bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of A 2-HP-β-Cyclodextrin Formulation on the Biological Transport and Delivery of Chemotherapeutic PLGA Nanoparticles
Authors: Zheng Kangyu , Huang Zeju , Huang Jiaying , Liu Xiangmei , BAN JUNFENG , Huang Xin , Luo Haosen , Chen Zhicong , Xie Qingchun , Chen Yanzhong , Lu Zhufen 
Published: December 2020

Abstract
Background: The aim of this work was to develop a novel and feasible modification strategy by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodexrin (2-HP-β-CD) for enhancing the biological transport efficiency of paclitaxel (PTX)-loaded poly(lactide-co-glycolide)(PLGA) nanoparticles.Methods: PTX-loaded 2-HP-β-CD-modified PLGA nanoparticles (2-HP-β-CD/PLGA NPs) were prepared using the modified emulsion method. Nano-characteristics, drug release behavior, in vitro cytotoxicity, cellular uptake profiles and in vivo bio-behavior of the nanoparticles were then characterized. Results: Compared with the plain PLGA NPs, 2-HP-β-CD/PLGA NPs exhibited smaller particle sizes (151.03±1.36 nm), increased entrapment efficiency (~49.12% increase) and sustained drug release. When added to A549 human lung cancer cells, compared with PLGA NPs, 2-HP-β-CD/PLGA NPs exhibited higher cytotoxicity in MTT assays and improved cellular uptake efficiency. Pharmacokinetic analysis showed that the AUC value of 2-HP-β-CD/PLGA NPs was 2.4-fold higher than commercial Taxol® and 1.7-fold higher than plain PLGA NPs. In biodistribution assays, 2-HP-β-CD/PLGA NPs exhibited excellent stability in the circulation.Conclusions: The results of this study suggest that formulation contains 2-HP-β-CD can prolong PTX release, enhance drug transpot efficiency and serve as a potential tumor targeting system for PTX.
Immunization Status and Challenges During COVID&nbsp;19 and Associated Factors Among Children Aged 10-23 Months in South Nation Nationality and People Region, Ethiopia 2020
Authors: Tegegne Alemnew Wale , Gidafie Aychew Kassie , Mammo Desalegn Girma , Wassie Semahegn Tilahun , Mengie Zinie Abita 
Published: December 2020

Abstract
BackgroundThe worldwide COVID-19 pandemic is overstressing health systems and Essential health services and vaccination services are disrupted. Immunization is a confirmed gizmo for governing and even eliminating communicable diseases. An immunization operation carried out by the World Health from 1967 to 1977 exterminated the usual existence of smallpox. When the program instigated, the disease endangered for 60% of the world's population and slayed every fourth victim. ObjectiveThis study aims to assess the challenge and status of immunization during Covid 19 and associated factors among children aged 10-23 months south Nation Nationality and People Region Ethiopia. Methods and Materialscommunity-based mixed quantitative and qualitative cross-sectional study was done in southwest Ethiopia. Data was collected using semi-structured questionnaires and in-depth interviews. After that, the data were edited, coded, and move in into Epi info version 7.2 for data management then transported to SPSS version 25 for analysis. The analyzed data were presented by tables, graphs, figures, and text form. Resultaccording to this study the prevalence of incomplete immunization was found to be 809(62.2%) with (95% CI: 59.5, 64.8). in multivariable analysis waiting time at a health facility (AOR=0.04, 95%CI 0.0001,0.004), education (AOR=5.08,95%CI2.31,11.14), place of delivery(AOR=2.34,95%CI 4.96,6.089), fearing of COVID19(AOR=3.62,95%CI 1.72,7.64) and do not understand the separation care of COVID 19 and other health services (AOR=2.85,95%CI1.38,5.9) were significantly associated factorsConclusionThe prevalence of incomplete immunization among children aged 10-23 months was very high in this study as compared to the other studies done in a different pocket of Ethiopia. Consecutively, reducing waiting time at a health facility, avoiding unnecessary fear of COVID 19, and promoting immunization in a different area of southwest Ethiopia along with health extension workers are recommended.
WITHDRAWN: Predictors of Discrimination Towards People Living With HIV/ AIDS Among People Aged 15–49 Years in Ethiopia: A Multilevel Analysis
Authors: Arefaynie Mastewal , Damtie Yitayish , Kefale Bereket , Yalew Melaku 
Published: December 2020

