bluuebunny/crossref_metadata_2025 huggingface dataset:
Where to enhance rural palliative care? Developing a spatial model to identify suitable communities most in need of service enhancement
Authors: Schuurman Nadine , Martin Michael E. , Crooks Valorie A. , Randall Ellen
Published: March 2020

Background

In Canada, access to palliative care is a growing concern, particularly in rural communities. These communities have constrained health care services and accessing local palliative care can be challenging. The Site Suitability Model (SSM) was developed to identify rural “candidate” communities with need for palliative care services and existing health service capacity that could be enhanced to support a secondary palliative care hub. The purpose of this study was to test the feasibility of implementing the SSM in Ontario by generating a ranked summary of rural “candidate” communities as potential secondary palliative care hubs.

Methods

Using Census data combined with community-level data, the SSM was applied to assess the suitability of 12 communities as rural secondary palliative care hubs. Scores from 0 to 1 were generated for four equally-weighted components: (1) population as the total population living within a 1-h drive of a candidate community; (2) isolation as travel time from that community to the nearest community with palliative care services; (3) vulnerability as community need based on a palliative care index score; and (4) community readiness as five dimensions of fit between a candidate community and a secondary palliative care hub. Component scores were summed for the SSM score and adjusted to range from 0 to 1.

Results

Population scores for the 12 communities ranged widely (0.19–1.00), as did isolation scores (0.16–0.94). Vulnerability scores ranged more narrowly (0.27–0.35), while community readiness scores ranged from 0.4–1.0. These component scores revealed information about each community’s particular strengths and weaknesses. Final SSM scores ranged from a low of 0.33 to a high of 0.76.

Conclusions

The SSM was readily implemented in Ontario. Final scores generated a ranked list based on the relative suitability of candidate communities to become secondary palliative care hubs. This list provides information for policy makers to make allocation decisions regarding rural palliative services. The calculation of each community’s scores also generates information for local policy makers about how best to provide these services within their communities. The multi-factorial structure of the model enables decision makers to adapt the relative weights of its components.
From malaria control to elimination within a decade: lessons learned from Timor Leste, a newly independent country
Authors: Manel Yapabandara A. M. G. , do Rosario de Fatima Mota Maria , Sarmento Raul , Bosco Johanes don , Wickremasinghe Rajitha
Published: March 2020

Background

Timor Leste has made remarkable progress from malaria control to malaria elimination in a span of 10 years during which organized malaria control efforts were instituted. The good practices and possible factors that have contributed to the remarkable transition from malaria control to elimination in a newly independent country devastated by civil unrest which left the entire administrative structure including the health sector in a disrupted non-functional state are highlighted.

Methods

Data from the National Malaria Control Programme were reviewed. A literature search was carried out using the key words “malaria”, “Timor Leste”, “East Timor”, and “malaria control” and “malaria elimination”. All relevant manuscripts and reports that were identified in the search were reviewed. Key personnel of the NMCP, WHO and the GFATM involved in the project were interviewed.

Results

With the setting up of the National Malaria Control Programme just after independence in 2003 with two officers, the programme expanded over the years and strategic malaria control activities in an organized manner commenced in 2009 with funding from the Global Fund to fight AIDS, Tuberculosis and Malaria. The incidence of malaria declined dramatically from 223,002 cases in 2006 with the last indigenous case being reported in June 2017. The decline in malaria was associated with strategic application of key evidence-based interventions taking into account the burden of disease, characteristics of vectors, and stratification of risk areas ensuring universal access to malaria prevention, and quality assured diagnostic tools and effective anti-malarial medicines at point of care, intensified surveillance, monitoring and evaluation, and capacity building, including training of staff, with adequate programme funding. The programme was provided with technical expertise and sustained political commitment that ensured uninterrupted implementation of interventions based on national strategic plans. The incorporation of the malaria control programme within an evolving health system helped the transition from malaria control to malaria elimination.

Conclusion

Universal access to quality assured malaria diagnosis and treatment and focussed vector control, implemented throughout the country in an organized manner with adequate funding and political commitment were key to the successful interruption of malaria transmission in the country. All the practices or factors listed did not work in isolation but rather synergistically in an integrated manner. Malaria elimination is possible even in tropical areas of South and Southeast Asia.
Factors impacting referral of JIA patients to a tertiary level pediatric rheumatology center in North India: a retrospective cohort study
Authors: Agarwal Manjari , Freychet Caroline , Jain Sumidha , Shivpuri Abhay , Singh Anju , Dinand Veronique , Sawhney Sujata
Published: March 2020

Background

JIA studies demonstrate that there is a “window of opportunity” early in the disease course during which appropriate management improves outcomes. No data is available regarding patients’ pathway, before first pediatric rheumatology (PR) evaluation in India, a country where health-care costs are self- paid by patients and where a significant shortage of pediatric rheumatologists (PRsts) is known. This study aimed to describe time from onset of symptoms to first PR visit of JIA patients to a tertiary center in India and factors that impact this.

Methods

This retrospective study is from data collected at the PR center, Sir Ganga Ram Hospital (SGRH) in New Delhi. JIA patients fulfilling ILAR 2004 criteria and seen at least twice from 1st October 2013 to 30th September 2018 were included. Data collected were: demographic details, history of disease, referral practitioner, clinical and laboratory features, treatments. Mann-Whitney U-test, Chi square and logistic regression were used as appropriate to study factors that determined time to first PR visit.

