bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting Glycolysis through Inhibition of Lactate Dehydrogenase Impairs Tumor Growth in Preclinical Models of Ewing Sarcoma
Authors: Yeung Choh , Gibson Anna E. , Issaq Sameer H. , Oshima Nobu , Baumgart Joshua T. , Edessa Leah D. , Rai Ganesha , Urban Daniel J. , Johnson Michelle S. , Benavides Gloria A. , Squadrito Giuseppe L. , Yohe Marielle E. , Lei Haiyan , Eldridge Sandy , Hamre John , Dowdy Tyrone , Ruiz-Rodado Victor , Lita Adrian , Mendoza Arnulfo , Shern Jack F. , Larion Mioara , Helman Lee J. , Stott Gordon M. , Krishna Murali C. , Hall Matthew D. , Darley-Usmar Victor , Neckers Leonard M. , Heske Christine M. 
Published: August 2019

Abstract

Altered cellular metabolism, including an increased dependence on aerobic glycolysis, is a hallmark of cancer. Despite the fact that this observation was first made nearly a century ago, effective therapeutic targeting of glycolysis in cancer has remained elusive. One potentially promising approach involves targeting the glycolytic enzyme lactate dehydrogenase (LDH), which is overexpressed and plays a critical role in several cancers. Here, we used a novel class of LDH inhibitors to demonstrate, for the first time, that Ewing sarcoma cells are exquisitely sensitive to inhibition of LDH. EWS-FLI1, the oncogenic driver of Ewing sarcoma, regulated LDH A (LDHA) expression. Genetic depletion of LDHA inhibited proliferation of Ewing sarcoma cells and induced apoptosis, phenocopying pharmacologic inhibition of LDH. LDH inhibitors affected Ewing sarcoma cell viability both in vitro and in vivo by reducing glycolysis. Intravenous administration of LDH inhibitors resulted in the greatest intratumoral drug accumulation, inducing tumor cell death and reducing tumor growth. The major dose-limiting toxicity observed was hemolysis, indicating that a narrow therapeutic window exists for these compounds. Taken together, these data suggest that targeting glycolysis through inhibition of LDH should be further investigated as a potential therapeutic approach for cancers such as Ewing sarcoma that exhibit oncogene-dependent expression of LDH and increased glycolysis.

Significance:
LDHA is a pharmacologically tractable EWS-FLI1 transcriptional target that regulates the glycolytic dependence of Ewing sarcoma.
Nanoparticle Encapsulation of Synergistic Immune Agonists Enables Systemic Codelivery to Tumor Sites and IFNβ-Driven Antitumor Immunity
Authors: Atukorale Prabhani U. , Raghunathan Shruti P. , Raguveer Vanitha , Moon Taylor J. , Zheng Carolyn , Bielecki Peter A. , Wiese Michelle L. , Goldberg Amy L. , Covarrubias Gil , Hoimes Christopher J. , Karathanasis Efstathios 
Published: August 2019

Abstract

Effective cancer immunotherapy depends on the robust activation of tumor-specific antigen-presenting cells (APC). Immune agonists encapsulated within nanoparticles (NP) can be delivered to tumor sites to generate powerful antitumor immune responses with minimal off-target dissemination. Systemic delivery enables widespread access to the microvasculature and draining to the APC-rich perivasculature. We developed an immuno-nanoparticle (immuno-NP) coloaded with cyclic diguanylate monophosphate, an agonist of the stimulator of interferon genes pathway, and monophosphoryl lipid A, and a Toll-like receptor 4 agonist, which synergize to produce high levels of type I IFNβ. Using a murine model of metastatic triple-negative breast cancer, systemic delivery of these immuno-NPs resulted in significant therapeutic outcomes due to extensive upregulation of APCs and natural killer cells in the blood and tumor compared with control treatments. These results indicate that NPs can facilitate systemic delivery of multiple immune-potentiating cargoes for effective APC-driven local and systemic antitumor immunity.

