bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studying and modulating schizophrenia-associated dysfunctions of oligodendrocytes with patient-specific cell systems
Authors: Raabe Florian J. , Galinski Sabrina , Papiol Sergi , Falkai Peter G. , Schmitt Andrea , Rossner Moritz J. 
Published: November 2018

AbstractPostmortem studies in patients with schizophrenia (SCZ) have revealed deficits in myelination, abnormalities in myelin gene expression and altered numbers of oligodendrocytes in the brain. However, gaining mechanistic insight into oligodendrocyte (OL) dysfunction and its contribution to SCZ has been challenging because of technical hurdles. The advent of individual patient-derived human-induced pluripotent stem cells (hiPSCs), combined with the generation of in principle any neuronal and glial cell type, including OLs and oligodendrocyte precursor cells (OPCs), holds great potential for understanding the molecular basis of the aetiopathogenesis of genetically complex psychiatric diseases such as SCZ and could pave the way towards personalized medicine. The development of neuronal and glial co-culture systems now appears to enable the in vitro study of SCZ-relevant neurobiological endophenotypes, including OL dysfunction and myelination, with unprecedented construct validity. Nonetheless, the meaningful stratification of patients before the subsequent functional analyses of patient-derived cell systems still represents an important bottleneck. Here, to improve the predictive power of ex vivo disease modelling we propose using hiPSC technology to focus on representatives of patient subgroups stratified for genomic and/or phenomic features and neurobiological cell systems. Therefore, this review will outline the evidence for the involvement of OPCs/OLs in SCZ in the context of their proposed functions, including myelination and axon support, the implications for hiPSC-based cellular disease modelling and potential strategies for patient selection.
Patterns of adenoid and tonsil growth in Japanese children and adolescents: A longitudinal study
Authors: Ishida Takayoshi , Manabe Asuka , Yang Shin-Sheng , Yoon Hyung Sik , Kanda Eiichiro , Ono Takashi 
Published: November 2018

AbstractLymphoid tissues, such as adenoids (Ad) and tonsils (Tn), are suggested to undergo hypertrophy during childhood and involution in adulthood. Enlargement of Ad and Tn can cause transient obstruction of the respiratory airways, thus inducing obstructive sleep apnoea. To date, the standard Ad and Tn sizes have not been reported, and there are no explicit objective criteria for evaluating their sizes or deducing whether they have enlarged, reduced, or remained constant over time. Our previous cross-sectional study revealed the age-dependent airway occupation ratio of Ad and Tn in Japanese individuals. We conducted a longitudinal observational study of the Ad and Tn sizes in Japanese individuals aged 6–20 years. Ninety individuals were retrospectively enrolled. The average and standard deviation of the sizes was calculated in 5 age-based groups.
High-throughput screens identify HSP90 inhibitors as potent therapeutics that target inter-related growth and survival pathways in advanced prostate cancer
Authors: Jansson Keith H. , Tucker John B. , Stahl Lauren E. , Simmons John K. , Fuller Caitlyn , Beshiri Michael L. , Agarwal Supreet , Fang Lei , Hynes Paul G. , Alilin Aian Neil , Lake Ross , Abbey Yasmine C. , Cawley Jacob , Tice Caitlin M. , Yin JuanJuan , McKnight Crystal , Klummp-Thomas Carleen , Zhang Xiaohu , Guha Rajarshi , Hoover Shelley , Simpson R. Mark , Nguyen Holly M. , Corey Eva , Thomas Craig J. , Proia David A. , Kelly Kathleen 
Published: November 2018

