bluuebunny/crossref_metadata_2025 huggingface dataset:
Stretching and Shearing Contamination Analysis for Liutex and Other Vortex Identification Methods
Authors: Shrestha Phushpa , Nottage Charles , Yu Yifei , Alvarez Oscar , Liu Chaoqun
Published: October 2020

The newly developed vortex-identification method, Liutex, has provided a new systematic description of the local fluid rotation, which includes scalar, vector, and tensor forms. However, the advantages of Liutex over the other widely used vortex-identification methods such as Q, Δ, λ2 , and λci have not been realized. These traditional methods count on shearing and stretching as a part of vortex strength. But, in the real flow, shearing and stretching do not contribute to fluid rotation. In this paper, the decomposition of the velocity gradient tensor is conducted in the Principal Coordinate for uniqueness. Then the contamination effects of stretching and shearing of the traditional methods are investigated and compared with the Liutex method in terms of mathematical analysis and numerical calculations. The results show that the Liutex method is the only method that is not affected by either stretching or shear, as it represents only the local fluid rigid rotation. These results provide supporting evidence that Liutex is the superior method over others.
Genome-wide association study reveals the genetic architecture of 27 yield-related traits in tomato
Authors: Ye Jie , Wang Xin , Wang Wenqian , Yu Huiyang , Ai Guo , Li Changxing , Sun Pengya , Wang Xianyu , Li Hanxia , Ouyang Bo , Zhang Jun-Hong , Zhang Yuyang , Giovannoni James , Fei Zhangjun , Ye Zhibiao
Published: October 2020

Tomato (Solanum lycopersicum) is a highly valuable vegetable crop and yield is one of the most important traits. Uncovering the genetic architecture of yield-related traits in tomato is critical for the management of vegetative and reproductive development, thereby enhancing yield. Here we perform a comprehensive genome-wide association study for 27 yield-related traits in tomato. A total of 239 significant associations corresponding to 129 loci, harboring many reported and novel genes related to vegetative and reproductive development, were identified, and these loci explained an average of ~8.8% of the phenotypic variance. A total of 51 loci associated with 25 traits have been under selection, especially during tomato improvement. Furthermore, a candidate gene, SlALMT15 that encodes an aluminum-activated malate transporter, was functionally characterized and shown to act as a pivotal regulator of leaf stomata formation through increasing photosynthesis and drought resistance. This study provides valuable information for tomato genetic research and breeding.
Facing COVID-19 via anti-inflammatory mechanism of action: Molecular docking and Pharmacokinetic studies of six anti-inflammatory compounds derived from Passiflora edulis
Authors: Matondo Aristote , Kilembe Jason T , Mwanangombo Domaine T , Nsimba Beaudrique M , Gbolo Benjamin Z , Bongo Gedeon N , Ngbolua Koto-te-Nyiwa , Tshilanda Dorothée D , Tshibangu Damien S T , Mudogo Virima , Mpiana Pius T
Published: October 2020

SARS-CoV-2 is the causative agent of the COVID-19 disease. Pathophysiologically, high levels of proinflammatory cytokines in the serum of SARS-CoV-2 patients are reported, which is so-called the cytokine storm. In this study, molecular docking calculations of six bioactive compounds from Passiflora edulis with anti-inflammatory activity in interaction with the main protease of SARS-CoV-2 were performed, and their pharmacokinetic properties were predicted. The results of their molecular simulations and the ADME-T profiles of each ligand (Absorption, Distribution, Metabolism, Excretion and Toxicity) suggest their use as potential treatment for SARS-CoV-2. Among the six investigated compounds in which four flavonoids and two alkaloids, the best docked ligands are quercetin (-8.2 kcal/mol), chrysin (-8.0 kcal/mol), kaempferol (-7.9 kcal/mol) and luteolin (-7.7 kcal/mol), both flavonoids compounds. Their pharmacokinetic studies using SwissADME, preADMET and pkCSM Web servers establish the good ADMET profile for each ligand.
Universal health care access for all residents reduce mortality in COVID-19 patients in Abu Dhabi, UAE: A retrospective multicenter cohort study
Authors: kaabi Nawal Al , Nuaimi Asma Al , Harbi Mariam Al , Abdalla Jehad , Khan Tehmina , Gasmelseed Huda , Khan Asad , Hamdoun Osama , Weber Stefan
Published: October 2020

