bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of BRCA1/2defects with genomic scores predictive of DNA damage repair deficiency among breast cancer subtypes
Authors: Timms Kirsten M , Abkevich Victor , Hughes Elisha , Neff Chris , Reid Julia , Morris Brian , Kalva Saritha , Potter Jennifer , Tran Thanh V , Chen Jian , Iliev Diana , Sangale Zaina , Tikishvili Eliso , Perry Michael , Zharkikh Andrey , Gutin Alexander , Lanchbury Jerry S 
Published: December 2014

Abstract
Introduction
Homologous recombination (HR) DNA repair is of clinical relevance in breast cancer. Three DNA-based homologous recombination deficiency (HRD) scores (HRD-loss of heterozygosity score (LOH), HRD-telomeric allelic imbalance score (TAI), and HRD-large-scale state transition score (LST)) have been developed that are highly correlated with defects in BRCA1/2, and are associated with response to platinum therapy in triple negative breast and ovarian cancer. This study examines the frequency of BRCA1/2 defects among different breast cancer subtypes, and the ability of the HRD scores to identify breast tumors with defects in the homologous recombination DNA repair pathway.

Methods
215 breast tumors representing all ER/HER2 subtypes were obtained from commercial vendors. Next-generation sequencing based assays were used to generate genome wide SNP profiles, BRCA1/2 mutation screening, and BRCA1 promoter methylation data.

Results
BRCA1/2 deleterious mutations were observed in all breast cancer subtypes. BRCA1 promoter methylation was observed almost exclusively in triple negative breast cancer. BRCA1/2 deficient tumors were identified with BRCA1/2 mutations, or BRCA1 promoter methylation, and loss of the second allele of the affected gene. All three HRD scores were highly associated with BRCA1/2 deficiency (HRD-LOH: P = 1.3 × 10-17; HRD-TAI: P = 1.5 × 10-19; HRD-LST: P = 3.5 × 10-18). A combined score (HRD-mean) was calculated using the arithmetic mean of the three scores. In multivariable analyses the HRD-mean score captured significant BRCA1/2 deficiency information not captured by the three individual scores, or by clinical variables (P values for HRD-Mean adjusted for HRD-LOH: P = 1.4 × 10-8; HRD-TAI: P = 2.9 × 10-7; HRD-LST: P = 2.8 × 10-8; clinical variables: P = 1.2 × 10-16).

Conclusions
The HRD scores showed strong correlation with BRCA1/2 deficiency regardless of breast cancer subtype. The frequency of elevated scores suggests that a significant proportion of all breast tumor subtypes may carry defects in the homologous recombination DNA repair pathway. The HRD scores can be combined to produce a more robust predictor of HRD. The combination of a robust score, and the FFPE compatible assay described in this study, may facilitate use of agents targeting homologous recombination DNA repair in the clinical setting.
Design, methods, and participant characteristics of the Impact of Personal Genomics (PGen) Study, a prospective cohort study of direct-to-consumer personal genomic testing customers
Authors: Carere Deanna Alexis , Couper Mick P , Crawford Scott D , Kalia Sarah S , Duggan Jake R , Moreno Tanya A , Mountain Joanna L , Roberts J Scott , Green Robert C ,   for the PGen Study Group
Published: December 2014

AbstractDesigned in collaboration with 23andMe and Pathway Genomics, the Impact of Personal Genomics (PGen) Study serves as a model for academic-industry partnership and provides a longitudinal dataset for studying psychosocial, behavioral, and health outcomes related to direct-to-consumer personal genomic testing (PGT). Web-based surveys administered at three time points, and linked to individual-level PGT results, provide data on 1,464 PGT customers, of which 71% completed each follow-up survey and 64% completed all three surveys. The cohort includes 15.7% individuals of non-white ethnicity, and encompasses a range of income, education, and health levels. Over 90% of participants agreed to re-contact for future research.
Synovial T cell hyporesponsiveness to myeloid dendritic cells is reversed by preventing PD-1/PD-L1 interactions
Authors: Moret Frederique M , van der Wurff-Jacobs Kim MG , Bijlsma Johannes WJ , Lafeber Floris PJG , van Roon Joel AG 
Published: November 2014

Abstract
Introduction
The aim of this study was to investigate PD-1/PD-L1 involvement in the hyporesponsiveness of rheumatoid arthritis (RA) synovial fluid (SF) CD4 T cells upon stimulation by thymic stromal lymphopoietin (TSLP)–primed CD1c myeloid dendritic cells (mDCs).

