bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using GRGDSPC peptides to improve re‐endothelialization of decellularized pancreatic scaffolds
Authors: Wan Jian , Wang Lei , Huang Yan , Fan Haowen , Chen Chunqiu , Yuan Xiaoqi , Guo Yibing , Yin Lu 
Published: November 2019

AbstractEngineering of functional vascularized pancreatic tissues offers an alternative way to solve the perpetual shortage of organs for transplantation. However, revascularization remains a major bottleneck in biological engineering, which limited the further clinical applications of this strategy. In this study, an efficient approach for enhancing re‐endothelialization of rat decellularized pancreatic scaffolds (DPS) was presented, by conjugating with GRGDSPC peptide to maximize coverage of the vessel walls with human umbilical vein endothelial cells (HUVECs). First, pancreas was perfused with 1% Triton X‐100 and 0.1% ammonium hydroxide to remove the cellular components. Subsequently, GRGDSPC was covalently coupled to the vasculature of DPS and re‐seeded with HUVECs via perfusion of the portal vein in the bioreactor. After the re‐endothelialized scaffolds were created, in vitro and in vivo experiments were undertaken to evaluate the angiogenesis. Our results demonstrated that GRGDSPC‐conjugated scaffolds could support the survival and accelerated the proliferation of HUVECs; angiogenesis was also significantly improved over untreated scaffolds. In conclusion, GRGDSPC‐conjugated scaffolds showed great potential for the generation of functional bioengineered pancreatic tissue suitable for long‐term transplantation.
Comparison of macular buckling and vitrectomy for the treatment of macular schisis and associated macular detachment in high myopia: a randomized clinical trial
Authors: Liu Bingqian , Chen Shida , Li Yonghao , Lian Ping , Zhao Xiujuan , Yu Xiling , Li Tao , Jin Chenjin , Liang Xiaoling , Huang Suber S. , Lu Lin 
Published: November 2019

AbstractObjectiveTo compare the efficacy and safety of macular buckling and vitrectomy for myopic traction maculopathy showing macular schisis (MS) and associated macular detachment (MD) but without full‐thickness macular hole (FTMH).DesignProspective, randomized, parallel, open‐label study.MethodsPatients were randomly assigned to either buckling or vitrectomy group. Macular buckling and intravitreal C3F8 gas injection were performed in the buckling group. Small gauge vitrectomy, internal limiting membrane peeling (ILMP) and C3F8 gas tamponade were performed in the vitrectomy group. The patients were followed for 12 months.Main outcome measuresBest‐corrected visual acuity (BCVA) at 12 months.ResultsA total of 85 patients were randomized, 80 eyes were included (41 receiving buckling, 39 received vitrectomy), and 78 patients completed the study. There were less eyes determined as surgical failure and required a second surgery in the buckling group than vitrectomy the group (2.4% versus 18.4%, p = 0.021). After surgery, macular buckling achieved more improvement in BCVA (+21.7 versus +4.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, p = 0.002). FTMH development was observed in only 1 (2.4%) eye, after removing of the implant due to recurrent conjunctival erosion, in the buckling group and 10 (26.3%) eyes (seven with‐, three without MD) in the vitrectomy group (p < 0.001). More eyes developed cataracts in the vitrectomy group than did in the buckling group (28.9% versus 7.5%, p = 0.014). Macular buckling‐associated strabismus (esotropia), binocular diplopia and implant exposure were observed in limited cases.Conclusions and relevanceMacular buckling is superior to vitrectomy with ILM peeling plus gas injection for surgical treatment of MS and associated MD in high myopia.
Aqueous humour cytokine changes during a loading phase of intravitreal ranibizumab or dexamethasone implant in diabetic macular oedema
Authors: Podkowinski Dominika , Orlowski‐Wimmer Eva , Zlabinger Gerhard , Pollreisz Andreas , Mursch‐Edlmayr Anna‐Sophie , Mariacher Siegfried , Ring Michael , Bolz Matthias 
Published: November 2019

