bluuebunny/crossref_metadata_2025 huggingface dataset:
Onset PrevenTIon of urinary retention in Orthopaedic Nursing and rehabilitation, OPTION—a study protocol for a randomised trial by a multi-professional facilitator team and their first-line managers’ implementation strategy
Authors: Eldh Ann Catrine , Joelsson-Alm Eva , Wretenberg Per , Hälleberg-Nyman Maria
Published: June 2021

Background

The Onset PrevenTIon of urinary retention in Orthopaedic Nursing and rehabilitation, OPTION, project aims to progress knowledge translation vis-à-vis evidence-based bladder monitoring in orthopaedic care, to decrease the risk of urinary retention, and voiding complications.

Urinary retention is common whilst in hospital for hip surgery. If not properly identified and managed, there is a high risk of complications, some lifelong and life threatening. Although evidence-based guidelines are available, the implementation is lagging.

Methods

Twenty orthopaedic sites are cluster randomised into intervention and control sites, respectively. The intervention sites assemble local facilitator teams among nursing and rehabilitation staff, including first-line managers. The teams receive a 12-month support programme, including face-to-face events and on-demand components to map and bridge barriers to guideline implementation, addressing leadership behaviours and de-implementation of unproductive routines. All sites have access to the guidelines via a public healthcare resource, but the control sites have no implementation support.

Baseline data collection includes structured assessments of urinary retention procedures via patient records, comprising incidence and severity of voiding issues and complications, plus interviews with managers and staff, and surveys to all hip surgery patients with interviews across all sites. Further assessments of context include the Alberta Context Tool used with staff, the 4Ps tool for preference-based patient participation used with patients, and data on economic aspects of urinary bladder care.

During the implementation intervention, all events are recorded, and the facilitators keep diaries.

Post intervention, the equivalent data collections will be repeated twice, and further data will include experiences of the intervention and guideline implementation.

Data will be analysed with statistical analyses, including comparisons before and after, and between intervention and control sites. The qualitative data are subjected to content analysis, and mixed methods are applied to inform both clinical outcomes and the process evaluation, corresponding to a hybrid design addressing effectiveness, experiences, and outcomes.

Discussion

The OPTION trial has a potential to account for barriers and enablers for guideline implementation in the orthopaedic context in general and hip surgery care in particular. Further, it may progress the understanding of implementation leadership by dyads of facilitators and first-line managers.

Trial registration

The study was registered as NCT04700969 with the U.S. National Institutes of Health Clinical Trials Registry on 8 January 2021, that is, prior to the baseline data collection.
Catheter, surgical, or hybrid procedure: what future for atrial fibrillation ablation?
Authors: Nasso Giuseppe , Lorusso Roberto , Moscarelli Marco , De Martino Giuseppe , Dell’Aquila Angelo M. , Motekallemi Arash , Di Bari Nicola , Condello Ignazio , Mastroroberto Pasquale , Santarpino Giuseppe , Speziale Giuseppe
Published: June 2021

Background

The debate on the best treatment strategy for atrial fibrillation (AF) has expanded following the introduction of the so-called “hybrid procedure” that combines minimally invasive epicardial ablation with endocardial catheter ablation. However, the advantage of the hybrid approach over conventional epicardial ablation remains to be established.

Methods

From June 2008 to December 2020, 609 surgical AF ablation procedures through a right minithoracotomy were performed at our institution. From 2008 to 2011, a unipolar radiofrequency (RF) device was used, whereas from 2011 to 2020 a bipolar RF device was used. In addition, between September 2016 and April 2017, 60 patients underwent endocardial completion of epicardial linear ablation. In 30 of these latter patients, surgical isolation of the Bachmann’s bundle (BB) was also performed. Starting from 2021, surviving patients at follow-up were asked to undergo electrocardiographic evaluation and left ventricular function assessment and to complete a questionnaire addressing quality of life and predisposing factors for recurrent AF.

Results

The ablation procedure was completed in all patients. Upon discharge, 30 (4.9%) patients showed recurrence of AF, whereas the remaining patients (95.1%) were in sinus rhythm. All patients in whom a hybrid approach was used either with or without BB ablation were discharged in sinus rhythm. After a mean follow-up of 74 months, 122 (20%) patients developed recurrent AF, including 19.9% in whom a unipolar RF device was used, 21% in whom a bipolar RF device was used, 23% who had undergone a hybrid procedure without BB ablation and 3.3% who had undergone a hybrid procedure with BB ablation. On multivariate analysis, reduced left ventricular ejection fraction, worsening of European Heart Rhythm Association symptom class, and cognitive impairment or depression during follow-up were found to be significantly associated with AF recurrence.

Conclusions

Surgical AF ablation through a right minithoracotomy is safe and may allow the creation of additional linear lesions, particularly in the BB. The placement of adjunctive linear lesions in the setting of a hybrid procedure can be more effective in reducing the risk for AF recurrence than isolated surgical ablation or hybrid ablation without the addition of further linear lesions, with no incremental risk to the patient.
Clinical and molecular characterization of craniofrontonasal syndrome: new symptoms and novel pathogenic variants in the EFNB1 gene
Authors: Bukowska-Olech Ewelina , Gawliński Paweł , Jakubiuk-Tomaszuk Anna , Jędrzejowska Maria , Obersztyn Ewa , Piechota Michał , Bielska Marta , Jamsheer Aleksander
Published: June 2021

Background

Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder that results from pathogenic variants in the EFNB1 gene. The syndrome paradoxically presents with greater severity of the symptoms in heterozygous females than hemizygous males.