Background: SARS‐CoV‐2 was first reported in December 2019. The severity of COVID-19 infection ranges from being asymptomatic to severe infection leading to death. The aim of the study is to describe the clinical characteristics and outcomes of hospitalized COVID-19 patients within the largest government healthcare facilities in the Emirate of Abu Dhabi, the capital of UAE. Methods: This paper is a retrospective cross-sectional study of all patients admitted to Abu Dhabi Healthcare services facilities (SEHA) between the period of March 1st until May 31st with a laboratory-confirmed test of SARS-CoV2, known as Coronavirus disease (COVID19). Variation in characteristics, comorbidities, laboratory values, length of hospital stay, treatment received and outcomes were examined. Data was collected from electronic health records available at SEHA health information system.Results: There were 9390 patients included; patients were divided into severe and non-severe groups. 721 (7.68%) patients required intensive care while the remaining majority (92.32 %) were mild-moderate cases. The mean age (41.8 years) is less than the mean age reported globally. Our population had a male predominance and variable representation of different nationalities. Three major comorbidities were noted, hypertension, diabetes mellitus and chronic kidney disease. The laboratory tests that were significantly different between the severe and the non-severe groups were LDH, Ferritin, CRP, neutrophil count, IL6 and creatinine level. The major antiviral therapies the patients have received were a combination of hydroxychloroquine and favipiravir. The overall in hospital mortality was 1.63% while severe group mortality rate was 19.56 %. The Death rate in the adults younger than 30 years was noted to be higher compared to elderly patients above 60 years, 2.3% and 0.9 % respectively. Conclusion: our analysis suggests that Abu Dhabi had a relatively low morbidity and mortality rate and a high recovery rate compared to published rates in China, Italy and The United States. The demographic of the population is younger and has an international representation. The country had the highest testing rate in relation to the population volume. We believe the early identification and younger demographic had affected the favorable comparative outcome in general with early identification of cases leading to a lower mortality rate.
Long-term cognitively challenging experiences modulate metabolite concentrations in the healthy brain: the case of bilingualism
Authors: Pliatsikas Christos , DeLuca Vincent , Soares Sergio Pereira , Voits Toms , Rothman Jason
Published: October 2020

Cognitively demanding experiences, including complex skills acquisition and processing, have been shown to induce brain adaptations, at least at the macroscopic level, e.g. on brain volume and/or functional connectivity. However, the neurobiological bases of these adaptations, including at the microstructural cellular level, remain poorly understood. Here we use bilingualism as a case study to investigate the microscopic correlates of experience-based brain adaptations. We employ Magnetic Resonance Spectroscopy to measure concentrations of metabolites in the ventral striatum, a region critical to language control which is reshaped by bilingualism. Our results revealed increased concentration of myo-Inositol in bilinguals compared to monolinguals. This metabolite is linked to synaptic pruning, a process underlying experience-based brain restructuring. Crucially, concentration was predicted by relative amount of bilingual engagement. Our results suggest that (degree of) long-term cognitive experiences have measurable effects at the microcellular level, which might accompany, if not drive, the observed macroscopic brain adaptations.
Phylogenetic analysis of variable and conserved genomic regions in severe acute respiratory syndrome coronavirus 2 (COVID-19)
Authors: Nahas Abeer F. El , Elkatatny Nasema M. , Abo-Al-Ela Haitham G.
Published: October 2020

