bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learning for identifying corneal diseases from ocular surface slit-lamp photographs
Authors: Gu Hao , Guo Youwen , Gu Lei , Wei Anji , Xie Shirong , Ye Zhengqiang , Xu Jianjiang , Zhou Xingtao , Lu Yi , Liu Xiaoqing , Hong Jiaxu 
Published: October 2020

AbstractTo demonstrate the identification of corneal diseases using a novel deep learning algorithm. A novel hierarchical deep learning network, which is composed of a family of multi-task multi-label learning classifiers representing different levels of eye diseases derived from a predefined hierarchical eye disease taxonomy was designed. Next, we proposed a multi-level eye disease-guided loss function to learn the fine-grained variability of eye diseases features. The proposed algorithm was trained end-to-end directly using 5,325 ocular surface images from a retrospective dataset. Finally, the algorithm’s performance was tested against 10 ophthalmologists in a prospective clinic-based dataset with 510 outpatients newly enrolled with diseases of infectious keratitis, non-infectious keratitis, corneal dystrophy or degeneration, and corneal neoplasm. The area under the ROC curve of the algorithm for each corneal disease type was over 0.910 and in general it had sensitivity and specificity similar to or better than the average values of all ophthalmologists. Confusion matrices revealed similarities in misclassification between human experts and the algorithm. In addition, our algorithm outperformed over all four previous reported methods in identified corneal diseases. The proposed algorithm may be useful for computer-assisted corneal disease diagnosis.
Crucial transcripts predict response to initial immunoglobulin treatment in acute Kawasaki disease
Authors: Geng Zhimin , Liu Jingjing , Hu Jian , Wang Ying , Tao Yijing , Zheng Fenglei , Wang Yujia , Fu Songling , Wang Wei , Xie Chunhong , Zhang Yiying , Gong Fangqi 
Published: October 2020

AbstractAlthough intravenous immunoglobulin (IVIG) can effectively treat Kawasaki disease (KD), 10–20% of KD patients show no beneficial clinical response. Developing reliable criteria to discriminate non-responders is important for early planning of appropriate regimens. To predict the non-responders before IVIG treatment, gene expression dataset of 110 responders and 61 non-responders was obtained from Gene Expression Omnibus. After weighted gene co-expression network analysis, we found that modules positively correlated with the non-responders were mainly associated with myeloid cell activation. Transcripts up-regulated in the non-responders, IL1R2, GK, HK3, C5orf32, CXCL16, NAMPT and EMILIN2, were proven to play key roles via interaction with other transcripts in co-expression network. The crucial transcripts may affect the clinical response to IVIG treatment in acute KD. And these transcripts may serve as biomarkers and therapeutic targets for precise diagnosis and treatment of the non-responders.
Calpain-2 participates in the process of calpain-1 inactivation
Authors: Shinkai-Ouchi Fumiko , Shindo Mayumi , Doi Naoko , Hata Shoji , Ono Yasuko 
Published: October 2020

Abstract
Calpain-1 and calpain-2 are highly structurally similar isoforms of calpain. The calpains, a family of intracellular cysteine proteases, cleave their substrates at specific sites, thus modifying their properties such as function or activity. These isoforms have long been considered to function in a redundant or complementary manner, as they are both ubiquitously expressed and activated in a Ca2+- dependent manner. However, studies using isoform-specific knockout and knockdown strategies revealed that each calpain species carries out specific functions in vivo. To understand the mechanisms that differentiate calpain-1 and calpain-2, we focused on the efficiency and longevity of each calpain species after activation. Using an in vitro proteolysis assay of troponin T in combination with mass spectrometry, we revealed distinctive aspects of each isoform. Proteolysis mediated by calpain-1 was more sustained, lasting as long as several hours, whereas proteolysis mediated by calpain-2 was quickly blunted. Calpain-1 and calpain-2 also differed from each other in their patterns of autolysis. Calpain-2–specific autolysis sites in its PC1 domain are not cleaved by calpain-1, but calpain-2 cuts calpain-1 at the corresponding position. Moreover, at least in vitro, calpain-1 and calpain-2 do not perform substrate proteolysis in a synergistic manner. On the contrary, calpain-1 activity is suppressed in the presence of calpain-2, possibly because it is cleaved by the latter protein. These results suggest that calpain-2 functions as a down-regulation of calpain-1, a mechanism that may be applicable to other calpain species as well.
The PAR-1 antagonist vorapaxar ameliorates kidney injury and tubulointerstitial fibrosis
Authors: Lok Sarah W.Y. , Yiu Wai Han , Li Hongyu , Xue Rui , Zou Yixin , Li Bin , Chan Kam Wa , Chan Loretta Y.Y. , Leung Joseph C.K. , Lai Kar Neng , Tang Sydney C.W. 
Published: October 2020

