bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic effects of high-intensity interval training on postprandial lipemia in healthy men
Authors: Wilhelmsen Andrew , Mallinson Joanne , Jones Robert , Cooper Scott , Taylor Tariq , Tsintzas Kostas 
Published: October 2019

The aim of this study was to determine the chronic (≥72 h postexercise) effects of high-intensity interval training (HIIT) on postprandial lipemia and metabolic markers in healthy volunteers. Eight physically active young men (mean ± SD: age 22 ± 3 yr, height 1.77 ± 0.07 m, body mass 67.7 ± 6.2 kg) underwent two 6-h mixed-meal tolerance tests and resting vastus lateralis muscle biopsies before the first session and ≥72 h after the final session of 4 wk of HIIT [16 sessions in total; 10 × 60-s bouts of cycling at 90% maximal oxygen uptake (V̇o2max), interspersed with 60-s intervals at 45% V̇o2max]. Arterialized and deep venous blood samples from across the forearm, brachial artery blood flow measurements, and whole-body indirect calorimetry data were obtained before, and at regular intervals for 6 h after, consumption of a standardized mixed meal. The main findings revealed that, when assessed ≥72 h postexercise, postprandial free fatty acid (FFA) uptake across the forearm was increased in response to exercise training ( P = 0.025). However, 4 wk of HIIT did not alter fasting or postprandial circulating triglyceride concentrations or their tissue uptake, despite a 10.2% ± 7.7% improvement in V̇o2max ( P = 0.004). Protein content of adipose triglyceride lipase in the vastus lateralis at rest was reduced by 25% ± 21% ( P = 0.01). Collectively, these findings suggest that 4 wk of HIIT enhances postprandial clearance of FFA when assessed ≥72 h postexercise but does not confer persisting (training) adaptations in postprandial triglyceridemia. NEW & NOTEWORTHY When assessed ≥72 h after the last exercise session, 4 wk of high-intensity interval training (HIIT) did not improve triglyceridemia but enhanced free fatty acid uptake into muscle with a concurrent reduction in skeletal muscle adipose triglyceride lipase protein content. This suggests that previously reported acute reductions in postprandial triglyceridemia following a single bout of HIIT do not translate to sustained improvements after 4 wk of HIIT, supporting the concept of frequent exercise for the maintenance of lipemic control.
Pilot Trial AMC-063: Safety and Efficacy of Bortezomib in AIDS-associated Kaposi Sarcoma
Authors: Reid Erin G. , Suazo Adrienne , Lensing Shelly Y. , Dittmer Dirk P. , Ambinder Richard F. , Maldarelli Frank , Gorelick Robert J. , Aboulafia David , Mitsuyasu Ronald , Dickson Mark A. , Wachsman William 
Published: October 2019

Abstract

Purpose:
AIDS-related Kaposi sarcoma is often incompletely controlled, requiring serial therapies. Kaposi sarcoma herpesvirus (KSHV) induces transformation of endothelial cells, where it resides in a predominately latent state. We hypothesized proteasome inhibition would have direct antitumor activity, induce lytic activation of KSHV, and inhibit HIV infectivity, improving control of both Kaposi sarcoma and HIV. The primary objective was determining the MTD of bortezomib in AIDS-Kaposi sarcoma. Secondary objectives included estimating the impact of bortezomib on Kaposi sarcoma response, KSHV plasma DNA copy number (PDCN), and HIV viral loads (VL).

Patients and Methods:
A 3+3 dose escalation design was employed evaluating four dose levels of bortezomib (0.75, 1, 1.2, or 1.6 mg/m2) administered intravenously on days 1, 8, and 15 of 28-day cycles in patients with relapsed/refractory (r/r) AIDS-Kaposi sarcoma taking antiretroviral therapy.

Results:
Seventeen patients enrolled. No dose-limiting toxicities occurred and the MTD was not reached. The most common adverse events included diarrhea, fatigue and nausea. Among 15 evaluable patients, partial response (PR) occurred in nine (60%), with a PR rate of 83% in the 1.6 mg/m2 cohort; the remainder had stable disease (SD). Median time to response was 2.1 months. Median change in KSHV PDCN was significantly different between those with PR versus SD. During cycle 1, seven of 11 evaluable patients had decreases in HIV VL.