Results

We have recruited and screened a female cohort affected with CFNS. Our primary finding was the description of monozygotic twins, i.e., patients 5 and 6, discordant for the CFNS phenotype. Intriguingly, patient 5 presented classical CFNS gestalt, whereas patient 6 manifested only very subtle craniofacial features, not resembling CFNS. Besides, we have expanded the mutational spectrum of the EFNB1 gene through reporting four novel pathogenic variants—p.(Trp12*), p.(Cys64Phe), p.(Tyr73Metfs*86), p.(Glu210*). All those alterations were found applying either targeted NGS of a custom gene panel or PCR followed by Sanger sequencing and evaluated using in silico predictors. Lastly, we have also expanded the CFNS phenotypic spectrum by describing in patient 3 several novel features of the syndrome, such as bifid hallux, bicornuate uterus, and abnormal right ovary segmented into six parts.

Conclusions

We have described the unreported so far differences of the clinical phenotype in the monozygotic twin patients 5 and 6 harboring an identical p.(Glu210*) variant located in the EFNB1 gene. With our finding, we have pointed to an unusual phenomenon of mildly affected females with CFNS, who may not manifest features suggestive of the syndrome. Consequently, this study may be valuable for geneticists consulting patients with craniofacial disorders.
Prevalence and characteristics of mouse mammary tumor virus-like virus associated breast cancer in China
Authors: Wang Fa-liang , Zhang Xiao-li , Yang Ming , Lin Jun , Yue Yong-fang , Li Ya-dan , Wang Xian , Shu Qiang , Jin Hong-chuan
Published: June 2021

Background

Despite extensive molecular epidemiological studies, the prevalence and characteristics of Mouse Mammary Tumor Virus-Like Virus (MMTV-LV) in Chinese women breast cancer are still unclear. Besides, the prevalence of MMTV-LV in women breast cancer tissue varies in different countries and its dependent factors remain inconclusive.

Methods

In the first part of the study, a case-control study was performed. 119 breast cancer samples (84 from Northern China and 35 from Southern China) and 50 breast fibroadenoma specimens were collected from Chinese women patients. MMTV-like env sequence and the homology to MMTV env gene were analysed by semi-nested polymerase chain reaction (PCR). We also explored the association of MMTV-LV prevalence with sample sources (Southern and Northern China) and patients’ clinicopathological characteristics. To investigate the dependent factors of the prevalence of MMTV-LV in breast cancer worldwide, a meta-analysis was conducted in the second part of the study.

Results

We found that the prevalence of MMTV-LV was much higher in breast cancer tissues (17.65%) than that in breast fibroadenoma specimens (4.00%) (P < 0.05). MMTV-LV prevalence in Chinese women breast cancer tissues was significantly different between Southern China (5.71%) and Northern China (22.62%) (P < 0.05). The prevalence of MMTV-LV also associates significantly with expression of HER2, but shows no significant correlation with other parameters. In the meta-analysis, we found that MMTV-LV prevalence in breast cancer tissue was dependent on the distribution of M. domesticus mouse (M. d), M. musculus mouse (M.m) and M.castaneus mouse (M.c) worldwide (P < 0.05).

Conclusion

The distribution of house mice may be a crucial environmental factor that explains the geographic differences in human breast cancer incidence. Our findings may provide a potential avenue of prevention, diagnosis and treatment for breast cancer.
Predictive value of the number of frozen blastocysts in live birth rates of the transferred fresh embryos
Authors: Song Jianyuan , Duan Cuicui , Cai Wangyu , Xu Jian
Published: June 2021

Background

Blastocyst development by extended culture in vitro allows the embryos to ‘select’ themselves, thus successful growth to the blastocyst stage is a reflection of the developmental competence of cleavage stage embryos in a cohort. The study aims to determine whether the number of frozen blastocysts is associated with live birth rates of the transferred fresh embryos.

Method

The retrospective study included 8676 cycles of first fresh embryo transfer from January 2016 to June 2019 at a fertility center of a university hospital. The patients with ≥ 10 oocytes retrieved were divided into three groups according to the number of frozen blastocysts: 0 (group 1), 1–2 (group 2), and ≥ 3 (group 3). The primary outcome measure was the live birth. The secondary outcome measures included clinical pregnancy rates and implantation rates. Logistic regression analysis was also performed.

Results

Live birth rates in patients with ≥ 3 and 1–2 frozen blastocysts were 47.6% and 46.1%, respectively, which were significantly higher than that in patients without blastocyst (36.0%). The clinical pregnancy rate in group 3 was 65.1%, which was also significantly higher than the other two groups (47.0% and 59.2%). The implantation rates were 35.5%, 47.6%, and 56.0% in the three groups, respectively (P < 0.001). Compared with groups of frozen blastocysts, 0 frozen blastocyst yielded a lower rate of live birth (the adjusted odds ratio: 0.526, 95% CI: 0.469, 0.612).