Results

Five hundred and twenty patients were included: 396 were diagnosed at this PR center (group A), 124 were previously diagnosed as JIA and managed by non PRsts before first PR visit (group B). Median time from symptom onset to first PR visit was 4.1 months and median distance travelled 119.5 km. Despite ongoing treatment, group B patients had more aggressive disease and resided further away as compared to Group A patients.

On univariate analysis, factors that predicted PR visit within 3 months were private patients, short distance to travel, family history of inflammatory disease, history of fever, history of acute uveitis or high ESR. On multivariate analysis all these factors were significant except high ESR and acute uveitis.

Conclusion

Time to first PR assessment at this center was comparable to that seen in western countries. Cost of care and long distance to the center delayed consultation; acuity of complaints and family history of rheumatologic condition hastened referral.

Possible solutions to improve referral to PR centers would be to increase the number of PRsts and to improve medical insurance coverage.
Non-invasive prenatal screening for Emanuel syndrome
Authors: Luo Yuqin , Lin Jie , Sun Yixi , Qian Yeqing , Wang Liya , Chen Min , Dong Minyue , Jin Fan
Published: March 2020

Objective

The aim of this study was to validate the results of two Emanuel syndromes detected by non-invasive prenatal screening (NIPS) screening using invasive methods, providing clinical performance of NIPS on chromosome microduplication detection.

Methods

NIPS was performed to diagnose the Emanuel syndrome. Amniocentesis or cordocentesis was performed to confirm the positive screening result of Emanuel syndrome cases. Fetal sample was detected by karyotyping, fluorescence in situ hybridization (FISH), and single nucleotide polymorphism array (SNP Array). Parental karyotyping and FISH were also carried out.

Results

Two cases with chromosomal abnormalities of 11q23.3q25 and 22q11.1q11.21 were found by NIPS. Chromosomal karyotyping showed that the two fetuses each have a small supernumerary marker chromosome (sSMC), SNP Array further demonstrated double duplications approximately 18 Mb in 11q23.3q25 and 3 Mb in 22q11.1q11.21. FISH confirmed that the small supernumerary marker chromosome (sSMC) was ish der(22)t(11;22) (TUPLE1+, ARSA-). Ultrasound scan and MRI showed some structure malformations in two fetuses. The two mothers were found to be a balanced carrier: 46,XX, t(11;22)(q23.3;q11.2).

Conclusion

NIPS could effectively identify Emanuel syndrome, which may indicate risks of a parent being a balanced rearrangement carrier. The followed confirmation test for positive sample is necessary and ensures the accuracy of the diagnosis.
Artificial intelligence algorithm to predict the need for critical care in prehospital emergency medical services
Authors: Kang Da-Young , Cho Kyung-Jae , Kwon Oyeon , Kwon Joon-myoung , Jeon Ki-Hyun , Park Hyunho , Lee Yeha , Park Jinsik , Oh Byung-Hee
Published: March 2020

Background

In emergency medical services (EMSs), accurately predicting the severity of a patient’s medical condition is important for the early identification of those who are vulnerable and at high-risk. In this study, we developed and validated an artificial intelligence (AI) algorithm based on deep learning to predict the need for critical care during EMS.

Methods

We conducted a retrospective observation cohort study. The algorithm was established using development data from the Korean national emergency department information system, which were collected during visits in real time from 151 emergency departments (EDs). We validated the algorithm using EMS run sheets from two EDs. The study subjects comprised adult patients who visited EDs. The endpoint was critical care, and we used age, sex, chief complaint, symptom onset to arrival time, trauma, and initial vital signs as the predicted variables.

Results

The number of patients in the development data was 8,981,181, and the validation data comprised 2604 EMS run sheets from two hospitals. The area under the receiver operating characteristic curve of the algorithm to predict the critical care was 0.867 (95% confidence interval, [0.864–0.871]). This result outperformed the Emergency Severity Index (0.839 [0.831–0.846]), Korean Triage and Acuity System (0.824 [0.815–0.832]), National Early Warning Score (0.741 [0.734–0.748]), and Modified Early Warning Score (0.696 [0.691–0.699]).

Conclusions

The AI algorithm accurately predicted the need for the critical care of patients using information during EMS and outperformed the conventional triage tools and early warning scores.
Factors associated with the access and continuum of vaccination services among children aged 12–23 months in the emerging regions of Ethiopia: evidence from the 2016 Ethiopian demography and health survey
Authors: Debie Ayal , Lakew Ayenew Molla
Published: March 2020

Background

Child vaccination is an instrument for saving millions of lives. Only one in twenty children has access to childhood vaccination in hard to reach areas in developing countries. Although studies have been done on childhood vaccination, factors associated with access and continuum were not considered in Ethiopia. Therefore, this study aimed to identify the factors associated with the access and continuum of childhood vaccination in the emerging regions of Ethiopia based on the 2016 EDHS datasets.

