bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of human placenta‐derived mesenchymal stem cells with NK4 gene expression on glioblastoma multiforme cell lines
Authors: Jabbarpour Zahra , Kiani Jafar , Keshtkar Somayeh , Saidijam Massoud , Ghahremani Mohammad H. , Ahmadbeigi Naser 
Published: October 2019

AbstractPoor prognosis and low survival are commonly seen in patients with glioblastoma multiforme (GBM). Due to the specific nature of solid tumors such as GBM, delivery of therapeutic agents to the tumor sites is difficult. So, one of the major challenges in the treatment of these tumors is a selection of appropriate method for drug delivery. Mesenchymal stem cells (MSCs) have a unique characteristic in migration toward the tumor tissue. In this regard, the present study examined the antitumor effects of manipulating human placenta‐derived mesenchymal stem cells (PDMSCs) with NK4 expression (PDMSC‐NK4) on GBM cells. After separation and characterization of PDMSCs, these cells were transduced with NK4 which was known as the antagonist of hepatocyte growth factor (HGF). The results indicated that engineered PDMSCs preferably migrate into GBM cells by transwell coculture system. In addition, the proliferation of the GBM cells significantly reduced after coculture with these cells. In fact, manipulated PDMSCs inhibited growth of tumor cells by induction of apoptosis. Our findings suggested that besides having antitumor effects, PDMSCs can also be applied as an ideal cellular vehicle to target the glioblastoma multiforme.
Microarray and RNA in situ hybridization assay for recurrence risk markers of breast carcinoma and ductal carcinoma in situ: Evidence supporting the use of diverse pathways panels
Authors: Evans Mark Francis , Vacek Pamela Mary , Sprague Brian Lee , Stein Gary Stephen , Stein Janet Lee , Weaver Donald Lee 
Published: October 2019

AbstractBreast tumor stratification by recurrence‐risk is critical for deciding patient treatment. Here an approach combining cancer pathways microarray data complemented by RNA in situ hybridization (ISH) was investigated as a means for recurrence marker discovery and visualization in pathology specimens. LncRNA and mRNA expressions in breast carcinomas with low (n = 8) vs intermediate/high (n = 10) recurrence‐scores as estimated by 21‐gene assay and pathology review were compared by microarray assay. Tissue microarrays were prepared from breast carcinomas (n = 20) and ductal carcinoma in situ (DCIS) specimens (n = 84 patients) with known outcomes. Thirteen RNA ISH assays were performed: lncRNAs (BBC3‐1, FER3, RAD21‐AS1, ZEB1‐2) and mRNAs (GLO1, GLTSCR2, TGFB1, TLR2) (implicated by the microarray data); MKI67; a pooled panel of recurrence‐associated proliferation markers (BIRC5, Cyclin B1, MKI67, MYBL2, STK15); a pooled panel of non‐proliferation recurrence‐associated markers (CEACAM5, HTF9C, NDRG1, TP53, SLC7A5); and lncRNAs H19 and HOTAIR. Seven lncRNAs and 10 mRNAs showed significantly (P < .05) altered upregulation or downregulation by microarray assay: carcinoma RNA ISH staining did not mirror these patterns. HOTAIR staining was associated with a higher breast cancer recurrence score (P = .0152); qualitatively, H19 was massively expressed in a metaplastic triple negative breast carcinoma. Among the DCIS cohort, significant associations with multiple outcome variables were noted for TGFB1 and the non‐proliferation panel (P‐value range: .0001 to .047); proliferation panel staining showed an association with increasing DCIS grade (P = .0269) but not with outcomes. The findings support recurrence‐risk estimation by the use of multi‐marker panels that are representative of diverse cellular pathways rather than over‐reliance on proliferation targets. H19, HOTAIR, and TGFB1 RNA ISH show potential for selective diagnostics.
The economic efficiency of clinical laboratories in public hospitals: A case study in Iran
Authors: Alinejhad Mina , Aghlmand Siamak , Feizollahzadeh Sadegh , Yusefzadeh Hasan 
Published: October 2019

