bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term in vitro treatment with telomerase inhibitor MST‐312 induces resistance by selecting long telomeres cells
Authors: Morais Karollyne da Silva , Arcanjo Daniel da Silva , de Faria Lopes Giselle Pinto , da Silva Guilherme Guimarães , da Mota Tales Henrique Andrade , Gabriel Thiago Rodrigues , Rabello Ramos Doralina do Amaral , Silva Fábio Pittella , de Oliveira Diêgo Madureira 
Published: April 2019

Telomerase is a good target for new anticancer drug development because it is present in over 85% of human tumours. However, despite chronic therapy is a condition for anti‐telomerase approach, the effects of long‐term treatment with telomerase inhibitors remain not well understood. In this work, it was evaluated the effects of long‐term treatment of human MDA‐MB‐231 breast cancer cells with the telomerase inhibitor MST‐312. Cells were treated for 72 hours or 140 days, and it was accessed their viability, proliferation rate, morphology, telomeric DNA content, and resistance mechanism. The drug had a clear short‐term effect, including chemosensitizing cells for docetaxel and irinotecan, but the chronic exposition led to selection of long telomeres clones, changing characteristics of original cell line. This effect was confirmed in a clonal culture with homogenous karyotype. MRP‐1 expression and alternative lengthening of telomeres (ALT) were discarded as additional mechanisms of resistance. This data suggest that, considering the intra‐tumour heterogeneity (ITH), what is already a big challenge for treatment of cancer, chronic exposition to telomerase inhibitors can promote tumour adaptations with potential clinical repercussion, drawing attention to ongoing clinical trials and pointing important considerations most times neglected on studies about use of these inhibitors on cancer therapy.Significance of the studyAntitumour action of telomerase inhibitors is well known, but it depends on a long‐term exposition because cells will undergo telomere erosion only after many duplication cycles. Recently, the frustrating results of clinical trials with these inhibitors aroused the interest of the scientific community to understand the mechanisms of resistance to anti‐telomerase therapy. In this study, we conducted an 18‐week experiment to show that telomerase inhibition can lead to cell adaptations and selection of long‐telomeres clones, leading to acquisition of resistance. However, we also showed that this inhibitor can sensitize cells to the chemotherapeutic drugs docetaxel and irinotecan.
Biocatalytic Reversal of Advanced Glycation End Product Modification
Authors: Kim Nam Y. , Goddard Tyler N. , Sohn Seungjung , Spiegel David A. , Crawford Jason M. 
Published: April 2019

AbstractAdvanced glycation end products (AGEs) are a heterogeneous group of molecules that emerge from the condensation of sugars and proteins through the Maillard reaction. Despite a significant number of studies showing strong associations between AGEs and the pathologies of aging‐related illnesses, it has been a challenge to establish AGEs as causal agents primarily due to the lack of tools in reversing AGE modifications at the molecular level. Herein, we show that MnmC, an enzyme involved in a bacterial tRNA‐modification pathway, is capable of reversing the AGEs carboxyethyl‐lysine (CEL) and carboxymethyl‐lysine (CML) back to their native lysine structure. Combining structural homology analysis, site‐directed mutagenesis, and protein domain dissection studies, we generated a variant of MnmC with improved catalytic properties against CEL in its free amino acid form. We show that this enzyme variant is also active on a CEL‐modified peptidomimetic and an AGE‐containing peptide that has been established as an authentic ligand of the receptor for AGEs (RAGE). Our data demonstrate that MnmC variants are promising lead catalysts toward the development of AGE‐reversal tools and a better understanding of AGE biology.
Dimeric C34 Derivatives Linked through Disulfide Bridges as New HIV‐1 Fusion Inhibitors
Authors: Kobayakawa Takuya , Ebihara Kento , Honda Yuzuna , Fujino Masayuki , Nomura Wataru , Yamamoto Naoki , Murakami Tsutomu , Tamamura Hirokazu 
Published: April 2019

