bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the proxy response bias of EQ–5D-3 L in general population: a study based on a large-scale representative household health survey using propensity score matching
Authors: Liang Ying , Che Tianle , Zhang Haiyue , Shang Lei , Zhang Yuhai , Xu Yongyong , Guo Lingxia , Tan Zhijun
Published: March 2020

Background

Proxy respondent-someone who assists the intended respondent or responds on their behalf-are widely applied in the measurement of health-related quality of life (HRQL). However, proxies may not provide the same responses as the intended respondents, which may bias the findings.

Objectives

To determine whether the use of proxies is related to socio-demographic characteristics of the intended respondent, and to assess the possible proxy response bias of Chinese version of EQ-5D-3 L in general population.

Methods

A cross-sectional study based on a provincially representative sample from 2013 National Health Service Survey (NHSS) in Shaanxi, China was performed. HRQL was measured by Chinese version of EQ-5D-3 L. Propensity score matching (PSM) was used to get matched pairs of self-reports and proxy-reports. Before and after PSM, univariate logistic and linear models including the indicator of proxy response as the only independent variable, were employed to assess the possible proxy response bias of the dimensional and overall health status of EQ-5D-3 L respectively.

Results

19.9% of the responses involved a proxy. Before PSM, the proxy-report group was younger in age and reported less unhealthy lifestyle, lower prevalence of disease, and less hospitalization than the self-report group. After PSM, it showed that the proxy-report group was statistically more likely to report health problem on each dimension of EQ-5D-3 L, with odds ratios larger than one comparing with self-report group. The means of EQ-5D-3 L index and EQ VAS of proxy-report group were 0.022 and 0.834 lower than self-report group.

Conclusions

Significantly negative proxy response bias was found in Chinese EQ-5D-3 L in general population, and the magnitude of the bias was larger in physical dimensions than psychological dimensions after using PSM to control confounders.
Assessment of traditional and non-traditional risk factors for premature atherosclerosis in children with juvenile dermatomyositis and pediatric controls
Authors: Wahezi Dawn M. , Liebling Emily J. , Choi Jaeun , Dionizovik-Dimanovski Marija , Gao Qi , Parekh Jillian
Published: March 2020

Background

Children with juvenile dermatomyositis (JDM), the most common inflammatory myopathy of childhood, may be at increased risk of premature atherosclerosis given a host of traditional and non-traditional risk factors. The primary aim of this study was to determine the underlying frequency of premature atherosclerosis in children with JDM compared to pediatric controls using flow-mediated dilation as a measure of endothelial function.

Methods

Children and adolescents with and without JDM were evaluated for traditional atherosclerotic risk factors and assessment of endothelial function, using Endothelial Pulse Amplitude Testing (Endo-PAT).

Results

In this study, 75% of pediatric controls were of Black or Hispanic descent (compared to 55% in the JDM group) and 70% were found to live in a household with a medium income less than $50,000/year (compared to 45% in the JDM group). Among traditional atherogenic risk factors, lipoprotein A appeared to be different between controls and JDM patients (66 nmol/L and 16.5 nmol/L, respectively). Using a reactive hyperemia index (RHI) < 1.67 as evidence of endothelial dysfunction, 75% of controls were defined as having endothelial dysfunction compared to 50% in JDM group. When controlled for lipoprotein A as an atherogenic confounder, JDM patients were found to have a 41% increase in RHI, thus indicating less endothelial dysfunction compared to controls.

Conclusions

In this study, we have shown that atherogenic risk factors are present in the pediatric population and may be associated with endothelial dysfunction, even at very young ages. Despite increasing concerns that children with rheumatologic disorders may be at increased risk of developing premature atherosclerosis, traditional and sociodemographic features may play a greater role in the ultimate development of cardiovascular disease.
Exploring reasons for discontinuing use of immediate post-partum intrauterine device in Nepal: a qualitative study
Authors: Puri Mahesh C. , Joshi Saugat , Khadka Aayush , Pearson Erin , Dhungel Yasaswi , Shah Iqbal H.
Published: March 2020

Background

Postpartum intrauterine device (PPIUD) use remains very low in Nepal despite high levels of unmet need for postpartum family planning and the national government’s efforts to promote its use. This study investigates reasons for continuing or discontinuing PPIUD use among Nepali women.

Methods

We conducted in-depth interviews (IDIs) with 13 women who had discontinued PPIUD use and 12 women who were continuing to use the method 9 months or longer following the insertion. All interviews were audio recorded, transcribed, translated into English, and analyzed using a thematic approach.

Results

Women discontinued PPIUD for several reasons: 1) side effects such as excessive bleeding during menstruation, nausea, back and abdominal pain; 2) poor quality of counselling and, relatedly, mismatched expectations in terms of device use; and 3) lack of family support from husbands and in-laws. In contrast, women who were continuing to use the method at the time of the study stated that they had not experienced side-effects, had received appropriate information during counselling sessions, and had the backing of their family members in terms of using PPIUD.

