bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glaucocalyxin A suppresses multiple myeloma progression in vitro and in vivo through inhibiting the activation of STAT3 signaling pathway
Authors: Li Mei , Chen Cailong , Wang Qian , Jiang Xiaolu , Tan Lanlan , Huang Ying , Zhang Yan , Zhang Zubin 
Published: December 2021

Abstract
Background
Multiple myeloma (MM) is the most common malignant hematological disease in the people worldwide. Glaucocalyxin A (GLA) is a bioactive ent-kauranoid diterpenoid, that is derived from Rabdosia japonica var. GLA has been demonstrated that it had various pharmacological activities, such as anti-coagulation, anti-bacterial, anti-tumor, anti-inflammation, antioxidant activities. Although GLA has effective anti-tumor properties, its effects on multiple myeloma remain unclear. The aim of this study was to examine the possible anti-cancer effects of GLA and their molecular mechanisms on MM cells in vitro and in vivo.

Methods
To evaluate the role of GLA on the proliferation of MM cells in vitro and in vivo, we used MTT method to detect the role of GLA on the proliferation of MM cells. Cell apoptosis and cell cycle assay were evaluated by flow cytometry. Protein expressions in GLA-treated and untreated MM cells were evaluated by western blot analyses. MM xenograft nude mice model was used to investigate the role of GLA on the proliferation of MM cells in vivo. IHC assay was used to examine the role of GLA on the MM xenograft model in vivo.

Results
In the present study, we firstly reported the potent anti-myeloma activity of GLA on MM cells. We found that GLA could induce apoptosis in vitro and in vivo. GLA could inhibit the phosphorylation of the signal transducer and activator of transcription 3 (STAT3) and downregulate interleukin IL-6 induced STAT3 phosphorylation in MM. Overexpression of STAT3 could significantly prevent apoptosis induced by GLA; while knockdown of STAT3 enhanced it. Moreover, GLA could inhibit cell proliferation by inducing the cell cycle arrest. GLA reduced the expression of cell cycle-related proteins CCNB1, CCND1, CCND2, and CCND3 and increased the expression of p21 in MM cell lines. In addition, in the MM xenograft nude mice model, GLA exhibited very good anti-myeloma activity. Administration of GLA almost completely inhibited tumor growth within 19 days without physical toxicity. And the IHC results showed GLA significantly inhibited cell proliferation and interfered STAT3 pathway on MM xenograft model tumor tissues.

Conclusions
Taken together, our present research indicated that GLA inhibits the MM cell proliferation, induces MM cell apoptosis and cell cycle arrest through blocking the activation of STAT3 pathway. Thus, GLA may be a potential therapeutic candidate for MM patients in the future.
Cervical cancer-derived exosomal miR-663b promotes angiogenesis by inhibiting vinculin expression in vascular endothelial cells
Authors: You Xuewu , Sun Wenxiong , Wang Ying , Liu Xiaoli , Wang Aihong , Liu Lu , Han Sai , Sun Yu , Zhang Junhua , Guo Lingyu , Zhang Youzhong 
Published: December 2021

Abstract
Background
Angiogenesis provides essential nutrients and oxygen for tumor growth and has become the main mechanism of tumor invasion and metastasis. Exosomes are nanoscale membrane vesicles containing proteins, lipids, mRNA and microRNA (miRNA), which mediate intercellular communication and play an important role in tumor progression. Accumulated evidence indicates that tumor-derived exosomal miRNAs participate in the tumor microenvironment and promote angiogenesis.

Methods
Bioinformatic target prediction and dual luciferase reporter assays were performed to identify the binding site between miR-663b and the 3′-UTR of vinculin (VCL). VCL overexpression lentivirus and miR-663b overexpression/inhibition lentivirus were used to create a VCL overexpression model and miR-663b overexpression/inhibition model in-vitro. Immunohistochemistry (IHC) assays and western blot assays were used to detect protein expression. Exosome-cell cocultures, wound healing assays, tube formation assays and transwell assays were used to measure the migration and tube formation ability of vascular endothelial cells [human umbilical vein endothelial cells (HUVECs)]. siRNA targeted VCL was used to knockdown VCL.

