bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of 0.05% cyclosporine ophthalmic emulsion in treatment of Chinese patients with moderate to severe dry eye disease: A 12-week, multicenter, randomized, double-masked, placebo-controlled phase III clinical study
Authors: Chen Di , Zhang Shunhua , Bian Ailing , Hong Jing , Deng Yingping , Zhang Mingchang , Chen Wei , Shao Yan , Zhao Jialiang 
Published: August 2019

Abstract

Background:
Dry eye disease (DED) is a chronic ocular surface disease that affects hundreds of millions of people worldwide. Although 0.05% cyclosporine ophthalmic emulsion (CsA OE) has long been prescribed in the U.S. for the treatment of DED, it is not commercially available in China. Our study aims to compare the efficacy and safety profile of 0.05% CsA OE versus vehicle in Chinese patients with moderate to severe DED.

Methods:
This was a multicenter, randomized, double-masked, 2-parallel-arm, 3-month phase III study. Patients with moderate to severe DED were randomized to receive twice-daily 0.05% CsA OE or its vehicle, along with unpreserved hypromellose eye drops 3 times per day. Patients were followed up at day 7, 28, 56, and 84, as well as 2 weeks after the medications were discontinued for safety assessment.

Results:
A total of 240 patients were randomized. The overall effective rate (OER) and efficacy index were significantly better in the CsA OE than vehicle group at all follow up times (all P < .05), and the OER of CsA OE and vehicle group at month 3 was 70.6% and 27.8%, respectively (P < .001) (primary endpoint). The patients in CsA OE group displayed a significant improvement in dry eye symptoms from day 28 and ocular surface test results from day 7 (all P < .05). The ocular surface disease index scores of 0.05% CsA OE treated patients were significantly better than those treated with vehicle control at day 56 and 84 (P = .0061 and <.001, respectively). Drug related adverse events (AEs) were recorded in 6(5%) and 3(2.5%) patients in the CsA OE and vehicle groups respectively (P = .4061) with ocular pain as the most frequently reported AEs, and it was mostly mild to moderate. There were no detrimental effects on visual acuity, intraocular pressure, or vital signs.

Conclusions:
Twice-daily instillation of 0.05% CsA OE was effective and well tolerated for the treatment of moderate to severe DED in Chinese population during the 3 months of the study.
Expression and prognostic impact of alpha thalassemia/mental retardation X-linked and death domain-associated protein in human lung cancer
Authors: Buentzel Judith , Yao Sha , Elakad Omar , Lois Anna-Maria , Brünies Jana , König Julia , Hinterthaner Marc , Danner Bernhard C. , Ströbel Philipp , Emmert Alexander , Bohnenberger Hanibal 
Published: August 2019

Abstract
Molecular characterization of lung cancer specimens after radical surgery offers additional prognostic information and may help to guide adjuvant therapeutic procedures. The transcriptional regulators alpha thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) have recently been described in different cancer entities as a useful prognostic biomarker. This study was initiated to explore their protein expression patterns and prognostic value in patients with operable lung cancer disease.
The protein abundance (in the following text also named protein expression) of ATRX and DAXX were analyzed by immunohistochemistry in 194 samples of squamous cell lung carcinoma (SQCLC), 111 samples of pulmonary adenocarcinoma (AC) and 40 samples of small cell lung cancer (SCLC). The protein levels of ATRX and DAXX were correlated with clinicopathological characteristics and patient outcome.
ATRX showed strong protein expression in 16.2% of AC, 11.9% of SQCLC, and 42.5% of SCLC. DAXX was highly expressed in 54.9% of AC, 76.2% of SQCLC, and 82.5% of SCLC. Immunostaining of both ATRX and DAXX were seen in 14.4% of AC, 11.3% of SQCLC, and 42.5% of SCLC. High protein expression of ATRX was a favorable prognostic marker for patients with AC (hazard ratio 0.38, P = .02). Sub-group analyses showed a significant correlation between ATRX and the clinical stage of SQCLC and SCLC. Histological grading and ATRX were also significantly associated in cases of SQCLC.
The presence of ATRX and DAXX are correlated with lung cancer histology. Strong ATRX protein expression is associated with a significantly longer overall survival in patients with AC.
Association of GTF2I gene polymorphisms with renal involvement of systemic lupus erythematosus in a Chinese population
Authors: Meng Yanming , He Yao , Zhang Junlong , Xie Qibing , Yang Min , Chen Yuning , Wu Yongkang 
Published: August 2019