Methods

The two-stage stratified sampling technique was used for the survey carried out on 642 mothers of children aged 12–23 months. Access is the provision of services in shorter waiting times and flexibly at all times and alternative methods of communication. Accordingly, continuum of care reflects the extent to which a series of discrete health care events are being experienced by people coherently and interconnected over time. As a result, access and continuum of childhood vaccination are determined using pentavalent-1 and measles vaccination status of children, respectively. A binary logistic regression model was fitted to identify the factors associated with access and continuum of the vaccination.

Results

Overall, 25.1% of children aged 12–23 months received all of the recommended childhood vaccines. Sixty-two percent of children accessed and 46.9% had continuum of childhood vaccination in the emerging regions of Ethiopia. Pentavalent_1 to 3 and BCG to measles dropout rates were 33.42 and 17.53%, respectively. Mothers’ formal education (AOR = 1.99; 95%CI: 1.20, 3.31), ANC (AOR = 4.13; 95%CI: 2.75,6.19), health facility delivery of last birth (AOR = 1.58; 95%CI: 1.19, 2.82), rich wealth (AOR = 1.57; 95%CI: 1.19, 3.14) and average child birth weight (AOR = 1.67; 95%CI: 1.03, 2.72) were positively associated with childhood access to vaccination. On the other hand, mothers’ ANC attendance (AOR = 3.68; 95%CI: 2.48, 5.47) and rich wealth (AOR = 2.07; 95%CI: 1.15, 3.71) were positively associated with the continuum of the services. On the contrary, children with rural resident mothers (AOR = 0.33; 95%CI: 0.14, 0.76) and small birth weight (AOR = 0.51; 95%CI: 0.33, 0.81) were negatively associated to the access and continuum of childhood vaccination, respectively.

Conclusion

Childhood vaccination status was low in the emerging regions of Ethiopia. Variables such as maternal education, birth weight of children, ANC, health facility delivery and wealth were associated with the access and continuum of the vaccination. Therefore, empowering women with education and strengthening maternal healthcare services might enhance childhood vaccination. In addition, the government needs to design a compensation mechanism for the cost relating to childhood vaccination to improve the access and continuum of the service.
Possible influence of Plasmodium/Trypanosoma co-infections on the vectorial capacity of Anopheles mosquitoes
Authors: Fofana Maty , Mitri Christian , Diallo Diawo , Rotureau Brice , Diagne Cheikh Tidiane , Gaye Alioune , Ba Yamar , Dieme Constentin , Diallo Mawlouth , Dia Ibrahima
Published: March 2020

Objective

In tropical Africa, trypanosomiasis is present in endemic areas with many other diseases including malaria. Because malaria vectors become more anthropo-zoophilic under the current insecticide pressure, they may be exposed to trypanosome parasites. By collecting mosquitoes in six study sites with distinct malaria infection prevalence and blood sample from cattle, we tried to assess the influence of malaria-trypanosomiasis co-endemicity on the vectorial capacity of Anopheles.

Results

Overall, all animal infections were due to Trypanosoma vivax (infection rates from 2.6 to 10.5%) in villages where the lowest Plasmodium prevalence were observed at the beginning of the study. An. gambiae s.l. displayed trophic preferences for human-animal hosts. Over 84 mosquitoes, only one was infected by Plasmodium falciparum (infection rate: 4.5%) in a site that displayed the highest prevalence at the beginning of the study. Thus, Anopheles could be exposed to Trypanosoma when they feed on infected animals. No Plasmodium infection was observed in the Trypanosoma-infected animals sites. This can be due to an interaction between both parasites as observed in mice and highlights the need of further studies considering Trypanosoma/Plasmodium mixed infections to better characterize the role of these infections in the dynamic of malaria transmission and the mechanisms involved.
Gamma-aminobutyric acid (GABA) production in milk fermented by specific wild lactic acid bacteria strains isolated from artisanal Mexican cheeses
Authors: Santos-Espinosa Alejandro , Beltrán-Barrientos Lilia María , Reyes-Díaz Ricardo , Mazorra-Manzano Miguel Ángel , Hernández-Mendoza Adrián , González-Aguilar Gustavo Adolfo , Sáyago-Ayerdi Sonia Guadalupe , Vallejo-Cordoba Belinda , González-Córdova Aarón Fernando
Published: March 2020

Purpose

The purpose of this study was to screen wild GABA-producing lactic acid bacteria (LAB) isolated from artisanal Mexican cheeses and to evaluate the fermentation conditions for the enhancement of the GABA yield in fermented milk.

Methods

A qualitative test was carried out to select the GABA-producing LAB and the GABA was quantified by reversed-phase high-performance liquid chromatography in fermented milk (FM). Two inoculum concentrations (107 and 109 CFU/mL), two incubation temperatures (30 and 37 °C), three glutamate concentrations (1, 3, and 5 g/L), and three pyridoxal 5′-phosphate (PLP) concentrations (0, 100, and 200 μM) were assessed to establish suitable conditions to enhance the GABA yield in FM.

Results

Results showed that, from a total of 94 LAB strains, fermented milk with two Lactococcus lactis strains (L-571 or L-572) presented the highest GABA production. However, 37 °C of incubation and 109 CFU/mL and 3 g/L of glutamate significantly led the highest GABA yield in FM with L-571. Further studies are needed to establish the optimum conditions for producing GABA by this strain, and in vivo studies may reveal its potential use as GABA-producing culture.

