bluuebunny/crossref_metadata_2025 huggingface dataset:
R132H IDH1 sensitizes glioma to the antiproliferative and cytotoxic effects of BET inhibition
Authors: Sears Thomas K , Woolard Kevin D
Published: February 2022

IntroductionMutations in isocitrate dehydrogenase 1/2 (IDHmut) identify a subset of gliomas that exhibit epigenetic dysregulation via aberrant DNA methylation. These tumors are ultimately fatal and lack effective therapeutic strategies. Considering the epigenetic dysregulation of IDHmut gliomas, we hypothesized that epigenetic-targeting drugs may yield therapeutic benefits in gliomas bearing IDHmut. One set of targets includes the Bromodomain and Extraterminal (BET) family of transcriptional coactivators.MethodsWe used TCGA data from glioma patients to determine whether BET proteins affect patient survival differently based on IDH status. Follow-up experiments using a set of IDH wildtype/mutant glioma cultures, as well as an IDH wildtype glioblastoma cell line expressing exogenous R132H IDH1, focused on cell health assays to investigate whether IDHmut was associated with increased sensitivity to the BET inhibitor JQ1. Immunoblots were used to evaluate the molecular response to JQ1 in these cultures.ResultsWe identified that high BRD4 expression associated with decreased survival only in IDHmut glioma patients. Cell viability analysis showed that IDHmut sensitized glioma cells to delayed cytotoxicity (10 days) in response to JQ1. Early effects of JQ1 (3 days) were primarily antiproliferative, with IDHmut glioma exhibiting a modest increase in sensitivity. Finally, exogenous R132H IDH1 expression in a resistant IDH wildtype cell line recapitulated the JQ1-mediated delayed cytotoxicity seen in our endogenous IDHmut glioma cells.ConclusionOverall, these data suggest that BRD4 enhances malignancy primarily in gliomas bearing IDHmut and is associated with greater sensitivity to BET inhibition. The finding that BET inhibition primarily exhibits delayed cytotoxicity may be overlooked in conventional short endpoint dose-response assays. Follow-up mechanistic and animal studies will help address the translational potential of these findings.
Resilience to chronic mild stress-induced anhedonia preserves the ability of the ventral hippocampus to respond to an acute challenge
Authors: Brivio Paola , Gallo Maria Teresa , Gruca Piotr , Lason Magdalena , Litwa Ewa , Fumagalli Fabio , Papp Mariusz , Calabrese Francesca
Published: February 2022

Stress is one of the main precipitating factors for psychiatric disorders and its effects may depend on its duration and intensity. Interestingly, the ability to react to stressful life events may alter the response to a subsequent novel stressor. However, there are differences in the individual susceptibility to stress, with some individuals displaying vulnerability and others showing resistance. Hence, we investigated whether the vulnerability and resilience to the chronic mild stress (CMS) paradigm, in terms of hedonic phenotype, may alter the ability to cope with a novel acute restraint stress by focusing on neuroplastic mechanisms within the ventral (vHip) and dorsal (dHip) hippocampus, the amygdala (Amy) and the prefrontal cortex (Pfc) of adult male rats. At molecular level, we found that the resilience to CMS was critical to preserving the ability to face a novel challenge measured as neuronal activation. Indeed, the resilient phenotype positively correlated with the enhancement of early response genes specifically in vHip. These results highlight the role of this hippocampal subregion for the development of therapeutic strategies to promote resilience against stress.
A prospective study assessing the pattern of response of local disease at DCE-MRI after salvage radiotherapy for prostate cancer
Authors: Bottero Marta , Faiella Adriana , Giannarelli Diana , Farneti Alessia , D’Urso Pasqualina , Bertini Luca , Landoni Valeria , Vici Patrizia , Sanguineti Giuseppe
Published: February 2022

Background: To assess the pattern of response of presumed local lesions at dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) after salvage radiotherapy (sRT).Methods: This is a prospective study conducted at a single Institution accruing patients with one or more local failures at DCE-MRI after radical prostatectomy between August 2017 and June 2020. Patients underwent exclusive sRT delivering 66-69 Gy and 73.5 Gy in 30 fractions to the whole prostatic fossa and to the local failure(s) seen at DCE-MRI, respectively. Patients were offered DCE-MRI at 3 month-intervals after sRT until complete dis-appearance (CR) of the lesion(s) or up to a maximum of 4 re-evaluations. Results: 62 patients with 72 nodules were enrolled. All patients underwent the 1st re-evaluation, and 33 patients (53.2%) showed a CR. The median time to CR was 4.7 months. Four patients did not undergo further testing before achieving a CR and even considering these patients as no responses, the vast majority (87.1%, 95%CI: 78.5-94.4%) of lesions would have completely disappeared by 12 months from the end of sRT. The volume of the lesion at pre-sRT DCE-MRI was an independent predictor of CR at the 1st re-evaluation (OR: 0.076, 95%CI: 0.009-0.667; p=0.020) along with time elapsed from sRT (OR: 3.399, 95% CI: 1.156-9.993, p=0.026). Conclusions: The present study documents the complete dis-appearance of the vast majority of local lesions after dose-escalated sRT though this requires several months after sRT; timing of CR is at least in part predictable based on the volume of the lesion.Trial registration: Clinicaltrials.gov NCT04703543, registered July 15 2020, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04703543.
The Impact of the Coronavirus Disease - 19 Pandemic on the Treatment of Acute Appendicitis: Presentation, Outcomes, Strategies of Acute Appendicitis During Coronavirus Disease -19 Pandemic
Authors: An Sanghyun , Kim Hae-Rim , Jang Sungwoo , Kim Kwangmin
Published: February 2022

