bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppressing ABA uridine diphosphate glucosyltransferase (SlUGT75C1) alters fruit ripening and the stress response in tomato
Authors: Sun Yufei , Ji Kai , Liang Bin , Du Yangwei , Jiang Li , Wang Juan , Kai Wenbin , Zhang Yushu , Zhai Xiawan , Chen Pei , Wang Hongqing , Leng Ping 
Published: May 2017

SummaryAbscisic acid (ABA) glucose conjugation mediated by uridine diphosphate glucosyltransferases (UGTs) is an important pathway in regulating ABA homeostasis. In the present study, we investigated three tomato SlUGTs that are highly expressed in fruit during ripening, and these SlUGTs were localized to the cytoplasm and cell nucleus. Among these three UGTs, SlUGT75C1 catalyzes the glucosylation of both ABA and IAA in vitro; SlUGT76E1 can only catalyze the conjugation of ABA; and SlUGT73C4 cannot glycosylate either ABA or IAA. Therefore, SlUGT75C1 was selected for further investigation. SlUGT75C1 RNA interference significantly up‐regulated the expression level of SlCYP707A2, which encodes an ABA 8′‐hydroxylase but did not affect the expression of SlNCED1, which encodes a key enzyme in ABA biosynthesis. Suppression of SlUGT75C1 significantly accelerated fruit ripening by enhancing ABA levels and promoting the early release of ethylene. SlUGT75C1‐RNAi altered the expression of fruit ripening genes (genes involved in ethylene release and cell wall catabolism). SlUGT75C1‐RNAi seeds showed delayed germination and root growth compared with wild‐type as well as increased sensitivity to exogenous ABA. SlUGT75C1‐RNAi plants were also more resistant to drought stress. These results demonstrated that SlUGT75C1 plays a crucial role in ABA‐mediated fruit ripening, seed germination, and drought responses in tomato.
Leaf primordium size specifies leaf width and vein number among row‐type classes in barley
Authors: Thirulogachandar Venkatasubbu , Alqudah Ahmad M. , Koppolu Ravi , Rutten Twan , Graner Andreas , Hensel Goetz , Kumlehn Jochen , Bräutigam Andrea , Sreenivasulu Nese , Schnurbusch Thorsten , Kuhlmann Markus 
Published: May 2017

SummaryExploring genes with impact on yield‐related phenotypes is the preceding step to accomplishing crop improvements while facing a growing world population. A genome‐wide association scan on leaf blade area (LA) in a worldwide spring barley collection (Hordeum vulgare L.), including 125 two‐ and 93 six‐rowed accessions, identified a gene encoding the homeobox transcription factor, Six‐rowed spike 1 (VRS1). VRS1 was previously described as a key domestication gene affecting spike development. Its mutation converts two‐rowed (wild‐type VRS1, only central fertile spikelets) into six‐rowed spikes (mutant vrs1, fully developed fertile central and lateral spikelets). Phenotypic analyses of mutant and wild‐type leaves revealed that mutants had an increased leaf width with more longitudinal veins. The observed significant increase of LA and leaf nitrogen (%) during pre‐anthesis development in vrs1 mutants also implies a link between wider leaf and grain number, which was validated from the association of vrs1 locus with wider leaf and grain number. Histological and gene expression analyses indicated that VRS1 might influence the size of leaf primordia by affecting cell proliferation of leaf primordial cells. This finding was supported by the transcriptome analysis of mutant and wild‐type leaf primordia where in the mutant transcriptional activation of genes related to cell proliferation was detectable. Here we show that VRS1 has an independent role on barley leaf development which might influence the grain number.
Ophthalmic parameters in adult lowland paca (Cuniculus paca) raised in captivity
Authors: Balthazar da Silveira Camila P. , Lima Tiago B. , Crivelaro Roberta M. , de Lacerda Luciana C. C. , Pádua Ivan R. M. , Renzo Roberta , de Barros Sobrinho Alexandre A. F. , Oliveira Fabrício S. , Aldrovani Marcela , Laus José L. 
Published: May 2017