Conclusion

Experiencing side-effects or complications following PPIUD insertion and poor quality of family planning counselling were the two main reasons for discontinuation. Family members appeared to play a major role in influencing a woman’s decision to continue or discontinue PPIUD suggesting that counseling may need to be expanded to them as well. Improving quality of counselling by providing complete and balanced information of family planning methods as well as ensuring sufficient time for counselling and extending PPIUD service availability at lower level clinics/health posts will potentially increase the uptake and continued use of postpartum family planning, including PPIUD, in Nepal.
Health systems influence on the pathways of care for lung cancer in low- and middle-income countries: a scoping review
Authors: Nwagbara Ugochinyere I. , Ginindza Themba G. , Hlongwana Khumbulani W.
Published: March 2020

Background

Globally, lung cancer is the most common cancer and cause of cancer-related deaths, responsible for nearly one in five deaths. Many health systems in low- and middle-income countries, including sub-Saharan Africa have weak organizational structure, which results in delayed lead time for lung cancer patient care continuum from diagnosis to palliative care.

Aim

To map evidence on the health systems issues impacting on the delays in timely lung cancer care continuum from diagnosis to palliative care in LMICs, including sub-Saharan Africa.

Methods

A scoping review was performed following the method of Arksey and O’Malley. Systematic searches were performed using EBSCOhost platform, a keyword search from the following electronic databases were conducted: PubMed/MEDLINE, Google Scholar, Science Direct, World Health Organization (WHO) library, and grey literature. The screening was guided by the inclusion and exclusion criteria. The quality of the included studies was determined by Mixed Method Appraisal Tool (MMAT).

Results

A total of 2886 articles were screened, and 236 met the eligibility criteria for this scoping review study. Furthermore, 155 articles were also excluded following abstract screening. Eighty-one articles were selected for full-article screening by two researchers with 10 being selected for independent detailed data extraction for synthesis. These studies were also subjected to methodological quality assessment. All included studies were conducted in LMICs mostly Asia, the Middle East, and Latin America and published between January 2008 and June 2018. The ten included studies described at least one interval in lung cancer care.

Conclusions

Reducing wait time across this care continuum is needed to improve easy access to healthcare, quality care, survival and patient outcomes, as many patients still face longer wait times for diagnosis and treatment of lung cancer than recommended in several healthcare settings. A multidisciplinary team approach will help to reduce wait time and ensure that all patients receive appropriate care. Interventions are needed to address delays in lung cancer care in LMICs. Health-care providers at all levels of care should be educated and equipped with skills to identify lung cancer symptoms and perform or refer for appropriate diagnostic tests.
Implementation of a novel return-to-work approach for persons with affective disorders in a traditional vocational rehabilitation context: a case study
Authors: Johanson Suzanne , Markström Urban , Larsson Maria E. , Bejerholm Ulrika
Published: March 2020

Background

The person-centred Individual Enabling and Support (IES) model is a novel return-to-work (RTW) intervention for people with affective disorders that was developed from evidence-based supported employment for persons with severe mental illness. Typically, supported employment is integrated into mental healthcare and provides a network around the service user and close collaboration with employment and insurance services and employers. Introducing integrated models into a highly sectored welfare system that includes traditional mental healthcare and vocational rehabilitation is challenging. Greater knowledge is needed to understand how facilitating or hindering factors influence this introduction. The aim of this study was to investigate essential components in implementation of the IES model.

Methods

A case-study was conducted and included four mental healthcare services. Data collection was comprised of semi-structured interviews with 19 key informants, documentation from meetings, and reflection notes. Analyses were performed according to directed content analysis, using the components of the Consolidated Framework of Implementation Research (CFIR) as a guiding tool. Fidelity assessments were performed at 6 and 12 months.

Results

Anticipating RTW support for the target group, and building collaborative relationships and a network with employment specialists that engaged staff in every organization were components that resulted in the greatest facilitation if IES implementation. Barriers consisted of difficulty in integrating employment specialists into the mental healthcare teams, insufficient engagement of first line managers, reorganization and differing perceptions of the IES model fit into a traditional vocational context. Delivery of the IES model had good fidelity.

Conclusions

The IES model can be implemented with good fidelity, several model advantages, and context adaptation. Team integration difficulties and negative perceptions of model fit in a traditional vocational rehabilitation context can be overcome to a certain degree, but this is insufficient for sustainable implementation on a larger scale. Policy and guidelines need to promote integrative and person-centred RTW approaches rather than a segregated stepwise approach. Further implementation studies in the traditional vocational rehabilitation context are needed.
Identification of cross-talk between m6A and 5mC regulators associated with onco-immunogenic features and prognosis across 33 cancer types
Authors: Chen Yu-Tong , Shen Jia-Yi , Chen Dong-Ping , Wu Chen-Fei , Guo Rui , Zhang Pan-Pan , Lv Jia-Wei , Li Wen-Fei , Wang Zi-Xian , Chen Yu-Pei
Published: March 2020

Methylation of RNA and DNA, notably in the forms of N6-methyladenosine (m6A) and 5-methylcytosine (5mC) respectively, plays crucial roles in diverse biological processes. Currently, there is a lack of knowledge regarding the cross-talk between m6A and 5mC regulators. Thus, we systematically performed a pan-cancer genomic analysis by depicting the molecular correlations between m6A and 5mC regulators across ~ 11,000 subjects representing 33 cancer types. For the first time, we identified cross-talk between m6A and 5mC methylation at the multiomic level. Then, we further established m6A/5mC epigenetic module eigengenes by combining hub m6A/5mC regulators and informed a comprehensive epigenetic state. The model reflected status of the tumor-immune-stromal microenvironment and was able to predict patient survival in the majority of cancer types. Our results lay a solid foundation for epigenetic regulation in human cancer and pave a new road for related therapeutic targets.
Trends, risk factors and outcomes of healthcare-associated infections in a neonatal intensive care unit in Italy during 2013–2017
Authors: Scamardo Marina Silvia , Dolce Pasquale , Esposito Eliana Pia , Raimondi Francesco , Triassi Maria , Zarrilli Raffaele
Published: March 2020

