bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeatability, interocular correlation and agreement of quantitative swept-source optical coherence tomography angiography macular metrics in healthy subjects
Authors: Fang Danqi , Tang Fang Yao , Huang Haifan , Cheung Carol Y , Chen Haoyu 
Published: May 2018

Purpose
To investigate the repeatability, interocular correlation and agreement of quantitative swept-source optical coherence tomography angiography (SS-OCTA) metrics in healthy subjects.

Methods
Thirty-three healthy normal subjects were enrolled. The macula was scanned four times by an SS-OCTA system using the 3 mm×3 mm mode. The superficial capillary map images were analysed using a MATLAB program. A series of parameters were measured: foveal avascular zone (FAZ) area, FAZ perimeter, FAZ circularity, parafoveal vessel density, fractal dimension and vessel diameter index (VDI). The repeatability of four scans was determined by intraclass correlation coefficient (ICC). Then the averaged results were analysed for intereye difference, correlation and agreement using paired t-test, Pearson’s correlation coefficient (r), ICC and Bland-Altman plot.

Results

The repeatability assessment of the macular metrics exported high ICC values (ranged from 0.853 to 0.996). There is no statistically significant difference in the OCTA metrics between the two eyes. FAZ area (ICC=0.961, r=0.929) and FAZ perimeter (ICC=0.884, r=0.802) showed excellent binocular correlation. Fractal dimension (ICC=0.732, r=0.578) and VDI (ICC=0.707, r=0.547) showed moderate binocular correlation, while parafoveal vessel density had poor binocular correlation. Bland-Altman plots showed the range of agreement was from −0.0763 to 0.0954 mm
2
for FAZ area and from −0.0491 to 0.1136 for parafoveal vessel density.

Conclusions
The macular metrics obtained using SS-OCTA showed excellent repeatability in healthy subjects. We showed high intereye correlation in FAZ area and perimeter, moderate correlation in fractal dimension and VDI, while vessel density had poor correlation in normal healthy subjects.
Clinical presentation and management of corneal fistula
Authors: Singhal Deepali , Sahay Pranita , Maharana Prafulla Kumar , Amar Sreelakshmi P , Titiyal Jeewan S , Sharma Namrata 
Published: May 2018

PurposeTo describe the clinical features and management of corneal fistula in patients of healed keratitis.MethodsMedical records of all patients of healed keratitis presenting to the cornea clinic from November 2016 to September 2017 were reviewed. Eightcases of corneal fistula (six true fistulas, two closed fistulas) were identified. Six patients were managed with autologous tenon patch graft while two patients were managed medically. Various risk factors and treatment outcomes of corneal fistulisation were evaluated.ResultsThe patients included two patients of failed therapeutic keratoplasty (with resolved graft infection) and six patients of healed keratitis. The age of the patients ranged between 10 and 60 years. Five of the patients were male while three were female. The size of the fistula measured between 1 and 2 mm. A surrounding cystic area of diameter ranging between 1 and 4.5 mm was seen in all the patients. In all of the patients, the treating physician missed the diagnosis. Complete healing was noted at 6–8 weeks in all the patients who underwent tenon graft. One patient refused to undergo any surgery and was lost to follow-up. In another case, surgery was deferred due to uncontrolled hypertension and he developed anterior staphyloma subsequently.ConclusionCorneal fistula can often be missed in an apparently healed perforated corneal ulcer. Tenon patch graft is an effective technique for the management of corneal fistula.
Validation, Intrarater and Interrater Reliability Study of the Lateral-Anterior Drawer Test for Detecting Posterior Cruciate Ligament Ruptures: Study Protocol of a Prospective Controlled Single-Blinded Cross-Sectional Study
Authors: Seeber Gesine H , Thalhamer Christoph , Hahne Julia , Matthijs Omer 
Published: May 2018

