bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychotropic prescribing in seriously violent men with schizophrenia or personality disorder in a UK high security hospital
Authors: Stone-Brown Keir , Naji Mahmood , Francioni Alex , Myers Kyle , Samarendra Harsh , Mushtaq-Chaudhry Haseeb , Heslop Stephen , Sengupta Samrat , Ross Callum C. , Larkin Fintan , Das Mrigendra 
Published: January 2016

ObjectivesTo analyze antipsychotic prescribing patterns in a UK high security hospital (HSH) that treats seriously violent men with either schizophrenia or personality disorder and examine how different groups consented to treatment and prescribing for metabolic conditions. We hypothesized that there would be high prevalence of antipsychotic polypharmacy, and high-dose antipsychotic and clozapine prescribing.BackgroundHSHs treat seriously violent, mentally disordered offenders, and the extant literature on prescribing patterns in forensic settings is sparse.MethodsPrescribing and clinical data on all 189 patients in a UK HSH were collected from the hospital’s databases. Data were analyzed using SPSS.ResultsThe population was split into the following groups: schizophrenia spectrum disorder (SSD-only), personality disorder (PD-only), and comorbid schizophrenia spectrum disorder and PD. The majority (93.7%) of all patients were prescribed at least one antipsychotic, and (27.5%) were on clozapine. Polypharmacy was prevalent in 22.2% and high-dose antipsychotic in 27.5%. Patients on clozapine were more likely to be prescribed antidiabetic, statins, or antihypertensive medication. Patients in the PD-only group were more likely to be deemed to have the capacity to consent to treatment and be prescribed clozapine in contrast to the SSD-only group.ConclusionsRates of clozapine and high-dose antipsychotic prescribing were higher than in other psychiatric settings, while polypharmacy prescribing rates were lower. Higher clozapine prescribing rates may be a function of a treatment-resistant and aggressive population. A higher proportion of PD-only patients consented to treatment and received clozapine compared with in-house SSD-only as well as other psychiatric settings. Implications of the findings are discussed.
ROR1 sustains caveolae and survival signalling as a scaffold of cavin-1 and caveolin-1
Authors: Yamaguchi Tomoya , Lu Can , Ida Lisa , Yanagisawa Kiyoshi , Usukura Jiro , Cheng Jinglei , Hotta Naoe , Shimada Yukako , Isomura Hisanori , Suzuki Motoshi , Fujimoto Toyoshi , Takahashi Takashi 
Published: January 2016

AbstractThe receptor tyrosine kinase-like orphan receptor 1 (ROR1) sustains prosurvival signalling directly downstream of the lineage-survival oncogene NKX2-1/TTF-1 in lung adenocarcinoma. Here we report an unanticipated function of this receptor tyrosine kinase (RTK) as a scaffold of cavin-1 and caveolin-1 (CAV1), two essential structural components of caveolae. This kinase-independent function of ROR1 facilitates the interactions of cavin-1 and CAV1 at the plasma membrane, thereby preventing the lysosomal degradation of CAV1. Caveolae structures and prosurvival signalling towards AKT through multiple RTKs are consequently sustained. These findings provide mechanistic insight into how ROR1 inhibition can overcome EGFR–tyrosine kinase inhibitor (TKI) resistance due to bypass signalling via diverse RTKs such as MET and IGF-IR, which is currently a major clinical obstacle. Considering its onco-embryonic expression, inhibition of the scaffold function of ROR1 in patients with lung adenocarcinoma is an attractive approach for improved treatment of this devastating cancer.
Unlocking new contrast in a scanning helium microscope
Authors: Barr M. , Fahy A. , Martens J. , Jardine A. P. , Ward D. J. , Ellis J. , Allison W. , Dastoor P. C. 
Published: January 2016

AbstractDelicate structures (such as biological samples, organic films for polymer electronics and adsorbate layers) suffer degradation under the energetic probes of traditional microscopies. Furthermore, the charged nature of these probes presents difficulties when imaging with electric or magnetic fields, or for insulating materials where the addition of a conductive coating is not desirable. Scanning helium microscopy is able to image such structures completely non-destructively by taking advantage of a neutral helium beam as a chemically, electrically and magnetically inert probe of the sample surface. Here we present scanning helium micrographs demonstrating image contrast arising from a range of mechanisms including, for the first time, chemical contrast observed from a series of metal–semiconductor interfaces. The ability of scanning helium microscopy to distinguish between materials without the risk of damage makes it ideal for investigating a wide range of systems.
Multistep assembly of DNA condensation clusters by SMC
Authors: Kim HyeongJun , Loparo Joseph J. 
Published: January 2016

