bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual‐drug RGD conjugates provide enhanced cytotoxicity to melanoma and non‐small lung cancer cells
Authors: Gilad Y. , Noy E. , Senderowitz H. , Albeck A. , Firer M. A. , Gellerman G. 
Published: December 2015

ABSTRACTTo enhance the efficacy of targeted drug delivery, four new peptide‐ligand conjugates were synthesized, each consisting of a cyclic RGDfK penta‐peptide loaded with two anticancer drugs. The drug release profiles in different media of these new compounds and their cytotoxic activity against melanoma and non‐small lung cancer cell lines were evaluated and compared with those of their singly loaded analogs. The cyclic RGDfK penta‐peptide was selected as a targeting moiety because of its high affinity and selectivity to the αvβ3integrin receptor, which is frequently over‐expressed in various types of cancer cells. The peptide's core was modified at the side chain of its Lys residue by coupling it with a sixth amino acid (AA) ‐ either Lys (5a) or Ser (5b) (Lys/Ser splitter), resulting in two functional sites which enabled the loading of two therapeutic equivalents onto a single targeting carrier. Using Lys as a splitter resulted in two primary amines. Consequently, conjugates 1a and 1b were synthesized by coupling of 2 Chlorambucils (CLBs) or 2 Camptothecins (CPTs), respectively, to the primary amines of 5a. Conjugate 1c was synthesized from 5b by loading two equivalents of CLB on the amine and the hydroxyl of the Ser splitter, resulting in a homodimeric system with two distinct conjugation sites – amide and ester. The heterodimeric conjugate 1d of CLB and CPT was synthesized by loading each one of the primary amines of 5a with two different drugs ‐ CLB and CPT. The doubling of drug equivalents loaded onto the targeting peptide correlated with enhanced cytotoxic efficacy of the conjugates towards cancer cells. The versatility of chemical linkages of the drugs to the peptides resulted in conjugates with different drug release profiles. Molecular dynamics simulations performed on conjugate 1d demonstrated that this compound occupies a conformational space similar to the bio‐active conformation of an integrin‐bound cyclic RGD peptide reference peptide (c(RGDf(NMe)V). The modified position in 1d (relative to the reference peptide) points away from the integrin, leading us to hypothesize that this peptide binds the integrin in a manner similar to that of the reference peptide thereby fulfilling a crucial requirement for targeted delivery. The strategy of dual drug loading on a single peptide carrier, gives rise to drugs with different mechanisms of action and release profiles, thus substantially increasing the efficacy of selective killing of tumor cells and while reducing the risk of the development of drug resistance. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 160–171, 2016.
Determination of the novel antiarrhythmic drug sulcardine sulfate in human plasma by liquid chromatography tandem mass spectrometry and its application in a clinical pharmacokinetic study
Authors: Jia Jingying , Liu Gangyi , Zhang Mengqi , Lu Youli , Lu Chuan , Liu Yun , Zheng Hongcao , Wang Wei , Gui Yuzhou , Yu Chen , Li Shuijun , Wang Yiping 
Published: December 2015

AbstractSulcardine sulfate (Sul), a novel antiarrhythmic agent, is currently in phase I and phase II clinical trials. To elucidate its clinical pharmacokinetic characteristics, a rapid and accurate liquid chromatography–tandem mass spectrometry (LC–MS/MS) method has been developed and validated for the quantification of Sul in human plasma. Plasma samples were precipitated by acetonitrile and isotope‐labeled sulcardine was added as internal standard. The analysis was carried out on a Capcell Pak C18 MG III column (100 × 2.0 mm, 5 μm) with 0.1% formic acid in acetonitrile solution and water (17:83, v/v) as mobile phase. The linear range was 5.0–1000 ng/mL for Sul, with a lower limit of quantification of 5.0 ng/mL. The intra‐ and inter‐batch CVs were within ±11.0% and the accuracies were 4.9–107.3%. Our method, for the first time, allows the rapid (only 3.0 min) and accurate quantification of Sul in human plasma. The method has been successfully applied in the pharmacokinetic study of Sul in a clinical trial following oral administration of Sul to healthy volunteers. Copyright © 2016 John Wiley & Sons, Ltd.
Retrospective analysis of systemic chemotherapy and total parenteral nutrition for the treatment of malignant small bowel obstruction
Authors: Chouhan Jay , Gupta Rohan , Ensor Joe , Raghav Kanwal , Fogelman David , Wolff Robert A. , Fisch Michael , Overman Michael J. 
Published: December 2015

