bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Loss of Profilin 1 Causes Early Onset Paget's Disease of Bone
Authors: Scotto di Carlo Federica , Pazzaglia Laura , Esposito Teresa , Gianfrancesco Fernando 
Published: January 2020

ABSTRACT
Paget's disease of bone (PDB) is a late-onset disorder frequently caused by mutations in the SQSTM1 gene, leading to hyperactive osteoclasts and resulting in bone pain, deformities, and fractures. However, some more severe forms of PDB—negative for SQSTM1 mutations—have been described, in which the disease degenerates into bone cancers and shows a poor prognosis. Osteosarcoma is the most frequent and aggressive tumor arising in PDB (OS/PDB), with a 5-year survival rate almost nil, but the underlying molecular mechanism is unknown. Here, we investigated an extended pedigree with 11 individuals affected by early onset and polyostotic PDB, mainly interesting the appendicular skeleton. Interestingly, three members also developed secondary osteosarcoma. We performed exome sequencing and identified a 4-bp deletion in the PFN1 gene, resulting in the degradation of the mutant protein. Copy number screening on 218 PDB individuals of our biobank disclosed that four of them (~2%) carry a germline heterozygous deletion of PFN1. The identification of these subjects, who exhibit a particularly severe form of disease, emphasizes the diagnostic value of this genetic screening to identify PDB individuals predisposed to develop osteosarcoma. In fact, we detected allelic imbalance at PFN1 locus also in 8 of 14 (57%) sporadic OS/PDB, further proving its causative role. in vitro experiments also confirmed PFN1 involvement in this form of PDB. Indeed, CRISPR-Cas9-mediated Pfn1 knockout in pre-osteoclasts resulted into enhanced osteoclast differentiation and resorption, with the formation of large osteoclasts never described before in PDB. In addition, Pfn1 lacking pre-osteoblasts lost their differentiation capability and failed to efficiently mineralize bone. Moreover, they acquired features of malignant transformation, including loss of focal adhesions and increased invasion ability. In conclusion, these findings disclose PFN1 haploinsufficiency as the pathological mechanism in OS/PDB. © 2020 American Society for Bone and Mineral Research.
Differential effects of N‐TiO2 nanoparticle and its photo‐activated form on autophagy and necroptosis in human melanoma A375 cells
Authors: Mohammadalipour Zahra , Rahmati Marveh , Khataee Alireza , Moosavi Mohammad A. 
Published: January 2020

AbstractThe manipulation of autophagy provides a new opportunity for highly effective anticancer therapies. Recently, we showed that photodynamic therapy (PDT) with nitrogen‐doped titanium dioxide (N‐TiO2) nanoparticles (NPs) could promote the reactive oxygen species (ROS)‐dependent autophagy in leukemia cells. However, the differential autophagic effects of N‐TiO2 NPs in the dark and light conditions and the potential of N‐TiO2‐based PDT for the treatment of melanoma cells remain unknown. Here we show that depending on the visible‐light condition, the autophagic response of human melanoma A375 cells to N‐TiO2 NPs switches between two different statuses (ie., flux or blockade) with the opposite outcomes (ie., survival or death). Mechanistically, low doses of N‐TiO2 NPs (1‐100 µg/ml) stimulate a nontoxic autophagy flux response in A375 cells, whereas their photo‐activation leads to the impairment of the autophagosome‐lysosome fusion, the blockade of autophagy flux and consequently the induction of RIPK1‐mediated necroptosis via ROS production. These results confirm that photo‐controllable autophagic effects of N‐TiO2 NPs can be utilized for the treatment of cancer, particularly melanoma.
Mitochondria‐targeted antioxidant mito‐TEMPO alleviate oxidative stress induced by antimycin A in human mesenchymal stem cells
Authors: Barzegari Abolfazl , Nouri Mohammad , Gueguen Virginie , Saeedi Nazli , Pavon‐Djavid Graciela , Omidi Yadollah 
Published: January 2020