Background: This study aimed to investigate the characteristics, severity, and treatment of patients with acute appendicitis in Korea over a 2-year period during the coronavirus disease (COVID-19) pandemic compared to those before the pandemic. We also investigated whether there were any changes in clinical characteristics of acute appendicitis before and after vaccination against the coronavirus.Methods: We retrospectively reviewed the medical records of patients who were diagnosed with acute appendicitis at our institution between March 1, 2019, and August 31, 2021. We divided the patients into three groups (pre-pandemic, before vaccination, and after vaccination) and analyzed the clinical outcomes.Results: The time from symptom onset to hospital arrival and the time from symptom onset to operation increased during the COVID-19 pandemic period compared to the pre-pandemic period. The rate of complicated appendicitis during the pandemic was higher than that before the pandemic. In addition, the number of new daily cases showed a positive correlation with the time from symptom onset to hospital arrival (OR, 0.03; 95% CI, 0.02 to 0.04; P<0.001) and complicated appendicitis (OR, 1.002; 95% CI, 1.001–1.002; P=0.0017). The vaccination rate showed a negative correlation with the time from symptom onset to hospital arrival (OR, -2.26; 95% CI, -3.42 to -1.11; P<0.001) and complicated appendicitis (OR, 0.915; 95% CI, 0.84 to 0.996; P=0.0404).Conclusions: Employing hospital-wide efforts, such as screening by rapid PCR testing, to avoid further time delays, and nationwide efforts, such as vaccination, to shorten the time from symptom onset to hospital arrival, are necessary to maintain the quality of treatment of acute appendicitis during an infectious disease pandemic.
FGFR1 is a Potential Therapeutic Target in Neuroblastoma
Authors: Cimmino Flora , Montella Annalaura , Tirelli Matilde , Avitabile Marianna , Lasorsa Vito Alessandro , Visconte Feliciano , Cantalupo Sueva , Maiorino Teresa , Angelis Biagio , Morini Martina , Castellano Aurora , Locatelli Franco , Capasso Mario , Iolascon Achille
Published: February 2022

Background: FGFR1 regulates cell-cell adhesion and extracellular matrix architecture and acts as oncogene in several cancers. Potential cancer driver mutations of FGFR1 occur in neuroblastoma NB, a neural crest-derived pediatric tumor arising in sympathetic nervous system but so far, they have not been studied experimentally. We investigated the driver-oncogene role of FGFR1 and the implication of N546K mutation in therapy-resistance in NB cells.Methods: Public datasets were used to predict the correlation of FGFR1 expression with NB clinical outcomes. Whole genome sequencing data of 19 paired diagnostic and relapse NB samples were used to find somatic mutations. In NB cell lines, silencing and transient overexpression of FGFR1 by short hairpin RNA were performed to evaluate the effect of the found mutation by cell growth, invasion and cologenicity assays. HEK293, SHSY5Y and SKNBE2 were selected to investigate subcellular wildtype and mutated protein localization. FGFR1 inhibitor (AZD4547), alone or in combination with PI3K inhibitor (GDC0941), was used to rescue malignant phenotypes induced by overexpression of FGFR1 wildtype and mutated protein.Results: High FGFR1 expression correlated with low relapse-free survival in two independent NB gene expression datasets. In addition, we found the somatic mutation N546K, the most recurrent point mutation of FGFR1 in all cancers and already reported in NB, in one out of 19 matched primary and recurrent tumors. Loss of FGFR1 function attenuated invasion and cologenicity in NB cells, whereas FGFR1 overexpression enhanced oncogenicity. The overexpression of FGFR1N546K protein showed a higher nuclear localization compared to wildtype protein and increased cellular invasion and cologenicity. Moreover, N546K mutation caused the failure in response to treatment with FGFR1 inhibitor by activation of ERK, STAT3 and AKT pathways. The combination of FGFR1 and PI3K pathway inhibitors was effective in reducing the invasive and colonigenic ability of cells overexpressing FGFR1 mutated protein.Conclusion: FGFR1 is an actionable driver oncogene in NB and a promising therapy may consist in targeting FGFR1 mutations in patients with therapy-resistant NB.
Molecular effects of the consumption of margarine and butter varying in trans fat composition: a parallel human intervention study
Authors: Vergères Guy , Guggisberg Dominik , Burton-Pimentel Kathryn J. , Walther Barbara , Portmann Reto , Schmid Alexandra , Radtke Thomas , Saner Hugo , Zangger Nadine , Bütikofer Ueli , Badertscher René , Blaser Carola
Published: February 2022

