bluuebunny/crossref_metadata_2025_split huggingface dataset:
KAP1 silencing relieves OxLDL-induced vascular endothelial dysfunction by down-regulating LOX-1
Authors: Yan Tianqing , Liang Chang , Fan Haidi , Zhou Wei , Huang Linyan , Qi Suhua , Wang Wan , Ma Ping 
Published: July 2020

Abstract
KRAB domain-associated protein 1 (KAP1) is highly expressed in atherosclerotic plaques. Here, we studied the role of KAP1 in atherosclerosis development using a cell model of endothelial dysfunction induced by oxidative low-density lipoprotein (OxLDL). The phosphorylation and protein levels of KAP1 were similar between OxLDL-treated and non-treated endothelial cells (ECs). KAP1 depletion significantly inhibited the production of OxLDL-enhanced reactive oxygen species and the expression of adhesion molecules in ECs. Treatment with OxLDL promoted the proliferation and migration of ECs, which was also confirmed by the elevated levels of the proliferative markers c-Myc and PCNA, as well as the migratory marker MMP-9. However, these effects were also abrogated by KAP1 depletion. Moreover, the depletion of KAP1 in OxLDL-treated ECs resulted in decreases in the LOX-1 level and increases in eNOS expression. Generally, the data suggest that strategies targeting KAP1 depletion might be particularly useful for the prevention or treatment of atherosclerosis.
Obeticholic acid ameliorates hepatorenal syndrome in ascitic cirrhotic rats by down-regulating the renal 8-iso-PGF2α-activated COX-TXA2 pathway
Authors: Tsai Yu-Lien , Liu Chih-Wei , Hsu Chien-Fu , Huang Chia-Chang , Lin Ming-Wei , Huang Shiang-Fen , Li Tzu-Hao , Lee Kuei-Chuan , Hsieh Yun-Cheng , Yang Ying-Ying , Lee Tzung-Yan , Liu Hsuan-Miao , Huang Yi-Hsiang , Hou Ming-Chih , Lin Han-Chieh 
Published: July 2020

Abstract
Backgrounds/Aims: The present study explores the potential of chronic treatment with the Foresaid X receptor (FXR) agonist obeticholic acid (OCA), which inhibits oxidative stress-related pathogenesis, in ascitic cirrhotic rats with hepatorenal syndrome (HRS) developed 6 weeks after bile duct ligation (BDL). Methods: Systemic, splanchnic, and renal hemodynamics and pathogenic cascades were measured in ascitic BDL and sham rats receiving 2-weeks of either vehicle or OCA treatments (sham-OCA and BDL-OCA groups), and NRK-52E cells, rat kidney tubular epithelial cells. Results: Chronic OCA treatment significantly normalized portal hypertension, glomerular filtration rate, urine output, renal blood flow; decreased ascites, renal vascular resistance, serum creatinine, and the release of renal tubular damage markers, including urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury moleculae-1 (uKim-1) in BDL-OCA rats. In the BDL group, inhibition of the renal oxidative stress (8-iso-PGF2α)-activated cyclooxygenase-thromboxane A2 [COX-TXA2] pathway, apoptosis, and tubular injury accompanied by a decrease in hyper-responsiveness to the vasoconstrictor 8-iso-PGF2α in perfused kidneys. In vitro experiments revealed that 8-iso-PGF2α induced oxidative stress, release of reactive oxygen species, and cell apoptosis, which were reversed by concomitant incubation with the FXR agonist. Conclusions: Through the inhibition of renal 8-iso-PGF2α production and the down-regulation of the COX-TXA2 pathway, our study suggests that chronic OCA treatment can ameliorate the HRS in ascitic cirrhotic rats. Thus, OCA is an agent with antioxidative stress, antivasoconstrictive, antiapoptotic properties which benefit ascitic, cirrhotic rats with systemic, hepatic, and renal abnormalities.
Patterns of Misidentified Vowels in Individuals With Dysarthria Secondary to Amyotrophic Lateral Sclerosis
Authors: Lee Jimin , Kim Heejin , Jung Yong 
Published: July 2020

Purpose
The current study examines the pattern of misidentified vowels produced by individuals with dysarthria secondary to amyotrophic lateral sclerosis (ALS).

