bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation
Authors: Amable Gastón , Martínez‐León Eduardo , Picco María Elisa , Nemirovsky Sergio I. , Rozengurt Enrique , Rey Osvaldo 
Published: April 2020

AbstractE‐cadherin, a central component of the adherens junction (AJ), is a single‐pass transmembrane protein that mediates cell–cell adhesion. The loss of E‐cadherin surface expression, and therefore cell–cell adhesion, leads to increased cell migration and invasion. Treatment of colorectal cancer (CRC)‐derived cells (SW‐480 and HT‐29) with 2.0 mM metformin promoted a redistribution of cytosolic E‐cadherin to de novo formed puncta along the length of the contacting membranes of these cells. Metformin also promoted translocation from the cytosol to the plasma membrane of p120‐catenin, another core component of the AJs. Furthermore, E‐cadherin and p120‐catenin colocalized with β‐catenin at cell–cell contacts. Western blot analysis of lysates of CRC‐derived cells revealed a substantial metformin‐induced increase in the level of p120‐catenin as well as E‐cadherin phosphorylation on Ser838/840, a modification associated with β‐catenin/E‐cadherin interaction. These modifications in E‐cadherin, p120‐catenin and β‐catenin localization suggest that metformin induces rebuilding of AJs in CRC‐derived cells. Those modifications were accompanied by the inhibition of focal adhesion kinase (FAK), as revealed by a significant decrease in the phosphorylation of FAK at Tyr397 and paxillin at Tyr118. These changes were associated with a reduction in the numbers, but an increase in the size, of focal adhesions and by the inhibition of cell migration. Overall, these observations indicate that metformin targets multiple pathways associated with CRC development and progression.
Matrix stiffness controls cardiac fibroblast activation through regulating YAP via AT1R
Authors: Niu Lele , Jia Yuanbo , Wu Mian , Liu Han , Feng Yanjing , Hu Yan , Zhang Xiaohui , Gao Dengfeng , Xu Feng , Huang Guoyou 
Published: April 2020

AbstractCardiac fibrosis is a common pathway leading to heart failure and involves continued activation of cardiac fibroblasts (CFs) into myofibroblasts during myocardium damage, causing excessive deposition of the extracellular matrix (ECM) and thus increases matrix stiffness. Increasing evidence has shown that stiffened matrix plays an important role in promoting CF activation and cardiac fibrosis, and several signaling factors mediating CF mechanotransduction have been identified. However, the key molecules that perceive matrix stiffness to regulate CF activation remain to be further explored. Here, we detected significantly increased expression and nuclear localization of Yes‐associated protein (YAP) in native fibrotic cardiac tissues. By using mechanically regulated in vitro cell culture models, we found that a stiff matrix‐induced high expression and nuclear localization of YAP in CFs, accompanied by enhanced cell activation. We also demonstrated that YAP knockdown decreased fibrogenic response of CFs and that YAP overexpression promoted CF activation, indicating that YAP plays an important role in mediating matrix stiffness‐induced CF activation. Further mechanistic studies revealed that the YAP pathway is an important signaling branch downstream of angiotensin II type 1 receptor in CF mechanotransduction. The findings help elucidate the mechanism of fibrotic mechanotransduction and may contribute to the development of new approaches for treating fibrotic diseases.
Retracted: HO‐1 overexpression alleviates senescence by inducing autophagy via the mitochondrial route in human nucleus pulposus cells
Authors: Yi Weiwei , Lan Haiyang , Wen Yafeng , Wang Yiyang , He Danshuang , Bai Zhibiao , Zhang Ye , Jiang Wei , Liu Bo , Shen Jieliang , Hu Zhenming 
Published: April 2020

AbstractIntervertebral disc degeneration (IDD) is closely associated with aging. Our previous studies have confirmed that heme oxygenase‐1 (HO‐1) can inhibit nucleus pulposus (NP) cell apoptosis. However, whether or not HO‐1 is involved in NP cell senescence and autophagy is unclear. Our results indicated that HO‐1 expression was reduced in IDD tissues and replicative senescent NP cells. HO‐1 overexpression using a lentiviral vector reduced the NP cell senescence level, protected mitochondrial function, and promoted NP cell autophagy through the mitochondrial pathway. Autophagy inhibitor 3‐MA pretreatment reversed the anti‐senescent and protective effects on the mitochondrial function of HO‐1, which promoted the degradation of the extracellular matrix (ECM) in the intervertebral disc. In vivo, HO‐1 overexpression inhibited IDD and enhanced autophagy. In summary, these results suggested that HO‐1 overexpression alleviates NP cell senescence by inducing autophagy via the mitochondrial route.
PLS3 predicts poor prognosis in pancreatic cancer and promotes cancer cell proliferation via PI3K/AKT signaling
Authors: Xin Zechang , Li Duguang , Mao Feiyu , Du Yan , Wang Xiaodong , Xu Peng , Li Zhennan , Qian Jianjun , Yao Jie 
Published: April 2020

