bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cdkn2a (Arf) loss drives NF1-associated atypical neurofibroma and malignant transformation
Authors: Rhodes Steven D , He Yongzheng , Smith Abbi , Jiang Li , Lu Qingbo , Mund Julie , Li Xiaohong , Bessler Waylan , Qian Shaomin , Dyer William , Sandusky George E , Horvai Andrew E , Armstrong Amy E , Clapp D Wade 
Published: May 2019

Abstract
Plexiform neurofibroma (PN) tumors are a hallmark manifestation of neurofibromatosis type 1 (NF1) that arise in the Schwann cell (SC) lineage. NF1 is a common heritable cancer predisposition syndrome caused by germline mutations in the NF1 tumor suppressor, which encodes a GTPase-activating protein called neurofibromin that negatively regulates Ras proteins. Whereas most PN are clinically indolent, a subset progress to atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP) and/or to malignant peripheral nerve sheath tumors (MPNSTs). In small clinical series, loss of 9p21.3, which includes the CDKN2A locus, has been associated with the genesis of ANNUBP. Here we show that the Cdkn2a alternate reading frame (Arf) serves as a gatekeeper tumor suppressor in mice that prevents PN progression by inducing senescence-mediated growth arrest in aberrantly proliferating Nf1−/− SC. Conditional ablation of Nf1 and Arf in the neural crest-derived SC lineage allows escape from senescence, resulting in tumors that accurately phenocopy human ANNUBP and progress to MPNST with high penetrance. This animal model will serve as a platform to study the clonal development of ANNUBP and MPNST and to identify new therapies to treat existing tumors and to prevent disease progression.
Mouse model of severe recessive RYR1-related myopathy
Authors: Brennan Stephanie , Garcia-Castañeda Maricela , Michelucci Antonio , Sabha Nesrin , Malik Sundeep , Groom Linda , Wei LaPierre Lan , Dowling James J , Dirksen Robert T 
Published: May 2019

Abstract
Ryanodine receptor type I (RYR1)-related myopathies (RYR1 RM) are a clinically and histopathologically heterogeneous group of conditions that represent the most common subtype of childhood onset non-dystrophic muscle disorders. There are no treatments for this severe group of diseases. A major barrier to therapy development is the lack of an animal model that mirrors the clinical severity of pediatric cases of the disease. To address this, we used CRISPR/Cas9 gene editing to generate a novel recessive mouse model of RYR1 RM. This mouse (Ryr1TM/Indel) possesses a patient-relevant point mutation (T4706M) engineered into 1 allele and a 16 base pair frameshift deletion engineered into the second allele. Ryr1TM/Indel mice exhibit an overt phenotype beginning at 14 days of age that consists of reduced body/muscle mass and myofibre hypotrophy. Ryr1TM/Indel mice become progressively inactive from that point onward and die at a median age of 42 days. Histopathological assessment shows myofibre hypotrophy, increased central nuclei and decreased triad number but no clear evidence of metabolic cores. Biochemical analysis reveals a marked decrease in RYR1 protein levels (20% of normal) as compared to only a 50% decrease in transcript. Functional studies at end stage show significantly reduced electrically evoked Ca2+ release and force production. In summary, Ryr1TM/Indel mice exhibit a post-natal lethal recessive form of RYR1 RM that pheno-copies the severe congenital clinical presentation seen in a subgroup of RYR1 RM children. Thus, Ryr1TM/Indel mice represent a powerful model for both establishing the pathomechanisms of recessive RYR1 RM and pre-clinical testing of therapies for efficacy.
The Tilting–Cotilting Correspondence
Authors: Positselski Leonid , Šťovíček Jan 
Published: May 2019