AbstractMalignant small bowel obstruction (MSBO) that does not resolve with conservative measures frequently leaves few treatment options other than palliative care. This single‐institution retrospective study assesses the outcomes of a more aggressive approach—concurrent systemic chemotherapy and total parenteral nutrition (TPN)—in the treatment of MSBO. The MD Anderson pharmacy database was queried to identify patients who received concurrent systemic chemotherapy and TPN between 2005 and 2013. Only patients with MSBO secondary to peritoneal carcinomatosis requiring TPN for ≥8 days were included. Survival and multivariate analyses were performed using the Kaplan–Meier method and Cox proportional hazard models. The study included 82 patients. MSBO resolution was observed in 10 patients. Radiographic assessments showed a response to chemotherapy in 19 patients; 6 of these patients experienced MSBO resolution. Patients spent an average of 38% of their remaining lives hospitalized, and 28% of patients required admission to the intensive care unit. In multivariate modeling, radiographic response to chemotherapy correlated with MSBO resolution (odds ratio [OR] 6.81; 95% confidence interval [CI], 1.68–27.85, P = 0.007). Median overall survival (OS) was 3.1 months, and the 1‐year OS rate was 12.6%. Radiographic response to chemotherapy (HR 0.30; 95% CI, 0.16–0.56, P < 0.001), and initiation of new chemotherapy during TPN (HR 0.55; 95% CI, 0.33–0.94, P = 0.026) independently predicted for longer OS. Concurrent treatment with systemic chemotherapy and TPN for persistent MSBO results in low efficacy and a high morbidity and mortality, and thus should not represent a standard approach.
Early treatment of complex located pediatric low‐grade gliomas using iodine‐125 brachytherapy alone or in combination with microsurgery
Authors: Kunz Mathias , Nachbichler Silke B. , Ertl Lorenz , Fesl Gunther , Egensperger Rupert , Niyazi Maximilian , Schmid Irene , Tonn Joerg Christian , Peraud Aurelia , Kreth Friedrich Wilhelm 
Published: December 2015

AbstractTo analyze efficacy, functional outcome, and treatment toxicity of low‐dose rate I‐125 brachytherapy (SBT) alone or in combination with best safe resection (in case of larger tumor volumes) as first‐line treatment for pediatric low‐grade gliomas (PLGGs) not suitable for complete resection. Consecutively treated (2000–2014) complex located circumscribed WHO grade I/II PLGGs were included. For small tumors (≤4 cm in diameter) SBT alone was performed; for larger tumors best safe resection and subsequent SBT was chosen. Temporary Iodine‐125 seeds were used (median reference dose: 54 Gy). Treatment response was estimated with the modified MacDonald criteria. Analysis of functional outcome included ophthalmological, endocrinological and neurological evaluation. Survival was analyzed with the Kaplan–Meier method. Prognostic factors were obtained from proportional hazards models. Toxicity was categorized according to the Common Terminology Criteria for Adverse Events. Fifty‐eight patients were included treated either with SBT alone (n = 39) or with SBT plus microsurgery (n = 19). Five‐year progression‐free survival was 87%. Two patients had died due to tumor progression. Among survivors, improvement/stabilization/deterioration of functional deficits was seen in 20/14/5 patients, respectively. Complete/partial response had beneficial impact on functional scores (P = 0.02). The 5‐year estimated risk to receive adjuvant radiotherapy/chemotherapy was 5.2%. The overall early (delayed) toxicity rate was 8.6% (10.3%), respectively. No permanent morbidity occurred. In complex located PLGGs, early SBT alone or combined with best safe resection preserves/improves functional scores and results in tumor control rates usually achieved with complete resection. Long‐term analysis is necessary for confirmation of these results.
The bio‐response of osteocytes and its regulation on osteoblasts under vibration
Authors: Wu Xin‐Tong , Sun Lian‐Wen , Qi Hong‐Yu , Shi Hao , Fan Yu‐Bo 
Published: December 2015

