bluuebunny/crossref_metadata_2025 huggingface dataset:
Is it feasible to predict lymph node metastasis intraoperatively or postoperatively in early-stage lung adenocarcinoma: the application of machine learning algorithms?
Authors: Wu Yijun , Chong Yuming , Liu Jianghao , Wu Pancheng , Wang Yanyu , Han Chang , Gong Liang , Liu Xinyu , Wang Zhile , Liang Naixin , Li Shanqing
Published: May 2020

BackgroundLymph node metastasis (LNM) status can be a critical decisive factor for clinical management of lung cancer. Accurately evaluating the risk of LNM during or after the surgery can be helpful for making clinical decisions. This study aims to incorporate clinicopathological characteristics to develop reliable machine learning (ML)-based models for predicting LNM in patients with early-stage lung adenocarcinoma.MethodsA total of 709 lung adenocarcinoma patients with tumor size ≤ 2 cm were enrolled for analysis and modeling by multiple ML algorithms. The receiver operating characteristic (ROC) curve and decision curve were used for evaluating model’s predictive performance and clinical usefulness. Feature selection based on potential models was performed to identify most-contributed predictive factors.ResultsLNM occurred in 11.3% (80/709) of patients with lung adenocarcinoma. Most models reached high areas under the ROC curve (AUCs) > 0.9. In the decision curve, all models performed better than the treat-all and treat-none lines. The random forest classifier (RFC) model, with a minimal number of 5 variables introduced (including carcinoembryonic antigen, solid component, micropapillary component, lymphovascular invasion and pleural invasion), was identified as the optimal model for predicting LNM, because of its excellent performance in both ROC and decision curves. The cost-efficient application of RFC model could precisely predict LNM during or after the operation of early-stage adenocarcinomas (sensitivity: 87.5%; specificity: 82.2%).ConclusionsIncorporating clinicopathological characteristics, it is feasible to predict LNM intraoperatively or postoperatively by ML algorithms.Trial registration: NA
Analgecine inhibits NF-kB to regulate microglia polarization by TLR4 MyD88-dependent and MyD88-independent pathways in ischemic stroke
Authors: Yang Cuicui , Gong Shili , Chen Xiaoping , Wang Mingyang , Zhang Li , Li Lin , Zhang Dongqing , Zhang Lan , Hu Chaoying
Published: May 2020

Background: Microglia polarization plays an important role in poststroke recovery. Inhibition of proinflammatory (M1) polarization and promotion of anti-inflammatory (M2) polarization of microglia are potential therapeutic strategies for inflammation reduction and neuronal recovery after stroke. Analgecine (AGC), the extracts of Vaccin a variola-inoculated rabbit skin, is used to treat patients with chronic low back pain due to degenerative vertebral disorders. Here, we evaluated the neuroprotective effect of AGC in stroke and investigate anti-inflammatory mechanism of AGC on microglia-mediated neural damage.Methods: Sprague-Dawley (SD) rats underwent 120 min of middle cerebral artery occlusion (MCAO) followed by reperfusion. We injected AGC intravenously into rats starting 3 h after the onset of MCAO. Then we investigated the effect of AGC on neurological impairment, neuronal loss and inflammatory cytokines. For in vitro study, we examined the effect of AGC on microglial polarization in oxygen-glucose deprivation/reperfusion (OGD/R) or LPS/IFN-γ induced microglia cells and further investigated neuroprotective effect of ACG in microglia-mediated neural damage based on the direct or indirect co-culture systems. Finally, TLR4/Myd88/ NF-κB pathway was detected in OGD/R-induced microglia cells with or without Myd88 siRNA transfection.Results: AGC treatment reduced the neurological deficits and suppressed neuronal loss. In terms of inflammatory cytokines, AGC inhibited the release of pro-inflammatory cytokines and elevated the content of anti-inflammatory cytokines in vivo (SD rats) and in vitro (microglia). We further showed that AGC promoted M1 to M2 phenotypic transition of microglia in OGD/R or LPS/IFN-γ induced microglia cells. Based on the direct or indirect co-culture systems, we found AGC indirectly inhibits LPS/IFN-γ-induced neuronal damage by modulating microglial polarization. Moreover, AGC suppressed the nuclear translocation of the phosphorylation of NF-κB p65 by inhibiting the TLR4/Myd88/TRAF6 but not TLR9 signaling. We also confirmed that AGC-regulated TLR4 inhibition partly dependent on Myd88 in a Myd88 depletion cell line.Conclusion: Our findings provide a new understanding of AGC in neuroprotection by inhibiting M1 microglial polarization and promoting anti-inflammation by suppressing TLR4 MyD88-dependent and MyD88-independent pathways. Thus, AGC treatment may represent a novel approach in inflammation reduction or poststroke recovery.
SILEX: A fast and inexpensive high-quality DNA extraction method suitable for multiple sequencing platforms and recalcitrant plant species
Authors: vilanova santiago , Alonso David , Gramazio Pietro , Plazas Mariola , Ferrante Paola , Schmidt Maximilian , Diez-Niclós María J. , Usadel Björn , Giuliano Giovanni , Prohens Jaime
Published: May 2020

