bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintenance efficacy designs in psychiatry: Randomized discontinuation trials – enriched but not better
Authors: Ghaemi S. N. , Selker Harry P. 
Published: July 2017

IntroductionAlthough classical randomized clinical trials (RCTs) are the gold standard for proof of drug efficacy, randomized discontinuation trials (RDTs), sometimes called “enriched” trials, are used increasingly, especially in psychiatric maintenance studies.MethodsA narrative review of two decades of experience with RDTs.ResultsRDTs in psychiatric maintenance trials tend to use a dependent variable as a predictor: treatment response. Treatment responders are assessed for treatment response. This tautology in the logic of RDTs renders them invalid, since the predictor and the outcome are the same variable. Although RDTs can be designed to avoid this tautologous state of affairs, like using independent predictors of outcomes, such is not the case with psychiatric maintenance studiesFurther, purported benefits of RDTs regarding feasibility were found to be questionable. Specifically, RDTs do not enhance statistical power in many settings, and, because of high dropout rates, produce results of questionable validity. Any claimed benefits come with notably reduced generalizability.ConclusionsRDTs appear to be scientifically invalid as used in psychiatric maintenance designs. Their purported feasibility benefits are not seen in actual trials for psychotropic drugs. There is warrant for changes in federal policy regarding marketing indications for maintenance efficacy using the RDT design.
Analyzing Free-Free Beams by Green's Functions and Fredholm Alternative Theorem
Authors: Rezaiee-Pajand M. , Aftabi Sani A. , Hozhabrossadati S. M. 
Published: July 2017

AbstractThis article deals with the analysis of free-free beams by an analytical method. The well-known Green's function method is employed, and exact solution for the problem is obtained. As a second problem, the simply supported-free beam with rotational rigid body motion is analyzed. It is initially shown that ordinary Green's functions cannot be constructed due to a mathematical contradiction. To remedy this limitation, the Fredholm Alternative Theorem is utilized. This theorem eliminates the contradiction and enables analysts to obtain modified Green's functions. The fundamental existence conditions are derived and thoroughly investigated from the structural point of view. Finally, the deflection functions of these beams are found using modified Green's functions.
A multinational and multidisciplinary approach to treat CHD in paediatric age in Angola: initial experience of a medical-surgical centre for children with heart disease in Angola
Authors: Nunes Maria Ana S. , Magalhães Manuel P. , Uva Miguel S. , Heitor Patrícia , Henriques Ana , Manuel Valdano , Miguel Gade , Júnior António F. 
Published: July 2017

AbstractBackgroundEpidemiological patterns of cardiac disease differ between developed countries and African nations. Despite the collaborative efforts of developed countries, several obstacles hinder the implementation of successful programmes for the management of children with heart disease in Africa.Materials and methodsThis study is a retrospective analysis of a bi-national two-institution partnership programme for the treatment of children with congenital and acquired heart disease. In April, 2011, a continuous medical-surgical programme was inaugurated at Clínica Girassol in Luanda. The main goals were to initiate permanent and local delivery of services while training local teams, allowing autonomous medical and surgical management of children with heart disease.ResultsBetween April, 2011 and August, 2015, a total of 1766 procedures were performed on 1682 children. Of them, 1539 had CHD and 143 had acquired heart disease; 94 children underwent interventional treatment. A total of 1672 paediatric surgeries were performed on 1588 children: 1087 (65%) were performed with extracorporeal circulation and 585 (35%) were off-pump. The age distribution of the children was 4.5% (n=76) neonatal, 40.4% (n=675) between 30 days and 1 year, and 55.1% (n=921) over 1 year. There were 76 re-operations (4.5%) due to complications. The 30-day mortality rate was 4.2% (71 patients). Education-wise, several Angolan medical and surgical specialists were trained, allowing near-autonomous cardiac care delivery in children with heart disease.ConclusionAn innovative cooperation model between a European and an African centre based on permanent delivery of care and education allowed for effective training of local teams and treatment of children with heart disease in their own environment.
Multiplex PCR effectively identifies tetraploid Triticum AABB – or AAGG-genome species
Authors: Tanno Ken-Ichi , Takeuchi Ayaka , Akahori Eri , Kobayashi Keiko , Kawahara Taihachi , Yamane Kyoko 
Published: July 2017

