing and folding the ribosomal RNA and incorporating ribosomal proteins. Biochemical approaches allowed the isolation and characterization of pre‐ribosomal particles from Saccharomyces cerevisiae, which lead to a spatiotemporal map of biogenesis intermediates along the path from the nucleolus to the cytoplasm. Here, we cloned almost the entire set (∼180) of ribosome biogenesis factors from the thermophilic fungus Chaetomium thermophilum in order to perform an in‐depth analysis of their protein–protein interaction network as well as exploring the suitability of these thermostable proteins for structural studies. First, we performed a systematic screen, testing about 80 factors for crystallization and structure determination. Next, we performed a yeast 2‐hybrid analysis and tested about 32,000 binary combinations, which identified more than 1000 protein–protein contacts between the thermophilic ribosome assembly factors. To exemplary verify several of these interactions, we performed biochemical reconstitution with the focus on the interaction network between 90S pre‐ribosome factors forming the ctUTP‐A and ctUTP‐B modules, and the Brix‐domain containing assembly factors of the pre‐60S subunit. Our work provides a rich resource for biochemical reconstitution and structural analyses of the conserved ribosome assembly machinery from a eukaryotic thermophile.
Myelodysplastic Syndromes and Acute Myeloid Leukemia After Radiotherapy for Prostate Cancer: A Population‐Based Study
Authors: Wang Rong , Zeidan Amer M. , Yu James B. , Soulos Pamela R. , Davidoff Amy J. , Gore Steven D. , Huntington Scott F. , Gross Cary P. , Ma Xiaomei 
Published: November 2016

BACKGROUNDTo understand the impact of radiotherapy on the development of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) among elderly prostate cancer patients.METHODSWe performed a retrospective cohort study of elderly prostate cancer patients diagnosed during 1999–2011 by using the National Cancer Institute's Surveillance, Epidemiology and End Results—Medicare linked database. Competing risk analyses adjusting for patient characteristics were conducted to assess the impact of radiotherapy on the development of subsequent MDS/AML, compared with surgery.RESULTSOf 32,112 prostate cancer patients, 14,672 underwent radiotherapy, and 17,440 received surgery only. The median follow‐up was 4.68 years. A total of 157 (0.47%) prostate cancer patients developed subsequent MDS or AML, and the median time to develop MDS/AML was 3.30 (range: 0.16–9.48) years. Compared with prostate cancer patients who received surgery only, patients who underwent radiotherapy had a significantly increased risk of developing MDS/AML (hazard ratio [HR] =1.51, 95% confidence interval [CI]: 1.07–2.13). When radiotherapy was further categorized by modalities (brachytherapy, conventional conformal radiotherapy, and intensity‐modulated radiotherapy [IMRT]), increased risk of second MDS/AML was only observed in the IMRT group (HR = 1.66, 95% CI: 1.09–2.54).CONCLUSIONSOur findings suggest that radiotherapy for prostate cancer increases the risk of MDS/AML, and the impact may differ by modality. Additional studies with longer follow‐up are needed to further clarify the role of radiotherapy in the development of subsequent myeloid malignancies. A better understanding may help patients, physicians, and other stakeholders make more informed treatment decisions. Prostate 77:437–445, 2017. © 2016 Wiley Periodicals, Inc.
The role of spin–orbit coupling in the electronic structure of iron‐based superconductors
Authors: Borisenko Sergey , Evtushinsky Daniil , Liu Zhonghao , Morozov Igor , Kappenberger Rhea , Wurmehl Sabine , Büchner Bernd , Yaresko Alexander , Kim Timur , Hoesch Moritz , Wolf Thomas , Zhigadlo Nikolai 
Published: November 2016

