bluuebunny/crossref_metadata_2025_split huggingface dataset:
A High-Content Screening of Anticancer Compounds Suggests the Multiple Tyrosine Kinase Inhibitor Ponatinib for Repurposing in Neuroblastoma Therapy
Authors: Sidarovich Viktoryia , De Mariano Marilena , Aveic Sanja , Pancher Michael , Adami Valentina , Gatto Pamela , Pizzini Silvia , Pasini Luigi , Croce Michela , Parodi Federica , Cimmino Flora , Avitabile Marianna , Emionite Laura , Cilli Michele , Ferrini Silvano , Pagano Aldo , Capasso Mario , Quattrone Alessandro , Tonini Gian Paolo , Longo Luca 
Published: April 2018

AbstractNovel druggable targets have been discovered in neuroblastoma (NB), paving the way for more effective treatments. However, children with high-risk NB still show high mortality rates prompting for a search of novel therapeutic options. Here, we aimed at repurposing FDA-approved drugs for NB treatment by performing a high-content screening of a 349 anticancer compounds library. In the primary screening, we employed three NB cell lines, grown as three-dimensional (3D) multicellular spheroids, which were treated with 10 μmol/L of the library compounds for 72 hours. The viability of 3D spheroids was evaluated using a high-content imaging approach, resulting in a primary hit list of 193 compounds. We selected 60 FDA-approved molecules and prioritized drugs with multi-target activity, discarding those already in use for NB treatment or enrolled in NB clinical trials. Hence, 20 drugs were further tested for their efficacy in inhibiting NB cell viability, both in two-dimensional and 3D models. Dose-response curves were then supplemented with the data on side effects, therapeutic index, and molecular targets, suggesting two multiple tyrosine kinase inhibitors, ponatinib and axitinib, as promising candidates for repositioning in NB. Indeed, both drugs showed induction of cell-cycle block and apoptosis, as well as inhibition of colony formation. However, only ponatinib consistently affected migration and inhibited invasion of NB cells. Finally, ponatinib also proved effective inhibition of tumor growth in orthotopic NB mice, providing the rationale for its repurposing in NB therapy. Mol Cancer Ther; 17(7); 1405–15. ©2018 AACR.
Tumor-Independent Host Secretomes Induced By Angiogenesis and Immune-Checkpoint Inhibitors
Authors: Mastri Michalis , Lee Christina R. , Tracz Amanda , Kerbel Robert S. , Dolan Melissa , Shi Yuhao , Ebos John M.L. 
Published: April 2018

Abstract
The levels of various circulating blood proteins can change in response to cancer therapy. Monitoring therapy-induced secretomes (TIS) may have use as biomarkers for establishing optimal biological effect (such as dosing) or identifying sources of toxicity and drug resistance. Although TIS can derive from tumor cells directly, nontumor “host” treatment responses can also impact systemic secretory programs. For targeted inhibitors of the tumor microenvironment, including antiangiogenic and immune-checkpoint therapies, host TIS could explain unexpected collateral “side effects” of treatment. Here, we describe a comparative transcriptomic and proteomic analysis of host TIS in tissues and plasma from cancer-free mice treated with antibody and receptor tyrosine kinase inhibitors (RTKI) of the VEGF, cMet/ALK, and PD-1 pathways. We found that all cancer therapies elicit TIS independent of tumor growth, with systemic secretory gene change intensity higher in RTKIs compared with antibodies. Our results show that host TIS signatures differ between drug target, drug class, and dose. Notably, protein and gene host TIS signatures were not always predictive for each other, suggesting limitations to transcriptomic-only approaches to clinical biomarker development for circulating proteins. Together, these are the first studies to assess and compare “off-target” host secretory effects of VEGF and PD-1 pathway inhibition that occur independent of tumor stage or tumor response to therapy. Testing treatment impact on normal tissues to establish host-mediated TIS signatures (or “therasomes”) may be important for identifying disease agnostic biomarkers to predict benefits (or limitations) of drug combinatory approaches. Mol Cancer Ther; 17(7); 1602–12. ©2018 AACR.
МОРФОЛОГО-АНАТОМІЧНІ ОЗНАКИ ТРАВИ МАРУНИ ДІВОЧОЇ (TANACETUM PARTHENIUM (L.) SСHULTZ. BIP.)
Authors: Hordiei K. R. , Gontova T. N. , Zolotaikina M. Yu. , Sira L. M. 
Published: April 2018

