bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of ADI-PEG 20 and FOLFOX6 in patients (pts) with advanced hepatocellular carcinoma (HCC).
Authors: Harding James J. , Qin Shukui , Yang Tsai-Sheng , Yen Chia-Jui , Chao Yee , Wang Tsang-En , Do Richard K. G. , El Dika Imane H. , Uhlitskykh Khrystyna , Millang Brittanie M , Feng Xiaoxing , Swe Wint , Johnston Amanda , Bomalaski John S. , Li Chien-Feng , O'Reilly Eileen Mary , Ho Ching-Liang , Chen Yen-Yang , Abou-Alfa Ghassan K. 
Published: January 2019

TPS477 Background: Arginine depletion interferes with pyrimidine metabolism as well as DNA damage repair pathways, and preclinical data indicate that pairing pegylated arginine deiminase (ADI-PEG 20) with fluoropyrimidines or platinum enhances cytotoxicity in vitro and in vivo in HCC models. A prior phase 1 study of FOLFOX6 and ADI-PEG 20 established the safety and recommended phase 2 dose of the combination in pts with advanced gastrointestinal tumors (Harding et al. CCP 2018). For 23 treatment-refractory HCC pts who were treated at the recommended phase 2 dose on an expansion cohort of the phase 1, the objective response rate (ORR) was 21% (95% CI 7.5-43.7) and median progression-free survival (PFS) was 7.3 months. These data were favorable when compared to historic data for FOLFOX alone where the ORR was ~8% and PFS was 2.93 months and suggest greater clinical activity of the combination (Qin et al. JCO 2013). Prospective confirmation of these results is required. Methods: This is an international, multicenter, single-arm, open-label phase 2 trial of ADI-PEG 20 and FOLFOX6 for advanced HCC pts with Child-Pugh A liver function who progressed on ≥ 2 prior lines of prior systemic therapy (NCT02102022). The primary objective is to define the ORR by RECIST 1.1 as assessed by blinded independent central review. Secondary objectives include determination of safety, disease control rate (DCR), duration of response (DOR), PFS, overall survival (OS), serum arginine, citrulline and anti-ADI-PEG 20 levels over 24 weeks, and alpha-fetoprotein response. Eligible pts receive intravenous FOLFOX6 biweekly at standard doses and ADI-PEG 20 intramuscularly weekly at 36 mg/m.2 Cross-sectional imaging will be completed every 8 weeks until progression of disease. Based on a two-sided exact test of a one-sample proportion with an alpha of 0.05, under a presumed ORR of 22%, there is 80% power to yield 95% confidence interval of 15-26%, which will require 46 objective responses in 225 subjects. Futility will be assessed three times during the study based on having ORR data available for 56, 110, and 166 patients. This Phase 2 will be stopped for futility if the conditional power drops below 20% at any of these time points. Clinical trial information: NCT02102022.
Avenger 500, a phase III open-label randomized trial of the combination of CPI-613 with modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) in patients with metastatic adenocarcinoma of the pancreas.
Authors: Philip Philip Agop , Buyse Marc E. , Alistar Angela Tatiana , Rocha Lima Caio Max Sao Pedro , Luther Sanjeev , Pardee Timothy S. , Van Cutsem Eric 
Published: January 2019

TPS479 Background: Metastatic pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Current treatments using FOLFIRINOX and gemcitabine plus nab-paclitaxel, provide median survivals of 11.1 and 8.5 months, respectively. PDAC cells have altered metabolism. CPI-613 is a novel TCA cycle inhibitor that targets cancer cells. In a phase I study mFFX plus CPI-613 resulted in a 61% objective response rate with 3 of 18 patients achieving a complete response. Methods: Avenger 500 (NCT03504423) is an open-label randomized trial of CPI-613 plus mFFX versus FFX in untreated patients with metastatic PDAC. 500 patients will be randomized 1:1 between arms. The experimental arm comprises CPI-613 500 mg/m2 on day 1 and 3 of a 14-day cycle. The mFFX regimen is the standard dose and schedule of 5-Fluorouracil but reduced doses of oxaliplatin (65 mg/m²) and irinotecan (140 mg/m²). The control arm is standard dose FFX. There are two co-primary endpoints: Overall Response Rate (ORR, Complete Response + Partial Response). Best response within the first 12 cycles will be used for this determination, to be confirmed by independent, blinded, central review. Progression-Free Survival (PFS), is the second co-primary endpoint. Secondary endpoints are overall survival, duration of response and safety. Patient reported outcomes will be compared using the NCCN-FACT FHSI-18. An interim analysis will be done after 167 patients are evaluable for response. The difference in ORR will be tested using a Lan-DeMets Pocock type boundary for futility and efficacy. Futility will be declared if the difference in ORR between the arms is smaller than 5%, while efficacy will be declared if it is larger than 20%. The PFS hazard ratio will be tested using a Lan-DeMets O’Brien-Fleming type boundary. Efficacy will be declared if the hazard ratio is less than 0.48. The final analysis will be done with 500 patients randomized, when ~375 PFS events are available. Significance will be reached if the PFS hazard ratio is less than 0.80, or the difference in ORR is at least 11%. If the trial reaches significance for either primary endpoint, overall survival will be tested. Clinical trial information: NCT03504423.
A phase II clinical trial platform for sensitization testing using total neoadjuvant therapy (TNT) in rectal cancer: Nrg-GI002.
Authors: George Thomas J. , Yothers Greg , Rahma Osama E. , Hong Theodore S. , Russell Marcia McGory , You Y. Nancy , Parker William , Jacobs Samuel A. , Lucas Peter C. , Gollub Marc Jeffrey , Hall William Adrian , Kachnic Lisa A. , Vijayvergia Namrata , Wolmark Norman 
Published: January 2019