Spin–orbit coupling (SOC) is a fundamental interaction in solids that can induce a broad spectrum of unusual physical properties from topologically non‐trivial insulating states to unconventional pairing in superconductors. In iron‐based superconductors (IBS) its role has so far been considered insignificant with the models based on spin‐ or orbital fluctuations pairing being the most advanced in the field. In this review we discuss the recent direct observation of SOC by angle‐resolved photoemission spectroscopy (ARPES).Electron‐like Fermi surface of LiFeAs split by SOC.
A method to realize traceability in development processes
Authors: Dreves Rainer , Hällmayer Frank , Haunert Lutz , Sechser Bernhard , Rieß Armin 
Published: November 2016

AbstractThe SoQrates Working Group “Traces” develops methods for documenting a continuous flow of information and takes into account the transparency of the activities of the different disciplines. Particularly, the level of detail, accuracy, and completeness of the interfaces are considered. These methods consider also the required traceability demanded by different standards. By using the developed methods, a platform development with reusable components is possible. In combination with an efficient variant management, existing components can be combined to new customer products in a very short time (design to market). The closed traceability approach increases quality and safety veritably without additional resources. This paper describes the current results of the SoQrates Working Group “Traces” as a method description with best practice examples of the participating companies and research institutions.
Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis
Authors: Hasebe Takashi , Fujimoto Kenta , Kajita Mitsuko , Fu Liezhen , Shi Yun-Bo , Ishizuya-Oka Atsuko 
Published: November 2016

Abstract
In Xenopus laevis intestine during metamorphosis, the larval epithelial cells are removed by apoptosis, and the adult epithelial stem (AE) cells appear concomitantly. They proliferate and differentiate to form the adult epithelium (Ep). Thyroid hormone (TH) is well established to trigger this remodeling by regulating the expression of various genes including Notch receptor. To study the role of Notch signaling, we have analyzed the expression of its components, including the ligands (DLL and Jag), receptor (Notch), and targets (Hairy), in the metamorphosing intestine by real-time reverse transcription-polymerase chain reaction and in situ hybridization or immunohistochemistry. We show that they are up-regulated during both natural and TH-induced metamorphosis in a tissue-specific manner. Particularly, Hairy1 is specifically expressed in the AE cells. Moreover, up-regulation of Hairy1 and Hairy2b by TH was prevented by treating tadpoles with a γ-secretase inhibitor (GSI), which inhibits Notch signaling. More importantly, TH-induced up-regulation of LGR5, an adult intestinal stem cell marker, was suppressed by GSI treatment. Our results suggest that Notch signaling plays a role in stem cell development by regulating the expression of Hairy genes during intestinal remodeling. Furthermore, we show with organ culture experiments that prolonged exposure of tadpole intestine to TH plus GSI leads to hyperplasia of secretory cells and reduction of absorptive cells. Our findings here thus provide evidence for evolutionarily conserved role of Notch signaling in intestinal cell fate determination but more importantly reveal, for the first time, an important role of Notch pathway in the formation of adult intestinal stem cells during vertebrate development.
NNLO QCD corrections for Drell-Yan p ZT and $$ {\phi}_{{}^{\eta}}^{\ast } $$ observables at the LHC
Authors: Gehrmann-De Ridder A. , Gehrmann T. , Glover E.W.N. , Huss A. , Morgan T.A. 
Published: November 2016

AbstractDrell-Yan lepton pairs with finite transverse momentum are produced when the vector boson recoils against (multiple) parton emission(s), and is determined by QCD dynamics. At small transverse momentum, the fixed order predictions break down due to the emergence of large logarithmic contributions. This region can be studied via thepTZdistribution constructed from the energies of the leptons, or through the$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗distribution that relies on the directions of the leptons. For sufficiently small transverse momentum, the$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗observable can be measured experimentally with better resolution. We study the smallpTZand$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗distributions up to next-to-next-to-leading order (NNLO) in perturbative QCD. We compute the$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗distributions for the fully inclusive production of lepton pairs via Z/γ∗to NNLO and normalise them to the NNLO cross sections for inclusive Z/γ∗production. We compare our predictions with the$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗distribution measured by the ATLAS collaboration during LHC operation at 8 TeV. We find that at moderate to large values of$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗, the NNLO effects are positive and lead to a substantial improvement in the theory-data comparison compared to next-to-leading order (NLO). At small values ofpTZand$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗, the known large logarithmic enhancements emerge through and we identify the region where resummation is needed. We find an approximate relationship between the values ofpTZand$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗where the large logarithms emerge and find perturbative consistency between the two observables.
Identification of Recurrence—Predictive Indicators in Stage I Colorectal Cancer
Authors: Lee Jun Ho , Lee Jong Lyul , Park In Ja , Lim Seok‐Byung , Yu Chang Sik , Kim Jin Cheon 
Published: November 2016

