bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of four‐layer porcine small intestinal submucosa alone as a scaffold for the treatment of deep corneal defects in dogs and cats: preliminary results
Authors: Barachetti Laura , Zanni Marco , Stefanello Damiano , Rampazzo Antonella 
Published: January 2020

BackgroundTo describe the efficacy of four‐layer porcine small intestinal submucosa (Vetrix BioSIS plus+) as single scaffold for the treatment of deep corneal lesions in dogs and cats.Methods10 dogs and 3 cats with deep or full thickness corneal defects were treated surgically with BioSIS plus graft. Corneal transparency scores and vision were evaluated.ResultsLesions in dogs were four perforations, three descemetoceles, two limbal melanocytomas and one deep corneal ulcer. In cats, there were one limbal melanocytoma and two perforations. The average length of the follow‐up was 86 days. In all, 12 out of 13 eyes treated were visual at last recheck (92.3 per cent). The scars were mild eight cases (66.7 per cent), but denser in four cases (33.4 per cent). Complication were partial collagenolysis in three cases (25 per cent), which resolved with medical therapy, mild corneal pigmentation in one case (8.4 per cent) and anterior synechia in one case (8.4 per cent). One case experienced severe collagenolysis and was enucleated 21 days postoperatively.ConclusionsFour‐layer porcine SIS graft was successfully used for surgical treatment of deep corneal lesions in selected corneal diseases in a small series of dogs and cats, with good results in terms of mechanic support and corneal transparency.
AMG-176, an Mcl-1 Antagonist, Shows Preclinical Efficacy in Chronic Lymphocytic Leukemia
Authors: Yi Xue , Sarkar Aloke , Kismali Gorkem , Aslan Burcu , Ayres Mary , Iles LaKesla R. , Keating Michael J. , Wierda William G. , Long James P. , Bertilaccio Maria Teresa Sabrina , Gandhi Varsha 
Published: January 2020

Abstract

Purpose:
Survival of CLL cells due to the presence of Bcl-2 and Mcl-1 has been established. Direct inhibition of Bcl-2 by venetoclax and indirect targeting of Mcl-1 with transcription inhibitors have been successful approaches for CLL. AMG-176 is a selective and direct antagonist of Mcl-1, which has shown efficacy in several hematologic malignancies; however, its effect on CLL is elusive. We evaluated biological and molecular effects of AMG-176 in primary CLL cells.

Experimental Design:
Using samples from patients (n = 74) with CLL, we tested effects of AMG-176 on CLL and normal hematopoietic cell death and compared importance of CLL prognostic factors on this biological activity. We evaluated CLL cell apoptosis in the presence of stromal cells and identified cell death pathway including stabilization of Mcl-1 protein. Finally, we tested a couplet of AMG-176 and venetoclax in CLL lymphocytes.

Results:
AMG-176 incubations resulted in time- and dose-dependent CLL cell death. At 100 and 300 nmol/L, there was 30% and 45% cell death at 24 hours. These concentrations did not result in significant cell death in normal hematopoietic cells. Presence of stroma did not affect AMG-176–induced CLL cell death. IGHV unmutated status, high β2M and Mcl-1 protein levels resulted in slightly lower cell death. Mcl-1, but not Bcl-2 protein levels, in CLL cells increased with AMG-176. Low concentrations of venetoclax (1–30 nmol/L) were additive or synergistic with AMG-176.

Conclusions:
AMG-176 is active in inducing CLL cell death while sparing normal blood cells. Combination with low-dose venetoclax was additive or synergistic.
A Combinatorial Strategy for TargetingBRAFV600E-Mutant Cancers with BRAFV600E Inhibitor (PLX4720) and Tyrosine Kinase Inhibitor (Ponatinib)
Authors: Ghosh Chandrayee , Kumar Suresh , Kushchayeva Yevgeniya , Gaskins Kelli , Boufraqech Myriem , Wei Darmood , Gara Sudheer Kumar , Zhang Lisa , Zhang Ya-qin , Shen Min , Mukherjee Sanjit , Kebebew Electron 
Published: January 2020