Background

Healthcare-associated infections (HAIs) occur frequently in intensive care units (NICUs). The aim of this study was to analyze the results of surveillance of HAIs in a III level NICU in Naples, Italy during 2013–2017 and to compare with those obtained during 2006–2010.

Methods

The surveillance included 1265 neonates of all birth weight (BW) classes with > 2 days NICU stay. Infections were defined using standard Centers for Disease Control and Prevention definitions adapted to neonatal pathology.

Results

A total of 125 HAIs were registered during 2013–2017 with a frequency of 9.9% and an incidence density of 3.2 per 1000 patient days. HAIs occurred in all BW classes with a decreasing trend from the lowest to the highest BW classes (p = < 0.001). Central line-associated blood stream infection (CLABSI) was the most frequent infection (69.6%), followed by ventilator associated pneumonia (VAP) (20%), urinary tract infection (UTI) (8.8%) and necrotizing enterocolitis (NEC) (1.6%). Also, CLABSI and VAP incidence density decreased from lower to highest BW classes showing a significant trend (p = 0.007). Most frequent pathogens responsible for CLABSI were: Coagulase-negative staphylococci (CONS) (25.3%), Candida parapsilosis (21.8%), Pseudomonas aeruginosa (5.7), Escherichia coli and Klebsiella pneumoniae (6.8%). No microbiological diagnosis was achieved for 20.7% of CLABSI. Pseudomonas aeruginosa (28%), Stenotrophomonas maltophilia (20%), and CONS (20%) were the most frequent pathogens responsible for VAP. CLABSI incidence density showed no differences between 2006 and 2010 and 2013–2017, while VAP incidence density for the 751–100 g BW class was higher during 2006–2010 than during 2013–2017 (p = 0.006). A higher incidence of the CLABSI caused by Gram positive bacteria (p = 0.002) or by undetermined etiology (p = 0.01) was observed during 2013–2017 than during 2006–2010, while a significant lower incidence of VAP caused by Gram-negative bacteria was found during 2013–2017 than during 2006–2010 (p = 0.007).

Conclusion

HAIs in the NICU developed in all BW classes with a decreasing trend from the lowest to the highest BW classes in both study periods. Differences in the aetiology of CLABSI and VAP were found between the two study periods. This reinforces the importance of HAIs surveillance protocol in the NICU, which monitors microbiological isolates and use of medical devices for all BW classes of neonates.
Methylome-based cell-of-origin modeling (Methyl-COOM) identifies aberrant expression of immune regulatory molecules in CLL
Authors: Wierzbinska Justyna A. , Toth Reka , Ishaque Naveed , Rippe Karsten , Mallm Jan-Philipp , Klett Lara C. , Mertens Daniel , Zenz Thorsten , Hielscher Thomas , Seifert Marc , Küppers Ralf , Assenov Yassen , Lutsik Pavlo , Stilgenbauer Stephan , Roessner Philipp M. , Seiffert Martina , Byrd John , Oakes Christopher C. , Plass Christoph , Lipka Daniel B.
Published: March 2020

Background

In cancer, normal epigenetic patterns are disturbed and contribute to gene expression changes, disease onset, and progression. The cancer epigenome is composed of the epigenetic patterns present in the tumor-initiating cell at the time of transformation, and the tumor-specific epigenetic alterations that are acquired during tumor initiation and progression. The precise dissection of these two components of the tumor epigenome will facilitate a better understanding of the biological mechanisms underlying malignant transformation. Chronic lymphocytic leukemia (CLL) originates from differentiating B cells, which undergo extensive epigenetic programming. This poses the challenge to precisely determine the epigenomic ground state of the cell-of-origin in order to identify CLL-specific epigenetic aberrations.

Methods

We developed a linear regression model, methylome-based cell-of-origin modeling (Methyl-COOM), to map the cell-of-origin for individual CLL patients based on the continuum of epigenomic changes during normal B cell differentiation.

Results

Methyl-COOM accurately maps the cell-of-origin of CLL and identifies CLL-specific aberrant DNA methylation events that are not confounded by physiologic epigenetic B cell programming. Furthermore, Methyl-COOM unmasks abnormal action of transcription factors, altered super-enhancer activities, and aberrant transcript expression in CLL. Among the aberrantly regulated transcripts were many genes that have previously been implicated in T cell biology. Flow cytometry analysis of these markers confirmed their aberrant expression on malignant B cells at the protein level.

