bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender Differences in the Experience of Infertility Concerning Polish Couples: Preliminary Research
Authors: Nagórska Małgorzata , Bartosiewicz Anna , Obrzut Bogdan , Darmochwał-Kolarz Dorota
Published: July 2019

The World Health Organization (WHO) determines infertility as a disease of the reproductive system defined clinically by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. Estimates indicate that the problem of infertility in the world is continuing to grow. The aim of the study was to compare approaches to disease in partners of both sexes diagnosed with infertility. The study was conducted among 61 couples treated for infertility using an original questionnaire developed by the authors. The Chi square independence test was used for statistical analysis. Both men and women responded to the diagnosis of infertility with negative emotions. Regardless of sex, sadness and anxiety were the dominant feelings associated with the diagnosis of infertility. Women believed in the success of the treatment to a greater extent than men. Mainly women attempted to talk openly about the problem of infertility, while men were more restrained in this respect. Women accepted the assisted reproductive technologies (ART) to a greater extent than men, but men would accept childlessness more often than women.
Measuring OPD Patient Satisfaction with Different Service Delivery Aspects at Public Hospitals in Pakistan
Authors: Hussain Abid , Asif Muhammad , Jameel Arif , Hwang Jinsoo
Published: July 2019

The satisfaction of the patient is believed to be one of the preferred results of healthcare, and it is directly connected with the usage of health services. This study aimed to assess how doctor services, nurses’ services, and waiting time predict patient satisfaction (PS) with the service delivery of healthcare in Southern Punjab, Pakistan. The study used an exploratory research method, in which 1000 participants were selected, and used a random technique, in which 850 responses were received. Multiple regression analysis and a confirmatory factor were employed to analyze the collected data. The findings showed that doctor services (β = 0.232; p = 0.01), nurses services (β = 0.256; p = 0.01), and waiting time (β = 0.091; p = 0.03) had positive significant impacts on PS, while registration services (β = 0.028; p = 0.390) had an insignificant association with PS. Hence, a significant gap existed in the registration services that were totally ignored in hospitals of Pakistan which needed proper considerations for improvements.
The Current Health and Wellbeing of the Survivors of the Rana Plaza Building Collapse in Bangladesh: A Qualitative Study
Authors: Kabir Humayun , Maple Myfanwy , Islam Md Shahidul , Usher Kim
Published: July 2019

This study aims to identify the ongoing physical and psychological health vulnerabilities of the readymade garment (RMG) factory workers involved in the Rana Plaza building collapse in 2013, along with their experiences within the current socioeconomic and political contexts of Bangladesh. Seventeen Rana Plaza survivors participated in unstructured, face-to-face, in-depth interviews. Interviews were thematically analyzed using Haddon’s matrix to examine pre-event, event, and post-event injury experiences. The collapse of the Rana Plaza building resulted in significant physical and emotional trauma for those who survived the event. The majority of the participants were forced to attend work on the day of the collapse. Participants reported physical health complaints related to bone injuries/fractures and amputation, severe headache, kidney problems, and functional difficulties. In addition to the reported physical health issues, the participants revealed psychological health issues including trauma, depression and suicidal ideation, sleep disorders, anxiety, and sudden anger. Participants described barriers to their potential for re-employment in the RMG sector and outlined their limited access to free healthcare for follow-up treatment. Those who survived the collapse of the Rana Plaza building continue to experience significant adverse physical and emotional outcomes related to the disaster. Yet, they have little recourse to ensure the availability of adequate health care and rehabilitation. Given the international reliance on the Bangladeshi RMG industry, continued pressure to ensure care is provided for these survivors, and to reduce the risk of future disasters, is necessary.
Reliability of the 30 s Chair Stand Test in Women with Fibromyalgia
Authors: Martín-Martínez Juan Pedro , Collado-Mateo Daniel , Domínguez-Muñoz Francisco Javier , Villafaina Santos , Gusi Narcís , Pérez-Gómez Jorge
Published: July 2019

Background: The 30 s chair stand test is often used to evaluate physical fitness in chronic pain populations. In patients with fibromyalgia, physical fitness is closely related to pain, quality of life, and fear of falling. However, the reliability of this test has only been evaluated concerning the number of repetitions. Objective: To evaluate the test–retest reliability of the 30 s chair stand test in women with fibromyalgia (n = 30), using data from the contact and non-contact time registered with an automatic chronometer (chronojump). Methods: Participants carried out the 30 s chair stand test twice with five minutes as a rest period, while an automatic chronometer recorded the time elapsed in contact with the chair (impulse phase) and not in contact (non-contact phase). Number and fear of falls in the last year and in the last six weeks were also recorded. Results: The reliability of duration of both phases was good. A relationship between these results and the number and fear of falling was also found. Conclusion: The analysis of movement phases in the 30 s chair stand test showed a good reliability in females with fibromyalgia, providing further useful information about the onset of muscle fatigue during the test.
Factors Correlating to the Development of Hepatitis C Virus Infection among Drug Users—Findings from a Systematic Review and Meta-Analysis
Authors: Zhou Biao , Cai Gao Feng , Lv Hua Kun , Xu Shuang Fei , Wang Zheng Ting , Jiang Zheng Gang , Hu Chong Gao , Chen Yong Di
Published: July 2019

