bluuebunny/crossref_metadata_2025_split huggingface dataset:
A canine case of malignant melanoma carrying a KIT c.1725_1733del mutation treated with toceranib: a case report and in vitro analysis
Authors: Tani Hiroyuki , Miyamoto Ryo , Noguchi Syunya , Kurita Sena , Nagashima Tomokazu , Michishita Masaki , Yayoshi Naoko , Tamura Kyoichi , Bonkobara Makoto 
Published: April 2021

Abstract
Background
Canine malignant melanoma is highly aggressive and generally chemoresistant. Toceranib is a kinase inhibitor drug that inhibits several tyrosine kinases including the proto-oncogene receptor tyrosine kinase KIT. Although canine malignant melanoma cells often express KIT, a therapeutic effect for toceranib has yet to be reported for this tumor, with only a small number of patients studied to date. This is a case report of a dog with malignant melanoma that experienced a transient response to toceranib. Furthermore, the KIT expressed in the tumor of this case was examined using molecular analysis.

Case presentation
A Shiba Inu dog presented with a gingival malignant melanoma extending into surrounding structures with metastasis to a submandibular lymph node. The dog was treated with toceranib (Palladia®; 2.6–2.9 mg/kg, orally, every other day) alone. Improvement of tumor-associated clinical signs (e.g., halitosis, tumor hemorrhage, trismus, and facial edema) with reduced size of the metastatic lymph node was observed on Day 15. The gingival tumor and associated masses in the masseter and pterygoid muscles decreased in size by Day 29 of treatment. Toceranib treatment was terminated on Day 43 due to disease progression and the dog died on Day 54. The tumor of this dog had a novel deletion mutation c.1725_1733del within KIT and the mutation caused ligand-independent phosphorylation of KIT, which was suppressed by toceranib. This mutation was considered to be an oncogenic driver mutation in the tumor of this dog, thereby explaining the anti-tumor activity of toceranib.

Conclusions
This is the first report that presents a canine case of malignant melanoma that responded to toceranib therapy. KIT encoded by KIT harboring a mutation c.1725_1733del is a potential therapeutic target for toceranib in canine malignant melanoma. Further investigation of the KIT mutation status and toceranib therapy in canine malignant melanoma will need to be undertaken.
Lung transplantation for late-onset non-infectious chronic pulmonary complications of allogenic hematopoietic stem cell transplant
Authors: Riddell Peter , Vasudevan-Nampoothiri Ram , Ma Jin , Singer Lianne G. , Lipton Jeff H. , Juvet Stephen C. 
Published: April 2021

Abstract
Background
Late onset non-infectious pulmonary complications (LONIPCs) following allogenic hematopoietic stem cell transplantation (allo-HSCT) confer a significant mortality risk. Lung transplantation (LTx) has the potential to provide survival benefit but the impact of prior allo-HSCT on post-LTx outcomes is not well studied.

Methods
This retrospective, single-centre cohort study assessed the post-LTx outcomes of adults with LONIPCs of allo-HSCT. Outcomes of LTx for LONIPCs were compared to propensity-score matched LTx controls (n = 38, non-HSCT) and recipients of re-LTx (n = 70) for chronic lung allograft dysfunction (CLAD).

Results
Nineteen patients underwent DLTx for LONIPCs of allo-HSCT between 2003 and 2019. Post-LTx survival was 50% at 5-years. Survival to 1-year post-LTx was similar to matched controls (p = 0.473). Survival, conditional on 1-year survival, was lower in the allo-HSCT cohort (p = 0.034). An increased risk of death due to infection was identified in the allo-HSCT cohort compared to matched controls (p = 0.003). Compared to re-LTx recipients, the allo-HSCT cohort had superior survival to 1-year post-LTx (p = 0.034) but conditional 1-year survival was similar (p = 0.145).

Conclusion
This study identifies an increased risk of post-LTx mortality in recipients with previous allo-HSCT, associated with infection. It supports the hypothesis that allo-HSCT LTx recipients are relatively more immunosuppressed than patients undergoing LTx for other indications. Optimisation of post-LTx immunosuppressive and antimicrobial strategies to account for this finding should be considered.
Whole cell-based catalyst for enzymatic production of the osmolyte 2-O-α-glucosylglycerol
Authors: Schwaiger Katharina N. , Cserjan-Puschmann Monika , Striedner Gerald , Nidetzky Bernd 
Published: April 2021