AbstractIntroductionClinical laboratories are identified as one of the most important and expensive units of the health system. Therefore, it is essential to pay attention to these units' cost efficiency. This study purpose was to evaluate the economic efficiency of hospitals' laboratory units affiliated to Urmia University of Medical Sciences (UMSU), in order to assess their performance.MethodsThis research was a descriptive‐analytic study that was accomplished in 2017. The statistical population of the study included all of the hospitals' clinical laboratories affiliated to UMSU. Moreover, DEA method and Deap2.1 software were used to analyze data. In this study, technical and allocative efficiencies of the studied laboratory units were also calculated in addition to the determination of the economic efficiency of the laboratories.ResultsThe average economic efficiency of clinical laboratories calculated by DEA in 2017 was 0.676. This value was lower than the allocative and technical efficiency scores, which indicates that these units could attain full efficiency by reducing their costs without having any effect on output values. Moreover, about 14 percent of the clinical laboratory units were economically efficient. In addition, it is noteworthy to state that, from total of university hospital laboratories, only three hospitals had no economic excess or deficiency values of inputs.ConclusionConsidering that 76% of laboratory units have not been economically efficient, it is necessary for the laboratory managers to consider optimum allocating of resources, with respect to the cost of laboratory equipment and inputs in order to increase their units' economic efficiency.
The circ_0021977/miR‐10b‐5p/P21 and P53 regulatory axis suppresses proliferation, migration, and invasion in colorectal cancer
Authors: Lu Chen , Jiang Wei , Hui Bingqing , Rong Dawei , Fu Kai , Dong Chaoxi , Tang Weiwei , Cao Hongyong 
Published: October 2019

AbstractAn in‐depth understanding of circular RNAs (circRNAs) indicates that they are abundant in the eukaryotic transcriptome. Many circRNAs act as microRNA sponges; thus, they represent a new type of regulatory factor. However, the role of circRNA in colorectal cancer (CRC) remains largely unknown. Low circ_0021977 expression in patients with CRC is associated with higher tug‐lymph node metastasis (TNM) stage and poorer prognosis compared with patients with high circ_0021977 expression. Moreover, miR‐10b‐5p was shown to be a target of circ_0021977, and p21 and p53 are suggested to be putative target genes of miR‐10b‐5p. The results showed that the circ_0021977/miR‐10b‐5p/p21&p53 regulatory axis suppresses proliferation, migration, and invasion by CRC cells. This evidence reveals new relationships and brings new highlights to the treatment of CRC.
RNA‐binding protein PUM2 regulates mesenchymal stem cell fate via repression of JAK2 and RUNX2 mRNAs
Authors: Lee Myon‐Hee , Wu Xinjun , Zhu Yong 
Published: October 2019

AbstractThe differentiation of mesenchymal stem cells (MSCs) into unwanted lineages can generate potential problems in clinical trials. Thus, understanding the molecular mechanisms, involved in this process, would help prevent unexpected complications. Regulation of gene expression, at the posttranscriptional level, is a new approach in cell therapies. PUMILIO is a conserved posttranscriptional regulator. However, the underlying mechanisms of PUMILIO, in vertebrate stem cells, remain elusive. Here, we show that depletion of PUMILIO2 (PUM2) blocks MSC adipogenesis and enhances osteogenesis. We also demonstrate that PUM2 works as a negative regulator on the 3′‐untranslated regions of JAK2 and RUNX2 via direct binding. CRISPR/Cas9‐mediated gene silencing of Pum2 inhibited lipid accumulation and induced excessive bone formation in zebrafish larvae. Our findings reveal novel roles of PUM2 in MSCs and provide potential therapeutic targets for related diseases.
Interactive effects of salinity and silicon application on Solanum lycopersicum growth, physiology and shelf‐life of fruit produced hydroponically
Authors: Costan Andrei , Stamatakis Aristeidis , Chrysargyris Antonios , Petropoulos Spyridon A , Tzortzakis Nikos 
Published: October 2019

