bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel Bcl-2 inhibitor, BM-1197, Induces apoptosis in Malignant Lymphoma Cells through the Endogenous Apoptotic Pathway
Authors: Sun Yue-Li , Jiang Wen-Qi , Luo Qiu-Yun , Yang Da-Jun , Cai Yu-Chen , Huang Hui-Qiang , Sun Jian 
Published: July 2019

Abstract
Background: Bcl-2 family members play an important role in the development of malignant lymphoma and can induce drug resistance in anticancer treatment. The development of small molecules targeting Bcl-2 family protein can be new strategy for malignant lymphoma treatment. In this study, we investigate the antitumor effect and the cellular mechanism of a novel Bcl-2/Bcl-xL dual inhibitor BM-1197 in DCBCL and Burkitt lymphoma cells. Methods: CCK-8 assay was used to detect cell viability. Apoptosis was determined by Hoechst 33258 staining and flow cytometry. The activity of caspase-3/caspase-9 was determined using the caspase-3/ caspase-9 activity kit. Western blotting analysis was performed to evaluate the change of protein expression. The functional analysis was evalueated via immunoprecipitation and siRNA interference. Human malignant lymphoma xenograft models in nude mice were established for in vivo efficacy detection. Results: We find that BM-1197 exerts potent growth-inhibitory activity against lymphoma cells which harbor Bcl-2 and Bcl-xL high expression in vitro and has synergistic effect with chemotherapeutic drugs. Mechanistically, we see that the intrinsic apoptosis pathway is activated upon BM-1197 treatment. BM-1197 affects the protein interaction of Bak/Bcl-xl, Bim/Bcl-2, Bim/Bcl-xl, PUMA/Bcl-2 and induced conformational change in the Bax protein.which results in activation of Bax and release cytochrome c, and activated caspase -9, -3, -7 and finally induce cell apoptosis. Furthermore, our data demonstrates that BM-1197 exhibits strong anti-tumor effects against established human malignant lymphoma xenograft models. Conclusions: Our study demonstrated BM-1197 exerts potent antitumor effects both in vitro and in vivo, and provides promising preclinical data for further development of BM-1197 in malignant lymphoma.
β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells
Authors: Huang Zhibin , Li Guihuan , Zhang Zhishuai , Gu Ruonan , Wang Wenyang , Lai Xiaoju , Cui Zhong-kai , Zeng Fangyin , Xu Shiyuan , Deng Fan 
Published: July 2019

Abstract
Background

Chronic stress is well known to promote tumor progression, however, the mechanisms that underlie the association of chronic stress with cancer metastasis remain elusive.

Methods

First, the changes in migration and invasion ability of prostate cancer cell lines PC-3 and DU145 were assessed by transwell migration assay. And HIF-1α expression of osteoblasts and the momentous proteins of epithelial-mesenchymal transition (EMT) of PC-3 and DU145 cells were examined by western blot. Then, an analysis of the main cytokines associated with bone metastasis was performed in osteoblasts by qRT-PCR. Finally, HIF-1α siRNA and inhibitor YC-1 were used to assess the reverse of isoproterenol (ISO)-induced changes of HIF-1α in osteoblasts, and β2-adrenergic receptor (β2AR) inhibitor ICI118,551 and CXCR4 inhibitor LY2510924 were used to antagonizes migration and invasion of PC-3 and DU145 cells induced by osteoblasts triggered by ISO.

Results

In this study, ISO, a non-selective β-adrenergic receptor (βAR) agonist, used as a pharmacological surrogate of sympathetic nerve activation induced by chronic stress, exhibits no direct effect on migration and invasion of PC-3 and DU145 prostate cancer cells. Whereas, osteoblasts pretreated with ISO promote EMT and migration as well as invasion of PC-3 and DU145 cells, which can be inhibited by β2AR inhibitor. Mechanically, ISO increases the secretion of CXCL12 via the β2AR-HIF-1α signaling in osteoblasts. Moreover, inhibiting CXCL12-CXCR4 signaling with LY2510924 blunts the effects of osteoblasts in response to ISO on EMT and migration as well as invasion of PC-3 and DU145 cells.