AbstractThe cell therapy of damaged tissue, which is linked to hypoxia condition might fail, in large part due to the emergence of oxidative stress (OS) and/or mitochondrial dysfunctions. Thus, the invigoration of stem cells against oxidative stress could be a reliable strategy to improve the cell therapy outcome. Of various antioxidants, mito‐Tempo (mito‐T) is one of the potent antioxidants that could target and neutralize the mitochondrial oxidative stress. In this study, for the induction of hypoxia and oxidative stress in mitochondria of the mesenchymal stem cells (MSCs) isolated from human adipose tissue, antimycin A (AMA) was used and then several parameters were analyzed, including cell viability and cell cycle arrest of MSCs exposed to AMA, mito‐T, antioxidant potential, redox homeostasis, and signaling pathways in MSCs under oxidative stress. Based on our findings, the treated MSCs were found to impose a high resistance to the OS‐induced apoptosis, which correlated with the nuclear factor erythroid 2‐related factor 2 (Nrf2) pathway required to manage OS. Upon exposure of the MSCs to high oxidative stress conditions using AMA, the cells failed to scavenge. The use of mito‐T was found to alleviate the damage induced by oxidative stress through both direct functions of the free radical scavenging and the interplay in terms of cell signaling pathways including the upregulation of the Nrf2 pathway. These findings may pave the way in the stem cell therapy for the hypoxia‐mediated tissue damage.
Real‐time measurement of E2: ERα transcriptional activity in living cells
Authors: Cipolletti Manuela , Leone Stefano , Bartoloni Stefania , Busonero Claudia , Acconcia Filippo 
Published: January 2020

AbstractKinetic analyses of diverse physiological processes have the potential to unveil new aspects of the molecular regulation of cell biology at temporal levels. 17β‐estradiol (E2) regulates diverse physiological effects by binding to the estrogen receptor α (ERα), which primarily works as a transcription factor. Although many molecular details of the modulation of ERα transcriptional activity have been discovered including the impact of receptor plasma membrane localization and its relative E2‐evoked signaling, the knowledge of real‐time ERα transcriptional dynamics in living cells is lacking. Here, we report the generation of MCF‐7 and HeLa cells stably expressing a modified luciferase under the control of an E2‐sensitive promoter, which activity can be continuously monitored in living cells and show that E2 induces a linear increase in ERα transcriptional activity. Ligand‐independent (e.g., epidermal growth factor) receptor activation was also detected in a time‐dependent manner. Kinetic profiles of ERα transcriptional activity measured in the presence of both receptor antagonists and inhibitors of ERα plasma membrane localization reveal a biphasic dynamic of receptor behavior underlying novel aspects of receptor‐regulated transcriptional effects. Finally, analysis of the rate of the dose‐dependent E2 induction of ERα transcriptional activity demonstrates that low doses of E2 induce an effect identical to that determined by high concentrations of E2 as a function of the duration of hormone administration. Overall, we present the characterization of sensitive stable cell lines were to study the kinetic of E2 transcriptional signaling and to identify new aspects of ERα function in different physiological or pathophysiological conditions.
Molecular mechanism underlying the difference in proliferation between placenta‐derived and umbilical cord‐derived mesenchymal stem cells
Authors: Feng Xudong , Liu Jingqi , Xu Yanping , Zhu Jiaqi , Chen Wenyi , Feng Bing , Pan Qiaoling , Yu Jiong , Shi Xiaowei , Yang Jinfeng , Li Yang , Li Lanjuan , Cao Hongcui 
Published: January 2020

