bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validating the pivotal role of the immune system in low‐dose radiation‐induced tumor inhibition in Lewis lung cancer‐bearing mice
Authors: Zhou Lei , Zhang Xiaoying , Li Hui , Niu Chao , Yu Dehai , Yang Guozi , Liang Xinyue , Wen Xue , Li Min , Cui Jiuwei 
Published: February 2018

AbstractAlthough low‐dose radiation (LDR) possesses the two distinct functions of inducing hormesis and adaptive responses, which result in immune enhancement and tumor inhibition, its clinical applications have not yet been elucidated. The major obstacle that hinders the application of LDR in the clinical setting is that the mechanisms underlying induction of tumor inhibition are unclear, and the risks associated with LDR are still unknown. Thus, to overcome this obstacle and elucidate the mechanisms mediating the antitumor effects of LDR, in this study, we established an in vivo lung cancer model to investigate the participation of the immune system in LDR‐induced tumor inhibition and validated the pivotal role of the immune system by impairing immunity with high‐dose radiation (HDR) of 1 Gy. Additionally, the LDR‐induced adaptive response of the immune system was also observed by sequential HDR treatment in this mouse model. We found that LDR‐activated T cells and natural killer cells and increased the cytotoxicity of splenocytes and the infiltration of T cells in the tumor tissues. In contrast, when immune function was impaired by HDR pretreatment, LDR could not induce tumor inhibition. However, when LDR was administered before HDR, the immunity could be protected from impairment, and tumor growth could be inhibited to some extent, indicating the induction of the immune adaptive response by LDR. Therefore, we demonstrated that immune enhancement played a key role in LDR‐induced tumor inhibition. These findings emphasized the importance of the immune response in tumor radiotherapy and may help promote the application of LDR as a novel approach in clinical practice.
Determinants of malignant pleural mesothelioma survival and burden of disease in France: a national cohort analysis
Authors: Chouaid Christos , Assié Jean Baptiste , Andujar Pascal , Blein Cecile , Tournier Charlène , Vainchtock Alexandre , Scherpereel Arnaud , Monnet Isabelle , Pairon Jean Claude 
Published: February 2018

AbstractThis study was undertaken to determine the healthcare burden of malignant pleural mesothelioma (MPM) in France and to analyze its associations with socioeconomic deprivation, population density, and management outcomes. A national hospital database was used to extract incident MPM patients in years 2011 and 2012. Cox models were used to analyze 1‐ and 2‐year survival according to sex, age, co‐morbidities, management, population‐density index, and social deprivation index. The analysis included 1,890 patients (76% men; age: 73.6 ± 10.0 years; 84% with significant co‐morbidities; 57% living in urban zones; 53% in highly underprivileged areas). Only 1% underwent curative surgical procedure; 65% received at least one chemotherapy cycle, 72% of them with at least one pemetrexed and/or bevacizumab administration. One‐ and 2‐year survival rates were 64% and 48%, respectively. Median survival was 14.9 (95% CI: 13.7–15.7) months. The mean cost per patient was 27,624 ± 17,263 euros (31% representing pemetrexed and bevacizumab costs). Multivariate analyses retained men, age >70 years, chronic renal failure, chronic respiratory failure, and never receiving pemetrexed as factors of poor prognosis. After adjusting the analysis to age, sex, and co‐morbidities, living in rural/semi‐rural area was associated with better 2‐year survival (HR: 0.83 [95% CI: 0.73–0.94]; P < 0.01); social deprivation index was not significantly associated with survival. With approximately 1,000 new cases per year in France, MPMs represents a significant national health care burden. Co‐morbidities, sex, age, and living place appear to be significant factors of prognosis.
Long noncoding RNA MALAT1 knockdown reverses chemoresistance to temozolomide via promoting microRNA‐101 in glioblastoma
Authors: Cai Tao , Liu Yu , Xiao Jie 
Published: February 2018