Abstract
Protease-activated receptor (PAR)-1 has emerged as a key profibrotic player in various organs including kidney. PAR-1 activation leads to deposition of extracellular matrix (ECM) proteins in the tubulointerstitium and induction of epithelial–mesenchymal transition (EMT) during renal fibrosis. We tested the anti-fibrotic potential of vorapaxar, a clinically approved PAR-1 antagonist for cardiovascular protection, in an experimental kidney fibrosis model of unilateral ureteral obstruction (UUO) and an AKI-to-chronic kidney disease (CKD) transition model of unilateral ischemia–reperfusion injury (UIRI), and dissected the underlying renoprotective mechanisms using rat tubular epithelial cells. PAR-1 is activated mostly in the renal tubules in both the UUO and UIRI models of renal fibrosis. Vorapaxar significantly reduced kidney injury and ameliorated morphologic changes in both models. Amelioration of kidney fibrosis was evident from down-regulation of fibronectin (Fn), collagen and α-smooth muscle actin (αSMA) in the injured kidney. Mechanistically, inhibition of PAR-1 inhibited MAPK ERK1/2 and transforming growth factor-β (TGF-β)-mediated Smad signaling, and suppressed oxidative stress, overexpression of pro-inflammatory cytokines and macrophage infiltration into the kidney. These beneficial effects were recapitulated in cultured tubular epithelial cells in which vorapaxar ameliorated thrombin- and hypoxia-induced TGF-β expression and ECM accumulation. In addition, vorapaxar mitigated capillary loss and the expression of adhesion molecules on the vascular endothelium during AKI-to-CKD transition. The PAR-1 antagonist vorapaxar protects against kidney fibrosis during UUO and UIRI. Its efficacy in human CKD in addition to CV protection warrants further investigation.
The role of DNA damage response in amyotrophic lateral sclerosis
Authors: Sun Yu , Curle Annabel J. , Haider Arshad M. , Balmus Gabriel 
Published: October 2020

Abstract
Amyotrophic lateral sclerosis (ALS) is a rapidly disabling and fatal neurodegenerative disease. Due to insufficient disease-modifying treatments, there is an unmet and urgent need for elucidating disease mechanisms that occur early and represent common triggers in both familial and sporadic ALS. Emerging evidence suggests that impaired DNA damage response contributes to age-related somatic accumulation of genomic instability and can trigger or accelerate ALS pathological manifestations. In this review, we summarize and discuss recent studies indicating a direct link between DNA damage response and ALS. Further mechanistic understanding of the role genomic instability is playing in ALS disease pathophysiology will be critical for discovering new therapeutic avenues.
Low-Frequency Repetitive Transcranial Magnetic Stimulation in Patients With Poststroke Aphasia: Systematic Review and Meta-Analysis of Its Effect Upon Communication
Authors: Yao Liqun , Zhao Hongjia , Shen Cuiling , Liu Fang , Qiu Li , Fu Lisang 
Published: October 2020

ObjectiveThe aim of the study was to investigate the effectiveness and safety of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) in patients with poststroke aphasia.MethodWe comprehensively searched for eligible studies from 11 electronic medical databases from their inception to February 20, 2019. Randomized controlled trials reporting the effectiveness of LF-rTMS for patients with poststroke aphasia were included. The primary outcome was language ability. The secondary outcomes were functional communication and adverse events. The methodological quality of the randomized controlled trials was evaluated by the Cochrane Back Review Group Risk of Bias Assessment Criteria.ResultsOf the 567 records retrieved, 18 studies with a total of 536 participants were included. All the included studies were of relatively acceptable methodological quality. All studies but one used LF-rTMS + speech and language therapy (SLT), not LF-rTMS alone. The meta-analysis showed that LF-rTMS had beneficial effects for patients with aphasia after a stroke in terms of naming, repetition, comprehension, written language, and functional communication. The subgroup analyses of language performance showed positive effects of LF-rTMS among stroke patients with chronic aphasia and acute aphasia. LF-rTMS + SLT had effects on language performance that were superior to the sham rTMS + SLT and SLT alone. A shorter LF-rTMS duration benefited language performance more than a longer duration. Additionally, 20 min of LF-rTMS per session produced a positive effect on language ability for patients with aphasia after a stroke. No adverse events were reported.ConclusionsLF-rTMS + SLT is an effective and safe method for patients with poststroke aphasia to improve their language performance. Additionally, the most commonly used LF-rTMS protocol for patients with aphasia after a stroke was 90% of the resting motor threshold 20 min per day, 5 days per week, for 2 weeks.
First sample of N2H+ nitrogen isotopic ratio measurements in low-mass protostars
Authors: Redaelli E. , Bizzocchi L. , Caselli P. 
Published: October 2020