SARS-CoV-2 has rapidly spread around the world. Several mutations have been detected in its genome, but they do not seem to affect the abilities of the virus to spread or infect. We aimed to explore the conserved genomic regions in coronavirus that could contain the key strengths of the virus. SARS-CoV-2 sequence data were retrieved from Genbank from the period of December 2019 to March 2020. Phylogenetic analyses were conducted for 207 sequences using MEGAX compared with the reference sequence (MN908947.3- CHN-Wuhan Dec-2019). The analysis included seven important genomic regions, the ORF1ab gene (21,290 bp), S gene (3,822 bp), Orf3a gene (827 bp), E gene (227 bp), M gene (669 bp), and N gene (1,259 bp), which play critical roles in virus invasion and replication. Furthermore, the variant nucleotides and amino acids were detected by MEGAX and BLAST. Through the phylogenetic analysis and amino acid substitution, the ORF1ab gene showed 11 conserved regions and also several variable sites. The E and M genes were mainly conserved, and all sequences were included in one clade, with one or two amino acid variants. Orf3a and the N gene have four conserved sites distributed along the genes. The S gene has 12 mutations and four main large conserved regionsWe conclude that the favored occurrence of mutations at the ORFab and Orf3a genes during the SARS-CoV epidemic is an important mechanism for virus pathogenesis. The E and M proteins have an almost conserved structure, whereas the S and N genes have many conserved regions, which could serve as possible targets for vaccine design for SARS-CoV.
Modelo de projeto para a gestão territorial em responsabilidade socioambiental quântica: a integração comunidade, universidade e sociedade civil
Authors: Camargo Luís Henrique Ramos de
Published: October 2020

Visando a gerar um modelo de gestão territorial que possa ser aplicado na prática da responsabilidade socioambiental apresentamos à comunidade científica uma metodologia que se baseia nos princípios filosóficos advindos da mecânica quântica. Esta gestão não se limita a pensar o lugar da pesquisa a partir de fragmentos e sim de sua totalidade em sua complexidade que será analisada a partir de uma rigorosa ação científica. Para a compreensão deste processo espaço-temporal, neste texto será feito um pequeno debate conceitual e um resumo da gestão. Este projeto foi aplicado em trabalhos de campo ao longo dos últimos 15 anos, representou a Universidade Estadual do Rio de Janeiro na Rio+20 e foi considerado excelente pelo Departamento de Extensão, da Universidade Estadual do Rio de Janeiro (DEPEXT/UERJ). Pensando em formar uma rede de negócios ecológicos em comunidades carentes, este mecanismo espaço-temporal pretende sua expansão exponencialmente em diferentes lugares propiciando valores universais, qualidade de vida e uma nova postura a frente dos antigos paradigmas econômicos.
Determinants of Internet Usage During COVID-19 on the Young People in Dhaka, Bangladesh
Authors: Das Apu Chandra , Roy Aninda , Salam Md Sakib Ibne
Published: October 2020

As the COVID-19 pandemic is spreading and becoming more contagious, people tend to stay home and face mental health challenges such as anxiety, fear, nervousness, and loneliness. In this time, students are using the internet heavily for their study purpose, and jobholders are for their official works. At the same time, the use of the internet might be a relief from those mental challenges. This manuscript assesses a correlation between daily internet usage before and during COVID-19 and found to be nearly strong positive (r=0.66). Then we determine the potential factors affecting daily internet usage during COVID-19 among Bangladeshi students and jobholders who are currently living in Dhaka city by the ordinary least square (OLS) regression method. Our results underpin that the type of internet, regular internet usage before COVID-19, and the effect of internet usage on the study are significantly affecting current internet usage.
Methodological aspects of the justification of control diagnostic levels of patient exposure in medical X-ray examinations
Authors: Kalinina M. V. , Zhukova T. V.
Published: October 2020

Optimization of medical exposure by substantiating the reference level of patients during diagnostic medical procedures in domestic health care requires harmonization with international recommendations. The paper sets out the history of the question of developing a reference level based on materials from international and domestic regulatory documents, draws attention to the formation of a glossary, presents possible ways of collecting information about the measured levels of patient exposure during x-ray studies obtained at the local, regional and national levels.
Incidence trend for colorectal cancer in the cohort of workers exposed to ionizing radiation
Authors: Zhuntova G. V. , Azizova T. V. , Bannikova M. V. , Zavarukhina T. P.
Published: October 2020

