bluuebunny/crossref_metadata_2025 huggingface dataset:
Importance of suberin biopolymer in plant function, contributions to soil organic carbon and in the production of bio-derived energy and materials
Authors: Harman-Ware Anne E. , Sparks Samuel , Addison Bennett , Kalluri Udaya C.
Published: March 2021

Suberin is a hydrophobic biopolymer of significance in the production of biomass-derived materials and in biogeochemical cycling in terrestrial ecosystems. Here, we describe suberin structure and biosynthesis, and its importance in biological (i.e., plant bark and roots), ecological (soil organic carbon) and economic (biomass conversion to bioproducts) contexts. Furthermore, we highlight the genomics and analytical approaches currently available and explore opportunities for future technologies to study suberin in quantitative and/or high-throughput platforms in bioenergy crops. A greater understanding of suberin structure and production in lignocellulosic biomass can be leveraged to improve representation in life cycle analysis and techno-economic analysis models and enable performance improvements in plant biosystems as well as informed crop system management to achieve economic and environmental co-benefits.
A survey of insecticide resistance-conferring mutations in multiple targets in Anopheles sinensis populations across Sichuan, China
Authors: Qian Weiping , Liu Nian , Yang Yan , Liu Juan , He Jianhan , Chen Zuhua , Li Mei , Qiu Xinghui
Published: March 2021

Background

Sichuan province is located in the southwest of China, and was previously a malaria-endemic region. Although no indigenous malaria case has been reported since 2011, the number of imported cases is on the rise. Insecticide-based vector control has played a central role in the prevention of malaria epidemics. However, the efficacy of this strategy is gravely challenged by the development of insecticide resistance. Regular monitoring of insecticide resistance is essential to inform evidence-based vector control. Unfortunately, almost no information is currently available on the status of insecticide resistance and associated mechanisms in Anopheles sinensis, the dominant malaria vector in Sichuan. In this study, efforts were invested in detecting the presence and frequency of insecticide resistance-associated mutations in three genes that encode target proteins of several classes of commonly used insecticides.

Methods

A total of 446 adults of An. sinensis, collected from 12 locations across Sichuan province of China, were inspected for resistance-conferring mutations in three genes that respectively encode acetylcholinesterase (AChE), voltage-gated sodium channel (VGSC), and GABA receptor (RDL) by DNA Sanger sequencing.

Results

The G119S mutation in AChE was detected at high frequencies (0.40–0.73). The predominant ace-1 genotype was GGC/AGC (119GS) heterozygotes. Diverse variations at codon 1014 were found in VGSC, leading to three different amino acid substitutions (L1014F/C/S). The 1014F was the predominant resistance allele and was distributed in all 12 populations at varying frequencies from 0.03 to 0.86. The A296S mutation in RDL was frequently present in Sichuan, with 296SS accounting for more than 80% of individuals in six of the 12 populations. Notably, in samples collected from Chengdu (DJY) and Deyang (DYMZ), almost 30% of individuals were found to be resistant homozygotes for all three targets.

Conclusions

Resistance-related mutations in three target proteins of the four main classes of insecticides were prevalent in most populations. This survey reveals a worrisome situation of multiple resistance genotypes in Sichuan malaria vector. The data strengthen the need for regular monitoring of insecticide resistance and establishing a region-customized vector intervention strategy.

Graphical abstract
RNA-seq analysis and gene expression dynamics in the salivary glands of the argasid tick Ornithodoros erraticus along the trophogonic cycle
Authors: Pérez-Sánchez Ricardo , Carnero-Morán Ángel , Soriano Beatriz , Llorens Carlos , Oleaga Ana
Published: March 2021

Background

The argasid tickOrnithodoros erraticusis the main vector of tick-borne human relapsing fever (TBRF) and African swine fever (ASF) in the Mediterranean Basin. Tick salivary proteins secreted to the host at the feeding interface play critical roles for tick feeding and may contribute to host infection by tick-borne pathogens; accordingly, these proteins represent interesting antigen targets for the development of vaccines aimed at the control and prevention of tick infestations and tick-borne diseases.

Methods

To identify these proteins, the transcriptome of the salivary glands ofO. erraticuswasde novoassembled and the salivary gene expression dynamics assessed throughout the trophogonic cycle using Illumina sequencing. The genes differentially upregulated after feeding were selected and discussed as potential antigen candidates for tick vaccines.

Results

Transcriptome assembly resulted in 22,007 transcripts and 18,961 annotated transcripts, which represent 86.15% of annotation success. Most salivary gene expression took place during the first 7 days after feeding (2088 upregulated transcripts), while only a few genes (122 upregulated transcripts) were differentially expressed from day 7 post-feeding onwards. The protein families more abundantly overrepresented after feeding were lipocalins, acid and basic tail proteins, proteases (particularly metalloproteases), protease inhibitors, secreted phospholipases A2, 5′-nucleotidases/apyrases and heme-binding vitellogenin-like proteins. All of them are functionally related to blood ingestion and regulation of host defensive responses, so they can be interesting candidate protective antigens for vaccines.