AbstractThe placenta and umbilical cord are pre‐eminent candidate sources of mesenchymal stem cells (MSCs). However, placenta‐derived MSCs (P‐MSCs) showed greater proliferation capacity than umbilical cord‐derived MSCs (UC‐MSCs) in our study. We investigated the drivers of this proliferation difference and elucidated the mechanisms of proliferation regulation. Proteomic profiling and Gene Ontology (GO) functional enrichment were conducted to identify candidate proteins that may influence proliferation. Using lentiviral or small interfering RNA infection, we established overexpression and knockdown models and observed changes in cell proliferation to examine whether a relationship exists between the candidate proteins and proliferation capacity. Real‐time quantitative polymerase chain reaction, western blot analysis, and immunofluorescence assays were conducted to elucidate the mechanisms underlying proliferation. Six candidate proteins were selected based on the results of proteomic profiling and GO functional enrichment. Through further validation, yes‐associated protein 1 (YAP1) and β‐catenin were confirmed to affect MSCs proliferation rates. YAP1 and β‐catenin showed increased nuclear colocalization during cell expansion. YAP1 overexpression significantly enhanced proliferation capacity and upregulated the expression of both β‐catenin and the transcriptional targets of Wnt signaling, CCND1, and c‐MYC, whereas silencing β‐catenin attenuated this influence. We found that YAP1 directly interacts with β‐catenin in the nucleus to form a transcriptional YAP/β‐catenin/TCF4 complex. Our study revealed that YAP1 and β‐catenin caused the different proliferation capacities of P‐MSCs and UC‐MSCs. Mechanism analysis showed that YAP1 stabilized the nuclear β‐catenin protein, and also triggered the Wnt/β‐catenin pathway, promoting proliferation.
Circular RNA circTET3 mediates migration of rat vascular smooth muscle cells by targeting miR‐351‐5p
Authors: Yao Qing‐Ping , Liu Ze , Yao Ai‐Hong , Liu Ji‐Ting , Jiang Jun , Chen Yi , Li Shan‐Shan , Han Yue , Jiang Zong‐Lai , Qi Ying‐Xin 
Published: January 2020

AbstractAbnormal migration and proliferation of vascular smooth muscle cells (VSMCs) are the pathological basis of hyperplasia during vein graft disease. It remains unknown if circular RNAs (circRNAs) are involved in vein graft disease. In the present study, a rat vein graft model was constructed by the “cuff” technique, and whole transcriptome deep sequencing was applied to identify differential circRNAs in the grafted vein compared to the control. We identified a novel circRNA, named circTET3, whose structure was verified by Sanger sequencing and RNase R digestion. CircTET3 was increased in the grafted vein and stably located in the cytoplasm as detected by fluorescence in situ hybridization. Knockdown of circTET3 suppressed VSMC migration by acting as an endogenous miR‐351‐5p sponge detected by RNA pull‐down and dual‐luciferase reporter assays. PTPN1 was the targeted gene due to the competitive binding of circTET3 to miR‐351‐5p. This regulatory pathway may serve as a potential therapeutic avenue against intimal hyperplasia in vein graft disease.
Therapeutic targeting of neutrophil exocytosis
Authors: Catz Sergio D. , McLeish Kenneth R. 
Published: January 2020

Abstract
Dysregulation of neutrophil activation causes disease in humans. Neither global inhibition of neutrophil functions nor neutrophil depletion provides safe and/or effective therapeutic approaches. The role of neutrophil granule exocytosis in multiple steps leading to recruitment and cell injury led each of our laboratories to develop molecular inhibitors that interfere with specific molecular regulators of secretion. This review summarizes neutrophil granule formation and contents, the role granule cargo plays in neutrophil functional responses and neutrophil-mediated diseases, and the mechanisms of granule release that provide the rationale for development of our exocytosis inhibitors. We present evidence for the inhibition of granule exocytosis in vitro and in vivo by those inhibitors and summarize animal data indicating that inhibition of neutrophil exocytosis is a viable therapeutic strategy.
Machine Learning for Predicting Complications in Head and Neck Microvascular Free Tissue Transfer
Authors: Formeister Eric J. , Baum Rachel , Knott P. Daniel , Seth Rahul , Ha Patrick , Ryan William , El‐Sayed Ivan , George Jonathan , Larson Andrew , Plonowska Karolina , Heaton Chase 
Published: January 2020