Background: Dietary intake of industrial trans fatty acids (iTFA) is associated with inflammation, cardiovascular disease and type 2 diabetes but it is unclear whether naturally occurring trans fatty acids (TFA) exert these effects.Methods: In a parallel study, the molecular effects of consuming dairy fat containing ruminant TFA (rTFA) or margarine containing iTFA were investigated. After a run-in period of margarine without TFA (wTFA), 42 healthy volunteers (45 to 69 y), were randomly assigned to diets enriched with margarine wTFA (control), margarine with iTFA, or alpine butter (rTFA) for 4 weeks. Changes in fasting blood values of lipid profiles (GC with flame-ionization detection), metabolome profiles (LC-MS, GC-MS) and gene expression (microarray) were measured.Results: Eighteen fatty acids, as well as 242 additional features measured by LC-MS (185) and GC-MS (54) showed significantly different responses to the diets (PFDR-adjusted < 0.05), mainly distinguishing butter from the margarines while gene expression was not differentially affected. The most abundant TFA in the dietary fats (elaidic and vaccenic acids) were reflected in the significantly different serum TFAs after the TFA interventions.Conclusions: The TFA interventions did not appear to regulate a common molecular pathway. This could be attributable to the different TFAs present in rTFA and iTFA, which could differentially affect cholesterol and lipid metabolism.Trial registration: ClinicalTrials.gov NCT00933322
Application of a new mathematical description of Epidemics to the COVID-19 Omicron wave in few strongly affected countries by the beginning of 2022: USA, UK and France
Authors: Petkov Pavel
Published: February 2022

Purpose By means of mathematical modeling, we studied the COVID-19 Omicron waves in the USA, the UK and France which were strongly affected in the beginning of 2022.The aims were to test a new tracking model and by using the derived parameters, learn more about the new variant properties and the consequences for the population.Methods A newly developed [6] mathematical modeling of Epidemics is applied together with a day by day normalization correction accounting for the different number of tests.Results The new infection cases per day are reasonably described before and around the peak maximum. There are indications that the decreasing part may be well described too. The position of the calculated peaks in time within the Omicron waves indicates everywhere a transition only from the 3th to the 4th generation of infected people. The small impact of the next, 5th generation and the decrease of the new cases per day seem to be related to the combined effect of vaccination and the acquired immunity in a very large part of the population due to Omicron in a short period of time. The calculated cumulative curves support such interpretation.Conclusions The tracking model describes well the Omicron wave after normalization. The results suggest that a very large part of the population in the three countries have (will have) got some protection against the virus. Therefore, controlling/stopping the Pandemic might be soon possible.
Distribution Characteristics of New AO Classification in Different Age Groups of Patients with Femoral Neck Fracture
Authors: Jiang Yuxuan , Feng Dongxu , Huang Wei , Wang Xiaolong , Jiang Wuqiang , Wu Chengxi , Zhu Yangjun
Published: February 2022

Objective: Femoral neck fractures(FNFs) patients from 2018 to 2020 were classified according to the new AO classification. To observe the proportion of new AO classification and provide reference for improving the upper age limit of internal fixation(IF) treatmentMethods: In this study, patients with femoral neck fracture hospitalized in Xi 'an Honghui Hospital from January 2018 to January 2021 were divided into four groups according to age: the young group (≤44 years old), the middle-aged group (45-59 years old),the young elderly group (60-74 years old), and the elderly group (≥75 years old) to analyze age,sex,side,injury mechanism,new AO classification and other features . A total of 2071 patients were included for analysis.Results: There were 742 males (35.8%) and 1,329 females (64.2%).There were 1,106 patient s(53.4%) on the left side and 965 on the right side (46.6%).There were 1781 patients of low energy injury (86%) and 290 patients of high energy injury (14%), and the main injury mechanism was falling.The number of patients with femoral neck fracture in each year was 719 patients in 2018, 694 patients in 2019, and 661 patients in 2020, respectively. The number of patients showed a decreasing trend year by year, and the gender ratio and injury mechanism showed no significant trend of change. In the age group, the proportion of the young group was increasing year by year.Among the new AO classification, there were 1023 patients of B1.3, accounting for the highest proportion of 49.4%.The proportion of B2.2 was the highest in the young group (32.4%) .B1.3 and B2.2 were the main types in the middle-aged group, accounting for 31.7% and 32.0, respectively.B1.3 was dominant in the young elderly and elderly group (47.1% and 63.4%, respectively).Conclusion: The new AO classification is more detailed and practical. 1/3 of the fracture types of middle aged and young elderly people may achieve satisfactory results through IF.Level of evidence: III.
Dynamical Modeling of COVID-19 and Use of Optimal Control to Reduce the Infected Population and Minimize the Cost of Vaccination and Treatment
Authors: Mahardika Yohannes Dhimas
Published: February 2022

The research described a model formulation of COVID-19 using a dynamic system of Ordinary Differential Equation (ODE) which involved four population systems (susceptible, exposed, infectious, and recovered). Then, the research analyzed the direction of the equilibrium, Disease Free Equilibrium (DFE), and Endemic Equilibrium (EE). The treatment and vaccination were the control functions applied to the dynamical system modeling of COVID-19. The research was done by determining dimensionless number R0 or Basic Reproduction Number and applying optimal control into the dynamical system using the Pontryagin Minimum Principle. Numerical calculations were also performed to illustrate and compare the graph of the dynamical system with and without a control function. From the results, there is a reduction in the number of susceptible and infected populations. It indicates that giving vaccines to susceptible populations and treating infected populations affect the number of susceptible and infected populations. It also means thatthis control can reduce the spread of the virus.
EXPLORING THE ROLE OF PROJECT GOVERNANCE AND STAKEHOLDER MANAGEMENT IN PUBLIC SECTOR INFRASTRUCTURE PROJECTS
Authors: Ismail Ishak , Khan Asadullah , Waris Muhammad , Haron Hasnah , Simamora Bachtiar H.
Published: February 2022

