bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethical considerations for research involving pregnant women living with HIV and their young children: a systematic review of the empiric literature and discussion
Authors: Raciti Catherine G. , Enane Leslie A. , MacDonald Katherine R. , Whipple Elizabeth C. , Ott Mary A. , McHenry Megan S.
Published: April 2021

Background

The proper and ethical inclusion of PWLHIV and their young children in research is paramount to ensure valid evidence is generated to optimize treatment and care. Little empirical data exists to inform ethical considerations deemed most critical to these populations. Our study aimed to systematically review the empiric literature regarding ethical considerations for research participation of PWLHIV and their young children.

Methods

We conducted this systematic review in partnership with a medical librarian. A search strategy was designed and performed within the following electronic databases: Ovid MEDLINE, Embase and CINAHL. We screened titles and abstracts using the following inclusion criteria: (1) a study population of PWLHIV or children under 5 years of age; and (2) collection of qualitative or quantitative data regarding ethics of research participation. Excluded were reviews, commentaries, policy statements, clinical care-related ethics concerns, abstracts, case studies, or studies unrelated to HIV research. Studies were appraised for quality, data were extracted, and studies were qualitatively analyzed using a principle-based ethical framework within the Belmont Report.

Results

Of the 7470 titles identified, 538 full-text articles were reviewed for eligibility and only three articles met full criteria for inclusion within this review. While we allowed for inclusion of studies involving young children born to mothers with HIV, only articles focused on PWLHIV were identified. Within the results of these studies, four themes emerged: (1) adequacy of informed consent; (2) consideration of paternal involvement; (3) balancing risks; and (4) access to research and treatment. A strength of this review is that it included perspectives of international research investigators, community leaders, and male partners. However, only two studies collected empiric data from PWLHIV regarding their experiences participating in research

Conclusion

Researchers and funding agencies should be aware of these considerations and appreciate the value of and critical need for formative research to ensure clinical trials involving PWLHIV promote ethical, well-informed research participation and, ultimately, improve care outcomes. More research is needed to create a comprehensive ethical framework for researchers when conducting studies with PWLHIV.
Relationships between nurse managers’ work activities, nurses’ job satisfaction, patient satisfaction, and medication errors at the unit level: a correlational study
Authors: Nurmeksela Anu , Mikkonen Santtu , Kinnunen Juha , Kvist Tarja
Published: April 2021

Background

Nurse managers play a critical role in enhancing nursing and patient outcomes. The work of nurse managers, who can be described as middle-managers at health care organizations, is complex and changes on a daily basis. Only a few studies have clarified how nurse managers divide their time across various work activities. This study aimed to describe the relationships between nurse managers’ work activities, nurses’ job satisfaction, patient satisfaction, and medication errors at the hospital unit level.

Methods

A cross-sectional and correlational study design was used. The data were collected from nurse managers (n = 29), nursing staff (n = 306), and patients (n = 651) from 28 units across three Finnish acute care hospitals between April and November 2017. In addition, data concerning medication errors (n = 468) over one calendar year (2017) were acquired from the hospitals’ incident reporting register. Analysis of covariance (ANCOVA) was used to estimate relationships between data from subareas of Nurse Managers’ Work Content Questionnaire, Kuopio University Hospital Job Satisfaction Scale, and Revised Humane Caring Scale, along with medication error reports. A significance level of 95% was applied when estimating the covariances between variables. Unstandardized regression coefficients (B) were used to explain the relationships between variables.

Results

Multiple relationships between nurse managers’ work activities, nurses’ job satisfaction, patient satisfaction, and medication errors were identified. Nurse managers’ work activities had both positive and negative relationships on the other studied variables. The Requiring factors of work (p < .001) subarea of nurses’ job satisfaction, total patient satisfaction (p < .001), and medication errors (p < .001) were identified as the variables most significantly affected by other factors.

Conclusions

The findings suggest that nurse managers should focus on improving nursing practices by managing and organizing nurses’ work in a way that makes their employees feel supported, motivated and secure. Furthermore, nurse managers should adopt a leadership style that emphasizes safe and patient-centered care. The results also suggest that the administration of today’s health care organizations should actively evaluate nurse managers’ share of work activities to ensure that their daily work is in line with the organizational goals.
Building on facilitators and overcoming barriers to implement active tuberculosis case-finding in Nepal, experiences of community health workers and people with tuberculosis
Authors: Biermann Olivia , Dixit Kritika , Rai Bhola , Caws Maxine , Lönnroth Knut , Viney Kerri
Published: April 2021

Background

Nepal has a high burden of undetected tuberculosis (TB). In line with the World Health Organization’s End TB Strategy, the National TB Programme promotes active case-finding (ACF) as one strategy to find people with TB who are unreached by existing health services. The IMPACT TB (Implementing proven community-based active TB case-finding intervention) project was implemented in four districts in Nepal, generating a substantial yield of previously undetected TB. We aimed to identify the facilitators and barriers linked to the implementation of ACF within IMPACT TB, as well as how those facilitators and barriers have been or could be addressed.