Hepatitis C remains a significant public health threat. However, the main routes of transmission have changed since the early 1990s. Currently, drug use is the main source of hepatitis C virus (HCV) infection, and some measures have been successively implemented and additional studies have been published. However, the factors correlating with HCV infection failed to clearly define. Our study pooled the odds ratios (ORs) with 95% confidence intervals (CIs) and analyzed sensitivity by searching data in the PubMed, Elsevier, Springer, Wiley, and EBSCO databases. Publication bias was determined by Egger’s test. In our meta-analysis, HCV-infected and non-HCV-infected patients from 49 studies were analyzed. The pooled ORs with 95% CIs for study factors were as follows: Injecting drug use 10.11 (8.54, 11.97); sharing needles and syringes 2.24 (1.78, 2.83); duration of drug use >5 years 2.39 (1.54, 3.71); unemployment 1.50 (1.22, 1.85); commercial sexual behavior 1.00 (0.73, 1.38); married or cohabiting with a regular partner 0.88 (0.79, 0.98), and sexual behavior without a condom 1.72 (1.07, 2.78). This study found that drug users with histories of injecting drug use, sharing needles and syringes, drug use duration of >5 years, and unemployment, were at increased risk of HCV infection. Our findings indicate that sterile needles and syringes should be made available to ensure safe injection. In view of that, methadone maintenance treatment can reduce or put an end to risky drug-use behaviors, and should be scaled up further, thereby reducing HCV infection.
S100B Protein Stimulates Proliferation and Angiogenic Mediators Release through RAGE/pAkt/mTOR Pathway in Human Colon Adenocarcinoma Caco-2 Cells
Authors: Seguella Luisa , Capuano Riccardo , Pesce Mirella , Annunziata Giuseppe , Pesce Marcella , de Conno Barbara , Sarnelli Giovanni , Aurino Laura , Esposito Giuseppe
Published: July 2019

Chronic inflammation and angiogenesis are associated with colonic carcinogenesis. Enteric glia-derived S100B protein has been proposed as an “ideal bridge”, linking colonic inflammation and cancer, given its dual ability to up-regulate nuclear factor-kappaB (NF-κB) transcription via receptor for advanced glycation end products (RAGE) signaling and to sequestrate wild type pro-apoptotic wild type (wt)p53. However, its pro-angiogenic effects on cancer cells are still uninvestigated. To this aim, we evaluated the effect of exogenous S100B (0.05–5 µM) protein alone or in the presence of S100B blocking monoclonal antibody (mAb) (1:105–1:104 v/v diluted) on (1) cultured Caco-2 cells proliferation, migration and invasiveness in vitro, respectively by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT)-formazan, wound healing and matrigel invasion assays and (2) its effect on the release of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF) by ELISA and immunofluorescence analyses. The effect of S100B alone or in the presence of S100BmAb was then investigated on RAGE/pAkt/mammalian target of rapamycin (mTOR) signaling pathway by immunoblot analysis. Our results showed that S100B markedly increases proliferation and invasiveness of Caco-2 cells, through the release of pro-angiogenic VEGF and NO paralleled to a significant decrease of wtp53 expression mediated by RAGE-p38 mitogen-activated protein kinase (MAPK)/pAkt-mTOR and hypoxia-inducible factor 1-alpha (HIF1α) pathways. Such effects were counteracted by S100BmAb, indicating that S100B targeting is a potential approach to inhibit colon carcinoma proliferation and angiogenesis.
Phytosterols Inhibit Side-Chain Oxysterol Mediated Activation of LXR in Breast Cancer Cells
Authors: Hutchinson Samantha A. , Lianto Priscilia , Moore J. Bernadette , Hughes Thomas A. , Thorne James L.
Published: July 2019

Low fruit and vegetable consumption and high saturated fat consumption causes elevated circulating cholesterol and are breast cancer risk factors. During cholesterol metabolism, oxysterols form that bind and activate the liver X receptors (LXRs). Oxysterols halt breast cancer cell proliferation but enhance metastatic colonization, indicating tumour suppressing and promoting roles. Phytosterols and phytostanols in plants, like cholesterol in mammals, are essential components of the plasma membrane and biochemical precursors, and in human cells can alter LXR transcriptional activity. Here, a panel of breast cancer cell lines were treated with four dietary plant sterols and a stanol, alone or in combination with oxysterols. LXR activation and repression were measured by gene expression and LXR-luciferase reporter assays. Oxysterols activated LXR in all cell lines, but surprisingly phytosterols failed to modulate LXR activity. However, phytosterols significantly inhibited the ability of oxysterols to drive LXR transcription. These data support a role for phytosterols in modulating cancer cell behaviour via LXR, and therefore suggest merit in accurate dietary recordings of these molecules in cancer patients during treatment and perhaps supplementation to benefit recovery.
Characterization of a Surface-Active Protein Extracted from a Marine Strain of Penicillium chrysogenum
Authors: Cicatiello Paola , Stanzione Ilaria , Dardano Principia , De Stefano Luca , Birolo Leila , De Chiaro Addolorata , Monti Daria Maria , Petruk Ganna , D’Errico Gerardino , Giardina Paola
Published: July 2019