Method
Twenty-three individuals with ALS and 22 typical individuals produced 10 monophthongs in an /h/-vowel-/d/ context. One hundred thirty-five listeners completed a forced-choice vowel identification test. Misidentified vowels were examined in terms of the target vowel categories (front–back; low–mid–high) and the direction of misidentification (the directional pattern when the target vowel was misidentified, e.g., misidentification “to a lower vowel”). In addition, acoustic predictors of vowel misidentifications were tested based on log first formant (F1), log second formant, log F1 vowel inherent spectral change, log second formant vowel inherent spectral change, and vowel duration.

Results
First, high and mid vowels were more frequently misidentified than low vowels for all speaker groups. Second, front and back vowels were misidentified at a similar rate for both the Mild and Severe groups, whereas back vowels were more frequently misidentified than front vowels in typical individuals. Regarding the direction of vowel misidentification, vowel errors were mostly made within the same backness (front–back) category for all groups. In addition, more errors were found toward a lower vowel category than toward a higher vowel category in the Severe group, but not in the Mild group. Overall, log F1 difference was identified as a consistent acoustic predictor of the main vowel misidentification pattern.

Conclusion
Frequent misidentifications in the vowel height dimension and the acoustic predictor, F1, suggest that limited tongue height control is the major articulatory dysfunction in individuals with ALS. Clinical implications regarding this finding are discussed.
Comparison of Diagnostic Auditory Processing Test Scores Measured in Clinical and School Settings
Authors: Mamatha Nerale Maraiah , Yathiraj Asha 
Published: July 2020

PurposeThe study aimed to compare auditory processing and cognitive test scores measured in a clinical setting with that measured in a school setting using a repeated-measures design. This was done on typically developing children and children with auditory processing disorder (APD).MethodThirty-two children (16 typically developing and 16 with APD), aged 7 years, were evaluated using three diagnostic auditory processing tests and a cognitive test. The tests included the Speech Perception in Noise Test in Kannada, the Gap Detection Threshold Test, the Dichotic Consonant–Vowel Test, and the Auditory Memory and Sequencing Test in Kannada. All the children were evaluated in an audiological diagnostic setting, as well as in their school.ResultsNo significant difference in scores was obtained in the two settings for all the four tests that were administered. This was seen in the typically developing children and the children with APD. Additionally, the pass/fail decision for each test did not alter in the two settings. Moderate to almost perfect agreement was seen between the tests carried out in the two settings in both groups, on a Kappa test of agreement. In both settings, the children with APD performed significantly poorer than the typically developing children on the four diagnostic tests.ConclusionsThe findings of the study indicate that the diagnostic auditory processing tests and the cognitive test can be carried out in school settings as effectively as tests carried out in an audiological diagnostic clinical setting. This will enable carrying out diagnostic tests on children in schools soon after they are referred on screening auditory processing tools, administered in the educational setting. This will prevent missing diagnosis of children who fail to report to a diagnostic audiological center for detailed auditory processing evaluation.
Colors of an Earth-like exoplanet
Authors: Groot A. , Rossi L. , Trees V. J. H. , Cheung J. C. Y. , Stam D. M. 
Published: July 2020

Context. Understanding the total flux and polarization signals of Earth-like planets and their spectral and temporal variability is essential for the future characterization of such exoplanets.
Aims. We provide computed total (F) and linearly (Q and U) and circularly (V) polarized fluxes, and the degree of polarization P of sunlight that is reflected by a model Earth, to be used for instrument designs, optimizing observational strategies, and/or developing retrieval algorithms.
Methods. We modeled a realistic Earth-like planet using one year of daily Earth-observation data: cloud parameters (distribution, optical thickness, top pressure, and particle effective radius), and surface parameters (distribution, surface type, and albedo). The Stokes vector of the disk-averaged reflected sunlight was computed for phase angles α from 0° to 180°, and for wavelengths λ from 350 to 865 nm.
Results. The total flux F is one order of magnitude higher than the polarized flux Q, and Q is two and four orders of magnitude higher than U and V, respectively. Without clouds, the peak-to-peak daily variations due to the planetary rotation increase with increasing λ for F, Q, and P, while they decrease for U and V. Clouds modify but do not completely suppress the variations that are due to rotating surface features. With clouds, the variation in F increases with increasing λ, while in Q, it decreases with increasing λ, except at the largest phase angles. In earlier work, it was shown that with oceans, Q changes color from blue through white to red. The α where the color changes increases with increasing cloud coverage. Here, we show that this unique color change in Q also occurs when the oceans are partly replaced by continents, with or without clouds. The degree of polarization P shows a similar color change. Our computed fluxes and degree of polarization will be made publicly available.
Current and Future Perspectives on ADAMTS13 and Thrombotic Thrombocytopenic Purpura
Authors: Roose Elien , Joly Bérangère S. 
Published: July 2020

