bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fundamental rights and private enforcement in the digital age
Authors: Bassini Marco 
Published: April 2019

AbstractThis article addresses the shift inthe paradigm of fundamental rights protection on the Internet. More and morethe enforcement of such rights is being delegated to private Internet operators, and the urgent question is how the task of balancing conflicting rights affects the status of Internet Service Providers (ISPs). The article examines the increasing privatisation of fundamental rights enforcementon the Internet, highlighting the impact of this trend. Following the analysisof recent developments, it argues that the pillars governing ISP liability should not be altered. In particular, the early determination that ISPs should not be presumptively saddled with content monitoring tasks should not be called into question. Therefore, the regulatory pressure on ISPs shouldbe lowered, as the spectre of liability, combined with ISPs' increasing role indeciding the proper balance between conflicting rights, unduly burdens the activity of ISPs and generates incentives to delete even lawful content.
Privacy as Europe's first Amendment
Authors: Petkova Bilyana 
Published: April 2019

AbstractThe protection of universal principles varies across jurisdictions: the prominence of free speech in the United States is undisputed. My argument is that the First Amendment took off only during the New Deal and later, the Civil Rights revolution as an identity‐formation and unifying tool in a deeply divided society. The symbolic significance of free speech in the US remains central to this day. In the midst of its identity crisis with looming Brexit, Europe is now experimenting with privacy‐as‐constitutional identity in a similar way. This article seeks to unpack the values encompassed in privacy and freedom of speech, looking into the different functional responses that two different democratic societies place their bets on. As data protection and privacy come to a clash with important trade and security interests in an evermore‐globalized world, the power of the outward‐oriented European privacy discourse is likely to remain above all rhetorical.
Melanosome maturation proteins Oca2, Mitfa and Vps11 are differentially required for cisplatin resistance in zebrafish melanocytes
Authors: Peterson Kersten A. , Neuffer Samantha , Bean Miranda E. , New Leslie , Coffin Allison B. , Cooper Cynthia D. 
Published: April 2019

AbstractMelanoma is the deadliest form of skin cancer, partially due to its inherent resistance to therapy. Here, we test in live larvae the hypothesis that mature melanosomes contribute to resistance to chemotherapeutic drug, cisplatin, via drug sequestration. We also compare three melanosome biogenesis proteins—microphthalmia‐associated transcription factor (Mitfa), vacuolar protein sorting 11 (Vps11) and oculocutaneous albinism 2 (Oca2) to determine their respective contributions to chemoresistance. Melanocytes in zebrafish larvae harbouring loss‐of‐function mutations in the mitfa, vps11 or oca2 genes are more sensitive to cisplatin damage than wild‐type larvae. As a comparison, we examined sensory hair cells of the lateral line, which are sensitive to cisplatin. Hair cells in oca2 and mitfa mutants do not show increased cisplatin sensitivity when compared to wild‐type larvae, suggesting the increase in cisplatin sensitivity could be melanocyte specific. However, hair cells in vps11 mutants are more sensitive to cisplatin than their wild‐type counterparts, suggesting that this mutation increases cisplatin susceptibility in multiple cell types. This is the first in vivo study to show an increase in chemotherapeutic drug sensitivity when melanosome maturation mutations are present. The proteins tested, especially Oca2, represent novel drug targets for increasing the efficiency of melanoma chemotherapy treatment.
The impact of psychosocial determinants on caregivers’ burden of children with haemophilia (results of the BBC study)
Authors: von Mackensen Sylvia , Myrin Westesson Linda , Kavakli Kaan , Klukowska Anna , Escuriola Carmen , Uitslager Nanda , Santoro Cristina , Holland Mike , Khair Kate 
Published: April 2019

