bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced Delta-Notch Lateral Inhibition Model Incorporating Intracellular Notch Heterogeneity and Tension-Dependent Rate of Delta-Notch Binding that Reproduces Sprouting Angiogenesis Patterns
Authors: Koon Yen Ling , Zhang Songjing , Rahmat Muhammad Bakhait , Koh Cheng Gee , Chiam Keng-Hwee 
Published: June 2018

AbstractEndothelial cells adopt unique cell fates during sprouting angiogenesis, differentiating into tip or stalk cells. The fate selection process is directed by Delta-Notch lateral inhibition pathway. Classical Delta-Notch models produce a spatial pattern of tip cells separated by a single stalk cell, or the salt-and-pepper pattern. However, classical models cannot explain alternative tip-stalk patterning, such as tip cells that are separated by two or more stalk cells. We show that lateral inhibition models involving only Delta and Notch proteins can also recapitulate experimental tip-stalk patterns by invoking two mechanisms, specifically, intracellular Notch heterogeneity and tension-dependent rate of Delta-Notch binding. We introduce our computational model and analysis where we establish that our enhanced Delta-Notch lateral inhibition model can recapitulate a greater variety of tip-stalk patterning which is previously not possible using classical lateral inhibition models. In our enhanced Delta-Notch lateral inhibition model, we observe the existence of a hybrid cell type displaying intermediate tip and stalk cells’ characteristics. We validate the existence of such hybrid cells by immuno-staining of endothelial cells with tip cell markers, Delta and CD34, which substantiates our enhanced model.
Estrogen promotes progression of hormone-dependent breast cancer through CCL2-CCR2 axis by upregulation of Twist via PI3K/AKT/NF-κB signaling
Authors: Han Rui , Gu Shanzhi , Zhang Yujiao , Luo Anqi , Jing Xin , Zhao Lin , Zhao Xinhan , Zhang Lingxiao 
Published: June 2018

AbstractThe chemokine (C-C motif) ligand 2 (CCL2) with its cognate receptor chemokine (C-C motif) receptor 2 (CCR2) plays important roles in tumor invasion and metastasis. However, the mechanisms and mediators for autocrine CCL2 and CCL2-CCR2 axis remain elusive in breast cancer. Here we examined the levels of CCL2 in 4 breast cancer cell lines along with 57 human breast cancer specimens and found them significantly increased with presence of 17β-estradiol (E2) in estrogen receptor (ER)-positive breast cancer cells, while anti-estrogen treatment weakened this enhancement. CCL2 expression positively correlated with Twist staining and aggressiveness of breast cancer. Estrogen exposure facilitated the proliferation, invasion and metastasis of hormone-dependent breast cancer and promoted angiogenesis via the increased secretion of CCL2in vitroandin vivo, which could be suppressed by disruption of CCL2-CCR2 axis with CCR2 antagonist RS102895. Knockdown of Twist in MCF-7 cells significantly inhibited E2-induced CCL2 production, indicating an essential role of Twist in CCL2 regulation under estrogenic condition. Our data show the hormonal regulation on CCL2-CCR2 axis is associated with enhanced Twist expression via activation of ERα and PI3K/AKT/NF-κB signaling. Thus, CCL2-CCR2 axis may represent as a novel therapeutic target eagerly needed for hormone-dependent breast cancer.
Combined effect of high hydrostatic pressure and ultraviolet radiation on quality parameters of refrigerated vacuum-packed tilapia (Oreochromis niloticus) fillets
Authors: Monteiro Maria Lúcia Guerra , Mársico Eliane Teixeira , Mano Sérgio Borges , da Silveira Alvares Thiago , Rosenthal Amauri , Lemos Mosar , Ferrari Elisa , Lázaro Cesar Aquiles , Conte-Junior Carlos Adam 
Published: June 2018