Conclusions

These findings indicate that β2AR-HIF-1α-CXCL12 signaling in osteoblasts facilitates migration and invasion as well as EMT of prostate cancer cells, and may play a potential role in affecting bone metastasis of prostate cancer.
Opportunities for selective reporting of harms in randomized clinical trials: Selection criteria for nonsystematic adverse events
Authors: Mayo-Wilson Evan , Fusco Nicole , Hong Hwanhee , Li Tianjing , Canner Joseph K. , Dickersin Kay 
Published: July 2019

Abstract
Background: Adverse events (AEs) in clinical trials may be reported in multiple sources. Different methods for reporting adverse events across trials, or across sources for a single trial, may produce inconsistent information about the adverse events associated with interventions.
Methods: We compared the methods authors use to decide which AEs to include in a particular source (i.e., “selection criteria”), including the number of different types of AEs reported (i.e., rather than the number of events). We compared sources (e.g., journal articles, clinical study reports [CSRs]) of trials for two drug-indications: gabapentin for neuropathic pain and quetiapine for bipolar depression. Electronic searches were completed in 2015. We identified selection criteria and assessed how criteria affected AE reporting.
Results: We identified 21 gabapentin and 7 quetiapine trials. We found 6 gabapentin CSRs and 2 quetiapine CSRs, all written by drug manufacturers. All CSRs reported all AEs without applying selection criteria; by comparison, no other source reported all AEs, and 15/68 (22%) gabapentin sources and 19/48 (40%) quetiapine sources reported using selection criteria. Selection criteria greatly affected the number of AEs reported. For example, 67/316 (21%) AEs in one quetiapine trial met the criterion “occurring in ≥2% of participants in any treatment group,” while only 5/316 (2%) AEs met the criterion, “occurring in ≥10% of quetiapine-treated patients and twice as frequent in the quetiapine group as the placebo group.”
Conclusions: Selection criteria for reporting AEs vary across trials and across sources for individual trials. If investigators do not pre-specify selection criteria, they might “cherry-pick” AEs based on results. Even if investigators pre-specify selection criteria, selective reporting will produce biased meta-analyses and clinical practice guidelines. Data about all AEs identified in clinical trials should be publicly available; however, sharing data will not solve all the problems identified in this study.
Early Adolescent Skills for Emotions (EASE) intervention for the treatment of psychological distress in adolescents: Study protocol for randomised controlled trials in Lebanon and Jordan
Authors: Brown Felicity Louise , Steen Frederik , Taha Karine , Aoun May , Bryant Richard A. , Jo Mark J.D. , Malik Aiysha , Ommeren Mark van , Abualhaija Adnan , Aqel Ibrahim Said , Ghatasheh Maha , Habashneh Rand , Sijbrandij Marit , Chammay Rabih El , Watts Sarah , Akhtar Aemal 
Published: July 2019

Abstract
Background
There are significant barriers to accessible, quality mental health care for young adolescents affected by adversity. In an attempt to overcome this, the World Health Organization (WHO) has developed the Early Adolescent Skills for Emotions (EASE) psychological intervention for young adolescents with internalizing problems. EASE is group-based (seven sessions for adolescents, three sessions for their caregivers) and can be delivered by non-specialist providers. This paper outlines the study protocols for two trials of EASE in the Middle-East - one in Lebanon and one in Jordan.

Methods
We will conduct two, single-blind, two-arm, individually randomised group treatment trials in Lebanon and Jordan, with at least 445 young adolescents per trial. Adolescents will be screened eligible for the trial if they demonstrate levels of psychological distress indicative of internalizing problems requiring treatment. Participants will be randomly assigned to receive the EASE intervention, or enhanced usual care (one home-visit psychoeducation session). The primary outcome is reduction in overall child-reported psychological distress over time, with 3 months post-treatment as the primary end-point. Secondary child-reported outcomes include post-traumatic stress symptoms, depression symptoms, daily functioning, and wellbeing. Secondary caregiver-reported outcomes include parenting style, overall child distress, and caregiver psychological distress. Coping strategy use will be explored as a mediator of treatment effects, and relevant moderators of treatment effects will be explored.

