bluuebunny/crossref_metadata_2025 huggingface dataset:
Research methodology and practical issues relating to the conduct of a medical device registry
Authors: Bisdas Theodosios , Bohan Patrick , Lescan Mario , Zeebregts Clark J , Tessarek Jörg , van Herwaarden Joost , van den Berg Jos C , Setacci Carlo , Riambau Vincent
Published: June 2019

Background

The postmarket research goal is to assess “generalizability” or “external validity” to see if the early results of clinical trials with investigational devices are reproducible in everyday practice in the real world and the longer term. Registries have an important but ambivalent role in achieving this goal.

Methods

Although registries are common, in practice they follow the regulatory processes that appear designed primarily for pharmaceutical clinical trials and confirmatory studies. We review the literature to assess different definitions and the role of registries in the hierarchy of scientific evidence. We analyze common characteristics affecting registry design, implementation, and governance as well as safety reporting and off-label use while describing the experience of setting up an international, prospective registry for an endovascular device used to treat abdominal aortic aneurysms.

Results

Key areas in which to distinguish registries from trials are as follows: eligibility, setting (patients and institutions), device configurations and iterations, the use of design and quality “spaces,” a focus on systematic quality checks (rather than source data monitoring), open-ended follow-up, flexibility in the definition of end points and sample sizes, data sharing, and publishing commitments.

Conclusion

Both clinical trials and registries are essential and complementary research methods and the strengths and weaknesses of each need to be recognized. The specific characteristics of registry research deserve to be acknowledged and safeguarded in the regulations governing clinical investigations with medical devices.
Spinal 5-HT3 receptor contributes to somatic hyperalgesia induced by sub-chronic stress
Authors: Li Zhuo-Lin , Xue Yang , Tao Zhuo-Ying , Du Wen-Zhi , Jiang Yue-Gui , Cao Dong-Yuan
Published: June 2019

Stress facilitates pain perception and sensitizes pain pathways, but the underlying mechanism is still unclear. The purpose of this study was to investigate whether the activation of 5-hydroxytryptamine (5-HT) subtype-3 receptor in the spinal cord contributes to somatic hyperalgesia induced by repeated three-day forced swim in the estradiol replacement rats after ovariectomy. Somatic sensitivity was assessed by thermal withdrawal latency to radiant heat and mechanical withdrawal threshold to von Frey filaments. The expression of 5-HT3A receptor in the L4–L5 dorsal spinal cord was examined by Western blot. Repeated forced swim stress reduced the thermal withdrawal latency and mechanical withdrawal threshold, and the presence of estradiol exaggerated this hyperalgesia. The expression of 5-HT3A receptor in the L4–L5 dorsal spinal cord increased significantly following repeated forced swim in estradiol replacement rats. Intrathecal injection of 5-HT3 receptor antagonist Y-25130 blocked the somatic hyperalgesia induced by forced swim stress. These data indicate that 5-HT3 receptor activation through the descending facilitation system contributes to the somatic hyperalgesia evoked by forced swim stress. The results may provide a new therapeutic avenue for alleviating pain induced by stress.
Assessments and accountability in secondary education: International trends
Authors: Teltemann Janna , Jude Nina
Published: June 2019

International Large-scale Student Assessments are the most prominent example of internationalization processes in education. A number of studies have analysed the policy reactions to such studies, particularly to the Organisation for Economic Co-operation and Development (OECD) Programme for International Student Assessment (PISA) study. PISA and comparable projects have also raised concerns of a feared increase of assessments and accountability procedures. So far, systematic empirical evidence that could corroborate such concerns has been scarce. In this paper, we examine the prevalence of assessment and accountability practices at secondary education level as well as changes in these practices over time. We explicitly focus on changes over time by drawing on data from PISA 2000 to PISA 2015. Analyses over time are not straightforward with PISA, as the questionnaires change between survey rounds. This leads to different coverage of specific indicators over time. We present descriptive analyses for 20 OECD countries. The results show an increasing trend for the vast majority of the generated indicators, indicating that assessments and the use of assessments for purposes of accountability increased within the larger part of the OECD during the last 15 years. Likewise, more horizontal, peer-oriented evaluation procedures focusing on organizational learning gained importance. A cluster analysis based on selected indicators of 2015 revealed that there are four distinct groups of countries, which are mainly distinguished by different levels of the prevalence of assessment, accountability and evaluation practices.
Actual and Perceived Emotional Similarity in Couples’ Daily Lives
Authors: Sels Laura , Ruan Yan , Kuppens Peter , Ceulemans Eva , Reis Harry
Published: June 2019

We used two experience sampling studies to examine whether close romantic partners’ feelings of love and perceived partner responsiveness are better predicted by their actual emotional similarity or by their perceived emotional similarity. Study 1 revealed that the more partners were emotionally similar, the more they perceived their partner as responsive. This effect was mediated by perceived similarity, indicating that emotional similarity had to be detected in order to exert an effect. Further, when people overperceived their emotional similarities, they also reported more perceived partner responsiveness. Study 2 replicated these findings, by revealing similar effects for actual and perceived similarity on the love people reported to feel toward their partner. Implications for understanding the factors that predict feelings of love and responsiveness in close relationships are discussed.
Use of the model of Inner Strength for analysing reflective interviews in a group of healthy middle-aged adults
Authors: Lundman Berit , Hammarström Anne , Ahlgren Christina , Norberg Astrid
Published: June 2019

Objective:

Inner Strength has been described as a human resource that promotes well-being linked to health. The aim of this study was to explore how Inner Strength and its four dimensions are manifested in interviews in a group of middle-aged healthy women and men.

