bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of brain cation-Cl− cotransport via the SPAK kinase inhibitor ZT-1a
Authors: Zhang Jinwei , Bhuiyan Mohammad Iqbal H. , Zhang Ting , Karimy Jason K. , Wu Zhijuan , Fiesler Victoria M. , Zhang Jingfang , Huang Huachen , Hasan Md Nabiul , Skrzypiec Anna E. , Mucha Mariusz , Duran Daniel , Huang Wei , Pawlak Robert , Foley Lesley M. , Hitchens T. Kevin , Minnigh Margaret B. , Poloyac Samuel M. , Alper Seth L. , Molyneaux Bradley J. , Trevelyan Andrew J. , Kahle Kristopher T. , Sun Dandan , Deng Xianming 
Published: January 2020

AbstractThe SLC12A cation-Cl− cotransporters (CCC), including NKCC1 and the KCCs, are important determinants of brain ionic homeostasis. SPAK kinase (STK39) is the CCC master regulator, which stimulates NKCC1 ionic influx and inhibits KCC-mediated efflux via phosphorylation at conserved, shared motifs. Upregulation of SPAK-dependent CCC phosphorylation has been implicated in several neurological diseases. Using a scaffold-hybrid strategy, we develop a novel potent and selective SPAK inhibitor, 5-chloro-N-(5-chloro-4-((4-chlorophenyl)(cyano)methyl)-2-methylphenyl)-2-hydroxybenzamide (“ZT-1a”). ZT-1a inhibits NKCC1 and stimulates KCCs by decreasing their SPAK-dependent phosphorylation. Intracerebroventricular delivery of ZT-1a decreases inflammation-induced CCC phosphorylation in the choroid plexus and reduces cerebrospinal fluid (CSF) hypersecretion in a model of post-hemorrhagic hydrocephalus. Systemically administered ZT-1a reduces ischemia-induced CCC phosphorylation, attenuates cerebral edema, protects against brain damage, and improves outcomes in a model of stroke. These results suggest ZT-1a or related compounds may be effective CCC modulators with therapeutic potential for brain disorders associated with impaired ionic homeostasis.
Immune-mediated genetic pathways resulting in pulmonary function impairment increase lung cancer susceptibility
Authors: Kachuri Linda , Johansson Mattias , Rashkin Sara R. , Graff Rebecca E. , Bossé Yohan , Manem Venkata , Caporaso Neil E. , Landi Maria Teresa , Christiani David C. , Vineis Paolo , Liu Geoffrey , Scelo Ghislaine , Zaridze David , Shete Sanjay S. , Albanes Demetrius , Aldrich Melinda C. , Tardón Adonina , Rennert Gad , Chen Chu , Goodman Gary E. , Doherty Jennifer A. , Bickeböller Heike , Field John K. , Davies Michael P. , Dawn Teare M. , Kiemeney Lambertus A. , Bojesen Stig E. , Haugen Aage , Zienolddiny Shanbeh , Lam Stephen , Le Marchand Loïc , Cheng Iona , Schabath Matthew B. , Duell Eric J. , Andrew Angeline S. , Manjer Jonas , Lazarus Philip , Arnold Susanne , McKay James D. , Emami Nima C. , Warkentin Matthew T. , Brhane Yonathan , Obeidat Ma’en , Martin Richard M. , Relton Caroline , Davey Smith George , Haycock Philip C. , Amos Christopher I. , Brennan Paul , Witte John S. , Hung Rayjean J. 
Published: January 2020

AbstractImpaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in lung cancer susceptibility. Investigation of the shared genetic basis of these phenotypes in the UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that lung cancer is genetically correlated with reduced forced expiratory volume in one second (FEV1: rg = 0.098, p = 2.3 × 10−8) and the ratio of FEV1 to forced vital capacity (FEV1/FVC: rg = 0.137, p = 2.0 × 10−12). Mendelian randomization analyses demonstrate that reduced FEV1 increases squamous cell carcinoma risk (odds ratio (OR) = 1.51, 95% confidence intervals: 1.21–1.88), while reduced FEV1/FVC increases the risk of adenocarcinoma (OR = 1.17, 1.01–1.35) and lung cancer in never smokers (OR = 1.56, 1.05–2.30). These findings support a causal role of pulmonary impairment in lung cancer etiology. Integrative analyses reveal that pulmonary function instruments, including 73 novel variants, influence lung tissue gene expression and implicate immune-related pathways in mediating the observed effects on lung carcinogenesis.
Automated mass spectrometry imaging of over 2000 proteins from tissue sections at 100-μm spatial resolution
Authors: Piehowski Paul D. , Zhu Ying , Bramer Lisa M. , Stratton Kelly G. , Zhao Rui , Orton Daniel J. , Moore Ronald J. , Yuan Jia , Mitchell Hugh D. , Gao Yuqian , Webb-Robertson Bobbie-Jo M. , Dey Sudhansu K. , Kelly Ryan T. , Burnum-Johnson Kristin E. 
Published: January 2020