TPS721 Background: Locally advanced rectal cancer (LARC) improvements have plateaued due to an inability to consistently deliver adjuvant therapy and effective novel therapies. Systematic testing of new chemotherapy and radiation sensitizers is needed to advance treatment outcomes. This NCTN multi-arm randomized phase II modular clinical trial platform utilizes TNT with parallel experimental arms (EA) in LARC. The EAs are not intended for direct comparison, but rather to test a variety of sensitizers or hypotheses in a consistent and homogenous high-risk patient (pt) population with correlative biomarkers. Success of any EA will be determined by achievement of pathologic endpoints compared to a control arm. Methods: The NRG-GI002 trial serves as a modular platform to assess novel sensitizers to neoadjuvant chemotherapy and/or chemoradiotherapy (chemoRT) in LARC. Eligibility includes LARC with any ONE of the following: distal location (cT3-4 ≤ 5 cm from anal verge, any N); bulky (any cT4 or tumor within 3 mm of the mesorectal fascia); high risk for metastatic disease (cN2); or not a candidate for sphincter-sparing surgical resection. After randomization, pts receive neoadjuvant FOLFOX x 4 mo→chemoRT (capecitabine with 50.4 Gy)→surgical resection 8-12 wks later. The first EA will assess activity of veliparib with standard chemoRT. Enrollment to this EA is complete (results anticipated late 2019). The second EA, testing pembrolizumab concurrently with and following chemoRT, is currently active, with several other EAs in development. Primary endpoint is demonstrated improvement in Neoadjuvant Rectal Cancer score for the EA v control representing a 20% relative risk reduction in DFS HR and 3-4% absolute OS improvement. Secondary endpoints include comparisons of OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter preservation, sphincter function including QOL, and exploratory assessments of molecular and radiographic predictors of response and distant failure. Target accrual is 79 evaluable pts/arm with additional EAs added through protocol amendments. NCT02921256. Support: U10CA180868, -180822, UG1-189867, U24-196067; AbbVie, Merck. Clinical trial information: NCT02921256.
JAK/STAT signaling in stem cells and regeneration: fromDrosophilato vertebrates
Authors: Herrera Salvador C. , Bach Erika A. 
Published: January 2019

ABSTRACTThe JAK/STAT pathway is a conserved metazoan signaling system that transduces cues from extracellular cytokines into transcriptional changes in the nucleus. JAK/STAT signaling is best known for its roles in immunity. However, recent work has demonstrated that it also regulates critical homeostatic processes in germline and somatic stem cells, as well as regenerative processes in several tissues, including the gonad, intestine and appendages. Here, we provide an overview of JAK/STAT signaling in stem cells and regeneration, focusing on Drosophila and highlighting JAK/STAT pathway functions in proliferation, survival and cell competition that are conserved between Drosophila and vertebrates.
Au Supracrystal Growth Processes: Unexpected Morphologies
Authors: Pileni M P 
Published: January 2019

