bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prices of medicines for the management of pain, diabetes and cardiovascular diseases in private pharmacies and the national health insurance in Tanzania
Authors: Kirua Rashid Bakari , Temu Mary Justin , Mori Amani Thomas 
Published: November 2020

Abstract

Background
High price is a major challenge limiting access to essential medicines especially among the poorest families in developing countries. The study aims to compare the prices of medicines used in the management of pain, diabetes, and cardiovascular diseases in private pharmacies and the National Health Insurance Fund (NHIF) in Tanzania. Pharmacy prices were also compared with the prices of medicines surveyed nationally by WHO/HAI in 2012.

Method
This cross-sectional study was conducted in Dar es Salaam, Morogoro, Dodoma, and Kilimanjaro regions from February to April 2015. Data were collected from 33 private pharmacies, NHIF and, the HAI database. The study used the WHO/HAI methodology. The analysis was done using non-parametric Kruskal-Wallis and post-hoc pair-wise comparison Dunn test, while a possible change in prices between our survey and 2012 WHO/HAI national survey data was tested using a Sign test in Stata version 16.1.

Results
Twenty-eight essential medicines, of which 9 are used for management of pain, 7 for diabetes, and 12 for cardiovascular diseases were analyzed. There was a significant difference in the mean pharmacy prices of some medicines between the regions and between the pharmacies and NHIF reference prices. NHIF reference prices were higher than the pharmacy prices for 16 of the 28 medicines. There was a significant increase in the prices of 5 out of the 8 medicines that were also nationally surveyed by the WHO/HAI in 2012.

Conclusion
The study found that medicine prices in private pharmacies vary a lot between the study regions, which raises equity concerns. Also, there was a significant difference between the pharmacy and the NHIF reimbursement prices, which may expose patients to fraudulent co-payments or hinder timely access to prescribed medicines. Therefore, effective price control policies and regulations for medicines are warranted in Tanzania.
Improving antitumor efficacy via combinatorial regimens of oncolytic virotherapy
Authors: Zhang Bin , Cheng Ping 
Published: November 2020

Abstract
As a promising therapeutic strategy, oncolytic virotherapy has shown potent anticancer efficacy in numerous pre-clinical and clinical trials. Oncolytic viruses have the capacity for conditional-replication within carcinoma cells leading to cell death via multiple mechanisms, including direct lysis of neoplasms, induction of immunogenic cell death, and elicitation of innate and adaptive immunity. In addition, these viruses can be engineered to express cytokines or chemokines to alter tumor microenvironments. Combination of oncolytic virotherapy with other antitumor therapeutic modalities, such as chemotherapy and radiation therapy as well as cancer immunotherapy can be used to target a wider range of tumors and promote therapeutic efficacy. In this review, we outline the basic biological characteristics of oncolytic viruses and the underlying mechanisms that support their use as promising antitumor drugs. We also describe the enhanced efficacy attributed to virotherapy combined with other drugs for the treatment of cancer.
Recent advances in (chemo-)radiation therapy for rectal cancer: a comprehensive review
Authors: Roeder F. , Meldolesi E. , Gerum S. , Valentini V. , Rödel C. 
Published: November 2020

AbstractThe role of radiation therapy in the treatment of (colo)-rectal cancer has changed dramatically over the past decades. Introduced with the aim of reducing the high rates of local recurrences after conventional surgery, major developments in imaging, surgical technique, systemic therapy and radiation delivery have now created a much more complex environment leading to a more personalized approach. Functional aspects including reduction of acute or late treatment-related side effects, sphincter or even organ-preservation and the unsolved problem of still high distant failure rates have become more important while local recurrence rates can be kept low in the vast majority of patients. This review summarizes the actual role of radiation therapy in different subgroups of patients with rectal cancer, including the current standard approach in different subgroups as well as recent developments focusing on neoadjuvant treatment intensification and/or non-operative treatment approaches aiming at organ-preservation.
Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques
Authors: Natunen Teemu , Martiskainen Henna , Marttinen Mikael , Gabbouj Sami , Koivisto Hennariikka , Kemppainen Susanna , Kaipainen Satu , Takalo Mari , Svobodová Helena , Leppänen Luukas , Kemiläinen Benjam , Ryhänen Simo , Kuulasmaa Teemu , Rahunen Eija , Juutinen Sisko , Mäkinen Petra , Miettinen Pasi , Rauramaa Tuomas , Pihlajamäki Jussi , Haapasalo Annakaisa , Leinonen Ville , Tanila Heikki , Hiltunen Mikko 
Published: November 2020