AbstractC34, a 34‐mer fragment peptide, is contained in the HIV‐1 envelope protein gp41. A dimeric derivative of C34 linked through a disulfide bridge at its C terminus was synthesized and found to display potent anti‐HIV activity, comparable with that of a previously reported PEGylated dimer of C34REG. The reduction in the size of the linker moiety for dimerization was thus successful, and this result might shed some light on the mechanism of the suppression of six‐helix bundle formation by these C34 dimeric derivatives. Addition of a Gly‐Cys(CH2CONH2)‐Gly‐Gly motif at the N‐terminal position of a C34 monomeric derivative significantly increased the anti‐HIV‐1 activity. This moiety functions as a new pharmacophore, and this might provide a useful insight into the design of potent HIV‐1 fusion inhibitors.
Physicochemical Characterization of Polymer‐Stabilized Coacervate Protocells
Authors: Yewdall N. Amy , Buddingh Bastiaan C. , Altenburg Wiggert J. , Timmermans Suzanne B. P. E. , Vervoort Daan F. M. , Abdelmohsen Loai K. E. A. , Mason Alexander F. , van Hest Jan C. M. 
Published: April 2019

AbstractThe bottom‐up construction of cell mimics has produced a range of membrane‐bound protocells that have been endowed with functionality and biochemical processes reminiscent of living systems. The contents of these compartments, however, experience semidilute conditions, whereas macromolecules in the cytosol exist in protein‐rich, crowded environments that affect their physicochemical properties, such as diffusion and catalytic activity. Recently, complex coacervates have emerged as attractive protocellular models because their condensed interiors would be expected to mimic this crowding better. Here we explore some relevant physicochemical properties of a recently developed polymer‐stabilized coacervate system, such as the diffusion of macromolecules in the condensed coacervate phase, relative to in dilute solutions, the buffering capacity of the core, the molecular organization of the polymer membrane, the permeability characteristics of this membrane towards a wide range of compounds, and the behavior of a simple enzymatic reaction. In addition, either the coacervate charge or the cargo charge is engineered to allow the selective loading of protein cargo into the coacervate protocells. Our in‐depth characterization has revealed that these polymer‐stabilized coacervate protocells have many desirable properties, thus making them attractive candidates for the investigation of biochemical processes in stable, controlled, tunable, and increasingly cell‐like environments.
Spatial‐spectral analysis method using texture features combined with PCA for information extraction in hyperspectral images
Authors: Xu Jun‐Li , Gowen Aoife A. 
Published: April 2019

AbstractThis work proposes a new method to treat spatial and spectral information interactively. The method extracts spatial features, ie, variogram, gray‐level co‐occurrence matrix (GLCM), histograms of oriented gradients (HOG), and local binary pattern (LBP) features, from each wavelength image of hypercube and principal component analysis (PCA) is applied on this spatial feature matrix to identify wavelength‐dependent variation in spatial patterns. Resultant image is obtained by projecting the score values to the original data. Three datasets, including a synthetic hyperspectral image (Dataset 1), a set of real hyperspectral images of salmon fillets (Dataset 2), and remote‐sensing images (Dataset 3), were utilized to evaluate the performance of the proposed method. Results from Dataset 1 showed that the spatial‐spectral methods had the potential of reducing baseline offset noise. Dataset 2 revealed that spatial‐spectral methods can alleviate noisy pixels with strong signal and reduce shadow effects. In addition, substantial improvements were obtained in case of classification between white stripe and red muscle pixels by using the HOG‐based approach with correct classification rate (CCR) of 0.97 compared with the models directly built from raw and standard normal variate (SNV) preprocessed spectra (CCR = 0.94). Samson image of Dataset 3 suggested the flexibility and effectiveness of the proposed method by improving CCR of 0.96 using conventional PCA on SNV pretreated spectra to 0.98 using GLCM‐based approach on SNV preprocessed spectra. Overall, experimental results demonstrated that the spatial‐spectral methods can improve the results found by using the spectral information alone because of the spatial information provided.
A General One‐Pot Methodology for the Preparation of Mono‐ and Bimetallic Nanoparticles Supported on Carbon Nanotubes: Application in the Semi‐hydrogenation of Alkynes and Acetylene
Authors: Lomelí‐Rosales Diego A. , Delgado Jorge A. , Díaz de los Bernardos Miriam , Pérez‐Rodríguez Sara , Gual Aitor , Claver Carmen , Godard Cyril 
Published: April 2019