Background: The use of sequencing and genotyping platforms has undergone dramatic improvements, enabling the generation of a wealth of genomic information. Despite this progress, the availability of high-quality genomic DNA (gDNA) in sufficient concentrations is often a main limitation, especially for third-generation sequencing platforms. A variety of DNA extraction methods and commercial kits are available. However, many of these are costly and frequently give either low yield or low-quality DNA, inappropriate for next generation sequencing (NGS) platforms. Here, we describe a fast and inexpensive DNA extraction method (SILEX) applicable to a wide range of plant species and tissues. Results: SILEX is a high-throughput DNA extraction protocol, based on the standard CTAB method with a DNA silica matrix recovery, which allows obtaining NGS-quality high molecular weight genomic plant DNA free of inhibitory compounds. SILEX was compared with a standard CTAB extraction protocol and a common commercial extraction kit in a variety of species, including recalcitrant ones, from different families. In comparison with the other methods, SILEX yielded DNA in higher concentrations and of higher quality. Manual extraction of 48 samples can be done in 96 min by one person at a cost of 0.12 €/sample of reagents and consumables. Hundreds of tomato gDNA samples obtained with either SILEX or the commercial kit were successfully genotyped with Single Primer Enrichment Technology (SPET) with the Illumina HiSeq 2500 platform. Furthermore, DNA extracted from Solanum elaeagnifolium using this protocol was assessed by Pulsed-field gel electrophoresis (PFGE), obtaining a suitable size ranges for most sequencing platforms that required high-molecular-weight DNA such as Nanopore or PacBio. Conclusions: A high-throughput, fast and inexpensive DNA extraction protocol was developed and validated for a wide variety of plants and tissues. SILEX offers an easy, scalable, efficient and inexpensive way to extract DNA for various next-generation sequencing applications including SPET and Nanopore among others.
The impact of growth differentiation factor 15 on the risk of cardiovascular disease: evidence from Mendelian randomization study
Authors: Wang Zhuo , Yang Fangkun , Ma Menghuai , Bao Qinyi , Shen Jinlian , Ye Feiming , xie xiaojie
Published: May 2020

Background: Growth differentiation factor 15(GDF-15) concentration is apparently associated with cardiovascular disease, but whether there is a causal relationship has not been testified. Methods: We utilized Mendelian randomization to assess the function of GDF-15 in incidence of cardiovascular disease. The single-nucleotide polymorphism- GDF-15 association evaluations came from meta-analysis of genome-wide association study (GWAS). Besides inverse-variance weighted, MR-Egger test and weighted median method were applied to examine sensitivity. Results: Base on the instruments, GDF-15 level linked to increased risk of cardioembolic stroke (1.06, OR 1.09 per SD increase, 95% CI 1.01, 1.19) and atrial fibrillation (OR 1.03 per SD increase, 95% CI 1.0, 1.06). However, the significant causal relationship between GDF-15 and the other cardiovascular diseases was not found in our work. Conclusions: The result suggested that GDF-15 is causally associated with the risk of cardioembolic stroke and atrial fibrillation, providing conceivable strategies to alleviate the burden of cardiovascular disease.
COVID-19: Impact of early decision and type of lock-down over the spread of the virus
Authors: Humaid Jehan Al , Khan Soban Qadir , Farooqi Faraz , Alhareky Muhanad , Alonaizan Faisal , Harbi Fahad Al
Published: May 2020

Objectives: Aim of the present study was to analyze the (1) partial vs complete lock down effects over the spread of COVID-19, (2) time taken for complete lock down decision in relation with the spread of disease. Method: COVID-19 data for the current observational study was taken up to 14th April since the outbreak of the virus. There were 28 countries which passed through the inclusion criteria and included for analysis.Results: Average number of reported cases during 1st, 2nd and 3rd week of lockdown (complete vs partial) were 6872.9 vs 8990, 13431 vs 20032 and 19005 vs 26859.5 respectively. However, differences were not statistically significant. Days taken to announce complete lockdown was found significantly correlated with number of cases reported during 1st and 2nd after lockdown announced. Similarly, number of reported cases when lockdown announced had direct and strong correlation with number of weekly reported cases after lockdown.Conclusion: Number of weekly reported cases among partially lockdown countries was found higher compare to complete lockdown countries. Furthermore, early decision of lockdown was extremely important as it had grave impact over the spread of disease.
Economic Impact of Clinical Decision Support Interventions Based on Electronic Health Records
Authors: Lewkowicz Daniel , Wohlbrandt Attila , Boettinger Erwin
Published: May 2020

