bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide Identification and Function Analysis of HMAD&nbsp;Gene Family in Cotton (Gossypium Spp.)
Authors: Wang Qinqin , Lu Xuke , Chen Xiugui , Zhao Lanjie , Han Mingge , Wang Shuai , Zhang Yuexin , Fan Yapeng , Ye Wuwei 
Published: November 2020

Abstract
Background: Soil salinized and heavy metal toxicity has become a major threat to sustainable crop production worldwide. Previous studies revealed that halophytes were supposed to tolerate other stress including heavy metal toxicity. Though HMAD (heavy-metal-associated domain) was reported to play various important functions in different plants, little is known in Gossypium.Results: A total of 169 G. hirsutum genes were identified belonging to the HMAD gene family and divided into five classes. Additionally, 84, 76 and 159 HMAD genes were identified in each G. arboreum, G. raimondii and G. barbadense, respectively. Furthermore, conserved sequence analysis found the conserved catalytic center containing an anion binding (CXXC) box. The HMAD gene family showed a differential expression levels among different tissues and developmental stages in G. hirsutum with the different cis-elements and transcription factor binding sites (TFBS) for abiotic stress.Conclusions: Current study provides important information about HMAD genes under salt-stress in Gossypium genome, which would be useful to understand its putative functions in different species of cotton.
Efficacy and Safety of Metastasis Directed Stereotactic Radiotherapy in NSCLC Patients Progressing Under Targeted- or Immunotherapy.
Authors: Kroeze Stephanie G.C. , Schaule Jana , Fritz Corinna , Kaul David , Blanck Oliver , Kahl Klaus Henning , Roeder Falk , Siva Shankar , Verhoeff Joost JC , Adebahr Sonja , Schymalla Markus M , Glatzer Markus , Szuecs Marcella , Geier Michael , Skazikis Georgios , Sackerer Irina , Lohaus Fabian , Eckert Franziska , Guckenberger Matthias 
Published: November 2020

Abstract
BackgroundMetastasis directed treatment (MDT) is increasingly performed with the attempt to improve outcome in non-small cell lung cancer (NSCLC) patients receiving targeted- or immunotherapy (TT/IT). This study aimed to assess the safety and efficacy of metastasis directed stereotactic radiotherapy (SRT) concurrent to TT/IT in NSCLC patients.MethodsA retrospective multicenter cohort of stage IV NSCLC patients treated with TT/IT and concurrent (≤30 days) MDT was established. 56% and 44% of patients were treated for oligoprogressive disease (OPD) or polyprogressive disease (PPD) under TT/IT, polyprogressive respectively. Survival was analyzed using Kaplan-Meier and log rank testing. Toxicity was scored using CTCAE v4.03 criteria. Predictive factors for overall survival (OS), progression free survival (PFS) and time to therapy switch (TTS) were analyzed with uni- and multivariate analysis.ResultsMDT of 192 lesions in 108 patients was performed between 07/2009 and 05/2018. Concurrent TT/IT consisted of EGFR/ALK-inhibitors (60%), immune checkpoint inhibitors (31%), VEGF-antibodies (8%) and PARP-inhibitors (1%). 2y-OS was 51% for OPD and 25% for PPD. After 1 year, 58% of OPD and 39% of PPD patients remained on the same TT/IT. Second progression after MDT was oligometastatic (≤5 lesions) in 59% of patients. Severe acute and late toxicity was observed in 5.5% and 1.9% of patients. In multivariate analysis, OS was influenced by the clinical metastatic status (p=0.002, HR 2.03, 95% CI 1.30-3.17). PFS was better in patients receiving their first line of systemic treatment (p=0.033, HR 1.7, 95% CI 1.05-2.77) and with only one metastases-affected organ (p=0.023, HR 2.04, 95% CI 1.10-3.79). TTS was 6 months longer in patients with one metastases-affected organ (p=0.031, HR 2.53, 95% CI 1.09-5.89). Death was never therapy-related.ConclusionsMetastases-directed SRT in NSCLC patients can be safely performed concurrent to TT/IT with a low risk of severe toxicity. To find the ideal sequence of the available multidisciplinary treatment options for NSCLC and determine what patients will benefit most, a further evaluated in a broader context within prospective clinical trials is needed continuation of TT/IT beyond progression combined with MDT for progressive lesions appears promising but requires prospective evaluation.Trial registrationretrospectively registered
Copy Number Variation and Transcription Regulation of Genes and Immune Microenvironment of Tumor Affect the Stemness of Prostate Cancer Cell
Authors: Dai Zao , Liu Ping 
Published: November 2020