Abstract
The purposes of the study was to validate the relationship between General transcription factor II-I (GTF2I) genetic variants and kidney involvements of systemic lupus erythematosus (SLE) patients in a Chinese Han population.
Samples from 400 SLE patients and 400 age- and sex-matched healthy controls were collected and genotyped by improved multiplex ligation detection reaction technique. The relationship between gene polymorphism of rs117026326, rs73366469, and susceptibility, progression of SLE were analyzed.
The present study provided evidence that rs117026326 and rs73366469 were both associated with SLE susceptibility (both C vs T: P < .001). The analysis of dominant, recessive disease model provided us with further validation (P < .001). Both gene polymorphisms are associated with a triad of disease manifestations among SLE patients. Patients carrying genotype TT of rs117026326 had lower 24-hour urinary total protein (24 hours UTP, g/24 hours), 24-hour urinary protein level (g/L·24 hours), lower frequency of the proteinuria and lupus nephritis (LN). Patients carrying genotype TT at rs73366469 had higher 24-hour urinary protein level, higher frequency of the proteinuria, LN and positive anti-dsDNA than those with other genotypes.
This study identified the involvement of GTF2I gene polymorphisms in development of SLE, particularly in renal involvement.
Protocol for Pilot Study on Self-Management of Depressive Symptoms in Pregnancy
Authors: Kinser Patricia A. , Moyer Sara , Mazzeo Suzanne , York Timothy P. , Amstadter Ananda , Thacker Leroy , Starkweather Angela 
Published: August 2019

Background
Pregnant women with depressive symptoms face significant treatment challenges and are in great need of safe, effective, accessible, inexpensive, and nonpharmacological self-management therapies to enhance well-being, reduce the burden of symptoms both during their pregnancy and postpartum, and prevent chronic sequelae.

Objectives
In this article, we describe the protocol for our pilot study testing a self-management intervention entitled, “Mindful Moms,” designed to foster women’s ability to address current depressive symptoms and enhance resilience to prevent recurrence.

Methods
We will conduct a longitudinal pilot trial of the 12-week intervention with pregnant women with depressive symptoms (n = 40); the primary aim is to determine the feasibility and acceptability of the intervention. The secondary aim is to examine preliminary effects of the intervention on maternal psychobehavioral outcomes in pregnancy and 6 weeks postpartum. The third aim will quantify genome-wide and gene-specific DNA methylation patterns associated with depressive symptoms during pregnancy and investigate whether intervention participation influences these patterns.

Results
This study is currently ongoing.

Discussion
Findings from this study will inform future research addressing the need for nonpharmacological self-management interventions for pregnant women with depressive symptoms.
Subbrow Blepharoplasty Combined with Periorbital Muscle Manipulation for Periorbital Rejuvenation in Asian Women
Authors: Wang Jianzhang , Su Yingjun , Zhang Juan , Guo Peng , Song Baoqiang 
Published: August 2019

Background:
With advancing age, Asian women are often plagued by lateral hooding of the upper eyelid skin, eyebrow ptosis, and obvious periorbital wrinkles. The authors propose a novel technique to revive the natural eyelid shape with a stable eyebrow position and alleviate periorbital wrinkles in Asian women.

Methods:
Sixty-six patients underwent subbrow blepharoplasty combined with periorbital muscle manipulation. An ellipse shape of the skin and subcutaneous tissue below the eyebrow was measured, demarcated, and removed. Then, the orbicularis oculi muscle beneath the subcutaneous tissue was exposed and dissected at the upper third. The lower muscle flap was fixed to the supraorbital rim periosteum and the upper musculocutaneous flaps, forming a cross flap for interlocking fixation. The lateral border of the orbicularis oculi muscle was detached from the subcutaneous tissue, splayed out, and sutured upward and inward to the periosteum. The corrugator supercilii muscle temporal to the origin of the supraorbital nerve notch was separated by 1 to 2 mm. The operation results were evaluated by patient satisfaction and comparisons between preoperative and postoperative photographs.

Results:
Subbrow blepharoplasty combined with periorbital muscle manipulation significantly corrected lateral hooding with a stable eyebrow position and reduced the crow’s feet and glabellar frown lines in all patients. The persistence of the improved outcome was stable during the follow-up period. Postoperative scarring was inconspicuous; however, eight cases had transient postoperative forehead numbness.

