bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of tensin homolog deleted on chromosome ten (PTEN) by ciglitazone sensitizes doxorubicin‐resistance leukemia cancer cells to treatment
Authors: Mashayekhi Samira , Yousefi Bahman , Tohidi Ehsan , Darband Saber Ghazizadeh , Mirza‐Aghazadeh‐Attari Mohammad , Sadighparvar Shirin , Kaviani Mojtaba , Shafiei‐Irannejad Vahid , Kafil Hossein Samadi , Karimian Ansar , Jadidi‐Niaragh Farhad , Majidinia Maryam
Published: May 2019

Overcoming multidrug resistance (MDR) is a final goal of various recent studies, in which combination of different compounds and conventional chemotherapeutics results in circumventing MDR and hence cancer progression. Therefore, we aimed to investigate the effects of peroxisome proliferator‐activated receptors (PPARs)‐γ on MDR in doxorubicin‐resistant human myelogenous leukemia cells. The effect of doxorubicin on cell viability following treatment with ciglitazone was measured using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay. The activity of P‐glycoprotein (P‐gp), as one of the membrane transporters, was determined by the rhodamine 123 (Rho 123) assay. Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and Western blot were used for the measurement of P‐gp, and tensin homolog deleted on chromosome ten (PTEN) expression at mRNA and protein, respectively. For evaluation of doxorubicin (DOX)‐induced apoptosis by annexin V/PI staining was used. Ciglitazone significantly increases the cytotoxic effects of DOX. In addition, ciglitazone considerably decreased the expression levels and activity of P‐gp in DOX‐resistant K562 cells. Furthermore, upon the ciglitazone treatment, PTEN expression could be increased in K562/DOX cells in a PPARγ–dependent manner. Moreover, ciglitazone significantly enhanced DOX‐induced apoptosis in K562/DOX cells. The combination treatment of K562/DOX leukemia cancer cells with doxorubicin and ciglitazone might be an effective strategy in inducing apoptosis and reversing developed MDR, and more importantly decreasing the adverse side effects of these agents.
Oxymatrine ameliorates insulin resistance in rats with type 2 diabetes by regulating the expression of KSRP, PETN, and AKT in the liver
Authors: Zuo Mei‐Ling , Wang Ai‐Ping , Tian Ying , Mao Li , Song Gui‐Lin , Yang Zhong‐Bao
Published: May 2019

Insulin resistance plays a key role in the development and progression of type 2 diabetes mellitus (T2DM). Recent studies found that insulin resistance was associated with the dysfunction of KH‐type splicing regulatory protein (KSRP) expression and AKT pathway, and that oxymatrine possesses an antidiabetic effect. The aim of the present study was to investigate whether the protection of oxymatrine against T2DM was associated with the modulation of the KSRP expression and AKT pathway. Sprague‐Dawley rats were fed a high‐fat diet and injected with streptozotocin intraperitoneally to induce T2DM, which led to an increase in blood glucose levels and insulin resistance, and a decrease in insulin sensitivity and glycogen synthesis concomitant with KSRP downregulation, PTEN upregulation, and AKT phosphorylation deficiency. The administration of oxymatrine decreased blood glucose levels and insulin resistance, increased insulin sensitivity, and improved glycogen synthesis in the liver of T2DM rats, through a reversal in the expression of KSRP, PTEN, and AKT. On the basis of these observations, we concluded that oxymatrine can protect T2DM rats from insulin resistance through the regulation of the KSRP, PETN, and AKT expression in the liver.
circLRP6 regulates high glucose‐induced proliferation, oxidative stress, ECM accumulation, and inflammation in mesangial cells
Authors: Chen Bin , Li Yanhua , Liu Yang , Xu Zhonggao
Published: May 2019

Aberrant regulation in mesangial cell proliferation, extracellular matrix (ECM) accumulation, oxidative stress, and inflammation under hyperglycemic condition contributes significantly to the occurrence and development of diabetic nephropathy (DN). However, the mechanisms underlying the hyperglycemia‐induced dysregulations have not been clearly elucidated. Here, we reported that high mobility group box 1 (HMGB1) was highly elevated in high glucose (HG)‐treated mesangial cells, and induced the phosphorylation, nuclear translocation, and DNA binding activity of NF‐κB via toll‐like receptor 4 (TLR4). Function assays showed that inhibition of HMGB1 mitigated HG‐induced proliferation, oxidative stress, ECM accumulation, and inflammation in mesangial cells via TLR4/NF‐κB pathway. Increasing evidence has shown that circRNA, a large class of noncoding RNAs, functions by binding with miRNAs and terminating regulation of their target genes. We further investigated whether HMGB1 is involved in circRNA–miRNA–mRNA regulatory network. First, HMGB1 was identified and confirmed to be the target of miR‐205, and miR‐205 played a protective role against HG‐induced cell injure via targeting HMGB1. Then circLRP6 was found to be upregulated in HG‐treated mesangial cells, and regulate HG‐induced mesangial cell injure via sponging miR‐205. Besides, overexpression of miR‐205 or knockdown of circLRP6 inhibited the NF‐κB signaling pathway. Collectively, these data suggest that circLRP6 regulates HG‐induced proliferation, oxidative stress, ECM accumulation, and inflammation in mesangial cells via sponging miR‐205, upregulating HMGB1 and activating TLR4/NF‐κB pathway. These findings provide a better understanding for the pathogenesis of DN.
Convergence of Wnt and Notch signaling controls ovarian cancer cell survival
Authors: Bocchicchio Sebastián , Tesone Marta , Irusta Griselda
Published: May 2019