Conclusion

In patients with optimal ovarian response that retrieved ≥ 10 oocytes, fresh embryos transfer followed by having blastocysts frozen is a strong indicator of pregnancy achievement, but the number of frozen blastocysts (if not = 0) has limited value in predicting live birth rates.
Replicative verification of susceptibility genes previously identified from families with segregating developmental dysplasia of the hip
Authors: Xu Xiaowen , Wang Binbin , Chen Yufan , Zhou Weizheng , Li Lianyong
Published: June 2021

Background

Developmental dysplasia of the hip (DDH) is a complex hip joint deformity with effects ranging from acetabulum malformation to irreversible hip dislocation. Previous studies suggest a significant association of four variations, teneurin transmembrane protein 3 (TENM3, OMIM * 610083) (chr4:183721398), heparan sulfate proteoglycan 2 (HSPG2, OMIM * 142461) (chr1:22201470), ATPase plasma membrane Ca2+ transporting 4 (ATP2B4, OMIM * 108732) (chr1:203682345), and prostaglandin F receptor (PTGFR, OMIM * 600563) (chr1:79002214), with DDH susceptibility in families with segregating DDH. However, the association was not validated in sporadic cases and remains controversial. To confirm the association of the reported variations in these four genes with DDH, we conducted replicative verification in 250 sporadic samples with DDH from a Chinese Han population.

Methods

We conducted Sanger sequencing after amplifying the variation sites. The results were compared with the reference sequence from the GRCh37 assembly in UCSC (http://genome.ucsc.edu).

Results

Replication analysis of 250 sporadic samples by Sanger sequencing indicated that the four variations, TENM3 (OMIM * 610083, chr4:183721398), HSPG2 (OMIM * 142461, chr1:22201470), ATP2B4 (OMIM * 108732, chr1:203682345), and PTGFR (OMIM * 600563, chr1:79002214), were not associated with the susceptibility to DDH in the Chinese Han population.

Conclusions

Further studies should be performed to identify other variations of these four genes that are potentially associated with DDH by whole-exome sequencing and the results should be verified in different populations.
Aedes albopictus diversity and relationships in south-western Europe and Brazil by rDNA/mtDNA and phenotypic analyses: ITS-2, a useful marker for spread studies
Authors: Artigas Patricio , Reguera-Gomez Marta , Valero María Adela , Osca David , da Silva Pacheco Raquel , Rosa-Freitas María Goreti , Fernandes Silva-do-Nascimento Teresa , Paredes-Esquivel Claudia , Lucientes Javier , Mas-Coma Santiago , Bargues María Dolores
Published: June 2021

Background

Aedes albopictusis a very invasive mosquito, which has recently colonized tropical and temperate regions worldwide. Of concern is its role in the spread of emerging or re-emerging mosquito-borne diseases.Ae. albopictusfrom south-western Europe and Brazil were studied to infer genetic and phenetic diversity at intra-individual, intra-population and inter-population levels, and to analyse its spread.

Methods

Genotyping was made by rDNA 5.8S-ITS-2 and mtDNAcox1 sequencing to assess haplotype and nucleotide diversity, genetic distances and phylogenetic networks. Male and female phenotyping included combined landmark-and outlined-based geometric morphometrics of wing size and shape.

Results

Specimens from seven populations from Spain, France and Brazil provided 12cox1 and 162 5.8S-ITS-2 haplotypes, with great genetic variability difference between both markers (0.9% vs 31.2%). Fivecox1 haplotypes were shared with other countries, mainly Italy, USA and China, but none was shared between Europe and Brazil. The 5.8S-ITS-2 showed 2–7 intra-individual (mean 4.7) and 16–34 intra-/inter-population haplotypes (24.7), including haplotypes shared between Spain, France and Brazil. A 4.3% of ITS-2 haplotypes were shared, mainly with Italy, USA and Thailand, evidencing worldwide spread and introductions from areas where recent outbreaks ofAe. albopictus-transmitted pathogens occurred. Wing size showed sex differences. Wing shape distinguished between Brazilian and European specimens. Both genetic and morphometric markers showed differences between insular Spain and continental Spain, France and Brazil.

Conclusions

ITS-2 proves to be a useful marker to assessAe. albopictusspread, providing pronouncedly more information thancox1, including intra-individual, intra-population and inter-population levels, furnishing a complete overview of the evolutionary exchanges followed by this mosquito. Wing morphometry proves to be a useful phenotyping marker, allowing to distinguish different populations at the level of both male and female specimens. Results indicate the need for periodic surveillance monitorings to verify that noAe. albopictuswith high virus transmission capacity is introduced into Europe.

Graphical Abstract
Five ixodid tick species including two morphotypes of Rhipicephalus turanicus on nestlings of Eurasian eagle owl (Bubo bubo) from south-eastern Bulgaria
Authors: Sándor Attila D. , Milchev Boyan , Takács Nóra , Kontschán Jenő , Szekeres Sándor , Hornok Sándor
Published: June 2021

Background

Birds are major hosts for many tick species (Acari: Ixodidae, Argasidae), and their role is especially important in transporting ticks over large distances along their seasonal migratory routes. Accordingly, most studies across Europe focus on the importance of avian hosts in tick dispersal, and less emphasis is laid on resident birds and their role in supporting tick life cycles. Eurasian eagle owls (Bubo bubo) exemplify the latter, but all the few studies on their tick infestation were carried out in Western Europe and even those did not involve a large sample size and did not assess infestation prevalence in natural habitats.

