bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leukemia cutis with IDH1, DNMT3A and NRAS mutations conferring resistance to venetoclax plus 5-azacytidine in refractory AML
Authors: Wang JingHan , Ye Xingnong , Fan Cuihua , Zhou Jie , Luo Shuna , Jin Jingxia , Chen Dan , Zheng Yan , Wu Cai , Zhu Xiaoqiong , Jin Jie , Huang Jian 
Published: November 2020

AbstractrRecently, novel drugs like venetoclax plus 5-azacytidine (VA) were reported to have promising efficacy in refractory acute myeloid leukemia (AML). However, there are still some cases presented with novel drugs resistance, and its genetics composition and clinical phenotype are urging to study. We described a 58-year-old patient who was resistant to intensive chemotherapy. This refractory AML was presented with the persistence of RUNX1, IDH1 and DNMT3A mutations. RUNX1 mutations disappeared and leukemia cutis ensued after multiple chemotherapies. Leukemia cutis exhibited NRAS mutations in addition to IDH1 and DNMT3A mutations. With the VA salvage treatment, platelets were recovered to the normal level and blasts in bone marrow and peripheral blood were moderately controlled. However, leukemia cutis did not resolve. Unexpectedly, BM blasts obtained the new NRAS mutations after VA treatment, and consequently experienced leukostasis with two distinct leukemia clones. After survival of 230 days, this patient died because of spontaneous cerebral hemorrhage. This case highlights presentation of leukemia cutis with simultaneous mutations of IDH1, DNMT3A and NRAS in AML patients might act as a resistant niche to avoid the toxicity of multiple drugs including VA. There is unmet need to validate this result in the clinical trials or a large cohort of patients in the future.
A DNA methylation-based test for esophageal cancer detection
Authors: Salta Sofia , Macedo-Silva Catarina , Miranda-Gonçalves Vera , Lopes Nair , Gigliano Davide , Guimarães Rita , Farinha Mónica , Sousa Olga , Henrique Rui , Jerónimo Carmen 
Published: November 2020

Abstract
Background
Esophageal cancer (ECa) is the 7th most incident cancer and the 6th leading cause of cancer-related death. Most patients are diagnosed with locally advanced or metastatic disease, enduring poor survival. Biomarkers enabling early cancer detection may improve patient management, treatment effectiveness, and survival, are urgently needed. In this context, epigenetic-based biomarkers such as DNA methylation are potential candidates.

Methods
Herein, we sought to identify and validate DNA methylation-based biomarkers for early detection and prediction of response to therapy in ECa patients. Promoter methylation levels were assessed in a series of treatment-naïve ECa, post-neoadjuvant treatment ECa, and normal esophagus tissues, using quantitative methylation-specific PCR for COL14A1, GPX3, and ZNF569.

Results
ZNF569 methylation (ZNF569me) levels significantly differed between ECa and normal samples (p < 0.001). Moreover, COL14A1 methylation (COL14A1me) and GPX3 methylation (GPX3me) levels discriminated adenocarcinomas and squamous cell carcinomas, respectively, from normal samples (p = 0.002 and p = 0.009, respectively). COL14A1me & ZNF569me accurately identified adenocarcinomas (82.29%) whereas GPX3me & ZNF569me identified squamous cell carcinomas with 81.73% accuracy. Furthermore, ZNF569me and GPX3me levels significantly differed between normal and pre-treated ECa.

Conclusion
The biomarker potential of a specific panel of methylated genes for ECa was confirmed. These might prove useful for early detection and might allow for the identification of minimal residual disease after adjuvant therapy.
Alternative Polyadenylation: a new frontier in post transcriptional regulation
Authors: Ren Fanggang , Zhang Na , Zhang Lan , Miller Eric , Pu Jeffrey J. 
Published: November 2020