Context. The nitrogen isotopic ratio is considered an important diagnostic tool of the star formation process, and N2H+ is particularly important because it is directly linked to molecular nitrogen N2. However, theoretical models still do not provide an exhaustive explanation for the observed 14N/15N values.
Aims. Recent theoretical works suggest that the 14N/15N behaviour is dominated by two competing reactions that destroy N2H+: dissociative recombination and reaction with CO. When CO is depleted from the gas phase, if the N2H+ recombination rate is lower with respect to that for N15NH+, the rarer isotopologue is destroyed more quickly. In prestellar cores, due to a combination of low temperatures and high densities, most CO is frozen in ices onto the dust grains, leading to high levels of depletion. On the contrary, in protostellar cores, where temperature are higher, CO ices evaporate back to the gas phase. This implies that the N2H+ isotopic ratio in protostellar cores should be lower than that in prestellar cores, and consistent with the elemental value of ≈440. We aim to test this hypothesis, producing the first sample of N2H+∕N15NH+ measurements in low-mass protostars.
Methods. We observe the N2H+ and N15NH+ lowest rotational transition towards six young stellar objects in the Perseus and Taurus molecular clouds. We model the spectra with a custom python code using a constant Tex approach to fit the observations. We discuss in the Appendix the validity of this hypothesis. The derived column densities are used to compute the nitrogen isotopic ratios.
Results. Our analysis yields an average of 14N/15N|pro = 420 ± 15 in the protostellar sample. This is consistent with the protosolar value of 440, and significantly lower than the average value previously obtained in a sample of prestellar objects.
Conclusions. Our results are in agreement with the hypothesis that, when CO is depleted from the gas-phase, dissociative recombinations with free electrons destroy N15NH+ faster than N2H+, leading to high isotopic ratios in prestellar cores where carbon monoxide is frozen onto dust grains.
Equines Choriongonadotropin: Biologie und veterinärmedizinische Bedeutung
Authors: Schuler Gerhard 
Published: October 2020

ZusammenfassungDie hypophysären Gonadotropine follikelstimulierendes Hormon (FSH) und luteinisierendes Hormon (LH) spielen eine zentrale Rolle bei der Steuerung der Gonadenfunktionen. Daher ist ihr Einsatz in der Therapie von Fruchtbarkeitsstörungen (z. B. Azyklie) sowie in der Biotechnologie (z. B. Superovulation, Hormonprogramme zur Zyklussynchronisation) prinzipiell von hohem Interesse. Präparationen von FSH bzw. LH sind aufgrund der aufwendigen Gewinnung aus Hypophysengewebe relativ teuer und daher besonderen Anwendungen vorbehalten. Bei Primaten- und Equidenarten wurde die Expression eines LH-ähnlichen Moleküls im Chorionepithel nachgewiesen (Choriongonadotropin, CG). Equines CG (eCG) weist außer bei Equiden, bei denen es ausschließlich an LH-Rezeptoren bindet, bei allen bei uns üblichen Haussäugetierspezies neben seiner LH-Aktivität eine außerordentlich hohe FSH-Aktivität auf („duale Wirkung“). Seit seiner Markteinführung kommt ihm daher eine hohe Bedeutung als vergleichsweise kostengünstiges FSH-Analogon vorwiegend zur Anwendung bei Wiederkäuern und Schwein zu. Im Gegensatz zu dem als LH-Analogon eingesetzten humanen CG (hCG), das nicht invasiv aus dem Urin schwangerer Frauen isoliert werden kann, muss die Gewinnung von eCG aus dem Blut trächtiger Spenderstuten erfolgen, da im Urin nur minimale eCG-Konzentrationen vorliegen. Nach Berichten über Todesfälle und Leiden von Spenderstuten im Zusammenhang mit der eCG-Gewinnung in südamerikanischen Haltungen ist das derzeitige Verfahren der eCG-Produktion zunehmend in die öffentliche Kritik geraten, was zuletzt in Forderungen nach einem generellen Verbot mündete. Ziel dieses Beitrags ist daher, den aktuellen Kenntnisstand zu Eigenschaften und Biologie dieses auch aus Sicht der Grundlagenwissenschaft hochinteressanten Moleküls kurz zusammenzufassen.
Impact of the COVID-19 pandemic on gastrointestinal endoscopy in the Netherlands: analysis of a prospective endoscopy database
Authors: Lantinga Marten A. , Theunissen Felix , ter Borg Pieter C. J. , Bruno Marco J. , Ouwendijk Rob J. T. , Siersema Peter D. ,   on behalf of the Trans.IT foundation study group
Published: October 2020