Methods

In this study, 320 ixodid ticks were collected from nestlings of Eurasian eagle owls during the period 2018–2020 in Bulgaria in south-eastern Europe. These ticks were analysed morphologically, and selected specimens molecularly based on cytochrome c oxidase subunit I (cox1) gene. The effects of environmental and habitat-related conditions and of the species of prey eaten by eagle owls on tick infestation were also evaluated.

Results

The majority of ticks were identified as adults of Rhipicephalus turanicus (n = 296). In addition, 15 Hyalomma marginatum (three males, 11 nymphs and a larva), one female of Haemaphysalis erinacei and of Ha. punctata, and a nymph of Ixodes ricinus were found. Among R. turanicus, two distinct morphotypes were observed, but they do not form a monophyletic clade in the phylogenetic tree based on the mitochondrial gene cox1. We found a positive correlation between the total number of ticks on nestlings from a particular nest and the number of medium-sized to large prey mammals brought to the nestling owls. Also, the most important predictor for tick abundance was the effect of the extent of arable land (negative), while forests and grasslands contributed less, with no effect observed in case of urbanized areas and watercourses.

Conclusions

The intensity of tick infestation can be high on nestling Eurasian eagle owls (mean intensity 16.59 ticks/nestling). In this study, five different tick species were recorded, among which R. turanicus dominated. Two male morphotypes of this tick species were found, but their morphological differences were not reflected by genetic diversity or phylogenetic clustering. The most important factor determining tick abundance was the land-use structure.

Graphical Abstract
A conserved female-specific larval requirement for MtnB function facilitates sex separation in multiple species of disease vector mosquitoes
Authors: Mysore Keshava , Sun Longhua , Roethele Joseph B. , Li Ping , Igiede Jessica , Misenti Joi K. , Duman-Scheel Molly
Published: June 2021

Background

Clusters of sex-specific loci are predicted to shape the boundaries of the M/m sex-determination locus of the dengue vector mosquito Aedes aegypti, but the identities of these genes are not known. Identification and characterization of these loci could promote a better understanding of mosquito sex chromosome evolution and lead to the elucidation of new strategies for male mosquito sex separation, a requirement for several emerging mosquito population control strategies that are dependent on the mass rearing and release of male mosquitoes. This investigation revealed that the methylthioribulose-1-phosphate dehydratase (MtnB) gene, which resides adjacent to the M/m locus and encodes an evolutionarily conserved component of the methionine salvage pathway, is required for survival of female larvae.

Results

Larval consumption of Saccharomyces cerevisiae (yeast) strains engineered to express interfering RNA corresponding to MtnB resulted in target gene silencing and significant female death, yet had no impact on A. aegypti male survival or fitness. Integration of the yeast larvicides into mass culturing protocols permitted scaled production of fit adult male mosquitoes. Moreover, silencing MtnB orthologs in Aedes albopictus, Anopheles gambiae, and Culex quinquefasciatus revealed a conserved female-specific larval requirement for MtnB among different species of mosquitoes.

Conclusions

The results of this investigation, which may have important implications for the study of mosquito sex chromosome evolution, indicate that silencing MtnB can facilitate sex separation in multiple species of disease vector insects.

Graphical Abstract
Circ-ACTR2 aggravates the high glucose-induced cell dysfunction of human renal mesangial cells through mediating the miR-205-5p/HMGA2 axis in diabetic nephropathy
Authors: Yun Jie , Ren Jinyu , Liu Yufei , Dai Lijuan , Song Liqun , Ma Xiaopeng , Luo Shan , Song Yexu
Published: June 2021

Background

Circular RNAs (circRNAs) have been considered as pivotal biomarkers in Diabetic nephropathy (DN). CircRNA ARP2 actin-related protein 2 homolog (circ-ACTR2) could promote the HG-induced cell injury in DN. However, how circ-ACTR2 acts in DN is still unclear. This study aimed to explore the molecular mechanism of circ-ACTR2 in DN progression, intending to provide support for the diagnostic and therapeutic potentials of circ-ACTR2 in DN.

Methods

RNA expression analysis was conducted by the quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cell growth was measured via Cell Counting Kit-8 and EdU assays. Inflammatory response was assessed by Enzyme-linked immunosorbent assay. The protein detection was performed via western blot. Oxidative stress was evaluated by the commercial kits. The molecular interaction was affirmed through dual-luciferase reporter and RNA immunoprecipitation assays.

Results

Circ-ACTR2 level was upregulated in DN samples and high glucose (HG)-treated human renal mesangial cells (HRMCs). Silencing the circ-ACTR2 expression partly abolished the HG-induced cell proliferation, inflammation and extracellular matrix accumulation and oxidative stress in HRMCs. Circ-ACTR2 was confirmed as a sponge for miR-205-5p. Circ-ACTR2 regulated the effects of HG on HRMCs by targeting miR-205-5p. MiR-205-5p directly targeted high-mobility group AT-hook 2 (HMGA2), and HMGA2 downregulation also protected against cell injury in HG-treated HRMCs. HG-mediated cell dysfunction was repressed by miR-205-5p/HMGA2 axis. Moreover, circ-ACTR2 increased the expression of HMGA2 through the sponge effect on miR-205-5p in HG-treated HRMCs.