AbstractGlioblastoma (GBM) is the most common and lethal tumor of the central nervous system with highly infiltrative and resistant to chemotherapy. Temozolomide (TMZ) is widely used as the first‐line treatment for the therapy of GBM. However, a considerable percentage inherent or acquired resistance in GBM accounts for many treatment failures of the TMZ chemotherapy. Therefore, a deeper understanding of the molecular characteristics underlying TMZ resistance and the identification of novel therapeutic target is urgent. Here, we show that MALAT1 was significantly upregulated in TMZ‐resistant GBM cells. On the other hand, MALAT1 knockdown reduces TMZ resistance of GBM cells both in vitro and in vivo by inhibiting cell proliferation and promoting apoptosis. We also show that miR‐101 overexpression reduced TMZ resistance of GBM cells and played an antagonistic role compared with MALAT1. Importantly, we demonstrate that MALAT1 promoted the chemoresistance through suppressing miR‐101 signaling pathway via directly binding it in GBM cells. In conclusion, our study indicates that knockdown of MALAT1 reverses chemoresistance to TMZ via promoting miR‐101 regulatory network in GBM and thus offers a novel prognostic marker and potential target for GBM TMZ‐based chemotherapy.
Efficient Synthesis of Light‐Triggered Circular Antisense Oligonucleotides Targeting Cellular Protein Expression
Authors: Yang Linlin , Kim Hyun Bum , Sul Jai‐Yoon , Yeldell Sean B. , Eberwine James H. , Dmochowski Ivan J. 
Published: February 2018

AbstractLight‐activated (“caged”) antisense oligonucleotides are powerful molecules for regulating gene expression at submicron spatial resolution through the focal modulation of endogenous cellular processes. Cyclized caged oligos are particularly promising structures because of their inherent stability and similarity to naturally occurring circular DNA and RNA molecules. Here, we introduce an efficient route for cyclizing an antisense oligodeoxynucleotide incorporating a photocleavable linker. Oligo cyclization was achieved for several sequences in nearly quantitative yields through intramolecular copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC). Caging stability and light activation were characterized by FRET efficiency, denaturing gel assay, and melting temperature measurements. Finally, a cyclized caged oligo was designed to target gfap, and it gave a tenfold reduction in glial fibrillary acidic protein upon photoactivation in astrocytes.
Substituents Have a Large Effect on Photochemical Generation of Benzyl Cations and DNA Cross‐Linking
Authors: Fan Heli , Sun Huabing , Peng Xiaohua 
Published: February 2018

AbstractPhotoactivated DNA interstrand cross‐linking agents have a wide range of biological applications. Recently, several aryl boronates have been reported to induce DNA interstrand cross‐link (ICL) formation via carbocations upon photoirradiation. Herein, we synthesized a series of new bifunctional phenyl compounds to test the generality of such a mechanism, and to understand how the chemical structure influences carbocation formation and the DNA cross‐linking process. These compounds efficiently form DNA ICLs via generated benzyl cations upon 350 nm irradiation. The DNA cross‐linking efficiency and the pathway for carbocation generation depend on both the aromatic substituents and the leaving groups. Bromine as a leaving group facilitates the DNA cross‐linking process in comparison with trimethyl ammonium salt. Both electron‐donating and ‐withdrawing substituents induce bathochromic shifts, which favor photoinduced DNA ICL formation. For the bromides, the benzyl cation intermediates were generated through oxidation of the corresponding benzyl radicals. However, for the ammonia salts, the benzyl cations were formed through two pathways: either through oxidation of the benzyl radicals or by direct heterolysis of the C−N bond. Photoinduced C−N homolysis to form benzyl radicals occurred with compounds having donating substituents, whereas direct heterolysis of the C−N bond occurred with those bearing withdrawing substituents. The adducts formed between 1 a and four natural nucleosides were characterized, indicating that the alkylation sites for the photogenerated benzyl cations are dG, dA, and dC.
Dinuclear Lanthanide(III)‐m‐ODO2A‐dimer Macrocyclic Complexes: Solution Speciation, DFT Calculations, Luminescence Properties, and Promoted Nitrophenyl‐Phosphate Hydrolysis Rates
Authors: Chang C. Allen , Lee Hwa‐Yu , Lin Syue‐Liang , Meng Ching‐Ning , Wu Tsung‐Ta 
Published: February 2018