AbstractBackgroundAlzheimer’s disease (AD) is the most common neurodegenerative disease and type 2 diabetes (T2D) plays an important role in conferring the risk for AD. Although AD and T2D share common features, the common molecular mechanisms underlying these two diseases remain elusive.MethodsMice with different AD- and/or tauopathy-linked genetic backgrounds (APPswe/PS1dE9, Tau P301L and APPswe/PS1dE9/Tau P301L) were fed for 6 months with standard diet or typical Western diet (TWD). After behavioral and metabolic assessments of the mice, the effects of TWD on global gene expression as well as dystrophic neurite and microglia pathology were elucidated. Consequently, mechanistic aspects related to autophagy, cell survival, phagocytic uptake as well as Trem2/Dap12 signaling pathway, were assessed in microglia upon modulation of PI3K-Akt signaling. To evaluate whether the mouse model-derived results translate to human patients, the effects of diabetic phenotype on microglial pathology were assessed in cortical biopsies of idiopathic normal pressure hydrocephalus (iNPH) patients encompassing β-amyloid pathology.ResultsTWD led to obesity and diabetic phenotype in all mice regardless of the genetic background. TWD also exacerbated memory and learning impairment in APPswe/PS1dE9 and Tau P301L mice. Gene co-expression network analysis revealed impaired microglial responses to AD-related pathologies in APPswe/PS1dE9 and APPswe/PS1dE9/Tau P301L mice upon TWD, pointing specifically towards aberrant microglial functionality due to altered downstream signaling of Trem2 and PI3K-Akt. Accordingly, fewer microglia, which did not show morphological changes, and increased number of dystrophic neurites around β-amyloid plaques were discovered in the hippocampus of TWD mice. Mechanistic studies in mouse microglia revealed that interference of PI3K-Akt signaling significantly decreased phagocytic uptake and proinflammatory response. Moreover, increased activity of Syk-kinase upon ligand-induced activation of Trem2/Dap12 signaling was detected. Finally, characterization of microglial pathology in cortical biopsies of iNPH patients revealed a significant decrease in the number of microglia per β-amyloid plaque in obese individuals with concomitant T2D as compared to both normal weight and obese individuals without T2D.ConclusionsCollectively, these results suggest that diabetic phenotype in mice and humans mechanistically associates with abnormally reduced microglial responses to β-amyloid pathology and further suggest that AD and T2D share overlapping pathomechanisms, likely involving altered immune function in the brain.
Measures of depression, generalized anxiety, and posttraumatic stress disorders amongst Yazidi female survivors of ISIS slavery and violence
Authors: Taha Perjan Hashim , Slewa-Younan Shameran 
Published: November 2020

AbstractBackgroundIn 2014 the Islamic State of Iraq and Syria (ISIS) undertook a systematic and deliberate campaign against minority groups and non-Sunni Muslim communities. Amongst some of the greatest atrocities were those targeted towards Yazidi communities and in particular their women. The mental health outcomes of those women held in captivity requires investigation. This study sought to examine and compare levels of general psychological distress, depression, generalized anxiety, posttraumatic stress disorder (PTSD) and self-reported suicidal thoughts and behaviors amongst Yazidi women held in captivity compared with those without such experiences.MethodBetween January to May 2019, a total 348 Yazidi women located in internal displaced person (IDP) camps were interviewed. Of these 348, 139 females were survivors of ISIS captivity. Measures used included Kessler Psychological Distress Scale (K10), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7), and Harvard Trauma Questionnaire part IV (HTQ part IV).ResultsFormerly enslaved Yazidi females showed a significantly higher prevalence of severe mental distress (97.1%; P < 0.001), more severe levels of depression (36.7%; P < 0.001) and general anxiety symptoms (37.4%; P < 0.001), greater rates of PTSD (90.6%; P < 0.001) and higher reported rates of suicidal ideation (38.1%; P < 0.001). Logistic regression analysis undertaken to examine the role of sociodemographic factors as predictors of the assessed mental health conditions. Amongst the formerly enslaved group, no such significance was found, however amongst the non-enslaved group, unemployment was found to statistically determine depression, generalized anxiety and PTSD. Specifically, women from the non-enslaved group who were unemployed were 2.5 times more likely to have depression, 3 times more likely to have generalized anxiety and 3.3 times more likely to have PTSD. Finally, amongst the non-enslaved group, those women with between 5 to 8 siblings were significantly less likely to have depression than those with fewer siblings.ConclusionRates of distress and trauma related symptomology were significantly higher amongst those with history of enslavement. Sociodemographic factors and duration of enslavement do not seem to predict mental disorders among enslaved females.
Exploring active ingredients and function mechanisms of Ephedra-bitter almond for prevention and treatment of Corona virus disease 2019 (COVID-19) based on network pharmacology
Authors: Gao Kai , Song Yan-Ping , Song Anna 
Published: November 2020