Conclusions

Methyl-COOM analysis of CLL identified disease-specific aberrant gene regulation. The aberrantly expressed genes identified in this study might play a role in immune-evasion in CLL and might serve as novel targets for immunotherapy approaches. In summary, we propose a novel framework for in silico modeling of reference DNA methylomes and for the identification of cancer-specific epigenetic changes, a concept that can be broadly applied to other human malignancies.
Clinical and molecular characterization of virus-positive and virus-negative Merkel cell carcinoma
Authors: Starrett Gabriel J. , Thakuria Manisha , Chen Tianqi , Marcelus Christina , Cheng Jingwei , Nomburg Jason , Thorner Aaron R. , Slevin Michael K. , Powers Winslow , Burns Robert T. , Perry Caitlin , Piris Adriano , Kuo Frank C. , Rabinowits Guilherme , Giobbie-Hurder Anita , MacConaill Laura E. , DeCaprio James A.
Published: March 2020

Background

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin caused by either the integration of Merkel cell polyomavirus (MCPyV) and expression of viral T antigens or by ultraviolet-induced damage to the tumor genome from excessive sunlight exposure. An increasing number of deep sequencing studies of MCC have identified significant differences between the number and types of point mutations, copy number alterations, and structural variants between virus-positive and virus-negative tumors. However, it has been challenging to reliably distinguish between virus positive and UV damaged MCC.

Methods

In this study, we assembled a cohort of 71 MCC patients and performed deep sequencing with OncoPanel, a clinically implemented, next-generation sequencing assay targeting over 400 cancer-associated genes. To improve the accuracy and sensitivity for virus detection compared to traditional PCR and IHC methods, we developed a hybrid capture baitset against the entire MCPyV genome and software to detect integration sites and structure.

Results

Sequencing from this approach revealed distinct integration junctions in the tumor genome and generated assemblies that strongly support a model of microhomology-initiated hybrid, virus-host, circular DNA intermediate that promotes focal amplification of host and viral DNA. Using the clear delineation between virus-positive and virus-negative tumors from this method, we identified recurrent somatic alterations common across MCC and alterations specific to each class of tumor, associated with differences in overall survival. Finally, comparing the molecular and clinical data from these patients revealed a surprising association of immunosuppression with virus-negative MCC and significantly shortened overall survival.

Conclusions

These results demonstrate the value of high-confidence virus detection for identifying molecular mechanisms of UV and viral oncogenesis in MCC. Furthermore, integrating these data with clinical data revealed features that could impact patient outcome and improve our understanding of MCC risk factors.
Glycogen synthase kinase 3 (GSK-3) controls T-cell motility and interactions with antigen presenting cells
Authors: Taylor Alison , Rudd Christopher E.
Published: March 2020

Objective

The threonine/serine kinase glycogen synthase kinase 3 (GSK-3) targets multiple substrates in T-cells, regulating the expression of Tbet and PD-1 on T-cells. However, it has been unclear whether GSK-3 can affect the motility of T-cells and their interactions with antigen presenting cells.

Results

Here, we show that GSK-3 controls T-cell motility and interactions with other cells. Inhibition of GSK-3, using structurally distinct inhibitors, reduced T-cell motility in terms of distance and displacement. While SB415286 reduced the number of cell-cell contacts, the dwell times of cells that established contacts with other cells did not differ for T-cells treated with SB415286. Further, the increase in cytolytic T-cell (CTL) function in killing tumor targets was not affected by the inhibition of motility. This data shows that the inhibition of GSK-3 has differential effects on T-cell motility and CTL function where the negative effects on cell–cell interactions is overridden by the increased cytolytic potential of CTLs.
BRAF V600 mutation profiling in primary skin nodular melanoma in Indonesia: an analysis using high resolution pyrosequencing
Authors: Rinonce Hanggoro Tri , Aji Rovi Panji Mustiko , Hayati Ni’mah , Pudjohartono Maria Fransiska , Kameswari Bidari , Anwar Sumadi Lukman , Irianiwati
Published: March 2020

Objective

We aimed to investigate the prevalence and type of BRAF V600 mutations and the associations with clinicopathological variables in primary skin nodular melanoma cases in Yogyakarta and Central Java, Indonesia using pyrosequencing.

Results

BRAF V600 mutations of the V600E type were found in 21 (53.85%) specimens. The variant allele frequencies (VAFs) ranged from 5.07 to 94.70%, averaging 29.05%. However, most cases had low VAFs, with 13 (61.9%) specimens below 20% and 4 (19.05%) below 10%.
Cell-free DNA screening for sex chromosomal aneuploidies in 9985 pregnancies: Italian single experience
Authors: Margiotti Katia , Cesta Anthony , Dello Russo Claudio , Cima Antonella , Barone Maria Antonietta , Viola Antonella , Sparacino Davide , Mesoraca Alvaro , Giorlandino Claudio
Published: March 2020

Objective

Non invasive prenatal testing (NIPT) using cell-free fetal DNA (cffDNA) has been widely accepted in recent years to detect common fetal autosomal chromosome aneuploidies and sex chromosome aneuploidies (SCAs). In this study, the clinical performance of our fetal DNA testing was investigated by analyzing the sex chromosome aneuploidy aberrations among 9985 pregnancies. The study was a retrospective analysis of collected NIPT data from the Ion S5 next-generation sequencing (NGS) platform obtained from Altamedica Medical Centre of Rome.

