bluuebunny/crossref_metadata_2025_split huggingface dataset:
SMAD4 Mutation in Small Cell Transformation of Epidermal Growth Factor Receptor Mutated Lung Adenocarcinoma
Authors: D'Haene Nicky , Le Mercier Marie , Salmon Isabelle , Mekinda Zita , Remmelink Myriam , Berghmans Thierry 
Published: November 2018

Abstract

The large screening of exons 18 to 21 of the epidermal growth factor receptor (EGFR) gene may lead to the discovery of rare, atypical molecular alterations for which the sensitivity to tyrosine kinase inhibitors (TKIs) remains uncertain. We are reporting a rare exon 18 EGFR mutation (p.E709_710 &gt; D) that confers sensitivity to second-generation EGFR TKI (afatinib), lasting for 1 year. Tumor progression biopsy showed small cell lung cancer transformation, associated with a SMAD4 mutation.

Key Points
A rare exon 18 epidermal growth factor receptor mutation with sensitivity to afatinib is reported. Small cell transformation was observed at tumor progression. Acquisition of a SMAD4 mutation was observed at tumor progression.
First-in-Human Phase I Study of MBC-11, a Novel Bone-Targeted Cytarabine-Etidronate Conjugate in Patients with Cancer-Induced Bone Disease
Authors: Zinnen Shawn Patrick , Karpeisky Alexander , Von Hoff Daniel D. , Plekhova Larisa , Alexandrov Alexander 
Published: November 2018

Abstract

Lessons Learned
Results are consistent with MBC-11 targeting and treating cancer-induced bone lesions by concentrating cytarabine and etidronate at the site of disease. MBC-11 was well tolerated, with an maximum tolerated dose of 5 mg/kg per day and myelosuppression as the principal toxicity. Treatment significantly reduced cancer cell activity in over half of bone lesions detected at baseline. MBC-11 pharmacokinetic and pharmacodynamic parameters are consistent with the novel drug design goals, and encouraging results warrant further clinical development.

Background
MBC-11 is a first-in-class conjugate of the bone-targeting bisphosphonate etidronate covalently linked to the antimetabolite cytarabine (araC). This first-in-human phase I dose escalation study assessed safety, tolerability, maximum tolerated dose (MTD), plasma pharmacokinetics, bone turnover, tumor biomarkers, and bone lesion activity by fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) imaging.

Methods
Fifteen patients with advanced solid cancers and cancer-induced bone disease (CIBD) were treated with 0.5–10 mg/kg per day of MBC-11 administered daily for 5 days of every 4 weeks for up to four cycles.

Results
Grade 1–2 myelosuppression, involving all lineages, was the principal toxicity. Two of three patients treated with 10 mg/kg experienced dose-limiting grade 4 neutropenia and thrombocytopenia (adverse event [AE] duration ≤5 days); the MTD was 5 mg/kg. Four of five patients with pretreatment elevations of the bone resorption marker TRAP5b (tartrate resistant acid phosphatase-5b) had persistent decrements. Six of 13 patients who reported baseline pain noted a reduction after MBC-11. 18F-FDG-PET/CT imaging demonstrated partial metabolic responses in three patients and stable metabolic responses in three other patients. SUVmax (standard unit of emission normalized to total uptake) was reduced by at least 25% in 110 (52%) of 211 bone lesions. Significant activity was noted across all doses, and myelosuppression increased with dose.

Conclusion
At MBC-11 doses that were well tolerated, substantial reductions in metabolic activity of bone-associated cancer cells provide a foundation for further disease-directed efficacy studies.
Electrocardiographic Changes in Athletes of Black Ethnicity
Authors: Ismail Dillan , Eriksson Anders , Mörner Stellan , Rydberg Annika 
Published: November 2018

AbstractIntensive participation in sport has positive physiological effects on the heart. The contractility of the heart improves, the ejection fraction increases and the muscle mass of the heart increases, thus leading to a greater cardiac output. Despite these positive effects, there is still an increased risk for acute cardiac events. The workload of the heart can be very high in some sports and may in some cases be the reason for sudden cardiac death. In these cases, there is often an underlying heart disease (cardiomyopathy) unknown before the actual event. Electrocardiographic examination (ECG) may reveal some of these diseases but although ECG examinations can be a useful tool to discover pathological conditions, there could be difficulties in interpreting different ECG patterns, especially in athletes. In some cases, athletes may exhibit ECG patterns that are similar to those in heart diseases such as cardiomyopathies (QRS-amplitudes, ST-segment elevation and T wave inversions in lateral leads). This pattern is even more common in athletes of African origins. Furthermore, cardiomyopathies such as hypertrophic cardiomyopathy (HCM) are more common among athletes with African heritage than in white athletes. Thus correct interpretation of ECG is crucial for several reasons: to distinguish between benign physiological (‘athlete’s heart’) and pathological changes, to lower the risk of sudden cardiac death, and to save time and money by not undertaking further examination of the heart.
Authors’ Responsibilities and Ethical Publishing
Authors: Shewan Louise Gabrielle , Stewart Coats Andrew J. , Henein Michael 
Published: November 2018