Conclusions

TheO. erraticussialotranscriptome contains thousands of protein coding sequences—many of them belonging to large conserved multigene protein families—and shows a complexity and functional redundancy similar to those observed in the sialomes of other argasid and ixodid tick species. This high functional redundancy emphasises the need for developing multiantigenic tick vaccines to reach full protection. This research provides a set of promising candidate antigens for the development of vaccines for the control ofO. erraticusinfestations and prevention of tick-borne diseases of public and veterinary health relevance, such as TBRF and ASF. Additionally, this transcriptome constitutes a valuable reference database for proteomics studies of the saliva and salivary glands ofO. erraticus.

Graphical Abstract
Sarcoptic mange in wild ruminants in Spain: solving the epidemiological enigma using microsatellite markers
Authors: Moroni Barbara , Angelone Samer , Pérez Jesús M. , Molinar Min Anna Rita , Pasquetti Mario , Tizzani Paolo , López-Olvera Jorge Ramón , Valldeperes Marta , Granados José Enrique , Lavín Santiago , Mentaberre Gregorio , Camacho-Sillero Leonor , Martínez-Carrasco Carlos , Oleaga Alvaro , Candela Mónica , Meneguz Pier Giuseppe , Rossi Luca
Published: March 2021

Background

In Spain, sarcoptic mange was first described in native wildlife in 1987 in Cazorla Natural Park, causing the death of nearly 95% of the local native population of Iberian ibex (Capra pyrenaica). Since then, additional outbreaks have been identified in several populations of ibex and other wild ungulate species throughout the country. Although the first epizootic outbreak in wildlife was attributed to the introduction of an infected herd of domestic goats, the origin and the cause of its persistence remain unclear. The main aims of this study are to understand (i) the number of Sarcoptes scabiei “strains” circulating in wild ruminant populations in Spain, and (ii) the molecular epidemiological relationships between S. scabiei and its hosts.

Methods

Ten Sarcoptes microsatellite markers were used to characterize the genetic structure of 266 mites obtained from skin scrapings of 121 mangy wild ruminants between 2011 and 2019 from 11 areas in Spain.

Results

Seventy-three different alleles and 37 private alleles were detected. The results of this study show the existence of three genetic strains of S. scabiei in the wild ruminant populations investigated. While two genetic clusters of S. scabiei were host- and geography-related, one cluster included multi-host mites deriving from geographically distant populations.

Conclusions

The molecular epidemiological study of S. scabiei in wild ruminants in Spain indicates that the spreading and persistence of the parasite may be conditioned by host species community composition and the permissiveness of each host population/community to the circulation of individual “strains,” among other factors. Wildlife–livestock interactions and the role of human-driven introduction or trade of wild and domestic animals should be better investigated to prevent further spread of sarcoptic mange in as yet unaffected natural areas of the Iberian Peninsula.

Graphical Abstract
Serious infections in ANCA-associated vasculitides in the biologic era: real-life data from a multicenter cohort of 162 patients
Authors: Thomas Konstantinos , Argyriou Evangelia , Kapsala Noemin , Panagiotopoulos Alexandros , Chalkia Aglaia , Hadziyannis Emilia , Boki Kyriaki , Katsimbri Pelagia , Boumpas Dimitrios T. , Giannou Panagiota , Petras Dimitrios , Vassilopoulos Dimitrios
Published: March 2021

Background

Serious infections (SI) are common in patients with ANCA-associated vasculitides (AAV) like granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Real-life data regarding their incidence and predisposing factors—after the introduction of B cell depleting agents—are limited while data quantifying the risk per treatment modality and year of the disease are missing. Here, we aim to describe in details the incidence and the risk factors for SI in a contemporary AAV cohort.

Methods

Multicenter, observational, retrospective study of AAV patients followed in three tertiary referral centers.

Results

We included 162 patients with GPA (63%) and MPA (37%), males 51.9%, mean age 60.9 years, ΑΝCA+ 86%, and generalized disease 80%. During follow-up (891.2 patient-years, mean 5.4 years), 67 SI were recorded in 50 patients at an incidence rate of 7.5 per 100 patient-years. The SI incidence rate was higher during induction with cyclophosphamide (CYC) compared to rituximab (RTX, 19.3 vs. 11.3 per 100 patient-years, respectively) while it was lower and comparable between RTX and other regimens (5.52 vs. 4.54 per 100 patient-years, respectively) in the maintenance phase. By multivariate analysis, plasmapheresis (PLEX) and/or dialysis was a strong predictor for an SI during the 1st year after diagnosis (OR = 3.16, 95% CI 1.001–9.96) and throughout the follow-up period (OR = 5.21, 95% CI 1.93–14.07). In contrast, a higher baseline BVAS (OR = 1.11, 95% CI 1.01–1.21) was associated with SI only during the 1st year.

