bluuebunny/crossref_metadata_2025 huggingface dataset:
Anthropogenic mortality in mammals increases with the human footprint
Authors: Hill Jacob E , DeVault Travis L , Wang Guiming , Belant Jerrold L
Published: November 2019

Over the Earth's terrestrial surface, wildlife species are adversely affected by an increasing number of anthropogenic impacts to the landscape, collectively termed the “human footprint”. However, there is limited understanding of how the human footprint influences cause‐specific mortality in wildlife. We conducted a synthesis of cause‐specific mortality of North American terrestrial mammals, compiling 247 studies that as a group determined the cause of death of 6607 adult mammals among 19,910 individuals monitored. Species lifespan as well as the interaction between lifespan and the human footprint were positively associated with the proportion of mortality attributed to anthropogenic sources. Our results indicate that anthropogenic mortality in mammals increases with increasing human‐associated impacts on the landscape, and that longer‐lived species are affected more than their shorter‐lived counterparts. This pattern likely accounts for the extirpation of longer‐lived, larger‐bodied mammals from many human‐dominated areas. We also found that as the human footprint increased in magnitude, harvest mortality declined while vehicle mortality increased. These shifts in mortality can have substantial implications for understanding wildlife population dynamics and managing wildlife populations across landscapes impacted by anthropogenic activities.
Quantifying the contribution of citizen science to broad‐scale ecological databases
Authors: Poisson Autumn C , McCullough Ian M , Cheruvelil Kendra S , Elliott Kevin C , Latimore Jo A , Soranno Patricia A
Published: November 2019

Ecological research increasingly relies on broad‐scale databases containing information collected by personnel from a variety of sources, including government agencies, universities, and citizen‐science programs. However, the contribution of citizen‐science programs to these databases is not well known. We analyzed one such database to quantify the contribution of citizen science to lake water‐quality data from sevenUSstates. Citizen‐science programs not only provided over half of the observations for commonly sampled water‐quality measures (water clarity, nutrients, and algal biomass) from the past 31 years, but also contributed to the majority of long‐term monitoring (>15 years) for selected measures in lakes. While previous studies have demonstrated the usefulness of citizen science for research, management, policy, and public engagement, our study demonstrates that citizen science can also make valuable contributions to populating broad‐scale ecological databases. Strengthening partnerships between citizen‐science programs and monitoring agencies can help maintain and expand spatial and temporal data coverage during the “big data” era of ecology.
New stratigraphic constraints for the Quaternary source‐to‐sink history of the Amatrice Basin (central Apennines, Italy)
Authors: Mancini Marco , Vignaroli Gianluca , Bucci Francesco , Cardinali Mauro , Cavinato Gian Paolo , Di salvo Cristina , Giallini Silvia , Moscatelli Massimiliano , Polpetta Federica , Putignano Maria Luisa , Santangelo Michele , Sirianni Pietro
Published: November 2019

New stratigraphic constraints have been detailed for the Amatrice Basin, an intermountain morpho‐structural depression of the central Apennines (Italy) hosting up to 60‐m‐thick Quaternary continental deposits. Through the results coming from a 1:5,000 scale field survey and from facies analyses, we documented the geometry, thickness, and extent of the post‐orogenic continental deposits filling this basin. The Quaternary deposits form a complex architecture of purely aggradational and aggradational/degradational terraces with a dominant component of conglomerates and gravels, at the bottom, and subordinate sands, at the top. The Quaternary deposits overlie an up to 1‐km‐thick succession of flysch sediments that accumulated in the western Laga Basin during the Miocene syn‐orogenic phases in central Apennines. The collected data are used to constrain the style and mechanisms of both syn‐orogenic (i.e., subsidence and terrigenous sedimentation in foredeep environment) and post‐orogenic (i.e., uplift, erosion, and continental sedimentation) phases documented for the central Apennines. In particular, the post‐orogenic history of the Amatrice Basin, if compared with those of surrounding intermountain basins of the central Apennines, includes limited basin subsidence, reduced thickness of the post‐orogenic covers and progressive deepening of the drainage network during the Quaternary. The results shed light on the source‐to‐sink history of the Amatrice Basin, which results from a long‐lived interaction between regional‐scale factors (climate changes, chain uplift, and extensional tectonic regime) that influenced the activity of the hydrodynamic pattern and the amount of intrabasinal sedimentation during the Quaternary.
Liver Fat and Cardiometabolic Risk Factors Among School‐Age Children
Authors: Geurtsen Madelon L. , Santos Susana , Felix Janine F. , Duijts Liesbeth , Vernooij Meike W. , Gaillard Romy , Jaddoe Vincent W.V.
Published: November 2019

Background and Aims

Nonalcoholic fatty liver disease is a major risk factor for cardiometabolic disease in adults. The burden of liver fat and associated cardiometabolic risk factors in healthy children is unknown. In a population‐based prospective cohort study among 3,170 10‐year‐old children, we assessed whether both liver fat accumulation across the full range and nonalcoholic fatty liver disease are associated with cardiometabolic risk factors already in childhood.

