bluuebunny/crossref_metadata_2025_split huggingface dataset:
Instrumental magnitude constraints for the 11 July 1889, Chilik earthquake
Authors: Krüger Frank , Kulikova Galina , Landgraf Angela 
Published: November 2015

Abstract
A series of large-magnitude earthquakes above 6.9 occurred in the northern Tien-Shan between 1885 and 1911. The Chilik earthquake of 11 July 1889, has been listed with a magnitude of 8.3, based on sparse macroseismic intensities, constrained by reported damage. Despite the existence of several juvenile fault scarps in the epicentral region, that are possibly associated with the 1889 earthquake, no through-going surface rupture having the dimensions expected for a magnitude 8.3 earthquake has been located – a puzzling dilemma. Could the magnitude have been overestimated? This would have major implications not only for the understanding of the earthquake series, but also for regional hazard estimates. Fortunately, a fragmentary record from an early Rebeur–Paschwitz seismometer exists for the Chilik event, recorded in Wilhelmshaven (Germany). To constrain the magnitude, we compare the late coda waves of this record with those of recent events from Central Asia, recorded on modern instruments in Germany and filtered with Rebeur–Paschwitz instrument characteristics. Additional constraints come from disturbances of historic magnetograms that exist from the Chilik and the 1911 Chon-Kemin earthquakes. Scaling of these historic records confirm a magnitude of about 8 for the 1889 Chilik earthquake, pointing towards a lower crustal contribution to the fault area.
Diagenetic pathways linked to labile Mg-clays in lacustrine carbonate reservoirs: a model for the origin of secondary porosity in the Cretaceous pre-salt Barra Velha Formation, offshore Brazil
Authors: Tosca Nicholas J. , Wright V. Paul 
Published: November 2015

Abstract
The lacustrine carbonate reservoirs of the South Atlantic host significant accumulations of chemically reactive and Al-free Mg-silicate minerals (e.g. stevensite, kerolite and talc). Petrographic data from units such as the Cretaceous Barra Velha Formation in the Santos Basin suggest that Mg-silicate minerals strongly influenced, and perhaps created, much of the observed secondary porosity. The diagenetic interactions between reactive Mg-silicate minerals and carbonate sediments are, however, poorly known. Here we develop a conceptual model for the origin of secondary porosity in the Barra Velha Formation guided by considerations of the chemistry that triggers Mg-silicate crystallization, as well as the geochemical and mineralogical factors that act as prerequisites for rapid Mg-silicate dissolution during early and late diagenesis. We conclude that sub-littoral zones of volcanically influenced rift lakes would have acted as the locus for widespread Mg-silicate accumulation and preservation. Organic-rich profundal sediments, however, would be especially prone to Mg-silicate dissolution and secondary porosity development. Here, organic matter diagenesis (especially methanogenesis) plays a major role in modifying the dissolved inorganic carbon budget and the pH of sediment porewaters, which preferentially destabilizes and then dissolves Mg-silicates. Together, the sedimentological, stratigraphic and geochemical predictions of the model explain many enigmatic features of the Barra Velha Formation, providing a novel framework for understanding how Mg-silicate–carbonate interactions might generate secondary porosity more broadly in other lacustrine carbonate reservoirs across the South Atlantic.
ImmunoPET with Anti-Mesothelin Antibody in Patients with Pancreatic and Ovarian Cancer before Anti-Mesothelin Antibody–Drug Conjugate Treatment
Authors: Lamberts Laetitia E. , Menke-van der Houven van Oordt Catharina W. , ter Weele Eva J. , Bensch Frederike , Smeenk Michiel M. , Voortman Johannes , Hoekstra Otto S. , Williams Simon P. , Fine Bernard M. , Maslyar Daniel , de Jong Johan R. , Gietema Jourik A. , Schröder Carolien P. , Bongaerts Alphons H.H. , Lub-de Hooge Marjolijn N. , Verheul Henk M.W. , Sanabria Bohorquez Sandra M. , Glaudemans Andor W.J.M. , de Vries Elisabeth G.E. 
Published: November 2015