Results

NIPT analysis of 9985 pregnancies revealed 31 cases with abnormal SCA results (0.31%). Among the 31 positive NIPT cases, 22 women agreed to undergo fetal karyotyping, whereas 9 refused further analyses. Of the 22 women verified by karyotyping analysis, 77.3% (17/22) were confirmed to be true positive SCAs, whereas 22.7% (5/22) were false positive. Among the true positive cases, 53.0% (9/17) were positive for monosomy X, 17.6% (3/17) were positive for 47, XXX aneuploidy, 23.5% (4/17) were positive for 47, XXY aneuploidy, and 5.9% (1/17) were positive for 47, XYY aneuploidy. In conclusion, the present results confirm that NIPT is a potential method for SCA screening, although this technology needs to be further investigated to improve the test performance.
Alterations in the methylome of the stromal tumour microenvironment signal the presence and severity of prostate cancer
Authors: Lawrence Mitchell G. , Pidsley Ruth , Niranjan Birunthi , Papargiris Melissa , Pereira Brooke A. , Richards Michelle , Teng Linda , Norden Sam , Ryan Andrew , Frydenberg Mark , Stirzaker Clare , Taylor Renea A. , Risbridger Gail P. , Clark Susan J.
Published: March 2020

Background

Prostate cancer changes the phenotype of cells within the stromal microenvironment, including fibroblasts, which in turn promote tumour progression. Functional changes in prostate cancer-associated fibroblasts (CAFs) coincide with alterations in DNA methylation levels at loci-specific regulatory regions. Yet, it is not clear how these methylation changes compare across CAFs from different patients. Therefore, we examined the consistency and prognostic significance of genome-wide DNA methylation profiles between CAFs from patients with different grades of primary prostate cancer.

Results

We used Infinium MethylationEPIC BeadChips to evaluate genome-wide DNA methylation profiles from 18 matched CAFs and non-malignant prostate tissue fibroblasts (NPFs) from men with moderate to high grade prostate cancer, as well as five unmatched benign prostate tissue fibroblasts (BPFs) from men with benign prostatic hyperplasia. We identified two sets of differentially methylated regions (DMRs) in patient CAFs. One set of DMRs reproducibly differed between CAFs and fibroblasts from non-malignant tissue (NPFs and BPFs). Indeed, more than 1200 DMRs consistently changed in CAFs from every patient, regardless of tumour grade. The second set of DMRs varied between CAFs according to the severity of the tumour. Notably, hypomethylation of the EDARADD promoter occurred specifically in CAFs from high-grade tumours and correlated with increased transcript abundance and increased EDARADD staining in patient tissue. Across multiple cohorts, tumours with low EDARADD DNA methylation and high EDARADD mRNA expression were consistently associated with adverse clinical features and shorter recurrence free survival.

Conclusions

We identified a large set of DMRs that are commonly shared across CAFs regardless of tumour grade and outcome, demonstrating highly consistent epigenome changes in the prostate tumour microenvironment. Additionally, we found that CAFs from aggressive prostate cancers have discrete methylation differences compared to CAFs from moderate risk prostate cancer. Together, our data demonstrates that the methylome of the tumour microenvironment reflects both the presence and the severity of the prostate cancer and, therefore, may provide diagnostic and prognostic potential.
A call for constructing a metric for monitoring CA-MRSA and other infectious diseases
Authors: Al Amiry Alaa
Published: March 2020

The use of metrics is necessary for decision making when it comes to evaluating the need for interventions and improve healthcare delivery (Adams, Metrics: What Counts in Global Health, 2016). They inform policy makers on the scale of the problem in hand, and whether it’s time to intervene. It quantifies the matter of interest and gives an indication whether the intervention taken was effective or not- as a means for monitoring and evaluation (Murray and Frenk, Lancet 371:1191-1199, 2008).

This article advocates for a new metric by suggesting criteria to construct it, in order to provide a “value-based” measurement for CA-MRSA as a starting point for all infectious diseases. It also discusses challenges to this suggested approach.
How municipalities support energy cooperatives: survey results from Germany and Switzerland
Authors: Meister Thomas , Schmid Benjamin , Seidl Irmi , Klagge Britta
Published: March 2020

Background

Energy cooperatives are a prominent and common form of community energy. Community energy has the potential to increase actor diversity and local acceptance of renewable energies and has therefore been highlighted to be conducive to energy transitions. While research has recognized the importance of both the national and the local governance levels for community energy, it remains unclear how these two levels are related. Against this backdrop, this paper investigates how municipalities support energy cooperatives at the local level and how this support is related to national context conditions.

Methods

The study takes a quantitative approach using own survey data from Germany and Switzerland. Based on a typology of municipal support, we compare limiting factors and municipal support for energy cooperatives between the two countries as well as between energy cooperatives with and without municipal membership. By means of this two-tiered comparison, we analyze how municipal support is related to national contexts, specifically regarding national energy policies, and to municipal involvement in the cooperatives.

Results

Our analysis shows that municipal support can benefit energy cooperatives as it addresses some of the major limiting factors for energy cooperatives in Germany and Switzerland. However, our data suggest that municipalities only specifically address cooperatives’ limitations with support measures if they are a member in the cooperative. This indicates that organizational involvement of a municipality in energy cooperatives leads to a more targeted support compared to non-members and thus is beneficial to meet the specific cooperatives’ challenges due to national energy policy.

