bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep-water plays in the western Black Sea: insights into sediment supply within the Maykop depositional system
Authors: Rees E. V. L. , Simmons M. D. , Wilson J. W. P. 
Published: September 2017

Abstract
The Oligocene–Early Miocene Maykop depositional system of the Western Black Sea Basin is investigated in terms of sediment supply and provenance. Potential sediment source regions and conduits for sediment supply into the deep-water portion of the basin are evaluated based on the tectonic history and framework of the region, and are supported by observations from published well, reflection seismic and isopach data. The outcrop geology of the present-day land areas adjacent to the basin is used as a guide to the likely provenance and, hence, quality of potential siliciclastic reservoirs. Reservoir presence and reservoir quality are key subsurface risks for exploration in deep-water plays involving Maykop turbidite sandstones and charge from the well-known Maykop organic carbon-rich mudstones that are widespread across the basin.
Sediments sourced from the NE Moesian Platform and Dobrogea, channelled into the offshore Black Sea via the Histria Trough, are considered moderate risk in terms of primary reservoir quality, as evidenced by thick packages of fine-grained sediment. In contrast, sediments derived from the southern Strandja Massif fed into the Burgas Basin, and potentially into the deeper-water Turkish Black Sea, are relatively low risk in terms of reservoir quality, given the abundance of acidic intrusions within the massif. Sediment derived from parts of the northern Strandja Massif, especially the volcaniclastics of the Srednogornie region, are likely to have poorer reservoir quality characteristics. Sediments derived from the granitic Bolu Massif within the Pontides might be of good reservoir quality but are likely to be ponded behind the offshore Kozlu Ridge. An important sediment source-to-sink system was derived from the Balkanides and entered the deeper-water western Black Sea via the Kamchia Trough. The present-day Kamchia river is a relatively minor sediment supplier to the Black Sea, but the palaeo-Kamchia river of the Oligocene–Early Miocene would have exploited a much greater drainage area consisting of an axial trunk stream, occupying the newly formed Kamchia Foredeep to the north of the Balkanides, and transverse rivers sourcing sediment from the granitic and gneissic bodies of the Balkan Mountains and from Early Cretaceous and Palaeogene sandstones. These would provide reasonable reservoir quality, and it is estimated from reference source-to-sink relationships that offshore sediment flux via this system was probably at least eight times greater than at present. Known shelf-edge canyons in offshore Bulgaria facilitated this sediment reaching the deep water offshore, where a sedimentary fan with a length in excess of 150 km is likely to have developed. This suggests that the potential is good for encountering good-quality reservoir sands in the Maykop succession deep water of the western Black Sea, and this aspect of regional play risk could be of less concern than was previously considered.
Geological evolution of the Central Pontides
Authors: Okay Aral I. , Altiner Demir , Sunal Gürsel , Aygül Mesut , Akdoğan Remziye , Altiner Sevinç , Simmons Mike 
Published: September 2017

