bluuebunny/crossref_metadata_2025_split huggingface dataset:
A liquid biopsy-based approach identifies myeloid cells, STAT3 and arginase-1 as predictors of glioma risk score and patients' survival
Authors: Bianco Paola Del , Pinton Laura , Magri Sara , Canè Stefania , Masetto Elena , Basso Daniela , Padovan Marta , Volpin Francesco , D'Avella Domenico , Lombardi Giuseppe , Zagonel Vittorina , Bronte Vincenzo , Puppa Alessandro Della , MANDRUZZATO SUSANNA 
Published: September 2021

Abstract
Background

Although gliomas are strictly confined to the central nervous system, their negative influence over the immune system can extend to peripheral circulation. The immune suppression exerted by myeloid cells is capable of affecting both response to therapy and disease outcome. Here we analyzed the expansion of several myeloid parameters in the blood of low- and high-grade gliomas and assessed their relevance as biomarkers of disease and clinical outcome.
Methods

Peripheral blood was obtained from 134 low- and high-grade glioma patients before surgery and treatment. Myeloid cell subsets such as total CD14+, CD14+/p-STAT3+, CD14+/PD-L1+, CD15+ cells and 4 myeloid derived suppressor cell (MDSC) subsets, were evaluated by multiparametric flow cytometry. Arginase-1 (ARG1) quantity and activity was determined in the plasma. Principal component analysis was performed to define correlations between myeloid markers. Multivariable logistic regression model was used to obtain a diagnostic score to discriminate glioma patients from healthy controls, and between each glioma grade. A glioblastoma prognostic model was determined by multiple Cox regression using clinical and myeloid parameters.
Results

In the blood of glioma patients, changes in myeloid parameters associated with immune suppression were identified and allowed us to define a diagnostic score calculating the risk of being a glioma patient, that included CD15+ cells, MDSC1, MDSC3, p-STAT3 and ARG1 activity. Of note, the same parameters, together with age, can also be used to calculate the risk score in differentiating each glioma grade. Finally, a prognostic model for glioblastoma patients stemmed out from a Cox multiple analysis, highlighting the role of MDSC, p-STAT3 and ARG1 activity together with clinical parameters in predicting the patient outcome.
Conclusions

This work emphasizes the role of systemic immune suppression carried out by myeloid cells in gliomas. The identification of biomarkers associated with immune landscape, diagnosis and outcome of glioblastoma patients lays the ground for their clinical use for stratification and follow up.
Markets Survey On Traditional Medicine of Lijiang City, Yunnan Province, China
Authors: mingshuo Zhang , tao li hai , junqi wang , xiaobo zhang , shaohua yang , yinglu bai , zijun sha , jianqin liu , ying li , xiulan huang , zhiyong li , luqi huang 
Published: September 2021

Abstract
Background: Traditional markets are important trading places for medicinal plants, and market surveys often engage in ethnobotanical research to record the herbal plants used locally and related traditional knowledge. However, information on the market traded medicinal plants is not well documented from traditional markets in Lijiang City, Yunnan. This research is an ethnobotanical survey focusing on medicinal plants traded in traditional markets of Lijiang City, and contributes to the understanding of medicinal plants and related information used by the Naxi people.Methods: Ethnobotanical surveys were carried out during two years (2019-2020). Three traditional markets in Lijiang City were investigated. The methods we used include literature research, participatory surveys, key insider interviews and group discussions.Results: As a result, 318 medicinal plants were recorded including 29 unidentified medicines. The plant medicines were from medicinal plants of 97 families belonged to Angiosperm, Gymnospermae, Pteridophyta, Bryophyta, Lichenes and Fungi. Asteraceae provided the maximum numbers of medicinal plants. Among them, there were 258 species (89.27%) of wild plants, 15 species (5.19%) were cultivated, and 16 species (5.54%) were wild or cultivated. There were 22 species of national protected plants in China, including 3 species of national first-level protected plants and 19 species of national second-level protected plants. Among the recorded diseases, 58.13% of medicinal plants are used to treat musculoskeletal system and connective tissue diseases and digestive system diseases. A total of 31 kinds of medicinal plants can be found in Dongba Sutra or Yu Long Ben Cao.Conclusion: This study surveyed herbal medicine in the market of Lijiang City, analyzing and revealing resource compositions and current market situations. The medicinal plants used by the Naxi people are diverse and are used to treat a wide spectrum of body disorders. There are many wild medicinal plants, and in order to ensure sustainable development, its natural protection should be strengthened. Knowledge of medicinal plants recorded in Naxi medical classics has ethnobotanical value and should be further developed.
m6A-Related lncRNAs Affect Tumor Immune Microenvironment And Prognosis In Acute Myeloid Leukemia
Authors: Zhong Fangmin , Yao Fangyi , Cheng Ying , Liu Jing , Zhang Nan , Li Shuqi , Li Meiyong , Huang Bo , Wang Xiaozhong 
Published: September 2021