Abstract
Purpose: Mesothelin (MSLN) is frequently overexpressed in pancreatic and ovarian cancers, making it a potential drug target. We performed an 89Zr-PET imaging study with MMOT0530A, a MSLN antibody, in conjunction with a phase I study with the antibody–drug conjugate DMOT4039A, containing MMOT0530A bound to MMAE. The aim was to study antibody tumor uptake, whole-body distribution, and relation between uptake, response to treatment, and MSLN expression.
Experimental Design: Before DMOT4039A treatment, patients received 37 MBq 89Zr-MMOT0530A followed by PET/CT imaging 2, 4, and 7 days postinjection. Tracer uptake was expressed as standardized uptake value (SUV). MSLN expression was determined with immunohistochemistry (IHC) on archival tumor tissue.
Results: Eleven patients were included, 7 with pancreatic and 4 with ovarian cancer. IHC MSLN expression varied from absent to strong. Suitable tracer antibody dose was 10 mg MMOT0530A and optimal imaging time was 4 and 7 days postinjection. Tumor tracer uptake occurred in 37 lesions with mean SUVmax of 13.1 (±7.5) on PET 4 days postinjection, with 11.5 (±7.5) in (N = 17) pancreatic and 14.5 (±8.7) in (N = 20) ovarian cancer lesions. Within patients, a mean 2.4-fold (±1.10) difference in uptake between tumor lesions existed. Uptake in blood, liver, kidneys, spleen, and intestine reflected normal antibody distribution. Tracer tumor uptake was correlated to IHC. Best response to DMOT4039A was partial response in one patient.
Conclusions: With 89Zr-MMOT0530A-PET, pancreatic and ovarian cancer lesions as well as antibody biodistribution could be visualized. This technique can potentially guide individualized antibody-based treatment. Clin Cancer Res; 22(7); 1642–52. ©2015 AACR.
Pericytes Promote Malignant Ovarian Cancer Progression in Mice and Predict Poor Prognosis in Serous Ovarian Cancer Patients
Authors: Sinha Devbarna , Chong Lynn , George Joshy , Schlüter Holger , Mönchgesang Susann , Mills Stuart , Li Jason , Parish Christopher , Bowtell David , Kaur Pritinder 
Published: November 2015

Abstract
Purpose: The aim of this study was to investigate the role of pericytes in regulating malignant ovarian cancer progression.
Experimental Design: The pericyte mRNA signature was used to interrogate ovarian cancer patient datasets to determine its prognostic value for recurrence and mortality. Xenograft models of ovarian cancer were used to determine if co-injection with pericytes affected tumor growth rate and metastasis, whereas co-culture models were utilized to investigate the direct effect of pericytes on ovarian cancer cells. Pericyte markers were used to stain patient tissue samples to ascertain their use in prognosis.
Results: Interrogation of two serous ovarian cancer patient datasets [the Australian Ovarian Cancer Study, n = 215; and the NCI TCGA (The Cancer Genome Atlas), n = 408] showed that a high pericyte score is highly predictive for poor patient prognosis. Co-injection of ovarian cancer (OVCAR-5 & -8) cells with pericytes in a xenograft model resulted in accelerated ovarian tumor growth, and aggressive metastases, without altering tumor vasculature. Pericyte co-culture in vitro promoted ovarian cancer cell proliferation and invasion. High αSMA protein levels in patient tissue microarrays were correlated with more aggressive disease and earlier recurrence.
Conclusions: High pericyte score provides the best means to date of identifying patients with ovarian cancer at high risk of rapid relapse and mortality (mean progression-free survival time &lt; 9 months). The stroma contains rare yet extremely potent locally resident mesenchymal stem cells—a subset of “cancer-associated fibroblasts” that promote aggressive tumor growth and metastatic dissemination, underlying the prognostic capacity of a high pericyte score to strongly predict earlier relapse and mortality. Clin Cancer Res; 22(7); 1813–24. ©2015 AACR.
EZH2 Inhibition Blocks Multiple Myeloma Cell Growth through Upregulation of Epithelial Tumor Suppressor Genes
Authors: Hernando Henar , Gelato Kathy A. , Lesche Ralf , Beckmann Georg , Koehr Silke , Otto Saskia , Steigemann Patrick , Stresemann Carlo 
Published: November 2015