In the last 40 years ovarian cancer mortality rates have slightly declined and, consequently, it continues to be the fifth cause of cancer death in women. In the present study, we showed that β‐catenin signaling is involved in the functions of ovarian cancer cells and interacts with the Notch system. Wnt and Notch systems showed to be prosurvival for ovarian cancer cells and their inhibition impaired cell proliferation and migration. We also demonstrated that the inhibition of β‐catenin by means of two molecules, XAV939 and ICG‐001, decreased the proliferation of the IGROV1 and SKOV3 ovarian cancer cell lines and that ICG‐001 increased the percentage of IGROV1 cells undergoing apoptosis. The simultaneous inhibition of β‐catenin and Notch signaling, by using the DAPT inhibitor, decreased ovarian cancer cell proliferation to the same extent as targeting only the Wnt/β‐catenin pathway. A similar effect was observed in IGROV1 cell migration with ICG‐001 and DAPT. ICG‐001 increased the Notch target genes Hes‐1 and Hey‐1 and increased Jagged1 expression. However, no changes were observed in Dll4 or Notch 1 and 4 expressions. Our results suggest that Notch and β‐catenin signaling co‐operate in ovarian cancer to ensure the proliferation and migration of cells and that this could be achieved, at least partly, by the upregulation of Notch Jagged1 ligand in the absence of Wnt signaling. We showed that the Wnt pathway crosstalks with Notch in ovarian cancer cell functions, which may have implications in ovarian cancer therapeutics.
Natural flavonoids for the prevention of colon cancer: A comprehensive review of preclinical and clinical studies
Authors: Afshari Khashayar , Haddadi Nazgol‐Sadat , Haj‐Mirzaian Arvin , Farzaei Mohammad Hosein , Rohani Mohammad Mojtaba , Akramian Freshteh , Naseri Rozita , Sureda Antoni , Ghanaatian Negar , Abdolghaffari Amir Hossein
Published: May 2019

Flavonoids comprise a group of natural polyphenols consisting of more than 5,000 subtypes mostly existing in fruits and vegetables. Flavonoids consumption could potentially attenuate the incidence and recurrence risk of colorectal cancers through their antiperoxidative, antioxidant, and anti‐inflammatory effects. In addition, these compounds regulate the mitochondrial function, balance the bacterial flora and promote the apoptosis process in cancerous cells. However, some previous data failed to show the effectiveness of flavonoids in reducing the risk of colorectal cancer. In this study, we have reviewed the efficacy of different flavonoids subtypes on the risk of colon cancer and molecular mechanisms involved in this process in both clinical and animal studies. In addition, we tried to elucidate the potential synergy between these compounds and current colorectal cancer treatments.
Mitochondrial proteomics reveals the mechanism of spermatogenic cells apoptosis induced by carbon ion radiation in zebrafish
Authors: Li Hongyan , Zhang Weihong , Zhang Hong , Xie Yi , Sun Chao , Di Cuixia , Si Jing , Gan Lu , Yan Junfang
Published: May 2019

The mitochondrial proteins involved in spermatogenic cells apoptosis in zebrafish after carbon ion radiation (CIR) were screened. The relative biological effectiveness (RBE) of CIR in zebrafish testes was investigated. Apoptosis of testicular cells was measured within 24 hr following 1 and 4 Gy CIR. Immunoblotting was used to assess the levels of mitochondrial apoptotic proteins in testes, and proliferative and apoptotic spermatogenic cells were detected by immunofluorescence after CIR. Label‐free quantitative (LFQ) and parallel reaction monitoring‐based target proteomics (PRM) were combined to screen and validate differential mitochondrial proteins in testes between 4 Gy and control groups at 24 hr after CIR. The RBE of CIR in zebrafish testes was 1.48 ± 0.04, and induction of apoptosis by CIR was higher than that of X‐rays in testicular cells. Mitochondrial apoptotic pathways play a crucial role in spermatogenic cells apoptosis after CIR, with 60 differential mitochondrial proteins identified. Among 20 target proteins, 12 were significantly upregulated, 2 were significantly downregulated in the 4 Gy CIR group. The results of PRM were consistent with label‐free analysis. This is the first study to screen the differential mitochondrial proteins and provide useful information to understand the underlying mechanisms of spermatogenic cell apoptosis in zebrafish following CIR.
The histomorphological structure of the male reproductive system of maize leaf weevil Tanymecus dilaticollis Gyllenhal, 1834 (Coleoptera: Curculionidae)
Authors: Ö. Koçakoğlu Nurcan , Candan Selami , Güllü Mustafa
Published: May 2019