Abstract
Before the Late Cretaceous opening of the Black Sea, the Central Pontides constituted part of the southern margin of Laurasia. Two features that distinguish the Central Pontides from the neighbouring Pontide regions are the presence of an extensive Lower Cretaceous submarine turbidite fan (the Çağlayan Formation) in the north, and a huge area of Jurassic–Cretaceous subduction–accretion complexes in the south.
The Central Pontides comprise two terranes, the Istanbul Zone in the west and the Sakarya Zone in the east, which were amalgamated before the Late Jurassic (Kimmeridgian), most probably during the Triassic. The basement in the western Central Pontides (the Istanbul Zone) is made up of a Palaeozoic sedimentary sequence, which ends with Carboniferous coal measures and Permo-Triassic red beds. In the eastern Central Pontides, the basement consists of Permo-Carboniferous granites and an Upper Triassic forearc sequence of siliciclastic turbidites with tectonic slivers of pre-Jurassic ophiolite (the Küre Complex). The Küre Complex is intruded by Middle Jurassic granites and porphyries, which constitute the western termination of a major magmatic arc.
Upper Jurassic–Lower Cretaceous shallow-marine limestones (the İnaltı Formation) lie unconformably over both the Istanbul and Sakarya sequences in the Central Pontides. Two new measured stratigraphic sections from the İnaltı Formation constrain the age of the İnaltı Formation as Kimmeridgian–Berriasian. After a period of uplift and erosion during the Valanginian and Hauterivian, the İnaltı Formation is unconformably overlain by an over 2 km-thick sequence of Barremian–Aptian turbidites. Palaeocurrent measurements and detrital zircons indicate that the major part of the turbidites was derived from the East European Platform, implying that the Black Sea was not open before the Aptian. The Çağlayan turbidites pass northwards to a coeval carbonate–clastic shelf exposed along the present Black Sea coast. In the southern part of the Central Pontides, the Lower Cretaceous turbidites were deformed and metamorphosed in the Albian. Albian times also witnessed accretion of Tethyan oceanic crustal and mantle sequences to the southern margin of Laurasia, represented by Albian eclogites and blueschists in the Central Pontides.
A new depositional cycle started in the Late Cretaceous with Coniacian–Santonian red pelagic limestones, which lie unconformably over the older units. The limestones pass up into thick sequences of Santonian–Campanian arc volcanic rocks. The volcanism ceased in the middle Campanian, and the interval between late Campanian and middle Eocene is represented by a thick sequence of siliciclastic and calciclastic turbidites in the northern part of the Central Pontides. Coeval sequences in the south are shallow marine and are separated by unconformities. The marine deposition in the Central Pontides ended in the Middle Eocene as a consequence of collision of the Pontides with the Kırşehir Massif.
Pharmacological and physiological assessment of serotonin formation and degradation in isolated preparations from mouse and human hearts
Authors: Gergs Ulrich , Jung Franziska , Buchwalow Igor B. , Hofmann Britt , Simm Andreas , Treede Hendrik , Neumann Joachim 
Published: September 2017

Using transgenic (TG) mice that overexpress the human serotonin (5-HT)4areceptor specifically in cardiomyocytes, we wanted to know whether 5-HT can be formed and degraded in the mammalian heart and whether this can likewise lead to inotropic and chronotropic effects in this TG model. We noted that the 5-HT precursor 5-hydroxy-tryptophan (5-HTP) can exert inotropic and chronotropic effects in cardiac preparations from TG mice but not from wild-type (WT) mice; similar results were found in human atrial preparations as well as in intact TG animals using echocardiography. Moreover, by immunohistochemistry we could detect 5-HT metabolizing enzymes and 5-HT transporters in mouse hearts as well as in human atria. Hence, in the presence of an inhibitor of aromatic l-amino acid decarboxylase, the positive inotropic effects of 5-HTP were absent in TG and isolated human atrial preparations, and, moreover, inhibitors of enzymes involved in 5-HT degradation enhanced the efficacy of 5-HT in TG atria. A releaser of neurotransmitters increased inotropy in the isolated TG atrium, and this effect could be blocked by a 5-HT4areceptor antagonist. Fluoxetine, an inhibitor of 5-HT uptake, elevated the potency of 5-HT to increase contractility in the TG atrium. In addition, inhibitors of organic cation and monoamine transporters apparently reduced the positive inotropic potency of 5-HT in the TG atrium. Hence, we tentatively conclude that a local production and degradation of 5-HT in the mammalian heart and more specifically in mammalian myocytes probably occurs. Conceivably, this formation of 5-HT and possibly impaired degradation may be clinically relevant in cases of unexplained tachycardia and other arrhythmias.NEW & NOTEWORTHY The present work suggests that inotropically active serotonin (5-HT) can be formed in the mouse and human heart and probably by cardiomyocytes themselves. Moreover, active degradation of 5-HT seems to occur in the mammalian heart. These findings may again increase the interest of researchers for cardiac effects of 5-HT.
Tenascin-C and Integrin α9 Mediate Interactions of Prostate Cancer with the Bone Microenvironment
Authors: San Martin Rebeca , Pathak Ravi , Jain Antrix , Jung Sung Yun , Hilsenbeck Susan G. , Piña-Barba María C. , Sikora Andrew G. , Pienta Kenneth J. , Rowley David R. 
Published: September 2017

