bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relation of comorbidities and patient navigation with the time to diagnostic resolution after abnormal cancer screening
Authors: Whitley Elizabeth M. , Raich Peter C. , Dudley Donald J. , Freund Karen M. , Paskett Electra D. , Patierno Steven R. , Simon Melissa , Warren‐Mears Victoria , Snyder Frederick R. ,   for the Patient Navigation Research Program Investigators
Published: September 2016

BACKGROUNDWhether patient navigation improves outcomes for patients with comorbidities is unknown. The aims of this study were to determine the effect of comorbidities on the time to diagnostic resolution after an abnormal cancer screening test and to examine whether patient navigation improves the timeliness and likelihood of diagnostic resolution for patients with comorbidities in comparison with no navigation.METHODSA secondary analysis of comorbidity data collected by Patient Navigation Research Program sites using the Charlson Comorbidity Index (CCI) was conducted. The participants were 6,349 patients with abnormal breast, cervical, colon, or prostate cancer screening tests between 2007 and 2011. The intervention was patient navigation or usual care. The CCI data were highly skewed across projects and cancer sites, and the CCI scores were categorized as 0 (CCI score of 0 or no comorbidities identified; 76% of cases); 1 (CCI score of 1; 16% of cases), or 2 (CCI score ≥ 2; 8% of cases). Separate adjusted hazard ratios for each site and cancer type were obtained, and then they were pooled with a meta‐analysis random effects methodology.RESULTSPatients with a CCI score ≥ 2 had delayed diagnostic resolution after an abnormal cancer screening test in comparison with those with no comorbidities. Patient navigation reduced delays in diagnostic resolution, with the greatest benefits seen for those with a CCI score ≥ 2.CONCLUSIONSPersons with a CCI score ≥ 2 experienced significant delays in timely diagnostic care in comparison with patients without comorbidities. Patient navigation was effective in reducing delays in diagnostic resolution among those with CCI scores > 1. Cancer 2017;123:312–318. © 2016 American Cancer Society.
Whole‐exome sequencing and targeted gene sequencing provide insights into the role of PALB2 as a male breast cancer susceptibility gene
Authors: Silvestri Valentina , Zelli Veronica , Valentini Virginia , Rizzolo Piera , Navazio Anna Sara , Coppa Anna , Agata Simona , Oliani Cristina , Barana Daniela , Castrignanò Tiziana , Viel Alessandra , Russo Antonio , Tibiletti Maria Grazia , Zanna Ines , Masala Giovanna , Cortesi Laura , Manoukian Siranoush , Azzollini Jacopo , Peissel Bernard , Bonanni Bernardo , Peterlongo Paolo , Radice Paolo , Palli Domenico , Giannini Giuseppe , Chillemi Giovanni , Montagna Marco , Ottini Laura 
Published: September 2016

BACKGROUNDMale breast cancer (MBC) is a rare disease whose etiology appears to be largely associated with genetic factors. BRCA1 and BRCA2 mutations account for about 10% of all MBC cases. Thus, a fraction of MBC cases are expected to be due to genetic factors not yet identified. To further explain the genetic susceptibility for MBC, whole‐exome sequencing (WES) and targeted gene sequencing were applied to high‐risk, BRCA1/2 mutation–negative MBC cases.METHODSGerm‐line DNA of 1 male and 2 female BRCA1/2 mutation–negative breast cancer (BC) cases from a pedigree showing a first‐degree family history of MBC was analyzed with WES. Targeted gene sequencing for the validation of WES results was performed for 48 high‐risk, BRCA1/2 mutation–negative MBC cases from an Italian multicenter study of MBC. A case‐control series of 433 BRCA1/2 mutation–negative MBC and female breast cancer (FBC) cases and 849 male and female controls was included in the study.RESULTSWES in the family identified the partner and localizer of BRCA2 (PALB2) c.419delA truncating mutation carried by the proband, her father, and her paternal uncle (all affected with BC) and the N‐acetyltransferase 1 (NAT1) c.97C>T nonsense mutation carried by the proband's maternal aunt. Targeted PALB2 sequencing detected the c.1984A>T nonsense mutation in 1 of the 48 BRCA1/2 mutation–negative MBC cases. NAT1 c.97C>T was not found in the case‐control series.CONCLUSIONSThese results add strength to the evidence showing that PALB2 is involved in BC risk for both sexes and indicate that consideration should be given to clinical testing of PALB2 for BRCA1/2 mutation–negative families with multiple MBC and FBC cases. Cancer 2017;123:210–218. © 2016 American Cancer Society.
Next‐generation sequencing adds value to the preoperative diagnosis of pancreatic cysts
Authors: Rosenbaum Matthew W. , Jones Martin , Dudley Jonathan C. , Le Long P. , Iafrate A. John , Pitman Martha B. 
Published: September 2016