Abstract
Background: Prostate cancer stem cells (pCSC) play an important role in tumor metastasis through multiple pathways. From gene, protein to microenvironment, there are many factors affecting the cell stemness of prostate cancer (PCa). However, the effective factors affecting the stemness of prostate cancer cells are still unclear.Methods: Based on the transcription data of prostate cancer in the TCGA database, WGCNA (Weighted Gene Co-expression Network Analysis) and stemness scores were used to find important stemness gene module. According to ATAC-seq and genomic data, analyze their relationship with stemness. The interaction of stemness genes was analyzed with STRING (functional protein association networks) database. Furthermore, based on the immune microenvironment score, the relationship between immune and stemness was analyzed.Results: The most important stemness gene module in prostate cancer was obtained with WGCNA method; then a positive correlation between the gene CNVs (Copy Number Variants) of the most important stemness gene module and PCa stemness was found, as well as a positive correlation between the gene CNVs and Gleason score of PCa was also drug out. Further, the key transcriptional regulators of the most important stemness genes in PCa were obtained. In addition, it's found that immune cells, especially CD8+T cells and M1 macrophages, suppressed the stemness of PCa cells. Finally, by analyzing the protein interactions and the relationship between genes and immune cells, we found that interaction of the proteins of the most important stemness genes module and the relationship between these genes and immune cells of microenvironment of PCa were all important in affecting the stemness of PCa cells.Conclusions: By analyzing multi-omics data of clinical specimen, we got the most important stemness genes and their important transcriptional regulators in PCa; and further mining analysis showed that the stemness of PCa cells is positive regulated by the CNVs and the interaction of the proteins of the most important stemness genes, and negatively regulated by the immune cells of the microenvironment of prostate cancer.
Multicentre Evaluation of a Newly Developed Anti-Calcium Dobesilate-Enzymatic Creatinine Assay Based on Real-World Data in China
Authors: Guo Xiuzhi , Hou Li’an , Lu Zhongxin , Zhi Guiru , Li Xiaoyan , Cheng Shiqing , Li Dexin , Zhang Yan , Wang Xuejing , Li Qi , Zhang Yufan , Niu Aijun , Wang Dandan , Ren Peng , Xu Anchun , Zhang Jianping , Zhang Yi , Qin Guangming , Yu Honglan , Liu Wentao , Min Xun , Hu Suhua , Hu Shenghe , Song Weiqing , Qiu Ling 
Published: November 2020

Abstract
BackgroundPreviously, we reported that calcium dobesilate (CaD), a vasoprotective agent mainly used for diabetic retinopathy, negatively interferes with enzymatic creatinine assays. Anewly developed enzymatic creatinine assay, the “Cr-R assay”, is commercially available and claims to have no interference from CaD. This study aimed to verify the performance of the Cr-R assay on clinical samples and to investigate the degree of CaD interference in a multicentre, real-world study.MethodsThe precision and accuracy ofthe Cr-R assay was evaluated in 23 hospitals in different regions of China. Interference was then calculated both in vitro and in clinical samples. Samples with potential interference were screened based on the different creatinine results between Cr-R and the creatinine assays commonly used in each participating hospital (Cr-C). Interference was confirmed by determining serum CaD concentration by directly using ultra-performance liquid chromatography (UPLC) methodand by assessing the “true” creatinine levels using the standard isotope dilution mass spectrometry (ID-MS/MS) method. ResultsTheprecision and bias and anti-interference ability of Cr-R assay on most platforms fulfilled the specification criteria. In the clinical setting, 67,469 samples were tested in 23 centres, and CaD concentration was measured in 818 samples, of which 257 contained CaD, accounting for 0.38% of the total and 31% of screened patients. In these 257 cases, the median CaD concentration was 11.356 (range, 1.350–121.519; IQR, 7.162–21.175) μg/mL. Creatinine levels measured using Cr-C assay were up to 35.1% (95%CI, 37.9–32.4 %; P < 0.001) lower than the “real” creatinine levels using the ID-MS/MSmethod. For Cr-R reagent, the average bias from the reference method was -6.2% (95%CI, -7.9–4.6%; P < 0.001), ranging from -17.9% to 7.1%.ConclusionsMulticentre tests confirmed that the precision, bias, and anti-CaD ability of the Cr-R assay met clinical needs. The prevalence of CaD interference should be considered when performing clinical enzymatic creatinine measurements.Other manufacturers should improve the anti-interference performance of creatinine reagents.
Ophiopogonin B-inducing Pyroptosis Through Caspase-1/gsdmd Pathway Contributes to Alleviation of Paclitaxel Resistance in Lung Cancer Cells&nbsp;
Authors: Cheng Ziyu , Li Zhihui , Gu Ling , Li Liqiu , Gao Qian , Zhang Xiongfei , Fu Jin , Guo Yuanyuan , Li Qirui , Gu Yang , Fu Hequn , Shen Xu , Chen Meijuan , Zhang Xu 
Published: November 2020