AbstractBackgroundCOVID-19 has caused a global pandemic, and there is no wonder drug for epidemic control at present. However, many clinical practices have shown that traditional Chinese medicine has played an important role in treating the outbreak. Among them, ephedra-bitter almond is a common couplet medicine in anti-COVID-19 prescriptions. This study aims to conduct an exploration of key components and mechanisms of ephedra-bitter almond anti-COVID-19 based on network pharmacology.Material and methodsWe collected and screened potential active components of ephedra-bitter almond based on the TCMSP Database, and we predicted targets of the components. Meanwhile, we collected relevant targets of COVID-19 through the GeneCards and CTD databases. Then, the potential targets of ephedra-bitter almond against COVID-19 were screened out. The key components, targets, biological processes, and pathways of ephedra-bitter almond anti-COVID-19 were predicted by constructing the relationship network of herb-component-target (H-C-T), protein-protein interaction (PPI), and functional enrichment. Finally, the key components and targets were docked by AutoDock Vina to explore their binding mode.ResultsEphedra-bitter almond played an overall regulatory role in anti-COVID-19 via the patterns of multi-component-target-pathway. In addition, some key components of ephedra-bitter almond, such as β-sitosterol, estrone, and stigmasterol, had high binding activity to 3CL and ACE2 by molecular docking simulation, which provided new molecular structures for new drug development of COVID-19.ConclusionEphedra-bitter almonds were used to prevent and treat COVID-19 through directly inhibiting the virus, regulating immune responses, and promoting body repair. However, this work is a prospective study based on data mining, and the findings need to be interpreted with caution.
Isolation and characterization of exosomes for cancer research
Authors: Zhu Le , Sun Hao-Ting , Wang Shun , Huang Sheng-Lin , Zheng Yan , Wang Chao-Qun , Hu Bei-Yuan , Qin Wei , Zou Tian-Tian , Fu Yan , Shen Xiao-Tian , Zhu Wen-Wei , Geng Yan , Lu Lu , Jia Hu-liang , Qin Lun-Xiu , Dong Qiong-Zhu 
Published: November 2020

AbstractExosomes are a subset of extracellular vesicles that carry specific combinations of proteins, nucleic acids, metabolites, and lipids. Mounting evidence suggests that exosomes participate in intercellular communication and act as important molecular vehicles in the regulation of numerous physiological and pathological processes, including cancer development. Exosomes are released by various cell types under both normal and pathological conditions, and they can be found in multiple bodily fluids. Moreover, exosomes carrying a wide variety of important macromolecules provide a window into altered cellular or tissue states. Their presence in biological fluids renders them an attractive, minimally invasive approach for liquid biopsies with potential biomarkers for cancer diagnosis, prediction, and surveillance. Due to their biocompatibility and low immunogenicity and cytotoxicity, exosomes have potential clinical applications in the development of innovative therapeutic approaches. Here, we summarize recent advances in various technologies for exosome isolation for cancer research. We outline the functions of exosomes in regulating tumor metastasis, drug resistance, and immune modulation in the context of cancer development. Finally, we discuss prospects and challenges for the clinical development of exosome-based liquid biopsies and therapeutics.
MiRNA-340-5p mediates the functional and infiltrative promotion of tumor-infiltrating CD8+ T lymphocytes in human diffuse large B cell lymphoma
Authors: Xu Yangyang , Liu Zhenchuan , Lv Lixin , Li Ping , Xiu Bing , Qian Wenbin , Liang Aibin 
Published: November 2020

Abstract

Background
CD8+ tumor-infiltrating T lymphocytes (T-TILs) in the tumor microenvironment (TME) play an important role in tumor development, and miRNAs regulate tumor cell interactions with the microenvironment. T-TIL-based tumor immunotherapy provides a promising treatment strategy in diffuse large B-cell lymphoma (DLBCL). MiRNAs tend to be attractive targets for novel antitumor interventions.