Colorectal cancer is one of the most common malignant neoplasms. Main causes inducing this type of cancer are factors related to the life style and occupational exposures to chemical agents. Some studies demonstrated an association of colorectal cancer incidence and mortality with ionizing radiation. The aim of the present study was to assess the trend in colorectal cancer incidence in a cohort of nuclear workers employed at the Mayak Production Association who had been exposed to ionizing radiation over prolonged periods. The cohort comprised 22,377 workers (25% of females) employed at one of the main plants (reactors, radiochemical and plutonium production plants) of the Mayak Production Association in 1948-1982 who had been externally exposed to gamma rays (cumulative absorbed colon doses were 0–5.85 Gy with the corresponding median dose of 0.16 Gy) and those who had inhaled aerosols containing plutonium particles had been also internally exposed to alpha radiation (cumulative absorbed colon doses were 0–0.18 Gy with the corresponding median dose of 0.0002 Gy). Over the period of 1948–2018, 239 colon cancers and 186 rectum cancers were diagnosed in the study cohort. The incidence of colorectal malignancies among workers of the study cohort was shown to increase with age above 50. Age-standardized incidence rates were higher in males than in females. The time trend analysis of age-standardized rates of colorectal malignancies among workers of the study cohort was performed using a spline regression. The trend of age-standardized rates of colorectal cancer incidence in the Mayak Production Association workers over the analyzed period was nonmonotonic. In general, the average annual percent change of incidence growth for colon cancer was less than 0.1% (for both sexes), while the corresponding estimates for rectum cancer were 1.1% in males and 30.3% in females. To assess the effect of occupational radiation exposure on the incidence of colorectal malignancies, a radiogenic risk analysis that would take into account non-radiation risk factors should be performed.
Radon survey in Chelyabinsk Oblast, Russia, in 2008–2011. Analysis of spatial variability of indoor radon concentration
Authors: Marennyy A. M. , Kononenko D. V. , Trufanova A. E.
Published: October 2020

An extensive radon survey was conducted in 2008-2011 in the framework of the Federal target program on the territory of 29 districts of Chelyabinsk Oblast. SSNTDs were used to measure indoor radon concentrations in public buildings, dwellings and industrial buildings. The results are stored in the database “Radon” owned by Research and Technical Center of Radiation-Chemical Safety and Hygiene of Federal Medical-Biological Agency. The paper presents the results of the analysis of spatial variability of indoor radon concentration and the relationship of this value with a set of geological predictors of radon potential of the territory integrated into a map of ecological and radiogeochemical zones. The results show that in all districts and the whole Chelyabinsk Oblast radon concentrations conform to a lognormal distribution, but in ten districts log-logistic distribution fits the data slightly better. Nevertheless, relative difference between the median values of indoor radon concentration calculated from the two fitted distributions yields zero. The results show that dose assessment based on the arithmetic means could lead to an overestimation of the doses from radon in 1.4 times on average compared to that based on the medians. The median value does not exceed 400 Bq/m3 in any of the surveyed territories and the 95th percentile lies between 96 and 1274 Bq/m3. The fraction of indoor radon concentrations above 400 Bq/m3 expected from the fitted distribution lies between less than 0.1 and 26.8%. The highest values of this fraction were obtained for the Sosnovsky, Kaslinsky, Bredinsky districts and the Miassky urban district (except for the city of Miass). A map of ecological and radiogeochemical zones in Chelyabinsk Oblast was released in 1993-1995 and it was based on a set of geological predictors of radon potential of the territory. We analyzed the relationship of these zones with the results of the radon survey. One-way ANOVA on ranks with the Bonferroni correction showed that there is no statistically significant difference at the 95% confidence level amongst the medians of indoor radon concentration on basement, ground and first floors in settlements, which are located on the territory of three of four of these zones and outside of the territory of all zones. In the fourth zone the median was even two times lower than outside of the zones. These results lead to the conclusion that the possibility of using this map as a map of radon-prone areas is very doubtful. Each datapoint stored in the “Radon” database has a number of additional properties, which allows analyzing other types of indoor radon concentration variability such as seasonal or floor-to-floor. It is expected that later this dataset could be used for estimating regional seasonal correction factors.
Solid cancer incidence risk in in the Ural cohort of the accidentally exposed population: 1956–2017
Authors: Krestinina L. Yu. , Silkin S. S. , Mikryukova L. D. , Epifanova S. B. , Akleyev A. V.
Published: October 2020