AbstractBiological tissues exhibit complex spatial heterogeneity that directs the functions of multicellular organisms. Quantifying protein expression is essential for elucidating processes within complex biological assemblies. Imaging mass spectrometry (IMS) is a powerful emerging tool for mapping the spatial distribution of metabolites and lipids across tissue surfaces, but technical challenges have limited the application of IMS to the analysis of proteomes. Methods for probing the spatial distribution of the proteome have generally relied on the use of labels and/or antibodies, which limits multiplexing and requires a priori knowledge of protein targets. Past efforts to make spatially resolved proteome measurements across tissues have had limited spatial resolution and proteome coverage and have relied on manual workflows. Here, we demonstrate an automated approach to imaging that utilizes label-free nanoproteomics to analyze tissue voxels, generating quantitative cell-type-specific images for >2000 proteins with 100-µm spatial resolution across mouse uterine tissue sections preparing for blastocyst implantation.
Generating ring-shaped engineered heart tissues from ventricular and atrial human pluripotent stem cell-derived cardiomyocytes
Authors: Goldfracht Idit , Protze Stephanie , Shiti Assad , Setter Noga , Gruber Amit , Shaheen Naim , Nartiss Yulia , Keller Gordon , Gepstein Lior 
Published: January 2020

AbstractThe functions of the heart are achieved through coordination of different cardiac cell subtypes (e.g., ventricular, atrial, conduction-tissue cardiomyocytes). Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) offer unique opportunities for cardiac research. Traditional studies using these cells focused on single-cells and utilized mixed cell populations. Our goal was to develop clinically-relevant engineered heart tissues (EHTs) comprised of chamber-specific hPSC-CMs. Here we show that such EHTs can be generated by directing hPSCs to differentiate into ventricular or atrial cardiomyocytes, and then embedding these cardiomyocytes in a collagen-hydrogel to create chamber-specific, ring-shaped, EHTs. The chamber-specific EHTs display distinct atrial versus ventricular phenotypes as revealed by immunostaining, gene-expression, optical assessment of action-potentials and conduction velocity, pharmacology, and mechanical force measurements. We also establish an atrial EHT-based arrhythmia model and confirm its usefulness by applying relevant pharmacological interventions. Thus, our chamber-specific EHT models can be used for cardiac disease modeling, pathophysiological studies and drug testing.
Ventromedial prefrontal cortex compression during concept learning
Authors: Mack Michael L. , Preston Alison R. , Love Bradley C. 
Published: January 2020

AbstractPrefrontal cortex (PFC) is thought to support the ability to focus on goal-relevant information by filtering out irrelevant information, a process akin to dimensionality reduction. Here, we test this dimensionality reduction hypothesis by relating a data-driven approach to characterizing the complexity of neural representation with a theoretically-supported computational model of learning. We find evidence of goal-directed dimensionality reduction within human ventromedial PFC during learning. Importantly, by using computational predictions of each participant’s attentional strategies during learning, we find that that the degree of neural compression predicts an individual’s ability to selectively attend to concept-specific information. These findings suggest a domain-general mechanism of learning through compression in ventromedial PFC.
Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity
Authors: Shapiro Mariya B. , Cheever Tracy , Malherbe Delphine C. , Pandey Shilpi , Reed Jason , Yang Eun Sung , Wang Keyun , Pegu Amarendra , Chen Xuejun , Siess Don , Burke David , Henderson Heidi , Lewinsohn Rebecca , Fischer Miranda , Stanton Jeffrey J. , Axthelm Michael K. , Kahl Christoph , Park Byung , Lewis Anne D. , Sacha Jonah B. , Mascola John R. , Hessell Ann J. , Haigwood Nancy L. 
Published: January 2020