Abstract
BackgroundThere is limited national representative evidence on determinants of discrimination towards people living with HIV/AIDS especially, community level factors are not investigated in Ethiopia. Thus, this study aimed to assess individual and community level factors associated with discrimination towards people living with HIV/AIDS among 15 to 49 age people in Ethiopia.MethodA secondary data analysis was done on the 2016 Ethiopian Demographic and Health Survey dataset which were collected cross-sectional. A total of 25,927 15 to 49 age people were included in the analysis. Multi-level mixed-effect logistic regression analysis was done by STATA version 14.0 to identify individual and community-level factors. Adjusted odds ratio with 95% confidence interval was used to show the strength and direction of association and statistical significance was declared at P value less than 0.05.Resultfrom individual variables, female [AOR=1.47, 95% CI= (1.18, 1.83)], rural dwellers [AOR=1.65, 95% CI= ( 1.23, 2.21)], not attend education[AOR=5.88,95% CI= (4.50, 7.67)], attending primary education [AOR=3.03, 95% CI= (2.40, 3.81)] and attending secondary education [AOR=1.48, 95% CI= ( 1.19, 1.82)] have discrimination attitude towards people living with HIV/AIDS. From community level factors, live in low proportion of educated communities [AOR=1.33, 95% CI= (1.01, 1.65)], live in low proportion of HIV tested communities [AOR=1.61, 95% CI= (1.33, 1.93)] were significantly associated with people living with HIV/AIDS.Conclusionsex of the respondent, religion, educational status, house hold wealth index, marital status, media exposure, internet use, HIV test status, region, residence, community level of education and community level of HIV test status have significant association with HIV related stigma in Ethiopia. Improving educational coverage, improving community level HIV/AIDS test coverage are important interventions to reduce discrimination towards people living with HIV/AIDS in the country.
Enhancement of Osteogenic Induction by LL37&nbsp;Modified With Collagen Binding Domain in Vitro and in Vivo
Authors: Lin Xiaoxuan , Chen Sipeng , Quan Jingjing , Zhang Qi , Liao Muzi , Ma Xinyue , Zheng Yuyan , Mai Sui 
Published: December 2020

Abstract
Bone defect diseases, particularly induced by inflammation, render a challenge for designing ideal drug-loading scaffold that could facilitate bone repairing and eliminate inflammatory pathogens. LL37 is considered as promising alternative loading drug due to its broad-spectrum antimicrobial effect and various bio-functions including osteogenic induction. In this study, we synthesized modified LL37 by adding collagen binding domain (CBD), which aim to provide a specific binding onto collagen and slow-releasing pattern. The modified peptide was proved to exhibit similar biological activities to nature LL37 on rat BMSCs including promoting migration activity, anti-inflammatory activity and osteogenic induction in vitro. Ectopic bone formation experiment further confirmed the angiogenesis and osteoinduction activities in vivo. Collectively, LL37-CBD may be a potential loaded drug for preventative and curative applications in Inflammation-induced bone diseases, exerting dual strategies including anti-inflammatory and osteogenic effects.
WITHDRAWN: OATP1B1 Plays an Important Role in the Transport and Treatment Efficacy of Sorafenib in Hepatocellular Carcinoma
Authors: Wen JinHua , Zhao Menghua 
Published: December 2020

Abstract
BackgroundSorafenib is an anticancer drug used in the treatment of unresectable hepatocellular carcinoma and advanced renal cell carcinoma. It is a substrate for the human OATP1B1. This study aimed to assess the role of OATP1B1 in transportation and uptake of sorafenib in hepatocellular carcinoma and how OATP1B1 affects the pharmacodynamics of sorafenib in vitro and in vivo.MethodsSorafenib transport was measured in HepG2, HepG2-OATP1B1*1a, HepG2-OATP1B1*1b, HepG2-OATP1B1*15, LO2, LO2-OATP1B1*1a, LO2-OATP1B1*1b, and LO2-OATP1B1*15 cells, as well as in HepG2 cells transfected with miR-148a mimics. The cell viability and apoptosis rate of cells treated with sorafenib were evaluated. A liver cancer rat model was established to explore the pharmacokinetics and pharmacodynamics of sorafenib after overexpression of Oatp2.ResultsChanges in expression and genetic mutations of OATP1B1 significantly affected the uptake of sorafenib in HepG2 and LO2 transgenic cells, and sorafenib uptake by HepG2 was higher than that by LO2. Genetic mutations of OATP1B1 significantly affected the cell viability and apoptosis rate of HepG2 cells after sorafenib treatment. Compared to control HepG2 cells, miR-148a mimic-transfected HepG2 cells had decreased sorafenib uptake. The inhibitory effect of sorafenib on cell growth was weakened. PCN significantly increased the expression of Oatp2 and affected the pharmacokinetics of sorafenib. Vascular endothelial growth factor levels and microvascular density in tumor-adjacent tissues decreased significantly, suggesting that increased Oatp2 expression improves the treatment effect of sorafenib in a rat model of liver cancer.ConclusionsOATP1B1 plays an important role in the pharmacokinetics and pharmacodynamics of sorafenib in hepatocellular carcinoma.
Effects of Hypoxia in Intestinal Tumors on Immune Cell Behavior in the Tumor Microenvironment
Authors: Zhang Luping , Wang Shaokun , Wang Yachen , Zhao Weidan , Zhang Yingli , Zhang Nan , Xu Hong 
Published: December 2020