Methods
Expression of PD-1 on naïve (Tn), central memory (Tcm) and effector memory (Tem) CD4 T cell subsets was assessed by flow cytometry. PD-L1 expression and its regulation upon TSLP stimulation of mDCs from peripheral blood (PB) and SF of RA patients were investigated by quantitative RT-PCR and flow cytometry. The involvement of PD-1/PD-L1 interactions in SF T cell hyporesponsiveness upon (TSLP-primed) mDC activation was determined by cell culture in the presence of PD-1 blocking antibodies, with or without interleukin 7 (IL-7) as a recognized suppressor of PD-1 expression.

Results
PD-1 expression was increased on CD4 T cells derived from SF compared with PB of RA patients. TSLP increased PD-L1 mRNA expression in both PB and SF mDCs. PD-L1 protein expression was increased on SF mDCs compared with PB mDCs and was associated with T cell hyporesponsiveness. Blockade of PD-1, as well as IL-7 stimulation, during cocultures of memory T cells and (TSLP-primed) mDCs from RA patients significantly recovered T cell proliferation.

Conclusion
SF T cell hyporesponsiveness upon (TSLP-primed) mDC stimulation in RA joints is partially dependent on PD-1/PD-L1 interactions, as PD-1 and PD-L1 are both highly expressed on SF T cells and mDCs, respectively, and inhibiting PD-1 availability restores T cell proliferation. The potential of IL-7 to robustly reverse this hyporesponsiveness suggests that such proinflammatory cytokines in RA joints strongly contribute to memory T cell activation.
Auricular or body acupuncture: which one is more effective in reducing abdominal fat mass in Iranian men with obesity: a randomized clinical trial
Authors: Darbandi Mahsa , Darbandi Sara , Owji Ali Akbar , Mokarram Pooneh , Mobarhan Majid Ghayor , Fardaei Majid , Zhao Baxiao , Abdi Hamid , Nematy Mohsen , Safarian Mohammad , Parizadeh Mohammad Reza , Dabbaghmanesh Mohammad Hossein , Abbasi Parisa , Ferns Gordon 
Published: December 2014

AbstractBackgroundThe prevalence of abdominal obesity is on the rise worldwide. Previous studies have indicated the higher diagnostic value of body fat distribution pattern compared with general body in abdominal obesity assessments. Several non-pharmacological methods have been suggested for obesity management, of which acupuncture has gained a great deal of research interest with promising results.This study aimed to comparatively evaluate the effects of conventional auricular and body electroacupuncture on abdominal fat mass in obese men.MethodsThe volunteers were randomly divided into four groups, including 2 interventions and 2 controls.This study was conducted on 80 obese volunteer men with Body Mass Index (BMI) range of 30–40 kg/m2.The intervention groups including real body electroacupuncture (A), real auricular acupuncture (C) and the control groups containing sham body electroacupuncture (B), and sham auricular acupuncture (D). All groups were in combination with a low-calorie diet for 6 weeks. BMI, Trunk Fat Mass (TFM), Waist Circumference (WC), and Hip Circumference (HC) were measured pre- and post-intervention.ResultsIn group A, respectively a significant reduction was shown in BMI (P < 0.005), TFM (P < 0.005), WC (P < 0.05, P < 0.005) and HC (P < 0.005) when compared with controls (Groups B and D). Interestingly, group C had significant decreases in BMI (P < 0.005), TFM (P < 0.01, P < 0.005), WC (P < 0.005) and HC (P < 0.001) after comparison with the sham. Likewise, WC (P < 0.05) and HC (P < 0.05) were significantly reduced post- intervention when compared with two treatment groups.ConclusionsIn our study, acupuncture treatment (body or auricular) seemed to have an effect on reducing BMI, TFM, WC and HC. Comparison of the two types of treatment (body and auricular acupuncture) suggests that the two types of acupuncture had similar effects on reducing BMI and TFM, but body electroacupuncture is more effective in reducing WC and auricular in HC. It seems that both auricular and body electro-acupuncture combined with a low-calorie diet are efficient, simple and painless methods to reduce respectively the HC and WC fat in obese men, compared with conventional techniques.Trial registrationIRCT201201127117N2
Rhinosinusitis in hematopoietic stem cell-transplanted patients: influence of nasosinus mucosal abnormalities?
Authors: Ortiz Erica , Altemani Albina , Vigorito Afonso Celso , Sakano Eulalia , Nicola Ester Maria Danielli 
Published: December 2014

