bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractBackgroundDisease-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.MethodsAn 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.ResultsThe 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.ConclusionThis 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

AbstractStreptococcus 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

AbstractAutophagy 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

Abstract
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

AbstractIn 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

Abstract
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

Abstract
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

AbstractLong 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

Abstract
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.