Marine microorganisms represent a reservoir of new promising secondary metabolites. Surface-active proteins with good emulsification activity can be isolated from fungal species that inhabit the marine environment and can be promising candidates for different biotechnological applications. In this study a novel surface-active protein, named Sap-Pc, was purified from a marine strain of Penicillium chrysogenum. The effect of salt concentration and temperature on protein production was analyzed, and a purification method was set up. The purified protein, identified as Pc13g06930, was annotated as a hypothetical protein. It was able to form emulsions, which were stable for at least one month, with an emulsification index comparable to that of other known surface-active proteins. The surface tension reduction was analyzed as function of protein concentration and a critical micellar concentration of 2 μM was determined. At neutral or alkaline pH, secondary structure changes were monitored over time, concurrently with the appearance of protein precipitation. Formation of amyloid-like fibrils of SAP-Pc was demonstrated by spectroscopic and microscopic analyses. Moreover, the effect of protein concentration, a parameter affecting kinetics of fibril formation, was investigated and an on-pathway involvement of micellar aggregates during the fibril formation process was suggested.
Pro-Apoptotic Effect of Grape Seed Extract on MCF-7 Involves Transient Increase of Gap Junction Intercellular Communication and Cx43 Up-Regulation: A Mechanism of Chemoprevention
Authors: Leone Antonella , Longo Cristiano , Gerardi Carmela , Trosko James E.
Published: July 2019

Growing evidence suggests dietary antioxidants reduce the risk of several cancers. Grape seeds extracts (GSE) are a rich source of polyphenols known to have antioxidant, chemopreventive and anticancer properties. Herein, we investigated the in vitro effects and putative action mechanisms of a grape seed extract (GSE) on human breast cancer cells (MCF-7). The effects of GSE were evaluated on cell proliferation, apoptosis and gap-junction-mediated cell-cell communications (GJIC), as basal mechanism involved in the promotion stage of carcinogenesis. GSE (0.05–100 μg/mL) caused a significant dose- and time-dependent inhibition of MCF-7 viability and induced apoptotic cell death, as detected by Annexin-V/Propidium Iodide. Concurrently, GSE induced transient but significant enhancement of GJIC in non-communicating MCF-7 cells, as demonstrated by the scrape-loading/dye-transfer (SL/DT) assay and an early and dose-dependent re-localization of the connexin-43 (Cx43) proteins on plasma membranes, as assayed by immunocytochemistry. Finally, real-time-PCR has evidenced a significant increase in cx43 mRNA expression. The results support the hypothesis that the proliferation inhibition and pro-apoptotic effect of GSE against this breast cancer cell model are mediated by the GJIC improvement via re-localization of Cx43 proteins and up-regulation of cx43 gene, and provide further insight into the action mechanisms underlying the health-promoting action of dietary components.
Influence of Cardiovascular Risk Factors, Comorbidities, Medication Use and Procedural Variables on Remote Ischemic Conditioning Efficacy in Patients with ST-Segment Elevation Myocardial Infarction
Authors: Pryds Kasper , Hjortbak Marie Vognstoft , Schmidt Michael Rahbek
Published: July 2019

Remote ischemic conditioning (RIC) confers cardioprotection in patients with ST-segment elevation myocardial infarction (STEMI). Despite intense research, the translation of RIC into clinical practice remains a challenge. This may, at least partly, be due to confounding factors that may modify the efficacy of RIC. The present review focuses on cardiovascular risk factors, comorbidities, medication use and procedural variables which may modify the efficacy of RIC in patients with STEMI. Findings of such efficacy modifiers are based on subgroup and post-hoc analyses and thus hold risk of type I and II errors. Although findings from studies evaluating influencing factors are often ambiguous, some but not all studies suggest that smoking, non-statin use, infarct location, area-at-risk of infarction, pre-procedural Thrombolysis in Myocardial Infarction (TIMI) flow, ischemia duration and coronary collateral blood flow to the infarct-related artery may influence on the cardioprotective efficacy of RIC. Results from the on-going CONDI2/ERIC-PPCI trial will determine any clinical implications of RIC in the treatment of patients with STEMI and predefined subgroup analyses will give further insight into influencing factors on the efficacy of RIC.
Effects on the Profile of Circulating miRNAs after Single Bouts of Resistance Training with and without Blood Flow Restriction—A Three-Arm, Randomized Crossover Trial
Authors: Vogel Johanna , Niederer Daniel , Engeroff Tobias , Vogt Lutz , Troidl Christian , Schmitz-Rixen Thomas , Banzer Winfried , Troidl Kerstin
Published: July 2019