Approach and Results

Liver fat fraction was measured by magnetic resonance imaging, and nonalcoholic fatty liver disease was defined as liver fat fraction ≥5.0%. We measured body mass index, blood pressure, and insulin, glucose, lipids, and C‐reactive protein concentrations. Cardiometabolic clustering was defined as having three or more risk factors out of high visceral fat mass, high blood pressure, low high‐density‐lipoprotein cholesterol or high triglycerides, and high insulin concentrations. Nonalcoholic fatty liver disease prevalences were 1.0%, 9.1%, and 25.0% among children who were normal weight, overweight, and obese, respectively. Both higher liver fat within the normal range (<5.0% liver fat) and nonalcoholic fatty liver disease were associated with higher blood pressure, insulin resistance, total cholesterol, triglycerides, and C‐reactive protein concentrations (P values < 0.05). As compared with children with <2.0% liver fat, children with ≥5.0% liver fat had the highest odds of cardiometabolic clustering (odds ratio 24.43 [95% confidence interval 12.25, 48.60]). The associations remained similar after adjustment for body mass index and tended to be stronger in children who were overweight and obese.

Conclusions

Higher liver fat is, across the full range and independently of body mass index, associated with an adverse cardiometabolic risk profile already in childhood. Future preventive strategies focused on improving cardiometabolic outcomes in later life may need to target liver fat development in childhood.
A Pilot Genome‐Wide Analysis Study Identifies Loci Associated With Response to Obeticholic Acid in Patients With NASH
Authors: Gawrieh Samer , Guo Xiuqing , Tan Jingyi , Lauzon Marie , Taylor Kent D. , Loomba Rohit , Cummings Oscar W. , Pillai Sreekumar , Bhatnagar Pallav , Kowdley Kris V. , Yates Katherine , Wilson Laura A. , Chen Yii‐Der Ida , Rotter Jerome I. , Chalasani Naga ,   NASH Clinical Research Network
Published: November 2019

A significantly higher proportion of patients with nonalcoholic steatohepatitis (NASH) who received obeticholic acid (OCA) had histological improvement relative to placebo in the FLINT (farnesoid X nuclear receptor ligand obeticholic acid for noncirrhotic, NASH treatment) trial. However, genetic predictors of response to OCA are unknown. We conducted a genome‐wide association study (GWAS) in FLINT participants to identify variants associated with NASH resolution and fibrosis improvement. Genotyping was performed using the Omni2.5 content GWAS chip. To avoid false positives introduced by population stratification, we focused our GWAS on white participants. Six regions on chromosomes 1, 4, 6, 7, 15, and 17 had multiple single nucleotide polymorphisms (SNPs) with suggestive association (P < 1 × 

) with NASH resolution. A sentinel SNP, rs75508464, near CELA3B on chromosome 1 was associated with NASH resolution, improvement in the nonalcoholic fatty liver disease activity score, portal inflammation, and fibrosis. Among individuals carrying this allele, 83% achieved NASH resolution with OCA compared with only 33% with placebo. Eight regions on chromosomes 1, 2, 3, 11, 13, and 18 had multiple SNPs associated with fibrosis improvement; of these, rs12130403 near TDRD10 on chromosome 1 was also associated with improvement in NASH and portal inflammation, and rs4073431 near ANO3 on chromosome 11 was associated with NASH resolution and improvement in steatosis. Multiple SNPs on chromosome 11 had suggestive association with pruritus, with rs1379650 near ANO5 being the top SNP. Conclusion: We identified several variants that may be associated with histological improvement and pruritus in individuals with NASH receiving OCA. The rs75508464 variant near CELA3B may have the most significant effect on NASH resolution in those receiving OCA.
The challenges of hepatitis C management in Iran: A qualitative study with patients
Authors: Behzadifar Masoud , Azari Samad , Gorji Hasan Abolghasem , Rezapour Aziz , Bragazzi Nicola Luigi
Published: November 2019

Background

The patient's perspective concerning the treatment process and the knowledge of the challenges and problems that they encounter can help to improve their treatment conditions.

Aim

The present study aimed at analyzing the experiences of hepatitis C virus (HCV) patients in Iran and the challenges encountered during the management and treatment process.

Methods

Semi‐structured in‐depth and face‐to‐face interviews were conducted. The criteria for selecting patients were as follows: HCV‐positive subjects, with confirmed diagnosis of HCV, and under treatment. Content analysis was used to analyze the data. MAXQDA Ver11 software was used to better manage data. This study is based on the “Consolidated Criteria for Reporting Qualitative Research” (COREQ) checklist.

Results

Twenty‐one HCV patients were interviewed. The mean age of participants was 36.14 ± 11.29 years. Seven themes with 20 subthemes emerged from the content analysis of the interviews, namely, (a) disease‐related stigma, (b) lack of knowledge, (c) psychological problems, (d) financial problems, (e) complications of treatment, (f) lack of family and community support, and (g) health‐care system.

Conclusion

The findings of this study showed that a range of economic, social, and cultural problems could affect the treatment of HCV patients. Health policy and decision makers should try to provide them with a better management.
The impact of primary health care reform on hospital emergency department overcrowding: Evidence from the Portuguese reform
Authors: Almeida Alvaro , Vales Joana
Published: November 2019

Context

The reduction in inappropriate utilization of hospitals' emergency departments (EDs) is usually an important objective of primary health care (PHC) reforms. Existing literature provides mixed evidence on the effectiveness of PHC reforms in reducing inappropriate utilization of ED. We assess whether the specific PHC reforms ongoing in Portugal since 2005, and in particular the creation of family health units (FHUs), were successful in reducing inappropriate utilization of EDs and provide a contribution to the debate of which PHC models contribute to reduce overuse of EDs.