Methods

This was an exploratory qualitative study based on 17 semi-structured key-informant interviews with people with TB who were identified through ACF, and community health workers who had implemented ACF. Thematic analysis was applied in NVivo 11, using an implementation science framework developed by Grol and Wensing to classify the data.

Results

We generated five main themes from the data: (1) ACF addressed the social determinants of TB by providing timely access to free healthcare, (2) knowledge and awareness about TB among people with TB, communities and community health workers were the ‘oil’ in the ACF ‘machine’, (3) trust in community health workers was fundamental for implementing ACF, (4) community engagement and support had a powerful influence on ACF implementation and (5) improved working conditions and enhanced collaboration with key stakeholders could further facilitate ACF. These themes covered a variety of facilitators and barriers, which we divided into 22 categories cutting across five framework levels: innovation, individual professional, patient, social context and organizational context.

Conclusions

This study provides new insights into facilitators and barriers for the implementation of ACF in Nepal and emphasizes the importance of addressing the social determinants of TB. The main themes reflect key ingredients which are required for successful ACF implementation, while the absence of these factors may convert them from facilitators into barriers for ACF. As this study outlined “how-to” strategies for ACF implementation, the findings can furthermore inform the planning and implementation of ACF in Nepal and similar contexts in low- and middle-income countries.
What influences the outcome of active disinvestment processes in healthcare? A qualitative interview study on five recent cases of active disinvestment
Authors: Rotteveel Adriënne H. , Lambooij Mattijs S. , van de Rijt Joline J. A. , van Exel Job , Moons Karel G. M. , de Wit G. Ardine
Published: April 2021

Background

Recent attempts of active disinvestment (i.e. withdrawal of reimbursement by means of a policy decision) of reimbursed healthcare interventions in the Netherlands have differed in their outcome: some attempts were successful, with interventions actually being disinvested. Other attempts were terminated at some point, implying unsuccessful disinvestment. This study aimed to obtain insight into recent active disinvestment processes, and to explore what aspects affect their outcome.

Methods

Semi-structured interviews were conducted from January to December 2018 with stakeholders (e.g. patients, policymakers, physicians) who were involved in the policy process of five cases for which the full or partial withdrawal of reimbursement was considered in the Netherlands between 2007 and 2017: benzodiazepines, medication for Fabry disease, quit smoking programme, psychoanalytic therapy and maternity care assistance. These cases covered both interventions that were eventually disinvested and interventions for which reimbursement was maintained after consideration. Interviews were transcribed verbatim, double coded and analyzed using thematic analysis.

Results

The 37 interviews showed that support for disinvestment from stakeholders, especially from healthcare providers and policymakers, strongly affected the outcome of the disinvestment process. Furthermore, the institutional role of stakeholders as legitimized by the Dutch health insurance system, their financial interests in maintaining or discontinuing reimbursement, and the possibility to relieve the consequences of disinvestment for current patients affected the outcome of the disinvestment process as well. A poor organization of patient groups may make it difficult for patients to exert pressure, which may contribute to successful disinvestment. No evidence was found of a consistent role of the formal Dutch package criteria (i.e. effectiveness, cost-effectiveness, necessity and feasibility) in active disinvestment processes.

Conclusions

Contextual factors as well as the possibility to relieve the consequences of disinvestment for current patients are important determinants of the outcome of active disinvestment processes. These results provide insight into active disinvestment processes and their determinants, and provide guidance to policymakers for a potentially more successful approach for future active disinvestment processes.
Perspectives on team communication challenges in caring for children with medical complexity
Authors: Adams Sherri , Beatty Madison , Moore Clara , Desai Arti , Bartlett Leah , Culbert Erin , Cohen Eyal , Stinson Jennifer , Orkin Julia
Published: April 2021

Background

Children with medical complexity (CMC) require the expertise of many care providers spanning different disciplines, institutions, and settings of care. This leads to duplicate health records, breakdowns in communication, and limited opportunities to provide comprehensive, collaborative care. The objectives of this study were to explore communication challenges and solutions/recommendations from multiple perspectives including (i) parents, (ii) HCPs – hospital and community providers, and (iii) teachers of CMC with a goal of informing patient care.

Methods

This qualitative study utilized an interpretive description methodology. In-depth semi-structured interviews were conducted with parents and care team members of CMC. The interview guides targeted questions surrounding communication, coordination, access to information and roles in the health system. Interviews were conducted until thematic saturation was reached. Interviews were audio-recorded, transcribed verbatim, and coded and analyzed using thematic analysis.

Results

Thirty-two individual interviews were conducted involving parents (n = 16) and care team members (n = 16). Interviews revealed 2 main themes and several associated subthemes (in parentheses): (1) Communication challenges in the care of CMC (organizational policy and technology systems barriers, inadequate access to health information, and lack of partnership in care) (2) Communication solutions (shared systems that can be accessed in real-time, universal access to health information, and partnered contribution to care).

