bluuebunny/crossref_metadata_2025 huggingface dataset:
CTHRC1 expression in primary biliary cholangitis
Authors: Li Yi Kang , Li Yan Mei , Li You , Wei Yi Ran , Zhang Jun , Li Bo , You Zheng Rui , Chen Yong , Huang Bing Yuan , Miao Qi , Wang Qi Xia , Peng Yan Shen , Gershwin M. Eric , Tang Ru Qi , Bian Zhao Lian , Ma Xiong
Published: May 2019

Objectives

Collagen triple helix repeat containing‐1 (CTHRC1) is a highly conserved extracellular matrix glycoprotein that is overexpressed in two murine models of cholestatic liver fibrosis. Elevated CTHRC1 has been found to attenuate liver fibrosis in these murine models, thus we aimed to study the expression of CTHRC1 in patients with cholestatic liver diseases and its correlation with hepatic conditions.

Methods

Ninety patients with chronic liver disease, including 48 had primary biliary cholangitis (PBC), 18 had primary sclerosing cholangitis (PSC) and 24 had chronic hepatitis B (CHB), together with five healthy controls (HC), were recruited to this study. Participants’ liver sections were analyzed using immunohistochemistry. Serum CTHRC1 levels in another cohort of 59 patients with PBC and 10 age‐matched HC were detected by enzyme‐linked immunosorbent assay.

Results

CTHRC1 protein was primarily expressed in activated hepatic stellate cells (HSC). CTHRC1 expression was significantly increased in the PBC and PSC groups, compared with the HC and CHB groups. Importantly, the hepatic fibrosis stage of the PBC group was positively correlated with hepatic CTHRC1 expression (r = 0.425, P = 0.003). Meanwhile, there were significant correlations between serum CTHRC1 levels and both the degrees of hepatic inflammation and fibrosis stage in the PBC group (r = 0.300, P = 0.022; r = 0.321, P = 0.012).

Conclusion

CTHRC1 may play a role in hepatic fibrogenesis in PBC and that serum CTHRC1 may be a potential novel noninvasive biomarker in the assessment of liver fibrosis and inflammation.
Adjuvant radiotherapy for stage pN1M0 esophageal squamous cell carcinoma: Results from a Chinese two‐center study
Authors: Ni Wenjie , Chen Junqiang , Xiao Zefen , Yu Shufei , Zhang Wencheng , Zhou Zongmei , Chen Dongfu , Feng Qinfu , Chen Xiaohui , Lin Yu , Zhu Kunshou , Gao Shugeng , Xue Qi , Mao Yousheng , Cheng Guiyu , Sun Kelin , Liu Xiangyang , Fang Dekang
Published: May 2019

Background

Whether postoperative radiotherapy is beneficial in the treatment of esophageal squamous cell carcinoma with one or two regional lymph node (LN) metastases (pN1) after esophagectomy is uncertain. This study aimed to explore the effect of postoperative radiotherapy (PORT) on survival.

Methods

Propensity score‐matching (PSM) analysis was conducted to balance the two arms (surgery only [S] or surgery plus postoperative radiotherapy [PORT]). The survival rate was calculated by the Kaplan‐Meier method and analyzed using the log‐rank test.

Results

A total of 992 cases confirmed positive for one or two regional LN metastases were eligible. After PSM, 622 patients were reviewed. Each group consisted of 311 cases. The median follow‐up was 80.7 months. For the overall cohort, the one‐, three‐ and five‐year overall survival (OS) were 90.6%, 51.9% and 38.2%, respectively. Disease‐free survival (DFS) was 76.0%, 41.4% and 32.1%, respectively. The five‐year OS and DFS were 45.0% and 39.8% for PORT, which was significantly higher than the S group (31.3% and 24.2%, both P < 0.001). On subgroup analysis, PORT was associated with improved OS and DFS for patients with pathological stage pT3–4N1M0, compared with S group (five‐year OS 41.3% vs. 23.5%, P < 0.001; five‐year DFS 35.8% vs. 18.8%, P < 0.001). However, for pT1–2N1M0 patients, PORT did not benefit OS and DFS compared with S (P = 0.063).

Conclusions

In summary, the addition of PORT after esophagectomy was associated with a statistically significant improvement in OS and DFS for patients with pathological one or two lymph‐node positive pathology, in particular for stage pT3–4N1M0 patients.
Geographic proximity is associated with transmission of suicidal behaviour among siblings
Authors: Edwards A. C. , Ohlsson H. , Mościcki E. K. , Sundquist J. , Sundquist K. , Kendler K. S.
Published: May 2019

Objective

The aim of this study was to clarify the role of ‘contagion’, or social transmission, in risk of suicidal behaviour (SB) among siblings.

Methods

We followed Swedish sibling pairs until one of them (S1; N = 111,848) was registered for a suicide attempt or completion. We tested the effect of geographic proximity between siblings on risk of a first SB registration of S1's sibling (S2). To control for familial confounding, we conducted complementary analyses of sibling trios (N = 701), comparing risk in different siblings as a function of their respective proximity to S1.

Results

The best‐fitting model across sibling pairs included an effect of distance between siblings (HR = 0.96, 95% CI = 0.93–0.99). Hazard ratios declined quickly up to 25 km and largely stabilized beyond 150 km. Across all pairs, a larger age difference between siblings was associated with reduced SB risk (HR = 0.96 95% CI = 0.93–0.98). Findings were consistent within the sibling trios.