Abstract
Background
Glucosylglycerol (2-O-α-d-glucosyl-sn-glycerol; GG) is a natural osmolyte from bacteria and plants. It has promising applications as cosmetic and food-and-feed ingredient. Due to its natural scarcity, GG must be prepared through dedicated synthesis, and an industrial bioprocess for GG production has been implemented. This process uses sucrose phosphorylase (SucP)-catalyzed glycosylation of glycerol from sucrose, applying the isolated enzyme in immobilized form. A whole cell-based enzyme formulation might constitute an advanced catalyst for GG production. Here, recombinant production in Escherichia coli BL21(DE3) was compared systematically for the SucPs from Leuconostoc mesenteroides (LmSucP) and Bifidobacterium adolescentis (BaSucP) with the purpose of whole cell catalyst development.

Results
Expression from pQE30 and pET21 plasmids in E. coli BL21(DE3) gave recombinant protein at 40–50% share of total intracellular protein, with the monomeric LmSucP mostly soluble (≥ 80%) and the homodimeric BaSucP more prominently insoluble (~ 40%). The cell lysate specific activity of LmSucP was 2.8-fold (pET21; 70 ± 24 U/mg; N = 5) and 1.4-fold (pQE30; 54 ± 9 U/mg, N = 5) higher than that of BaSucP. Synthesis reactions revealed LmSucP was more regio-selective for glycerol glycosylation (~ 88%; position O2 compared to O1) than BaSucP (~ 66%), thus identifying LmSucP as the enzyme of choice for GG production. Fed-batch bioreactor cultivations at controlled low specific growth rate (µ = 0.05 h−1; 28 °C) for LmSucP production (pET21) yielded ~ 40 g cell dry mass (CDM)/L with an activity of 2.0 × 104 U/g CDM, corresponding to 39 U/mg protein. The same production from the pQE30 plasmid gave a lower yield of 6.5 × 103 U/g CDM, equivalent to 13 U/mg. A single freeze–thaw cycle exposed ~ 70% of the intracellular enzyme activity for GG production (~ 65 g/L, ~ 90% yield from sucrose), without releasing it from the cells during the reaction.

Conclusions
Compared to BaSucP, LmSucP is preferred for regio-selective GG production. Expression from pET21 and pQE30 plasmids enables high-yield bioreactor production of the enzyme as a whole cell catalyst. The freeze–thaw treated cells represent a highly active, solid formulation of the LmSucP for practical synthesis.
Historical trends and new surveillance of Plasmodium falciparum drug resistance markers in Angola
Authors: Ebel Emily R. , Reis Fátima , Petrov Dmitri A. , Beleza Sandra 
Published: April 2021

Abstract
Background
Plasmodium falciparum resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) has historically posed a major threat to malaria control throughout the world. The country of Angola officially replaced CQ with artemisinin-based combination therapy (ACT) as a first-line treatment in 2006, but malaria cases and deaths have recently been rising. Many classic resistance mutations are relevant for the efficacy of currently available drugs, making it important to continue monitoring their frequency in Angola.

Methods
Plasmodium falciparum DNA was sampled from the blood of 50 hospital patients in Cabinda, Angola from October-December of 2018. Each infection was genotyped for 13 alleles in the genes crt, mdr1, dhps, dhfr, and kelch13, which are collectively involved in resistance to six common anti-malarials. To compare frequency patterns over time, P. falciparum genotype data were also collated from studies published from across Angola in the last two decades.

Results
The two most important alleles for CQ resistance, crt 76T and mdr1 86Y, were found at respective frequencies of 71.4% and 6.5%. Historical data suggest that mdr1 N86 has been steadily replacing 86Y throughout Angola in the last decade, while the frequency of crt 76T has been more variable across studies. Over a third of new samples from Cabinda were ‘quintuple mutants’ for SP resistance in dhfr/dhps, with a sixth mutation at dhps A581G present at 9.6% frequency. The markers dhfr 51I, dhfr 108N, and dhps 437G have been nearly fixed in Angola since the early 2000s, whereas dhfr 59R may have risen to high frequency more recently. Finally, no non-synonymous polymorphisms were detected in kelch13, which is involved in artemisinin resistance in Southeast Asia.