AbstractMultiple myeloma is a plasma cell malignancy characterized by marked heterogeneous genomic instability including frequent genetic alterations in epigenetic enzymes. In particular, the histone methyltransferase Enhancer of Zeste Homolog 2 (EZH2) is overexpressed in multiple myeloma. EZH2 is the catalytic component of the polycomb repressive complex 2 (PRC2), a master transcriptional regulator of differentiation. EZH2 catalyzes methylation of lysine 27 on histone H3 and its deregulation in cancer has been reported to contribute to silencing of tumor suppressor genes, resulting in a more undifferentiated state, and thereby contributing to the multiple myeloma phenotype. In this study, we propose the use of EZH2 inhibitors as a new therapeutic approach for the treatment of multiple myeloma. We demonstrate that EZH2 inhibition causes a global reduction of H3K27me3 in multiple myeloma cells, promoting reexpression of EZH2-repressed tumor suppressor genes in a subset of cell lines. As a result of this transcriptional activation, multiple myeloma cells treated with EZH2 inhibitors become more adherent and less proliferative compared with untreated cells. The antitumor efficacy of EZH2 inhibitors is also confirmed in vivo in a multiple myeloma xenograft model in mice. Together, our data suggest that EZH2 inhibition may provide a new therapy for multiple myeloma treatment and a promising addition to current treatment options. Mol Cancer Ther; 15(2); 287–98. ©2015 AACR.
Retuning of Mouse NK Cells after Interference with MHC Class I Sensing Adjusts Self-Tolerance but Preserves Anticancer Response
Authors: Wagner Arnika Kathleen , Wickström Stina Linnea , Tallerico Rossana , Salam Sadia , Lakshmikanth Tadepally , Brauner Hanna , Höglund Petter , Carbone Ennio , Johansson Maria Helena , Kärre Klas 
Published: November 2015

Abstract
Natural killer (NK) cells are most efficient if their targets do not express self MHC class I, because NK cells carry inhibitory receptors that interfere with activating their cytotoxic pathway. Clinicians have taken advantage of this by adoptively transferring haploidentical NK cells into patients to mediate an effective graft-versus-leukemia response. With a similar rationale, antibody blockade of MHC class I–specific inhibitory NK cell receptors is currently being tested in clinical trials. Both approaches are challenged by the emerging concept that NK cells may constantly adapt or “tune” their responsiveness according to the amount of self MHC class I that they sense on surrounding cells. Hence, these therapeutic attempts would initially result in increased killing of tumor cells, but a parallel adaptation process might ultimately lead to impaired antitumor efficacy. We have investigated this question in two mouse models: inhibitory receptor blockade in vivo and adoptive transfer to MHC class I–disparate hosts. We show that changed self-perception via inhibitory receptors in mature NK cells reprograms the reactivity such that tolerance to healthy cells is always preserved. However, reactivity against cancer cells lacking critical MHC class I molecules (missing self-reactivity) still remains or may even be increased. This dissociation between activity against healthy cells and tumor cells may provide an answer as to why NK cells mediate graft-versus-leukemia effects without causing graft-versus-host disease and may also be utilized to improve immunotherapy. Cancer Immunol Res; 4(2); 113–23. ©2015 AACR.
Identification of Anti-CA125 Antibody Responses in Ovarian Cancer Patients by a Novel Deep Sequence–Coupled Biopanning Platform
Authors: Frietze Kathryn M. , Roden Richard B.S. , Lee Ji-Hyun , Shi Yang , Peabody David S. , Chackerian Bryce 
Published: November 2015

Abstract
High-grade epithelial ovarian cancer kills more women than any other gynecologic cancer and is rarely diagnosed at an early stage. We sought to identify tumor-associated antigens (TAA) as candidate diagnostic and/or immunotherapeutic targets by taking advantage of tumor autoantibody responses in individuals with ovarian cancer. Plasma-derived IgG from a pool of five patients with advanced ovarian cancer was subjected to iterative biopanning using a library of bacteriophage MS2 virus-like particles (MS2-VLPs) displaying diverse short random peptides. After two rounds of biopanning, we analyzed the selectant population of MS2-VLPs by Ion Torrent deep sequencing. One of the top 25 most abundant peptides identified (DISGTNTSRA) had sequence similarity to cancer antigen 125 (CA125/MUC16), a well-known ovarian cancer–associated antigen. Mice immunized with MS2-DISGTNTSRA generated antibodies that cross-reacted with purified soluble CA125 from ovarian cancer cells but not membrane-bound CA125, indicating that the DISGTNTSRA peptide was a CA125/MUC16 peptide mimic of soluble CA125. Preoperative ovarian cancer patient plasma (n = 100) was assessed for anti-DISGTNTSRA, anti-CA125, and CA125. Patients with normal CA125 (&lt;35 IU/mL) at the time of diagnosis had significantly more antibodies to DISGTNTSRA and to CA125 than those patients who had high CA125 (&gt;35 IU/mL). A statistically significant survival advantage was observed for patients who had either normal CA125 and/or higher concentrations of antibodies to CA125 at the time of diagnosis. These data show the feasibility of using deep sequence–coupled biopanning to identify TAA autoantibody responses from cancer patient plasma and suggest a possible antibody-mediated mechanism for low CA125 plasma concentrations in some ovarian cancer patients. Cancer Immunol Res; 4(2); 157–64. ©2015 AACR.
Radiologic Heterogeneity in Responses to Anti–PD-1/PD-L1 Therapy in Metastatic Renal Cell Carcinoma
Authors: de Velasco Guillermo , Krajewski Katherine M. , Albiges Laurence , Awad Mark M. , Bellmunt Joaquim , Hodi F. Stephen , Choueiri Toni K. 
Published: November 2015