Methods

We use patient‐level data of 117 391 ED visits from two nonurban hospitals in Portugal to estimate a multivariate logistic regression that assesses the impact of different PHC models on inappropriate ED visits. Patients in our sample had four different models of PHC provision: the new FHU type A or type B and the old personalized health care units (PHUs), with or without a specific family physician assigned.

Results

The percentage of episodes that correspond to appropriate visits to the ED is 2% higher for patients enrolled in an FHU type B and 0.8% higher for users of FHU type A, when compared with users enrolled in PHU. Having an assigned family physician increases appropriate use of the ED by 1%.

Conclusion

Portugal's PHC reform was successful in reducing inappropriate utilization of EDs.
Extrinsic motivation as a determinant of knowledge exchange in sales teams: A social network approach
Authors: David Natalie , Brennecke Julia , Rank Olaf
Published: November 2019

This paper investigates extrinsic motivation as a determinant of knowledge exchange among employees in sales teams. Applying a social network approach, we study different forms of knowledge‐exchange behaviors from the perspective of a focal employee and from the perspective of the dyad. From the focal employees' perspective, we disentangle knowledge seeking from knowledge providing, and argue that these two behaviors are affected differently by employees' extrinsic motivation. From the dyad perspective, we take similarity in motivation of tied‐to employees and reciprocity of exchange ties into account. To test our hypotheses, we apply exponential random graph models to data gathered from 138 employees in five different sales teams distributed across three companies in Central Europe. The results of our analysis from the focal employees' perspective show that extrinsically motivated employees generally engage in less knowledge exchange. The dyad perspective further highlights that sales employees proceed purposefully when they exchange knowledge with coworkers. For instance, two employees' relative levels of extrinsic motivation determine their willingness to engage in reciprocal knowledge exchange. We discuss the implications of our findings for research on the microfoundations of organizational knowledge management and draw conclusions concerning HRM practices used to foster extrinsic motivation, thereby affecting knowledge exchange.
A qualitative study on measuring patient‐centered care: Perspectives from clinician‐scientists and quality improvement experts
Authors: Ahmed Sadia , Djurkovic Andrea , Manalili Kimberly , Sahota Balreen , Santana Maria J.
Published: November 2019

Background and aims

Patient‐centered care (PCC) benefits patients, health‐care providers, and health‐care systems by providing delivery of care that addresses patient values and needs while improving provider experiences, and by decreasing health‐care expenditure. To improve PCC, health‐care systems need to measure it. Recently, we developed a PCC framework that is evidence based and patient informed. The purpose of this study was to gather the perspective of clinician‐scientists and quality improvement experts regarding the PCC domains included in the framework. Their perspectives were used to refine these domains, which ultimately will inform the development of PCC quality indicators.

Methods

Participants were recruited via expert and snowball sampling. Semi‐structured interviews were conducted with clinician‐scientists and quality improvement experts from Canada, the United States, and the United Kingdom from October 2017 to January 2018. With the use of an interview guide developed using the PCC framework, interviews were audio recorded and transcribed for a thematic analysis using NVivo qualitative data analysis software. Inductive thematic analysis was used to identify themes and subthemes.

Results

Sixteen semi‐structured interviews were conducted, which included four clinician‐scientists and 12 quality improvement experts. Twelve of the participants were from Canada, three from the United Kingdom, and one from the United States. From the thematic analysis, three major themes were identified: (a) measurability of PCC, (b) practical considerations for implementing measurement, and (c) policy and practice implications. Participants discussed barriers and recommendations to improve and increase the clarity of the PCC domains in health system reporting, resulting in several future directions to refine and target specific PCC domains.

Conclusion

Clinician‐scientists and quality improvement experts provided key recommendations for the measurement of PCC. The perspectives of key stakeholders in PCC measurement will inform strategies for the implementation and uptake of patient‐centered quality indicators in health‐care systems. The views of these key experts can lay the foundation for the development of standardized measures of PCC, to ensure monitoring and improvement of PCC.
The impact of institutional investors on firms' performance in the context of financialization
Authors: Alexiou Constantinos , Mohamed Abdulkadir , Nellis Joe
Published: November 2019

This paper investigates the impact of U.K. institutional holdings on the financialization process. Using panel data analysis, we find that their holdings have a positive impact on the financialization. Investigating the source of this impact, we find that their portfolio companies outperform their peers matched by industry and size. Together, these findings suggest that institutional investors add value to the capital market and play an instrumental role in shaping the financialization process. Granger's causality test reveals that institutional holdings Granger cause financialization process, and the relationship is one‐way direction.
Pharmacist impact on the HIV Care Continuum: Decreasing time to care
Authors: Kilcrease Christin , Miller Misty M. , Neely Stephen , Liedtke Michelle D.
Published: November 2019

Introduction

The human immunodeficiency virus (HIV) Care Continuum is a model used to describe the process of care for people living with HIV infection. National goals exist for each step of this continuum including linkage to care and time to viral suppression. Achieving these goals is hindered by an ongoing shortage of HIV care providers.

Objectives

The objective of this study was to examine the effectiveness of a pharmacist service providing initial evaluation of people with HIV infection referred for care. Effectiveness was defined as a decrease in time to care along with other pertinent clinical end points associated with the HIV Care Continuum.