AbstractPolyadenylation of pre-messenger RNA (pre-mRNA) specific sites and termination of their downstream transcriptions are signaled by unique sequence motif structures such as AAUAAA and its auxiliary elements. Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism that processes RNA products depending on its 3′-untranslated region (3′-UTR) specific sequence signal. APA processing can generate several mRNA isoforms from a single gene, which may have different biological functions on their target gene. As a result, cellular genomic stability, proliferation capability, and transformation feasibility could all be affected. Furthermore, APA modulation regulates disease initiation and progression. APA status could potentially act as a biomarker for disease diagnosis, severity stratification, and prognosis forecast. While the advance of modern throughout technologies, such as next generation-sequencing (NGS) and single-cell sequencing techniques, have enriched our knowledge about APA, much of APA biological process is unknown and pending for further investigation. Herein, we review the current knowledge on APA and how its regulatory complex factors (CFI/IIm, CPSF, CSTF, and RBPs) work together to determine RNA splicing location, cell cycle velocity, microRNA processing, and oncogenesis regulation. We also discuss various APA experiment strategies and the future direction of APA research.
powerLang: a probabilistic attack simulation language for the power domain
Authors: Hacks Simon , Katsikeas Sotirios , Ling Engla , Lagerström Robert , Ekstedt Mathias 
Published: November 2020

AbstractCyber-attacks on power-related IT and OT infrastructures can have disastrous consequences for individuals, regions, as well as whole nations. In order to respond to these threats, the cyber security assessment of IT and OT infrastructures can foster a higher degree of safety and resilience against cyber-attacks. Therefore, the use of attack simulations based on system architecture models is proposed. To reduce the effort of creating new attack graphs for each system under assessment, domain-specific languages (DSLs) can be employed. DSLs codify the common attack logics of the considered domain.Previously, MAL (the Meta Attack Language) was proposed, which serves as a framework to develop DSLs and generate attack graphs for modeled infrastructures. In this article, powerLang as a MAL-based DSL for modeling IT and OT infrastructures in the power domain is proposed. Further, it allows analyzing weaknesses related to known attacks. To comprise powerLang, two existing MAL-based DSL are combined with a new language focusing on industrial control systems (ICS). Finally, this first version of the language was validated against a known cyber-attack.
Recent advances of non-ionic surfactant-based nano-vesicles (niosomes and proniosomes): a brief review of these in enhancing transdermal delivery of drug
Authors: G Durga Bhavani , P Veera Lakshmi 
Published: November 2020

Abstract
Background
Hepatic first-pass metabolism and poor therapeutic efficiency at targeted region are the endemic problems of new drug molecules. Thus, comprehensive research has been carried out on the novel vesicular drug delivery systems in nanotechnology from the last few years. These nano-carrier systems have developed to overcome the limitations that are associated with hepatic first-pass metabolism in conventional oral dosage forms and the barrier properties of the lipid bilayer in stratum corneum via transdermal drug delivery for improving the bioavailability of various drugs.

Main body
In recent years, several targeted vesicular drug delivery carriers are developing like liposomes, niosomes, proniosomes, transferosomes, ethosomes, and electrosomes. Among them, niosomes and proniosomes are to be better carriers to increase therapeutic efficiency and bioavailability by reducing the side effects and acting as a promising approach for transdermal drug delivery. Both are non-ionic surfactant-based vesicles and are amphiphilic. This article concisely reviews the possible mechanisms within niosomes and pronisomes to enhance transdermal drug delivery, types, composition, preparation techniques, characterizations, and its applications.

Conclusion
As per the researches done in the formulation of various nano-carrier systems through transdermal approach for the enhancement of bioavailability, it can be stated that the hepatic first pass metabolism can be reduced as well as therapeutic efficiency can be increased by many folds compared to their oral marketed formulations.
Ultrasound as a bedside tool for diagnosis of post-intubation tracheal stenosis
Authors: Farghaly Shereen , El-Abdeen Ashraf Zin , Shaaban Lamiaa H. , El-Malah Hossam El-Deen Galal M. , Kamal Maida 
Published: November 2020

Abstract
Background
Screening of post-intubation stenosis can allow early diagnosis, early management of stenosis, and possible prevention of progress. Fiberoptic bronchoscope is the gold standard for diagnosis of tracheal stenosis. Other imaging modalities as computed tomography can be considered but are not available in intensive care unit.