Abstract
Introduction
Rhinosinusitis is characterized by inflammation extending from the mucosa of the nasal cavity into the paranasal sinuses. There are some aggravating features, such as immunosuppression, that can cause the nasal mucosal inflammation to linger for a long period, resulting in chronic or recurrent episodes. Such immunosuppression is the major feature of patients undergoing a hematopoietic stem cell transplant (HSCT); rhinosinusitis prevalence is higher in this group compared to immunocompetent patients. Nasal epithelial abnormalities have been described in, and may have some influence over, recurrent sinus infections among those patients. However, it is not clear whether rhinosinusitis can trigger mucosal abnormalities or whether a preexisting vulnerability for sinusitis recurrence is more likely. The objective of the study was to verify the influence of rhinosinusitis on nasal epithelial damage in patients undergoing hematopoietic stem cell transplantation.

Method
A total of 30 allogeneic HSCT patients were divided into two groups: 24 patients with chronic or recurrent rhinosinusitis and 6 patients without rhinosinusitis. These patients underwent a biopsy of the uncinate process that was analyzed by transmission electron microscopy and optical microscopy.

Results
The nasal mucosa analysis by optical microscopy showed no significant abnormalities. The ciliary orientation was obviously normal in the transplanted patients without rhinosinusitis. There was a trend toward a difference in the amount of cilia (decreased) and the primary modification of the ultrastructure of transplanted patients with rhinosinusitis.

Conclusion
HSCT patients, with and without rhinosinusitis, showed no significant histological abnormalities, except for ciliary disorientation and a possible decrease in ciliary and ultrastructural abnormalities in HSCT patients with rhinosinusitis.
Facile Synthesis of Silver Nanoparticles and Their Synergistic Antibacterial Activity in Combination with Commercial Antibiotics
Authors: Dey Jahar , Biswas Koel , Thapa Uttam , Joshi Santaram , Kharbangar Ibapalei Shisha , Sultana Nazima , Ismail Kochi 
Published: November 2014

Abstract
We demonstrate a facile method for the synthesis of silver nanoparticles (Ag NPs) by using silver nitrate (AgNO3) as precursor, p-toluidine as reducing agent and cetyltrimethylammonium bromide (CTAB) as capping agent. The main highlight of the present synthesis is the formation of NPs at near neutral pH. The effect of the concentrations of precursor, reducing agent and capping agent, and of pH on the stability and size of the NPs has been studied using UV–vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) techniques. Critical concentrations of AgNO3, reducing agent and CTAB required for the synthesis of Ag NPs are found to be 0.002 mol dm−3. The NPs prepared have been tested for antibacterial properties for a series of bacteria and they are found to have good antibacterial efficacy. In combination with some commercially available antibiotics, synergism in the antibacterial activity of the NPs has also been observed.
Substituent Effects at the 5-Position of 3-[Bis(pyridine-2-ylmethyl)amino]-BODIPY Cation Sensor Used for Ratiometric Quantification of Cu2+
Authors: Hafuka Akira , Kando Ryosuke , Ohya Kohei , Yamada Koji , Okabe Satoshi , Satoh Hisashi 
Published: December 2014