Abstract
Deposition of the extracellular matrix protein tenascin-C is part of the reactive stroma response, which has a critical role in prostate cancer progression. Here, we report that tenascin C is expressed in the bone endosteum and is associated with formation of prostate bone metastases. Metastatic cells cultured on osteo-mimetic surfaces coated with tenascin C exhibited enhanced adhesion and colony formation as mediated by integrin α9β1. In addition, metastatic cells preferentially migrated and colonized tenascin-C–coated trabecular bone xenografts in a novel system that employed chorioallantoic membranes of fertilized chicken eggs as host. Overall, our studies deepen knowledge about reactive stroma responses in the bone endosteum that accompany prostate cancer metastasis to trabecular bone, with potential implications to therapeutically target this process in patients. Cancer Res; 77(21); 5977–88. ©2017 AACR.
YAP Suppresses Lung Squamous Cell Carcinoma Progression via Deregulation of the DNp63–GPX2 Axis and ROS Accumulation
Authors: Huang Hsinyi , Zhang Wenjing , Pan Yafang , Gao Yijun , Deng Lei , Li Fuming , Li Fei , Ma Xueyan , Hou Shenda , Xu Jing , Li Peixue , Li Xiaoxun , Hu Guohong , Li Cheng , Chen Haiquan , Zhang Lei , Ji Hongbin 
Published: September 2017

Abstract
Lung squamous cell carcinoma (SCC), accounting for approximately 30% of non–small cell lung cancer, is often refractory to therapy. Screening a small-molecule library, we identified digitoxin as a high potency compound for suppressing human lung SCC growth in vitro and in vivo. Mechanistic investigations revealed that digitoxin attenuated YAP phosphorylation and promoted YAP nuclear sequestration. YAP activation led to excessive accumulation of reactive oxygen species (ROS) by downregulating the antioxidant enzyme GPX2 in a manner related to p63 blockade. In patient-derived xenograft models, digitoxin treatment efficiently inhibited lung SCC progression in correlation with reduced expression of YAP. Collectively, our results highlight a novel tumor-suppressor function of YAP via downregulation of GPX2 and ROS accumulation, with potential implications to improve precision medicine of human lung SCC. Cancer Res; 77(21); 5769–81. ©2017 AACR.
LSD1-Mediated Epigenetic Reprogramming Drives CENPE Expression and Prostate Cancer Progression
Authors: Liang Yi , Ahmed Musaddeque , Guo Haiyang , Soares Fraser , Hua Junjie T. , Gao Shuai , Lu Catherine , Poon Christine , Han Wanting , Langstein Jens , Ekram Muhammad B. , Li Brian , Davicioni Elai , Takhar Mandeep , Erho Nicholas , Karnes R. Jeffrey , Chadwick Dianne , van der Kwast Theodorus , Boutros Paul C. , Arrowsmith Cheryl H. , Feng Felix Y. , Joshua Anthony M. , Zoubeidi Amina , Cai Changmeng , He Housheng H. 
Published: September 2017

Abstract
Androgen receptor (AR) signaling is a key driver of prostate cancer, and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease. However, patients receiving ADT eventually develop incurable castration-resistant prostate cancer (CRPC). Here, we report that the chromatin modifier LSD1, an important regulator of AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 reprogramming in this setting activated a subset of cell-cycle genes, including CENPE, a centromere binding protein and mitotic kinesin. CENPE was regulated by the co-binding of LSD1 and AR to its promoter, which was associated with loss of RB1 in CRPC. Notably, genetic deletion or pharmacological inhibition of CENPE significantly decreases tumor growth. Our findings show how LSD1-mediated epigenetic reprogramming drives CRPC, and they offer a mechanistic rationale for its therapeutic targeting in this disease. Cancer Res; 77(20); 5479–90. ©2017 AACR.
Tethering IL2 to Its Receptor IL2Rβ Enhances Antitumor Activity and Expansion of Natural Killer NK92 Cells
Authors: Jounaidi Youssef , Cotten Joseph F. , Miller Keith W. , Forman Stuart A. 
Published: September 2017