AbstractVertical transmission accounts for most human immunodeficiency virus (HIV) infection in children, and treatments for newborns are needed to abrogate infection or limit disease progression. We showed previously that short-term broadly neutralizing antibody (bNAb) therapy given 24 h after oral exposure cleared simian-human immunodeficiency virus (SHIV) in a macaque model of perinatal infection. Here, we report that all infants given either a single dose of bNAbs at 30 h, or a 21-day triple-drug ART regimen at 48 h, are aviremic with almost no virus in tissues. In contrast, bNAb treatment beginning at 48 h leads to tight control without adaptive immune responses in half of animals. We conclude that both bNAbs and ART mediate effective post-exposure prophylaxis in infant macaques within 30–48 h of oral SHIV exposure. Our findings suggest that optimizing the treatment regimen may extend the window of opportunity for preventing perinatal HIV infection when treatment is delayed.
Hydrogen bonding interactions of H2O and SiOH on a boroaluminosilicate glass corroded in aqueous solution
Authors: Ngo Dien , Liu Hongshen , Chen Zhe , Kaya Huseyin , Zimudzi Tawanda J. , Gin Stéphane , Mahadevan Thiruvillamalai , Du Jincheng , Kim Seong H. 
Published: January 2020

AbstractHydrogen bonding interactions play an important role in many chemical and physical processes occurring in bulk liquids and at interfaces. In this study, hydrous species (H2O and Si-OH) on nano-porous alteration layers (gels) formed on a boroaluminosilicate glass called International Simple Glass corroded in aqueous solutions at pH 7 and pH 9, and initially saturated with soluble silicon-containing species were analyzed using linear and non-linear vibrational spectroscopy in combination with molecular dynamics simulations. The simulation results revealed various possible types of hydrogen bonds among these hydrous species in nanoconfinement environments with their populations depending on pore-size distribution. The nano-porous gels formed on corroded glass surfaces enhance hydrogen bond strength between hydrous species as revealed by attenuated total reflectance infrared spectroscopy. Sum frequency generation spectroscopy showed some significant differences in hydrogen bonding interactions on alteration layers formed at pH 7 and pH 9. The glass dissolution under the leaching conditions used in this study has been known to be ten times faster at pH 7 in comparison to that at pH 9 due to unknown reasons. The simulation and experimental results obtained in this study indicate that the water mobility in the gel formed at pH 9 could be slower than that in the gel formed at pH 7, and as a result, the leaching rate at pH 9 is slower than that at pH 7.
Whole-genome sequencing of 128 camels across Asia reveals origin and migration of domestic Bactrian camels
Authors: Ming Liang , Yuan Liyun , Yi Li , Ding Guohui , Hasi Surong , Chen Gangliang , Jambl Tuyatsetseg , Hedayat-Evright Nemat , Batmunkh Mijiddorj , Badmaevna Garyaeva Khongr , Gan-Erdene Tudeviin , Ts Batsukh , Zhang Wenbin , Zulipikaer Azhati , Hosblig  , Erdemt  , Natyrov Arkady , Mamay Prmanshayev , Narenbatu  , Meng Gendalai , Narangerel Choijilsuren , Khongorzul Orgodol , He Jing , Hai Le , Lin Weili , Sirendalai  , Sarentuya  , Aiyisi  , Li Yixue , Wang Zhen , Jirimutu  
Published: January 2020

AbstractThe domestic Bactrian camels were treated as one of the principal means of locomotion between the eastern and western cultures in history. However, whether they originated from East Asia or Central Asia remains elusive. To address this question, we perform whole-genome sequencing of 128 camels across Asia. The extant wild and domestic Bactrian camels show remarkable genetic divergence, as they were split from dromedaries. The wild Bactrian camels also contribute little to the ancestry of domestic ones, although they share close habitat in East Asia. Interestingly, among the domestic Bactrian camels, those from Iran exhibit the largest genetic distance and the earliest split from all others in the phylogeny, despite evident admixture between domestic Bactrian camels and dromedaries living in Central Asia. Taken together, our study support the Central Asian origin of domestic Bactrian camels, which were then immigrated eastward to Mongolia where native wild Bactrian camels inhabit.
Treatment of Advanced Hormone Receptor-Positive (HR+) HER2-negative Breast Cancer
Authors: Ditsch Nina , Schmidt Marcus 
Published: January 2020