AbstractPurpose:Most aggressive thyroid cancers are commonly associated with a BRAFV600E mutation. Preclinical and clinical data in BRAFV600E cancers suggest that combined BRAF and MEK inhibitor treatment results in a response, but resistance is common. One mechanism of acquired resistance is through persistent activation of tyrosine kinase (TK) signaling by alternate pathways. We hypothesized that combination therapy with BRAF and multitargeting TK inhibitors (MTKI) might be more effective in BRAFV600E thyroid cancer than in single-agent or BRAF and MEK inhibitors.Experimental Design:The combined drug activity was analyzed to predict any synergistic effect using high-throughput screening (HTS) of active drugs. We performed follow-up in vitro and in vivo studies to validate and determine the mechanism of action of synergistic drugs.Results:The MTKI ponatinib and the BRAF inhibitor PLX4720 showed synergistic activity by HTS. This combination significantly inhibited proliferation, colony formation, invasion, and migration in BRAFV600E thyroid cancer cell lines and downregulated pERK/MEK and c-JUN signaling pathways, and increased apoptosis. PLX4720-resistant BRAFV600E cells became sensitized to the combination treatment, with decreased proliferation at lower PLX4720 concentrations. In an orthotopic thyroid cancer mouse model, combination therapy significantly reduced tumor growth (P &lt; 0.05), decreased the number of metastases (P &lt; 0.05), and increased survival (P &lt; 0.05) compared with monotherapy and vehicle control.Conclusions:Combination treatment with ponatinib and PLX4720 exhibited significant synergistic anticancer activity in preclinical models of BRAFV600E thyroid cancer, in addition to overcoming PLX4720 resistance. Our results suggest this combination should be tested in clinical trials.
Gene Expression Signatures Identify Novel Therapeutics for Metastatic Pancreatic Neuroendocrine Tumors
Authors: Scott Aaron T. , Weitz Michelle , Breheny Patrick J. , Ear Po Hien , Darbro Benjamin , Brown Bart J. , Braun Terry A. , Li Guiying , Umesalma Shaikamjad , Kaemmer Courtney A. , Maharjan Chandra K. , Quelle Dawn E. , Bellizzi Andrew M. , Chandrasekharan Chandrikha , Dillon Joseph S. , O'Dorisio Thomas M. , Howe James R. 
Published: January 2020

Abstract

Purpose:
Pancreatic neuroendocrine tumors (pNETs) are uncommon malignancies noted for their propensity to metastasize and comparatively favorable prognosis. Although both the treatment options and clinical outcomes have improved in the past decades, most patients will die of metastatic disease. New systemic therapies are needed.

Experimental Design:
Tissues were obtained from 43 patients with well-differentiated pNETs undergoing surgery. Gene expression was compared between primary tumors versus liver and lymph node metastases using RNA-Seq. Genes that were selectively elevated at only one metastatic site were filtered out to reduce tissue-specific effects. Ingenuity pathway analysis (IPA) and the Connectivity Map (CMap) identified drugs likely to antagonize metastasis-specific targets. The biological activity of top identified agents was tested in vitro using two pNET cell lines (BON-1 and QGP-1).

Results:
A total of 902 genes were differentially expressed in pNET metastases compared with primary tumors, 626 of which remained in the common metastatic profile after filtering. Analysis with IPA and CMap revealed altered activity of factors involved in survival and proliferation, and identified drugs targeting those pathways, including inhibitors of mTOR, PI3K, MEK, TOP2A, protein kinase C, NF-kB, cyclin-dependent kinase, and histone deacetylase. Inhibitors of MEK and TOP2A were consistently the most active compounds.

Conclusions:
We employed a complementary bioinformatics approach to identify novel therapeutics for pNETs by analyzing gene expression in metastatic tumors. The potential utility of these drugs was confirmed by in vitro cytotoxicity assays, suggesting drugs targeting MEK and TOP2A may be highly efficacious against metastatic pNETs. This is a promising strategy for discovering more effective treatments for patients with pNETs.
Incidence of Sports-Related Traumatic Brain Injury of All Severities: A Systematic Review
Authors: Theadom Alice , Mahon Susan , Hume Patria , Starkey Nicola , Barker-Collo Suzanne , Jones Kelly , Majdan Marek , Feigin Valery L. 
Published: January 2020

