bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analytical performance evaluation of a commercial next generation sequencing liquid biopsy platform using plasma ctDNA, reference standards, and synthetic serial dilution samples derived from normal plasma
Authors: Verma Suman , Moore Mathew W. , Ringler Rebecca , Ghosal Abhisek , Horvath Kyle , Naef Theodore , Anvari Sheri , Cotter Philip D. , Gunn Shelly 
Published: October 2020

Abstract
Background
Circulating tumor (ct) DNA assays performed in clinical laboratories provide tumor biomarker testing support for biopharmaceutical clinical trials. Yet it is neither practical nor economically feasible for many of these clinical laboratories to internally develop their own liquid biopsy assay. Commercially available ctDNA kits are a potential solution for laboratories seeking to incorporate liquid biopsy into their test menus. However, the scarcity of characterized patient samples and cost of purchasing validation reference standards creates a barrier to entry. In the current study, we evaluated the analytical performance of the AVENIO ctDNA liquid biopsy platform (Roche Sequencing Solutions) for use in our clinical laboratory.

Method
Intra-laboratory performance evaluation of AVENIO ctDNA Targeted, Expanded, and Surveillance kits (Research Use Only) was performed according to College of American Pathologists (CAP) guidelines for the validation of targeted next generation sequencing assays using purchased reference standards, de-identified human plasma cell-free (cf) DNA samples, and contrived samples derived from commercially purchased normal and cancer human plasma. All samples were sequenced at read depths relevant to clinical settings using the NextSeq High Output kit (Illumina).

Results
At the clinically relevant read depth, Avenio ctDNA kits demonstrated 100% sensitivity in detecting single nucleotide variants (SNVs) at ≥0.5% allele frequency (AF) and 50% sensitivity in detecting SNVs at 0.1% AF using 20–40 ng sample input amount. The assay integrated seamlessly into our laboratory’s NGS workflow with input DNA mass, target allele frequency (TAF), multiplexing, and number of reads optimized to support a high-throughput assay appropriate for biopharmaceutical trials.

Conclusions
Our study demonstrates that AVENIO ctDNA liquid biopsy platform provides a viable alternative for efficient incorporation of liquid biopsy assays into the clinical laboratory for detecting somatic alterations as low as 0.5%. Accurate detection of variants lower than 0.5% could potentially be achieved by deeper sequencing when clinically indicated and economically feasible.
The FeverApp registry – ecological momentary assessment (EMA) of fever management in families regarding conformity to up-to-date recommendations
Authors: Martin David , Wachtmeister Jana , Ludwigs Kai , Jenetzky Ekkehart 
Published: October 2020

Abstract
Background
Fever is one of the most common symptoms of pediatric consultations and its mismanagement is a health care burden. Guidelines on fever management are incoherent and data on fever management are still missing. This study protocol describes an app-based registry to evaluate the fever management of parents.

Objective
The primary objectives are to assess guideline adherence (primary outcome) and parental confidence in managing fever, and thus to reduce overuse of antipyretics, antibiotics and healthcare providers.
Secondary objectives include creating a “FeverApp” that will enable parents to handle fever safely and to use the FeverApp registry as symptom and fever management diary. Further objectives include developing and testing a symptom-led registry model by app-based acquisition of parental entries of febrile illness cycle data and developing and testing models of how an interactive app-based registry can enable nationwide EMA information to inform science, guideline and policy makers, and the public.

Methods
A FeverApp, guiding parents and carers in handling and documenting fever, will be developed with family pediatricians according to current guidelines and recommended for all parents in Germany. A registry will anonymously document features, management and outcomes of febrile episodes: basic sociodemographic and medical information, initial symptoms, course of fever, pharmacological and non-pharmacological interventions, consultations with doctors, outcomes, fever-associated fears, and app satisfaction.

Results
This app may improve communication quality and health, e.g. asthma and antimicrobial resistance. Results will be published via website www.feverapp.de.