BackgroundUnnecessary healthcare utilization, non-adherence to current clinical guidelines or insufficient personalized care are perpetual challenges and remain potential major cost-drivers for healthcare systems around the world. Implementing decision support systems into clinical care is promised to increase quality of care and thereby yield substantial effects onreducing healthcare expenditure. Inthis articleweevaluate the economic impact of clinical decision support (CDS) interventions which are based on electronic health records (EHR).MethodsWe searched for studies published after 2014 using MEDLINE, CENTRAL, WEB OF SCIENCE, EBSCO, and TUFTS CEA registrydatabases that encompass an economic evaluation or consider cost outcome measures of EHR based CDS interventions. Thereupon, we identified best practiceapplication areas and categorized the investigated interventions according to an existing taxonomy of front-endCDS tools. Results and discussionTwenty-sevenstudies are investigated in this review. Of those, twenty-twostudies indicate a reduction of healthcare expenditure after implementingan EHRbased CDS system, especiallytowardsprevalent application areas, such as unnecessarylaboratory testing, duplicate order entry, efficient transfusion practice or reduction of antibiotic prescriptions.On the contrary, order facilitators and undiscovered malfunctions revealed to be threats and could lead to new cost drivers in healthcare. While high upfront and maintenance cost of CDS systems are a worldwide implementation barrier, most studies do not consider implementation cost. Finally, four included economic evaluation studies report mixed monetary outcome results and thus highlight the importance for further high quality economic evaluations for these CDS systems. ConclusionCurrent research studies lack to consider comparative cost-outcome metrics as well as detailed cost-components in their analyses. Nonetheless, thepositive economic impact of EHR based CDS interventions especially with regard to reducing waste in healthcare is highly promising.
A rational drug designing: What bioinformatics approach tells about the wisdom of practicing traditional medicines for screening the potential of Ayurvedic and natural compounds for their inhibitory effect against COVID-19 Spike, Indian strain Spike, Papain-like protease and Main Protease protein
Authors: Ranjan Prashant , Mohapatra Bhagyalaxmi , Das Parimal
Published: May 2020

The new outbreak of Coronavirus disease (COVID-19) has been entitled as a pandemic by W.H.O. It spreads to almost 211 countries due to its contagious nature. There is an urgent need for developing specific therapeutic agents against COVID-19. We have performed virtual screening of 52 ligands; most of which are essential components of traditional Ayurvedic medicine as well as natural compounds and three were standard repurposing drugs against COVID-19 Spike, Indian strain Spike (IS-Spike), PL-Pro and M-Pro to find potential inhibitor effects. Based on the docking results, it is estimated that compounds have a better binding affinity with M-Pro and PL-Pro than Spike as well as IS-Spike so it can be beneficial as therapeutics against COVID-19. We also conclude that the binding affinity of ligands with IS-Spike gets low as compared to Spike so the inhibitory potential of drugs may get weak. Based on the calculation of average binding energy (B.E) with the three targets, Spike, PL-Pro, and M-Pro, we found10 best ligands viz. (1) Punicafolin (2) Emblicanin A (3) Punigluconin (4) Lopinavir (5) Kuwanon X (6) Rutin (7) Lithospermic Acid (8) Phyllanemblinin A (9) Amarogentin and (10) Amaroswerin for inhibition. These ligands may act as potential inhibitors against COVID-19 druggable tri-targets. Network analysis revealed that four ligands out of 10 leading compounds are common in all four different networks (Spike, IS-Spike, PL-Pro, and M-Pro) which come under Phyllanthus emblica. Notably, a compound of Azadirachta indica out of 4 and a single compound of Swertia chirata was found common in all networks. Additionally, a standard drug Lopinavir and a compound of Salvia miltiorrhiza are frequently found in all networks. In principle, it appears plausible that the compounds which are common in the entire network should have more inhibitory potential against COVID19 due to the better binding potential among all targets, thus providing better candidacy for drug development.
Investigation of Some Corticosteroids as Glutathione Reductase Inhibitor
Authors: ŞENTÜRK Esra , ŞENTÜRK Murat
Published: May 2020

The detection of glutathione reductase inhibitors (GRIs) has recently become very popular due to their use as malarial and cancer drugs. Today, steroidal compounds have several clinical roles due to their potent immunomodulating and anti-inflammatory properties. In this study, GR inhibitory capacity of some corticosteroids (dexamethasone, prednisolone and methylprednisolone) has been reported. Amongst these steroidal molecules dexamethasone showed the weakest inhibitory effect on GR enzyme. IC50 values were determined by drawing % activity-[I] graphs for these corticosteroids showing inhibition effects. These corticosteroids have inhibition ranging micromolar for GR with IC50 values. These corticosteroids exhibit very potent inhibitory activity against GR enzyme at low micromolar concentrations when compared to well-known GRIs.
Landmarks and outlines of the Russian tax system-2050
Authors: Viktorova Natalya G. , Yevstigneev Yevgeniy N.
Published: May 2020

In the current situation, where new progressive technologies transform the social relations, the topic of this article becomes especially relevant. The reason is that an insight into global trends for the next three decades and their extrapolation to individual socio-economic systems is important for the effective functioning and development of such systems. However, such futurological issues in the subject areas have not been sufficiently studied or developed by researchers so far. This also applies directly to the tax sphere, where practitioners have established the tasks for the development and implementation of a digital platform and the creation of a fiscal ecosystem. The object of this research involves the Russian tax system. The purpose is to develop landmarks and outlines for the development of such a system for the period up to 2050. The research is based on systemic and integrative approaches, as well as the methods of analysis and synthesis. The research provided the following solutions: 1) contemporary economic theories and concepts related to the changing global technological landscape were organized into a system; 2) some trends in the development of society in 2025-2050 were analyzed in the context of advancements in technology (the report of Huawei and the study by K. Kelly); 3) a brief description was given of the current state of the Russian tax system and its prospects of development; 4) based on the analysis and synthesis of information on the theories, global trends and the current situation in the taxation system, a matrix of system transformations was developed — it reflects the genesis of the smart-society and one of its components, the tax system; 5) some promising development directions of the taxation theory and practice were suggested, in particular, the rationale and methodology of the tax ecosystem as a highly complex system.
Tax risk zones and the specifics of tax offenses in Russia and France for VAT
Authors: Tifin Pierre , Ogorodnikova Irina I. , Stepanov Alexander A.
Published: May 2020

