bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rare diseases in Chile: challenges and recommendations in universal health coverage context
Authors: Encina Gonzalo , Castillo-Laborde Carla , Lecaros Juan A. , Dubois-Camacho Karen , Calderón Juan F. , Aguilera Ximena , Klein Andrés D. , Repetto Gabriela M. 
Published: January 2020

AbstractRare diseases (RDs) are a large number of diverse conditions with low individual prevalence, but collectively may affect up to 3.5–5.9% of the population. They have psychosocial and economic impact on patients and societies, and are a significant problem for healthcare systems, especially for countries with limited resources. In Chile, financial protection exists for 20 known RDs through different programs that cover diagnosis and treatments. Although beneficial for a number of conditions, most RD patients are left without a proper legal structure that guarantees a financial coverage, and in a vulnerable situation. In this review, we present and analyze the main challenges of the Chilean healthcare system and legislation on RDs, and other ambits of the RD ecosystem, including patient advocacy groups and research. Finally, we propose a set of policy recommendations that includes creating a patient registry, eliciting social preferences on health and financial coverage, improving access to clinical genetic services and therapies, promoting research on RDs and establishing a Latin-American cooperation network, all aimed at promoting equitable quality healthcare access for people living with RDs.
Management and current status of spinal muscular atrophy: a retrospective multicentre claims database analysis
Authors: Darbà Josep 
Published: January 2020

Abstract
Introduction
The interest in patient demographics and disease management has increased in the past years due to their utility in developing measures that allow healthcare providers to reflect disease complexity.

Objective
To revise the current status of spinal muscular atrophy in the region of Catalonia, and to validate the utility of the database for this aim.

Methods
Five hundred twenty-four patients diagnosed with a spinal muscular atrophy were identified in the region of Catalonia via the novel program of data analysis for research and innovation in health (PADRIS). Patient records included in the analysis corresponded to primary care, hospital, emergency room, extended care and mental health admissions between 2007 and 2017.

Results
58.02% of patients with a SMA diagnosis were males while 40.84% were females. Average age of diagnosis was 38.31 ± 24.49 years ±SD. Significantly lower was the age of diagnosis of spinal muscular atrophy type I, 1.81 ± 3.01 years. An average of 22 patients died per year during the study period, with a mean decease age of 62.96 ± 25.41 years. Patients were generally attended in hospitals, and the use of healthcare resources was focused on resolving respiratory issues and scoliosis. The highest ratio of admissions per patient was registered in those aged 0 to 4 years. Patients presented a higher risk than the general population and a higher frequency of multimorbidites.

Conclusions
Patients exhibited similar characteristics to prior European studies. Multiple admissions in younger patients, mostly due to respiratory issues, have a central role in increasing medical costs of SMA. Equally, the higher risk of patients and increased number of multimorbidity groups translate in an elevated number of admissions in health centres and ER, deriving in higher expenses.
Immunological features of patients affected by Barraquer-Simons syndrome
Authors: Corvillo Fernando , Ceccarini Giovanni , Nozal Pilar , Magno Silvia , Pelosini Caterina , Garrido Sofía , López-Lera Alberto , Moraru Manuela , Vilches Carlos , Fornaciari Silvia , Gabbriellini Sabrina , Santini Ferruccio , Araújo-Vilar David , López-Trascasa Margarita 
Published: January 2020

Abstract
Background
C3 hypocomplementemia and the presence of C3 nephritic factor (C3NeF), an autoantibody causing complement system over-activation, are common features among most patients affected by Barraquer-Simons syndrome (BSS), an acquired form of partial lipodystrophy. Moreover, BSS is frequently associated with autoimmune diseases. However, the relationship between complement system dysregulation and BSS remains to be fully elucidated. The aim of this study was to provide a comprehensive immunological analysis of the complement system status, autoantibody signatures and HLA profile in BSS. Thirteen subjects with BSS were recruited for the study. The circulating levels of complement components, C3, C4, Factor B (FB) and Properdin (P), as well as an extended autoantibody profile including autoantibodies targeting complement components and regulators were assessed in serum. Additionally, HLA genotyping was carried out using DNA extracted from peripheral blood mononuclear cells.