Background: The effects of blood flow restriction (training) may serve as a model of peripheral artery disease. In both conditions, circulating micro RNAs (miRNAs) are suggested to play a crucial role during exercise-induced arteriogenesis. We aimed to determine whether the profile of circulating miRNAs is altered after acute resistance training during blood flow restriction (BFR) as compared with unrestricted low- and high-volume training, and we hypothesized that miRNA that are relevant for arteriogenesis are affected after resistance training. Methods: Eighteen healthy volunteers (aged 25 ± 2 years) were enrolled in this three-arm, randomized-balanced crossover study. The arms were single bouts of leg flexion/extension resistance training at (1) 70% of the individual single-repetition maximum (1RM), (2) at 30% of the 1RM, and (3) at 30% of the 1RM with BFR (artificially applied by a cuff at 300 mm Hg). Before the first exercise intervention, the individual 1RM (N) and the blood flow velocity (m/s) used to validate the BFR application were determined. During each training intervention, load-associated outcomes (fatigue, heart rate, and exhaustion) were monitored. Acute effects (circulating miRNAs, lactate) were determined using pre-and post-intervention measurements. Results: All training interventions increased lactate concentration and heart rate (p < 0.001). The high-intensity intervention (HI) resulted in a higher lactate concentration than both lower-intensity training protocols with BFR (LI-BFR) and without (LI) (LI, p = 0.003; 30% LI-BFR, p = 0.008). The level of miR-143-3p was down-regulated by LI-BFR, and miR-139-5p, miR-143-3p, miR-195-5p, miR-197-3p, miR-30a-5p, and miR-10b-5p were up-regulated after HI. The lactate concentration and miR-143-3p expression showed a significant positive linear correlation (p = 0.009, r = 0.52). A partial correlation (intervention partialized) showed a systematic impact of the type of training (LI-BFR vs. HI) on the association (r = 0.35 remaining after partialization of training type). Conclusions: The strong effects of LI-BFR and HI on lactate- and arteriogenesis-associated miRNA-143-3p in young and healthy athletes are consistent with an important role of this particular miRNA in metabolic processes during (here) artificial blood flow restriction. BFR may be able to mimic the occlusion of a larger artery which leads to increased collateral flow, and it may therefore serve as an external stimulus of arteriogenesis.
Endothelial Colony Forming Cells as an Autologous Model to Study Endothelial Dysfunction in Patients with a Bicuspid Aortic Valve
Authors: van de Pol Vera , Bons Lidia R. , Lodder Kirsten , Kurakula Konda Babu , Sanchez-Duffhues Gonzalo , Siebelink Hans-Marc J. , Roos-Hesselink Jolien W. , DeRuiter Marco C. , Goumans Marie-José
Published: July 2019

Bicuspid aortic valve (BAV), the most common congenital heart defect, is associated with an increased prevalence of aortic dilation, aortic rupture and aortic valve calcification. Endothelial cells (ECs) play a major role in vessel wall integrity. Little is known regarding EC function in BAV patients due to lack of patient derived primary ECs. Endothelial colony forming cells (ECFCs) have been reported to be a valid surrogate model for several cardiovascular pathologies, thereby facilitating an in vitro system to assess patient-specific endothelial dysfunction. Therefore, the aim of this study was to investigate cellular functions in ECFCs isolated from BAV patients. Outgrowth and proliferation of ECFCs from patients with BAV (n = 34) and controls with a tricuspid aortic valve (TAV, n = 10) were determined and related to patient characteristics. Interestingly, we were only able to generate ECFCs from TAV and BAV patients without aortic dilation, and failed to isolate ECFC colonies from patients with a dilated aorta. Analyzing EC function showed that while proliferation, cell size and endothelial-to-mesenchymal transition were similar in TAV and BAV ECFCs, migration and the wound healing capacity of BAV ECFCs is significantly higher compared to TAV ECFCs. Furthermore, calcification is blunted in BAV compared to TAV ECFCs. Our results reveal ECs dysfunction in BAV patients and future research is required to unravel the underlying mechanisms and to further validate ECFCs as a patient-specific in vitro model for BAV.
Effects of Cholesterol on Water Permittivity of Biomimetic Ion Pair Amphiphile Bilayers: Interplay between Membrane Bending and Molecular Packing
Authors: Tien Wu-jhao , Chen Kun-you , Huang Fong-yin , Chiu Chi-cheng
Published: July 2019

Ion pair amphiphile (IPA), a molecular complex composed of a pair of cationic and anionic amphiphiles, is an inexpensive phospholipid substitute to fabricate vesicles with various pharmaceutical applications. Modulating the physicochemical and permeation properties of IPA vesicles are important for carrier designs. Here, we applied molecular dynamics simulations to examine the cholesterol effects on the structures, mechanics, and water permittivity of hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS) and dodecyltrimethylammonium- hexadecylsulfate (DTMA-HS) IPA bilayers. Structural and mechanical analyses indicate that both IPA systems are in gel phase at 298 K. Adding cholesterol induces alkyl chain ordering around the rigid sterol ring and increases the cavity density within the hydrophilic region of both IPA bilayers. Furthermore, the enhanced alkyl chain ordering and the membrane deformation energy induced by cholesterol increase the permeation free energy penalty. In contrast, cholesterol has minor effects on the water local diffusivities within IPA membranes. Overall, the cholesterol reduces the water permittivity of rigid IPA membranes due to the synergistic effects of increased alkyl chain ordering and enhanced membrane mechanical modulus. The results provide molecular insights into the effects of molecular packing and mechanical deformations on the water permittivity of biomimetic IPA membranes, which is critical for designing IPA vesicular carriers.
3D Printing PLA/Gingival Stem Cells/ EVs Upregulate miR-2861 and -210 during Osteoangiogenesis Commitment
Authors: Pizzicannella Jacopo , Diomede Francesca , Gugliandolo Agnese , Chiricosta Luigi , Bramanti Placido , Merciaro Ilaria , Orsini Tiziana , Mazzon Emanuela , Trubiani Oriana
Published: July 2019