IntroductionCaring for a child with haemophilia is burdensome and impacting on caregivers’ emotional and financial status. This paper assesses the impact of psychosocial determinants on caregivers’ burden across European countries.MethodsThis non‐interventional study enrolled caregiver/child dyads at haemophilia treatment centres (HTCs) using the “HEMOphilia associated CAregiver Burden scale” (HEMOCAB). Socio‐demographic characteristics and clinical data were collected.ResultsA total of 144 dyads from Germany (n = 19), Italy (n = 19), Netherlands (n = 19), Turkey (n = 20), Sweden (n = 21), UK (n = 21) and Poland (n = 25) participated. Caregivers’ mean age was 39.84 ± 7 (range 24‐57); 81.3% were mothers, married (80.4%), living with a partner (86.6%), had a college/university degree (66.5%) and worked (74.2%). Around two thirds of caregivers (66.2%) reported that haemophilia affected their life; 26.8% reported an economic impact; 57.6% reported their child cannot do certain things because of his condition. Caregivers lost an average of 8.35 ± 14.5 days due to haemophilia. The highest burden was reported in the HEMOCAB domains “Perception of Child” (37.9 ± 24.7), “Emotional Stress” (37.4 ± 22.6) and “Medical Management” (33.1 ± 22.8). Significantly, higher burden was found in caregivers who reported that haemophilia “affects their life” (P < 0.0001), “has an economic impact” (P < 0.0001), “their child cannot do certain things” (P < 0.0001), “they spent ≥5 h/mo infusing” (P < 0.003) and “they needed ≥3 h/mo to reach the HTC” (P < 0.0001).ConclusionThis “snapshot” analysis of burden related to caring for a child with haemophilia across Europe revealed the greatest burdens are economic, including days lost from work, and things that a child cannot do, impacting on both child and caregiver.
Loss of expression of MLH1 in non‐dysplastic crypts is a harbinger of neoplastic progression in sessile serrated adenomas/polyps
Authors: Yozu Masato , Kem Marina , Cenaj Odise , Mino‐Kenudson Mari , Odze Robert D , Misdraji Joseph 
Published: April 2019

AimsDysplasia in colonic sessile serrated adenomas (SSAs)/sessile serrated polyps often shows loss of MLH1 expression as determined with immunohistochemistry, but the significance of loss of MLH1 expression in non‐dysplastic crypts in these polyps is less well studied. The purpose of this study was to evaluate the prevalence of loss of MLH1 expression in non‐dysplastic crypts in SSAs, and to evaluate its significance with regard to progression of these polyps.Methods and resultsFour hundred SSAs, including 158 SSAs without dysplasia, 219 SSAs with dysplasia (SSAD), and 23 SSAs with invasive adenocarcinoma (SSAC), were evaluated immunohistochemically for loss of MLH1 expression in both non‐dysplastic and dysplastic portions of the polyps. Seventy‐one of 400 (18%) SSAs showed loss of MLH1 expression in non‐dysplastic crypts. The prevalence of MLH1‐deficient non‐dysplastic crypts was higher in polyps with dysplasia or carcinoma (7%, 22%, and 52% in SSAs, SSADs, and SSACs, respectively; P < 0.0001). When SSAs with MLH1‐deficient dysplasia and those with MLH‐1‐proficient dysplasia were compared, those with MLH1‐deficient dysplasia were more likely to have MLH1‐deficient non‐dysplastic crypts (66% versus 8.1%, P < 0.0001) and a greater number of discrete foci (3.6 foci versus 1.1 foci, P = 0.008). Also, non‐dysplastic crypts with loss of MLH1 expression were more likely to be contiguous with the dysplasia when the dysplasia also showed loss of MLH1 expression (26% versus 0%, P = 0.02).ConclusionsOur results suggest that loss of MLH1 expression in non‐dysplastic crypts in SSAs precedes the development of MLH1‐deficient dysplasia and adenocarcinoma, and may be a biomarker of an advanced serrated polyp even in the absence of dysplasia.
Numerical and experimental study of blow and blow for perfume bottles to predict glass thickness and blank mold influence
Authors: Biosca Adrià , Borrós Salvador , Pedret Clemente Vicenç , Hyre Matthew R. , García Granada Andrés‐Amador 
Published: April 2019

AbstractGlass forming to produce perfume bottles with specific thickness distribution profiles is based on trial and error and requires several tests in production line. These tests are expensive and time‐consuming, which increases time to market. The use of a numerical model aims to reduce the number of prototypes by performing virtual tests of the mold equipment and the process conditions. This article presents results of numerical simulations of the blow and blow forming process to predict glass thickness distribution. Correlation of the simulation results of the glass temperature with experimental infrared measurements on the glass skin and experimental validation of glass forming simulations and influence of the blank mold cavity in the thickness distributions of perfume bottles are provided. Finally validation of the results of axisymmetrical and three‐dimensional models for axisymmetric bottles defining a useful technique to use the right blank mold for desired thickness distribution while reducing the trial and error testing.
Fibroblastic reticular cells at the nexus of innate and adaptive immune responses
Authors: Perez‐Shibayama Christian , Gil‐Cruz Cristina , Ludewig Burkhard 
Published: April 2019