Conclusion

All data have manifested that circ-ACTR2 contributed to the HG-induced DN progression in HRMCs by the mediation of miR-205-5p/HMGA2 axis.
Detecting cord blood cell type-specific epigenetic associations with gestational diabetes mellitus and early childhood growth
Authors: Lu Tianyuan , Cardenas Andres , Perron Patrice , Hivert Marie-France , Bouchard Luigi , Greenwood Celia M. T.
Published: June 2021

Background

Epigenome-wide association studies (EWAS) have provided opportunities to understand the role of epigenetic mechanisms in development and pathophysiology of many chronic diseases. However, an important limitation of conventional EWAS is that profiles of epigenetic variability are often obtained in samples of mixed cell types. Here, we aim to assess whether changes in cord blood DNA methylation (DNAm) associated with gestational diabetes mellitus (GDM) exposure and early childhood growth markers occur in a cell type-specific manner.

Results

We analyzed 275 cord blood samples collected at delivery from a prospective pre-birth cohort with genome-wide DNAm profiled by the Illumina MethylationEPIC array. We estimated proportions of seven common cell types in each sample using a cord blood-specific DNAm reference panel. Leveraging a recently developed approach named CellDMC, we performed cell type-specific EWAS to identify CpG loci significantly associated with GDM, or 3-year-old body mass index (BMI) z-score. A total of 1410 CpG loci displayed significant cell type-specific differences in methylation level between 23 GDM cases and 252 controls with a false discovery rate < 0.05. Gene Ontology enrichment analysis indicated that LDL transportation emerged from CpG specifically identified from B-cells DNAm analyses and the mitogen-activated protein kinase pathway emerged from CpG specifically identified from natural killer cells DNAm analyses. In addition, we identified four and six loci associated with 3-year-old BMI z-score that were specific to CD8+ T-cells and monocytes, respectively. By performing genome-wide permutation tests, we validated that most of our detected signals had low false positive rates.

Conclusion

Compared to conventional EWAS adjusting for the effects of cell type heterogeneity, the proposed approach based on cell type-specific EWAS could provide additional biologically meaningful associations between CpG methylation, prenatal maternal GDM or 3-year-old BMI. With careful validation, these findings may provide new insights into the pathogenesis, programming, and consequences of related childhood metabolic dysregulation. Therefore, we propose that cell type-specific analyses are worth cautious explorations.
Comparison of three embolic materials at partial splenic artery embolization for hypersplenism: clinical, laboratory, and radiological outcomes
Authors: Zaitoun Mohamed M. A. , Basha Mohammad Abd Alkhalik , Elsayed Saeed Bakry , El Deen Dalia Salah , Zaitoun Nahla A. , Alturkistani Husain , Farag Alaa A. , Abdelsalam Hassan , El-Kenawy Hossam A. , Mahmoud Nader E. M. , Alayouty Nader Ali , Eladl Ibrahim M. , Shahin Shahenda , Almarzooqi Mohamed-Karji , Hendi Ali M. , El-Morsy Ahmad , Elmokadem Ali Hassan
Published: June 2021

Purpose

To compare effectiveness of three widely used embolic agents in partial splenic embolization (PSE) by analyzing their clinical, laboratory, and radiological outcomes within one year of follow-up.

Materials and methods

This retrospective study examined 179 patients who underwent PSE to manage hypersplenism secondary to cirrhosis. Patients were divided into 3 groups according to embolic agent used. Group 1 (gelatin sponge) included 65 patients, group 2 (embospheres) included 58 patients, and group 3 (PVA) included 56 patients. Clinical, laboratory, and radiological outcomes were compared between groups.

Results

The technical success rate was 100% in all groups. Pain as a major complication was lower in the gelatin sponge group (20%) compared to the embosphere group (31%) and PVA group (32.3%). Major complications other than pain were found in 20.1%; 24.6% in gelatin sponge group, 15.5% in embosphere group and 19.6% in PVA group (p = 0.045). WBCs and platelet counts showed a significant increase after PSE in all groups. Entire splenic volume as measured by computed tomography after PSE showed no significant difference among the 3 groups; however, the volume of infarcted spleen was significantly lower in the gelatin sponge group compared to other two groups (p = 0.001). The splenic span was significantly reduced one-year post-procedure in three groups (p = 0.006), and it was significantly less in embosphere and PVA groups compared to gelatin sponge group (p < 0.05). Recurrent bleeding was higher in gelatin sponge group (p < 0.05).

Conclusions

Permanent embolic materials achieved better laboratory and radiological outcomes than gelatin sponge particles in PSE of cirrhotic hypersplenism patients. However, permanent particles were associated with greater abdominal pain.
Percutaneous administration of allogeneic bone-forming cells for the treatment of delayed unions of fractures: a pilot study
Authors: Jayankura Marc , Schulz Arndt Peter , Delahaut Olivier , Witvrouw Richard , Seefried Lothar , Berg Bruno Vande , Heynen Guy , Sonnet Wendy
Published: June 2021

Background

Overall, 5–10% of fractures result in delayed unions or non-unions, causing major disabilities and a huge socioeconomic burden. Since rescue surgery with autologous bone grafts can cause additional challenges, alternative treatment options have been developed to stimulate a deficient healing process. This study assessed the technical feasibility, safety and preliminary efficacy of local percutaneous implantation of allogeneic bone-forming cells in delayed unions of long bone fractures.

