bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergism between ATM and PARP1 Inhibition Involves DNA Damage and Abrogating the G2 DNA Damage Checkpoint
Authors: Mak Joyce P.Y. , Ma Hoi Tang , Poon Randy Y.C. 
Published: October 2019

Abstract
PARP inhibitors have emerged as effective chemotherapeutic agents for BRCA1/BRCA2-deficient cancers. Another DNA damage response protein, ATM, is also increasingly being recognized as a target for synthetic lethality with PARP inhibitors. As ATM functions in both cell cycle arrest and DNA repair after DNA damage, how cells respond to inhibition of ATM and PARP1 is yet to be defined precisely. We found that loss of ATM function, either in an ATM-deficient background or after treatment with ATM inhibitors (KU-60019 or AZD0156), results in spontaneous DNA damage and an increase in PARylation. When PARP1 is also deleted or inhibited with inhibitors (olaparib or veliparib), the massive increase in DNA damage activates the G2 DNA damage checkpoint kinase cascade involving ATR, CHK1/2, and WEE1. Our data indicated that the role of ATM in DNA repair is critical for the synergism with PARP inhibitors. Bypass of the G2 DNA damage checkpoint in the absence of ATM functions occurs only after a delay. The relative insensitivity of PARP1-deficient cells to PARP inhibitors suggested that other PARP isoforms played a relatively minor role in comparison with PARP1 in synergism with ATMi. As deletion of PARP1 also increased sensitivity to ATM inhibitors, trapping of PARP1 on DNA may not be the only mechanism involved in the synergism between PARP1 and ATM inhibition. Collectively, these studies provide a mechanistic foundation for therapies targeting ATM and PARP1.
Role of Dimerized C16orf74 in Aggressive Pancreatic Cancer: A Novel Therapeutic Target
Authors: Kushibiki Toshihiro , Nakamura Toru , Tsuda Masumi , Tsuchikawa Takahiro , Hontani Koji , Inoko Kazuho , Takahashi Mizuna , Asano Toshimichi , Okamura Keisuke , Murakami Soichi , Kurashima Yo , Ebihara Yuma , Noji Takehiro , Nakanishi Yoshitsugu , Tanaka Kimitaka , Maishi Nako , Sasaki Katsunori , Park Woong-Ryeon , Shichinohe Toshiaki , Hida Kyoko , Tanaka Shinya , Hirano Satoshi 
Published: October 2019

Abstract
Over the past 30 years, the therapeutic outcome for pancreatic ductal adenocarcinoma (PDAC) has remained stagnant due to the lack of effective treatments. We performed a genome-wide analysis to identify novel therapeutic targets for PDAC. Our analysis showed that Homo sapiens chromosome 16 open reading frame 74 (C16orf74) was upregulated in most patients with PDAC and associated with poor prognosis. Previously, we demonstrated that C16orf74 interacts with the catalytic subunit alpha of protein phosphatase 3 and plays an important role in PDAC invasion. However, the pathophysiologic function of C16orf74 is still unclear. In this study, through the analysis of C16orf74 interaction, we demonstrate a new strategy to inhibit the growth and invasion of PDAC. C16orf74 exists in the homodimer form under the cell membrane and binds integrin αVβ3 and is also involved in invasion by activating Rho family (Rac1) and MMP2. Considering that this dimeric form was found to be involved in the function of C16orf74, we designed an 11R-DB (dimer block) cell-permeable dominant-negative peptide that inhibits the dimer form of C16orf74. 11R-DB suppressed invasion and proliferation of PDAC cell lines by inhibiting phosphorylation of Akt and mTOR and also by inactivation of MMP2. 11R-DB also showed antitumor effects in an orthotopic xenograft model and peritoneal metastasis model. Thus, this study demonstrates that dimerized C16orf74, present in the cell membrane, is involved in pancreatic cancer invasion and proliferation. In addition, the C16orf74 dimer block cell-permeable peptide (11R-DB) has a potent therapeutic effect on PDAC in vitro and in vivo.
Estimation of Peer Effects in Endogenous Social Networks: Control Function Approach
Authors: Johnsson Ida , Moon Hyungsik Roger 
Published: October 2019

