bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiangiogenic effects of the chemopreventive agent tributyrin, a butyric acid prodrug, during the promotion phase of hepatocarcinogenesis
Authors: Andrade Fabia de Oliveira , Furtado Kelly Silva , Heidor Renato , Sandri Silvana , Hebeda Cristina Bichels , Miranda Mayara Lilian Paulino , Fernandes Laura Helena Gasparini , Yamamoto Roberto Carvalho , Horst Maria Aderuza , Farsky Sandra Helena Poliselli , Moreno Fernando Salvador 
Published: December 2018

AbstractAgents that inhibit angiogenic factors may prevent the development of hepatocellular carcinoma (HCC). Thus, the objective of this study was to kinetically evaluate the antiangiogenic activity of tributyrin (TB), a butyric acid prodrug, in the promotion stage of hepatocarcinogenesis. For this purpose, the resistant hepatocyte (RH) model was used for induction of preneoplastic lesions in Wistar rats. During the promotion phase, the animals received TB or maltodextrin (MD) as control daily. The rats were killed at three time-points (P1, P2 and P3). Increased expression of Vegfa and Vegfr2 was observed during promotion phase of hepatocarcinogenesis, which was not reversed by TB treatment. However, TB treatment reduced the expression of cluster of differentiation (CD) 34-positive vessels at P3 and α-smooth muscle actin (α-SMA)-positive vessels at P2 compared with MD. Enhanced levels of hypoxia inducible factor-1α (HIF-1α) and phosphorylated extracellular signal-regulated kinases (pERK) were detected at P3 when compared with P1 and P2 in the MD treatment. TB treatment reduced the levels of HIF-1α and pERK at P3 relative to the MD control. Experiments with human umbilical vein endothelial cells (HUVEC) showed that sodium butyrate (NaBu) inhibited cell migration and tube formation, confirming the antiangiogenic activity of its prodrug TB. In conclusion, antiangiogenic activity of TB is an early event that already occurs in preneoplastic livers, reinforcing its potential chemopreventive effects against HCC.
Human Papillomavirus (HPV) Vaccine Effectiveness and Potential Herd Immunity for Reducing Oncogenic Oropharyngeal HPV-16 Prevalence in the United Kingdom: A Cross-sectional Study
Authors: Mehanna Hisham , Bryant Tyler S , Babrah Jaspreet , Louie Karly , Bryant Jennifer L , Spruce Rachel J , Batis Nikolaos , Olaleye Oladejo , Jones June , Struijk Linda , Molijn Anco , Vorsters Alex , Rosillon Dominique , Taylor Sylvia , D’Souza Gypsyamber 
Published: December 2018

AbstractBackgroundOropharyngeal cancer incidence is rapidly rising due to human papillomavirus (HPV) type 16 infection. The dearth of data on effectiveness of national female-only vaccination programs in preventing oral HPV infection and potential herd immunity in unvaccinated males has resulted in considerable controversy regarding the need to vaccinate males, especially in countries with high female vaccination coverage.MethodsSubjects aged 0–65 years undergoing tonsillectomy for nonmalignant indications were recruited in 6 hospitals in the United Kingdom. Oral samples were collected as follows: oral rinse, tongue base, and pharyngeal wall brushes, then tonsil tissue (tonsillectomy). Vaccination data were obtained from regional health authorities. All samples were centrally tested for HPV DNA by polymerase chain reaction.ResultsOf 940 subjects, 243 females and 69 males were aged 12–24 years (median age, 18.6 years), with 189 (78%) females and no males vaccinated against HPV. Overall, oropharyngeal HPV-16 prevalence was significantly lower in vaccinated versus unvaccinated females (0.5% vs 5.6%, P = .04). In contrast, prevalence of any oropharyngeal HPV type was similar in vaccinated and unvaccinated females (19% vs 20%, P = .76). Oropharyngeal HPV-16 prevalence in unvaccinated males was similar to vaccinated females (0% vs 0.5%, P > .99), and lower than unvaccinated females (0% vs 5.6%, P = .08).ConclusionsOur findings indicate that the UK female-only vaccination program is associated with significant reductions in oropharyngeal HPV-16 infections. These are also the first data to suggest potential herd immunity from female-only vaccination against oropharyngeal HPV infection in contemporaneously aged males.
Frailty Is an Independent Risk Factor for Mortality, Cardiovascular Disease, Bone Disease, and Diabetes Among Aging Adults With Human Immunodeficiency Virus
Authors: Kelly Sean G , Wu Kunling , Tassiopoulos Katherine , Erlandson Kristine M , Koletar Susan L , Palella Frank J 
Published: December 2018