Abstract
Background: Drug resistance has become the main reason for the failure of tumor chemotherapy. In our previous study, ophiopogonin B (OP-B) has been verified to inhibit cell proliferation in numerous non-small cell lung cancer (NSCLC) cells. However, it is still unknown whether it can improve the drug resistance of lung cancer cells. Herein, we compared the inhibition effects of OP-B on NCI-H460, A549, A549/DDP and A549/PTX cells, and tried to find out the most sensible cell line to OP-B and the underlying reasons. Methods: The sensitivity of NCI-H460, A549, A549/DDP, and A549/PTX cells to OP-B was determined by CCK-8 assay, and the results were further verified in orthotopic tumor nude mice model and zebrafish tumor model. To identify pyroptosis in the cells, electron microscopy was used to observe cell morphology, flow cytometry was used to detect the mitochondrial membrane potential, and the LDH release rate was analyzed by microplate reader. Otherwise, immunofluorescence and immunohistochemical staining assay, western blot and qRT-PCR were used for detection of pyroptosis-correlated pathway.Results: In vitro, A549/DDP cell was verified to be most sensitive to OP-B than NCI-H460, A549, or A549/PTX cells. In vivo, OP-B inhibited the growth of A549/DDP orthotopic tumor more significantly than that of A549 both in nude mice and zebrafish models. Cell morphological feature, mitochondrial membrane potential, LDH release rate, production of IL-1β and expression of Caspase-1/GSDMD all showed that pyroptosis happened more significantly in A549/DDP cells than that in A549 cells after OP-B treatment.Conclusion: Though inducing more significantly pyroptosis by activating Caspase-1/GSDMD pathway, OP-B relieved DDP resistance of A549 cells.
The FAM3C Locus that Encodes Interleukin-like EMT Inducer (ILEI) is Frequently Co-amplified in MET-amplified Cancers and Contributes to Invasiveness
Authors: Schmidt Ulrike , Heller Gerwin , Timelthaler Gerald , Heffeter Petra , Somodi Zsolt , Schweifer Norbert , Sibilia Maria , Berger Walter , Csiszar Agnes 
Published: November 2020