Methods

This retrospective cohort study was conducted in an academic‐based, outpatient clinic from October 2013 to September 2017. Patients were assigned to one of two groups based on time of presentation, pre‐service (October 2013 to September 2015) and post‐service (October 2015 to September 2017). The primary outcome examined time to care from referral to visit scheduling and attendance. Secondary outcomes included time to antiretroviral initiation and viral suppression. The primary outcome analysis included all patients who attended at least one clinic visit. Secondary outcomes included only patients newly diagnosed with HIV (≤12 months prior to clinic referral).

Results

Significant decreases in both primary and secondary outcomes were observed for patients in the pharmacist service cohort compared with the pre‐service cohort. Days to scheduled appointment decreased from 69 to 38 days (P < .001). Time to antiretroviral initiation and viral suppression also decreased from 122 to 95 days (P < .0488) and 316 to 208 days (P < .005), respectively.

Conclusion

The pharmacist service exhibited a significant decrease in several HIV Care Continuum measures including linkage to care, initiation of antiretroviral therapy, and viral suppression. Utilizing existing HIV care providers in novel roles may help achieve national goals for care.
Acoustic resolution photoacoustic microscopy based on microelectromechanical systems scanner
Authors: Moothanchery Mohesh , Dev Kapil , Balasundaram Ghayathri , Bi Renzhe , Olivo Malini
Published: November 2019

Photoacoustic microscopy (PAM) can be classified as optical resolution (OR)‐PAM and acoustic resolution (AR)‐PAM depending on the type of resolution achieved. Using microelectromechanical systems (MEMS) scanner, high‐speed OR‐PAM system was developed earlier. Depth of imaging limits the use of OR‐PAM technology for many preclinical and clinical imaging applications. Here, we demonstrate the use of a high‐speed MEMS scanner for AR‐PAM imaging. Lateral resolution of 84 μm and an axial resolution of 27 μm with ~2.7 mm imaging depth was achieved using a 50 MHz transducer‐based AR‐PAM system. Use of a higher frequency transducer at 75 MHz has further improved the resolution characteristics of the system with a reduction in imaging depth and a lateral resolution of 53 μm and an axial resolution of 18 μm with ~1.8 mm imaging depth was achieved. Using the two‐axis MEMS scanner a 2 × 2 .5 mm2 area was imaged in 3 seconds. The capability of achieving acoustic resolution images using the MEMS scanner makes it beneficial for the development of high‐speed miniaturized systems for deeper tissue imaging.
miR‐181b/Oncostatin m axis inhibits prostate cancer bone metastasis via modulating osteoclast differentiation
Authors: Han Ziwei , Zhan Ruisen , Chen Shijie , Deng Jia , Shi Jian , Wang Weiguo
Published: November 2019

The activation of osteoblasts is significantly correlated to prostate tumor bone metastasis and bone loss. Oncostatin M (OSM) could promote breast cancer metastasis to bone. However, its role and mechanism in prostate cancer bone metastasis remain unclear. MicroRNAs (miRNAs) could play important roles in cancers via post‐transcriptionally regulating target genes via binding to specific sequences in the 3′ UTR of downstream target genes. In the present study, we performed microarray profiling analyses to identify differentially‐expressed miRNAs in preosteoclast before and after osteoclast differentiation that could target OSM. miR‐181b‐5p was downregulated during Raw264.7 cells differentiation into osteoclast. By direct targeting OSM 3′ UTR, miR‐181b‐5p inhibited OSM messenger RNA expression and protein levels, subsequently decreasing IL‐6 and AREG and increasing OPG, while OSM overexpression exerted an opposing effect. More importantly, co‐culture with miR‐181b‐5p‐overexpressing differentiated Raw264.7 cells suppressed proliferation, migration, and invasion of mouse prostate cancer RM‐1 cells, while co‐culture with OSM‐overexpressing Raw264.7 cells led to opposing cellular effects. More importantly, the effects of miR‐181b‐5p on osteoclastogenic factors and RM‐1 cells could be significantly reversed by OSM overexpression. In summary, miR‐181b‐5p/OSM axis could be a viable therapeutic target for patients with surgically removed primary tumors to reduce bone metastasis and prevent bone loss.
11 Long noncoding RNA UCA1 functions as miR‐135a sponge to promote the epithelial to mesenchymal transition in glioma
Authors: Li Zhi‐guo , Xiang Wei‐chu , Shui Shao‐feng , Han Xin‐wei , Guo Dong , Yan Lei
Published: November 2019

The dysregulation of long noncoding (lncRNA) UCA1 may play an important role in tumor progression. However, the function in gliomas is unclear. Therefore, this experiment was designed to explore the pathogenesis of glioma based on lncRNA UCA1. Real‐time quantitative polymerase chain reaction (RT‐qPCR) was used to detect the expression of lncRNA UCA1, miR‐135a, and HOXD9 in gliomas tissues. The effect of lncRNA UCA1 and miR‐135a on tumor cell proliferation and migration invasiveness was examined by CCK‐8 and transwell assays. Target gene prediction and screening, luciferase reporter assay were used to verify downstream target genes of lncRNA UCA1. Expression of E‐cadherin, N‐cadherin, vimentin, and HOXD9 was detected by RT‐qPCR and Western blotting. The tumor changes in mice were detected by in vivo experiments in nude mice. lncRNA UCA1 was highly expressed in glioma tissues and cell lines. lncRNA UCA1 expression was associated with significantly poor overall survival in gliomas. Moreover, lncRNA UCA1 significantly enhanced cell proliferation and migration, and promoted the occurrence of EMT. In addition, lncRNA UCA1 promoted the development of EMT by positively regulating HOXD9 expression as a miR‐135a sponge. In vivo experiments indicated that UCA1 exerted its biological functions by modulating miR‐135a and HOXD9. In conclusion, lncRNA UCA1 can induce the activation of HOXD9 by inhibiting the expression of miR‐135a and promote the occurrence of EMT in glioma.
LncRNA‐cCSC1 modulates cancer stem cell properties in colorectal cancer via activation of the Hedgehog signaling pathway
Authors: Zhou He , Xiong Yongfu , Peng Linglong , Wang Rong , Zhang Hairong , Fu Zhongxue
Published: November 2019