Conclusions:
Bortezomib is well-tolerated and active in AIDS-Kaposi sarcoma. The 60% PR rate is notable given the dose-finding nature of the study in a r/r population. Changes in KSHV PDCN and HIV VL trended as hypothesized.
ELF4 Is a Target of miR-124 and Promotes Neuroblastoma Proliferation and Undifferentiated State
Authors: Kosti Adam , Du Liqin , Shivram Haridha , Qiao Mei , Burns Suzanne , Garcia Juan Gabriel , Pertsemlidis Alexander , Iyer Vishwanath R. , Kokovay Erzsebet , Penalva Luiz O.F. 
Published: October 2019

Abstract

13-Cis-retinoic acid (RA) is typically used in postremission maintenance therapy in patients with neuroblastoma. However, side effects and recurrence are often observed. We investigated the use of miRNAs as a strategy to replace RA as promoters of differentiation. miR-124 was identified as the top candidate in a functional screen. Genomic target analysis indicated that repression of a network of transcription factors (TF) could be mediating most of miR-124's effect in driving differentiation. To advance miR-124 mimic use in therapy and better define its mechanism of action, a high-throughput siRNA morphologic screen focusing on its TF targets was conducted and ELF4 was identified as a leading candidate for miR-124 repression. By altering its expression levels, we showed that ELF4 maintains neuroblastoma in an undifferentiated state and promotes proliferation. Moreover, ELF4 transgenic expression was able to counteract the neurogenic effect of miR-124 in neuroblastoma cells. With RNA sequencing, we established the main role of ELF4 to be regulation of cell-cycle progression, specifically through the DREAM complex. Interestingly, several cell-cycle genes activated by ELF4 are repressed by miR-124, suggesting that they might form a TF–miRNA regulatory loop. Finally, we showed that high ELF4 expression is often observed in neuroblastomas and is associated with poor survival.

Implications:
miR-124 induces neuroblastoma differentiation partially through the downregulation of TF ELF4, which drives neuroblastoma proliferation and its undifferentiated phenotype.
Head and Neck Cancers Promote an Inflammatory Transcriptome through Coactivation of Classic and Alternative NF-κB Pathways
Authors: Yang Xinping , Cheng Hui , Chen Jianhong , Wang Ru , Saleh Anthony , Si Han , Lee Steven , Guven-Maiorov Emine , Keskin Ozlem , Gursoy Attila , Nussinov Ruth , Fang Jugao , Van Waes Carter , Chen Zhong 
Published: October 2019

AbstractHead and neck squamous cell carcinomas (HNSCC) promote inflammation in the tumor microenvironment through aberrant NF-κB activation, but the genomic alterations and pathway networks that modulate NF-κB signaling have not been fully dissected. Here, we analyzed genome and transcriptome alterations of 279 HNSCC specimens from The Cancer Genome Atlas (TCGA) cohort and identified 61 genes involved in NF-κB and inflammatory pathways. The top 30 altered genes were distributed across 96% of HNSCC samples, and their expression was often correlated with genomic copy-number alterations (CNA). Ten of the amplified genes were associated with human papilloma virus (HPV) status. We sequenced 15 HPV− and 11 HPV+ human HNSCC cell lines, and three oral mucosa keratinocyte lines, and supervised clustering revealed that 28 of 61 genes exhibit altered expression patterns concordant with HNSCC tissues and distinct signatures related to their HPV status. RNAi screening using an NF-κB reporter line identified 16 genes that are induced by TNFα or Lymphotoxin-β (LTβ) and implicated in the classic and/or alternative NF-κB pathways. Knockdown of TNFR, LTBR, or selected downstream signaling components established cross-talk between the classic and alternative NF-κB pathways. TNFα and LTβ induced differential gene expression involving the NF-κB, IFNγ, and STAT pathways, inflammatory cytokines, and metastasis-related genes. Improved survival was observed in HNSCC patients with elevated gene expression in T-cell activation, immune checkpoints, and IFNγ and STAT pathways. These gene signatures of NF-κB activation, which modulate inflammation and responses to the immune therapy, could serve as potential biomarkers in future clinical trials.
Natriuretic Peptides Attenuate Retinal Pathological Neovascularization Via Cyclic Guanosine Monophosphate Signaling in Pericytes and Astrocytes
Authors: Špiranec Spes Katarina , Hupp Sabrina , Werner Franziska , Koch Franziska , Völker Katharina , Krebes Lisa , Kämmerer Ulrike , Heinze Katrin G. , Braunger Barbara M. , Kuhn Michaela 
Published: October 2019

Objective:
In proliferative retinopathies, complications derived from neovascularization cause blindness. During early disease, pericyte’s apoptosis contributes to endothelial dysfunction and leakage. Hypoxia then drives VEGF (vascular endothelial growth factor) secretion and pathological neoangiogenesis. Cardiac ANP (atrial natriuretic peptide) contributes to systemic microcirculatory homeostasis. ANP is also formed in the retina, with unclear functions. Here, we characterized whether endogenously formed ANP regulates retinal (neo)angiogenesis.

