bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the next generation of RSV intervention strategies: a mathematical modelling study and cost-effectiveness analysis
Authors: Hodgson David , Pebody Richard , Panovska-Griffiths Jasmina , Baguelin Marc , Atkins Katherine E. 
Published: November 2020

Abstract
Background
With a suite of promising new RSV prophylactics on the horizon, including long-acting monoclonal antibodies and new vaccines, it is likely that one or more of these will replace the current monoclonal Palivizumab programme. However, choosing the optimal intervention programme will require balancing the costs of the programmes with the health benefits accrued.

Methods
To compare the next generation of RSV prophylactics, we integrated a novel transmission model with an economic analysis. We estimated key epidemiological parameters by calibrating the model to 7 years of historical epidemiological data using a Bayesian approach. We determined the cost-effective and affordable maximum purchase price for a comprehensive suite of intervention programmes.

Findings
Our transmission model suggests that maternal protection of infants is seasonal, with 38–62% of infants born with protection against RSV. Our economic analysis found that to cost-effectively and affordably replace the current monoclonal antibody Palivizumab programme with long-acting monoclonal antibodies, the purchase price per dose would have to be less than around £4350 but dropping to £200 for vaccinated heightened risk infants or £90 for all infants. A seasonal maternal vaccine would have to be priced less than £85 to be cost-effective and affordable. While vaccinating pre-school and school-age children is likely not cost-effective relative to elderly vaccination programmes, vaccinating the elderly is not likely to be affordable. Conversely, vaccinating infants at 2 months seasonally would be cost-effective and affordable if priced less than £80.

Conclusions
In a setting with seasonal RSV epidemiology, maternal protection conferred to newborns is also seasonal, an assumption not previously incorporated in transmission models of RSV. For a country with seasonal RSV dynamics like England, seasonal programmes rather than year-round intervention programmes are always optimal.
Evaluation of an autologous cancer vaccine for the treatment of metastatic canine hemangiosarcoma: a preliminary study
Authors: Lucroy Michael D. , Clauson Ryan M. , Suckow Mark A. , El-Tayyeb Ferris , Kalinauskas Ashley 
Published: November 2020

Abstract
Background
Canine hemangiosarcoma (HSA) is an aggressive cancer arising from multipotential bone marrow-derived stem cells. Anthracycline chemotherapy drugs have been the mainstay adjuvant chemotherapy following surgery with only modest improvement in survival and an attendant risk for adverse events. Immunotherapy, using a whole cell autologous cancer vaccine adjuvanted with MIM-SIS, may improve outcomes for dogs with HSA with a lower risk for adverse events compared with chemotherapy.

Results
In cultured DH82 canine monocyte-like cells, autologous cancer vaccines prepared from 13 dogs with HSA increased MHC-II surface expression ranging from 20.0-60.4% on single-stained cells, CD80 surface expression ranging from 23.7–45.9% on single-stained cells, and MHC-II/CD80 surface expression ranging from 7.2–20.1% on double-stained cells. Autologous cancer vaccines were able to, on average, stimulate an up-regulation of MHC-II and CD80 by 48-fold as compared to media only (MHC-II + CD80 + cells: 12.19 ± 3.70% vs. 0.25 ± 0.06%; p < 0.001). The overall median survival time for dogs treated with the autologous cancer vaccine was 142 days (range, 61 to 373 days). Dogs treated with the autologous cancer vaccine or maximum tolerated dose (MTD) chemotherapy had significantly (P < 0.001) longer survival than dogs treated with surgery alone. The 1-year survival rate was 12.5% for dogs treated with the autologous cancer vaccine, and 0% for dogs treated with surgery alone or MTD chemotherapy. No adverse events were observed in the dogs treated with the autologous cancer vaccine.

