bluuebunny/crossref_metadata_2025_split huggingface dataset:
A ten N6‐methyladenosine‐related long non‐coding RNAs signature predicts prognosis of triple‐negative breast cancer
Authors: Wu Jie , Cai Yan , Zhao Gaiping , Li Maolan 
Published: May 2021

AbstractBackgroundPatients with triple‐negative breast cancer (TNBC) face a major challenge of the poor prognosis, and N6‐methyladenosine‐(m6A) mediated regulation in cancer has been proposed. Therefore, this study aimed to explore the prognostic roles of m6A‐related long non‐coding RNAs (LncRNAs) in TNBC.MethodsClinical information and expression data of TNBC samples were collected from TCGA and GEO databases. Pearson correlation, univariate, and multivariate Cox regression analysis were employed to identify independent prognostic m6A‐related LncRNAs to construct the prognostic score (PS) risk model. Receiver operating characteristic (ROC) curve was used to evaluate the performance of PS risk model. A competing endogenous RNA (ceRNA) network was established for the functional analysis on targeted mRNAs.ResultsWe identified 10 independent prognostic m6A‐related LncRNAs (SAMD12‐AS1, BVES‐AS1, LINC00593, MIR205HG, LINC00571, ANKRD10‐IT1, CIRBP‐AS1, SUCLG2‐AS1, BLACAT1, and HOXB‐AS1) and established a PS risk model accordingly. Relevant results suggested that TNBC patients with lower PS had better overall survival status, and ROC curves proved that the PS model had better prognostic abilities with the AUC of 0.997 and 0.864 in TCGA and GSE76250 datasets, respectively. Recurrence and PS model status were defined as independent prognostic factors of TNBC. These ten LncRNAs were all differentially expressed in high‐risk TNBC compared with controls. The ceRNA network revealed the regulatory axes for nine key LncRNAs, and mRNAs in the network were identified to function in pathways of cell communication, signaling transduction and cancer.ConclusionOur findings proposed a ten‐m6A‐related LncRNAs as potential biomarkers to predict the prognostic risk of TNBC.
CYLD deficiency causes auditory neuropathy due to reduced neurite outgrowth
Authors: Yang Song , Ma Nan , Wu Xuemei , Ni Hua , Gao Siqi , Sun Lei , Zhou Peng , Tala  , Ran Jie , Zhou Jun , Liu Min , Li Dengwen 
Published: May 2021

AbstractBackgroundAuditory neuropathy is a cause of hearing loss that has been studied in a number of animal models. Signal transmission from hair cells to spiral ganglion neurons plays an important role in normal hearing. CYLD is a microtubule‐binding protein, and deubiquitinase involved in the regulation of various cellular processes. In this study, we used Cyld knockout (KO) mice and nerve cell lines to examine whether CYLD is associated with auditory neuropathy.MethodsHearing of Cyld KO mice was studied using the TDT RZ6 auditory physiology workstation. The expression and localization of CYLD in mouse cochlea and cell lines were examined by RT‐PCR, immunoblotting, and immunofluorescence. CYLD expression was knocked down in SH‐SY5Y cells by shRNAs and in PC12 and N2A cells by siRNAs. Nerve growth factor and retinoic acid were used to induce neurite outgrowth, and the occurrence and length of neurites were statistically analyzed between knockdown and control groups.ResultsCyld KO mice had mild hearing impairment. Moreover, CYLD was widely expressed in mouse cochlear tissues and different nerve cell lines. Knocking down CYLD significantly reduced the length and proportion of neurites growing from nerve cells.ConclusionsThe abnormal hearing of Cyld KO mice might be caused by a decrease in the length and number of neurites growing from auditory nerve cells in the cochlea, suggesting that CYLD is a key protein affecting hearing.
PCR array analysis identified hyperproliferation but not autophagy or apoptosis in fibrous epulis
Authors: Jiang Yangyang , Fang Bing , Xu Bin 
Published: May 2021