AbstractWe developed a multiplex PCR DNA marker for quick and easy identification of the AAGG-genome timopheevii lineage, including Triticum timopheevii, Triticum araraticum and hexaploid Triticum zhukovskyi (AAAmAmGG), and the AABB-genome emmer wheat lineage, including Triticum durum, Triticum dicoccum and Triticum dicoccoides. Distinguishing between tetraploid AAGG- and AABB-genome wheat species based on morphology is known to be difficult. This multiplex PCR system is based on the simultaneous PCR amplification of two chloroplast regions, matK and rbcL. The matK region molecularly distinguishes the two lineages, whereas the rbcL region is a positive control amplicon. We also examined whether the simple sequence repeat is a fixed mutation within species, using genetic resources in the collection of KOMUGI, Kyoto University, which comprises accessioned species collected across diverse geographical areas. The multiplex PCR marker distinguished AAGG from AABB species with complete accuracy.
Wafer-scale single-crystal perovskite patterned thin films based on geometrically-confined lateral crystal growth
Authors: Lee Lynn , Baek Jangmi , Park Kyung Sun , Lee Yong-EunKoo , Shrestha Nabeen K. , Sung Myung M. 
Published: July 2017

AbstractWe report a facile roll-printing method, geometrically confined lateral crystal growth, for the fabrication of large-scale, single-crystal CH3NH3PbI3perovskite thin films. Geometrically confined lateral crystal growth is based on transfer of a perovskite ink solution via a patterned rolling mould to a heated substrate, where the solution crystallizes instantly with the immediate evaporation of the solvent. The striking feature of this method is that the instant crystallization of the feeding solution under geometrical confinement leads to the unidirectional lateral growth of single-crystal perovskites. Here, we fabricated single-crystal perovskites in the form of a patterned thin film (3 × 3 inch) with a high carrier mobility of 45.64 cm2 V−1 s−1. We also used these single-crystal perovskite thin films to construct solar cells with a lateral configuration. Their active-area power conversion efficiency shows a highest value of 4.83%, which exceeds the literature efficiency values of lateral perovskite solar cells.
Generation and comparison of CRISPR-Cas9 and Cre-mediated genetically engineered mouse models of sarcoma
Authors: Huang Jianguo , Chen Mark , Whitley Melodi Javid , Kuo Hsuan-Cheng , Xu Eric S. , Walens Andrea , Mowery Yvonne M. , Van Mater David , Eward William C. , Cardona Diana M. , Luo Lixia , Ma Yan , Lopez Omar M. , Nelson Christopher E. , Robinson-Hamm Jacqueline N. , Reddy Anupama , Dave Sandeep S. , Gersbach Charles A. , Dodd Rebecca D. , Kirsch David G. 
Published: July 2017

AbstractGenetically engineered mouse models that employ site-specific recombinase technology are important tools for cancer research but can be costly and time-consuming. The CRISPR-Cas9 system has been adapted to generate autochthonous tumours in mice, but how these tumours compare to tumours generated by conventional recombinase technology remains to be fully explored. Here we use CRISPR-Cas9 to generate multiple subtypes of primary sarcomas efficiently in wild type and genetically engineered mice. These data demonstrate that CRISPR-Cas9 can be used to generate multiple subtypes of soft tissue sarcomas in mice. Primary sarcomas generated with CRISPR-Cas9 and Cre recombinase technology had similar histology, growth kinetics, copy number variation and mutational load as assessed by whole exome sequencing. These results show that sarcomas generated with CRISPR-Cas9 technology are similar to sarcomas generated with conventional modelling techniques and suggest that CRISPR-Cas9 can be used to more rapidly generate genotypically and phenotypically similar cancers.
Comparative effectiveness of a portion-controlled meal replacement program for weight loss in adults with and without diabetes/high blood sugar
Authors: Coleman C D , Kiel J R , Mitola A H , Arterburn L M 
Published: July 2017

Abstract
Background:
Individuals with type 2 diabetes (DM2) may be less successful at achieving therapeutic weight loss than their counterparts without diabetes. This study compares weight loss in a cohort of adults with DM2 or high blood sugar (D/HBS) to a cohort of adults without D/HBS. All were overweight/obese and following a reduced or low-calorie commercial weight-loss program incorporating meal replacements (MRs) and one-on-one behavioral support.

Subjects/Methods:
Demographic, weight, body composition, anthropometric, pulse and blood pressure data were collected as part of systematic retrospective chart review studies. Differences between cohorts by D/HBS status were analyzed using Mann–Whitney U-tests and mixed model regression.