Results
C3, C4 and FB levels were significantly reduced in patients with BSS as compared with healthy subjects. C3NeF was the most frequently found autoantibody (69.2% of cases), followed by anti-C3 (38.5%), and anti-P and anti-FB (30.8% each). Clinical data showed high prevalence of autoimmune diseases (38.5%), the majority of patients (61.5%) being positive for at least one of the autoantibodies tested. The HLA allele DRB1*11 was present in 54% of BSS patients, and the majority of them (31%) were positive for *11:03 (vs 1.3% allelic frequency in the general population).

Conclusions
Our results confirmed the association between BSS, autoimmunity and C3 hypocomplementemia. Moreover, the finding of autoantibodies targeting complement system proteins points to complement dysregulation as a central pathological event in the development of BSS.
Type-5 abomasal ulcer and omental bursitis in 14 cows
Authors: Braun Ueli , Reif Christina , Hilbe Monika , Gerspach Christian 
Published: January 2020

Abstract
Background
Type-5 abomasal ulcer (U5) is a perforated ulcer that causes peritonitis limited to the omental bursa. This retrospective study describes the clinical and laboratory findings in 14 cattle with omental bursitis due to U5. The medical records of 14 cows aged 2.5 to 14.6 years (5.4 ± 3.1 years) with U5 were scrutinised.

Results
The most common clinical findings were partial or complete anorexia (100%), abdominal guarding (100%), obtunded demeanour (93%), congested scleral vessels (79%), tachypnoea (71%), rumen atony (64%), diminished faecal output (64%), reduced skin surface temperature (64%) and fever (46%). Four (29%) cows had between one and four concomitant diseases. The most common abnormal laboratory findings were hypokalemia (71%), haemoconcentration (57%), metabolic acidosis (57%) and azotaemia (43%). All cows were euthanased; five immediately after the initial examination, one after exploratory laparotomy and eight after unsuccessful treatment. A diagnosis of U5 was made in all cows during postmortem examination.

Conclusions
There is a need for improvement of the antemortem diagnosis of U5 because reliable differentiation of this disease from other conditions with a similar clinical presentation is currently not feasible.
Trends in suicide-related research in Australia
Authors: Schlichthorst Marisa , Reifels Lennart , Krysinska Karolina , Ftanou Maria , Machlin Anna , Robinson Jo , Pirkis Jane 
Published: January 2020

Abstract
Background
Despite continuous research over the past 20 years in Australia there is still limited understanding of what works and what does not work in suicide prevention and where to invest research efforts that will help to expand this knowledge base. There is a recursive relationship between research activities, knowledge gain and the development of strategy and action plans as these in turn guide future decisions on research funding. In this context, the first step to continuous improvement in knowledge is to better understand where research has been invested in the past until now and where it has not.

Methods
We conducted a study that collected data over two periods. The first data collection was done in 2006 for the period of 1999 to 2006 and the second data collection was in 2017 for the period from 2010 to 2017. This allowed us to examine changes in published suicide-related journal articles, and grants/fellowships funded between the two periods. Published articles and grants/fellowships were classified according to a pre-determined framework.

Results
The number of suicide-related articles and grants/fellowships increased over the two periods. We noted shifts in the types of research that were funded and published, and in the emphasis that was given to different types of suicidal behavior, suicide methods, and settings. Research target groups showed a trend towards increasing diversification.

Conclusions
Our findings help to identify current research priorities and inform where future priorities for suicide-related research in Australia lie by linking findings to other external data sources (population risk data, stakeholder consultations, national strategies and action plan documents).
Highly specific PCR-RFLP assays for karyotyping the widespread 2Rb inversion in malaria vectors of the Anopheles gambiae complex
Authors: Montanez-Gonzalez Raquel , Pichler Verena , Calzetta Maria , Love Rachel R. , Vallera Alexandra , Schaecher Lydia , Caputo Beniamino , Pombi Marco , Petrarca Vincenzo , della Torre Alessandra , Besansky Nora J. 
Published: January 2020

Abstract
Background
Chromosomal inversion polymorphisms play a role in adaptation to heterogeneous environments. Inversion polymorphisms are implicated in the very high ecological flexibility of the three main malaria vector species of the Afrotropical Anopheles gambiae complex, facilitating the exploitation of anthropogenic environmental modifications and promoting a strong association with humans. In addition to extending the species’ spatial and temporal distribution, inversions are associated with epidemiologically relevant mosquito behavior and physiology, underscoring their medical importance. We here present novel PCR-RFLP based assays strongly predictive of genotype for the cosmopolitan 2Rb inversion in An. coluzzii and An. gambiae, a development which overcomes the numerous constraints inherent to traditional cytological karyotyping.