IntroductionCommonly used clinical tests for posterior cruciate ligament (PCL) rupture detection exhibit several limitations, thus requiring more precise clinical PCL tests. The lateral-anterior drawer (LAD) test has been proposed as a manually applied testing alternative but not yet been evaluated in vivo.Methods and analysisFifteen patients presenting with an MRI-confirmed acute or chronic unilateral PCL rupture and 15 subjects with no prior knee injury in their medical history will be included in this prospective single-blinded cross-sectional cohort study. Three examiners with different lengths of working experience (range 1–30 years), blinded to MRI outcomes and patient history, will use the LAD test on both knees of each participant to test for PCL integrity. Examiners will independently document the PCL status of each knee on a blank case report form. Fleiss-Kappa values will be calculated to investigate whether the LAD test shows clinically significant interrater and intrarater reliability. Furthermore, LAD test outcomes will be compared with MRI which serves as reference standard to check for concurrent validity. Moreover, LAD test accuracy with respect to tester experience will be evaluated.Ethics and disseminationThe study will be conducted in agreement with the World Medical Association Declaration of Helsinki (2013). Ethical permission (EK16-081-0616) to conduct this study was obtained from the review board of the city of Vienna on 1 September 2016. All personal and research data will be used in accordance with the Austrian Federal Data Protection Act and will be anonymised before publication in relevant international peer-reviewed journals.Trial registrationnumberDRKS00013268; Pre-results.
Restraining Network Response to Targeted Cancer Therapies Improves Efficacy and Reduces Cellular Resistance
Authors: Das Tirtha K. , Esernio Jessica , Cagan Ross L. 
Published: May 2018

Abstract
A key tool of cancer therapy has been targeted inhibition of oncogene-addicted pathways. However, efficacy has been limited by progressive emergence of resistance as transformed cells adapt. Here, we use Drosophila to dissect response to targeted therapies. Treatment with a range of kinase inhibitors led to hyperactivation of overall cellular networks, resulting in emergent resistance and expression of stem cell markers, including Sox2. Genetic and drug screens revealed that inhibitors of histone deacetylases, proteasome, and Hsp90 family of proteins restrained this network hyperactivation. These “network brake” cocktails, used as adjuncts, prevented emergent resistance and promoted cell death at subtherapeutic doses. Our results highlight a general response of cells, transformed and normal, to targeted therapies that leads to resistance and toxicity. Pairing targeted therapeutics with subtherapeutic doses of broad-acting “network brake” drugs may provide a means of extending therapeutic utility while reducing whole body toxicity.
Significance: These findings with a strong therapeutic potential provide an innovative approach of identifying effective combination treatments for cancer. Cancer Res; 78(15); 4344–59. ©2018 AACR.
Integrative Modeling Identifies Key Determinants of Inhibitor Sensitivity in Breast Cancer Cell Lines
Authors: Jastrzebski Katarzyna , Thijssen Bram , Kluin Roelof J.C. , de Lint Klaas , Majewski Ian J. , Beijersbergen Roderick L. , Wessels Lodewyk F.A. 
Published: May 2018

Abstract
Cancer cell lines differ greatly in their sensitivity to anticancer drugs as a result of different oncogenic drivers and drug resistance mechanisms operating in each cell line. Although many of these mechanisms have been discovered, it remains a challenge to understand how they interact to render an individual cell line sensitive or resistant to a particular drug. To better understand this variability, we profiled a panel of 30 breast cancer cell lines in the absence of drugs for their mutations, copy number aberrations, mRNA, protein expression and protein phosphorylation, and for response to seven different kinase inhibitors. We then constructed a knowledge-based, Bayesian computational model that integrates these data types and estimates the relative contribution of various drug sensitivity mechanisms. The resulting model of regulatory signaling explained the majority of the variability observed in drug response. The model also identified cell lines with an unexplained response, and for these we searched for novel explanatory factors. Among others, we found that 4E-BP1 protein expression, and not just the extent of phosphorylation, was a determinant of mTOR inhibitor sensitivity. We validated this finding experimentally and found that overexpression of 4E-BP1 in cell lines that normally possess low levels of this protein is sufficient to increase mTOR inhibitor sensitivity. Taken together, our work demonstrates that combining experimental characterization with integrative modeling can be used to systematically test and extend our understanding of the variability in anticancer drug response.
Significance: By estimating how different oncogenic mutations and drug resistance mechanisms affect the response of cancer cells to kinase inhibitors, we can better understand and ultimately predict response to these anticancer drugs.
Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/15/4396/F1.large.jpg. Cancer Res; 78(15); 4396–410. ©2018 AACR.
SNHG6 Acts as a Genome-Wide Hypomethylation Trigger via Coupling of miR-1297–Mediated S-Adenosylmethionine–Dependent Positive Feedback Loops
Authors: Guo Tao , Wang Hongling , Liu Pengpeng , Xiao Yushao , Wu Ping , Wang Yitao , Chen Baiyang , Zhao Qiu , Liu Zhisu , Liu Quanyan 
Published: May 2018