AbstractThe development of new treatments for castrate resistant prostate cancer (CRPC) must address such challenges as intrinsic tumor heterogeneity and phenotypic plasticity. Combined PTEN/TP53 alterations represent a major genotype of CRPC (25–30%) and are associated with poor outcomes. Using tumor-derived, castration-resistant Pten/Tp53 null luminal prostate cells for comprehensive, high-throughput, mechanism-based screening, we identified several vulnerabilities among >1900 compounds, including inhibitors of: PI3K/AKT/mTOR, the proteasome, the cell cycle, heat shock proteins, DNA repair, NFκB, MAPK, and epigenetic modifiers. HSP90 inhibitors were one of the most active compound classes in the screen and have clinical potential for use in drug combinations to enhance efficacy and delay the development of resistance. To inform future design of rational drug combinations, we tested ganetespib, a potent second-generation HSP90 inhibitor, as a single agent in multiple CRPC genotypes and phenotypes. Ganetespib decreased growth of endogenous Pten/Tp53 null tumors, confirming therapeutic activity in situ. Fifteen human CRPC LuCaP PDX-derived organoid models were assayed for responses to 110 drugs, and HSP90 inhibitors (ganetespib and onalespib) were among the select group of drugs (<10%) that demonstrated broad activity (>75% of models) at high potency (IC50 <1 µM). Ganetespib inhibits multiple targets, including AR and PI3K pathways, which regulate mutually compensatory growth and survival signals in some forms of CRPC. Combined with castration, ganetespib displayed deeper PDX tumor regressions and delayed castration resistance relative to either monotherapy. In all, comprehensive data from near-patient models presents novel contexts for HSP90 inhibition in multiple CRPC genotypes and phenotypes, expands upon HSP90 inhibitors as simultaneous inhibitors of oncogenic signaling and resistance mechanisms, and suggests utility for combined HSP90/AR inhibition in CRPC.
Defining Coronary Flow Patterns: Comprehensive Automation of Transthoracic Doppler Coronary Blood Flow
Authors: Sunyecz Ian L. , McCallinhart Patricia E. , Patel Kishan U. , McDermott Michael R. , Trask Aaron J. 
Published: November 2018

AbstractThe coronary microcirculation (CM) plays a critical role in the regulation of blood flow and nutrient exchange to support the viability of the heart. In many disease states, the CM becomes structurally and functionally impaired, and transthoracic Doppler echocardiography can be used as a non-invasive surrogate to assess CM disease. Analysis of Doppler echocardiography is prone to user bias and can be laborious, especially if additional parameters are collected. We hypothesized that we could develop a MATLAB algorithm to automatically analyze clinically-relevant and non-traditional parameters from murine PW Doppler coronary flow patterns that would reduce intra- and inter-operator bias, and analysis time. Our results show a significant reduction in intra- and inter-observer variability as well as a 30 fold decrease in analysis time with the automated program vs. manual analysis. Finally, we demonstrated good agreement between automated and manual analysis for clinically-relevant parameters under baseline and hyperemic conditions. Resulting coronary flow velocity reserve calculations were also found to be in good agreement. We present a MATLAB algorithm that is user friendly and robust in defining and measuring Doppler coronary flow pattern parameters for more efficient and potentially more insightful analysis assessed via Doppler echocardiography.
Big bottlenecks in cardiovascular tissue engineering
Authors: Huang Ngan F. , Serpooshan Vahid , Morris Viola B. , Sayed Nazish , Pardon Gaspard , Abilez Oscar J. , Nakayama Karina H. , Pruitt Beth L. , Wu Sean M. , Yoon Young-sup , Zhang Jianyi , Wu Joseph C. 
Published: November 2018

AbstractAlthough tissue engineering using human-induced pluripotent stem cells is a promising approach for treatment of cardiovascular diseases, some limiting factors include the survival, electrical integration, maturity, scalability, and immune response of three-dimensional (3D) engineered tissues. Here we discuss these important roadblocks facing the tissue engineering field and suggest potential approaches to overcome these challenges.
Confocal laser scanning microscopy for rapid optical characterization of graphene
Authors: Panchal Vishal , Yang Yanfei , Cheng Guangjun , Hu Jiuning , Kruskopf Mattias , Liu Chieh-I. , Rigosi Albert F. , Melios Christos , Hight Walker Angela R. , Newell David B. , Kazakova Olga , Elmquist Randolph E. 
Published: November 2018

AbstractTwo-dimensional (2D) materials such as graphene have become the focus of extensive research efforts in condensed matter physics. They provide opportunities for both fundamental research and applications across a wide range of industries. Ideally, characterization of graphene requires non-invasive techniques with single-atomic-layer thickness resolution and nanometer lateral resolution. Moreover, commercial application of graphene requires fast and large-area scanning capability. We demonstrate the optimized balance of image resolution and acquisition time of non-invasive confocal laser scanning microscopy (CLSM), rendering it an indispensable tool for rapid analysis of mass-produced graphene. It is powerful for analysis of 1–5 layers of exfoliated graphene on Si/SiO2, and allows us to distinguish the interfacial layer and 1–3 layers of epitaxial graphene on SiC substrates. Furthermore, CLSM shows excellent correlation with conventional optical microscopy, atomic force microscopy, Kelvin probe force microscopy, conductive atomic force microscopy, scanning electron microscopy and Raman mapping.
Emergence of traveling waves in linear arrays of electromechanical oscillators
Authors: Dou Yong , Pandey Shashank , Cartier Charles A. , Miller Olivia , Bishop Kyle J. M. 
Published: November 2018