AbstractIL2 is an immunostimulatory cytokine for key immune cells including T cells and natural killer (NK) cells. Systemic IL2 supplementation could enhance NK-mediated immunity in a variety of diseases ranging from neoplasms to viral infection. However, its systemic use is restricted by its serious side effects and limited efficacy due to activation of T regulatory cells (Tregs). IL2 signaling is mediated through interactions with a multi-subunit receptor complex containing IL2Rα, IL2Rβ, and IL2Rγ. Adult natural killer (NK) cells express only IL2Rβ and IL2Rγ subunits and are therefore relatively insensitive to IL2. To overcome these limitations, we created a novel chimeric IL2-IL2Rβ fusion protein of IL2 and its receptor IL2Rβ joined via a peptide linker (CIRB). NK92 cells expressing CIRB (NK92CIRB) were highly activated and expanded indefinitely without exogenous IL2. When compared with an IL2-secreting NK92 cell line, NK92CIRB were more activated, cytotoxic, and resistant to growth inhibition. Direct contact with cancer cells enhanced the cytotoxic character of NK92CIRB cells, which displayed superior in vivo antitumor effects in mice. Overall, our results showed how tethering IL2 to its receptor IL2Rβ eliminates the need for IL2Rα and IL2Rβ, offering a new tool to selectively activate and empower immune therapy. Cancer Res; 77(21); 5938–51. ©2017 AACR.
Biallelic Dicer1 Loss Mediated by aP2-Cre Drives Angiosarcoma
Authors: Hanna Jason A. , Drummond Catherine J. , Garcia Matthew R. , Go Jonathan C. , Finkelstein David , Rehg Jerold E. , Hatley Mark E. 
Published: September 2017

Abstract
Angiosarcoma is an aggressive vascular sarcoma with an extremely poor prognosis. Because of the relative rarity of this disease, its molecular drivers and optimal treatment strategies are obscure. DICER1 is an RNase III endoribonuclease central to miRNA biogenesis, and germline DICER1 mutations result in a cancer predisposition syndrome, associated with an increased risk of many tumor types. Here, we show that biallelic Dicer1 deletion with aP2-Cre drives aggressive and metastatic angiosarcoma independent of other genetically engineered oncogenes or tumor suppressor loss. Angiosarcomas in aP2-Cre;Dicer1Flox/- mice histologically and genetically resemble human angiosarcoma. miR-23 target genes, including the oncogenes Ccnd1 as well as Adam19, Plau, and Wsb1 that promote invasiveness and metastasis, were enriched in mouse and human angiosarcoma. These studies illustrate that Dicer1 can function as a traditional loss-of-function tumor suppressor gene, and they provide a fully penetrant animal model for the study of angiosarcoma development and metastasis. Cancer Res; 77(22); 6109–18. ©2017 AACR.
Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy
Authors: Zhao Yang , Zhang Chenran , Gao Liquan , Yu Xinhe , Lai Jianhao , Lu Dehua , Bao Rui , Wang Yanpu , Jia Bing , Wang Fan , Liu Zhaofei 
Published: September 2017

Abstract
Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021–32. ©2017 AACR.
Monoclonal Antibodies Directed against Cadherin RGD Exhibit Therapeutic Activity against Melanoma and Colorectal Cancer Metastasis
Authors: Bartolomé Rubén A. , Aizpurua Carmen , Jaén Marta , Torres Sofía , Calviño Eva , Imbaud Juan I. , Casal J. Ignacio 
Published: September 2017

Abstract
Purpose: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAb).
Experimental Design: Cadherin 17 (CDH17) fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation, and invasion assays using cell lines from different cancer types (colorectal, pancreatic, melanoma, and breast cancer). Effects of the mAbs on cell signaling were determined by Western blot analysis. Nude mice were used for survival analysis after treatment with RGD-specific mAbs and metastasis development.
Results: Antibodies against full-length CDH17 failed to block the binding to α2β1 integrin. However, CDH17 RGD peptides generated highly selective RGD mAbs that blocked CDH17 and vascular-endothelial (VE)-cadherin–mediated β1 integrin activation in melanoma and breast, pancreatic, and colorectal cancer cells. Antibodies provoked a significant reduction in cell adhesion and proliferation of metastatic cancer cells. Treatment with mAbs impaired the integrin signaling pathway activation of FAK in colorectal cancer, of JNK and ERK kinases in colorectal and pancreatic cancers, and of JNK, ERK, Src, and AKT in melanoma and breast cancer. In vivo, RGD-specific mAbs increased mouse survival after inoculation of melanoma and colorectal cancer cell lines to cause lung and liver metastasis, respectively.
Conclusions: Blocking the interaction between RGD cadherins and α2β1 integrin with highly selective mAbs constitutes a promising therapy against advanced metastatic disease in colon cancer, melanoma, and, potentially, other cancers. Clin Cancer Res; 24(2); 433–44. ©2017 AACR.
See related commentary by Marshall, p. 253
Risk Prediction of Cervical Cancer and Precancers by Type-Specific Human Papillomavirus: Evidence from a Population-Based Cohort Study in China
Authors: Dong Li , Hu Shang-Ying , Zhang Qian , Feng Rui-Mei , Zhang Li , Zhao Xue-Lian , Zhang Xun , Qiao You-Lin , Zhao Fang-Hui 
Published: September 2017