AbstractTo a big $n$-tilting object in a complete, cocomplete abelian category ${\textsf{A}}$ with an injective cogenerator we assign a big $n$-cotilting object in a complete, cocomplete abelian category ${\textsf{B}}$ with a projective generator and vice versa. Then we construct an equivalence between the (conventional or absolute) derived categories of ${\textsf{A}}$ and ${\textsf{B}}$. Under various assumptions on ${\textsf{A}}$, which cover a wide range of examples (for instance, if ${\textsf{A}}$ is a module category or, more generally, a locally finitely presentable Grothendieck abelian category), we show that ${\textsf{B}}$ is the abelian category of contramodules over a topological ring and that the derived equivalences are realized by a contramodule-valued variant of the usual derived Hom functor.
Impact of window views on recovery—an example of post-cesarean section women
Authors: Wang Chia-Hui , Kuo Nai-Wen , Anthony Kathryn 
Published: May 2019

Abstract

Objective
The objective of this study was to examine the impact of urban landscape from window views on quality of care for women who underwent Cesarean Section (C-section) in Taiwan.

Design
The participants were randomly assigned into 46 different hospital rooms to see the effects of various window views and daylight exposure on women’s recovery from post C-section care.

Setting
We carried out this study in the obstetrics departments of three tertiary hospitals located in two major cities of Taiwan: Taipei City and New Taipei City.

Participants
A total of 296 women who underwent C-sections and used patient-controlled analgesic (PCA) for pain control after their surgery during the 10-month data collection period were recruited for this study.

Intervention
The 46 different patient rooms provided diverse window views and different daylight exposure for the participants.

Main Outcome Measures
Recovery for the women who underwent C-sections in this study was defined as PCA usage and perceived pain measured by Brief Pain Inventory (BFI).

Results
Higher satisfaction of window view significantly decreased analgesic usage (P = 0.057), reduced the scores of overall perceived pain (P = 0.046), pain severity (P = 0.004), and ‘pain’s interference with relations with others, enjoyment of life, and mood (REM).’ (P = 0.095).

Conclusions
To maximize benefit and well-being of patients recovering from surgery, health care architects should design patient rooms to create maximum satisfaction with visual impacts and optimize window views. By doing so, it may decrease the use of pain medication and substantially reduce healthcare costs.
Fatwa, Discursivity, and the Art of Ethical Embedding
Authors: Awass Omer 
Published: May 2019

AbstractThis paper theorizes the role of iftāʾ, the process of producing fatwas (Islamic legal opinions), on the formation of Muslim societies. I argue in this paper that iftāʾ is an ethical embedding mechanism that historically carried out this function through a set of discursive and nondiscursive relations. “Ethical embedding” signifies the situating of the various spheres of the social world into an ethical domain. As for iftāʾs discursive relations, the historical manifestations of its procedures and the production of fatwas represented a discursive formation because they manifested a particular regularity in their discursive operations. As for their nondiscursive relations, fatwas position actions and practices within the Islamic moral field through a definite social process. Finally, these operations generate a social field of power that structures the relations between the individuals and institutions of iftāʾ and induces personal dispositions that facilitate the practice of the norms embedded in the fatwa.
Genome-wide association study and genomic predictions for exterior traits in Yorkshire pigs1
Authors: Lee Jungjae , Lee SeokHyun , Park Jong-Eun , Moon Sung-Ho , Choi Sung-Woon , Go Gwang-Woong , Lim Dajeong , Kim Jun-Mo 
Published: May 2019

AbstractThe objectives of this study were to identify informative genomic regions that affect the exterior traits of purebred Korean Yorkshire pigs and to investigate and compare the accuracy of genomic prediction for response variables. Phenotypic data on body height (BH), body length (BL), and total teat number (TTN) from 2,432 Yorkshire pigs were used to obtain breeding values including as response variable the estimated breeding value (EBV) and 2 types of deregressed EBVs—one including the parent average (DEBVincPA) and the other excluding it (DEBVexcPA). A final genotype panel comprising 46,199 SNP markers was retained for analysis after quality control for common SNPs. The BayesB and BayesC methods—with various π and weighted response variables (EBV, DEBVincPA, or DEBVexcPA)—were used to estimate SNP effects, through the genome-wide association study. The significance of genomic windows (1 Mb) was obtained at 1.0% additive genetic variance and was subsequently used to identify informative genomic regions. Furthermore, SNPs with a high model frequency (≥0.90) were considered informative. The accuracy of genomic prediction was estimated using a 5-fold cross-validation with the K-means clustering method. Genomic accuracy was measured as the genomic correlation between the molecular breeding value and the individual weighted response variables (EBV, DEBVincPA, or DEBVexcPA). The number of identified informative windows (1 Mb) for BH, BL, and TTN was 4, 3, and 4, respectively. The number of significant SNPs for BH, BL, and TTN was 6, 4, and 5, respectively. Diversity π did not influence the accuracy of genomic prediction. The BayesB method showed slightly higher genomic accuracy for exterior traits than BayesC method in this study. In addition, the genomic accuracy using DEBVincPA as response variable was higher than that using other response variables. Therefore, the genomic accuracy using BayesB (π = 0.90) with DEBVinPA as a response variable was the most effective in this study. The genomic accuracy values for BH, BL, and TTN were calculated to be 0.52, 0.60, and 0.51, respectively.
Slovak Telekom/Deutsche Telekom AG: The Interplay Between EU Competition Law and Sector Specific Rules in the Electronic Communications Sector
Authors: Liberatore Francesco , Tsochas Kety , Buckwell Matthew 
Published: May 2019

