bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of SLICC criteria in a large, diverse lupus registry enables SLE classification of a subset of ACR-designated subjects with incomplete lupus
Authors: Aberle Teresa , Bourn Rebecka L , Chen Hua , Roberts Virginia C , Guthridge Joel M , Bean Krista , Robertson Julie M , Sivils Kathy L , Rasmussen Astrid , Liles Meghan , Merrill Joan T , Harley John B , Olsen Nancy J , Karp David R , James Judith A 
Published: March 2017

ObjectiveSLE is traditionally classified using the American College of Rheumatology (ACR) criteria. The Systemic Lupus International Collaborating Clinics (SLICC) recently validated an alternative system. This study examined large cohorts of subjects with SLE and incomplete lupus erythematosus (ILE) to compare the impact of ACR and SLICC criteria.MethodsMedical records of subjects in the Lupus Family Registry and Repository were reviewed for documentation of 1997 ACR classification criteria, SLICC classification criteria and medication usage. Autoantibodies were assessed by indirect immunofluorescence (ANA, antidouble-stranded DNA), precipitin (Sm) and ELISA (anticardiolipin). Other relevant autoantibodies were detected by precipitin and with a bead-based multiplex assay.ResultsOf 3575 subjects classified with SLE under at least one system, 3312 (92.6%) were classified as SLE by both systems (SLEboth), 85 only by ACR criteria (SLEACR-only) and 178 only by SLICC criteria (SLESLICC-only). Of 440 subjects meeting 3 ACR criteria, 33.9% (149/440) were SLESLICC-only, while 66.1% (n=291, designated ILE) did not meet the SLICC classification criteria. Under the SLICC system, the complement criterion and the individual autoantibody criteria enabled SLE classification of SLESLICC-onlysubjects, while SLEACR-onlysubjects failed to meet SLICC classification due to the combined acute/subacute cutaneous criterion. The SLICC criteria classified more African-American subjects by the leucopenia/lymphopenia criterion than did ACR criteria. Compared with SLEACR-onlysubjects, SLESLICC-onlysubjects exhibited similar numbers of affected organ systems, rates of major organ system involvement (∼30%: pulmonary, cardiovascular, renal, neurological) and medication history.ConclusionsThe SLICC criteria classify more subjects with SLE than ACR criteria; however, individuals with incomplete lupus still exist under SLICC criteria. Subjects who gain SLE classification through SLICC criteria exhibit heterogeneous disease, including potential major organ involvement. These results provide supportive evidence that SLICC criteria may be more inclusive of SLE subjects for clinical studies.
ABCD2risk score does not predict the presence of cerebral microemboli in patients with hyper-acute symptomatic critical carotid artery stenosis
Authors: Saedon Mahmud , Hutchinson Charles E , Imray Christopher H E , Singer Donald R J 
Published: March 2017