AbstractBackgroundWe characterized associations between frailty and incident cardiovascular disease (CVD), diabetes mellitus (DM), bone disease, and mortality within a cohort of aging persons with human immunodeficiency virus (PWH).MethodsParticipants underwent frailty evaluations using the Fried frailty assessment (baseline and annually). Frailty was defined as having ≥3 frailty criteria. Clinical outcomes of mortality, CVD events, DM, and bone disease events were recorded throughout the study period (baseline to most recent study or clinic visit, or date of clinical outcome, whichever came first). Poisson regression models were used to evaluate associations between baseline frailty, change in frailty score over 48 weeks, and each clinical outcome.ResultsAmong 821 men and 195 women (median age 51 years), 62 (6%) were frail at baseline. Frailty scores increased by ≥1 component among 194 participants (19%) from baseline to 48 weeks. Baseline frailty was associated with an increased risk of incident CVD and DM, with a trend toward a significant association with bone events. Among frailty components, slow gait speed was associated with incident DM and borderline associated with incident CVD. An increase in frailty from baseline to week 48 was associated with mortality but not with the other clinical outcomes.ConclusionsBaseline frailty was associated with multiple adverse health outcomes (incident CVD, DM, and bone disease), while increase in frailty score was associated with mortality among PWH engaged in care. Incorporation of frailty assessments into the care of PWH may assist in improvement of functional status and risk stratification for age-related chronic diseases.
A Cluster of Cefepime-induced Neutropenia During Outpatient Parenteral Antimicrobial Therapy
Authors: Foong Kap Sum , Hsueh Kevin , Bailey Thomas C , Luong Lan , Iqbal Ayesha , Hoehner Christine , Connor Lee , Casabar Ed , Lane Michael , Burnett Yvonne , Ritchie David , Krekel Tamara , Newland Helen , Weilmuenster Lori , Heuring Brett , Durkin Michael J , Hamad Yasir 
Published: December 2018

Abstract
A cluster of cefepime-induced neutropenia (CIN) was identified from June 2017 to May 2018 in a regional outpatient parenteral antimicrobial therapy population. Our data suggest prolonged courses of cefepime (≥2 weeks), administered by rapid intravenous push, were associated with a higher risk of CIN.
Inhibition of heat shock protein 70 blocks the development of cardiac hypertrophy by modulating the phosphorylation of histone deacetylase 2
Authors: Yoon Somy , Kim Mira , Min Hyun-Ki , Lee Yeong-Un , Kwon Duk-Hwa , Lee Miyoung , Lee Sumin , Kook Taewon , Joung Hosouk , Nam Kwang-Il , Ahn Youngkeun , Kim Young-Kook , Kim Jaetaek , Park Woo Jin , McMullen Julie R , Eom Gwang Hyeon , Kook Hyun 
Published: December 2018

Abstract

Aims
Previously, we reported that phosphorylation of histone deacetylase 2 (HDAC2) and the resulting activation causes cardiac hypertrophy. Through further study of the specific binding partners of phosphorylated HDAC2 and their mechanism of regulation, we can better understand how cardiac hypertrophy develops. Thus, in the present study, we aimed to elucidate the function of one such binding partner, heat shock protein 70 (HSP70).