Bone tissue regeneration strategies require approaches that provide an osteogenic and angiogenic microenvironment able to drive the bone growth. Recently, the development of 3D printing biomaterials, including poly(lactide) (3D-PLA), enriched with mesenchymal stem cells (MSCs) and/or their derivatives, such as extracellular vesicles (EVs) has been achieving promising results. In this study, in vitro results showed an increased expression of osteogenic and angiogenic markers, as RUNX2, VEGFA, OPN and COL1A1 in the living construct 3D-PLA/human Gingival MSCs (hGMSCs)/EVs. Considering that EVs carry and transfer proteins, mRNA and microRNA into target cells, we evaluated miR-2861 and miR-210 expression related to osteoangiogenesis commitment. Histological examination of rats implanted with 3D-PLA/hGMSCs/EVs evidenced the activation of bone regeneration and of the vascularization process, confirmed also by MicroCT. In synthesis, an upregulation of miR-2861 and -210 other than RUNX2, VEGFA, OPN and COL1A1 was evident in cells cultured in the presence of the biomaterial and EVs. Then, these results evidenced that EVs may enhance bone regeneration in calvaria defects, in association with an enhanced vascularization offering a novel regulatory system in the osteoangiogenesis evolution. The application of new strategies to improve biomaterial engraftment is of great interest in the regenerative medicine and can represent a way to promote bone regeneration.
A Pilot Study towards the Impact of Type 2 Diabetes on the Expression and Activities of Drug Metabolizing Enzymes and Transporters in Human Duodenum
Authors: Gravel Sophie , Panzini Benoit , Belanger Francois , Turgeon Jacques , Michaud Veronique
Published: July 2019

To characterize effects of type 2 diabetes (T2D) on mRNA expression levels for 10 Cytochromes P450 (CYP450s), two carboxylesterases, and three drug transporters (ABCB1, ABCG2, SLCO2B1) in human duodenal biopsies. To compare drug metabolizing enzyme activities of four CYP450 isoenzymes in duodenal biopsies from patients with or without T2D. mRNA levels were quantified (RT-qPCR) in human duodenal biopsies obtained from patients with (n = 20) or without (n = 16) T2D undergoing a scheduled gastro-intestinal endoscopy. CYP450 activities were determined following incubation of biopsy homogenates with probe substrates for CYP2B6 (bupropion), CYP2C9 (tolbutamide), CYP2J2 (ebastine), and CYP3A4/5 (midazolam). Covariables related to inflammation, T2D, demographic, and genetics were investigated. T2D had no major effects on mRNA levels of all enzymes and transporters assessed. Formation rates of metabolites (pmoles mg protein−1 min−1) determined by LC-MS/MS for CYP2C9 (0.48 ± 0.26 vs. 0.41 ± 0.12), CYP2J2 (2.16 ± 1.70 vs. 1.69 ± 0.93), and CYP3A (5.25 ± 3.72 vs. 5.02 ± 4.76) were not different between biopsies obtained from individuals with or without T2D (p > 0.05). No CYP2B6 specific activity was measured. TNF-α levels were higher in T2D patients but did not correlate with any changes in mRNA expression levels for drug metabolizing enzymes or transporters in the duodenum. T2D did not modulate expression or activity of tested drug metabolizing enzymes and transporters in the human duodenum. Previously reported changes in drug oral clearances in patients with T2D could be due to a tissue-specific disease modulation occurring in the liver and/or in other parts of the intestines.
Activation of the IGF Axis in Thyroid Cancer: Implications for Tumorigenesis and Treatment
Authors: Manzella Livia , Massimino Michele , Stella Stefania , Tirrò Elena , Pennisi Maria Stella , Martorana Federica , Motta Gianmarco , Vitale Silvia Rita , Puma Adriana , Romano Chiara , Di Gregorio Sandra , Russo Marco , Malandrino Pasqualino , Vigneri Paolo
Published: July 2019

The Insulin-like growth factor (IGF) axis is one of the best-established drivers of thyroid transformation, as thyroid cancer cells overexpress both IGF ligands and their receptors. Thyroid neoplasms encompass distinct clinical and biological entities as differentiated thyroid carcinomas (DTC)—comprising papillary (PTC) and follicular (FTC) tumors—respond to radioiodine therapy, while undifferentiated tumors—including poorly-differentiated (PDTC) or anaplastic thyroid carcinomas (ATCs)—are refractory to radioactive iodine and exhibit limited responses to chemotherapy. Thus, safe and effective treatments for the latter aggressive thyroid tumors are urgently needed. Despite a strong preclinical rationale for targeting the IGF axis in thyroid cancer, the results of the available clinical studies have been disappointing, possibly because of the crosstalk between IGF signaling and other pathways that may result in resistance to targeted agents aimed against individual components of these complex signaling networks. Based on these observations, the combinations between IGF-signaling inhibitors and other anti-tumor drugs, such as DNA damaging agents or kinase inhibitors, may represent a promising therapeutic strategy for undifferentiated thyroid carcinomas. In this review, we discuss the role of the IGF axis in thyroid tumorigenesis and also provide an update on the current knowledge of IGF-targeted combination therapies for thyroid cancer.
Comparison of Radiosensitization by HDAC Inhibitors CUDC-101 and SAHA in Pancreatic Cancer Cells
Authors: Moertl Simone , Payer Sarah , Kell Rosemarie , Winkler Klaudia , Anastasov Natasa , Atkinson Michael J.
Published: July 2019