Methods

In this phase I/IIA open-label pilot trial, 22 adult patients with non-infected delayed unions of long bone fractures, which failed to consolidate after 3 to 7 months, received a percutaneous implantation of allogeneic bone-forming cells derived from bone marrow mesenchymal stem cells (ALLOB; Bone Therapeutics) into the fracture site (50 × 106 to 100 × 106 cells). Patients were monitored for adverse events and need for rescue surgery for 30 months. Fracture healing was monitored by Tomographic Union Score (TUS) and modified Radiographic Union Score. The health status was evaluated using the Global Disease Evaluation (GDE) score and pain at palpation using a visual analogue scale. The presence of reactive anti-human leukocyte antigen (HLA) antibodies was evaluated.

Results

During the 6-month follow-up, three serious treatment-emergent adverse events were reported in two patients, of which two were considered as possibly treatment-related. None of the 21 patients in the per-protocol efficacy population needed rescue surgery within 6 months, but 2/21 (9.5%) patients had rescue surgery within 30 months post-treatment. At 6 months post-treatment, an improvement of at least 2 points in TUS was reached in 76.2% of patients, the GDE score improved by a mean of 48%, and pain at palpation at the fracture site was reduced by an average of 61% compared to baseline. The proportion of blood samples containing donor-specific anti-HLA antibodies increased from 8/22 (36.4%) before treatment to 13/22 (59.1%) at 6 months post-treatment, but no treatment-mediated allogeneic immune reactions were observed.

Conclusion

This pilot study showed that the percutaneous implantation of allogeneic bone-forming cells was technically feasible and well tolerated in patients with delayed unions of long bone fractures. Preliminary efficacy evidence is supporting the further development of this treatment.

Trial registration

NCT02020590. Registered on 25 December 2013. ALLOB-DU1, A pilot Phase I/IIa, multicentre, open proof-of-concept study on the efficacy and safetyof allogeneic osteoblastic cells (ALLOB®) implantation in non-infected delayed-union fractures.
Bone marrow-derived mesenchymal stem/stromal cells in patients with acute myeloid leukemia reveal transcriptome alterations and deficiency in cellular vitality
Authors: Zhang Leisheng , Chi Ying , Wei Yimeng , Zhang Wenxia , Wang Fuxu , Zhang Lei , Zou Linglin , Song Baoquan , Zhao Xing , Han Zhongchao
Published: June 2021

Background

State-of-the-art advances have indicated the pivotal characteristics of bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) in hematopoietic microenvironment as well as coordinate contribution to hematological malignancies. However, the panoramic view and detailed dissection of BM-MSCs in patients with acute myeloid leukemia (AML-MSCs) remain obscure.

Methods

For the purpose, we isolated and identified AML-MSCs together with healthy donor-derived HD-MSCs from the bone marrow mononuclear cells (BM-MNCs) by using the standard density gradient centrifugation based on clinical diagnosis and cellular phenotypic analysis. Subsequently, we systematically compared the potential similarities and discrepancy both at the cellular and molecular levels via flow cytometry, multilineage differentiation, chromosome karyotyping, cytokine quantification, and transcriptome sequencing and bioinformatic analysis including single-nucleotide polymorphism (SNP), gene ontology (GO), HeatMap, principal component analysis (PCA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA).

Results

On the one hand, AML-MSCs exhibited undistinguishable signatures in cytomorphology, surface biomarker expression pattern, stemness, chromosome karyotype, and chondrogenesis as HD-MSCs, whereas with impaired adipogenesis, enhanced osteogenesis, and variations in cytokine expression pattern. On the other hand, with the aid of genomic and bioinformatic analyses, we verified that AML-MSCs displayed multidimensional discrepancy with HD-MSCs both in genome-wide gene expression profiling and genetic variation spectrum. Simultaneously, the deficiency of cellular vitality including proliferation and apoptosis in AML-MSCs was largely rescued by JAK-STAT signaling inhibition.

Conclusions

Overall, our findings elucidated that AML-MSCs manifested multifaceted alterations in biological signatures and molecular genetics, and in particular, the deficiency of cellular vitality ascribed to over-activation of JAK-STAT signal, which collectively provided systematic and overwhelming new evidence for decoding the pathogenesis of AML and exploring therapeutic strategies in future.
Pattern formation in a 2-population homogenized neuronal network model
Authors: Kolodina Karina , Wyller John , Oleynik Anna , Sørensen Mads Peter
Published: June 2021