Several long noncoding RNAs (lncRNAs) have been identified in various malignant tumors and determined to contribute to the process of tumorigenesis, including that of colorectal cancer (CRC). Cancer stem cells (CSCs) have been demonstrated to promote the expansion and maintain the invasion and metastasis of cancer cells, owing to their self‐renewal capacity. However, the underlying modulation mechanism of CSC‐associated lncRNAs in CRC remains largely unclear. Using integrated bioinformatic analysis, we identified a novel lncRNA (lncRNA‐cCSC1) that is highly expressed in CRC and colorectal cancer stem cells (CRCSCs). The biological functions of lncRNA‐cCSC1 were assessed in vitro and vivo through the silencing or upregulation of its expression. The depletion of lncRNA‐cCSC1 markedly inhibited the self‐renewal capacity of the CRCSCs and reduced their drug resistance to 5‐fluorouracil. In contrast, lncRNA‐cCSC1 overexpression increased the self‐renewal effect. Furthermore, aberrant lncRNA‐cCSC1 expression resulted in a concomitant alteration of smoothened (SMO) and GLI family zinc finger 1 (Gli1) expression in the Hedgehog (Hh) signaling pathway. Our study is the first to identify a novel lncRNA‐cCSC1 in CRC and to indicate that it may regulate CSC‐like properties via the Hh signaling pathway. Thus, lncRNA‐cCSC1 could be a potential biomarker and promising therapeutic target for CRC.
DNA methylation data–based molecular subtype classification related to the prognosis of patients with cervical cancer
Authors: Li Chunxiao , Ke Jinxiu , Liu Jiangyi , Su Jingjing
Published: November 2019

Cervical cancer is one of the leading female health‐killers among all types of malignancies globally. Human papillomavirus infection combined with genetic and epigenetic alterations have been indicated to be closely associated with the pathogenesis, progression, and malignant transformation of cervical cancer. Notably, during the complex tumorigenesis process, a series of DNA methylations occurs early and is the most frequent molecular behavior. In this study, to exploit the specific DNA methylation sites influencing the prognosis of patients with cervical cancer, 275 samples were downloaded from The Cancer Genome Atlas database and further analyzed. As a result, 1253 CpGs were found to have a significant correlation with patient prognosis and were further selected for the consistent clustering of samples into six subgroups. Specifically, the samples in every subgroup were different regarding the following: race, age, tumor stage, receptor status, histological type, metastasis status, and patient prognosis. In addition, we calculated the levels of methylation sites in all subgroups, with 79 methylation sites (corresponding to 81 genes) screened as the intrasubgroup‐specific methylation sites. Moreover, signaling pathway enrichment analysis was conducted on the genes of the corresponding promoter regions of the above‐described specific methylation sites, revealing that these genes were enriched in biological pathways closely associated with tumors, such as the cyclic guanosine monophosphate–dependent protein kinase and focal adhesion signaling pathways. Finally, the least absolute shrinkage and selection operator algorithm was employed to establish a prognostic prediction model for cervical cancer patients, with training and test sets used for testing and validation, respectively. In summary, the specific DNA methylation site–based classification is able to reflect the heterogeneity of cervical cancer tissue, contributing to the development of personalized therapy and the accurate prediction of patient prognosis.
AGEs induces apoptosis and autophagy via reactive oxygen species in human periodontal ligament cells
Authors: Mei You‐Min , Li Lu , Wang Xiao‐Qian , Zhang Min , Zhu Li‐Fang , Fu Yong‐Wei , Xu Yan
Published: November 2019

The apoptosis of human periodontal ligament cells (HPDLCs) may be an important factor of the negative effect of advanced glycation end products (AGEs) on the periodontal tissue of diabetic patients. However, the pathways or potential effects of apoptosis in AGEs‐treated HPDLCs have not been fully elucidated. Autophagy is closely related to apoptosis. Herein, we investigated the potential mechanism of apoptosis and autophagy in HPDLCs treated with AGEs via an in vitro model. We found that AGEs‐treated HPDLCs showed a time‐ and concentration‐dependent reduction in the cell survival rate. The mitochondrial‐dependent apoptosis was induced in AGEs‐treated HPDLCs, as confirmed by the mitochondrial membrane potential depolarization, decreased Bcl‐2 expression, increased Bax expression, and increased caspase‐3 and PARP cleavage. Autophagy was also induced in AGEs‐treated HPDLCs, as indicated by the conversion of LC3‐II/LC3‐I and the presence of autophagosomes. Interestingly, our study results suggested that apoptosis and autophagy were related to reactive oxygen species (ROS) production. In addition, AGEs‐induced autophagy acted as a latent factor in decreasing the generation of ROS in HPDLCs and protecting against the AGEs‐induced apoptosis. In summary, our study shows that ROS are essential in AGEs‐induced HPDLCs apoptosis and autophagy, which may be a molecular mechanism for the repairment of ROS‐induced damage in HPDLCs treated with AGEs to promote cell survival. The present study might provide new insights into the therapeutic targeting of HPDLCs autophagy, which could be an additional strategy for periodontitis in patients with diabetes mellitus.
Progression or suppression: Two sides of the innate lymphoid cells in cancer
Authors: Hosseini S. Haleh , Sharafkandi Nadia , Seyfizadeh Narges , Hemmatzadeh Maryam , Marofi Faroogh , Shomali Navid , Karimi Mohammad , Mohammadi Hamed
Published: November 2019