AbstractObjectiveTo investigate the ophthalmic parameters of lowland pacas, including the anatomic features, tear production, intraocular pressure, central corneal thickness, and morphology of the corneal endothelium.Animals studiedThirteen adult, anesthetized Cuniculus paca.ProcedureEyes were evaluated using slit‐lamp biomicroscopy, the Schirmer tear test I, digital applanation tonometry, binocular indirect ophthalmoscopy, and noncontact specular microscopy.ResultsThe biomicroscopy findings showed blue/brown pigmented bulbar conjunctivae, well‐developed cilia (only in the upper eyelid margin), superior and inferior lacrimal puncta, brown irides, round pupils, and vestiges of the nictitating membrane. The results of the Schirmer tear test I revealed (mean ± SD) a lacrimation rate of 4.10 ± 0.44 mm/min. The intraocular pressure was 6.34 ± 0.43 mmHg. Central corneal thickness measured by specular microscopy was 0.35 ± 0.01 mm. The mean values of density, hexagonality, and the area of the endothelial cells were 2083.15 ± 42.47 cells/mm2, 67.07 ± 3.30%, and 486.30 ± 9.56 μm2, respectively.ConclusionsThe ocular parameters defined in this study may be used for reference in future studies and might also contribute to therapeutic approaches appropriate to this species.
Abstract B47: A novel combination of Biochanin-A/ 5-Fluorouracil against colon cancer: Impact on Wnt/beta-catenin signaling
Authors: Mahmoud Mohamed , El-Sesy Mohamed , Tolba Mai F. , Ella Dalal A. Abou El 
Published: May 2017

Abstract
Giza, Egypt.
Colon cancer is one of the most common types of cancer worldwide. It is considered the second leading cause of cancer deaths in both women and men combined. Although 5-fluorouracil (5FU) is the first line of therapy for colon cancer, its use is significantly hampered by drug toxicity and development of tumor resistance. Therefore, it is important to investigate strategies to overcome such stumbling block. Biochanin-A (Bio-A) is a promising natural isoflavone that has selective cytotoxicity against cancer cells. This study aimed at investigating the modulatory impact of Bio-A on 5FU cytotoxicity in colon cancer cells and exploring the possible underlying mechanisms with emphasis on Wnt/beta catenin signals. Cytotoxicity and Calcusyn synergy analyses were conducted to assess IC50 and synergism between Bio-A and 5FU in both Caco-2 and HCT-116 cell lines. The effect of the different treatments on Wnt/ β-catenin signals was assessed using phospho-tracer enzyme linked immunoassays. Bio-A alone showed cytotoxic activity against Caco-2 and HCT-116 colon cancer cells with IC50 values of 34.34 and 34.41 μM respectively using sulforhodamine-B cytotoxicity assay. Combined treatment of 5FU/ Bio-A at 1:2 and 1:4 ratios reduced the IC50 of 5FU significantly by 26.7 and 57% in Caco-2 cell line. The same treatments produced reduction of 5FU IC50 by 13.2 and 39.6% in HCT-116. Calcusyn® analysis indicated that the combinations were synergistic in both cell lines with combination index CI&lt;1. Since Wnt/ β-catenin signaling plays an important role in the pathogenesis of colon cancer, the study was substantiated to investigate the effects of Bio-A and Bio-A/5FU combination on some key signals in addition to cell cycle analysis and assessment of cyclin D1 expression. Bio-A significantly suppressed Akt-phosphorylation and hence reduced GSK3β phosphorylation and preserved it in the active form. Hence, treatment with Bio-A boosted the ratio of phosphorylated β-catenin(p-S45)/total β-catenin indicating an increased degradation of β-catenin and reduced signaling. In conclusion, these results underscore the potential merit of Bio-A as an adjuvant to 5FU for the management of colon cancer. Further tumor xenograft studies are encouraged in order to verify this effect in vivo.
Citation Format: Mohamed Mahmoud, Mohamed El-Sesy, Mai F. Tolba, Dalal A. Abou El Ella. A novel combination of Biochanin-A/ 5-Fluorouracil against colon cancer: Impact on Wnt/beta-catenin signaling. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B47.
Alterations in post-movement beta event related synchronization throughout the migraine cycle: A controlled, longitudinal study
Authors: Mykland Martin Syvertsen , Bjørk Marte Helene , Stjern Marit , Sand Trond 
Published: May 2017