SummaryLymphoid organs guarantee productive immune cell interactions through the establishment of distinct microenvironmental niches that are built by fibroblastic reticular cells (FRC). These specialized immune‐interacting fibroblasts coordinate the migration and positioning of lymphoid and myeloid cells in lymphoid organs and provide essential survival and differentiation factors during homeostasis and immune activation. In this review, we will outline the current knowledge on FRC functions in secondary lymphoid organs such as lymph nodes, spleen and Peyer's patches and will discuss how FRCs contribute to the regulation of immune processes in fat‐associated lymphoid clusters. Moreover, recent evidence indicates that FRC critically impact immune regulatory processes, for example, through cytokine deprivation during immune activation or through fostering the induction of regulatory T cells. Finally, we highlight how different FRC subsets integrate innate immunological signals and molecular cues from immune cells to fulfill their function as nexus between innate and adaptive immune responses.
Compartmentalization of dendritic cell and T‐cell interactions in the lymph node: Anatomy of T‐cell fate decisions
Authors: León Beatriz , Lund Frances E. 
Published: April 2019

SummaryUpon receiving cognate and co‐stimulatory priming signals from antigen (Ag)‐presenting dendritic cells (DCs) in secondary lymphoid tissues, naïve CD4+ T cells differentiate into distinct effector and memory populations. These alternate cell fate decisions, which ultimately control the T‐cell functional attributes, are dictated by programming signals provided by Ag‐bearing DCs and by other cells that are present in the microenvironment in which T‐cell priming occurs. We know that DCs can be subdivided into multiple populations and that the various DC subsets exhibit differential capacities to initiate development of the different CD4+ T‐helper populations. What is less well understood is why different subanatomic regions of secondary lymphoid tissues are colonized by distinct populations of Ag‐presenting DCs and how the location of these DCs influences the type of T‐cell response that will be generated. Here we review how chemokine receptors and their ligands, which position allergen and nematode‐activated DCs within different microdomains of secondary lymphoid tissues, contribute to the establishment of IL‐4 committed follicular helper T and type 2 helper cell responses.
T‐cell positioning by chemokines in autoimmune skin diseases
Authors: Richmond Jillian M. , Strassner James P. , Essien Kingsley I. , Harris John E. 
Published: April 2019

SummaryAutoimmune skin diseases are complex processes in which autoreactive cells must navigate through the skin tissue to find their targets. Regulatory T cells in the skin help to mitigate autoimmune inflammation and may in fact be responsible for the patchy nature of these conditions. In this review, we will discuss chemokines that are important for global recruitment of T cell populations to the skin during disease, as well as signals that fine‐tune their localization and function. We will describe prototypical disease responses and chemokine families that mediate these responses. Lastly, we will include an overview of chemokine‐targeting drugs that have been tested as new treatment strategies for autoimmune skin diseases.
Studying the multilevel impact of cohesion versus structural holes in knowledge networks on adaptation to IT‐enabled patient‐care practices
Authors: Raman Roopa , Grover Varun 
Published: April 2019

AbstractWe investigate the impact of cohesion versus structural holes in two different types of knowledge networks—help‐seeking networks and voluntary contribution networks—on adaptation to health IT‐enabled patient‐care practices. In a multimethod study conducted within a large hospital system, qualitative and quantitative data were collected from 806 clinicians working with electronic medical record systems in 27 inpatient patient‐care units. Multilevel analysis of the data revealed that overall network cohesiveness versus location in structural hole positions related to adaptation differently, depending on the type of network. In help‐seeking networks, location in structural hole positions was negatively related to adaptation, while network cohesion had a bell‐shaped curvilinear relationship with adaptation; in voluntary contribution networks, the overall cohesiveness of the network was negatively related to adaptation, but location in structural hole positions was irrelevant to adaptation. Our findings suggest a more nuanced way of monitoring and utilising different sets of informal social interactions at work to maximise employees' adaptation to IT‐enabled work.
Triggering efficient photocatalytic water oxidation reactions over BaNbO2N by incorporating Ca at B site
Authors: Wei Shunhang , Jin Shu , Pan Guoxiang , Li Zuxin , Liu Gang , Xu Xiaoxiang 
Published: April 2019