Purpose of the study
To evaluate the validity of ultrasound (US) as a bedside test for early diagnosis of post-intubation stenosis compared to multidetector computed tomography (MDCT) and fiberoptic bronchoscope (FOB).

Results
Out of the 50 included patients, 12 patients were found to have definite stenosis by FOB. Compared to CT, significant positive correlation was found between all ultrasound parameters (laryngeal width, tracheal diameter) and corresponding CT parameters (r = 0.798, p < 0.001; r = 0.714, p < 0.001 respectively). Compared to FOB results, the yield of MDCT chest for diagnosis of stenosis had 91.6% sensitivity and 100% specificity, while the yield of US detected by mucosal irregularity as a diagnostic tool for tracheal stenosis had comparable sensitivity (91.6%) but lower specificity (88.9%).

Conclusion
Due to its high sensitivity, US could help in detection of possible post-intubation laryngotracheal stenosis in critically ill MV patients.
Barriers and facilitators for treatment-seeking for mental health conditions and substance misuse: multi-perspective focus group study within the military
Authors: Bogaers Rebecca , Geuze Elbert , van Weeghel Jaap , Leijten Fenna , van de Mheen Dike , Varis Piia , Rozema Andrea , Brouwers Evelien 
Published: November 2020

BackgroundGlobally, millions are exposed to stressors at work that increase their vulnerability to develop mental health conditions and substance misuse (such as soldiers, policemen, doctors). However, these types of professionals especially are expected to be strong and healthy, and this contrast may worsen their treatment gap. Although the treatment gap in the military has been studied before, perspectives of different stakeholders involved have largely been ignored, even though they play an important role.AimsTo study the barriers and facilitators for treatment-seeking in the military, from three different perspectives.MethodIn total, 46 people participated, divided into eight homogeneous focus groups, including three perspectives: soldiers with mental health conditions and substance misuse (n= 20), soldiers without mental health conditions and substance misuse (n= 10) and mental health professionals (n= 16). Sessions were audio-taped and transcribed verbatim. Content analysis was done by applying a general inductive approach using ATLAS.ti-8.4.4 software.ResultsFive barriers for treatment-seeking were identified: fear of negative career consequences, fear of social rejection, confidentiality concerns, the ‘strong worker’ workplace culture and practical barriers. Three facilitators were identified: social support, accessibility and knowledge, and healthcare within the military. The views of the different stakeholder groups were highly congruent.ConclusionsBarriers for treatment-seeking were mostly stigma related (fear of career consequences, fear of social rejection and the ‘strong worker’ workplace culture) and this was widely recognised by all groups. Social support from family, peers, supervisors and professionals were identified as important facilitators. A decrease in the treatment gap for mental health conditions and substance misuse is needed and these findings provide direction for future research and destigmatising interventions.
Rapid systematic review of systematic reviews: what befriending, social support and low intensity psychosocial interventions, delivered remotely, are effective in reducing social isolation and loneliness among older adults? How do they work?
Authors: Boulton Elisabeth , Kneale Dylan , Stansfield Claire , Heron Paul , Sutcliffe Katy , Hayanga Brenda , Hall Alex , Bower Peter , Casey Dympna , Craig Dawn , Gilbody Simon , Hanratty Barbara , McMillan Dean , Thomas James , Todd Chris 
Published: November 2020