AbstractTraveling waves of mechanical actuation provide a versatile strategy for locomotion and transport in both natural and engineered systems across many scales. These rhythmic motor patterns are often orchestrated by systems of coupled oscillators such as beating cilia or firing neurons. Here, we show that similar motions can be realized within linear arrays of conductive particles that oscillate between biased electrodes through cycles of contact charging and electrostatic actuation. The repulsive interactions among the particles along with spatial gradients in their natural frequencies lead to phase-locked states characterized by gradients in the oscillation phase. The frequency and wavelength of these traveling waves can be specified independently by varying the applied voltage and the electrode separation. We demonstrate how traveling wave synchronization can enable the directed transport of material cargo. Our results suggest that simple energy inputs can coordinate complex motions with opportunities for soft robotics and colloidal machines.
QRREM method for the isolation of high-quality RNA from the complex matrices of coconut
Authors: Iqbal Amjad , Yang Yaodong , Qadri Rashad , Wu Yi , Li Jing , Shah Farooq , Hamayun Muhammad , Hussain Anwar 
Published: November 2018

Abstract
Complex plant tissues vary in hardness, i.e. some are succulent, while others are complex to break. Besides, plant metabolites, such as polysaccharides, proteins, polyphenols and lipids, can greatly interfere with the RNA extraction. So, in order to obtain a high-quality RNA from the complex tissues (like coconut endosperm, coconut apple and coconut leaf bud) rich in secondary metabolites, a robust method is demanded. Several methods (MRIP, CTAB and TRIZOL) have been used previously for the isolation of quality RNA from the coconut tissues, but without any success. The present study will provide with the details of a new method (Quick and Reliable RNA Extraction Method or QRREM), which have efficiently isolated the intact RNA form the complex tissues of coconut compared with CTAB, Trizol and RNA plant. The method has been validated for the isolation of high-quality intact RNA from the other available plant species (Areca/betel nut, mint and spring onion). The method has various advantages over the other methods in terms of time and cost effectiveness. Furthermore, the resulted RNA from various tissues of coconut performed well in the downstream experiments, i.e. reverse transcription and PCR for the production and amplification of cDNA.
Incomplete family as a factor of crime in adolescents and youth
Authors: Kantemirova Galina 
Published: November 2018

This work is devoted to one of the most important problems of our time, the problem of juvenile delinquency. The study of juvenile delinquency now has a special significance, since in many regions of our country the percentage of crimes committed by adolescents and young people is quite large, the crime rate is on the rise. The article aims to address the problem and the causes of crime. The publication touches on the topic of crime in the youth and adolescent families. Particular attention is paid by the author to the fact that the family is the main factor in the upbringing and socialization of children. Considerable attention is paid to an incomplete family, as a factor and a source of increased criminality.
It is important not only to find out what are the causes of the increase in crime in adolescents and youth, but also to understand which preventive measures are the most effective one in combating crime.
Carney Complex
Authors: Kamilaris Crystal , Faucz Fabio , Voutetakis Antonis , Stratakis Constantine 
Published: November 2018

AbstractCarney complex is a rare, autosomal dominant, multiple endocrine neoplasia and lentiginosis syndrome, caused in most patients by defects in the PRKAR1A gene, which encodes the regulatory subunit type 1α of protein kinase A. Inactivating defects of PRKAR1A lead to aberrant cyclic-AMP-protein kinase A signaling. Patients may develop multiple skin abnormalities and a variety of endocrine and non-endocrine tumors. Endocrine manifestations include primary pigmented nodular adrenocortical disease, that may cause Cushing syndrome, growth-hormone secreting pituitary adenoma or pituitary somatotropic hyperplasia which can result in acromegaly, as well as gonadal and thyroid tumors. Non-endocrine tumors associated with Carney complex include myxomas of the heart, breast, and other sites, psamommatous melanotic schwannomas, breast ductal adenomas, osteochondromyxomas, and a predisposition to a number of malignancies from adrenal to pancreatic and liver cancer.
TRPA1 ankyrin repeat six interacts with a small molecule inhibitor chemotype
Authors: Tseng Wei Chou , Pryde David C. , Yoger Katrina E. , Padilla Karen M. , Antonio Brett M. , Han Seungil , Shanmugasundaram Veerabahu , Gerlach Aaron C. 
Published: November 2018