The International Cardiovascular Forum Journal requires authors to abide by the following guidelines:Manuscript: The corresponding author declares that the manuscript has not been published and is not under consideration elsewhere.Authorship: The corresponding author takes full responsibility for the list of authors. Any modification to the author list including order and composition can only be approved by the Editor-in-Chief following signed agreement from all the authors listed on the original submission.Ethics: The corresponding author states that the material presented has been obtained with the approval of all appropriate animal and/or human ethics committee(s).Permissions: The corresponding author on behalf of all authors confirms whether explicit written consent to publish has been received from any people described, pictured, or recorded and that formal copyright clearance is obtained to publish any video or audio recordings.Registration of Clinical Trials: Prospective registration of any clinical trial in a publically accessible database is a requirement for later publication of such trials in ICFJ. In exceptional circumstance if the trial is not registered, or is registered retrospectively, the reasons for this must be given.Competing Interests: All authors must declare all relevant competing interests (financial, or non-financial, professional, or personal) and state all funding sources.Attribution: The corresponding author accepts full responsibility for the accurate citation and acknowledgement of any material reproduced from other publications including the author’s own prior work.It is incumbent upon the corresponding author to consult the Editor-in-Chief should there be any variance of the above. The Editor-in-Chief retains the right to retract any submission found to be in breach of the above guidelines.
Alterations in the Expression of Amyloid Precursor Protein Cleaving Enzymes mRNA in Alzheimer Peripheral Blood
Authors: Wongchitrat Prapimpun , Pakpian Nattaporn , Kitidee Kuntida , Phopin Kamonrat , Dharmasaroja Pornpatr A. , Govitrapong Piyarat 
Published: November 2018

Background:
Alzheimer’s disease (AD) is the most common cause of dementia in elderly
populations. Changes in the expression of the Amyloid Precursor Protein (APP)-cleaving enzymes directly
affect the formation of Amyloid Beta (Aβ) plaques, a neuropathological hallmark of AD.

Objective:
We used peripheral blood from AD patients to investigate the expression of genes related to
APP-processing [(β-site APP-cleaving enzyme 1 (BACE1), presenilin1 (PSEN1), and a disintegrin and
metalloproteinase family 10 (ADAM10) and 17 (ADAM17)] and the epigenetic genes sirtuin (SIRT)1-3,
which regulate Aβ production.

Method: Real-time polymerase chain reactions were performed to determine the specific mRNA levels
in plasma. The mRNA levels in AD patients were compared to those in healthy persons and assessed in
relation to the subjects’ cognitive performance.

Results:

BACE1 mRNA level in AD subjects was significantly higher than those of healthy controls,
whereas ADAM10 level was significantly lower in the AD subjects. The SIRT1 level was significantly
decreased, while that of SIRT2 was increased in AD subjects and elderly controls compared to levels in
healthy young control. In addition, correlations were found between the expression levels of BACE1,
ADAM10 and SIRT1 and cognitive performance scores. Total Aβ (Aβ40+Aβ42) levels and the Aβ40/Aβ42
ratio were significantly increased in the AD subjects, whereas decrease in plasma Aβ42 was found in AD
subjects. There was a negative correlation between Aβ40 or total Aβ and Thai Mental State Examination
(TMSE) while there was no correlation between Aβ40/Aβ42 ratio or Aβ42 and TMSE.