Results:
A total of 816 charts were included (125 with self-reported D/HBS). The cohort with D/HBS had more males (40.8 vs 25.6%), higher BMI (39.0 vs 36.3 kg m−2) and was older (56 vs 48 years). Among clients continuing on program, the cohorts with and without D/HBS lost, on average, 5.6 vs 5.8 kg (NS) (5.0 vs 5.6%; P=0.005) of baseline weight at 4 weeks, 11.0 vs 11.6 kg (NS) (9.9 vs 11.1%; P=0.027) at 12 weeks and 16.3 vs 17.1 kg (13.9 vs 15.7%; NS) at 24 weeks, respectively. In a mixed model regression controlling for baseline weight, gender and meal plan, and an intention-to-treat analysis, there was no significant difference in weight loss between the cohorts at any time point. Over 70% in both cohorts lost ⩾5% of their baseline weight by the final visit on their originally assigned meal plan. Both cohorts had significant reductions from baseline in body fat, blood pressure, pulse and abdominal circumference.

Conclusion:
Adults who were overweight/obese and with D/HBS following a commercial weight-loss program incorporating MRs and one-on-one behavioral support achieved therapeutic weight loss. The program was equally effective for weight loss and reductions in cardiometabolic risk factors among adults with and without D/HBS.
Spontaneous loss of B lineage transcription factors leads to pre-B leukemia in Ebf1+/–Bcl-xLTg mice
Authors: Ramírez-Komo J A , Delaney M A , Straign D , Lukin K , Tsang M , Iritani B M , Hagman J 
Published: July 2017

AbstractEarly B-cell factor 1 (EBF1) plays a central role in B-cell lineage specification and commitment. Loss of this critical transcription factor is strongly associated with high-risk, relapsed and therapy-resistant B–cell-acute lymphoblastic leukemia, especially in children. However, Ebf1 haploinsufficient mice exhibit a normal lifespan. To determine whether prolonged survival of B cells would enable tumorigenesis in Ebf1 haploinsufficient animals, we generated Ebf1+/–Bcl-xLTg mice, which express the anti-apoptotic factor Bcl-xL in B cells. Approximately half of Ebf1+/–Bcl-xLTg mice develop aggressive oligoclonal leukemia as they age, which engrafts in congenic wild-type recipients without prior conditioning. The neoplastic cells display a pre-B phenotype and express early developmental- and natural killer cell/myeloid-markers inappropriately. In addition, we found tumor cell-specific loss of several transcription factors critical for maintaining differentiation: EBF1, TCF3 and RUNX1. However, in the majority of tumors, loss of Ebf1 expression was not due to loss of heterozygosity. This is the first spontaneous mouse model of pre-B leukemia to demonstrate inappropriate expression of non-B-cell-specific genes associated with loss of Ebf1, Tcf3 and Runx1 expression.
Epigenetic silencing of microRNA-137 enhances ASCT2 expression and tumor glutamine metabolism
Authors: Dong J , Xiao D , Zhao Z , Ren P , Li C , Hu Y , Shi J , Su H , Wang L , Liu H , Li B , Gao P , Qing G 
Published: July 2017

AbstractTumor cells must activate specific transporters to meet their increased glutamine metabolic demands. Relative to other glutamine transporters, the ASC family transporter 2 (ASCT2, also called SLC1A5) is profoundly elevated in a wide spectrum of human cancers to coordinate metabolic reprogramming and malignant transformation. Understanding the molecular mechanisms whereby tumor cells frequently upregulate this transporter is therefore vital to develop potential strategies for transporter-targeted therapies. Combining in-silico algorithms with systemic experimental screening, we herein identify the tumor suppressor microRNA, miR-137, as an essential regulator that targets ASCT2 and cancer cell glutamine metabolism. Metabolic analysis shows that miR-137 derepression, similar to ASCT2 inactivation, significantly inhibits glutamine consumption and TCA cycle anaplerosis. Mechanistically, methyl-CpG-binding protein 2 (MeCP2) and DNA methyltransferases (DNMTs) cooperate to promote active methylation of the miR-137 promoter and inhibit its transcription, conversely reactivating ASCT2 expression and glutamine metabolism. Moreover, expression between miR-137 and ASCT2 is inversely correlated in tumor specimens from multiple cancer types, and ectopic ASCT2 expression markedly rescued miR-137 suppression of tumorigenesis. These findings thus elucidate a previously unreported mechanism responsible for ASCT2 deregulation in human cancers and identify ASCT2 as a critical downstream effector of miR-137, revealing a molecular link between DNA methylation, microRNA and tumor metabolism.
Reduced ultrafine particle levels in São Paulo’s atmosphere during shifts from gasoline to ethanol use
Authors: Salvo Alberto , Brito Joel , Artaxo Paulo , Geiger Franz M. 
Published: July 2017