Conclusions

Consistent with the concept of suicide contagion, risk of suicidal behaviour subsequent to a sibling's suicide completion or attempt is higher as a function of sibling closeness. These findings are robust to potentially confounding familial factors.
Dark side of the epididymis: tails of sperm maturation
Authors: Hermo L. , Oliveira R. L. , Smith C. E. , Au C. E. , Bergeron J. J. M.
Published: May 2019

Background

The Hermes body (HB) previously called the cytoplasmic droplet is a focal distension of the flagellar cytoplasm of epididymal spermatozoa consisting mainly of isolated flattened Golgi cisternae.

Objective

To define a functional role for the HB of epididymal spermatozoa.

Methods

Isolated fractions of HBs of epididymal spermatozoa were prepared and by quantitative tandem mass spectrometry revealed 1511 proteins.

Results

The glucose transporter GLUT‐3 was the most abundant protein followed by hexokinase 1, which along with the presence of all glycolytic enzymes suggested a role for the HB in glycolysis. Several TMED/p24 Golgi trafficking proteins were abundant with TMED7/p27 and TMED2/p24 defining the identity of the flattened cisternae within the HB as Golgi, along with the known Golgi proteins, GBF1, GOLPH3, Man2α1, and ManIIX. The Golgi trafficking protein TMED7/p27 via small 50‐nm vesicles emanating from the Golgi cisternae was proposed to transport GLUT‐3 to the plasma membrane for ATP production related to sperm motility. The internal membranes revealed abundant proteins not only of Golgi cisternae, but also of endoplasmic reticulum and endosomes. COPI and COPII coats, clathrin, SNAREs, annexins, atlastins, and GTPases were identified for vesicular trafficking and membrane fusion, in addition to ribosomes, stress proteins for protection, proteasome proteins involved in degradation, and cytoskeletal elements for migration of the HB along the flagellum. The biogenesis of the HB occurring at step 19 spermatids of the testis just prior to their release was uncovered as a key step in germ cell differentiation, where several proteins were expressed, some for the first time.

Conclusion

As epididymal spermatozoa undergo remodeling of their protein makeup through selective degradation of sperm proteins during epididymal transit, then remodeling as a consequence of new protein synthesis is not excluded by our observations.
Cervical modifications after pessary placement in singleton pregnancies with maternal short cervical length: 2D and 3D ultrasound evaluation
Authors: Mendoza Cobaleda Manel , Ribera Irene , Maiz Nerea , Goya Maria , Carreras Elena
Published: May 2019

Introduction

The use of a pessary proved to prevent preterm birth in asymptomatic women with mid‐trimester short cervical length (CL); however, the precise mechanisms by which the pessary confers its benefit remain unclear. The aim of this study was to evaluate multiple cervical characteristics assessed by 2‐dimensional and 3‐dimensional ultrasound before and after placement of a cervical pessary to ascertain its mechanism of action.

Material and methods

In this prospective cohort study, we assessed the cervical characteristics in singleton pregnancies with maternal short CL and compared them with matched reference women with normal CL. The variables evaluated were: CL, uterocervical angles, cervical consistency indices (cervical consistency index and CL consistency index), cervical volume and vascular indices. All variables were re‐assessed immediately after pessary placement and 4‐6 weeks later in all participants. Mann‐Whitney U test was used to assess differences between groups and paired samples t test for comparisons in two different examinations in the same women. The aim of this study was to evaluate multiple cervical ultrasound variables before and after the placement of a cervical pessary and compare the evolution of these variables with a reference group with normal CL to better understand the device's mechanism of action.

Results

Thirty‐three women with short CL and 24 reference women with normal CL were enrolled. At the time of enrollment, gestational age and maternal baseline characteristics did not differ between groups. Immediately after pessary placement, CL increased, uterocervical angles were narrower and cervical consistency increased significantly. When the magnitude of change in cervical variables was compared over time between the reference group and the study group, median CL had increased in the study group (1.47 mm) but it had shortened in the reference group (−2.56 mm). These inverse trends were statistically significant (P = 0.006).

Conclusions

Cervical pessary reduces both uterocervical angles and corrects cervical angulation by pushing the cervix up toward the uterus. Maintaining the cervix aligned to the uterine axis leads to reduced cervical tissue stretch, so avoiding further cervical shortening. All these changes were present after pessary placement; however, the clinical implications of these findings remain unknown.
Regulation of erythrocyte function: Multiple evolutionary solutions for respiratory gas transport and its regulation in fish
Authors: Nikinmaa Mikko , Berenbrink Michael , Brauner Colin J.
Published: May 2019

Gas transport concepts in vertebrates have naturally been formulated based on human blood. However, the first vertebrates were aquatic, and fish and tetrapods diverged hundreds of millions years ago. Water‐breathing vertebrates live in an environment with low and variable O2 levels, making environmental O2 an important evolutionary selection pressure in fishes, and various features of their gas transport differ from humans. Erythrocyte function in fish is of current interest, because current environmental changes affect gas transport, and because especially zebrafish is used as a model in biomedical studies, making it important to understand the differences in gas transport between fish and mammals to be able to carry out meaningful studies. Of the close to thirty thousand fish species, teleosts are the most species‐numerous group. However, two additional radiations are discussed: agnathans and elasmobranchs. The gas transport by elasmobranchs may be closest to the ancestors of tetrapods. The major difference in their haemoglobin (Hb) function to humans is their high urea tolerance. Agnathans differ from other vertebrates by having Hbs, where cooperativity is achieved by monomer‐oligomer equilibria. Their erythrocytes also lack the anion exchange pathway with profound effects on CO2 transport. Teleosts are characterized by highly pH sensitive Hbs, which can fail to become fully O2‐saturated at low pH. An adrenergically stimulated Na+/H+ exchanger has evolved in their erythrocyte membrane, and plasma‐accessible carbonic anhydrase can be differentially distributed among their tissues. Together, and differing from other vertebrates, these features can maximize O2 unloading in muscle while ensuring O2 loading in gills.
Psychological Research on Organisational Democracy: A Meta‐Analysis of Individual, Organisational, and Societal Outcomes
Authors: Weber Wolfgang G. , Unterrainer Christine , Höge Thomas
Published: May 2019