In developing countries, governance of public sector projects is becoming increasingly more complex due to the varying nature of stakeholders and their expectations from the government to address their interest. As a result, policymakers and sponsoring agencies are more focusing on stakeholder management to ensure smooth execution, high performance and achieving desired outcomes. This study has conducted a systematic appraisal of the relevant literature to explore the thematic discussions on the role of project governance and stakeholder management in public sector infrastructure projects of Pakistan. The analysis reveals that project governance and stakeholder management is not widely been discussed in the Pakistan specific studies. Therefore, this research proposes project governance and stakeholder management as key concerns of government decision-making strategies.
GENDER STEREOTYPE ROLE IN THE BUSINESS SUCCESS OF WOMEN ENTREPRENEURS IN INDONESIA
Authors: Hartono Hendry , Luhur Wella , Sasmoko Sasmoko , Setiadi Nugroho Juli , Abdulah Abdul Aziz
Published: February 2022

Having good business relationships with stakeholders and have innovative behaviours that are competitive, full of challenges, as well as risks to achieve success in the business.In relationships and behaviours, human beings are inseparable from their views on the attributes or characteristics of women and that have to be performed by women and men who are subconsciously embedded and absorbed in each individual's subconscious, which is commonly referred to as gender stereotypes.This is notapart from its influences on business relationships and innovative behaviours of women entrepreneurs in their business to achieve business success.It is interesting to examine whether gender stereotypes are moderate business relationships and innovative behaviours towards the success of women entrepreneur business in Indonesia.Sources of data obtained by distributing questionnaires and interviewing 109 women entrepreneurs.This research is a quantitative research using the Hierarchical Regression Analysis research method.The findings of this study show that women are more likely to have a relationship with women entrepreneurs.Gender stereotype as a moderating variable does not affect business relationships with a moderate relationship between innovativebehaviour towards business success in women entrepreneurs in Indonesia, and the result shows gender stereotype decrease the influence of innovative behaviours of women entrepreneurs to the success of their business.
EFFECT OF WORK ENVIRONMENT AND EMPLOYEE ENGAGEMENT ON JOB PERFORMANCE OF PUBLIC RELATION STAFF IN LUXURY HOTELS IN JAKARTA
Authors: Suyoto Yohanes Totok , Murtiharso Yosaphat Danis
Published: February 2022

The aim of this study is to examine the relationship between working environment and employee engagement toward job performance of the employees of public relation (PR) staff in five-star hotels in province of Jakarta, Indonesia. From a preliminary survey of 100 customers to measure customers' perceptions of the performance indicatedthat 34% of respondents rated the performance of those employees in the is still poor and needs to be improved. This research using structural equation modeling as an analysis tools. Observed variables are work environment (6 indicators) and employee engagement (34 indicators) as exogeneous variable and job performance (15 indicators) as endogenous variable. The structural model analysis that measure the effect of work environment on job performanceshowedt value and regression coefficient are 4.78 and 0.64 respectively. Analysis result of the effect of employee engagement on job performance, obtained t value and regression coefficient are 5.39 and 0.75 respectively. The R² value of 0.565 shows how work environment and employee engagement can play a positive and significant role together to improve job performance of PR staff of five stars hotelsin province of Jakarta, Indonesia.
ANALYSIS OF THE PRODUCTION PROCESS AT PT TBA.ALAM SUTERA USING THE VALUE STREAM MAPPING METHOD
Authors: Sarjono Haryadi , Yusuf Stevin Dewa , Ferrial Gilang Ananta
Published: February 2022

Each Production Process must have a shortage that may not have very short-term effects but in the long run waste can disrupt the effectiveness of the resources in the company. Minimizing waste in the production process is one of the goals of a company. Value stream mapping is one of the lean methods that can minimize waste in the production process. In this study, the method used to reduce production time at PT. TBA.is a fishbone and Value Stream Mapping (VSM). VSM is used to see the condition of production time in the company. To look for waste in the use of fishbone and to reduce it using line balancing. Found 2 line balancing that is unnecessary motion and unnecessary inventory. With this method we know the total cycle time of 69.06 minutes and the company can reduce 43.4% or 30 minutes of lead time from the total cycle time.
[4 + 3] Cycloaddition Reactions of Cyclic Oxyallyls in Natural Product Synthesis
Authors: Cha J. K. , Oh J.
Published: February 2022

The [4 + 3] cycloadditions of oxyallyls and related allyl cations to
1,3-dienes have been widely utilized for the stereocontrolled construction of seven-membered carbocycles. By virtue of the spectator skeleton, the key variant of utilizing cyclic oxyallyls, i.e., by embedding an oxyallyl function in cyclic compounds, provides a conceptually attractive and operationally efficient route to other medium-sized carbocycles and heterocycles in addition to seven-membered rings. The resulting architecturally complex, polycyclic cycloadducts contain not only sufficient functionality, but also well­ defined facial differentiation useful for subsequent elaboration.
Transition Metal Complexes as Auxiliary Chromophores in Chiroptical Studies on Carbohydrates
Authors: Frelek Jadwiga , Geiger Marcela , Voelter Wolfgang
Published: February 2022