Methods and results
Primary cultures of rat neonatal ventricular cardiomyocytes and H9c2 cardiomyoblasts were used for in vitro cellular experiments. HSP70 knockout (KO) mice and transgenic (Tg) mice that overexpress HSP70 in the heart were used for in vivo analysis. Peptide-precipitation and immunoprecipitation assay revealed that HSP70 preferentially binds to phosphorylated HDAC2 S394. Forced expression of HSP70 increased phosphorylation of HDAC2 S394 and its activation, but not that of S422/424, whereas knocking down of HSP70 reduced it. However, HSP70 failed to phosphorylate HDAC2 in the cell-free condition. Phosphorylation of HDAC2 S394 by casein kinase 2α1 enhanced the binding of HSP70 to HDAC2, whereas dephosphorylation induced by the catalytic subunit of protein phosphatase 2A (PP2CA) had the opposite effect. HSP70 prevented HDAC2 dephosphorylation by reducing the binding of HDAC2 to PP2CA. HSP70 KO mouse hearts failed to phosphorylate S394 HDAC2 in response to isoproterenol infusion, whereas Tg overexpression of HSP70 increased the phosphorylation and activation of HDAC2. 2-Phenylethynesulfonamide (PES), an HSP70 inhibitor, attenuated cardiac hypertrophy induced either by phenylephrine in neonatal ventricular cardiomyocytes or by aortic banding in mice. PES reduced HDAC2 S394 phosphorylation and its activation by interfering with the binding of HSP70 to HDAC2.

Conclusion
These results demonstrate that HSP70 specifically binds to S394-phosphorylated HDAC2 and maintains its phosphorylation status, which results in HDAC2 activation and the development of cardiac hypertrophy. Inhibition of HSP70 has possible application as a therapeutic.
Towards a Complete Prohibition on the Immigration Detention of Children
Authors: Smyth Ciara M 
Published: December 2018

Abstract
The legal position on the immigration detention of children is unclear: is it permissible, subject to the ultima ratio (last resort) principle, or is it prohibited outright? International opinion is divided, with different human rights bodies favouring one or the other position. In November 2017, the Committee on the Rights of the Child and the Committee on the Protection of the Rights of All Migrant Workers and Members of Their Families issued a Joint General Comment in which they stated forthrightly that the immigration detention of children is prohibited and that the ultima ratio principle does not apply to the immigration context. This article situates the Joint General Comment in the broader context, interrogates its conceptual foundations and explores the extent to which it is likely to settle the debate. The key finding is that the position adopted in the Joint General Comment is correct but founded on a faulty premise and a misplaced emphasis. A more theoretically solid foundation for the prohibition on the immigration detention of children is advanced based on a teleological interpretation of the right of the child to liberty in the Convention on the Rights of the Child, with a particular focus on the concept of arbitrariness.
Numerical analysis of a time domain elastoacoustic problem
Authors: Araya Rodolfo , Rodríguez Rodolfo , Venegas Pablo 
Published: December 2018

AbstractThis paper deals with the numerical analysis of a system of second order in time partial differential equations modeling the vibrations of a coupled system that consists of an elastic solid in contact with an inviscid compressible fluid. We analyze a weak formulation with the unknowns in both media being the respective displacement fields. For its numerical approximation, we propose first a semidiscrete in space discretization based on standard Lagrangian elements in the solid and Raviart–Thomas elements in the fluid. We establish its well-posedness and derive error estimates in appropriate norms for the proposed scheme. In particular, we obtain an $\mathrm L^{\infty }(\mathrm L^2)$ optimal rate of convergence under minimal regularity assumptions of the solution, which are proved to hold for appropriate data of the problem. Then we consider a fully discrete approximation based on a family of implicit finite difference schemes in time, from which we obtain optimal error estimates for sufficiently smooth solutions. Finally, we report some numerical results, which allow us to assess the performance of the method. These results also show that the numerical solution is not polluted by spurious modes as is the case with other alternative approaches.
From Timbuktu to The Hague and Beyond
Authors: Drumbl Mark A 
Published: December 2018

Abstract
This essay refracts the criminal conviction and reparations order of the International Criminal Court (ICC) in the Al Mahdi case into the much broader frame of increasingly heated public debates over the protection, removal, defacement, relocation, display and destruction of cultural heritage in all forms: monuments, artefacts, language instruction, art and literature. What might the work product of the ICC in the Al Mahdi proceedings — and international criminal law more generally — add, contribute or excise from these debates? This essay speculatively explores connections between the turn to penal law to protect cultural property and the transformative impulses that undergird transitional justice which, in turn, often insist upon cultural change, including to cultures of oppression and impunity. Along the way, this essay also unpacks thorny questions as to how to value cultural property; how to determine what, exactly, constitutes the kind of property whose destruction should be criminalized; and which ‘cultures’ should be protected by ‘whom’ and in ‘whose’ interests.
‘Culture is who we are.’1
Controversies in relation to neck management in N0 early oral tongue cancer
Authors: Hanai Nobuhiro , Asakage Takahiro , Kiyota Naomi , Homma Akihiro , Hayashi Ryuichi 
Published: December 2018