BACKGROUNDThe diagnosis of a pancreatic cyst as mucinous or high‐risk dictates the need for follow‐up or surgery. Molecular analysis of aspirated pancreatic cyst fluid (PCF) can provide valuable information not obtained by carcinoembryonic antigen (CEA) analysis or cytology.METHODSAll patients who underwent molecular analysis of PCF between March 2013 and June 2015 were reviewed, including pathology, imaging, and follow‐up. Molecular testing was performed using a patented, anchored multiplex polymerase chain reaction next‐generation sequencing (NGS) platform, which sequenced numerous hotspots in 39 genes linked with malignancy. Performance of NGS and cytology was calculated using final outcome, as determined by clinicopathologic follow‐up.RESULTSThe study cohort included 113 PCFs from 105 patients. In total, 119 variants were detected in 67 PCFs (59%). Variants were more common in intraductal papillary mucinous neoplasms (IPMNs)/cancer than in nonmucinous cysts (P < .005). The inclusion of v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)/guanine nucleotide‐binding protein (GNAS) variants improved the classification of IPMNs as mucinous from 50% by microscopy to 100%. Seventy‐five percent of cancers had high‐grade atypia versus 0% of IPMNs and nonmucinous cysts (P < .002). Variants in tumor protein 53 (TP53), SMAD family member 4 (SMAD4), cyclin‐dependent kinase inhibitor 2A (CDKN2A), and notch1 (NOTCH1) were detected only in malignant cysts. Cytology was similarly specific (100%) for detecting malignant cysts but was more sensitive than the identification of late mutations by NGS (75% vs 46%).CONCLUSIONSThe detection of KRAS/GNAS variants improves the identification of mucinous neoplasms. Variants in TP53, SMAD4, CDKN2A, and NOTCH1 support the diagnosis of a high‐risk cyst requiring surgery or additional sampling. Although molecular analysis is not a replacement for cytopathology, it does provide valuable information for accurate preoperative diagnosis, helping to classify mucinous neoplasms and high‐risk cysts that require surgical resection. Cancer Cytopathol 2017;125:41‐47. © 2016 American Cancer Society.
0.3‐V bulk‐driven programmable gain amplifier in 0.18‐µm CMOS
Authors: Kulej Tomasz , Khateb Fabian 
Published: September 2016

SummaryA new solution for an ultra low voltage bulk‐driven programmable gain amplifier (PGA) is described in the paper. While implemented in a standard n‐well 0.18‐µm complementary metal–oxide–semiconductor (CMOS) process, the circuit operates from 0.3 V supply, and its voltage gain can be regulated from 0 to 18 dB with 6‐dB steps. At minimum gain, the PGA offers nearly rail‐to‐rail input/output swing and the input referred thermal noise of 2.37 μV/Hz1/2, which results in a 63‐dB dynamic range (DR). Besides, the total power consumption is 96 nW, the signal bandwidth is 2.95 kHz at 5‐pF load capacitance and the third‐order input intercept point (IIP3) is 1.62 V. The circuit performance was simulated with LTspice. Copyright © 2016 John Wiley & Sons, Ltd.
Catalyst recycling in the hydroaminomethylation of methyl oleate: A route to novel polyamide monomers
Authors: Vorholt Andreas J. , Immohr Sarah , Ostrowski Karoline A. , Fuchs Sarah , Behr Arno 
Published: September 2016