Trial registration
This app-based registry protocol is registered in the German Clinical Trials Register (DRKS) with registration number: DRKS00016591.
Persistent domestic circulation of African swine fever virus in Tanzania, 2015–2017
Authors: Yona Clara M. , Vanhee Merijn , Simulundu Edgar , Makange Mariam , Nauwynck Hans J. , Misinzo Gerald 
Published: October 2020

Abstract
Background
African swine fever (ASF) is a highly fatal viral hemorrhagic disease of domestic pigs that threatens livelihoods and food security. In Africa, ASF virus (ASFV) circulates in sylvatic (transmission between warthogs and soft argasid ticks) and domestic (transmission between domestic pigs) cycles, with outbreaks resulting from ASFV spill-over from sylvatic cycle. A number of outbreaks were reported in different parts of Tanzania between 2015 and 2017. The present study investigated ASFV transmission patterns through viral DNA sequencing and phylogenetic analysis. A total of 3120 tissue samples were collected from 2396 domestic pigs during outbreaks at different locations in Tanzania between 2015 and 2017. Partial sequencing of the B646L (p72) gene was conducted for diagnostic confirmation and molecular characterization of ASFV. Phylogenetic analysis to study the relatedness of current ASFV with those that caused previous outbreaks in Tanzania and representatives of all known 24 ASFV was performed using the Maximum Composite Likelihood model with 1000 bootstrap replications in MEGA 6.0.

Results
ASFV was confirmed to cause disease in sampled domestic pigs. ASFV genotypes II, IX, and X were detected from reported outbreaks in 2015–2017. The current ASFV isolates were similar to those recently documented in the previous studies in Tanzania. The similarities of these isolates suggests for continuous circulation of ASFV with virus maintenance within the domestic pigs.

Conclusions
Genetic analysis confirmed the circulation of ASFV genotypes II, IX, and X by partial B646L (p72) gene sequencing. The similarities of current isolates to previously isolated Tanzanian isolates and pattern of disease spread suggest for continuous circulation of ASF with virus’ maintenance in the domestic pigs. Although certain viral genotypes seem to be geographically restricted into certain zones within Tanzania, genotype II seems to expand its geographical range northwards with the likelihood of spreading to other states of the East African Community. The spread of ASFV is due to breach of quarantine and transportation of infected pigs via major highways. Appropriate control measures including zoosanitary measures and quarantine enforcement are recommended to prevent ASF domestic circulation in Tanzania.
Production and identification of two antifungal terpenoids from the Posidonia oceanica epiphytic Ascomycota Mariannaea humicola IG100
Authors: Botta Lorenzo , Saladino Raffaele , Barghini Paolo , Fenice Massimiliano , Pasqualetti Marcella 
Published: October 2020

Abstract
Background
Marine fungi are an important repository of bioactive molecules with great potential in different technological fields, the annual number of new compounds isolated from marine fungi is impressive and the general trend indicates that it is still on the rise. In this context, the antifungal and antimicrobial activity of the marine strain Mariannaea humicola IG100 was evaluated and two active terpenoids were isolated and characterized.

Methods
Preliminary screening of activity of marine strain IG100 was carried out by agar plug diffusion methods against fungal (Penicillium griseofulvum TSF04) and bacterial (Bacillus pumilus KB66 and Escherichia coli JM109) strains. Subsequently, inhibition tests were done by using the cultural broth and the organic extract (ethyl acetate, EtOAc) by the agar well diffusion methods. The main active fractions were identified and tested for their antifungal activity against P. griseofulvum TSF04 in a 24 wells microplate at different concentrations (1000, 100, 10 and 1.0 µg/mL). Two active compounds were characterized and their relative MIC measured by the broth micro-dilution methods in a 96-well microplate against Aspergillus flavus IG133, P. griseofulvum TSF04, and Trichoderma pleuroticola IG137.

Results
Marine strain IG100 presented significant antifungal activity associated with two active compounds, the terpenoids terperstacin 1 and 19-acetyl-4-hydroxydictyodiol 2. Their MIC values were measured for A. flavus (MIC of 7.9 µg/mL and 31.3 µg/mL for 1 and 2, respectively), P. griseofulvum (MIC of 25 µg/mL and 100 µg/mL for 1 and 2, respectively) and T. pleuroticola (MIC > 500 µg/mL and 125 µg/mL for 1 and 2, respectively). They showed a rather good fungistatic effect.