The histomorphology of the reproductive system and the germ cells has been useful to establish phylogenetic relationships in many insects. However, these elements remain little known in the Curculionidae. In this study, histomorphological structure of the male reproductive system of Tanymecus dilaticollis, which is economically important, is described, illustrated using stereomicroscopy, light microscopy, and scanning electron microscopy techniques, and discussed in relation to other Coleoptera species. Results showed that distinctive features of the male reproductive system of T. dilaticollis consist of a pair of yellowish testes, a pair of seminal vesicles, a pair of vasa deferentia, an ejaculatory duct, accessory glands, prostate glands, and aedeagus. Each testis is subdivided into two testicular follicles, enclosed by a peritoneal sheath. Each follicle of the mature testes is full sperm cysts with germ cells at various stages development of spermatogenesis. The testes have four types of germ cells (spermatogonia, spermatocytes, spermatids, and spermatozoa). They are occupied by the growth zone containing spermatogonia and spermatocytes, the maturation zone containing spermatids, while differentiation zone containing spermatozoa. There is a seminal vesicle at the center of each testis. Most mature sperms are stored in the seminal vesicle. Each testis is attached to the vas deferens by a stalk‐like seminal vesicle. In the distal part, vasa deferentia fuse with the ejaculatory duct. It is linked to the aedeagus. The provided results will contribute to the understanding of the reproductive cell biology of Curculionidae.
Gastrointestinal neoplasia in patients with inflammatory bowel disease: Opportunities to enhance preventative strategies
Authors: Young Edward , Lawrence Matthew , Thomas Michelle , Andrews Jane
Published: May 2019

Background and Aims

Gastrointestinal (GI) adenocarcinoma, especially colorectal cancer (CRC), is a devastating complication of inflammatory bowel disease (IBD). We sought to examine the role of chronic inflammation and other possible predictors of the development of CRC, as well as assess as yet unexamined factors such as psychological comorbidity and engagement in care.

Methods

This study included all patients involved in a tertiary hospital IBD service diagnosed with CRC between 2007 and 2017. Reports from histological specimens were assessed, and all those with adenocarcinoma, high‐grade dysplasia (HGD), or multifocal low‐grade dysplasia (LGD) originating within IBD‐affected mucosa were included in the study.

Results

A total of 32 patients were included in the study (17 with adenocarcinoma and 15 with HGD/multifocal LGD). The majority had a duration of disease >20 years. Eleven patients (34%, CI 20–52%) had previous disease‐related surgery, and 16 (50%, CI 34–66%) had multiple previous disease‐related admissions. Thirteen patients (62%, CI 41–79%) had >50% of CRP results higher than 8 mg/L. Psychiatric comorbidities were common, with 19 patients (59%, CI 42–74%) having a psychiatric comorbidity or poor engagement in treatment.

Conclusion

In this cohort, we have highlighted poor engagement, hesitation to up‐titrate therapy when indicated, and psychological comorbidities as likely contributors to poor disease control and development of GI adenocarcinoma. Based on our data, these easily identifiable clinical care factors should not be overlooked when addressing IBD‐related GI malignancy prevention. Additional research is required to assess a direct causal relationship, but this study would support the incorporation of psychology services into IBD clinics.
Feasibility to Perform T2* Mapping Postcontrast Administration in Reperfused STEMI Patients for the Detection of Intramyocardial Hemorrhage
Authors: Bulluck Heerajnarain , Chowdhury Nazia , Lim Mei Xing , Allen John C. , Bryant Jennifer A. , Chan Mark Y. , Chan Mervyn H.H. , Chin Calvin W.L. , Ho Hee Hwa , Lim Soo T. , Tan Ru‐San , Tan Jack W. , Wong Philip E. , Yeo Khung K. , Cook Stuart A. , Hausenloy Derek J.
Published: May 2019

Level of Evidence: 1

Technical Efficacy: Stage 2
Ethanol production by simultaneous saccharification and cofermentation of pretreated corn stalk
Authors: Zhao Wenxuan , Zhao Fuguang , Zhang Sitong , Gong Qinglong , Chen Guang
Published: May 2019

The recalcitrance of lignocellulosic biomass is a major factor limiting its conversion into biofuels. Therefore, in this study, we pretreated corn stalk with 2% Na2CO3 and 2% H2O2 for time 70 min at 130°C using a corn stalk to liquid ratio of 1:10. The fermentation broth from multicopy Saccharomyces cerevisiae strains engineered for lignocellulase synthesis was used to enzymatically hydrolyze the pretreated corn stalk. The highest monosaccharide yield (102 mmol/L) was obtained using 15 IU endocellulase, 10 IU exocellulase, and 15 IU β‐glucosidase per gram of cellulose and 20 IU xylanase per gram of hemicellulose. Subsequently, the high‐efficiency ethanol‐producing S. cerevisiae strain WXY12, which can produce ethanol from glucose and xylose simultaneously, was added to the fermentation system. The entire process involved ethanol production through simultaneous saccharification and fermentation (SSF). Optimization of the fermentation conditions (yeast powder as a nitrogen source, temperature of 30°C, MgSO4 as a metal ion inducer, rotation speed of 180 rpm, solid–liquid ratio of 1:8, and inoculation amount of 2%) resulted in an ethanol output of 46.87 g/L and a theoretical conversion rate of 27.4%. The results of this study improved corn stalk utilization, reduced hydrolysis costs, and generated high ethanol yields.
Classification of facial peri‐implant soft tissue dehiscence/deficiencies at single implant sites in the esthetic zone
Authors: Zucchelli Giovanni , Tavelli Lorenzo , Stefanini Martina , Barootchi Shayan , Mazzotti Claudio , Gori Guido , Wang Hom‐Lay
Published: May 2019

Background

The incidence of a peri‐implant soft tissue dehiscence/deficiency (PSTD) is not a rare finding. Despite multiple previous attempts aimed at correcting the PSTDs, a classification of these conditions has not yet been proposed. This lack in the literature may also lead to discrepancies in the reported treatment outcomes and thus misinform the clinician or the readers. The aim of the present article was therefore to present a classification of peri‐implant PSTD at a single implant site.