Abstract
Acute myeloid leukemia (AML) is a complex hematologic malignancy. Survival rate of AML patients is low. N6-methyladenosine (m6A) and long-chain non-coding RNAs (lncRNAs) play important roles in AML tumorigenesis and progression. However, the relationship between lncRNAs and biological characteristics of AML, as well as how lncRNAs influence the prognosis of AML patients, remain unclear. In this study, we identified m6A-related lncRNAs, and analyzed their roles and prognostic values in AML. m6A-related lncRNAs associated with patient prognosis were screened using univariate Cox regression analysis, followed by systematic analysis of the relationship between these genes and AML clinicopathologic and biologic characteristics. Furthermore, we examined the characteristics of tumor immune microenvironment (TIME) using different IncRNA clustering models. Using LASSO regression, we identified the risk signals related to prognosis of AML patients. We then constructed and verified a risk model based on m6A-related lncRNAs for independent prediction of overall survival in AML patients. Our results indicate that risk scores, calculated based on risk-related signaling, were related to the clinicopathologic characteristics of AML and level of immune infiltration. Finally, we examined the expression level of TRAF3IP2-AS1 in patient samples through real-time polymerase chain reaction analysis and in GEO datasets, and we identified SRSF10 as a regulator of TRAF3IP2-AS1 through in vitro assays. Our study shows that m6A-related lncRNAs, evaluated using the risk prediction model, can potentially be used to predict prognosis and design immunotherapy in AML patients.
Short-Term and Highly Efficient Cas9 Expression System Using Adenovirus Vector and Site-Specific Recombinase Cre
Authors: Nagamoto Sayaka , Agawa Miyuki , Tsuchitani Emi , Akimoto Kazunori , Kondo Saki , Kanegae Yumi 
Published: September 2021

Abstract
Genome editing techniques such as CRISPR/Cas9 have both become common gene engineering technologies and have been applied to gene therapy. However, the problems of increasing the efficiency of genome editing and reducing off-target effects that induce double-stranded breaks at unexpected sites in the genome remain. In this study, we developed a novel Cas9 transduction system, Exci-Cas9, using an adenovirus vector (AdV). Cas9 was expressed on a circular molecule excised by the site-specific recombinase Cre and succeeded in shortening the expression period compared to AdV, which expresses the gene of interest for at least six months. As an example, we chose hepatitis B, which currently has more than 200 million carriers in the world and frequently progresses to liver cirrhosis or hepatocellular carcinoma. The efficiencies of hepatitis B virus genome disruption by Exci-Cas9 and Cas9 expression by AdV directly (Avec) were the same, about 80–90%. Furthermore, Exci-Cas9 enabled cell- or tissue-specific genome editing by expressing Cre from a cell- or tissue-specific promoter. We believe that Exci-Cas9 developed in this study is useful not only for resolving the persistent expression of Cas9, which has been a problem in genome editing, but also for eliminating long-term DNA viruses such as human papilloma virus.
Chemo-Photodynamic Therapy With Light-Triggered Disassembly of Theranostic Nanoplatform In Combination With Checkpoint Blockade For Immunotherapy of Hepatocellular Carcinoma
Authors: Xu Jianjun , Zheng Qichang , Cheng Xiang , Hu Shaobo , Zhang Chen , Zhou Xing , Sun Ping , Wang Weimin , Su Zhe , Zou Tianhao , Song Zifang , Xia Yun , Yi Xiaoqing , Gao Yang 
Published: September 2021