Approach and Results:

Retinal vascular development and ischemia-driven neovascularization were studied in mice with global deletion of GC-A (guanylyl cyclase-A), the cGMP (cyclic guanosine monophosphate)-forming ANP receptor. Mice with a floxed GC-A gene were interbred with
Tie2-Cre, GFAP-Cre, or PDGF-Rβ-Cre

ERT2

lines to dissect the endothelial, astrocyte versus pericyte-mediated actions of ANP in vivo. In neonates with global GC-A deletion (KO), vascular development was mildly delayed. Moreover, such KO mice showed augmented vascular regression and exacerbated ischemia-driven neovascularization in the model of oxygen-induced retinopathy. Notably, absence of GC-A in endothelial cells did not impact retinal vascular development or pathological neovascularization. In vitro ANP/GC-A/cGMP signaling, via activation of cGMP-dependent protein kinase I, inhibited hypoxia-driven astrocyte’s VEGF secretion and TGF-β (transforming growth factor beta)–induced pericyte apoptosis. In neonates lacking ANP/GC-A signaling in astrocytes, vascular development and hyperoxia-driven vascular regression were unaltered; ischemia-induced neovascularization was modestly increased. Remarkably, inactivation of GC-A in pericytes retarded physiological retinal vascularization and markedly enhanced cell apoptosis, vascular regression, and subsequent neovascularization in oxygen-induced retinopathy.

Conclusions:
Protective pericyte effects of the ANP/GC-A/cGMP pathway counterregulate the initiation and progression of experimental proliferative retinopathy. Our observations indicate augmentation of endogenous pericyte ANP signaling as target for treatment of retinopathies associated with neovascularization.
Dōgen and Continental Philosophy
Authors: Wirth Jason M. 
Published: October 2019

Abstract
Continental philosophy, beginning with Kant, has found itself exposed to the abyss of reason. This crisis makes it a more ready dialogue partner with some of the Zen tradition. I explore this opening by bringing Eihei Dōgen (1200–1253) into an encounter with Continental thought, broadly construed. Rather than demonstrate how Dōgen already fits within Continental thought or re-engineering the latter so that he can fit, I argue that this encounter, already precipitated by Continental philosophy’s own acknowledgement of the felix culpa of Western philosophy’s otherwise indefensible overreach, transforms and expands the manners in which thinking counts as philosophical. This is no less than to recover a sense of philosophy as genetic and creative, rather than a shopworn tool kit of universal insights.
Knowing Limits
Authors: Davis Bret W. 
Published: October 2019

Abstract
This essay is about “knowing limits,” both in the sense of acknowledging the inevitable perspectival limits of our knowledge, and in the sense in which the act of knowing delimits the parameters of that which is known. Moreover, it aims to cultivate a versatile perspectivism that is ethically oriented by a capacity for ecstatic empathy rather than an egocentric will to power. The essay begins with an examination of the mind/body problem as a paradigmatic case of perspectival ambiguity, making reference to a wide range of authors. The focus of the central sections of the essay is on Nietzsche and Heidegger, while the final sections are devoted to developing a phenomenological reading of Zhuangzi and Zen. At issue throughout is the articulation of a versatile perspectivism responsive to both the demarcative and disclosive senses of knowing limits.
The Non-Native Speakers of International Law: The Case of Russia
Authors: Dolidze Anna 
Published: October 2019