Conclusions

In this real-life study of patients with AAV, the SI incidence was higher during CYC compared to RTX induction while there was no difference between RTX and other agents used for maintenance therapy. Higher disease activity at baseline and need for PLEX and/or dialysis were independent factors associated with an SI.
Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis
Authors:   for the Research Committee of Intractable Vasculitis Syndrome and the Research Committee of Intractable Renal Disease of the Ministry of Health, Labour and Welfare of Japan, Ishizaki Jun , Takemori Ayako , Horie Kenta , Hiraoka Daisuke , Suemori Koichiro , Matsumoto Takuya , Sada Ken-ei , Amano Koichi , Harigai Masayoshi , Arimura Yoshihiro , Makino Hirofumi , Takenaka Katsuto , Takemori Nobuaki , Hasegawa Hitoshi
Published: March 2021

Background

We previously identified tissue inhibitor of metalloproteinase 1 (TIMP-1) as a biomarker of disease activity that distinguished mildly or highly active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) from remission 6 months after the initiation of remission-induction therapy. In the present study, we investigated whether TIMP-1 is clinically useful as a predictor of relapse and sustained remission in AAV patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) during maintenance therapy.

Methods

The relationship between serum TIMP-1 levels and clinical outcomes in AAV patients receiving maintenance therapy was assessed using the follow-up data of a Japanese large-cohort study (the RemIT-JAV-RPGN study) and data collected from AAV patients on maintenance therapy in our hospital (the MAAV-EU study).

Results

In the RemIT-JAV RPGN study, serum levels of TIMP-1 were significantly higher in mildly active AAV patients with MPA and GPA 6 months after the initiation of remission-induction therapy than in patients in remission. Regarding maintenance therapy, elevated levels of TIMP-1 in patients in remission were associated with relapse and/or difficulty reducing the glucocorticoid dosage after 6 to 12 months. In the MAAV-EU study, serum levels of TIMP-1 were elevated in relapsed patients 6 months before relapse, earlier than the increase in serum levels of CRP. Analyses of both studies revealed that approximately 30% of patients in remission with a serum TIMP-1 level ≥ 150 ng/mL relapsed after 6 to 12 months, while the majority of patients with a TIMP-1 level < 150 ng/mL sustained remission for at least 12 months.

Conclusion

We herein demonstrated that TIMP-1 is more useful as a predictive biomarker of sustained remission than as a predictor of relapse in maintenance therapy for AAV. TIMP-1 levels < 150 ng/mL are important for the long-term maintenance of remission and may be an indicator for the tapering or cessation of treatment.
Propofol impairs specification of retinal cell types in zebrafish by inhibiting Zisp-mediated Noggin-1 palmitoylation and trafficking
Authors: Fan Xiaoqing , Yang Haoran , Hu Lizhu , Wang Delong , Wang Ruiting , Hao Aijun , Chen Xueran
Published: March 2021

Background

Propofol can have adverse effects on developing neurons, leading to cognitive disorders, but the mechanism of such an effect remains elusive. Here, we aimed to investigate the effect of propofol on neuronal development in zebrafish and to identify the molecular mechanism(s) involved in this pathway.

Methods

The effect of propofol on neuronal development was demonstrated by a series of in vitro and in vivo experiments. mRNA injections, whole-mount in situ hybridization and immunohistochemistry, quantitative real-time polymerase chain reaction, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, 5-ethynyl-2′-deoxyuridine labeling, co-immunoprecipitation, and acyl–biotin exchange labeling were used to identify the potential mechanisms of propofol-mediated zisp expression and determine its effect on the specification of retinal cell types.

Results

Propofol impaired the specification of retinal cell types, thereby inhibiting neuronal and glial cell formation in retinas, mainly through the inhibition of Zisp expression. Furthermore, Zisp promoted the stabilization and secretion of a soluble form of the membrane-associated protein Noggin-1, a specific palmitoylation substrate.

Conclusions

Propofol caused a severe phenotype during neuronal development in zebrafish. Our findings established a direct link between an anesthetic agent and protein palmitoylation in the regulation of neuronal development. This could be used to investigate the mechanisms via which the improper use of propofol might result in neuronal defects.
Stem/progenitor cell in kidney: characteristics, homing, coordination, and maintenance
Authors: Huang Jiewu , Kong Yaozhong , Xie Chao , Zhou Lili
Published: March 2021

Renal failure has a high prevalence and is becoming a public health problem worldwide. However, the renal replacement therapies such as dialysis are not yet satisfactory for its multiple complications. While stem/progenitor cell-mediated tissue repair and regenerative medicine show there is light at the end of tunnel. Hence, a better understanding of the characteristics of stem/progenitor cells in kidney and their homing capacity would greatly promote the development of stem cell research and therapy in the kidney field and open a new route to explore new strategies of kidney protection. In this review, we generally summarize the main stem/progenitor cells derived from kidney in situ or originating from the circulation, especially bone marrow. We also elaborate on the kidney-specific microenvironment that allows stem/progenitor cell growth and chemotaxis, and comment on their interaction. Finally, we highlight potential strategies for improving the therapeutic effects of stem/progenitor cell-based therapy. Our review provides important clues to better understand and control the growth of stem cells in kidneys and develop new therapeutic strategies.
Extracellular vesicles released from hiPSC-derived MSCs attenuate chronic prostatitis/chronic pelvic pain syndrome in rats by immunoregulation
Authors: Peng Xufeng , Guo Hailin , Yuan Ji , Chen Yu , Xia Yuguo , Wang Lin , Wang Ying , Huang Yichen , Xie Hua , Wang Yang , Chen Fang
Published: March 2021

Background

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an intractable nonbacterial inflammatory disease. Mesenchymal stem cells (MSCs) derived from human induced pluripotent stem cells (hiPSCs, iMSCs) have been well documented for the management of inflammatory and autoimmune disorders because of their powerful immunoregulatory and anti-inflammatory capacities. Recently, studies have indicated that extracellular vesicles (EVs) released from iMSCs hold biological functions similar to their parental cells. This study aimed to evaluate the therapeutic efficacy of EVs released from iMSCs (iMSCs-EVs) on CP/CPPS and to explore the underlying mechanisms.