Abstract
Aberrant genome-wide hypomethylation and long noncoding RNA (lncRNA) dysregulation are associated with hepatocarcinogenesis. However, whether a relationship between the two exists remains largely unknown. S-adenosylmethionine (SAMe)-dependent methylation is a critical factor in genomic methylation. We previously found that SNHG6 lncRNA acted as an oncogene in hepatocarcinogenesis and could be considered a potential prognostic indicator for hepatocellular carcinoma (HCC). Here we verify that SNHG6 leads to genome-wide hypomethylation in hepatoma cells and that SNHG6 negatively correlates with the steady-state SAMe concentration in vivo and in vitro. SNHG6 suppressed MAT1A protein expression by activating the miR-1297/FUS pathway to regulate nucleocytoplasmic shuttling of MAT1A mRNA. In addition, SNHG6 promoted expression of MAT2A by suppressing direct binding of miR-1297 to the MAT2A 3′UTR. SNHG6 regulated steady-state SAMe levels via coupling of two miR-1297–mediated SAMe-dependent positive feedback loops. Interestingly, the effect of SNHG6 on genome-wide methylation was inhibited by exogenous SAMe within a certain concentration range. These results suggest that single lncRNA dysregulation can lead to aberrant genome-wide hypomethylation by inhibiting SAMe production in HCC and that exogenous SAMe may be beneficial in the treatment of HCC.
Significance: These findings explore the role of SNHG6 lncRNA in suppressing production of the universal methyl donor SAMe and its impact on global DNA methylation levels in liver cancer and highlight the potential benefit of SAMe for the treatment of liver cancer. Cancer Res; 78(14); 3849–64. ©2018 AACR.
Glycosyltransferase Gene Expression Identifies a Poor Prognostic Colorectal Cancer Subtype Associated with Mismatch Repair Deficiency and Incomplete Glycan Synthesis
Authors: Noda Masaru , Okayama Hirokazu , Tachibana Kazunoshin , Sakamoto Wataru , Saito Katsuharu , Thar Min Aung Kyi , Ashizawa Mai , Nakajima Takahiro , Aoto Keita , Momma Tomoyuki , Katakura Kyoko , Ohki Shinji , Kono Koji 
Published: May 2018

Abstract
Purpose: We aimed to discover glycosyltransferase gene (glycogene)-derived molecular subtypes of colorectal cancer associated with patient outcomes.
Experimental Design: Transcriptomic and epigenomic datasets of nontumor, precancerous, cancerous tissues, and cell lines with somatic mutations, mismatch repair status, clinicopathologic and survival information were assembled (n = 4,223) and glycogene profiles were analyzed. IHC for a glycogene, GALNT6, was conducted in adenoma and carcinoma specimens (n = 403). The functional role and cell surface glycan profiles were further investigated by in vitro loss-of-function assays and lectin microarray analysis.
Results: We initially developed and validated a 15-glycogene signature that can identify a poor-prognostic subtype, which closely related to deficient mismatch repair (dMMR) and GALNT6 downregulation. The association of decreased GALNT6 with dMMR was confirmed in multiple datasets of tumors and cell lines, and was further recapitulated by IHC, where approximately 15% tumors exhibited loss of GALNT6 protein. GALNT6 mRNA and protein was expressed in premalignant/preinvasive lesions but was subsequently downregulated in a subset of carcinomas, possibly through epigenetic silencing. Decreased GALNT6 was independently associated with poor prognosis in the IHC cohort and an additional microarray meta-cohort, by multivariate analyses, and its discriminative power of survival was particularly remarkable in stage III patients. GALNT6 silencing in SW480 cells promoted invasion, migration, chemoresistance, and increased cell surface expression of a cancer-associated truncated O-glycan, Tn-antigen.
Conclusions: The 15-glycogene signature and the expression levels of GALNT6 mRNA and protein each serve as a novel prognostic biomarker, highlighting the role of dysregulated glycogenes in cancer-associated glycan synthesis and poor prognosis. Clin Cancer Res; 24(18); 4468–81. ©2018 AACR.
IG VII 53, an epigraphic rara avis in the corpus of greek metrical inscriptions
Authors: Guijarro Ruano Paloma 
Published: May 2018