Conclusion

Parents, HCPs, and teachers face multiple barriers to communication and information accessibility in their efforts to care for CMC. Parents and care providers in this study suggested potential strategies to improve communication including facilitating communication in real-time, universal access to health information and meaningful partnerships.
Zonal characterization and differential trilineage potentials of equine intrasynovial deep digital flexor tendon-derived cells
Authors: Quam Vivian G. , Altmann Nadine N. , Brokken Matthew T. , Durgam Sushmitha S.
Published: April 2021

Background

Intrasynovial deep digital flexor tendon (DDFT) injuries occur frequently and are often implicated in cases of navicular disease with poor outcomes and reinjuries. Cell-based approaches to tendon healing are gaining traction in veterinary medicine and ultimately may contribute to improved DDFT healing in horses. However, a better understanding of the innate cellular characteristics of equine DDFT is necessary for developing improved therapeutic strategies. Additionally, fibrocartilaginous, intrasynovial tendons like the DDFT are common sites of injury and share a poor prognosis across species, offering translational applications of this research. The objective of this study is to isolate and characterize tendon-derived cells (TDC) from intrasynovial DDFT harvested from within the equine forelimb podotrochlear bursa. TDC from the fibrocartilaginous and tendinous zones are separately isolated and assessed. Flow cytometry is performed for mesenchymal stem cell (MSC) surface markers (CD 29, CD 44, CD 90). Basal tenogenic, osteogenic and chondrogenic markers are assessed via quantitative real time-PCR, and standard trilineage differentiation is performed with third passage TDC from the fibrocartilaginous (fTDC) and tendinous (tTDC) zones of DDFT.

Results

Low-density plating isolated homogenous TDC populations from both zones. During monolayer passage, both TDC subpopulations exhibited clonogenicity, high in vitro proliferation rate, and fibroblast-like morphology. fTDC and tTDC were positive for MSC surface markers CD90 and CD29 and negative for CD44. There were no significant differences in basal tenogenic, osteogenic or chondrogenic marker expression between zones. While fTDC were largely restricted to chondrogenic differentiation, tTDC underwent osteogenic and chondrogenic differentiation. Both TDC subpopulations displayed weak adipogenic differentiation potentials.

Conclusions

TDC at the level of the podotrochlear bursa, that potentially could be targeted for enhancing DDFT injury healing in horses were identified and characterized. Pending further investigation, promoting chondrogenic properties in cells administered exogenously into the intrasynovial space may be beneficial for intrasynovial tendon regeneration.
Cystic echinococcosis: an emerging zoonosis in southern regions of Khyber Pakhtunkhwa, Pakistan
Authors: Khan Shahid Niaz , Ali Rehman , Khan Sanaullah , Norin Sadia , Rooman Muhammad , Akbar Noor Ul , Khan Taj Ali , Haleem Sumbal , Khan Murad Ali , Ali Ijaz
Published: April 2021

Background

Cystic echinococcosis (CE) is one of the principal causes of economic loss to the livestock industry because of its morbidity and mortality of food-producing animals and condemnation of important visceral organs. Pakistan being an agricultural country having an extensive livestock sector, is mostly practiced by poor people, which has a fundamental role in the economy. The present study was aimed to conduct a cross-sectional survey and PCR based confirmation of Echinococcus granulosus in sheep, goats, cows, and buffaloes from southern regions (three districts: Lakki Marwat, Bannu, and Karak) of Khyber Pakhtunkhwa, Pakistan. During the study, a total of 2833 animals were examined randomly including; sheep (n = 529), goats (n = 428), cows (n = 1693), and buffaloes (n = 183). Hydatid cysts were collected and examined for the presence of protoscoleces using microscopy. Detection of DNA was performed by using PCR and two mitochondrial genetic markers namely; NAD-1 and COX-1 were amplified.

Results

The overall prevalence of CE was found to be (9%) among the examined animals. The hydatid cyst infection was highly prevalent in buffaloes (12%), followed by sheep (10%), cows (9%), and goats (5.1%). Cystic echinococcosis was more prevalent (10%; 96/992) in district Lakki Marwat followed by district Bannu (9%; 112/1246) and Karak (7%; 39/595). Female animals were more likely to be infected with CE (11.6%) than male animals (5.3%) (p = 0.001). Similarly, the infection was higher in the older group of animals as compared to younger (p = 0.001). Mostly (52.2%; n = 129) of hydatid cysts were found in the liver, while (64.4%; n = 159) cysts of the infected animals were infertile. PCR based identification confirmed the presence of E. granulosus sensu stricto (s.s) in the study area.

Conclusion

Cystic echinococcosis was found to be highly prevalent in southern regions of Khyber Pakhtunkhwa and could be a potential threat to human health. Moreover, molecular sequencing and phylogenetic analyses should be carried out in future to identify the prevailing genotype (s) of E. granulosus s.s.
Apigenin role as cell-signaling pathways modulator: implications in cancer prevention and treatment
Authors: Javed Zeeshan , Sadia Haleema , Iqbal Muhammad Javed , Shamas Shazia , Malik Kausar , Ahmed Rais , Raza Shahid , Butnariu Monica , Cruz-Martins Natalia , Sharifi-Rad Javad
Published: April 2021