Abstract
Radiologic assessment of tumor response remains a challenge in patients treated with immune checkpoint inhibitors. In metastatic melanoma, for example, a spectrum of imaging patterns in response to immunotherapies have been recognized and associated with clinical benefit. In metastatic renal cell carcinoma (mRCC), less than half of patients treated with immune checkpoint inhibitors achieve objective responses, but some of the responses have been durable. In this series, five different imaging patterns of response and progression are described in mRCC patients treated with anti–PD-1/PD-L1 agents: (i) early and complete response, (ii) pseudoprogression, (iii) disease stability before ultimate response, (iv) mixed response with new lesions, and (v) early progression/primary refractory disease. The implications of the different imaging patterns of patient responses on disease prognosis are discussed and highlight the need for individualized patient assessment when using these novel immune-targeted agents. Cancer Immunol Res; 4(1); 12–17. ©2015 AACR.
Residual Cardiovascular Risk in Individuals on Blood Pressure–Lowering Treatment
Authors: Lieb Wolfgang , Enserro Danielle M. , Sullivan Lisa M. , Vasan Ramachandran S. 
Published: November 2015

Background

Hypertensive individuals on blood pressure (
BP
)–lowering treatment with
BP
in the normal or high‐normal range have higher cardiovascular risk than untreated persons with usual
BP
in the same range. This residual risk (relative and absolute) is not well quantified and may be attributable in part to the higher burden of subclinical disease in treated individuals.

Methods and Results

We assigned 3024 Framingham Offspring Cohort participants to 5 categories based on systolic
BP
(
SBP
) and diastolic
BP
(
DBP
) and use of
BP
‐lowering treatment: (1) untreated
SBP
/
DBP
<120/80 mm Hg; (2) untreated
SBP
/
DB
≥120/80 to <140/90 mm Hg; (3) treated
SBP
/
DBP
<140/90 mm Hg; (4) untreated
SBP
/
DBP
≥140/90 mm Hg; and (5) treated
SBP
/
DBP
≥140/90 mm Hg. A composite subclinical disease score was constructed, including information on left ventricular hypertrophy, systolic dysfunction, carotid ultrasound abnormality, peripheral artery disease, and microalbuminuria. The prevalence of subclinical disease rose across
BP
groups, as did the event rates for incident cardiovascular disease (449 events, median follow‐up of 11 years; group 1, 0.65 event per 100 person‐years; group 5, 3.20 events per 100 person‐years;
P
<0.0001 for trend). On multivariable adjustment, treated hypertensives in groups 3 and 5 had 50% (95%
CI
13% to 99%) and 28% (95%
CI
−6% to 73%) higher hazards, respectively, of developing cardiovascular disease compared with their untreated counterparts with similar levels of
BP
(groups 1 and 2 and group 4, respectively). The increased risk of cardiovascular disease in treated hypertensives was attributable in part to greater subclinical disease burden.

Conclusions

Treated hypertensives have higher subclinical cardiovascular disease burden, which partly explains their higher cardiovascular disease risk compared with untreated persons with similar
BP
levels.
A direct assay for the routine measurement of testosterone, androstenedione, dihydrotestosterone and dehydroepiandrosterone by liquid chromatography tandem mass spectrometry
Authors: Owen Laura J , Wu Frederick C , Büttler Rahel M , Keevil Brian G 
Published: November 2015