AbstractBackgroundThe pathogenesis of fibrous epulis is still quite unclear. Our recent genome‐wide RNA sequencing analysis revealed that in fibrous epulis, RAS‐PI3K‐AKT‐NF‐κB pathway regulates the expression of Bcl‐2 family and IAP family genes, leading to increased proliferation and the inhibition of apoptosis. The PI3K/AKT signaling pathway can promote autophagy in human gingival fibroblasts; therefore, the purpose of the present study was to identify whether autophagy is involved in the pathogenesis of fibrous epulis.MethodsDifferentially expressed genes (DEGs) between fibrous epulis lesions and normal gingival tissues were identified using the PCR array. The expression levels of eighteen autophagy‐related (ATG) family genes, twelve B‐cell lymphoma 2 (Bcl‐2) family genes, and eleven cysteine‐dependent aspartate‐directed protease (caspase) family genes were validated using quantitative real‐time PCR (qRT‐PCR). Autophagy induction was determined by measuring microtubule‐associated protein light chain 3 (LC3) conversion (LC3‐I to LC3‐II) by immunoblot analysis.ResultsThe PCR array identified six upregulated genes, whereas no genes were expressed at significantly lower levels. The upregulated genes were BCL2, BCL2L1, CXCR4, HSP90AA1, HSPA8, and IGF1, which all belong to the “regulation of autophagy” group but not the “autophagy machinery components” group. qRT‐PCR verified that the expression levels of BCL2, BCL2L1 (also known as BCL‐XL), and BCL2L2 (also known as BCL‐W) were significantly increased in fibrous epulis. No LC3‐I to LC3‐II conversion was observed.ConclusionsThe present study reveals that in fibrous epulis, Bcl‐2 and Bcl‐xL coordinately mediate gingival cell escape from apoptosis, leading to uncontrolled proliferation. Moreover, ATG family genes are not activated, and autophagy is not involved in this process.
Single‐cell transcriptomes reveal characteristic features of cell types within the human adrenal microenvironment
Authors: Huang Lin , Liao Jinling , Chen Yang , Zou Chunlin , Zhang Haiying , Yang Xiaobo , Zhang Qinyun , Li Tianyu , Mo Linjian , Zeng Yanyu , Bao Mengying , Zhang Fangxing , Ye Yu , Yang Zhanbin , Cheng Jiwen , Mo Zengnan 
Published: May 2021

AbstractVarious cells within the adrenal microenvironment are important in maintaining the body homeostasis. However, our understanding of adrenal disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ's multiple homeostatic functions. We report a cellular landscape of the human adrenal gland using single‐cell RNA sequencing. We reveal characteristic features of cell types within the human adrenal microenvironment and found immune activation of nonimmune cells in the adrenal endothelial cells. We also reveal that abundant immune cells occupied a lot of space in adrenal gland. Additionally, Sex‐related diversity in the adrenocortical cells and different gene expression profiles between the left and right adrenal gland are also observed at single‐cell resolution. Together, at single‐cell resolution, the transcriptomic map presents a comprehensive view of the human adrenal gland, which serves as a fundamental baseline description of this organ and paves a way for the further studies of adrenal diseases.
Modulating stemness of mesenchymal stem cells from exfoliated deciduous and permanent teeth by IL‐17 and bFGF
Authors: Jauković Aleksandra , Kukolj Tamara , Trivanović Drenka , Okić‐Đorđević Ivana , Obradović Hristina , Miletić Maja , Petrović Vanja , Mojsilović Slavko , Bugarski Diana 
Published: May 2021

AbstractMesenchymal stem cells (MSCs) have been identified within dental pulp tissues of exfoliated deciduous (SHEDs) and permanent (DPSCs) teeth. Although differences in their proliferative and differentiation properties were revealed, variability in SHEDs and DPSCs responsiveness to growth factors and cytokines have not been studied before. Here, we investigated the influence of interleukin‐17 (IL‐17) and basic fibroblast growth factor (bFGF) on stemness features of SHEDs and DPSCs by analyzing their proliferation, clonogenicity, cell cycle progression, pluripotency markers expression and differentiation after 7‐day treatment. Results indicated that IL‐17 and bFGF differently affected SHEDs and DPSCs proliferation and clonogenicity, since bFGF increased proliferative and clonogenic potential of both cell types, while IL‐17 similarly affected SHEDs, exerting no effects on adult counterparts DPSCs. In addition, both factors stimulated NANOG, OCT4, and SOX2 pluripotency markers expression in SHEDs and DPSCs showing diverse intracellular expression patterns dependent on MSCs type. As for the differentiation capacity, both factors displayed comparable effects on SHEDs and DPSCs, including stimulatory effect of IL‐17 on early osteogenesis in contrast to the strong inhibitory effect showed for bFGF, while having no impact on SHEDs and DPSCs chondrogenesis. Moreover, bFGF combined with IL‐17 reduced CD90 and stimulated CD73 expression on both types of MSCs, whereas each factor induced IL‐6 expression indicating its' role in IL‐17/bFGF‐modulated properties of SHEDs and DPSCs. All these data demonstrated that dental pulp MSCs from primary and permanent teeth exert intrinsic features, providing novel evidence on how IL‐17 and bFGF affect stem cell properties important for regeneration of dental pulp at different ages.
Improvement of d‐lactic acid productivity by introducing Escherichia coli acetyl‐CoA synthesis pathway in engineered Saccharomyces cerevisiae
Authors: Zhong Wei , Yang Maohua , Hao Xuemi , Sharshar Moustafa M , Wang Qinhong , Xing Jianmin 
Published: May 2021