The predominance of indirect taxation in the formation of Federal budget revenues in the Russian Federation is largely due to the introduction of a value-added tax in 1992. By 2019, the share of VAT in the consolidated budget is about 20 %. But the realities of modern taxation are still associated with tax risks. Tax risk analysis is related to the study of negative financial consequences for both the state and taxpayers, which in turn is due to a number of internal and external factors. Value-added tax in many countries of the world occupies an absolute leading position and is budget-forming, and VAT evasion is fraught both for the country’s economy and budget filling. Digitalization of the tax administration process and the use of IT technologies allowed to increase the revenue of the value added tax, but at the same time failed to eliminate tax violations that occur during its calculation and collection. The introduction of digital tax administration technologies strengthens the state’s position in the field of tax control. Setting the VAT rate from 2019 to 20% as an indirect tax resulted in an increase in the tax burden and did not eliminate the problems that arise with tax offenses in the calculation and collection of tax. This aspect is typical for all countries that apply value-added tax in their tax system. The purpose of this work is to identify the causes of VAT evasion, as well as typical violations in its calculation and collection. Studying, including foreign experience, and adapting it to Russian realities will reduce the tax risks of repeated occurrence of tax offenses and in the future will prevent the fact of tax evasion and minimization, which will be an element of scientific novelty.
VAT and its influence on Russian macroindicators
Authors: Koroleva Lyudmila P.
Published: May 2020

The importance of this research links to the controversial discussion about the role of the value-added tax (VAT) in the sphere of macroeconomic regulation. The assumption of its neutral influence on economic growth has led to increasing VAT rate in Russia from 18% to 20%. However, the reduction of consumer expenditures, revenues, and profits is a possible negative effect. In addition, people criticize the mechanism of VAT refund for the absence of any impact on export and investment. Thus, the goal of this research lies in verifying the most popular visions on VAT’s influence on Russian macroindicators. The methodology of the research comes from the concepts recognizing taxes as an effective tool. The author applies general scientific and econometric methods (correlation, analysis of variance, and regression analysis) using MS Excel. The author formulates four hypotheses that have shown stable views about VAT’s influence on macroeconomy. They have been tested via six equations of linear regression; the significance of the equations has been estimated via the coefficient of determination, Fisher criterion, the average error of approximation; the significance of the coefficients d — via p-value and Student’s t-criterion. Each equation is statistically significant reliably reflecting the relationship between the resulting and factor. The obtained results have proven the 2nd and 4th hypotheses. Conclusion: VAT is directly related to consumer spending, gross profit and gross mixed income, intermediate consumption, and export. VAT refund stimulates export and investments to capital assets. The results of research could be considered as an arguments of proposals to changing the procedure for calculating and paying VAT in Russia.
Indirect taxation of cross-border e-trade: features of national and intergovernmental regulation
Authors: Pogorletskiy Alexander I. , Keshner Mariya V.
Published: May 2020

The contemporary research in the field of economic and legal assessment of e-trade development, published in Russia, provides a general description of the situation and prospects for the development of international online transactions. At the same time, the aggregate features of taxation of cross-border e-commerce (which is the paper’s subject) are highlighted, without focusing on indirect methods of tax regulation (which are the object of the paper). Based on previous theoretical, methodological and practical studies, the authors systematize the knowledge about cross-border e-commerce operations’ indirect tax regulation both at the national and interstate level, defining the main approaches to taxation in this area. They also propose to focus on the priority of the regulatory (stimulating) role of taxes in their application as tools for influencing international online trading transactions.
The main provisions of the paper reveal the principles and features of collecting value-added tax (VAT), excise, customs, and postal duties in the field of export-import e-trade operations with goods, digital content, and electronic services in national tax systems. In addition, this paper characterizes the main directions of international coordination of cross-border e-commerce indirect taxation.
The authors have proven their hypothesis that the rapid development of cross-border e-trade in the modern world makes this field of international economic relations attractive enough to enhance the fiscal role of indirect taxation at the national level; however, the difficulties for the global economy early in the third decade of the 21st century require prioritizing the regulating (stimulating) role of indirect taxes to support global economic and trade operations growth, including its electronic segment.
Fires as a socio-environmental threat in the minds of students from southern Russia
Authors: Diakova Vera V. , Kargopolova Ekaterina V. , Dulina Nadezhda V.
Published: May 2020