Abstract
We propose methods of estimating the linear-in-means model of peer effects in which the peer group, defined by a social network, is endogenous in the outcome equation for peer effects. Endogeneity is due to unobservable individual characteristics that influence both link formation in the network and the outcome of interest. We propose two estimators of the peer effect equation that control for the endogeneity of the social connections using a control function approach. We leave the functional form of the control function unspecified, estimate the model using a sieve semiparametric approach and establish asymptotics of the semiparametric estimator.
Ascetic and Nonascetic Layers in the Qurʾan: A Case Study
Authors: Dye Guillaume 
Published: October 2019

AbstractUsing the methods of redaction criticism, this article analyzes two Qurʾanic parallel passages, Q 23:1–11 and Q 70:22–35, and the chronology of their redaction. Relying on discernable traces of editorial work, it argues that these texts of instruction, which initially exhorted their audience to live a pious and ascetic life, have known a process of rewriting, which substantially softened the ascetic injunction of continence present in the earliest versions. This analysis might shed light on the background and development of the Qurʾan and early Islamic piety.
Promoter of shrimp translationally controlled tumor protein (TCTP) gene has higher activity than cytomegavirus (CMV) promoter in driving foreign genes to express in primary shrimp cells
Authors: Wang Jing , Lin Yuqi , Song Xin , Pu Longjun , Ji Guangdong , Li Guorong , Guo Huarong 
Published: October 2019

Abstract
Active promoters are urgently needed for shrimp cells which are hard to be immortalized. Translationally controlled tumor protein (TCTP) is a widely and abundantly expressed, growth-related protein. In this study we successfully isolated the promoter (Ptctp) and ORF (= open reading frame) of the TCTP gene from Litopenaeus vannamei and analysed the promoter activity of Ptctp and the growth-promoting effects of over-expressed TCTP protein in the primary Oka organ (lymphoid tissue) cells. It was found, that cytomegavirus (CMV) promoter, highly active in mammalian and fish cells, had a driving activity too low to be detected in shrimp cells. However, shrimp Ptctp had a higher driving activity than Pcmv in the shrimp cells and an obvious fluorescent signal was observed in the shrimp cells transfected by a Pcmv-Ptctp-driven plasmid. However, no obvious growth-promoting effects were observed in the eGFP/TCTP [eGFP = enhanced green fluorescent protein] or TCTP-transfected shrimp cells possibly due to the relatively low expression efficiency.
Characterization and expression analysis of E75 during ovarian development and juvenile growth of the mud crab, Scylla paramamosain Estampador, 1950 (Brachyura, Portunidae)
Authors: Gong Jie , Shi Wenyuan , Zhang Ming , Wang Tianfa , Yu Kun , Ye Haihui 
Published: October 2019

Abstract
In arthropods, E75 is an important nuclear receptor to regulate various physiological processes, such as development and reproduction. In this study, a 3551 bp cDNA of E75 (SpE75) with a typical domain organization of the nuclear hormone receptor was cloned from Scylla paramamosain. A qRT-PCR analysis revealed that, during ovarian development, the expression of SpE75 significantly increased after the onset of vitellogenesis and reached its peak value at the early vitellogenic stage. In vitro and in vivo experiments showed that 20-hydroxyecdysone significantly induced the transcriptions of the genes of both SpE75 and vitellogenin in the ovary. During juvenile crab (C1) development, the expression of SpE75 increased from 0 h (postmoult stage) to 96 h (premoult stage) and kept a low level in the fasting crabs. Together, these results indicate that SpE75 may be playing an important role in the regulation of ovarian development and somatic growth, as a component of ecdysone signalling in crustaceans.
Length-weight relationship of three stomatopod species from the Mumbai coast, India
Authors: Kesavan S. , Jenishma J. S. , Nirmal T. , Kamath S. S. , Xavier K. M. , Bhutia T. P. , Shenoy L. 
Published: October 2019