Significance:
Systemic administration of an immuno-nanoparticle in a murine breast tumor model drives a robust tumor site–specific APC response by delivering two synergistic immune-potentiating molecules, highlighting the potential of nanoparticles for immunotherapy.
ОКИСЛЮВАЛЬНИЙ СТРЕС ЯК ОДИН З ВАЖЛИВІШИХ ЧИННИКІВ ГОСТРОГО УРАЖЕННЯ ЕНДОТЕЛІЮ
Authors: Nikitin Ye. V. , Vereshchahinа O. I. 
Published: August 2019

Метою роботи було дослідження динаміки вмісту циркулюючих ендотеліальних клітин у периферичній крові та визначення ролі процесів вільнорадикального окислення в пошкодженні ендотеліоцитів. На основі проведеного дослідження вдосконалити лікування хворих на грип А.
На підставі обстеження 158 пацієнтів віком від 18 до 45 років, хворих на грип А, з яких у 32 осіб ступінь тяжкості був легким, у 62 – середнім та у 64 хворих – тяжким, було встановлено взаємозв’язок між зростанням рівня циркулюючих ендотеліальних клітин і активністю процесів вільнорадикального окислення, показано ефективність комплексного лікування. На підставі проведених досліджень установлено, що в патогенезі грипу суттєву роль відіграє надмірне підвищення активності процесів перекисного окислення ліпідів зі зниженням рівня антиоксидантного захисту. Була встановлена пряма залежність між підвищеннями концентрації малонового діальдегіду, дієнових кон’югат і кетодієнів у крові хворих на грип з тяжким ступенем. При дослідженні циркулюючих ендотеліальних клітин також було виявлено збільшення їх загальної кількості залежно від ступеня тяжкості захворювання. Посилене відшарування ендотеліоцитів від базальної мембрани у групах дослідження є доказом поєднаної дії токсинів грипу та цитотоксичних продуктів вільнорадикального окислення. З метою зниження токсичного впливу продуктів перекисного окислення ліпідів (ПОЛ) при грипі 32 хворим із середнім ступенем тяжкості до базисної терапії додавали 2-етил-6-метил-3-гідроксипіридину сукцинат, механізм дії якого зумовлений його антиоксидантною та мембранопротекторною дією. Проведені дослідження дозволили дійти наступних висновків: дисбаланс у системі ПОЛ/АОЗ призводить до пригнічення та виснаження антиоксидантної системи, пошкодження ендотеліоцитів з подальшим розвитком дисфункції ендотелію; підвищення загальної кількості циркулюючих ендотеліальних клітин у крові розвивається у відповідь на оксидативний стрес; комплексний підхід до лікування грипу з призначенням препаратів з антирадикальним механізмом дії сприятливо впливає на перебіг захворювання та зменшує ураження ендотелію судин.
ANTIHERPETIC EFFICACY OF LACTOBACILLI AND BIFIDOBACTERIA PROBIOTIC STRAINS IN EXPERIMENTAL GENITAL HERPES IN GUINEA PIGS
Authors: Starosyla D. B. , Lazarenko L. M. , Hryhorieva S.M. , Babenko L. P. , Rybalko S. L. , Spivak M. Ya. 
Published: August 2019

Метою було визначення антигерпетичної ефективності пробіотичного штаму Lacto­bacillus casei ІМВ В-7280 та композиції L. caseі ІМВ В-7280 – Bifidobacterium animalis VKL – B. animalis VKВ (В-7280 – VKL – VKВ) за експериментального генітального герпесу в мурчаків, індукованого вірусом простого герпесу 2-го типу (ВПГ-2).
Матеріали і методи. Генітальну герпетичну інфекцію моделювали за допомогою ВПГ-2 (штам ВН) у самиць безпородних мурчаків. Критеріями оцінки ступеня тяжкості інфекційного процесу були: площа і ступінь специфічних уражень, а також наявність набряку, гіперемії й виразок. У сироватці крові тварин визначали титр ВПГ-2 за допомогою загальноприйнятих вірусологічних методів дослідження. Спектр мікробіоти піхви тварин визначали за допомогою загальноприйнятих мікробіологічних методів дослідження. Ефективність дії пробіотичних бактерій оцінювали за максимального розвитку патологічного процесу: за згасанням клінічних проявів захворювання та інфекційного титру ТЦД ID50 ВПГ-2, а також скороченням термінів захворювання та індексом лікувальної дії (ІЛД).
Результати досліджень та їх обговорення. Встановлено, що за експериментального генітального герпесу у мурчаків при застосуванні пробіотичного штаму L. caseі ІМВ В-7280 та композиції В-7280 – VKL – VKВ зменшувались: ступінь клінічних симптомів захворювання, його тривалість, а також інфекційний титр ВПГ-2, хоч ІЛД не перевищував 50 %. Під впливом L. caseі ІМВ В-7280 та композиції відбувалось зменшення інфекційного титру ТЦД ID50 ВПГ-2, що свідчить про антигерпетичну ефективність цих пробіотичних штамів бактерій, у механізми якої може залучатись зміна мікробіоти піхви. Мікробіологічний пейзаж піхви за максимальної яскравості клінічних симптомів генітального герпесу характеризувався зниженням кількості стафілококів у піхві інфікованих мурчаків, яким вводили L. caseі ІМВ В-7280, при високому рівні цих бактерій за умови застосування композиції В-7280 – VKL – VKВ, а також появою в окремих тварин лактобацил (ЛАБ). Зауважимо, що виділені нами в кінці експерименту ЛАБ за своєю морфологією відрізнялися від лактобактерій, використаних в експерименті. Тобто можна припустити, що відбулося відновлення характерної для мурчаків нормальної мікробіоти піхви.
Висновок. Штам L. caseі ІМВ В-7280 та композиція В-7280 – VKL – VKВ є перспективними для розробки цільових пробіотиків для профілактики й лікування інфекційно-запальних хвороб сечостатевої системи.
Disembodied Cognition and Assimilation: Thirteenth-Century Debates on an Epistemological Puzzle
Authors: Perler Dominik 
Published: August 2019