Este artigo tem como objetivo estudar a inscrição publicada no IG VII 53 de uma perspectiva liguística. Ele consiste de uma seção em prosa que inclui um epigrama dedicado aos Mégaros caídos em combate nas guerras Pérsicas. A inscrição foi supostamente composta no século V a. C., mas o texto preservado não foi inscrito antes do IV século a. C. Após reavaliar a bibliografia principal sobre o texto, que estudou a inscrição principalmente do ponto de vista arqueológico, histórico ou literário, nós aplicamos uma análise linguística em dois níveis, baseada: a) na comparação dos dados linguísticos com a prosa epigráfica ou outras influências literárias, e b) nas restrições métricas que poderiam determinar a escolha entre formas locais ou literárias. Como complemento ao que os estudos atuais sugerem, essa abordagem metodológica nos permite distinguir até que ponto é possível traçar as características linguísticas originais de uma versão anterior do epigrama, bem como se e como a métrica contribui para os preservar.
Intake of Different Dietary Proteins and Risk of Heart Failure in Men
Authors: Virtanen Heli E.K. , Voutilainen Sari , Koskinen Timo T. , Mursu Jaakko , Tuomainen Tomi-Pekka , Virtanen Jyrki K. 
Published: May 2018

Background:
Animal and plant protein intakes have indicated opposite associations with cardiovascular mortality risk. Whether dietary proteins are associated with risk of heart failure (HF) is unclear. Thus, we examined the associations of proteins from different food sources with risk of HF.

Methods and Results:

The study included 2441 men aged 42 to 60 years at the baseline examinations in 1984 to 1989 in the Kuopio Ischaemic Heart Disease Risk Factor Study. Protein intakes at baseline were assessed with 4-day dietary records. Data on incident HF cases were obtained from national registers. HF risk according to protein intake was estimated by Cox proportional hazard ratios. During the mean follow-up of 22.2 years, 334 incident HF cases occurred. Higher intake of total protein indicated a trend toward increased risk of HF (multivariable-adjusted hazard ratio in the highest versus lowest quartile=1.33; 95% confidence interval: 0.95–1.85;
P
-trend=0.05). The associations between specific types and sources of protein with incident HF were consistent with this overall finding although not all associations reached statistical significance. For example, the hazard ratio in the highest versus lowest quartile was 1.43 (95% confidence interval: 1.00–2.03;
P
-trend=0.07) for total animal protein and 1.17 (95% confidence interval: 0.72–1.91;
P
-trend=0.35) for total plant protein.

Conclusions:
In middle-aged men, higher protein intake was marginally associated with increased risk of HF.

CLINICAL TRIAL REGISTRATION:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT03221127
Diverse Inflammatory Response After Cerebral Microbleeds Includes Coordinated Microglial Migration and Proliferation
Authors: Ahn Sung Ji , Anrather Josef , Nishimura Nozomi , Schaffer Chris B. 
Published: May 2018

Background and Purpose—
Cerebral microbleeds are linked to cognitive decline, but it remains unclear how they impair neuronal function. Infarction is not typically observed near microbleeds, suggesting more subtle mechanisms, such as inflammation, may play a role. Because of their small size and largely asymptomatic nature, real-time detection and study of spontaneous cerebral microbleeds in humans and animal models are difficult.

Methods—
We used in vivo 2-photon microscopy through a chronic cranial window in adult mice to follow the inflammatory response after a cortical microhemorrhage of ≈100 µm diameter, induced by rupturing a targeted cortical arteriole with a laser.

Results—

The inflammatory response included the invasion of blood-borne leukocytes, the migration and proliferation of brain-resident microglia, and the activation of astrocytes. Nearly all inflammatory cells responding to the microhemorrhage were brain-resident microglia, but a small number of CX3CR1
+
and CCR2
+
macrophages, ultimately originating from the invasion of blood-borne monocytes, were also found near the lesion. We found a coordinated pattern of microglia migration and proliferation, where microglia within 200 µm of the microhemorrhage migrated toward the lesion over hours to days. In contrast, microglia proliferation was not observed until ≈40 hours after the lesion and occurred primarily in a shell-shaped region where the migration of microglia decreased their local density. These data suggest that local microglia density changes may trigger proliferation. Astrocytes activated in a similar region as microglia but delayed by a few days. By 2 weeks, this inflammatory response had largely resolved.

Conclusions—
Although microhemorrhages are small in size, the brain responds to a single bleed with an inflammatory response that involves brain-resident and blood-derived cells, persists for weeks, and may impact the adjacent brain microenvironment.
Continuation or Discontinuation of Anticoagulation in the Early Phase After Acute Ischemic Stroke
Authors: Groot Adrien E. , Vermeij Jan-Dirk M. , Westendorp Willeke F. , Nederkoorn Paul J. , van de Beek Diederik , Coutinho Jonathan M. 
Published: May 2018

Background and Purpose—
There is no consensus on whether anticoagulation should be continued or temporarily stopped in patients suffering acute ischemic stroke while using anticoagulation. We assessed treatment variations and outcomes in these patients.