AbstractThis study investigated the effects of high hydrostatic pressure (HHP) and ultraviolet radiation (UV-C), individually and combined, on the physical, chemical and bacterial parameters of Nile tilapia (Oreochromis niloticus) fillets stored at 4 °C for 14 days. Tilapia fillets were divided into four groups: control (untreated samples), UV-C, HHP, and UV-C combined with HHP (UV-C+HHP); UV-C was applied at dose of 0.103 ± 0.002 J/cm2, and HHP at a pressure of 220 MPa for 10 min at 25 °C. All samples were analyzed for total aerobic mesophilic count (TAMC), total aerobic psychrotrophic count (TAPC), Enterobacteriaceae count, pH, lipid oxidation, total volatile basic nitrogen (TVB-N), ammonia (NH3), and biogenic amines. Although UV-C accelerated (P ≤ 0.05) the formation of cadaverine, both UV-C and HHP, alone or together, retarded bacterial growth and delayed the increase (P ≤ 0.05) in pH, TVB-N, NH3 and biogenic amines during refrigerated storage, extending the shelf life of refrigerated tilapia fillets at least 2.5 times considering the TAMC counts. Lipid oxidation was unaffected (P > 0.05) by UV-C radiation, and decreased (P ≤ 0.05) by HHP and UV-C+HHP. HHP alone or combined with UV-C showed higher potential benefits for tilapia fillets preservation considering the positive influence on cadaverine levels and lipid oxidation.
Stellenwert der matrixaugmentierten Knochenmarkstimulation in der Behandlung von Knorpelschäden des Kniegelenks: Konsensusempfehlungen der AG Klinische Geweberegeneration der DGOU
Authors: Niemeyer Philipp , Becher Christoph , Brucker Peter , Buhs Matthias , Fickert Stefan , Gelse Kolja , Günther Daniel , Kaelin Raphael , Kreuz Peter , Lützner Jörg , Nehrer Stefan , Madry Henning , Marlovits Stefan , Mehl Julian , Ott Henning , Pietschmann Matthias , Spahn Gunther , Tischer Thomas , Volz Martin , Walther Markus , Welsch Götz , Zellner Johannes , Zinser Wolfgang , Angele Peter 
Published: June 2018

ZusammenfassungFür die operative Sanierung lokalisiert vollschichtiger Knorpelschäden der großen Gelenke stehen mit den Transplantationstechniken (autologe Knorpelzelltransplantation, autologe osteochondrale Transplantation) und knochenmarkstimulierenden Techniken unterschiedliche Therapieoptionen zur Verfügung. Vor allem für das Kniegelenk konnte aufgrund der verbesserten Studienlage das jeweils geeignete Anwendungsspektrum dieser Verfahren in letzter Zeit weiter präzisiert werden. Für die matrixaugmentierte Mikrofrakturierung als einzeitige Methode besteht jedoch noch keine genauere Indikationsabgrenzung, insbesondere auch nicht gegenüber den bereits etablierten Verfahren. In der vorliegenden Arbeit werden die derzeit für diese Methode zur Verfügung stehenden Biomaterialien und Anwendungsvarianten beschrieben und ihre präklinische und klinische Evidenz zusammengefasst. Grundsätzlich kann dabei festgestellt werden, dass sich die verschiedenen in diesem Bereich angebotenen Produkte hinsichtlich der Zahl und Qualität zugehöriger Studien (Evidenzlevel) noch erheblich voneinander unterscheiden. Um die matrixaugmentierte Mikrofrakturierung im Sinne einer ersten Indikationsempfehlung als Methode in den therapeutischen Algorithmus der knorpelrekonstruktiven Verfahren im Knie einzuordnen, wurde durch die Mitglieder der Arbeitsgemeinschaft (AG) Klinische Geweberegeneration der Deutschen Gesellschaft für Orthopädie und Unfallchirurgie (DGOU) im Rahmen eines Konsensusprozesses eine Bewertung der verfügbaren Evidenz vorgenommen. Vor dem Hintergrund der aktuellen Datenlage wird ihre Anwendung derzeit im Grenzbereich zwischen Zelltransplantations- und knochenmarkstimulierenden Techniken sowie als Verbesserung der klassischen Mikrofrakturierung und überwiegend im Indikationsbereich der Mikrofrakturierung gesehen. Die Empfehlungen der AG haben vorläufigen und orientierenden Charakter und bedürfen einer erneuten Überprüfung nach Verbesserung der Studienlage.
Approximation of minimal surfaces with free boundaries: convergence results
Authors: Jenschke Tristan 
Published: June 2018