Discussion
These trials will provide the first assessments of the effectiveness of the EASE intervention for use in the middle-east, with important implications for the use of low intensity, non-specialist interventions for this age range.
Identification of a novel mutation in the CACNA1C gene in a Chinese family with autosomal dominant cerebellar ataxia
Authors: Chen Jiajun , Sun Yajuan , Liu Xiaoyang , Li Jia 
Published: July 2019

Abstract
Background: Hereditary ataxia is a group of neurodegenerative diseases with progressive cerebellar ataxia of the gait and limbs as the main symptoms. The genetic patterns of the disease are diverse but it is mainly divided into autosomal dominant cerebellar ataxia (ADCA) and autosomal recessive cerebellar ataxia (ARCA), and about 45 pathogenic loci have been found in ADCA. The purpose of this study was to explore the genetic defect in a Chinese family with ADCA. Methods: A three-generation Chinese family with ADCA was enrolled in this study, Exome sequencing was conducted in four family members, including the proband, and verified by Sanger sequencing. Results: The rs779393130 mutation of the CACNA1C gene co-segregated with the ataxia phenotype in this family. The mutation was not detected in 50 unaffected controls. Conclusions: The rs779393130 mutation of CACNA1C may be associated with the phenotype of the disease. The CACNA1C gene encodes the Cav1.2 (alpha-1) subunit of an L-type calcium channel and this subunit may be related to the ADCA phenotype. These findings may have implications for family clinical monitoring and genetic counseling and may also help in understanding pathogenesis of this disease.
Cone-beam Computed Tomography Investigation of Middle Mesial Canals and Isthmuses in Mandibular First Molars in a Chinese Population
Authors: Xu Shuaimei , Dao Junfeng , Liu Zhongjun , Zhang Zhiyong , Lu Yu , Zeng Xiongqun 
Published: July 2019

Abstract
Background: While there is ample research into the anatomy of mandibular molars, little is known regarding isthmuses and middle mesial (MM) canals in Chinese populations. The goal of this study was to determine the prevalence of MM canals and isthmuses in the mesial root of mandibular first molars using Cone-beam Computed Tomography.
Methods: Cone-beam Computed Tomography images of 357 mature mandibular first molars were retrospectively analyzed. Presence of isthmuses and MM canals, and the length of isthmuses in the mesial root were recorded. Meanwhile, we also recorded possible correlated factors such as demographics, side of mandible, presence of separated distal-lingual roots.
Results: Of these 357 teeth, 209 showed evidence of either complete or partial communication in the mesial root. Of these, 11(3.08%) exhibited true MM canals while 198(55.46%) exhibited isthmuses. Sex or side of mandible was not correlated with the prevalence of communication (isthmuses or MM canals) (P> 0.05). However, there was a significant association between the presence of a distal-lingual root and the prevalence of such communication (P< 0.05). The average length of isthmuses was 4.3 ± 3.1mm.
Conclusions: We detected high rate of isthmuses and low rate of MM canals in mesial roots of mandibular first molars, which is important as such areas should be identified and cleaned during root canal treatment.
PENERAPAN SURGICAL SAFETY CHECKLIST WHO DI RSUD JARAGA SASAMEH KABUPATEN BARITO SELATAN
Authors: Klase Suryanti , Pinzon Rizaldy Taslim , Meliala Andreasta 
Published: July 2019

Latar Belakang: Penerapan pemakaian Surgical Safety Checklist (SSC) dari
World Health Organization (WHO) adalah untuk meningkatkan keselamatan
pasien dalam proses pembedahan dikamar operasi dan mengurangi terjadinya
kesalahan dalam prosedur pembedahan. Tingginya angka komplikasi dan
kematian akibat pembedahan menyebabkan tindakan pembedahan seharusnya
menjadi perhatian kesehatan global. Penggunaan checklist terstruktur dalam
proses pembedahan akan sangat efektif karena standarisasi kinerja manusia
dalam memastikan prosedur telah diikuti. Untuk itu diperlukan juga proses
penerapan Surgical Safety Checklist WHO di RSUD Jaraga Sasameh Kabupaten
Barito Selatan.
Metode: Jenis penelitian ini adalah penelitian deskriptif dengan rancangan
penelitian kualitatif, studi kasus. Subyek penelitian ini adalah semua personel
kamar bedah RSUD Jaraga Sasameh Kabupaten Barito Selatan, Propinsi
Kalimantan Tengah selama bulan Maret - Mei 2015. Kuesioner menjelaskan
tentang karakteristik umum dari sampel (umur, jenis kelamin, pekerjaan, lama
kerja di rumah sakit), pengetahuan tentang Surgical Safety Checklist WHO,
penerimaan checklist dan penerapannya, dan kerja sama team kamar bedah.
Hasil: Dari 21 personel kamar bedah yang menjawab kuesioner, 100%
menyadari keberadaan Surgical Safety Checklist WHO dan mengetahui tujuannya.
Kebanyakan personel berpikir bahwa menggunakan checklist keselamatan Bedah
WHO bermanfaat dan pelaksanaannya di kamar bedah merupakan keputusan
yang tepat. Ada 90,5% personel yang menyatakan bahwa penggunaan Surgical
Safety Checklist WHO cukup mudah untuk dilaksanakan.
Kesimpulan: Meskipun terdapat penerimaan yang besar terhadap
pelaksanaan penerapan checklist ini diantara personel kamar bedah, tetapi
terdapat sedikit perbedaan dalam pengetahuan tentang tata cara pengisian
ataupun penggunaan checklist.
Exploring private water wells for fecal sources and evidence of pathogen presence in the context of current testing practices for potability in Ontario
Authors: Felleiter Sophie , McDermott Kevin , Hall Geof , Sheth Prameet , Majury Anna 
Published: July 2019