AbstractThe article gives an overview of current treatment options for metastatic hormone receptor-positive and HER2-negative breast cancer. The focus is on combined therapies, e.g., with CDK4/6 inhibition compared with purely endocrine-based therapies in the pre- and postmenopause, presenting the latest study results. The addition of a CDK4/6 inhibitor to endocrine-based therapy with an aromatase inhibitor or fulvestrant leads to a marked improvement in progression-free survival and is independently beneficial whether palbociclib, ribociclib or abemaciclib is involved. The particular clinical status of inhibition of cyclin-dependent kinases argues for its use in the first-line treatment of women with metastatic, hormone receptor-positive and HER2-negative breast cancer compared with the available purely endocrine-based therapies.
Challenging News: Pädiatrische Hämatologie und Onkologie
Authors: Sparber-Sauer Monika , Bielack Stefan 
Published: January 2020

ZUSAMMENFASSUNGNeuigkeiten aus der pädiatrischen Onkologie gibt es in diesem Jahr u. a. im Feld der Targeted-Therapies. So erzielten Tyrosinkinase(TRK)-Inhibitoren hohe Ansprechensraten und lange Ansprechensdauern bei einigen seltenen, durch NTRK-Fusionen (NTRK = Neurotrophe Gene der Tyrosin-Rezeptorkinase) charakterisierten Tumorerkrankungen wie dem Infantilen Fibrosarkom. Als erster TRK-Inhibitor wurde Larotrectinib mittlerweile sowohl in den USA wie in Europa zur Behandlung von NTRK-Fusionstumoren jeglicher Histologie, also tumoragnostisch, zugelassen. Die akuten Nebenwirkungen der Therapie scheinen überschaubar, zu Langzeitrisiken gibt es noch keine belastbaren Daten. Da zudem viele NTRK-Fusionstumoren auch durch vollständige Resektion oder Resektion plus Chemotherapie beherrschbar sind, sollte die Indikation zur Therapie mit TRK-Inhibitoren derzeit noch streng gestellt werden. Interessante Ergebnisse kommen auch aus an Langzeit-Überlebenden nach Krebserkrankung im Kindesalter durchgeführten Untersuchungen: So war in einer Studie die Mortalität von an Brustkrebs erkrankten Langzeitüberlebenden höher als bei der nicht vorbelasteten Vergleichspopulation.Neue Entwicklungen sind auch aus der pädiatrischen Hämatologie zu berichten: Seit diesem Jahr steht mit Emicizumab die erste subkutan applizierbare Therapie zur Behandlung der schweren Hämophilie A zur Verfügung.
Wie werden Schilddrüsenknoten diagnostiziert?
Authors: Eilsberger Friederike , Librizzi Damiano , Metzger Giulia , Luster Markus , Pfestroff Andreas 
Published: January 2020

ZUSAMMENFASSUNGDie Prävalenz von Schilddrüsenknoten liegt in Deutschland – je nach Untersuchungstechnik – bei 20–50 %. Die Inzidenz steigt, denn durch moderne Ultraschalltechniken können immer kleinere morphologische Veränderungen entdeckt werden. Die meisten Knoten sind asymptomatisch – und daher häufig Zufallsbefunde. In diesem Beitrag erfahren Sie, wie Sie mithilfe verschiedener diagnostischer Methoden Schilddrüsenknoten erkennen und differenzieren können.
Synergies in lobbying? Conceptualising and measuring lobbying coalitions to study interest group strategies, access, and influence
Authors: Junk Wiebke Marie 
Published: January 2020

AbstractTreating interest groups mainly as independent units of observation overlooks highly frequent coalition activities between actors and risks affecting the results of studies of lobbying and political influence. Yet, conceptualising and measuring lobbying coalitions is inherently difficult. In order to facilitate important future research, this article provides a roadmap of the main conceptual and methodological choices involved in studying lobbying coalitions. It distinguishes three main approaches to identify coalescing actors: a preference similarity approach, a behavioural approach, and an organisational approach. The article presents concrete operationalisations of coalitions from these vantage points and provides empirical evidence that various forms of cooperation activities on specific issues, as well as general cooperation structures, are highly frequent in lobbying in European countries. The article is relevant for scholars of interest groups and political advocacy more broadly by informing the design of new research on lobbying strategies, access, or influence.
Voters’ involvement, attitude, and confidence in the era of new media
Authors: Lee Hang 
Published: January 2020