This article describes the development of an effective thermomorphic multicomponent solvent (TMS) system for the production of branched polyamide monomers. In this system, methyl oleate, a renewable from fats and oils, and a functionalized amine are used as starting materials in a tandem catalytic reaction, which merges different reaction steps into a single preparative step. This particular TMS system consisted of a heptane/acetonitrile solvent mixture and made reusing the precious rhodium catalyst possible in three recycle runs. A constant yield of 61–65% was obtained for each run due to low‐catalyst leaching. Fortunately, the catalyst system does not require any additional phosphorous ligands and allows high yields. A scale‐up for the production of 10–11 g of the desired product in each run was realized. Subsequent hydrogenation of the product directly provided an amine ester, which is a valuable polyamide monomer.Practical applications: A method was developed to enable access to primary amines via hydroaminomethylation and hydrogenation. The product, a nitrile ester, is a valuable intermediate for polyamide monomers. This nitrile ester was successfully hydrogenated to an amine ester, which features a potential polyamide monomer directly. A catalyst recycle of the homogeneous rhodium complex within the hydroaminomethylation of methyl oleate and an amino nitrile was successfully carried out, enabling constant homogeneous catalyst activity over the course of three recycle runs. A scale‐up to obtain 10–11 g of the hydroaminomethylation product was realized.A general method is described for the conversion of methyl oleate within a hydroaminomethylation reaction. The catalyst can be recovered and reused. Valuable polyamide intermediates were obtained.
Investigation of the sensitivity of turbulent closures and coupling of hybrid RANS‐LES models for predicting flow fields with separation and reattachment
Authors: Kumar G. , Lakshmanan S. K. , Gopalan H. , De A. 
Published: September 2016

SummaryHybrid models have found widespread applications for simulation of wall‐bounded flows at high Reynolds numbers. Typically, these models employ Reynolds‐averaged Navier–Stokes (RANS) and large eddy simulation (LES) in the near‐body and off‐body regions, respectively. A number of coupling strategies between the RANS and LES regions have been proposed, tested, and applied in the literature with varying degree of success. Linear eddy‐viscosity models (LEVM) are often used for the closure of turbulent stress tensor in RANS and LES regions. LEVM incorrectly predicts the anisotropy of Reynolds normal stress at the RANS‐LES interface region. To overcome this issue, use of non‐linear eddy‐viscosity models (NLEVM) have started receiving attention. In this study, a generic non‐linear blended modeling framework for performing hybrid simulations is proposed. Flow over the periodic hills is used as the test case for model evaluation. This case is chosen due to complex flow physics with simplified geometry. Analysis of the simulations suggests that the non‐linear hybrid models show a better performance than linear hybrid models. It is also observed that the non‐linear closures are less sensitive to the RANS‐LES coupling and grid resolution. Copyright © 2016 John Wiley & Sons, Ltd.
Gray matter regions statistically mediating the cross‐sectional association of eotaxin and set‐shifting among older adults with major depressive disorder
Authors: Smagula Stephen F. , Karim Helmet T. , Lenze Eric J. , Butters Meryl A. , Wu Gregory F. , Mulsant Benoit H. , Reynolds Charles F. , Aizenstein Howard J. 
Published: September 2016

ObjectiveEotaxin is a chemokine that exerts negative effects on neurogenesis. We recently showed that peripheral eotaxin levels correlate with both lower gray matter volume and poorer executive performance in older adults with major depressive disorder. These findings suggest that the relationship between eotaxin and set‐shifting may be accounted for by lower gray matter volume in specific regions. Prior studies have identified specific gray matter regions that correlate with set‐shifting performance, but have not examined whether these specific gray matter regions mediate the cross‐sectional association between eotaxin and set‐shifting.MethodIn 27 older adults (mean age: 68 ± 5.2 years) with major depressive disorder, we performed a whole brain (voxel‐wise) analysis testing whether/where gray matter density statistically mediates the cross‐sectional association of eotaxin and set‐shifting performance.ResultsWe found the association between eotaxin and set‐shifting performance was fully statistically mediated by lower gray matter density in left middle cingulate, right pre‐/post‐central, lingual, inferior/superior frontal, cuneus, and middle temporal regions.ConclusionThe regions identified above may be both susceptible to a potential neurodegenerative effect of eotaxin, and critical to preserving set‐shifting function. Longitudinal and intervention studies are needed to further evaluate whether targeting eotaxin levels will prevent neurodegeneration and executive impairment in older adults with depression. Copyright © 2016 John Wiley & Sons, Ltd.
Separate spatial and temporal frequency tuning to visual motion in human MT+ measured with ECoG
Authors: Gaglianese Anna , Harvey Ben M. , Vansteensel Mariska J. , Dumoulin Serge O. , Ramsey Nick F. , Petridou Natalia 
Published: September 2016