Pancreatic cancer has a poor prognosis. New treatment options are urgently required to improve patient outcomes. One promising new class of anticancer drugs are synthetic histone deacetylase inhibitors (HDACi) which modulate chromatin structure and gene expression by blocking histone deacetylation. In this study, we aimed at comparing the in vitro capacities of the HDACi SAHA and CUDC-101 to increase radiosensitivity of human pancreatic tumor cell lines. Therefore, three pancreatic cancer cell lines (Su.86.86, MIA Paca-2, T3M-4) were treated with SAHA (1.5–5 µM) or CUDC-101 (0.25–3 µM) and after 24 h irradiated. Cell proliferation, clonogenic survival and apoptosis was determined. Additionally, cell lysates were investigated for the expression of apoptosis-related proteins. CUDC-101 and SAHA increased the radiation sensitivity of pancreatic tumor cell lines in a dose-dependent manner. This was evidenced by cell proliferation and clonogenic survival. Furthermore, enhanced radiation sensitivity after CUDC-101 or SAHA treatment was confirmed for Su.86.86 and T3M-4 cells in a 3-D microtissue approach. Increased amounts of subG1 cells and diminished full length PARP-1 suggest increased radiation-induced apoptosis after SAHA or CUDC-101 treatment. The comparison of both inhibitors in these assays manifested CUDC-101 as more potent radiosensitizer than SAHA. In line, western blot quantification of the apoptosis-inhibitory proteins XIAP and survivin showed a stronger down-regulation in response to CUDC-101 treatment than after SAHA application. These proteins may contribute to the synergy between HDAC inhibition and radiation response. In conclusion, these preclinical results suggest that treatment with the HDAC inhibitors CUDC-101 or SAHA can enhance radiation-induced cytotoxicity in human pancreatic cells. However, comparison of both inhibitors identified the multi target inhibitor CUDC-101 as more potent radiosensitizer than the HDAC inhibitor SAHA.
Modulation of CAT-2B-Mediated l-Arginine Uptake and Nitric Oxide Biosynthesis in HCT116 Cell Line Through Biological Activity of 4′-Geranyloxyferulic Acid Extract from Quinoa Seeds
Authors: Franceschelli Sara , Gatta Daniela Maria Pia , Pesce Mirko , Ferrone Alessio , Quiles José Luis , Genovese Salvatore , Epifano Francesco , Fiorito Serena , Taddeo Vito Alessandro , Patruno Antonia , Grilli Alfredo , Felaco Mario , Speranza Lorenza
Published: July 2019

Chenopodium quinoa Wild is a “pseudocereal” grain which attracts a lot of attention in the scientific community as it has a positive effect on health. Here, we investigate the presence of biologically active O-prenylated phenylpropanoids in the ethanol extract of commercially available quinoa seeds. We claim that 4′-Geranyloxyferulic acid (GOFA) was the only phytochemical product found that belongs to quinoa’s group secondary metabolites. We studied the changes in the oxidative and inflammatory status of the cellular environment in HCT 116 cell line processed with quinoa extract and its component GOFA; the implementation was done through the analysis of the antioxidant enzymes (SOD and CAT), the pro-inflammatory components (iNOS, IL-6 and TNF-α), and the products of intermediary metabolism (ONOO−, O2−). Moreover, the l-arginine uptake was proposed as a target of the tested compounds. We demonstrated that the GOFA, through a decrease of the CAT-2B expression, leads to a reduction of the l-arginine uptake, downregulating the harmful iNOS and restoring the altered redox state. These results propose a new molecular target involved in the reduction of the critical inflammatory process responsible for the cancer progression.
Analysis of Pedestrian Crossing Speed and Waiting Time at Intersections in Dhaka
Authors: Zafri Niaz Mahmud , Rony Atikul Islam , Adri Neelopal
Published: July 2019

Pedestrian crossing speed and waiting time are critical parameters for designing traffic signals and ensuring pedestrian safety. This study aimed to carry out microscopic level research on pedestrian crossing speed and waiting time at intersections in Dhaka. To fulfill this aim, crossing-related data of 560 pedestrians were collected from three intersections in Dhaka using a videography survey method. Descriptive and statistical analyses were carried out, and then two multiple linear regression (MLR) models were developed for these two parameters by using the collected data. From the results, 1.15 m/s was found to be the design pedestrian crossing speed. Results also show that the crossing speed of pedestrians was associated with intersection control type, gender, age, crossing type, crossing group size, compliance behavior with control direction, and crossing location. In case of waiting time, findings show that pedestrians did not want to wait more than 20–30 s to cross the road. Furthermore, the waiting time of the pedestrians varied with intersection control type, gender, age, minimum gap, waiting location, and vehicle flow. Findings of this study will help to alleviate traffic safety problems by designing an effective intersection control system.
Nearshore Wave Dynamics at Mangalia Beach Simulated by Spectral Models
Authors: Anton Iulia Alina , Rusu Liliana , Anton Catalin
Published: July 2019

The objective of this paper is to present an integrated picture of the relationship between the waves and the modifications induced by them in the Romanian shoreline. Thus, the hydrodynamic processes at the Mangalia beaches, located in the southern side of the Romanian nearshore, are simulated using the modeling system Mike 21 SW (MIKE 21 Spectral Waves), developed by the Danish Hydration Institute (DHI). This is one of the newest spectral wave models, which can be used for regional- and local-scale simulations. The model has been calibrated and validated using buoy measurements. The analysis of the statistical parameters shows a good match between the model and the observed data. Furthermore, a model to compare the differences that occur on the beach profiles between the cold and warm seasons was developed. The results obtained indicate a reinforcement of the coastal erosion in the winter, when the waves are stronger (especially in January and February).
Identification of Mucorales by Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry
Authors: Schwarz Patrick , Guedouar Houssem , Laouiti Farah , Grenouillet Frédéric , Dannaoui Eric
Published: July 2019