This article presents a metaphor that might explain Russia’s approach to international law. Drawing on linguistics, the article proposes that Russia has been a non-native speaker of international law. A non-native speaker’s experiences range from estrangement and disengagement from the foreign language and its speech community to that of empowerment and inspiration nurtured by the acquisition of a new language and a new multilingual identity. Thus, as a non-native speaker, Russia has approached international law with two rhetorical moves: as a disaffected foreigner and as an empowered multilingual subject who aspires to uphold and interpret the rules of the language recently acquired. As a multilingual speaker fluent in the language of international law, Russia has asserted control over judgments of grammaticality and has disagreed with previously determined linguistic rules established by the native-speaking community.
The notion of a non-native speaker of international law can apply to states other than Russia. Policymakers and intellectual leaders of other countries, including China, might perceive themselves as non-native speakers in their encounters with the western European foundations of the language of international law. Finally, the article explores the future of international law by asking whether non-native speakers who have been gaining fluency in the parlance of international law will continue to develop their own linguistic repertoire, build their own vocabularies, and advance their own assertions regarding rules of grammar. The future of international law might be diglossic, as two varieties of its language, shared by different speech communities and practiced in different contexts, may be established.
The MILAN Campaign: Studying Diel Light Effects on the Air–Sea Interface
Authors: Stolle Christian , Ribas-Ribas Mariana , Badewien Thomas H. , Barnes Jonathan , Carpenter Lucy J. , Chance Rosie , Damgaard Lars Riis , Durán Quesada Ana María , Engel Anja , Frka Sanja , Galgani Luisa , Gašparović Blaženka , Gerriets Michaela , Hamizah Mustaffa Nur Ili , Herrmann Hartmut , Kallajoki Liisa , Pereira Ryan , Radach Franziska , Revsbech Niels Peter , Rickard Philippa , Saint Adam , Salter Matthew , Striebel Maren , Triesch Nadja , Uher Guenther , Upstill-Goddard Robert C. , van Pinxteren Manuela , Zäncker Birthe , Zieger Paul , Wurl Oliver 
Published: October 2019

AbstractThe sea surface microlayer (SML) at the air–sea interface is <1 mm thick, but it is physically, chemically, and biologically distinct from the underlying water and the atmosphere above. Wind-driven turbulence and solar radiation are important drivers of SML physical and biogeochemical properties. Given that the SML is involved in all air–sea exchanges of mass and energy, its response to solar radiation, especially in relation to how it regulates the air–sea exchange of climate-relevant gases and aerosols, is surprisingly poorly characterized. MILAN (Sea Surface Microlayer at Night) was an international, multidisciplinary campaign designed to specifically address this issue. In spring 2017, we deployed diverse sampling platforms (research vessels, radio-controlled catamaran, free-drifting buoy) to study full diel cycles in the coastal North Sea SML and in underlying water, and installed a land-based aerosol sampler. We also carried out concurrent ex situ experiments using several microsensors, a laboratory gas exchange tank, a solar simulator, and a sea spray simulation chamber. In this paper we outline the diversity of approaches employed and some initial results obtained during MILAN. Our observations of diel SML variability show, for example, an influence of (i) changing solar radiation on the quantity and quality of organic material and (ii) diel changes in wind intensity primarily forcing air–sea CO2 exchange. Thus, MILAN underlines the value and the need of multidiciplinary campaigns for integrating SML complexity into the context of air–sea interaction.
Landfalling Tropical Cyclone Research Project (LTCRP) in China
Authors: Duan Yihong , Wan Qilin , Huang Jian , Zhao Kun , Yu Hui , Wang Yuqing , Zhao Dajun , Feng Jianing , Tang Jie , Chen Peiyan , Lu Xiaoqin , Wang Yuan , Liang Jianyin , Wu Liguang , Cui Xiaopeng , Xu Jing , Chan Pak-Wai 
Published: October 2019

AbstractLandfalling tropical cyclones (TCs) often experience drastic changes in their motion, intensity, and structure due to complex multiscale interactions among atmospheric processes and among the coastal ocean, land, and atmosphere. Because of the lack of comprehensive data and low capability of numerical models, understanding of and ability to predict landfalling TCs are still limited. A 10-yr key research project on landfalling TCs was initiated and launched in 2009 in China. The project has been jointly supported by the China Ministry of Science and Technology, China Meteorological Administration (CMA), Ministry of Education, and Chinese Academy of Sciences. Its mission is to enhance understanding of landfalling TC processes and improve forecasting skills on track, intensity, and distributions of strong winds and precipitation in landfalling TCs. This article provides an overview of the project, together with highlights of some new findings and new technical developments, as well as planned future efforts.
Clinical Analysis and CT 3D-Mediated Precise Internal Fixation in Maxillofacial Fracture
Authors: Wubulihasimu Zainure , Tuerhong Meiheriban , Zhang Zhifei , Li Huilin , Kadir Nurahmat , Xie Maxian , Abulaiti Maiheba , Abulaiti Aerzigu , Tulamaiti Nuermaimaiti , Maimaitiming Baikeri , Aili Wurelika , Ni Yusu 
Published: October 2019