IntroductionABCD2risk score and cerebral microemboli detected by transcranial Doppler (TCD) have been separately shown to the predict risk of recurrent acute stroke. We studied whether ABCD2risk score predicts cerebral microemboli in patients with hyper-acute symptomatic carotid artery stenosis.Participants and methodsWe studied 206 patients presenting within 2 weeks of transient ischaemic attack or minor stroke and found to have critical carotid artery stenosis (≥50%). 86 patients (age 70±1 (SEM: years), 58 men, 83 Caucasian) had evidence of microemboli; 72 (84%) of these underwent carotid endarterectomy (CEA). 120 patients (age 72±1 years, 91 men, 113 Caucasian) did not have microemboli detected; 102 (85%) of these underwent CEA. Data were analysed usingX2and Mann–Whitney U tests and receiver operating characteristic (ROC) curves.Results140/206 (68%: 95% CI 61.63 to 74.37) patients with hyper-acute symptomatic critical carotid stenosis had an ABCD2risk score ≥4. There was no significant difference in the NICE red flag criterion for early assessment (ABCD2risk score ≥4) for patients with cerebral microemboli versus those without microemboli (59/86 vs 81/120 patients: OR 1.05 ABCD2risk score ≥4 (95% CI 0.58 to 1.90, p=0.867)). The ABCD2risk score was <4 in 27 of 86 (31%: 95% CI 21 to 41) embolising patients and in 39 of 120 (31%: 95% CI 23 to 39) without cerebral microemboli. After adjusting for pre-neurological event antiplatelet treatment (APT), area under the curve (AUC) of ROC for ABCD2risk score showed no prediction of cerebral microemboli (no pre-event APT, n=57: AUC 0.45 (95% CI 0.29 to 0.60, p=0.531); pre-event APT, n=147: AUC 0.51 (95% CI 0.42 to 0.60, p=0.804)).ConclusionsThe ABCD2score did not predict the presence of cerebral microemboli or carotid disease in over one-quarter of patients with symptomatic critical carotid artery stenosis. On the basis of NICE guidelines (refer early if ABCD2≥4), assessment of high stroke risk based on ABCD2scoring may lead to inappropriate delay in urgent treatment in many patients.
The 35/9-7 Skarfjell discovery: a genuine stratigraphic trap, NE North Sea, Norway
Authors: Koch Jens-Ole , Frischbutter Andreas , Øygard Kjell , Cater John 
Published: March 2017

Abstract
The Skarfjell oil and gas discovery, situated 50 km north of the Troll Field in the NE North Sea, was discovered by well 35/9-7 and was appraised by three additional wells operated by Wintershall, in the period 2012–14.
The Skarfjell discovery is an example of a combined structural/stratigraphic trap. The trap formed along the northern edge of a deep WNW–ESE-trending submarine canyon, which was created by Volgian erosion of intra-Heather, Oxfordian-aged sandstones and then infilled with Draupne Formation shales. This mud-filled canyon forms the top and side seal, with the bottom seal provided by Heather shales. The reservoir comprises mid-Oxfordian deep-water turbidites and sediment gravity flows, which formed in response to tectonic hinterland uplift and erosion of the basin margin, 10–20 km to the east.
The Skarfjell discovery contains light oil and gas, and may be subdivided into Skarfjell West, in which the main oil reservoir and gas cap have known contacts, and Skarfjell Southeast, which comprises thinner oil and gas reservoirs with slightly lower pressure and unknown hydrocarbon contacts.
The Upper Jurassic Draupne and Heather formations are excellent source rocks in the study area. They have generated large volumes of oil and gas reservoired in fields, and discoveries for which the dominant source rock and its maturity have been established by oil to source rock correlation and geochemical biomarker analysis. The Skarfjell fluids were expelled from mid-mature oil source rocks of mixed Heather and Draupne Formation origin.

The recoverable resources are estimated at between 9 and 16 million standard cubic metres (Sm
3
) of recoverable oil and condensate, and 4–6 billion Sm
3
of recoverable gas. The Skarfjell discovery is currently in the pre-development phase and is expected to come on stream in 2021.
Chemical relationships of ambers using attenuated total reflectance Fourier transform infrared spectroscopy
Authors: Cotton L. J. , Vollrath F. , Brasier M. D. , Dicko C. 
Published: March 2017

Abstract
Amber is known for its remarkably well-preserved fossils, but the chemical complexity of amber and its history are less well known. Amber is highly variable in both its physical and chemical properties, which are dependent on factors such as the source tree and the diagenetic history. Amber from a given locality therefore has a unique chemical composition. Fourier transform infrared (FTIR) spectroscopy is often used to determine the chemical composition of amber and to provide a fingerprint for amber samples. We used FTIR spectroscopy to analyse samples spanning the time period from the Early Cretaceous to the Oligo-Miocene from 17 localities in the Americas, Europe and Asia. We then used cluster analysis to examine the trends in amber chemistry and to increase our understanding of its formation through time. A detailed analysis of the clustering followed by modelling of the variables of importance suggested that the exocyclic methylene group content and conformation play a major part in explaining the clustering. Other variables, such as the ester and alkyl contents, contribute to identification. Placed in a broader perspective, our study indicates that the dominant factor in clustering is the age of the amber, followed by the locality.