Abstract
Background Gene amplification of MET, which encodes for the receptor tyrosine kinase c-MET, occurs in a variety of human cancers. High c-MET levels often correlate with poor cancer prognosis. Interleukin-like EMT inducer (ILEI) is also overexpressed in many cancers and is associated with metastasis and poor survival. The gene for ILEI, FAM3C, is located close to MET on chromosome 7q31 in an amplification “hotspot”, but it is unclear whether FAMC3 amplification contributes to elevated ILEI expression in cancer. In this study we have investigated FAMC3 copy number gain in different cancers and its potential connection to MET amplifications.Methods FAMC3 and MET copy numbers were investigated in various cancer samples and 200 cancer cell lines. Copy numbers of the two genes were correlated with mRNA levels, with relapse-free survival in lung cancer patient samples as well as with clinicopathological parameters in primary samples from 49 advanced stage colorectal cancer patients. ILEI knock-down and c-MET inhibition effects on proliferation and invasiveness of five cancer cell lines and growth of xenograft tumors in mice were then investigated. Results FAMC3 was amplified in strict association with MET amplification in several human cancers and cancer cell lines. Increased FAM3C and MET copy numbers were tightly linked and correlated with increased gene expression and poor survival in human lung cancer and with extramural invasion in colorectal carcinoma. Stable ILEI shRNA knock-down did not influence proliferation or sensitivity towards c-MET-inhibitor induced proliferation arrest in cancer cells but impaired both c-MET-independent and -dependent cancer cell invasion. c-MET inhibition reduced ILEI secretion, and shRNA mediated ILEI knock-down prevented c-MET-signaling induced elevated expression and secretion of matrix metalloproteinase (MMP)-2 and MMP-9. Combination of ILEI knock-down and c-MET-inhibition significantly reduced the invasive outgrowth of NCI-H441 and NCI-H1993 lung tumor xenografts by inhibiting proliferation, MMP expression and E-cadherin membrane localization.Conclusions These novel findings suggest MET amplifications are often in reality MET-FAM3C co-amplifications with tight functional cooperation. Therefore, the clinical relevance of this frequent cancer amplification hotspot, so far dedicated purely to c-MET function, should be re-evaluated to include ILEI as a target in the therapy of c-MET-amplified human carcinomas.
WITHDRAWN: Innovative Surgical System for Breast Cancer Based on Real-time Excising of Hypoxic Lesions Significantly Reduced the Positive Cavity Side Margin
Authors: Miripour Zohreh Sadat , Abbasvandi Fereshteh , Aghaee Parisa , Shojaeian Fatemeh , Faramarzpour Mahsa , Mohaghegh Pooneh , Hoseinpour Parisa , Namdar Naser , Amiri Morteza Hassanpour , Ghafari Hadi , Sanati Hassan , Mapar Mahna , Sadeghian Nastaran , Akbari Mohammad Esmaeil , Khayamian Mohammad Ali , Abdolahad mohamad 
Published: November 2020

Abstract
Background: For most people, the first step in treatment is to take out the tumor (surgery), so precise and fast diagnosis of any sign of high-risk cells in surgical cavity margins is significant. The frozen pathology method is the conventional standard of intraoperative diagnosis, but the low number of slides prepared from non-fixed tissues prevents us to achieve a perfect diagnosis. Although many improvements in intraoperative margin detection were achieved, still no clinically approved intra-operative technique has been reported for the detection of surgical margins with pathologically approved classification in breast cancer.Methods: From November 2018 to April 2020, 227 patients were registered and 213 with different types of breast tumors (IDC: n=151 (70.9%), ILC: n=6 (2.8%), DCIS: n=38 (17.8%), Atypia: n=8 (3.8%), Benign tumors: n=10 (%4.7)) were randomly assigned for CDP clinical trials. Men made up 2 (1%) of the patients; 211 (99%) were women. Functionalized carbon nanotubes grown on the electrode needles lively and selectively determine the H2O2 released from cancer/atypical cells, through reverse Warburg effect and hypoxia assisted glycolysis pathways, in a quantitative electrochemical manner. The study is registered at Iran National Committee for Ethics in Biomedical Research (IR.TUMS.VCR.REC.1397.355).Result: A real-time electrotechnical system, named cancer diagnostic probe (CDP) (Patent Pub. No.: US 2018/0299401A1), has been developed and clinically approved for breast cancer surgery (National Certificate ID:14006918495) to find the presence of pre-neoplastic/neoplastic cells in-vivo. Here, Functionalized carbon nanotubes grown on the electrode needles lively and selectively determine the H2O2 released from cancer or atypical cells, through reverse Warburg effect and hypoxia assisted glycolysis pathways, in quantitative electrochemical manner. A matched clinical diagnostic categorization between the pathological results and response peaks of CDP was proposed based on pathological classifications of WHO. Conclusion: The clinical ability of CDP was verified on more than 1300 human in-vivo breast samples with sensitivity and specificity of 93%, and 97%, respectively. After passing many trials and standard examinations, the system received production and clinical use certifications as a surgeon assistant system for usage in the operating room.
Protein Nanoparticle Osmotic Pressure Modifies Nonselective Permeability of the Blood Brain Barrier by Increasing Membrane Fluidity
Authors: Li Chen , Chen LinLin , Wang YuanYuan , Wang TingTing , Di Dong , Zhang Hao , Zhao HuanHuan , Shen Xu , Guo Jun 
Published: November 2020