Methods:

Retrospective reflective interviews with middle-aged healthy women (n = 5) and men (n = 4) selected from a population study were content analysed deductively.

Results:

The following themes and their constituents were found in the respective dimensions of the Model of Inner Strength. Firmness: having a drive to act, being purposeful, having trust in one’s competence, and having a positive view of life. Connectedness: being in community, receiving and giving support, and, receiving and giving care. Creativity: changing unsatisfactory life situations, seeing new opportunities, and realizing dreams. Stretchability: balancing between options, and extending oneself.

Conclusions:

Expressions that were interpreted as belonging to Inner Strength could be referred the different dimensions of Inner Strength. The Model of Inner Strength is suitable for analysing Inner Strength among middle-aged men and women. The findings indicate that Inner Strength can be identified in human beings’ narratives if asked for.
Assessing the consequences of decentralizing biomedical research
Authors: Bot Brian M , Wilbanks John T , Mangravite Lara M
Published: June 2019

Advancements in technology are shifting the ways that biomedical data are collected, managed, and used. The pervasiveness of connected devices is expanding the types of information that are defined as ‘health data.’ Additionally, cloud-based mechanisms for data collection and distribution are shifting biomedical research away from traditional infrastructure towards a more distributed and interconnected ecosystem. This shift provides an opportunity for us to reimagine the roles of scientists and participants in health research, with the potential to more meaningfully engage in partnership across the research process. At the same time, these emerging practices present a potential to expose research participants to unanticipated and unintended consequences. Social norms and policy can help to mitigate these risks, but their development is often slow relative to the pace of technological advances and, as such, they can become reactive rather than prospective. As an alternative, the integrated development of data governance structures within technological advancements, supports their effective implementation, evaluation and evolution in a manner that can balance the benefits and risks of biomedical researcher in a decentralized ecosystem.
Is dialysis vintage a perioperative risk for end-stage renal disease patients receiving total knee and hip arthroplasty
Authors: Wang Yi-Chia , Cheng Ya-Jung , Yang Ju-Yeh , Chao Chia-Der , Huang Jenq-Wen , Hung Kuan-Yu
Published: June 2019

Background:

End-stage renal disease is an independent risk factor for postoperative mortality and cardiovascular events, but dialysis vintage and its relationship with perioperative complication is not well studied. We did a population-based study to investigate this issue.

Materials and methods:

We identified patients who had total knee arthroplasty (TKA) or total hip arthroplasty (THA) surgeries during 1999–2010 from the National Health Insurance Research Database of Taiwan. Patients who had regular dialysis before surgery were recruited in our analysis. The outcome of interest was mortality, morbidities, intensive care unit admission rate, hospitalization duration, readmission rate, and medical costs. We did multivariate regression to adjust for age, sex, and Charlson comorbidity index (CCI) and to analyze the relationship of dialysis vintage and clinical outcomes.

Results:

A total of 518 patients were enrolled for analysis. A total of 286 patients had TKA surgeries and 232 patients had THA surgeries. Patients who had TKA surgery were older and had more medical comorbidities than patients who had THA. After adjustment for age, sex, and CCI, TKA patients who had dialysis vintage <3 years had significantly higher medical costs ( p < 0.05). For THA patients, dialysis vintage is not an independent risk factor for outcomes of interest.

Conclusion:

Perioperative complication is associated with age and medical comorbidities. Longer dialysis vintage is not related to perioperative morbidities and mortalities or higher medical costs in either TKA or THA patients.
An etiological role for the Epstein-Barr virus in the pathogenesis of classical Hodgkin lymphoma
Authors: Murray Paul G. , Young Lawrence S.
Published: June 2019

Although a pathogenic role for the Epstein-Barr virus (EBV) is largely undisputed for tumors that are consistently EBV genome positive (eg, nasopharyngeal carcinoma, endemic Burkitt lymphoma), this is not the case for classical Hodgkin lymphoma (cHL), a tumor with only a variable EBV association. In light of recent developments in immunotherapeutics and small molecules targeting EBV, we believe it is now timely to reevaluate the role of EBV in cHL pathogenesis.
Elucidation of relationship between clothing silhouette and motifs with Indian Mughal architecture
Authors: Kumari Annu
Published: June 2019

Fashion adopts numerous creative ideas and the designers source them. Architecture is also not left out from the eye of designers. Fashion designers used to take their inspiration from architectural buildings normally to create new clothing silhouettes. But what is important to understand here is the nature of relationship between these two disciplines which made them to do so. Keeping this fact in mind, researcher tried to find the connection between ‘Fashion’ and ‘Architecture,’ which can serve as fashion element for designers. Clothing Silhouette and motif were the two criteria on which the relationship was investigated. Indian Mughal architectural monuments were selected, since Mughals were considered as the most influential rulers on Indian sub-continent, having unique heritage in terms of religion, arts, music and other ornamental techniques which are in vogue even in the modern era. The outcomes show that similar kind of motifs was used to ornament both textiles as well as walls of architectural monuments at same time frame. Clothing silhouettes of that time were also inspired from the outer shape of the monument. Further, while investigating, a functional aspect—one of the common causes of relationship in terms of comfort in both the disciplines was also found.
Case study of creativity in asynchronous online discussions
Authors: Corfman Timothy , Beck Dennis
Published: June 2019