Abstract
Background: Hepatocellular carcinoma (HCC) is a common malignant tumor with high rate of metastasis and recurrence. Although immune checkpoint blockade (ICB) has emerged as a promising type of immunotherapy in advanced HCC, treatment with ICB alone achieves an objective remission rate less than 20%. Thus, combination therapy strategies is needed to improve the treatment response rate and therapeutic effect. Methods: A light-triggered disassembly of nanoplatform (TB/PTX@RTK) co-loaded an aggregation induced emission (AIE) photosensitizer (TB) and paclitaxel (PTX) was prepared for on-command drug release and synergistic chemo-photodynamic therapy (chemo-PDT). Nano-micells were characterized for drug loading content, hydrodynamic size, absorption and emission spectra, reactive oxygen species production, and PTX release from micells. The targeted fluorescence imaging of TB/PTX@RTK micells and the synergistic antitumor efficacy of TB/PTX@RTK micells-mediated chemo-PDT combined with anti-PD-L1 were assessed both in vitro and in vivo.Results: The TB/PTX@RTK micells could specifically accumulate at the tumor site through cRGD-mediated active target and facilitate image-guided PDT for tumor ablation. Once irradiated by light, the AIEgens photosensitizer of TB could produce ROS for PDT, and the thioketal linker could be cleaved by ROS to precise release of PTX in tumor cells. Chemo-PDT could not only synergistically inhibit tumor growth, but also induce immunogenic cell death and elicit anti-tumor immune response. Meanwhile, chemo-PDT significantly upregulated the expression of PD-L1 on tumor cell surface which could efficiently synergize with anti-PD-L1 monoclonal antibodies to induce an abscopal effect, and establish long-term immunological memory to inhibit tumor relapse and metastasis.Conclusion: Our results suggest that the combination of TB/PTX@RTK micell-mediated chemo-PDT therapy with anti-PD-L1 monoclonal antibodies can synergistically enhance systemic antitumor effects, and provide a novel insight into the development of new nanomedicine with precise controlled release and multimodal therapy to enhance the therapeutic efficacy of HCC.
The Impact of Post-Traumatic Stress on Symptom Presentation of Women With Gulf War Illness
Authors: Shastry Nandan , Sultana Esha , Jeffrey Mary , Collado Fanny , Kibler Jeffrey , DeLucia Christian , Fletcher Mary Ann , Klimas Nancy , Craddock Travis J. A. 
Published: September 2021

Abstract
Background: Gulf War Illness (GWI) is a chronic, multi-symptomatic disorder characterized by fatigue, muscle pain, cognitive problems, insomnia, rashes, and gastrointestinal issues affecting an estimated 30% of the ~750,000 returning military Veterans of the 1990–1991 Persian Gulf War. Female Veterans deployed to combat in this war report medical symptoms, like cognition and respiratory troubles, at twice the rate compared to non-deployed female Veterans of the same era. The heterogeneity of GWI symptom presentation complicates diagnosis as well as the identification of effective treatments. This is exacerbated by the presence of co-morbidities. Defining subgroups of the illness may help alleviate these complications. One clear grouping is along the lines of gender. Our aim is to determine if women with GWI can be further subdivided into distinct subgroups based on post-traumatic stress disorder (PTSD) symptom presentation.Methods: Veterans diagnosed with GWI (n = 35) and healthy sedentary controls (n = 35) were recruited through the Miami Veterans Affairs Medical Health Center. Symptoms were assessed via the RAND short form health survey, the multidimensional fatigue inventory, and the Davidson trauma scale. Hierarchal regression modeling was performed on measures of health and fatigue with PTSD symptoms as a covariate. This was followed by univariate analyses conducted with two separate GWI groups based on a cut-point of 70 for their total Davidson trauma scale value and performing heteroscedastic t-tests across all measures.Results: Based on the distinct differences found in PTSD symptomology regarding all health and trauma symptoms, two subgroups were derived within female GWI Veterans. Hierarchical regression models displayed the comorbid effects of GWI and PTSD, as both conditions had measurable impacts on physical and social outcomes of poor health (ΔR2 = 0.08- 0.672), with notable differences in mental and emotional measures. Overall, in women with GWI individuals with PTSD, a cut point analysis indicated poorer health outcomes within all measures in comparison to those of women without PTSD symptoms and healthy controls.Conclusions: Our current findings support the understanding that comorbid symptoms of GWI and PTSD subsequently result in poorer experienced health outcomes, along with establishing the possibility of varying clinical presentations.
Stage Specific Comparative Transcriptomic Analysis To Reveal Gene Networks Regulating Iron And Zinc Content In Pearl Millet [Pennisetum glaucum (L.) R. Br.]
Authors: Satyavathi C. Tara , Tomar Rukam S. , Ambawat Supriya , Kheni Jasminkumar , Padhiyar Shital M. , Desai Hiralben , Bhatt S. B. , Shitap M. S. , Meena Ramesh Chand , Singhal Tripti , Sankar S. Mukesh , Singh S. P. , Khandelwal Vikas 
Published: September 2021