Background: During the 2020 COVID-19 pandemic, millions of older adults are advised to avoid contact with those outside their household. ‘Social distancing’ has highlighted the need to minimise loneliness and isolation through the provision of remotely delivered befriending, social support and low intensity psychosocial interventions. We wanted to know what interventions are effective and how they work to help inform decisions about different approaches.Methods: We followed a systematic ‘review of reviews’ approach and included systematic reviews focussed on the effectiveness or implementation of remote interventions to reduce levels of social isolation or loneliness in adults aged 50+. Searches of 11 databases were undertaken during April 2020 and eligible reviews were critically appraised using AMSTAR2. Narrative synthesis was used at a review and study level to develop a typology of intervention types and their effectiveness. Intervention Component Analysis (ICA) and Qualitative Comparative Analysis (QCA) were used at a study level to explore the characteristics of successful interventions.Results: We synthesised evidence from five systematic reviews and 18 primary studies. Remote befriending, social support and low intensity psychosocial interventions took the form of: (i) supported video-communication; (ii) online discussion groups and forums; (iii) telephone befriending; (iv) social networking sites; and (v) multi-tool interventions. The majority of studies utilised the first two approaches, and were generally regarded positively by older adults, although with mixed quantitative evidence around effectiveness. Focussing on processes and mechanisms, using ICA and QCA, we found that the interventions that were most effective in improving social support: (i) enabled participants to speak freely and to form close relationships; (ii) ensured participants have shared experiences/characteristics; (iii) included some form of pastoral guidance.Conclusions: The findings highlight a set of intervention processes that should be incorporated into interventions, although they do not lead us to recommend particular modes of remote support.
Scientific Potential of Teachers: Mechanisms for Identification and Improvement
Authors: Bychkov Anatoliy 
Published: November 2020

Monitoring the levels of scientific potential of teachers is due to the need to improve the methodology for determining compliance with the position and the requirements of the first and highest qualification categories in accordance with the new procedure for certification of teachers.
On this basis, there are opportunities to develop mechanisms for increasing scientific potential in order to introduce it functionally into the structure of professional pedagogical activity of teachers in accordance with the job description and the requirements of Federal state educational standards to improve the effectiveness of educational activities.
When assessing the levels of scientific potential of teachers, along with other parameters, it is advisable to take into account the influence of age, educational level and retraining of specialists. It is necessary to take into account the level of teaching experience and work experience in the subject taught.
EU POLICY AGAINST FALSIFIED MEDICINES: OPTIONS FOR FURTHER DEVELOPMENT
Authors: Valcheva Krasimira 
Published: November 2020

The globalization of trade and internet access significantly increased the health risks associated with falsified medicines. International organizations, pharmaceutical companies and national governments developed a wide variety of measures to combat their pervasive penetration into the legal supply chains. However, the lack of harmonization, broad acceptance and legally bound enforcement obstructed their endeavours. The unsatisfying outcomes resulted in enhanced supranational cooperation focused on strengthening the pharmaceutical regulatory frameworks and the improvement of patient protection.
In 2011 the European Union joined the global fight with the adoption of Directive 2011/62/EU that became known as the Falsified Medicine Directive. It is legally binding for Member States and amends the fundamental for the pharmaceutical sector Directive 2001/83/EC. The objective of the present paper is to verify if it represents a comprehensive tool for effective prevention of the access of falsified medicines in the European legal pharmaceutical supply chains. The results revealed that although it is rather detailed, there are areas that could be further developed and improved when compared to analogical policies and initiatives.
METHODS TO DETERMINE COMPLEX DEGREES OF MUTUAL ANISOTROPY FOR THE DIFFERENTIATION OF HEMORRHAGES IN THE HUMAN BRAIN SUBSTANCE RESULTING FROM TRAUMATIC AND NON-TRAUMATIC GENESIS
Authors: Garazdiuk Marta , Bachynskіy Viktor , Nechytailo Olena , Garazdiuk Oleksandr , Malanchuk Svitlana 
Published: November 2020