Background The migraine brain is believed to have altered cortical excitability compared to controls and between migraine cycle phases. Our aim was to evaluate post-activation excitability through post-movement beta event related synchronization (PMBS) in sensorimotor cortices with and without sensory discrimination. Subjects and methods We recorded EEG of 41 migraine patients and 31 healthy controls on three different days with classification of days in relation to migraine phases. During each recording, subjects performed one motor and one sensorimotor task with the right wrist. Controls and migraine patients in the interictal phase were compared with repeated measures (R-) ANOVA and two sample Student’s t-test. Migraine phases were compared to the interictal phase with R-ANOVA and paired Student’s t-test. Results The difference between PMBS at the contralateral and ipsilateral sensorimotor cortex was altered throughout the migraine cycle. Compared to the interictal phase, we found decreased PMBS at the ipsilateral sensorimotor cortex in the ictal phase and increased PMBS in the preictal phase. Lower ictal PMBS was found in bilateral sensorimotor cortices in patients with right side headache predominance. Conclusion The cyclic changes of PMBS in migraine patients may indicate that a dysfunction in deactivation and interhemispheric inhibition of the sensorimotor cortex is involved in the migraine attack cascade.
Dimethyl fumarate induces changes in B- and T-lymphocyte function independent of the effects on absolute lymphocyte count
Authors: Longbrake Erin E , Cantoni Claudia , Chahin Salim , Cignarella Francesca , Cross Anne H , Piccio Laura 
Published: May 2017

Background: Dimethyl fumarate (DMF) is used to treat relapsing multiple sclerosis and causes lymphopenia in a subpopulation of treated individuals. Much remains to be learned about how the drug affects B- and T-lymphocytes. Objectives: To characterize changes in B- and T-cell phenotype and function induced by DMF and to investigate whether low absolute lymphocyte count (ALC) is associated with unique functional changes. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from DMF-treated patients, untreated patients, and healthy controls. A subset of DMF-treated patients was lymphopenic (ALC < 800). Multiparametric flow cytometry was used to evaluate cellular phenotypes. Functional response to non-specific and viral peptide stimulation was assessed. Results: DMF reduced circulating memory B-cells regardless of ALC. Follicular T-helper cells (CD4+ CXCR5+) and mucosal invariant T-cells (CD8+ CD161+) were also reduced. DMF reduced T-cell production of pro-inflammatory cytokines in response to polyclonal (PMA/ionomycin) and viral peptide stimulation, regardless of ALC. No differences in activation-induced cell death or circulating progenitors were observed between lymphopenic and non-lymphopenic DMF-treated patients. Conclusion: These data implicate DMF-induced changes in lymphocytes as an important component of the drug’s efficacy and expand our understanding of the functional significance of DMF-induced lymphopenia.
Digital otoscopy versus microscopy: How correct and confident are ear experts in their diagnoses?
Authors: Moberly Aaron C , Zhang Margaret , Yu Lianbo , Gurcan Metin , Senaras Caglar , Teknos Theodoros N , Elmaraghy Charles A , Taj-Schaal Nazhat , Essig Garth F 
Published: May 2017

Introduction With the growing popularity of telemedicine and tele-diagnostics, clinical validation of new devices is essential. This study sought to investigate whether high-definition digital still images of the eardrum provide sufficient information to make a correct diagnosis, as compared with the gold standard view provided by clinical microscopy. Methods Twelve fellowship-trained ear physicians (neurotologists) reviewed the same set of 210 digital otoscope eardrum images. Participants diagnosed each image as normal or, if abnormal, they selected from seven types of ear pathology. Diagnostic percentage correct for each pathology was compared with a gold standard of diagnosis using clinical microscopy with adjunct audiometry and/or tympanometry. Participants also rated their degree of confidence for each diagnosis. Results Overall correctness of diagnosis for ear pathologies ranged from 48.6–100%, depending on the type of pathology. Neurotologists were 72% correct in identifying eardrums as normal. Reviewers’ confidence in diagnosis varied substantially among types of pathology, as well as among participants. Discussion High-definition digital still images of eardrums provided sufficient information for neurotologists to make correct diagnoses for some pathologies. However, some diagnoses, such as middle ear effusion, were more difficult to diagnose when based only on a still image. Levels of confidence of reviewers did not generally correlate with diagnostic ability.
Cross-circulation thrombectomy with use of a stent retriever: A case report
Authors: Sultan-Qurraie Ali , Rozansky Gregory , Cox John Andrew , Lazzaro Marc 
Published: May 2017