Cancer is a complex disease orchestrated by various extrinsic and intrinsic pathways. In recent years, there has been a keen interest towards the development of natural extracts-based cancer therapeutics with minimum adverse effects. In pursuit of effective strategy, a wide variety of natural products-derived compounds have been addressed for their anticancer effects. Apigenin is a naturally-occurring flavonoid present abundantly in various fruits and vegetables. Decades of research have delineated the pharmacological and biological properties of apigenin. Specifically, the apigenin-mediated anticancer activities have been documented in various types of cancer, but the generalized scientific evidence encompassing various molecular interactions and processes, such as regulation of the apoptotic machinery, aberrant cell signaling and oncogenic protein network have not been comprehensively covered. In this sense, in this review we have attempted to focus on the apigenin-mediated regulation of oncogenic pathways in various cancers. We have also addressed the cutting-edge research which has unveiled the remarkable abilities of apigenin to interact with microRNAs to modulate key cellular processes, with special emphasis on the nano-formulations of apigenin that can help their targeted delivery and can be a therapeutic solution for the treatment of various cancers.
Expression of tissue factor and tissue factor pathway inhibitors during ovulation in rats: a relevance to the ovarian hyperstimulation syndrome
Authors: Jang You Jee , Kim Hee Kyung , Choi Bum Chae , Song Sang Jin , Park Jae Il , Chun Sang Young , Cho Moon Kyoung
Published: April 2021

Background

Blood coagulation has been associated with ovulation and female infertility. In this study, the expression of the tissue factor system was examined during ovulation in immature rats; the correlation between tissue factor and ovarian hyperstimulation syndrome (OHSS) was evaluated both in rats and human follicular fluids.

Methods

Ovaries were obtained at various times after human chorionic gonadotropin (hCG) injection to investigate the expression of tissue factor system. Expression levels of ovarian tissue factor, tissue factor pathway inhibitor (Tfpi)-1 and Tfpi-2 genes and proteins were determined by real-time quantitative polymerase chain reaction (qPCR), and Western blot and immunofluorescence analyses, respectively. Expression levels of tissue factor system were also investigated in ovaries of OHSS-induced rats and in follicular fluid of infertile women.

Results

The expression of tissue factor in the preovulatory follicles was stimulated by hCG, reaching a maximum at 6 h. Tissue factor was expressed in the oocytes and the preovulatory follicles. Tfpi-2 mRNA levels were mainly increased by hCG in the granulosa cells whereas the mRNA levels of Tfpi-1 were decreased by hCG. Human CG-stimulated tissue factor expression was inhibited by the progesterone receptor antagonist. The increase in Tfpi-2 expression by hCG was decreased by the proliferator-activated receptor γ (PPARγ) antagonist. Decreased expression of the tissue factor was detected in OHSS-induced rats. Interestingly, the tissue factor concentrations in the follicular fluids of women undergoing in vitro fertilization were correlated with pregnancy but not with OHSS.

Conclusions

Collectively, the results indicate that tissue factor and Tfpi-2 expression is stimulated during the ovulatory process in rats; moreover, a correlation exists between the levels of tissue factor and OHSS in rats but not in humans.
Anticentromere antibody induced by immunization with centromere protein a and Freund’s complete adjuvant may interfere with mouse oocyte meiosis
Authors: Ying Ying , Liu Shuang , Wu Yixuan , Li Sichen , Huang Qing
Published: April 2021

Background

Anticentromere antibody (ACA) is a member of the antinuclear antibody (ANA) family, and recent studies have found that ACA may be associated with oocyte maturation disorders; however, the possible mechanism behind this phenomenon remains unknown. We conducted this study to investigate whether ACA could penetrate into the living oocytes and interfere with oocyte meiosis in a mouse model.

Methods

We divided mice into three groups: human recombinant centromere protein-A (human CENP-A, HA) and complete Freund’s adjuvant (CFA) were used to immunize mice for the study group (HA + CFA), and mice injected with CFA (CFA group) or saline (Saline group), respectively, served as controls. After immunization, serum anti-CENP-A antibody was detected by indirect immunofluorescence assay (IIFT) and enzyme-linked immunosorbent assay (ELISA). Chromosome alignment and intracellular IgG localization in MI- and MII-stage oocytes were investigated by immunofluorescence analysis.

Results

Positive ACAs were successfully induced by immunization with CENP-A and CFA, and results showed that the serum level of anti-CENP-A antibody was significantly higher in the HA + CFA group compared with the control groups. There was marked increase of chromosome misalignments in MI and MII oocytes in the HA + CFA group compared to the control groups. However, no oocytes from any of the three groups showed intracellular antibody immunofluorescence.

Conclusions

The development and maturation of oocytes were impaired in peripheral ACA positive mice, which exhibited severe chromosomal misalignments in metaphase meiosis; however, no evidence of ACAs entering the oocytes was observed, thus the underlying mechanism needs further exploration.
Selection of key indicators for European policy monitoring and surveillance for dietary behaviour, physical activity and sedentary behaviour
Authors:   on behalf of the PEN Consortium, Garnica Rosas Lina , Mensink Gert B. M. , Finger Jonas D. , Schienkiewitz Anja , Do Stefanie , Wolters Maike , Stanley Isobel , Abu Omar Karim , Wieczorowska-Tobis Katarzyna , Woods Catherine B. , Murrin Celine , Ahrens Wolfgang , Hebestreit Antje
Published: April 2021

Background

A pan-European approach to evaluate policy impact on health behaviour requires the employment of a consensus set of established and relevant indicators.