AbstractPurposeTo determine the effect of intravitreal ranibizumab and a dexamethasone implant on aqueous humour cytokine, protein and enzyme levels and to correlate findings to morphologic and functional changes.MethodsIn a prospective, randomized, controlled, double‐blind study, patients with clinically significant diabetic macular oedema (CSME) were randomly allocated to receive either monthly intravitreal injections of ranibizumab (Lucentis, Novartis Pharma) or a single dexamethasone implant (Ozurdex, Pharm‐Allergan) at baseline (BL). Aqueous humour samples were collected at BL and weeks 2, 8 and 20.ResultsThe study included 18 eyes of 18 patients. In the dexamethasone implant group, soluble intercellular adhesion molecule 1 (sICAM‐1) (weeks 2 and 8), CXCL9/monokine induced by gamma interferon (MIG) (weeks 2 and 8), soluble vascular cell adhesion protein 1 (sVCAM‐1) (weeks 2 and 8) and monocyte chemo‐attractant protein 1 (MCP‐1) (week 2) levels were significantly decreased compared with baseline. In the ranibizumab group, placental growth factor (PIGF) (week 2) and vascular endothelial growth factor (VEGF) (week 2 and 8) levels were significantly decreased compared with baseline. No significant changes in central retinal thickness (CRT) or Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) were observed in the Ozurdex group at any time‐points. ETDRS scores significantly increased at week 20 (84.88 ± 8.88 letters) compared with baseline (74.78 ± 14.85 letters), and the CRT decreased significantly at week 4 (381.00 ± 114.64 μm) compared with baseline (440 ± 144 μm) in the Lucentis group.ConclusionThe dexamethasone implant affected the aqueous cytokines and proteins MCP‐1, sICAM‐1, sVCAM‐1 and MIG, whereas ranibizumab treatments reduced VEGF and PIGF levels. Morphological changes may diverge from cytokine changes. Results may indicate a rationale for a combination therapy for CSME using both agents, the dexamethasone implant and repeatedly administered ranibizumab injections.
Multivariate hierarchical frameworks for modeling delayed reporting in count data
Authors: Stoner Oliver , Economou Theo 
Published: November 2019

AbstractIn many fields and applications, count data can be subject to delayed reporting. This is where the total count, such as the number of disease cases contracted in a given week, may not be immediately available, instead arriving in parts over time. For short‐term decision making, the statistical challenge lies in predicting the total count based on any observed partial counts, along with a robust quantification of uncertainty. We discuss previous approaches to modeling delayed reporting and present a multivariate hierarchical framework where the count generating process and delay mechanism are modeled simultaneously in a flexible way. This framework can also be easily adapted to allow for the presence of underreporting in the final observed count. To illustrate our approach and to compare it with existing frameworks, we present a case study of reported dengue fever cases in Rio de Janeiro. Based on both within‐sample and out‐of‐sample posterior predictive model checking and arguments of interpretability, adaptability, and computational efficiency, we discuss the relative merits of different approaches.
What are the costs of stillbirth? Capturing the direct health care and macroeconomic costs in Australia
Authors: Callander Emily J. , Thomas Joseph , Fox Haylee , Ellwood David , Flenady Vicki 
Published: November 2019

AbstractBackgroundReducing stillbirth rates is an international priority; however, little is known about the cost of stillbirth. This analysis sought to quantify the costs of stillbirth in Australia.MethodsMothers and costs were identified by linking a state‐based registry of all births between 2012 and 2015 to other administrative data sets. Costs from time of birth to 2 years postbirth were included. Propensity score matching was used to account for differences between women who had a stillbirth and those that did not. Macroeconomic costs were estimated using value of lost output analysis and value of lost welfare analysis.ResultsCost to government was on average $3774 more per mother who had a stillbirth compared with mothers who had a live birth. After accounting for gestation at birth, the cost of a stillbirth was 42% more than a live birth (P < .001). Costs for inpatient services, emergency department services, services covered under Medicare (such as primary and specialist care, diagnostic tests and imaging), and prescription pharmaceuticals were all significantly higher for mothers who had a stillbirth. Mothers who had a stillbirth paid on average $1479 out of pocket, which was 52% more than mothers who had a live birth after accounting for gestation at birth (P < .001). The value of lost output was estimated to be $73.8 million (95% CI: 44.0 million‐103.9 million). The estimated value of lost social welfare was estimated to be $18 billion.DiscussionStillbirth has a sustained economic impact on society and families, which demonstrates the potential resource savings that could be generated from stillbirth prevention.
Extended experience with a non‐cytotoxic DNMT1‐targeting regimen of decitabine to treat myeloid malignancies
Authors: Awada Hassan , Mahfouz Reda Z. , Kishtagari Ashwin , Kuzmanovic Teodora , Durrani Jibran , Kerr Cassandra M. , Patel Bhumika J. , Visconte Valeria , Radivoyevitch Tomas , Lichtin Alan , Carraway Hetty E. , Maciejewski Jaroslaw P. , Saunthararajah Yogen 
Published: November 2019