Conclusions

Cooperatives can benefit from municipal support, especially if the municipality is a cooperative member. Municipal support is likely to become even more important for energy cooperatives in the future, due to reduced national support for renewable energies in Germany and Switzerland. On their part, municipalities can benefit from collaborating with energy cooperatives, as they gain an additional instrument to implement municipal energy policy. Hence, supporting and seeking membership in energy cooperatives appear to be adequate strategies for municipalities to foster a decentralized energy transition.
Best practice for collar deployment of tri-axial accelerometers on a terrestrial quadruped to provide accurate measurement of body acceleration
Authors: Dickinson Eleanor R. , Stephens Philip A. , Marks Nikki J. , Wilson Rory P. , Scantlebury David M.
Published: March 2020

Background

Tri-axial accelerometers are frequently deployed on terrestrial quadrupedal mammals using collars, because they are easy to fit and are thought to have minimal impact on the subject. Collar-attached devices are not fixed to the body and can move independently of the body. This may result in inaccurate measures of acceleration, reducing the accuracy of measured body movement. We determined the effect of collar size and collar weight on acceleration measured by a collar-mounted accelerometer on a quadruped mammal. The aim was to suggest best practice for sizes and weights of collars on which to deploy tri-axial accelerometers. Using pygmy goats,Capra aegagrus hircus, which were trained to walk at different speeds (0.8–3.0 km/h) on a treadmill, we measured body acceleration using a collar-mounted tri-axial accelerometer, with different collar sizes (individual neck circumference + 1 cm to + 9 cm) and collar weight (0.4% to 1.2% of individual weight).

Results

There was a significant effect of collar size, collar weight and walking speed on measured acceleration. Measured acceleration was less accurate and more variable when collars were looser and heavier. To measure body acceleration more accurately, we found that collar size should be within 5 cm or 16% of an individual’s neck circumference when it was heavy (up to 1.2% of animal’s body weight) or within 7 cm (33%) of neck circumference if the collar was light (up to 0.6% of animal body weight).

Conclusion

We suggest that not only reporting collar size and weight for welfare purposes, but it is also important to consider these aspects for scientific rigour, to ensure data are collected as accurately as possible. We provide guidelines for researchers fitting collar-attached devices to ensure a higher degree of accuracy of recorded body acceleration.
Comparative study between biological and chemical control programs of certain sweet pepper pests in greenhouses
Authors: El Arnaouty S. A. , El-Heneidy A. H. , Afifi Amal I. , Heikal I. H. , Kortam Mona N.
Published: March 2020

Sweet pepper is an important vegetable crop in Egypt. It is cultivated for local consumption and exportation. The crop is attacked by a large number of pest species such as Western flower thrips, Frankliniella occidentalis (Pergande), whitefly, Bemisia tabaci (Genn.), the two-spotted spider mite, Tetranychu surticae Koch, and the beet armyworm, Spodoptera exigua (Hubner). The present study was conducted on the sweet pepper cultivated in greenhouses, during the winter plantation 2016/17 in a commercial farm located at Berkash district, Giza Governorate, Egypt. Three control programs were practiced: the first used biological control agents (BC), the predators, Orius albidipennis (Reuter), Macrolophus caliginosus (Wagner), Chrysoperla carnea (Steph.), and the egg parasitoid, Trichogramma euproctidis (Girault); the second was sprayed by the recommended chemical control program of the farm (CC); and the third was untreated as a control. Obtained results revealed that the BC program was the most significant one for controlling the complex of sweet pepper pests. Also, applying the BC program resulted to a high yield of sweet pepper production (35.06% increasing than the control).
The immunohistochemical landscape of the VEGF family and its receptors in glioblastomas
Authors: Loureiro Luiz Victor Maia , Neder Luciano , Callegaro-Filho Donato , de Oliveira Koch Ludmila , Stavale João Norberto , Malheiros Suzana Maria Fleury
Published: March 2020

Background

Angiogenesis is one of the hallmarks of cancer. This complex mechanism of tumor progression provides tumors cells with essential nutrients. There have been a limited number of investigations of markers of angiogenesis in Glioblastomas (GBMs), and most previous studies have focused on VEGF-A. Recent evidence suggests that there is a complex lymphatic system in central nervous system (CNS), which suggests VEGF-C and VEGF–D as interesting biomarker candidates. This study was designed to evaluate the expressions of VEGF-A, −C, −D and their co-receptors, VEGFR-1, VEGFR-2, and VEGFR-3 by immunohistochemistry (IHC) using a series of GBMs. In addition, we evaluate any putative correlations between IHC expression levels of VEGF and clinical data of patients.

Methods

Tumor samples of 70 GBM patients (64 isocitrate dehydrogenase-1 wildtype (wtIDH-1) and 6 mutant (mutIDH-1)) were assessed by IHC using tissue microarray platforms for VEGF subunits and their co-receptors. The medical records were reviewed for clinical and therapeutic data.