Conclusion:

The present findings provide evidence and support for the potential roles of these enzymes
that drive Aβ synthesis and for epigenetic regulation in AD progression and development, which can
possibly be considered peripheral markers of AD.
An Environmentally-Benign Synthesis of Spiro-benzo[1,4]diazepines Using Multi Phase Nano-titania as a Highly Efficient Catalyst via MAOS Technique
Authors: Gupta Sharoni , Punjabi Pinki B. , Ameta Chetna , Ameta Rakshit 
Published: November 2018

Aim and Objective:
Benzodiazepines and indole fused heterocycles are pharmacologically
significant scaffolds. Trivial work on indole fused benzodiazepine compounds is reported in the literature.
Hence, it is imperative to explore the synthesis of indole-fused benzodiazepines that may act as a template for
biological studies in the future. Hence, in the present work, the synthesis of indole fused benzodiazepine
derivatives was undertaken using multi-phase nano-titania as catalyst under microwave irradiation.

Materials and Methods:
MAOS technique was used to carry out the synthesis of spiro-benzo [1,4]diazepine
derivatives in the presence of multiphase nano-titania as a catalyst. Nano-titania was prepared by sol-gel
method and characterized by XRD, FT-IR, FESEM, EDS and thermogravimetric techniques. The synthesized
spiro-benzo [1,4] diazepine derivatives were identified by physical and spectral methods.

Results:
Synthesized compounds were obtained in excellent yields in a short span of time. The synthesis was
also carried out in the presence of conventional catalysts in addition to nano-titania. Among all the catalysts,
the best result was obtained with nano-titania. The amount of nano-titania was optimized to be 0.05g giving 93-
95% yield of products. The study of reusability of nano-titania revealed that it could be reused up to four times
with a negligible change in efficiency.

Conclusion:
The paper reports an efficient, cost-effective and environmentally benign approach for the
synthesis of spiro-benzo [1,4] diazepine derivatives in the presence of multiphase nano-titania catalyst under
microwave irradiation.
Design, Synthesis, Antimicrobial and Anti-biofilm Evaluation, and Molecular Docking of Newly Substituted Fluoroquinazolinones
Authors: Zayed Mohamed F. , Ibrahim Sabrin R.M. , Habib EL-Sayed E. , Hassan Memy H. , Ahmed Sahar , Rateb Heba S. 
Published: November 2018

Background:
Quinazolines and quinazolinones derivatives are well known for their
important range of therapeutic activities.

Objective:
The study aims to carry out the synthesis of some derivatives of substituted
fluoroquinazolinones based on structure-based design and evaluation of their antibacterial, antifungal,
and anti-biofilm activities.

Methods:
Compounds were chemically synthesized by conventional methods. Structures were established
on the basis of spectral and elemental analyses. The antimicrobial potential was tested
against various microorganisms using the agar disc-diffusion method. MIC and MBC as well as
anti-biofilm activity for the highly active compounds were assessed. Moreover, the computational
studies were performed using Auto dock free software package (version 4.0) to explain the predicted
mode of binding.

Results:
All derivatives (5-8), (10a-g), and (A-H) were biologically tested and showed significant
antimicrobial activity comparable to the reference compounds. Compounds 10b, 10c, and 10d had
a good MIC and MBC against Gram-positive bacteria, whereas 10b and 10d showed significant
MIC and MBC against Gram-negative bacteria. However, compounds E and F exhibited good
MIC and MBC against fungi. Compound 10c and 8 exhibited significant anti-biofilm activity towards
S. aureus and M. luteus. Molecular docking study revealed a strong binding of these derivatives
with their receptor-site and detected their predicted mode of binding.

Conclusion:
The synthesized derivatives showed promising antibacterial, antifungal, and antibiofilm
activities. Modeling study explained their binding mode and showed strong binding affinity
with their receptor-site. The highly active compounds 5 and 10c could be subjected to future
optimization and investigation to be effective antimicrobial agents.
Spirocyclohexadienones as an Uncommon Scaffold for Acetylcholinesterase Inhibitory Activity
Authors: Gomes Ralph C. , Sakata Renata P. , Almeida Wanda P. , Coelho Fernando 
Published: November 2018