Supplementary material:
Detailed sample list and combined spectra of all samples are available at
https://doi.org/10.6084/m9.figshare.c.3704920
Body Size Indicators and Risk of Gallbladder Cancer: Pooled Analysis of Individual-Level Data from 19 Prospective Cohort Studies
Authors: Campbell Peter T. , Newton Christina C. , Kitahara Cari M. , Patel Alpa V. , Hartge Patricia , Koshiol Jill , McGlynn Katherine A. , Adami Hans-Olov , Berrington de González Amy , Beane Freeman Laura E. , Bernstein Leslie , Buring Julie E. , Freedman Neal D. , Gao Yu-Tang , Giles Graham G. , Gunter Marc J. , Jenab Mazda , Liao Linda M. , Milne Roger L. , Robien Kim , Sandler Dale P. , Schairer Catherine , Sesso Howard D. , Shu Xiao-Ou , Weiderpass Elisabete , Wolk Alicja , Xiang Yong-Bing , Zeleniuch-Jacquotte Anne , Zheng Wei , Gapstur Susan M. 
Published: March 2017

Abstract
Background: There are few established risk factors for gallbladder cancer beyond gallstones. Recent studies suggest a higher risk with high body mass index (BMI), an indicator of general heaviness, but evidence from other body size measures is lacking.
Methods: Associations of adult BMI, young adult BMI, height, adult weight gain, waist circumference (WC), waist–height ratio (WHtR), hip circumference (HC), and waist–hip ratio (WHR) with gallbladder cancer risk were evaluated. Individual-level data from 1,878,801 participants in 19 prospective cohort studies (14 studies had circumference measures) were harmonized and included in this analysis. Multivariable Cox proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI).
Results: After enrollment, 567 gallbladder cancer cases were identified during 20.1 million person-years of observation, including 361 cases with WC measures. Higher adult BMI (per 5 kg/m2, HR: 1.24; 95% CI, 1.13–1.35), young adult BMI (per 5 kg/m2, HR: 1.12; 95% CI, 1.00–1.26), adult weight gain (per 5 kg, HR: 1.07; 95% CI, 1.02–1.12), height (per 5 cm, HR: 1.10; 95% CI, 1.03–1.17), WC (per 5 cm, HR: 1.09; 95% CI, 1.02–1.17), WHtR (per 0.1 unit, HR: 1.24; 95% CI, 1.00–1.54), and HC (per 5 cm, HR: 1.13; 95% CI, 1.04–1.22), but not WHR (per 0.1 unit, HR: 1.03; 95% CI, 0.87–1.22), were associated with higher risks of gallbladder cancer, and results did not differ meaningfully by sex or other demographic/lifestyle factors.
Conclusions: These findings indicate that measures of overall and central excess body weight are associated with higher gallbladder cancer risks.
Impact: Excess body weight is an important, and potentially preventable, gallbladder cancer risk factor. Cancer Epidemiol Biomarkers Prev; 26(4); 597–606. ©2017 AACR.
Selinexor (KPT-330) Induces Tumor Suppression through Nuclear Sequestration of IκB and Downregulation of Survivin
Authors: Nair Jayasree S. , Musi Elgilda , Schwartz Gary K. 
Published: March 2017