AbstractPotentiometric speciation studies, mass spectrometry, and DFT calculations helped to predict the various structural possibilities of the dinuclear trivalent lanthanide ion (LnIII, Ln=La, Eu, Tb, Yb, Y) complexes of a novel macrocyclic ligand, m‐ODO2A‐dimer (H4L), to correlate with their luminescence properties and the promoted BNPP and HPNP phosphodiester bond hydrolysis reaction rates. The stability constants of the dinuclear Ln2(m‐ODO2A‐dimer) complexes and various hydrolytic species confirmed by mass spectrometry were determined. DFT calculations revealed that the Y2LH−1 and the Y2LH−2 species tended to form structures with the respective closed‐ and open‐form conformations. Luminescence lifetime data for the heterodimetallic TbEuL system confirmed the fluorescence resonance energy transfer from the TbIII to EuIII ion. The internuclear distance RTbEu values were estimated to be in the range of 9.4–11.3 Å (pH 6.7–10.6), which were comparable to those of the DFT calculated open‐form conformations. Multiple linear regression analysis of the kobs data was performed using the equation: kobs,corr.=kobs−kobs,OH=k
[Ln2LH−1]+k
[Ln2LH−2] for the observed Ln2L‐promoted BNPP/HPNP hydrolysis reactions in solution pH from 7 to 10.5 (Ln=Eu, Yb). The results showed that the second‐order rate constants for the Eu2LH−2 and Yb2LH−2 species were about 50–400 times more reactive than the structural analogous Zn2(m‐12 N3O‐dimer) system.
Elevated lipoprotein(a) and familial hypercholesterolemia in the coronary care unit: Between Scylla and Charybdis
Authors: Ellis Katrina L. , Pang Jing , Chieng David , Bell Damon A. , Burnett John R. , Schultz Carl J. , Hillis Graham S. , Watts Gerald F. 
Published: February 2018

BackgroundElevated lipoprotein(a) (Lp[a]) and familial hypercholesterolemia (FH) are inherited lipid disorders. Their frequencies, coexistence, and associations with premature coronary artery disease (CAD) in patients admitted to the coronary care unit (CCU) remain to be defined.HypothesisElevated Lp(a) and FH are commonly encountered among CCU patients and independently associated with increased premature CAD risk.MethodsPlasma Lp(a) concentrations were measured in consecutive patients admitted to the CCU with an acute coronary syndrome (ACS) or prior history of CAD for 6.5 months. Elevated Lp(a) was defined as concentrations ≥0.5 g/L. Patients with LDL‐C ≥ 5 mmol/L exhibited phenotypic FH. Premature CAD was diagnosed in those age < 60 years, and the relationship between this and elevated Lp(a) and FH was determined by logistic regression.Results316 patients were screened; 163 (51.6%) had premature CAD. Overall, elevated Lp(a) and FH were identified in 27.0% and 11.6% of patients, respectively. Both disorders were detected in 4.4% of individuals. Elevated Lp(a) (32.0% vs 22.2%; P = 0.019) and FH phenotype (15.5% vs 8.0%; P = 0.052) were more common with premature vs nonpremature CAD. Elevated Lp(a) alone conferred a 1.9‐fold, FH alone a 3.2‐fold, and the combination a 5.3‐fold increased risk of premature CAD (P = 0.005).ConclusionsElevated Lp(a) and phenotypic FH were commonly encountered and more frequent with premature CAD. The combination of both disorders is especially associated with increased CAD risk. Patients admitted to the CCU with ACS or previously documented CAD should be routinely screened for elevated Lp(a) and FH.
NT‐proBNP is associated with mortality and adverse cardiac events in patients with atrial fibrillation presenting to the emergency department
Authors: Holl Marijn J. , van den Bos Ewout J. , van Domburg Ron T. , Fouraux Michael A. , Kofflard Marcel J. 
Published: February 2018

BackgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia in the emergency department. The CHA2DS2‐VASc score helps to predict thromboembolic risk; however, the rate of other adverse cardiac events is more difficult to predict.HypothesisThe biomarker N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) has prognostic value in patients presenting to the emergency department with AF.MethodsDuring a 1.5‐year period, a prospective study was performed in consecutive patients presenting to the emergency department with AF on the presenting electrocardiogram. At baseline, NT‐proBNP was measured. The primary endpoints were all‐cause death and major adverse cardiac events (MACE: all‐cause mortality, myocardial infarction, or revascularization).ResultsA total of 355 patients were included (mean age, 71 years; 55% male). The median duration of follow‐up was 2 years. After adjustment for baseline variables, the logNT‐proBNP was independently correlated with death (hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.18‐1.99) and MACE (HR: 1.27, 95% CI: 1.03‐1.58). After adjustment for baseline variables, a high NT‐proBNP value (>500 pmol/L) was independently correlated with death (HR: 2.26, 95% CI: 1.19‐4.28), and for MACE a trend was seen (HR: 1.67, 95% CI: 0.96‐2.91) compared with a low value (<250 pmol/L).ConclusionsIn patients presenting to the emergency department with AF, higher NT‐proBNP values are independently associated with an increased mortality and MACE. Therefore, this biomarker may be a useful prognostic marker in the management and treatment of these patients.
Ultrasound‐Assisted Anti‐Solvent Crystallization of Telmisartan Using Dimethyl Sulfoxide as Organic Solvent
Authors: Sharma Chetan , Desai Meghal A. , Patel Sanjaykumar R. 
Published: February 2018