Abstract
The standard local treatment for early-stage tongue cancer with no clinical lymph node metastases is partial glossectomy. The frequency of occult lymph node metastasis is ~20–30%. Thus, whether prophylactic neck dissection with glossectomy or glossectomy alone should be performed has been a controversial issue since the 1980s. Both treatments have advantages and disadvantages; however, especially in cases involving prophylactic neck dissection, surgical invasion and complications including the cosmetic disadvantage caused by neck skin incision, accessory nerve paralysis or facial nerve (mandibular marginal branch) paralysis, stiffness of the shoulder or neck and a feeling of neck tightness have been considered issues that could be solved by providing less-invasive treatment to the 70–80% of patients without occult lymph node metastasis.
A more accurate preoperative diagnosis and strict follow-up are required to provide minimally invasive treatment while ensuring the therapeutic effect. It is also necessary to narrow down the target based on the risk–benefit balance. The depth of invasion should be considered in cases involving oral cavity malignancies. This was also taken into account in recent revisions of eighth edition of the TNM Classification of Malignant Tumors and it is an important factor for N0 neck management. This review article summarizes previous and recent reports on neck management, focusing on the risk–benefit and future perspectives of the diagnosis and treatment of early-stage oral tongue cancer. This effort is an attempt to establish treatment from the patient’s point of view, with the patient’s quality of life taken into account.
Semiconductor quantum computation
Authors: Zhang Xin , Li Hai-Ou , Cao Gang , Xiao Ming , Guo Guang-Can , Guo Guo-Ping 
Published: December 2018

AbstractSemiconductors, a significant type of material in the information era, are becoming more and more powerful in the field of quantum information. In recent decades, semiconductor quantum computation was investigated thoroughly across the world and developed with a dramatically fast speed. The research varied from initialization, control and readout of qubits, to the architecture of fault-tolerant quantum computing. Here, we first introduce the basic ideas for quantum computing, and then discuss the developments of single- and two-qubit gate control in semiconductors. Up to now, the qubit initialization, control and readout can be realized with relatively high fidelity and a programmable two-qubit quantum processor has even been demonstrated. However, to further improve the qubit quality and scale it up, there are still some challenges to resolve such as the improvement of the readout method, material development and scalable designs. We discuss these issues and introduce the forefronts of progress. Finally, considering the positive trend of the research on semiconductor quantum devices and recent theoretical work on the applications of quantum computation, we anticipate that semiconductor quantum computation may develop fast and will have a huge impact on our lives in the near future.
Intensity of Withdrawal Symptoms During Opioid Taper in Patients with Chronic Pain—Individualized or Fixed Starting Dosage?
Authors: Bienek Natalia , Maier Christoph , Kaisler Miriam , Michel-Lauter Beate , Schwarzer Andreas , Meyer-Frießem Christine H 
Published: December 2018

AbstractObjectiveControlled opioid withdrawal is recommended for patients with chronic noncancer pain (CNCP) with insufficient pain reduction or intolerable side effects while on opioid treatment. Few studies have investigated the management of opioid withdrawal (OW). Most common are protocols with an individualized starting dosage (ISD), calculated from the last opioid intake. After two cases of overdose, we introduced a novel withdrawal protocol using a low fixed starting dosage (FSD) for safety reasons. The present study compares the intensity of withdrawal symptoms using the Subjective Opioid Withdrawal Scale (SOWS) and incidences of serious adverse events (SAE) and dropouts in each taper schedule in 195 CNCP patients with OW in an inpatient facility.MethodsTwo protocols were compared: FSD (2014–2016): N = 68, starting dose: 90 mg morphine/d; and ISD (2010–2014): N = 127, starting dose: 70% of the patient’s daily morphine equivalent dose (MED). Outcome criteria: primary: mean daily SOWS score during the first 10 days (16 questions, daily score 0–64); secondary: change in pain intensity on a numeric rating scale (0–10), rate of dropouts and SAEs. Statistics: Student test, Mann-Whitney U test, chi-square test, analysis of variance, P &lt; 0.05.ResultsThe mean daily SOWS score was lower in the FSD group (14.9 ± 9.4 vs 16.1 ± 10, P &lt; 0.05) due to a lower rate of high-intensity withdrawal symptoms (12.4% vs 17.6%, P &lt; 0.01), particularly in patients on &gt;180 mg MED (9.7% vs 18.4%, P &lt; 0.01). Pain intensity decreased after withdrawal, and the incidence of SAEs and dropouts was low in both groups.ConclusionsThe FSD protocol provides a lesser burden of withdrawal symptoms and equal patient safety. It can be recommended for OW in CNCP patients.
Stock Volatility and the Great Depression
Authors: Cortes Gustavo S , Weidenmier Marc D 
Published: December 2018