Abstract
Risk stratification of human papillomavirus (HPV)-positive women is needed to avoid excessive colposcopy and overtreatment in cervical cancer screening. We aimed to evaluate the predictive value of type-specific HPV in detecting cervical cancer and precancers in a Chinese population–based cohort and provide evidence of HPV genotyping to triage HPV-positive women. We typed all Hybrid Capture 2–positive cytologic samples of 1,742 women in Shanxi Province Cervical Cancer Screening Study cohort. Cumulative risks of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among HPV-positive women and cumulative detection rates of CIN2+ among general women by type-specific HPV were estimated during the course of 10-year follow-up. HPV 16 and HPV 52 were most prevalent types among the screening population. Ten-year cumulative risk of CIN2+ was 47.5% [95% confidence interval (CI), 31.6–62.3] for HPV 16–positive women and 46.3% (95% CI, 15.3–75.4) for HPV 31–positive women. Ten-year cumulative risks of CIN2+ among HPV 58, 39, 33, 18, and 52 positive women ranged from 34.3% to 12.0% in a decreasing order. CIN2+ risks were found to be positively associated with infection times of the same genotypes of HPV 16, 31, 33, and 58 (all Ptrend &lt; 0.001). Cumulative detection rates of CIN2+ within 10 years were predominantly contributed by HPV 16, 31, and 58. Our results support the risk-based management of HPV-positive women using HPV genotyping and also indicate the significance of including HPV 31 and 58 apart from commonly acknowledged HPV 16 and HPV 18 in achieving better risk stratification. Cancer Prev Res; 10(12); 745–51. ©2017 AACR.
Outcomes of Telemedicine Video-Conferencing Clinic Versus In-Person Clinic Follow-Up for Implantable Cardioverter-Defibrillator Recipients
Authors: Dalouk Khidir , Gandhi Nainesh , Jessel Peter , MacMurdy Karen , Zarraga Ignatius Gerardo , Lasarev Michael , Raitt Merritt 
Published: September 2017

Background:
Implantable cardioverter-defibrillator (ICD) recipients require close follow-up that can be difficult for patients who have to travel long distances for clinic follow-up. We aimed to compare clinical outcomes between ICD patients followed-up in a telemedicine video-conferencing clinic (TMVC) and a conventional in-person clinic (CIC). We hypothesized that outcomes of patients followed in the TMVC are noninferior to the CIC.

Methods and Results:

This retrospective study compares time to first appropriate ICD therapy, time to first inappropriate ICD therapy, time to first shock, and overall survival in patients followed in TMVC compared with CIC between 2001 and 2016. Two hundred and eighty-seven patients were followed in the TMVC group and 236 patients in the CIC. The average age of the TMVC and CIC groups was 64.13±9.38 and 65.23±8.57 years, respectively (
P
=0.164). There was no difference in the modified Seattle heart failure model score between the 2 groups (−0.12±1.0 versus −0.21±0.99;
P
=0.287). The Charlson comorbidity index score was higher in the CIC group compared with the TMVC group (7.0 versus 6.0;
P
=0.01). Mean duration of follow-up was 4.8 years. Adjusted and unadjusted tests of noninferiority found TMVC was not inferior to in-person follow-up for the prespecified outcomes.

Conclusions:
Video-conferencing ICD follow-up for patients in areas where electrophysiology subspecialty care is not available leads to outcomes that are noninferior to CIC follow-up.