AbstractThrombotic thrombocytopenic purpura (TTP) is a rare, relapsing, and life-threatening disorder with an annual incidence of 10 cases per million people. TTP is a thrombotic microangiopathy characterized by severe thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia. The disease is caused by a severe deficiency of the enzyme ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13), which can either be acquired, mainly by autoantibodies targeting ADAMTS13, or congenital due to mutations in the ADAMTS13 gene. Thanks to the establishment of national registries worldwide, fundamental and translational research, major advances have been made on the diagnosis, treatment, and fundamental understanding of TTP, since the description of the first TTP case almost 100 years ago. The introduction of therapeutic plasma exchange in the 1970s has significantly improved patient survival, but novel diagnostic assays, targeted treatments (rituximab, caplacizumab, recombinant ADAMTS13), and the unraveling of both ADAMTS13 function and TTP pathophysiology should help to further improve the patients' quality of life. However, differential diagnosis of TTP remains challenging and still a lot of questions remain unanswered to completely understand this rare and devastating disease.
The Evolution of Hemophilia Care: Clinical and Laboratory Advances, Opportunities, and Challenges
Authors: Trinchero Alice , Sholzberg Michelle , Matino Davide 
Published: July 2020

AbstractHemophilia A (HA) and B (HB) are X-linked bleeding disorders caused by mutations in the F8 or F9 gene that result in the absence, or reduced activity, of the corresponding clotting factor. The severity of bleeding and related complications is proportional to the amount of residual circulating functional factor. The development of a safe and effective hemophilia treatment lasted several decades and has been mainly based on clotting factor replacement. Advances in the engineering and manufacturing of clotting concentrates have led to the widespread availability of extended half-life products that reduced the number of intravenous infusions needed to achieve adequate trough levels. The recent development of new nonfactor replacement treatments and biotechnology techniques has offered therapeutic alternatives for hemophilia patients with and without inhibitors. These are characterized by an easier route of administration, low immunogenicity, and, regarding gene therapy and cell-based treatments, potential long-term protection from bleeding after a single treatment course. In this review, we analyze recent progresses in the management of hemophilia and discuss opportunities and challenges.
Role of Platelet Cytoskeleton in Platelet Biomechanics: Current and Emerging Methodologies and Their Potential Relevance for the Investigation of Inherited Platelet Disorders
Authors: Zaninetti Carlo , Sachs Laura , Palankar Raghavendra 
Published: July 2020

AbstractCytoskeleton is composed of more than 100 proteins and represents a dynamic network of the cellular cytoplasm. Cytoskeletal functions include spatial organization of cellular components, structural connection of the cell with external environment, and biomechanical force generation. Cytoskeleton takes part, at different levels, in all phases of platelet biogenesis: megakaryocyte (MK) differentiation, MK maturation, and platelet formation. In addition, it also plays a major role in each stage of platelet function. Inherited platelet disorders (IPDs) are a group of rare diseases featured by low platelet count and/or impaired platelet function. Over the past decade, the investigation of platelet biomechanics has become a major and highly relevant theme of research due to its implications at every stage of development of human life. The initial use of diverse biophysical techniques (e.g., micropipette aspiration, atomic force and scanning ion conductance microscopy, real-time deformability cytometry) started unraveling biomechanical features of platelets that are expected to provide new explanations for physiological and pathological mechanisms. Although the impact of cytoskeletal alterations has been largely elucidated in various IPDs' pathogenesis, the understanding of their impact on biomechanical properties of platelets represents an unmet need. Regarding IPDs, improving biomechanical studies seems promising for diagnostic and prognostic implications. Potentially, these characteristics of platelets may also be used for the prediction of bleeding risk. This review addresses the current available methods for biophysical investigations of platelets and the possible implementations in the field of IPDs.
Understanding and Preventing Placenta-Mediated Pregnancy Complications
Authors: Skeith Leslie , Blondon Marc , Ní Áinle Fionnuala 
Published: July 2020