Мета роботи. Провести ідентифікацію трави Tanacetum parthenium за макро- та мікроскопічними ознаками згідно з ДФУ 2.0. Встановити основні діагностичні ознаки стебла, листя, кошиків та квіток.Матеріали і методи. Об’єктом дослідження були зразки трави маруни дівочої, зібрані у період із початку до масового цвітіння у 7 областях України. Для макроскопічного опису використовували цільну, різану, свіжу та висушену сировину. Мікроскопічні дослідження проводили на сировині фіксованій у суміші спирт-гліцерин-вода (1:1:1). В роботі використовували фотоапарат OLYMPUS Lens FE-140, мікроскоп МБИ-6, мікроскоп БИОЛАМ - М.Результати й обговорення. Визначено основні морфолого-анатомічні ознаки у вітчизняних серіях трави маруни дівочої згідно з ДФУ 2.0. Виявлено додаткові діагностичні ознаки: 4–6-клітинні головчасті волоски; стебло ребристе, в ребрах субепідермально розташована 5–6-шарова кутова коленхіма; склеренхіма розташована над пучками і між ними; судини ксилеми спіральні та пористі; схізо-лізигенні вмістища з брунатним вмістом в паренхімі ложа кошика; сосочкоподібна епідерма несправжньоязичкових квіток; паренхімні, прямостінні клітини епідерми трубчастих квіток; кристали кальцію оксалату в листочках обгортки представлено друзами.Висновки Проведено ідентифікацію трави Tanacetum parthenium за макро- та мікроскопічними ознаками згідно з ДФУ 2.0. Визначено основні діагностичні ознаки стебла, листя, кошиків та квіток. Встановлено додаткові діагностичні ознаки, які запропоновано додати при розробці національної частини монографії «Маруни дівочої трава» для ДФУ.
ФОКУС НА ВАКЦИНАЦІЮ: ПОГЛЯД ЛІКАРІВ ТА БАТЬКІВ І АНАЛІЗ ЇЇ ФАРМАЦЕВТИЧНОГО ЗАБЕЗПЕЧЕННЯ ЩОДО КЕРОВАНИХ ДИТЯЧИХ БАКТЕРІЙНИХ ІНФЕКЦІЙ
Authors: Fedyak I. O. , Bilyk I. P. , Mateyko G. B. 
Published: April 2018

Мета. Висвітлення результатів опитування лікарів та батьків щодо проблем подолання в Україні вакцинокерованих дитячих бактерійних інфекцій (кашлюку та менінгококової інфекції) насамперед шляхом вакцинації, а також вивчення стану фізичної та соціально-економічної доступності вакцин для проведення імунопрофілактики за кошти батьків.Методи і матеріали. У роботі використані методи анонімного анкетування, маркетингового аналізу, графічного представлення результатів.Результати дослідження. 50 % опитаних лікарів вважають, що основна причина відмови батьків від вакцинації – негативна суспільна думка, сформована ЗМІ. Водночас батьки-респонденти заперечують значний вплив ЗМІ на їхній вибір щодо імунопрофілактики, бо в основу відмови вакцинувати дітей ставлять сумніви щодо безпеки (38 %) та якості (32 %) вакцин. Загалом 96 % батьків дали згоду на вакцинацію, а 58 % – за власний кошт. Разом з тим, вітчизняний фармацевтичний ринок виявився неготовим до цього, бо показав недостатню фізичну доступність при умовно фінансовій доступності вакцин проти кашлюку та повну відсутність вакцин для попередження менінгококової інфекції.Висновки. Установлено, що у 2015 і 2017 роках вакцина проти менінгококової інфекції Менактра (США) та вакцини для первинної імунізації від кашлюку АКДП–Біолік (Україна), Інфанрикс (Великобританія) демонстрували незадовільну присутність на українському фармацевтичному ринку. Водночас моніторинг ринку виявив, що присутні на ньому вакцини мали позитивні тенденції їх соціально-економічної доступності при умові матеріального забезпечення сімей, не нижче середньонаціонального рівня.
Endovascular Therapy in Ischemic Stroke With Acute Large‐Vessel Occlusion: Recovery by Endovascular Salvage for Cerebral Ultra‐Acute Embolism Japan Registry 2
Authors: Yoshimura Shinichi , Sakai Nobuyuki , Uchida Kazutaka , Yamagami Hiroshi , Ezura Masayuki , Okada Yasushi , Kitagawa Kazuo , Kimura Kazumi , Sasaki Makoto , Tanahashi Norio , Toyoda Kazunori , Furui Eisuke , Matsumaru Yuji , Minematsu Kazuo , Morimoto Takeshi , Kuwayama Naoya , Ogasawara Kuniaki , Iihara Koji , Takeuchi Masataka , Morimoto Masafumi , Onda Toshiyuki , Shibata Masunari , Ohta Takahiro , Imai Keisuke , Itabashi Ryo , Yamashita Taro , Fukawa Norihito , Kimura Naoto , Doijiri Ryosuke , Ohta Hajime , Enomoto Yukiko , Kanbayashi Chisaku , Yamaura Ikuya , Ishihara Hideyuki , Kamiya Yuki , Hayase Makoto , Nii Kouhei , Kobayashi Junya , Yasuda Hiroaki , Kondo Ryushi , Yamamoto Daisuke , Sakaguchi Manabu , Satomi Junichiro , Yagita Yoshiki , Handa Akira , Shindo Atsushi , Hiyama Nagayasu , Toma Naoki , Tsumoto Tomoyuki , Tsuruta Wataro , Matsumoto Keigo , Kiura Yoshihiro , Yamazaki Takaaki , Hatano Taketo , Matsumoto Yoshihisa , Kojima Takao , Ikeda Norio , Sakamoto Shigeyuki , Ohnishi Hiroyuki , Haraguchi Koichi , Uchiyama Naoyuki 
Published: April 2018