Methods

Four classes of PSTDs were discussed based on the position of the gingival margin of the implant‐supported crown in relation to the homologous natural tooth. In addition, the bucco‐lingual position of the implant head was also taken into consideration. Each class was further subdivided based on the height of the anatomical papillae.

Results

Subsequently, for each respective category a surgical approach (including bilaminar techniques, the combined prosthetic‐surgical approach or soft tissue augmentation with a submerged healing) was also suggested.

Conclusion

This paper provides a new classification system for describing PSTDs at single implant sites, with the appropriate recommended treatment protocol.
Oxidation delay of sunflower oil under frying by moringa oil addition: more than just a blend
Authors: Boukandoul Silia , Santos Carla SP , Casal Susana , Zaidi Farid
Published: May 2019

Background

Blending Moringa oleifera oil (MOO) with other oils of recognized lower stability under prolonged frying results in oxidation delay. The present study aimed to detail the probable molecular interactions supporting these observations, using a small amount of MOO (20%) and sunflower oil (SFO; 80%) under domestic deep‐frying conditions (intermittent frying of fresh potatoes, 180 °C, 2 × 90 min day−1, 5 days).

Results

Blending 20% MOO with SFO resulted in a significantly lower formation of polymers (<43 to 85%) and oxidized triglycerides (<20 to 60%), a 25–60% reduction in p‐anisidine value and total volatile aldehydes, particularly alkadienals, and a better performance than the one predicted from the oils' mass ratio. Blending was particularly effective in vitamin E and antioxidant activity preservation, probably from interaction with some MOO components such as sterols and vitamin E, while carotenoids and phenolics do not seem to be implicated.

Conclusions

These results provide an interesting use for MOO, improving the thermo‐oxidative performance of SFO while providing nutritional benefits and lowering the formation of toxic compounds during prolonged deep‐frying. © 2019 Society of Chemical Industry
Continuous separation of maslinic and oleanolic acids from olive pulp by high‐speed countercurrent chromatography with elution‐extrusion mode
Authors: Huang Xin‐Yi , Zhang Xia , Pei Dong , Liu Jian‐Fei , Gong Yuan , Aisa Haji Akber , Di Duo‐Long
Published: May 2019

In this work, a continuous high‐speed countercurrent chromatography method has been developed on the basis of elution‐extrusion mode and this method was successfully applied to the separation of maslinic and oleanolic acid from the extract of olive pulp. In the process of ‘elution’, the sample solution was continuously loaded into the column and the maslinic acid was steadily eluted out in this step while highly retained oleanlic acid always stayed in the column. In the process of ‘extrusion’, the oleanlic acid was pushed out of the column with the stationary phase. In this way, we achieved a large sample loading. A total of 120 mL sample solution (about 89.55% of the column volume) which contains 600 mg olive pulp extract was pumped in the apparatus by a constant‐flow pump and the maslinic and oleanolic acids were largely separated within 120 min. Both of these two compounds presented high yields and high purities (271.6 mg for maslinic acid with 86.7% and 83.9 mg oleanolic acids with 83.4%).
Functional outcomes of the modified submandibular gland transfer procedure
Authors: Murray Scott , Chung Jeffson , Zhang Han , Baker Sarah , Jha Naresh , Scrimger Rufus , Debenham Brock , Biron Vincent , Harris Jeffery , O'Connell Daniel , Seikaly Hadi
Published: May 2019

Objectives

Treatment for advanced head and neck cancers typically includes surgery followed by radiation therapy (RT). Radiation‐induced xerostomia is a common sequela of these treatments. The modified submandibular gland transfer (M‐SGT) procedure was developed to decrease xerostomia in the treatment of oral cavity cancer by sparing one submandibular gland (SMG) from radiation. This study's objectives were to: 1) elucidate the radiation‐sparing capacity of the M‐SGT, and 2) study the xerostomia‐reducing potential of the M‐SGT based on the University of Washington Quality‐of‐Life Questionnaire (UW‐QOL).

Methods

Radiation therapy treatment plans were reviewed for all patients treated with surgery and RT who had a M‐SGT at the University of Alberta Hospital during the study period. Outcomes included: 1) radiation dose received by the transferred SMG within the periparotid area compared to the submandibular triangle (ST), and 2) patient‐reported saliva scores on the UW‐QOL compared to historical controls without a gland transfer.

Results

Twenty‐two patients were included. The mean radiation dose received by the transferred SMG was 29.00 grays (Gy) (standard deviation 14.59 Gy), thus reducing the mean radiation dose to the SMG by a statistically significant 18.34 Gy (confidence interval 95% (13.37, 23.32), P < 0.01) compared to the ST and below the D50 of the SMG (34 Gy). Sixty‐five percent of patients rated their saliva as normal or mildly reduced on the UW‐QOL as compared to 16% of controls (P = 0.01).

Conclusion

The M‐SGT technique is successful at reducing the radiation dose sustained by the SMG during adjuvant treatment and provides a significant improvement in xerostomia‐related functional outcomes as compared to historical controls not receiving a gland transfer.