It is vital for online educators to know whether the strategies they use help students gain twenty-first-century skills like creativity. Unfortunately, very little research exists on this topic. Thus, the purpose of this study was to determine whether participation in online courses can help students develop creativity using asynchronous online discussions, textbooks, and teacher developed materials. A case-study approach was used and one professor, recognized by her peers for her expertise in online education, and three of her students were interviewed. Asynchronous online discussions (29) were also collected and analyzed using a sequential process of building an explanation, checking the explanation against the data, and repeating the process. Key results from the study indicated that project-based prompts, problem-based prompts, and heuristics used in asynchronous online discussions can help promote creativity. Future research should explore a more diverse group of participants and academic subject areas.
The Queensland mental health court: a unique model
Authors: Coghlan Suzanne , Harden Scott
Published: June 2019

There is a longstanding but sometimes controversial belief that a person is not criminally responsible for a crime if they were suffering from a mental illness at the time of the offence. The Queensland Mental Health Court (QMHC) system, in which assisting clinicians have a central role, is underwritten by this belief. This paper describes the QMHC system.
Presentation, Treatment, Histology, and Outcomes in Adrenal Medullary Hyperplasia Compared With Pheochromocytoma
Authors: Falhammar Henrik , Stenman Adam , Calissendorff Jan , Juhlin Carl Christofer
Published: June 2019

Context

Information about adrenal medullary hyperplasia (AMH) is scarce.

Objective

To study a large cohort of AMHs.

Design, Setting, and Participants

Nineteen AMH cases were compared with 95 pheochromocytomas (PCCs) without AMH. AMH without (n = 7) and with PCC (n = 12) were analyzed separately.

Results

Of 936 adrenalectomies, 2.1% had AMH. Mean age was 47.2 ± 15.1 years. Only two (11%) AMHs had no concurrent PCC or adrenocortical adenoma. In AMHs, a genetic syndrome was present in 58% vs 4% in PCCs (P < 0.001). The noradrenaline/metanephrine levels were lower in AMHs, whereas suppression of dexamethasone was less than in PCCs. Cushing syndrome was found in 11% of AMHs. More AMHs were found during screening and less as incidentalomas. PCC symptoms were less prevalent in AMHs. Surgical management was similar; however, fewer of the AMHs were pretreated with alpha-blockers. Adrenalectomy improved blood pressure slightly less in AMHs. The disappearance of glycemic disturbances was similar to the PPCs. During a period of 11.2 ± 9.4 years, a new PCC developed in 32% of patients with AMH, 11% died, but no PCC metastasis occurred (PCCs: 4%, P < 0.001; 14% and 5%). AMHs without PCC had milder symptoms but more often Cushing disease than patients with PCC, whereas AMH with PCC more often displayed a familiar syndrome with more PCC recurrences.

Conclusion

A total of 2.1% of all adrenalectomies displayed AMH. AMH seemed to be a PCC precursor. The symptoms and signs were milder than PCCs. AMHs were mainly found due to screening. Outcomes seemed favorable, but new PCCs developed in many during follow-up.
Grammatical Reanalysis and the Multiple N-Words in African American English
Authors: Jones Taylor , Hall Christopher
Published: June 2019

African American Vernacular English (AAVE) is developing a class of previously undescribed function words, facilitated by the semantic generalization of the word nigga. The authors demonstrate that nigga is unspecified for race, gender, or humanness. They argue that there are multiple n-words, fulfilling different grammatical and social functions. Using a variety of sources, they show that there are new pronouns in AAVE based on nigga—moreover, they pattern with pronouns, not imposters, with respect to binding, agreement, and theta-role assignment. Vocatives and honorics are also explored. The article concludes with a discussion of the origin of these forms and their relevance both to linguistic controversy and to societal controversy around the taboo word and the stigmatized dialect.
The asymmetric chemical structures of two mating pheromones reflect their differential roles in mating of fission yeast
Authors: Seike Taisuke , Maekawa Hiromi , Nakamura Taro , Shimoda Chikashi
Published: June 2019

In the fission yeast Schizosaccharomyces pombe, the mating reaction is controlled by two mating pheromones, M-factor and P-factor, secreted by M- and P-type cells, respectively. M-factor is a C-terminally farnesylated lipid peptide, whereas P-factor is a simple peptide. To examine whether this chemical asymmetry in the two pheromones is essential for conjugation, we constructed a mating system in which either pheromone can stimulate both M- and P-cells, and examined whether the resulting autocrine strains can mate. Autocrine M-cells responding to M-factor successfully mated with P-factor-less P-cells, indicating that P-factor is not essential for conjugation; by contrast, autocrine P-cells responding to P-factor were unable to mate with M-factor-less M-cells. The sterility of the autocrine P-cells was completely restored by expressing the M-factor receptor. These observations indicate that the different chemical characteristics of the two types of pheromone, a lipid and a simple peptide, are not essential; however, a lipid peptide might be required for successful mating. Our findings allow us to propose a model of the differential roles of M-factor and P-factor in conjugation of S. pombe.
A cognitive map in a poison frog
Authors: Liu Yuxiang , Day Lainy B. , Summers Kyle , Burmeister Sabrina S.
Published: June 2019