Abstract
In a previous paper we developed a penalty method to approximate solutions of the free boundary problem for minimal surfaces by solutions of certain variational problems depending on a parameter $\lambda $. There we showed existence and $C^2$-regularity of these solutions as well as convergence to the solution of the free boundary problem for $\lambda \to \infty $. In this paper we develop a fully discrete finite element procedure for approximating solutions of these variational problems and prove a convergence estimate, which includes an order of convergence with respect to the grid size.
Investigating consumer responses to online group buying service failures
Authors: Lin Hsin-Hui , Yen Wan-Chu , Wang Yi-Shun , Yeh Yen-Min 
Published: June 2018

Purpose
The purpose of this paper is to explore the effects of consumer role (involved vs observing) on consumer responses in the context of online group buying (OGB) service failures.

Design/methodology/approach
A scenario simulation method with a 2×3 factorial design was used to investigate the impact of consumer role (i.e. involved consumers and observing consumers) on consumer responses (i.e. perceived quality, negative electronic word-of-mouth (eWOM), and switching intention). The moderating role of seller offering type (i.e. physical products, true services, and pseudo services) on the relationship between the consumer role and responses was also tested.

Findings
The differences in perceived quality, negative eWOM, and switching intention between involved consumers and observing consumers were significant. Further, seller offering type moderated the relationship between consumer role and consumer response.

Practical implications
These findings provide several important theoretical and practical implications in regard to OGB service failure and recovery.

Originality/value
This study enriches OGB and service failure literature by a pioneering investigation of how consumer roles respond to OGB service failures and how different seller offering types influence the relationship between consumer role and consumer response. The results will help service providers of OGB benefit from enhancing their service recovery strategies to cope with OGB service failures.
Post-harvest malpractices in fresh fruits and vegetables: food safety and health issues in India
Authors: Panghal Anil , Yadav D.N. , Khatkar Bhupender S. , Sharma Himanshu , Kumar Vikas , Chhikara Navnidhi 
Published: June 2018

Purpose
Fruits and vegetables, being good source of energy, health promoting and protecting compounds with unique taste and flavor, are attracting consumers since ages. These horticultural produces start deterioration just after harvest; therefore, their proper storage is must during transportation and storage to retain maximum quality parameters and for good market value. Best storage conditions are required to prevent growth of micro flora and to maintain the nutritional values of harvested produce. Retailers and processors in every corner of world want to move toward the cheaper ways to increase the shelf life and texture of horticultural crops for better consumer preference. The purpose of this paper is to make consumers and researchers aware about different post harvest malpractices in fresh fruits and vegetables.

Design/methodology/approach
Lot of chemicals like colors, artificial ripening agents, sweeteners and waxes are applied on surface of horticulture produce to siphon off money from consumers, and these have adverse health effects directly or indirectly. Various regulatory agencies have launched various programs, acts and laws for monitoring and avoiding such unhealthy ways. Regulatory bodies launched training programs also for the food handlers and consumers to ensure the food safety from farm to fork.

Findings
This paper will throw light on different malpractices followed by retailers to manipulate the quality which causes adverse health effects and to create consumer awareness regarding such malpractices.