Level of Evidence

4 Laryngoscope, 130:925–929, 2020
The Intention‐to‐Treat Effect of Bridging Treatments in the Setting of Milan Criteria–In Patients Waiting for Liver Transplantation
Authors: Lai Quirino , Vitale Alessandro , Iesari Samuele , Finkenstedt Armin , Mennini Gianluca , Onali Simona , Hoppe‐Lotichius Maria , Manzia Tommaso M. , Nicolini Daniele , Avolio Alfonso W. , Mrzljak Anna , Kocman Branislav , Agnes Salvatore , Vivarelli Marco , Tisone Giuseppe , Otto Gerd , Tsochatzis Emmanuel , Rossi Massimo , Viveiros Andre , Ciccarelli Olga , Cillo Umberto , Lerut Jan ,   for the European Hepatocellular Cancer Liver Transplant Study Group
Published: May 2019

In patients with hepatocellular carcinoma (HCC) meeting the Milan criteria (MC), the benefit of locoregional therapies (LRTs) in the context of liver transplantation (LT) is still debated. Initial biases in the selection between treated and untreated patients have yielded conflicting reported results. The study aimed to identify, using a competing risk analysis, risk factors for HCC‐dependent LT failure, defined as pretransplant tumor‐related delisting or posttransplant recurrence. The study was registered at www.clinicaltrials.gov (identification number NCT03723304). In order to offset the initial limitations of the investigated population, an inverse probability of treatment weighting (IPTW) analysis was used: 1083 MC‐in patients (no LRT = 182; LRT = 901) were balanced using 8 variables: age, sex, Model for End‐Stage Liver Disease (MELD) value, hepatitis C virus status, hepatitis B virus status, largest lesion diameter, number of nodules, and alpha‐fetoprotein (AFP). All the covariates were available at the first referral. After the IPTW, a pseudo‐population of 2019 patients listed for LT was analyzed, comparing 2 homogeneous groups of untreated (n = 1077) and LRT‐treated (n = 942) patients. Tumor progression after LRT was the most important independent risk factor for HCC‐dependent failure (subhazard ratio [SHR], 5.62; P < 0.001). Other independent risk factors were major tumor diameter, AFP, MELD, patient age, male sex, and period of wait‐list registration. One single LRT was protective compared with no treatment (SHR, 0.51; P < 0.001). The positive effect was still observed when 2‐3 treatments were performed (SHR, 0.66; P = 0.02), but it was lost in the case of ≥4 LRTs (SHR, 0.80; P = 0.27). In conclusion, for MC‐in patients, up to 3 LRTs are beneficial for success in intention‐to‐treat LT patients, with a 49% to 34% reduction in failure risk compared with untreated patients. This benefit is lost if more LRTs are required. A poor response to LRT is associated with a higher risk for HCC‐dependent transplant failure.
Mimicking the Ice Recrystallization Activity of Biological Antifreezes. When is a New Polymer “Active”?
Authors: Biggs Caroline I. , Stubbs Christopher , Graham Ben , Fayter Alice E. R. , Hasan Muhammad , Gibson Matthew I.
Published: May 2019

Antifreeze proteins and ice‐binding proteins have been discovered in a diverse range of extremophiles and have the ability to modulate the growth and formation of ice crystals. Considering the importance of cryoscience across transport, biomedicine, and climate science, there is significant interest in developing synthetic macromolecular mimics of antifreeze proteins, in particular to reproduce their property of ice recrystallization inhibition (IRI). This activity is a continuum rather than an “on/off” property and there may be multiple molecular mechanisms which give rise to differences in this observable property; the limiting concentrations for ice growth vary by more than a thousand between an antifreeze glycoprotein and poly(vinyl alcohol), for example. The aim of this article is to provide a concise comparison of a range of natural and synthetic materials that are known to have IRI, thus providing a guide to see if a new synthetic mimic is active or not, including emerging materials which are comparatively weak compared to antifreeze proteins, but may have technological importance. The link between activity and the mechanisms involving either ice binding or amphiphilicity is discussed and known materials assigned into classes based on this.
CNBP controls tumor cell biology by regulating tumor‐promoting gene expression
Authors: Lee Eunhye , Lee Taeyun A. , Yoo Hye Jin , Lee Sungwook , Park Boyoun
Published: May 2019

Cellular nucleic acid‐binding protein (CNBP) is associated with cell proliferation, and its expression is elevated in human tumors, but the molecular mechanisms of CNBP in tumor cell biology have not been fully elucidated. In this study, we report that CNBP is a transcription factor essential for regulating matrix metalloproteinases mmp‐2, mmp‐14, and transcription factor e2f2 gene expression by binding to their promoter regions via a sequence‐specific manner. Importantly, epidermal growth factor stimulation is required to induce CNBP phosphorylation and nuclear transport, thereby promoting the expression of mmp‐2, mmp‐14, and e2f2 genes. As a consequence, loss of cnbp attenuates the ability of tumor cell growth, invasion, and migration. Conversely, overexpression of cnbp is associated with tumor cell biology. Collectively, our findings reveal CNBP as a key transcriptional regulator of tumor‐promoting target genes to control tumor cell biology.
Social enterprises and the performance measurement challenge: Could the data envelopment analysis be the solution?
Authors: Dia Mohamed , Bozec Richard
Published: May 2019

The objective of this paper is to show how data envelopment analysis (DEA) could be used to assess the performance of social enterprises (SEs). This paper is based on a general review of the literature dealing with both the DEA and SEs. Despite its popularity, the DEA has rarely been employed to analyse the efficiency of SEs. This is quite surprising considering the analytical strength of the DEA and its adaptability to different organizational forms and contexts. This paper highlights the advantages of the DEA for dual‐function organizations such as SEs and proposes DEA formulation guidelines tailored for these organizations.
Identification of novel biomarkers and small molecule drugs in human colorectal cancer by microarray and bioinformatics analysis
Authors: Chen Juan , Wang Ziheng , Shen Xianjuan , Cui Xiaopeng , Guo Yuehua
Published: May 2019

Background

Colorectal cancer (CRC) is one of the most common malignant tumors. In the present study, the expression profile of human multistage colorectal mucosa tissues, including healthy, adenoma, and adenocarcinoma samples was downloaded to identify critical genes and potential drugs in CRC.