Methods

As part of the Joint Programming Initiative on a Healthy Diet for a Healthy Life, the Policy Evaluation Network PEN identified key indicators of health behaviours and their determinants. These key indicators are already, or have the potential to be, adopted by large European Union surveillance systems for the assessment of policy impact. The iterative selection process included consultations in two rounds via email prior to a 2-days expert workshop. The experts collated a list of dietary behaviour, physical activity and sedentary behaviour indicators for European policy monitoring in young and adult populations based on existing frameworks and literature reviews. The expert panel was composed of researchers, policy makers and representatives of major European surveillance systems and related initiatives, as well as, representatives of organisations providing monitoring data, such as the European Commission and Eurostat.

Results

The process provided two lists of key indicators including 37 diet ‘policy’ indicators and 35 indicators for dietary behaviour and their ‘determinants’; as well as 32 physical activity ‘policy’ indicators and 35 indicators for physical activity, sedentary behaviour and their ‘determinants’.

Conclusion

A total of 139 key indicators related to the individual, the setting and the population level, and suitable for the assessment of dietary behaviour, physical activity and sedentary behaviour were prioritised by policy makers and researchers with the ultimate aim to embed policy evaluation measures in existing surveillance systems across the European Union. In a next step, data sources and suitable instruments will be identified to assess these key indicators.
Src is essential for the endosomal delivery of the FGFR4 signaling complex in hepatocellular carcinoma
Authors: Shin Ji-Yon , Ahn Sung-Min
Published: April 2021

Background

Hepatocytes usually express fibroblast growth factor receptor 4 (FGFR4), but not its ligand, fibroblast growth factor 19 (FGF19). A subtype of hepatocellular carcinoma (HCC) expresses FGF19, which activates the FGFR4 signaling pathway that induces cell proliferation. FGFR4 inhibitors that target this mechanism are under clinical development for the treatment of HCCs with FGF19 amplification or FGFR4 overexpression. Src plays an essential role in the FGFR1 and FGFR2 signaling pathways. However, it is yet to be understood whether Src has any role in the FGF19-FGFR4 pathway in HCCs. In this study, we aimed to elucidate the role of Src in the FGF19-FGFR4 axis in HCC.

Methods

3 HCC cell lines expressing both FGF19 and FGFR4 were selected. The expression of each protein was suppressed by siRNA treatment, and the activity-regulating relationship between FGFR4 and Src was investigated by westernblot. Co-immunoprecipitation was performed using the FGFR4 antibody to identify the endosomal complex formation and receptor endocytosis. The intracellular migration pathways of the endosomal complex were observed by immuno-fluorescence and nuclear co-immunoprecipitation. Dasatinib and BLU9931 were used for cytotoxicity comparison.

Results

FGFR4 modulates the activity of Src and Src modulates the expression of FGFR4, showing a mutual regulatory relationship. FGFR4 activated by FGF19 formed an endosomal complex with Src and STAT3 and moved to the nucleus. However, when Src was suppressed, the formation of the endosomal complex was not observed. FGFR4 was released from the complex transferred into the nucleus and the binding of Src and STAT3 was maintained. Dasatinib showed cytotoxic results comparable to BLU9931. The results of our study demonstrated that Src is essential for the nuclear transport of STAT3, as it induces the endosomal delivery of FGFR4 in FGF19-expressing HCC cell lines.

Conclusions

We found that Src is essential for the endosomal delivery of the FGFR4 signaling complex in HCC. Our findings provide a scientific rationale for repurposing Src inhibitors for the treatment of HCCs in which the FGFR4 pathway is activated.
Single nucleotide polymorphisms associated with methotrexate-induced nausea in juvenile idiopathic arthritis
Authors: Kyvsgaard Nini , Mikkelsen Torben Stamm , Als Thomas D. , Christensen Anne Estmann , Corydon Thomas J. , Herlin Troels
Published: April 2021

Background

Context: Methotrexate (MTX) is a cornerstone in the treatment of juvenile idiopathic arthritis (JIA). MTX treatment is commonly associated with nausea. Large inter-individual variation exists in the level of MTX-induced nausea, possibly due to genetic factors.

Purpose: To investigate whether MTX-induced nausea was associated with single nucleotide polymorphisms (SNPs) in genes encoding MTX-transporter proteins, a MTX metabolizing enzyme and a nausea receptor.

Findings

Methods: Children aged ≥9 years treated with MTX for JIA were eligible. MTX-induced nausea was registered by the children’s completion of a nausea diary (min. 7 days) and the parents’ completion of the MTX intolerance severity score (MISS). The selected SNPs were: SLCO1B1 (rs4149056; rs4149081), SLCO1B3 (rs2117032), SLC19A1 (rs1051266), ABCC2 (rs2273697; rs3740066; rs717620), ABCB1 (rs2032582; rs1045642), MTHFR (rs1801131, rs1801133), HTR3A (rs1062613; rs1985242; rs1176713) and HTR3B (rs1176744).