The issues of understanding environmental pollution factors, their prevention and reduction of harmful consequences are relevant both for public discussions and for scientific analysis. This article focuses on the significant experience of scientific research of environmental problems, as there is a tendency to form the ecological consciousness of the world community. The main purpose of this article is to analyze fires as an environmental threat through sociological analysis. The authors explain the relevance of this issue of preventing and minimizing the consequences of fires, as well as improving the fire safety system, both from the point of view of Russia’ contemporary development and through the prism of the necessity for a sociological understanding of these processes and phenomena. The authors highlight the main directions of a sociological research of this phenomenon: formation and development of ecological consciousness; a systemic sociological analysis of specific situations; fire safety sociology through the prism of macro- (as a resource-saving system of society) and microsociology (the level of social groups, applied aspects of implementation and improvement of fire safety. The authors refer to the results of a specific sociological study (initiated by the Russian society of sociologists) conducted among students of Russian higher education institutions. Their responses are analyzed and compared with the all-Russian indicators, including the official statistics on the causes of fires, damage and destruction of forest areas, results of content analysis of the news feed, and official information about the area of forest areas. In conclusion, the authors highlight the importance of further studies of the anthropogenic factor in the framework of this environmental threat and the role of man in the fire safety system. This may help in understanding the process of formation and development of environmental consciousness.
Contemporary secondary school: what is the competitive edge of a school graduate?
Authors: Shafranov-Kutsev Gennadiy F. , Gulyaeva Lyudmila V.
Published: May 2020

In the context of the contemporary educational process, researchers consider competitiveness as a system-forming category. On the one hand, they reflect on the level of formation of basic skills and competencies of a person, and on the other — on the range of adaptive capabilities of a person in a system of the changing social relations. This article aims to analyze the main factors affecting the formation of competitiveness among the contemporary high school students. The results of this study indicate that the most significant factors contributing to the development of competitiveness include social activity, initiative, hard work, readiness for constant self-development, and actualization of personal potential. According to the surveyed respondents, the listed qualities become a prerequisite for successful studying and socializing of high school students, as well as for their further and professional development after graduation.
Criminal liability of individuals leading a traditional lifestyle in the Russian North for the crimes under the articles 260 and 222, 222.1 of the Criminal Code of the Russian Federation
Authors: Dyadkin Dmitry S.
Published: May 2020

This paper summarizes the key issues of rights protection of indigenous minor peoples of the Russian North (Khanty and Mansi), who lead a traditional lifestyle, exploiting their ancestral lands: hunting, fishing, and using other resources. In the Khanty-Mansi Autonomous Area, individuals are often prosecuted for illegal felling (Article 260, Criminal Code of the Russian Federation), as well as for illegal acquisition, transfer, sale, possession, transportation or carrying of explosives or explosive devices (Article 222.1, RF Criminal Code). However, land management allows for the general public to perform these activities as well, not only for the relatives or friends of the owner of these ancestral lands. Following the casework, the author has found that in a significant number of cases, the investigation fails to establish either the direct ownership of items limited in circulation (gunpowder and ammunition) or specific individuals who performed the felling. Such being the case, the legal owner of the land or its part is held liable. The purpose of this article is to justify the need for amendments to the Criminal Code of the Russian Federation, i. e. providing for exempting those individuals from criminal liability, who have committed acts, set forth formally, sustaining their traditional lifestyle in the North. This new law will allow the protection of indigenous minorities of the North from inconsistent criminal reprisals and to preserve their cultural practices.
Aminoalkylated Phenolic Chalcones: Investigation of Biological Effects on Acetylcholinesterase and Carbonic Anhydrase I and II as Potential Lead Enzyme Inhibitors
Authors: Yamali Cem , Gul Halise Inci , Cakir Tahir , Demir Yeliz , Gulcin Ilhami
Published: May 2020

Background:

Phenolic Mannich bases have been reported as acetylcholinesterase
(AChE) inhibitors for the medication of Alzheimer's disease. Carbonic Anhydrases (CAs) are molecular
targets for anticonvulsant, diuretic and antiglaucoma drugs in the clinic. Phenolic compounds
have also been mentioned as CA inhibitors. The importance of Mannich bases in drug design inspired
our research group to design novel phenolic Mannic bases as potent enzyme inhibitors.

Objective:

In this study, novel Mannich bases, 1-(3,5-bis-aminomethyl-4-hydroxyphenyl)-3-(4-
substitutedphenyl)-2-propen-1-ones (1-9), were designed to discover new and potent AChE inhibitors
for the treatment of Alzheimer's disease and also to report their carbonic anhydrase inhibitory
potency against the most studied hCA I and hCA II isoenzymes with the hope to find out promising
enzyme inhibitors.

Methods:

Mannich bases were synthesized by the Mannich reaction. The structures of the compounds
were elucidated by 1H NMR, 13C NMR, and HRMS. Enzyme inhibitory potency of the compounds
was evaluated spectrophotometrically towards AChE, hCA I and hCA II enzymes.

Results and Discussion:

The compounds showed inhibition potency in nanomolar concentrations
against AChE with Ki values ranging from 20.44±3.17 nM to 43.25±6.28 nM. They also showed
CAs inhibition potency with Ki values in the range of 11.76±1.29-31.09±2.7 nM (hCA I) and 6.08 ±
1.18-23.12±4.26 nM (hCA II). Compounds 1 (hCA I), 5 (hCA II), and 4 (AChE) showed significant
inhibitory potency against the enzymes targeted.