AbstractSocial network sites have now become one of the important media channels for election campaigns. Researches in the domain of social sciences are starting to form a picture of how social network site itself might affect political participation. However, there has not been much attention given to the influence of the determinants of social network site usage on voters’ involvement and their attitude and confidence. Thus, this research extends the concept of previous research and aims to examine the relationship between the determinants of social network site usage, voters’ involvement with politics, voters’ attitude toward voting, and their confidence of voting decision. This research uses a mediation regression model to run a Likert scaled dataset from 211 questionnaires. The results of this research show that the three determinants of social network site usage have positive impact on voters’ involvement with politics, which further affects voters’ attitude toward voting and their confidence of decisions. More specifically, social network site users’ ‘need to belong’ and their ‘perceived ease of use’ towards the sites significantly increase their involvement with politics and further enhance their attitude toward voting and their confidence of voting decisions. This research has several contributions in the field of academic and management. First, it provides a framework to explain the impact of social network sites usage on voters’ attitude and confidence. Second, it provides an empirical support for using actual data from actual social network site users. Third, the findings of this research indicate that when intending to strengthen voters’ attitude toward voting in order to enhance voting rate or to raise voters’ confidence of their voting decisions on a specific candidate or party, political campaign managers and candidates are suggested to take into account users’ feel of belongings in a certain online community and their perceived effort when using a certain social network site.
Editions, translations, transformations: refashioning the Arabic Aristotle in Egypt and metropolitan Europe, 1940–1980
Authors: Karimullah Kamran I. 
Published: January 2020

AbstractLike translations, critical editions can play an important role in the language-mediated evolution of political concepts. This paper offers a case-study of a modern edition of Aristotle’s Nicomachean Ethics by the famous twentieth-century Egyptian philosopher and father of ‘Arab existentialism’ Abd al-Rahman Badawi (d. 2002). It draws on ancient Greek and medieval Arabic corpora developed by the Genealogies of Knowledge project and a modern Arabic corpus accessible through Sketch Engine to examine the lexical patterning of key political items relating to the concept of citizen in the Arabic and Greek versions of Aristotle’s Nicomachean Ethics. This corpus-based analysis of lexical patterns is contextualised against discursive and disciplinary parameters that shaped Badawi’s edition. Supplementing this collocational analysis of relevant lexical items with a more traditional analysis of Badawi’s paratexts, I argue that the editing process produces a hybrid ‘third text’ that is neither a transcription of the original manuscript nor a reconstruction of the manuscript’s archetype. The paper concludes that, like translations, editions transform the texts they are based on.
Collective efficacy: toward a new narrative of its development and role in achievement
Authors: Hoogsteen T. J. 
Published: January 2020

AbstractThe body of collective teacher efficacy (CTE) research has developed considerably since Goddard referred to the school-level factor as a “neglected construct” in the study of schools and achievement. The research base has identified quantitative effects, antecedents, and consequences, all of which support the claim that collective efficacy is important to schools and achievement while also supporting the claim by Goddard et al. that schools should be led in a direction that will develop collective efficacy, which will in turn spur continuous growth in CTE and student achievement. Even with all of this, a gap in the literature remains, and instead of considering the reciprocal relationship between collective efficacy and achievement, the excitement behind the positive outcomes of collective efficacy has led to wider exposure of the concept and, as argued, a misguided attempt to treat CTE as the main catalyst for enacting school improvement. Considering this latter point, general school improvement literature from the realms of leadership and collaboration is drawn upon and connected to CTE research in an endeavor to create a more holistic narrative of collective efficacy, its development, and its role in school improvement and student achievement.
Land-use history impacts functional diversity across multiple trophic groups
Authors: Le Provost Gaëtane , Badenhausser Isabelle , Le Bagousse-Pinguet Yoann , Clough Yann , Henckel Laura , Violle Cyrille , Bretagnolle Vincent , Roncoroni Marilyn , Manning Peter , Gross Nicolas 
Published: January 2020

SignificanceThe world’s agricultural landscapes have seen dramatic declines in their biodiversity. Because biodiversity responses to land-use changes can be delayed, understanding how current biodiversity is impacted by historical land-use changes is crucial to protect and restore agricultural biodiversity. By utilizing a long-term land-use record database, we show that historical land-use changes continue to shape current biodiversity. Our study expands our understanding of global biodiversity change by identifying land-use history effects to be as strong as the effects of current management and the amount of seminatural land cover, often assumed to be the major drivers of biodiversity change in agricultural landscapes. Accordingly, land-use legacy effects must be considered in management programs that aim to protect and restore biodiversity.