Methods
Weighted gene coexpression network analysis (WGCNA), CIBERSORT analysis and Cox regression analysis were used to identify CD8+ T-TIL-related miRNAs. RT-PCR, western blotting, immunohistochemistry (IHC), in situ hybridization (ISH), luciferase reporter assay, coimmunoprecipitation and ubiquitination analyses were used to detect miRNA, mRNA and protein expression and their combination. The viability and function of CD8+ T cells after stimulation were evaluated by enzyme-linked immunosorbent assay (ELISA), cytotoxicity assay, functional avidity assessment, flow cytometry and Cell Counting Kit-8 (CCK-8) assay. DLBCL cell lines, primary cells and a murine xenograft model established with A20 cell injection were used as in vitro and in vivo experimental models.

Results
MiR-340-5p was positively correlated with CD8+ T-TILs in DLBCL patients, and KMT5A was a direct target gene of miR-340-5p. CD8+ T-cell function was significantly enhanced by miR-340-5p mimics both in vitro and in vivo, which was reversed by KMT5A overexpression. We demonstrated that COP1/CD73 was involved in the downstream mechanism of the miR-340-5p/KMT5A axis involving ubiquitination. In vivo, we validated an improved CD8+ T-TIL infiltration rate and tumor suppression with miR-340-5p treatment. Furthermore, miR-340-5p directly regulated the biological activity of DLBCL cells without CD8+ T-cell participation.

Conclusions
MiR-340-5p promoted CD8+ T-TIL infiltration and antitumor function by regulating KMT5A and COP1 and further activating CD73 ubiquitination. MiR-340-5p is potentially a novel target for DLBCL immunotherapy.
ATPase-based implementation of enforced ATP wasting in Saccharomyces cerevisiae for improved ethanol production
Authors: Zahoor Ahmed , Messerschmidt Katrin , Boecker Simon , Klamt Steffen 
Published: November 2020

Abstract

Background
Enforced ATP wasting has been recognized as a promising metabolic engineering strategy to enhance the microbial production of metabolites that are coupled to ATP generation. It also appears to be a suitable approach to improve production of ethanol by Saccharomyces cerevisiae. In the present study, we constructed different S. cerevisiae strains with heterologous expression of genes of the ATP-hydrolyzing F1-part of the ATPase enzyme to induce enforced ATP wasting and quantify the resulting effect on biomass and ethanol formation.

Results
In contrast to genomic integration, we found that episomal expression of the αβγ subunits of the F1-ATPase genes of Escherichia coli in S. cerevisiae resulted in significantly increased ATPase activity, while neither genomic integration nor episomal expression of the β subunit from Trichoderma reesei could enhance ATPase activity. When grown in minimal medium under anaerobic growth-coupled conditions, the strains expressing E. coli’s F1-ATPase genes showed significantly improved ethanol yield (increase of 10% compared to the control strain). However, elevated product formation reduces biomass formation and, therefore, volumetric productivity. We demonstrate that this negative effect can be overcome under growth-decoupled (nitrogen-starved) operation with high and constant biomass concentration. Under these conditions, which mimic the second (production) phase of a two-stage fermentation process, the ATPase-expressing strains showed significant improvement in volumetric productivity (up to 111%) compared to the control strain.