Results

All VEGF subunits and receptors were highly expressed in GBMs: 57 out of 62 (91.9%), 53 out of 56 (94.6%) and 55 out of 63 cases (87.3%) showed VEGF-A, VEGF-C and -D imunoexpression, respectively. Interestingly, we had found both nuclear and cytoplasmic localization of VEGF-C staining in GBM tumor cells. The frequency of immunoexpression of VEGF receptors was the following: VEGFR-1, 65 out of 66 cases (98.5%); VEGFR-2, 63 out of 64 cases (98.4%); VEGFR-3, 49 out of 50 cases (90.0%). There were no significant differences in the patient overall survival (OS) related to the VEGF staining. A weak and monotonous correlation was observed between VEGF and its cognate receptors. The pattern of VEGF IHC was found to be similar when GBM mutIDH-1 subtypes were compared to wtIDH-1.

Conclusion

Both VEGF-C and –D, together with their receptors, were found to be overexpressed in the majority GBMs, and the IHC expression levels did not correlate with OS or IDH status. To understand the significance of the interactions and increased expression of VEGF-C, VEGF-D, VEGFR-2, and VEGFR-3 axis in GBM requires more extensive studies. Also, functional assays using a larger series of GBM is also necessary to better address the biological meaning of nuclear VEGF-C expression in tumor cells.
Sorting Through the Maze of Treatment Options for Metastatic Castration-Sensitive Prostate Cancer
Authors: Schulte Brian , Morgans Alicia K. , Shore Neal D. , Pezaro Carmel
Published: March 2020

Since 1944, when Huggins and Hodges demonstrated the effectiveness of bilateral orchiectomy for metastatic prostate cancer (PCa), androgen deprivation therapy (ADT) has been the first-line treatment for men with advanced PCa. The proportion of PCa cases that are metastatic at diagnosis ranges globally, from 5%–20% in countries with widespread screening practices to upward of 30%–60% where screening is minimal. In the United States alone, there will be an estimated 191,000 new cases of PCa diagnosed in the year 2020, of which approximately 20% will be metastatic. 1 Ongoing controversy around prostate-specific antigen (PSA) screening practices, increased access to novel imaging modalities, and a globally aging population will drive increased rates of metastatic castration-sensitive prostate cancer (mCSPC). 2 , 3 At the same time, advances in upfront hormonal or chemohormonal therapy have driven a dramatic shift in treatment paradigms. In this article, we review recent advances in treatment choices for men with newly diagnosed mCSPC and the impact of upfront treatment on subsequent disease biology. Options include treatment with chemohormonal therapy, androgen receptor (AR)–directed therapy in addition to ADT, or, less commonly, ADT alone. Treatment choice must include consideration of clinical and disease characteristics, as well as patient preferences and limitations of geography and financial concerns.
ACA Litigation: Politics Pursued through Other Means
Authors: Jost Timothy Stoltzfus , Keith Katie
Published: March 2020

Despite its passage a decade ago, the Affordable Care Act (ACA) remains a politically divisive law. These political divisions have long been on display in Congress, in the White House, and in states. A long-standing stalemate in Congress—where Republicans cannot repeal the law and Democrats cannot improve it—has emboldened efforts by the executive branch to act unilaterally to implement, or undermine, the ACA. In turn, the law's opponents and supporters have turned to the courts to promote their favored policy agendas through both broadside attacks on the law and targeted challenges to its implementation. Litigation has become politics pursued through other means. These challenges have often been brought, or opposed, by state attorneys general and governors, with red-state coalitions facing off against blue-state coalitions. ACA litigation has also been characterized by forum shopping, nationwide injunctions, and questions about the court as a truly adversarial forum. This article briefly reviews the history of ACA litigation, discusses these legal norms in the context of the historic health reform law, and considers the implications of this history and the changing judiciary for future health reform efforts.
The Affordable Care Act and Mass Policy Feedbacks
Authors: Campbell Andrea Louise
Published: March 2020

The Affordable Care Act (ACA) has allowed researchers to examine mass policy feedback effects—how public policies affect individuals' attitudes and political behaviors—in real time while using causal models. These efforts help address criticisms of the extant feedbacks literature and have revealed new policy feedback effects and new information on the conditions under which policy feedbacks occur. The ACA case also raises empirical and theoretical questions about the types of data needed to assess feedback effects, the magnitude of policy effects required for detection, the time frame in which feedbacks occur, and the suitability of various empirical approaches for assessing policy feedback effects. Thus, the ACA not only adds an important empirical case to the study of policy feedbacks but also helps refine policy feedback theory.
The ACA a Decade In: Resilience, Impact, and Vulnerabilities
Authors: Peterson Mark A.
Published: March 2020

A decade after its enactment, the Affordable Care Act remains both politically viable and consequential, despite Republican efforts to end it. The law's impact on insurance coverage is substantial but remains distant from universal coverage, while its contributions to cost control are at best limited. National public opinion data collected by the author in 2018 reveal both strengths and vulnerabilities in the act.
Medicaid's Post-ACA Paradoxes
Authors: Grogan Colleen M.
Published: March 2020

Medicaid's experience one decade after the passage of the Affordable Care Act represents extreme divergence across the American states in health care access and utilization, policy designs that either expand or restrict eligibility, and delivery model reforms. The past decade has also witnessed a growing ideological divide about the very purpose and intent of the Medicaid program and its place within the US health care system. While liberal-leaning states have actively embraced the program and used it to expand health coverage to working adults and families as an effort to improve health and prevent poverty and the insecurity and instability that comes with high medical costs (evictions, bankruptcy), conservative states have actively rejected this expanded idea of Medicaid and argued instead that the program should revert back to its “original” purpose and be used only for the “truly” needy. This article highlights several paradoxes within Medicaid that have led to this growing bifurcation, and it concludes by shedding light on important targets for future reform.
The Administrative Presidency, Waivers, and the Affordable Care Act
Authors: Gusmano Michael K. , Thompson Frank J.
Published: March 2020