Conclusions
In this study, the first marine strain of M. humicola (IG100) was investigated for the production of bioactive molecules. Strain IG100 produced significant amounts of two bioactive terpenoids, terperstacin 1 and 19-acetyl-4-hydroxydictyodiol 2. The two compounds showed significant antifungal activities against A. flavus IG133, T. pleuroticola IG137 and P. griseofulvum TSF04. Compound 2 was identified for the first time in fungi.
Malaria case management and elimination readiness in health facilities of five districts of Madagascar in 2018
Authors: Anand Anjoli , Favero Rachel , Dentinger Catherine , Ralaivaomisa Andrianandraina , Ramamonjisoa Sitraka , Rabozakandraina Oliva , Razafimandimby Eliane , Razafindrakoto Jocelyn , Wolf Katherine , Steinhardt Laura , Gomez Patricia , Rabary Malanto , Andriamananjara Mauricette Nambinisoa , Mioramalala Sedera Aurélien , Rakotovao Jean-Pierre 
Published: October 2020

Abstract
Background
Madagascar’s Malaria National Strategic Plan 2018–2022 calls for progressive malaria elimination beginning in low-incidence districts (< 1 case/1000 population). Optimizing access to prompt diagnosis and quality treatment and improving outbreak detection and response will be critical to success. A malaria elimination readiness assessment (MERA) was performed in health facilities (HFs) of selected districts targeted for malaria elimination.

Methods
A mixed methods survey was performed in September 2018 in five districts of Madagascar. Randomly selected HFs were assessed for availability of malaria commodities and frequency of training and supervision conducted. Health providers (HPs) and community health volunteers (CHVs) were interviewed, and outpatient consultations at HFs were observed. To evaluate elimination readiness, a composite score ranging from 0 to 100 was designed from all study tools and addressed four domains: (1) resource availability, (2) case management (CM), (3) data management and use, and (4) training, supervision, and technical assistance; scores were calculated for each HF catchment area and district based on survey responses. Stakeholder interviews on malaria elimination planning were conducted at national, regional and district levels.

Results
A quarter of the 35 HFs surveyed had no rapid diagnostic tests (RDTs). Of 129 patients with reported or recorded fever among 300 consultations observed, HPs tested 56 (43%) for malaria. Three-quarters of the 35 HF managers reviewed data for trends. Only 68% of 41 HPs reported receiving malaria-specific training. Of 34 CHVs surveyed, 24% reported that treating fever was no longer among their responsibilities. Among treating CHVs, 13 (50%) reported having RDTs, and 11 (42%) had anti-malarials available. The average district elimination readiness score was 52 out of 100, ranging from 48 to 57 across districts. Stakeholders identified several challenges to commodity management, malaria CM, and epidemic response related to lack of training and funding disruptions.

Conclusion
This evaluation highlighted gaps in malaria CM and elimination readiness in Madagascar to address during elimination planning. Strategies are needed that include training, commodity provision, supervision, and support for CHVs. The MERA can be repeated to assess progress in filling identified gaps and is a feasible tool that could be used to assess elimination targets in other countries.
The (cost-)effectiveness and cost-utility of a novel integrative care initiative for patients with chronic musculoskeletal pain: the pragmatic trial protocol of Network Pain Rehabilitation Limburg
Authors: Lamper Cynthia , Huijnen Ivan P. J. , Goossens Mariëlle E. J. B. , Winkens Bjorn , Ruwaard Dirk , Verbunt Jeanine A. M. C. F. , Kroese Mariëlle E. 
Published: October 2020

Abstract
Background
Rehabilitation care for patients with chronic musculoskeletal pain (CMP) is not optimally organized. The Network Pain Rehabilitation Limburg 2.0 (NPRL2.0) provides integrated care with a biopsychosocial approach and strives to improve the Quadruple Aim outcomes: pain-related disability of patients with CMP; experiences of care of patients with CMP; meaning in the work of healthcare professionals; and healthcare costs. Firstly, in this study, the effectiveness (with regard to the functioning and participation of patients) of primary care for patients with CMP will be assessed, comparing care organized following the NPRL2.0 procedure with usual care. Secondly, the cost-effectiveness and cost-utility with regard to health-related quality of life and healthcare costs will be assessed. And thirdly, the effect of duration of participation in a local network in primary care will be studied.