Abstract
Background: Imbalanced nutritional supply and demand in the tumor microenvironment often leads to hypoxia. The subtle interaction between hypoxia and immune cell behavior plays an important role in tumor occurrence and development. However, the functional relationship between hypoxia and the tumor microenvironment remains unclear. Therefore, we aimed to investigate the effect of hypoxia on the intestinal tumor microenvironment.Method: We extracted the names of hypoxia-related genes from the Gene Set Enrichment Analysis (GSEA) database and screened them for those associated with the prognosis of colorectal cancer, with the final list including ALDOB, GPC1, ALDOC, and SLC2A3. Using the sum of the expression levels of these four genes, provided by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the expression coefficients, we developed a hypoxia risk score model. Using the median risk score value, we divided the patients in the two databases into high- and low-risk groups.GSEA was used to compare the enrichment differences between the two groups.We used the CIBERSORT computational method to analyze immune cell infiltration.Finally,the correlation between these five genes and hypoxia was analyzed. Result: The prognosis of the two groups differed significantly, with a higher survival rate in the low-risk group than in the high-risk group.We found that the different risk groups were enriched by immune-related and inflammatory pathways. We identified activated CD4 memory T cells and M0 macrophages in TCGA and GEO databases and found that CCL2/4/5, CSF1, and CX3CL1 contributed toward the increased infiltration rate of these immune cell types. Finally, we observed a positive correlation between the five candidate genes’ expression and the risk of hypoxia, with significant differences in the level of expression of each of these genes between patient risk groups.Conclusion: Overall, our data suggest that hypoxia is associated with the prognosis and rate of immune system infiltration in patients with colorectal cancer. This finding may improve immunotherapy for colorectal cancer.
Clinical Verification of Body Mass Index and Tumor Immune Response in Patients With Breast Cancer Receiving Preoperative Chemotherapy
Authors: Takada Koji , Kashiwagi Shinichiro , Asano Yuka , Goto Wataru , Kouhashi Rika , Yabumoto Akimichi , Ishihara Sae , Morisaki Tamami , Shibutani Masatsune , Tanaka Hiroaki , Hirakawa Kosei , Ohira Masaichi 
Published: December 2020

Abstract
Background: The body mass index (BMI) is commonly used as a simple indicator of obesity; patients with early-stage breast cancer who are obese (OB) per BMI measurements have been shown to have high postoperative recurrence and low survival rates. On the other hand, it has been shown that lymphocytes present in the vicinity of malignant growths that are involved in the tumors’ immune responses influence the efficacy chemotherapy. Therefore, we hypothesized that OB patients with breast cancer have a lower density of tumor-infiltrating lymphocytes (TILs), which may influence the therapeutic effect of preoperative chemotherapy (POC). In this study, we measured pretreatment BMI and TILs in patients with breast cancer who underwent POC, examined the correlations between these two factors, and retrospectively analyzed their therapeutic outcomes and prognoses.Methods: The participants in this study were 421 patients with breast cancer who underwent surgical treatment after POC between February 2007 and January 2019. The patient’s height and weight were measured before POC to calculate the BMI (weight [kg] divided by the square of the height [m2]). According to the World Health Organization categorization, patients who weighed under 18.5 kg/m2 were classified as underweight (UW), those ≥18.5 kg/m2 and >25 kg/m2 were considered normal weight (NW), those ≥25 kg/m2 and <30 kg/m2 were overweight (OW), and those ≥30 kg/m2 were OB. The TILs were those lymphocytes that infiltrated the tumor stroma according to the definition of the International TILs Working Group 2014.Results: The median BMI was 21.9 kg/m2 (range, 14.3–38.5 kg/m2); most patients (244; 64.5%) were NW. Among all 378 patients with breast cancer, the TIL density was significantly lower in OB than in NW and OW patients (vs. NW: p=0.001; vs. OW: p=0.003). Furthermore, when examining patients with each breast cancer type individually, the OS of those with TNBC who had low BMIs was significantly poorer than that of their high-BMI counterparts (log rank p=0.031).Conclusion: Our data did not support the hypothesis that obesity affects the tumor immune microenvironment; however, we showed that being UW does affect the tumor immune microenvironment.
Hyperthermia combined chemotherapy regulates energy metabolism of cancer cells under hypoxic microenvironment
Authors: Shi Fan , Luo Dan , Xuexiao Zhou , Sun Qiaozhen , Shen Pei , Wang Shengzhi 
Published: December 2020