Innate lymphoid cells (ILCs) as key players in innate immunity have been shown to be significantly associated with inflammation, lymphoid neogenesis, tissue remodeling, mucosal immunity and lately have been considered a remarkable nominee for either tumor‐promoting or tumor‐inhibiting functions. This dual role of ILCs, which is driven by intrinsic and extrinsic factors like plasticity of ILCs and the tumor microenvironment, respectively, has aroused interest in ILCs subsets in past decade. So far, numerous studies in the cancer field have revealed ILCs to be key players in the initiation, progression and inhibition of tumors, therefore providing valuable insights into therapeutic approaches to utilize the immune system against cancer. Herein, the most recent achievements regarding ILCs subsets including new classifications, their transcription factors, markers, cytokine release and mechanisms that led to either progression or inhibition of many tumors have been evaluated. Additionally, the available data regarding ILCs in most prevalent cancers and new therapeutic approaches are summarized.
LINC00467 promotes cell proliferation and stemness in lung adenocarcinoma by sponging miR‐4779 and miR‐7978
Authors: Chang Yanxiang , Yang Lisheng
Published: November 2019

Lung adenocarcinoma (LAD), as one of the most common types of lung tumors, is lethal and malignant. Long noncoding RNAs (lncRNAs) play important roles in various cancers according to many previous studies. LINC00467 was proposed to be a tumor promoter. Despite the validated promotive effect of LINC00467 on neuroblastoma progression, its regulatory mechanism in LAD remains unclear. In this study, LINC00467 expressed higher in LAD tissues and cell lines, and increased LINC00467 indicated a poor prognosis. Knockdown of LINC00467 inhibited cell proliferation, the expressions of tumor stem cell‐related genes, and cell spheroid formation ability, while it promoted cell apoptosis. miR‐4779 and miR‐7978 were reported to play antitumor roles in several cancers before. LINC00467 could combine with miR‐4779 and miR‐7978, and negatively regulated miR‐4779 and miR‐7978. miR‐4779 and miR‐7978 inhibitor could partly rescue the LINC00467 knockdown‐induced influence on cell proliferation, apoptosis, and stemness. In a word, this study innovatively investigated the mechanism of LINC00467 in LAD and verified LINC00467 exerted its carcinogenesis function by sponging miR‐4779 and miR‐7978, which may become a catalyst for generating new therapeutic targets for LAD treatment.
Development and validation of a five‐lncRNA signature with prognostic value in colon cancer
Authors: Lv Ji , Guo Ying , Yan Lili , Lu Yang , Liu Dongfeng , Niu Jia
Published: November 2019

Dysregulation of long noncoding RNAs (lncRNAs) has been found in a large number of human cancers, including colon cancer. Therefore, the implementation of potential lncRNAs biomarkers with prognostic prediction value are very much essential. GSE39582 data set was downloaded from database of Gene Expression Omnibus. Re‐annotation analysis of lncRNA expression profiles was performed by NetAffx annotation files. Univariate and multivariate Cox proportional analyses helped select prognostic lncRNAs. Algorithm of random survival forest‐variable hunting (RSF‐VH) together with stepwise multivariate Cox proportional analysis were performed to establish lncRNA signature. The log‐rank test was carried out to analyze and compare the Kaplan‐Meier survival curves of patients’ overall survival (OS). Receiver operating characteristic (ROC) analysis was used for comparing the survival prediction regarding its specificity and sensitivity based on lncRNA risk score, followed by calculating the values of area under the curve (AUC). The single‐sample GSEA (ssGSEA) analysis was used to describe biological functions associated with this signature. Finally, to determine the robustness of this model, we used the validation sets including GSE17536 and The Cancer Genome Atlas data set. After re‐annotation analysis of lncRNAs, a total of 14 lncRNA probes were obtained by univariate and multivariate Cox proportional analysis. Then, the RSF‐VH algorithm and stepwise multivariate Cox analysis helped to build a five‐lncRNA prognostic signature for colon cancer. The patients in group with high risk showed an obviously shorter survival time compared with patients in group with low risk with AUC of 0.75. In addition, the five‐lncRNA signature can be used to independently predict the survival of patients with colon cancer. The ssGSEA analysis revealed that pathways such as extracellular matrix‐receptor interaction was activated with an increase in risk score. These findings determined the strong power of prognostic prediction value of this five‐lncRNA signature for colon cancer.
BMP9 promotes osteogenic differentiation of SMSCs by activating the JNK/Smad2/3 signaling pathway
Authors: Zheng Weiwei , Chen Qian , Zhang Yu , Xia Rui , Gu Xueping , Hao Yuefeng , Yu Zepeng , Sun Xingwei , Hu Dan
Published: November 2019