Abstract
Length-weight relationship (LWR) was estimated for three stomatopod species, namely Oratosquillina perpensa (Kemp, 1911), Harpiosquilla raphidea (Fabricius, 1798) and Miyakella nepa (Latreille, 1828) for the first time from the north-eastern Arabian Sea. Experimental fishing, using a shrimp trawl, was conducted fortnightly during September 2017 up to April 2018 along the Maharashtra coast. A total of 821 samples were collected. Length-weight relationship showed good fit with coefficient of determination () values varying from 0.9190 to 0.9612. In this study, b values ranged from 2.758 to 3.140. The LWRs of Oratosquillina perpensa and Miyakella nepa have not yet been reported in the SealifeBase.
Mixed Company in the Contact Zone: the “Glocal” Diplomatic Efforts of a Prussian East Indiaman in 1750s Cape Verde
Authors: Gottmann Felicia 
Published: October 2019

Abstract
This article takes a micro-historical actor-centered approach to study the encounter between the officers of a Prussian East India Company Ship and local elites in 1750s Praia, Cape Verde. Combining recent advances in New Diplomatic History and in Company Studies with insights from the study of Contact Zones and transculturation, it analyzes the diplomatic strategies marginalized and hybrid players could adopt to project themselves onto the early modern global stage and locally counterbalance the hegemonic Northern European Atlantic powers. It thus proposes an alternative model of nonprofessional diplomatic interaction in the early modern period.
Sweden’s Early-Modern Neutrality: Neutral Vessels, Prize Cases and Diplomatic Actors in London in the Late Eighteenth Century
Authors: Müller Leos 
Published: October 2019

Abstract
Early modern shipping under neutral flags was an activity that required many capacities, combining practices from three different fields: commerce and shipping, diplomacy, and international law. This complexity of neutral shipping is the reason why traditional diplomatic history paid limited attention to it, despite the fact that shipping and prize cases consumed much of the attention and time of diplomats of neutral nations. The neutral agents had to be able to understand, communicate and move between all three fields. This article studies seizures of Swedish neutral vessels by British privateers and the Royal Navy between 1770 and 1800, including the years of the War of American Independence and the French Revolutionary Wars. It provides examples of how exchanges between different field actors—e.g. shipmasters, ship-owners, merchants, agents, lawyers, naval officers and diplomats—were communicated and understood from the perspective of Sweden’s representatives in London.
Early Christian Martyrdom and the End of the Ur-Arché
Authors: Lehmann Sandra 
Published: October 2019

Abstract
This essay follows the assumption that the first principle of classical metaphysics has its counterpart in political sovereignty as suprema potestas. Therefore, both can be equally described as arché. Their epitome is the God of so-called ontotheology, who thus proves to be what I call the Ur-Arché. In contrast to current post-metaphysical approaches, however, I suggest overcoming ontotheology through a different metaphysics, which emphasizes the self-transcending surplus character of being. I regard early Christian martyrdom as an eminent way in which the surplus of being is manifested. This has two interwoven aspects, one ontological and one political, both arising from the excessive idea of the Christ event, or the notion that there is life beyond life unto death. I will analyse the mechanism allowing early Christian martyrs to counteract Roman imperial sovereignty. Finally, I will relate this to contemporary life systems in which sovereignty has become anonymous biopower.
Unconditional Responsibility in the Face of Disastrous Violence
Authors: Liebsch Burkhard 
Published: October 2019

Abstract
This essay draws attention to the question how a strong notion of unconditional responsibility in the face of the other’s mortality (as it was claimed by Emmanuel Levinas) is related to the historical experience of a disastrous violence that seems to annihilate not only numerous bodies, lives, identities and histories but, rather, any responsible religio to the other – whether living or dead. It is well known, that Levinas claimed that human responsibility demands not to let the other alone in his death. But if the other is already dead – like numerous others who share the same fate – keeps human responsibility silent, then? And how is this religio of human responsibility related to forms of disastrous violence which seem to deny it?
Surface Turbulent Fluxes during Persistent Cold-Air Pool Events in the Salt Lake Valley, Utah. Part I: Observations
Authors: Sun Xia , Holmes Heather A. 
Published: October 2019