AbstractBACKGROUNDUsing water with high salinity for plant fertigation may have detrimental effects on plant development and total yield and on the quality of the crop produced. As a possible means to alleviate the negative effects of salinity, silicon (Si) can be incorporated in the nutrient solution supplied to plants. In the present study, hydroponically grown tomato (Solanum lycopersicum Mill.) plants were subjected to two different salinity levels (0 and 50 mmol L−1 NaCl) with and without the application of Si (0 and 2 mmol L−1 K2SiO3) in order to evaluate its possible positive impact on mitigation of salinity stress‐induced symptoms. An additional experiment was implemented with postharvest Si application (sodium silicate) to investigate effects on the shelf‐life of tomato fruit.RESULTSSalinity (50 mmol L−1 NaCl) decreased plant size, total yield and fresh fruit weight while a high percentage of blossom end rot symptoms of tomato fruit was also observed. The application of Si in the nutrient solution counteracted these detrimental effects, generating a higher yield and healthier fruit (lower blossom end rot incidence) compared to the untreated plants (no application of Si). Salinity improved several quality‐related traits in tomato fruit, resulting in higher marketability, whereas the addition of Si (pre‐ and postharvest) maintained fruit firmness following storage thereby increasing the shelf‐life of tomato fruit.CONCLUSIONSThese findings indicate that Si application (pre‐ and postharvest) could provide an effective means of alleviating the unfavorable effects of using low‐quality water in plant fertigation on tomato plant development, fruit yield and post‐harvest quality, through increased fruit firmness. © 2019 Society of Chemical Industry
Two novel proteins, TtpB2 and TtpD2, are essential for iron transport in the TonB2 system of Vibrio vulnificus
Authors: Barnes Adel D. , Pfeifer Hailey J. , Zbylicki Brianne R. , Roberts Elena K. , Rudd Justin C. , Manzo Mario A. , Phillips Elysse A. , Berry Michael M. , Kenton Ryan J. 
Published: October 2019

AbstractIn gram‐negative bacteria, energy‐dependent active transport of iron‐bound substrates across the outer membrane is achieved through the TonB systems of proteins. Three TonB systems have been identified in the human pathogen Vibrio vulnificus. The TonB1 system contains three proteins: TonB1, ExbB1, and ExbD1. Both the TonB2 and TonB3 systems have been shown to also contain a fourth protein, TtpC2 and TtpC3, respectively. Here, we report and begin to characterize two additional proteins in the TonB2 and TonB3 systems: TtpB and TtpD. Both TtpB2 and TtpD2 are absolutely required for the function of the TonB2 system in V. vulnificus. However, although both TtpB3 and TtpD3 in the TonB3 system are related to the proteins in the TonB2 system, neither are active in iron transport. All six protein components of the TonB2 system—TonB2, ExbB2, ExbD2, TtpB2, TtpC2, and TtpD2—are essential for the uptake of both endogenously produced iron‐bound siderophores and exogenous siderophores produced from other organisms. Through complementation, we have shown that V. vulnificus is capable of using different TtpD2 proteins from other Vibrio species to bring in multiple siderophores. In contrast, we also demonstrate that TtpB2 must come from V. vulnificus, and not other species within the genus, to complement mutations in the TonB2 system.
Drug and Disease Effects in Parkinson's Psychosis: Revisiting the Role of Dopamine
Authors: Dave Sonali , Weintraub Daniel , Aarsland Dag , ffytche Dominic H. 
Published: October 2019

ABSTRACTBackgroundLevodopa and dopamine agonists (dopamine replacement therapy [DRT]) are implicated in Parkinson's disease psychosis (PDP), but the relationship between DRT and neurotransmitter dysfunction inherent to PD remains unclear.ObjectivesTo examine the relationship between baseline striatal dopamine transporter (DAT) binding in drug‐naïve idiopathic PD, introduction of DRT, or dose change and incident early‐onset PDP.MethodsBaseline DAT binding was compared between patients with and without incident psychosis (defined here as hallucinations or delusions), controlling for age, sex, baseline cognition, and prospective DRT in the Parkinson's Progression Markers Initiative cohort. Incident illusions were not considered psychosis symptoms.ResultsOf 386 patients, 30 (8%) developed PDP (predominantly hallucinations, mean onset 42 months) and 355 (92%) had either no PDP symptoms (mean follow‐up 64 months) or reported illusions only (111/355, 31%). Incident PDP was associated with reduced baseline striatal DAT binding, controlling for confounders (F1,377 = 10.9; P = 0.001), but not with a specific DRT regime. A total of 6 patients developed PDP when DRT free. There was no suggestion that PDP onset was coincident with starting levodopa or levodopa dose increase. Incident illusions were not associated with reduced DAT binding.ConclusionThe findings highlight the role of disease‐related dopamine mechanisms in the pathophysiology of hallucinations in Parkinson's disease alongside medication. It remains to be determined how dopamine mechanisms, medication, and other neurotransmitter systems implicated in PDP interact.
Towards fast and robust 4D optimization for moving tumors with scanned proton therapy
Authors: Buti Gregory , Souris Kevin , Montero Ana Maria Barragán , Lee John Aldo , Sterpin Edmond 
Published: October 2019