Abstract
In this paper, we investigated the effects of substitution at the 5-position of an asymmetric BODIPY cation sensor to tune its spectroscopic, photophysical, and cation-sensing properties. We introduced substituent groups with differing electron density at the 5-position of 3-[bis(pyridine-2-ylmethyl)amino]-BODIPY, which contains a cation recognition moiety at the 3-position of the BODIPY core, to develop four sensors which all exhibited distinctive ratiometric spectral changes in the presence of Cu2+. Aromatic substitution increased the Stokes shift. Substitution with the electron-withdrawing sulfonylphenyl group resulted in the highest fluorescence quantum yield, largest absorption coefficient, and largest spectral shift in the presence of Cu2+. The sulfonylphenyl-substituted sensor also exhibited excellent selectivity for Cu2+.
Odd–Even Effect Observed in [Ni(dmit)2] Complex Salts of Quaternary Ammonium Cation with Both Benzyl Groups and ω-Phenylalkyl Groups
Authors: Saeki Masahiro , Dai Kotaro , Ichimura Shuhei , Tamaki Yoshinori , Tomono Kazuaki , Miyamura Kazuo 
Published: November 2014

Abstract
A series of [Ni(dmit)2] (dmit: 1,3-dithiole-2-thione-4,5-dithiolate) complex salts of benzyldimethyl(ω-phenylalkyl)ammonium cation (BnCnPh: n represents the alkylene chain length; n = 1–4) have been prepared and characterized by X-ray crystallographic structural analysis. All complex salts were found to be composed of alternant stacks of layers of [Ni(dmit)2] anion dimers and cations (Layer I), and isolated cation layers (Layer II). In BnC3Ph complex salt, polymorphs, P&lt;span style="text-decoration: overline;"&gt;1&lt;/span&gt; (α-form) and P2(1)/c (β-form) crystals are obtained from similar crystallizing conditions. One of the biggest structural differences is the arrangement of [Ni(dmit)2] anion dimers; herringbone in α-form, while nearly parallel in β-form. Other BnCnPh complex salts adopt herringbone structure. Interestingly, BnCnPh series (n = 1, 2, 3α, 4) exhibit three types of pronounced odd–even effect in the crystal structures; 1. Dihedral angles between the two kinds of terminal phenyl groups, 2. Angles between [Ni(dmit)2] anion dimers, and 3. Ni–N+ distances. Such a structural feature is a consequence of the bulkiness of cation involving two phenyl groups. Introduction of terminal phenyl group is concluded to have increased the steric effect and led to the formation of the novel crystal structure of [Ni(dmit)2] complex salts.
Newborn Screening for Lysosomal Storage Diseases
Authors: Gelb Michael H , Scott C Ronald , Turecek Frantisek 
Published: December 2014

Abstract

BACKGROUND
There is worldwide interest in newborn screening for lysosomal storage diseases because of the development of treatment options that give better results when carried out early in life. Screens with high differentiation between affected and nonaffected individuals are critical because of the large number of potential false positives.

CONTENT
This review summarizes 3 screening methods: (a) direct assay of enzymatic activities using tandem mass spectrometry or fluorometry, (b) immunocapture-based measurement of lysosomal enzyme abundance, and (c) measurement of biomarkers. Assay performance is compared on the basis of small-scale studies as well as on large-scale pilot studies of mass spectrometric and fluorometric screens.