Conclusion

These results highlight the importance of wild LAB strains in order to generate new alternatives and opportunities in the development of functional foods containing GABA.
Relationship between serum inhibitory activity for IgE and efficacy of Artemisia pollen subcutaneous immunotherapy for allergic rhinitis: a preliminary self-controlled study
Authors: Wang Wenping , Yin Jinshu , Wang Xueyan , Ma Tingting , Lan Tianfei , Song Qingkun , Guo Yifan
Published: March 2020

Background

Biomarkers of clinical efficacy for subcutaneous immunotherapy (SCIT) on allergic rhinitis (AR) have not been identified yet. This study aims to assess the clinical relevance of serum inhibitory activity for IgE by the method of enzyme-linked immunosorbent facilitated antigen binding (ELIFAB) during SCIT for Artemisia-sensitized AR patients.

Methods

19 AR patients were studied who had undergone Artemisia-specific SCIT for more than 8 months (19.68 months on average, ranging from 9 to 33 months). Peripheral bloods were collected before and after treatment. The serum inhibitory activity for IgE was tested by ELIFAB and the level of Artemisia-specific IgG4 (Artemisia-sIgG4) was determined by ELISA. Clinical improvement was evaluated based on the symptom scores and rescue medication use (SMS). The 2-tailed Wilcoxon signed-rank test and the Spearman rank test (two-tailed) were used to analyze data by using SPSS 20.0, with P values of less than 0.05 considered as significant.

Results

The SMS decreased significantly after SCIT (before: 12.79 ± 4.250, after: 6.11 ± 3.828, P = 0.000 < 0.01), the treatment was remarkably effective for 6 patients, effective for 10 and ineffective for 3, along with a total effective rate 84.21%. The serum inhibitory activity for IgE increased significantly after SCIT (P < 0.05) and was correlated with the levels of Artemisia-sIgG4 (r = − 0.501, P = 0.002 < 0.01). The levels of Artemisia-sIgG4 elevated dramatically after treatment (P < 0.01) and were related with the duration of treatment (r = 0.558, P = 0.000 < 0.01). But there was no relationship between clinical improvements and the serum inhibitory activity for IgE.

Conclusions

The serum inhibitory activity for IgE increased significantly after SCIT, however, there was no correlation between it and clinical improvements by statistics analysis. So whether the serum inhibitory activity for IgE can act as biomarker of efficacy for SCIT or not needs to be studied further.
Protective effects of human iPS-derived retinal pigmented epithelial cells on retinal degenerative disease
Authors: Zhu Deliang , Xie Mengyuan , Gademann Fabian , Cao Jixing , Wang Peiyuan , Guo Yonglong , Zhang Lan , Su Ting , Zhang Jun , Chen Jiansu
Published: March 2020

Background

Retinitis pigmentosa (RP) is an inherited retinal disease characterized by progressive loss of photoreceptor cells. This study aim at exploring the effect of retinal pigment epithelium (RPE) derived from human-induced pluripotent stem cell (hiPSC-RPE) on the retina of retinal degeneration 10 (rd10) mice, which are characterized with progressive photoreceptor death.

Methods

We generated RPE from hiPSCs by sequential supplementation with retinal-inducing factors and RPE specification signaling factors. The three-dimensional (3D) spheroid culture method was used to obtain optimal injectable hiPSC-RPE cells. Subretinal space transplantation was conducted to deliver hiPSC-RPE cells into the retina of rd10 mice. Neurotrophic factor secretion from transplanted hiPSC-RPE cells was detected by enzyme-linked immunosorbent assay (ELISA). Immunostaining, Western blotting, electroretinography (ERG), and visual behavior testing were performed to determine the effects of hiPSC-RPE on the retinal visual function in rd10 mice.

Results

Our data demonstrated that hiPSC-RPE cells exhibited classic RPE properties and phenotype after the sequential RPE induction from hiPSCs. hiPSC-RPE cells co-cultured with mouse retinal explants or retinal ganglion cells 5 (RGC5) exhibited decreased apoptosis. The viability and functional properties of hiPSC-RPE cells were enhanced by 3D spheroid culture. Transplanted hiPSC-derived RPE cells were identified by immunostaining with human nuclear antigen staining in the retina of rd10 14 days after subretinal space injection. The pigment epithelium-derived factor level was increased significantly. The expression of CD68, microglial activation marker, reduced after transplantation. The light avoidance behavior and ERG visual function in rd10 mice improved by the transplantation of hiPSC-RPE cells.

Conclusion

Our findings suggest that injectable hiPSC-RPE cells after 3D spheroid culture can rescue the structure and function of photoreceptors by sub-retinal transplantation, which lay the foundation for future clinical cell therapy to treat RP and other retinal degeneration diseases.
Disruption of histamine/H1R signaling pathway represses cardiac differentiation and maturation of human induced pluripotent stem cells
Authors: Zhu Xiaowei , Ding Suling , Li Hui , Zhang Zhiwei , Xu Lili , Wu Jian , Wang Xiangfei , Zou Yunzeng , Yang Xiangdong , Ge Junbo
Published: March 2020

Background

The efficiency and quality of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are crucial for regenerative medicine, disease modeling, drug screening, and the study of the development events during cardiac specification. However, their applications have been hampered by the differentiation efficiency, poor maturation, and high interline variability. Recent studies have reported that histamine plays important roles in hematopoietic stem cell proliferation and neutrophil maturation. However, its roles in cardiovascular tissue regeneration have not been thoroughly investigated. In the current study, we identified a novel physiological function of the histamine/histamine 1 receptor (H1R) signal in regulating the differentiation of hiPSC-CMs and heart development.