Our meta‐analytic review investigates how employee participation in democratic enterprises is related to psychological outcomes. We gathered 60 studies through a systematic literature search of quantitative field studies (published between January 1970 and May 2017) and extracted 138 effect sizes related to three indicators of organisational democracy (OD) and 15 psychological outcomes. The overall findings suggest that employees’ individually perceived participation in organisational decision making (IPD) had a stronger relation to job satisfaction (ρ = .25), job involvement/work motivation (ρ = .36), prosocial work behaviours (ρ = .24), civic and democratic behaviours (ρ = .21) and perceived supportive climate (ρ = .44) than the other two OD indicators: structurally anchored employee participation (SAEP) and employee participation in collective ownership (EO). This was not the case for value‐based commitment: the relations of SAEP (ρ = .40), EO (ρ = .34), and IPD (ρ = .46) with commitment were nearly equal. Mediation analyses indicated that IPD partially mediated most of the effects of SAEP and EO on the outcomes mentioned. The cross‐sectional database and a small number of studies for some of the outcomes are the main limitations of this study.
Developing a performance assessment task in the Finnish higher education context: Conceptual and empirical insights
Authors: Hyytinen Heidi , Toom Auli
Published: May 2019

Background

Performance assessment development is a three‐phase process of (1) defining the construct of what is to be measured, (2) constructing the test items, task, and scoring criteria, and (3) collecting empirical evidence on extent to which they tap into the intended construct.

Aims

In the light of the three‐phase process, this pilot study presents the development of performance assessment for research on critical thinking and moral judgement to be utilized in the Finnish higher education context. In particular, it explores the cognitive processes and moral judgement that occur while completing the assessment and how both task and respondent characteristics are associated with these processes.

Sample

The study was conducted with five participants drawn from purposeful sampling.

Methods

We collected the data from cognitive laboratories with think‐alouds and interviews. The data were analysed using a qualitative abductive approach.

Results

The instructions together with sources given for completing the assessment triggered participants’ critical and moral judgement. The results also indicate that the performance assessment being developed has relevance to everyday life. The theme of assessment was experienced meaningful, and it maintained the participants’ interest throughout the completion of the task. The assessment was open‐ended and allowed multiple lines of thinking. The participants perceived the task as being challenging. The prior knowledge of the participants, their integrity, and capability to monitor thinking and performance was related to the ways of performing the task.

Conclusions

Based on preliminary evidence drawn from the pilot data, the study concludes by outlining the strengths of the task as well as modifications that are needed in order to develop this specific performance assessment further.
Regulatory T (Treg) cells in cancer: Can Treg cells be a new therapeutic target?
Authors: Ohue Yoshihiro , Nishikawa Hiroyoshi
Published: May 2019

Regulatory T (Treg) cells suppress abnormal/excessive immune responses to self‐ and nonself‐antigens to maintain immune homeostasis. In tumor immunity, Treg cells are involved in tumor development and progression by inhibiting antitumor immunity. There are several Treg cell immune suppressive mechanisms: inhibition of costimulatory signals by CD80 and CD86 expressed by dendritic cells through cytotoxic T‐lymphocyte antigen‐4, interleukin (IL)‐2 consumption by high‐affinity IL‐2 receptors with high CD25 (IL‐2 receptor α‐chain) expression, secretion of inhibitory cytokines, metabolic modulation of tryptophan and adenosine, and direct killing of effector T cells. Infiltration of Treg cells into the tumor microenvironment (TME) occurs in multiple murine and human tumors. Regulatory T cells are chemoattracted to the TME by chemokine gradients such as CCR4‐CCL17/22, CCR8‐CCL1, CCR10‐CCL28, and CXCR3‐CCL9/10/11. Regulatory T cells are then activated and inhibit antitumor immune responses. A high infiltration by Treg cells is associated with poor survival in various types of cancer. Therefore, strategies to deplete Treg cells and control of Treg cell functions to increase antitumor immune responses are urgently required in the cancer immunotherapy field. Various molecules that are highly expressed by Treg cells, such as immune checkpoint molecules, chemokine receptors, and metabolites, have been targeted by Abs or small molecules, but additional strategies are needed to fine‐tune and optimize for augmenting antitumor effects restricted in the TME while avoiding systemic autoimmunity. Here, we provide a brief synopsis of these cells in cancer and how they can be controlled to achieve therapeutic outcomes.
Hyaluronic acid synthase 2 promotes malignant phenotypes of colorectal cancer cells through transforming growth factor beta signaling
Authors: Kim Young‐Heon , Lee Seung Bum , Shim Sehwan , Kim Areumnuri , Park Ji‐Hye , Jang Won‐Suk , Lee Sun‐Joo , Myung Jae Kyung , Park Sunhoo , Lee Su‐Jae , Kim Min‐Jung
Published: May 2019