We study pattern formation in a 2-population homogenized neural field model of the Hopfield type in one spatial dimension with periodic microstructure. The connectivity functions are periodically modulated in both the synaptic footprint and in the spatial scale. It is shown that the nonlocal synaptic interactions promote a finite band width instability. The stability method relies on a sequence of wave-number dependent invariants of$2\times 2$2×2-stability matrices representing the sequence of Fourier-transformed linearized evolution equations for the perturbation imposed on the homogeneous background. The generic picture of the instability structure consists of a finite set of well-separated gain bands. In the shallow firing rate regime the nonlinear development of the instability is determined by means of the translational invariant model with connectivity kernels replaced with the corresponding period averaged connectivity functions. In the steep firing rate regime the pattern formation process depends sensitively on the spatial localization of the connectivity kernels: For strongly localized kernels this process is determined by the translational invariant model with period averaged connectivity kernels, whereas in the complementary regime of weak and moderate localization requires the homogenized model as a starting point for the analysis. We follow the development of the instability numerically into the nonlinear regime for both steep and shallow firing rate functions when the connectivity kernels are modeled by means of an exponentially decaying function. We also study the pattern forming process numerically as a function of the heterogeneity parameters in four different regimes ranging from the weakly modulated case to the strongly heterogeneous case. For the weakly modulated regime, we observe that stable spatial oscillations are formed in the steep firing rate regime, whereas we get spatiotemporal oscillations in the shallow regime of the firing rate functions.
Economic burden of lung cancer in Turkey: a cost of illness study from payer perspective
Authors: Cicin Irfan , Oksuz Ergun , Karadurmus Nuri , Malhan Simten , Gumus Mahmut , Yilmaz Ulku , Cansever Levent , Cinarka Halit , Cetinkaya Erdogan , Kiyik Murat , Ozet Ahmet ,   Lung Cancer Report Study Group Turkey, Cicin Irfan , Oksuz Ergun , Karadurmus Nuri , Malhan Simten , Gumus Mahmut , Yilmaz Ulku , Cansever Levent , Cinarka Halit , Cetinkaya Erdogan , Kiyik Murat , Ozet Ahmet ,   on behalf of the Turkish Society of Lung Cancer,   Lung Health and Intensive Care Association,   University of Health Sciences,   Turkish Society of Medical Oncology,   National Cancer Institute,   Turkish Respiratory Society
Published: June 2021

Background

This study was designed to estimate economic burden of lung cancer in Turkey from payer perspective based on expert panel opinion on practice patterns in clinical practice.

Methods

In this cost of illness study, direct medical cost was calculated based on cost items related to outpatient visits, laboratory and radiological tests, hospitalizations/interventions, drug treatment, adverse events and metastasis. Indirect cost was calculated based on lost productivity due to early retirement, morbidity and premature death resulting from the illness, the value of lost productivity due to time spent by family caregivers and cost of formal caregivers.

Results

Cost analysis revealed the total per patient annual direct medical cost for small cell lung cancer to be €8772), for non-small-cell lung cancer to be €10,167. Total annual direct medical cost was €497.9 million, total annual indirect medical cost was €1.1 billion and total economic burden of lung cancer was €1.6 billion. Hospitalization/interventions (41%) and indirect costs (68.6%) were the major cost drivers for total direct costs and the overall economic burden of lung cancer, respectively.

Conclusions

Our findings indicate per patient direct medical costs of small cell lung cancer and non-small-cell lung cancer to be substantial and comparable, indicating the substantial economic burden of lung cancer in terms of both direct and indirect costs. Our findings indicate that hospitalization/interventions cost item and indirect costs were the major cost drivers for total direct costs and the overall economic burden of lung cancer, respectively. Our findings emphasize the potential role of improved cancer prevention and early diagnosis strategies, by enabling cost savings related to drug treatment and metastasis management cost items, in sustainability of cancer treatments.
An image denoising method based on BP neural network optimized by improved whale optimization algorithm
Authors: Wang Chunzhi , Li Min , Wang Ruoxi , Yu Han , Wang Shuping
Published: June 2021

As an important part of smart city construction, traffic image denoising has been studied widely. Image denoising technique can enhance the performance of segmentation and recognition model and improve the accuracy of segmentation and recognition results. However, due to the different types of noise and the degree of noise pollution, the traditional image denoising methods generally have some problems, such as blurred edges and details, loss of image information. This paper presents an image denoising method based on BP neural network optimized by improved whale optimization algorithm. Firstly, the nonlinear convergence factor and adaptive weight coefficient are introduced into the algorithm to improve the optimization ability and convergence characteristics of the standard whale optimization algorithm. Then, the improved whale optimization algorithm is used to optimize the initial weight and threshold value of BP neural network to overcome the dependence in the construction process, and shorten the training time of the neural network. Finally, the optimized BP neural network is applied to benchmark image denoising and traffic image denoising. The experimental results show that compared with the traditional denoising methods such as Median filtering, Neighborhood average filtering and Wiener filtering, the proposed method has better performance in peak signal-to-noise ratio.
A four-quadrant mobility model-based routing protocol for post-earthquake emergency communication network
Authors: Wang Xiaoming , Guo Chang
Published: June 2021

Emergency communication network (ECN) is the important infrastructure to acquire the real-time information after disaster, which is essential for rescue task. However, the existed routing protocols seldom consider the uneven distribution of rescue area so that cannot satisfy the ECN’s requirement and the quality of rescue needs improvement. In this paper, we avoided the traditional linear propulsion from rim to core and proposed a novel four-quadrant mobility model (FQMM), which makes rescuers arrive the most intensity core area first, which can improve the rescue quality. Then, a FQMM-based protocol (FQMMBP) for ECN is designed, which aims to improve the performance of ECN in terms of package delivery rate (PDR) and end-to-end delay. Finally, we set up a virtual earthquake scenario to simulate our proposed protocol in NS2. Results show that the proposed protocol outperforms to the three compared routing protocols, i.e., AODV, DSDV and DSR. The average FDR is improved by 16.31%, and the average reduction of delay is 64.45%, which shows our proposed scheme’s advantages in quality of rescue.
Therapeutic potential of pluripotent stem cell-derived dopaminergic progenitors in Parkinson’s disease: a systematic review protocol
Authors: Karimi Aliasghar , Elmi Mitra , Shiri Zahra , Baharvand Hossein
Published: June 2021

Background

Parkinson’s disease (PD) is the second most common age-dependent neurodegenerative disease that causes motor and cognitive disabilities. This disease is associated with a loss of dopamine content within the putamen, which stems from the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Several approved drugs are available that can effectively treat symptoms of PD. However, long-term medical management is often complicated and does not delay or halt disease progression. Alternatively, cell replacement strategies can address these shortcomings and provide dopamine where it is needed. Although using human pluripotent stem cells (hPSCs) for treatment of PD is a promising alternative, no consensus in the literature pertains to efficacy concerns of hPSC-based therapy for PD. This systematic review aims to investigate the efficacy of primate PSC-derived DA progenitor transplantation to treat PD in preclinical studies.