AbstractSMC (structural maintenance of chromosomes) family members play essential roles in chromosome condensation, sister chromatid cohesion and DNA repair. It remains unclear how SMCs structure chromosomes and how their mechanochemical cycle regulates their interactions with DNA. Here we used single-molecule fluorescence microscopy to visualize how Bacillus subtilis SMC (BsSMC) interacts with flow-stretched DNAs. We report that BsSMC can slide on DNA, switching between static binding and diffusion. At higher concentrations, BsSMCs form clusters that condense DNA in a weakly ATP-dependent manner. ATP increases the apparent cooperativity of DNA condensation, demonstrating that BsSMC can interact cooperatively through their ATPase head domains. Consistent with these results, ATPase mutants compact DNA more slowly than wild-type BsSMC in the presence of ATP. Our results suggest that transiently static BsSMC molecules can nucleate the formation of clusters that act to locally condense the chromosome while forming long-range DNA bridges.
PAM50 gene signatures and breast cancer prognosis with adjuvant anthracycline- and taxane-based chemotherapy: correlative analysis of C9741 (Alliance)
Authors: Liu Minetta C , Pitcher Brandelyn N , Mardis Elaine R , Davies Sherri R , Friedman Paula N , Snider Jacqueline E , Vickery Tammi L , Reed Jerry P , DeSchryver Katherine , Singh Baljit , Gradishar William J , Perez Edith A , Martino Silvana , Citron Marc L , Norton Larry , Winer Eric P , Hudis Clifford A , Carey Lisa A , Bernard Philip S , Nielsen Torsten O , Perou Charles M , Ellis Matthew J , Barry William T 
Published: January 2016

AbstractPAM50 intrinsic breast cancer subtypes are prognostic independent of standard clinicopathologic factors. CALGB 9741 demonstrated improved recurrence-free (RFS) and overall survival (OS) with 2-weekly dose-dense (DD) versus 3-weekly therapy. A significant interaction between intrinsic subtypes and DD-therapy benefit was hypothesized. Suitable tumor samples were available from 1,471 (73%) of 2,005 subjects. Multiplexed gene-expression profiling generated the PAM50 subtype call, proliferation score, and risk of recurrence score (ROR-PT) for the evaluable subset of 1,311 treated patients. The interaction between DD-therapy benefit and intrinsic subtype was tested in a Cox proportional hazards model using two-sided alpha=0.05. Additional multivariable Cox models evaluated the proliferation and ROR-PT scores as continuous measures with selected clinical covariates. Improved outcomes for DD therapy in the evaluable subset mirrored results from the complete data set (RFS; hazard ratio=1.20; 95% confidence interval=0.99–1.44) with 12.3-year median follow-up. Intrinsic subtypes were prognostic of RFS (P<0.0001) irrespective of treatment assignment. No subtype-specific treatment effect on RFS was identified (interaction P=0.44). Proliferation and ROR-PT scores were prognostic for RFS (both P<0.0001), but no association with treatment benefit was seen (P=0.14 and 0.59, respectively). Results were similar for OS. The prognostic value of PAM50 intrinsic subtype was greater than estrogen receptor/HER2 immunohistochemistry classification. PAM50 gene signatures were highly prognostic but did not predict for improved outcomes with DD anthracycline- and taxane-based therapy. Clinical validation studies will assess the ability of PAM50 and other gene signatures to stratify patients and individualize treatment based on expected risks of distant recurrence.
Effects of Testosterone Administration on Strategic Gambling in Poker Play
Authors: van Honk Jack , Will Geert-Jan , Terburg David , Raub Werner , Eisenegger Christoph , Buskens Vincent 
Published: January 2016