A fundamental question in cognitive science is whether an animal can use a cognitive map. A cognitive map is a mental representation of the external world, and knowledge of one's place in this world, that can be used to determine efficient routes to any destination. Many birds and mammals are known to employ a cognitive map, but whether other vertebrates can create a cognitive map is less clear. Amphibians are capable of using beacons, gradients and landmarks when navigating, and many are proficient at homing. Yet only one prior study directly tested for a cognitive map in amphibians, with negative results. Poison frogs exhibit unusually complex social and spatial behaviors and are capable of long-distance homing after displacement, suggesting that they may be using complex spatial navigation strategies in nature. Here, we trained the poison frog Dendrobates auratus in a modified Morris water maze that was designed to suppress thigmotaxis to the maze wall, promoting exploration of the arena. In our moat maze, the poison frogs were able to use a configuration of visual cues to find the hidden platform. Moreover, we demonstrate that they chose direct paths to the goal from multiple random initial positions, a hallmark of a cognitive map. The performance of the frogs in the maze was qualitatively similar to that of rodents, suggesting that the potential to evolve a cognitive map is an evolutionarily conserved trait of vertebrates.
Assessment of cardiovascular risk in post-menopausal women in Ghana
Authors: Afrifa Justice , Botchway Felix A. , Opoku Yeboah Kwaku , Badohu Joyce , Ocran Henrietta Ekua , Asare Kwame Kumi , Essien-Baidoo Samuel
Published: June 2019

Background: Cardiovascular diseases (CVD) continue to be a major cause of death among post-menopausal women. We sought to assess cardiovascular risk among pre- and post-menopausal women living within the Cape Coast Municipality by comparing the lipid profiles and other emerging biomarkers of CVD, i.e. the atherogenic index of plasma (AIP), visceral adiposity index (VAI), body adiposity index (BAI) and Castelli index I (CRI-I).

Methods: A comparative cross-section of 150 women (75 pre-menopausal women and 75 post-menopausal women) visiting the University of Cape Coast hospital for regular checkups were randomly recruited into the study. Socio-demographic and clinical characteristics of participants were obtained with the aid of a structured questionnaire. Blood pressure (BP) was measured and lipid profile was estimated using fasting blood samples. Other markers of cardiovascular risk such as BMI, AIP, VAI, BAI and CRI-I were estimated.

Results: We report elevated levels of total cholesterol (TC) (p<0.0001), low density lipoprotein (LDL) (p<0.0001), very low-density lipoprotein (VLDL) (p=0.0021), triglycerides (TG) (p<0.0001) and non-high-density lipoprotein (non-HDL-C) cholesterol (p<0.0001) in post-menopausal women compared with pre-menopausal women. High-density lipoprotein (HDL) (p<0.0001) was, however, decreased in post-menopausal women. Mean AIP (p< 0.0001), VAI (p< 0.0001), BAI (p< 0.0038) and CRI-I (p<0.0001) were significantly increased in post-menopausal women compared to pre-menopausal women. We also report a positive correlation of TC, TG, VLDL and non-HDL with atherogenic markers AIP, VAI and CRI-I in post-menopausal women. A negative correlation of HDL with AIP, VAI, and CR in post-menopausal women was also observed.

Conclusions: Menopause could lead to changes in lipid profile to atherogenicity with associated increase in the risk of CVD. Atherogenic markers such as AIP, VAI, BAI, and CR can serve as potential biomarkers for predicting CVD.
The effectiveness and safety of anti-fibrinolytics in patients with acute intracranial haemorrhage: statistical analysis plan for an individual patient data meta-analysis
Authors: Ker Katharine , Prieto-Merino David , Sprigg Nikola , Mahmood Abda , Bath Philip , Kang Law Zhe , Flaherty Katie , Roberts Ian
Published: June 2019

Abstract

Introduction: The Anti-fibrinolytics Trialists Collaboration aims to increase knowledge about the effectiveness and safety of anti-fibrinolytic treatment by conducting individual patient data (IPD) meta-analyses of randomised trials. This article presents the statistical analysis plan for an IPD meta-analysis of the effects of anti-fibrinolytics for acute intracranial haemorrhage.

Methods: The protocol for the IPD meta-analysis has been registered with PROSPERO (CRD42019128260). We will conduct an individual patient data meta-analysis of randomised controlled trials with 500 patients or more assessing the effects of anti-fibrinolytics in acute intracranial haemorrhage. The primary outcomes will be 1) death from stroke or head injury within 30 days of randomisation, and 2) death from stroke or head injury, or dependency within 90 days of randomisation. The primary outcomes will be limited to patients treated within three hours of injury or stroke onset. We will report treatment effects using odds ratios and 95% confidence intervals. We use logistic regression models to examine how the effect of anti-fibrinolytics vary by time to treatment, severity of intracranial bleeding, and age. We will also examine the effect of anti-fibrinolytics on secondary outcomes including death, dependency, vascular occlusive events, seizures, and neurological outcomes. Secondary outcomes will be assessed in all patients irrespective of time of treatment. All analyses will be conducted on an intention-to-treat basis.