Conclusions:
This novel procedure provides a simple, effective, and comprehensive technique for improving periorbital aging in Asian women. The surgical outcomes are predictable, and the postoperative scarring is inconspicuous.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Genetic tool development in marine protists: Emerging model organisms for experimental cell biology
Authors: Faktorová Drahomíra , Nisbet R. Ellen R. , Robledo José A. Fernández , Casacuberta Elena , Sudek Lisa , Allen Andrew E. , Ares Manuel , Aresté Cristina , Balestreri Cecilia , Barbrook Adrian C. , Beardslee Patrick , Bender Sara , Booth David S. , Bouget François-Yves , Bowler Chris , Breglia Susana A. , Brownlee Colin , Burger Gertraud , Cerutti Heriberto , Cesaroni Rachele , Chiurillo Miguel A. , Clemente Thomas , Coles Duncan B. , Collier Jackie L. , Cooney Elizabeth C. , Coyne Kathryn , Docampo Roberto , Dupont Christopher L. , Edgcomb Virginia , Einarsson Elin , Elustondo Pía A. , Federici Fernan , Freire-Beneitez Veronica , Freyria Nastasia J. , Fukuda Kodai , García Paulo A. , Girguis Peter R. , Gomaa Fatma , Gornik Sebastian G. , Guo Jian , Hampl Vladimír , Hanawa Yutaka , Haro-Contreras Esteban R. , Hehenberger Elisabeth , Highfield Andrea , Hirakawa Yoshihisa , Hopes Amanda , Howe Christopher J. , Hu Ian , Ibañez Jorge , Irwin Nicholas A.T. , Ishii Yuu , Janowicz Natalia Ewa , Jones Adam C. , Kachale Ambar , Fujimura-Kamada Konomi , Kaur Binnypreet , Kaye Jonathan Z. , Kazana Eleanna , Keeling Patrick J. , King Nicole , Klobutcher Lawrence A. , Lander Noelia , Lassadi Imen , Li Zhuhong , Lin Senjie , Lozano Jean-Claude , Luan Fulei , Maruyama Shinichiro , Matute Tamara , Miceli Cristina , Minagawa Jun , Moosburner Mark , Najle Sebastián R. , Nanjappa Deepak , Nimmo Isabel C. , Noble Luke , Vanclová Anna M.G. Novák , Nowacki Mariusz , Nuñez Isaac , Pain Arnab , Piersanti Angela , Pucciarelli Sandra , Pyrih Jan , Rest Joshua S. , Rius Mariana , Robertson Deborah , Ruaud Albane , Ruiz-Trillo Iñaki , Sigg Monika A. , Silver Pamela A. , Slamovits Claudio H. , Smith G. Jason , Sprecher Brittany N. , Stern Rowena , Swart Estienne C. , Tsaousis Anastasios D. , Tsypin Lev , Turkewitz Aaron , Turnšek Jernej , Valach Matus , Vergé Valérie , von Dassow Peter , von der Haar Tobias , Waller Ross F. , Wang Lu , Wen Xiaoxue , Wheeler Glen , Woods April , Zhang Huan , Mock Thomas , Worden Alexandra Z. , Lukeš Julius 
Published: August 2019

ABSTRACTDiverse microbial ecosystems underpin life in the sea. Among these microbes are many unicellular eukaryotes that span the diversity of the eukaryotic tree of life. However, genetic tractability has been limited to a few species, which do not represent eukaryotic diversity or environmentally relevant taxa. Here, we report on the development of genetic tools in a range of protists primarily from marine environments. We present evidence for foreign DNA delivery and expression in 13 species never before transformed and advancement of tools for 8 other species, as well as potential reasons for why transformation of yet another 17 species tested was not achieved. Our resource in genetic manipulation will provide insights into the ancestral eukaryotic lifeforms, general eukaryote cell biology, protein diversification and the evolution of cellular pathways.
Long-term, functional culture andin vitromanipulation of adult mouse cardiomyocytes
Authors: Callaghan Neal I. , Lee Shin-Haw , Hadipour-Lakmehsari Sina , Lee Xavier A. , Siraj M. Ahsan , Driouchi Amine , Yip Christopher M. , Husain Mansoor , Simmons Craig A. , Gramolini Anthony O. 
Published: August 2019

AbstractPrimary adult cardiomyocyte (aCM) culture is challenged by poor survival and loss of phenotype, rendering extendedin vitroexperiments unfeasible. Here, we establish murine aCM culture methods that enhance survival and maintain sarcomeric structure and Ca2+cycling to enable physiologically-relevant contractile force measurements. We also demonstrate genetic and small-molecule manipulations that probe mechanisms underlying myocyte functional performance.
Maternal circulating syncytiotrophoblast-derived extracellular vesicles contain biologically active 5’-tRNA halves
Authors: Cooke William R , Cribbs Adam , Zhang Wei , Kandzija Neva , Motta-Mejia Carolina , Dombi Eszter , Ri Rannya , Cerdeira Ana Sofia , Redman Christopher , Vatish Manu 
Published: August 2019