Conclusions
Genetic markers of P. falciparum resistance to CQ are likely declining in frequency in Angola, consistent with the official discontinuation of CQ in 2006. The high frequency of multiple genetic markers of SP resistance is consistent with the continued public and private use of SP. In the future, more complete haplotype data from mdr1, dhfr, and dhps will be critical for understanding the changing efficacy of multiple anti-malarial drugs. These data can be used to support effective drug policy decisions in Angola.
Dutch patients, caregivers and healthcare professionals generate first nationwide research agenda for juvenile idiopathic arthritis
Authors: Verwoerd Anouk , Armbrust Wineke , Cowan Katherine , van den Berg Lotte , de Boer Joke , Bookelman Sanne , Britstra Marjan , Cappon Jeannette , Certan Maria , Dedding Christine , van den Haspel Karin , Muller Petra Hissink , Jongsma Karin , Lelieveld Otto , van Loosdregt Jorg , Olsder Wendy , Rocha Johanna , Schatorjé Ellen , Schouten Natasja , Swart Joost F. , Vastert Sebastiaan , Walter Margot , Schoemaker Casper G. 
Published: April 2021

Abstract
Background
Involving the end-users of scientific research (patients, carers and clinicians) in setting research priorities is important to formulate research questions that truly make a difference and are in tune with the needs of patients. We therefore aimed to generate a national research agenda for Juvenile Idiopathic Arthritis (JIA) together with patients, their caregivers and healthcare professionals through conducting a nationwide survey among these stakeholders.

Methods
The James Lind Alliance method was used, tailored with additional focus groups held to involve younger patients. First, research questions were gathered through an online and hardcopy survey. The received questions that were in scope were summarised and a literature search was performed to verify that questions were unanswered. Questions were ranked in the interim survey, and the final top 10 was chosen during a prioritisation workshop.

Results
Two hundred and seventy-eight respondents submitted 604 questions, of which 519 were in scope. Of these 604 questions, 81 were generated in the focus groups with younger children. The questions were summarised into 53 summary questions. An evidence checking process verified that all questions were unanswered. A total of 303 respondents prioritised the questions in the interim survey. Focus groups with children generated a top 5 of their most important questions. Combining this top 5 with the top 10s of patients, carers, and clinicians led to a top 21. Out of these, the top 10 research priorities were chosen during a final workshop. Research into pain and fatigue, personalised treatment strategies and aetiology were ranked high in the Top 10.

Conclusions
Through this study, the top 10 research priorities for JIA of patients, their caregivers and clinicians were identified to inform researchers and research funders of the research topics that matter most to them. The top priority involves the treatment and mechanisms behind persisting pain and fatigue when the disease is in remission.
In vitro and in vivo analyses of co-infections with peste des petits ruminants and capripox vaccine strains
Authors: Zhang Dajun , Yang Bo , Zhang Ting , Shi Xijuan , Shen Chaochao , Zheng Haixue , Liu Xiangtao , Zhang Keshan 
Published: April 2021

Abstract
Background
Peste des petits ruminants (PPR) and goat pox (GTP) are two devastating animal epidemic diseases that affect small ruminants. Vaccination is one of the most important measures to prevent and control these two severe infectious diseases.

Methods
In this study, we vaccinated sheep with PPR and POX vaccines to compare the changes in the antibody levels between animals vaccinated with PPRV and POX vaccines alone and those co-infected with both vaccines simultaneously. The cell infection model was used to explore the interference mechanism between the vaccines in vitro. The antibody levels were detected with the commercial ELISA kit. The Real-time Quantitative PCR method was employed to detect the viral load changes and cytokines expression after the infection.

Results
The concurrent immunization of GTP and PPR vaccine enhanced the PPR vaccine's immune effect but inhibited the immune effect of the GTP vaccine. After the infection, GTP and PPR vaccine strains caused cytopathic effect; co-infection with GTP and PPR vaccine strains inhibited the replication of PPR vaccine strains; co-infection with GTP and PPR vaccine strains enhanced the replication of GTP vaccine strains. Moreover, virus mixed infection enhanced the mRNA expressions of TNF-α, IL-1β, IL-6, IL-10, IFN-α, and IFN-β by 2–170 times. GTP vaccine strains infection alone can enhanced the mRNA expression of IL-1β, TNF-α, IL-6, IL-10, while the expression of IFN-α mRNA is inhibited. PPR vaccine strains alone can enhanced the mRNA expression of IFN-α, IFN-β, TNF-α, and has little effect the mRNA expression of IL-1β, IL-6 and IL-10. The results showed that GTP and PPR vaccine used simultaneously in sheep enhanced the PPR vaccine's immune effect but inhibited the immune effect of the GTP vaccine in vivo. Furthermore, an infection of GTP and PPR vaccine strains caused significant cell lesions in vitro; co-infection with GTP + PPR vaccine strains inhibited the replication of PPR vaccine strains, while the co-infection of GTP followed by PPR infection enhanced the replication of GTP vaccine strains. Moreover, virus infection enhanced the expressions of TNF-α, IL-1β, IL-6, IL-10, IFN-α, and IFN-β.