AbstractMedieval Aristotelians assumed that we cannot assimilate forms unless our soul abstracts them from sensory images. But what about the disembodied soul that has no senses and hence no sensory images? How can it assimilate forms? This article discusses this problem, focusing on two thirteenth-century models. It first looks at Thomas Aquinas’ model, which invokes divine intervention: the separated soul receives forms directly from God. The article examines the problems this explanatory model poses and then turns to a second model, defended by Matthew of Aquasparta: the separated soul actively apprehends forms that are present to it. It will be argued that this model explains assimilation in terms of appropriation, rather than reception, of forms and thereby radically changes the traditional account of cognition. Finally, the article draws some methodological conclusions, arguing that the focus on the ‘limit case’ of separated souls made theoretical change possible.
A Critical Appraisal of Initial Coin Offerings
Authors: Nestarcova Dominika 
Published: August 2019

AbstractInitial Coin Offerings (ICOs) emerged in 2017 as a revolutionary form of raising capital by technology companies and investment vehicles. ICOs enable start-up companies to issue blockchain-based assets (‘digital tokens’) to the public in return for a payment in cryptocurrencies or fiat money. The fundraising objective is to finance technology projects carried out by the ‘ICO issuer’. The ICO funding model represents a financial revolution as it provides additional pools of liquidity for capital formation purposes and a powerful tool for incentivizing communities through network effects. More importantly, the latent value of ICOs lies in the usage of the raised funds to develop cutting-edge distributed ledger technologies (DLTs). The advent of ICOs mushrooming worldwide promises to democratize financing, yet the commonly unregulated space in which ICOs operate, opens up a Pandora’s Box of investment and legal risks. The present paper argues that regulation needs to be goal-orientated and for that purpose, it is crucial to identify the nature of the ICO funding model, the cryptoeconomics behind it and the legal nature of digital tokens. With ICOs, academia, economists and regulators are at ground zero. Practitioners’ first instinct is to apply the knowledge of capital markets, but ICOs are a fundamentally new model of raising funds that have spawned different dynamics from ‘traditional’ capital markets. If we can establish how to approach ICOs within their own right, then choosing the correct regulatory stance will become a matter of identifying how ICOs and markets interact and how the investment risks can be allocated. Keeping with the spirit of ICOs as a financial innovation, the paper proposes self-regulation by ICO issuers to be a suitable regulatory approach, while limiting the role of regulators to policing the secondary market of crypto-intermediaries. For the purpose of fully rationalizing this position, the paper outlines the process of carrying out an ICO, relevant benefits and risks to the model, the current state of ICO regulation, digital token characterization and merits of different regulatory approaches.
Reliability and Construct Validity of the Penetration‐Aspiration Scale for Quantifying Pediatric Outcomes after Interarytenoid Augmentation
Authors: Wick Elizabeth H. , Johnson Kaalan , Demarre Kim , Faherty Amy , Parikh Sanjay , Horn David L. 
Published: August 2019