Abstract
Case T-827/14, Deutsche Telekom AG v Commission, and Case T-851/14 Slovak Telekom a.s. v Commission, Judgments of 13 December 2018.
Granting access to a product or service, which is required under sector specific regulation, on unfair, unreasonably complicated or delayed terms amounts to constructive refusal to supply, without the need to demonstrate that the regulated access product or service is an indispensable input. In addition, a margin squeeze test, to assess whether the difference between wholesale and retail prices is negative, should be carried out on a year-by-year basis, and not on a multi-period basis. Finally, when a parent is jointly and severally liable for anti-competitive conduct of its subsidiary, the liability of the parent can exceed that of the subsidiary only if it reflects the parent’s individual conduct in the infringement at issue.
The Governance of Global Banking in the Face of Complexity
Authors: Ortino Matteo 
Published: May 2019

ABSTRACT
The Basel Committee on Banking Supervision and the composite wider legal and institutional environment to which it is part provide a useful case study to illustrate how complexity is addressed in the public policy realm. As its central proposition, this article argues that it is possible to identify a specific pattern and logic underlying the governance of global banking today. The pattern concerns the institutional dimension of global banking regulation, particularly with respect to the distribution of regulatory powers among the various actors involved, and the legal relationships between these actors. The overall pattern seems to follow a certain logic, which will be explored and explained borrowing the military distinction between strategy, operations, and tactics.
Public Administrative Law in a Globalized Concept: Legal Nature of the Collaboration of the EU and the Basel Committee
Authors: Csatlós Erzsébet 
Published: May 2019

Abstract
Multilevel governance describes a global system that enrolls some State functions to perform global solutions for global problems. Multilevel-governance and multilevel administration has legality and accountability concerns on their own, although, there are multilevel structures with non-State playground of trans-regulatory nature at the supranational level of cooperation which means additional shades to the colourful palette. The procedure and the structure concerning the creation and the evaluation of effective banking supervision standards in Europe is unique. Given the fact that the European administrative system is also unique, and as Basel rules are produced in a trans-regulatory network, the collaboration of the two sui generis systems requires the rethinking of the classical legal order features. Rule of law which is the basis of classical international relations in the view of public administration of States is challenged by the newly emerged solutions. Necessity and proportionality are put on a scale with classical values and requirements of public administration and efficiency and effectiveness seem to put it on the side of the new type of collaboration. The normative background of such structure is still immature. The multilevel administrative system of financial supervision including the European Union and the Basel Committee for Banking Supervision at supranational level or speaking in a wider context: the framework for multilevel governance with non-state actors at supranational level, is therefore an example for global administrative law of infant status.
Casein kinase 2 regulates telomere protein complex formation through Rap1 phosphorylation
Authors: Inoue Haruna , Horiguchi Mayuri , Ono Kota , Kanoh Junko 
Published: May 2019