AbstractA facile and straightforward methodology for the preparation of monometallic (copper and palladium) and bimetallic nanocatalysts (NiCu and PdCu) stabilized by a N‐heterocyclic carbene ligand is reported. Both colloidal and supported nanoparticles (NPs) on carbon nanotubes (CNTs) were prepared in a one‐pot synthesis with outstanding control on their size, morphology and composition. These catalysts were evaluated in the selective hydrogenation of alkynes and alkynols. PdCu/CNTs revealed an efficient catalytic system providing high selectivity in the hydrogenation of terminal and internal alkynes. Moreover, this catalyst was tested in the semi‐hydrogenation of acetylene in industrially relevant acetylene/ethylene‐rich model gas feeds and showed excellent stability even after 40 h of reaction.
Synthesis of New Cyclomarin Derivatives and Their Biological Evaluation towards Mycobacterium Tuberculosis and Plasmodium Falciparum
Authors: Kiefer Alexander , Bader Chantal D. , Held Jana , Esser Anna , Rybniker Jan , Empting Martin , Müller Rolf , Kazmaier Uli 
Published: April 2019

AbstractCyclomarins are highly potent antimycobacterial and antiplasmodial cyclopeptides isolated from a marine bacterium (Streptomyces sp.). Previous studies have identified the target proteins and elucidated a novel mode of action, however there are currently only a few studies examining the structure–activity relationship (SAR) for both pathogens. Herein, we report the synthesis and biological evaluation of 17 novel desoxycyclomarin‐inspired analogues. Optimization via side chain modifications of the non‐canonical amino acids led to potent lead structures for each pathogen.
Auslegung von Blasensäulen mithilfe von Compartmentmodellen
Authors: Rieth Iris , Grünewald Marcus 
Published: April 2019

AbstractIn Blasensäulen sind die Phänomene des Stoff‐ und Wärmetransportes sowie der Reaktion eng mit der komplexen Fluiddynamik verknüpft. Die Compartmentmodellierung mehrphasiger Reaktoren bietet in diesem Zusammenhang einen Lösungsansatz, der zum einen die o. g. Einzelphänomene integriert und zum anderen bei vertretbarem Rechenaufwand neben der axialen auch eine radiale Auflösung der Modellparameter innerhalb des Reaktors bietet. Im Rahmen dieses Beitrags werden Methoden zur Generierung eines Compartmentmodells aufgezeigt, das dann der Optimierung einer Produktionsblasensäule dienen kann.
Phase 1/2 study of fractionated dose lutetium‐177–labeled anti–prostate‐specific membrane antigen monoclonal antibody J591 (177Lu‐J591) for metastatic castration‐resistant prostate cancer
Authors: Tagawa Scott T. , Vallabhajosula Shankar , Christos Paul J. , Jhanwar Yuliya S. , Batra Jaspreet S. , Lam Linda , Osborne Joseph , Beltran Himisha , Molina Ana M. , Goldsmith Stanley J. , Bander Neil H. , Nanus David M. 
Published: April 2019