Circular dichroism is obtained only within absorption bands. Carbohydrates, but also alcohols, amines, ethers etc. are transparent in the UV-VIS region of commercially CD spectropolarimeters. In order to see Cotton effects of such compounds, new chromophors have to be introduced in their molecules to form so-called cottonogenic derivatives. One procedure for this is the in situ formation of chiral complexes by mixing the optically active but non­ absorbing substance with a solution of an achiral transition metal complex. By examination of the CD bands of these chiral complexes, configurational and conformational features of the ligands can be determined. Some of our investigations exemplify the application of this approach to carbohydrates: a) Pyranose sugars, bearing free 1,2,3-hydroxyl groups, react with acidic molybdate solutions and form stable Mo-sugar complexes in the pH-range 5-6. They exibit, depending on the sugar structure, two kinds of typical CD curves, whose parameters are correlated, according to a chirality rule, with the sugar configurations. b) Cuprammonium complexes were used first by Reeves to determine configurations and conformations of sugars. Cotton effects of 1,2-diol and 1,2,3-triol pyranoside sugar-cuprammonium complexes are closely examined; for these compounds a helicity rule is verified and proposed. c) Dinuclear transition metal acylates have bee·n widely used recently as chromophores for cottonogenic derivatives. CD spectra of 1,2- and 1,3-diols (including sugar dials) with dimolybdenum tetraacetate as well as the corresponding chirality and sector rules are presented in detail and discussed. d) It is shown that dimolybdenum tetraacetate does not form chiral complexes with monohydroxyalcohols. Dirhodium acetate has more affinity to such ligation. Some complexes of dirhodium tetracis(trifluoroacetate) with monohydroxyalcohols of sugar series have been prepared in situ. Finally the possibility is discussed applying a bulkiness rule to correlate the alcohol geometry with the sign of one of the CD bands of the corresponding rhodium-alcohol-complex.
No Effect of PXR (8055C>T) Polymorphism on the Pharmacokinetic Profiles of
Piperaquine in Healthy Chinese Subjects
Authors: Liu Huixiang , Xie Yuewu , Cai Tianyu , Xing Jie
Published: February 2022

Background:

Significant inter-subject variability in pharmacokinetics and clinical outcomes has been
observed for the antimalarial agent piperaquine (PQ). PQ is metabolized by CYP3A4, mainly regulated by the pregnane
X receptor (PXR). CYP3A4(*1B) polymorphism did not affect PQ clearance.

Objectives:

The effect of PXR (8055C>T) polymorphism on the pharmacokinetic profiles of PQ was investigated.

Method:

The pharmacokinetic profiles of PQ and its major metabolite PQ N-oxide (PQM) were studied in healthy
Chinese subjects after recommended oral doses of artemisinin-PQ. Twelve subjects were genotyped using PCRRFLP
(six in each group with PXR 8055CC and 8055TT), and plasma concentrations were determined by a validated
LC/MS/MS method. The dose-adjusted exposure (AUC and Cmax) to PQ or PQM was investigated, and the metabolic
capability of PQ N-oxidation was determined by AUCPQM/AUCPQ. The antimalarial outcome of PQ was evaluated
using its day 7 concentration.

Results:

PQM formation was mediated by CYP3A4/3A5. Interindividual variability in dose-adjusted AUC of PQ and
PQM was relatively low (%CV, <30.0%), whereas a larger inter-variability was observed for Cmax values (%CV,
68.1% for PQ). No polymorphic effect was found for PXR (C8055T) on the pharmacokinetic profiles of PQ or its
Cday 7 concentrations.

Conclusions:

Both CYP3A4 and CYP3A5 were involved in PQ clearance. The genotypes of PXR (C8055T) may not
contribute to the variability in PQ pharmacokinetics as well as antimalarial outcomes. There might be a low risk of
variable exposures to PQ in malaria patients carrying mutated PXR (8055C>T) genes, which deserves further study,
especially in a larger sample size.
Ligands for Abasic Site-containing DNA and their Use as Fluorescent
Probes
Authors: Ihmels Heiko , Schlosser Julika
Published: February 2022

Apurinic and apyrimidinic sites, also referred to as abasic or AP sites, are residues of duplex DNA in which one DNA base is removed from a Watson-Crick base pair. They are formed during the enzymatic repair of DNA and offer binding sites for a variety of guest molecules. Specif-ically, the AP site may bind an appropriate ligand as a substitute for the missing nucleic base, thus stabilizing the abasic site-containing DNA (AP-DNA). Notably, ligands that bind selectively to abasic sites may be employed for analytical and therapeutical purposes. As a result, there is a search for structural features that establish a strong and selective association of a given ligand with the abasic position in DNA. Against this background, this review provides an overview of the different classes of ligands for abasic site-containing DNA (AP-DNA). This review covers covalently binding sub-strates, namely amine and oxyamine derivatives, as well as ligands that bind to AP-DNA by non-covalent association, as represented by small heterocyclic aromatic compounds, metal-organic com-plexes, macrocyclic cyclophanes, and intercalator-nucleobase conjugates. As the systematic devel-opment of fluorescent probes for AP-DNA has been somewhat neglected so far, this review article contains a survey of the available reports on the fluorimetric response of the ligand upon binding to the AP-DNA. Based on these data, this compilation shall present a perspective for future develop-ments of fluorescent probes for AP-DNA.
Covid-19 Study, Pathology and Therapeutics
Authors: Lu Da-Yong
Published: February 2022