Abstract
Private water wells provide drinking water for an estimated 4.1 million households in Canada yet remain understudied in the context of microbial water quality or human health impacts. As there exists little systematic surveillance for enteric infections or outbreaks related to well water sources, consumers may be at risk of waterborne infectious diseases. A standard protocol in Ontario requires 200 mL of water, collected, and submitted by well owners, half of which is used to analyze for Escherichia coli and total coliforms (TCs). The aim of this study was to determine the efficacy of testing small water volumes and to survey for other contaminants in addition to bacterial indicators to inform pathogen prevalence and fecal source in drinking water wells. Samples were assessed for E. coli and TCs, by culture, and genetic markers of Bacteroides spp., Campylobacter spp., Salmonella spp., and Shiga toxin-producing E. coli, using qPCR. The source of fecal contamination varied by the geographic region and may be explained by septic tank density and underlying geology, among other factors. A small number of samples (1.9%) showed the evidence of contamination with enteric pathogens. Lastly, E. coli measured by qPCR, as opposed to culture, correlated more strongly to Bacteroides markers.
Removal of multiple heavy metal ions using a macromolecule chelating flocculant xanthated chitosan
Authors: Yang Kai , Wang Gang , Liu Fulong , Wang Xin , Chen Xuemin 
Published: July 2019

Abstract
In this paper, the removal performance and mechanism of xanthated chitosan (XCTS) towards heavy metal ions are investigated. XCTS possesses both strong chelating abilities and excellent flocculation properties, which can effectively remove several kinds of heavy metal ions, such as Cr3+, Cu2+, Mn2+, Ni2+, Pb2+ and Zn2+. It has a good potential for practical application. In a flocculation test of a mixed component solution, the removal rates of Cr3+, Cu2+ and Cd2+ reach 100%, 100% and 99.1%, respectively. The removal rates are significantly greater than that of a single component solution. It indicates that there is a synergistic effect between different metal ions. Moreover, the selectivity of XCTS for Cr3+ and Cu2+ is obviously superior to that for Cd2+; XCTS is easier to combine with the heavy metal ions belonging to hard acids.
Причини повторних оперативних утручань у пацієнтів, які перенесли хірургічне лікування гриж міжхребцевих дисків поперекового відділу хребта
Authors: Piontkovsky V.K. , Fishchenko І.V. 
Published: July 2019