AbstractStock return volatility during the Great Depression has been labeled a “volatility puzzle” because the standard deviation of stock returns was 2 to 3 times higher than any other period in American history. We investigate this puzzle using a new series of building permits and leverage. Our results suggest that volatility in building permit growth and financial leverage largely explain the high level of stock volatility during the Great Depression. Markets factored in the possibility of a forthcoming economic disaster.Received September 30, 2017; editorial decision August 27, 2018 by Editor Philip E. Strahan. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online
Masking Release for Speech in Modulated Maskers: Electrophysiological and Behavioral Measures
Authors: Tanner A. Michelle , Spitzer Emily R. , Hyzy JP , Grose John H. 
Published: December 2018

Objectives:
The purpose of this study was to obtain an electrophysiological analog of masking release using speech-evoked cortical potentials in steady and modulated maskers and to relate this masking release to behavioral measures for the same stimuli. The hypothesis was that the evoked potentials can be tracked to a lower stimulus level in a modulated masker than in a steady masker and that the magnitude of this electrophysiological masking release is of the same order as that of the behavioral masking release for the same stimuli.

Design:
Cortical potentials evoked by an 80-ms /ba/ stimulus were measured in two steady maskers (30 and 65 dB SPL), and in a masker that modulated between these two levels at a rate of 25 Hz. In each masker, a level series was undertaken to determine electrophysiological threshold. Behavioral detection thresholds were determined in the same maskers using an adaptive tracking procedure. Masking release was defined as the difference between signal thresholds measured in the steady 65-dB SPL masker and the modulated masker. A total of 23 normal-hearing adults participated.

Results:
Electrophysiological thresholds were uniformly elevated relative to behavioral thresholds by about 6.5 dB. However, the magnitude of masking release was about 13.5 dB for both measurement domains.

Conclusions:
Electrophysiological measures of masking release using speech-evoked cortical auditory evoked potentials correspond closely to behavioral estimates for the same stimuli. This suggests that objective measures based on electrophysiological techniques can be used to reliably gauge aspects of temporal processing ability.
An Update of Eye Shape and Myopia
Authors: Matsumura Saiko , Kuo Anthony N. , Saw Seang-Mei 
Published: December 2018

Abstract:
Myopia is one of the most prevalent eye diseases, and its advanced form, high myopia, is a leading cause of subsequent pathologic myopia, which in turn results in an increased risk of retinal diseases. The prevalence of myopia and high myopia is 28.3% and 4.0% of the global population, respectively, and these numbers are estimated to increase to 49.8% for myopia 9.8% for high myopia by 2050, thus making myopia a severe global socioeconomic problem. The eye shape has been receiving increasing attention as a possible biomarker for myopia. Among several modalities, magnetic resonance imaging (MRI) is currently considered to be the best to measure the 3-dimensional eye shape, and one study using MRI revealed that myopic eyes became much larger in all 3 dimensions, but more so in length (0.35 mm/D) than in height (0.19 mm/D) or in width (0.10 mm/D), which fitted in global and axial elongation models. Another recent study reported that emmetropic retinas were oblate but oblateness decreased with myopia progression. According to a study to evaluate eye shapes in high myopia, although all emmetropic eyes had a blunt shape, almost half of the high myopic eyes had a pointed shape. Multiple lines of evidence suggest that abnormal eye shape changes can cause not only simple myopia but also various ocular complications through biomechanical stretching. In this review, we highlight recent findings on eye shape changes in myopic eyes and abnormal eye shapes in pathologic myopia.