Methods
In this pragmatic study, it is expected that two local networks with 105 patients will participate in the prospective cohort study and six local networks with 184 patients in the stepped-wedge based design. Healthcare professionals in the local networks will recruit patients. Inclusion criteria: age ≥ 18 years; having CMP; willing to improve functioning despite pain; and adequate Dutch literacy. Exclusion criteria: pregnancy; and having a treatable medical or psychiatric disease. Patients will complete questionnaires at baseline (T1), 3 months (T2), 6 months (T3), and 9 months (T4). Questionnaires at T1 and T4 will include the Pain Disability Index and Short Form Health Survey. Questionnaires at T1, T2, T3, and T4 will include the EQ-5D-5L, and iMTA Medical Consumption and Productivity Cost Questionnaires. Outcomes will be compared using linear mixed-model analysis and costs will be compared using bootstrapping methods.

Discussion
NPRL2.0 is a multidimensional, complex intervention, executed in daily practice, and therefore needing a pragmatic study design. The current study will assess NPRL2.0 with respect to the Quadruple Aim outcomes: patient health and costs. This will provide more information on the (cost-) effectiveness of the organization of care in a network structure regarding patients with CMP. The other two Quadruple Aim outcomes will be examined alongside this study.

Trial registration Netherlands Trial Register: NL7643. https://www.trialregister.nl/trial/7643.
Neurological consequences of COVID-19: what have we learned and where do we go from here?
Authors: Jarrahi Abbas , Ahluwalia Meenakshi , Khodadadi Hesam , da Silva Lopes Salles Evila , Kolhe Ravindra , Hess David C. , Vale Fernando , Kumar Manish , Baban Babak , Vaibhav Kumar , Dhandapani Krishnan M. 
Published: September 2020

AbstractThe coronavirus disease-19 (COVID-19) pandemic is an unprecedented worldwide health crisis. COVID-19 is caused by SARS-CoV-2, a highly infectious pathogen that is genetically similar to SARS-CoV. Similar to other recent coronavirus outbreaks, including SARS and MERS, SARS-CoV-2 infected patients typically present with fever, dry cough, fatigue, and lower respiratory system dysfunction, including high rates of pneumonia and acute respiratory distress syndrome (ARDS); however, a rapidly accumulating set of clinical studies revealed atypical symptoms of COVID-19 that involve neurological signs, including headaches, anosmia, nausea, dysgeusia, damage to respiratory centers, and cerebral infarction. These unexpected findings may provide important clues regarding the pathological sequela of SARS-CoV-2 infection. Moreover, no efficacious therapies or vaccines are currently available, complicating the clinical management of COVID-19 patients and emphasizing the public health need for controlled, hypothesis-driven experimental studies to provide a framework for therapeutic development. In this mini-review, we summarize the current body of literature regarding the central nervous system (CNS) effects of SARS-CoV-2 and discuss several potential targets for therapeutic development to reduce neurological consequences in COVID-19 patients.
A scoping review of school-based indigenous substance use prevention in preteens (7–13 years)
Authors: Maina Geoffrey , Mclean Maeve , Mcharo Solomon , Kennedy Megan , Djiometio Joseph , King Alexandra 
Published: October 2020

AbstractBackgroundEarly-onset substance use is a risk factor for continued use, dependency, and poor long-term health outcomes. Indigenous youth are more likely to engage in early-onset substance use than their non-Indigenous counterparts. In Canada, culturally appropriate prevention programs are needed for Indigenous youth in elementary schools. Therefore, this scoping review aims to explore the published, international literature examining school-based substance use prevention programs for Indigenous children aged 7–13.Main textMethods:This scoping review followed a six-step approach: 1) identifying the research questions, 2) identifying relevant studies, 3) selecting the studies, 4) charting the data, 5) collating, summarizing, and reporting the results, and 6) consulting with experts. The review was reported using guidelines from Preferred Reporting Items for Systematic reviews and Meta-Analyses extensions for Scoping Reviews (PRISMA-ScR).Results:Eleven articles (3 Canadian; 7 American and; 1 Australian) were included in the review. The prevention programs they studied were based on existing research or were adapted from existing interventions. The programs were tailored to each communities’ culture by including Indigenous stakeholders in developing or adapting prevention programs to be culturally safe and responsive. The articles evaluated the programs’ Effectiveness in changing student knowledge, attitudes, and behaviors using pre- and post-intervention surveys, randomized control trials, longitudinally designed analysis, and mixed methods. Mixed quantitative findings and qualitative findings highlighted the programs’ value in building community capacity and fostering cultural revitalization.ConclusionThis review highlights best practices for developing school-based substance use prevention programs for Indigenous youth. Findings suggest that prevention programs should be culturally responsive and provide students with the knowledge and skills to prevent and manage substance use in real-life situations. Making Indigenous beliefs, values, languages, images, and worldviews central to the prevention curriculum enhanced the Effectiveness, appropriateness, and sustainability of prevention programs. Indigenous communities are best positioned to facilitate cultural tailoring without compromising the fidelity of evidence-based prevention programs.
Endovascular strategies for post-dissection aortic aneurysm (PDAA)
Authors: Zeng Zhaoxiang , Zhao Yuxi , Wu Mingwei , Bao Xianhao , Li Tao , Feng Jiaxuan , Feng Rui , Jing Zaiping 
Published: October 2020