PurposeRobust optimization is becoming the gold standard for generating robust plans against various kinds of treatment uncertainties. Today, most robust optimization strategies use a pragmatic set of treatment scenarios (the so‐called uncertainty set) consisting of combinations of maximum errors, of each considered uncertainty source (such as tumor motion, setup and image‐conversion errors). This approach presents two key issues. First, a subset of considered scenarios is unnecessarily improbable which could potentially compromise the plan quality. Second, the resulting large uncertainty set leads to long plan computation times, which limits the potential for robust optimization as a standard clinical tool. In order to address these issues, a method is introduced which is able to preselect a limited set of relevant treatment error scenarios.MethodsUncertainties due to systematic setup errors, image‐conversion errors and respiratory tumor motion are considered. A four‐dimensional (4D)‐equiprobability hypersurface is defined, which takes into account the joint probabilities of the above‐mentioned uncertainty sources. Only scenarios that lie on the predefined 4D hypersurface are considered, guaranteeing statistical consistency of the uncertainty set. In this regard, twelve scenarios are selected that cover maximum spatial displacements of the tumor during breathing. Subsequently, additional scenarios are considered (sampled from the aforementioned 4D hypersurface) in order to cover any estimated residual range errors. Two different scenario‐selection procedures were tested: (a) the maximum displacements (MD) method that only considers twelve scaled maximum displacement scenarios and (b) maximum displacements and residual range (MDR) method which, in addition to the scaled maximum displacement scenarios, considers additional maximum range uncertainty scenarios. The methods were tested for five lung cancer patients by performing comprehensive Monte Carlo robustness evaluations.ResultsA plan computation time gain of 78% is achieved by applying the MD method, whilst obtaining a target robustness of D larger than 95% of the prescribed dose, for the worst‐case scenario. Additionally, the MD method has the potential to be fully automatic which makes it a promising candidate for fast automatic planning workflows. The MDR method produced plans with excellent target robustness (D larger than 95% of the prescribed dose, even for the worst‐case scenario), whilst still obtaining a significant plan computation time gain of 57%.ConclusionsTwo scenario‐selection procedures were developed which achieved significant reduction of plan computation time and memory consumption, without compromising plan quality or robustness.
ALDH1A1‐related stemness in high‐grade serous ovarian cancer is a negative prognostic indicator but potentially targetable by EGFR/mTOR‐PI3K/aurora kinase inhibitors
Authors: Kaipio Katja , Chen Ping , Roering Pia , Huhtinen Kaisa , Mikkonen Piia , Östling Päivi , Lehtinen Laura , Mansuri Naziha , Korpela Taina , Potdar Swapnil , Hynninen Johanna , Auranen Annika , Grénman Seija , Wennerberg Krister , Hautaniemi Sampsa , Carpén Olli 
Published: October 2019

AbstractPoor chemotherapy response remains a major treatment challenge for high‐grade serous ovarian cancer (HGSC). Cancer stem cells are the major contributors to relapse and treatment failure as they can survive conventional therapy. Our objectives were to characterise stemness features in primary patient‐derived cell lines, correlate stemness markers with clinical outcome and test the response of our cells to both conventional and exploratory drugs. Tissue and ascites samples, treatment‐naive and/or after neoadjuvant chemotherapy, were prospectively collected. Primary cancer cells, cultured under conditions favouring either adherent or spheroid growth, were tested for stemness markers; the same markers were analysed in tissue and correlated with chemotherapy response and survival. Drug sensitivity and resistance testing was performed with 306 oncology compounds. Spheroid growth condition HGSC cells showed increased stemness marker expression (including aldehyde dehydrogenase isoform I; ALDH1A1) as compared with adherent growth condition cells, and increased resistance to platinum and taxane. A set of eight stemness markers separated treatment‐naive tumours into two clusters and identified a distinct subgroup of HGSC with enriched stemness features. Expression of ALDH1A1, but not most other stemness markers, was increased after neoadjuvant chemotherapy and its expression in treatment‐naive tumours correlated with chemoresistance and reduced survival. In drug sensitivity and resistance testing, five compounds, including two PI3K‐mTOR inhibitors, demonstrated significant activity in both cell culture conditions. Thirteen compounds, including EGFR, PI3K‐mTOR and aurora kinase inhibitors, were more toxic to spheroid cells than adherent cells. Our results identify stemness markers in HGSC that are associated with a decreased response to conventional chemotherapy and reduced survival if expressed by treatment‐naive tumours. EGFR, mTOR‐PI3K and aurora kinase inhibitors are candidates for targeting this cell population. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Exposure‐Response Assessment of Enzalutamide and Its Major Metabolites in a Real‐World Cohort of Patients with Metastatic Castration‐Resistant Prostate Cancer
Authors: van Nuland Merel , Bergman Andries M. , Rosing Hilde , de Vries Niels , Huitema Alwin D.R. , Beijnen Jos H. 
Published: October 2019