AbstractVibration, especially at low magnitude and high frequency (LMHF), was demonstrated to be anabolic for bone, but how the LMHF vibration signal is perceived by osteocytes is not fully studied. On the other hand, the mechanotransduction of osteocytes under shear stress has been scientists' primary focus for years. Due to the small strain caused by low‐magnitude vibration, whether the previous explanation for shear stress will still work for LMHF vibration is unknown. In this study, a finite element method (FEM) model based on the real geometrical shape of an osteocyte was built to compare the mechanical behaviors of osteocytes under LMHF vibration and shear stress. The bio‐response of osteocytes to vibration under different frequencies, including the secretion of soluble factors and the concentration of intracellular calcium, were studied. The regulating effect of the conditioned medium (CM) from vibrated osteocytes on osteoblasts was also studied. The FEM analysis result showed the cell membrane deformation under LMHF vibration was very small (with a peak value of 1.09%) as compared to the deformation caused by shear stress (with a peak value of 6.65%). The F‐actin stress fibers of osteocytes were reorganized, especially on the nucleus periphery after LMHF vibration. The vibration at 30 Hz has a promoting effect on osteocytes and the osteogenesis of osteoblasts, whereas vibration at 90 Hz was suppressive. These results lead to a conclusion that the bio‐response of osteocytes to LMHF vibration is frequency‐dependent and is more related to the cytoskeleton on nuclear periphery rather than the membrane deformation.
Isolable Boron Persulfide: Activation of Elemental Sulfur with a 2‐Chloro‐Azaborolyl Anion
Authors: Chen Peixing , Cui Chunming 
Published: December 2015

AbstractThe novel boron persulfide 2 LB(η2‐S2) (L=[ArNC(R)CHC(R)]−; Ar=2,6‐Me2C6H3, R=tBu) was obtained by the reaction of the 2‐chloro‐azaborolyl anion 1 (LBCl)K(THF) with 0.25 equiv of elemental sulfur (S8). Persulfide 2 is labile in solution and could be converted to the cyclic tetrasulfide LBS4 (3) and hexasulfide LBS6 (4) in the presence of sulfur at room temperature and 50 °C, respectively. Desulfination of 2 with triphenylphosphine resulted in the formation of the thioxoborane LB=S (5). Alternatively, 3 and 4 could be obtained by the reaction of 1 with an excess of sulfur. Structural analysis of 2 disclosed the relatively long S−S bond of 2.1004(8) Å due to the lone‐pair repulsions of the two sulfur atoms, as disclosed by DFT calculations.
Efficacy of adjuvant chemotherapy for small bowel adenocarcinoma: A propensity score–matched analysis
Authors: Ecker Brett L. , McMillan Matthew T. , Datta Jashodeep , Mamtani Ronac , Giantonio Bruce J. , Dempsey Daniel T. , Fraker Douglas L. , Drebin Jeffrey A. , Karakousis Giorgos C. , Roses Robert E. 
Published: December 2015