Abstract
In this account we describe the various morphologies of crystalline structures called supracrystals of 5 nm Au nanocrystals used as building blocks. The Au nanocrystals are coated with dodecanthiol, except when it is mentioned in the text. It is shown that traces of water molecules markedly change the average distance between nanocrystals. Similarly, the way to solvent evaporation, solvent vapor pressure and excess of coating agents induces a transition from films to shaped supracrystals. Furthermore, segregation between single domain and polycrystalline 5 nm Au nanocrystals takes place during the supracrystal formation. By mixing single domain Au and Co nanocrystals, vicinal surfaces are produced. A mechanism of such spontaneous formation of high index planes in Au single domain nanocrystal superlattices is proposed.
Evaluation of stray radiation to the operator for five hand-held dental X-ray devices
Authors: Smith Richard , Tremblay Richard , Wardlaw Graeme M 
Published: January 2019

Objectives: Evaluate stray radiation to the operator, as represented by a plane within the significant zone of occupancy (SZO), produced by five models of hand-held intraoral dental X-ray devices (HIDXDs). Methods: The stray radiation for five models of HIDXDs was measured, using an anthropomorphic tissue-equivalent head phantom as a scattering object. An ionization chamber was used to measure the air kerma (μGy) at 63 positions in a 160 cm high by 60 cm wide plane that was 10 cm behind the X-ray device, identified as being within the SZO. Results: Based on the measured air kerma from stray radiation of five different HIDXDs, the estimated annual air kerma at all measured spatial positions was calculated. When calculated using a median air kerma of 0.8 mGy at the distal end of the cone, as typically required for digital image receptors, 1 the ranges for estimated annual air kerma in the SZO across the devices were 0.14–0.77 mGy for the median, 0.41–1.01 mGy for the mean, and 1.32–2.55 mGy for the maximum. Similarly, when calculated using a median air kerma of 1.6 mGy as typically required for D-speed film, 2 the ranges for estimated annual air kerma across the devices were 0.28–1.54 mGy for the median, 0.83–2.03 mGy for the mean, and 2.64–5.10 mGy for the maximum. Conclusions: From measured air kerma values of stray radiation in the SZO, estimated annual exposures to the operator for HIDXDs are expected to be greater than from conventional wall-mounted or portable devices activated from a protected area (at a distance or behind shielding). HIDXDs should therefore only be used when patient accessibility makes their use necessary and the use of a portable device on a stand or a wall-mounted device is not reasonably feasible. This approach would keep occupational radiation exposures of dental workers as low as reasonably achievable.
First record of the isopod Idotea hectica (Pallas, 1772) (Idoteidae) and of the brachyuran crab Matuta victor (Fabricius, 1781) (Matutidae) in the Hellenic waters
Authors: KONDYLATOS GERASIMOS , CORSINI-FOKA MARIA , PERAKIS EMMANOUIL 
Published: January 2019

The presence and the establishment of Idotea hectica is reported for the first time in the Hellenic seas on the basis of three adult specimens and a juvenile collected from Posidonia oceanica meadows close to the main town of Rhodes Island, Aegean Sea. Common and contrasting characters between this and other species of the genera Idotea and Pentidotea are briefly discussed. Furthermore, following a westward expansion along the eastern Mediterranean coasts, Matuta victor was discovered for the first time in Hellenic waters on the basis of a single specimen from the northeast of Rhodes Island.
DOLORisk: study protocol for a multi-centre observational study to understand the risk factors and determinants of neuropathic pain
Authors: Pascal Mathilde M.V. , Themistocleous Andreas C. , Baron Ralf , Binder Andreas , Bouhassira Didier , Crombez Geert , Finnerup Nanna B. , Gierthmühlen Janne , Granovsky Yelena , Groop Leif , Hebert Harry L. , Jensen Troels S. , Johnsen Kristinn , McCarthy Mark I. , Meng Weihua , Palmer Colin N.A. , Rice Andrew S.C. , Serra Jordi , Solà Romà , Yarnitsky David , Smith Blair H. , Attal Nadine , Bennett David L.H. 
Published: February 2019

Background: Neuropathic pain is an increasingly prevalent condition and has a major impact on health and quality of life. However, the risk factors for the development and maintenance of neuropathic pain are poorly understood. Clinical, genetic and psychosocial factors all contribute to chronic pain, but their interactions have not been studied in large cohorts. The DOLORisk study aims to study these factors. Protocol: Multicentre cross-sectional and longitudinal cohorts covering the main causes leading to neuropathic pain (e.g. diabetes, surgery, chemotherapy, traumatic injury), as well as rare conditions, follow a common protocol for phenotyping of the participants. This core protocol correlates answers given by the participants on a set of questionnaires with the results of their genetic analyses. A smaller number of participants undergo deeper phenotyping procedures, including neurological examination, nerve conduction studies, threshold tracking, quantitative sensory testing, conditioned pain modulation and electroencephalography. Ethics and dissemination: All studies have been approved by their regional ethics committees as required by national law. Results are disseminated through the DOLORisk website, scientific meetings, open-access publications, and in partnership with patient organisations. Strengths and limitations: Large cohorts covering many possible triggers for neuropathic painMulti-disciplinary approach to study the interaction of clinical, psychosocial and genetic risk factorsHigh comparability of the data across centres thanks to harmonised protocolsOne limitation is that the length of the questionnaires might reduce the response rate and quality of responses of participants
Intercontinental Liner Shipping Service Design
Authors: Wang Yadong , Meng Qiang , Kuang Haibo 
Published: January 2019