Background:The most important cause of dementia affecting elderly people is the Alzheimer’s disease (AD). Patients affected by this progressive and neurodegenerative disease have severe memory and cognitive function impairments. Some medicines used for treating this disease in the early stages are based on inhibition of acetylcholinesterase. Population aging should contribute to increase the cases of patients suffering from Alzheimer's disease, thus requiring the development of new therapeutic entities for the treatment of this disease.Methods:The objective of this work is to identify new substances that have spatial structural similarity with donepezil, an efficient commercial drug used for the treatment of Alzheimer's disease, and to evaluate the capacity of inhibition of these new substances against the enzyme acetylcholinesterase.Results:Based on a previous results of our group, we prepared a set of 11 spirocyclohexadienones with different substitutions patterns in three steps and overall yield of up to 59%. These compounds were evaluated in vitro against acetylcholinesterase. We found that eight of them are able to inhibit the acetylcholinesterase activity, with IC50 values ranging from 0.12 to 12.67 µM. Molecular docking study indicated that the spirocyclohexadienone, 9e (IC50 = 0.12 µM), a mixedtype AChE inhibitor, showed a good interaction at active site of the enzyme, including the cationic (CAS) and the peripheral site (PAS).Conclusion:We described the first study aimed at investigating the biological properties of spirocyclohexadienones as acetylcholinesterase inhibitors. Thus, we have identified an inhibitor, which provided valuable insights for further studies aimed at the discovery of more potent acetylcholinesterase inhibitors.
Quantitative Determination of Ginsenoside Rg1 in Rat Plasma by Ultrahigh Performance Liquid Chromatography-tandem Mass Spectrometry (UHPLC-MS/MS) and its Application in a Pharmacokinetics and Bioavailability Study
Authors: Weng Qinghua , Zhang Zhenan , Chen Linglong , You Weiwei , Liu Jinlai , Li Feifei , Chen Lianguo , Jiang Xiajuan 
Published: November 2018

Background:Ginsenoside Rg1 (Rg1) is the main active compound of ginseng herbs.Objective:The aim of this study is to develop a rapid, selective and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine the levels of Rg1 in rat plasma and investigate the pharmacokinetics and bioavailability of Rg1 in rats.Methods:Chromatographic separation was achieved on an UHPLC-MS/MS system with an UPLC BEH C18 column using an elution gradient of a mixture of acetonitrile and water (with 0.1% formic acid). The analytes were quantitatively determined by negative-mode electrospray tandem MS.Results:The linearity of the calibration curve was from 2 to 1,000 ng/mL (r ≥ 0.9956), and the lower limit of quantification was 2 ng/mL. The inter-day and intra-day precision were both lower than 12.0%, and the accuracy ranged from 90.6 to 109.7%. The recovery of the targets was higher than 87.0%, and the matrix effect at three different analyte concentrations were from 89.0 to 97.2%. The bioavailability of Rg1 was only 6.1% due to a poor oral absorption.Conclusion:This new quantitative method was found to be sensitive, rapid and selective, and was successfully used to study the pharmacokinetics of Rg1 after intravenous and oral administration in rats.
Delayed Hemolytic Anemia after Treatment with Artesunate: Case Report and Literature Review
Authors: Salehi Mohammadreza , Masoumi-Asl Hosein , Assarian Mehrdad , Khoshnam-Rad Niloofar , Haghi Afsaneh Motevalli , Nikbakht Mehran , Khalili Hossein 
Published: November 2018

Background:
In recent years, few cases of post-artemisinin delayed hemolysis have been reported.

Objective:
All cases of post-artemisinin delayed hemolysis were reported from non-middle east areas.
No case of post-artemisinin delayed hemolysis has yet been reported from this region. In this paper, we
describe a case of post-artemisinin delayed hemolysis in an Iranian female. Moreover, previous reports
have been reviewed.

Methods:
Patient’s data including demographic characteristics, past medical, drug and travelling
history, present illness, vital signs, laboratory data, clinical course of current illness and follow-up
findings were considered.

Results:
A 27-year-old female with a recent travel history to Ghana admitted with severe falciparum
malaria. She was successfully treated with parenteral artesunate. However after 12 days of post
artesunate treatment, she returned with dark urine, malaise and fatigue.

Conclusion:
Considering the clinical course and base on a reliable causality assessment scale, post
artesunate delay hemolytic anemia was possible.
Withdrawal Notice: The Effectiveness of Hierarchical Structure on Cloud Systems
Authors: Alshamrani Sultan 
Published: November 2018

The article has been withdrawn at the request of the authors and editor of the journal Recent Advances in Computer Science
and Communications.;

The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php

Bentham Science Disclaimer:
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of their article is transferred to the publishers if and when the article is accepted for publication.
Микробный пейзаж у больных острой парапневмонической эмпиемой плевры и оптимизация эмпирической антибактериальной терапии
Authors: Savchenko S.I. 
Published: November 2018