Methods

Transgenic zebrafish model (cmlc2: mCherry) was treated with histamine and histamine receptor (HR) antagonists. Histological morphology and ultrastructure of zebrafish heart were measured. Histamine-deficient pregnant mice (HDC−/−) were treated with H1R antagonist (pyrilamine) by intragastric administration from E8.5 to E18.5. Cardiac histological morphology and ultrastructure were analyzed in neonatal mice, and cardiac function in adult mice was measured. In vitro, histamine and HR antagonists were administrated in the culture medium during hiPSC-CM differentiation at different stages. The efficiency and maturation of cardiac differentiation were evaluated. Finally, histamine-treated hiPSC-CMs were transplanted into ischemic myocardium to detect the possible therapeutic effect.

Results

Administration of H1R antagonist during heart development induced cardiac dysplasia in zebrafish. Furthermore, using histidine decarboxylase (HDC) knockout mice, we examined abnormal swelling of myocardial mitochondria and autophagy formation under the condition of endogenous histamine deficiency. Histamine significantly promoted myocardial differentiation from human induced pluripotent stem cells (hiPSCs) with better structure and function via a H1R-dependent signal. The activation of histamine/H1R signaling pathway augmented hiPSC-derived cardiomyocyte (hiPSC-CM) differentiation through the ERK1/2-STAT3 signaling pathway. In addition, histamine-pre-treated hiPSC-CMs were transplanted into the ischemic hearts of myocardial injured mice and exhibited better survival and myocardial protection.

Conclusions

Thus, these findings indicated that histamine/H1R and its downstream signals were not only involved in cardiac differentiation but also provided a better survival environment for stem cell transplanted into ischemic myocardium.
A cooperative construction method for the measurement matrix and sensing dictionary used in compression sensing
Authors: Shen Zhi Yuan , Cheng Xin Miao , Wang Qian Qian
Published: March 2020

A measurement matrix and sensing dictionary are the basic tools for signal compression sampling and reconstruction, respectively, which are important aspects in the field of compression sensing. Previous studies which have divided the measurement matrix and sensing dictionary into two separate processes did not make full use of their inherent intercorrelations. In case of which could be fully utilized, the mutual coherence of the atoms of measurement matrix and sensing dictionary can be further reduced under the premise of ensuring that the original signal information is stored, which could improve the accuracy of signal recovery. The present study attempted to reduce the mutual coherence between the sensing dictionary and measurement matrix by proposing the t-average mutual coherence coefficient as an evaluation index for the sensing dictionary. A mathematical model for co-constructing a measurement matrix and sensing dictionary is firstly proposed. Then, the measurement matrix and sensing dictionary cooperative construction(MSCA)algorithm is proposed to solve the model at a faster rate. The simulated results for sparse signal and binary image show that the proposed algorithm has faster computing speed and higher solution precision than the state-of-the-art construction algorithms.
Salvage therapy for progressive, treatment-refractory or recurrent pediatric medulloblastoma: a systematic review protocol
Authors: Adile Ashley A. , Kameda-Smith Michelle M. , Bakhshinyan David , Banfield Laura , Salim Sabra K. , Farrokhyar Forough , Fleming Adam J.
Published: March 2020

Background

Central nervous system tumors remain the leading cause of cancer-related mortality amongst children with solid tumors, with medulloblastoma (MB) representing the most common pediatric brain malignancy. Despite best current therapies, patients with recurrent MB experience have an alarmingly high mortality rate and often have limited therapeutic options beyond inadequate chemotherapy or experimental clinical trials. Therefore, a systematic review of the literature regarding treatment strategies employed in recurrent pediatric MB will evaluate previous salvage therapies in order to guide future clinical trials. The aim of this systematic review will be to investigate the efficacy and safety of salvage therapies for the management of children with progressive, treatment-refractory, or recurrent MB.

Methods

We will conduct literature searches (from 1995 onwards) in MEDLINE, EMBASE, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and Cochrane Central Register of Controlled Trials. Studies examining the survival and toxicity of therapies administered to treatment-refractory pediatric MB patients will be included. Two reviewers will independently assess the search results based on predefined selection criteria, complete data abstraction, and quality assessment. The primary outcomes of this review will be overall and progression-free survival. Secondary outcomes will include safety and toxicity of each therapy administered. The study methodological quality (or bias) will be appraised using an appropriate tool. Due to the nature of the research question and published literature, we expect large inter-study heterogeneity and therefore will use random effects regression analysis to extract the combined effect. In additional analyses, we will investigate the role of re-irradiation and mono- vs. poly-therapy in recurrent disease, and whether molecular subgrouping of MB influences salvage therapy.