To date, the study of the effects of chronic exposure of the South Ural population has been carried out in two separate cohorts – in the Techa River Cohort and in the East Urals Radioactive Trace Cohort. In 2019, the Ural cohort of accidentally exposed population was formed. It included the population exposed in two radiation situations in the Southern Urals in the 1950s. The number of the combined cohort for the cancer incidence analysis was about 60 thousand people, the follow-up period was extended to 2017, the number of solid cancers was 4537, and the number of person-years was 1283267, which is 3 times more than when analyzing the effects of exposure in each of the two radiation situations separately. In the incidence analysis of all solid cancer types, we used the dose accumulated in the walls of the stomach, which corresponds to the dose accumulated in most organs and tissues with the exception of bone tissue and red bone marrow. The mean dose to the stomach accumulated over the entire follow-up period for cohort members was 38 mGy, the maximum -1.13 Gy. The paper presents the first results of solid cancer incidence risk analysis in the combined cohort, which show a statistically significant dose dependence of the incidence in case of chronic exposure in the range of low and medium doses. The sex and age-averaged excess relative risk value of 0.075/100 mGy (the 95% confidence interval is 0.039–0.113) is comparable to that obtained in the studies of the Japanese cohort of atomic bomb survivors. The statistically significant excess relative risk value of 0.047/100 mGy, obtained separately for men, is in good agreement with that in professional cohorts where men prevail – in the cohort of the Chernobyl NPP accident clean-up workers and in the cohort of professional workers in the three countries (UK, France, USA). The established cohort with a long follow-up period has a great potential for furthermore detailed studies of the effects of radiation and non-radiation factors on public health.
A new approach for the methodology of the assessment of the predicted doses to the public of the Bryansk region in the remote period after the Chernobyl NPP accident
Authors: Yakovlev V. A. , Bruk G. Ya.
Published: October 2020

This study is aimed at the evaluation of the trends of the doses from internal exposure of the adult public of the Bryansk region due to the consumption of the main dose-forming food products in the remote period after the Chernobyl NPP accident and the methodical features of the assessment of the predicted doses form the internal exposure. A new methodical approach to the calculation of the predicted doses of the public from internal exposure is based on the single exponential model of the change of the dose with a time-dependent period of a half-decrease. Results of the study allowed increasing the precision of calculation of the predicted doses to the public of the Bryansk region up to 2056. A similar method (single exponential model) can be applied for the external exposure as well. That allowed calculating predicted doses of total (external + internal) exposure. As an example, the paper includes the distribution of all settlements in the Bryansk region referred to the zones of radioactive contamination by the predicted average annual effective dose to the public and critical groups in the different time periods after the accident.
Evaluation of dose parameters defining the probability of deterministic effects in the skin of patients undergoing interventional radiological examinations
Authors: Sarycheva S. S.
Published: October 2020

The study is devoted to the assessment of dose parameters determine the probability of deterministic effects in the skin for patients undergoing high-dose interventional radiological examinations. Particular attention is paid to the analysis of the geometry of the absorbed dose distribution over the patient’s skin for the main types of interventional examinations. The aim of this study was to clarify the methodology for assessment of the maximum absorbed dose in the patients’ skin, taking into account new data. The data collection was carried out in nine city hospitals from Sankt-Petersburg; detailed information about more than 400 procedures was obtained. The data about operation technique for the main types of interventional examinations, physical, technical, geometric and dosimetric parameters for each procedure were registered. Based on the statistical data on distribution of geometric procedure parameters (fields size and projections) possible localizations and values of the absorbed dose in certain areas of the patients’ skin were determined. An updated methodology for skin dose assessment based on the recorded dosimetric value of dose area product considering the radiation fields size was presented. As an alternative, an estimation of the maximum skin dose based on the cumulative air kerma at the patient’s reference point – «representative» point for the patient’s skin considering the tube rotation was proposed. This method does not require the information on used field size. The conservative conversion coefficients from the measured dosimetric values to the peak skin dose and trigger values to prevent deterministic effects in the patients’ skin were calculated.
Internal doses to the public in the Fukushima prefecture from the Fukushima Daiichi NPP accident
Authors: Zvonova I. A.
Published: October 2020