Methods

An experimental autoimmune prostatitis (EAP) model was established in rats by subcutaneous injection of prostate antigen with adjuvant. Then, iMSCs-EVs were injected into EAP rats via the tail vein. Pain behavioral measurements, urodynamic tests, and histopathological analyses were performed at 2, 4, and 6 weeks. The expression of cyclooxygenase-2 (COX-2) was evaluated by immunofluorescence staining and Western blot. The alterations of B cells, Th1 cells, Th2 cells, Th17 cells, and Treg cells in peripheral blood and spleen were analyzed using flow cytometry. The levels of Th1-, Th2-, Th17-, and Treg-related inflammatory mediators were determined by ELISA.

Results

After iMSCs-EVs administration, rats had reduced pain as indicated by the recovery of nociceptive responses to baseline. The voiding pressure was significantly reduced, and the intercontraction interval was increased. The findings of histopathological analysis revealed that iMSCs-EVs could significantly decrease inflammatory cell infiltration and promote basal lamina and glandular epithelial tissue repair. Further studies demonstrated that the overexpression of COX-2 was downregulated by iMSCs-EVs. Meanwhile, the increases in the percentages of Th1 and Th17 cells were dramatically reversed. Also, rats that received iMSCs-EVs showed markedly increased percentages of Treg cells. The levels of those inflammatory mediators showed the same changing tendency.

Conclusions

iMSCs-EVs administration has the potential to ameliorate chronic pelvic pain, improve voiding dysfunction, suppress inflammatory reactions, and facilitate prostatic tissue repair. The functions are mediated by downregulating the overexpression of COX-2 and restoring the imbalance of Th1/Th2 and Treg/Th17 cells.
Development of a pharmacoeconomic registry: an example using hormonal contraceptives
Authors: White Annesha , Srinivasan Meenakshi , Wingate La Marcus , Peasah Samuel , Fleming Marc
Published: March 2021

Background

Disease-specific registries, documenting costs and probabilities from pharmacoeconomic studies along with health state utility values from quality-of-life studies could serve as a resource to guide researchers in evaluating the published literature and in the conduct of future economic evaluations for their own research. Registries cataloging economic evaluations currently exist, however they are restricted by the type of economic evaluations they include. There is a need for intervention-specific registries, that document all types of complete and partial economic evaluations and auxiliary information such as quality of life studies. The objective of this study is to describe the development of a pharmacoeconomic registry and provide best practices using an example of hormonal contraceptives.

Methods

An expert panel consisting of researchers with expertise in pharmacoeconomics and outcomes research was convened and the clinical focus of the registry was finalized after extensive discussion. A list of key continuous, categorical and descriptive variables was developed to capture all relevant data with each variable defined in a data dictionary. A web-based data collection tool was designed to capture and store the resulting metadata. A keyword based search strategy was developed to retrieve the published sources of literature. Finally, articles were screened for relevancy and data was extracted to populate the registry. Expert opinions were taken from the panel at each stage to arrive at consensus and ensure validity of the registry.

Results

The registry focused on economic evaluation literature of hormonal contraceptives used for contraception. The registry consisted of 65 articles comprising of 22 cost-effectiveness analyses, 9 cost-utility analyses, 7 cost-benefit analyses, 1 cost-minimization, 14 cost analyses, 10 cost of illness studies and 2 quality of life studies. The best practices followed in the development of the registry were summarized as recommendations. The completed registry, data dictionary and associated data files can be accessed in the supplementary information files.

Conclusion

This registry is a comprehensive database of economic evaluations, including costs, clinical probabilities and health-state utility estimates. The collated data captured from published information in this registry can be used to identify trends in the literature, conduct systematic reviews and meta-analysis and develop novel pharmacoeconomic models.
Review of the speculative role of co-infections in Streptococcus suis-associated diseases in pigs
Authors: Obradovic Milan R. , Segura Mariela , Segalés Joaquim , Gottschalk Marcelo
Published: March 2021

Streptococcus suisis one of the most important bacterial swine pathogens affecting post-weaned piglets, causing mainly meningitis, arthritis and sudden death. It not only results in severe economic losses but also raises concerns over animal welfare and antimicrobial resistance and remains an important zoonotic agent in some countries. The definition and diagnosis ofS. suis-associated diseases can be complex. ShouldS. suisbe considered a primary or secondary pathogen? The situation is further complicated when referring to respiratory disease, since the pathogen has historically been considered as a secondary pathogen within the porcine respiratory disease complex (PRDC). IsS. suisa respiratory or strictly systemic pathogen?S. suisis a normal inhabitant of the upper respiratory tract, and the presence of potentially virulent strains alone does not guarantee the appearance of clinical signs. Within this unclear context, it has been largely proposed that co-infection with some viral and bacterial pathogens can significantly influence the severity ofS. suis-associated diseases and may be the key to understanding how the infection behaves in the field. In this review, we critically addressed studies reporting an epidemiological link (mixed infections or presence of more than one pathogen at the same time), as well as in vitro and in vivo studies of co-infection ofS. suiswith other pathogens and discussed their limitations and possibilities for improvement and proposed recommendations for future studies.
Is targeting autophagy mechanism in cancer a good approach? The possible double-edge sword effect
Authors: Lim Su Min , Mohamad Hanif Ezanee Azlina , Chin Siok-Fong
Published: March 2021