Hyaluronic acid synthase 2 (HAS2) is suggested to play a critical role in malignancy and is abnormally expressed in many carcinomas. However, its role in colorectal cancer (CRC) malignancy and specific signaling mechanisms remain obscure. Here, we report that HAS2 was markedly increased in both CRC tissue and malignant CRC cell lines. Depletion of HAS2 in HCT116 and DLD1 cells, which express high levels of HAS2, critically increased sensitivity of radiation/oxaliplatin‐mediated apoptotic cell death. Moreover, downregulation of HAS2 suppressed migration, invasion and metastasis in nude mice. Conversely, ectopic overexpression of HAS2 in SW480 cells, which express low levels of HAS2, showed the opposite effect. Notably, HAS2 loss‐ and gain‐of‐function experiments revealed that it regulates CRC malignancy through TGF‐β expression and SMAD2/Snail downstream components. Collectively, our findings suggest that HAS2 contributes to malignant phenotypes of CRC, at least partly, through activation of the TGF‐β signaling pathway, and shed light on the novel mechanisms behind the constitutive activation of HAS2 signaling in CRC, thereby highlighting its potential as a therapeutic target.
Structure‐dependent activation of gene expression by bis‐indole and quinoline‐derived activators of nuclear receptor 4A2
Authors: Li Xi , Tjalkens Ronald B. , Shrestha Rupesh , Safe Stephen
Published: May 2019

Bis‐indole derivatives including 1,1‐bis(3′‐indolyl)‐1‐(4‐chlorophenyl)methane (DIM‐C‐pPhCl) and substituted quinolines such as chloroquine (CQ) and amodiaquine (AQ) are nuclear receptor 4A2 (NR4A2, Nurr1) ligands, and they exhibit anti‐inflammatory activities in mouse and rat models of Parkinson's disease, respectively. However, computational modeling demonstrates that the quinoline derivatives interact with the ligand‐binding domain, whereas the bis‐indoles preferentially interact with a C‐terminal cofactor binding site of NR4A2. In this study, the effects of DIM‐C‐pPhCl and related analogs were compared with CQ/AQ as inducers of NR4A2‐responsive genes including vasoactive intestinal peptide, osteopontin, proopiomelanocortin, and neuropilin 1 in Panc1 and Panc28 pancreatic cancer cells. The results demonstrate that, among the bis‐indole analogs, their relative potencies as inducers were structure‐gene‐ and cell context dependent. In contrast, CQ and AQ were significantly less potent than the bis‐indole derivatives and, for some of the NR4A2‐regulated genes, CQ and AQ were inactive as inducers. These results demonstrate that although bis‐indole and quinoline derivatives have been characterized as activators of NR4A2‐dependent gene expression, these two classes of compounds exhibit different activities, indicating that they are selective NR4A2 modulators.
IL-17 and TNF-α co-operation contributes to the proinflammatory response of hepatic stellate cells
Authors: Beringer A , Miossec P
Published: May 2019

Hepatic stellate cells (HSCs) have a central role in liver inflammation and fibrosis by producing inflammatory and fibrotic mediators. Their activation is regulated through direct cell–cell interactions, but also through systemic and local effects of soluble factors such as cytokines. The effects of the proinflammatory cytokines interleukin (IL)-17 and tumor necrosis factor (TNF)-α and cell interactions with hepatocytes on HSC activation were assessed. Human HSC and HepaRG cells were exposed to IL-17 and/or TNF-α. IL-17 and TNF-α contribution from immune cells was determined in a co-culture model with phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells (PBMC), HSC and/or hepatocytes. IL-17 enhanced TNF-α effects on the induction of IL-6, IL-1β, and the chemokine IL-8, chemokine (C-C motif) ligand 20 (CCL20) and monocyte chemoattractant protein-1 (MCP-1) expression/secretion in isolated HSC cultures. HSC–hepatocyte interactions did not enhance IL-6, IL-8 and CCL20 production compared to hepatocyte alone. However, HSC–hepatocyte interactions increased C-reactive protein expression. IL-17 and/or TNF-α had no direct profibrotic effects on collagen 1 α1, tissue inhibitor of matrix metalloproteinase (TIMP) and matrix metalloproteinase (MMP) 2 gene expression, whereas mRNA levels of MMP3, an enzyme involved in matrix destruction, were up-regulated in HSCs. The use of specific inhibitors of IL-17 and TNF-α indicated their contribution to the strong increase of IL-6 and IL-8 production induced by PBMC, HSC and/or hepatocyte interactions. As chronic liver inflammation leads to liver fibrosis, IL-17 and/or TNF-α neutralization can be of interest to control liver inflammation and therefore its effects on fibrosis.
Progranulin serum levels and gene expression in subcutaneous vs visceral adipose tissue of severely obese patients undergoing bariatric surgery
Authors: Brock Judith , Schmid Andreas , Karrasch Thomas , Pfefferle Petra , Schlegel Jutta , Busse Inga , Hauenschild Annette , Schmidt Barbara , Koukou Maria , Arapogianni Efthymia , Schultz Andreas , Thomalla Miriam , Akinci Secil , Kruse Johannes , Padberg Winfried , Schäffler Andreas , Albrecht Jens
Published: May 2019

Background

Progranulin represents an adipokine putatively mediating insulin resistance and inflammation. Data in humans are sparse, and the source of circulating progranulin in obesity is unknown.