Conclusions: This IPD meta-analysis will examine important clinical questions about the effects of anti-fibrinolytic treatment in patients with intracranial haemorrhage that cannot be answered using aggregate data. With IPD we can examine how effects vary by time to treatment, bleeding severity, and age, to gain better understanding of the balance of benefit and harms on which to base recommendations for practice.
Perceived usefulness of receiving a potential smoking cessation intervention via mobile phones among smokers in Indonesia
Authors: Wibowo Mochammad Fadjar , Kumar Anil A. , Sumarsono Surahyo , Rodrigues Rashmi
Published: June 2019

Background: The use of technology to support healthcare in Indonesia holds new promise in light of decreasing costs of owning mobile devices and ease of access to internet. However, it is necessary to assess end-user perceptions regarding mobile health interventions prior to its implementation. This would throw light on the acceptability of mobile phone communication in bringing about behavioural changes among the target Indonesian population. The aim of this study was to explore the perceived usefulness of receiving a potential smoking cessation intervention via mobile phones.

Methods: This is an exploratory cross-sectional study involving current and former adult tobacco smokers residing in Indonesia. Online advertisement and snowballing were used to recruit respondents. Data was collected using a web-based survey over a period of 4 weeks. Those willing to participate signed an online consent and were subsequently directed to the online questionnaire that obtained demographics, tobacco usage patterns, perceived usefulness of a mobile phone smoking cessation application and its design.

Results: A total of 161 people who smoked tobacco responded to the online survey. The mean age of the participants was 29.4. Of the 123 respondents, 102 were men. Prior experience with using a mobile phone for health communication (OR 3.6, P=0.014) and those willing to quit smoking (OR 5.1, P=0.043) were likely to perceive a mobile phone smoking cessation intervention as useful. A smartphone application was preferred over text messages, media messages or interactive voice response technology. Content comprising of motivational messages highlighting the methods and benefits of quitting smoking were requested.

Conclusion: People who smoke in Indonesia perceived receiving a potential smoking cessation intervention via mobile phones as useful. A multi-component, personalized smartphone application was the desired intervention technique. Such an intervention developed and implemented within a public health program could help address the tobacco epidemic in Indonesia.
Infant contact in day-care centres in Vietnam: A cross-sectional study to understand infant infection risk
Authors: Toizumi Michiko , Yoshida Lay-Myint , Suzuki Motoi , Nguyen Hien Anh Thi , Pinsent Amy , Dang Duc Anh , Flasche Stefan
Published: June 2019

Background: Infant contact information (skin-to-skin contact between infants and others) is important to understand Streptococcus pneumoniae transmission patterns. A few studies have investigated infant contact patterns by asking the mother/guardian to record all contacts a child makes in one day. However, this approach does not capture contact behaviour in day-care. Our study describes the frequency and nature of physical contacts of infants in day-care to understand infant infection risk in day-care in Nha Trang, Vietnam.

Methods: This cross-sectional study enrolled infants aged <12 months, attending 10 randomly selected day-care centres in Nha Trang. Physical contacts of each infant for one day at the day-care centre were observed. The mean number of infants’ contacts and factors associated with contact numbers were assessed using negative binomial regression.

Results: In total 14 infants, aged 6-11 months, were enrolled, and a total of 96 contacts were recorded. The mean number of contacts an infant made in one day was 6.9. Infants who walked independently (age-adjusted rate ratio 1.68, 95% confidence interval 1.06-2.68) and those cared for in a larger group (1.99, 1.42-2.79) had more contacts at day-care. About 50% of infants made contact with at least one person from a commune different from the infant’s, and 50% made contact with at least one other infant at day-care.

Conclusion: This study found that day-care attendance may be one factor that increases contact rates of infants in Nha Trang and diversifies those contacts in terms of age and geographical spread. In this study, day-care attendance not only increased contact rates beyond those usually experienced by young children cared for at home but specifically increased contact rates with other children and adults from other communes. Day-care may play a key role in the transmission of respiratory pathogens like Streptococcus pneumoniae to infants.
Intratumoral Estrogen Receptor Heterogeneity of Expression in Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer as Evaluated by a Brightfield Multiplex Assay
Authors: Masuda Shinobu , Nitta Hiroaki , Kelly Brian D. , Zhang Wenjun , Farrell Michael , Dennis Eslie
Published: June 2019