AbstractPlacenta-mediated pregnancy complications are clinically important conditions and include preeclampsia, placental abruption, intrauterine growth restriction, and late fetal loss. Pathophysiology is complex, and may be linked to prothrombotic disorders such as antiphospholipid syndrome, whose understanding is still evolving. In this narrative review, we will present the latest evidence to better understand hemostatic mechanisms of preeclampsia, as well as in women with placenta-mediated pregnancy complications and inherited thrombophilia or antiphospholipid antibodies. Using four clinical scenarios, the mixed results of preventive efforts through the use of antithrombotic drugs (aspirin, heparin) will be discussed. We will also review knowledge gaps and ongoing research.
Welchen Einfluss hat die Dauer der Oberarzttätigkeit auf die Berufsausübung und Zufriedenheit urologischer OberärztInnen in Deutschland?
Authors: Necknig Ulrike H. , Wolff Ingmar , Bründl Johannes , Kriegmair Maximilian C. , Marghawal David , Wagener Nina , Hegemann Miriam , Eder Elisabeth , Wülfing Christian , Burger Maximilian , Leyh Herbert , May Matthias , Kiesewetter Jan , Weidenbusch Marc 
Published: July 2020

Zusammenfassung
Hintergrund Urologische OberärztInnen in Deutschland stellen eine heterogene Berufsgruppe mit verschiedenen klinischen Schwerpunkten und Karriereabsichten dar. Bisher gibt es keine gesicherten Kenntnisse darüber, welchen Einfluss die Anzahl der Berufsjahre in dieser Position auf die aktuelle Berufsausübung und Zufriedenheit hat.
Material und Methoden Ziel der vorliegenden Studie war die vergleichende Analyse der berufsbezogenen Sichtweisen, des privaten und beruflichen Umfelds, der konkreten Tätigkeiten und der fachlichen Zielvorstellungen urologischer OberärztInnen in Deutschland anhand der Anzahl der Berufsjahre in dieser Position (Dichotomisierung bei 8 Jahren Oberarzttätigkeit). Im Rahmen einer Querschnittsstudie wurde ein 55 Items umfassender, webbasierter Fragebogen entwickelt, der als Link über den E-Mail-Verteiler der Deutschen Gesellschaft für Urologie versendet wurde und zwischen Februar und April 2019 für urologische OberärztInnen geöffnet war. Unterschiede zwischen beiden Gruppen wurden mittels multivariater Regressionsmodelle geprüft.
Ergebnisse 192 Studienfragebögen urologischer OberärztInnen waren auswertbar, von denen 107 (55,7 %) und 85 (44,3 %) eine Oberarzttätigkeit < 8 Jahre (< 8J-OÄ) bzw. ≥ 8 Jahre (≥ 8J-OÄ) aufwiesen. In der Gruppe < 8J-OÄ arbeiteten signifikant mehr Teilnehmer an Universitätskliniken (42,1 % vs. 18,8 %, p = 0,002). Insgesamt gaben 82,4 % der Teilnehmer in der Gruppe ≥ 8J-OÄ an, die offen operative Chirurgie eigenständig sicher durchzuführen, während dies in der Gruppe < 8J-OÄ nur von 39,3 % so eingeschätzt wurde (p < 0,001). Keine signifikanten Unterschiede bez. des eigenen Kompetenzniveaus fanden sich bei endourologischen Verfahren (94,1 % vs. 87,9 %) sowie bez. der insgesamt eher niedrig eingeschätzten eigenen Kompetenz in der Laparoskopie (29,4 % vs. 20,6 %) und der robotischen Chirurgie (14,1 % vs. 10,3 %). Trotz der hohen organisatorischen Verantwortung als urologische OberärztInnen hat nur ungefähr ein Drittel der Teilnehmer (34,8 %) eine Weiterbildungsmaßnahme zur Vorbereitung auf Leitungs- und Führungsaufgaben erhalten.
Schlussfolgerung Die vorliegende Studie zeigt deutliche Unterschiede bez. der operativen Fertigkeiten in Abhängigkeit von der Dauer der bisherigen OA-Tätigkeit. Außerdem wird eine erhebliche Unzufriedenheit mit der Förderung von Führungsqualitäten und der Vorbereitung auf Führungsaufgaben deutlich. Um qualifiziertes Personal langfristig als urologische OberärztInnen an den Kliniken im Fach Urologie zu binden, erscheint es notwendig, die Bedürfnisse der Berufsgruppe zu berücksichtigen und Defizite durch strategische Förderungen zu beheben.
New Alkenylresorcinols with Cytotoxic and Antimicrobial Activities from the Leaves of Embelia schimperi
Authors: Togue Tatiana Arlette M. , Ndontsa Blanche Laure , Bitchagno Gabin Thierry M. , Schüffler Anja , Opatz Till , Tane Pierre , Tene Mathieu 
Published: July 2020

