bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractMethylation 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

Abstract
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

Abstract
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

Abstract
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

AbstractObjectiveThe 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.ResultsHere, 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

Abstract
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

Abstract
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

Abstract
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

AbstractThe 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

AbstractBackgroundEnergy 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.MethodsThe 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.ResultsOur 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.ConclusionsCooperatives 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

AbstractBackgroundTri-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).ResultsThere 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).ConclusionWe 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.