AbstractTestosterone has been associated with economically egoistic and materialistic behaviors, but -defensibly driven by reputable status seeking- also with economically fair, generous and cooperative behaviors. Problematically, social status and economic resources are inextricably intertwined in humans, thus testosterone’s primal motives are concealed. We critically addressed this issue by performing a placebo-controlled single-dose testosterone administration in young women, who played a game of bluff poker wherein concerns for status and resources collide. The profit-maximizing strategy in this game is to mislead the other players by bluffing randomly (independent of strength of the hand), thus also when holding very poor cards (cold bluffing). The profit-maximizing strategy also dictates the players in this poker game to never call the other players’ bluffs. For reputable-status seeking these materialistic strategies are disadvantageous; firstly, being caught cold bluffing damages one’s reputation by revealing deceptive intent and secondly, not calling the other players’ bluffs signals submission in blindly tolerating deception. Here we show that testosterone administration in this game of bluff poker significantly reduces random bluffing, as well as cold bluffing, while significantly increasing calling. Our data suggest that testosterone in humans primarily motivates for reputable-status seeking, even when this elicits behaviors that are economically disadvantageous.
Disorder-assisted quantum transport in suboptimal decoherence regimes
Authors: Novo Leonardo , Mohseni Masoud , Omar Yasser 
Published: January 2016

AbstractWe investigate quantum transport in binary tree structures and in hypercubes for the disordered Frenkel-exciton Hamiltonian under pure dephasing noise. We compute the energy transport efficiency as a function of disorder and dephasing rates. We demonstrate that dephasing improves transport efficiency not only in the disordered case, but also in the ordered one. The maximal transport efficiency is obtained when the dephasing timescale matches the hopping timescale, which represent new examples of the Goldilocks principle at the quantum scale. Remarkably, we find that in weak dephasing regimes, away from optimal levels of environmental fluctuations, the average effect of increasing disorder is to improve the transport efficiency until an optimal value for disorder is reached. Our results suggest that rational design of the site energies statistical distributions could lead to better performances in transport systems at nanoscale when their natural environments are far from the optimal dephasing regime.
Single-photon-multi-layer-interference lithography for high-aspect-ratio and three-dimensional SU-8 micro-/nanostructures
Authors: Ghosh Siddharth , Ananthasuresh G. K. 
Published: January 2016

AbstractWe report microstructures of SU-8 photo-sensitive polymer with high-aspect-ratio, which is defined as the ratio of height to in-plane feature size. The highest aspect ratio achieved in this work exceeds 250. A multi-layer and single-photon lithography approach is used in this work to expose SU-8 photoresist of thickness up to 100 μm. Here, multi-layer and time-lapsed writing is the key concept that enables nanometer localised controlled photo-induced polymerisation. We use a converging monochromatic laser beam of 405 nm wavelength with a controllable aperture. The reflection of the converging optics from the silicon substrate underneath is responsible for a trapezoidal edge profile of SU-8 microstructure. The reflection induced interfered point-spread-function and multi-layer-single-photon exposure helps to achieve sub-wavelength feature sizes. We obtained a 75 nm tip diameter on a pyramid shaped microstructure. The converging beam profile determines the number of multiple optical focal planes along the depth of field. These focal planes are scanned and exposed non-concurrently with varying energy dosage. It is notable that an un-automated height axis control is sufficient for this method. All of these contribute to realising super-high-aspect-ratio and 3D micro-/nanostructures using SU-8. Finally, we also address the critical problems of photoresist-based micro-/nanofabrication and their solutions.
A general way for quantitative magnetic measurement by transmitted electrons
Authors: Song Dongsheng , Li Gen , Cai Jianwang , Zhu Jing 
Published: January 2016

AbstractEMCD (electron magnetic circular dichroism) technique opens a new door to explore magnetic properties by transmitted electrons. The recently developed site-specific EMCD technique makes it possible to obtain rich magnetic information from the Fe atoms sited at nonequivalent crystallographic planes in NiFe2O4, however it is based on a critical demand for the crystallographic structure of the testing sample. Here, we have further improved and tested the method for quantitative site-specific magnetic measurement applicable for more complex crystallographic structure by using the effective dynamical diffraction effects (general routine for selecting proper diffraction conditions, making use of the asymmetry of dynamical diffraction for design of experimental geometry and quantitative measurement, etc) and taken yttrium iron garnet (Y3Fe5O12, YIG) with more complex crystallographic structure as an example to demonstrate its applicability. As a result, the intrinsic magnetic circular dichroism signals, spin and orbital magnetic moment of iron with site-specific are quantitatively determined. The method will further promote the development of quantitative magnetic measurement with high spatial resolution by transmitted electrons.
Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum
Authors: Jenum Synne , Dhanasekaran S. , Lodha Rakesh , Mukherjee Aparna , Kumar Saini Deepak , Singh Sarman , Singh Varinder , Medigeshi Guruprasad , Haks Marielle C. , Ottenhoff Tom H. M. , Doherty Timothy Mark , Kabra Sushil K. , Ritz Christian , Grewal Harleen M. S. 
Published: January 2016