ObjectiveTo assess the reliability and construct validity of the Penetration‐Aspiration Scale in children.Study DesignThis was a retrospective cohort study of pre‐ and postoperative video modified barium swallow studies from children who underwent interarytenoid injection augmentation for unexplained persistent pharyngeal dysphagia. Two pediatric speech and language pathologists reviewed each study twice in a blinded and randomized fashion.SettingTertiary academic pediatric hospital.Subjects and MethodsThirty children were identified with adequate pre‐ and postoperative modified barium swallow studies within 4 weeks of intervention. Children were separated into clinical outcome groups based on ability to advance to thinner diet consistencies postoperatively. Construct validity was assessed with a mixed linear model to test the hypothesis that only the clinically improved group would receive better Penetration‐Aspiration Scale scores after surgery. Reliability was assessed by calculating chance‐corrected agreement between raters (interrater) and raters’ repeat evaluations (intrarater).ResultsInter‐ and intrarater reliabilities (Cohen’s κ) were both excellent. Results of the mixed model revealed a significant interaction between outcome group and pre‐ and postoperative time interval. As hypothesized, this involved a significant improvement in Penetration‐Aspiration Scale score only in the improved group.ConclusionsThese findings suggest that the Penetration‐Aspiration Scale is a reliable and valid measure of clinical response to interarytenoid injection augmentation in children.
Good Samaritan Law and bystander cardiopulmonary resuscitation: Cross-sectional study of 1223 first-aid learners in Hong Kong
Authors: Hung Kevin KC , Leung CY , Siu Axel , Graham Colin A 
Published: August 2019

Background:Similar to many Asian cities, there is no statutory provision for the determination of the duty borne by bystander first aiders when assisting victims in Hong Kong.Objectives:The aim of this study was to explore the views of a Good Samaritan Law by first-aid learners in Hong Kong.Methods:A cross-sectional survey was conducted among first-aid course participants from the two largest training providers in Hong Kong using a self-administered questionnaire.Results:In total, 1223 questionnaires were completed and returned. Only 12.1% (147/1211) of participants have ever heard of Good Samaritan Law. After a short description of Good Samaritan Law was provided, 71.4% (848/1188) agreed or strongly agreed on a Likert-type scale that a Good Samaritan Law is necessary; 95.2% (1148/1223) support the enactment of a Good Samaritan Law in Hong Kong.Conclusion:The majority of first-aid learners in Hong Kong supported the enactment of Good Samaritan Law. Overcoming the fear of litigation and improving bystander cardiopulmonary resuscitation rate is a priority for improving survival rates from sudden cardiac arrest in Hong Kong.
Hematopoietic stem cell response to acute thrombocytopenia requires signaling through distinct receptor tyrosine kinases
Authors: Ramasz Beáta , Krüger Anja , Reinhardt Julia , Sinha Anupam , Gerlach Michael , Gerbaulet Alexander , Reinhardt Susanne , Dahl Andreas , Chavakis Triantafyllos , Wielockx Ben , Grinenko Tatyana 
Published: August 2019

Key Points
A dual signal from c-Kit and VEGFR-2 determines selective activation of HSCs and MPP2 in response to acute immune thrombocytopenia. VEGF-A and PDGF-BB relocalize stem cell factor in megakaryocytes, triggering proliferation of HSPCs.
Collagen structure changes during chrome tanning in propylene carbonate
Authors: Zhang Yi , Buchanan Jenna Kate , Holmes Geoff , Mansel Bradley William , Prabakar Sujay 
Published: August 2019

Abstract
Green solvents, such as propylene carbonate (PC), can be used in leather processing to improve the efficiency of chrome tanning and reduce wastewater. Here we report a combined small-angle X-ray scattering (SAXS) and differential scanning calorimetry (DSC) study on PC and its efficacy as a carrier medium during chrome tanning. SAXS analysis on the collagen structure of chrome tanned leather using PC, compared to conventionally tanned leather using water, showed an increase in Cr uptake in addition to the more uniform penetration of Cr through the leather cross-section. The increased binding of Cr to the collagen matrix drives the decreased hydration environment of the collagen triple helix. Furthermore, DSC studies show a uniform hydrothermal stability for the PC samples due to the more even distribution of Cr through the collagen matrix. Understanding the mechanisms by which chrome tanning occurs in non-aqueous solvents can guide us towards a more sustainable future for the leather industry.