Methods
We designed PCR-RFLP genotyping assays based on tag SNPs previously computationally identified as strongly predictive (> 95%) of 2Rb genotype. We targeted those tags whose alternative allelic states destroyed or created the recognition site of a commercially available restriction enzyme, and designed assays with distinctive cleavage profiles for each inversion genotype. The assays were validated on 251 An. coluzzii and 451 An. gambiae cytologically karyotyped specimens from nine countries across Africa and one An. coluzzii laboratory colony.

Results
For three tag SNPs, PCR-RFLP assays (denoted DraIII, MspAI, and TatI) reliably produced robust amplicons and clearly distinguishable electrophoretic profiles for all three inversion genotypes. Results obtained with the DraIII assay are ≥ 95% concordant with cytogenetic assignments in both species, while MspAI and TatI assays produce patterns highly concordant with cytogenetic assignments only in An. coluzzii or An. gambiae, respectively. Joint application of species-appropriate pairs of assays increased the concordance levels to > 99% in An. coluzzii and 98% in An. gambiae. Potential sources of discordance (e.g. imperfect association between tag and inversion, allelic dropout, additional polymorphisms in the restriction target site, incomplete or failed restriction digestion) are discussed.

Conclusions
The availability of highly specific, cost effective and accessible molecular assays for genotyping 2Rb in An. gambiae and An. coluzzii allows karyotyping of both sexes and all developmental stages. These novel tools will accelerate deeper investigations into the role of this ecologically and epidemiologically important chromosomal inversion in vector biology.
E-test versus agar dilution for antibiotic susceptibility testing of Helicobacter pylori: a comparison study
Authors: Miftahussurur Muhammad , Fauzia Kartika Afrida , Nusi Iswan Abbas , Setiawan Poernomo Boedi , Syam Ari Fahrial , Waskito Langgeng Agung , Doohan Dalla , Ratnasari Neneng , Khomsan Ali , Adnyana I. Ketut , Akada Junko , Yamaoka Yoshio 
Published: January 2020

AbstractObjectiveFor evaluating the antibiotic resistance ofHelicobacter pylori, the agar dilution method is the gold standard; however, using this method in daily practice is laborious. E-test has been proposed to be an uncomplicated method. This study was aimed at validating the E-test and detecting the presence of any bias between the agar dilution method and E-test.ResultsThe agar dilution method and E-test were performed using five antibiotics for 72 strains ofH. pyloriobtained from clinical patients in Indonesia. The E-test’s results showed a higher prevalence of resistance to all the antibiotics tested but the difference was not significant. Results showed high essential agreement (> 90.0%) for all the antibiotics, but only 84.7% for metronidazole. The agreement for MIC value was acceptable for levofloxacin, clarithromycin, and metronidazole. For amoxicillin, it showed only fair agreement (0.25) by the Kappa analysis and significant difference by Passing-Bablok regression. Even though some discrepancies were found, the E-test has an acceptable agreement for levofloxacin, metronidazole, tetracycline, and clarithromycin but further confirmation may be necessary for amoxicillin.
Design and implementation of an educational game considering issues for visually impaired people inclusion
Authors: Neto Luiz Valério , Fontoura Junior Paulo H.F. , Bordini Rogério A. , Otsuka Joice L. , Beder Delano M. 
Published: January 2020

AbstractIn recent years there has been an increase in research focusing on the effectiveness of using video games as educational digital resources that can contribute to the learning process at different levels, which has also subsidised the development of educational games. However, these games are mostly visual and not accessible to people with visual impairments. As an educational resource, it is essential that the design of educational games be conducted not only with a focus on the balance between playful and educational aspects, but also with a focus on including the largest number of people. This article, therefore, aims to describe the design, implementation and evaluation processes of an accessible version of the educational game Em Busca do Santo Grau, based on EduGameAccess – a set of recommendations that integrates educational, playability and accessibility aspects for people with visual impairments.
18F-FDG PET/CT imaging findings in anaplastic large cell lymphoma, a rare subtype of lymphoma
Authors: Jiang Yanping , Wang Lijuan , Zhou Wenlan , Gu Jiamei , Tian Ying , Dong Ye , Fu Lilan , Wu Hu-bing 
Published: January 2020

Abstract
Objective
To investigate the 18F-FDG PET/CT imaging manifestations for anaplastic large cell lymphoma (ALCL), a rare subtype of T/NK cell lymphoma.