Significance
TRPA1 channels are expressed primarily in sensory neurons with human genetic linkage to pain disorders. Despite the strong confidence for TRPA1 as a therapeutic target, few modulators have advanced to the clinic being hindered by poor physiochemical properties and narrow structure-activity relationships related to their site of interaction. We report the discovery of a potent and selective thiadiazole small molecule class of TRPA1 inhibitor that interacts with the N-terminal ankyrin repeat (ankyrinR) domain. The discovery of this interaction site provides opportunities to broaden TRPA1 small molecule drug discovery for the treatment of pain and adds insight into TRPA1 channel gating mechanisms.
The Impulse to Rhetoric in India: Rhetorical and Deliberative Practices and Their Relation to the Histories of Rhetoric and Democracy
Authors: Lloyd Keith 
Published: November 2018

ABSTRACT
Scholars of rhetoric have long held that there is such a thing as a “rhetorical tradition” and that that tradition began within the context of ancient Athenian democracy. Recently this tradition has been expanded to “traditions” that include “non-Western” approaches. Scholars of democracy have similarly dislodged the notion that democracy, broadly understood, developed only in ancient Greece. This essay expands our understanding of both rhetorical traditions and their relation to democracy by studying the interrelation of rhetorical and deliberative practices found in the history of India. Specifically, it explores how one highly influential school of Indian deliberation, Nyaya, grew alongside practices of public reasoning and self-rule in the gaṇa/saṁgha (so-called ancient Indian “republics”), revealing a similar, but unique, impulse to rhetoric beyond the Athenian/Western context. From this study we also gain insight into the current struggle for democracy worldwide.
The Pluralistic Style and the Demands of Intercultural Rhetoric: Swami Vivekananda at the World’s Parliament of Religions
Authors: Stroud Scott R. 
Published: November 2018

ABSTRACT
Intercultural contexts introduce unique sources of complexity into our theories of rhetoric and persuasion. This study examines one of the most successful cases of intercultural rhetoric concerning religion: the case of Swami Vivekananda, a Hindu monk from India who came to the United States in 1893 for the World’s Parliament of Religions. He arrived as an unknown monk, but he left America years later as the nationally known face of Hinduism. Facing a tense scene in 1893 that featured a plurality of religions and American organizers and audiences who judged Hinduism as inferior to Christianity, Vivekananda enacted a unique rhetoric of pluralism to assert the value of his form of Hinduism while simultaneously respecting other religions. This study extracts from Vivekananda’s popular performance at the parliament a pluralistic style of rhetorical advocacy, one that builds upon his unique reading of Hindu religious-philosophical traditions. This pluralistic style can be used to unravel some of the theoretical issues created by invitational rhetoric’s reading of persuasion as inherently violent to disagreeing others.
Enterprise culture and the ethics of entitlement: How ‘indispensable’ employees turn into disruptive mavericks
Authors: Ekman Susanne 
Published: November 2018

ABSTRACT
This paper contributes to the debate about the enterprise culture by analysing the work ethic among talented employees who are seen as indispensable by their organisations. It describes the drama surrounding the ‘high talent’ IT-consultant Clark, a real individual used as emblematic here, and his quest for power and influence at work. The analysis adds nuance to the claims of both proponents and critics of the enterprise culture by showing how it leads neither to win-win scenarios nor to culturally duped employees. Instead, the enterprise ethic, with its focus on talent and excellence, has produced a group of elite workers who are driven by a sense of entitlement. This leads them to display maverick and disruptive behaviour that endangers the social cohesion of their organisations. But they are still driven by a deep sense of dedication and thus cannot be considered simply self-serving.
Clinical outcomes, edoxaban concentration, and anti-factor Xa activity of Asian patients with atrial fibrillation compared with non-Asians in the ENGAGE AF-TIMI 48 trial
Authors: Chao Tze-Fan , Chen Shih-Ann , Ruff Christian T , Hamershock Rose A , Mercuri Michele F , Antman Elliott M , Braunwald Eugene , Giugliano Robert P 
Published: November 2018

Abstract

Aims
Prior studies suggested that the risks of ischaemic stroke and bleeding in patients of Asian race with atrial fibrillation (AF) may be higher than that of non-Asians. In the analysis of ENGAGE AF-TIMI 48 trial, we compared clinical outcomes, edoxaban concentration, and anti-factor Xa (anti-FXa) activity, between Asian and non-Asian races.