Intercontinental liner container shipping service connects trades between different continents in the global logistic system. This paper proposes a single intercontinental service design problem that aims to jointly determine the optimal serviced ports from a set of candidate ports, the port rotation, the ship sailing speed on each voyage between adjacent serviced ports and the number of containers transported for each type of shipping demand. A mixed integer linear programming model is formulated for the proposed problem based on mild assumptions to maximize the service profit, which is calculated as the freight revenue minus the total operating cost that includes port stay cost, container handling cost, bunker consumption cost, and other ship operating costs. The formulated model is also able to produce a service route with a more general topological structure than the simple cycle or butterfly cycle routes considered in most current studies. In view of the unique features of the model, a tailored and exact branch-and-cut algorithm is developed based on Benders decomposition to expedite the model solution. Numerical experiments demonstrate the efficiency of the developed branch-and-cut algorithm and show the applicability of the proposed model for designing the intercontinental liner shipping services. The e-companion is available at https://doi.org/10.1287/trsc.2018.0831 .
Effects of mechanical forces on osteogenesis and osteoclastogenesis in human periodontal ligament fibroblasts
Authors: Li M. , Zhang C. , Yang Y. 
Published: January 2019

Objectives Many in vitro studies have investigated the mechanism by which mechanical signals are transduced into biological signals that regulate bone homeostasis via periodontal ligament fibroblasts during orthodontic treatment, but the results have not been systematically reviewed. This review aims to do this, considering the parameters of various in vitro mechanical loading approaches and their effects on osteogenic and osteoclastogenic properties of periodontal ligament fibroblasts. Methods Specific keywords were used to search electronic databases (EMBASE, PubMed, and Web of Science) for English-language literature published between 1995 and 2017. Results A total of 26 studies from the 555 articles obtained via the database search were ultimately included, and four main types of biomechanical approach were identified. Compressive force is characterized by static and continuous application, whereas tensile force is mainly cyclic. Only nine studies investigated the mechanisms by which periodontal ligament fibroblasts transduce mechanical stimulus. The studies provided evidence from in vitro mechanical loading regimens that periodontal ligament fibroblasts play a unique and dominant role in the regulation of bone remodelling during orthodontic tooth movement. Conclusion Evidence from the reviewed studies described the characteristics of periodontal ligament fibroblasts exposed to mechanical force. This is expected to benefit subsequent research into periodontal ligament fibroblasts and to provide indirectly evidence-based insights regarding orthodontic treatment. Further studies should be performed to explore the effects of static tension on cytomechanical properties, better techniques for static compressive force loading, and deeper analysis of underlying regulatory systems. Cite this article: M. Li, C. Zhang, Y. Yang. Effects of mechanical forces on osteogenesis and osteoclastogenesis in human periodontal ligament fibroblasts: A systematic review of in vitro studies. Bone Joint Res 2019;8:19–31. DOI: 10.1302/2046-3758.81.BJR-2018-0060.R1.
Emotions in Language Teaching: A Review of Studies on Teacher Emotions in Brazil
Authors: Barcelos Ana Maria F. , Aragão Rodrigo Camargo 
Published: February 2019

Abstract
In this paper, we wish to respond to the call for expansion on our knowledge about teacher beliefs (Kubanyiova & Feryok, 2015) and discuss findings of studies on teacher emotions conducted in Brazil with both in-service and pre-service teachers of English. More specifically, we focus 1) on the kinds of emotions these teachers have reported feeling, and 2) on the relationship between beliefs and emotions. The results have shown: 1) the diversity of emotions teachers experience in their teacher education; and 2) how these emotions interact in dynamic and complex ways with their beliefs about teaching English in Brazil. The findings suggest that looking into the interrelationships between emotions and beliefs can shed light onto our understanding of the teachers’ thinking and practices in their contexts. Implications and questions for further research will be discussed in light of the studies reviewed.
Influence of the contractor’s payment method on the economic effectiveness of the construction project from the contractor’s point of view
Authors: Zawistowski Jacek , Kulejewski Janusz 
Published: January 2019