Conclusion:

Enzyme assays showed that Mannich derivatives might be considered as lead enzyme
inhibitors to design more selective and potent compounds targeting enzyme-based diseases.
Study of Plasmid-Mediated Quinolone Resistance in Escherichia coli from Nosocomial Urinary Tract Infections
Authors: Zaki Maysaa El Sayed , El Salam Mostafa Abd , Faried Osama Ahmed
Published: May 2020

Objective:

The aim of the present study was to study the prevalence of plasmid-mediated
quinolone resistance (PMQR) genes (qnrA, qnrB, qnrC, qnrD, qnrS, qepA, oqxA, oqxB and aac)
in Escherichia coli (E. coli) isolated from patients with nosocomial urinary tract infections (UTIs)
and its relation to the extended-spectrum β-lactamase (ESBL) production.

Methods:

A cross-sectional study was carried out on 200 non-duplicated isolates of E. coli isolated
from patients with nosocomial UTIs. E.coli isolates were subjected to antibiotic susceptibility testing
by disc diffusion method, determination of minimum inhibitory concentrations (MICs) of
ciprofloxacin by Epsillometer (E) test strips, detection of ESBL production by double disc synergy
method and detection of qnrA, qnrB, qnrC, qnrD, qnrS, qepA, oqxA, oqxB and aac genes by polymerase
chain reaction (PCR).

Results:

The antimicrobial susceptibility testing of the isolated E. coli revealed a high frequency of
resistance to ampicillin (73.5%), ceftazidime (72%) and imipenem (71.5%). The less frequent resistance
was for aztreonam (21.5%), amikacin (36.5%) and gentamicin (38.5%). ESBL production
was found in 131 isolates (65.5%) and phenotypic quinolone resistance was detected by MIC in 65
isolates (32.5%), with 52.3% of them showed high resistance to ciprofloxacin with an MIC more
than 32 μg/ml. PMQR genes were found in 40 isolates. The frequency of the detected genes was
40%, 37.5%, 35%, 20% and 5% for qnrA, qnrS, qepA, qnrB and oqxA, respectively. Significant association
was found between the presence of PMQR genes and ESBL production (P=0.0001).

Conclusion:

The study highlights the prevalence of PMQR genes in E. coli with high association
with the ESBL phenotype. This finding is a sign of limited therapeutic options for E. coli.
Insights into Transdermal Drug Delivery: Approaches for Redressal of a Burgeoning Issue of Osteoporosis
Authors: Zakir Foziyah , Kohli Kanchan , Ahmad Farhan J. , Iqbal Zeenat , Ahmad Adil
Published: May 2020

Osteoporosis is a progressive bone disease that remains unnoticed until a fracture occurs. It
is more predominant in the older age population, particularly in females due to reduced estrogen levels
and ultimately limited calcium absorption. The cost burden of treating osteoporotic fractures is too
high, therefore, primary focus should be treatment at an early stage. Most of the marketed drugs are
available as oral delivery dosage forms. The complications, as well as patient non-compliance, limit
the use of oral therapy for prolonged drug delivery. Transdermal delivery systems seem to be a promising
approach for the delivery of anti-osteoporotic active moieties. One of the confronting barriers is the
passage of drugs through the SC layers followed by penetration to deeper dermal layers. The review
focuses on how anti-osteoporotic drugs can be molded through different approaches so that they can be
exploited for the skin to systemic delivery. Insights into the various challenges in transdermal delivery
and how the novel delivery system can be used to overcome these have also been detailed.
Incidence of ESBL-Producing Gram-Negative Bacteria of Lower Respiratory Tract Infection in Bharatpur Hospital, Nepal
Authors: Lamichhane Asmita , Sapkota Sanjeep , Khadka Sujan , Adhikari Sanjib , Thapa Alina , Rana Jid Chani , Ghimire Albert , Thagunna Shova , Pathak Sudipa , Koirala Niranjan
Published: May 2020

Background:

Antimicrobial resistance is a global threat in the medical society. Extended-
Spectrum β-lactamase (ESBL) producing bacteria are increasing worldwide, including Nepal and
causing more severe infections because of their continuous mutation and multidrug resistance
(MDR) nature.

Objective:

The objective of this study was to assess Gram-negative bacterial etiology of lower respiratory
tract infections (LRTIs) and determine their antibiotic susceptibility pattern with a special
focus on MDR, including ESBL production.

Methods:

A total of 109 sputum specimens were analyzed. The bacterial isolates were identified by
standard microbiological procedures, including Analytical Profile Index (API) 20E test panels for
Enterobacteriaceae and subjected to antimicrobial susceptibility testing. Screening of ESBL producers
among Gram-negative isolates was done by using third-generation cephalosporins (ceftazidime
and cefotaxime) and confirmed by the combined disk method as recommended by CLSI (2019).

Results:

Out of 109 sputum specimens, Gram-negative bacterial etiology was determined in
31(28.4%) cases. The age-wise distribution of LRTIs patients was found to be statistically significant
with bacterial incidence (p<0.05). Altogether, 15(46.9%) isolates were multidrug-resistant.
ESBL producers were observed only among Klebsiella spp. and Escherichia coli isolates. On the
ESBL screening test of 9 isolates (3 of E. coli and 6 of Klebsiella spp.) 5(55.6%) gave a positive result,
and only 3(33.3%) of them were further confirmed as ESBL producers. The majority of ESBL
producers (66.7%) were Klebsiella spp.