SUMMARY
Tandem mass spectrometry and fluorometry techniques for direct assay of lysosomal enzymatic activity in dried blood spots have emerged as the most studied approaches. Comparative mass spectrometry vs fluorometry studies show that the former better differentiates between nonaffected vs affected individuals. This in turn leads to a manageable number of screen positives that can be further evaluated with second-tier methods.
Flexibility Policies and Re-employment Probabilities in Italy
Authors: Mussida Chiara , Sciulli Dario 
Published: December 2014

Abstract
We analyze the effects of Italian labor market reforms “at the margin” on the probability of exiting from non-employment and entering permanent and temporary contracts, using WHIP data for the period 1985–2004. We find that the reforms have strengthened the duration dependence parameter, meaning a stronger labor market gap in employment opportunities between the short- and long-term non-employed. We suggest that in a flexible labor market, long-term unemployment is used by firms as a screening device to detect less productive workers. We also find evidence of greater differences in employment opportunities according to gender, and of reduced differences between regional labor markets.
Comparison of approaches and measurement of continuing professional development for specialists in laboratory medicine within four European countries
Authors: Martin Jan , Gasljevic Visnja , Šálek Tomáš , Horvath Attila , Borg Charles , Flegar-Meštrić Zlata , Jakovcic Mladen , Silhavik Josef , Adonics Adrienn , Szlamka Zsófia , Brincat Ian , Buttigieg Dorianne , Ciantar Noel , Sciortino Anna Lisa , Mifsud Antoinette , Adkins Alison , Bennett Tracey , Rice Kirstie , Taylor Yvette 
Published: December 2014

AbstractThis study investigated approaches to continuing professional development (CPD) for specialists in laboratory medicine within four European countries: Croatia, the Czech Republic, Malta and the UK.The research questions focussed on ascertaining if continued registration/licence was linked to CPD and if so, were there requirements for certain amounts and types of CPD and for CPD activities to meet specified accreditation criteria. The Professional Associations Research Network (PARN) model of CPD measurement was applied to each country’s registration/licencing body’s CPD requirements.Our results indicate a spectrum of approaches to CPD within participating countries.It will be necessary for European employers to be familiar with these differences and to take them into account for this increasingly mobile European workforce.
Interrelatedness between C-reactive protein and oxidized low-density lipoprotein
Authors: Obradovic Milan M. , Trpkovic Andreja , Bajic Vladan , Soskic Sanja , Jovanovic Aleksandra , Stanimirovic Julijana , Panic Milos , Isenovic Esma R. 
Published: December 2014

AbstractC-reactive protein (CRP) is a marker of inflammation. Atherosclerosis is now recognized as inflammatory disease, and it seems that CRP directly contributes to atherogenesis. Oxidation of low-density lipoprotein (LDL) molecule increases the uptake of lipid products by macrophages leading to cholesterol accumulation and subsequent foam cell formation. The elevated levels of high sensitivity CRP (hsCRP) and oxidized LDL (OxLDL) in the blood were found to be associated with cardiovascular diseases (CVD). In this review, we highlighted the evidence that CRP and OxLDL are involved in interrelated (patho) physiological pathways. The findings on association between hsCRP and OxLDL in the clinical setting will be also summarized.
Crystal structures of KM(AsF6)3 (M2+ = Mg, Co, Mn, Zn), KCu(SbF6)3 and [Co(HF)2]Sr[Sr(HF)]2[Sr(HF)2]2[AsF6]12
Authors: Mazej Zoran , Goreshnik Evgeny 
Published: December 2014

Abstract
The KM(AsF6)3 (M2+ = Mg, Co, Mn, Zn) and KCu(SbF6)3 compounds crystallize isotypically to previously known KNi(AsF6)3. The main features of the structure of these compounds are rings of MF6 octahedra sharing apexes with AsF6 octahedra connected into infinite tri-dimensional frameworks. In this arrangement cavities are formed where K+ cations are placed. Single crystals of CoSr5(AsF6)12·8HF were obtained as one of the products after the crystallization of 3KF/CoF2/SrF2 mixture in the presence of AsF5 in anhydrous HF. The CoSr5(AsF6)12·8HF is monoclinic, C/2c (No.15), with a = 26.773(5) Å, b = 10.087(2) Å, c = 21.141(5) Å, β = 93.296(13) °, V = 5699.9(19) Å3 at 200 K, and Z = 4. There are three crystallographically non-equivalent Sr2+ cations in the crystal structure of CoSr5(AsF6)12·8HF. The Sr1 is coordinated by ten fluorine atoms from eight different [AsF6]- anions, meanwhile Sr2 and Sr3 are bound to nine fluorine atoms provided by one HF and eight AsF6 units or by two HF and six AsF6 units, respectively. The Co2+ is coordinated distorted-octahedrally by six fluorine atoms from two HF molecules and four different AsF6 units. All those moieties in the crystal strucutre of [Co(HF)2]Sr[Sr(HF)]2[Sr(HF)2]2[AsF6]12 are connected into tridimensional framework. The CoSr5(AsF6)12·8HF is a unique example of compound where HF molecules are directly bound via fluorine atoms to two different metal centres.
High-pressure behavior of synthetic mordenite-Na: an in situ single-crystal synchrotron X-ray diffraction study
Authors: Lotti Paolo , Gatta G. Diego , Merlini Marco , Liermann Hanns-Peter 
Published: December 2014