AbstractPlastin‐3 plays a key role in cancer cell proliferation and invasion, but its prognostic value in pancreatic cancer (PACA) remains poorly defined. In this study, we show that PLS3 messenger RNA is overexpressed in PACA tissue compared with normal tissue. We accumulated 207 cases of PACA specimens to perform immunohistochemical analysis and demonstrated that PLS3 levels correlate with T‐classification (p < .001) and pathology (p < .001). Furthermore, overall survival rates (p < .001) in tumors with high PLS3 expression were poor, as assessed through Kaplan–Meier survival analysis. PLS3 was found to be an independent prognostic factor for PACA through multivariate Cox regression analysis. Moreover, we found that PLS3 enhances the proliferation and invasion of tumor cells as assessed through Cell Counting Kit‐8, wounding healing assays, and Transwell assays. The upregulation of PLS3 also led to enhanced phosphatidylinositol‐3 kinase/protein kinase B signaling in PACA cells. These data suggest that PLS3 is a biomarker to estimate PACA progression and represents a molecular target for PACA therapy.
TORS Base‐of‐Tongue Mucosectomy in Human Papilloma Virus‐Negative Carcinoma of Unknown Primary
Authors: Kubik Mark W. , Channir Hani I. , Rubek Niclas , Kim Seungwon , Ferris Robert L. , von Buchwald Christian , Duvvuri Umamaheswar 
Published: April 2020

ObjectiveTo analyze the role of transoral robotic base‐of‐tongue mucosectomy in a cohort of patients with human papilloma virus negative unknown primary carcinoma.Study DesignRetrospective database analysis.MethodsA retrospective database review from 2012 to 2018 was performed at two large tertiary centers to study patients with human papilloma virus (HPV)‐negative unknown primary carcinoma who underwent transoral robotic base‐of‐tongue mucosectomy. P16 testing was used as a surrogate for HPV status. Patients were included that had squamous cell carcinoma metastatic to the lateral neck based on fine needle aspiration or open biopsy. Preoperatively, all patients were classified as having an unknown primary based on normal clinical and flexible endoscopic exam, normal operative endoscopy, nonlocalizing imaging, and tonsillectomy. All patients underwent robotic base‐of‐tongue mucosectomy. The primary outcome measure was the incidence of pathologic identification of a mucosal primary.ResultsTwenty‐three patients with p16‐negative unknown primary carcinoma were identified and studied. All patients underwent transoral robotic base‐of‐tongue mucosectomy. Median age was 60 years at the time of diagnosis, and 18 of 23 (78.2%) were male. Pathologic analysis of the base‐of‐tongue specimens showed a primary tumor in only three of 23 (13.0%) of patients.ConclusionDespite prior evidence suggesting a high rate of primary site identification in HPV‐related disease, robotic base‐of‐tongue mucosectomy may not be indicated for HPV‐negative unknown primary carcinoma based on a low likelihood of finding the primary.Level of Evidence4 Laryngoscope, 131:78–81, 2021
Compartmental Surgery for Oral Tongue Cancer: Objective and Subjective Functional Evaluation
Authors: Grammatica Alberto , Piazza Cesare , Montalto Nausica , Del Bon Francesca , Frittoli Barbara , Mazza Monica , Paderno Alberto , Lancini Davide , Fior Milena , Deganello Alberto , Lombardi Davide , Nicolai Piero 
Published: April 2020