AbstractTelomeres located at the ends of linear chromosomes play important roles in the maintenance of life. Rap1, a component of the shelterin telomere protein complex, interacts with multiple proteins to perform various functions; further, formation of shelterin requires Rap1 binding to other components such as Taz1 and Poz1, and telomere tethering to the nuclear envelope (NE) involves interactions between Rap1 and Bqt4, a nuclear membrane protein. Although Rap1 is a hub for telomere protein complexes, the regulatory mechanisms of its interactions with partner proteins are not fully understood. Here, we show that Rap1 is phosphorylated by casein kinase 2 (CK2) at multiple sites, which promotes interactions with Bqt4 and Poz1. Among the multiple CK2-mediated phosphorylation sites of Rap1, phosphorylation at Ser496 was found to be crucial for both Rap1–Bqt4 and Rap1–Poz1 interactions. These mechanisms mediate proper telomere tethering to the NE and the formation of the silenced chromatin structure at chromosome ends.
Acute depletion of CTCF directly affects MYC regulation through loss of enhancer–promoter looping
Authors: Hyle Judith , Zhang Yang , Wright Shaela , Xu Beisi , Shao Ying , Easton John , Tian Liqing , Feng Ruopeng , Xu Peng , Li Chunliang 
Published: May 2019

Abstract
Numerous pieces of evidence support the complex, 3D spatial organization of the genome dictates gene expression. CTCF is essential to define topologically associated domain boundaries and to facilitate the formation of insulated chromatin loop structures. To understand CTCF’s direct role in global transcriptional regulation, we integrated the miniAID-mClover3 cassette to the endogenous CTCF locus in a human pediatric B-ALL cell line, SEM, and an immortal erythroid precursor cell line, HUDEP-2, to allow for acute depletion of CTCF protein by the auxin-inducible degron system. In SEM cells, CTCF loss notably disrupted intra-TAD loops and TAD integrity in concurrence with a reduction in CTCF-binding affinity, while showing no perturbation to nuclear compartment integrity. Strikingly, the overall effect of CTCF’s loss on transcription was minimal. Whole transcriptome analysis showed hundreds of genes differentially expressed in CTCF-depleted cells, among which MYC and a number of MYC target genes were specifically downregulated. Mechanically, acute depletion of CTCF disrupted the direct interaction between the MYC promoter and its distal enhancer cluster residing ∼1.8 Mb downstream. Notably, MYC expression was not profoundly affected upon CTCF loss in HUDEP-2 cells suggesting that CTCF could play a B-ALL cell line specific role in maintaining MYC expression.
Modulation of endothelial cell responses and vascular function by dietary fatty acids
Authors: Du Youjia , Taylor Carla G , Zahradka Peter 
Published: May 2019

AbstractHealthy and functional endothelial cells play important roles in maintaining vascular homeostasis, whereas endothelial dysfunction initiates and exacerbates vascular disease progression. Interventional studies with dietary fatty acids have shown that these molecules have varying effects on vascular function. It is hypothesized that the actions of dietary fatty acids on vascular function may be mediated in part through endothelial cells. This review summarizes the results of studies that have examined the acute and chronic effects of dietary fatty acids on endothelial function and vascular properties in humans, as well as the potential mechanisms by which n-3 polyunsaturated fatty acids regulate endothelial function. Altogether, this article provides an extensive review of how fatty acids contribute to vascular function through their ability to modulate endothelial cells and discusses relationships between dietary fatty acids and endothelial cells in the context of vascular dysfunction.
Potential health benefits of (poly)phenols derived from fruit and 100% fruit juice
Authors: Ho Kacie K H Y , Ferruzzi Mario G , Wightman JoLynne D 
Published: May 2019