Objectives/HypothesisMachine learning (ML) is a type of artificial intelligence wherein a computer learns patterns and associations between variables to correctly predict outcomes. The objectives of this study were to 1) use a ML platform to identify factors important in predicting surgical complications in patients undergoing head and neck free tissue transfer, and 2) compare ML outputs to traditionally employed logistic regression models.Study DesignRetrospective cohort study.MethodsUsing a dataset of 364 consecutive patients who underwent head and neck microvascular free tissue transfer at a single institution, 14 clinicopathologic characteristics were analyzed using a supervised ML algorithm of ensemble decision trees to predict surgical complications. The relative importance values of each variable in the ML analysis were then compared to logistic regression models.ResultsThere were 166 surgical complications, which included bleeding or hematoma in 30 patients (8.2%), fistulae in 25 patients (6.9%), and infection or dehiscence in 52 patients (14.4%). There were 59 take‐backs (16.2%), and six total (1.6%) and five partial (1.4%) flap failures. ML models were able to correctly classify outcomes with an accuracy of 65% to 75%. Factors that were identified in ML analyses as most important for predicting complications included institutional experience, flap ischemia time, age, and smoking pack‐years. In contrast, the significant factors most frequently identified in traditional logistic regression analyses were patient age (P = .03), flap type (P = .03), and primary site of reconstruction (P = .06).ConclusionsIn this single‐institution dataset, ML algorithms identified factors for predicting complications after free tissue transfer that were distinct from traditional regression models.Level of Evidence2c Laryngoscope, 2020
Thistle crops in marginal lands after compost addition: Plant biomass and effect on soil physical, chemical and biological properties
Authors: Domínguez María T. , Panettieri Marco , Madejón Engracia , Madejón Paula 
Published: January 2020

AbstractThe growing interest in bioenergy crops that do not compete with food production for land use has promoted the implementation of low‐input crops on marginal lands. However, these crops can be highly limited by the low soil nutrient and water availability in these lands. In this work, biosolid compost (BC) was applied to improve the quality of a degraded, C‐poor soil under Mediterranean conditions. We evaluated the effects of BC addition on soil physical, chemical and biochemical properties in a field experiment with two native species with potential as bioenergy crops (Cynara cardunculusandSilybum marianum). The addition of BC significantly increased soil C content from <0.9% to >1%, and produced a two‐fold increase in soil P availability. Respiration rates and microbial activity were only slightly improved by BC, while significant increases in the PLFA molar content assigned to general classes of bacteria were recorded. The beneficial effects of BC triggered the percentage of seed germination inS. marianum(from 64% in control plots to 85% in the compost treatment) as well as the production of biomass in both species (two‐fold increase in the second year).Application of BC led to increases in energy yield of 58% forC. cardunculusand of 71% forS. marianum. Considering the low economic cost of BC, its application on marginal soils in combination withC. cardunculuscrops, producing much larger biomass thanS. marianum, could be considered as an option for degraded Mediterranean soils.
Efficacy of Fractional CO2 Laser, Promestriene, and Vaginal Lubricant in the Treatment of Urinary Symptoms in Postmenopausal Women: A Randomized Clinical Trial
Authors: Aguiar Luiza Borges , Politano Carlos Alberto , Costa‐Paiva Lúcia , Juliato Cássia Raquel Teatin 
Published: January 2020

Background and ObjectivesEvaluating the efficacy of the fractional CO2 laser, promestriene, and vaginal lubricant to treat urinary symptoms in women with genitourinary syndrome of menopause.Study Design/Materials and MethodsWe conducted a randomized clinical trial with 72 postmenopausal women aged 50 years or older. The participants were randomized to one intervention each in three treatment groups fractional CO2 laser, promestriene, and vaginal lubricant. Urinary symptoms were assessed prior to treatment and 2 weeks after treatment completion using validated questionnaires, the International Consultation on Incontinence Questionnaire (ICIQ‐UI SF), and the International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ‐OAB).ResultsThere was a significant reduction in the total ICIQ‐UI SF score in the intragroup comparison (baseline vs. week 14) of the CO2 laser group (P = 0.004). This group also showed a statistically significant reduction in nocturia (1.33 ± 0.87 vs. 1.00 ± 0.76, respectively; P = 0.031). In the intergroup comparison after treatment, nocturia in the lubricant group had worsened compared with that of the other two groups (P = 0.002). Regarding the total ICIQ‐OAB score, the results of the CO2 laser group were superior to those of the lubricant group in the intergroup comparison (7.76 ± 3.36, P = 0.020; analysis of variance P = 0.038).ConclusionThe results were significantly different between the intravaginal fractional CO2 laser and topical estrogen groups for treating urinary symptoms related to the genitourinary syndrome of menopause. Further controlled and randomized studies are needed. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.
Understanding the intention to buy secondhand clothing on sharing economy platforms: The influence of sustainability, distance from the consumption system, and economic motivations
Authors: Ek Styvén Maria , Mariani Marcello M. 
Published: January 2020