<b><i>Introduction:</i></b> Whilst there are many benefits to participating in sports and recreational activities, there is also a risk of injury including sports-related traumatic brain injury ­(SR-TBI). To inform injury prevention initiatives, it is important to explore the burden of SR-TBI at the population level. This review aimed to estimate the incidence of SR-TBI in the general population across injury severities. <b><i>Methods:</i></b> Systematic search of electronic databases using keywords from 1965 until June 2019 facilitated by hand searches of reference lists. Original research reporting on the incidence of SR-TBI, capturing people of all ages in a well-defined population area was included. Studies were excluded if they focused on a specific sport(s) or population group. All studies were required to be published in the English language. Quality of studies was determined as poor, moderate or good based on the standards of reporting of neurological disorders criteria. Data on year(s) of data collection, diagnostic criterion, case ascertainment sources, population denominator and incidence per 100,000 and by age, sex, injury severity and sport were extracted by 2 authors independently using a standard data extraction form. <b><i>Results:</i></b> Following review of 11 studies meeting the inclusion criteria, the incidence of SR-TBI within hospital-based studies ranged between 3.5 and 31.5 per 100,000. One community-based study using multiple case ascertainment sources identified a higher incidence of 170 per 100,000. SR-TBI accounted for 1.2–30.3% of all TBIs. One study provided incidence data across a 5-year period suggesting an increasing trend in incidence over time. Males were more at risk than females (66.1–75.6%), and adolescents and young adults had the highest incidence of SR-TBI. <b><i>Conclusion:</i></b> The primary objective of this review was to provide a summary of descriptive data on SR-TBI epidemiology at the population level. SR-TBI represented up to one-third of all causes of TBI. Trends in incidence by age and sport were challenging to determine due to lack of consistency in reporting as well as the small number of studies overall. Undertaking injury surveillance at all levels of TBI will assist with understanding the nature, mechanism of and surrounding events where injuries occur in sport.
Racial Differences in Malignant Left Ventricular Hypertrophy and Incidence of Heart Failure
Authors: Lewis Alana A. , Ayers Colby R. , Selvin Elizabeth , Neeland Ian , Ballantyne Christie M. , Nambi Vijay , Pandey Ambarish , Powell-Wiley Tiffany M. , Drazner Mark H. , Carnethon Mercedes R. , Berry Jarett D. , Seliger Stephen L. , DeFilippi Christopher R. , de Lemos James A. 
Published: January 2020

Background:
A malignant subphenotype of left ventricular hypertrophy (LVH) has been described, in which minimal elevations in cardiac biomarkers identify individuals with LVH at high risk for developing heart failure (HF). We tested the hypothesis that a higher prevalence of malignant LVH among blacks may contribute to racial disparities in HF risk.

Methods:
Participants (n=15 710) without prevalent cardiovascular disease were pooled from 3 population-based cohort studies, the ARIC Study (Atherosclerosis Risk in Communities), the DHS (Dallas Heart Study), and the MESA (Multi-Ethnic Study of Atherosclerosis). Participants were classified into 3 groups: those without ECG-LVH, those with ECG-LVH and normal biomarkers (hs-cTnT (high sensitivity cardiac troponin-T) <6 ng/L and NT-proBNP (N-terminal pro-B-type natriuretic peptide) <100 pg/mL), and those with ECG-LVH and abnormal levels of either biomarker (malignant LVH). The outcome was incident HF.

Results:
Over the 10-year follow-up period, HF occurred in 512 (3.3%) participants, with 5.2% in black men, 3.8% in white men, 3.2% in black women, and 2.2% in white women. The prevalence of malignant LVH was 3-fold higher among black men and women versus white men and women. Compared with participants without LVH, the adjusted hazard ratio for HF was 2.8 (95% CI, 2.1–3.5) in those with malignant LVH and 0.9 (95% CI, 0.6–1.5) in those with LVH and normal biomarkers, with similar findings in each race/sex subgroup. Mediation analyses indicated that 33% of excess hazard for HF among black men and 11% of the excess hazard among black women was explained by the higher prevalence of malignant LVH in blacks. Of black men who developed HF, 30.8% had malignant LVH at baseline, with a corresponding population attributable fraction of 0.21. The proportion of HF cases occurring among those with malignant LVH, and the corresponding population attributable fraction, were intermediate and similar among black women and white men and lowest among white women.