Background The measurement of androgens in many laboratories is often limited to testosterone. To more accurately determine the androgen status in both sexes, the measurement of other androgens such as dihydrotestosterone, the more potent metabolite of testosterone, and androstenendione and dehydroepiandrosterone, the most abundant circulating androgens in women would be informative. We report a combined liquid chromatography tandem mass spectrometry method for the measurement of these androgens. Methods Internal standards in methanol (10  µL) were added to 100  µL serum followed by the addition of zinc sulphate (100  µL). After mixing, 100  µL of acetonitrile was added and was further mixed. The samples were centrifuged and the steroids extracted using an automated online solid phase extraction on a C18 cartridge by a Waters Acquity with online sample manager coupled to a TQS mass spectrometer. Results Separation of the androgens was achieved by liquid chromatography. The run time was 6.5 min per sample. The lower limit of quantitation was 0.1 nmol/L for testosterone, androstenedione and dihydrotestosterone and 1 nmol/L for dehydroepiandrosterone. The coefficient of variation of the assay in serum for testosterone was <6%, androstenedione <8% and dihydrotestosterone and dehydroepiandrosterone <10%. Discussion We have developed a rapid assay for the liquid chromatography tandem mass spectrometry measurement of testosterone, androstenedione, dihydrotestosterone and dehydroepiandrosterone in a routine clinical laboratory. The assay requires a small volume of serum, and all analytes are measured simultaneously. The assay is rapid and simple to execute offering the potential for routine clinical application.
Type 2 Diabetes and Depression
Authors: Kaltman Stacey , Serrano Adriana , Talisman Nicholas , Magee Michelle F. , Cabassa Leopoldo J. , Pulgar-Vidal Olga , Peraza Dorys 
Published: November 2015

Purpose The purpose of the current study was to determine the feasibility, acceptability, and preliminary effectiveness of an integrated self-management intervention that simultaneously targets diabetes and depression self-management in a primary care clinic that serves the Latino immigrant community. Methods The integrated intervention included behavioral activation and motivational interviewing techniques. It was developed with patient, family member, and provider stakeholders, and it comprised 6 individual sessions, followed by 2 monthly booster sessions. Eighteen Latino immigrants participated in an open trial of the intervention. A1C levels were examined at baseline and postintervention. Participants also completed measures of depression, diabetes self-management behaviors, patient activation, and diabetes-related self-efficacy and gave open-ended feedback about the intervention. Results Feasibility of delivering the intervention in the primary care setting and acceptability to the target population were demonstrated. Among participants completing the intervention, A1C levels decreased significantly from baseline. A significant reduction in depressive symptoms and an improvement in diabetes self-management behaviors, patient activation, and diabetes-related self-efficacy were observed. Qualitative responses from participants indicated unilateral positive responses to the intervention and endorsed its continuation in the clinic. Conclusions This pilot trial demonstrated the feasibility and acceptability of an integrated self-management intervention for diabetes and depression. In addition, preliminary data suggest that the intervention may have a positive impact on diabetes and depression-related outcomes. Further evaluation is warranted.
A systematic review of the safety and efficacy of distal coronary artery anastomotic devices in MIDCAB and TECAB surgery
Authors: Soylu Erdinc , Harling Leanne , Ashrafian Hutan , Attaran Saina , Athanasiou Christina , Punjabi Prakash P , Casula Roberto , Athanasiou Thanos 
Published: November 2015

Background: Minimally invasive direct coronary artery bypass (MIDCAB) and totally endoscopic coronary artery bypass (TECAB) techniques may improve recovery and reduce hospital stay following coronary artery bypass surgery (CABG). However, working in a limited space with indirect visualisation would greatly benefit from a simple, high-quality and reproducible automated distal anastomotic method. Several devices have been developed; however, their uptake has been limited due to uncertainty around their impact on patient outcomes. Methods: A systematic review of the literature identified six studies, incorporating 139 subjects undergoing MIDCAB or TECAB surgery using a distal anastomotic device. Results: The overall 30-day mortality was 0.7% (1/137). No cardiac specific mortality was observed. For each outcome of perioperative myocardial infarction (MI), postoperative stroke and haemorrhage, only a single event was observed for each (n=1/136, 1/138 and 1/136, respectively). The overall device failure rates were low, with the use of additional sutures only reported in a single case with the Magnetic Vascular Port (MVP) device. Anastomotic time ranged from a mean of 3.32 minutes with the MVP device to 20 minutes with the C-Port device. Conclusions: These results demonstrate the overall acceptable early outcomes of distal anastomotic devices for use in minimally invasive coronary bypass surgery. Future research should focus on designing adequately powered, comparative, randomised trials, focusing on major adverse cardiac and cerebrovascular events (MACCE) outcomes in both the short and long-term, with clear case-by-case reasons for device failure and a comparison of anastomotic times. In this way, we may determine whether such devices will facilitate the minimal access and robotic coronary procedures of the future.