Conclusion:

The present study revealed that multidrug resistance is prevalent among Gram-negative
bacterial pathogens isolated from the patients with lower respiratory tract infections, requiring routine
laboratory testing for MDR and ESBL production in clinical isolates for better prophylaxis and
reducing the risk of ESBL transmission.
Evidence-Based Decision Aid for Patients With Parkinson Disease: Protocol for Interview Study, Online Survey, and Two Randomized Controlled Trials
Authors: Bientzle Martina , Kimmerle Joachim , Eggeling Marie , Cebi Idil , Weiss Daniel , Gharabaghi Alireza
Published: May 2020

Background

Shared decision making is particularly important in situations with different treatment alternatives. For the treatment of idiopathic Parkinson disease, both pharmacological and surgical approaches can be applied.

Objective

In this research project, a series of studies will be conducted to investigate how decision aids for patients with idiopathic Parkinson disease should be designed in order to support the decision-making process.

Methods

In Study 1a, qualitative interviews will be conducted to determine which needs frequently occur for patients with idiopathic Parkinson disease. In Study 1b, the identified needs will then be rated for personal relevance by an independent group of patients in an online survey. In Study 2, a randomized controlled trial will be used to pretest different decision aids in a sample group of people who do not have a medical background and who do not have Parkinson disease. In Study 3, a randomized controlled trial will be used to investigate the effect of the decision aids that had been evaluated as positive in Study 2 with patients who have idiopathic Parkinson disease.

Results

This series of studies received ethical approval in January 2020. As of June 2020, data collection for Study 1a has started, and it is estimated that Studies 1a, 1b, 2, and 3 will take approximately 4, 4, 6, and 6 months to complete, respectively. It is planned to present the results and analyses at international conferences and to submit the results to peer-reviewed journals for publication, once the studies have been completed. The findings will also be shared with clinicians and patients through presentations at information events.

Conclusions

This series of studies is intended to result in an evidence-based decision aid for patients with idiopathic Parkinson disease in order to support the informed and reflected shared decision-making process. We further intend to contribute to a deeper understanding of the individual preferences of patients with idiopathic Parkinson disease and the impact of those preferences on treatment decisions.
Wearable Device Heart Rate and Activity Data in an Unsupervised Approach to Personalized Sleep Monitoring: Algorithm Validation
Authors: Liu Jiaxing , Zhao Yang , Lai Boya , Wang Hailiang , Tsui Kwok Leung
Published: May 2020

Background

The proliferation of wearable devices that collect activity and heart rate data has facilitated new ways to measure sleeping and waking durations unobtrusively and longitudinally. Most existing sleep/wake identification algorithms are based on activity only and are trained on expensive and laboriously annotated polysomnography (PSG). Heart rate can also be reflective of sleep/wake transitions, which has motivated its investigation herein in an unsupervised algorithm. Moreover, it is necessary to develop a personalized approach to deal with interindividual variance in sleep/wake patterns.

Objective

We aimed to develop an unsupervised personalized sleep/wake identification algorithm using multifaceted data to explore the benefits of incorporating both heart rate and activity level in these types of algorithms and to compare this approach’s output with that of an existing commercial wearable device’s algorithms.

Methods

In this study, a total of 14 community-dwelling older adults wore wearable devices (Fitbit Alta; Fitbit Inc) 24 hours a day and 7 days a week over period of 3 months during which their heart rate and activity data were collected. After preprocessing the data, a model was developed to distinguish sleep/wake states based on each individual’s data. We proposed the use of hidden Markov models and compared different modeling schemes. With the best model selected, sleep/wake patterns were characterized by estimated parameters in hidden Markov models, and sleep/wake states were identified.

Results

When applying our proposed algorithm on a daily basis, we found there were significant differences in estimated parameters between weekday models and weekend models for some participants.

Conclusions

Our unsupervised approach can be effectively implemented based on an individual’s multifaceted sleep-related data from a commercial wearable device. A personalized model is shown to be necessary given the interindividual variability in estimated parameters.
Googling for Ticks and Borreliosis in Germany: Nationwide Google Search Analysis From 2015 to 2018
Authors: Scheerer Cora , Rüth Melvin , Tizek Linda , Köberle Martin , Biedermann Tilo , Zink Alexander
Published: May 2020

Background

Borreliosis is the most frequently transmitted tick-borne disease in Europe. It is difficult to estimate the incidence of tick bites and associated diseases in the German population due to the lack of an obligation to register across all 16 federal states of Germany.

Objective

The aim of this study is to show that Google data can be used to generate general trends of infectious diseases on the basis of borreliosis and tick bites. In addition, the possibility of using Google AdWord data to estimate incidences of infectious diseases, where there is inconsistency in the obligation to notify authorities, is investigated with the perspective to facilitate public health studies.

Methods

Google AdWords Keyword Planner was used to identify search terms related to ticks and borreliosis in Germany from January 2015 to December 2018. The search volume data from the identified search terms was assessed using Excel version 15.23. In addition, SPSS version 24.0 was used to calculate the correlation between search volumes, registered cases, and temperature.