Originality/value
The paper emphasizes on current malpractices followed by retailers to mislead the consumers about fruits’ and vegetable’ quality by using sweeteners, colors and other chemical. On prolonged consumption, such substances lead to major health issues such as attention disorder.
Acupuncture and herbal formulation compared with artificial tears alone: evaluation of dry eye symptoms and associated tests in randomised clinical trial
Authors: Tong Louis , Htoon Hla Myint , Hou Aihua , Acharya Rajendra Udyavara , Tan Jen-Hong , Wei Qi-Ping , Lim Pat 
Published: June 2018

ObjectiveDry eye is a common disease with great health burden and no satisfactory treatment. Traditional Chinese medicine, an increasingly popular form of complementary medicine, has been used to treat dry eye but studies have been inconclusive. To address this issue, we conducted a randomised investigator-masked study which included the robust assessment of disease mechanisms.Methods and analysisEligible participants (total 150) were treated with artificial tear (AT) alone, with added eight sessions of acupuncture (AC) or additional daily oral herb (HB) over a month.ResultsParticipants treated with AC were more likely to respond symptomatically than those on AT (88% vs 72%, p=0.039) with a difference of 16% (95% CI: 0.18 to 31.1). The number-to-treat with AC to achieve response in one person was 7 (3 to 157). Participants in the AC group also had reduced conjunctival redness (automatic grading with Oculus keratograph) compared with AT (p=0.043) and reduced tear T helper cell (Th1)-cytokine tumour necrosis factor α (p=0.027) and Th2-cytokine interleukin 4 concentrations (p=0.038). AC was not significantly superior to AT in other outcomes such as tear osmolarity, tear evaporation rates, corneal staining and tear break-up times. No significant adverse effects were encountered. HB was not significantly different in the primary outcome from AT (80% vs 72%, p=0.26).ConclusionsAC is safe and provides additional benefit in mild to moderate dry eye up to 1 month, compared with ATs alone. Treatment is associated with demonstrable molecular evidence of reduced inflammation. Provided that suitably qualified practitioners are available to implement standardised treatment, AC may be recommended as adjunctive therapy to AT.Trial registration numberClinicalTrials.gov (NCT02219204)registered on 14 August 2014.
A propensity matched analysis of robotic, minimally invasive, and conventional mitral valve surgery
Authors: Hawkins Robert B , Mehaffey J Hunter , Mullen Matthew G , Nifong Wiley L , Chitwood W Randolph , Katz Marc R , Quader Mohammed A , Kiser Andy C , Speir Alan M , Ailawadi Gorav 
Published: June 2018

ObjectivesInstitutional studies suggest robotic mitral surgery may be associated with superior outcomes. The objective of this study was to compare the outcomes of robotic, minimally invasive (mini), and conventional mitral surgery.MethodsA total of 2300 patients undergoing non-emergent isolated mitral valve operations from 2011 to 2016 were extracted from a regional Society of Thoracic Surgeons database. Patients were stratified by approach: robotic (n=372), mini (n=576) and conventional sternotomy (n=1352). To account for preoperative differences, robotic cases were propensity score matched (1:1) to both conventional and mini approaches.ResultsThe robotic cases were well matched to the conventional (n=314) and mini (n=295) cases with no significant baseline differences. Rates of mitral repair were high in the robotic and mini cohorts (91%), but significantly lower with conventional (76%, P<0.0001) despite similar rates of degenerative disease. All procedural times were longest in the robotic cohort, including operative time (224 vs 168 min conventional, 222 vs 180 min mini; all P<0.0001). The robotic approach had comparable outcomes to the conventional approach except there were fewer discharges to a facility (7% vs 15%, P=0.001) and 1 less day in the hospital (P<0.0001). However, compared with the mini approach, the robotic approach had more transfusions (15% vs 5%, P<0.0001), higher atrial fibrillation rates (26% vs 18%, P=0.01), and 1 day longer average hospital stay (P=0.02).ConclusionDespite longer procedural times, robotic and mini patients had similar complication rates with higher repair rates and shorter length of stay metrics compared with conventional surgery. However, the robotic approach was associated with higher atrial fibrillation rates, more transfusions and longer postoperative stays compared with minimally invasive approach.
Osteoporosis in psoriatic arthritis: a cross-sectional study of an outpatient clinic population
Authors: Gulati Agnete Malm , Michelsen Brigitte , Diamantopoulos Andreas , Grandaunet Berit , Salvesen Øyvind , Kavanaugh Arthur , Hoff Mari , Haugeberg Glenn 
Published: June 2018