Autophagy is a conserved cellular process required to maintain homeostasis. The hallmark of autophagy is the formation of a phagophore that engulfs cytosolic materials for degradation and recycling to synthesize essential components. Basal autophagy is constitutively active under normal conditions and it could be further induced by physiological stimuli such as hypoxia, nutrient starvation, endoplasmic reticulum stress,energy depletion, hormonal stimulation and pharmacological treatment. In cancer, autophagy is highly context-specific depending on the cell type, tumour microenvironment, disease stage and external stimuli. Recently, the emerging role of autophagy as a double-edged sword in cancer has gained much attention. On one hand, autophagy suppresses malignant transformation by limiting the production of reactive oxygen species and DNA damage during tumour development. Subsequently, autophagy evolved to support the survival of cancer cells and promotes the tumourigenicity of cancer stem cells at established sites. Hence, autophagy is an attractive target for cancer therapeutics and researchers have been exploiting the use of autophagy modulators as adjuvant therapy. In this review, we present a summary of autophagy mechanism and controlling pathways, with emphasis on the dual-role of autophagy (double-edged sword) in cancer. This is followed by an overview of the autophagy modulation for cancer treatment and is concluded by a discussion on the current perspectives and future outlook of autophagy exploitation for precision medicine.
The effect of age on the incidence of COVID-19 complications: a systematic review and meta-analysis
Authors: Tiruneh Sofonyas Abebaw , Tesema Zemenu Tadese , Azanaw Melkalem Mamuye , Angaw Dessie Abebaw
Published: March 2021

Background

The coronavirus (COVID-19) pandemic was reported from Wuhan, China, on December 31, 2019, and the pandemic was spread to more than 212 countries in the globe. This meta-analysis aimed to assess the pooled incidence of COVID-19 complications and to identify the association between the incidence of complications and age.

Methods

Comprehensive databases, PubMed, Hinari, and Google Scholar, were used to locate potential articles for this review. Data were extracted using Microsoft Excel and imported to the STATA/MP version 16.0 software for analysis. Heterogeneity between studies was assessed using the Cochrane Q test statistics and I2 test, and small study effect was checked using Egger’s statistical test at 5% significant level. Sensitivity analysis was checked. A random-effects model was conducted to estimate the pooled incidence of COVID-19 complications. Univariate meta-regression was conducted to identify the association between the mean ages with each complication.

Results

From the total of 1237 studies, 12 studies were included with a total of 3064 COVID-19 patients. The most complications were acute respiratory distress syndrome (30.93%, 95%CI 21.3–40.6%) followed by acute liver injury (22.8%, 95%CI 14–31.5%), shock (10.9%, 95%CI 7.4–14.4%), acute kidney injury (7%, 95%CI 3.8–10.4%), and acute cardiac injury (6.4%, 95%CI 2.8–15.6%). Univariate meta-regression revealed that as the mean age increased by 1 year, the incidence of acute respiratory distress syndrome, acute kidney injury, acute cardiac injury, and shock increased by a factor of 2.9 (β = 2.9, 95%CI 2.4–3.4, adjusted R2 = 88), 0.4 (β = 0.4, 95%CI 0.04–0.72, adjusted R2 = 54), 1.6 (β = 1.6, 95%CI 1.1–2.1, adjusted R2 = 85), and 1.1 (β = 1.1, 95%CI 0.8–1.5, adjusted R2 = 26) times respectively.

Conclusion

Significant complications of COVID-19 viral infections were reported. Older populations were a high-risk group of developing adverse complications as compared to their counterparts. Health care professionals should give primary attention to those risk group individuals.
Oscillatory behavior of nonlinear Hilfer fractional difference equations
Authors: Yalçın Uzun Tuğba
Published: March 2021

In this paper, we study the oscillation behavior for higher order nonlinear Hilfer fractional difference equations of the type $$\begin{aligned}& \Delta _{a}^{\alpha ,\beta }y(x)+f_{1} \bigl(x,y(x+\alpha ) \bigr) =\omega (x)+f_{2} \bigl(x,y(x+ \alpha ) \bigr),\quad x\in \mathbb{N}_{a+n-\alpha }, \\& \Delta _{a}^{k-(n-\gamma )}y(x) \big|_{x=a+n-\gamma } = y_{k}, \quad k= 0,1,\ldots,n, \end{aligned}$$

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Health-related quality of life of multiple sclerosis patients: a European multi-country study
Authors: Visser Laurenske A. , Louapre Celine , Uyl-de Groot Carin A. , Redekop William K.
Published: March 2021

Background

Inconsistent use of generic and disease-specific health-related quality of life (HRQOL) instruments in multiple sclerosis (MS) studies limits cross-country comparability. The objectives: 1) investigate real-world HRQOL of MS patients using both generic and disease-specific HRQOL instruments in the Netherlands, France, the United Kingdom, Spain, Germany and Italy; 2) compare HRQOL among these countries; 3) determine factors associated with HRQOL.