Conclusions:
A higher prevalence of malignant LVH may in part explain the higher risk of HF among blacks versus whites. Strategies to prevent development or attenuate risk associated with malignant LVH should be investigated as a strategy to lower HF risk and mitigate racial disparities.
Tracking the Effects of Top–Down Attention on Word Discrimination Using Frequency-tagged Neuromagnetic Responses
Authors: Niesen Maxime , Vander Ghinst Marc , Bourguignon Mathieu , Wens Vincent , Bertels Julie , Goldman Serge , Choufani Georges , Hassid Sergio , De Tiège Xavier 
Published: January 2020

Abstract
Discrimination of words from nonspeech sounds is essential in communication. Still, how selective attention can influence this early step of speech processing remains elusive. To answer that question, brain activity was recorded with magnetoencephalography in 12 healthy adults while they listened to two sequences of auditory stimuli presented at 2.17 Hz, consisting of successions of one randomized word (tagging frequency = 0.54 Hz) and three acoustically matched nonverbal stimuli. Participants were instructed to focus their attention on the occurrence of a predefined word in the verbal attention condition and on a nonverbal stimulus in the nonverbal attention condition. Steady-state neuromagnetic responses were identified with spectral analysis at sensor and source levels. Significant sensor responses peaked at 0.54 and 2.17 Hz in both conditions. Sources at 0.54 Hz were reconstructed in supratemporal auditory cortex, left superior temporal gyrus (STG), left middle temporal gyrus, and left inferior frontal gyrus. Sources at 2.17 Hz were reconstructed in supratemporal auditory cortex and STG. Crucially, source strength in the left STG at 0.54 Hz was significantly higher in verbal attention than in nonverbal attention condition. This study demonstrates speech-sensitive responses at primary auditory and speech-related neocortical areas. Critically, it highlights that, during word discrimination, top–down attention modulates activity within the left STG. This area therefore appears to play a crucial role in selective verbal attentional processes for this early step of speech processing.
Neural Control of Emotional Actions in Response to Affective Vocalizations
Authors: Koch Saskia B. J. , Galli Alessandra , Volman Inge , Kaldewaij Reinoud , Toni Ivan , Roelofs Karin 
Published: January 2020

Abstract
Social–emotional cues, such as affective vocalizations and emotional faces, automatically elicit emotional action tendencies. Adaptive social–emotional behavior depends on the ability to control these automatic action tendencies. It remains unknown whether neural control over automatic action tendencies is supramodal or relies on parallel modality-specific neural circuits. Here, we address this largely unexplored issue in humans. We consider neural circuits supporting emotional action control in response to affective vocalizations, using an approach–avoidance task known to reliably index control over emotional action tendencies elicited by emotional faces. We isolate supramodal neural contributions to emotional action control through a conjunction analysis of control-related neural activity evoked by auditory and visual affective stimuli, the latter from a previously published data set obtained in an independent sample. We show that the anterior pFC (aPFC) supports control of automatic action tendencies in a supramodal manner, that is, triggered by either emotional faces or affective vocalizations. When affective vocalizations are heard and emotional control is required, the aPFC supports control through negative functional connectivity with the posterior insula. When emotional faces are seen and emotional control is required, control relies on the same aPFC territory downregulating the amygdala. The findings provide evidence for a novel mechanism of emotional action control with a hybrid hierarchical architecture, relying on a supramodal node (aPFC) implementing an abstract goal by modulating modality-specific nodes (posterior insula, amygdala) involved in signaling motivational significance of either affective vocalizations or faces.
Effects of Experience on Spatial Frequency Tuning in the Visual System: Behavioral, Visuocortical, and Alpha-band Responses
Authors: Friedl Wendel M. , Keil Andreas 
Published: January 2020

Abstract
Using electrophysiology and a classic fear conditioning paradigm, this work examined adaptive visuocortical changes in spatial frequency tuning in a sample of 50 undergraduate students. High-density EEG was recorded while participants viewed 400 total trials of individually presented Gabor patches of 10 different spatial frequencies. Patches were flickered to produce sweep steady-state visual evoked potentials (ssVEPs) at a temporal frequency of 13.33 Hz, with stimulus contrast ramping up from 0% to 41% Michelson over the course of each 2800-msec trial. During the final 200 trials, a selected range of Gabor stimuli (either the lowest or highest spatial frequencies, manipulated between participants) were paired with an aversive 90-dB white noise auditory stimulus. Changes in spatial frequency tuning from before to after conditioning for paired and unpaired gratings were evaluated at the behavioral and electrophysiological level. Specifically, ssVEP amplitude changes were evaluated for lateral inhibition and generalization trends, whereas change in alpha band (8–12 Hz) activity was tested for a generalization trend across spatial frequencies, using permutation-controlled F contrasts. Overall time courses of the sweep ssVEP amplitude envelope and alpha-band power were orthogonal, and ssVEPs proved insensitive to spatial frequency conditioning. Alpha reduction (blocking) was most pronounced when viewing fear-conditioned spatial frequencies, with blocking decreasing along the gradient of spatial frequencies preceding conditioned frequencies, indicating generalization across spatial frequencies. Results suggest that alpha power reduction—conceptually linked to engagement of attention and alertness/arousal mechanisms—to fear-conditioned stimuli operates independently of low-level spatial frequency processing (indexed by ssVEPs) in primary visual cortex.
Beat-based and Memory-based Temporal Expectations in Rhythm: Similar Perceptual Effects, Different Underlying Mechanisms
Authors: Bouwer Fleur L. , Honing Henkjan , Slagter Heleen A. 
Published: January 2020