ObjectiveTo assess functional outcomes in patients treated by compartmental tongue surgery (CTS) and reconstruction for advanced oral tongue/floor‐of‐mouth cancer.Study DesignRetrospective case series.MethodsA retrospective cohort of patients (n = 48) treated by CTS and free flap reconstruction was prospectively evaluated concerning postoperative functional outcomes at different time points (6 months and 1 year). Swallowing was studied by videonasal endoscopic evaluation (VEES) and videofluoroscopy (VFS), testing various food consistencies and grading the results with the Donzelli scale. Speech articulation, lingual strength, and endurance were studied by phone call and Iowa Oral Performance Instrument (IOPI). Subjective tests (EORTC H&N35 and UWQOL) were administered.ResultsAfter 1 year, VEES showed a Donzelli scale of 67% level 1, 23% level 2, and 10% level 3. Vallecular pouch was present in 81% of patients. VFS showed levels 1, 2, and 3 in 42%, 25%, and 33%, respectively, with liquids (L); 48%, 19%, and 33%, with semi‐liquids (SL); and 54%, 33%, and 13%, with semi‐solids (SS). Vallecular pouch residue was present in 69% with L, 73% with SL, and 87% with SS. The mean number of words recognized at phone call was 56 of 75 (range, 27–74). IOPI showed a mean tongue strength of 19.2 kPa (range, 0–40), and a mean endurance of 16.2 seconds (range, 0–60).ConclusionCTS does not significantly affect speech. Sub‐clinical food aspiration and vallecular pouch are present in a significant proportion of patients, especially when adjuvant treatments are administered. Residual tongue strength is not affected when proper reconstruction is performed.Level of Evidence4 Laryngoscope, 131:E176–E183, 2021
Urban expansion or poor productivity: Explaining regional differences in cropland abandonment in China during the early 21st century
Authors: Qiu Bingwen , Yang Xin , Tang Zhenghong , Chen Chongcheng , Li Haiwen , Berry Joe 
Published: April 2020

AbstractCropland abandonment has long been recognized as a marginalization process in rural regions but recently also as a precursor to urbanization in peri‐urban regions. This study aimed to evaluate the relative importance of urbanization and poor productivity in cropland abandonment. A thorough investigation was conducted on 345 cities/towns at the prefecture level or higher in China using 500‐m annual maps for 2003–2016. Cropland abandonment was spatiotemporally coupled with the urbanization. At a national scale, approximately 0.55% of the total cropland area (approximately 862 km2 per year) has been abandoned. Cropland abandonment increased significantly until 2009, declined in the early 2010s, and then leveled off in recent years. In particular, the new first‐tier cities suffered the greatest abandonment per capita. However, cropland abandonment was increasingly shifted to lower‐tier cities, particularly the high‐quality cropland abandonment in the medium‐tier cities. Low‐quality cropland in rural regions of the medium‐ and lower‐tier cities experienced incessant abandonment. Results showed that the extent of cropland abandonment increased with city sizes described either by population/GDP or by built‐up area. High‐quality cropland abandonment was more closely related to the built‐up area than to population and GDP for total abandonment. Urbanization‐induced abandonment in peri‐urban areas was dominant for most cities, with exceptions only for a few small cities. Contrary to expectation, cropland abandonment for most cities/towns in rural regions was not more driven by poor productivity, compared to peri‐urban regions. Our study highlights that urbanization mainly accounted for the regional differences in cropland abandonment in China during the past two decades.
Multi‐level analysis of the learning health system: Integrating contributions from research on organizations and implementation
Authors: Harrison Michael I. , Shortell Stephen M. 
Published: April 2020

AbstractIntroductionOrganizations and systems that deliver health care may better adapt to rapid change in their environments by acting as learning organizations and learning health systems (LHSs). Despite widespread recognition that multilevel forces shape capacity for learning within care delivery organizations, there is no agreed‐on, comprehensive, multilevel framework to inform LHS research and practice.MethodsWe develop such a framework, which can enhance both research on LHSs and practical steps toward their development. We draw on existing frameworks and research within organization and implementation science and synthesize contributions from three influential frameworks: the Consolidated Framework for Implementation Research, the social‐ecological framework, and the organizational change framework. These frameworks come, respectively, from the fields of implementation science, public health, and organization science.ResultsOur proposed integrative framework includes both intraorganizational levels (individual, team, mid‐management, organization) and the operating and general environments in which delivery organizations operate. We stress the importance of examining interactions among influential factors both within and across system levels and focus on the effects of leadership, incentives, and culture. Additionally, we indicate that organizational learning depends substantially on internal and cross‐level alignment of these factors. We illustrate the contribution of our multilevel perspective by applying it to the analysis of three diverse implementation initiatives that aimed at specific care improvements and enduring system learning.ConclusionsThe framework and perspective developed here can help investigators and practitioners broadly scan and then investigate forces influencing improvement and learning and may point to otherwise unnoticed interactions among influential factors. The framework can also be used as a planning tool by managers and practitioners.
Porcine deltacoronavirus infection alters bacterial communities in the colon and feces of neonatal piglets
Authors: Li Hai‐Yan , Li Bing‐Xiao , Liang Qing‐Qing , Jin Xiao‐Hui , Tang Lei , Ding Qing‐Wen , Wang Zhi‐Xiang , Wei Zhan‐Yong 
Published: April 2020

