bluuebunny/crossref_metadata_2025_split huggingface dataset:
Jobactive and young job seekers: Strengths, limitations, and suggested improvements to current practices
Authors: Moore Katherine 
Published: May 2019

AbstractThis paper explores the efficacy of current employment services in Australia, jobactive, from the perspectives of young job seekers and their employment officers. As high youth unemployment rates and the efficacy of jobactive employment services are currently areas of priority for the Australian Government, the study offers a timely contribution to the social policy and youth employment literature by exploring the tensions experienced by young job seekers while registered with a jobactive provider, and employment officers when assisting young people to find sustainable employment. The study analyses data from 46 interviews with young job seekers and their employment officers in an outer western Melbourne region. The findings reveal particular concerns about appropriate and adequate service provision for marginalized young job seekers that are similar to those in evaluations of previous marketwise employment service contracts, Job Network and Job Services Australia. Suggestions for tailored employment assistance for young job seekers to gain sustainable employment are offered for future consideration.
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

ObjectivesCollagen 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.MethodsNinety 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.ResultsCTHRC1 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).ConclusionCTHRC1 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

BackgroundWhether 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.MethodsPropensity 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.ResultsA 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).ConclusionsIn 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

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

AbstractBackgroundThe 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.ObjectiveTo define a functional role for the HB of epididymal spermatozoa.MethodsIsolated fractions of HBs of epididymal spermatozoa were prepared and by quantitative tandem mass spectrometry revealed 1511 proteins.ResultsThe 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.ConclusionAs 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

AbstractIntroductionThe 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 methodsIn 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.ResultsThirty‐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).ConclusionsCervical 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

AbstractGas 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.
Developing a performance assessment task in the Finnish higher education context: Conceptual and empirical insights
Authors: Hyytinen Heidi , Toom Auli 
Published: May 2019

BackgroundPerformance 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.AimsIn 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.SampleThe study was conducted with five participants drawn from purposeful sampling.MethodsWe collected the data from cognitive laboratories with think‐alouds and interviews. The data were analysed using a qualitative abductive approach.ResultsThe 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.ConclusionsBased 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

AbstractRegulatory 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

AbstractHyaluronic 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

AbstractBis‐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

SummaryHepatic 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.