Methods—
Post hoc analysis of PASS (Preventive Antibiotics in Stroke Study). We included patients with acute ischemic stroke who used anticoagulation at admission. We compared clinical outcomes, thrombotic, and major bleeding events at 3 months.

Results—

Nine percent (192/2101) of the patients with acute ischemic stroke used anticoagulation at admission (186 vitamin K antagonists). Anticoagulation was discontinued in 35/192 (18%) patients. These patients had higher National Institutes of Health Stroke Scale scores than patients in whom anticoagulation was continued (median, 13 versus 4;
P
<0.001). Thrombotic events occurred more frequently in patients in whom anticoagulation was discontinued (11% versus 3%;
P
=0.038). There were no major bleeding events in either group. Mortality and clinical outcomes at 90 days were worse in patients in whom anticoagulation was discontinued (mortality, 31% versus 15%;
P
=0.019 and modified Rankin Scale score of 0–2, 20% versus 55%;
P
<0.001). After adjustment for potential confounders, there were no statistically significant differences between groups.

Conclusions—
In our study, clinicians tended to continue anticoagulation in patients with acute ischemic stroke. Discontinuation was associated with an increased risk of thrombotic events and worse clinical outcome. Risk of major bleeding was not increased in patients in whom anticoagulation was continued.

Clinical Trial Registration—

URL:
https://www.controlled-trials.com
. Unique identifier: ISRCTN66140176.
Muʿtazila in der arabischen Bibelübersetzung des Bišr b. al-Sirrī
Authors: Blumenthal Christian 
Published: May 2018

Abstract
In his significant Arabic translation and interpretation of the Pauline Epistles and the Acts of the Apostles, Bišr b. al-Sirrī used muʿtazila to translate Pharisee throughout his work. This paper elaborates upon the multiple difficulties in revealing the connotations of muʿtazila in Bišr’s work from the middle of the third/tenth century. Furthermore, it offers an explication of his particular use of this term by taking into consideration several aspects, especially the nuance of ascetic piety.
Unity through Omission: Literary Strategies of Recension in Ibn al-Aṯīr’s al-Kāmil fī l-Ta⁠ʾrīḫ
Authors: Hagler Aaron M. 
Published: May 2018

Abstract
The historical chronicle al-Kāmil fī l-ta⁠ʾrīḫ (The Complete History) of Ibn al-Aṯīr al-Ǧazarī (555/1160-630/1233) treats conservatively the existing corpus of narratives of the fitna, the first Muslim civil war (36/656-41/661). Ibn al-Aṯīr alters his main source’s accounts of troublesome moments, usually through omission, to present a universal history that serves to rehabilitate the reputation of the Umayyads without criticizing the partisans of ʿAlī. While this approach may be understood as remarkable scholarly detachment from perhaps the most contentious episode of the early Islamic narrative, in fact this narrative strategy is carefully calculated to present a past that can serve as an example for the future: one in which the disagreements that had fractured the umma were surmountable, and its unity was recoverable. Such changes, while small, had a large qualitative impact due to the narrative centrality of the fitna within the wider early Islamic narrative.
Les terres de l’Alitaje (Grenade) et le pouvoir socio-politique et économique dans l’al-Andalus naṣride : édition, traduction et étude de deux actes notariés de 878/1473-879/1474
Authors: Rodríguez-Gómez María Dolores , Vidal-Castro Francisco 
Published: May 2018

Résumé
Dans l’al-Andalus de l’époque naṣride (629/1232-897/1492) et son épilogue mudéjar-morisque (IXe/XVe-Xe/XVIe siècles), la propriété de la terre fut une stratégie du pouvoir à trois niveaux (politique, économique et social) excercée par trois acteurs principaux (les souverains, les notables et les familles aisées). Dans le présent travail, nous allons démontrer (1) que le souverain naṣride possédait des terres ayant une grande valeur économique, (2) que ces mêmes terres furent acquises plus tard par des personnes et des familles notables, (3) que ces terres furent transmises à d’autres propriétaires qui avaient un haut pouvoir d’achat et (4) qu’après la conquête, celles-ci passèrent aux mains de propriétaires chrétiens, mudéjars et morisques ainsi que castillans. À ces fins, nous présentons dans cet article l’édition, la traduction et l’étude d’un document arabe fondamental, spécial et inédit, reproduisant deux actes notariés datant des années 878/1473-879/1474.