Background
Endovascular therapy has been shown to be effective in patients with acute cerebral large‐vessel occlusion, but real‐world efficacies are unknown.

Methods and Results

We conducted a prospective registry at 46 centers between October 2014 and January 2017. Eligible patients were those who were aged 20 years or older, with acute cerebral large‐vessel occlusion, and who were hospitalized within 24 hours of the onset. We enrolled both consecutive patients who were treated with or without endovascular therapy. Endovascular therapy included thrombectomy, balloon angioplasty, stenting, local fibrinolysis, and piercing. The primary outcome was a favorable outcome as defined by a modified Rankin Scale of 0 to 2 at 90 days after onset. Secondary outcomes were modified Rankin Scale of 0 to 1 and mortality. Safety outcomes were intracerebral hemorrhage or a recurrence of ischemic stroke. We constructed the 2242 (1121 each) propensity score–matched patients cohort based on a propensity score for endovascular therapy and estimated the adjusted odds ratio, followed by sensitivity analyses on original 2399 (1278 in endovascular therapy versus 1121 in no endovascular therapy) patients. In the propensity score–matched cohort, favorable outcomes were observed in 35.3% and 30.7% of patients in the endovascular therapy and no endovascular therapy groups, respectively (
P=
0.02). The adjusted odds ratio for the favorable outcome was 1.44 (95% confidence interval, 1.10–1.86,
P
=0.007). The efficacy of endovascular therapy in achieving favorable outcomes did not differ between our subgroups and in the sensitivity analyses.

Conclusions
Endovascular therapy decreased disabilities at 90 days in real‐world patients with acute cerebral large‐vessel occlusion.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02419794.
Innovative Magnetic Resonance Imaging Markers of Hereditary Cerebral Amyloid Angiopathy at 7 Tesla
Authors: Koemans Emma A. , van Etten Ellis S. , van Opstal Anna M. , Labadie Gerda , Terwindt Gisela M. , Wermer Marieke J.H. , Webb Andrew G. , Gurol Edip M. , Greenberg Steven M. , van Buchem Mark A. , van der Grond Jeroen , van Rooden Sanneke 
Published: April 2018

Background and Purpose—
The aim of the present study is to explore whether using 7 Tesla magnetic resonance imaging, additional brain changes can be observed in hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) patients as compared with the established magnetic resonance imaging features of sporadic cerebral amyloid angiopathy.

Methods—

The local institutional review board approved this prospective cohort study. In all cases, informed consent was obtained. This prospective parallel cohort study was conducted between 2012 and 2014. We performed T
2
*-weighted magnetic resonance imaging performed at 7 Tesla in presymptomatic mutation carriers (n=11, mean age 35±12 years), symptomatic HCHWA-D patients (n=15, mean age 45±14 years), and in control subjects (n=29, mean age 45±14 years). Images were analyzed for the presence of changes that have not been reported before in sporadic cerebral amyloid angiopathy and HCHWA-D. Innovative observations comprised intragyral hemorrhaging and cortical changes. The presence of these changes was systematically assessed in all participants of the study.