SummaryThe nucleoside analogue decitabine can deplete the epigenetic regulator DNA methyltransferase 1 (DNMT1), an effect that occurs, and is saturated at, low concentrations/doses. A reason to pursue this molecular‐targeted effect instead of the DNA damage/cytotoxicity produced with high concentrations/doses, is that non‐cytotoxic DNMT1‐depletion can cytoreduce even p53‐null myeloid malignancies while sparing normal haematopoiesis. We thus identified minimum doses of decitabine (0·1–0·2 mg/kg) that deplete DNMT1 without off‐target anti‐metabolite effects/cytotoxicity, and then administered these well‐tolerated doses frequently 1–2X/week to increase S‐phase dependent DNMT1‐depletion, and used a Myeloid Malignancy Registry to evaluate long‐term outcomes in 69 patients treated this way. Consistent with the scientific rationale, treatment was well‐tolerated and durable responses were produced (~40%) in genetically heterogeneous disease and the very elderly.
Changes in cellular prion protein expression, processing and localisation during differentiation of the neuronal cell line CAD 5
Authors: Fremuntova Zuzana , Mosko Tibor , Soukup Jakub , Kucerova Johanka , Kostelanska Marie , Hanusova Zdenka Backovska , Filipova Marcela , Cervenakova Larisa , Holada Karel 
Published: November 2019

Background informationCellular prion protein (PrPC) is infamous for its role in prion diseases. The physiological function of PrPC remains enigmatic, but several studies point to its involvement in cell differentiation processes. To test this possibility, we monitored PrPC changes during the differentiation of prion‐susceptible CAD 5 cells, and then we analysed the effect of PrPC ablation on the differentiation process.ResultsNeuronal CAD 5 cells differentiate within 5 days of serum withdrawal, with the majority of the cells developing long neurites. This process is accompanied by an up to sixfold increase in PrPC expression and enhanced N‐terminal β‐cleavage of the protein, which suggests a role for the PrPC in the differentiation process. Moreover, the majority of PrPC in differentiated cells is inside the cell, and a large proportion of the protein does not associate with membrane lipid rafts. In contrast, PrPC in proliferating cells is found mostly on the cytoplasmic membrane and is predominantly associated with lipid rafts. To determine the importance of PrPC in cell differentiation, a CAD 5 PrP−/− cell line with ablated PrPC expression was created using the CRISPR/Cas9 system. We observed no considerable difference in morphology, proliferation rate or expression of molecular markers between CAD 5 and CAD 5 PrP−/− cells during the differentiation initiated by serum withdrawal.ConclusionsPrPC characteristics, such as cell localisation, level of expression and posttranslational modifications, change during CAD 5 cell differentiation, but PrPC ablation does not change the course of the differentiation process.SignificanceAblation of PrPC expression does not affect CAD 5 cell differentiation, although we observed many intriguing changes in PrPC features during the process. Our study does not support the concept that PrPC is important for neuronal cell differentiation, at least in simple in vitro conditions.
Clinical and genetic features in pyridoxine‐dependent epilepsy: a Chinese cohort study
Authors: Jiao Xianru , Xue Jiao , Gong Pan , Wu Ye , Zhang Yuehua , Jiang Yuwu , Yang Zhixian 
Published: November 2019

AimTo characterize the clinical and genetic characteristics of a large cohort of patients with pyridoxine‐dependent epilepsy (PDE).MethodWe retrospectively collected clinical and genetic information of 33 (15 males, 18 females; mean [SD] age 4y 11mo [2y 5mo]; 1y 3mo–10y 4mo) patients with PDE from 31 unrelated families at a single centre.ResultsThere were many types of seizures, with focal seizures in 32 cases. Dravet syndrome was suspected clinically in two patients. Electroencephalogram (EEG) was normal in seven patients at the initial stage and then in 17 patients during pyridoxine maintenance therapy. Genetic studies revealed 26 kinds of variants in ALDH7A1 and four in PLPBP with 18 variants unreported previously, and 48 ALDH7A1 variants were located in exon 11, 12, 14, and 17 or intron 9 and 11. In addition, three patients carried different exons deletion. Among these, seizures could be controlled for several years in one patient by levetiracetam monotherapy. Another patient remained seizure free for up to 7 months without therapy. All patients received oral pyridoxine treatment, with only one case (with exon 8–13 deletion) showing poor control.InterpretationThis study illustrates the range of clinical presentations and genetic causes in PDE, as well as responsiveness to antiepileptic drugs. A relationship between EEG and pyridoxine therapy could be seen in many cases. Seizure control was seen in all with pyridoxine monotherapy except for one patient.What this paper adds

There is a parallel relationship between electroencephalogram and pyridoxine therapy in many patients.