Abstract
Predicting the timing of incoming information allows the brain to optimize information processing in dynamic environments. Behaviorally, temporal expectations have been shown to facilitate processing of events at expected time points, such as sounds that coincide with the beat in musical rhythm. Yet, temporal expectations can develop based on different forms of structure in the environment, not just the regularity afforded by a musical beat. Little is still known about how different types of temporal expectations are neurally implemented and affect performance. Here, we orthogonally manipulated the periodicity and predictability of rhythmic sequences to examine the mechanisms underlying beat-based and memory-based temporal expectations, respectively. Behaviorally and using EEG, we looked at the effects of beat-based and memory-based expectations on auditory processing when rhythms were task-relevant or task-irrelevant. At expected time points, both beat-based and memory-based expectations facilitated target detection and led to attenuation of P1 and N1 responses, even when expectations were task-irrelevant (unattended). For beat-based expectations, we additionally found reduced target detection and enhanced N1 responses for events at unexpected time points (e.g., off-beat), regardless of the presence of memory-based expectations or task relevance. This latter finding supports the notion that periodicity selectively induces rhythmic fluctuations in neural excitability and furthermore indicates that, although beat-based and memory-based expectations may similarly affect auditory processing of expected events, their underlying neural mechanisms may be different.
Local, Cross-cultural, and Global: Japoniste Ceramics in Limoges
Authors: Coman Sonia 
Published: January 2020

Abstract
Ever since its inception Japonisme presented a creative tension between local traditions and cross-cultural practices. Adding to this formative relationship was the simultaneous development of Japonisme across Europe, the United States, and Japan itself. This paper focuses on one place of intersection – Limoges – and one medium – ceramics – to identify the local (Limoges’s rich ceramic history), the cross-cultural (French and Japanese influences), and the global (similar practices in other regions). A constellation of producers and collectors inextricably connected Limoges, a centuries-old hub of French ceramics, with the increasingly global realm of japoniste ceramics. How did the Limoges tradition blend with a Paris-based Japonisme in Limoges-produced japoniste ceramics? And what was the international reception of these ceramics? Cross-regional and cross-temporal emulation was a driving force bridging Japonisme with the latest experiments in the arts, from early abstractionism to revisions of hierarchies of genre and medium.
“The Magic-Making Misṭar Rinālḍs” and the Development of Urdu Prose Fiction
Authors: Naim C.M. 
Published: January 2020

Abstract
In histories of the Urdu novel, the name of G.W.M. Reynolds (1814-1879) is either not mentioned at all or only in passing reference to his possible influence on Sharar, Urdu’s first writer of historical romances. But the actual role that this ill-reputed contemporary of Dickens played in the development of Urdu prose fiction was far greater. By 1918, twenty-four of his massive works were available in Urdu, some in more than one translation, and all reprinted more than once. Among his translators were a number of significant poets and fiction writers of the time. Arguably, between 1890s and 1920, Reynolds was not only the most widely read author in Urdu but also the most admired. He influenced not only writers of historical romances, but also inspired what can be best described as the earliest original crime tales in Urdu.
Tradition and Islamic Philosophy: Some Recent Urdu Publications on Mullā Ṣadrā
Authors: Rizvi Sajjad 
Published: January 2020

Abstract
The reception of Mullā Ṣadrā in South Asia began soon after his death through the dissemination and commentary culture on his Sharḥ al-Hidāyah that was adopted into the Dars-e Niz̤āmī pedagogy in the eighteenth century. However, the modern reception of his thought in Urdu has been somewhat removed from that initial scholastic engagement. I examine four modalities of this reception: translation of his major work the Asfār; analytic engagement by a philosophy doctorate; triumphalism in the literary sphere; and responses to the intellectual challenge of the West by a Shiʿi seminary student. I attempt to show that these varied receptions are indicative of trends and developments in the modern intellectual history of Pakistan.