Abstract
Objective: Oral squamous cell carcinoma (OSCC) represents one of the main types of head and neck malignant tumors with high incidence and mortality as well extremely poor prognosis. Hyperthermia (HT) shows great promises for tumor therapy. However it can promote autophagy in tumor microenvironment, which is found to serve as a surviving mechanism for cancer cells. Inhibiting autophagy has been considered as an adjuvant anti-cancer strategy. The present study investigated the role of HT-induced autophagy, while attempting to combine chemotherapy and autophagy blocking with HT in OSCC cells under hypoxia and starvation microenvironment.Materials and methods: HIF-1α and Beclin-1 expression in tissues was determined by immunohistochemistry in 80 OSCC sample pairs. The IC50 of CoCl2, YC-1 (an inhibitor of HIF-1α) and 3-MA (an inhibitor of autophagy) was detected by CCK-8. CoCl2 and complete culture medium without serum were used to achieve the hypoxic and nutrient deficient microenvironment, respectively. HT was performed by heating in a 42 ℃ water bath. The role of HT and YC-1,3-MA on autophagy in vitro were assessed by qRT-PCR and Western blot, and the secretion of high mobility group box1 (HMGB1) was determined by ELISA. The migration and apoptosis rates of cells were assessed by wound healing assay and flow cytometry.Results: We observed that HIF-1α and Beclin1 were highly expressed in OSCC tissues, which were correlated with more advanced malignancy features. CoCl2 could establish hypoxia microenvironment, induce HIF-1α expression with dose-dependence as well as promote cell migration in Cal-27 and SCC-15 cells. Notably, hyperthermia and hypoxia could activate the HIF-1α/BNIP3/Beclin1 signaling pathway and promote HMGB1 secretion, which triggered cytoprotective autophagy to counteract the hypoxia and starvation cellular stresses, as indicated by downregulation of p62 and light chain 3-II (LC3 II). Furthermore, we found that hyperthermia combined YC-1 and/or 3-MA suppressed autophagy and cell migration whereas facilitated cell apoptosis.Conclusion: The present study demonstrated that combined use of YC-1 and 3-MA might increase death of tumor cells in physiological and hyperthermia conditions, which could be relevant with the inhibition of autophagy in OSCC tumor cells under hypoxia microenvironment in vitro.
What is the optimal timing of thawing for transferring vitrified-warmed cleavage stage of slow-growing embryos? A cohort retrospective study
Authors: Geng Lan , Wu Jia-hui , Luo Jia-qi , Shi Yu , Qian Wei-ping , Kallen Amanda , Xia Xi 
Published: December 2020

Abstract
Background

To evaluate optimal thawing time, the early thawing or the routine thawing time, for transferring vitrified-warmed, and cultured overnight cleavage stage of the slow-growing embryos on Day 3 in frozen embryo transfer (FET) cycle.
Methods

This was a retrospective cohort study from January 2017 to July 2018, a total of 705 slow-growing embryos FET cycles in which the patients were aged < 40. Thawing cleavage stage slow-growing Day 3 embryos on either the 2nd or 3rd day after ovulation in natural cycle or the equivalent timing of the artificial cycles.
Results

For slow growing embryos, the clinical pregnancy rate of early thawing group (152/468 (32.5%)) was significantly higher than that of routine thawing group (55/235 (23.4%)) (OR 1.39(CI 1.06–1.81), p = 0.01), while there was no statistically significant difference in pregnancy loss in early thawing group (39/170 (22.9%)) versus in routine thawing group (16/62 (25.8%)) (OR 0.89 (CI 0.53–1.47), p = 0.65).
Conclusion

For slow-growing embryos, higher pregnancy outcomes were shown in early thawing strategy as compared to the routine thawing, which suggested that the improvement of endometrium-embryo synchronism may correct the time difference brought by the slow-growing embryos.
Evaluation of Anti-Bacterial Drugs Using Silkworms Infected by&nbsp;Cutibacterium Acnes
Authors: Matsumoto Yasuhiko , Tateyama Yuki , Sugita Takashi 
Published: December 2020