BackgroundThe risk of osteoporosis in patients with psoriatic arthritis (PsA) still remains unclear. The aim of this study was to investigate bone mineral density (BMD) at the hip and lumbar spine measured by dual-energy X-ray absorptiometry in patients with PsA.MethodsFrom an outpatient clinic in southern Norway, 140 patients with PsA were consecutively recruited and assessed for osteoporosis as part of a prospective study from January 2013 to May 2014. An extensive data collection was performed including demographic data and measures reflecting disease activity and health status.ResultsMean age was 52.4 years and 71 (50.7%) were women. Median disease duration was 7.8 years. The proportion of patients with low BMD (defined as Z score≤−1.0 SD) was comparable to the expected value of 16%, according to the normal distribution of the Z score in the population. Osteoporosis was only found in 6.4% (95% CI3% to 11%) of the patients. No significant associations were found between BMD and disease activity measures.ConclusionThe prevalence of PsA patients with osteoporosis or low BMD was low and in the range seen in the reference population. This supports that patients with PsA are not at high risk for osteoporosis compared with the general population. Therefore, clinicians may follow the general population guidelines for monitoring of osteoporosis for patients with PsA.
Enhancement of Peptide Vaccine Immunogenicity by Increasing Lymphatic Drainage and Boosting Serum Stability
Authors: Moynihan Kelly D. , Holden Rebecca L. , Mehta Naveen K. , Wang Chensu , Karver Mark R. , Dinter Jens , Liang Simon , Abraham Wuhbet , Melo Mariane B. , Zhang Angela Q. , Li Na , Gall Sylvie Le , Pentelute Bradley L. , Irvine Darrell J. 
Published: June 2018

Abstract
Antitumor T-cell responses have the potential to be curative in cancer patients, but the induction of potent T-cell immunity through vaccination remains a largely unmet goal of immunotherapy. We previously reported that the immunogenicity of peptide vaccines could be increased by maximizing delivery to lymph nodes (LNs), where T-cell responses are generated. This was achieved by conjugating the peptide to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG (DSPE-PEG) to promote albumin binding, which resulted in enhanced lymphatic drainage and improved T-cell responses. Here, we expanded upon these findings and mechanistically dissected the properties that contribute to the potency of this amphiphile-vaccine (amph-vaccine). We found that multiple linkage chemistries could be used to link peptides with DSPE-PEG, and further, that multiple albumin-binding moieties conjugated to peptide antigens enhanced LN accumulation and subsequent T-cell priming. In addition to enhancing lymphatic trafficking, DSPE-PEG conjugation increased the stability of peptides in serum. DSPE-PEG peptides trafficked beyond immediate draining LNs to reach distal nodes, with antigen presented for at least a week in vivo, whereas soluble peptide presentation quickly decayed. Responses to amph-vaccines were not altered in mice deficient in the albumin-binding neonatal Fc receptor (FcRn), but required Batf3-dependent dendritic cells (DCs). Amph-peptides were processed by human DCs equivalently to unmodified peptides. These data define design criteria for enhancing the immunogenicity of molecular vaccines to guide the design of next-generation peptide vaccines. Cancer Immunol Res; 6(9); 1025–38. ©2018 AACR.
Determining the Pathogenicity of a Genomic Variant of Uncertain Significance Using CRISPR/Cas9 and Human-Induced Pluripotent Stem Cells
Authors: Ma Ning , Zhang Joe Z. , Itzhaki Ilanit , Zhang Sophia L. , Chen Haodong , Haddad Francois , Kitani Tomoya , Wilson Kitchener D. , Tian Lei , Shrestha Rajani , Wu Haodi , Lam Chi Keung , Sayed Nazish , Wu Joseph C. 
Published: June 2018