Study ObjectiveEnzalutamide is an oral agent for the treatment of metastatic castration‐resistant prostate cancer (mCRPC); N‐desmethyl enzalutamide is its active metabolite, which has clinically relevant anti‐androgen capacities similar to enzalutamide, and carboxylic acid enzalutamide is an inactive metabolite. The aim of our study was to investigate the relationship between enzalutamide and N‐desmethyl enzalutamide exposure and treatment response in a real‐world cohort of patients with mCRPC.DesignRetrospective, observational, pharmacokinetic study.SettingOutpatient clinic at a tertiary cancer center in Amsterdam, the Netherlands.PatientsSixty‐five patients with mCRPC who were treated with enzalutamide 160 mg daily and had at least one steady‐state enzalutamide plasma concentration between May 2015 and June 2018; of these patients, 38 were prostate‐specific antigen (PSA) responders and 27 were nonresponders.Measurements and Main ResultsPlasma concentrations, determined by using liquid chromatography with tandem mass spectrometry (LC‐MS/MS), were compared between PSA responders and nonresponders. Three clinical end points were evaluated separately in this study: PSA‐independent progression‐free survival (PFS), time to PSA progression (TTPP), and rate of PSA response (defined as ≥ 50% decrease in PSA level from baseline). Enzalutamide toxicity was defined as discontinuation due to adverse events, dose reductions due to adverse events, or temporary treatment interruption. For these analyses, plasma concentrations of enzalutamide and N‐desmethyl enzalutamide were divided into quartiles. Mean ± SD plasma concentrations in the 65 patients were as follows: enzalutamide 11.2 ± 2.8 μg/ml, N‐desmethyl enzalutamide 9.9 ± 2.9 μg/ml, and carboxylic acid enzalutamide 6.1 ± 4.3 μg/ml. Plasma concentrations were not significantly different in the PSA responder versus nonresponder groups for enzalutamide (11.5 vs 10.6 μg/ml, p=0.20), N‐desmethyl enzalutamide (10.1 vs 9.6 μg/ml, p=0.48), and carboxylic acid enzalutamide (6.5 vs 5.5 μg/ml, p=0.34). Univariate and multivariate analyses did not show a relationship between plasma concentrations and PSA‐independent PFS, TTPP, or toxicity.ConclusionThis study confirmed that enzalutamide plasma concentrations were not related to PSA‐independent PFS, TTPP, or toxicity in patients with mCRPC, and demonstrated that plasma concentrations of its major metabolites were also not associated with treatment response. Based on these findings, there is no role for therapeutic drug monitoring of enzalutamide in patients with mCRPC in daily practice.
Hybrid Solution Moves Boundaries of Copper Welding
Authors: Rütering Markus 
Published: October 2019

AbstractFor copper joining, blue diode lasers have made it possible to control heat conduction welding for the very first time. The technology, however, has reached its current limits with copper deep welding, where infrared lasers have also not achieved satisfactory results. A hybrid concept by Laserline that connects blue and infrared diode lasers has now opened up new manufacturing options. The approach does not only prove itself at the joining of sheets, but also at the static welding of hairpins – and in so doing moves the boundaries of copper welding altogether.
Synthesis and biological characterization of clicked chloroquine copolymers as macromolecular inhibitors of cancer cell migration
Authors: Yu Fei , Wang Yazhe , Hang Yu , Tang Weimin , Zhao Zhifeng , Oupický David 
Published: October 2019

ABSTRACTWe report synthesis of nondegradable chloroquine (CQ)‐containing N‐(2‐hydroxyethyl)methacrylamide (HPMA) copolymers (pCQ2) by a combination of reversible addition‐fragmentation chain‐transfer (RAFT) polymerization and click chemistry. The ability of the copolymers to inhibit cancer cell migration was compared to our previously reported degradable pCQ1 in breast cancer cells utilizing transwell and wound healing assays. Both cleavable and noncleavable pCQ demonstrated enhanced inhibitory activity when compared with small‐molecule CQ. This study validates that pCQ2 functions as a macromolecular inhibitor of cancer cell migration without the need for CQ release and provides support for pCQ as a new class of antimetastatic polymer agents with a possibly unique mechanism of action. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2235–2242