AbstractDespite ethanol’s penetration into urban transportation, observational evidence quantifying the consequence for the atmospheric particulate burden during actual, not hypothetical, fuel-fleet shifts, has been lacking. Here we analyze aerosol, meteorological, traffic, and consumer behavior data and find, empirically, that ambient number concentrations of 7–100-nm diameter particles rise by one-third during the morning commute when higher ethanol prices induce 2 million drivers in the real-world megacity of São Paulo to substitute to gasoline use (95% confidence intervals: +4,154 to +13,272 cm−3). Similarly, concentrations fall when consumers return to ethanol. Changes in larger particle concentrations, including US-regulated PM2.5, are statistically indistinguishable from zero. The prospect of increased biofuel use and mounting evidence on ultrafines’ health effects make our result acutely policy relevant, to be weighed against possible ozone increases. The finding motivates further studies in real-world environments. We innovate in using econometrics to quantify a key source of urban ultrafine particles.
Deletion of the B-B’ and C-C’ regions of inverted terminal repeats reduces rAAV productivity but increases transgene expression
Authors: Zhou Qingzhang , Tian Wenhong , Liu Chunguo , Lian Zhonghui , Dong Xiaoyan , Wu Xiaobing 
Published: July 2017

AbstractInverted terminal repeats (ITRs) of the adeno-associated virus (AAV) are essential for rescue, replication, packaging, and integration of the viral genome. While ITR mutations have been identified in previous reports, we designed a new truncated ITR lacking the B-B’ and C-C’ regions named as ITRΔBC and investigated its effects on viral genome replication, packaging, and expression of recombinant AAV (rAAV). The packaging ability was compared between ITRΔBC rAAV and wild-type (wt) ITR rAAV. Our results showed the productivity of ITRΔBC rAAV was reduced 4-fold, which is consistent with the 8-fold decrease in the replication of viral genomic DNA of ITRΔBC rAAV compared with wt ITR rAAV. Surprisingly, transgene expression was significantly higher for ITRΔBC rAAV. A preliminary exploration of the underlying mechanisms was carried out by inhibiting and degrading the ataxia telangiectasia mutated (ATM) protein and the Mre11 complex (MRN), respectively, since the rAAV expression was inhibited by the ATM and/or MRN through cis interaction or binding with wt ITRs. We demonstrated that the inhibitory effects were weakened on ITRΔBC rAAV expression. This study suggests deletion in ITR can affect the transgene expression of AAV, which provides a new way to improve the AAV expression through ITRs modification.
Spatiotemporal expression patterns of wheat amino acid transporters reveal their putative roles in nitrogen transport and responses to abiotic stress
Authors: Wan Yongfang , King Robert , Mitchell Rowan A. C. , Hassani-Pak Keywan , Hawkesford Malcolm J. 
Published: July 2017

AbstractAmino acid transporters have roles in amino acid uptake from soil, long-distance transport, remobilization from vegetative tissues and accumulation in grain. Critically, the majority of wheat grain nitrogen is derived from amino acids remobilized from vegetative organs. However, no systematic analysis of wheat AAT genes has been reported to date. Here, 283 full length wheat AAT genes representing 100 distinct groups of homeologs were identified and curated by selectively consolidating IWGSC CSSv2 and TGACv1 Triticum aestivum genome assemblies and reassembling or mapping of IWGSC CSS chromosome sorted reads to fill any gaps. Gene expression profiling was performed using public RNA-seq data from root, leaf, stem, spike, grain and grain cells (transfer cell (TC), aleurone cell (AL), and starchy endosperm (SE)). AATs highly expressed in roots are good candidates for amino acid uptake from soil whilst AATs highly expressed in senescing leaves and stems may be involved in translocation to grain. AATs in TC (TaAAP2 and TaAAP19) and SE (TaAAP13) may play important roles in determining grain protein content and grain yield. The expression levels of AAT homeologs showed unequal contributions in response to abiotic stresses and development, which may aid wheat adaptation to a wide range of environments.
Phthalide Derivatives from Angelica Sinensis Decrease Hemoglobin Oxygen Affinity: A New Allosteric-Modulating Mechanism and Potential Use as 2,3-BPG Functional Substitutes
Authors: Chen Wei-Ren , Yu Youqing , Zulfajri Muhammad , Lin Ping-Cheng , Wang Chia C. 
Published: July 2017