Methods

A cross-sectional, observational online web-based survey amongst MS patients was conducted in June–October 2019. Patient demographics, clinical characteristics, and two HRQOL instruments: the generic EuroQOL (EQ-5D-5L) and disease-related Multiple Sclerosis Quality of Life (MSQOL)-54, an extension of the generic Short Form-36 (SF-36) was collected. Health utility scores were calculated using country-specific value sets. Mean differences in HRQOL were analysed and predictors of HRQOL were explored in regression analyses.

Results

In total 182 patients were included (the Netherlands: n = 88; France: n = 58; the United Kingdom: n = 15; Spain: n = 10; living elsewhere: n = 11). Mean MSQOL-54 physical and mental composite scores (42.5, SD:17.2; 58.3, SD:21.5) were lower, whereas the SF-36 physical and mental composite scores (46.8, SD:22.6; 53.1, SD:22.5) were higher than reported in previous clinical trials. The mean EQ-5D utility was 0.65 (SD:0.26). Cross-country differences in HRQOL were found. A common predictor of HRQOL was disability status and primary progressive MS.

Conclusions

The effects of MS on HRQOL in real-world patients may be underestimated. Combined use of generic and disease-specific HRQOL instruments enhance the understanding of the health needs of MS patients. Consequent use of the same instruments in clinical trials and observational studies improves cross-country comparability of HRQOL.
Predictors of lost to follow up from antiretroviral therapy among adults in sub-Saharan Africa: a systematic review and meta-analysis
Authors: Kebede Hafte Kahsay , Mwanri Lillian , Ward Paul , Gesesew Hailay Abrha
Published: March 2021

Background

It is known that ‘drop out’ from human immunodeficiency virus (HIV) treatment, the so called lost-to-follow-up (LTFU) occurs to persons enrolled in HIV care services. However, in sub-Saharan Africa (SSA), the risk factors for the LTFU are not well understood.

Methods

We performed a systematic review and meta-analysis of risk factors for LTFU among adults living with HIV in SSA. A systematic search of literature using identified keywords and index terms was conducted across five databases: MEDLINE, PubMed, CINAHL, Scopus, and Web of Science. We included quantitative studies published in English from 2002 to 2019. The Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) was used for methodological validity assessment and data extraction. Mantel Haenszel method using Revman-5 software was used for meta-analysis. We demonstrated the meta-analytic measure of association using pooled odds ratio (OR), 95% confidence interval (CI) and heterogeneity using I2 tests.

Results

Thirty studies met the search criteria and were included in the meta-analysis. Predictors of LTFU were: demographic factors including being: (i) a male (OR = 1.2, 95% CI 1.1–1.3, I2 = 59%), (ii) between 15 and 35 years old (OR = 1.3, 95% CI 1.1–1.3, I2 = 0%), (iii) unmarried (OR = 1.2, 95% CI 1.2–1.3, I2 = 21%), (iv) a rural dweller (OR = 2.01, 95% CI 1.5–2.7, I2 = 40%), (v) unemployed (OR = 1.2, 95% CI 1.04–1.4, I2 = 58%); (vi) diagnosed with behavioral factors including illegal drug use(OR = 13.5, 95% CI 7.2–25.5, I2 = 60%), alcohol drinking (OR = 2.9, 95% CI 1.9–4.4, I2 = 39%), and tobacco smoking (OR = 2.6, 95% CI 1.6–4.3, I2 = 74%); and clinical diagnosis of mental illness (OR = 3.4, 95% CI 2.2–5.2, I2 = 1%), bed ridden or ambulatory functional status (OR = 2.2, 95% CI 1.5–3.1, I2 = 74%), low CD4 count in the last visit (OR = 1.4, 95% CI 1.1–1.9, I2 = 75%), tuberculosis co-infection (OR = 1.2, 95% CI 1.02–1.4, I2 = 66%) and a history of opportunistic infections (OR = 2.5, 95% CI 1.7–2.8, I2 = 75%).

Conclusions

The current review identifies demographic, behavioral and clinical factors to be determinants of LTFU. We recommend strengthening of HIV care services in SSA targeting the aforementioned group of patients.