AbstractThe World Health Organization (WHO) calls for an accurate, rapid and simple point-of-care (POC) test for the diagnosis of pediatric tuberculosis (TB) in order to make progress “Towards Zero Deaths”. Whereas the sensitivity of a POC test based on detection of Mycobacterium tuberculosis (MTB) is likely to have poor sensitivity (70–80% of children have culture-negative disease), host biomarkers reflecting the on-going pathological processes across the spectrum of MTB infection and disease may hold greater promise for this purpose. We analyzed transcriptional immune biomarkers direct ex-vivo and translational biomarkers in MTB-antigen stimulated whole blood in 88 Indian children with intra-thoracic TB aged 6 months to 15 years and 39 asymptomatic siblings. We identified 12 biomarkers consistently associated with either clinical groups “upstream” towards culture-positive TB on the TB disease spectrum (CD14, FCGR1A, FPR1, MMP9, RAB24, SEC14L1 and TIMP2) or “downstream” towards a decreased likelihood of TB disease (BLR1, CD3E, CD8A, IL7R and TGFBR2), suggesting a correlation with MTB-related pathology and high relevance to a future POC test for pediatric TB. A biomarker signature consisting of BPI, CD3E, CD14, FPR1, IL4, TGFBR2, TIMP2 and TNFRSF1B separated children with TB from asymptomatic siblings (AUC of 88%).
Overexpression of HER-2 in MDA-MB-435/LCC6 Tumours is Associated with Higher Metabolic Activity and Lower Energy Stress
Authors: Dragowska Wieslawa H. , Ginj Mihaela , Kozlowski Piotr , Yung Andrew , Ruth Thomas J. , Adam Michael J. , Sossi Vesna , Bally Marcel B. , Yapp Donald T. T. 
Published: January 2016

AbstractOverexpresssion of HER-2 in the MDA-MB-435/LCC6 (LCC6HER-2) tumour model is associated with significantly increased hypoxia and reduced necrosis compared to isogenic control tumours (LCC6Vector); this difference was not related to tumour size or changes in vascular architecture. To further evaluate factors responsible for HER-2-associated changes in the tumour microenvironment, small animal magnetic resonance imaging (MRI) and positron emission tomography (PET) were used to measure tumour tissue perfusion and metabolism, respectively. The imaging data was further corroborated by analysis of molecular markers pertaining to energy homeostasis and measurements of hypoxia and glucose consumption. The results showed a strong trend towards higher perfusion rates (~58% greater, p = 0.14) and significantly higher glucose uptake in LCC6HER-2 (~2-fold greater; p = 0.025), relative to control tumours. The expression of proteins related to energy stress (P-AMPK, P-ACC) and glucose transporters (GLUT1) were lower in LCC6HER-2 tumours (~2- and ~4-fold, respectively). The in vitro analysis showed that LCC6HER-2 cells become more hypoxic in 1% oxygen and utilise significantly more glucose in normoxia compared to LCC6Vectorcells (p < 0.005). Amalgamation of all the data points suggests a novel metabolic adaptation driven by HER-2 overexpression where higher oxygen and glucose metabolic rates produce rich energy supply but also a more hypoxic tumour mass.
An Intriguing Correlation Based on the Superimposition of Residue Pairs with Inhibitors that Target Protein-Protein Interfaces
Authors: Nakadai Masakazu , Tomida Shuta , Sekimizu Kazuhisa 
Published: January 2016

AbstractDruggable sites on protein-protein interfaces are difficult to predict. To survey inhibitor-binding sites onto which residues are superimposed at protein-protein interfaces, we analyzed publicly available information for 39 inhibitors that target the protein-protein interfaces of 8 drug targets. By focusing on the differences between residues that were superimposed with inhibitors and non-superimposed residues, we observed clear differences in the distances and changes in the solvent-accessible surface areas (∆SASA). Based on the observation that two or more residues were superimposed onto inhibitors in 37 (95%) of 39 protein-inhibitor complexes, we focused on the two-residue relationships. Application of a cross-validation procedure confirmed a linear negative correlation between the absolute value of the dihedral angle and the sum of the ∆SASAs of the residues. Finally, we applied the regression equation of this correlation to four inhibitors that bind to new sites not bound by the 39 inhibitors as well as additional inhibitors of different targets. Our results shed light on the two-residue correlation between the absolute value of the dihedral angle and the sum of the ∆SASA, which may be a useful relationship for identifying the key two-residues as potential targets of protein-protein interfaces.
Efficient Solar Energy Conversion Using CaCu3Ti4O12 Photoanode for Photocatalysis and Photoelectrocatalysis
Authors: Kushwaha H. S. , Madhar Niyaz A , Ilahi B. , Thomas P. , Halder Aditi , Vaish Rahul 
Published: January 2016