AbstractBACKGROUNDd‐Lactic acid (d‐LA) is gaining increased attention as it can be applied in the food, pharmaceutical, cosmetic, polylactic acid and textile industries. Acid‐tolerant Saccharomyces cerevisiae is often engineered to produce organic acids. For the pyruvate decarboxylases (PDCs) or alcohol dehydrogenase 1 (ADH1) disrupted strains, the productivity of d‐LA significantly decreases due to the accumulation of acetaldehyde and acetic acid. To overcome the problem, Escherichia coli acetylating acetaldehyde dehydrogenase (A‐ALD) enzyme genes (MHPF and EUTE) (EC 1.2.1.10) were integrated into the d‐LA producing strain YIP‐A15G12 strain (CGMCC2.5803). The function of these genes is to directly convert acetaldehyde into acetyl‐CoA without energy consumption. This strain was integrated with Escherichia coli d‐lactate dehydrogenase and Issatchenkia orientalis glycosylphosphatidylinositol‐anchored protein IoGas1gene and several attenuated key pathway genes, including PDC1, PDC6, ADH1, ADH5, JEN1 (a monocarboxylate transporter), d‐lactate dehydrogenase 1 (DLD1), l‐lactate cytochrome c oxidoreductase (CYB2) and glycerol‐3‐phosphate dehydrogenases (GPD1, GPD2).RESULTSThe strain expressions of the A‐ALD enzymes effectively complemented the attenuated acetaldehyde dehydrogenase (ALD) acetyl‐CoA synthetase (ACS) pathway and significantly improved the levels of acetyl‐CoA and the productivity of d‐LA. Finally, the resulting strainYIP‐m‐ald6 (CGMCC2.5826) produced 86.9 g L–1 d‐LA with a yield of 0.77 g g–1 glucose and a volumetric productivity of 1.77 g L–1 h–1 at pH 3.58 under fed‐batch fermentation conditions.CONCLUSIONIntroducing the E. coli acetyl‐CoA synthesis pathway into the yeast strain can significantly enhance the growth of the strain and improve the d‐LA productivity, as a benefit for d‐LA production in industry. © 2021 Society of Chemical Industry (SCI).
Recovery of roseoflavin from a recombinant Streptomyces davaonensis strain by using biphasic aqueous systems
Authors: Ibarra‐Herrera Celeste C , Meza‐Dorantes Aranza , Mora‐Lugo Rodrigo , González‐Valdez José , Mack Matthias , Mata‐Gómez Marco A 
Published: May 2021

AbstractBACKGROUNDRoseoflavin (RoS) is a naturally occurring red color riboflavin analog compound, produced mainly by Streptomyces davaonensis, with a rising profile owing to its antibacterial potential. However, there is a lack of strategies for its downstream processing and the existing ones are limited to chromatographic techniques involving harmful reagents. The use of aqueous two‐phase systems (ATPS), a liquid–liquid extraction method, is explored in this work as an alternative strategy to recover and purify RoS from S. davaonensis cultures.RESULTSPolymer‐phosphate, alcohol‐phosphate and ionic liquid (IL)‐phosphate systems that varied in composition were tested, where polyethylene glycol (PEG), ethanol (EtOH) and 1‐ethyl‐3‐methylimidazolium acetate ([C2mim] [OAC]) represent the top phases, and phosphate the bottom phase. The partition behavior of either RoS alone or with contaminants was evaluated. In both cases, RoS showed a preference for top phase in all the systems tested. When cell‐free cultures were added to the systems, IL‐salt (13% and 30% w/w), EtOH‐phosphate [50% tie‐line length (TLL)] and PEG8000‐phosphate (35% w/w TLL) systems presented the highest RoS recovery (>95%), but separation of RoS and contaminants was not accomplished. The systems that demonstrated separation of RoS and contaminants were the PEG3350‐ and PEG8000‐salt systems, both with a 15% w/w TLL, as RoS and contaminants partitioned to top and bottom phases, respectively.CONCLUSIONThis is the first attempt at using ATPS to recover RoS from S. davaonensis cultures. It has been proven that RoS can be recovered directly from S. davaonensis cultures using biphasic systems. This strategy may represent a greener alternative to chromatographic techniques. © 2021 Society of Chemical Industry (SCI).
Poly (L‐lactic acid) nanofibrous scaffolds support the proliferation and neural differentiation of mouse neural stem and progenitor cells
Authors: Miri Vahideh , Asadi Asadollah , Sagha Mohsen , Najafzadeh Nowruz , Golmohammadi Mohammad Ghasem 
Published: May 2021