Results—

Symptomatic HCHWA-D-patients had a higher incidence of intragyral hemorrhage (47% [7/15], controls 0% [0/29],
P
<0.001), and a higher incidence of specific cortical changes (40% [6/15] versus 0% [0/29],
P
<0.005). In presymptomatic HCHWA-D-mutation carriers, the prevalence of none of these markers was increased compared with control subjects.

Conclusions—
The presence of cortical changes and intragyral hemorrhage are imaging features of HCHWA-D that may help recognizing sporadic cerebral amyloid angiopathy in living patients.
Adsorptive hydrogen chloride and combined hydrogen chloride–hydrogen sulphide removal from biogas for solid oxide fuel cell application
Authors: Weinlaender Christof , Neubauer Raphael , Hauth Martin , Hochenauer Christoph 
Published: April 2018

In order to reduce the toxic effect on solid oxide fuel cells performance caused by biogas contaminated with hydrogen chloride and hydrogen sulphide, the purification of biogas is essential. Adsorptive gas purification is a highly auspicious technology to provide pollution-free biogas for solid oxide fuel cell-based power units. In this work the authors examined the influence of different parameters onto the adsorption capacity of three commercially available sorbents. Experimental runs in a laboratory glass downflow fixed-bed reactor were carried out to analyse the adsorption capacity of a potassium carbonate impregnated activated carbon and two sorbents based on a mixture of aluminium oxide and silicon dioxide. Hydrogen chloride removal was accomplished with the impregnated activated carbon and metal oxide-based sorbents. Hydrogen chloride adsorption capacity was analysed under space velocities 8000 and 16,000 h−1. In addition, the effect of a hydrogen chloride inlet concentration of 100 and 1000 ppmv was investigated. Furthermore, pellets in the size of 3–4 mm in diameter were crushed into a fraction between 500 and 1000 µm to investigate the influence of particle size on hydrogen chloride adsorption capacity. Additionally, the combined adsorption of hydrogen chloride and hydrogen sulphide was realized using the impregnated activated carbon. The experimental runs and the results obtained in this work provide useful data for designing an adsorption reactor to clean up biogas and optimizing the process.
Pilot investigation of the effect of carvedilol on stress-precipitated smoking-lapse behavior
Authors: Verplaetse Terril L , Weinberger Andrea H , Ashare Rebecca L , Pittman Brian P , Shi Julia M , Tetrault Jeanette M , Lavery Meaghan , McKee Sherry A 
Published: April 2018

Introduction: Separate α1- and β-adrenergic antagonists have shown efficacy in reducing nicotine-motivated behaviors in rodents and humans, supporting a role for the noradrenergic system in mediating the reinforcing properties of drugs of abuse. However, the effect of the combined α1- and β-adrenergic antagonist, carvedilol, on stress-related smoking is unknown. Methods: Using a well-established human laboratory model of stress-precipitated smoking-lapse behavior, we examined whether carvedilol (0 or 50 mg/day; between subject, n=17 per group), administered to steady-state, would attenuate the ability to resist smoking following stress imagery (vs. neutral imagery) and reduce subsequent smoking self-administration in nicotine-deprived smokers ( n = 34 total). Tobacco craving, withdrawal, and physiologic reactivity were also assessed. Results: Latency to start smoking and number of cigarettes smoked during the self-administration period did not differ by medication condition. Counter to our hypothesis, tobacco craving demonstrated a medication × time effect, with greater craving in the carvedilol condition. Systolic blood pressure and heart rate demonstrated lower values in the carvedilol versus placebo group, consistent with known effects of carvedilol. Conclusion: While carvedilol attenuated physiologic reactivity consistent with its clinical indication, beneficial effects on smoking outcomes were absent in this preliminary investigation and may suggest possible worsening. Future work may benefit from discerning the single versus combined effects of α1- and β-adrenergic antagonism on smoking outcomes.
Multicentered Study Evaluating Pharmacy Students’ Perception of Palliative Care and Clinical Reasoning Using Script Concordance Testing
Authors: Atayee Rabia S. , Lockman Kashelle , Brock Cara , Abazia Daniel T. , Brooks Tracy L. , Pawasauskas Jayne , Edmonds Kyle P. , Herndon Christopher M. 
Published: April 2018