Conclusions
The adjuvanted autologous cancer vaccine is capable of up-regulating MHC-II and CD80 in cultured canine monocyte-derived cells, which are important stimulatory molecules in generating an immune response and improves survival time in dogs with metastatic (stage III) HSA when compared to surgical treatment alone. Autologous cancer vaccine-treated dogs had survival similar to those dogs treated with MTD chemotherapy without any observed adverse events. This autologous cancer vaccine represents an effective form of individualized immunotherapy that is an appealing option for dog owners not wanting to pursue adjuvant chemotherapy for HSA.
Comparative analysis of adeno-associated virus serotypes for gene transfer in organotypic heart slices
Authors: Liu Zihou , Klose Kristin , Neuber Sebastian , Jiang Meng , Gossen Manfred , Stamm Christof 
Published: November 2020

Abstract
Background
Vectors derived from adeno-associated viruses (AAVs) are widely used for gene transfer both in vitro and in vivo and have gained increasing interest as shuttle systems to deliver therapeutic genes to the heart. However, there is little information on their tissue penetration and cytotoxicity, as well as the optimal AAV serotype for transferring genes to diseased hearts. Therefore, we aimed to establish an organotypic heart slice culture system for mouse left ventricular (LV) myocardium and use this platform to analyze gene transfer efficiency, cell tropism, and toxicity of different AAV serotypes.

Methods
LV tissue slices, 300 µm thick, were prepared from 15- to 17-day-old transgenic alpha-myosin heavy-chain-mCherry mice using a vibrating microtome. Tissue slice viability in air-liquid culture was evaluated by calcein-acetoxymethyl ester staining, mCherry fluorescence intensity, and the tetrazolium assay. Four recombinant AAV serotypes (1, 2, 6, 8) expressing green fluorescent protein (GFP) under the CAG promoter were added to the slice surface. Gene transfer efficiency was quantified as the number of GFP-positive cells per slice. AAV cell tropism was examined by comparing the number of GFP-positive cardiomyocytes (CMs) and fibroblasts within heart slices.

Results
Slices retained viability in in vitro culture for at least 5 days. After adding AAV particles, AAV6-infected slices showed the highest number of GFP-expressing cells, almost exclusively CMs. Slice incubation with AAV1, 2, and 8 resulted in fewer GFP-positive cells, with AAV2 having the lowest gene transfer efficiency. None of the AAV serotypes tested caused significant cytotoxicity when compared to non-infected control slices.

Conclusions
We have established a readily available mouse organotypic heart slice culture model and provided evidence that AAV6 may be a promising gene therapy vector for heart failure and other cardiac diseases.
Tandem Mass Tag-based quantitative proteomics analysis of metabolic associated fatty liver disease induced by high fat diet in mice
Authors: Li Hu , Huang Wei , Wang Mingjie , Chen Peizhan , Chen Li , Zhang Xinxin 
Published: November 2020

Abstract
Background
Although metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide, the exact molecular mechanism of MAFLD progression remains unknown. In the present study, Tandem Mass Tag-labeled quantitative proteomic technology was used to elucidate the protein expression patterns of liver tissues in the progression of MAFLD, providing new potential therapeutic targets of it.

Methods
Five 6-week-old male C57BL/6 mice were fed with high fat diet (HFD) for 22 weeks to establish the MAFLD mouse models. Five C57BL/6 mice of the same age were fed with normal diet (ND) and taken as controls. Mice serum were sampled for biochemical tests, and livers were isolated for histopathological examinations. Six mouse liver samples (three from each group) were performed for proteomic analysis. Differentially expressed proteins were defined using fold change of > 1.5 or < 0.67 and p value < 0.05 as thresholds. Bioinformatic analysis was used to identify the hub proteins. Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), Gene Expression Omnibus dataset, western blotting and immunohistochemistry were used to validate the expression of identified hub proteins.

Results
After 22 weeks on HFD diet, all mice developed MAFLD demonstrated by histopathological examination. Mouse body weights, liver weights, serum alanine transaminase and aspartate transaminase levels were significantly higher in the HFD group than ND group. Proteomics technology identified 4915 proteins in the mouse livers, among which 71 proteins were differentially expressed. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that majority of the differentially expressed proteins were involved in the peroxisome and peroxisome proliferator-activated receptor signaling pathway, as well as biosynthesis of unsaturated fatty acids. Protein–protein interaction analysis showed that these differentially expressed proteins interacted with each other and formed a complex network. Ten hub proteins were identified and validated using RT-qPCR. Five of these proteins were validated in the Gene Expression Omnibus dataset. Finally, Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase protein was validated in mouse liver tissue samples using western blotting and immunohistochemistry.