AbstractThe human middle temporal complex (hMT+) has a crucial biological relevance for the processing and detection of direction and speed of motion in visual stimuli. Here, we characterized how neuronal populations in hMT+ encode the speed of moving visual stimuli. We evaluated human intracranial electrocorticography (ECoG) responses elicited by square‐wave dartboard moving stimuli with different spatial and temporal frequency to investigate whether hMT+ neuronal populations encode the stimulus speed directly, or whether they separate motion into its spatial and temporal components. We extracted two components from the ECoG responses: (1) the power in the high‐frequency band (HFB: 65–95 Hz) as a measure of the neuronal population spiking activity and (2) a specific spectral component that followed the frequency of the stimulus's contrast reversals (SCR responses). Our results revealed that HFB neuronal population responses to visual motion stimuli exhibit distinct and independent selectivity for spatial and temporal frequencies of the visual stimuli rather than direct speed tuning. The SCR responses did not encode the speed or the spatiotemporal frequency of the visual stimuli. We conclude that the neuronal populations measured in hMT+ are not directly tuned to stimulus speed, but instead encode speed through separate and independent spatial and temporal frequency tuning. Hum Brain Mapp 38:293–307, 2017. © 2016 Wiley Periodicals, Inc.
Subcortical roles in lexical task processing: Inferences from thalamic and subthalamic event‐related potentials
Authors: Tiedt Hannes O. , Ehlen Felicitas , Krugel Lea K. , Horn Andreas , Kühn Andrea A. , Klostermann Fabian 
Published: September 2016

AbstractSubcortical functions for language capacities are poorly defined, but may be investigated in the context of deep brain stimulation. Here, we studied event‐related potentials recorded from electrodes in the subthalamic nucleus (STN) and the thalamic ventral intermediate nucleus (VIM) together with surface‐EEG. Participants completed a lexical decision task (LDT), which required the differentiation of acoustically presented words from pseudo‐words by button press. Target stimuli were preceded by prime‐words. In recordings from VIM, a slow potential shift apparent at the lower electrode contacts persisted during target stimulus presentation (equally for words and pseudo‐words). In contrast, recordings from STN electrodes showed a short local activation on prime‐words but not target‐stimuli. In both depth‐recording regions, further components related to contralateral motor responses to target words were evident. On scalp level, mid‐central activations on (pseudo)lexical stimuli were obtained, in line with the expression of N400 potentials. The prolonged activity recorded from VIM, exclusively accompanying the relevant LDT phase, is in line with the idea of thalamic “selective engagement” for supporting the realization of the behavioral focus demanded by the task. In contrast, the phasic prime related activity rather indicates “procedural” STN functions, for example, for trial sequencing or readiness inhibition of prepared target reactions. Hum Brain Mapp 38:370–383, 2017. © 2016 Wiley Periodicals, Inc.
Creative females have larger white matter structures: Evidence from a large sample study
Authors: Takeuchi Hikaru , Taki Yasuyuki , Nouchi Rui , Yokoyama Ryoichi , Kotozaki Yuka , Nakagawa Seishu , Sekiguchi Atsushi , Iizuka Kunio , Yamamoto Yuki , Hanawa Sugiko , Araki Tsuyoshi , Makoto Miyauchi Carlos , Shinada Takamitsu , Sakaki Kohei , Sassa Yuko , Nozawa Takayuki , Ikeda Shigeyuki , Yokota Susumu , Daniele Magistro , Kawashima Ryuta 
Published: September 2016

AbstractThe importance of brain connectivity for creativity has been theoretically suggested and empirically demonstrated. Studies have shown sex differences in creativity measured by divergent thinking (CMDT) as well as sex differences in the structural correlates of CMDT. However, the relationships between regional white matter volume (rWMV) and CMDT and associated sex differences have never been directly investigated. In addition, structural studies have shown poor replicability and inaccuracy of multiple comparisons over the whole brain. To address these issues, we used the data from a large sample of healthy young adults (776 males and 560 females; mean age: 20.8 years, SD = 0.8). We investigated the relationship between CMDT and WMV using the newest version of voxel‐based morphometry (VBM). We corrected for multiple comparisons over whole brain using the permutation‐based method, which is known to be quite accurate and robust. Significant positive correlations between rWMV and CMDT scores were observed in widespread areas below the neocortex specifically in females. These associations with CMDT were not observed in analyses of fractional anisotropy using diffusion tensor imaging. Using rigorous methods, our findings further supported the importance of brain connectivity for creativity as well as its female‐specific association. Hum Brain Mapp 38:414–430, 2017. © 2016 Wiley Periodicals, Inc.
Proteasome inhibitors in AL amyloidosis: focus on mechanism of action and clinical activity
Authors: Jelinek T. , Kryukova E. , Kufova Z. , Kryukov F. , Hajek R. 
Published: September 2016