Synovial mesenchymal stem cells (SMSCs) with high proliferation and multi differentiation ability, and low immunogenicity have attracted research attention for their potential application in tissue engineering. Once their ability of osteogenesis is strengthened, it will be of practical value to apply the SMSCs in the field of bone regeneration. The current study aimed to investigate the osteogenic characteristics of SMSCs induced by bone morphogenetic protein 9 (BMP9) both in vitro and in vivo and to elucidate the mechanism underlying these characteristics. Specifically, different BMPs were assessed to determine the protein that would be the most favorable for stimulating osteogenic differentiation of SMSCs following their separation. The BMP9‐enhanced osteogenesis of SMSCs was fully investigated in vitro and in vivo, and the c‐Jun N‐terminal kinase (JNK)/Smad2/3 signaling pathway stimulated by BMP9 was further explored. Our data suggested that BMP9 could significantly promote gene and protein expression of runt‐related transcription factor 2, alkaline phosphatase, osteopontin, and osteocalcin, and SP600125, a JNK‐specific inhibitor, could effectively decrease this tendency. Similar results were also confirmed in rats with cranial defects. In conclusion, our study indicated that BMP9 promotes bone formation both in vitro and in vivo possibly by activating the JNK/Smad2/3 signaling pathway.
There are 3155 nonisomorphic perfect one‐factorizations of K16
Authors: Meszka Mariusz
Published: November 2019

We enumerate all nonisomorphic perfect one‐factorizations of .
Sabellaria alveolata sandcastle worm from the Mediterranean Sea: new insights on tube architecture and biocement
Authors: Sanfilippo Rossana , Rosso Antonietta , Mastandrea Adelaide , Viola Alfio , Deias Claudia , Guido Adriano
Published: November 2019

The Atlantic‐Mediterranean polychaete Sabellaria alveolata lives in agglutinated tubes adjoined to each other to form discrete reef‐like bioconstructions in shallow‐water settings characterised by high hydrodynamic energy where sediment particles are constantly resuspended. Tubes are built with sand grains glued by proteinaceous secretions. Analyses of a reef fragment collected near Sampieri (SE Sicily, Sicily Strait) allowed the first detailed description of the tube architecture and biocement of this worms from the Mediterranean. The tube consists of an inner thin organic membrane and three agglutinated layers including: (a) a thin inner layer of flat grains arranged side by side; (b) a thick mid layer with a frame of relatively large sub‐rounded grains with cavities partly filled by small grains; and (c) a thin outer layer of large, flat to curved, usually biogenic clasts diverging towards the opening. This particular architecture is distinctive of the family. Morphological and epifluorescence observations revealed that biocement consists of drops at the contact between sub‐spherical grains and strips along edges of flat grains. Biocement is a solid foam‐like material characterised by high abundance of carbon; the presence of phosphorous and nitrogen confirms its proteinaceous composition. Due to the electrostatic interaction with the proteins, calcium and magnesium are most likely complexed to the cement rather than being trapped in the cells. These elements contribute to the solidification of the glue and stabilisation of the tube structure. However, the organic nature of cement and the high energy of their habitat, make sabellariid reefs dynamic and ephemeral, and the preservation as fossils unlikely, with a confident record only extending back to the Miocene.
Study of As‐resistant bacteria from Nadia, India and a survey of two As resistance‐related proteins
Authors: Rahman Zeeshanur , Thomas Lebin , Singh Ved P.
Published: November 2019

The present investigation deals with the characterisation of three As‐resistant bacteria, Bacillus aryabhattai strain VPS1, Bacillus licheniformis strain VPS6 and Sporosarcina thermotolerans strain VPS7 isolated from the rhizosphere of a contaminated paddy field in Chakdaha, Nadia, West Bengal, India. Two strains, VPS6 and VPS7 showed ureolytic activity, which can be used for microbial‐induced calcite precipitation of As as a bioremediation option. However, As reduction and oxidation capacities were not reported in any of these bacteria. A phylogenetic tree of 16S ribosomal RNA gene sequences was constructed for all three bacterial isolates, including different species of As‐resistant Bacillus and Sporosarcina. Furthermore, literature survey and genome mining were employed to explore the diversity of As resistance‐related proteins, arsenite S‐adenosylmethyltransferase (ArsM) and arsenical pump membrane protein (ArsB) among different bacteria, and the phylogenetic relatedness was studied to understand the distribution and evolution of their amino acid sequences. ArsB was predominantly present in a wide variety of bacteria (347 taxa); however, ArsM was reported in comparatively fewer isolates (109 taxa). There were a total of 60 similar taxa that contained both ArsM and ArsB. Both proteins were most abundantly present in phylum Proteobacteria. Overall, this investigation enumerates As‐resistant bacteria to understand the As metabolism in the environment, and the phylogenetic analysis of As resistance‐related proteins helps in understanding the functional relationship in different bacteria for their role in As mobility in the environment.
Robot‐assisted surgical care delivery at a hospital: Policies for maximizing clinical outcome benefits and minimizing costs
Authors: Mukherjee Ujjal K. , Sinha Kingshuk K.
Published: November 2019