Introduction The efficacy of the endovascular treatment of acute ischemic stroke has been substantiated by several recent randomized clinical trials. While intra-arterial therapy has significantly evolved in recent years, anatomic cerebrovascular variants and disease burden can present challenges to timely recanalization. We present the first reported case of anterior-to-posterior mechanical clot retrieval with use of a stent retriever. Case description A 53-year-old man presented with basilar artery thrombosis. Endovascular mechanical clot retrieval was performed. The typical, antegrade, access to the basilar artery thrombus was precluded by the findings of a hypoplastic left vertebral artery and an occluded proximal right vertebral artery. Given a number of factors including the patient’s worsening symptoms and the high morbidity and mortality associated with basilar stroke, cross-circulation—anterior-to-posterior—intra-arterial therapy was performed. Thrombectomy of the basilar thrombus was achieved via the right internal carotid artery and right posterior communicating artery. Conclusion To our knowledge, we report the first case of cross-circulation, anterior-to-posterior thrombectomy, with the use of a stent-retriever device. Cross-circulation stroke treatment may be beneficial in cases of proximal vessel occlusion or anatomical constraints. Larger studies will need to evaluate the safety and efficacy of these approaches.
A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma
Authors: Martin Thomas , Baz Rachid , Benson Don M. , Lendvai Nikoletta , Wolf Jeffrey , Munster Pamela , Lesokhin Alexander M. , Wack Claudine , Charpentier Eric , Campana Frank , Vij Ravi 
Published: May 2017

Key Points
Isatuximab (anti-CD38 monoclonal antibody) given with lenalidomide/ dexamethasone is active in heavily pretreated relapsed/refractory myeloma Overall, the safety profile of this combination is similar to the characteristic safety profiles of the individual agents.
The effect of pre- and post-operative physical activity on recovery after colorectal cancer surgery (PHYSSURG-C): study protocol for a randomised controlled trial
Authors: Onerup Aron , Angenete Eva , Bock David , Börjesson Mats , Fagevik Olsén Monika , Grybäck Gillheimer Elin , Skullman Stefan , Thörn Sven-Egron , Haglind Eva , Nilsson Hanna 
Published: May 2017

Abstract
Background
Surgery for colorectal cancer is associated with a high risk of post-operative adverse events, re-operations and a prolonged post-operative recovery. Previously, the effect of prehabilitation (pre-operative physical activity) has been studied for different types of surgery, including colorectal surgery. However, the trials on colorectal surgery have been of limited methodological quality and size. The aim of this trial is to compare the effect of a combined pre- and post-operative intervention of moderate aerobic physical activity and inspiratory muscle training (IMT) with standard care on post-operative recovery after surgery for colorectal cancer.

Methods/design
We are conducting a randomised, controlled, parallel-group, open-label, multi-centre trial with physical recovery within 4 weeks after cancer surgery as the primary endpoint. Some 640 patients planned for surgery for colorectal cancer will be enrolled. The intervention consists of pre- and post-operative physical activity with increased daily aerobic activity of moderate intensity as well as IMT. In the control group, patients will be advised to continue their normal daily exercise routine. The primary outcome is patient-reported physical recovery 4 weeks post-operatively. Secondary outcomes are length of sick leave, complication rate and severity, length of hospital stay, re-admittances, re-operations, post-operative mental recovery, quality of life and mortality, as well as changes in insulin-like growth factor 1 and insulin-like growth factor-binding protein 3, perception of pain and a health economic analysis.

Discussion
An increase in moderate-intensity aerobic physical activity is a safe, cheap and feasible intervention that would be possible to implement in standard care for patients with colorectal cancer. If shown to be effective, this lifestyle intervention could be a clinical parallel to pre-operative smoke cessation that has already been implemented with good clinical results.