Objectives

Serum progranulin concentrations and subcutaneous (sc) as well as visceral (vis) adipose tissue (AT) progranulin expression were quantified in a large cohort of patients with obesity undergoing bariatric surgery (BS) (n = 153) or a low‐calorie diet (LCD) (n = 121).

Cohorts and methods

Paired serum and AT mRNA samples were obtained from patients with severe obesity undergoing BS (ROBS cohort; Research in Obesity and Bariatric Surgery). Serum progranulin was measured by ELISA in both cohorts, and AT mRNA expression was analysed by quantitative real‐time PCR in bariatric patients.

Results

There was no gender‐specific effect in serum progranulin or AT progranulin expression. Importantly, circulating progranulin was independent from adipose tissue gene expression in paired samples. sc AT progranulin expression was higher than in vis AT (P = 0.027), and there was a positive correlation between sc AT and vis AT gene expression (P < 0.001; r = +0.34). Serum progranulin strongly and rapidly increased after BS within 3 days and remained elevated up to 12 months. Serum progranulin was strongly correlated with serum CTRP‐3 levels.

Conclusions

The present study provides detailed progranulin gene expression data in sc and vis AT in a large, prospective and observational cohort of patients with severe obesity. Serum progranulin concentrations are not predicted by sc or vis AT progranulin gene expression. Thus, AT seems not to be the main source of circulating progranulin levels in obesity.
Intra‐oral single‐site comparisons of periodontal and peri‐implant microbiota in health and disease
Authors: Yu Xiao‐Lin , Chan Yuki , Zhuang Longfei , Lai Hong‐Chang , Lang Niklaus P. , Keung Leung Wai , Watt Rory M.
Published: May 2019

Objective

Periodontitis and peri‐implantitis are oral infectious–inflammatory diseases that share similarities in their pathology and etiology. Our objective was to characterize the single‐site subgingival and submucosal microbiomes of implant‐rehabilitated, partially dentate Chinese subjects (n = 18) presenting with both periodontitis and peri‐implantitis.

Materials and methods

Subgingival/submucosal plaque samples were collected from four clinically distinct sites in each subject: peri‐implantitis submucosa (DI), periodontal pocket (DT), clinically healthy (unaffected) peri‐implant submucosa (HI), and clinically healthy (unaffected) subgingival sulcus (HT). The bacterial microbiota present was analyzed using Illumina MiSeq sequencing.

Results

Twenty‐six phyla and 5,726 operational taxonomic units (OTUs, 97% sequence similarity cutoff) were identified. Firmicutes, Proteobacteria, Fusobacteria, Bacteroidetes, Actinobacteria, Synergistetes, TM7, and Spirochaetes comprised 99.6% of the total reads detected. Bacterial communities within the DI, DT, HI, and HT sites shared high levels of taxonomic similarity. Thirty‐one “core species” were present in >90% sites, with Streptococcus infantis/mitis/oralis (HMT‐070/HMT‐071/HMT‐638/HMT‐677) and Fusobacterium sp. HMT‐203/HMT‐698 being particularly prevalent and abundant. Beta‐diversity analyses (PERMANOVA test, weighted UniFrac) revealed the largest variance in the microbiota was at the subject level (46%), followed by periodontal health status (4%). Differing sets of OTUs were associated with periodontitis and peri‐implantitis sites, respectively. This included putative “periodontopathogens,” such as Prevotella, Porphyromonas, Tannerella, Bacteroidetes [G‐5], and Treponema spp. Interaction network analysis identified several putative patterns underlying dysbiosis in periodontitis/peri‐implantitis sites.

Conclusions

Species (OTU) composition of the periodontal and peri‐implant microbiota varied widely between subjects. The inter‐subject variations in subgingival/submucosal microbiome composition outweighed differences observed between implant vs. tooth sites, or between diseased vs. healthy (unaffected) peri‐implant/periodontal sites.
LncRNA FOXD1‐AS1 acts as a potential oncogenic biomarker in glioma
Authors: Gao Yuan‐Feng , Liu Jun‐Yan , Mao Xiao‐Yuan , He Zheng‐Wen , Zhu Tao , Wang Zhi‐Bin , Li Xi , Yin Ji‐Ye , Zhang Wei , Zhou Hong‐Hao , Liu Zhao‐Qian
Published: May 2019

Aims

Altered activities of long noncoding RNAs (lncRNAs) have been associated with cancer development, and lncRNA FOXD1‐AS1 (FOXD1‐AS1) is the antisense transcript of the gene encoding for FOXD1, known for its role as an oncogene in several tumor types including glioma. However, the role of FOXD1‐AS1 in the differentiation and progression of glioma is not well known.

Methods

Expression profile chip and qPCR were used to screen and identify FOXD1‐AS1. Glioma cells were transfected with siRNA or eukaryotic expression vector to observe FOXD1‐AS1 function in vitro and in vivo. Dual luciferase reporter gene analysis, Western blot, and ChIRP‐MS were used to detect microRNAs and protein that combine with FOXD1‐AS1.

Results

FOXD1‐AS1 was upregulated and directly correlated with the glioma grade, and it was localized in both the nucleus and the cytoplasm of the glioma cell. FOXD1‐AS1 silencing caused tumor suppressive effects via inhibiting cell proliferation, migration, and apoptosis, while FOXD1‐AS1 overexpression resulted in opposite effects. Additionally, in vivo experiments showed that FOXD1‐AS1 knockdown reduced tumor volume and weight. More importantly, mechanical studies revealed that FOXD1‐AS1 targeted both miR339‐5p and miR342‐3p (miR339/342). Furthermore, protein eukaryotic translation initiation factor 5 subunit A (eIF5a) resulted a direct target of FOXD1‐AS1.