Abstract
Pearl millet is an important staple food crop of poor people which is rich in micronutrients like iron and zinc and amenable for focused breeding for these micronutrients along with high yield. Transcriptome sequencing using ION S5 Next Generation Sequencer generated 43.5 million sequence reads resulting in 83,721 transcripts with N50 of 597 bp and 84.35% of transcripts matched with the pearl millet genome assembly. The genotypes having high Fe and Zn showed differential gene expression during different stages. Of which, 155 were up-regulated and 251were down-regulated while during flowering stage and milking stage 349 and 378 transcripts were differentially expressed, respectively. Gene annotation and GO term showed the presence of transcripts involved in metabolic activities associated with uptake and transport of iron and zinc. In the present study, the 83,721 transcripts were also examined for identification of SSRs. A total of 4,327 SSRs were identified with dominance of tri-nucleotide SSRs in comparison to di-nucleotide SSRs. These EST-SSRs can be used in molecular breeding, genetic diversity analysis and determination of heterozygosity of the allelic loci. Information generated will help in gaining insights into iron and zinc metabolism and develop genotypes with high yield, grain iron and zinc content.
Specific Reprogramming of Alpha Cells to Insulin-Producing Cells by Short Glucagon Promoter-Driven Pdx1 and MafA
Authors: Guo Ping , Zhang Ting , Lu Aiping , Shiota Chiyo , Huard Matthieu , Whitney Kaitlyn , Huard Johnny 
Published: September 2021

Abstract
Endogenous reprogramming of pancreas-derived non-beta cells into insulin-producing cells is a promising approach to treat type 1 diabetes (T1D). One strategy that has yet to be explored is the specific delivery of insulin-producing essential genes, Pdx1 and MafA, to pancreatic alpha cells to reprogram the cells into insulin-producing cells in an adult pancreas. In this study, we utilized an alpha cell-specific glucagon (GCG) promoter to drive Pdx1 and MafA transcription factors to reprogram alpha cells to insulin-producing cells in chemically induced and autoimmune diabetic mice. Our results showed that a combination of a short glucagon-specific promoter with AAV serotype 8 can be used to successfully deliver Pdx1 and MafA into alpha cells in the mouse pancreas. Pdx1 and MafA expression specifically in alpha cells was also able to correct hyperglycemia in both induced and autoimmune diabetic mice. With this technology, targeted gene specificity and reprogramming were accomplished with an alpha-specific promotor combined with an AAV-specific serotype and provide an initial basis to develop a novel therapy for the treatment of T1D.
Machine Learning-based Approaches for Identifying Human Cells Harboring Fetal Chromatin Domain Ablations
Authors: Li Yi , Zaheri Shadi , Nguyen Khai , Liu Li , Hassanipour Fatemeh , Bleris Leonidas 
Published: September 2021

Abstract
Two common hemoglobinopathies, sickle cell disease (SCD) and β-thalassemia, arise from genetic mutations within the β-globin gene. A 500-bp motif termed Fetal Chromatin Domain (FCD), upstream of human ϒ-globin locus, may function as a transcriptional regulatory element driving inhibition of the ϒ-globin gene. Here, we hypothesize that the removal of this motif using CRISPR technology may reactivate the expression of ϒ-globin and subsequently restore fetal hemoglobin functionality. In this work we present two different cell morphology-based machine learning approaches that can be used identify cells that harbor FCD genetic modifications. Three candidate models from the first, which uses multilayer perceptron algorithm (MLP 20–26, MLP26-18, and MLP 30 − 26) and flow cytometry-derived cellular data, yielded 0.83 precision, 0.80 recall, 0.82 accuracy, and 0.90 area under the ROC (receiver operating characteristic) curve when predicting the edited cells. In comparison, the candidate model from the second approach, which uses deep learning (T2D5) and DIC microscopy-derived imaging data, performed with less accuracy (0.80) and ROC AUC (0.87). We envision both assays could be valuable and complementary to currently available genotyping protocols for specific genetic modifications which result in morphological changes in human cells.
RNF24 is a Novel Biomarker of Prognosis and Immunological Cell Infiltration in Cancers
Authors: Yu Bin , mei ma 
Published: September 2021