Abstract(Poly)phenol-rich diets have been associated with reduced risk of various diseases. Coffee and tea are typically identified as dietary sources of chlorogenic acid and flavan-3-ols; however, 100% fruit juice greatly contributes to anthocyanin, flavonol, flavan-3-ols, and flavanone intake, making them complementary sources of dietary (poly)phenols. Thus, the aim of this narrative review was to provide an overview of fruit (poly)phenols and their potential health benefits. Fruit (poly)phenols have been associated with several health benefits (eg, reduced risk of cardiovascular disease and neurocognitive benefits). Although perspectives on 100% fruit juice consumption are controversial due to the perception of sugar content, growing evidence supports the role of fruit in whole and 100% juice forms to provide consumer benefits in alignment with dietary guidance. However, differences in (poly)phenol profiles and bioavailability likely exist between whole fruit and 100% fruit juice due to processing and the presence/absence of fiber. Ongoing studies are better defining similarities and differences between whole fruit and 100% fruit juice to elucidate protective mechanisms and align with processing and consumer products.
Diagnostic Delays and Treatment Implications for Patients with Isoniazid-Resistant Tuberculosis: A Case Report and Review of the Literature
Authors: Olson Gregory , Nathavitharana Ruvandhi R , Lederer Philip A 
Published: May 2019

Abstract
Drug-resistant tuberculosis (DR-TB) remains a major public health threat. A 23-year-old man presented with fever, dyspnea, and a pleural effusion. After a delay, he was diagnosed with isoniazid (INH)-resistant TB. We review the literature describing the epidemiological and clinical significance of INH-resistant TB and its relevance for low-incidence countries, such as the United States.
Mechanisms of Action by Which Local Anesthetics Reduce Cancer Recurrence: A Systematic Review
Authors: Grandhi Ravi K , Perona Barbara 
Published: May 2019

Abstract

Background
Surgery in concert with anesthesia is a key part of the management of advanced-stage cancers. Anesthetic agents such as opioids and volatile anesthetics have been shown to promote recurrence in preclinical models, whereas some animal models have shown that the use of lidocaine may be beneficial in reducing cancer recurrence. The purpose of this article is to review the current literature to highlight the mechanisms of action by which local anesthetics are thought to reduce cancer recurrence.

Methods
A systematic review was conducted using the PubMed (1966 to 2018) electronic database. Search terms included “lidocaine,” “ropivicaine,” “procaine,” “bupivicaine,” “mepivicaine,” “metastasis,” “cancer recurrence,” “angiogenesis,” and “local anesthetics” in various combinations. The search yielded 146 total abstracts for initial review, 20 of which met criteria for inclusion. Theories for lidocaine’s effect on cancer recurrence were recorded. All studies were reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist.

Results
Numerous mechanisms were proposed based on the local anesthetic used and the type of cancer. Mechanisms include those that are centered on endothelial growth factor receptor, voltage-gated sodium and calcium channels, transient receptor melanoplastin 7, hyperthermia, cell cycle, and demyelination.

Conclusions
In vivo models suggest that local anesthetic administration leads to reduced cancer recurrence. The etiology of this effect is likely multifactorial through both inhibition of certain pathways and direct induction of apoptosis, a decrease in tumor migration, and an association with cell cycle–mediated and DNA-mediated effects. Additional research is required to further define the clinical implications.
Indwelling pleural catheters: an overview and real-life experience
Authors: Messeder S J , Thomson M C , Hu M K , Chetty M , Currie G P 
Published: May 2019

Abstract

Background
Indwelling pleural catheters (IPCs) are most frequently used in those with malignant pleural effusions, although their use is expanding to patients with non-malignant diseases.

Aim
To provide an overview of IPCs and highlight how, when and why they can be used including our own real-life experience.

Design
Data were collected retrospectively from a large tertiary centre for all individuals who received an IPC between June 2010 and February 2018 inclusive. The data collected included gender, age, origin of malignancy, number of drains prior to IPC, whether they had received pleurodesis prior to IPC, presence of a trapped lung, date of insertion, documented complications, overall outcome and date of death.

Results
A total of 68 patients received an IPC, the majority were female (n = 38, 57%) with an overall median age of 68 years (range 40–90 years). The most common site of cancer origin was lung (n = 33, 49%) followed by pleura (n = 10, 15%) and breast (n = 9, 13%). The median survival of all patients was 141 days (IQR 26–181). Sixteen percent (n = 11) of patients underwent a spontaneous pleurodesis resulting in their IPC being removed. Only three individuals had a complication (4.4%).

Conclusions
IPC insertion is a safe procedure and represents an exciting and expanding field in the management of pleural disease. Further longitudinal studies are required to fully delineate their place in the management of both malignant and benign effusions.