Methods
Fifty patients with ALCL, including 32 anaplastic lymphoma kinase (ALK)-positive patients and 18 ALK-negative patients, were enrolled. The positive detection, maximal standardized uptake value (SUVmax), and distribution of nodal and extranodal involvement were recorded and analysed. Fifty patients with diffuse large B cell lymphoma (DLBCL) were collected as a control group.

Results
ALCL lesions were demonstrated to be 18F-FDG-avid tumours with a mean SUVmax of 19.4 ± 12.6. Most (76%) ALCL patients presented with stage III-IV disease, and nodal and extranodal involvement occurred in 74.0 and 72.0% of the patients, respectively. ALCL and DLBCL showed many similarities in tumour stage, 18F-FDG uptake and tumour involvement (P > 0.05), although the preferred extranodal organs of involvement (bone and the gastrointestinal tract, respectively) were different (P < 0.05). Compared to ALK-negative lesions, a higher uptake of 18F-FDG was found in the ALK-positive lesions (SUVmax: 22.1 ± 14.3 vs. 15.1 ± 6.6, t = 2.354, P = 0.023). ALK-positive ALCL was more likely to involve the lymph nodes than ALK-negative ALCL (84.3% vs. 55.5%, χ2 = 4.973, P = 0.043), while ALK-negative ALCL was more prone to involve the extranodal organs compared to ALK-positive ALCL (88.9% vs. 62.5%, χ2 = 3.979, P = 0.046).

Conclusion
The present study demonstrated that ALCL is a systemic 18F-FDG-avid lymphoma with many imaging manifestations similar to DLBCL on PET/CT. The present study also showed that ALK expression actually influenced tumour 18F-FDG uptake and lesion distribution. These findings may be useful to improve the understanding of the biological characteristics of ALCL.
Performance evaluation of a new custom, multi-component DNA isolation method optimized for use in shotgun metagenomic sequencing-based aerosol microbiome research
Authors: Bøifot Kari Oline , Gohli Jostein , Moen Line Victoria , Dybwad Marius 
Published: January 2020

Abstract
Background
Aerosol microbiome research advances our understanding of bioaerosols, including how airborne microorganisms affect our health and surrounding environment. Traditional microbiological/molecular methods are commonly used to study bioaerosols, but do not allow for generic, unbiased microbiome profiling. Recent studies have adopted shotgun metagenomic sequencing (SMS) to address this issue. However, SMS requires relatively large DNA inputs, which are challenging when studying low biomass air environments, and puts high requirements on air sampling, sample processing and DNA isolation protocols. Previous SMS studies have consequently adopted various mitigation strategies, including long-duration sampling, sample pooling, and whole genome amplification, each associated with some inherent drawbacks/limitations.

Results
Here, we demonstrate a new custom, multi-component DNA isolation method optimized for SMS-based aerosol microbiome research. The method achieves improved DNA yields from filter-collected air samples by isolating DNA from the entire filter extract, and ensures a more comprehensive microbiome representation by combining chemical, enzymatic and mechanical lysis. Benchmarking against two state-of-the-art DNA isolation methods was performed with a mock microbial community and real-world air samples. All methods demonstrated similar performance regarding DNA yield and community representation with the mock community. However, with subway samples, the new method obtained drastically improved DNA yields, while SMS revealed that the new method reported higher diversity. The new method involves intermediate filter extract separation into a pellet and supernatant fraction. Using subway samples, we demonstrate that supernatant inclusion results in improved DNA yields. Furthermore, SMS of pellet and supernatant fractions revealed overall similar taxonomic composition but also identified differences that could bias the microbiome profile, emphasizing the importance of processing the entire filter extract.