AbstractThe land surface is coupled to the atmospheric boundary layer through surface turbulent fluxes. Persistent cold-air pools (PCAPs) form in topographic depressions where cold, dense air fills the valley basin and in the presence of air pollution is accompanied by poor air quality. For the first time, the surface turbulence dataset from seven monitors during the Persistent Cold-Air Pool Study conducted in Salt Lake Valley, Utah (December 2010–February 2011), are analyzed. We found that the surface sensible (H) and latent (LE) heat fluxes were lower during strong PCAP events compared with non-PCAPs. The higher ratio of heat flux to net radiation (H/Rn and LE/Rn) for strong PCAPs compared with weak PCAPs is suspected to be related to the presence of boundary layer clouds, which could enhance the turbulent mixing through cloud top–down mixing. The daily average ground heat flux (G) was a similar order of magnitude toHand LE during wintertime. The highest surface turbulent fluxes and energy balance closure occurred in the stability range of −0.05 <ξ≤ −0.02, or under slightly unstable conditions, near the neutral stability range. The median surface exchange coefficient (Ch), a crucial parameter to determine surface turbulent fluxes in land surface models, was slightly higher at the bare land site (BL) than the short vegetation sites (PH and CR) in wintertime, suggesting the importance of dynamic land-use information in numerical models.
Secondary Cleft Rhinoplasty in 1720 Patients: Are National Practices Consistent With Guidelines?
Authors: Chouairi Fouad , Torabi Sina J. , Gabrick Kyle S. , Persing John A. , Alperovich Michael 
Published: October 2019

Objective: To assess the timing, type, and associated adjunct procedures for secondary cleft rhinoplasty nationally. Design: Data were extracted from a national database of all secondary cleft rhinoplasty procedures (Current Procedural Terminology [CPT] codes 30460 and 30462). Frequency statistics were utilized to analyze demographics, comorbidities, surgical procedures, and timing. Chi-squared analysis and Fisher exact test were used for analysis. Setting: National Surgical Quality Improvement Program-Pediatric Database. Participants: A total of 1720 patients met inclusion criteria for secondary cleft rhinoplasty repair. Interventions: No relevant intervention. Main Outcomes and Measures: Age, demographics, comorbidities, and associated procedures. Results: Over 5 consecutive years, 1720 patients underwent secondary cleft lip rhinoplasty nationally. Mean patient age was 9.3 ± 5.3 years. Unilateral cleft rhinoplasty patients were older (9.0 years) than bilateral patients (7.8 years; P = .001). Rib grafting was performed in 6.3% of patients at a mean age of 10.6 years with a higher proportion of Asian and female patients. Auricular grafts were more commonly performed by otolaryngology than plastic surgery. The most common adjunct procedures included secondary cleft lip revision (33.1%) and tympanostomy tube placement (10.2%). When subdividing by type of cleft rhinoplasty, tip rhinoplasty was performed at a mean age of 7.3 years compared to rhinoplasty with osteotomies and a major septal component at 12.1 years ( P < .001). Conclusions: This study reveals that a large proportion of cleft rhinoplasties are performed in skeletally immature patients. Although patients undergoing rib grafting, nasal osteotomies, and a major septal component were older, these procedures are still performed in a large proportion of patients who are younger than expected.
Clinical Outcomes of Percutaneous Plantar Fasciotomy Using Microdebrider Coblation Wand
Authors: Colberg Ricardo E. , Ketchum Monte , Javer Avani , Drogosz Monika , Gomez Melissa , Fleisig Glenn S. 
Published: October 2019