BackgroundProstate cancer is radiosensitive. Prostate‐specific membrane antigen (PSMA) is selectively overexpressed on advanced, castration‐resistant tumors. Lutetium‐177–labeled anti‐PSMA monoclonal antibody J591 (177Lu‐J591) targets prostate cancer with efficacy and dose‐response/toxicity data when delivered as a single dose. Dose fractionation may allow higher doses to be administered safely.MethodMen with metastatic castration‐resistant prostate cancer refractory to or refusing standard treatment options with normal neutrophil and platelet counts were enrolled in initial phase 1b dose‐escalation cohorts followed by phase 2a cohorts treated at recommended phase 2 doses (RP2Ds) comprising 2 fractionated doses of 177Lu‐J591 2 weeks apart. 177Lu‐J591 imaging was performed after treatment, but no selection for PSMA expression was performed before enrollment. Phase 2 patients had circulating tumor cell (CTC) counts assessed before and after treatment.ResultsForty‐nine men received fractionated doses of 177Lu‐J591 ranging from 20 to 45 mCi/m2 ×2 two weeks apart. The dose‐limiting toxicity in phase 1 was neutropenia. The RP2Ds were 40 mCi/m2 and 45 mCi/m2 ×2. At the highest RP2D (45 mCi/m2 ×2), 35.3% of patients had reversible grade 4 neutropenia, and 58.8% of patients had thrombocytopenia. This dose showed a greater decrease in prostate‐specific antigen (PSA) levels and longer survival (87.5% with any PSA decrease, 58.8% with >30% decrease, 29.4% with >50% decrease; median survival, 42.3 months [95% confidence interval, 19.9‐64.7]). Fourteen of 17 (82%) patients with detectable CTCs experienced a decrease in CTC count. Overall, 79.6% of patients had positive PSMA imaging; those with less intense PSMA imaging tended to have poorer responses.ConclusionFractionated administration of 177Lu‐J591 allowed higher cumulative radiation dosing. The frequency and depth of PSA decrease, overall survival, and toxicity (dose‐limiting myelosuppression) increased with higher doses.
Trends in pediatric thyroid cancer incidence in the United States, 1998‐2013
Authors: Bernier Marie‐Odile , Withrow Diana R. , Berrington de Gonzalez Amy , Lam Clara J. K. , Linet Martha S. , Kitahara Cari M. , Shiels Meredith S. 
Published: April 2019

BackgroundPediatric differentiated thyroid cancer (DTC) rates have increased over time in the United States and worldwide. Improvements in imaging for the diagnosis of DTC have been hypothesized as a potential driver of these increases. This study stratifies temporal trends in pediatric DTC by stage and tumor size to assess whether rates of large, late‐stage cancers, which are likely to be clinically meaningful, are increasing over time.MethodsAge‐standardized incidence rates (ASRs) of DTC and annual percent changes (APCs) in primary DTC rates were estimated for 0‐ to 19‐year‐olds with data from 39 US cancer registries during 1998‐2013.ResultsDuring 1998‐2013, 7296 cases of DTC were diagnosed (6652 papillary cases and 644 follicular cases). APCs of pediatric DTCs significantly increased by 4.43%/y [95% CI, 3.74%/y‐5.13%/y], primarily because of increases in papillary histologies. Increasing trends were observed for children aged 10 to 19 years for both sexes and for non‐Hispanic whites, non‐Hispanic blacks, and Hispanics. Rates increased significantly over the time period for all tumor stages (APClocalized, +4.06%/y [95% CI, 2.84%/y‐5.29%/y]; APCregional, +5.68%/y [95% CI, 4.64%/y‐6.73%/y]; APCdistant, +8.55%/y [95% CI, 5.03%/y‐12.19%/y]) and across tumor sizes (APC<1 cm, +9.46%/y [95% CI, 6.13%/y‐12.90%/y]; APC1‐2 cm, +6.92%/y [95% CI, 4.31%/y‐9.60%/y]; APC>2 cm, +4.69%/y [95% CI, 2.75%/y‐6.67%/y]).ConclusionsSignificantly increasing rates of DTC over time among 10‐ to 19‐year‐olds in the United States are unlikely to be entirely explained by increases in medical surveillance during childhood because rates of large and late‐stage DTC are increasing over time. Future studies should examine environmental and other factors that may be contributing to rising DTC rates.
A phase 1 trial of the oral DNA methyltransferase inhibitor CC‐486 and the histone deacetylase inhibitor romidepsin in advanced solid tumors
Authors: Gaillard Stéphanie L. , Zahurak Marianna , Sharma Anup , Durham Jennifer N. , Reiss Kim A. , Sartorius‐Mergenthaler Susan , Downs Melinda , Anders Nicole M. , Ahuja Nita , Rudek Michelle A. , Azad Nilofer 
Published: April 2019