Abstract
Background The RNF family engaged in diverse biological and pathological processes, including tumorigenesis and cancer advance. However, studies about Ring Finger Protein 24 (RNF24) were limited and have not been reported in cancer. A systematic analysis in pan-cancer is a benefit to understand the function of RNF24. Methods RNF24 expression was evaluated in pan-cancer based on the data from The Cancer Genome Atlas (TCGA) analyzed by TIMER, UALCAN, GEPIA, and HPA. Then, the effect of RNF24 on the prognostic value was assessed by clinical survival data in Kaplan–Meier Plotter and GEPIA. And mutation burden and related survival of RNF24 was observed in cBioPortal. Furthermore, protein-protein interaction (PPI) networks of RNF24 and pathway enrichment analysis were explored on multiple websites. Lastly, relationships between RNF24 expression and immune cells infiltration were analyzed in the TIMER2 online database with various algorithms. Results The mRNA and protein levels of RNF24 were significantly upregulated in most types of cancer compared to normal tissues. And RNF24 was a reliable biomarker to predict prognosis in at least 10 types of cancer, including liver hepatocellular carcinoma (LIHC). In addition, we showed the genetic alteration, PPI networks, and functional pathway of RNF24. Moreover, immune cell infiltration exhibited RNF24 expression negatively linked to CD8+ T cells, but positively to Tregs, MDSCs, HSC, and macrophages in pan-cancer.Conclusions Our pan-cancer analysis revealed RNF24 as an oncogene and its expression predicted OS in multiple human cancers, especially in LIHC. RNF24 might predict the immunotherapy response for cancer patients based on its expression with infiltration of immune and immunosuppressive cells.
Sodium Alginate Supplementation Plus HIIT and MICT Can Induce CCK and PYY Increment in Men With Metabolic Syndrome
Authors: Ebrahimi Alireza , azizi Mohammad , Tahmasebi Worya , Hoseini Rastegar 
Published: September 2021

Abstract
Background: Abdominal obesity is a common phenomenon in metabolic syndrome (MetS). Inducing satiety by weight management plays an important role in reducing the risk of obesity and consequently MetS. This study was investigated effect of sodium alginate supplementation plus HIIT and MICT on CCK and PYY increment in MetS men. Methods: For this purpose, 40 men with MetS volunteered and were randomly divided into five groups as follow: HIIT groups with supplement (n=8, 4*4 min bouts at 85-95% of HRpeak, with 3 min of active recovery at 50-70% HRpeak, 3 ses/week), HIIT (n=8, 4*4 min bouts at 85-95% of HRpeak, with 3 min of active recovery at 50-70% HRpeak, 3 ses/week), MICT with supplement (n=8, 30 min at 60-70% HRpeak, 3 ses/week), MICT (n=8, 30 min at 60-70% HRpeak, 3 ses/week) and control group (n = 8, no exercise). The HITT+S and MICT+S groups consumed 1.5 g of Sigma sodium alginate (made in the USA) solution in 100 mg of sweet water (7 g of fructose), 30 minutes before 3 main meals three days per week during 8 weeks. Results: After 8 weeks of interventions, CCK and PYY were markedly increased in the studied groups, this increase was significantly greater in the HIIT+S than other groups. Also, the MetS Z score was significantly decreased in all studied groups and this decrease was significantly higher in the HIIT+S than other groups (P <0.05). Conclusion: The results showed that HIIT and MICT led to an overall improvement in men with MetS. However, combining sodium alginate supplementation triggers these improvements.Trial registration: IRCT20190916044788N1. Registered 12 march 2020, https://www.irct.ir/
High resolution ancient sedimentary DNA shows that alpine plant biodiversity is a result of human land use
Authors: Garcés-Pastor Sandra , Coissac Eric , Lavergne Sebastien , Schwoerer Christoph , Theurillat Jean-Paul , Heintzman Pete , Wangensteen Owen , Tinner Willy , Rey Fabian , Heer Martina , Rutzer Astrid , Walsh Kevin , Lammers Youri , Brown Antony , Goslar Tomasz , . PhyloAlps Consortium , Heiri Oliver , Alsos Inger 
Published: September 2021

Abstract
Alpine areas are well known biodiversity hotspots, but their future may be threatened by expanding forest and changing human land use. Here, we reconstructed past vegetation, climate, and livestock over the past ~ 12,000 years from Lake Sulsseewli (European Alps), based on sedimentary ancient DNA, pollen, spores, chironomids, and microcharcoal. We assembled a highly-complete local DNA reference library (PhyloAlps, 3,923 plant species), and used this to obtain an exceptionally rich sedaDNA record of 366 plant taxa. The vegetation mainly responded to temperature during the first half of the Holocene, while human activity drove changes from 6 ka onwards. Land-use shifted from episodic grazing (Neolithic, Bronze Age) to agropastoral intensification (Medieval Age). This prompted a coexistence of species typically found at different elevational belts, thereby increasing plant richness to levels that characterise present-day alpine diversity. Our results indicate that traditional agropastoral activities should be maintained to prevent reforestation and preserve alpine plant biodiversity.