BACKGROUNDThe role of adjuvant chemotherapy (AC) in the treatment of small bowel adenocarcinoma is poorly defined. Previous analyses have been limited by small sample sizes and have failed to demonstrate a survival advantage.METHODSPatients with resected small bowel adenocarcinoma (American Joint Committee on Cancer [AJCC] pathologic stage I‐III) who were receiving AC (n = 1674) or surgery alone (SA; n = 3072) were identified in the NCDB (1998‐2011). Cox regression identified covariates associated with overall survival (OS). AC and SA cohorts were matched (1:1) by propensity scores based on the likelihood of receiving AC or the survival hazard from Cox modeling. OS was compared with Kaplan‐Meier estimates.RESULTSThe omission of AC conferred an increased risk of death (hazard ratio, 1.36; 95% confidence interval, 1.24‐1.50; P < .001). After propensity score matching, there was a nonsignificant trend toward improved OS with AC in AJCC stage I patients (158.8 vs 110.7 months; P = .226) and AJCC stage II patients (104.0 vs 79.6 months; P = .185), including the subset with a T4 tumor classification (64.0 vs 47.4 months; P = .130) or a positive resection margin (44.4 vs 31.0 months; P = .333). Median OS was superior for patients with AJCC stage III disease who were receiving AC versus SA (42.4 vs 26.1 months; P < .001).CONCLUSIONSThese data support the use of AC for resected stage III small bowel adenocarcinoma. The trend toward improved OS for patients without nodal metastasis, including those who have T4 tumors or have undergone positive‐margin resection, may justify the use of AC in select patients with earlier stage disease. Cancer 2016;122:693–701. © 2015 American Cancer Society.
Direct costs of care for hepatocellular carcinoma in patients with hepatitis C cirrhosis
Authors: Tapper Elliot B. , Catana Andreea M. , Sethi Nidhi , Mansuri Daniel , Sethi Saurabh , Vong Annie , Afdhal Nezam H. 
Published: December 2015

BACKGROUNDHepatitis C virus (HCV) is the commonest cause of hepatocellular carcinoma (HCC) in the United States. The benefits of HCV therapy may be measured in part by the prevention of HCC and other complications of cirrhosis. The true cost of care of the HCV patient with HCC is unknown.METHODSOne hundred patients were randomly selected from a cohort of all HCC patients with HCV at a US transplant center between 2003 and 2013. Patients were categorized by the primary treatment modality, Barcelona class, and ultimate transplant status. Costs included the unit costs of procedures, imaging, hospitalizations, medications, and all subsequent care of the HCC patient until either death or the end of follow‐up. Associations with survival and cost were assessed in multivariate regression models.RESULTSOverall costs included a median of $176,456 (interquartile range [IQR], $84,489‐$292,192) per patient or $6279 (IQR, $4043‐$9720) per patient‐month of observation. The median costs per patient‐month were $7492 (IQR, $5137‐$11,057) for transplant patients and $4830 for nontransplant patients. The highest median monthly costs were for transplant patients with Barcelona A4 disease ($11,349) and patients who received chemoembolization whether they underwent transplantation ($10,244) or not ($8853). Transarterial chemoembolization and radiofrequency ablation were independently associated with a 28% increase and a 22% decrease in costs, respectively, with adjustments for the severity of liver disease and Barcelona class.CONCLUSIONSThese data represent real‐world estimates of the cost of HCC care provided at a transplant center and should inform economic studies of HCV therapy. Cancer 2016;122:852–8. © 2015 American Cancer Society.
Radiation modality use and cardiopulmonary mortality risk in elderly patients with esophageal cancer
Authors: Lin Steven H. , Zhang Ning , Godby Joy , Wang Jingya , Marsh Gary D. , Liao Zhongxing , Komaki Ritsuko , Ho Linus , Hofstetter Wayne L. , Swisher Stephen G. , Mehran Reza J. , Buchholz Thomas A. , Elting Linda S. , Giordano Sharon H. 
Published: December 2015