AbstractProteasome inhibitors are the backbone in the treatment of multiple myeloma with 3 of its representatives (bortezomib, carfilzomib, and ixazomib) having already been approved. There is a different situation altogether in the treatment of amyloid light chain (AL) amyloidosis where owing to the rarity of this entity neither of these drugs has currently gained approval. Amyloid light chain plasma cells are possibly more vulnerable to bortezomib than myeloma plasmocytes because of a slightly distinct mechanism of action, which is described in depth in this manuscript. Bortezomib is highly active and rapidly effective as a single agent and even more potent in combination with dexamethasone and alkylators. Bortezomib‐based regimens have become a standard part of the initial treatment of AL amyloidosis in the majority of centers. We have reviewed all available data on bortezomib in various combinations and settings. Carfilzomib seems to be effective but also toxic in these fragile patients with a high rate of cardiac events. Oral ixazomib has shown a surprisingly high efficacy with manageable toxicity and has received the Food and Drug Administration Breakthrough Therapy designation in 2014 for relapsed AL amyloidosis patients. In this review we have comprehensively described the current available knowledge of these 3 proteasome inhibitors and their use in AL amyloidosis.
Water isotopic variability in Mallorca: a path to understanding past changes in hydroclimate
Authors: Dumitru Oana A. , Forray Ferenc L. , Fornós Joan J. , Ersek Vasile , Onac Bogdan P. 
Published: September 2016

AbstractThis paper reports the first results on δ18O and δ2H analysis of precipitations, cave drip waters, and groundwaters from sites in Mallorca (Balearic Islands, western Mediterranean), a key region for paleoclimate studies. Understanding the isotopic variability and the sources of moisture in modern climate systems is required to develop speleothem isotope‐based climate reconstructions. The stable isotopic composition of precipitation was analysed in samples collected between March 2012 and March 2013. The values are in the range reported by GNIP Palma station. Based on these results, the local meteoric water line (LMWL) δ2H = 7.9 (±0.3) δ18O + 10.8 (±2.5) was derived, with slightly lower slope than Global Meteoric Water Line. The results help tracking two main sources of air masses affecting the study sites: rain events with the highest δ18O values (> −5‰) originate over the Mediterranean Sea, whereas the more depleted samples (< −8‰) are sourced in the North Atlantic region. The back trajectory analysis and deuterium excess values, ranging from 0.4 to 18.4‰, further support our findings. To assess the isotopic variation across the island, water samples from eight caves were collected. The δ18O values range between −6.9 and −1.6‰. With one exception (Artà), the isotopic composition of waters in caves located along the coast (Drac, Vallgornera, Cala Varques, Tancada, and Son Sant Martí) indicates Mediterranean‐sourced moisture masses. By contrast, the drip water δ18O values for inland caves (Campanet, ses Rates Pinyades) or developed under a thick (>50 m) limestone cap (Artà) exhibit more negative values. A well‐homogenized aquifer supplied by rainwaters of both origins is clearly indicated by groundwater δ18O values, which show to be within 2.4‰ of the unweighted arithmetic mean of −7.4‰. Although limited, the isotopic data presented here constitute the baseline for future studies using speleothem δ18O records for western Mediterranean paleoclimate reconstructions. Copyright © 2016 John Wiley & Sons, Ltd.
Mutant formC115HofClostridium sporogenesmethionine γ‐lyase efficiently cleavesS‐Alk(en)yl‐l‐cysteine sulfoxides to antibacterial thiosulfinates
Authors: Kulikova Vitalia V. , Anufrieva Natalya V. , Revtovich Svetlana V. , Chernov Alexander S. , Telegin Georgii B. , Morozova Elena A. , Demidkina Tatyana V. 
Published: September 2016

AbstractPyridoxal 5'‐phosphate‐dependent methionine γ‐lyase (MGL) catalyzes the β‐elimination reaction of S‐alk(en)yl‐l‐cysteine sulfoxides to thiosulfinates, which possess antimicrobial activity. Partial inactivation of the enzyme in the course of the reaction occurs due to oxidation of active site cysteine 115 conserved in bacterial MGLs. In this work, the C115H mutant form ofClostridium sporogenesMGL was prepared and the steady‐state kinetic parameters of the enzyme were determined. The substitution results in an increase in the catalytic efficiency of the mutant form towards S‐substitutedl‐cysteine sulfoxides compared to the wild type enzyme. We used a sulfoxide/enzyme system to generate antibacterial activityin situ. Two‐component systems composed of the mutant enzyme and three S‐substitutedl‐cysteine sulfoxides were demonstrated to be effective against Gram‐positive and Gram‐negative bacteria and three clinical isolates from mice. © 2016 IUBMB Life, 68(10):830–835, 2016