AbstractPorcine deltacoronavirus (PDCoV) is a novel enteropathogenic coronavirus that causes watery diarrhea in piglets. Little is known regarding the alteration of the gut microbiota in PDCoV‐induced diarrhea piglets. In this study, 5‐day‐old piglets were experimentally infected with PDCoV strain CH‐01, and all piglets developed typical clinical disease, characterized by acute and severe watery diarrhea. Histologic lesions were limited to the villous epithelium of the duodenum and ileum. Gut microbiota profiles in the colon and feces of piglets inoculated with PDCoV were investigated using 16S rRNA sequencing. The results showed that PDCoV infection reduced bacterial diversity and significantly altered the composition of the microbiota from the phylum to the genus level in the colon and feces of piglets. Firmicutes (phylum), Lactobacillaceae (family), and Lactobacillus (genus) were significantly increased (p < .01), while the abundance of Bacteroidetes (phylum) was markedly reduced in the colon and feces of the PDCoV‐infected piglets (p < .01) when compared to those of the healthy piglets. Furthermore, microbial function prediction indicated that the changes in the intestinal flora also affected the nucleotide transport and metabolism, defense, translation, and transcription function of the intestinal microbiota. The current study provides new insight into the pathology and physiology of PDCoV.
Lepidiline A Improves the Balance of Endogenous Sex Hormones and Increases Fecundity by Targeting HSD17B1
Authors: Cheng Chuanjing , Shen Fukui , Ding Guoyu , Liu Aina , Chu Simeng , Ma Yuejiao , Hou Xiaotao , Hao Erwei , Wang Xiaoying , Hou Yuanyuan , Bai Gang 
Published: April 2020

ScopeMaca (Lepidium meyenii), a well‐known plant from the Andean highlands of Peru, has been used widely as a nutritional supplement to increase sexual function and fecundity. However, the identity of its active ingredients and how they function remain unknown.Methods and resultsChemical substances in maca are identified by UPLC‐Q‐TOF, and the active ingredients are screened through HotMap coupled with an artificial neural network. Lepidiline A (LA), an imidazole alkaloid, is identified as the key active compound. LA affects the balance of endogenous sex hormones in mice and improves fecundity in Drosophila. Using a molecular LA probe, 17ß‐hydroxysteroid dehydrogenase type 1 (HSD17B1) is revealed to be the potential target of LA using a fishing‐rod strategy. It is demonstrated with experimental data that LA targets HSD17B1 to enhance the enzyme's activity and increases its bioconversion efficiency of actively formed sex hormones including estrogen to 17β‐estradiol and 4‐androsten‐3,7‐dione to testosterone, which ultimately improves reproductive activity.ConclusionLA improves the balance of endogenous sex hormones and increases fecundity by targeting HSD17B1. This underlying mechanism of action provides a useful insight into the application of maca in the regulation of dietary nutrition and healthy fertility.
Frequency‐dependent signal and noise in spectroscopic x‐ray imaging
Authors: Tanguay Jesse , Kim Jinwoo , Kim Ho Kyung , Iniewski Kris , Cunningham Ian A. 
Published: April 2020