Актуальность. Эмпиема плевры (ЭП), как и любое гнойно-воспалительное заболевание, требует назначения антибактериальной терапии и определения чувствительности микроорганизмов к антибиотикам. Однако микробный пейзаж и антибиотикорезистентность бактерий постоянно меняются. Это делает актуальным изучение спектра и свойств возбудителей ЭП. Цель исследования: изучить микробиологическую характеристику больных острой ЭП плевры и разработать рекомендации по оптимизации эмпирической антибактериальной терапии. Материалы и методы. Проведено комплексное ретроспективное исследование 124 случаев заболевания острой неспецифической парапневмонической ЭП. Мужчин было 92 (74,2 %). Медиана возраста больных составила 50,3 (38; 61) года. Результаты. При микробиологическом исследовании плеврального экссудата положительный результат получен в 34 (27,4 %) случаях. Необходимо отметить, что большинство больных (101 — 81,5 %) получали предшествующую антибактериальную терапию. Так, среди пациентов, ранее не получавших лечения, этот показатель был существенно выше — 12 (52,2 %) vs 22 (21,8 %), p < 0,01. Грамотрицательные и грамположительные микроорганизмы встречались одинаково часто — 19 (51,4 %) и 18 (48,6 %) изолятов соответственно. Среди причинной микрофлоры выделяются 5 основных возбудителей: Ps. aeruginosa, St. epidermidis, St. aureus, Str. pneumoniae, Str. mitis, которые суммарно составили 59,4 % изолятов. Выводы. Культуральные исследования при ЭП характеризуются значительным количеством негативных результатов (72,6 %). С учетом чувствительности основных возбудителей к антибиотикам рекомендованная эмпирическая антибактериальная терапия первой линии должна состоять из комбинации производных имидазола (метронидазол, орнидазол) и цефоперазона с сульбактамом. В качестве препарата второй линии целесообразно использование гатифлоксацина, а антибиотика резерва — гентамицина или тобрамицина.
Современные возможности ургентной фиброэзофагогастродуоденоскопии в диагностическо-лечебном алгоритме больных с острой хирургической патологией
Authors: Filonenko V.A. , Lesnoy V.V. , Lesnaya A.S. 
Published: November 2018

Актуальность. Роль фиброэзофагогастродуоденоскопии неоспорима в диагностике осложнений язвенной болезни, но эндоскопический этап лечения занимает ведущее место в терапии механической желтухи, псевдокист поджелудочной железы, острой высокой тонкокишечной непроходимости, что требует дальнейшего совершенствования метода и расширения возможностей для его ургентного использования. Цель исследования. Проанализировать роль ургентной фиброэзофагогастродуоденоскопии в лечебно-диагностическом алгоритме у больных с острой хирургической патологией. Материалы и методы. Проведен ретроспективный анализ историй болезни пациентов, госпитализированных в хирургическое отделение с подозрением на острую хирургическую абдоминальную патологию, которым по экстренным показаниям была выполнена фиброэзофагогастродуоденоскопия. 377 пациентам выполнено 489 ургентных фиброэзофагогастродуоденоскопий. Показанием к ургентной фиброэзофагогастродуоденоскопии были: подозрение или клиника острого желудочно-кишечного кровотечения — 225 (59,7 %) больных; подозрение на острую хирургическую патологию брюшной полости — 123 (32,6 %) больных; подозрение или клиника инородного тела верхних отделов желудочно-кишечного тракта — 29 (7,7 %) больных. Результаты. У пациентов с подозрением на острое желудочно-кишечное кровотечение диагностировали неварикозное кровотечение у 171 (76 %) пациента и произвели комбинированный эндоскопический гемостаз у 61 больного. У 22 пациентов выполнена успешная эндоскопическая экстракция инородных тел пищевода. У 33 (26,8 %) больных с помощью фиброэзофагогастродуоденоскопии верифицировали прикрытую перфоративную язву. У 22 (17,8 %) больных были выявлены признаки сдавления извне, что у 8 больных соответствовало эндоскопическому симптому панкреатического порога (псевдопанкреатическая киста, парапанкреатический инфильтрат), а у 14 больных выявлено сдавление латеральной стенки двенадцатиперстной кишки (подпеченочный абсцесс, паравезикальный инфильтрат). В 17 % случаев с помощью фиброэзофагогастродуоденоскопии была исключена острая хирургическая патология и верифицировано гастроэнтерологическое заболевание. Выводы. Ургентная фиброэзофагогастродуоденоскопия является высокоинформативным диагностическим методом, что позволяет своевременно подтвердить острую хирургическую патологию и произвести ее коррекцию.