Abstract
Purpose: Selinexor, a small molecule that inhibits nuclear export protein XPO1, has demonstrated efficacy in solid tumors and hematologic malignancies with the evidence of clinical activity in sarcoma as a single agent. Treatment options available are very few, and hence the need to identify novel targets and strategic therapies is of utmost importance.
Experimental Design: The mechanistic effects of selinexor in sarcomas as a monotherapy and in combination with proteasome inhibitor, carfilzomib, across a panel of cell lines in vitro and few in xenograft mouse models were investigated.
Results: Selinexor induced IκB nuclear localization as a single agent, and the effect was enhanced by stabilization of IκB when pretreated with the proteasome inhibitor carfilzomib. This stabilization and retention of IκB in the nucleus resulted in inhibition of NFκB and transcriptional suppression of the critical antiapoptotic protein, survivin. Treatment of carfilzomib followed by selinexor caused selinexor-sensitive and selinexor-resistant cell lines to be more sensitive to selinexor as determined by an increase in apoptosis. This was successfully demonstrated in the MPNST xenograft model with enhanced tumor suppression.
Conclusions: The subcellular distributions of IκB and NFκB are indicative of carcinogenesis. Inhibition of XPO1 results in intranuclear retention of IκB, which inhibits NFκB and thereby provides a novel mechanism for drug therapy in sarcoma. This effect can be further enhanced in relatively selinexor-resistant sarcoma cell lines by pretreatment with the proteasome inhibitor carfilzomib. Because of these results, a human clinical trial with selinexor in combination with a proteasome inhibitor is planned for the treatment of sarcoma. Clin Cancer Res; 23(15); 4301–11. ©2017 AACR.
The PARP Inhibitor Veliparib Can Be Safely Added to Bendamustine and Rituximab and Has Preliminary Evidence of Activity in B-Cell Lymphoma
Authors: Soumerai Jacob D. , Zelenetz Andrew D. , Moskowitz Craig H. , Palomba M. Lia , Hamlin Paul A. , Noy Ariela , Straus David J. , Moskowitz Alison J. , Younes Anas , Matasar Matthew J. , Horwitz Steven M. , Portlock Carol S. , Konner Jason A. , Gounder Mrinal M. , Hyman David M. , Voss Martin H. , Fury Matthew G. , Gajria Devika , Carvajal Richard D. , Ho Alan L. , Beumer Jan H. , Kiesel Brian , Zhang Zhigang , Chen Alice , Little Richard F. , Jarjies Christine , Dang Thu O. , France Fallon , Mishra Nishant , Gerecitano John F. 
Published: March 2017

AbstractPurpose: The PARP inhibitor veliparib enhances the cytotoxicity of alkylating agents. This phase I study evaluated veliparib with the bifunctional alkylator bendamustine (VB) in patients with relapsed/refractory lymphoma, multiple myeloma, and solid malignancies, with a cohort expansion of VB with rituximab (VBR) in patients with B-cell lymphomas.Experimental Design: This dose-escalation study evaluated safety, pharmacokinetics, and preliminary efficacy of veliparib (20–400 mg twice a day, days 1–7 of 28-day cycle) and bendamustine (70 and 90 mg/m2 intravenously, days 1 and 2). A cohort expansion was conducted, which combined veliparib and bendamustine at the maximum tolerated dose (MTD) with rituximab (375 mg/m2, day 1) in patients with B-cell lymphomas. Thirty-four patients were treated in seven dose-escalation cohorts and seven patients in the dose-expansion cohort.Results: The MTD was veliparib 300 mg twice daily plus bendamustine 90 mg/m2. Dose-limiting toxicities (DLT) were anemia, nausea, hypertension, and hyperhidrosis. Grade ≥3 toxicities included lymphopenia (87.8%), anemia (19.5%), neutropenia (12.2%), thrombocytopenia (9.8%), leukopenia (9.8%), nausea (7.3%), and hypophosphatemia (7.3%). Apparent veliparib clearance was slightly lower than previously reported. Of 14 patients with lymphoma evaluable for response, five of seven (71%) on VB and six of seven (86%) on VBR achieved objective response. One patient with multiple myeloma achieved partial response.Conclusions: VB and VBR were generally well-tolerated. VBR had preliminary clinical activity in patients with B-cell lymphoma, which warrants further investigation in a phase II trial. This trial was registered at www.clinicaltrials.gov as NCT01326702. Clin Cancer Res; 23(15); 4119–26. ©2017 AACR.
Abituzumab Targeting of αV-Class Integrins Inhibits Prostate Cancer Progression
Authors: Jiang Yuan , Dai Jinlu , Yao Zhi , Shelley Greg , Keller Evan T. 
Published: March 2017