Discussion

This systematic review will provide an overview of the current literature regarding salvage therapies for relapsed MB patients. Investigation of clinically tested therapies for children with recurrent MB has significant implications for clinical practice. By reviewing the efficacy and toxicity of MB salvage therapies, this study will identify effective therapeutic strategies administered to recurrent MB patients and can inform future clinical trials aimed to improve patient survivorship and quality of life.

Systematic review registration

PROSPERO CRD42020167421
Comprehensive evaluation of the metabolic effects of insect meal from Tenebrio molitor L. in growing pigs by transcriptomics, metabolomics and lipidomics
Authors: Meyer Sandra , Gessner Denise K. , Braune Maria S. , Friedhoff Theresa , Most Erika , Höring Marcus , Liebisch Gerhard , Zorn Holger , Eder Klaus , Ringseis Robert
Published: March 2020

Background

The hypothesis was tested that insect meal (IM) as protein source influences intermediary metabolism of growing pigs. To test this, 30 male, 5-week-old crossbred pigs were randomly assigned to 3 groups of 10 pigs each with similar body weights (BW) and fed isonitrogenous diets either without (CON) or with 5% IM (IM5) or 10% IM (IM10) from Tenebrio molitor L. for 4 weeks and key metabolic tissues (liver, muscle, plasma) were analyzed using omics-techniques.

Results

 Most performance parameters did not differ across the groups, whereas ileal digestibilities of most amino acids were 6.7 to 15.6%-units lower in IM10 than in CON (P < 0.05). Transcriptomics of liver and skeletal muscle revealed a total of 166 and 198, respectively, transcripts differentially expressed between IM10 and CON (P < 0.05). Plasma metabolomics revealed higher concentrations of alanine, citrulline, glutamate, proline, serine, tyrosine and valine and a lower concentration of asparagine in IM10 than in CON (P < 0.05). Only one out of fourteen quantifiable amino acid metabolites, namely methionine sulfoxide (MetS), in plasma was elevated by 45% and 71% in IM5 and IM10, respectively, compared to CON (P < 0.05). Plasma concentrations of both, major carnitine/acylcarnitine species and bile acids were not different across groups. Lipidomics of liver and plasma demonstrated no differences in the concentrations of triacylglycerols, cholesterol and the main phospholipids, lysophospholipids and sphingolipids between groups. The percentages of all individual phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species in the liver showed no differences between groups, except those with 6 double bonds (PC 38:6, PC 40:6, PE 38:6, PE 40:6), which were markedly lower in IM10 than in CON (P < 0.05). In line with this, the percentage of C22:6n-3 in hepatic total lipids was lower in IM10 than in the other groups (P < 0.05).

Conclusions

Comprehensive analyzes of the transcriptome, lipidome and metabolome of key metabolic tissues indicate that partial or complete replacement of a conventional protein source by IM in the diet has only a weak impact on the intermediary metabolism of growing pigs. Thus, it is concluded that IM from Tenebrio molitor L. can be used as a dietary source of protein in pigs without causing adverse effects on metabolism.
Swipe-based dating applications use and its association with mental health outcomes: a cross-sectional study
Authors: Holtzhausen Nicol , Fitzgerald Keersten , Thakur Ishaan , Ashley Jack , Rolfe Margaret , Pit Sabrina Winona
Published: March 2020

Background

Swipe-Based Dating Applications (SBDAs) function similarly to other social media and online dating platforms but have the unique feature of “swiping” the screen to either like or dislike another user’s profile. There is a lack of research into the relationship between SBDAs and mental health outcomes.

The aim of this study was to study whether adult SBDA users report higher levels of psychological distress, anxiety, depression, and lower self-esteem, compared to people who do not use SBDAs.

Methods

A cross-sectional online survey was completed by 437 participants. Mental health (MH) outcomes included the Kessler Psychological Distress Scale, Generalised Anxiety Disorder-2 scale, Patient Health Questionnaire-2, and Rosenberg Self-Esteem Scale. Logistic regressions were used to estimate odds ratios of having a MH condition. A repeated measures analysis of variance was used with an apriori model which considered all four mental health scores together in a single analysis. The apriori model included user status, age and gender.

Results

Thirty percent were current SBDA users. The majority of users and past users had met people face-to-face, with 26.1%(60/230) having met > 5 people, and only 22.6%(52/230) having never arranged a meeting. Almost 40%(39.1%; 90/230) had previously entered into a serious relationship with someone they had met on a SBDA. More participants reported a positive impact on self-esteem as a result of SBDA use (40.4%; 93/230), than a negative impact (28.7%;66/230).

Being a SBDA user was significantly associated with having psychological distress (OR = 2.51,95%CI (1.32–4.77)), p = 0.001), and depression (OR = 1.91,95%CI (1.04–3.52), p = 0.037) in the multivariable logistic regression models, adjusting for age, gender and sexual orientation. When the four MH scores were analysed together there was a significant difference (p = 0.037) between being a user or non-user, with SDBA users having significantly higher mean scores for distress (p = 0.001), anxiety (p = 0.015) and depression (p = 0.005). Increased frequency of use and longer duration of use were both associated with greater psychological distress and depression (p < 0.05).