Conclusions
Our study shows that expression of genes of the F1-portion of E. coli’s ATPase induces ATPase activity in S. cerevisiae and can be a promising way to improve ethanol production. This ATP-wasting strategy can be easily applied to other metabolites of interest, whose formation is coupled to ATP generation.
Parasites and vector-borne diseases disseminated by rehomed dogs
Authors: Wright Ian , Jongejan Frans , Marcondes Mary , Peregrine Andrew , Baneth Gad , Bourdeau Patrick , Bowman Dwight D. , Breitschwerdt Edward B. , Capelli Gioia , Cardoso Luís , Dantas-Torres Filipe , Day Michael J. , Dobler Gerhard , Ferrer Lluis , Gradoni Luigi , Irwin Peter , Kempf Volkhard A. J. , Kohn Barbara , Krämer Friederike , Lappin Michael , Madder Maxime , Maggi Ricardo G. , Maia Carla , Miró Guadalupe , Naucke Torsten , Oliva Gaetano , Otranto Domenico , Pennisi Maria Grazia , Penzhorn Barend L. , Pfeffer Martin , Roura Xavier , Sainz Angel , Shin SungShik , Solano-Gallego Laia , Straubinger Reinhard K. , Tasker Séverine , Traub Rebecca , Little Susan 
Published: November 2020

AbstractThe Companion Vector-Borne Diseases (CVBD) World Forum is a working group of leading international experts who meet annually to evaluate current scientific findings and future trends concerning the distribution, pathogenesis, clinical presentation, diagnosis and prevention of vector-borne infections of dogs and cats. At the 14th Symposium of the CVBD World Forum in Trieste, Italy (March 25–28, 2019), we identified the need to (i) bring attention to the potential spread of parasites and vectors with relocated dogs, and (ii) provide advice to the veterinary profession regarding the importance of surveillance and treatment for parasites and vector-borne infections when rehoming dogs. This letter shares a consensus statement from the CVBD World Forum as well as a summary of the problem faced, including the role of veterinary professionals in parasite surveillance, causal issues, and the importance of interdisciplinary cooperation in addressing the problem. To limit opportunities for dissemination of parasites and vectors, whenever possible, underlying problems creating the need for dog rehoming should be addressed. However, when it is necessary to rehome dogs, this should ideally take place in the country and national region of origin. When geographically distant relocation occurs, veterinary professionals have a vital role to play in public education, vigilance for detection of exotic vectors and infections, and alerting the medical community to the risk(s) for pathogen spread. With appropriate veterinary intervention, dog welfare needs can be met without inadvertently allowing global spread of parasites and their vectors.
Multispecies reservoir of Spirometra erinaceieuropaei (Cestoda: Diphyllobothridae) in carnivore communities in north-eastern Poland
Authors: Kondzior Eliza , Kowalczyk Rafał , Tokarska Małgorzata , Borowik Tomasz , Zalewski Andrzej , Kołodziej-Sobocińska Marta 
Published: November 2020

Abstract
Background
Spirometra erinaceieuropaei is a diphylobothriid tapeworm with a complex life-cycle including definitive, intermediate and paratenic (transport) hosts. Multiple routes of parasite transmission often make it impossible to determine what type of host a specific infected animal is considered to be. Spargana larvae cause sparganosis, a severe food- and water-borne disease mainly found in Asia. In Poland, Spirometra sp. was reported in large carnivores in Białowieża Primeval Forest for the first time in the 1940s and was recently confirmed as S. erinaceieuropaei in several mammals and snakes using molecular methods.

Methods
In total, 583 carcasses of 9 carnivore species were necropsied between 2013 and 2019 in north-eastern (NE) Poland. The larvae of S. erinaceieuropaei (spargana) were isolated from subcutaneous tissue, counted, and preserved for genetic analyses. We calculated the prevalence and intensity of infection. To assess spatial variation in S. erinaceieuropaei infection probability in NE Poland, we applied a generalized additive model (GAM) with binomial error distribution. To confirm the species affiliation of isolated larvae, we amplified a partial fragment of the 18S rRNA gene (240 bp in length).

Results
Spirometra larvae were found in the subcutaneous tissue of 172 animals of 7 species and confirmed genetically as S. erinaceieuropaei. The overall prevalence in all studied hosts was 29.5% with a mean infection intensity of 14.1 ± 33.8 larvae per individual. Native European badgers and invasive raccoon dogs were characterized by the highest prevalence. An analysis of parasite spread showed a spatially diversified probability of infection with the highest values occurring in the biodiversity hot spot, Białowieża Primeval Forest.

Conclusions
Our study revealed that various mammal species (both native and non-native) can serve as S. erinaceieuropaei reservoirs. The frequency and level of infection may differ between selected hosts and likely depend on host diversity and habitat structure in a given area. Further studies are needed to assess the distribution of the parasite throughout Europe and the environmental and biological factors influencing infection severity in wild mammals.