Trial registration Protocol: the PROSPERO Registration Number is CRD42018114418
Toward mission-dependent long robotic arm enhancement: design method of flying watch attachment allocation based on thrust drivability
Authors: Pan Siyi , Endo Gen
Published: March 2021

Long robotic arms are useful for many applications such as nuclear plant decommissioning, inspection, and firefighting. A major problem for designing and operating long robotic arms is that even small end effector reaction forces and arm gravity can result in large loads on proximal arm joints because of long moment arms. To solve that problem, previous researches focus on specifically designed long arms with certain compensation mechanisms. However, those specialized arm designs are difficult to be applied to existing long robotic arms and to be customized for different missions. To overcome those two drawbacks, we recently proposed a watch-like thrust-generating modular device, called flying watch, with the following two major advantages. Firstly, flying watch can be attached to different kinds of existing long robotic arms and generate thrusts to enhance arm strength. And we have proposed a thrust planning method for flying watch in our previous work. Secondly, since different flying watch attachment allocations can enhance the same robotic arm in different ways, flying watch attachment allocations can be customized to meet the needs of a specific mission. However, up to now, customizing flying watch attachment allocations to different missions is still based on human experience and there is no clear performance metric and automated design method for flying watch attachment allocation. To facilitate mission-dependent long arm enhancement, in this paper, we first propose a novel performance metric, called thrust drivability, which measures the ability of a flying watch attachment allocation to counteract unexpected end effector reaction forces. Then based on thrust drivability, we propose an automated design method, called Allocation Optimization based on Weighted Situations (AOWS), for generating mission-dependent flying watch attachment allocations counteracting both unexpected and known external forces. Simulations show that AOWS based allocation designs can counteract both known and unexpected external forces much better than human-experience-based allocation designs.
Three resected cases of esophageal carcinoma considered as being secondary solid tumors after bone marrow transplantation
Authors: Ninomiya Yamato , Ozawa Soji , Koyanagi Kazuo , Yamamoto Miho , Higuchi Tadashi , Yatabe Kentaro , Tajima Kohei
Published: March 2021

Background

Bone marrow transplantation is now an established treatment for some hematopoietic disorders and hematopoietic malignancies, and secondary solid tumors that develop after bone marrow transplantation have begun to attract attention.

Case presentation

Herein, we report 3 cases of esophageal carcinoma that developed after bone marrow transplantation. Case 1: 40-year-old female received cyclophosphamide and total body irradiation at 12 Gy for acute myeloid leukemia, followed by related bone marrow transplantation. She developed chronic graft-versus-host disease manifesting as pulmonary complications and was administered cyclosporine. Nine years after the transplantation, she was diagnosed as having esophageal carcinoma Stage II and underwent radical surgery. She died of the primary disease 17 months after the surgery. Case 2: A 45-year-old male patient received cyclophosphamide, VP-16 and total body irradiation at 13.2 Gy for acute lymphocytic leukemia, followed by related bone marrow transplantation. He developed chronic graft-versus-host disease manifesting as liver dysfunction. Fifteen years after the transplantation, he was diagnosed as having esophageal carcinoma Stage II and underwent radical surgery. Seven months after the surgery, he died of the primary disease. Case 3: A 30-year-old female patient received cyclophosphamide and total body irradiation at 3 Gy for Fanconi anemia, followed by unrelated bone marrow transplantation. She developed chronic graft-versus-host disease manifesting as a rash and was administered tacrolimus and methotrexate. Fifteen years after the transplantation, she was diagnosed as having esophageal carcinoma Stage III and underwent radical surgery. She died of sepsis 7 months after the surgery.

Conclusion

The esophageal carcinomas developing after bone marrow transplantation had the characteristics of secondary solid tumors in all 3 patients, such as early onset, after total body irradiation, association with chronic graft-versus-host disease, and history of use of immunosuppressive drugs. Patients undergoing bone marrow transplantation require long-term follow-up after the transplantation, considering the possible development of secondary solid tumors, and in regard to secondary solid tumors developing in the gastrointestinal tract, it must be borne in mind that the risk of esophageal carcinoma is particularly high.
Cobalt-containing calcium phosphate induces resorption of biomineralized collagen by human osteoclasts
Authors: de Melo Pereira Daniel , Schumacher Matthias , Habibovic Pamela
Published: March 2021

Background

Biomineralized collagen, consisting of fibrillar type-I collagen with embedded hydroxyapatite mineral, is a bone-mimicking material with potential application as a bone graft substitute. Despite the chemical and structural similarity with bone extracellular matrix, no evidence exists so far that biomineralized collagen can be resorbed by osteoclasts. The aim of the current study was to induce resorption of biomineralized collagen by osteoclasts by a two-fold modification: increasing the calcium phosphate content and introducing cobalt ions (Co
2+
), which have been previously shown to stimulate resorptive activity of osteoclasts.

Methods

To this end, we produced biomineralized collagen membranes and coated them with a cobalt-containing calcium phosphate (CoCaP). Human osteoclasts, derived from CD14+ monocytes from peripheral blood, were differentiated directly on the membranes. Upon fluorescent staining of nuclei, F-actin and tartrate-resistant alkaline phosphatase, the cells were analyzed by laser confocal microscopy. Their resorption capacity was assessed by scanning electron microscopy (SEM), as well as indirectly quantified by measuring the release of calcium ions into cell culture medium.

Results

The CoCaP coating increased the mineral content of the membranes by 4 wt.% and their elastic modulus from 1 to 10 MPa. The coated membranes showed a sustained Co
2+
release in water of about 7 nM per 2 days. In contrast to uncoated membranes, on CoCaP-coated biomineralized collagen membranes, osteoclasts sporadically formed actin rings, and induced formation of resorption lacunae, as observed by SEM and confirmed by increase in Ca
2+
concentration in cell culture medium. The effect of the CoCaP layer on osteoclast function is thought to be mainly caused by the increase of membrane stiffness, although the effect of Co
2+
, which was released in very low amounts, cannot be fully excluded.