Conclusion

SBDA use is common and users report higher levels of depression, anxiety and distress compared to those who do not use the applications. Further studies are needed to determine causality and investigate specific patterns of SBDA use that are detrimental to mental health.
A computer programming hybrid MOOC for Greek secondary education
Authors: Koutsakas Philippos , Karagiannidis Charalampos , Politis Panagiotis , Karasavvidis Ilias
Published: March 2020

The present paper presents the planning, implementation, observation and analysis of both quantitative and qualitative data of a participatory action research, aiming to study the potential role, value and uses of MOOCs in secondary education. Within the context of this research, a computer programming hybrid MOOC (named PROG15) which combined aspects of both x- and c-MOOCs architecture and pedagogy was designed, implemented and openly provided to Greek Secondary Education students.

The MOOC completion rate (xMOOC dimension) was relatively low, but similar to that of typical xMOOCs for adults, while the degree of collaboration with other students and contribution to the course content (the cMOOC dimension) was relatively average. Before their involvement in the MOOC, the participating students recorded particularly high learning expectations from the specific course and from the collaborative learning model it proposed and quite positive views regarding the impact of this new educational tool on secondary education. Their attitude towards these issues was even more positive after their involvement in the MOOC, while their overall experience was particularly positive.

The above findings, although they resulted from a comparatively small sample of students for the measures of MOOCs and within a very specific educational context, they form a particularly promising background for the utilization of this new tool in secondary education in general and specifically for the preparation of students for higher education studies, in subjects related to computer programming. Of course, further research and investigation is required on the design, development and implementation of the next generation of MOOCs and the practical and theoretical research outcomes resulted from this research can be a quite valuable input.
Polymorphisms in the CTLA4 promoter sequence are associated with canine hypoadrenocorticism
Authors: Boag Alisdair M. , Short Andrea , Kennedy Lorna J. , Syme Hattie , Graham Peter A. , Catchpole Brian
Published: March 2020

Background

Canine hypoadrenocorticism is an immune-mediated endocrinopathy that shares both clinical and pathophysiological similarities with Addison’s disease in humans. Several dog breeds are overrepresented in the disease population, suggesting that a genetic component is involved, although this is likely to be polygenic. Previous research has implicated CTLA4 as a potential susceptibility gene. CTLA4 is an important regulator of T cell function and polymorphisms/mutations in CTLA4 have been associated with a number of autoimmune phenotypes in both humans and rodent models of autoimmunity. The aim of the current study was to undertake a case:control association study of CTLA4 promotor polymorphisms in three dog breeds, cocker spaniels, springer spaniels and West Highland white terriers (WHWT).

Results

Polymorphisms in the CTLA4 promoter were determined by PCR and sequence-based typing. There were significant associations with three promoter haplotypes in cocker spaniels (p = 0.003). A series of SNPs were also associated with hypoadrenocorticism in cocker spaniels and springer spaniels, including polymorphisms in predicted NFAT and SP1 transcription factor binding sites.

Conclusions

This study provides further evidence that CTLA4 promotor polymorphisms are associated with this complex genetic disease and supports an immune mediated aetiopathogenesis of canine hypoadrenocorticism.
Preparation zones for large crustal earthquakes consequent on fault-valve action
Authors: Sibson Richard H.
Published: March 2020

A combination of geological evidence (in the form of hydrothermal vein systems in exhumed fault systems) and geophysical information around active faults supports the localized invasion of near-lithostatically overpressured aqueous fluids into lower portions of the crustal seismogenic zone which commonly extends to depths between 10 and 20 km. This is especially the case for compressional–transpressional tectonic regimes which, beside leading to crustal thickening and dewatering through prograde metamorphism, are also better at containing overpressure and are ‘load-strengthening’ (mean stress rising with increasing shear stress), the most extreme examples being associated with areas undergoing active compressional inversion where existing faults are poorly oriented for reactivation. In these circumstances, ‘fault-valve’ action from ascending overpressured fluids is likely to be widespread with fault failuredual-drivenby a combination of rising fluid pressure in the lower seismogenic zone lowering fault frictional strength, as well as rising shear stress. Localized fluid overpressuring nucleates ruptures at particular sites, but ruptures on large existing faults may extend well beyond the regions of intense overpressure. Postfailure, enhanced fracture along fault rupture zones promotes fluid discharge through the aftershock period, increasing fault frictional strength before hydrothermal sealing occurs and overpressures begin to reaccumulate. The association of rupture nucleation sites with local concentrations of fluid overpressure is consistent with selective invasion of overpressured fluid into the roots of major fault zones and with observed non-uniform spacing of major hydrothermal vein systems along exhumed brittle–ductile shear zones. A range of seismological observations in compressional–transpressional settings are compatible with this hypothesis. There is a tendency for large crustal earthquakes to be associated with extensive (L ~ 100–200 km) low-velocity zones in the lower seismogenic crust, with more localVp/Vsanomalies (L ~ 10–30 km) associated with rupture nucleation sites. In some instances, these low-velocity zones also exhibit high electrical conductivity. Systematic, rigorous evaluation is needed to test how widespread these associations are in different tectonic settings, and to see whether they exhibit time-dependent behaviour before and after major earthquake ruptures.
Femoral derotational osteotomy level does not effect resulting torsion
Authors: Edmonds Eric W. , Fuller Corey B. , Jeffords Megan E. , Farnsworth Christine L. , Lindgren Amelia M. , Pennock Andrew T. , Upasani Vidyadhar V.
Published: March 2020

Purpose

The purpose of this study was to assess the effect on femoral torsion by rotational osteotomies at three different levels as measured in 3D using both the mechanical and the anatomic axes.