Results

A total of 1999 tick-related and 542 borreliosis-related search terms were identified, with a total of 209,679,640 Google searches in all 16 German federal states in the period under review. The analysis showed a high correlation between temperature and borreliosis (r=0.88), and temperature and tick bite (r=0.83), and a very high correlation between borreliosis and tick bite (r=0.94). Furthermore, a high to very high correlation between Google searches and registered cases in each federal state was observed (Brandenburg r=0.80, Mecklenburg-West Pomerania r= 0.77, Saxony r= 0.74, and Saxony-Anhalt r=0.90; all P<.001).

Conclusions

Our study provides insight into annual trends concerning interest in ticks and borreliosis that are relevant to the German population exemplary in the data of a large internet search engine. Public health studies collecting incidence data may benefit from the results indicating a significant correlation between internet search data and incidences of infectious diseases.
Agile Health Care Analytics: Enabling Real-Time Disease Surveillance With a Computational Health Platform
Authors: Schulz Wade L , Durant Thomas J S , Torre Jr Charles J , Hsiao Allen L , Krumholz Harlan M
Published: May 2020

The ongoing coronavirus disease outbreak demonstrates the need for novel applications of real-time data to produce timely information about incident cases. Using health information technology (HIT) and real-world data, we sought to produce an interface that could, in near real time, identify patients presenting with suspected respiratory tract infection and enable monitoring of test results related to specific pathogens, including severe acute respiratory syndrome coronavirus 2. This tool was built upon our computational health platform, which provides access to near real-time data from disparate HIT sources across our health system. This combination of technology allowed us to rapidly prototype, iterate, and deploy a platform to support a cohesive organizational response to a rapidly evolving outbreak. Platforms that allow for agile analytics are needed to keep pace with evolving needs within the health care system.
Computer-Controlled Virtual Humans in Patient-Facing Systems: Systematic Review and Meta-Analysis
Authors: Chattopadhyay Debaleena , Ma Tengteng , Sharifi Hasti , Martyn-Nemeth Pamela
Published: May 2020

Background

Virtual humans (VH) are computer-generated characters that appear humanlike and simulate face-to-face conversations using verbal and nonverbal cues. Unlike formless conversational agents, like smart speakers or chatbots, VH bring together the capabilities of both a conversational agent and an interactive avatar (computer-represented digital characters). Although their use in patient-facing systems has garnered substantial interest, it is unknown to what extent VH are effective in health applications.

Objective

The purpose of this review was to examine the effectiveness of VH in patient-facing systems. The design and implementation characteristics of these systems were also examined.

Methods

Electronic bibliographic databases were searched for peer-reviewed articles with relevant key terms. Studies were included in the systematic review if they designed or evaluated VH in patient-facing systems. Of the included studies, studies that used a randomized controlled trial to evaluate VH were included in the meta-analysis; they were then summarized using the PICOTS framework (population, intervention, comparison group, outcomes, time frame, setting). Summary effect sizes, using random-effects models, were calculated, and the risk of bias was assessed.

Results

Among the 8,125 unique records identified, 53 articles describing 33 unique systems, were qualitatively, systematically reviewed. Two distinct design categories emerged — simple VH and VH augmented with health sensors and trackers. Of the 53 articles, 16 (26 studies) with 44 primary and 22 secondary outcomes were included in the meta-analysis. Meta-analysis of the 44 primary outcome measures revealed a significant difference between intervention and control conditions, favoring the VH intervention (SMD = .166, 95% CI .039-.292, P=.012), but with evidence of some heterogeneity, I2=49.3%. There were more cross-sectional (k=15) than longitudinal studies (k=11). The intervention was delivered using a personal computer in most studies (k=18), followed by a tablet (k=4), mobile kiosk (k=2), head-mounted display (k=1), and a desktop computer in a community center (k=1).

Conclusions

We offer evidence for the efficacy of VH in patient-facing systems. Considering that studies included different population and outcome types, more focused analysis is needed in the future. Future studies also need to identify what features of virtual human interventions contribute toward their effectiveness.
Sudden Lockdown and Unseen Challenges in India due to COVID19: An Outbreak Analysis (Preprint)
Authors: Taneja Neeraj , Alam Aftab , Patnaik Ranjana S , Taneja Tannu , Bhardwaj Arun , Rana Vikram , Dhanda Harish Rai , Miglani Rohit
Published: May 2020

UNSTRUCTURED

The world is facing an unprecedented situation, because of spread of coronavirus that causes the disease COVID-19 which is totally new, where no one can see light at the end of the tunnel. In last 3 months, this pandemic has spread to 204 countries, regardless of its being developed, developing or under developed. In comparison to developed countries and being a developing nation, India has to date curtailed the spread of virus to stage 2 of local transmissions, by limiting its progression. The government of India together with its states has taken stringent actions to prevent its spread, including a nationwide lockdown. The sudden lockdown in country of 1.4 billion have brought in many unseen challenges, which has created panic, confusion and inconvenience to the general public at large. Though the remedial steps are taken, but that may cause collateral damage in the long run, if not planned earlier. The main objective of the article is to apprise the world about certain hard realities, ignored situations and unseen challenges that are being faced by world’s 2nd most populous country due to sudden locking down.