Results
In the present study, we found that miR-663b was elevated in cervical cancer tissue and exosomes. miR-663b could bind the 3′-UTR of VCL and inhibit its expression. VCL is downregulated in cervical cancer, and decreased VCL has a negative correlation with a high level of miR-663b. Further studies demonstrated that exosomes secreted by cervical cancer cells can deliver miR-663b to HUVECs and inhibit the expression of VCL, thereby promoting angiogenesis and tumor growth.

Conclusions
miR-663b derived from cancer cell exosomes acts as a driving factor for angiogenesis and a potential target of antiangiogenic therapy in cervical cancer. Our findings illustrated a new signaling pathway, including exosomes, miRNAs and target genes, which provides potential targets for antiangiogenic therapy.
Identification of a VHL gene mutation in atypical Von Hippel-Lindau syndrome: genotype–phenotype correlation and gene therapy perspective
Authors: Tong Dali , Zhang Yao , Jiang Jun , Bi Gang 
Published: December 2021

Abstract
Background
Classical von Hippel Lindau (VHL) disease/syndrome includes CNS hemangioblastoma, renal or pancreatic cysts, pheochromocytoma, renal carcinoma and exodermic cystadenoma. The syndrome is caused by mutation of VHL tumor suppressor gene. The most prevalent mutations are present in VHL syndrome. To date, > 500 mutations of gene related to the progression of VHL syndrome have been reported. VHL gene mutation presented in single lung or pancreatic tumor has been reported occasionally, but there is no report of both.

Methods
In this paper, we used CT scan, pathological and genetic examination methods to diagnose a rare atypical VHL syndrome.

Results
We reported a rare case of atypical VHL syndrome with authenticated VHL mutation at p.Arg167Gln, that was associated with not only bilateral pheochromocytoma but also lung carcinoid and neuroendocrine tumor of pancreas. Based on literature reviews, the patient was recommended to be further subjected to octreotide-based radionuclide therapy.

Conclusions
Combined with gene detection and clinical diagnosis, we found the inherent relationship between VHL genotype and phenotype, and constructed the standard diagnosis and treatment process of disease with rare VHL mutation from the perspective of gene therapy.
NK cell upraise in the dark world of cancer stem cells
Authors: Shokouhifar Alireza , Firouzi Javad , Nouri Masoumeh , Sarab Gholamreza Anani , Ebrahimi Marzieh 
Published: December 2021

AbstractOne of the obstacles in treating different cancers, especially solid tumors, is cancer stem cells (CSCs) with their ability in resistance to chemo/radio therapy. The efforts for finding advanced treatments to overcome these cells have led to the emergence of advanced immune cell-based therapy (AICBT). Today, NK cells have become the center of attention since they have been proved to show an appropriate cytotoxicity against different cancer types as well as the capability of detecting and killing CSCs. Attempts for reaching an off-the-shelf source of NK cells have been made and resulted in the emergence of chimeric antigen receptor natural killer cells (CAR-NK cells). The CAR technology has then been used for generating more cytotoxic and efficient NK cells, which has increased the hope for cancer treatment. Since utilizing this advanced technology to target CSCs have been published in few studies, the present study has focused on discussing the characteristics of CSCs, which are detected and targeted by NK cells, the advantages and restrictions of using CAR-NK cells in CSCs treatment and the probable challenges in this process.
Epigenetic modification and BRAF gene mutation in thyroid carcinoma
Authors: Huang Guo , Chen Juan , Zhou Jun , Xiao Shuai , Zeng Weihong , Xia Jiliang , Zeng Xi 
Published: December 2021

AbstractThyroid cancer remains the most prevailing endocrine malignancy, and a progressively increasing incidence rate has been observed in recent years, with 95% of thyroid cancer represented by differentiated thyroid carcinomas. The genetics and epigenetics of thyroid cancer are gradually increasing, and gene mutations and methylation changes play an important roles in its occurrence and development. Although the role of RAS and BRAF mutations in thyroid cancer have been partially clarified,but the pathogenesis and molecular mechanisms of thyroid cancer remain to be elucidated. Epigenetic modification refer to genetic modification that does not change the DNA sequence of a gene but causes heritable phenotypic changes in its expression. Epigenetic modification mainly includes four aspects: DNA methylation, chromatin remodelling, noncoding RNA regulation, and histone modification. This article reviews the importance of thyroid cancer epigenetic modification and BRAF gene mutation in the treatment of thyroid cancer.
Population genetics of Anopheles arabiensis, the primary malaria vector in the Republic of Sudan
Authors: Mustafa Mashair Sir El Khatim , Jaal Zairi , Abu Kashawa Sumia , Mohd Nor Siti Azizah 
Published: December 2021