Background: Plantar fasciitis is the most common cause of heel pain in adults. Multiple conservative treatment plans exist; however, some cases do not obtain significant clinical improvement with conservative treatment and require further intervention. This retrospective case study evaluated the success rate of percutaneous plantar fasciotomy and confounding comorbidities that negatively affect outcomes. Methods: A series of 41 patients treated with percutaneous plantar fasciotomy using the Topaz EZ microdebrider coblation wand were invited to participate in this retrospective follow-up study, and 88% ( N = 36) participated. A limited chart review was completed and the patients answered a survey with the visual analog scale (VAS) for pain and the Foot and Ankle Ability Measure (FAAM) questionnaire. Average outcomes were calculated and 45 variables were analyzed to determine if they were statistically significant confounders. Patients had symptoms for an average of 3 years before the procedure and were contacted for follow-up at an average of 14 months after the procedure. Results: The average VAS for pain score was 1.3 ± 1.8 and the average FAAM score was 92 ± 15. Eighty-nine percent of patients had a successful outcome, defined as FAAM greater than 75. In addition, patients at 18 months postprocedure reported complete or near-complete resolution of symptoms with an FAAM score greater than 97. Concurrent foot pathologies (eg, tarsal tunnel syndrome), oral steroid treatment prior to the procedure, and immobilization with a boot prior to the procedure were statistically significant negative confounders ( P < .05). Being an athlete was a positive confounder ( P = .02). Conclusion: Percutaneous plantar fasciotomy using a microdebrider coblation was an effective treatment for plantar fasciitis, particularly without concurrent foot pathology, with a low risk of complications. Level of Evidence: Level IV, retrospective case series.
A patient’s decision aid for vascular access placement in the emergency department
Authors: Obadeyi Oluseyi , Baffoe Nana , Paxton James 
Published: October 2019

Background: Vascular access device placement is one of the most routinely performed procedures in the emergency department. Despite its high usage, most patients have limited knowledge about vascular access device placement. Patient decision aids have been utilized heavily in non-emergency department settings to provide basic clinical information regarding a patient’s medical care options. In this study, we investigated whether exposure to a patient decision aid on vascular access devices and patients’ experiences with vascular access devices would influence their vascular access device preference during an acute care episode. Methods: Patients in this institutional review board–approved study were enrolled prospectively in the emergency department at a busy level 1 trauma institution. A patient decision aid on vascular access device was constructed using criteria developed by the International Patient Decision Aid Standards. All participants were exposed to the patient decision aid and were asked to complete two questionnaires, and two tests. Results: Fifty subjects (50) were enrolled prospectively in the emergency department. The mean pretest score was 17.2% (95% confidence interval, 0.54–1.18), while the mean post-test score was 72.4% (95% confidence interval, 3.15–4.09). We found that patients who were exposed to the patient decision aid preferred landmark-based peripheral intravenous lines over ultrasound-guided peripheral intravenous lines in this data set. Conclusion: The result from this analysis indicated that most patients visiting the emergency department are not knowledgeable about their options related to vascular access device placement. The observed increase in the average correct responses on the post-test indicates that a patient decision aid can be an effective educational tool in the emergency department.
Pertuzumab and Trastuzumab Emtansine for Human Epidermal Growth Factor Receptor-2–Positive Metastatic Breast Cancer: Contemporary Population-Based Outcomes
Authors: Lupichuk Sasha , Cheung Winson Y , Stewart Douglas 
Published: October 2019

Background: Real-world outcomes for patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC) treated with pertuzumab in combination with taxane chemotherapy plus trastuzumab (TaxTP) in the first line setting and trastuzumab emtansine (TE) in any line of treatment are lacking. Methods: Cohorts of patients treated with (1) TaxTP and (2) TE from January 1, 2013 through December 31, 2016 were retrospectively obtained from a population-based database. Cohorts were described according to age, hormone receptor (HR) status, prior systemic therapies, event-free survival (EFS) defined as time from start of treatment to start of next line of treatment or death, and overall survival (OS). Results: A total of 122 patients were treated with TaxTP and 104 with TE. In the TaxTP cohort, EFS was significantly longer in the trastuzumab-naïve group compared with the adjuvant trastuzumab group (median EFS = 27.0 vs 12.4 months; P = .002). In the TaxTP cohort, median OS was not reached. In the TE cohort, EFS was significantly longer in the pertuzumab-naïve group compared with pertuzumab-exposed group (median time to treatment failure [TTF] = 18.7 vs 5.5 months; P < .001). Overall survival was also significantly longer in the pertuzumab-naïve group compared with the pertuzumab-exposed group (median OS = 23.2 vs 14.1 months; P = .022). In multivariable analyses, adjuvant trastuzumab and prior pertuzumab exposure in the metastatic setting remained significant predictors of inferior EFS for patients treated with TaxTP and TE, respectively. Conclusions: New anti-HER2 therapies appear to be clinically relevant in the real-world.