Methods

This is a systematic review of preclinical studies in animal models of PD. We intend to use the following databases as article sources: MEDLINE (via PubMed), Web of Science, and SCOPUS without any restrictions on language or publication status for all related articles published until the end of April 2021. Two independent reviewers will select the titles and abstracts, extract data from qualifying studies, and assess the risk of bias using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool and the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist. Apomorphine-induced rotation test (APO-IR) and amphetamine-induced rotation test (AMP-IR) are defined as the primary outcomes. The standardized mean difference (SMD) by Hedges’ g method (r) and odds ratio (OR) and related 95% confidence interval (CI) will be calculated to determine the size effect of the treatment. The heterogeneity between studies will be calculated by “I2 inconsistency of values and Cochran’s Q statistical test,” where I2 > 50% and/or p < 0.10 suggests high heterogeneity. Meta-analyses of random effects will be run when appropriate.

Discussion

This study will present an overview of preclinical research on PSCs and their therapeutic effects in PD animal models. This systematic review will point out the strengths and limitations of studies in the current literature while encouraging the funding of new studies by public health managers and governmental bodies.
Application of weighting methods for presenting risk-of-bias assessments in systematic reviews of diagnostic test accuracy studies
Authors: Vali Yasaman , Leeflang Mariska M. G. , Bossuyt Patrick M. M.
Published: June 2021

Background

An assessment of the validity of individual diagnostic accuracy studies in systematic reviews is necessary to guide the analysis and the interpretation of results. Such an assessment is performed for each included study and typically reported at the study level. As studies may differ in sample size and disease prevalence, with larger studies contributing more to the meta-analysis, such a study-level report does not always reflect the risk of bias in the total body of evidence. We aimed to develop improved methods of presenting the risk of bias in the available evidence on diagnostic accuracy of medical tests in systematic reviews, reflecting the relative contribution of the study to the body of evidence in the review.

Methods

We applied alternative methods to represent evaluations with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2), weighting studies according to their relative contribution to the total sample size or their relative effective sample size. We used these methods in four existing systematic reviews of diagnostic accuracy studies, including 9, 13, 22, and 32 studies, respectively.

Results

The risk-of-bias summaries for each domain of the QUADAS-2 checklist changed in all four sets of studies after replacing unit weights for the studies with relative sample sizes or with the relative effective sample size. As an example, the risk of bias was high in the patient selection domain in 31% of the studies in one review, unclear in 23% and low in 46% of studies. Weighting studies according to the relative sample size changed the corresponding proportions to 4%, 4%, and 92%, respectively. The difference between the two weighting methods was small and more noticeable when the reviews included a smaller number of studies with wider range of sample size.

Conclusions

We present an alternative way of presenting the results of risk-of-bias assessments in systematic reviews of diagnostic accuracy studies. Weighting studies according to their relative sample size or their relative effective sample size can be used as more informative summaries of the risk of bias in the total body of available evidence.

Systematic review registrations

Not applicable
A scoping review of researchers’ involvement in health policy dialogue in Africa
Authors: Yimgang Doris , Danhoundo Georges , Kusi-Appiah Elizabeth , Sunder Vijit , Campbell Sandra , Yaya Sanni
Published: June 2021

Background

Improving evidence-informed policy dialogue to support the development and implementation of national health policies is vital, but there is limited evidence on researchers’ roles in policy dialogue processes in Africa. The objective of this study is to examine researchers’ involvement in health policy dialogue in Africa.

Methods

The database search of this scoping review was conducted from inception to January 24, 2021, by an expert searcher/librarian to determine the extent of evidence, barriers, and facilitators of researchers’ involvement in health policy dialogues in Africa. PROSPERO, Wiley Cochrane Library, OVID Medline, OVID EMBASE, OVID PsycINFO, OVID Global Health, EBSCO CINAHL, BASE (Bielefeld Academic Search Engine), and Google/Google Scholar were searched using key words representing the concepts “policy dialogue”, “health”, and “Africa”. No limits were applied. A narrative summary of results was presented.

Results

There were 26 eligible studies representing 21 African countries. Significant discrepancies in researchers’ involvement existed across countries. In 62% of the countries, there was suboptimal involvement of researchers in policy dialogues due to no or partial participation in policy dialogues. Major barriers included limited funding, lack of evidence in the public health field of interest, and skepticism of policymakers. The presence of an interface for exchange, demand for scientific evidence, and donors’ funding were the most reported facilitators.

Conclusions

To improve the uptake of evidence in health policy-making processes, an environment of trust and communication between policymakers and researchers must be established. Policymakers need to demonstrate that they value research, by providing adequate funding, promoting knowledge translation activities, and supporting personal and professional development opportunities for researchers.