Result: Enrolled were 121 JIA patients (82 girls: 39 boys) with a median age of 13.3 years (IQR: 11.3–15.1). The median MTX dose was 9.7 mg/m2/week (IQR: 9.0–10.9). The median MTX treatment duration prior to enrolment was 340 days (IQR: 142–766). The SNP analysis was available for 119 patients. MTX intolerance was associated with the genotype distribution of rs1801133 (MTHFR) (p = 0.02). There was no additive effect of the minor alleles for any of the selected SNPs, nor any significant haplotype associations.

Conclusion

Summary: MTX-induced nausea may be influenced by genetic polymorphisms in a MTX metabolizing enzyme (rs1801133; MTHFR).

Implications: Further analyses involving inclusion of larger cohorts are needed to understand the impact of SNPs on MTX-induced nausea in JIA.
Foreign investment in emerging legal medicinal cannabis markets: the Jamaica case study
Authors: Rychert Marta , Emanuel Machel Anthony , Wilkins Chris
Published: April 2021

Introduction

The establishment of a legal market for medicinal cannabis under the Dangerous Drugs Amendment Act 2015 has positioned Jamaica at the forefront of cannabis law reform in the developing world. Many local cannabis businesses have attracted investment from overseas, including from Canada, US and Europe.

Aim

To explore the opportunities and risks of foreign investment in an emerging domestic legal cannabis market in a developing country.

Methods

Thematic analysis of semi-structured face-to-face interviews with 22 key informants (KIs) from the Jamaican government, local cannabis industry, academia and civil society, and field observations of legal and illegal cannabis cultivators.

Results

KIs from the Jamaican public agencies and domestic cannabis entrepreneurs saw foreign investment as an essential source of capital to finance the start-up costs of legal cannabis businesses. Local cannabis entrepreneurs prioritised investors with the greatest financial resources, brand reputation and export networks. They also considered how allied an investor was with their business vision (e.g., organic cultivation, medical vs. recreational). The key benefits of partnering with a foreign investor included transfer of technical knowledge and financial capital, which enhanced production, quality assurance and seed-to-sale tracking. Some KIs expressed concern over investors’ focus on increasing production efficiency and scale at the expense of funding research and development (R&D) and clinical trials. KIs from the local industry, government agencies and civil society highlighted the risks of ‘predatory’ shareholder agreements and domestic political interference. Concerns were raised about the impact of foreign investment on the diversity of the domestic cannabis sector in Jamaica, including the commitment to transition traditional illegal small-scale cannabis cultivators to the legal sector.

Conclusion

While foreign investment has facilitated the commercialisation of the cannabis sector in Jamaica, regulatory measures are also needed to protect the domestic industry and support the transition of small-scale illegal cultivators to the legal regime. Foreign investments may alter the economic, social and political determinants of health in transitioning from illegal to legal cannabis market economy.
L2MXception: an improved Xception network for classification of peach diseases
Authors: Yao Na , Ni Fuchuan , Wang Ziyan , Luo Jun , Sung Wing-Kin , Luo Chaoxi , Li Guoliang
Published: April 2021

Background

Peach diseases can cause severe yield reduction and decreased quality for peach production. Rapid and accurate detection and identification of peach diseases is of great importance. Deep learning has been applied to detect peach diseases using imaging data. However, peach disease image data is difficult to collect and samples are imbalance. The popular deep networks perform poor for this issue.

Results

This paper proposed an improved Xception network named as L2MXception which ensembles regularization term of L2-norm and mean. With the peach disease image dataset collected, results on seven mainstream deep learning models were compared in details and an improved loss function was integrated with regularization term L2-norm and mean (L2M Loss). Experiments showed that the Xception model with L2M Loss outperformed the current best method for peach disease prediction. Compared to the original Xception model, the validation accuracy of L2MXception was up to 93.85%, increased by 28.48%.

Conclusions

The proposed L2MXception network may have great potential in early identification of peach diseases.
A stable isotope dilution method for a highly accurate analysis of karrikins
Authors: Hrdlička Jakub , Gucký Tomáš , van Staden Johannes , Novák Ondřej , Doležal Karel
Published: April 2021

Background

Karrikins (KARs) are recently described group of plant growth regulators with stimulatory effects on seed germination, seedling growth and crop productivity. So far, an analytical method for the simultaneous targeted profiling of KARs in plant tissues has not been reported.

Results

We present a sensitive method for the determination of two highly biologically active karrikins (KAR1 and KAR2) in minute amounts of plant material (< 20 mg fresh weight). The developed protocol combines the optimized extraction and efficient single-step sample purification with ultra-high performance liquid chromatography-tandem mass spectrometry. Newly synthesized deuterium labelled KAR1 was employed as an internal standard for the validation of KAR quantification using a stable isotope dilution method. The application of the matrix-matched calibration series in combination with the internal standard method yields a high level of accuracy and precision in triplicate, on average bias 3.3% and 2.9% RSD, respectively. The applicability of this analytical approach was confirmed by the successful analysis of karrikins in Arabidopsis seedlings grown on media supplemented with different concentrations of KAR1 and KAR2 (0.1, 1.0 and 10.0 µmol/l).