Methods

Ten cadaveric lower extremities underwent femoral osteotomies perpendicular to the anatomic axis (AA) at three levels: subtrochanteric, mid-diaphyseal and supracondylar. Parallel pins were placed, one in each femur segment. Computed tomography (CT) was acquired in post-osteotomies neutral position, then post-external rotation of the femur at each osteotomy level. Femurs were returned to neutral rotation between imaging exams. Using 3D CT reconstructions, custom software calculated femoral torsion (angle between the femoral neck axis and the posterior condylar axis in the transverse plane) and pin angle between segments, reoriented to both the mechanical axis (MA) and the AA. Pin angle and torsion change were compared for the three osteotomy locations (regression analysis and ANOVA performed).

Results

Two specimens were omitted (inadequate imaging); the remaining eight donors were 55–90 years old (mean: 64 ± 15 years), CT confirmed no bony defects. All three levels of osteotomy demonstrated significant correlations between the amount of rotation at the osteotomy (pin angle change) and the resulting change in femoral torsion (R square range 0.658–0.847). No significant differences were found between osteotomy level in torsion (MA:p = 0.285, AA:p = 0.156) or in pin angle (MA:p = 0.756, AA:p = 0.753).

Conclusions

Performing a corrective rotational osteotomy orthogonal to the AA achieves the desired effect on MA regardless of location. This suggests that a surgeon’s osteotomy level choice may be based on other risks/benefits of the various techniques.
Comparison of the Biograph Vision and Biograph mCT for quantitative 90Y PET/CT imaging for radioembolisation
Authors: Kunnen Britt , Beijst Casper , Lam Marnix G. E. H. , Viergever Max A. , de Jong Hugo W. A. M.
Published: March 2020

Background

New digital PET scanners with improved time of flight timing and extended axial field of view such as the Siemens Biograph Vision have come on the market and are expected to replace current generation photomultiplier tube (PMT)-based systems such as the Siemens Biograph mCT. These replacements warrant a direct comparison between the systems, so that a smooth transition in clinical practice and research is guaranteed, especially when quantitative values are used for dosimetry-based treatment guidance. The new generation digital PET scanners offer increased sensitivity. This could particularly benefit 90Y imaging, which tends to be very noisy owing to the small positron branching ratio and high random fraction of 90Y. This study aims to determine the ideal reconstruction settings for the digital Vision for quantitative 90Y imaging and to evaluate the image quality and quantification of the digital Vision in comparison with its predecessor, the PMT-based mCT, for 90Y imaging in radioembolisation procedures.

Methods

The NEMA image quality phantom was scanned to determine the ideal reconstruction settings for the Vision. In addition, an anthropomorphic phantom was scanned with both the Vision and the mCT, mimicking a radioembolisation patient with lung, liver, tumour, and extrahepatic deposition inserts. Image quantification of the anthropomorphic phantom was assessed by the lung shunt fraction, the tumour to non-tumour ratio, the parenchymal dose, and the contrast to noise ratio of extrahepatic depositions.

Results

For the Vision, a reconstruction with 3 iterations, 5 subsets, and no post-reconstruction filter is recommended for quantitative 90Y imaging, based on the convergence of the recovery coefficient. Comparing both systems showed that the noise level of the Vision is significantly lower than that of the mCT (background variability of 14% for the Vision and 25% for the mCT at 2.5·103 MBq for the 37 mm sphere size). For quantitative 90Y measures, such as needed in radioembolisation, both systems perform similarly.

Conclusions

We recommend to reconstruct 90Y images acquired on the Vision with 3 iterations, 5 subsets, and no post-reconstruction filter for quantitative imaging. The Vision provides a reduced noise level, but similar quantitative accuracy as compared with its predecessor the mCT.
A review on Zika virus outbreak, epidemiology, transmission and infection dynamics
Authors: Kazmi Syeda Sidra , Ali Waqar , Bibi Nousheen , Nouroz Faisal
Published: March 2020

Zika virus (ZIKV) is a newly emergent relative of the Flaviviridae family and linked to dengue (DENV) and Chikungunya (CHIVKV). ZIKV is one of the rising pathogens promptly surpassing geographical borders. ZIKV infection was characterized by mild disease with fever, headache, rash, arthralgia and conjunctivitis, with exceptional reports of an association with Guillain–Barre syndrome (GBS) and microcephaly. However, since the end of 2015, an increase in the number of GBS associated cases and an astonishing number of microcephaly in fetus and new-borns in Brazil have been related to ZIKV infection, raising serious worldwide public health concerns. ZIKV is transmitted by the bite of infected female mosquitoes of Aedes species. Clarifying such worrisome relationships is, thus, a current unavoidable goal. Here, we extensively described the current understanding of the effects of ZIKV on heath, clinical manifestation, diagnosis and treatment options based on modern, alternative and complementary medicines regarding the disease.