AbstractThe placenta releases syncytiotrophoblast-derived extracellular vesicles (STB-EV) into the maternal circulation throughout gestation. STB-EV dependent signalling is believed to contribute to the widespread maternal adaptive physiological changes seen in pregnancy. Transfer RNA (tRNA) halves have been identified in vesicles released from other human and murine organ systems, which alter gene expression in target cells. Here, we characterise tRNA-half expression in STB-EV and demonstrate biological activity of a highly abundant tRNA-half. Short RNA from ex-vivo, dual-lobe placental perfusion STB-EV was sequenced, showing that most (>95%) comprised tRNA species. Whole placental tissue contained <50% tRNA species, suggesting selective packaging and export of tRNA into STB-EV. Most tRNA within STB-EV were 5’-tRNA halves cleaved at 30-32 nucleotides. The pattern of tRNA expression differed depending on the size/origin of the STB-EV; this was confirmed by qPCR. Protein synthesis was suppressed in human fibroblasts when they were cultured with a 5’-tRNA half identified from STB-EV sequencing. This study is the first to evaluate tRNA species in STB-EV. The presence of biologically active 5’-tRNA halves, specific to a vesicular origin, suggests a novel mechanism for maternal-fetal signalling in normal pregnancy.
Odorant receptors fromCulex quinquefasciatusandAedes aegyptisensitive to floral compounds
Authors: Zeng Fangfang , Xu Pingxi , Leal Walter S. 
Published: August 2019

AbstractMosquitoes rely heavily on the olfactory system to find a host for a bloodmeal, plants for a source of energy and suitable sites for oviposition. Here, we examined a cluster of 8 odorant receptors (ORs), which includes one OR, CquiOR1, previously identified to be sensitive to plant-derived compounds. We cloned 5 ORs fromCulex quinquefasciatusand 2 ORs fromAedes aegypti, ie, CquiOR2, CquiOR4, CquiOR5, CquiOR84, CquiOR85, AaegOR14, and AaegOR15 and then deorphanized these receptors using theXenopusoocyte recording system and a large panel of odorants. 2-Phenylethanol, phenethyl formate, and phenethyl propionate were the best ligands for CquiOR4 somewhat resembling the profile of AaegOR15, which gave the strongest responses to phenethyl propionate, phenethyl formate, and acetophenone. In contrast, the best ligands for CquiOR5 were linalool, PMD, and linalool oxide. CquiOR4 was predominantly expressed in antennae of nonblood fed female mosquitoes, with transcript levels significantly reduced after a blood meal. 2-Phenylethanol showed repellency activity comparable to that of DEET at 1%. RNAi experiments suggest that at least in part 2-phenylethanol-elicited repellency is mediated by CquiOR4 activation.
Priority effects, consumer pressure, and soil resources independently alter plant diversity and resource strategies during a multi-year successional field experiment
Authors: Wilfahrt Peter A. , Halliday Fletcher W. , Heckman Robert W. 
Published: August 2019

SummaryPlant community succession is structured by priority effects, plant consumer pressure, and soil resource supply. Importantly, these drivers may interact, their effects may vary temporally, and they may influence different facets of plant community diversity by promoting different plant tradeoff strategies.In an herbaceous successional system, we manipulated priority effects by altering initial plant richness, consumer pressure via pesticide spraying, and soil resource supply via fertilization. We examined how these processes jointly influenced succession, including taxonomic diversity and functional traits, over four years.Diversity decreased in different years in response to more diverse priority effects, lower consumer pressure, and increased soil resource supply. Functionally, higher soil resource supply increased community height, SLA, and seed mass; higher consumer pressure decreased intraspecific community height, and increased interspecific SLA; priority effects led to decreased seed mass only when plots were unplanted.Our results suggest species’ resource strategies underlie plant diversity responses. Resource addition promoted resource-acquisitive species, consumer pressure disadvantaged resource-conservative species, and diversity of priority effects altered subsequent community composition through persistence of early residents, not via traits. We show that community responses to drivers of succession depend on underlying trait tradeoffs of resident species, and these tradeoffs influence community diversity across succession.
Functional properties of habenular neurons are determined by developmental stage and sequential neurogenesis
Authors: Fore Stephanie , Cosacak Mehmet Ilyas , Diaz Verdugo Carmen , Kizil Caghan , Yaksi Emre 
Published: August 2019