Within the American system of shared power among institutions, the executive branch has played an increasingly prominent policy role relative to Congress. The vast administrative discretion wielded by the executive branch has elevated the power of the president. Republican and Democratic presidents alike have employed an arsenal of administrative tools to pursue their policy goals: high-level appointments, administrative rule making, executive orders, proclamations, memoranda, guidance documents, directives, dear colleague letters, signing statements, reorganizations, funding decisions, and more. Presidents Obama and Trump employed most of these tools in an effort to shape the implementation and outcomes of the Affordable Care Act (ACA) during its first decade. This article focuses on the Obama and Trump administrations' use of comprehensive waivers to shape ACA implementation. The Obama administration had mixed success using waivers to convince Republican states to expand Medicaid. Compared to Obama, the Trump administration has found it harder to accomplish its policy goals through waivers, but if the courts support the Trump administration's work requirement and 1332 waiver initiatives, it would enable the president to use waivers to achieve an ever broader set of goals, including program retrenchment.
Have the ACA's Exchanges Succeeded? It's Complicated
Authors: Jones David K. , Gordon Sarah H. , Huberfeld Nicole
Published: March 2020

The fight over health insurance exchanges epitomizes the rapid evolution of health reform politics in the decade since the passage of the Affordable Care Act (ACA). The ACA's drafters did not expect the exchanges to be contentious because they would expand private insurance coverage to low- and middle-income individuals who were increasingly unable to obtain employer-sponsored health insurance. Instead, exchanges became one of the primary fronts in the war over Obamacare. Have the exchanges been successful? The answer is not straightforward and requires a historical perspective through a federalism lens. What the ACA has accomplished has depended largely on whether states were invested in or resistant to implementation, as well as individual decisions by state leaders working with federal officials. Our account demonstrates that the states that have engaged with the ACA most consistently appear to have experienced greater exchange-related success. But each aspect of states' engagement with or resistance to the ACA must be counted to fully paint this picture, with significant variation among states. This variation should give pause to those considering next steps in health reform, because state variation can mean innovation and improvement but also lack of coverage, disparities, and diminished access to care.
The transcription factor Nurr1 is up-regulated in amyotrophic lateral sclerosis patients and SOD1-G93A mice
Authors: Valsecchi Valeria , Boido Marina , Montarolo Francesca , Guglielmotto Michela , Perga Simona , Martire Serena , Cutrupi Santina , Iannello Andrea , Gionchiglia Nadia , Signorino Elena , Calvo Andrea , Fuda Giuseppe , Chiò Adriano , Bertolotto Antonio , Vercelli Alessandro
Published: March 2020

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both lower and upper motor neurons (MNs) in the central nervous system (CNS). ALS etiology is highly multifactorial and multifarious, and an effective treatment is still lacking. Neuroinflammation is a hallmark of ALS and could be targeted to develop new therapeutic approaches. Interestingly, the transcription factor Nurr1 has been demonstrated to play an important role in inflammatory process in several neurological disorders, such as Parkinson's disease (PD) and Multiple Sclerosis (MS).

In the present paper, we demonstrated for the first time that Nurr1 expression levels were up-regulated in the peripheral blood of ALS patients. Moreover, we investigated Nurr1 function in the SOD1-G93A mouse model of ALS. Interestingly, Nurr1 was strongly up-regulated in the spinal cord during the asymptomatic and early symptomatic phases of the disease, where it promoted the up-regulation of the BDNF mRNA and the repression of NF-kB pro-inflammatory targets, such as iNOS. Therefore, we hypothesize that Nurr1 is activated in an early phase of the disease as survival endogenous anti-inflammatory mechanism, although not sufficient to revert disease progression.

Based on these observations, Nurr1 could represent a potential biomarker for ALS and a promising target for future therapies for ASL.
Preparation and Dynamic Behavior of Protein-Polymer Complexes Formed with Polymer-Binding Peptides
Authors: Ravishankar Samyukta , Suzuki Seigo , Sawada Toshiki , Lim Sierin , Serizawa Takeshi
Published: March 2020

The development of protein-polymer complexes using protein cages is garnering attention as a strategy to overcome challenges that relate to immunogenicity and protease degradation. We propose the use of thermoresponsive polymers such as poly(N-isopropylacrylamide) (PNIPAM) to form ferritin-polymer complexes through non-covalent interactions. Ferritin is observed to be released from the complexes after 1–2 days incubation at 37 °C.
“The Declaration on the Common Language”: A View from the Inside
Authors: Bugarski Ranko
Published: March 2020

The editor of the special issue of AWPEL on former Yugoslavia has kindly invited me to provide the journal’s readership with more information on this document, evaluated in distinctly negative terms by Professor Christian Voß in his contribution to the present collection of articles. I will gladly do so, in my capacity as a native speaker of Serbo-Croatian, a consultant in the drafting process of the Declaration and one of its initial signatories and public supporters. [...]