Background/Purpose: To retrospectively analyze the epidemiological features, clinical diagnosis, and treatment of 610 patients with maxillofacial fractures, while providing a reference for the prevention and optimized treatment of maxillofacial fractures. Methods: Data of patients with maxillofacial fractures who were treated and followed up at the Second People’s Hospital of Kashi Prefecture from June 2012 to April 2018 were summarized. The epidemiological features, clinical manifestations, fracture sites, treatment methods, and results were analyzed. Results: The highest incidence was in the age range of 20 to 49 years. The main cause of fracture was traffic injury. Mandibular fractures accounted for 37.77%, zygoma and zygomatic arch fractures for 37.00%, and maxillary fractures for 21.19%. Atypical zygomatic arch fractures were more common in the maxilla, followed by Le Fort I and II fractures. Closed fractures accounted for 85.97%. Many (73.39%) patients were treated with computed tomography 3-dimensional (3D)-mediated precision modified incision internal fixation with satisfactory results. Conclusions: There is a high incidence of maxillofacial fractures among young men, especially in summer, with the most common injuries being traffic-related injuries. The most common site is the mandible, followed by the zygomatic arch, zygomatic complex, and maxilla. Computed tomography 3D-mediated precision modified incision internal fixation can achieve satisfactory results.
Preoperative opioid use in patients undergoing shoulder surgery
Authors: Nadarajah Vidushan , Meredith Sean J , Jauregui Julio J , Smuda Michael P , Medina Shaun , Gilotra Mohit N , Hasan S Ashfaq , Henn R Frank 
Published: October 2019

Background Opioids are commonly used to manage pain from acute injury or chronic degenerative diseases. The objective of this study was to assess the prevalence of preoperative opioid use in patients undergoing shoulder surgery and the clinical factors associated with preoperative opioid use. Methods This was an analytical cross-sectional study of 175 patients undergoing shoulder surgery at an urban hospital from June 2015 to June 2017. Multivariable regression models were used to determine independent associations. Results Fifty-three patients reported preoperative opioid use, which was significantly associated with primary procedure performed (Current Procedural Terminology [CPT]), higher body mass index (BMI), unemployment, lower income, smoking, higher American Society of Anesthesiologists score, greater number of previous surgeries, higher comorbidity burden, and decreased expectations to exercise and do recreational activities (p < 0.05). Preoperative opioid use was independently associated with worse scores on the: Numeric Pain Scale, ASES, IPAQ, and PROMIS domains of Physical Function, Pain Interference, and Social Satisfaction (p < 0.05). Conclusion More than one in four patients reported preoperative opioid use. Several health measures, including worse pain, function, and social satisfaction were independently associated with preoperative opioid use. These findings suggest that orthopaedic surgeons need to identify patients using opioids preoperatively in order to effectively establish and execute a plan for pain management, which may include weaning off opioids prior to surgery, managing psychological distress, and optimizing coping strategies. Level of Evidence: III.
Racial disparities in treatment patterns and outcomes among patients with multiple myeloma: a SEER-Medicare analysis
Authors: Ailawadhi Sikander , Parikh Kejal , Abouzaid Safiya , Zhou Zhou , Tang Wenxi , Clancy Zoe , Cheung Claudia , Zhou Zheng-Yi , Xie Jipan 
Published: October 2019

Abstract
The objective of the study was to assess racial disparities in the treatment and outcomes among white, African American, and Hispanic patients with multiple myeloma (MM). Patients with an MM diagnosis from the Surveillance Epidemiology and End Results (SEER)–Medicare (2007-2013) database were included. Continuous Medicare enrollment for 6 months before (baseline) and after MM diagnosis was required unless death occurred. Time from MM diagnosis to novel therapy initiation and autologous stem cell transplant (ASCT), overall survival (OS), and MM-specific survival (MSS) was evaluated. Unadjusted and multivariable regressions compared African Americans and Hispanics vs whites. Trends of novel therapy and ASCT use across MM diagnosis years were assessed using linear regression models. The study included 3504 whites, 858 African Americans, and 468 Hispanics. African Americans and Hispanics had a longer time from MM diagnosis to novel therapy initiation vs whites (median: 5.2 and 4.6 vs 2.7 months, respectively). All cohorts had an increasing trend of novel therapy initiation within 6 months of MM diagnosis, particularly whites (all P &lt; .05). Median MSS was significantly longer for African Americans (5.4 years) than whites (4.5 years; P &lt; .05), and was comparable for Hispanics and whites. Median OS was similar overall (2.6-2.8 years). ASCT rate within 1 year of MM diagnosis rose among whites and African Americans (P &lt; .05), but not Hispanics, who were less likely to receive ASCT vs whites. Significant variations in novel therapy and ASCT use were observed among different racial/ethnic groups with MM. Although OS was similar, both African Americans and Hispanics may not be fully benefitting from the introduction of novel therapies, as they receive them later than whites.