SUMMARYNeural development is not just a linear expansion of the brain. Instead, the structure and function of developing brain circuits undergo drastic alterations that have a direct impact on the animals’ expanding behavioural repertoire. Here we investigated the developmental changes in the habenula, a brain region that mediates behavioural flexibility during learning, social interactions and aversive experiences. We showed that developing habenular circuits exhibit multiple alterations, which increase the structural and functional diversity of cell types, inputs and functional modules within habenula. As the neural architecture of habenula develops, it sequentially transforms into a multi-sensory brain region that can process visual and olfactory information. Moreover, we also observed that already at early developmental stages, the habenula exhibits spatio-temporally structured spontaneous neural activity that shows prominent alterations and refinement with age. Interestingly, these alterations in spontaneous activity are accompanied by sequential neurogenesis and integration of distinct neural clusters across development. Finally, by combining an in vivo neuronal birthdating method with functional imaging, we revealed that clusters of habenular neurons with distinct functional properties are born sequentially at distinct developmental time windows. Our results highlight a strong link between the function of habenular neurons and their precise birthdate during development, which supports the idea that sequential neurogenesis leads to an expansion of neural clusters that correspond to distinct functional modules in the brain.
Oxidative stress in retinal pigment epithelial cells increased endogenous complement-dependent inflammatory and angiogenic responses - independent from exogenous complement sources
Authors: Trakkides Timon-Orest , Schäfer Nicole , Reichenthaler Maria , Kühn Konstanze , Enzmann Volker , Pauly Diana 
Published: August 2019

ABSTRACTOxidative stress-induced damage of the retinal pigment epithelium (RPE) together with chronic inflammation has been suggested as major contributors to retinal diseases. Here, we examine the effects of oxidative stress and endogenous complement components on the RPE and its pro-inflammatory and –angiogenic responses.The RPE cell line, ARPE-19, treated with H2O2 reduced cell-cell contacts, increased marker for epithelial–mesenchymal transition but showed less cell death. Stressed ARPE-19 cells increased the expression of complement receptors CR3 and C5aR1. CR3 was co-localized with cell-derived complement protein C3, which was observed in its activated form in ARPE-19 cells. C3 as well as its regulators CFH and properdin accumulated in ARPE-19 cells after oxidative stress independent from external complement sources. This cell-associated complement accumulation promoted nlrp3 and foxp3 expression and subsequent increased secretion of pro-inflammatory and pro-angiogenic factors. The complement-associated ARPE-19 reaction to oxidative stress, independent from external complement source, was increased by the PARP-inhibitor olaparib.Our results indicated that RPE cell-derived complement proteins and receptors are involved in RPE cell homeostasis following oxidative stress and should be considered as targets for treatment developments for retinal degeneration.
GRAPHICAL ABSTRACTWe show a functional link between oxidative stress, complement receptors, endogenous complement proteins, pro-angiogenic and -inflammatory responses in ARPE-19 cells. These effects are independent from extracellularly added complement proteins or receptor ligands. We suggest an oxidative stress-associated autocrine mechanism of complement receptor regulation in ARPE-19 cells in connection with upregulated intracellular proteases.HIGHLIGHTSOxidative stress accumulates complement proteins and receptors in RPE cellsOxidative stress activates the RPE inflammasome without external complement proteinsOxidative stress increases foxp3 expression and IL-8/VEGF secretion in RPE cellsOlaparib enhances pro-inflammatory response of RPE
In-silicodefinition of theDrosophila melanogastermatrisome
Authors: Davis Martin N. , Horne-Badovinac Sally , Naba Alexandra 
Published: August 2019

ABSTRACTThe extracellular matrix (ECM) is an assembly of hundreds of proteins that structurally supports the cells it surrounds and biochemically regulates their functions.Drosophilahas emerged as a powerful model organism to study fundamental mechanisms underlying ECM protein secretion, ECM assembly, and ECM roles in pathophysiological processes. However, as of today, we do not possess a well-defined list of the components forming the ECM of this organism. We previously reported the development of computational pipelines to define the matrisome - the ensemble of genes encoding ECM and ECM-associated proteins - of humans, mice, zebrafish andC. elegans. Using a similar approach, we report here that theDrosophilamatrisome is composed of 641 genes. We further classify these genes into different structural and functional categories, including an expanded way to classify genes encoding proteins forming apical ECMs. We illustrate how having a comprehensive list ofDrosophilamatrisome proteins can be used to annotate large proteomic datasets and identify unsuspected roles for the ECM in pathophysiological processes. Last, to aid the dissemination and usage of the proposed definition and categorization of theDrosophilamatrisome by the scientific community, our list has been made available through three public portals: The Matrisome Project, FlyBase, and GLAD.