Abstract
BackgroundIntracellular tension plays a crucial role in the destruction of the blood brain barrier (BBB) in response to lesion stimuli. Tight junction structure could be primarily affected by tension activity. In this study, we aimed to determine the effects of extracellular BBB damage on intracellular tension activity, and elucidate the mechanism underlying the effects of intracellular protein nanoparticle-dependent osmotic pressure on BBB permeability.MethodsThe intracellular tension for tight junction proteins occludin and ZO1 were evaluated using the fluorescence resonance energy transfer (FRET)-based tension probes and cpstFRET analysis. The efficiency of the probes was examined by acceptor photobleaching FRET (FRET-AB) analysis. The changes in mobility ratios of the transmembrane protein occludin were evaluated via the fluorescence recovery after photobleaching (FRAP) test. The cytoplasmic osmotic pressure (OP) was measured using the Osmomat 3000 Freezing Point Osmometer and 050 Membrane Osmometer. The count rate of cytoplasmic nanoparticles was detected by Nanosight NS300. The activation of cofilin and stathmin was examined by Western blot analysis. The BBB permeability in vivo was determined via investigating the changes of Evans Blue (EB) injected into the SD rats. The tight junction formation was assessed by the measurement of transendothelial electrical resistance (TEER). Intracellular calcium or chloride ions were measured using Fluo-4 AM or MQAE dyes. ResultsBBB lesions were accompanied by changes in occludin/ZO1 tension. Increases in intracellular osmotic pressure were involved in alteration of BBB permeability, possibly through the depolymerization of microfilaments or microtubules and mass production of protein nanoparticles according to the Donnan effect. Recovery of protein nanoparticle osmotic pressure could effectively reverse the effects of changes in occludin/ZO1 tension and BBB lesions. Outward tension of intracellular osmotic potential also caused upregulation of membrane fluidity, which promoted nonselective drug influx.ConclusionsOur results suggest a crucial mechanical mechanism underlying BBB lesions, and protein nanoparticle osmotic pressure could be a novel therapeutic target for BBB lesion-related brain diseases. Our results also provide a basis for further studies on the regulation of intracellular tension activity and its effect on the permeability of the BBB, and development of novel drugs that cross the blood-brain barrier.
Combined Treatment with Prednisone and Bromocriptine&nbsp;does not Influence the Pregnancy Outcome in Fresh Embryo Transfer Cycles
Authors: Wang Tao , Xia Yan 
Published: November 2020

Abstract
Background: Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). The aim of this study was to evaluate if the combined treatment with prednisone and bromocriptine will reduce the risks of ovarian hyperstimulation syndrome (OHSS) and influence the pregnancy outcomes in fresh embryo transfer cycles. Method: Retrospective study was performed and Infertile patients undergoing assisted reproduction techniques were recruited. Results: The cancellation rate for OHSS in the combined group was 31.45%, while the control group was 40.88%. There was a significant reduction of the OHSS cancellation rate between the combined group and the control group (P<0.001). The single embryo transfer had been completed in 350 cycles in the combined group, and 495 cycles for double embryos transfer. Single embryo transfer were just only 227 cycles for the control group, while 517 cycles for double embryos transfer (P<0.001). As for the total successful embryo implantation, 509 cycles were in the combined-treated group (40.88%), while the 442 cycles in the control group which have the statistical differences between them (38.30%, P= 0.012). There was no statistical difference in clinical pregnancy rate (P=0.492), miscarriage rate(P=0.792), ongoing pregnancy rate(P=0.719), live birth rate(P=0.295), the congenital abnormalities rate (P=0.081), and the ectopic pregnancy occurrence rate(P=0.649) between the combined group and the control group. Conclusion Compared with the bromocriptine single using, combined-treated bromocriptine with prednisone can better reduce the OHSS occurrence rate dramatically and effectively and not affect the pregnancy outcomes in fresh embryo transfer cycles.