Conclusion
Our data showed that lipid metabolism-related pathways are closely associated with the development of MAFLD. The identified hub proteins might be novel targets for treating MAFLD.
Approaches to cervical spine mobilization for neck pain: a pilot randomized controlled trial
Authors: Lagoutaris Claire , Sullivan Justin , Hancock Michelle , Leaver Andrew M. 
Published: November 2020

Abstract
Study design
Pilot randomized controlled trial.

Background
Better understanding of the relative effectiveness of different approaches to cervical spine mobilization has been identified as a research priority in manual therapy practice. Two distinct approaches to the practice of mobilization have emerged in recent years, based on different reasoning models for selection of mobilization techniques. The objective of this pilot study was to assess feasibility aspects for a future randomized clinical trial by exploring short-term pain and disability outcomes after a single treatment with pragmatic versus prescriptive approaches to cervical mobilization for people with recent-onset neck pain at 48-h follow-up after randomization.

Methods
Twenty adults with a new episode of mechanical neck pain were randomly allocated to either pragmatic or prescriptive mobilization intervention groups. The pragmatic group received a single treatment of cervical mobilization with the technique, target segment, and grade selected by their treating therapist. The prescriptive group received a single treatment of standardized mobilization with techniques similar to a previous mobilization clinical trial. Feasibility outcomes were recruitment rates, randomization audit and completion of treatment and follow-up per protocol. The primary clinical outcome of interest was disability level measured at 48-h follow-up after randomization.

Results
Recruitment rates were approximately 2.5 participants per week and 100% of eligible participants were deemed suitable for treatment with cervical mobilization. There was sufficient variety in the range of pragmatic treatments selected and the data collection process imposed minimal burden on participants.

Conclusions
Our results provide supporting evidence for the feasibility of a future larger scale randomized clinical trial.

Trial registration
Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12616000446460). Registered 6th April 2016. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370448&isReview=true
The impact of twenty-first century personalized medicine versus twenty-first century medicine’s impact on personalization
Authors: Abettan Camille , Welie Jos V. M. 
Published: November 2020

AbstractBackgroundOver the past decade, the exponential growth of the literature devoted to personalized medicine has been paralleled by an ever louder chorus of epistemic and ethical criticisms. Their differences notwithstanding, both advocates and critics share an outdated philosophical understanding of the concept of personhood and hence tend to assume too simplistic an understanding of personalization in health care.MethodsIn this article, we question this philosophical understanding of personhood and personalization, as these concepts shape the field of personalized medicine. We establish a dialogue with phenomenology and hermeneutics (especially with E. Husserl, M. Merleau-Ponty and P. Ricoeur) in order to achieve a more sophisticated understanding of the meaning of these concepts We particularly focus on the relationship between personal subjectivity and objective data.ResultsWe first explore the gap between the ideal of personalized healthcare and the reality of today’s personalized medicine. We show that the nearly exclusive focus of personalized medicine on the objective part of personhood leads to a flawed ethical debate that needs to be reframed. Second, we seek to contribute to this reframing by drawing on the phenomenological-hermeneutical movement in philosophy. Third, we show that these admittedly theoretical analyses open up new conceptual possibilities to tackle the very practical ethical challenges that personalized medicine faces.ConclusionFinally, we propose a reversal: if personalization is a continuous process by which the person reappropriates all manner of objective data, giving them meaning and thereby shaping his or her own way of being human, then personalized medicine, rather than being personalized itself, can facilitate personalization of those it serves through the data it provides.
Clinical features of a Chinese female nongestational choriocarcinoma cohort: a retrospective study of 37 patients
Authors: Shao Yuming , Xiang Yang , Jiang Fang , Pan Boju , Wan Xirun , Yang Junjun , Feng Fengzhi , Ren Tong , Zhao Jun 
Published: November 2020

Abstract
Background
Choriocarcinoma is a rare malignant neoplasm, which is classified as either gestational choriocarcinoma or nongestational choriocarcinoma. The purpose of this study was to examine the clinical characteristics of Chinese female nongestational choriocarcinoma patients and discuss our experience in treating this rare disease.