AbstractAlthough BaNbO2N has visible light absorption as far as 740 nm, its photocatalytic activity is generally very poor under ordinary conditions, being incommensurate to its light absorption properties. In this work, we introduce Ca into the B site of BaNbO2N to form a complex perovskite BaNb1−x/3Cax/3O2+yN1−y (0 ≤ x, y ≤ 1). The presence of Ca in BaNbO2N has great impact on a number of important properties such as band gap value, nitrogen content, surface hydrophilicity, and defects levels. In particular, defects such as Nb4+ species are effectively suppressed in Ca‐modified BaNbO2N. More importantly, photocatalytic activity of BaNbO2N for water oxidation reactions is substantially improved after Ca modifications. Compared with pristine BaNbO2N, more than twofold enhancement in photocatalytic oxygen evolution is observed for BaNb0.8Ca0.2O2+yN1−y (x = 0.6). Such improvements probably stem from the suppression of Nb4+ species in the structure as well as enhanced surface hydrophilicity after Ca modification. The facile approach by incorporating alkaline earth cations into crystal structure can be well extended to other perovskite oxynitrides whose photocatalytic activity is subject to those defective species.
Retrospective chart review of spectacle prescription prevalence in adults with learning disabilities in Scotland
Authors: Butchart Maggie , Colahan Craig 
Published: April 2019

AbstractBackgroundEvidence suggests that people with learning disabilities are less likely to have an up‐to‐date eye examination as sight loss is characteristically underdiagnosed in people with complex needs.MethodA retrospective study of records from 576 Service Users of RNIB UK Vision, learning disability and Complex Needs Services was carried out.ResultsThe record review found a higher prevalence of spectacle prescription in a learning disability (LD) population in agreement with findings from other LD studies. There was a higher prevalence of severe myopia in people with LD compared with a general adult population.ConclusionThis study found a higher prevalence of spectacle prescription in people with learning disabilities compared to a general adult population, which has implications for people with learning disabilities to ensure that they have access to eye care and regularly attended eye tests. It also has implications for healthcare professionals working with people with complex needs to ensure they have access to eye care.
Association of thyroid function with white coat hypertension and sustained hypertension
Authors: Cai Peng , Peng Yan , Chen YuXi , Li Li , Chu Wei , Wang Yan , Wang Xukai 
Published: April 2019

This study aimed to explore the relationship of thyroid‐stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels with hypertension subtypes. 1056 euthyroid adults were included as research samples. They underwent measurement of clinic blood pressure and 24‐hours ambulatory blood pressure monitoring. Then, they were divided into normotension (NT), white coat hypertension (WCH), masked hypertension (MHT), and sustained hypertension (SHT) groups. The 24‐hours dynamic electrocardiogram was performed to analyze the heart rate variability (HRV), so as to reflect the cardiac autonomic function. The relationship between hypertension subtypes, thyroid function, and HRV was analyzed. The TSH concentration was significantly higher in the SHT group than in the NT group (P = 0.001). The FT3 concentration was higher in the SHT group than in the NT and MHT groups (P = 0.013, P = 0.008), while the FT4 concentration was significantly higher in the WCH group than in the NT group (P = 0.002). The changes in HRV were observed between the SHT, WCH, and MHT groups and the NT groups, as well as between the SHT and the MHT groups. The multiple linear regression analysis also showed that FT3, HRV (RMSSD and PNN50), and blood pressure levels linearly correlated with one another (P < 0.05). Meanwhile, the linear regression analysis showed a linear negative correlation between FT4 and HRV (SDANN) in the WCH + NT group (P = 0.001). Thyroid function was closely related to hypertension subtypes such as WCH probably due to the changes in the cardiac autonomic function.
The role of autophagy in the pathogenesis of exposure keratitis
Authors: Wang Guoliang , Xue Yuhua , Wang Yanzi , Dong Fei , Shen Mei , Zong Rongrong , Liu Zuguo , Li Cheng 
Published: April 2019