BACKGROUNDIt is currently unclear whether the superior normal organ‐sparing effect of intensity‐modulated radiotherapy (IMRT) compared with 3‐dimensional radiotherapy (3D) has a clinical impact on survival and cardiopulmonary mortality in patients with esophageal cancer (EC).METHODSThe authors identified 2553 patients aged > 65 years from the Surveillance, Epidemiology, and End Results (SEER)‐Medicare and Texas Cancer Registry‐Medicare databases who had nonmetastatic EC diagnosed between 2002 and 2009 and were treated with either 3D (2240 patients) or IMRT (313 patients) within 6 months of diagnosis. The outcomes of the 2 cohorts were compared using inverse probability of treatment weighting adjustment.RESULTSExcept for marital status, year of diagnosis, and SEER region, both radiation cohorts were well balanced with regard to various patient, tumor, and treatment characteristics, including the use of IMRT versus 3D in urban/metropolitan or rural areas. IMRT use increased from 2.6% in 2002 to 30% in 2009, whereas the use of 3D decreased from 97.4% in 2002 to 70% in 2009. On propensity score inverse probability of treatment weighting‐adjusted multivariate analysis, IMRT was not found to be associated with EC‐specific mortality (hazard ratio [HR], 0.93; 95% confidence interval [95% CI], 0.80‐1.10) or pulmonary mortality (HR, 1.11; 95% CI, 0.37‐3.36), but was significantly associated with lower all‐cause mortality (HR, 0.83; 95% CI, 0.72‐0.95), cardiac mortality (HR, 0.18; 95% CI, 0.06‐0.54), and other‐cause mortality (HR, 0.54; 95% CI, 0.35‐0.84). Similar associations were noted after adjusting for the type of chemotherapy, physician experience, and sensitivity analysis removing hybrid radiation claims.CONCLUSIONSIn this population‐based analysis, the use of IMRT was found to be significantly associated with lower all‐cause mortality, cardiac mortality, and other‐cause mortality in patients with EC. Cancer 2016;122:917–28. © 2015 American Cancer Society.
Human‐specific increase of dopaminergic innervation in a striatal region associated with speech and language: A comparative analysis of the primate basal ganglia
Authors: Raghanti Mary Ann , Edler Melissa K. , Stephenson Alexa R. , Wilson Lakaléa J. , Hopkins William D. , Ely John J. , Erwin Joseph M. , Jacobs Bob , Hof Patrick R. , Sherwood Chet C. 
Published: December 2015

ABSTRACTThe dopaminergic innervation of the striatum has been implicated in learning processes and in the development of human speech and language. Several lines of evidence suggest that evolutionary changes in dopaminergic afferents of the striatum may be associated with uniquely human cognitive and behavioral abilities, including the association of the human‐specific sequence of the FOXP2 gene with decreased dopamine in the dorsomedial striatum of mice. To examine this possibility, we quantified the density of tyrosine hydroxylase‐immunoreactive axons as a measure of dopaminergic innervation within five basal ganglia regions in humans, great apes, and New and Old World monkeys. Our results indicate that humans differ from nonhuman primate species in having a significant increase in dopaminergic innervation selectively localized to the medial caudate nucleus. This region of the striatum is highly interconnected, receiving afferents from multiple neocortical regions, and supports behavioral and cognitive flexibility. The medial caudate nucleus also shows hyperactivity in humans lacking a functional FOXP2 allele and exhibits altered dopamine concentrations in humanized Foxp2 mice. Additionally, striatal dopaminergic input was not altered in chimpanzees that used socially learned attention‐getting sounds versus those that did not. This evidence indicates that the increase in dopamine innervation of the medial caudate nucleus in humans is a species‐typical characteristic not associated with experience‐dependent plasticity. The specificity of this increase may be related to the degree of convergence from cortical areas within this region of the striatum and may also be involved in human speech and language. J. Comp. Neurol. 524:2117–2129, 2016. © 2015 Wiley Periodicals, Inc.
The colour of the granite that built the city of São Paulo, Brazil
Authors: Del Lama Eliane Aparecida , Dehira Lauro Kazumi , Grossi Danielle , Kuzmickas Luciane 
Published: December 2015