AbstractBackgroundAnopheles arabiensisis a member ofAnopheles gambiaecomplex and the main malaria vector in Sudan. There is insufficient population genetics data available onAn. arabiensisfor an understanding of vector population structure and genetics, which are important for the malaria vector control programmes in this country. The objective of this investigation is to study the population structure, gene flow and isolation by distance amongAn. arabiensispopulations for developing control strategies.MethodsMosquitoes were collected from six sites located in three different states in Sudan, Khartoum, Kassala and Sennar, using pyrethrum spray catch of indoor resting mosquitoes. Anopheline mosquitoes were identified morphologically and based on species specific nucleotide sequences in the ribosomal DNA intergenic spacers (IGS). Seven publishedAn. gambiaemicrosatellite loci primers were used to amplify the DNA ofAn. arabiensissamples.ResultsPCR confirmed thatAn. arabiensiswas the main malaria vector found in the six localities. Of the seven microsatellite loci utilized, six were found to be highly polymorphic across populations, with high allelic richness and heterozygosity with the remaining one being monomorphic. Deviation from Hardy–Weinberg expectations were found in 21 out of 42 tests in the six populations due to heterozygote deficiency. Bayesian clustering analysis revealed two gene pools, grouping samples into two population clusters; one includes four and the other includes two populations. The clusters were not grouped according to the three states but were instead an admixture. The genetic distances between pairs of populations ranged from 0.06 to 0.24. Significant FSTwas observed between all pairwise analyses ofAn. arabiensispopulations. The Kassala state population indicated high genetic differentiation (FSTranged from 0.17 to 0.24) from other populations, including one which is also located in the same state. High gene flow (Nm = 1.6–8.2) was detected among populations within respective clusters but limited between clusters particularly with respect to Kassala state. There was evidence of a bottleneck event in one of the populations (Al Haj Yousif site). No isolation by distance pattern was detected among populations.ConclusionsThis study revealed low levels of population differentiation with high gene flow among theAn. arabiensispopulations investigated in Sudan, with the exception of Kassala state.
A molybdenum oxide-based degradable nanosheet for combined chemo-photothermal therapy to improve tumor immunosuppression and suppress distant tumors and lung metastases
Authors: Qiu Na , Yang Xiaoye , Zhang Yanan , Zhang Jicheng , Ji Jianbo , Zhang Yu , Kong Xinru , Xi Yanwei , Liu Dongzhu , Ye Lei , Zhai Guangxi 
Published: December 2021

AbstractMolybdenum oxide (MoOx) nanosheets have drawn increasing attention for minimally invasive cancer treatments but still face great challenges, including complex modifications and the lack of efficient accumulation in tumor. In this work, a novel multifunctional degradable FA-BSA-PEG/MoOx nanosheet was fabricated (LA-PEG and FA-BSA dual modified MoOx): the synergistic effect of PEG and BSA endows the nanosheet with excellent stability and compatibility; the FA, a targeting ligand, facilitates the accumulation of nanosheets in the tumor. In addition, DTX, a model drug for breast cancer treatment, was loaded (76.49%, 1.5 times the carrier weight) in the nanosheets for in vitro and in vivo antitumor evaluation. The results revealed that the FA-BSA-PEG/MoOx@DTX nanosheets combined photothermal and chemotherapy could not only inhibit the primary tumor growth but also suppress the distant tumor growth (inhibition rate: 51.7%) and lung metastasis (inhibition rate: 93.6%), which is far more effective compared to the commercial Taxotere®. Exploration of the molecular mechanism showed that in vivo immune response induced an increase in positive immune responders, suppressed negative immune suppressors, and established an inflammatory tumor immune environment, which co-contributes towards effective suppression of tumor and lung metastasis. Our experiments demonstrated that this novel multifunctional nanosheet is a promising platform for combined chemo-photothermal therapy.
Graphical Abstract
The Physical Activity Messaging Framework (PAMF) and Checklist (PAMC): International consensus statement and user guide
Authors: Williamson Chloë , Baker Graham , Tomasone Jennifer R. , Bauman Adrian , Mutrie Nanette , Niven Ailsa , Richards Justin , Oyeyemi Adewale , Baxter Beelin , Rigby Benjamin , Cullen Benny , Paddy Brendan , Smith Brett , Foster Charlie , Drummy Clare , Vandelanotte Corneel , Oliver Emily , Dewi Fatwa Sari Tetra , McEwen Fran , Bain Frances , Faulkner Guy , McEwen Hamish , Mills Hayley , Brazier Jack , Nobles James , Hall Jennifer , Maclaren Kaleigh , Milton Karen , Olscamp Kate , Campos Lisseth Villalobos , Bursle Louise , Murphy Marie , Cavill Nick , Johnston Nora J. , McCrorie Paul , Wibowo Rakhmat Ari , Bassett-Gunter Rebecca , Jones Rebecca , Ruane Sarah , Shilton Trevor , Kelly Paul 
Published: December 2021