The coronavirus (COVID-19, SARS-Co-2) swept the globe almost two years. However, the outside condition of Covide-19 is unevenly distributed among regions and countries due to various medical efforts and preparedness. The more effective vaccines, drug or other therapeutic strategy was on the road. The origin and hidden nature of Covid-19 pandemics remains to be poorly understood. The positive side of past global effort was about 30% global vaccinations. Advanced knowledge and opinion can safe guide the quality of preventive and therapeutic strategies. To speed up global efforts against Covid-19 spread, new knowledge should be explored and distributed in the future. The epidemic condition, countrywide vaccination and therapeutic variability worldwide collectively determine our armament and capability against Covid-19. Different strategic platforms can reach optimal therapeutic responses and benefiting against viral spread and pathogenesis. By facilitating global alertness and mechanisms against viral-induced social damage, a possibility of futuristic guidelines should be established in upcoming decade. This article addresses this spectrum of diagnostic and therapeutic achievements and insights in the past.
Obesity and Adipose Tissue-derived Cytokines in the Pathogenesis of
Multiple Sclerosis
Authors: Daryabor Gholamreza , Amirghofran Zahra , Gholijani Nasser , Bemani Peyman
Published: February 2022

Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disease of the central nervous system (CNS) characterized by demyelination, neuronal loss, and permanent neu-rological impairments. The etiology of MS is not clearly understood, but genetics and environ-mental factors can affect the susceptibility of individuals. Obesity or a body mass index of (BMI) > 30 kg/m2 is associated with serious health consequences such as lipid profile abnormal-ities, hypertension, type 2 diabetes mellitus, reduced levels of vitamin D, and a systemic low-grade inflammatory state. The inflammatory milieu can negatively affect the CNS and promote MS pathogenesis due in part to the increased blood-brain barrier permeability by the actions of adipose tissue-derived cytokines or adipokines. By crossing the blood-brain barrier, the pro-in-flammatory adipokines such as leptin, resistin, and visfatin activate the CNS-resident immune cells, and promote the inflammatory responses; subsequently, demyelinating lesions occur in the white matter of the brain and spinal cord. Therefore, better knowledge of the adipokines’ role in the induction of obesity‐related chronic inflammation and subsequent events leading to the dys-functional blood-brain barrier is essential. In this review, recent evidence regarding the possible roles of obesity and its related systemic low-grade inflammation, and the roles of adipokines and their genetic variants in the modulation of immune responses and altered blood-brain barrier per-meability in MS patients, has been elucidated. Besides, the results of the current studies regarding the potential use of adipokines in predicting MS disease severity and response to treatment have been explored.
MicroRNAs as Biomarkers for Birth Defects
Authors: Seelan Ratnam S. , Pisano M. Michele , Greene Robert M.
Published: February 2022

It is estimated that 2-4% of live births will have a birth defect (BD). The availability of bi-omarkers for the prenatal detection of BDs will facilitate early risk assessment, prompt medical interven-tion and ameliorating disease severity. miRNA expression levels are often found to be altered in many diseases. There is, thus, a growing interest in determining whether miRNAs, particularly extracellular miRNAs, can predict, diagnose, or monitor BDs. These miRNAs, typically encapsulated in exosomes, are released by cells (including those of the fetus and placenta) into the extracellular milieu, such as blood, urine, saliva and cerebrospinal fluid, thereby enabling interaction with target cells. Exosomal miRNAs are stable, protected from degradation, and retain functionality. The observation that placental and fetal miRNAs can be detected in maternal serum, provides a strong rationale for adopting miRNAs as non-invasive prenatal biomarkers for BDs. In this mini-review, we examine the current state of research in-volving the use of miRNAs as prognostic and diagnostic biomarkers for BD.
German Mobile Apps for Patients With Psoriasis: Systematic Search and Evaluation
Authors: Lull Christian , von Ahnen Jan Alwin , Gross Georg , Olsavszky Victor , Knitza Johannes , Leipe Jan , Schmieder Astrid
Published: February 2022

Background

Psoriasis is a chronic inflammatory skin disease. The visibility of erythematous plaques on the skin as well as the pain and itchiness caused by the skin lesions frequently leads to psychological distress in patients. Smartphone apps are widespread and easily accessible. Earlier studies have shown that apps can effectively complement current management strategies for patients with psoriasis. However, no analysis of such apps has been published to date.

Objective

The aim of this study is to systematically identify and objectively assess the quality of current publicly available German apps for patients with psoriasis using the Mobile Application Rating Scale (MARS) and compile brief ready-to-use app descriptions.

Methods

We conducted a systematic search and assessment of German apps for patients with psoriasis available in the Google Play Store and Apple App Store. The identified apps were randomly assigned to 1 of 3 reviewers, who independently rated them using the German MARS (MARS-G). The MARS-G includes 15 items from 4 different sections (engagement, functionality, aesthetics, and information) to create an overall mean score for every app. Scores can range from 1 for the lowest-quality apps to 5 for the highest-quality apps. Apps were ranked according to their mean MARS-G rating, and the highest-ranked app was evaluated independently by 2 patients with psoriasis using the user version of the MARS-G (uMARS-G). Furthermore, app information, including origin, main function, and technical aspects, was compiled into a brief overview.