Abstract
The high-pressure behavior of a synthetic mordenite-Na (space group: Cmcm or Cmc21) was studied by in situ single-crystal synchrotron X-ray diffraction with a diamond anvil cell up to 9.22(7) GPa. A phase transition, likely displacive in character, occurred between 1.68(7) and 2.70(8) GPa, from a C-centered to a primitive space group: possibly Pbnm, Pbnn or Pbn21. Fitting of the experimental data with III-BM equations of state allowed to describe the elastic behavior of the high-pressure polymorph with a primitive lattice. A very high volume compressibility [K

V0 = 25(2) GPa, β
V0 = 1/K

V0 = 0.040(3) GPa–1; K

V

′ = (?K

V
/?P)
T
= 2.0(3)], coupled with a remarkable elastic anisotropy (β
b
>>β
c
>β
a
), was found. Interestingly, the low-P and high-P polymorphs show the same anisotropic compressional scheme. A structure collapse was not observed up to 9.22(7) GPa, even though a strong decrease of the number of observed reflections at the highest pressures suggests an impending amorphization. The structure refinements performed at room-P, 0.98(2) and 1.68(7) GPa allowed to describe, at a first approximation, the mechanisms that govern the framework deformation in the low-P regime: the bulk compression is strongly accommodated by the increase of the ellipticity of the large 12-membered ring channels running along [001].
Europäische Fusionskontrolle bei konglomeraten Fusionen nach Intel/McAfee und Cisco/Kommission
Authors: Bardong Andreas 
Published: December 2014

Zusammenfassung
Die neueren Fusionskontrollentscheidungen Intel/McAfee (2011) und Microsoft/Skype (2011) sowie die zu letztgenanntem Fall ergangene Gerichtsentscheidung des EuG Cisco/Kommission (2013) geben Anlass, auf die praktische Relevanz konglomerater Schadenstheorien wieder neu hinzuweisen. Die verschiedenen Fallgruppen und Prüfungspunkte werden in dem Beitrag rekapituliert und die genannten Entscheidungen entsprechend eingeordnet. Darüber hinaus werden drei Themenkomplexe vertieft: Abschreckungswirkung kartellrechtlicher Verbote im Kontext der Anreizbetrachtung, Beweisanforderungen, sowie Verhaltenszusagen und Interoperabilität.
Zugangserfordernis zu Forschungsergebnissen nach der VO Nr. 1217/2010 – besteht die Gruppenfreistellung für Forschungs- und Entwicklungsvereinbarungen im Praxistest?
Authors: Pautke Stephanie , Schultze Jörg-Martin 
Published: December 2014

Zusammenfassung
Der Beitrag befasst sich mit der Gruppenfreistellungsverordnung für Forschungs- und Entwicklungsverträge. Die Autoren gehen der Frage nach, ob es nach der Reform dieser Verordnung noch Forschungs- und Entwicklungsvereinbarungen sowie Auftragsforschungsverträge gibt, in denen die Zugangsrechte zu den Ergebnissen der F&E bzw. Auftragsforschung abweichend von den Freistellungsvoraussetzungen der Verordnung geregelt werden können, ohne dass diese Klauseln einem erheblichen Nichtigkeitsrisiko unterliegen.