AbstractEffective physical activity messaging plays an important role in the pathway towards changing physical activity behaviour at a population level. The Physical Activity Messaging Framework (PAMF) and Checklist (PAMC) are outputs from a recent modified Delphi study. This sought consensus from an international expert panel on how to aid the creation and evaluation of physical activity messages. In this paper, we (1) present an overview of the various concepts within the PAMF and PAMC, (2) discuss in detail how the PAMF and PAMC can be used to create physical activity messages, plan evaluation of messages, and aid understanding and categorisation of existing messages, and (3) highlight areas for future development and research. If adopted, we propose that the PAMF and PAMC could improve physical activity messaging practice by encouraging evidence-based and target population-focused messages with clearly stated aims and consideration of potential working pathways. They could also enhance the physical activity messaging research base by harmonising key messaging terminologies, improving quality of reporting, and aiding collation and synthesis of the evidence.
Characterizing children’s eating patterns: does the choice of eating occasion definition matter?
Authors: Leech Rebecca M. , Spence Alison C. , Lacy Kathleen E. , Zheng Miaobing , Timperio Anna , McNaughton Sarah A. 
Published: December 2021

Abstract
Background
Recommendations to define eating occasions (EO) currently exist for research in adults, but not for children or adolescents. We examined how varying EO definitions affect the characterization of eating patterns in children and adolescents.

Methods
Cross-sectional dietary data collected using a 24-h recall data during the 2011–12 Australian National Nutrition and Physical Activity Survey (1364 boys and 1337 girls aged 2–18 years) were analyzed. Eight definitions were applied: participant-identified, time-of-day, and 6 neutral definitions (EO separated by 15- or 60-min and/or an additional energy criterion of 21 or 210 kJ). Frequency of and total energy intake from meals, snacks, and all EO were estimated. F tests stratified by gender and age-group, were used to assess differences between definitions. Agreement between definitions of meal and snack frequencies was assessed using intraclass correlation coefficients (ICC). Linear regression was used to estimate the proportion of variance in total energy intake (kJ) and BMI z-score predicted by each definition.

Results
Mean frequencies of meals and snacks differed between the participant-identified and time-of-day definitions, in boys and girls and for all age groups (P < 0.01). Across the six neutral definitions, there were differences between mean frequencies of EO with the largest mean difference observed for children aged 2–3 y (boys: 2.3, girls: 2.5; P < 0.003). Between the participant-identified and time-of-day definitions, there was good agreement for frequencies of snacks (ICC for both genders: 0.93) but not meals (boys: 0.36; girls: 0.38). The 15-min time interval plus 210 kJ definition of an EO consistently predicted the most variance in total energy intake (R2 range = 8.1–34.8). Definitions that delineated meals and snacks better predicted variance in BMI z-score, when compared to the neutral definitions.