AbstractBackgroundThe distribution and growth of cells on nanofibrous scaffolds seem to be an indispensable precondition in cell tissue engineering. The potential use of biomaterial scaffolds in neural stem cell therapy is increasingly attracting attention.AimIn this study, we produced porous nanofibrous scaffolds fabricated from random poly‐L‐lactic acid (PLLA) to support neurogenic differentiation of neural stem and progenitor cells (NSPCs), isolated from the subventricular zone (SVZ) of the adult mouse brain.MethodsThe viability and proliferation of the NSPCs on the nanofibrous PLLA scaffold were also tested by nuclear staining with 4, 6‐diamidino‐2‐phenylindole dihydrochloride (DAPI), 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyl tetrazolium bromide (MTT) assay and scanning electron microscopy (SEM). To investigate the differentiation potential of NSPCs on the scaffolds, the cells were treated with a neurogenic differentiation medium, and immunostaining was done to detect neuronal and glial cells after 14 and 21 days of cultivation. Furthermore, the morphology of differentiated cells on the scaffold was examined using SEM.ResultsThe DAPI staining revealed the proliferation of NSPCs onto the surface of the nanofibrous PLLA scaffold. DAPI‐positive cells were counted on days 2 and 5 after cultivation. The mean number of cells in each microscopic field was significantly (p < .05) increased (51 ± 19 on day 2 compared to 77 ± 25 cells on day 5). The results showed that the cell viability on PLLA scaffolds significantly increased compared to control groups. Moreover, cell viability was significantly increased 5 days after culturing (262.3 ± 50.2) as compared to 2 days culture in Vitro (174.2 ± 28.3, p < .05). Scanning electron micrographs also showed that the NSPCs adhered and differentiated on PLLA scaffolds. We found that the neural cell markers, microtubule‐associated protein 2 (MAP2) and glial ﬁbrillary acidic protein (GFAP), were expressed in NSPCs seeded on random PLLA scaffolds after 21 days of cultivation.ConclusionThese results suggest that the PLLA nano‐scaffolds, due to their biocompatible property, are an appropriate structure for the proliferation, differentiation, and normal growth of NSPCs.
Understanding patients' views and willingness toward the use of telehealth in a cancer genetics service in Asia
Authors: Sim Jackie , Shaw Tarryn , Li Shao‐Tzu , Courtney Eliza , Yuen Jeanette , Chiang Jianbang , Nazir Maryam , Tan Ryan , Ngeow Joanne 
Published: May 2021

AbstractTelehealth is a growing field, its pertinence magnified by COVID‐19 causing the accelerated digitalization of the world. Given the significant global demand to provide telehealth services, it is important to explore patient receptiveness toward this alternative service model, particularly from regions where it has yet to be implemented. We conducted a cross‐sectional study to understand the views and willingness of patients toward the use of telehealth for cancer genetic counseling. A survey was completed by 160 patients of the National Cancer Centre Singapore, and descriptive statistics were used to analyze the data. The study found that 95.6% (n = 153/160) of participants did not have prior telehealth experience. Most participants were willing or neutral toward having genetic counseling by phone (n = 114/160, 71.3%) and video (n = 106/160, 66.3%). However, majority prefer in‐person appointments for first (n = 127/160, 79.4%) and follow‐up (n = 97/160, 60.6%) visits over telehealth. Majority agreed that a phone/video consultation would meet most of their needs but voiced concerns regarding privacy and sharing of information (n = 79/160, 49.4% for phone; n = 74/160, 46.3% for video) and whether their emotional needs could be met (n = 61/160, 38.1%). Participants’ age, employment status, income, mode of transportation to the appointment, and whether special arrangements were made to attend the in‐person appointment were associated with receptivity to telehealth genetic counseling (p ≤ .05 for all). This study adds diversity to existing literature and demonstrates that patients from Asia are generally willing and accepting of the use of telehealth in a cancer genetics service. This will help meet increasing global demand of telehealth consultations in the post‐pandemic new norm. Furthermore, it will also provide services for underserved populations and patients requiring urgent testing in a timely manner. Further studies are needed to explore the cost‐effectiveness and fair billing methods, as well as willingness and acceptability of telehealth genetic counseling in post‐COVID times.
Can reducing planning safety margins broaden the inclusion criteria for lung stereotactic ablative body radiotherapy?
Authors: Ghandourh Wsam , Batumalai Vikneswary , Boxer Miriam , Holloway Lois 
Published: May 2021