Conclusions

These data indicated that FOXD1‐AS1, a miR339/342 target, affected biological processes via protein eIF5a; thus, it might be considered as a new therapeutic target for glioblastoma.
Serum prealbumin is a prognostic indicator in idiopathic pulmonary fibrosis
Authors: Li Biyun , Zhang Xinran , Xu Guodong , Zhang Shu , Song Huifang , Yang Kaiyuan , Dai Huaping , Wang Chen
Published: May 2019

Introduction

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by variable progression. The prealbumin (PA) is a parameter in a routine blood biochemistry examination. We sought to investigate the prognostic value in IPF patients.

Objectives

To evaluate the prognosis value in patients with IPF.

Methods

Blood biochemistry examination, demographics, pulmonary function data from patients with IPF consulted in Beijing Chao‐Yang Hospital and China‐Japan Friendship Hospital between July 2012 and December 2016 were collected. Infection, liver and kidney dysfunction and lung transplantation are excluded from the cohort.

Results

The result of multivariate Cox analysis showed that PA was significant prognostic indicator of survival along with BMI, FVC, serum albumin protein and serum global protein. The patients with PA concentration <0.2 mg/L had shorter survival compared with those whose PA were normal. Although the survival had no significant difference between the patients with PA concentration < 0.2 mg/L and albumin < 35 g/L and those with PA concentration < 0.2 mg/L, the average survival time of patients with PA concentration < 0.2 mg/L and albumin < 35 g/L were shorter.

Conclusions

Our study indicated that IPF patients with PA concentration < 0.2 mg/L have poorer outcome. Further studies are warranted to indentify PA as a predictor for IPF patients outcomes and explore the role of PA in the pathogenesis of IPF.
Elective or emergency heart transplantation: Cost comparison in a single center
Authors: Farrero Marta , Flores‐Umanzor Eduardo J. , Pomar Jose Luis , Sagarra Joan , Santiago Evelyn , Perez‐Villa Felix
Published: May 2019

Background and aims

Heart transplantation (HT) is the treatment of choice for selected cases of advanced heart failure. There is an increasing rate of emergency HT in our country. The aim of this study was to determine the cost of HT in our hospital according to emergent vs. elective transplantation status.

Methods

The costs of all consecutive HTs performed in our center between January 2010 and May 2015 were analyzed. The cost of elective and emergent HT was compared.

Results

HT mean cost at our institution was €62 203 ± 47 976. Elective HT mean cost was €47 540 ± 25 140, whereas emergent HT cost was €102 733 ± 68 050 (emergency status 1, as regional priority, was €66 077 ± 28 067 and emergency status 0, as the highest national priority, was €136 056 ± 77 080; P < 0.001). Increased emergent HT cost was mainly related to a longer admission (32 ± 24 days vs. 69 ± 53 days; P = 0.006; accounting for a cost of €14 517 ± 12 475 vs. €37 846 ± 31 702; P < 0.001) and increased drug‐related expenses (€6622 ± 7465 vs. €15,171 ± 15,758; P < 0.02). Elective HT survival rate was 96%, compared to 68% for emergent HT; P = 0.002.

Conclusions

Elective HT showed a high survival rate with a relatively low and less variable cost, leading to a favorable economic balance in today's public health reimbursement system. In contrast, emergent HT showed a higher cost and a lower survival rate. New treatment strategies should be identified for heart failure patients at risk of requiring emergency HT.
The development of executive function in early childhood is inversely related to change in body mass index: Evidence for an energetic tradeoff?
Authors: Blair Clancy , Kuzawa Christopher W. , Willoughby Michael T.
Published: May 2019

A well‐established literature demonstrates executive function (EF) deficits in obese children and adults relative to healthy weight comparisons. EF deficits in obesity are associated with overeating and impulsive consumption of high calorie foods leading to excess weight gain and to problems with metabolic regulation and low‐grade inflammation that detrimentally affect the structure and function of prefrontal cortex. Here, we test a complementary explanation for the relation between EF and body mass index (BMI) grounded in the energy demand of the developing brain. Recent work shows that the brain accounts for a lifetime peak of 66% of resting metabolic rate in childhood and that developmental changes in brain energetics and normative changes in body weight gain are closely inversely related. This finding suggests a trade‐off in early childhood between energy used to support brain development versus energy used to support physical growth and fat deposition. To test this theorized energetic trade‐off, we analyzed data from a large longitudinal sample (N = 1,292) and found that change in EF from age 3 to 5 years, as a proxy for brain development in energetically costly prefrontal cortex, is inversely related to change in BMI from age 2 to 5 years. Greater linear decline in BMI predicted greater linear increase in EF. We interpret this finding as tentative support for a brain–body energetic trade‐off in early childhood with implications for lifetime obesity risk.
New Firm Survival in Developing Countries: Evidence From Kosovo
Authors: Esteve‐Pérez Silviano , Sahiti Fadil
Published: May 2019

This paper examines both newborn firm survival and firm turnover in Kosovo using the population of new firms and registry information on active firms from 2008 to 2012. Survival analysis is employed to analyze the impact of firm‐ and industry‐level characteristics on survival. We find that the hazard rate has an inverted U‐shape relationship with both firm age and firm size. The risk of failure increases over the first two years and later decreases. In addition, firms with one employee and more than 10 employees enjoy better survival prospects than medium‐sized companies. Interestingly, very large firms do not face fewer risks than very small companies. When compared to other developing countries, entry rates are lower but survival rates are higher. These features seem to be a distinctive characteristic of Kosovo.
New approaches to studying early brain development in Down syndrome
Authors: Baburamani Ana A , Patkee Prachi A , Arichi Tomoki , Rutherford Mary A
Published: May 2019