AbstractSharing economy (SE) platforms are increasingly providing an effective means of connecting providers and users of secondhand goods. While media seem to emphasize that the trend of selling/buying secondhand has been growing due to the consolidation and development of peer‐to‐peer (P2P) sharing platforms, a comprehensive identification of the antecedents of buying secondhand on SE platforms is virtually missing. This study addresses this gap by (a) identifying different sets of motivations and attitudes leading consumers to adopt SE platforms for secondhand buying and (b) testing a model on a sample of UK consumers in the context of P2P sharing platforms for secondhand clothing. This study reveals that there are three major antecedents of consumers' attitude towards buying secondhand clothes on P2P–SE platforms: perceived sustainability, economic motivations, and taking a distance from the consumption system. Perceived sustainability and economic motivations influence positively attitude toward buying secondhand, as well as motivations in the form of distance from the consumption system. Attitude toward buying secondhand is positively influenced also by distance from the system and, in turn, has a strong positive influence on behavioral intention to buy secondhand clothes. Moreover, past experience of buying secondhand online has a positive moderating effect on the relationship between perceived sustainability and distance from the consumption system.
CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly
Authors: Xie Wangkai , Chen Chao , Han Zheng , Huang Jingjing , Liu Xin , Chen Hongjun , Zhang Teming , Chen Sian , Chen Chenbin , Lu Mingdong , Shen Xian , Xue Xiangyang 
Published: January 2020

AbstractDiffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2‐associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F‐actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.
Survey of Ehlers‒Danlos Patients’ ophthalmic surgery experiences
Authors: Louie Anita , Meyerle Catherine , Francomano Clair , Srikumaran Divya , Merali Farhan , Doyle Jefferson J. , Bower Kraig , Bloom Lara , Boland Michael V. , Mahoney Nicholas , Daoud Yassine , Singman Eric L. 
Published: January 2020

AbstractBackgroundEhlers‒Danlos Syndrome (EDS) is a rare disease affecting approximately 1 in 5,000 people. Although ophthalmic conditions associated with EDS have been described, little data exist concerning ophthalmic surgical outcomes experienced by EDS patients.MethodsPatients with EDS were surveyed via the EDS Society and asked about their ophthalmic surgical experiences including procedure, complications, and the timing with respect to receiving the EDS diagnosis. Complications were confirmed as such by subspecialists.ResultsOf 579 respondents, 467 reported confirmed EDS, and 112 of those had an ophthalmic procedure, including refractive surgery, cataract/lens surgery, retinal surgery, strabismus surgery, oculoplastic surgery, corneal surgery, and laser surgery for glaucoma. The rate of confirmed complications was: 23%‐refractive, 33%‐lens/cataract, 33%‐retina, 59%‐strabismus, 23%‐ oculoplastics, 0%‐cornea, and 25%‐glaucoma laser. In addition, 76% of patients underwent surgery prior to the EDS diagnosis.ConclusionsPatients with EDS may have elevated risk of postoperative ophthalmic surgical complications. It would seem reasonable to systemically and prospectively explore how patients with EDS respond to ophthalmic surgery. Furthermore, it would seem circumspect to ask surgical candidates patients about whether they carry a diagnosis of EDS or have signs and symptoms of EDS prior to surgery.