Trial registration
ClinicalTrials.gov identifier: NCT02299596. Registered on 17 November 2014.
Clinical Data Reuse or Secondary Use: Current Status and Potential Future Progress
Authors: Meystre S. M. , Lovis C. , Bürkle T. , Tognola G. , Budrionis A. , Lehmann C. U. 
Published: May 2017

Summary
Objective: To perform a review of recent research in clinical data reuse or secondary use, and envision future advances in this field.
Methods: The review is based on a large literature search in MEDLINE (through PubMed), conference proceedings, and the ACM Digital Library, focusing only on research published between 2005 and early 2016. Each selected publication was reviewed by the authors, and a structured analysis and summarization of its content was developed.
Results: The initial search produced 359 publications, reduced after a manual examination of abstracts and full publications. The following aspects of clinical data reuse are discussed: motivations and challenges, privacy and ethical concerns, data integration and interoperability, data models and terminologies, unstructured data reuse, structured data mining, clinical practice and research integration, and examples of clinical data reuse (quality measurement and learning healthcare systems).
Conclusion: Reuse of clinical data is a fast-growing field recognized as essential to realize the potentials for high quality healthcare, improved healthcare management, reduced healthcare costs, population health management, and effective clinical research.
Secondary Use and Analysis of Big Data Collected for Patient Care
Authors: Martin-Sanchez F. J. , Aguiar-Pulido V. , Lopez-Campos G. H. , Peek N. , Sacchi L. 
Published: May 2017

Summary
Objectives: To identify common methodological challenges and review relevant initiatives related to the re-use of patient data collected in routine clinical care, as well as to analyze the economic benefits derived from the secondary use of this data. Through the use of several examples, this article aims to provide a glimpse into the different areas of application, namely clinical research, genomic research, study of environmental factors, and population and health services research. This paper describes some of the informatics methods and Big Data resources developed in this context, such as electronic phenotyping, clinical research networks, biorepositories, screening data banks, and wide association studies. Lastly, some of the potential limitations of these approaches are discussed, focusing on confounding factors and data quality.
Methods: A series of literature searches in main bibliographic databases have been conducted in order to assess the extent to which existing patient data has been repurposed for research. This contribution from the IMIA working group on “Data mining and Big Data analytics” focuses on the literature published during the last two years, covering the timeframe since the working group’s last survey.
Results and Conclusions: Although most of the examples of secondary use of patient data lie in the arena of clinical and health services research, we have started to witness other important applications, particularly in the area of genomic research and the study of health effects of environmental factors. Further research is needed to characterize the economic impact of secondary use across the broad spectrum of translational research.
Added Value from Secondary Use of Person Generated Health Data in Consumer Health Informatics
Authors: Hsueh P.-Y. , Cheung Y.-K. , Dey S. , Kim K. K. , Martin-Sanchez F. J. , Petersen S. K. , Wetter T. 
Published: May 2017

Summary
Introduction: Various health-related data, subsequently called Person Generated Health Data (PGHD), is being collected by patients or presumably healthy individuals as well as about them as much as they become available as measurable properties in their work, home, and other environments. Despite that such data was originally just collected and used for dedicated predefined purposes, more recently it is regarded as untapped resources that call for secondary use.
Method: Since the secondary use of PGHD is still at its early evolving stage, we have chosen, in this paper, to produce an outline of best practices, as opposed to a systematic review. To this end, we identified key directions of secondary use and invited protagonists of each of these directions to present their takes on the primary and secondary use of PGHD in their sub-fields. We then put secondary use in a wider perspective of overarching themes such as privacy, interpretability, interoperability, utility, and ethics.
Results: We present the primary and secondary use of PGHD in four focus areas: (1) making sense of PGHD in augmented Shared Care Plans for care coordination across multiple conditions; (2) making sense of PGHD from patient-held sensors to inform cancer care; (3) fitting situational use of PGHD to evaluate personal informatics tools in adaptive concurrent trials; (4) making sense of environment risk exposure data in an integrated context with clinical and omics-data for biomedical research.
Discussion: Fast technological progress in all the four focus areas calls for a societal debate and decision-making process on a multitude of challenges: how emerging or foreseeable results transform privacy; how new data modalities can be interpreted in light of clinical data and vice versa; how the sheer mass and partially abstract mathematical properties of the achieved insights can be interpreted to a broad public and can consequently facilitate the development of patient-centered services; and how the remaining risks and uncertainties can be evaluated against new benefits. This paper is an initial summary of the status quo of the challenges and proposals that address these issues. The opportunities and barriers identified can serve as action items individuals can bring to their organizations when facing challenges to add value from the secondary use of patient-generated health data.