Methods

Expression profiles, GSE33113 and GSE44076, were integrated using bioinformatics methods. Differentially expressed genes (DEGs) were analyzed by R language. Functional enrichment analyses of the DEGs were performed using the Database for Annotation, visualization, and integrated discovery (DAVID) database. Then, the search tool for the retrieval of interacting genes (STRING) database and Cytoscape were used to construct a protein–protein interaction (PPI) network and identify hub genes. Subsequently, survival analysis was performed among the key genes using Gene Expression Profiling Interactive Analysis (GEPIA). Connectivity Map (CMap) was used to query potential drugs for CRC.

Results

A total of 428 upregulated genes and 751 downregulated genes in CRC were identified. The functional changes of these DEGs were mainly associated with cell cycle, oocyte meiosis, DNA replication, p53 signaling pathway, and progesterone‐mediated oocyte maturation. A PPI network was identified by STRING with 482 nodes and 2,368 edges. Survival analysis revealed that high mRNA expression of AURKA, CCNB1, CCNF, and EXO1 was significantly associated with longer overall survival. Moreover, CMap predicted a panel of small molecules as possible adjuvant drugs to treat CRC.

Conclusion

Our study found key dysregulated genes involved in CRC and potential drugs to combat it, which may provide novel insights and potential biomarkers for prognosis, as well as providing new CRC treatments.
Impact of magnetic fields on dose measurement with small ion chambers illustrated in high‐resolution response maps
Authors: Lehmann Joerg , Beveridge Toby , Oliver Chris , Bailey Tracy E. , Lye Jessica E. , Livingstone Jayde , Stevenson Andrew W. , Butler Duncan J.
Published: May 2019

Purpose

Dosimetry of ionizing radiation in the presence of strong magnetic fields is gaining increased relevance in light of advances for MRI‐guided radiation therapy. While the impact of strong magnetic fields on the overall response of ionization chambers has been simulated and measured before, this work investigates the local impact of the magnetic field on dose response in an ion chamber. High‐resolution 1D and 2D response maps have been created for two small clinical thimble ionization chambers, the PinPoint chambers 31006 and 31014 (Physikalisch Technische Werkstaetten Freiburg, Germany).

Methods

Working on the Imaging and Medical Beam Line of the Australian Synchrotron an intense kilovoltage radiation beam with very low divergence, collimated to 0.1 mm was used to scan the chambers by moving them on a 2D motion platform. Measured current and beam position were correlated to create the response maps. Small neodymium magnets were used to create a field of about 0.25 T. Chamber axis, magnetic field, and beam direction were perpendicular to each other. Measurements were performed with both orientations of the magnetic field as well as without it. Chamber biases of 5 and 250 V in both polarities were used.

Results

The local distribution of the response of small thimble‐type ionization chambers was found to be impacted by a magnetic field. Depending on the orientation of the magnetic field, the chamber response near the stem was either enhanced or reduced with the response near the tip behaving the opposite way. Local changes were in the order of up to 40% compared to measurements without the magnetic field present. Bending of the central electrode was observed for the chamber with the steel electrode. The size of the volume of reduced collection near the guard electrode was impacted by the magnetic field.

As the here investigated beam and field parameters differ from those of clinical systems, quantitatively different results would be expected for the latter. However, the gyroradii encountered here were similar to those of a 6–7 MV MRI linac with a 1.5 T magnet.

Conclusions

Magnetic fields impact the performance of ionization chambers also on a local level. For practical measurements this might mean a change in the effective point of measurement, in addition to any global corrections. Further knowledge about the local response will help in selecting or constructing optimized chambers for use in magnetic fields.
Reconstruction of a high‐quality volumetric image and a respiratory motion model from patient CBCT projections
Authors: Guo Minghao , Chee Geraldine , O’Connell Dylan , Dhou Salam , Fu Jie , Singhrao Kamal , Ionascu Dan , Ruan Dan , Lee Percy , Low Daniel A. , Zhao Jun , Lewis John H.
Published: May 2019

Purpose

To develop and evaluate a method of reconstructing a patient‐ and treatment day‐ specific volumetric image and motion model from free‐breathing cone‐beam projections and respiratory surrogate measurements. This Motion‐Compensated Simultaneous Algebraic Reconstruction Technique (MC‐SART) generates and uses a motion model derived directly from the cone‐beam projections, without requiring prior motion measurements from 4DCT, and can compensate for both inter‐ and intrabin deformations. The motion model can be used to generate images at arbitrary breathing points, which can be used for estimating volumetric images during treatment delivery.

Methods

The MC‐SART was formulated using simultaneous image reconstruction and motion model estimation. For image reconstruction, projections were first binned according to external surrogate measurements. Projections in each bin were used to reconstruct a set of volumetric images using MC‐SART. The motion model was estimated based on deformable image registration between the reconstructed bins, and least squares fitting to model parameters. The model was used to compensate for motion in both projection and backprojection operations in the subsequent image reconstruction iterations. These updated images were then used to update the motion model, and the two steps were alternated between. The final output is a volumetric reference image and a motion model that can be used to generate images at any other time point from surrogate measurements.