Down syndrome is the most common genetic developmental disorder in humans and is caused by partial or complete triplication of human chromosome 21 (trisomy 21). It is a complex condition which results in multiple lifelong health problems, including varying degrees of intellectual disability and delays in speech, memory, and learning. As both length and quality of life are improving for individuals with Down syndrome, attention is now being directed to understanding and potentially treating the associated cognitive difficulties and their underlying biological substrates. These have included imaging and postmortem studies which have identified decreased regional brain volumes and histological anomalies that accompany early onset dementia. In addition, advances in genome‐wide analysis and Down syndrome mouse models are providing valuable insight into potential targets for intervention that could improve neurogenesis and long‐term cognition. As little is known about early brain development in human Down syndrome, we review recent advances in magnetic resonance imaging that allow non‐invasive visualization of brain macro‐ and microstructure, even in utero. It is hoped that together these advances may enable Down syndrome to become one of the first genetic disorders to be targeted by antenatal treatments designed to ‘normalize’ brain development.

What this paper adds

Magnetic resonance imaging can provide non‐invasive characterization of early brain development in Down syndrome.

Down syndrome mouse models enable study of underlying pathology and potential intervention strategies.

Potential therapies could modify brain structure and improve early cognitive levels.

Down syndrome may be the first genetic disorder to have targeted therapies which alter antenatal brain development.
A critical assessment of anti‐corruption strategies for economic development in sub‐Saharan Africa
Authors: Senu Oluwafemi
Published: May 2019

Motivation

Many countries in sub‐Saharan Africa (SSA) experience thwarted economic development and corrupt public administration. As the United Nations Convention Against Corruption (UNCAC) focuses on implementation mechanisms in SSA, there is a need to examine the causes of the setbacks affecting these mechanisms, looking at the current trends of corruption and their impact on socioeconomic development.

Purpose

This article focuses on assessing setbacks in anti‐corruption strategies to advance economic development in SSA, primarily looking at how and in what conditions UNCAC prevents corruption and manages responses in SSA.

Approach

This article adopts a descriptive and an explanatory perspective, using case studies of Kenya and Nigeria to explain and show how far the objectives of anti‐corruption strategies have been met, and assessing the causes of setbacks. In this context, the article also explores the challenges facing the UK’s Department for International Development (DFID).

Conclusions

Socioeconomic development in SSA is hard to separate from maladministration and large‐scale corruption. The findings reveal the gravity of this impact and its interrelated factors of “active” and “benign” corruption. This article concludes that for SSA to create sustainable economic environments, the causes of the failure to stamp out corruption need to be addressed, and dishonesty, maladministration, illicit activities, nepotism curtailed, along with corrupt influences on anti‐corruption legislation.

Policy implications

The article concludes that if governance does not prevent the failures of anti‐corruption strategies, an interventionist response will only weaken national endeavours, making it difficult to reach UNCAC’s vision of sustainable and corruption‐free economic environments.
Climate effects on fish body size–trophic position relationship depend on ecosystem type
Authors: Dantas Danyhelton D. F. , Caliman Adriano , Guariento Rafael D. , Angelini Ronaldo , Carneiro Luciana S. , Lima Sergio M. Q. , Martinez Pablo A. , Attayde José L.
Published: May 2019

The energetic demand of consumers increases with body size and temperature. This implies that energetic constraints may limit the trophic position of larger consumers, which is expected to be lower in tropical than in temperate regions to compensate for energy limitation. Using a global dataset of 3635 marine and freshwater ray‐finned fish species, we addressed if and how climate affects the fish body size–trophic position relationship in both freshwater and marine ecosystems, while controlling for the effects of taxonomic affiliation. We observed significant fish body size–trophic position relationships for different ecosystems. However, only in freshwater systems larger tropical fish presented a significantly lower trophic position than their temperate counterparts. Climate did not affect the fish body size–trophic position relationship in marine systems. Our results suggest that larger tropical freshwater fish may compensate for higher energetic constraints feeding at lower trophic positions, compared to their temperate counterparts of similar body size. The lower latitudinal temperature range in marine ecosystems and/or their larger ecosystem size may attenuate and/or compensate for the energy limitation of larger marine fish. Based on our results, temperature may determine macroecological patterns of aquatic food webs, but its effect is contingent on ecosystem type. We suggest that freshwater ecosystems may be more sensitive to warming‐induced alterations in food web topology and food chain length than marine ecosystems.
Leadership and career development curriculum in Australian dental and oral health programmes
Authors: Hayes Melanie J. , Ingram Kelsey
Published: May 2019

Introduction

There is very little evidence of dental schools offering leadership or career development training for students. Given that tertiary students come from diverse backgrounds with differing experiences, it is important that all students learn skills that improve their employability by preparing them for a range of career paths and equipping them with the confidence to lead their profession into the future. This study mapped current leadership and career development training in dental education programmes throughout Australia, focusing on the capacity, barriers and enablers.

Methods

In 2018, an electronic survey was sent to the Program Convenors of all nineteen dental programmes in Australia. Survey questions were sourced from existing literature and the current regulatory competencies.