Conclusions
Peste des petits ruminants and capripox vaccine strains interfere with each other in vivo and vitro.
Pineapple consumption reduced cardiac oxidative stress and inflammation in high cholesterol diet-fed rats
Authors: Seenak Porrnthanate , Kumphune Sarawut , Malakul Wachirawadee , Chotima Ratanon , Nernpermpisooth Nitirut 
Published: April 2021

Abstract
Background
Hypercholesterolemia is a major risk factor for cardiovascular disease. It has been reported that pineapple contains healthy nutrients and phytochemicals associated with antioxidant and anti-inflammatory capacities. No investigation exists concerning the effect of pineapple consumption modulating hypercholesterolemia-induced cardiac damage in high-cholesterol diet (HCD)-fed rats. This study evaluated the effect of pineapple consumption on lipid-lowering, cardiac oxidative stress and inflammation in HCD-fed rats.

Methods
Male Sprague–Dawley rats were fed with HCD, in the presence and absence of Pineapple (Ananas comosus L.) cv. Pattavia powder for 8 weeks. Then, serum lipid profiles, liver and renal function tests, cardiac oxidative stress and pro-inflammatory cytokines were determined.

Results
Daily pineapple consumption reduced weight gain, serum lipid profiles, atherogenic coefficient (AC), cardiac risk ratio (CRR), and liver enzyme activity, without causing renal dysfunction. Pineapple consumption also restores cardiac protein carbonyl (cPC) content, reduces cardiac malondialdehyde (MDA), cardiac pro-inflammation cytokine IL-6 and IL-1β levels.

Conclusion
Pineapple possesses antioxidant and lipid-lowering properties and daily consumption alleviates hypercholesterolemia-induced cardiac lipid peroxidation and pro-inflammation elevation in an in vivo model. This study demonstrates that pineapple is a potential candidate for cardioprotection against hypercholesterolemia.
Perceived stress among university students in south-east Serbia during the COVID-19 outbreak
Authors: Kostić Jelena , Žikić Olivera , Đorđević Vladimir , Krivokapić Žilijeta 
Published: April 2021

Abstract
Background
The COVID-19 pandemic has brought into focus the mental health of the student population. The study aimed to analyze the psychological response to the COVID-19 outbreak in terms of perceived stress and its related factors among university students in south-east Serbia. The study was conducted during the increased incidence of COVID-19 in Serbia.

Method
A total of 434 students from the public university in south-east Serbia enrolled in the study and completed the measures of socio-demographic data, the perceived stress scale (PSS-10), the Coping Strategy Indicator (CSI) and the General Health Questionnaire (GHQ-28). The data were analyzed through quantitative and qualitative methods.

Results
Study findings suggest that the mean perceived stress score was placed to 20.43 (± 7.67). Our model showed that female gender, higher scores on anxiety/insomnia and depression subscale as well as the coping strategy avoidance predicted higher perceived stress, while higher scores on social dysfunction were related to the reduced perceived stress scores.

Conclusion
Notwithstanding the study limitation, findings provided authentic data of stress reactions of the students in south-east Serbia during the COVID-19 outbreak. The findings confirm the need to examine students' experiences in emergencies and crises, as well as to make a plan for online stress management programs that would help alleviate stress during a global pandemic.
Quality blues: traditional knowledge used for natural indigo identification in southern China
Authors: Shi Yuru , Zhang Libin , Wang Lu , Li Shan , Qiu Zuchuan , Ding Xiaoyong , Wang Yuhua 
Published: April 2021

Abstract
Background
As one of the oldest traditional dyes, people worldwide have used natural indigo for centuries. Local people have unique knowledge about indigo identification, which is crucial for indigo quality control and determining the dyeing effects. However, such traditional knowledge is rarely documented and explained. Therefore, the aims of this study were to document and assess the traditional knowledge used by local people when identifying natural indigo paste as well as quantitatively explore the characteristics and material basis of such traditional knowledge.

Method
Three field surveys were conducted between 2019 and 2020. A total of 283 traditional indigo-paste artisans were interviewed in Guizhou, Yunnan, and Fujian Provinces. The frequency of citation, mention index, and fidelity level of each indigo-paste quality criterion were calculated to determine the most commonly used, recognized, and important quality criteria. To explore the characteristics and material basis of the traditional knowledge, we analyzed 21 indigo-paste samples using high-performance liquid chromatography with diode-array detection (HPLC-DAD), pH, and particle size analyses.