Abstract
The scope of the paper is the problem of the economic effectiveness of the construction project from the contractor’s point of view. The two main construction contract types are taken under consideration: the unit price contract based on the bill of quantities and the lump sum contract.
The net present value (NPV) is adopted in this paper as the basic economic efficiency criterion of the construction project. The NPV of the project for the contractor is calculated here as the sum of all future monthly contractor’s cash flows (both incoming and outgoing) discounted by using the monthly cost of contractor’s capital invested into the project. For the cash flow calculations, two basic payment methods are considered, depending on the type of the contract: the monthly payments in the case of the unit price contract and the payments for the WBS (Work Breakdown Structure) billing elements in the case of the lump sum contract. The contractor’s monthly cash flow analysis also makes it possible to determine the monthly cash requirements for the contractor to finance the works each month and the total cash requirement to finance the project as the whole. This allows the contractor to correctly plan the financing of the project depending on the type of contract and the payment method. Moreover, using the optimization techniques known in the scheduling theory, for example based on the priority rules as in the case of the RCSP, one may try to improve the economic effectiveness of the project or to lower the cash requirement for the project.However, as shown by the authors, it does not have bring the expected results in the case of the lump sum contract.
Organic anion transporters 1 and 3 influence cellular energy metabolism in renal proximal tubule cells
Authors: Vriend Jelle , Hoogstraten Charlotte A. , Venrooij Kevin R. , van den Berge Bartholomeus T. , Govers Larissa P. , van Rooij Arno , Huigen Marleen C.D.G. , Schirris Tom J.J. , Russel Frans G.M. , Masereeuw Rosalinde , Wilmer Martijn J. 
Published: January 2019

Abstract
Organic anion transporters (OATs) 1 and 3 are, besides being uptake transporters, key in several cellular metabolic pathways. The underlying mechanisms are largely unknown. Hence, we used human conditionally immortalized proximal tubule epithelial cells (ciPTEC) overexpressing OAT1 or OAT3 to gain insight into these mechanisms. In ciPTEC-OAT1 and -OAT3, extracellular lactate levels were decreased (by 77% and 71%, respectively), while intracellular ATP levels remained unchanged, suggesting a shift towards an oxidative phenotype upon OAT1 or OAT3 overexpression. This was confirmed by increased respiration of ciPTEC-OAT1 and -OAT3 (1.4-fold), a decreased sensitivity to respiratory inhibition, and characterized by a higher demand on mitochondrial oxidative capacity. In-depth profiling of tricarboxylic acid (TCA) cycle metabolites revealed reduced levels of intermediates converging into α-ketoglutarate in ciPTEC-OAT1 and -OAT3, which via 2-hydroxyglutarate metabolism explains the increased respiration. These interactions with TCA cycle metabolites were in agreement with metabolomic network modeling studies published earlier. Further studies using OAT or oxidative phosphorylation (OXPHOS) inhibitors confirmed our idea that OATs are responsible for increased use and synthesis of α-ketoglutarate. In conclusion, our results indicate an increased α-ketoglutarate efflux by OAT1 and OAT3, resulting in a metabolic shift towards an oxidative phenotype.
Crystal structure of 5,4′-dihydroxy-7,3′-dimethoxyflavanone, C17H16O6
Authors: Cisterna Jonathan , Bórquez Jorge , Muñoz Rubén , Simirgiotis Mario , Cárdenas Alejandro , Brito Iván 
Published: January 2019

Abstract
C17H16O6, orthorhombic, P212121 (no. 19), a = 5.2601(3) Å, b = 12.7161(6) Å, c = 22.0116(11) Å, V = 1472.31(13) Å3, Z = 4, R
gt(F) = 0.0430, wR
ref(F
2) = 0.1089, T = 296(2) K.
Crystal structure of 6-cyclohexyl-6,7-dihydrodibenzo[c,f][1,5]azabismocin-12(5H)-yl nitrate, C20H23O3N2Bi
Authors: Tan Nianyuan , Wu Shuisheng , Huiqiong Yang , Lan Donghui , Au Chak-Tong , Yi Bing 
Published: February 2019

Abstract
C20H23O3N2Bi, monoclinic, P21/n (no. 14), a = 10.6897(5) Å, b = 10.5590(5) Å, c = 17.4099(9) Å, β = 105.491(2)°, V = 1893.71(16) Å3, Z = 4, R
gt(F) = 0.0253, wR(F
2) = 0.0576, T = 296(2) K.