PurposeWe present a new framework for theoretical analysis of the noise power spectrum (NPS) of photon‐counting x‐ray detectors, including simple photon‐counting detectors (SPCDs) and spectroscopic x‐ray detectors (SXDs), the latter of which use multiple energy thresholds to discriminate photon energies.MethodsWe show that the NPS of SPCDs and SXDs, including spatio‐energetic noise correlations, is determined by the joint probability density function (PDF) of deposited photon energies, which describes the probability of recording two photons of two different energies in two different elements following a single‐photon interaction. We present an analytic expression for this joint PDF and calculate the presampling and digital NPS of CdTe SPCDs and SXDs. We calibrate our charge sharing model using the energy response of a cadmium zinc telluride (CZT) spectroscopic x‐ray detector and compare theoretical results with Monte Carlo simulations.ResultsOur analysis shows that charge sharing increases pixel signal‐to‐noise ratio (SNR), but degrades the zero‐frequency signal‐to‐noise performance of SPCDs and SXDs. In all cases considered, this degradation was greater than 10%. Comparing the presampling NPS with the sampled NPS showed that degradation in zero‐frequency performance is due to zero‐frequency noise aliasing induced by charge sharing.ConclusionsNoise performance, including spatial and energy correlations between elements and energy bins, are described by the joint PDF of deposited energies which provides a method of determining the photon‐counting NPS, including noise‐aliasing effects and spatio‐energetic effects in spectral imaging. Our approach enables separating noise due to x‐ray interactions from that associated with sampling, consistent with cascaded systems analysis of energy‐integrating systems. Our methods can be incorporated into task‐based assessment of image quality for the design and optimization of spectroscopic x‐ray detectors.
Pulmonary nodule detection using hybrid two‐stage 3D CNNs
Authors: Tan Man , Wu Fa , Yang Bei , Ma Jinlian , Kong Dexing , Chen Zengsi , Long Dan 
Published: April 2020

PurposeEarly detection of pulmonary nodules is an effective way to improve patients’ chances of survival. In this work, we propose a novel and efficient way to build a computer‐aided detection (CAD) system for pulmonary nodules based on computed tomography (CT) scans.MethodsThe system can be roughly divided into two steps: nodule candidate detection and false positive reduction. Considering the three‐dimensional (3D) nature of nodules, the CAD system adopts 3D convolutional neural networks (CNNs) in both stages. Specifically, in the first stage, a segmentation‐based 3D CNN with a hybrid loss is designed to segment nodules. According to the probability maps produced by the segmentation network, a threshold method and connected component analysis are applied to generate nodule candidates. In the second stage, we employ three classification‐based 3D CNNs with different types of inputs to reduce false positives. In addition to simple raw data input, we also introduce hybrid inputs to make better use of the output of the previous segmentation network. In experiments, we use data augmentation and batch normalization to avoid overfitting.ResultsWe evaluate the system on 888 CT scans from the publicly available LIDC‐IDRI dataset, and our method achieves the best performance by comparing with the state‐of‐the‐art methods, which has a high detection sensitivity of 97.5% with an average of only one false positive per scan. An additional evaluation on 115 CT scans from local hospitals is also performed.ConclusionsExperimental results demonstrate that our method is highly suited for the detection of pulmonary nodules.
Response of Out-Migrating Adult American Shad Guided by Spill and Ultrasound as They Approach Rivière-des-Prairies Hydroelectric Generating Station (Québec, Canada)
Authors: Caumartin Jean , Verdon Richard , Desrochers Denis , Guindon Alexandre , Lafleur François , Guay Frédéric 
Published: April 2020

Abstract
Fish entrainment and mortality at hydropower generating stations constitute a major concern for power producers and government agencies. The American Shad Alosa sapidissima is particularly at risk at higher latitudes because of the large percentage of repeat spawners and the vulnerability of many populations. Total or partial turbine shutdowns at powerhouses and concurrent increased spillage are generally considered an effective way to enable fish to bypass the turbines and to reduce associated mortality, but this strategy is unappealing to hydropower producers because of the loss of power generation revenue. Two approaches were tested to repel out-migrating adult American Shad from the turbine intakes of the Rivière-des-Prairies Generating Station powerhouse and guide them toward the adjacent spillway. The first approach consisted of shutting down the powerhouse and increasing spillage. The second approach consisted of testing the effectiveness of an ultrasonic field to deter American Shad from getting close to turbine intakes and to guide them toward the partially opened spillway. On average, fish density observed in front of the 54-MW powerhouse was reduced by 93% as a result of a powerhouse shutdown lasting about 1 h and a concurrent spillage increase. Similarly, our results showed a decrease in shad abundance of 78–90% in front of the turbine intakes when a pulsed ultrasonic field (125 kHz) was activated. Measurements of sound pressure levels (SPLs) in the forebay suggested that the deterrent effect could be perceived by American Shad more than 100 m away, before they could sense higher water velocities near the powerhouse intakes. These results indicate that the combination of high-SPL pulsed ultrasounds (125 kHz) and the concurrent opening of adjacent spillway gates could guide postspawn American Shad away from powerhouse intakes.