Patients with pyridoxine‐dependent epilepsy may respond well to low‐dose pyridoxine.
Conditioning‐based outcomes after allogeneic transplantation for myeloma following a prior autologous transplant (1991‐2012) on behalf of EBMT CMWP
Authors: Hayden Patrick J. , Iacobelli Simona , Pérez‐Simón José Antonio , van Biezen Anja , Minnema Monique , Niittyvuopio Riitta , Schönland Stefan , Meijer Ellen , Blaise Didier , Milpied Noel , Márquez‐Malaver Francisco J. , Veelken Joan Hendrik , Maertens Johan , Michallet Mauricette , Cammenga Jörg , N'Guyen Stephanie , Niederwieser Dietger , Hunault‐Berger Mathilde , Bourhis Jean Henri , Passweg Jakob , Bermudez Arancha , Chalandon Yves , Yakoub‐Agha Ibrahim , Garderet Laurent , Kröger Nicolaus 
Published: November 2019

AbstractObjectivesThe aim of this study was to compare the effect of the intensity of conditioning approaches used in allogeneic transplantation in myeloma—reduced intensity conditioning (RIC), non‐myeloablative (NMA), myeloablative conditioning (MAC) or Auto‐AlloHCT—on outcomes in patients who had had a prior autologous transplant.MethodsA retrospective analysis of the EBMT database (1991‐2012) was performed.ResultsA total of 344 patients aged between 40 and 60 years at the time of alloHCT were identified: 169 RIC, 69 NMA, 65 MAC and 41 Auto‐Allo transplants. At a median follow‐up of 54 months, the probabilities of overall survival (OS) at 5 years were 39% (95% CI 31%‐47%), 45% (95% CI 32%‐57%), 19% (95% CI 6%‐32%) and 34% (95% CI 17%‐51%), respectively. Status at allogeneic HCT other than CR or PR conferred a 70% higher risk of death and a 40% higher risk of relapse. OS was markedly lower in the MAC group (P = .004). MAC alloHCT was associated with a higher risk of death than RIC alloHCT until 2002 (HR = 4.1, P < .001) but not after 2002 (HR = 1.2, P = .276).ConclusionFrom 1991 to 2002, MAC was associated with poorer OS. Between 2003 and 2012, there were no significant differences in outcomes based on these different approaches.
Threat‐of‐shock decreases emotional interference on affective stroop performance in healthy controls and anxiety patients
Authors: Lago Tiffany R. , Blair Karina S. , Alvarez Gabriella , Thongdarong Amanda , Blair James R. , Ernst Monique , Grillon Christian 
Published: November 2019

AbstractPatients with anxiety disorders suffer from impaired concentration, potentially as a result of stronger emotional interference on attention. Studies using behavioural measures provide conflicting support for this hypothesis. Elevated state anxiety may be necessary to reliably document differences in emotional interference in patients versus healthy controls. The present study examines the effect of experimentally induced state anxiety (threat‐of‐shock) on attention interference by emotional stimuli. Anxiety patients (n = 36) and healthy controls (n = 32) completed a modified affective Stroop task during periods of safety and threat‐of‐shock. Results indicated that in both patients and controls, threat decreased negative, but not positive or neutral, emotional interference on attention (both p < .001). This finding supports a threat‐related narrowing of attention whereby a certain level of anxiety decreases task‐irrelevant processing.
Cholesterol impacts chemokine CCR5 receptor ligand‐binding activity
Authors: Calmet Pierre , Cullin Christophe , Cortès Sandra , Vang Maylou , Caudy Nada , Baccouch Rim , Dessolin Jean , Maamar Nada Taib , Lecomte Sophie , Tillier Bruno , Alves Isabel D. 
Published: November 2019