Results

Whilst the majority of respondents (n = 17, 89% response rate) indicated that their programmes included both leadership training (72%) and career development activities (88%), it is clear that the content focus, hours allocated and assessment items vary widely across the country. Further, curriculum appeared to focus almost exclusively on clinical work, which does not provide an avenue for students to explore alternative, non‐clinical career options or pathways or develop their skills beyond treating individual patients. Time constraints and ideological differences were reported as the biggest barriers to implementing leadership and career development curricula.

Conclusion

Despite an inconsistent approach nationally, it appears there is an opportunity for faculty across institutions to collaborate, potentially to develop a set of leadership and career development competencies and best practice teaching and learning activities.
A very potent factor V inhibitor interferes with the levels of all coagulation factors and causes a fatal hemorrhagic syndrome
Authors: Hoffmann Claire , Amiral Jean , Rezig Schéhérazade , Kerspern Hélène , Jantzem Hélène , Robin Sara , Collins Adam , Mornet Clelia , Mingant Fanny , Pan Petesch Brigitte , Ianotto Jean‐Christophe , Lippert Eric , Galinat Hubert
Published: May 2019

We report a very high factor V inhibitor affecting the measurement of all coagulation factors besides fibrinogen, all these factors being dramatically decreased. This inhibitor could be linked to antibiotic use. The patient died of massive hemorrhage before a plasma exchange could be initiated.
How to define chronic prurigo?
Authors: Pereira Manuel P. , Ständer Sonja
Published: May 2019

Chronic prurigo impairs quality of life and is immensely challenging to treat. Until recently, no clear definition or classification system was available for this disease. A European task force specialized in pruritus defined chronic prurigo as a distinct disease characterized by chronic pruritus, a lengthy scratching behaviour and the presence of pruriginous lesions. Papular, nodular, plaque, umbilicated and linear prurigo were identified as clinical subtypes according to the most prominent lesion type observed in the physical examination. Various clinical and pathophysiological aspects, which are common across the range of clinical manifestations of chronic prurigo, argue for chronic prurigo as a disease in its own right. Chronic prurigo should be clearly demarcated from other conditions such as so‐called acute or subacute prurigo forms as well as from psychogenic self‐inflicted skin lesions, since different diagnostic criteria apply for these diseases. This viewpoint essay provides a detailed definition and classification of chronic prurigo including its obligatory and associated diagnostic criteria and discusses chronic prurigo as a distinct disease as well as the demarcation to other relevant conditions.
Clinical features of Kaposi's sarcoma: experience from a Taiwanese medical center
Authors: Huang Alice Ya‐Yun , Lin Chi‐Ling , Chen Gwo‐Shing , Hu Stephen Chu‐Sung
Published: May 2019

Background

Most of the previous reports regarding the clinical features of Kaposi's sarcoma (KS) have been performed in Western and African countries. The clinical characteristics of KS have not been well defined in Han Chinese or Taiwanese patients. In this study, we analyzed the clinical features of KS patients in a Taiwanese medical center.

Methods

Medical records from Kaohsiung Medical University Hospital over the past 20 years (1996–2016) were comprehensively reviewed.

Results

There were 55 patients with KS (50 males and 5 females), including 37 patients (67%) with classic disease, 17 patients (31%) with AIDS‐associated disease, and one patient (2%) with immunosuppressive medication‐related disease. The average age was 58.7 years (range 20–87 years), and the average age was younger for AIDS patients (33.8 years) compared with non‐AIDS patients (69.8 years). Among patients with classic KS, lesions were mostly localized to the lower extremities, whereas AIDS‐associated KS patients were more likely to develop disseminated skin lesions, skin lesions on atypical sites (head and neck, trunk), and extracutaneous involvement (particularly oral cavity). The most common underlying diseases were diabetes mellitus (20% of patients) and hepatitis B (15% patients), and 38% of KS patients were smokers. Patients with AIDS‐associated KS usually responded well to chemotherapy, whereas only 32% of patients with non‐AIDS‐associated KS showed complete response to radiotherapy.

Conclusions

The findings of the current study will serve as important references for clinicians in the diagnosis of KS and may form the basis for the implementation of KS clinical practice guidelines in Taiwan.
Effect of glass composition on the physical properties and luminescence of Pr3+ ion‐doped chalcogenide glasses
Authors: Ma Chengcheng , Guo Haitao , Xu Yinsheng , Wu Zhihao , Li Mingming , Jia Xiaomeng , Nie Qiuhua
Published: May 2019

In this work, Pr3+ ion‐doped Ge20Ga15−xSbxSe65 (x = 0, 5, 10, in mol%), Ge20Sb15−yInySe65 (y = 5, 10, in mol%), Ge20Ga15−zInzSe65 (z = 0, 5, 10, in mol%), and Ge20Ga5Sb10Se60I5 glasses were prepared. The structural units, thermal properties, and optical properties of these glasses were analyzed. In addition, a comprehensive comparison study of the effects of metal ions (Sb, Ga, and In), S/Se ratio, and I content on the mid‐infrared (MIR) luminescence of Pr3+ ions was conducted. Under a 1.55‐μm laser pump, 0.2 mol% of Pr3+ ion‐doped chalcogenide glasses performed strong photoluminescence in the wavelength range of 3.5‐5.5 μm. Results indicated that the Sb‐containing glass performed the strongest emission intensity among the studied glasses. Moreover, halogen element I can reduce the phonon energy of the matrix, which is beneficial to the luminescence of Pr3+ ions and provide significant possibilities for developing MIR lasers and amplifiers.