Abstract
Background COVID-19 has dramatically affected gastrointestinal endoscopy practice. We aimed to investigate its impact on procedure types, indications, and findings.
Methods We retrospectively analyzed endoscopies performed in 15 Dutch hospitals by comparing periods 15 March to 25 June of 2019 and 2020 using the prospective Trans.IT database.
Results During lockdown in 2020, 9776 patients underwent endoscopy compared with 19 296 in 2019. Gastroscopies decreased by 57 % (from 7846 to 4467) and colonoscopies by 45 % (from 12219 to 5609), whereas endoscopic retrograde cholangiopancreatography volumes remained comparable (from 578 to 522). Although endoscopy results indicative of cancer decreased (from 524 to 340), the likelihood of detecting cancer during endoscopy increased (2.7 % [95 % confidence interval (CI) 2.5 – 3.0] in 2019 versus 3.5 % [95 %CI 3.1 – 3.9] in 2020; P < 0.001). After lifting of lockdown, endoscopy volumes started to return to normal, except for colorectal cancer screening.
Conclusions Fewer endoscopies were performed during the COVID-19 lockdown, leading to a significant reduction in the absolute detection of cancer. Endoscopies increased rapidly after lockdown, except for colorectal cancer screening.
Determining the Relative Configuration of Propargyl Cyclopropanes by Co-Crystallization
Authors: Richert Clemens , Krupp Felix , Picher Marie-Idrissa , Frey Wolfgang , Plietker Bernd 
Published: October 2020

AbstractDetermining the diastereoselectivity of new synthetic mo­lecules can be a challenge when NMR methods fail and the compounds are difficult to crystallize. Encapsulating organic crystals can be used to overcome this challenge. Here we show that the diastereomeric confi­guration of racemic mixtures of propargyl cyclopropanes can be determined by co-crystallization with 1,3,5,7-tetrakis(2-bromo-4-methoxyphenyl)adamantane and X-ray crystallography. Three crystal structures are reported that unambiguously identify the products of Fe-catalyzed cyclopropanations as cis- or trans-isomers. These findings expand the scope of co-crystallization with tetraaryladamantanes as a method to determine the stereochemical configuration of organic molecules that are difficult to crystallize by themselves.
Recent Developments in Transition-Metal-Catalyzed Asymmetric Hydrogenation of Enamides
Authors: Phansavath Phannarath , Ratovelomanana-Vidal Virginie , Ponra Sudipta , Boudet Bernard 
Published: October 2020

AbstractThe catalytic asymmetric hydrogenation of prochiral olefins is one of the most widely studied and utilized transformations in asymmetric synthesis. This straightforward, atom economical, inherently direct and sustainable strategy induces chirality in a broad range of substrates and is widely relevant for both industrial applications and academic research. In addition, the asymmetric hydrogenation of enamides has been widely used for the synthesis of chiral amines and their derivatives. In this review, we summarize the recent work in this field, focusing on the development of new catalytic systems and on the extension of these asymmetric reductions to new classes of enamides.1	Introduction2	Asymmetric Hydrogenation of Trisubstituted Enamides2.1	Ruthenium Catalysts2.2	Rhodium Catalysts2.3	Iridium Catalysts2.4	Nickel Catalysts2.5	Cobalt Catalysts3	Asymmetric Hydrogenation of Tetrasubstituted Enamides3.1	Ruthenium Catalysts3.2	Rhodium Catalysts3.3	Nickel Catalysts4	Asymmetric Hydrogenation of Terminal Enamides4.1	Rhodium Catalysts4.2	Cobalt Catalysts5	Rhodium-Catalyzed Asymmetric Hydrogenation of Miscellaneous Enamides6	Conclusions
Biobased Spiroimides from Itaconic Acid and Formamides: Molecular Targets for a Novel Synthetic Application of Renewable Chemicals
Authors: Andrade Leandro Helgueira , Hornink Milene Macedo , Lopes Alice Uva 
Published: October 2020