AbstractA highly efficient third generation catalyst, CaCu3Ti4O12 (CCTO) shows excellent photoelectrochemical (PEC) and photocatalytic ability. As only 4% part of the solar spectrum covers UV light, thus it is highly desirable to develop visible light active photocatalyst materials like CCTO for effective solar energy conversion. A direct band transition with a narrow band gap (1.5 eV) was observed. Under light irradiation, high photocurrent density was found to be 0.96 mA/cm2, indicating the visible light induced photocatalytic ability of CCTO. Visible light mediated photocatalytic and photoelectrocatalytic degradation efficiency of CaCu3Ti4O12 pellets (CCTO) was investigated for three classes of pharmaceutical waste: erythrosin (dye), ciprofloxacin (antibiotic) and estriol (steroid). It is found that the degradation process follows first order kinetic reaction in electrocatalysis, photocatalysis and photoelectrocatalysis and high kinetic rate constant was observed in photoelectrocatalysis. This was quite high in comparison to previously reported methods.
The basal function of teleost prolactin as a key regulator on ion uptake identified with zebrafish knockout models
Authors: Shu Yuqin , Lou Qiyong , Dai Ziru , Dai Xiangyan , He Jiangyan , Hu Wei , Yin Zhan 
Published: January 2016

AbstractProlactin (PRL) is an anterior pituitary hormone with a broad range of functions. Its ability to stimulate lactogenesis, maternal behavior, growth and development, osmoregulation and epithelial ion transport has been reported in many vertebrates. In our present study, we have targeted the zebrafish prl locus via transcription activator-like effector nucleases (TALENs). Two independent targeted mutant lines with premature termination of the putative sequence of PRL peptides were generated. All prl-deficient zebrafish progeny died at 6–16 days post-fertilization stage (dpf) in egg water. However, the prl-deficient larvae thrived and survived through adulthood in brackish water (5175 mg/L ocean salts), without obvious defects in somatic growth or reproduction. When raised in egg water, the expression levels of certain key Na+/Cl− cotransporters in the gills and Na+/K+-ATPase subunits, Na+/H+ exchangers and Na+/Cl− transporters in the pronephros of prl-deficient larvae were down-regulated at 5 dpf, which caused Na+/K+/Cl− uptake defects in the mutant fish at 6 dpf. Our present results demonstrate that the primary function of zebrafish prl is osmoregulation via governing the uptake and homeostasis of Na+, K+ and Cl−. Our study provides valuable evidence to understand the mechanisms of PRL function better through both phylogenetic and physiological perspectives.
Snord116 is critical in the regulation of food intake and body weight
Authors: Qi Yue , Purtell Louise , Fu Melissa , Lee Nicola J. , Aepler Julia , Zhang Lei , Loh Kim , Enriquez Ronaldo F. , Baldock Paul A. , Zolotukhin Sergei , Campbell Lesley V. , Herzog Herbert 
Published: January 2016

AbstractPrader-Willi syndrome (PWS) is the predominant genetic cause of obesity in humans. Recent clinical reports have suggested that micro-deletion of the Snord116 gene cluster can lead to PWS, however, the extent of the contributions of the encoded snoRNAs is unknown. Here we show that mice lacking Snord116 globally have low birth weight, increased body weight gain, energy expenditure and hyperphagia. Consistent with this, microarray analysis of hypothalamic gene expression revealed a significant alteration in feeding related pathways that was also confirmed by in situ hybridisation. Importantly, selective deletion of Snord116 only from NPY expressing neurons mimics almost exactly the global deletion phenotype including the persistent low birth weight, increased body weight gain in early adulthood, increased energy expenditure and hyperphagia. Mechanistically, the lack of Snord116 in NPY neurons leads to the upregulation of NPY mRNA consistent with the hyperphagic phenotype and suggests a critical role of Snord116 in the control of NPY neuronal functions that might be dysregulated in PWS.