AbstractThe city of São Paulo, until the 1900s, was restricted to a small central nucleus, also called the Historic Triangle, where there is a concentration of the oldest monuments and buildings of the city. They are built with a number of ornamental stones, but one of these predominates: Itaquera Granite. Currently, it is not quarried, but its exploitation dated from 1888. It was replaced by Gray Mauá Granite after the 1940s, partly because the Itaquera quarry was becoming exhausted and partly due to better technological characteristics of Mauá Granite. There are numerous examples of cultural heritage monuments and buildings made with Itaquera Granite in São Paulo's city. The examples selected for this study are: Saint Anthony's Church, The Girl and the Calf, Nostalgia, the Law School of the University of São Paulo, After the Bath and Amerindian Hunter. The purpose of this article is to characterize Itaquera Granite according to its colorimetric aspects and its colour variation. Colorimetric changes in the stone can be caused by many factors, such as cleaning methods, deposition of atmospheric pollutants, biological colonization, leaching of bronze, dissolution and reprecipitation of mortar, or even by natural causes such as the oxidation or alteration of minerals present in the stone. Measuring the change in colour can be useful for monitoring the development of natural changes, analyzing the effectiveness of treatments, and monitoring the degree of biological colonization in the monuments. In the long run, these data may aid in the treatment and restoration of these monuments. © 2015 Wiley Periodicals, Inc. Col Res Appl 41, 241–245, 2016
Unraveling the Role of Monovalent Halides in Mixed‐Halide Organic–Inorganic Perovskites
Authors: Deepa Melepurath , Ramos F. Javier , Shivaprasad S. M. , Ahmad Shahzada 
Published: December 2015

AbstractThe performance of perovskite solar cells is strongly influenced by the composition and microstructure of the perovskite. A recent approach to improve the power conversion efficiencies utilized mixed‐halide perovskites, but the halide ions and their roles were not directly studied. Unraveling their precise location in the perovskite layer is of paramount importance. Here, we investigated four different perovskites by using X‐ray photoelectron spectroscopy, and found that among the three studied mixed‐halide perovskites, CH3NH3Pb(I0.74Br0.26)3 and CH3NH3PbBr3−xClx show peaks that unambiguously demonstrate the presence of iodide and bromide in the former, and bromide and chloride in the latter. The CH3NH3PbI3−xClx perovskite shows anomalous behavior, the iodide content far outweighs that of the chloride; a small proportion of chloride, in all likelihood, resides deep within the TiO2/absorber layer. Our study reveals that there are many distinguishable structural differences between these perovskites, and that these directly impact the photovoltaic performances.
Resonance Raman Intensities Demonstrate that C5 Substituents Affect the Initial Excited‐State Structural Dynamics of Uracil More than C6 Substituents
Authors: Teimoory Faranak , Loppnow Glen R. 
Published: December 2015

AbstractResonance Raman derived initial excited‐state structural dynamics provide insight into the photochemical mechanisms of pyrimidine nucleobases, in which the photochemistry appears to be dictated by the C5 and C6 substituents. The absorption and resonance Raman spectra and excitation profiles of 5,6‐dideuterouracil were measured to further test this photochemical dependence on the C5 and C6 substituents. The resulting set of excited‐state reorganization energies of the observed internal coordinates were calculated and compared to those of other 5‐ and 6‐substituted uracils. The results show that the initial excited‐state dynamics along the C5C6 stretch responds to changes in mass at C5 and C6 in the same manner but that the in‐plane bends at C5 and C6 are more sensitive to substituents at the C5 position than at the C6 position. In addition, the presence of two deuterium substituents at C5 and C6 decreases the initial excited‐state structural dynamics along these in‐plane bends, in contrast to what is observed in the presence of two CH3 groups on C5 and C6. The results are discussed in the context of DNA nucleobase photochemistry.