Conclusions
By demonstrating and benchmarking a new DNA isolation method optimized for SMS-based aerosol microbiome research with both a mock microbial community and real-world air samples, this study contributes to improved selection, harmonization, and standardization of DNA isolation methods. Our findings highlight the importance of ensuring end-to-end sample integrity and using methods with well-defined performance characteristics. Taken together, the demonstrated performance characteristics suggest the new method could be used to improve the quality of SMS-based aerosol microbiome research in low biomass air environments.
Atypical citizenship regimes: comparing legal and political conceptualizations
Authors: Naujoks Daniel 
Published: January 2020

AbstractNotions, features, and forms of citizenship, understood as legal membership in a state, are changing the world over. While contestations of the monolithic understanding of citizenship generally focus on the content of individuals’ rights and their belonging and participation in social and political institutions, this essay shows that official membership categories that are labeled ‘citizenship’ by state actors vary. Drawing on the experiences of the Overseas Citizenship of India, the British Overseas Citizenship, and Citizenship of the European Union the essay proposes an analytical framework that aims at advancing the comparative study of state membership policies by introducing six key dimensions that policy actors consider when designing citizenship policies. Apart from systematizing the content of citizenship, the framework sheds light on the importance of citizenship terminology, as states employ the label of citizenship and use the status as a vehicle of communication. The essay highlights differences in the construction of special subjects, moral obligations and the exercise of power, analyzes the aspirations of political actors, the political rhetoric, and explores the interplay between tangible rights and intangible narratives. The discussion of the three atypical membership regimes reveals that states operate in grey areas of membership statuses that partly mimic existing forms of state membership and partly push the boundaries of what state membership means. This has significant repercussions for comparative citizenship and democracy theory and the meaning of membership.
Adequacy of decision-making based on each kidney function estimation method for Japanese living kidney donor candidates: a retrospective observational study
Authors: Hashimoto Koji , Harada Makoto , Yamada Yosuke , Sugano Mitsutoshi , Minagawa Tomonori , Ogawa Teruyuki , Ishizuka Osamu , Kamijo Yuji 
Published: January 2020

Abstract
Background
Living kidney transplantation comprises the majority of kidney transplantations in Japan. Living kidney donors should be assured of their own health. Therefore, Japanese guidelines define the criterion of kidney function for living donors. Glomerular filtration rates (GFR) ≥ 70 mL/min/1.73 m2 are required for marginal donors. The guidelines require that GFRs of donors be measured by the inulin (In) clearance method (CIn) or the radioisotope method, but these methods can be substituted with the creatinine (Cr) clearance method (CCr). Methods for estimating kidney function are susceptible to error, and decision-making regarding donor eligibility could be affected by the estimation method used. We investigated the adequacy of decision-making based on kidney function estimation methods used in Japanese living kidney donor candidates by comparing CCr or estimated GFR (eGFR), calculated by several equations, and CIn as measured GFR (mGFR).

Methods
In total, 210 people, including 36 actual kidney donor candidates, who had both CIn and CCr measured at Shinshu University Hospital from April 2011 to April 2015, were included. Cr and cystatin C (Cys) levels measured at the same time were used to calculate eGFR (eGFRCr and sGFRCys, respectively). We evaluated the concordance rates of cases whose GFR levels were ≥ 70 mL/min/1.73 m2 in this study and assumed that they were living kidney donor candidates. Only kidney donor candidates underwent an additional sensitivity analysis.

Results
Median CIn and CCr were 55.5 mL/min/1.73 m2 and 68.0 mL/min/1.73 m2, respectively. CCr had the highest tendency to overestimate kidney function. Some participants were incorrectly evaluated as adequate using CCr, despite their mGFR being inadequate for living kidney donors according to the guidelines. These results were independent of sex or actual living kidney donor candidates. The average of eGFRCr and eGFRCys was well correlated with CIn.

Conclusions
Kidney function estimated by CCr is not equal to the mGFR. When using CCr as a kidney function estimation method to determine the adequacy of a living kidney donor, it should be noted that CCr overestimates kidney function. In evaluating adequacy for a marginal donor, GFR estimated by CIn should be assessed.