The article is devoted to the analysis of internal dosimetry in residents of Fukushima Prefecture due to the accident at the Fukushima-Daiichi NPP. On March 24-30, 2011, screening studies were conducted on measurements of 131I content in thyroid gland of children in those municipalities where the Japanese program for assessing the radiological consequences of the radiation accident “SPEEDI” predicted doses in the thyroid of one-year children from 100 to 500 mSv. Among 1080 children measured, 55% had results below the background, and the maximum estimate of the equivalent dose in the thyroid was 43 mSv. Measurements of several dozen inhabitants with other instruments and methods confirmed low levels of 131I in the thyroid. In total, the 131I thyroid direct measurement database of Fukushima residents contains approximately 1300 individuals. 75% quartile of individual thyroid dose distributions was below 10 mSv, the median was from 0 to 3.7 mSv among children aged from 0 to 15 years in the five examined municipalities. The contribution of short-lived iodine radionuclides was estimated as 15% of the dose from 131I for the main radioactive release on March 15. The effective dose of internal exposure to cesium radionuclides (134Cs + 137Cs), estimated from 10 thousand whole body measurements for the first year after the accident, was below 0.1 mSv in 90% of the examined people. Whole body measurements of children 6-15 years old in the second year after the accident confirmed the values of the effective dose of internal exposure less than 0.1 mSv, while the estimates of the effective dose of external exposure in the same children with using individual dosimeters determined the median distribution as 0.66 mSv with a maximum value of 3.45 mSv . The measurement results do not provide any basis to expect a future increase in the incidence of thyroid cancer and other radiogenic diseases among the Fukushima residents. Preventive evacuation of the population before the radioactive release, stay in enclosed dwellings, strict radiation control of food products have effectively reduced the expected doses of internal exposure to residents. In the predictions of the radiological consequences of the accident, it is necessary to take into account the actually implemented measures to protect the population, and local characteristics of the style of life and living.
Yer Bağlılığının Sosyo-Mekânsal Farklar Bakımından İncelenmesi: Niğde Örneği
Authors: Ağbaba Derya
Published: October 2020

İnsan ve mekân arasındaki ilişkiyi ele alan coğrafya bilimi, yerin birey için önemi ile de yakından ilgilenmektedir. Bireyin yerin sosyal ve fiziksel özelliklerine ilişkin olumlu hisleri yer bağlılığı olarak bilinmektedir. Bireysel/kültürel tecrübelerin veya farkındalıkların geliştiği, belli bir süreç dâhilinde duygu, biliş ve davranışları da etkileme boyutu olan yer bağlılığı bu çalışmanın konusunu oluşturmaktadır. Yer bağlılığı, yer duygusunu da kapsayacak şekilde ele alınmıştır. Bu bağlamda iki farklı sosyo-kültürel özellikteki (yerli ve mübadil) katılımcı grubunun yer bağlılığına yönelik tercih veya yönelimlerinin sebeplerini anlamak amacıyla bir çalışma hazırlanmıştır. Araştırma sahası olarak üçü köy, biri şehir özelliği gösteren dört yerleşim yeri seçilmiştir. Bunlar Niğde İli, Merkez İlçesi içinde yer alan çokkültürlü bir yapıdaki Niğde şehri, homojen yerli kültür grubunun ikamet ettiği Kırkpınar Köyü, homojen mübadil kültürün yaşadığı Yeşilburç Köyü ve hem yerli hem de mübadil nüfusun bir arada yaşadığı Taşlıca Köyü’dür. 559 katılımcının gönüllü olarak dâhil olduğu bu çalışma için kartopu örnekleme metodu kullanılmış ve yüz yüze uygulanan yapılandırılmış anket soruları yardımıyla veri elde edilmiştir. Sonuç olarak da kültürel farktan ziyade mekânsal ölçekteki farka dayanan bir yer bağlılığı olduğu tespit edilmiştir.
Mitophagy: A Novel Therapeutic Target for Treating DN
Authors: Yang Ming , Li Chenrui , Yang Shikun , Xiao Ying , Chen Wei , Gao Peng , Jiang Na , Xiong Shan , Wei Ling , Zhang Qin , Yang Jinfei , Zeng Lingfeng , Sun Lin
Published: October 2020

Diabetic nephropathy (DN) is a common microvascular complication of diabetes
and one of the leading causes of end-stage renal disease. Tubular damage is an early change
and characteristic of DN, and mitochondrial dysfunction plays an important role in the development
of DN. Therefore, the timely removal of damaged mitochondria in tubular cells is an
effective treatment strategy for DN. Mitophagy is a type of selective autophagy that ensures
the timely elimination of damaged mitochondria to protect cells from oxidative stress. In this
review, we summarize our understanding of mitochondrial dysfunction and dynamic disorders
in tubular cells in DN and the molecular mechanism of mitophagy. Finally, the role of mitophagy
in DN and its feasibility as a therapeutic target for DN are discussed.
Proteomic Analysis of Huntington’s Disease
Authors: Kumar Shobhit , Singh Priyanka , Sharma Shrestha , Ali Javed , Baboota Sanjula , Pottoo Faheem Hyder
Published: October 2020