The chemokine CCR5 receptor is target of maraviroc, a negative allosteric modulator of CCR5 that blocks the HIV protein gp120 from associating with the receptor, thereby inhibiting virus cellular entry. As noted with other G‐protein‐coupled receptor family members, the role of the lipid environment in CCR5 signaling remains obscure and very modestly investigated. Controversial literature on the impact of cholesterol (Chol) depletion in HIV infection and CCR5 signaling, including the hypothesis that Chol depletion could inhibit HIV infection, lead us to focus on the understanding of Chol impact in the first stages of receptor activation. To address this aim, the approach chosen was to employ reconstituted model lipid systems of controlled lipid composition containing CCR5 from two distinct expression systems: Pichia pastoris and cell‐free expression. The characterization of receptor/ligand interaction in terms of total binding or competition binding assays was independently performed by plasmon waveguide resonance and fluorescence anisotropy, respectively. Maraviroc, a potent receptor antagonist, was the ligand investigated. Additionally, coarse‐grained molecular dynamics simulation was employed to investigate Chol impact in the receptor‐conformational flexibility and dynamics. Results obtained with receptor produced by different expression systems and using different biophysical approaches clearly demonstrate a considerable impact of Chol in the binding affinity of maraviroc to the receptor and receptor‐conformational dynamics. Chol considerably decreases maraviroc binding affinity to the CCR5 receptor. The mechanisms by which this effect occurs seem to involve the adoption of distinct receptor‐conformational states with restrained structural dynamics and helical motions in the presence of Chol.
Stochastic Modeling of Groundwater Fluoride Contamination: Introducing Lazy Learners
Authors: Khosravi Khabat , Barzegar Rahim , Miraki Shaghayegh , Adamowski Jan , Daggupati Prasad , Alizadeh Mohammad Reza , Pham Binh Thai , Alami Mohammad Taghi 
Published: November 2019

AbstractWhile it remains the primary source of safe drinking and irrigation water in northwest Iran's Maku Plain, the region's groundwater is prone to fluoride contamination. Accordingly, modeling techniques to accurately predict groundwater fluoride concentration are required. The current paper advances several novel data mining algorithms including Lazy learners [instance‐based K‐nearest neighbors (IBK); locally weighted learning (LWL); and KStar], a tree‐based algorithm (M5P), and a meta classifier algorithm [regression by discretization (RBD)] to predict groundwater fluoride concentration. Drawing on several groundwater quality variables (e.g.,concentrations), measured in each of 143 samples collected between 2004 and 2008, several models predicting groundwater fluoride concentrations were developed. The full dataset was divided into two subsets: 70% for model training (calibration) and 30% for model evaluation (validation). Models were validated using several statistical evaluation criteria and three visual evaluation approaches (i.e., scatter plots, Taylor and Violin diagrams). Although Na+and Ca2+showed the greatest positive and negative correlations with fluoride (r = 0.59 and −0.39, respectively), they were insufficient to reliably predict fluoride levels; therefore, other water quality variables, including those weakly correlated with fluoride, should be considered as inputs for fluoride prediction. The IBK model outperformed other models in fluoride contamination prediction, followed by KStar, RBD, M5P, and LWL. The RBD and M5P models were the least accurate in terms of predicting peaks in fluoride concentration values. Results of the current study can be used to support practical and sustainable management of water and groundwater resources.
Prognostic significance of nucleolar assessment in invasive breast cancer
Authors: Elsharawy Khloud A , Toss Michael S , Raafat Sara , Ball Graham , Green Andrew R , Aleskandarany Mohammed A , Dalton Leslie W , Rakha Emad A 
Published: November 2019

AimsNucleolar morphometric features have a potential role in the assessment of the aggressiveness of many cancers. However, the role of nucleoli in invasive breast cancer (BC) is still unclear. The aims of this study were to investigate the optimal method for scoring nucleoli in IBC and their prognostic significance, and to refine the grading of breast cancer (BC) by incorporating nucleolar score.Methods and resultsDigital images acquired from haematoxylin and eosin‐stained sections from a large BC cohort were divided into training (n = 400) and validation (n = 1200) sets for use in this study. Four different assessment methods were evaluated in the training set to identify the optimal method associated with the best performance and significant prognostic value. These were: (i) a modified Helpap method; (ii) counting prominent nucleoli (size ≥2.5 µm) in 10 field views (FVs); (iii) counting prominent nucleoli in five FVs; and (iv) counting prominent nucleoli in one FV. The optimal method was applied to the validation set and to an external validation set, i.e. data from The Cancer Genome Atlas (n = 743). Scoring prominent nucleoli in five FVs showed the highest interobserver concordance rate (intraclass correlation coefficient of 0.8) and a significant association with BC‐specific survival (P < 0.0001). A high nucleolar score was associated with younger age, larger tumour size, and higher grade. Incorporation of nucleolar score in the Nottingham grading system resulted in a higher significant association with survival than the conventional grade.ConclusionsQuantification of nucleolar prominence in five FVs is a cost‐efficient and reproducible morphological feature that can predict BC behaviour and can provide an alternative to pleomorphism to improve BC grading performance.