AbstractA phytochemical study of the methanol extract of the leaves of Embelia schimperi resulted in the isolation of three new alkenylresorcinols, 1 – 3, together with the known analogs 4 – 7. Their structures were established by a combination of spectroscopic techniques. Compounds 1 – 7 exhibited moderate cytotoxic activity against human cervical cancer cells HeLa-S3 and more pronounced antimicrobial properties towards bacteria and filamentous fungi. The present study falls into an ongoing research project on the characterization of bioactive phenolic lipids from plants of the family Primulaceae.
A deep learning-based system for identifying differentiation status and delineating the margins of early gastric cancer in magnifying narrow-band imaging endoscopy
Authors: Ling Tingsheng , Wu Lianlian , Fu Yiwei , Xu Qinwei , An Ping , Zhang Jun , Hu Shan , Chen Yiyun , He Xinqi , Wang Jing , Chen Xi , Zhou Jie , Xu Youming , Zou Xiaoping , Yu Honggang 
Published: July 2020

AbstractBackground Accurate identification of the differentiation status and margins for early gastric cancer (EGC) is critical for determining the surgical strategy and achieving curative resection in EGC patients. The aim of this study was to develop a real-time system to accurately identify differentiation status and delineate the margins of EGC on magnifying narrow-band imaging (ME-NBI) endoscopy.Methods 2217 images from 145 EGC patients and 1870 images from 139 EGC patients were retrospectively collected to train and test the first convolutional neural network (CNN1) to identify EGC differentiation status. The performance of CNN1 was then compared with that of experts using 882 images from 58 EGC patients. Finally, 928 images from 132 EGC patients and 742 images from 87 EGC patients were used to train and test CNN2 to delineate the EGC margins.Results The system correctly predicted the differentiation status of EGCs with an accuracy of 83.3 % (95 % confidence interval [CI] 81.5 % – 84.9 %) in the testing dataset. In the man – machine contest, CNN1 performed significantly better than the five experts (86.2 %, 95 %CI 75.1 % – 92.8 % vs. 69.7 %, 95 %CI 64.1 % – 74.7 %). For delineating EGC margins, the system achieved an accuracy of 82.7 % (95 %CI 78.6 % – 86.1 %) in differentiated EGC and 88.1 % (95 %CI 84.2 % – 91.1 %) in undifferentiated EGC under an overlap ratio of 0.80. In unprocessed EGC videos, the system achieved real-time diagnosis of EGC differentiation status and EGC margin delineation in ME-NBI endoscopy.Conclusion We developed a deep learning-based system to accurately identify differentiation status and delineate the margins of EGC in ME-NBI endoscopy. This system achieved superior performance when compared with experts and was successfully tested in real EGC videos.
Unconventional Transformations of Morita–Baylis–Hillman Adducts
Authors: Companyó Xavier , Calcatelli Alessio , Cherubini-Celli Alessio , Carletti Edoardo 
Published: July 2020

Morita–Baylis–Hillman (MBH) adducts are versatile starting materials widely employed in Lewis base catalysis. A myriad of different transformations have been reported based on either allylic alkylations with stabilised nucleophiles or annulations with diverse dipolarophiles. Apart from these two conventional types of reactivity, MBH adducts have recently been implemented in alternative and complementary catalytic strategies, including: (i) one-pot and cascade transformations, where additional chemical bonds are formed following the asymmetric allylic alkylation event in a single synthetic operation; (ii) regioselective α-allylations for the synthesis of trisubstituted alkenes; and (iii) dual activation strategies, involving Lewis base catalysis together with transition metal complexes or light, enabling allylic alkylations with nonstabilised nucleophiles and cascade processes. The present Short Review summarises the most significant unconventional catalytic transformations of racemic MBH adducts reported within the last decade.1	Introduction2	Multi-Step Single-Vessel Transformations (path iii)2.1	One-Pot Transformations2.2	Cascade Transformations3	α-Allylations (path iv)3.1	SN2′ Mechanism3.2	SN2′–SN2 Mechanism3.3	Miscellaneous Mechanisms4	Dual Activation (path v)4.1	MBH Adduct as Electrophile4.2	MBH Adduct as Nucleophile5	Summary and Outlook