Abstract
Objective: Cutibacterium acnes is a causative agent of inflammatory skin diseases and systemic infections. Systemic infections caused by C. acnes are difficult to treat, and the development of a systemic infection model for C. acnes would be useful for elucidating the mechanisms of infection and searching for therapeutic agents. In this study, we established a silkworm infection model as a new experimental system to evaluate the interaction between C. acnes and the host, and the efficacy of antibacterial drugs.Results: Silkworms infected with C. acnes died when reared at 37˚C. The dose of injected bacterial cells required to kill half of the silkworms (LD50) was determined under rearing conditions at 37˚C. Silkworms injected with autoclaved C. acnes cells did not die during the study period. The survival time of silkworms injected with C. acnes was prolonged by the injection of antibacterial drugs such as tetracycline and clindamycin. These findings suggest that the silkworm C. acnes infection model can be used to evaluate host toxicity caused by C. acnes and the in vivo efficacy of antimicrobial drugs.
Ambiguities in Neutrophil Extracellular Traps. Ongoing Concepts and Potential Biomarkers for Rheumatoid Arthritis: A Narrative Review
Authors: Trofimenko Andrei S. , Mozgovaya Elena E. , Bedina Svetlana A. , Spasov Alexander A. 
Published: December 2020

Objective:
This study aims to provide consolidation of current research findings as well
as the most important concepts regarding neutrophil extracellular traps (NETs) in rheumatoid arthritis.

Data sources:
Relevant publications from 2004 to 2018 were identified using PubMed, Web of
Science, Scopus, and eLibrary databases. Primary search terms used were “neutrophil extracellular
traps” or “NETs” in combination with “rheumatoid arthritis”.

Data Synthesis:
NETs are distinctive structures promoting capture and non-phagocytic cleavage of
foreign substances. NETs usually consist of thin chromatin fibers decorated with various molecules
of granular, cytosolic, and cytoskeletal origin. NETosis can develop in two ways: either with neutrophil
death or when the viability of the cell prolongs. ROS generation and pronounced protein citrullination
are essential during the initial phase of NETs formation. NETosis is considered to have
certain immunological consequences, including DAMPs-mediated signalling, proinflammatory cytokine
secretion, and contact of extensively modified self and foreign epitopes with antigen-presenting
cells. There are several putative pathogenetic links between NETosis, citrullination, neoepitope
formation, and production of anticitrullined autoantibodies that can strongly influence rheumatoid
arthritis progression. NET-induced vascular injury in rheumatoid arthritis can arise directly from
NETs and indirectly through enhanced thrombosis and atherosclerosis.

Conclusion:
NETs are currently estimated as a possible influential factor of rheumatoid arthritis
initiation and/or progression, especially in the context of vascular involvement. NETs can also
serve as a source of novel antigenic biomarkers for the diagnosis of rheumatoid arthritis.
Déficit de vitamina D en hombres y mujeres con deseo sexual hipoactivo: estudio de prevalencia
Authors: Espitia De La Hoz Franklin José 
Published: December 2020

Objetivo: Establecer la prevalencia del déficit de vitamina D en hombres y mujeres con deseo sexual hipoactivo.
Materiales y métodos: Estudio de corte transversal en el período 2011- 2017 en Armenia, Colombia en una muestra de 107 participantes. Se incluyeron hombres y mujeres con diagnóstico en la consulta externa, de una clínica privada de carácter universitario de referencia, de deseo sexual hipoactivo (DSH). Se les realizó cuantificación de 25-hidroxivitamina D [25(OH)D] (calcidiol) y se consideró que en la historia clínica tuvieran diligenciados los cuestionarios: Decreased Sexual Desire Screener (DSDS) o Prueba del Deseo Sexual Inhibido (PDSI), en las mujeres , y el cuestionario Sexual desire inventory (SDI) en los hombres. Muestreo no probabilístico por conveniencia. Se aplicó estadística descriptiva. Los resultados se exponen de manera agrupada para el total de la población.
Resultados: La prevalencia del déficit de vitamina D fue del 63.55 % (34.57 % en hombres y 28.97 % en mujeres). Los niveles de vitamina D fueron inferiores en los hombres respecto a las mujeres, (34.57 vs. 41.36; p<0.001), con mayor porcentaje de deficiencia (21.49 vs. 14.95 % p<0.007) y de insuficiencia (16.82 vs. 10.28 %, p<0.001).
Conclusiones: Es considerablemente alta la prevalencia (63.55 %) del déficit de vitamina D, en hombres y mujeres con deseo sexual hipoactivo. Se hace necesaria la cuantificación de sus niveles a fin de establecer la suplencia como parte del tratamiento.