AbstractSpiroimides exhibit a wide range of biological activities, such as anticonvulsant, antiarrhythmic, and antihyperglycemic activities. Herein, a novel synthetic application of renewable chemicals, itaconic acid and formamides, is described. Proper exploitation of the reactivity of itaconic acid and formamide allows for the development of an efficient synthetic approach for the production of several new biobased spiroimides, spiro[dihydroquinolin-2-one-succinimides] and spiro[indolin-2-one-glutarimides], in excellent overall yields (up to 98%).
Predictive Value of Alvarado Score and Pediatric Appendicitis Score in the Success of Nonoperative Management for Simple Acute Appendicitis in Children
Authors: Fuhrer Audelia Eshel , Sukhotnik Igor , Ben-Shahar Yoav , Weinberg Mark , Koppelmann Tal 
Published: October 2020

AbstractIntroduction During the past decade, nonoperative management (NOM) for simple acute appendicitis (SAA) in children has been proven safe with noninferior complications rate. The aim of this study was to examine Alvarado score and pediatric appendicitis score (PAS) together with other factors in predicting failure of NOM in children presenting with SAA.Materials and Methods Patients aged 5 to 18 years admitted to our department between 2017 and 2019 diagnosed with SAA were given a choice between surgical management and NOM. We divided the NOM patients into two groups: successful treatment and failed NOM, comparing their files for Alvarado score and PAS and other clinical and demographic factors, with a mean follow-up of 7 months. Failure was determined as need for appendectomy following conservative treatment due to any reason.Results A total of 85 patients answered criteria and chose NOM. Overall failure rate was 32.9%. We found no difference in the mean Alvarado score and PAS as well as in each component of both scores between success and failed NOM groups. However, when using the risk classification of the scores, we found a significant correlation between high-risk Alvarado score and failed NOM. After adjusting for age, gender, duration of symptoms, diagnosis of tip appendicitis, and presence of appendicolith, the odds of failure were four times higher among high-risk Alvarado group.Conclusion Alvarado score of 7 or higher, older age, and diagnosis of an appendicolith on imaging are possible predictors for failure of NOM for SAA in children.
The Dental, Oral, Medical Epidemiological (DOME) Study: Protocol and Study Methods
Authors: Almoznino Galit , Kedem Ron , Turgeman Ronit , Bader Tarif , Yavnai Nirit , Zur Dorit , Shay Boaz 
Published: October 2020

AbstractObjectives To develop and present the methods utilized for the Dental, Oral, Medical Epidemiological (DOME) study.Methods The DOME is an electronic record-based cross-sectional study, that was conducted to measure the dental, periodontal, and oral morbidities and their associations with systemic morbidities, among a nationally representative sample of young to middle-aged adults military personnel from the IDF (Israel Defense Forces). To that end, we developed a strict protocol including standardized terminology, data collection, and handling.Results Data for the DOME study was derived simultaneously from three electronic records of the IDF: (1) a central demographic database, (2) the dental patient record (DPR), and (3) the medical computerized patient record (CPR). The established DOME repository includes socio-demographic, dental and medical records of 132,354 young to middle-age military personnel from the IDF, who attended the dental clinics during the year 2015. Records of general military personnel (N > 50,000), with no recorded dental visits during the study period, served as a control group regarding all other parameters except dental. The DOME study continues and is currently collecting longitudinal data from the year 2010 until 2020. The IDF employs a standardized uniform administrative and clinical work-up and treatment protocols as well as uniform computerized codes. We describe the standardized definitions for all the parameters that were included: socio-demographics, health-related habits, medical and dental attendance patterns, and general and dental health status. Multicollinearity analysis results of the sociodemographic and medical study parameters are presented.Conclusion Standardized work-up and definitions are essential to establish the centralized DOME data repository to study the extent of dental and systemic morbidities and their associations.