Conclusions
How eating patterns are characterized vary depending on the EO definitions employed, particularly in young children. Variance in total energy intake was best predicted by a variation of the neutral definition whereas definitions that delineated meals and snacks performed better in relation to predicting BMI variance. Further international research that compares EO definitions in children will help inform a standard approach.
Cognitive testing of a survey instrument to assess sexual practices, behaviours, and health outcomes: a multi-country study protocol
Authors: Gonsalves Lianne , Hunter Erin C. , Brizuela Vanessa , Tucker Joseph D. , Srinivas Megan L. , Gitau Evelyn , Mercer Catherine H. , Bajos Nathalie , Collins Debbie 
Published: December 2021

AbstractBackgroundPopulation level data on sexual practices, behaviours and health-related outcomes can ensure that responsive, relevant health services are available for all people of all ages. However, while billions of dollars have been invested in attempting to improve sexual and reproductive health (including HIV) outcomes, far less is understood about associated sexual practices and behaviours. Therefore, the World Health Organization embarked on a global consultative process to develop a short survey instrument to assess sexual health practices, behaviours and health outcomes. In order for the resulting draft survey instrument to be published as a ‘global’ standard instrument, it is important to first determine that the proposed measures are globally comprehensible and applicable.This paper describes a multi-country study protocol to assess the interpretability and comparability of the survey instrument in a number of diverse countries.MethodsThis study will use cognitive interviewing, a qualitative data collection method that uses semi-structured interviews to explore how participants process and respond to survey instruments. We aim to include study sites in up to 20 countries. The study procedures consist of: (1) localizing the instrument using forward and back-translation; (2) using a series of cognitive interviews to understand how participants engage with each survey question; (3) revising the core instrument based on interview findings; and (4) conducting an optional second round of cognitive interviews. Data generated from interviews will be summarised into a predeveloped analysis matrix.The entire process (a ‘wave’ of data collection) will be completed simultaneously by 5+ countries, with a total of three waves. This stepwise approach facilitates iterative improvements and sharing across countries.DiscussionAn important output from this research will be a revised survey instrument, which when subsequently published, can contribute to improving the comparability across contexts of measures of sexual practices, behaviours and health-related outcomes. Site-specific results of the feasibility of conducting this research may help shift perceptions of who and what can be included in sexual health-related research.
Combination antiretroviral therapy is associated with reduction in liver fibrosis scores in patients with HIV and HBV co-infection
Authors: Yang Rongrong , Gui Xien , Ke Hengning , Xiong Yong , Gao Shicheng 
Published: December 2021

Abstract
Background
Liver fibrosis is common in individuals with HIV/HBV co-infection, but whether cART could reverses liver fibrosis is unclear.

Methods
This was a retrospective observational study. Binary logistic regression was used to assess predictors of liver fibrosis in individuals with HIV/HBV co-infection. Comparison of FIB-4 scores before and after cART were compared using X2 test and t test.

Results
Four hundred and fifty-eight individuals with HIV/HBV co-infection were included in this study. It was found that cART (HR 0.016, 95% CI: 0.009–0.136; P < 0.001) was one of protection factors to against liver fibrosis. Forty individuals who had normal levels of ALT, AST and PLT during the whole course of diseases were stratified into FIB-4 < 1.45 (n = 14), 1.45 ≤ FIB-4 ≤ 3.25 (n = 19) and FIB-4 > 3.25 (n = 7) groups by their FIB-4 scores before cART. In 1.45 ≤ FIB-4 ≤ 3.25 group, 57.9%(11/19) of the individuals dropped to FIB-4 < 1.45 group by cART; in FIB-4 > 3.25 group, 85.7%(6/79) dropped to 1.45 ≤ FIB-4 ≤ 3.25 group, while 14.3%(1/7) dropped to FIB-4 < 1.45 group. In cART-naive group, 1 year, 2–5 years and 5–10 years post-cART groups, FIB-4 scores were 4.29 ± 0.43, 3.63 ± 0.38, 2.90 ± 0.36 and 2.52 ± 0.38, respectively (P = 0.034); and the incidence of liver fibrosis were 7.38%(104/141), 63.6%(98/154), 60.8%(62/102) and 47.5%(29/61), respectively (P = 0.004).

Conclusion
cART was associated with decreased FIB-4 scores and the benefit of cART in reversing liver fibrosis can sustain for a decade in patients with HIV/HBV co-infection.