AbstractIntegrins that contain an integrin αV subunit contribute to multiple functions that promote cancer progression. The goal of this study was to determine whether abituzumab (DI17E6, EMD 525797), a humanized monoclonal antibody (mAb) against integrin αV impacts, prostate cancer progression. To evaluate this, prostate cancer cells were treated with DI17E6 and its effects on proliferation, apoptosis, cell-cycle, adhesion, detachment, migration, invasion and phosphorylation of downstream targets, including FAK, Akt, and ERK, were determined. DI17E6 promoted detachment and inhibited adhesion of prostate cancer cells to several extracellular matrix (ECM) proteins and cells found in the bone microenvironment but had no impact on cell viability, cell-cycle, and caspase-3/7 activity. DI17E6 inhibited migration and invasion of prostate cancer cells. In addition, DI7E6 decreased phosphorylation of FAK, Akt, and ERK. These results indicate that inhibition of integrin αV with DI17E6 inhibits several prometastatic phenotypes of prostate cancer cells and therefore provide a rationale for further evaluation of DI17E6 for diminishing prostate cancer progression.Implications: This work identifies that therapeutic targeting of integrins containing an αV integrin unit inhibits cancer progression and thus may be of clinical benefit. Mol Cancer Res; 15(7); 875–83. ©2017 AACR.
Quantitative Proteome Heterogeneity in Myeloproliferative Neoplasm Subtypes and Association with JAK2 Mutation Status
Authors: Socoro-Yuste Nuria , Čokić Vladan P. , Mondet Julie , Plo Isabelle , Mossuz Pascal 
Published: March 2017

Abstract
Apart from well-known genetic abnormalities, several studies have reported variations in protein expression in Philadelphia-negative myeloproliferative neoplasm (MPN) patients that could contribute toward their clinical phenotype. In this context, a quantitative mass spectrometry proteomics protocol was used to identify differences in the granulocyte proteome with the goal to characterize the pathogenic role of aberrant protein expression in MPNs. LC/MS-MS (LTQ Orbitrap) coupled to iTRAQ labeling showed significant and quantitative differences in protein content among various MPN subtypes [polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)], and according to the genetic status of JAK2 (JAK2V617F presence and JAK2V617F allele burden). A number of differentially expressed proteins were identified, with the most frequent being members of the RAS GTPase family and oxidative stress regulatory proteins. Subsequent analysis found that calreticulin (CALR), known to be involved in calcium homeostasis and apoptotic signaling, was overexpressed in JAK2V617F granulocytes compared with JAK2 wild type and independently of the JAK2V617F allele burden. Finally, it was demonstrated, in a Ba/F3 cell model, that increased calreticulin expression was directly linked to JAK2V617F and could be regulated by JAK2 kinase inhibitors.
Implications: In conclusion, these results reveal proteome alterations in MPN granulocytes depending on the phenotype and genotype of patients, highlighting new oncogenic mechanisms associated with JAK2 mutations and overexpression of calreticulin. Mol Cancer Res; 15(7); 852–61. ©2017 AACR.
Distribution and Prognostic Significance of Fragmented QRS in Patients With Brugada Syndrome
Authors: Morita Hiroshi , Watanabe Atsuyuki , Morimoto Yoshimasa , Kawada Satoshi , Tachibana Motomi , Nakagawa Koji , Nishii Nobuhiro , Ito Hiroshi 
Published: March 2017

Background—
Fragmented QRS complexes (fQRS) in the right precordial leads are associated with occurrence of ventricular fibrillation (VF) in Brugada syndrome. Recently, epicardial mapping has revealed abnormal electrograms at the right ventricular (RV) outflow tract and inferior region of the right ventricle. fQRS may reflect the extent of the area of abnormal potentials, but whether the distribution of fQRS has prognostic value is not known.