:

Huntington’s disease (HD) is a neurodegenerative disease that is genetically inherited
through an autosomal dominant gene located on chromosome 4. HD is caused by DNA mutation
(generally 37 or more repetition of CAG nucleotides) that leads to an excessive stretch of glutamine
residues. However, the main pathogenesis pathway resulted by polyglutamine expansion in
mutant HD is unknown. The characteristics of this disease mostly appear in adults. Patients who
suffer from this disease have shown an inability to control physical movements, emotional
problems, speech disturbance, dementia, loss of thinking ability and death occurs between 15-20
years from the time of symptomatic onset. This review article suggested that investigation of mutation
in the HD gene can be done by proteomic analysis such as mass spectroscopy, gel electrophoresis,
western blotting, chromatographic based technology, and X-ray crystallography. The primary
aim of proteomics is to focus on the molecular changes occurring in HD, there by enhancing the effectiveness
of treatment.
The Association between Polygenic Hazard and Markers of Alzheimer’s Disease Following Stratification for APOE Genotype
Authors: De Marco Matteo , Manca Riccardo , Kirby Janine , Hautbergue Guillaume M. , Blackburn Daniel J. , Wharton Stephen B. , Venneri Annalena , Alzheimer’s Disease Neuroimaging Initiative
Published: October 2020

Background:

Research indicates that polygenic indices of risk of Alzheimer’s disease are linked to clinical profiles.

Objective:

Given the “genetic centrality” of the APOE gene, we tested whether this held true for both APOE-ε4 carriers and non-carriers.

Methods:

A polygenic hazard score (PHS) was extracted from 784 non-demented participants recruited in the Alzheimer’s Disease Neuroimaging Initiative and stratified by APOE ε4 status. Datasets were split into sub-cohorts defined by clinical (unimpaired/MCI) and amyloid status (Aβ+/Aβ-). Linear models were devised in each sub-cohort and for each APOE-ε4 status to test the association between PHS and memory, executive functioning and grey-matter volumetric maps.

Results:

PHS predicted memory and executive functioning in ε4ε3 MCI patients, memory in ε3ε3 MCI patients, and memory in ε4ε3 Aβ+ participants. PHS also predicted volume in sensorimotor regions in ε3ε3 Aβ+ participants.

Conclusion:

The link between polygenic hazard and neurocognitive variables varies depending on APOE-ε4 allele status. This suggests that clinical phenotypes might be influenced by complex genetic interactions.
The Activation of Procarcinogens by CYP1A1/1B1 and Related Chemo-Preventive Agents: A Review
Authors: Li Yubei , Cui Jiahua , Jia Jinping
Published: October 2020

CYP1A1 and CYP1B1 are extrahepatic P450 family members involved in the
metabolism of procarcinogens, such as PAHs, heterocyclic amines and halogen-containing organic
compounds. CYP1A1/1B1 also participate in the metabolism of endogenous 17-β-estradiol, producing
estradiol hydroquinones, which are the intermediates of carcinogenic semiquinones and quinones.
CYP1A1 and CYP1B1 proteins share approximately half amino acid sequence identity but
differ in crystal structures. As a result, CYP1A1 and CYP1B1 have different substrate specificity
to chemical procarcinogens. This review will introduce the general molecular biology knowledge
of CYP1A1/1B1 and the metabolic processes of procarcinogens regulated by these two enzymes.
Over the last four decades, a variety of natural products and synthetic compounds which interact
with CYP1A1/1B1 have been identified as effective chemo-preventive agents against chemical carcinogenesis.
These compounds are mainly classified as indirect or direct CYP1A1/1B1 inhibitors
based on their distinct mechanisms. Indirect CYP1A1/1B1 inhibitors generally impede the transcription
and translation of CYP1A1/1B1 genes or interfere with the translocation of aryl hydrocarbon
receptor (AHR) from the cytosolic domain to the nucleus. On the other hand, direct inhibitors
inhibit the catalytic activities of CYP1A1/1B1. Based on the structural features, the indirect inhibitors
can be categorized into the following groups: flavonoids, alkaloids and synthetic aromatics,
whereas the direct inhibitors can be categorized into flavonoids, coumarins, stilbenes, sulfur containing
isothiocyanates and synthetic aromatics. This review will summarize the in vitro and in
vivo activities of these chemo-preventive agents, their working mechanisms, and related SARs.
This will provide a better understanding of the molecular mechanism of CYP1 mediated carcinogenesis
and will also give great implications for the discovery of novel chemo-preventive agents in
the near future.
Inhibition Profiling of Urease and Carbonic Anhydrase II by High- Throughput Screening and Molecular Docking Studies of Structurally Diverse Organic Compounds
Authors: Ali Majid , Bukhari Syed Majid , Zaidi Asma , Khan Farhan A. , Rashid Umer , Tahir Neelum , Rabbani Baseerat , Farooq Umar
Published: October 2020