Background:
The progression toward low-cost and rapid next-generation sequencing has uncovered a multitude of variants of uncertain significance (VUS) in both patients and asymptomatic “healthy” individuals. A VUS is a rare or novel variant for which disease pathogenicity has not been conclusively demonstrated or excluded, and thus cannot be definitively annotated. VUS, therefore, pose critical clinical interpretation and risk-assessment challenges, and new methods are urgently needed to better characterize their pathogenicity.

Methods:

To address this challenge and showcase the uncertainty surrounding genomic variant interpretation, we recruited a “healthy” asymptomatic individual, lacking cardiac-disease clinical history, carrying a hypertrophic cardiomyopathy (HCM)-associated genetic variant (NM_000258.2:c.170C>A, NP_000249.1:p.Ala57Asp) in the sarcomeric gene
MYL3
, reported by the ClinVar database to be “likely pathogenic.” Human-induced pluripotent stem cells (iPSCs) were derived from the heterozygous VUS
MYL3
(170C>A)
carrier, and their genome was edited using CRISPR/Cas9 to generate 4 isogenic iPSC lines: (1) corrected “healthy” control; (2) homozygous VUS
MYL3
(170C>A
)
; (3) heterozygous frameshift mutation
MYL3
(170C>A/fs
)
; and (4) known heterozygous
MYL3
pathogenic mutation (NM_000258.2:c.170C>G), at the same nucleotide position as VUS
MYL3
(170C>A)
, lines. Extensive assays including measurements of gene expression, sarcomere structure, cell size, contractility, action potentials, and calcium handling were performed on the isogenic iPSC-derived cardiomyocytes (iPSC-CMs).

Results:

The heterozygous VUS
MYL3
(170C>A)
-iPSC-CMs did not show an HCM phenotype at the gene expression, morphology, or functional levels. Furthermore, genome-edited homozygous VUS
MYL3
(170C>A)
- and frameshift mutation
MYL3
(170C>A/fs)
-iPSC-CMs lines were also asymptomatic, supporting a benign assessment for this particular
MYL3
variant. Further assessment of the pathogenic nature of a genome-edited isogenic line carrying a known pathogenic
MYL3
mutation,
MYL3
(170C>G)
, and a carrier-specific iPSC-CMs line, carrying a
MYBPC3
(961G>A)
HCM variant, demonstrated the ability of this combined platform to provide both pathogenic and benign assessments.

Conclusions:
Our study illustrates the ability of clustered regularly interspaced short palindromic repeats/Cas9 genome-editing of carrier-specific iPSCs to elucidate both benign and pathogenic HCM functional phenotypes in a carrier-specific manner in a dish. As such, this platform represents a promising VUS risk-assessment tool that can be used for assessing HCM-associated VUS specifically, and VUS in general, and thus significantly contribute to the arsenal of precision medicine tools available in this emerging field.
The Use of the Peshitta of Isaiah in Rendering Isaiah Quotations in the Old Syriac and Peshitta Gospels
Authors: Bodor Attila 
Published: June 2018

Abstract
Previous research has argued that the Old Syriac and Peshitta Gospels tend to follow the Old Testament Peshitta to render Old Testament quotations, a practice that supposedly goes back to Tatian’s Diatessaron. This article argues that this conclusion should be reconsidered. At least in the rendering of the Isaiah quotations, the Old Syriac, and especially the Peshitta version of the Gospels, tends not to depart from the Greek text, but rather to render its sense as faithfully as possible. Even in the few cases where the dependence on the Peshitta of Isaiah appears to be verifiable, the phenomenon does not need to be explained as a result of influence from Tatian’s harmony.