Results
We conducted a single-center retrospective study on a sample of 37 nongestational choriocarcinoma patients who were diagnosed and treated at Peking Union Medical College Hospital from March 1982 to March 2020. Their demographic, clinical, laboratory, and therapeutic data were collected. Detailed information was available for all 37 individuals in our sample. The primary lesions included 34 in the ovaries, 2 in the pituitary and 1 in the stomach. The median age of onset was 22 years, and the median follow-up period spanned 41 months. The lungs (40.5%) were the most commonly observed metastatic site. All subjects were treated with surgery and multidrug chemotherapies, and a median of 4.0 courses was required to achieve complete remission. The overall complete response rate, relapse rate, and 3-year and 5-year survival rates were 81.1%, 16.7%, 80.0%, and 75.5%, respectively.

Conclusions
Nongestational choriocarcinoma can be managed well using surgery and multidrug chemotherapies, but the overall outcome of nongestational choriocarcinoma is still worse than that of gestational choriocarcinoma. Mixed nongestational choriocarcinoma seems to have similar therapeutic outcomes as pure tumors.
The role of the surgical resection distance from the pylorus after laparoscopic sleeve gastrectomy: a prospective cohort study from an academic medical center in Egypt
Authors: Hussein Ahmed H. , Khaled Islam , Faisal Mohammed 
Published: November 2020

Abstract
Background
Laparoscopic sleeve gastrectomy was recently described as an effective approach for the operative treatment of obesity, but the ideal procedure remains controversial. One of the most debated issues is the resection distance from the pylorus. We conducted this study to elucidate any potential differences in the short-term outcomes between 2 and 6 cm distance from the pylorus in laparoscopic sleeve gastrectomy.

Methods
A prospective observational cohort study in a selected cohort of 96 patients was conducted from January 2018 to March 2019 in morbidly obese patients who had laparoscopic sleeve gastrectomy performed at Suez Canal University Hospital. Outcome was expressed by excess weight loss percentage, resolution of comorbidities, improvement of quality of life, and incidence of complications after laparoscopic sleeve gastrectomy. The morbidly obese patients (body mass index [BMI] > 40 kg/m2 or > 35 kg/m2 with obesity-related comorbidities) in the study were divided into two equal groups: (1) Group 1 (48 patients) underwent laparoscopic sleeve gastrectomy with a 2 cm distance from the pylorus resection distance and (2) Group 2 (48 patients) underwent laparoscopic sleeve gastrectomy with a 6 cm distance from the pylorus resection distance. Body weight, BMI, bariatric quality of life, lipid profile, and comorbidities were evaluated pre- and post-operatively for a duration of 12 months.

Results
Statistically, no significant differences between the two study groups regarding the excess weight loss percentage, comorbidity resolution throughout the postoperative follow-up, enhancement of the quality of life score throughout the postoperative follow-up, or incidence of complications (25% in Group 1 versus 25% in Group 2, p > 0.05) were found.

Conclusion
Laparoscopic sleeve gastrectomy was an effective and safe management for morbid obesity and obesity-related comorbidities with significant short-term weight loss; it also improved weight-related quality of life and had an acceptable complication rate. The distance from the pylorus resection distance did not affect the short-term effects of laparoscopic sleeve gastrectomy regarding excess weight loss percentage, resolution of comorbidities, change in quality of life, or occurrence of complications.
The impact of mass drug administration on Schistosoma haematobium infection: what is required to achieve morbidity control and elimination?
Authors: Kura Klodeta , Hardwick Robert J. , Truscott James E. , Toor Jaspreet , Hollingsworth T. Deirdre , Anderson Roy M. 
Published: November 2020