More than 20 different species of Mucorales can be responsible for human mucormycosis. Accurate identification to the species level is important. The morphological identification of Mucorales is not reliable, and the currently recommended identification standard is the molecular technique of sequencing the internal transcribed spacer regions. Nevertheless, matrix-assisted laser desorption ionization time-of-flight mass spectrometry has been shown to be an accurate alternative for the identification of bacteria, yeasts, and even filamentous fungi. Therefore, 38 Mucorales isolates, belonging to 12 different species or varieties, mainly from international collections, including 10 type or neo-type strains previously identified by molecular methods, were used to evaluate the usefulness of matrix-assisted laser desorption ionization time-of-flight mass spectrometry for the identification of human pathogenic Mucorales to the species level. One to three reference strains for each species were used to create a database of main spectrum profiles, and the remaining isolates were used as test isolates. A minimum of 10 spectra was used to build the main spectrum profile of each database strain. Interspecies discrimination for all the isolates, including species belonging to the same genus, was possible. Twenty isolates belonging to five species were used to test the database accuracy, and were correctly identified to the species level with a log-score >2. In summary, matrix-assisted laser desorption ionization time-of-flight mass spectrometry is a reliable and rapid method for the identification of most of the human pathogenic Mucorales to the species level.
The Conceptualization of English Phrasal Verbs by Greek Primary School Learners: An Empirical Cognitive Approach
Authors: Tsaroucha Efthymia
Published: July 2019

This study investigates the way Greek EFL elementary students conceptualize English phrasal verbs of the form component verb (take) plus component particle (up, down, in, out, back, off, on, apart). It is suggested image schemas play a facilitatory role in the conceptualization and interpretation of the figurative meanings of English phrasal verbs. The study argues that within the phrasal verb construct, the component particle prompts for the extension from literal to figurative meanings since the particle designates image schematic experiences (bodily-kinesthetic). The study conducted two types of test: (1) meaning of the sentence and (2) image-matching from the sentence. In test 1, participants were asked to read sentences which contained the verb take plus particles and they had to select the most appropriate meaning of the phrasal verb that matched the overall meaning of the sentence. In test 2, participants were asked to read sentences wherein phrasal verbs of the form take plus particles were highlighted. They were asked to match the meaning of the phrasal verb with one image. Each image represented a different type of image schema such as container, front-back orientation and proximity-distance.
[Dicyclohexyl(sulfanylidene)-λ5-phosphanyl]methanol
Authors: Henderson William , Okpareke Obinna , Azizan Ainnul , Tiekink Edward
Published: July 2019

The title compound, [dicyclohexyl(sulfanylidene)-λ5-phosphanyl]methanol, Cy2P(=S)CH2OH (1), was obtained from the reaction between [Cy2P(CH2OH)2]Cl with one molar equivalent of NaOH and an excess of elemental sulfur (powdered). Characterization was by a single-crystal X-ray structure determination as well as IR, and 1D-NMR (1H, 13C{1H}, 31P{1H}), and 2D-NMR (DEPT-135 and HSQC) spectroscopy, ESI mass spectrometry, and elemental analysis. X-ray crystallography on Compound 1 shows the phosphorus atom to be tetrahedrally coordinated within a non-symmetric C3S donor set but with relatively minor distortions from the ideal geometry. In the molecular packing, hydroxyl-O–H⋯S(thione) hydrogen bonds led to supramolecular helical chains along the b-axis direction.
Microstructure and Mechanical Properties of Al–(12-20)Si Bi-Material Fabricated by Selective Laser Melting
Authors: Zhang Shikai , Ma Pan , Jia Yandong , Yu Zhishui , Sokkalingam Rathinavelu , Shi Xuerong , Ji Pengcheng , Eckert Juergen , Prashanth Konda Gokuldoss
Published: July 2019

In this study, a combination of Al–12Si and Al–20Si (Al–(12-20)Si) alloys was fabricated by selective laser melting (SLM) as a result of increased component requirements such as geometrical complexity and high dimensional accuracy. The microstructure and mechanical properties of the SLM Al–(12-20)Si in as-produced as well as in heat-treated conditions were investigated. The Al–(12-20)Si interface was in the as-built condition and it gradually became blurry until it disappeared after heat treatment at 673 K for 6 h. This Al–(12-20)Si bi-material displayed excellent mechanical properties. The hardness of the Al–20Si alloy side was significantly higher than that of the Al–12Si alloy side and the disparity between both sides gradually decreased and tended to be consistent after heat treatment at 673 K for 6 h. The tensile strength and elongation of the Al–(12-20Si) bi-material lies in between the Al–12Si and Al–20Si alloys and fracture occurs in the Al–20Si side. The present results provide new insights into the fabrication of bi-materials using SLM.
Conductivity Size Effect of Square Cross-Section Polycrystalline Nanowires
Authors: Li Rui , Mi Lan , Wang Jian , Mao Mao , Gu Wenhua , Zhu Yongkai
Published: July 2019