AbstractResidual patent false lumen (FL) after type B aortic dissection (TBAD) repair is independently associated with poor long-term survival. Open surgery and endovascular repair result in good clinical outcomes in patients with AD. However, both treatments focus on proximal dissection but not distal dissection. About 13.4–62.5% of these patients present with different degrees of distal aneurysmal dilatation after primary repair. Although open surgery is the first-choice treatment for post-dissection aortic aneurysm (PDAA), there is a need for high technical demand since open surgery is associated with high mortality and morbidity. As a treatment strategy with minimal invasion, endovascular repair shows early benefits and low morbidity. For PDAA, the narrow true lumen (TL), rigid initial flap and branch arteries originating from FL have increased difficulties in operation. The aim of endovascular treatment is to promote FL thrombosis and aortic remodeling. Endovascular repair includes intervention from FL and TL sides. TL intervention techniques (parallel stent-graft, branched and fenestrated stent-graft among others) have been proven to be safe and effective in PDAA. Other FL intervention techniques that have been used in selected patients include FL embolization and candy-plug techniques. This article introduces available endovascular techniques and their outcomes for the treatment of PDAA.
Safety of vaccines administration in hereditary fructose intolerance
Authors: Maiorana Arianna , Sabia Antonella , Corsetti Tiziana , Dionisi-Vici Carlo 
Published: October 2020

AbstractPatients with hereditary fructose intolerance need to follow a life-long fructose dietary and drug restriction to prevent symptoms of intoxication. Concerns about vaccines administration have been manifested overtime, for the risk of a life-threatening acute intoxication. For this reason, at Ospedale Pediatrico Bambino Gesù we performed a deepen research from open sources, datasheets and Pharmaceutical Companies informations from the most common Italian and European vaccines, which are carried out in infancy and childhood. As a safe threshold of 2.4 mg/kg/dose was recently established for oral and parenteral (other than i.v.) route, the manuscript clarifies the safe administration of majority of vaccines in patients with hereditary fructose intolerance.
The role of microenvironment in tumor angiogenesis
Authors: Jiang Xianjie , Wang Jie , Deng Xiangying , Xiong Fang , Zhang Shanshan , Gong Zhaojian , Li Xiayu , Cao Ke , Deng Hao , He Yi , Liao Qianjin , Xiang Bo , Zhou Ming , Guo Can , Zeng Zhaoyang , Li Guiyuan , Li Xiaoling , Xiong Wei 
Published: September 2020

AbstractTumor angiogenesis is necessary for the continued survival and development of tumor cells, and plays an important role in their growth, invasion, and metastasis. The tumor microenvironment—composed of tumor cells, surrounding cells, and secreted cytokines—provides a conducive environment for the growth and survival of tumors. Different components of the tumor microenvironment can regulate tumor development. In this review, we have discussed the regulatory role of the microenvironment in tumor angiogenesis. High expression of angiogenic factors and inflammatory cytokines in the tumor microenvironment, as well as hypoxia, are presumed to be the reasons for poor therapeutic efficacy of current anti-angiogenic drugs. A combination of anti-angiogenic drugs and antitumor inflammatory drugs or hypoxia inhibitors might improve the therapeutic outcome.