Results

In total, we were able to identify 95 unique apps for psoriasis, of which 15 were available in both app stores. Of these apps, 5 were not specifically intended for patients with psoriasis, 1 was designed for clinical trials only, and 1 was no longer available at the time the evaluation process began. Consequently, the remaining 8 apps were included in the final evaluation. The mean MARS-G scores ranged from 3.51 to 4.18. The app with the highest mean MARS-G score was Psoriasis Helferin (4.18/5.00). When rated by patients, however, the app was rated lower in all subcategories, resulting in a mean uMARS-G score of 3.48. Most apps had a commercial background and a focus on symptom tracking. However, only a fraction of the apps assessed used validated instruments to measure the user’s disease activity.

Conclusions

App quality was heterogeneous, and only a minority of the identified apps were available in both app stores. When evaluated by patients, app ratings were lower than when evaluated by health care professionals. This discrepancy highlights the importance of involving patients when developing and evaluating health-related apps as the factors that make an app appealing to users may differ between these 2 groups.

Trial Registration

Deutsches Register Klinischer Studien DRKS00020963; https://tinyurl.com/ye98an5b
Taliban Rule in Afghanistan—Impact on India-Afghanistan Relations
Authors: Manzoor Aafreen
Published: February 2022

This paper emphasizes on the Taliban rule with its impact on the relationship between India and Afghanistan. This paper is based on the empirical study already provided by the professed researchers. This paper tries to make an understanding to the general public with regard to the Taliban rule, its historical perspective and the steps taken by the Indian government for furtherance of the relationship between the two nations. The current study was based on pre articulated policies and programmes conducted for the understanding of the relationship between India and Afghanistan. Therefore, the study was entirely based on secondary data. The secondary data pertaining to the Taliban rule in Afghanistan with the impact on India- Afghanistan relations has been collected from various published books, journals, dissertations and Internet. The data was analysed and modified for deriving meaningful conclusion regarding the impact on India -Afghanistan relations due to the Taliban rule in Afghanistan.
Smart Energy Grid using IOT
Authors: Lingayat Vaishnavi , Hajare Amit , Dhoke Shubhangi , Parvin Sheerin , Tembhurne Mansi , Bhaisare Swati , Mam Prof. Gayatri Padole , Mam Dr. Neetu Gyanchandani
Published: February 2022

Abstract: With increase in population and infrastructure, need for energy production is gradually increasing and to full fill the demanding needs of consumers is in organization hands. This brings the issue of energy production and energy distribution for the organization. Existing meters are not so consumer friendly and always need a periodic checking from utility to inform about their monthly tariff, which requires more man power and is a time consuming process. Also the organization is not able to maintain proper record of consumer data. This project aims to reduce this burden and it makes a real time observation of energy consumption for the consumer as well as the organization. The consumer as well as the organization is able to monitor the real time usage of energy and receive notification to their mobile or on organization website. Also, it notifies the consumer about the peak hours and the grid is able to monitor their geographical area. This project involves Node MCU as main controller and for internet communication and sending real time data over internet, current and voltage sensors.
Medieval Azerbaijan and the development of its visual media
Authors: Badalova Firuza T.
Published: February 2022

Introduction. One of the main features of medieval structures created by Azerbaijani architects and sculptors is the artistic form decorated with elegant designs. Monuments with ornaments are found on buildings that serve as information carriers of the epoch (cult and memorial buildings, baths, castles, palaces, bridges). Since the 11th–12th centuries, the placement of various ornaments on monuments has become an integral part of Azerbaijani art.

Materials and methods. The use of various types of ornaments has led to the emergence of new architectural schools.

Results. Monuments created by medieval architects: Ibrahim ibn Osman (Ganja Gate, 1063), Adjami Abubekr oglu Nakhchivani (Yusif ibn Kusayr mausoleum in Nakhchivan, 1162), Momuna Khatun (Mausoleum of Momuna Khatun, 1186), etc. highlighted by their visual representations. Brief information about the history and architecture of the monument is inscribed on the stone slabs (Sayyed Yahya Bakuwi mausoleum, Maiden Tower, decorative patterns on the portal of the eastern gate of the Shirvanshah complex, etc.). Beginning in the Middle Ages, emergence of Azerbaijani architectural schools began in Arran, Nakhchivan, Shirvano-Absheron and Tabriz schools. Unlike the Middle Ages, nowadays visual information is more widely used on roads, in parks, on crossroads.

Conclusions. The formation of the architectural environment in the 11th–12th centuries revealed the styles of Baku, Ganja, Nakhchivan, Gabala and Arran. The Middle Ages played elegant ornaments in the form of a rose, geometrical, plot, le­gendary, mixed, and stamped. It has been established that the model of the city, based on ancient historical and theoretical studies, can be improved. The increasing importance of information requires the use of architectural, artistic, and aesthetic elements. In the 21st century elegant ornaments with visual power remain relevant in the urban environment.
Regionally Alt-Right? #Wexit as a Digital Public Sphere
Authors: Ruiz-Soler Javier , Chun Wendy Hui Kyong
Published: February 2022

Background: Wexit, a movement for the secession of the provinces in Western Canada, gained national attention and visibility in the federal elections of 2019, boosted by social media platforms.

Analysis: This article explores #wexit interactions on Twitter as a Canadian digital issue public by analyzing the main actors spreading and controlling information and interactions to see if the public Wexit conversation on Twitter engages in alt-right discourse and rhetoric.