AbstractAngelica sinensis (AS), one of the most versatile herbal medicines remains widely used due to its multi-faceted pharmacologic activities. Besides its traditional use as the blood-nourishing tonic, its anti-hypertensive, anti-cardiovascular, neuroprotective and anti-cancer effects have been reported. Albeit the significant therapeutic effects, how AS exerts such diverse efficacies from the molecular level remains elusive. Here we investigate the influences of AS and four representative phthalide derivatives from AS on the structure and function of hemoglobin (Hb). From the spectroscopy and oxygen equilibrium experiments, we show that AS and the chosen phthalides inhibited the oxygenated Hb from transforming into the high-affinity “relaxed” (R) state, decreasing Hb’s oxygen affinity. It reveals that phthalides cooperate with the endogenous Hb modulator, 2,3-bisphosphoglycerate (2,3-BPG) to synergetically regulate Hb allostery. From the docking modeling, phthalides appear to interact with Hb mainly through its α1/α2 interface, likely strengthening four (out of six) Hb “tense” (T) state stabilizing salt-bridges. A new allosteric-modulating mechanism is proposed to rationalize the capacity of phthalides to facilitate Hb oxygen transport, which may be inherently correlated with the therapeutic activities of AS. The potential of phthalides to serve as 2,3-BPG substitutes/supplements and their implications in the systemic biology and preventive medicine are discussed.
Defining thresholds of sustainable impact on benthic communities in relation to fishing disturbance
Authors: Lambert G. I. , Murray L. G. , Hiddink J. G. , Hinz H. , Lincoln H. , Hold N. , Cambiè G. , Kaiser M. J. 
Published: July 2017

AbstractWhile the direct physical impact on seabed biota is well understood, no studies have defined thresholds to inform an ecosystem-based approach to managing fishing impacts. We addressed this knowledge gap using a large-scale experiment that created a controlled gradient of fishing intensity and assessed the immediate impacts and short-term recovery. We observed a mosaic of taxon-specific responses at various thresholds. The lowest threshold of significant lasting impact occurred between 1 and 3 times fished and elicited a decrease in abundance of 39 to 70% for some sessile epifaunal organisms (cnidarians, bryozoans). This contrasted with significant increases in abundance and/or biomass of scavenging species (epifaunal echinoderms, infaunal crustaceans) by two to four-fold in areas fished twice and more. In spite of these significant specific responses, the benthic community structure, biomass and abundance at the population level appeared resilient to fishing. Overall, natural temporal variation in community metrics exceeded the effects of fishing in this highly dynamic study site, suggesting that an acute level of disturbance (fished over six times) would match the level of natural variation. We discuss the implications of our findings for natural resources management with respect to context-specific human disturbance and provide guidance for best fishing practices.
Brain specific Lamellipodin knockout results in hyperactivity and increased anxiety of mice
Authors: Bodo Cristian , Fernandes Cathy , Krause Matthias 
Published: July 2017

AbstractLamellipodin (Lpd) functions as an important signalling integrator downstream of growth factor and axon guidance receptors. Mechanistically, Lpd promotes actin polymerization by interacting with F-actin and the actin effectors Ena/VASP proteins and the SCAR/WAVE complex. Thereby, Lpd supports lamellipodia protrusion, cell migration and endocytosis. In the mammalian central nervous system, Lpd contributes to neuronal morphogenesis, neuronal migration during development and its C. elegans orthologue MIG-10 also supports synaptogenesis. However, the consequences of loss of Lpd in the CNS on behaviour are unknown. In our current study, we crossed our Lpd conditional knockout mice with a mouse line expressing Cre under the CNS specific Nestin promoter to restrict the genetic ablation of Lpd to the central nervous system. Detailed behavioural analysis of the resulting Nestin-Cre-Lpd knockout mouse line revealed a specific behavioural phenotype characterised by hyperactivity and increased anxiety.