AbstractIn recent years, ultrasound assisted anti‐solvent crystallization has emerged as an excellent approach to reduce the particle size of poorly water‐soluble drugs, thereby achieving improvement in the solubility and bioavailability. In the present study, this concept is employed for telmisartan by studying various critical parameters like the effect of sonication time, sonication amplitude, drug solution concentration, solvent to anti‐solvent ratio, injection rate and crystallization temperature. The particle size of the commercial telmisartan is reduced from 10 µm to 200 nm by anti‐solvent crystallization method by applying 60% ultrasound amplitude for 15 min with 10 mg mL−1 drug concentration, 1:3 of solvent to anti‐solvent ratio, and 10 mL min−1 of injection rate at 30 °C. Physicochemical characteristics; morphology, crystalline structure, the presence of other chemical compounds, enthalpy change, and the melting point of a recovered drug are analyzed using various analytical tools. It is possible to achieve nanoparticles of telmisartan by symbiotic effect of sonication with anti‐solvent crystallization.
Cellular endogenous NAD(P)H fluorescence as a label‐free method for the identification of erythrocytes and reticulocytes
Authors: Tauzin L. , Campos V. , Tichet M. 
Published: February 2018

AbstractReticulocytes and erythrocytes are the ultimate differentiated stages of erythropoiesis. In addition to being anucleate cells, they are characterized by the clearance of their mitochondrial pool or lack thereof. Given that for most research‐oriented flow cytometry experiments erythrocytes and reticulocytes are often undesirable cell types, their identification and exclusion from analyses can be essential. Here, we describe a flow cytometric method based on cellular NAD(P)H‐related autofluorescence, whose localization is mainly associated with mitochondria. By increasing the sensitivity of the specific NAD(P)H‐fluorescence detector, we discovered a population with weak levels of NAD(P)H fluorescence signals whose immunophenotypical and physiological characterization in mouse bone marrow led to its identification as both erythrocytes and reticulocytes. Our method showed comparable sensitivity and specificity to the detection of red blood cells based on the absorption of light by oxyhemoglobin. This NAD(P)H‐based approach consistently identified over 95% of the total pool of erythrocytes and reticulocytes in bone marrow samples and revealed robust as over 93% of these two erythropoietic subsets were identified in melanoma tumor samples with the same method. The measurement of cellular endogenous NAD(P)H fluorescence, therefore, offers a reliable and straightforward alternative to identify erythrocytes and reticulocytes without additional immunostaining or the need to modify the cytometer's optical configuration. © 2018 International Society for Advancement of Cytometry
Development of Nonthermal Sterilization Treatment System without Impacting to Enzyme in Vegetable Drink by Pulsed Electric Field
Authors: SAITO KOKI , NOZAWA YASUHITO , MINAMITANI YASUSHI , FUKATA HIDEKI 
Published: February 2018

SUMMARYFor the sterilization of food, heat sterilization, chemical sterilization, and similar methods are available. However, they cause the change of the quality and flavor of the food. As the solution, the intense pulsed high electric field (IPEF) sterilization method has been studied. IPEF sterilization is used for the nonthermal sterilization of the foods because it destroys the cell membrane of bacteria physically. In this study, we have attempted to apply the IPEF sterilization for green juice. The development of a circulation sterilization system for a practical test was carried out. It was confirmed that enzyme included in the green juice was not deactivated when IPEF was applied. As a result, at applying 20‐min pulse electric field in 30 kV/cm and 40 kV/cm, survival ratios of viable bacteria in the green juice were reduced to about 40% and 12%, respectively. Also, deactivation of superoxide dismutase did not occur when the bacteria were sterilized.
Understanding social–ecological interdependence using ecosystem services perspective in Bhutan, Eastern Himalayas
Authors: Kandel Pratikshya , Tshering Dago , Uddin Kabir , Lhamtshok Tshering , Aryal Kamal , Karki Seema , Sharma Bikash , Chettri Nakul 
Published: February 2018