Breast cancer (BC) is a heterogeneous disease with evolving genetic alterations and expressions of receptor proteins. Intratumoral heterogeneity (ITH) is considered to be a resistance factor in response to targeted therapies. The current single-slide, single-marker immunohistochemistry techniques cannot accurately assess ITH at the individual cancer cell level. In this study, we develop a novel brightfield multiplex assay to simultaneously assess estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) protein markers, together with the HER2 gene and the centromere of chromosome 17 ( CEP17) copy numbers, using a single tissue section. The data presented herein demonstrate heterogeneous cancer cell subpopulations in 11 HER2-positive/ER-positive (HER2+/ER+) tumors among 33 BCs analyzed immunohistochemically (HER2 score of 2+ or 3+). The predominant cancer cell subpopulation was HER2+/ER− (50.18%), followed by HER2+/ER+ (39.05%), HER2−/ER+ (4.26%), ER− with HER2 microheterogeneity cancer cells (3.58%), and ER+ with HER2 microheterogeneity cancer cells (2.93%). The three other tumor subtypes, namely, HER2−/ER+, HER2+/ER−, and HER2−/ER−, were more homogeneous, representing 82.59%, 99.22%, and 100% of cancer cells, respectively. This novel assay revealed that HER2+ cancer cells were more predominant than ER+ cancer cells in HER2+/ER+ tumors and provided new insights toward our understanding of BC carcinogenesis.
ADAMTS13 maintains cerebrovascular integrity to ameliorate Alzheimer-like pathology
Authors: Cao Yongliang , Xu Haochen , Zhu Yuanbo , Shi Mei-Juan , Wei Lixiang , Zhang Jin , Cheng Shuo , Shi Yiqian , Tong Haiyang , Kang Lijing , Lu Lu , Luo Haiyu , Yang Xing , Bai Xiaofei , Wang Ranran , Ma Yuanyuan , Wang Yun , Wang Zhongfeng , Zhong Kai , Zhao Bing-Qiao , Fan Wenying
Published: June 2019

Blood-brain barrier (BBB) defects and cerebrovascular dysfunction contribute to amyloid-β (Aβ) brain accumulation and drive Alzheimer disease (AD) pathology. By regulating vascular functions and inflammation in the microvasculature, a disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS13) plays a significant protective effect in atherosclerosis and stroke. However, whether ADAMTS13 influences AD pathogenesis remains unclear. Using in vivo multiphoton microscopy, histological, behavioral, and biological methods, we determined BBB integrity, cerebrovascular dysfunction, amyloid accumulation, and cognitive impairment in APPPS1 mice lacking ADAMTS13. We also tested the impact of viral-mediated expression of ADAMTS13 on cerebrovascular function and AD-like pathology in APPPS1 mice. We show that ADAMTS13 deficiency led to an early and progressive BBB breakdown as well as reductions in vessel density, capillary perfusion, and cerebral blood flow in APPPS1 mice. We found that deficiency of ADAMTS13 increased brain plaque load and Aβ levels and accelerated cerebral amyloid angiopathy (CAA) by impeding BBB-mediated clearance of brain Aβ, resulting in worse cognitive decline in APPPS1 mice. Virus-mediated expression of ADAMTS13 attenuated BBB disruption and increased microvessels, capillary perfusion, and cerebral blood flow in APPPS1 mice already showing BBB damage and plaque deposition. These beneficial vascular effects were reflected by increase in clearance of cerebral Aβ, reductions in Aβ brain accumulation, and improvements in cognitive performance. Our results show that ADAMTS13 deficiency contributes to AD cerebrovascular dysfunction and the resulting pathogenesis and cognitive deficits and suggest that ADAMTS13 may offer novel therapeutic opportunities for AD.
Disciplina e capacidade de convivência em sala de aula
Authors: Hees Luciane Weber Baia , Lopes Raquel Pierini , Rachel Daniele Castro , Silva Simone Roganti
Published: June 2019

O presente artigo tem como objetivo abordar as principais regras existentes dentro de sala de aula. A falta de disciplina e habilidade de convivência entre professor-aluno e aluno-aluno tem gerado conflitos em sala de aula que podem interferir no convívio social e no ensino-aprendizagem. A partir de pesquisas científicas, foram abordados elementos que causam a falta desses valores e princípios em sala de aula e também pontos que contribuem para uma melhoria em que o professor tem como objetivo a interação do professor-aluno e aluno-aluno, a qualidade do convívio em sala de aula, a resolução de conflitos, o diálogo e rever práticas pedagógicas, o que fará do ambiente escolar um lugar adequado para que efetivamente ocorra o aprendizado.
Por uma narrativa dos gestos: os bebês e a subversão da sacralidade do livro
Authors: Salutto Nazareth
Published: June 2019

O artigo discute a relação dos bebês com o livro de literatura infantil, observando de que modo a interface com esse objeto constitui uma gestualidade própria do bebê no seu processo de imersão na cultura. Por um lado, se olha para os bebês nos seus movimentos inaugurais, exploratórios, intensos. De outro, se tem o livro como potente, por vezes sacralizado, artefato da cultura. Quais são as faces desse encontro? O que se pode aprender, inferir, ao mapear itinerários que observam corpo, ações e gestos dos bebês?
A clinical case of combined differentiated thyroid cancer and primary hyperparathyroidism: the complexity of topical differential diagnosis
Authors: Slashchuk Konstantin Yu. , Degtyarev Mikhail V. , Serzhenko Sergey S. , Rumyantsev Pavel O. , Sheremeta Marina S. , Yasuchenia Valentina S. , Trukhin Alexey A. , Sirota Yaroslav I. , Baranova Olga D. , Nikiforovich Petr A.
Published: June 2019