Conclusions

This work shows the potential of this relatively simple approach to induce osteoclast resorption of biomineralized collagen, although the extent of osteoclast resorption was limited, and the method needs further optimization. Moreover, the coating method is suitable for incorporating bioactive ions of interest into biomineralized collagen, which is typically not possible using the common biomineralization methods, such as polymer-induced liquid precursor method.
A realist evaluation of a collaborative model to support research co-production in long-term care settings in England: the ExCHANGE protocol
Authors: Wilkinson K. , Day J. , Thompson-Coon J. , Goodwin V. , Liabo K. , Coxon G. , Cox G. , Marriott C. , Lang I. A.
Published: March 2021

Background

Collaborative working between academic institutions and those who provide health and social care has been identified as integral in order to produce acceptable, relevant, and timely research, and for outputs to be useful and practical to implement. The ExCHANGE Collaboration aims to bring together researchers and people working, living in and visiting care homes to build capacity, share and mobilise knowledge, and identify key areas for future research. This paper describes an embedded, formative, realist and theory-driven evaluation which aims to gather information about how successful the ExCHANGE Collaboration is perceived to be in achieving its aims. An existing realist programme theory from the literature – Closer Collaboration – will be supplemented by two substantive theories: Co-production and Knowledge Brokering. This will result in an initial programme theory which will be tested by this formative evaluation to refine understanding of how the ExCHANGE Collaboration works.

Methods

The evaluation will employ mixed qualitative methods, including: analysis of documents such as feedback forms, Knowledge Broker journal/diary, event attendance records, risk and issues logs and other relevant paperwork gathered as part of project delivery; observations of events/activities; and interviews with care home providers and staff, care home residents, residents’ family members, and researchers who are involved in the project (both project design/delivery, and also attendance or involvement in project activities/events). Framework Analysis will be used to interpret the data collected; analysis will be strategic, by focusing on particular key areas of importance in the developing theory of how the ExCHANGE Collaboration might achieve change.

Results

The results of this study are expected to be published in 2022.

Discussion

This evaluation will investigate how successful the ExCHANGE Collaboration is perceived to be in achieving its aims, in what way, in which contexts, and how this may differ for those involved. It will do this by testing an initial programme theory about how the collaboration works, for whom, under which circumstances, and in what way. Findings will be shared through written publication, an end of project learning event for those involved/interested in the project, and a lay summary to be made publically available.
Standard protocol for the PIGRET assay, a high-throughput reticulocyte Pig-a assay with an immunomagnetic separation, used in the interlaboratory trial organized by the Mammalian Mutagenicity Study Group of the Japanese Environmental Mutagen and Genome Society
Authors: Chikura Satsuki , Kimoto Takafumi , Itoh Satoru , Sanada Hisakazu , Muto Shigeharu , Horibata Katsuyoshi
Published: March 2021

The PIGRET assay is one of the Pig-a assays targeting reticulocytes (RETs), an in vivo genotoxicity evaluation method using flow cytometry with endogenous reporter glycosylphosphatidylinositol anchor protein. The PIGRET assay with RETs selectively enriched with anti-CD71 antibodies has several desirable features: high-throughput assay system, low background frequency of mutant cells, and early detection of mutation. To verify the potential and usefulness of the PIGRET assay for short-term testing, an interlaboratory trial involving 16 laboratories organized by the Mammalian Mutagenicity Study Group of the Japanese Environmental Mutagen and Genome Society was conducted. The collaborating laboratories assessed the mutagenicities of a total of 24 chemicals in rats using a single-treatment design and standard protocols for conducting the Pig-a assay on the total red blood cell assay and the PIGRET assay. Here the standard protocol for the PIGRET assay was described in detail.
A theoretical insight in interactions of some chemical compounds as mTOR inhibitors
Authors: Arthur David Ebuka , Akoji Jibrin Noah , Sahnoun Riadh , Okafor Greatman C. , Abdullahi Karimatu Lami , Abdullahi Samira A. , Mgbemena Charles
Published: March 2021

Background

A series of known Food and Drug Administration (FDA) approved anticancer drugs were collected from the literature and docked against mTOR receptor which has been identified in present time as a target for therapeutic anticancer agents. The compounds binding affinity were calculated after minimising the interaction within the binding pockets’ of the mTOR (4JT6) receptor.

Results

The result shows that PF-04691502 ligand best inhibited mTOR while occupying the Adenosine triphosphate (ATP)-binding site on the receptor. PF-04691502 had the best binding affinity with a reported value of − 39.261 kcal/mol, and a hydrogen bond energy contribution of − 8.326 kcal/mol. Polamid529 is also found to have a good binding affinity of − 36.75 kcal/mol with the receptor, but was less significant than that calculated for the reference or standard inhibitor (X6K) used (− 37.862 kcal/mol). Further analysis revealed that Palomid529 formed a more stable complex with the receptor than torin2 and X6K due to the significant hydrogen bond contributions it adds to its overall binding score.

Conclusion

PF-04691502 ligand was identified as the best inhibitor due to its high binding affinity for mTOR and should be considered as the best alternative to the reference inhibitor X6K.