Conclusions

Our results demonstrate the usage of methodology for routine analyses and for monitoring KARs in complex biological matrices. The proposed method will lead to better understanding of the roles of KARs in plant growth and development.
Forms and functions of bridging factors: specifying the dynamic links between outer and inner contexts during implementation and sustainment
Authors: Lengnick-Hall Rebecca , Stadnick Nicole A. , Dickson Kelsey S. , Moullin Joanna C. , Aarons Gregory A.
Published: April 2021

Background

Bridging factors are relational ties, formal arrangements, and processes that connect outer system and inner organizational contexts. They may be critical drivers of evidence-based practice (EBP) implementation and sustainment. Yet, the complex interplay between outer and inner contexts is often not considered. Bridging factors were recently defined in the updated Exploration, Preparation, Implementation, Sustainment (EPIS) framework. Further identification and specification of this construct will advance implementation models, measures, and methods. Our goal is to advance bridging factor research by identifying relevant dimensions and exemplifying these dimensions through illustrative case studies.

Methods

We used a multiple case study design. Each case (n= 10) represented different contexts, EBPs, and bridging factor types. Inclusion criteria were the presence of clearly distinguishable outer and inner contexts, identifiable bridging factor, sufficient information to describe how the bridging factor affected implementation, and variation from other cases. We used an iterative qualitative inquiry process to develop and refine a list of dimensions. Case data were entered into a matrix. Dimensions comprised the rows and case details comprised the columns. After a review of all cases, we collectively considered and independently coded each dimension as function or form.

Results

We drew upon the concepts of functions and forms, a distinction originally proposed in the complex health intervention literature. Function dimensions help define the bridging factor and illustrate its purpose as it relates to EBP implementation. Form dimensions describe the specific structures and activities that illustrate why and how the bridging factor has been customized to a local implementation experience. Function dimensions can help researchers and practitioners identify the presence and purpose of bridging factors, whereas form dimensions can help us understand how the bridging factor may be designed or modified to support EBP implementation in a specific context. We propose five function and three form bridging factor dimensions.

Conclusions

Bridging factors are described in many implementation models and studies, but without explicit reference or investigation. Bridging factors are an understudied and critical construct that requires further attention to facilitate implementation research and practice. We present specific recommendations for a bridging factors research agenda.
Discovery of two novel laccase-like multicopper oxidases from Pleurotus citrinopileatus and their application in phenolic oligomer synthesis
Authors: Zerva A. , Pentari C. , Termentzi A. , America A. H. P. , Zouraris D. , Bhattacharya S. K. , Karantonis A. , Zervakis G. I. , Topakas E.
Published: April 2021

Background

Laccases and laccase-like multicopper oxidases (LMCOs) oxidize a vast array of phenolic compounds and amines, releasing water as a byproduct. Their low substrate specificity is responsible for their tremendous biotechnological interest, since they have been used for numerous applications. However, the laccases characterized so far correspond to only a small fraction of the laccase genes identified in fungal genomes. Therefore, the knowledge regarding the biochemistry and physiological role of minor laccase-like isoforms is still limited.

Results

In the present work, we describe the isolation, purification and characterization of two novel LMCOs, PcLac1 and PcLac2, from Pleurotus citrinopileatus. Both LMCOs were purified with ion-exchange chromatographic methods. PcLac2 was found to oxidize a broader substrate range than PcLac1, but both LMCOs showed similar formal potentials, lower than those reported previously for laccases from white-rot fungi. Proteomic analysis of both proteins revealed their similarity with other well-characterized laccases from Pleurotus strains. Both LMCOs were applied to the oxidation of ferulic and sinapic acid, yielding oligomers with possible antioxidant activity.

Conclusions

Overall, the findings of the present work can offer new insights regarding the biochemistry and variability of low-redox potential laccases of fungal origin. Low-redox potential biocatalysts could offer higher substrate selectivity than their high-redox counterparts, and thus, they could be of applied value in the field of biocatalysis.
Three Babesia species in Ixodes ricinus ticks from migratory birds in Sweden
Authors: Wilhelmsson Peter , Pawełczyk Olga , Jaenson Thomas G. T. , Waldenström Jonas , Olsen Björn , Forsberg Pia , Lindgren Per-Eric
Published: April 2021

Background

Migratory birds can cross geographical and environmental barriers and are thereby able to facilitate transmission of tick-borne pathogens both as carriers of infected ticks and as reservoirs of pathogenic microorganisms. Ixodes ricinus is one of the most abundant tick species in the Northern Hemisphere and a main vector of several Babesia species, some which pose a potential threat to human and animal health. At present only two cases of overt babesiosis in humans have so far been reported in Sweden. To better understand the potential role of birds as disseminators of zoonotic Babesia protozoan parasites, we investigated the presence of Babesia species in ticks removed from migratory birds.

Methods

Ticks were collected from birds captured at Ottenby Bird Observatory, south-eastern Sweden, from March to November 2009. Ticks were molecularly identified to species, and morphologically to developmental stage, and the presence of Babesia protozoan parasites was determined by real-time PCR.