In recent years, the understanding of the epidemiology, symptoms and strategies for managing patients with hyperparathyroidism has changed significantly. The most common cases in clinical practice are of sporadic primary hyperparathyroidism, which today ranks third in prevalence among endocrine diseases (the frequency of occurrence in the adult population is, on average, 12%). In primary hyperparathyroidism, solitary parathyroid adenoma is detected in up to 85% of all cases. The only treatment is radical surgical removal of pathologically altered parathyroid tissue. Early diagnosis and treatment of hyperparathyroidism makes it possible to avoid severe lesions of the skeletal bones and visceral organs. A diagnostically challenging clinical case of a combined onco-endocrine pathology in a 70-year-old patient is presented. The main difficulties in the initial diagnosis were associated with the absence of pathognomonic symptoms of the disease, which was often completely asymptomatic. The most urgent problem appears to be the topical diagnosis of pathologically altered parathyroid glands. Therefore, there is a need to develop an algorithm for the combining and sequential use of existing medical imaging methods.
Aproximaciones epistemológicas de la evaluación educativa: entre el deber ser y lo relativo
Authors: Jiménez Moreno José Alfonso
Published: June 2019

Todas las prácticas educativas requieren de la delimitación epistemológica que permita el entendimiento conceptual y analítico de su objeto de estudio. En el caso de la evaluación educativa –herramienta de gran uso dentro de los sistemas educativos a nivel mundial– los textos teóricos que enmarcan su definición y quehacer han dejado a un lado la delimitación analítica que subyace en su definición y objetivo. Las discusiones sobre la evaluación educativa se han centrado fuertemente en los elementos técnicos que fundamentan su actividad, y, en algunas ocasiones, en las implicaciones políticas de su uso. Bajo ese problema, el presente manuscrito resalta la necesidad de establecer un posicionamiento epistemológico de la evaluación educativa. Mediante un análisis de los textos teóricos clásicos y contemporáneos de la evaluación (particularmente aquellos de habla hispana) se cuestionan tres ejes de esta práctica: el concepto mismo de la evaluación educativa, su función en la delimitación del deber ser educativo, y el énfasis en la necesidad de la objetividad en sus diferentes métodos y objetos de análisis. Como conclusión se pone en duda la solidez epistemológica de su definición, además, se resalta la necesidad de reflexionar sobre la fundamentación del concepto de evaluación, así como sobre su objetivo.
The Influence of Anticholinergic Drug Selection on the Effectiveness of Oximes Against Soman-Induced Supralethal Poisoning in Mice
Authors: Kassa Jiří
Published: June 2019

1. The influence of anticholinergic drugs (atropine, benactyzine, biperiden) on the efficacy of monopyridinium and bispyridinium oximes (HI-6, BI-6, obidoxime, pralidoxime, methoxime) on soman-induced supralethal poisoning was studied in mice. 2. While methoxime combined with benactyzine or biperiden seems to be more efficacious in the elimination of toxic effects of supralethal dose of soman than its combination with atropine, the efficacy of the other oximes studied against soman-induced toxic effects is not significantly influenced by the anticholinergic drug selection. 3. On the other hand, there are big differences in the effectiveness of oximes tested as to their ability to eliminate toxic effects of soman at supralethal doses. 4. The findings support the fact that the choice of acetylcholinesterase reactivator is more important than the anticholinergic drug selection for the effectivenes of antidotal mixture in the case of prophylactic administration of antidotes.
Does anonymity matter? Examining quality of online peer assessment and students’ attitudes
Authors: Kobayashi Michiko
Published: June 2019

The study investigated the effects of anonymity on online peer assessment and compared three different conditions. Fifty-eight preservice teachers at a mid-size US university engaged in a series of online peer assessments during fall 2017. Peer assessment was embedded in a blended course as a required asynchronous activity using the Canvas learning management system. Students were randomly assigned to three different peer assessment conditions: anonymous, partially anonymous, and identifiable. They were asked to provide feedback comments and rate the quality of peers’ work. The researcher examined to what extent three different conditions had influenced the quality of feedback comments, measured quantitatively through the number of words and negative statements. At the end of the semester, a survey that included a 5-point Likert scale and several open-ended questions was also distributed to analyse students’ perceptions about peer assessment and anonymity. The results indicate that although students prefer anonymity, it may not be a necessary condition for increasing student engagement.
European Humanities in the Perception of Chinese Students: A Reflection Based on A Personal Teaching Experience
Authors: Untea Ionut
Published: June 2019

As a young teacher and researcher, the prospective of introducing western philosophical themes to a public of students from a non-western country, came in 2016 as a once-in-a lifetime opportunity, which I met with great enthusiasm. However, as in any situation involving pre-conceived expectations, facing and dealing with the real situation on the ground opens up a pathway for a closer understanding of both the new culture explored, a perception of one’s own limits and the willingness to overcome them. The following lines are intended to cover the way my approach to teaching to a Chinese public has evolved from pre-conceptions and empty enthusiasm to an attitude of pedagogical creativity in identifying and presenting the key topics that would attract my students’ attention. As I will show, students’ expectations were to approach the western ideas not directly, but via a more complex process of being acquainted with the major historical and cultural movements in Europe and the western world. This meant the involvement in the teaching process of a wider number of elements taken not only from philosophy but from other humanistic disciplines.
Przysięga
Authors: Seyfettin Ömer
Published: June 2019

Ömer Seyfettin, Przysięga. Tłumaczenie i opracowanie: Aleksandra Kunysz, Uniwersytet im. Adama Mickiewicza, Poznań
Cost-Effectiveness Analysis of Psoriasis Treatment Modalities in Malaysia
Authors: Azizam Nor Azmaniza , Ismail Aniza , Sulong Saperi , Nor Norazirah Md
Published: June 2019