Methods and Results—
We evaluated the existence of fQRS in 456 patients with Brugada syndrome, including 117 patients with syncope and 23 patients with VF. The region of fQRS was defined as inferior (II, III, and aVF), lateral (I, aVL, and V5 and V6), anterior (V3 and V4), RV (V1 and V2), and RV outflow tract (V1 and V2 at the third intercostal space). fQRS were present in 229 patients (RV outflow tract in 175, inferior in 135, RV in 90, and lateral in 16 patients). During follow-up (mean 91 months), 39 patients experienced VF. In univariable analyses, fQRS in any distribution and fQRS in each region excluding the RV were associated with VF. Multivariable analysis showed that fQRS in the inferior (hazard ratio, 3.9; confidence interval, 1.9–8.5), lateral (hazard ratio, 3.5; confidence interval, 1.2–8.2), and RV outflow tract (hazard ratio, 2.5; confidence interval, 1.2–5.6) were associated with VF events. The presence of multiple regions of fQRS was associated with worse prognosis.

Conclusions—
The distribution of fQRS is associated with prognosis in Brugada syndrome, further supporting the association of fQRS and arrhythmia substrate.
Performance of the Atherosclerotic Cardiovascular Disease Pooled Cohort Risk Equations by Social Deprivation Status
Authors: Colantonio Lisandro D. , Richman Joshua S. , Carson April P. , Lloyd‐Jones Donald M. , Howard George , Deng Luqin , Howard Virginia J. , Safford Monika M. , Muntner Paul , Goff David C. 
Published: March 2017

Background

The atherosclerosis cardiovascular disease (
ASCVD
) Pooled Cohort risk equations have shown different calibration across
US
populations with varied levels of social deprivation.

Methods and Results

We analyzed the calibration and discrimination of the Pooled Cohort risk equations by social deprivation status among 9066
REGARDS
(REasons for Geographic And Racial Differences in Stroke) study participants not taking statins for whom
ASCVD
risk may lead to statin initiation. Patients were aged 45 to 79 years, had no
ASCVD
or diabetes mellitus, and had a low‐density lipoprotein cholesterol level 70 to 189 mg/dL. Social deprivation was defined using 3 indicators: annual household income <$25 000, less than a high school education, and living without a partner. At baseline in 2003–2007, 54.6%, 27.4%, and 18.0% of participants had 0, 1, and 2 or 3 indicators showing deprivation, respectively. From baseline through December 2012, 457 participants developed
ASCVD
(nonfatal/fatal stroke, myocardial infarction, or coronary heart disease death). Predicted and observed
ASCVD
incidence per 1000 person‐years were 8.02 and 6.23 (95%
CI
, 5.31–7.31), respectively, among participants with 0 indicators of deprivation (Hosmer–Lemeshow
P
=0.01); 8.05 and 6.61 (95%
CI
, 5.29–8.24), respectively, with 1 indicator (
P
=0.09); and 9.83 and 11.40 (95%
CI
, 9.23–14.05), respectively, with 2 or 3 indicators (
P
=0.12). The C‐index (95%
CI
) was 0.72 (0.69–0.75), 0.73 (0.69–0.78), and 0.70 (0.65–0.75) among participants with 0, 1, and 2 or 3 indicators of deprivation, respectively. The net reclassification improvement after adding deprivation data to the Pooled Cohort risk equations was modest (0.12; 95%
CI
, 0.03–0.21).

Conclusions

The Pooled Cohort risk equations have good calibration among individuals with social deprivation but overestimate
ASCVD
risk among those with less social deprivation.
Bone marrow transplantation prevents right ventricle disease in the caveolin-1–deficient mouse model of pulmonary hypertension
Authors: Asosingh Kewal , Wanner Nicholas , Weiss Kelly , Queisser Kimberly , Gebreab Liya , Kassa Biruk , Stuehr Eric , Graham Brian , Erzurum Serpil 
Published: March 2017

Key PointsCaveolin-1 deficiency in hematopoietic stem cells induces right heart disease. Healthy BM protects the right heart from maladaptation.