Results

In total, 4601 migratory birds of 65 species were examined for tick infestation. Ticks removed from these birds have previously been investigated for the presence of Borrelia bacteria and the tick-borne encephalitis virus. In the present study, a total of 1102 ticks were available for molecular analysis of Babesia protozoan parasites. We found that 2.4% of the ticks examined, all I. ricinus, were positive for mammal-associated Babesia species. Out of all Babesia-positive samples, Babesia venatorum was the most prevalent (58%) species, followed by Babesia microti (38%) and Babesia capreoli (4.0%). B. venatorum and B. capreoli were detected in I. ricinus larvae, whereas B. microti was only present in I. ricinus nymphs. This supports the view that the two first-mentioned species are vertically (transovarially) transmitted in the tick population, in contrast to B. microti. The largest number of Babesia-infected ticks was removed from the common redstart (Phoenicurus phoenicurus) and European robin (Erithacus rubecula).

Conclusions

This study reveals that Babesia protozoan parasites are present in ticks infesting migratory birds in south-eastern Sweden, which could potentially lead to the dissemination of these tick-borne microorganisms into new areas, thus posing a threat to humans and other mammals.

Graphical Abstract
Generative adversarial network-based rogue device identification using differential constellation trace figure
Authors: Chen Zekun , Peng Linning , Hu Aiqun , Fu Hua
Published: April 2021

With the dramatic development of the internet of things (IoT), security issues such as identity authentication have received serious attention. The radio frequency (RF) fingerprint of IoT device is an inherent feature, which can hardly be imitated. In this paper, we propose a rogue device identification technique via RF fingerprinting using deep learning-based generative adversarial network (GAN). Being different from traditional classification problems in RF fingerprint identifications, this work focuses on unknown accessing device recognition without prior information. A differential constellation trace figure generation process is initially employed to transform RF fingerprint features from time-domain waveforms to two-dimensional figures. Then, by using GAN, which is a kind of unsupervised learning algorithm, we can discriminate rogue devices without any prior information. An experimental verification system is built with 54 ZigBee devices regarded as recognized devices and accessing devices. A universal software radio peripheral receiver is used to capture the signal and identify the accessing devices. Experimental results show that the proposed rogue device identification method can achieve 95% identification accuracy in a real environment.
Colorimetry to assess the visual impact of dust deposition on mosaics at sheltered archaeological sites
Authors: Cabello Briones Cristina , Mayorga Pinilla Santiago , Vázquez Moliní Daniel , Álvarez Fernández-Balbuena Antonio
Published: April 2021

One of the most important alteration factors for archaeological sites is the deposition of dust, primarily onto horizontal surfaces, because it affects both the conservation state of the remains and their appearance. The deposition is responsible for visual changes that prevent proper appreciation of the site, and this is especially negative for the decorative elements such as mosaics. Dust deposition has been seen as a significant problem in sheltered sites as opposed to those located in the open air, where deposits are regularly washed away. However, there is a lack of knowledge on the visual effects of dust on sheltered archaeological remains despite the fact that this information could help to determine cleaning regimes. This research has been undertaken at the House of Hippolytus, a Roman villa located on the outskirts of Complutum, situated where the city of Alcalá de Henares (Spain) stands today. The site was covered with a partially enclosed shelter in 1999 and it contains a magnificent mosaic in the central area. This ornamental floor is the center of attention for visitors and has often been used as a promotional image because of its high artistic value. This study has objectively evaluated the visual changes (color and spectral characteristics) of the mosaic at the House of Hippolytus before and after being cleaned with dry and wet systems using a novel approach based not only on a spectrophotometer (CM-2600d Konica Minolta®) but also on a LumiCam® 1300 camera (Instrument Systems GmbH). Although wet cleaning implies the use of water, which is a decay factor, it has been found to be the best option for recovering the original aspect of the mosaic.
Acute exudative polymorphous paraneoplastic vitelliform maculopathy (AEPPVM) associated with choroidal melanoma
Authors: Gameiro Filho Aluisio Rosa , Sturzeneker Guilherme , Rodriguez Ever Ernesto Caso , Maia André , Morales Melina Correia , Belfort Rubens N.
Published: April 2021

Background

To report a case of acute exudative polymorphous paraneoplastic vitelliform maculopathy in a patient with a history of choroidal melanoma, with metastases to the pancreas, liver, and central nervous system.

Case presentation

A 63-year-old patient, with a history of enucleation of the right eye due to choroidal melanoma, complained of progressive visual loss during a follow-up visit. Fundoscopic examination revealed multiple small areas of serous retinal detachment scattered throughout the posterior pole and ancillary tests confirmed the diagnosis of acute exudative polymorphous paraneoplastic vitelliform maculopathy (AEPPVM). Screening for systemic metastases showed pancreatic, hepatic, and central nervous system involvement.

Conclusions

We describe a rare case of acute exudative polymorphous paraneoplastic vitelliform maculopathy, which should be considered in patients with or without a history of melanoma, who have vitelliform retinal detachments. Nevertheless, no previous reviews of literature have shown a correlation between AEPPVM and pancreatic metastasis.