AbstractIntroductionStereotactic ablative body radiotherapy (SABR) is currently indicated for inoperable, early‐stage non‐small cell lung carcinoma (NSCLC). Advancements in image‐guidance technology continue to improve treatment precision and enable reductions in planning safety margins. We investigated the dosimetric benefits of margin reduction, its potential to extend SABR to more NSCLC patients and the factors influencing plan acceptability.MethodsThis retrospective analysis included 61 patients (stage IA–IIIA) treated with conventional radiotherapy. Patients were ineligible for SABR due to tumour size or proximity to organs at risk (OAR). Using Pinnacle auto‐planning, three SABR plans were generated for each patient: a regular planning target volume margin plan, a reduced margin plan (gross tumour volume GTV+3 mm) and a non‐margin plan. Targets were planned to 48Gy/4 or 50Gy/5 fractions depending on location. Plans were compared in terms of target coverage, OAR doses and dosimetric acceptability based on local guidelines. Predictors of acceptability were investigated using logistic regression analysis.ResultsCompared to regular margin plans, both reduced margin and non‐margin plans resulted in significant reductions to almost all dose constraints. Dose conformity was significantly worse in non‐margin plans (P < 0.05) and strongly correlated with targets’ surface area/volume ratio (R2 = 0.9, P < 0.05). 26% of reduced margin plans were acceptable, compared to 54% of non‐margin plans. GTV overlap with OARs significantly affected plan acceptability (OR 0.008, 95% CI 0.001–0.073).ConclusionMargin reduction significantly reduced OAR doses enabling acceptable plans to be achieved for patients previously excluded from SABR. Indications for lung SABR may broaden as treatment accuracy continues to improve; further work is needed to identify patients most likely to benefit.
Comparison of MMCFS and SINTEX‐F2 for seasonal prediction of Indian summer monsoon rainfall
Authors: Pradhan Maheswar , Rao Suryachandra A. , Doi Takeshi , Pillai Prasanth A. , Srivastava Ankur , Behera Swadhin 
Published: May 2021

AbstractA comparison of the Indian summer Monsoon Rainfall (ISMR) in two different coupled models (viz., Scale Interaction Experiment‐Frontier‐F2; SINTEX‐F2, and Monsoon Mission Climate Forecast System; MMCFS) is carried out to ascertain the predictability sources in these models and their strengths and weaknesses. SINTEX‐F2 has a stronger cold sea surface temperature (SST) bias in the central equatorial Pacific, and it simulates mean ISMR better while underestimating the interannual variability of ISMR. On the other hand, MMCFS has warmer SST bias in the tropical Pacific off the equator, simulates a drier mean monsoon, but has a more realistic ISMR interannual variability. Further, the cold SST bias in the central tropical Pacific adversely affects the ability of the SINTEX‐F2 to capture the El Niño–Southern Oscillation (ENSO) related interannual variability and teleconnection patterns with monsoon by shifting it further westward in the tropical Pacific Ocean. The models' skill in simulating various climate indices are compared by considering criteria such as anomaly correlation coefficient (ACC), spread to root mean square error (RMSE) ratio, and signal to noise ratio (SNR). The prediction skill for ISMR in terms of ACC in MMCFS (.53) and SINTEX‐F2 (.45) are comparable for hindcasts initialized in February month. However, RMSE for ISMR from February initial conditions in SINTEX‐F2 (1.43 mm/day) is small compared to MMCFS (2.34 mm/day). A simple multi‐model ensemble prediction system based on MMCFS and SINTEX‐F2 results in better prediction skill in terms of ACC for tropical SST and ISMR. The spread/RMSE ratio for ISMR is similar in both the models but is better for ENSO indices in MMCFS at a longer lead time than in SINTEX‐F2. Considering the SNR as performance criteria, MMCFS has an advantage due to better predictability of SST and vertical wind shear in several parts of the Indo‐Pacific domain.