AbstractBackgroundPatients with stage I colorectal cancer (CRC) rarely experience recurrences; therefore, few risk factors for recurrence are known. This study was designed to evaluate oncologic outcomes of patients with stage I CRC and to identify risk factors for recurrence after curative surgery.MethodsA retrospective cohort of 860 patients from a single institution who underwent curative surgery for stage I CRC between July 1995 and June 2010 was enrolled. Patients who were diagnosed with hereditary, synchronous, or metachronous cancer and those who received preoperative chemoradiotherapy were excluded. Patients from whom fewer than 12 lymph nodes were retrieved were also excluded.ResultsThe 860 patients included 402 (46.7%) with colon tumors and 458 (53.3%) with rectal tumors. Thirty‐five patients (4.1%) experienced recurrences; local and systemic recurrence rates were 1.1 and 3.0%, respectively. The 5‐year overall survival and recurrence‐free survival (RFS) rates were 93.5 ± 0.8% and 95.7 ± 0.8%, respectively. Multivariate analysis showed that preoperative serum carcinoembryonic antigen (CEA) concentration ≥6 ng/mL (hazard ratio [HR] 3.354, 95% confidence interval [CI] 1.373–8.195, p = 0.008) and lymphovascular invasion (LVI) (HR 2.676, 95% CI 1.097–6.531, p = 0.031) were independent risk factors for RFS.ConclusionsThe overall recurrence rate among patients with stage I CRC after curative surgery was 4.1%. Elevated serum CEA and LVI were significantly associated with recurrence. Large‐scale, multicenter studies are needed to confirm the prognostic value of these risk factors.
Development and Validation of a Scoring System to Predict Surgical Site Infection After Ventral Hernia Repair: A Michigan Surgical Quality Collaborative Study
Authors: Karamanos Efstathios , Kandagatla Pridvi , Watson Jenna , Schmoekel Nathan , Siddiqui Aamir 
Published: November 2016

AbstractIntroductionSurgical site infections (SSIs) are a rare but significant complication following an elective ventral hernia repair. This study aims to develop a risk assessment tool in order to predict the risk of developing SSIs postoperatively.MethodsAll patients undergoing an elective ventral hernia repair were identified using the Michigan Surgical Quality Collaborative (MSQC) database. Patients’ demographics, comorbidities and technical aspects of the operations were extracted. Logistic regressions were used to create a predictive scoring system for SSIs.ResultsA total of 4983 were included. SSIs occurred in 3.4% of the patient population. A stepwise forward logistic regression identified the need to use drains, BMI, wound classification at the end of the surgery, presence of severe adhesions, a history of CAD, the need for intensive care after surgery, the use of pressors, EtOH abuse and history of PVD as being independently associated with the development of postoperative surgical site infections.ConclusionIn patients undergoing an elective hernia repair, the incidence of SSI is low. Several preoperative and perioperative factors can contribute to the development of SSIs.
Metabolism of sn‐1(3)‐Monoacylglycerol and sn‐2‐Monoacylglycerol in Caecal Enterocytes and Hepatocytes of Brown Trout (Salmo trutta)
Authors: Li Keshuai , Olsen Rolf Erik 
Published: November 2016