Graphical abstract
Differential Actions of Estrogen Receptor α and β via Nongenomic Signaling in Human Prostate Stem and Progenitor Cells
Authors: Majumdar Shyama , Rinaldi Jaqueline C , Malhotra Neha R , Xie Lishi , Hu Dan-Ping , Gauntner Timothy D , Grewal Harinder S , Hu Wen-Yang , Kim Sung Hoon , Katzenellenbogen John A , Kasper Susan , Prins Gail S 
Published: August 2019

AbstractHuman prostate stem and progenitor cells express estrogen receptor (ER)α and ERβ and exhibit proliferative responses to estrogens. In this study, membrane-initiated estrogen signaling was interrogated in human prostate stem/progenitor cells enriched from primary epithelial cultures and stem-like cell lines from benign and cancerous prostates. Subcellular fractionation and proximity ligation assays localized ERα and ERβ to the cell membrane with caveolin-1 interactions. Exposure to 17β-estradiol (E2) for 15 to 60 minutes led to sequential phosphorylation of signaling molecules in MAPK and AKT pathways, IGF1 receptor, epidermal growth factor receptor, and ERα, thus documenting an intact membrane signalosome that activates diverse downstream cascades. Treatment with an E2–dendrimer conjugate or ICI 182,870 validated E2-mediated actions through membrane ERs. Overexpression and knockdown of ERα or ERβ in stem/progenitor cells identified pathway selectivity; ERα preferentially activated AKT, whereas ERβ selectively activated MAPK cascades. Furthermore, prostate cancer stem-like cells expressed only ERβ, and brief E2 exposure activated MAPK but not AKT cascades. A gene subset selectively regulated by nongenomic E2 signaling was identified in normal prostate progenitor cells that includes BGN, FOSB, FOXQ1, and MAF. Membrane-initiated E2 signaling rapidly modified histone methyltransferases, with MLL1 cleavage observed downstream of phosphorylated AKT and EZH2 phosphorylation downstream of MAPK signaling, which may jointly modify histones to permit rapid gene transcription. Taken together, the present findings document ERα and ERβ membrane-initiated signaling in normal and cancerous human prostate stem/progenitor cells with differential engagement of downstream effectors. These signaling pathways influence normal prostate stem/progenitor cell homeostasis and provide novel therapeutic sites to target the elusive prostate cancer stem cell population.
Year One: Reflections on Turkey's Second Founding and the Politics of Division
Authors: Bargu Banu 
Published: August 2019

Abstract
This essay analyzes Turkey's contemporary moment in light of the significance of the coup attempt on July 15, 2016 and the countrywide state of emergency it precipitated. The essay specifically examines two different forces unleashed by July 15: on the one hand, an assertive raison d'état that seeks to re-establish unity among state apparatuses and to enhance state power from above, and, on the other, the popular energies of resistance that have countered the coup attempt from below. Scrutinizing the conjuncture that has enabled the AKP to assume leadership over both forces, I investigate how a process of restoration has been transformed into a process of remaking the polity. In light of the crisis of hegemony of political Islamism, I explore both the nationalist politics of division that is mobilized to sustain the movement toward Turkey's “second” founding and the possibilities for opposition that might counter it.
The Strike that Made a Difference
Authors: Rudan Paola , Precarie ∫connessioni , Non Una di Meno Roma  
Published: August 2019

Abstract
Commenting on three activist documents on the global women's strike published by the Italian network Non Una di Meno and by the collective ∫connessioni precarie, this text reads the March 8 strike in Italy as part of a transnational process that was both deepened and accelerated by the use of the strike as a feminist practice. The March 8 strike was a political and social strike. It made a difference because it allowed feminism to go beyond the borders of the “woman question,” to become both a mass political practice and a means by which to question the whole neoliberal order at the very moment in which patriarchal violence had begun to be recognized as fundamental to it.
Call to the International Women's Strike – March 8, 2018
Authors: Menos Ni Una 
Published: August 2019

Abstract
In this call to strike, the members of Ni Una Menos define the strike as a tool that they reinvent to dismantle the scheme of violence against women. The strike, they write, allows them to map new colonial and imperial forms deployed against women's economies and territories. Those who strike investigate and activate resistances and disobediences, the production of alternate forms of life, and rebellious bodies. Those who organize—women, lesbians, trans people, feminized bodies of the world—seek to propagate a virus of defiance. In a demonstration of force and with a collective shout for March 8, 2018, women strike: ¡Ni Una Menos, Vivas Nos Queremos! (Not One Woman Less! We Want to Stay Alive!)
Hostages to Democracy
Authors: Sundar Nandini 
Published: August 2019

AbstractThis article explores the aporias of democracy to show how both procedural and substantive democracy, or at least certain constructions of “need,” operate to render the lives of sections of the citizenry precarious. More specifically, in the context of an ongoing civil war in central India between Maoist guerillas and the Indian state, I argue that, far from being a palliative for or alternative to insurgency, Indian democracy as practiced today—both in its procedural electoral aspects and its substantive welfare aspects—may serve as an active tool of counterinsurgency and a means of evading accountability.