BackgroundEpigenetic abnormalities are manifold in all solid tumors and include changes in chromatin configuration and DNA methylation. The authors designed a phase 1 study to evaluate the oral DNA methyltransferase inhibitor CC‐486 combined with the histone deacetylase inhibitor romidepsin in advanced solid tumors with dose expansion to further evaluate pharmacodynamics and possible clinical benefit of the recommended phase 2 dose (RP2D).MethodsThis was a phase 1 study with a 3 + 3 dose‐escalation design and an expansion phase for patients with virally mediated cancers. The disease control rate (DCR) was the primary outcome for the expansion cohort. Correlative studies included long interspersed nucleotide element 1 (LINE‐1) methylation and drug exposure in blood samples (clinicaltrials.gov identifier NCT01537744).ResultsFourteen patients were enrolled in the dose‐escalation portion at 3 dose levels. Three patients experienced dose‐limiting toxicities; the RP2D was oral CC‐486 300 mg daily on days 1 through 14 and romidepsin 8 mg/m2 on days 8 and 15. Because of slow accrual into the expansion phase, the trial was closed after 4 patients enrolled. Common toxicities of the combination included nausea (83.3%), anorexia (72.2%), fatigue (61.1%), and constipation (55.6%). There were 12 patients evaluable for response, 5 with stable disease, of whom 2 received >4 cycles; there were no responses. Exposure to CC‐486 and romidepsin was consistent with prior data. LINE‐1 methylation on C1D8 was significantly reduced (mean, −6.23; 95% CI, −12.23, −0.24; P = .04).ConclusionsAlthough, at the RP2D, the combination of CC‐486 and romidepsin was tolerable, no significant anticancer activity was observed. Significant demethylation in post‐treatment circulating tumor DNA and biopsies provided proof of target acquisition.
Maintenance of physical activity and sedentary behavior change, and physical activity and sedentary behavior change after an abridged intervention: Secondary outcomes from the ACTIVATE Trial
Authors: Lynch Brigid M. , Nguyen Nga H. , Moore Melissa M. , Reeves Marina M. , Rosenberg Dori E. , Boyle Terry , Milton Shakira , Friedenreich Christine M. , Vallance Jeff K. , English Dallas R. 
Published: April 2019