Abstractsn‐2‐Monoacylglycerol (2‐MAG) and sn‐1(3)‐monoacylglycerol [1(3)‐MAG] are important but yet little studied intermediates in lipid metabolism. The current study compared the metabolic fate of 2‐MAG and 1(3)‐MAG in isolated caecal enterocytes and hepatocytes of brown trout (Salmo trutta). 1(3)‐Oleoyl [9,10‐3H(N)]‐glycerol and 2‐Oleoyl [9,10‐3H(N)]‐glycerol were prepared by pancreatic lipase digestion of triolein [9,10‐3H(N)]. The 1(3)‐MAG and 2‐MAG were efficiently absorbed by enterocytes and hepatocytes at similar rates. The 2‐MAG was quickly resynthesized into TAG through the monoacylglycerol acyltransferase (EC: 2.3.1.22, MGAT) pathway in both tissues, whereas 1(3)‐MAG was processed into TAG and phospholipids at a much slower rate, suggesting 2‐MAG was the preferred substrates for MGAT. Further analysis showed that 1(3)‐MAG was synthesized into 1,3‐DAG, but there were no accumulation of 1,3‐DAG in either enterocytes or hepatocytes, which contrasts that of mammalian studies. Some of the 1(3)‐MAG may be acylated to 1,2(2,3)‐DAG and then utilized for TAG synthesis. Alternatively, 1(3)‐MAG can be hydrolyzed to free fatty acid and glycerol, and re‐synthesized into TAG through the glycerol‐3‐phosphate (Gro‐3‐P) pathway. The overall data suggested that the limiting step of the intracellular 1(3)‐MAG metabolism is the conversion of 1(3)‐MAG itself.
Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data
Authors: Barlev Arie , Lin Vincent W. , Katz Aaron , Hu Kuolung , Cong Ze , Barber Beth 
Published: November 2016

AbstractIntroductionBlinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(−) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years.MethodsThe objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset. Conditional survival probabilities of blinatumomab-treated patients beyond month 60 were assumed to be the same as the US general population.ResultsAt month 60, the estimated proportion of blinatumomab-treated patients alive was more than double that of historical patients (12.6% vs 5.4%). The mean overall survival was 76.1 months for blinatumomab patients and 39.8 months for historical patients. Sensitivity analyses including additional follow-up data from the clinical study showed consistent results.ConclusionsThese findings suggest that blinatumomab provides substantial overall survival benefit to patients with (R/R) Ph(−) B-precursor ALL compared with salvage chemotherapy.FundingAmgen.Trial RegistrationClinicalTrials.gov identifier NCT01466179 and NCT02003612.
Evaluation of the drug solubility and rush ageing on drug release performance of various model drugs from the modified release polyethylene oxide matrix tablets
Authors: Shojaee Saeed , Nokhodchi Ali , Maniruzzaman Mohammed 
Published: November 2016

AbstractHydrophilic matrix systems are currently some of the most widely used drug delivery systems for controlled-release oral dosage forms. Amongst a variety of polymers, polyethylene oxide (PEO) is considered an important material used in pharmaceutical formulations. As PEO is sensitive to thermal oxidation, it is susceptible to free radical oxidative attack. The aim of this study was to investigate the stability of PEO based formulations containing different model drugs with different water solubility, namely propranolol HCl, theophylline and zonisamide. Both polyox matrices 750 and 303 grade were used as model carriers for the manufacture of tablets stored at 40 °C. The results of the present study suggest that the drug release from the matrix was affected by the length of storage conditions, solubility of drugs and the molecular weight of the polymers. Generally, increased drug release rates were prevalent in soluble drug formulations (propranolol) when stored at the elevated temperature (40 °C). In contrast, it was not observed with semi soluble (theophylline) and poorly soluble (zonisamide) drugs especially when formulated with PEO 303 polymer. This indicates that the main parameters controlling the drug release from fresh polyox matrices are the solubility of the drug in the dissolution medium and the molecular weight of the polymer. DSC traces indicated that that there was a big difference in the enthalpy and melting points of fresh and aged PEO samples containing propranolol, whereas the melting point of the aged polyox samples containing theophylline and zonisamide was unaffected.