An issue that is often debated in forensic traumatology is the differential diagnosis of hemorrhages into the human brain substance (HBS) of traumatic and non-traumatic genesis.
Objectives. This study aims to identify new criteria for objective forensic differentiation of hemorrhages of traumatic origin, cerebral infarction of ischemic and hemorrhagic genesis by using the method of complex degree of mutual anisotropy. For this study native sections of HBS from 125 corpses were used in the case of: death from coronary heart disease - 35 (28%) of native sections (Group 1 - control); hemorrhages of traumatic genesis - 30 (24%) sections (Group 2); ischemic cerebral infarction - 30 (24%) native sections(Group 3); and hemorrhages of non-traumatic genesis - 30 (24%) native sections (Group 4).
Results. The statistical moments of the third and fourth orders, which characterize the asymmetry and excess of the complex degree of mutual anisotropy module size distributions, the strength of the method of polarization-correlation microscopy in the differentiation of the samples of the histological sections of the brain of control and experimental groups reached a good level — 87%-90%.
Conclusion. The method of complex degree of mutual anisotropy allows differentiating with great precision the genesis of hemorrhage into the substance of the brain.
ACCUMULATION AND MOBILE FORMS OF SOME HEAVY METALS IN ROADSIDE URBAN SOILS
Authors: Nikolov Bogdan , Petrova Slaveya , Velcheva Iliana , Angelov Nikola , Valcheva Ekaterina , Zapryanova Penka , Hristozova Gergana , Varbanova Evelina , Georgieva Deyana , Stefanova Violeta 
Published: November 2020

The accumulation of heavy metals and toxic elements in the topsoil horizon of urban areas is a big environmental problem as they could have long-term implications not only for the soils themselves but also on the human health and well-being. Many studies have shown that there is a clear relationship between the level of urbanization, volume of traffic, intensity of anthropogenic activities and heavy metal load.
We aimed to analyze the accumulation of heavy metals at urban roadside soils and to assess the proportion of their mobile forms. The total content and mobile forms of Cu, Mn, Pb and Zn in soils samples collected along the main boulevards of Plovdiv (Bulgaria) was determined by two instrumental methods - ICP-OES and ICP-MS.
The maximal concentrations were found in the Central and Eastern administrative regions of the city of Plovdiv. This finding well correlated with the wind rose characteristics and urban gradient theory. Our results revealed that the mobile forms of Mn represented 1.38-2.21% of total content and the mobile forms of Zn represented 8.48-11.81% of total content in studied urban soils. Mobile forms of Cu and Pb varied significantly and were in the range of 7.04-14.2% and 7.3-18.67% of the total content, respectively.
PSYCHOMETRIC INDICATORS OF THE SOCIAL AND EMOTIONAL LONELINESS SCALE FOR ADULTS - SHORT VERSION (SELSA-S) IN BULGARIA
Authors: Alexandrova Nataliya , Babakova Liliya 
Published: November 2020

This article examines the psychometric indicators of Social and Emotional Loneliness Scale for Adults, the short version (SELSA-S; DiTommaso, Brannen, & Best, 2004). The scale contains 15 items, divided into three scales: social loneliness, emotional loneliness, and romantic loneliness. The survey was attended by 1713 persons over 60 years of which were 1042 women and 671 men; and 383 of whom were in early-to-middle adulthood (20-55 years). The results showed high-reliability ratios for both the full scale (α = 0.825) and the three subscales (α = 0.727-0.845) versions. The factor analysis showed a four-factor structure of the scale. There were also statistically significant correlations between the three subscales. It was found that social and emotional loneliness had the strongest influence among older people. Therefore, it was necessary to create more opportunities for satisfactory communication, forms, and functioning of social contacts. It was found that the romantic loneliness had the strongest influence on younger people, i.e., they experienced significantly the lack of a partner by them or dissatisfaction with him.
LONG-TERM UNEMPLOYMENT OF THE RISK GROUPS IN THE SLOVAK LABOUR MARKET
Authors: Ladňáková Veronika , Špániková Martina 
Published: November 2020

Long-term unemployment is a persistent problem for Slovakia. Despite the number of long-term unemployed people in Slovakia has decreased significantly in recent years, it still presents a high proportion of the total unemployment rate. According to the European Commission Report about Slovakia in 2019, while the long-term unemployment rate fell to 4% on a year-on-year basis, it is still well above the EU average of 2.9%. Although growth is expected in the upcoming years, spending on active labour market policies in Slovakia has been one of the lowest in the EU. The study aims at investigating the current situation of long-term unemployment among risk groups in the labour market in Slovakia and labour market measures taken to curb it. It also examines the consequences of unemployment on the family and to seek solutions for the long-term unemployment in Slovakia. The data has been analyzed by a statistical method and proposes solutions to reduce long-term unemployment in the northern part of Slovakia