Results
Local people possess unique knowledge to identify natural indigo. Based on this knowledge accumulated over thousands of years, four criteria (color, taste, touch, and dyeing ability) were chosen by local people, and using these criteria, nature indigo was divided into five quality grades. The best quality indigo paste was judged according to the following folk criteria: dark blue in color with a purple-red luster; smooth and difficult to wipe off; having a sweet, bitter or spicy taste; and easy cloth dyeing. Additionally, the higher the contents of indigo and indirubin—especially indirubin—the better is the quality of the indigo paste. Within the pH range of 9–12, high-quality indigo-paste was more acidic. There was no significant relationship between particle size and quality.

Conclusion
The ancient methods used by local people for identifying natural indigo are comprehensive and unique. By documenting the various folk quality criteria and conducting quantitative analyses, this study revealed the importance of indirubin and pH for assessing the quality of indigo paste. These findings differ from existing quality standards for synthetic indigo. Amid rapid modernization, traditional knowledge remains invaluable as a world heritage of humanity that warrants preservation.
The FRAME-IS: a framework for documenting modifications to implementation strategies in healthcare
Authors: Miller Christopher J. , Barnett Miya L. , Baumann Ana A. , Gutner Cassidy A. , Wiltsey-Stirman Shannon 
Published: April 2021

Abstract
Background
Implementation strategies are necessary to ensure that evidence-based practices are successfully incorporated into routine clinical practice. Such strategies, however, are frequently modified to fit local populations, settings, and contexts. While such modifications can be crucial to implementation success, the literature on documenting and evaluating them is virtually nonexistent. In this paper, we therefore describe the development of a new framework for documenting modifications to implementation strategies.

Discussion
We employed a multifaceted approach to developing the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS), incorporating multiple stakeholder perspectives. Development steps included presentations of initial versions of the FRAME-IS to solicit structured feedback from individual implementation scientists (“think-aloud” exercises) and larger, international groups of researchers. The FRAME-IS includes core and supplementary modules to document modifications to implementation strategies: what is modified, the nature of the modification (including the relationship to core elements or functions), the primary goal and rationale for the modification, timing of the modification, participants in the modification decision-making process, and how widespread the modification is. We provide an example of application of the FRAME-IS to an implementation project and provide guidance on how it may be used in future work.

Conclusion
Increasing attention is being given to modifications to evidence-based practices, but little work has investigated modifications to the implementation strategies used to implement such practices. To fill this gap, the FRAME-IS is meant to be a flexible, practical tool for documenting modifications to implementation strategies. Its use may help illuminate the pivotal processes and mechanisms by which implementation strategies exert their effects.
Obstructive sleep apnea in Norwegian adults with achondroplasia: a population-based study
Authors: Fredwall Svein O. , Øverland Britt , Berdal Hanne , Berg Søren , Weedon-Fekjær Harald , Lidal Ingeborg B. , Savarirayan Ravi , Månum Grethe 
Published: April 2021

Abstract
Background
Previous studies have found a high prevalence of obstructive sleep apnea (OSA) in children with achondroplasia, but clinical studies on this complication in adults with achondroplasia are lacking.

Objectives
This population-based, cross-sectional study investigated the prevalence, severity, and predictive factors of OSA in Norwegian adults with achondroplasia.

Methods
We collected clinical data on 49 participants. Participants without a preexisting diagnosis of OSA had an overnight sleep registration. OSA was defined as an apnea–hypopnea index (AHI) ≥ 5 plus characteristic clinical symptoms, or AHI ≥ 15. We used the Berlin Questionnaire to assess clinical symptoms of OSA.

Results
OSA was found in 59% (29/49) of the participants (95% confidence interval 44 to 73%), of whom 59% (17/29) had moderate to severe OSA (AHI ≥ 15), and 48% (14/29) were previously undiagnosed. Variables predictive of OSA were: excessive daytime sleepiness; unrested sleep; loud snoring; observed nocturnal breathing stops; hypertension; age > 40 years; and BMI > 30 kg/m2.

Conclusion
OSA was highly prevalent in Norwegian adults with achondroplasia, which we believe is representative of this population worldwide. Follow-up of adults with achondroplasia should include assessment of symptoms and signs of OSA, with a low threshold for conducting an overnight sleep registration if findings suggestive of OSA are present.