A theoretical model for the electrical conductivity size effect of square nanowires is proposed in this manuscript, which features combining the three main carrier scattering mechanisms in polycrystalline nanowires together, namely, background scattering, external surface scattering, as well as grain boundary scattering. Comparisons to traditional models and experiment data show that this model achieves a higher correlation with the experiment data.
Effect of Conformational Diversity on the Bioactivity of µ-Conotoxin PIIIA Disulfide Isomers
Authors: Paul George Ajay Abisheck , Heimer Pascal , Leipold Enrico , Schmitz Thomas , Kaufmann Desiree , Tietze Daniel , Heinemann Stefan H. , Imhof Diana
Published: July 2019

Cyclic µ-conotoxin PIIIA, a potent blocker of skeletal muscle voltage-gated sodium channel NaV1.4, is a 22mer peptide stabilized by three disulfide bonds. Combining electrophysiological measurements with molecular docking and dynamic simulations based on NMR solution structures, we investigated the 15 possible 3-disulfide-bonded isomers of µ-PIIIA to relate their blocking activity at NaV1.4 to their disulfide connectivity. In addition, three µ-PIIIA mutants derived from the native disulfide isomer, in which one of the disulfide bonds was omitted (C4-16, C5-C21, C11-C22), were generated using a targeted protecting group strategy and tested using the aforementioned methods. The 3-disulfide-bonded isomers had a range of different conformational stabilities, with highly unstructured, flexible conformations with low or no channel-blocking activity, while more constrained molecules preserved 30% to 50% of the native isomer’s activity. This emphasizes the importance and direct link between correct fold and function. The elimination of one disulfide bond resulted in a significant loss of blocking activity at NaV1.4, highlighting the importance of the 3-disulfide-bonded architecture for µ-PIIIA. µ-PIIIA bioactivity is governed by a subtle interplay between an optimally folded structure resulting from a specific disulfide connectivity and the electrostatic potential of the conformational ensemble.
Telepharmacy Services: Present Status and Future Perspectives: A Review
Authors: Baldoni Simone , Amenta Francesco , Ricci Giovanna
Published: July 2019

Background and Objectives: The term “telepharmacy” indicates a form of pharmaceutical care in which pharmacists and patients are not in the same place and can interact using information and communication technology (ICT) facilities. Telepharmacy has been adopted to provide pharmaceutical services to underserved areas and to address the problem of pharmacist shortage. This paper has reviewed the multi-faceted phenomenon of telepharmacy, summarizing different experiences in the area. Advantages and limitations of telepharmacy are discussed as well. Materials and Methods: A literature analysis was carried out on PubMed, using as entry term “telepharmacy” and including articles on the topic published between 2012 and 2018. Results: The studies reviewed were divided into three categories of pharmacy practice, namely (1) support to clinical services, (2) remote education and handling of “special pharmacies”, and (3) prescription and reconciliation of drug therapies. In general, different telepharmacy services were effective and accompanied by a satisfaction of their targets. Conclusions: Nowadays, the shortage of health personnel, and in particular pharmacists, is a challenging issue that the health systems have to face. The use of a new technology such as telepharmacy can represent a possible option to solve these problems. However, there are unsolved limitations (e.g., legal implications) that make greater diffusion of telepharmacy difficult. Stronger data on the effectiveness of this area of pharmacy care, together with a critical evaluation of its limits, can make actors involved aware about the potentialities of it and could contribute to a larger diffusion of telepharmacy services in the interest of communities and citizens.
A Review on Inorganic Nanoparticles Modified Composite Membranes for Lithium-Ion Batteries: Recent Progress and Prospects
Authors: Asghar Muhammad Rehman , Anwar Muhammad Tuoqeer , Naveed Ahmad
Published: July 2019

Separators with high porosity, mechanical robustness, high ion conductivity, thin structure, excellent thermal stability, high electrolyte uptake and high retention capacity is today’s burning research topic. These characteristics are not easily achieved by using single polymer separators. Inorganic nanoparticle use is one of the efforts to achieve these attributes and it has taken its place in recent research. The inorganic nanoparticles not only improve the physical characteristics of the separator but also keep it from dendrite problems, which enhance its shelf life. In this article, use of inorganic particles for lithium-ion battery membrane modification is discussed in detail and composite membranes with three main types including inorganic particle-coated composite membranes, inorganic particle-filled composite membranes and inorganic particle-filled non-woven mates are described. The possible advantages of inorganic particles application on membrane morphology, different techniques and modification methods for improving particle performance in the composite membrane, future prospects and better applications of ceramic nanoparticles and improvements in these composite membranes are also highlighted. In short, the contents of this review provide a fruitful source for further study and the development of new lithium-ion battery membranes with improved mechanical stability, chemical inertness and better electrochemical properties.
The Search for Clinically Useful Biomarkers of Complex Disease: A Data Analysis Perspective
Authors: Considine Elizabeth C.
Published: July 2019

Unmet clinical diagnostic needs exist for many complex diseases, which it is hoped will be solved by the discovery of metabolomics biomarkers. However, as yet, no diagnostic tests based on metabolomics have yet been introduced to the clinic. This review is presented as a research perspective on how data analysis methods in metabolomics biomarker discovery may contribute to the failure of biomarker studies and suggests how such failures might be mitigated. The study design and data pretreatment steps are reviewed briefly in this context, and the actual data analysis step is examined more closely.