Introduction: As the role of the pharmacist on the transdisciplinary palliative care team grows, the need for adequate instruction on palliative care and clinical reasoning skills in schools of pharmacy grows accordingly. Methods: This study evaluates second- and third-year pharmacy students from 6 accredited schools of pharmacy that participated in surveys before and after the delivery of a didactic palliative care elective. The survey collected student demographics, perceptions of the importance of and student skill level in palliative care topics. The script concordance test (SCT) was used to assess clinical decision-making skills on patient cases. Student scores on the SCT were compared to those of a reference panel of experts. Results: A total of 89 students completed the pre-/postsurveys and were included in data analysis. There was no statistically significant difference in student perceived importance of palliative care skills before and after the elective. Students from all 6 institutions showed significant increase in confidence in their palliative care skills at the end of the course. There was also a significant improvement across all institutions in clinical reasoning skills in most of the SCT questions used to assess these skills. Conclusions: Students choosing an elective in palliative care likely do so because they already have an understanding of the importance of these topics in their future practice settings. Delivery of a palliative care elective in the pharmacy curriculum significantly increases both student confidence in their palliative care skills and their clinical reasoning skills in these areas.
Building New Approaches to Risk Reduction With Social Networks and People Who Smoke Illegal Drugs From Participatory Community-Based Research
Authors: Jozaghi Ehsan , Buxton Jane A. , Thomson Erica , Marsh Samona , Gregg Delilah , Bouchard Martin 
Published: April 2018

Background: Global cases of overdose-related deaths attributed to synthetic opioids are reaching epidemic proportion in many jurisdictions. While the main focus of health agencies and the different levels of government has been to combat the cases linked to injection drug use, the deaths attributed to smoking illegal drugs have not gained the same attention. Moreover, little attention has been given to the role of people with past or current experiences of illegal drug use and how their social networks can mitigate the risk of a highly stigmatized behavior such as smoking illegal drugs. Methods: The study concerns the first social network research conducted via a community-based participatory action methodology in two distinct urban (Vancouver) and rural (Abbotsford) centers in British Columbia, Canada. The study will identify the influence of social networks on people who smoke illegal drugs (PWSID) and their adherence to interventions aimed at reducing harm. Through community consultations, members of the Vancouver Area Network of Drug Users and the British Columbia/Yukon Association of Drug War Survivors not only assisted with the design of this research project but also assisted with the data collection, management, protection and entry of demographic, and network information. Discussion: Many traditional qualitative and quantitative methods have not effectively engaged people who use drugs as researchers or collaborators due to stigma related to illegal drug use. The aim of this study is to recognize that everyone within the network of PWSID is a few steps away from harm. Therefore, we aim to reduce the harm associated with smoking of illegal drugs, especially for PWSID that are at the highest risk. At the same time, we hope that the social network research via a participatory community-based approach will mobilize PWSID in the process and offer a different method of knowledge construction from the traditional positivist approaches.
Characterization of a rare variant (c.2635-2A>G) of the MSH2 gene in a family with Lynch syndrome
Authors: Cariola Filomena , Disciglio Vittoria , Valentini Anna M. , Lotesoriere Claudio , Fasano Candida , Forte Giovanna , Russo Luciana , Di Carlo Antonio , Guglielmi Floranna , Manghisi Andrea , Lolli Ivan , Caruso Maria L. , Simone Cristiano 
Published: April 2018

Introduction: Lynch syndrome is caused by germline mutations in one of the mismatch repair genes ( MLH1, MSH2, MSH6, and PMS2) or in the EPCAM gene. Lynch syndrome is defined on the basis of clinical, pathological, and genetic findings. Accordingly, the identification of predisposing genes allows for accurate risk assessment and tailored screening protocols. Case Description: Here, we report a family case with three family members manifesting the Lynch syndrome phenotype, all of which harbor the rare variant c.2635-2A>G affecting the splice site consensus sequence of intron 15 of the MSH2 gene. This mutation was previously described only in one family with Lynch syndrome, in which mismatch repair protein expression in tumor tissues was not assessed. In this study, we report for the first time the molecular characterization of the MSH2 c.2635-2A>G variant through in silico prediction analysis, microsatellite instability, and mismatch repair protein expression experiments on tumor tissues of Lynch syndrome patients. The potential effect of the splice site variant was revealed by three splicing prediction bioinformatics tools, which suggested the generation of a new cryptic splicing site. The potential pathogenic role of this variant was also revealed by the presence of microsatellite instability and the absence of MSH2/MSH6 heterodimer protein expression in the tumor cells of cancer tissues of the affected family members. Conclusions: We provide compelling evidence in favor of the pathogenic role of the MSH2 variant c.2635-2A>G, which could induce an alteration of the canonical splice site and consequently an aberrant form of the protein product (MSH2).