Robot‐assisted surgery is a major advancement in minimally invasive surgical care delivery. It allows surgeons to gain additional dexterity, improved precision in surgical tasks, enhanced three‐dimensional vision of the surgical field, and superior accessibility to the surgical field. Notwithstanding the clinical outcome benefits (such as reduced blood loss and surgical duration, and shorter length‐of‐stay at a hospital), the cost of performing robot‐assisted surgery is significantly high, due to the investments needed for robot acquisition, maintenance, and procurement of surgical accessories. In this study, we address the twin objectives of a hospital where robot‐assisted surgery is performed: maximize the clinical outcome benefits and minimize the total cost of robot‐assisted surgery. The surgical robot that is the focus of the study is a da Vinci surgical system. The surgical procedure that serves as the context of this study is hysterectomy. We demonstrate the application of an integrated methodological approach—combining empirical analysis involving an on‐site, prospective investigation at a hospital and retrospective analysis of archival data from the hospital for robustness checks, analytical modeling, and discrete event simulation—to identify and analyze actionable policies that a hospital can implement. The specific policies we analyze are related to: (a) patient triaging for robot‐assisted surgery based on the criticality of disease condition of a patient; (b) the optimal size of surgeon pool to facilitate the development of surgeon experience and learning; and (c) the minimum experience level of a surgeon with a robot needed to be included in the surgeon pool for robot‐assisted surgery. The key contributions of this article are in demonstrating the following: First, hospital‐level policies can help to realize both the clinical outcome and cost benefits of a surgical robot. Second, the criticality of patient condition is a significant determinant of surgeon learning in robot‐assisted surgery. Third, application of the proposed integrated methodological approach can yield nuanced and actionable insights into an operational setting where data availability is limited and generalizability of study insights is a concern, as is the case in this study.
Assessing the effects of cyclosporine A on the osteoblastogenesis, osteoclastogenesis, and angiogenesis mediated by human periodontal ligament stem cells
Authors: Kim Hyun‐Joo , Yoo Ji Hyun , Choi YunJeong , Joo Ji‐Young , Lee Ju‐Youn , Kim Hyung Joon
Published: November 2019

Background

This study was performed to investigate the effects of cyclosporine A (CsA) on the osteogenic differentiation, osteoclastogenic‐supporting ability, and angiogenic potential of human periodontal ligament stem cells (hPDLSCs).

Methods

hPDLSCs were isolated from the extracted teeth of orthodontic patients. Cell proliferation was assessed using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide assay, and osteogenic differentiation was evaluated by alkaline phosphatase (ALP) and alizarin red (ARS) staining. Real‐time polymerase chain reaction (PCR) was used to quantify transcripts. Tartrate‐resistant acid phosphatase staining of bone marrow‐derived macrophages (BMMs) and tube formation assays on human umbilical vein endothelial cells (HUVECs) were performed after treating cells with the conditioned media from CsA‐exposed or non‐exposed hPDLSCs. Signaling pathways mediating the angiogenic activity were investigated using western blotting.

Results

CsA suppressed the proliferation of hPDLSCs but enhanced osteogenic differentiation as determined by ALP and ARS staining and PCR of osteogenic transcripts. The expressions of osteoclastogenic transcripts in hPDLSCs and the differentiation of BMMs treated with conditioned medium from CsA‐exposed hPDLSCs were unaffected by CsA. However, the expressions of angiogenic transcripts and the transcripts known to support angiogenesis—phosphorylation of extracellular signal p‐regulated kinase (ERK) and p38, and c‐fos—were inhibited. Conditioned medium from CsA‐exposed hPDLSCs suppressed the tube forming abilities of HUVECs.

Conclusions

CsA enhanced the osteogenic differentiation and reduced angiogenesis by blocking the ERK and p38/c‐fos pathway in hPDLSCs. It is necessary to confirm whether this phenomenon is also observed in vivo in subsequent animal experiments.
The Late Holocene tephra record of the central Mediterranean Sea: Mapping occurrences and new potential isochrons for the 4.4–2.0 ka time interval
Authors: Insinga D. D. , Petrosino P. , Alberico I. , de Lange G. J. , Lubritto C. , Molisso F. , Sacchi M. , Sulpizio R. , Wu J. , Lirer F.
Published: November 2019

Five cores from the southern Tyrrhenian and Ionian seas were studied for their tephra and cryptotephra content in the 4.4–2.0 ka time interval. The chronological framework for each core was obtained by accelerator mass spectrometry 14C dating, the occurrence of distinct marker tephra and stratigraphic correlation with adjacent records. Tephrochronology allowed us to correlate the analyzed deposits with tephra markers associated with Somma‐Vesuvius (79 ad), Ischia Island (Cretaio), Mt Etna (FG, FL and FS) and Campi Flegrei (Astroni‐Agnano Monte Spina) events. For the first time in the marine setting, a large single glass data set is provided for the Late Holocene Etnean marker beds including the FS tephra (ca. 4.3 ka). Moreover, unknown deposits from Lipari (ca. 2.2–2.0 ka) and Vulcano (3.6–3.3 ka) are also recognized at more distal sites than previously reported. These results contribute to improve the high‐resolution tephrostratigraphic framework of the central Mediterranean Sea. They also provide new insights into the chemical composition and dispersal pattern of tephras that can be used as inter‐archive tools for regional and ‘local’ stratigraphic correlations and for addressing paleoclimate research.