BackgroundThis brief report examines the maintenance of moderate to vigorous physical activity (MVPA) and sedentary behavior changes approximately 12 weeks after the delivery of the ACTIVATE Trial primary intervention (use of the Garmin Vivofit 2 activity tracker coupled with a behavioral feedback and goal‐setting session and 5 telephone‐delivered health coaching sessions). We also examine the efficacy of an abridged intervention (use of the Garmin Vivofit 2 only) in the waitlist control group.MethodsA pre‐post design was employed to examine the secondary aims of the ACTIVATE Trial (n = 80; mean age = 62 years). MVPA and sedentary behavior were measured using Actigraph and activPAL accelerometers after delivery of the primary intervention (T2), and again 12 weeks later (T3). Linear mixed models with random effects were used to examine within‐group changes in MVPA and sitting time variables.ResultsAfter the 12‐week follow‐up period, women in the primary intervention group had maintained their higher levels of MVPA (change from T2 to T3 = 14 min/wk; 95% CI = −18 to 46; P = .37). However, their sitting time increased slightly, by 7 min/d (95% CI = −20 to 34; P = .58), but it did not return to its preintervention level. After receiving the Garmin Vivofit 2, the waitlist control group increased their MVPA by 33 min/wk (95% CI = 3‐64; P = .03) and reduced their sitting time by 38 min/d (95% CI = −69 to −7; P = .02) over the same 12‐week period.ConclusionThe secondary outcomes from the ACTIVATE Trial suggest that wearable technology may generate sustainable changes in MVPA and sitting time. Wearable technology alone may be sufficient to change behavior, at least in the short term.
A randomized controlled trial of a wearable technology‐based intervention for increasing moderate to vigorous physical activity and reducing sedentary behavior in breast cancer survivors: The ACTIVATE Trial
Authors: Lynch Brigid M. , Nguyen Nga H. , Moore Melissa M. , Reeves Marina M. , Rosenberg Dori E. , Boyle Terry , Vallance Jeff K. , Milton Shakira , Friedenreich Christine M. , English Dallas R. 
Published: April 2019

BackgroundThe benefits of an active lifestyle after a breast cancer diagnosis are well recognized, but the majority of survivors are insufficiently active. The ACTIVATE Trial examined the efficacy of an intervention (use of the Garmin Vivofit 2 activity monitor coupled with a behavioral feedback and goal‐setting session and 5 telephone‐delivered health coaching sessions) to increase moderate to vigorous physical activity (MVPA) and reduce sedentary behavior in breast cancer survivors.MethodsThis randomized controlled trial recruited 83 inactive, postmenopausal women diagnosed with stage I‐III breast cancer who had completed primary treatment. Participants were randomly assigned to the intervention group or to the control group, and the intervention was delivered over a 12‐week period. MVPA and sedentary behavior were measured with Actigraph and activPAL accelerometers at baseline (T1) and at the end of the intervention (T2).ResultsRetention in the trial was high, with 80 (96%) of participants completing T2 data collection. At T2, there was a significant between‐group difference in MVPA (69 min/wk; 95% CI = 22‐116) favoring the intervention group. The trial resulted in a statistically significant decrease in both total sitting time and prolonged bouts (≥20 min) of sitting, with between‐group reductions of 37 min/d (95% CI = −72 to −2) and 42 min/d (95% CI = −83 to −2), respectively, favoring the intervention group.ConclusionResults from the ACTIVATE Trial suggest that the use of wearable technology presents an inexpensive and scalable opportunity to facilitate more active lifestyles for cancer survivors. Whether or not such wearable technology‐based interventions can create sustainable behavioral change should be the subject of future research.
Cl2 Production by Photocatalytic Oxidation of HCl over TiO2
Authors: Rath Tobias , Uhrich Andrej , Lüken Alexander , Zhao Guixia , Rittermeier André , Muhler Martin 
Published: April 2019

AbstractWe studied the photocatalytic aerobic oxidation of HCl over TiO2 for producing Cl2. Steady‐state Cl2 production rates were determined with a photocatalytic fixed‐bed gas‐phase reactor equipped with UV light‐emitting diodes (LEDs) using iodometric titration as online analytics. We found stable Cl2 production rates of up to 16 mmol h−1 m−2 for commercial anatase TiO2 Hombikat UV100. The rate increased linearly with temperature from 21 to 140 °C, indicating the acceleration of the limiting desorption rate of the coupled product water. Comparing different TiO2 polymorphs revealed that anatase possesses higher activity than rutile. The adsorption of HCl was monitored in situ by IR spectroscopy. The IR spectra indicated that HCl chemisorption chlorinates the surface of TiO2 under the reaction conditions, suggesting it to be the first step of the reaction mechanism. High stability opens up the opportunity of developing a promising photocatalytic process of HCl recycling at lower temperatures suitable for reaching full conversion.