AbstractBiophysical and economic values are often used to aid understanding of the complex interplay between ecosystems, their services, and human well‐being, but community values are rarely considered. In a case study of Barshong gewog in Bhutan, we used mapping methods that involved (1) local knowledge and perceptions collected using participatory rural appraisal tools, (2) a household survey, and (3) geospatial inputs, to understand the linkages between human well‐being and ecosystem services at the local level, as perceived by the community. The study identified three major ecosystems—forest, agriculture, and freshwater—that contribute highly to local livelihoods. Collectively, these ecosystems provide a wide range of goods and services, including 22 provisioning, 13 regulating, 4 supporting, and 6 cultural services. About 85% of the households depend directly upon provisioning ecosystem services for their livelihoods and income. The study also identified the importance of the ecosystems in terms of three value domains—ecological, socioeconomic, and cultural.
Expanding spectrum of RARS2 gene disorders: Myoclonic epilepsy, mental retardation, spasticity, and extrapyramidal features
Authors: Mathew Thomas , Avati Amrutha , D'Souza Delon , Therambil Manjusha 
Published: February 2018

SummaryPontocerebellar hypoplasia type 6 (PCH6) is an autosomal recessive mitochondrial disease, typically characterized by pontine atrophy, vermian hypoplasia, infantile encephalopathy, generalized hypotonia, and intractable seizures. The purpose of this study is to describe the seizures and other neurological manifestations of RARS2 gene mutations and to compare the clinical features with other causes of progressive myoclonic epilepsy. Detailed history, physical examination, and clinical and genetic work‐up were performed in 2 siblings who presented with progressive myoclonic epilepsy. One sibling, a 20‐year‐old woman, and the other a 24‐year‐old man, had a homozygous missense variant (c.848T>A; p.Leu283Gln) in exon 10 of the RARS2 gene. The female patient had action and audiogenic myoclonic jerks, postural tremors, spastic dysarthria, and bradykinesia, and her male sibling had similar features with oculomotor apraxia. The RARS2 gene mutation can present with myoclonic epilepsy, mental retardation, and pyramidal and extrapyramidal features, and is an important differential for causes of progressive myoclonic epilepsy.
Combined effects of interspecies interaction, temperature, and zinc on Daphnia longispina population dynamics
Authors: Van de Perre Dimitri , Janssen Colin R. , De Schamphelaere Karel A.C. 
Published: February 2018

Abstract

Under natural conditions, organisms can experience a variety of abiotic (e.g., temperature, pH) and biotic (e.g., species interactions) factors, which can interact with toxicant effects. By ignoring species interactions conventional ecotoxicological studies (i.e., single-species tests) oversimplify the actual field situation. We investigated whether temperature and interspecific competition affected the effects of zinc (Zn) on a Daphnia longispina population. The D. longispina populations were exposed in a full factorial design to 3 different Zn treatments (background, 29, and 110 μg Zn/L), 2 different temperature regimes (cold, 17–18 °C; warm, 21–22 °C), and 2 interspecific competition levels (no interspecific Brachionus competition = no Brachionus calyciflorus added; interspecific Brachionus competition = B. calyciflorus added). Interspecific Brachionus competition and temperature by itself had a limited effect on the Daphnia abundance but significantly interacted with the highest Zn concentration. Without Brachionus competition the D. longispina juvenile and adult abundances under warm conditions were up to 5.5 and 21 times lower, respectively, in the high Zn treatment in comparison with the Zn control, whereas under cold conditions no significant Zn effect was observed. However, with Brachionus competition the highest Zn treatment was on average 2.2 times less toxic to the D. longispina juvenile abundance at higher temperatures. Under cold conditions the highest Zn treatment affected the juvenile abundance sooner and up to 9 times more negatively when simultaneously faced with Brachionus competition. It is possible that the competition for food reduced the amount of energy that could be used by D. longispina for reproduction, and the metabolic costs increased as a result of Zn stress. The present study clearly illustrated the influence of temperature and competition on the effects of a chemical stressor. Thus, not considering such factors in ecological risk assessment may underestimate or overestimate risks in aquatic ecosystems when extrapolating data from standard single-species tests to the field. Environ Toxicol Chem 2018;37:1668–1678. © 2018 SETAC