Conclusion and implications: The analysis shows how #wexit, as a Canadian alternative to mainstream conservative movements, engages regional concerns and/or petrocultures about “Western culture.”
Building Multiple Access Channels with a Single Particle
Authors: Zhang Yujie , Chen Xinan , Chitambar Eric
Published: February 2022

A multiple access channel describes a situation in which multiple senders are trying to forward messages to a single receiver using some physical medium. In this paper we consider scenarios in which this medium consists of just a single classical or quantum particle. In the quantum case, the particle can be prepared in a superposition state thereby allowing for a richer family of encoding strategies. To make the comparison between quantum and classical channels precise, we introduce an operational framework in which all possible encoding strategies consume no more than a single particle. We apply this framework to an N-port interferometer experiment in which each party controls a path the particle can traverse. When used for the purpose of communication, this setup embodies a multiple access channel (MAC) built with a single particle.We provide a full characterization of the N-party classical MACs that can be built from a single particle, and we show that every non-classical particle can generate a MAC outside the classical set. To further distinguish the capabilities of a single classical and quantum particle, we relax the locality constraint and allow for joint encodings by subsets of 1<K≤N parties. This generates a richer family of classical MACs whose polytope dimension we compute. We identify a "generalized fingerprinting inequality'' as a valid facet for this polytope, and we verify that a quantum particle distributed among N separated parties can violate this inequality even when K=N−1. Connections are drawn between the single-particle framework and multi-level coherence theory. We show that every pure state with K-level coherence can be detected in a semi-device independent manner, with the only assumption being conservation of particle number.
Aspectos empírico-gramaticais para uma proposta acerca do domínio da sintaxe da fala (Empirical-grammatical aspects to a proposal on the dominion of spoken syntax)
Authors: Silva Luis Filipe Lima
Published: February 2022

A Language into Act Theory propõe que o domínio da sintaxe da fala é a unidade informacional, que restringe ou barra qualquer relação sintática possível entre os elementos lexicais. O objetivo deste trabalho é discutir e problematizar essa abordagem oferecendo uma proposta alternativa para essa questão. A partir de uma incursão em aspectos empírico-gramaticais, propõe-se que o domínio da sintaxe da fala é o constituinte. Uma das evidências a favor dessa proposta é a existência de constituintes descontínuos entre unidades informacionais, que atestam sua existência mesmo quando interpolados por outros elementos morfossintáticos. A percepção dos constituintes descontínuos é atestada também por meio de experimentação. A partir da proposta de que o constituinte é o domínio da sintaxe da fala, propõe-se alguns princípios da sintaxe dessa diamesia extraídos a partir de dados de corpora.
O verbo de elocução disse em notícias on-line (The presentation verb disse in online news)
Authors: Rodrigues Roberta  Rego
Published: February 2022

A Apresentação do Discurso é um dos temas abordados pela Estilística de Corpus e compreende o estudo da Fala, da Escrita e do Pensamento em corpora. O objetivo deste artigo é pesquisar como se dá a Apresentação da Fala através do Verbo de Elocução disse em um corpus de notícias on-line. O corpus foi anotado com rótulos relativos às categorias de Fala e foram quantificados no programa AntConc. Os resultados mostram que, das seis categorias empregadas, quatro se manifestam no referido corpus. Pode-se concluir que as categorias de Apresentação da Fala são mais recorrentemente realizadas mediante projeções, visto que a Fala Direta e a Fala Indireta se realizam com mais frequência.
O falar caiçara: subsídios para os estudos sobre a contribuição de línguas indígenas para a formação do português brasileiro (Caiçara-speaking: subsidies for studies on the contribution of indigenous languages to Brazilian Portuguese formation)
Authors: Ivo Ivana
Published: February 2022

O presente trabalho pretende pensar a formação e o desenvolvimento do português falado no Brasil, interpretando dados de fala de uma comunidade caiçara à luz das suas matrizes indígenas constitutivas, procurando identificar dados de inovação linguística e, também, formas conservadas do português antigo. Com o intuito de registrar o falar caiçara, foram feitas entrevistas semiestruturadas, conforme pressupostos da Sociolinguística Variacionista, com 10 adultos, acima de 40 anos, considerando-se as variáveis idade e escolaridade. Os dados foram analisados comparativamente aos de uma pesquisa desenvolvida no sul de Portugal, com uma comunidade rural, e aos dados de uma pesquisa entre caiçaras da Ilha dos Búzios/SP, área pertencente à sub-região que envolve os litorais paulista e sul-fluminense. Como resultado, foram identificados dados de conservação linguística do português antigo e, também, inovações que podem ser interpretadas à luz das teorias do contato.
GAN-based Deep Neural Networks for Graph Representation Learning
Authors: Zhao Ming , zhang yinglong
Published: February 2022

Graph representation learning has attracted increasing attention in a
variety of applications that involve learning on non-Euclidean data.
Recently, generative adversarial networks(GAN) have been increasingly
applied to the field of graph representation learning, and large
progress has been made. However, most GAN-based graph representation
learning methods use adversarial learning strategies directly on the
update of the vector representation instead of the embedding mechanism,
which does not make full use of the essential advantages of GAN. The
essential advantage of GAN is the final embedding mechanism rather than
the embedding representation itself. To address this problem, we propose
to use adversarial idea on the reconstruction mechanism of deep
autoencoders. Specifically, the generator and the discriminator are the
two basic components of the GAN structure. We use the deep autoencoder
as the discriminator, which can capture the highly non-linear structure
of the graph. In addition, the generator another generative model is
introduced into the adversarial learning system as a competitor. A
series of empirical results proved the effectiveness of the new
approach.