Methods and results
There were 2909 patients of Asian race and 18 195 non-Asian race in the ENGAGE AF-TIMI 48 trial. The risks of thromboembolism and bleeding events were compared for Asians and non-Asians treated with warfarin. The trough levels of edoxaban concentration and anti-FXa activity were also compared and correlated with the efficacy and safety of edoxaban vs. warfarin. Compared to non-Asian patients, the Asian population was on average 2 years younger and 20 kg lighter. In the warfarin group, the adjusted risk of ischaemic stroke did not differ significantly for patients of Asian and non-Asian race [adjusted hazard ratio (aHR) = 1.12, P = 0.56). Asians treated with warfarin had a higher-adjusted risk of intracranial haemorrhage (ICH: aHR 1.71, P = 0.03) compared with non-Asians. The trough edoxaban concentration and anti-FXa activity were 20–25% lower for Asians compared with non-Asians. Compared to warfarin, higher dose edoxaban significantly reduced ICH while preserving the efficacy of stroke prevention in both Asians and non-Asians. Two of three net clinical outcomes appeared to be more favourably reduced with edoxaban in Asians compared with non-Asians (P int = 0.063 for primary, 0.037 for secondary, and 0.032 for third net clinical outcomes, respectively).

Conclusion
Compared to warfarin, higher dose edoxaban preserved the efficacy for stroke prevention and was associated with a favourable safety profile for Asians, which may be due to the lower trough edoxaban concentration and anti-FXa activity achieved in patients of Asian race.
β-blockers, calcium antagonists, and mortality in stable coronary artery disease: an international cohort study
Authors: Sorbets Emmanuel , Steg Philippe Gabriel , Young Robin , Danchin Nicolas , Greenlaw Nicola , Ford Ian , Tendera Michal , Ferrari Roberto , Merkely Bela , Parkhomenko Alexander , Reid Christopher , Tardif Jean-Claude , Fox Kim M ,   for the CLARIFY investigators
Published: November 2018

Abstract

Aims
The effect of first-line antianginal agents, β-blockers, and calcium antagonists on clinical outcomes in stable coronary artery disease (CAD) remains uncertain.

Methods and results
We analysed the use of β-blockers or calcium antagonists (baseline and annually) and outcomes in 22 006 stable CAD patients (enrolled 2009–2010) followed annually to 5 years, in the CLARIFY registry (45 countries). Primary outcome was all-cause death. Secondary outcomes were cardiovascular death and the composite of cardiovascular death/non-fatal myocardial infarction (MI). After multivariable adjustment, baseline β-blocker use was not associated with lower all-cause death [1345 (7.8%) in users vs. 407 (8.4%) in non-users; hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.84–1.06; P = 0.30]; cardiovascular death [861 (5.0%) vs. 262 (5.4%); HR 0.91, 95% CI 0.79–1.05; P = 0.20]; or cardiovascular death/non-fatal MI [1272 (7.4%) vs. 340 (7.0%); HR 1.03, 95% CI 0.91–1.16; P = 0.66]. Sensitivity analyses according to β-blocker use over time and to prescribed dose produced similar results. Among prior MI patients, for those enrolled in the year following MI, baseline β-blocker use was associated with lower all-cause death [205 (7.0%) vs. 59 (10.3%); HR 0.68, 95% CI 0.50–0.91; P = 0.01]; cardiovascular death [132 (4.5%) vs. 49 (8.5%); HR 0.52, 95% CI 0.37–0.73; P = 0.0001]; and cardiovascular death/non-fatal MI [212 (7.2%) vs. 59 (10.3%); HR 0.69, 95% CI 0.52–0.93; P = 0.01]. Calcium antagonists were not associated with any difference in mortality.

Conclusion
In this contemporary cohort of stable CAD, β-blocker use was associated with lower 5-year mortality only in patients enrolled in the year following MI. Use of calcium antagonists was not associated with superior mortality, regardless of history of MI.