Results

A retrospective patient dataset consisting of eight lung cancer patients was used to evaluate the method. The absolute intensity differences in the lung regions compared to ground truth were 50.8 ± 43.9 HU in peak exhale phases (reference) and 80.8 ± 74.0 in peak inhale phases (generated). The 50th percentile of voxel registration error of all voxels in the lung regions with >5 mm amplitude was 1.3 mm. The MC‐SART was also applied to measured patient cone‐beam projections acquired with a linac‐mounted CBCT system. Results from this patient data demonstrate the feasibility of MC‐SART and showed qualitative image quality improvements compared to other state‐of‐the‐art algorithms.

Conclusion

We have developed a simultaneous image reconstruction and motion model estimation method that uses Cone‐beam computed tomography (CBCT) projections and respiratory surrogate measurements to reconstruct a high‐quality reference image and motion model of a patient in treatment position. The method provided superior performance in both HU accuracy and positional accuracy compared to other existing methods. The resultant reference image and motion model can be combined with respiratory surrogate measurements to generate volumetric images representing patient anatomy at arbitrary time points.
Detecting anomalies in diaphragm walls with electrical resistance measurements
Authors: Spruit Rodriaan , Van Tol Frits , Broere Wout , Slob Evert
Published: May 2019

Quality control of diaphragm walls prior to excavation is often difficult. One technique that can be used to detect anomalies in diaphragm walls involves electrical resistance. Electrical resistance measurements across a diaphragm wall can (within a strict framework) be used to verify the presence of leaks in diaphragm walls as a supplement to crosshole sonic logging. From measurements around a test wall conducted in this study, it is concluded that the detectability of anomalies with electrical resistance decreases exponentially with the increasing distance between the measurement electrodes and the wall. Electrical resistance setups with two and four electrodes have been compared. For usable results, a four‐electrode setup must be used in which the potential electrodes need to be placed very close to the wall (less than 0.2 m away). Based upon the test experience, a field setup for verification of a building pit consisting of diaphragm walls is suggested, as well as a setup for determining the quality of the concrete covering the rebar in quay walls constructed with diaphragm walls.
Boost retention, attract students with a graduate research symposium
Authors: Hope Joan
Published: May 2019

TORONTO — When students decide to attend graduate school, they look forward to conducting research and sharing it with others in their field. A graduate research symposium can give them an opportunity to showcase their work. The event can help you retain those students — and you can even use it to recruit new students.
Map out your journey to the college presidency
Authors: McCarthy Claudine
Published: May 2019

As a young woman from the projects arriving on a college campus with all her belongings in just “two trash bags and a trunk,” Tyjaun Lee couldn't have imagined herself as a college graduate who would go on to earn her master's degree and then her Ph.D. while working her way up through the ranks in student affairs and eventually becoming a college president. But that's indeed what she did. And it certainly took much determination and sacrifice along the way.
gem‐Diethyl Pyrroline Nitroxide Spin Labels: Synthesis, EPR Characterization, Rotamer Libraries and Biocompatibility
Authors: Bleicken Stephanie , Assafa Tufa E. , Zhang Hui , Elsner Christina , Ritsch Irina , Pink Maren , Rajca Suchada , Jeschke Gunnar , Rajca Andrzej , Bordignon Enrica
Published: May 2019

The availability of bioresistant spin labels is crucial for the optimization of site‐directed spin labeling protocols for EPR structural studies of biomolecules in a cellular context. As labeling can affect proteins’ fold and/or function, having the possibility to choose between different spin labels will increase the probability to produce spin‐labeled functional proteins. Here, we report the synthesis and characterization of iodoacetamide‐ and maleimide‐functionalized spin labels based on the gem‐diethyl pyrroline structure. The two nitroxide labels are compared to conventional gem‐dimethyl analogs by site‐directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy, using two water soluble proteins: T4 lysozyme and Bid. To foster their use for structural studies, we also present rotamer libraries for these labels, compatible with the MMM software. Finally, we investigate the “true” biocompatibility of the gem‐diethyl probes comparing the resistance towards chemical reduction of the NO group in ascorbate solutions and E. coli cytosol at different spin concentrations.
Electrochemical Synthesis of Fluorinated Orthoesters from 1,3‐Benzodioxoles
Authors: Röckl Johannes L. , Hauck Adrian V. , Schollmeyer Dieter , Waldvogel Siegfried R.
Published: May 2019

A scalable, dehydrogenative, and electrochemical synthesis of novel highly fluorinated orthoesters is reported. This protocol provides easy and direct access to a wide variety of derivatives, using a very simple electrolysis setup. These compounds are surprisingly robust towards base and acid with an unusual high lipophilicity, making them interesting motifs for potentially active compounds in medicinal chemistry or agro applications. The use of electricity enables a safe and environmentally benign chemical transformation as only electrons serve as oxidants.
Clinical analysis of early death in children with pleuropulmonary blastoma in a single center in China
Authors: Chai Xi , Zhang Na , Zhang Dawei , Fu Libing , Yu Tong , Su Yan , Gao Hengmiao , Qian Suyun , Zeng Qi , Ma Xiaoli
Published: May 2019

Objective

Pleuropulmonary blastoma (PPB) is a rare malignant tumor in childhood that is highly invasive and has poor prognosis. We retrospectively analyzed patients with PPB who died within 30 days in hopes of providing a basis for improving diagnosis and treatment.

Methods

We retrospectively reviewed six children with PPB who died within 30 days of admission at our hospital from January 2004 to March 2018, including their clinical features, pathological diagnosis, course of treatment, and major causes of death.