Abstract
Background
Schistosomiasis remains an endemic parasitic disease causing much morbidity and, in some cases, mortality. The World Health Organization (WHO) has outlined strategies and goals to combat the burden of disease caused by schistosomiasis. The first goal is morbidity control, which is defined by achieving less than 5% prevalence of heavy intensity infection in school-aged children (SAC). The second goal is elimination as a public health problem (EPHP), achieved when the prevalence of heavy intensity infection in SAC is reduced to less than 1%.
Mass drug administration (MDA) of praziquantel is the main strategy for control. However, there is limited availability of praziquantel, particularly in Africa where there is high prevalence of infection. It is therefore important to explore whether the WHO goals can be achieved using the current guidelines for treatment based on targeting SAC and, in some cases, adults.
Previous modelling work has largely focused on Schistosoma mansoni, which in advance cases can cause liver and spleen enlargement. There has been much less modelling of the transmission of Schistosoma haematobium, which in severe cases can cause kidney damage and bladder cancer. This lack of modelling has largely been driven by limited data availability and challenges in interpreting these data.

Results
In this paper, using an individual-based stochastic model and age-intensity profiles of S. haematobium from two different communities, we calculate the probability of achieving the morbidity and EPHP goals within 15 years of treatment under the current WHO treatment guidelines. We find that targeting SAC only can achieve the morbidity goal for all transmission settings, regardless of the burden of infection in adults. The EPHP goal can be achieved in low transmission settings, but in some moderate to high settings community-wide treatment is needed.

Conclusions
We show that the key determinants of achieving the WHO goals are the precise form of the age-intensity of infection profile and the baseline SAC prevalence. Additionally, we find that the higher the burden of infection in adults, the higher the chances that adults need to be included in the treatment programme to achieve EPHP.

Graphical Abstract
Variation in IgE binding potencies of seven Artemisia species depending on content of major allergens
Authors: Zhao Lan , Fu Wanyi , Gao Biyuan , Liu Yi , Wu Shandong , Chen Zhi , Zhang Xianqi , Wang Huiying , Feng Yan , Wang Xueyan , Wang Hongtian , Lan Tianfei , Liu Meiling , Wang Xuefeng , Sun Yuemei , Luo Fangmei , Gadermaier Gabriele , Ferreira Fatima , Versteeg Serge A. , Akkerdaas Jaap H. , Wang Deyun , Valenta Rudolf , Vrtala Susanne , Gao Zhongshan , van Ree Ronald 
Published: November 2020

Abstract
Background
Artemisia weed pollen allergy is important in the northern hemisphere. While over 350 species of this genus have been recorded, there has been no full investigation into whether different species may affect the allergen diagnosis and treatment. This study aimed to evaluate the variations in amino acid sequences and the content of major allergens, and how these affect specific IgE binding capacity in representative Artemisia species.

Methods
Six representative Artemisia species from China and Artemisia vulgaris from Europe were used to determine allergen amino acid sequences by transcriptome, gene sequencing and mass spectrometry of the purified allergen component proteins. Sandwich ELISAs were developed and applied for Art v 1, Art v 2 and Art v 3 allergen quantification in different species. Aqueous pollen extracts and purified allergen components were used to assess IgE binding by ELISA and ImmunoCAP with mugwort allergic patient serum pools and individual sera from five areas in China.

Results
The Art v 1 and Art v 2 homologous allergen sequences in the seven Artemisia species were highly conserved. Art v 3 type allergens in A. annua and A. sieversiana were more divergent compared to A. argyi and A. vulgaris. The allergen content of Art v 1 group in the seven extracts ranged from 3.4% to 7.1%, that of Art v 2 from 1.0% to 3.6%, and Art v 3 from 0.3% to 10.5%. The highest IgE binding potency for most Chinese Artemisia allergy patients was with A. annua pollen extract, followed by A. vulgaris and A. argyi, with A. sieversiana significantly lower. Natural Art v 1-3 isoallergens from different species have almost equivalent IgE binding capacity in Artemisia allergic patients from China.

Conclusion and clinical relevance
There was high sequence similarity but different content of the three group allergens from different Artemisia species. Choice of Artemisia annua and A. argyi pollen source for diagnosis and immunotherapy is recommended in China.