Актуальність. У статті подано ретроспективний аналіз причин, що призводять до негативних результатів хірургічного лікування людей літнього віку з грижами міжхребцевих дисків на рівні поперекового відділу хребта. Мета. Визначення причин негативних результатів хірургічного лікування гриж міжхребцевих дисків у людей літнього і старечого віку порівняно з молодими пацієнтами, що дозволить у подальшому вибрати правильну хірургічну тактику та запобігти виникненню ускладнень. Матеріали та методи. Проведено ретроспективний аналіз хірургічного лікування гриж міжхребцевих дисків поперекового відділу хребта у 170 пацієнтів. Група молодих людей становила 92 пацієнти, група осіб літнього і старечого віку (60 років і старше) — 78 пацієнтів. Першу операцію з приводу грижі міжхребцевого диска було проведено у термін від 3 місяців до 7 років до дослідження в різних лікувальних закладах України. Результати. Рецидив грижі диска на тому самому рівні виявлено у 61 % молодих пацієнтів і майже в 4 рази рідше (14,1 %) у старших. Грижа диска на суміжному рівні виявлена також частіше у молодих пацієнтів (10,0 %), ніж у старшої вікової категорії (3,8 %). Цей факт автори пов’язують з тим, що з віком міжхребцевий диск більш дегідратований, а висота міжтілового проміжку значно зменшується, тоді як у молодих людей об’єм матеріалу диска значний, що збільшує ризик утворення нових секвестрів. Висновки. Результати проведеної роботи вказують на те, що причини повторних оперативних хірургічних втручань з приводу гриж міжхребцевих дисків залежать від віку пацієнта; найчастішою причиною повторних оперативних втручань у старших пацієнтів є нестабільність на оперованому та суміжному рівнях, що спонукає хірургів до більш широкого застосування стабілізуючих оперативних втручань та більш детального передопераційного планування щодо вибору рівня стабілізації; у старшої вікової категорії переважають процеси стенозування, отже, у них необхідно застосовувати більш широку декомпресію.
Assessment and Utilization of Uncommitted Reserves of the Pension System Stabilization
Authors: Pitilyak D. A. , Dranenko L. P. , Basil T. V. , Chernyaeva M. A. 
Published: July 2019

The subject of the research is the reserves intended for stabilization of the Russian pension system that could be activated to ensure Russia’s entry into the five largest economies of the world.The purpose of the research was to assess the uncommitted reserves of the Russian pension system stabilization taking into account the fact that an increase in the burden on one worker exhausts the already committed functional resources of the pension system. The May presidential address to the Federal Assembly in 2018 outlined the main goals: Russia’s entry into the five largest economies of the world and an increase in the GDP per capita. The increase in the welfare of the population is, notably, the most important internal source of the country’s economic development. Moreover, the Russian President particularly stressed the need to improve the quality of life of the older generation, since an increase in the burden on one employed worker exhausts the existing functional resources of the pension system. Therefore, the government sent a bill to the State Duma on changes in the pension system by raising the retirement age. The following arguments were voiced in favor of the adoption of the bill: the increase in life expectancy in Russia and the threat of insufficient amount of incoming per-worker contributions to finance current pensioners. In view of the above, the paper examines currently uncommitted reserves that might be involved for improving the sustainability of the pension system and demonstrates the economic effect from the implementation of these measures.
Comparative Analysis of the NEO and Ethereum Cryptocurrencies in the Context of the Digital Economy of the Future
Authors: Bauer V. P. , Smirnov V. V. 
Published: July 2019

The subject of the research is the NEO and Ethereum cryptocurrencies. The relevance of the research is due to the following.First, these cryptocurrencies are expected to play the key role in establishing the future digital economy. Second, cryptocurrency developers are competing to gain leading positions in the development of financial technologies of the digital revolution. Third, the above cryptocurrencies are designed to perform almost identical functions, therefore, to determine the advantages of either of them, a comparative analysis is needed and appropriate conclusions for the Russian economy should be made.The purpose of the paper was to perform a comparative analysis of the Ethereum and NEO cryptocurrencies to identify trends in the digital economy of the future and determine the main targets to enable Russia’s entry into the top five largest world economies.The information sources include articles, books, regulations, departmental documents and conference materials on FinTech, crypto-markets and the digital economy. The research made it possible to reveal specific features of the cryptocurrencies and the corresponding digital platforms that are important for the development of the digital economy of the future. The goal of Ethereum developers is to create a platform for decentralized applications, based on which it will be possible to form a global, easy-to-access, free and reliable Internet of the future.The paper concludes that at present, the NEO has advantages over the Ethereum in terms of both the transaction speed and operational fitness for the development of prospective technologies of the digital economy. However, it may happen that in the near future, the Ethereum developers will be able to improve their blockchain technology so as to ensure the priority of their project in the competition for leadership in the development of the digital economy of the future. Given the contradictions revealed and taking into account the raw materials orientation of the Russian economy, a number of targets are proposed to bring Russia into the five largest world economies.