AbstractIncomplete tear film spreading and eyelid closure can cause defective renewal of the ocular surface and air exposure‐induced epithelial keratopathy (EK). In this study, we characterized the role of autophagy in mediating the ocular surface changes leading to EK. Human corneal epithelial cells (HCECs) and C57BL/6 mice were employed as EK models, respectively. Transmission electron microscopy (TEM) evaluated changes in HCECs after air exposure. Each of these models was treated with either an autophagy inhibitor [chloroquine (CQ) or 3‐methyladenine (3‐MA)] or activator [Rapamycin (Rapa)]. Immunohistochemistry assessed autophagy‐related proteins, LC3 and p62 expression levels. Western blotting confirmed the expression levels of the autophagy‐related proteins [Beclin1 and mammalian target of rapamycin (mTOR)], the endoplasmic reticulum (ER) stress‐related proteins (PERK, eIF2α and CHOP) and the PI3K/Akt/mTOR signalling pathway‐related proteins. Real‐time quantitative PCR (qRT‐PCR) determined IL‐1β, IL‐6 and MMP9 gene expression levels. The TUNEL assay detected apoptotic cells. TEM identified autophagic vacuoles in both EK models. Increased LC3 puncta formation and decreased p62 immunofluorescent staining and Western blotting confirmed autophagy induction. CQ treatment increased TUNEL positive staining in HCECs, while Rapa had an opposite effect. Similarly, CQ injection enhanced air exposure‐induced apoptosis and inflammation in the mouse corneal epithelium, which was inhibited by Rapa treatment. Furthermore, the phosphorylation status of PERK and eIF2α and CHOP expression increased in both EK models indicating that ER stress‐induced autophagy promoted cell survival. Taken together, air exposure‐induced autophagy is indispensable for the maintenance of corneal epithelial physiology and cell survival.
Oral hygiene phase revisited: How different study designs have affected results in intervention studies
Authors: Preus Hans R. , Maharajasingam Nisha , Rosic Jovana , Baelum Vibeke 
Published: April 2019

AbstractEvery periodontal researcher have been taught, and every textbook in periodontics have advocated, that a phase in which the patient is meticulously motivated and instructed in proper oral hygiene—the oral hygiene phase—must be included in any periodontal intervention. However, how is this oral hygiene phase actually portrayed in periodontal intervention studies, and how much space have this important phase received in the planning and carry‐through of intervention studies? The purpose of this letter to the editor was to review current literature in the period 1975/01/01–2017/12/31 on periodontal, mechanical intervention studies in order to see what focus the oral hygiene phase had received in these articles. The result showed that the oral hygiene phase is variable in length and content, variable in claimed result, insufficiently described, and invariably amalgamated with the scaling and root planing which is the intervention or part of an intervention. The consequences of these findings are discussed and suggestions proposed for more harmonized and calibrated oral hygiene phase introduced to avoid biased and inflated results of interventions.
External validation and comparison of four confocal microscopic scores for melanoma diagnosis on a retrospective series of highly suspicious melanocytic lesions
Authors: Pampena R. , Borsari S. , Lai M. , Benati E. , Longhitano S. , Mirra M. , Kyrgidis A. , Pellacani G. , Longo C. 
Published: April 2019

AbstractBackgroundIn vivo reflectance confocal microscopy significantly improves melanoma diagnosis as compared to clinical/dermoscopic examination alone. Several confocal criteria have been described allowing to differentiate melanoma from nevi; by combining different criteria, three pure confocal scores (Pellacani 2005, Segura 2009 and Pellacani 2012) and one mixed dermoscopic/confocal score (Borsari 2018) were constructed.ObjectiveOur aim was to externally validate and compare the performance of these confocal scores.MethodsWe retrospectively enrolled excised melanocytic lesions which underwent confocal examination in a 2‐year period. Lesions located on the face and acral sites were excluded. Both dermoscopic and confocal criteria considered in the four scores were evaluated by experts. Subsequently, specificity and sensitivity levels for each score were calculated, together with the positive and negative predictive values and likelihood ratios; also, receiver operating characteristic curves were constructed.ResultsA total of 389 patients with 422 lesions were retrospectively enrolled, of which 162 (38.4%) were melanomas and 260 (61.6%) were nevi (189 common and 71 Spitz/Reed nevi). The highest sensitivity levels were recorded for Segura 2009 with cut‐off ≥−1 (92.0%), while Pellacani 2005 with cut‐off ≥5 achieved the highest specificity (69.6%). The score by Borsari et al. showed the highest levels of positive and negative predictive values (59.8% and 91.5%) and likelihood ratios (2.4 and 0.1) as well as the highest area under the curve values (0.76; 95% CI 0.72–0.81; P < 0.001).ConclusionsHigh levels of accuracy were found for each of the four considered scores. No differences were found among scores in confirming melanoma diagnosis when positive; however, the score by Borsari 2018 was the best in excluding melanoma diagnosis when negative.