Background: There is limited evidence detailing the cost-effectiveness of psoriasis treatments in the Asian region. Therefore, this study is aimed to evaluate the cost-effectiveness of 3 psoriasis treatments tailored for moderate to severe psoriasis, namely topical and phototherapy (TP), topical and systemic (TS), and topical and biologic (TB) regimens, respectively. Methods: This has been achieved by the participation of a prospective cohort involving a total of 90 moderate to severe psoriasis patients, which has been conducted at 5 public hospitals in Malaysia. The main outcome measures have been evaluated via cost and effectiveness psoriasis area severity index (PASI)-75 and/or body surface area (BSA) <5 and/or dermatology life quality index (DLQI) ≤5), estimated from the societal perspective over a 6-months duration. All costs are based on 2015’s recorded Malaysian Ringgit (RM) currency. Results: Consequently, TS has been found to be the most cost-effective treatment with the lowest cost/PASI-75/and/or BSA <5 and/or DLQI ≤5, valued at RM9034.56 (US$2582.55). This is followed by TP, which is valued at RM28 080.71 (US$8026.93) and TB, valued at RM54 287.02 (US$15 518.06). Furthermore, one-way sensitivity analysis has highlighted the cost of medication as the most sensitive parameter. Conclusion: Thus, the input from this study is helpful for policy-makers in determining the first line treatment for moderate to severe psoriasis with consideration of the costs and its effectiveness in Malaysia. This will consequently allow hospitals to justify and provide the essential resources for further research and development, as well as the adoption of better treatment options.
Development of the Translating Allied Health Knowledge (TAHK) Framework
Authors: Hitch Danielle , Pepin Genevieve , Lhuede Kate , Rowan Sue , Giles Susan
Published: June 2019

Background: While evidence-based practice is a familiar concept to allied health clinicians, knowledge translation (KT) is less well known and understood. The need for a framework that enables allied health clinicians to access and engage with KT was identified. The aim of this paper is to describe the development of the Translating Allied Health Knowledge (TAHK) Framework. Methods: An iterative and collaborative process involving clinician and academic knowledge partners was utilised to develop the TAHK Framework. Multiple methods were utilised during this process, including a systematic literature review, steering committee consultation, mixed methods survey, benchmarking and measurement property analysis. Results: The TAHK Framework has now been finalised, and is described in detail. The framework is structured around four domains – Doing Knowledge Translation, Social Capital for Knowledge Translation, Sustaining Knowledge Translation and Inclusive Knowledge Translation – under which 14 factors known to influence allied health KT are classified. The formulation of the framework to date has laid a rigorous foundation for further developments, including clinician support and outcome measurement. Conclusion: The method of development adopted for the TAHK Framework has ensured it is both evidence and practice based, and further amendments and modifications are anticipated as new knowledge becomes available. The Framework will enable allied health clinicians to build on their existing capacities for KT, and approach this complex process in a rigorous and systematic manner. The TAHK Framework offers a unique focus on how knowledge is translated by allied health clinicians in multidisciplinary settings.
Moving Towards Accountability for Reasonableness – A Systematic Exploration of the Features of Legitimate Healthcare Coverage Decision-Making Processes Using Rare Diseases and Regenerative Therapies as a Case Study
Authors: Wagner Monika , Samaha Dima , Casciano Roman , Brougham Matthew , Abrishami Payam , Petrie Charles , Avouac Bernard , Mantovani Lorenzo , Sarría-Santamera Antonio , Kind Paul , Schlander Michael , Tringali Michele
Published: June 2019

Background: The accountability for reasonableness (A4R) framework defines 4 conditions for legitimate healthcare coverage decision processes: Relevance, Publicity, Appeals, and Enforcement. The aim of this study was to reflect on how the diverse features of decision-making processes can be aligned with A4R conditions to guide decision-making towards legitimacy. Rare disease and regenerative therapies (RDRTs) pose special decision-making challenges and offer therefore a useful case study. Methods: Features operationalizing each A4R condition as well as three different approaches to address these features (cost-per-QALY-focused and multicriteria-based) were defined and organized into a matrix. Seven experts explored these features during a panel run under the Chatham House Rule and provided general and RDRT-specific recommendations. Responses were analyzed to identify converging and diverging recommendations. Results: Regarding Relevance, recommendations included supporting deliberation, stakeholder participation and grounding coverage decision criteria in normative and societal objectives. Thirteen of 17 proposed decision criteria were recommended by a majority of panelists. The usefulness of universal cost-effectiveness thresholds to inform allocative efficiency was challenged, particularly in the RDRT context. RDRTs raise specific issues that need to be considered; however, rarity should be viewed in relation to other aspects, such as disease severity and budget impact. Regarding Publicity, panelists recommended transparency about the values underlying a decision and value judgements used in selecting evidence. For Appeals, recommendations included a life-cycle approach with clear provisions for re-evaluations. For Enforcement, external quality reviews of decisions were recommended. Conclusion: Moving coverage decision-making processes towards enhanced legitimacy in general and in the RDRT context involves designing and refining approaches to support participation and deliberation, enhancing transparency, and allowing explicit consideration of multiple decision criteria that reflect normative and societal objectives.