Results

Six patients (two female, four male; median age, 38 months) were included. All patients presented with respiratory symptoms. Chest imaging showed that all tumors had diameters greater than 10 cm, with varying degrees of serous effusion. Four patients underwent ultrasound‐guided fine‐needle aspiration (FNA), one patient underwent exploratory thoracotomy, and one underwent partial tumor resection. Five cases were type III, and another was type II. Four patients developed adverse events while waiting for pathological results after FNA, and four patients were treated with chemotherapy but their tumors failed to decrease in size one to two weeks later. The median hospitalization to death time was 17 days (range, 5–24 days).

Conclusions

PPB often presents with respiratory symptoms that rapidly develop into respiratory distress. The rapid tumor enlargement contributes to the disease's progression. Chemoreduction in such tumors is not obviously effective, and the mortality rate is high. The main causes of death were respiratory failure and sepsis. Further clinical studies will be required to evaluate the role of initial biopsy compared with upfront total excision.
The performance of cardio‐biparietal ratio measured by 2D ultrasound in predicting fetal hemoglobin Bart disease during midpregnancy: A pilot study
Authors: Traisrisilp Kuntharee , Sirilert Sirinart , Tongsong Theera
Published: May 2019

Objective

The aim of this study was to assess the performance of cardio‐biparietal ratio measured by real‐time two‐dimensional ultrasound in predicting hemoglobin (Hb) Bart disease among fetuses at risk.

Method

This prospective diagnostic study recruited pregnancies at risk for Hb Bart disease at 17 to 22 weeks' gestation. Cardio‐biparietal ratio and cardiothoracic ratio were measured before cordocentesis for Hb typing. The performance of the cardio‐biparietal ratio and cardiothoracic ratio for identifying affected fetuses was evaluated.

Results

Among 72 fetuses at risk, 31 were diagnosed as affected by Hb Bart disease. By using a cutoff 0.45, cardio‐biparietal ratio had a sensitivity of 83.9%, specificity of 92.7%, positive predictive value of 89.7%, and negative predictive value of 88.4%, whereas cardiothoracic ratio using cutoff 0.5 had a sensitivity of 94.3%, specificity of 65.1%, positive predictive value of 68.8%, and negative predictive value of 93.3%.

Conclusion

Cardio‐biparietal ratio is a new sonomarker to predict Hb Bart disease among fetuses at risk. This sonomarker is relatively effective and may be useful in areas of high prevalence of alpha thalassemia disease, limited number of experts in prenatal ultrasound, and difficult access to prenatal diagnosis.
High‐Performance UV Protective Waterborne Polymer Coatings Based on Hybrid Graphene/Carbon Nanotube Radicals Scavenging Filler
Authors: Prosheva Marija , Aboudzadeh Mohammad Ali , Leal Gracia Patricia , Gilev Jadranka Blazhevska , Tomovska Radmila
Published: May 2019

Ultraviolet (UV) degradation is one of the most important challenges of waterborne coatings in exterior applications. One of the ways to address this issue is addition of radical scavenging species within the polymer matrix. Herein, hybrids of graphene (G) and multiwall carbon nanotubes (CNTs) in different ratios are used as radical scavenging species. Evaluated by electron paramagnetic resonance spectroscopy, it is found that the hybrid made of G/CNTs in ratio of 10:1 efficiently captures and quenches the free radicals. The waterborne polymer composites containing 1 wt% of hybrid G/CNT are synthesized by in situ miniemulsion free radical polymerization using a water soluble initiator. However, due to excellent efficiency to capture free radicals, the polymerization performed using water soluble initiators in the presence of 10:1 G/CNT filler is hindered. This is resolved by physical separation of the free radicals and the scavenging materials within different phases by use of oil soluble initiator. The resulting polymer composites, beside having excellent mechanical resistance, present exceptional stability under accelerated aging conditions during 400 h, suppressing almost completely the UV photodegradation. This is attributed to the efficient radical scavenging of the G/CNTs hybrid filler distributed within polymer matrix, resulting in high‐performance UV protective waterborne composite coatings.
Quantitative Systems Pharmacology: An Exemplar Model‐Building Workflow With Applications in Cardiovascular, Metabolic, and Oncology Drug Development
Authors: Helmlinger Gabriel , Sokolov Victor , Peskov Kirill , Hallow Karen M. , Kosinsky Yuri , Voronova Veronika , Chu Lulu , Yakovleva Tatiana , Azarov Ivan , Kaschek Daniel , Dolgun Artem , Schmidt Henning , Boulton David W. , Penland Robert C.
Published: May 2019

Quantitative systems pharmacology (QSP), a mechanistically oriented form of drug and disease modeling, seeks to address a diverse set of problems in the discovery and development of therapies. These problems bring a considerable amount of variability and uncertainty inherent in the nonclinical and clinical data. Likewise, the available modeling techniques and related software tools are manifold. Appropriately, the development, qualification, application, and impact of QSP models have been similarly varied. In this review, we describe the progressive maturation of a QSP modeling workflow: a necessary step for the efficient, reproducible development and qualification of QSP models, which themselves are highly iterative and evolutive. Furthermore, we describe three applications of QSP to impact drug development; one supporting new indications for an approved antidiabetic clinical asset through mechanistic hypothesis generation, one highlighting efficacy and safety differentiation within the sodium‐glucose cotransporter‐2 inhibitor drug class, and one enabling rational selection of immuno‐oncology drug combinations.