Background::

Structurally diverse organic compounds and available drugs were screened
against urease and carbonic anhydrase II in a formulation acceptable for high-throughput screening.

Objective:

The study was conducted to find out potential inhibitors of urease and carbonic anhydrase
II.

Methods::

Quantification of the possible HITs was carried out by determining their IC50 values.

Results:

The results of several screened compounds, including derivatives of oxadiazole, coumarins,
chromane-2, 4-diones and metal complexes of cysteine-omeprazole showed promising inhibitory
activities with IC50 ranging from 47 μM to 412 μM against the urease. The interactions of active
compounds with active sites of enzymes were investigated through molecular docking studies
which revealed that (R)-1-(4-amino-4-(5-(thiophen-2-yl)-1,3,4-oxadiazol-2-yl) butyl) guanidine
possessing IC50 of 47 μM interacts with one of the nickel metal atoms of urease besides further
interactions as predictable hydrogen bonds with KCX490, Asp633, His492, His407 and His409
along with Ala440 and 636. Bi-ligand metal complexes of 4-aminoantipyrine based Schiff bases
showed activation of urease with AC50 ranging from 68 μM to 112 μM. Almost 21 compounds with
varying functional groups including pyrimidines, oxadiazoles, imidazoles, hydrazides and tin based
compounds were active carbonic anhydrase II inhibitors presenting 98 μM to 390 μM IC50 values.
Several N-substituted sulfonamide derivatives were inactive against carbonic anhydrase II.

Conclusion::

Among all the screened compounds, the highly active inhibitor of carbonic anhydrase
II was (4-(3-hydroxyphenyl)-6-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl) methanone
with IC50 of 98.0 μM. This particular compound showed metallic interaction with Zn ion of
carbonic anhydrase II through the hydroxyl group of the phenyl ring.
Sulfonamides and Sulphonyl Ester of Quinolines as Non-Acidic, Non- Steroidal, Anti-inflammatory Agents
Authors: Bano Bilquees , Kanwal  , Khan Khalid Mohammed , Jabeen Almas , Faheem Aisha , Taha Muhammad , Haider Syed Moazzam , Perveen Shahnaz
Published: October 2020

Background:

Quinolines are an important class of heterocyclic compounds possessing a
wide range of biological activities. Previously, we had identified Schiff bases of quinoline as potential
anti-inflammatory agents, thus the current work is the continuation of our previous study.

Objective:

In the current study, 3-, 5-, and 8-sulfonamide and 8-sulfonate derivatives of quinoline
(1-50) were synthesized and their anti-inflammatory potential was evaluated. These synthetic analogs
were evaluated for their anti-inflammatory activity via ROS (Reactive oxygen species) inhibitory
effect produced from phagocytes from human whole blood.

Methods:

The sulfonamide and sulfonate derivatives of quinoline were synthesized via treating 5-,
3-, 8-amino, and 8-hydroxy quinolines with different substituted sulfonyl chlorides in pyridine. The
synthetic molecules were characterized using various spectroscopic techniques and screened for
their anti-inflammatory potential.

Results:

Among the synthetic derivatives 1-50, six compounds showed good to moderate antiinflammatory
activity. Compounds 47 (IC50 = 2.9 ± 0.5 μg/mL), 36 (IC50 = 3.2 ± 0.2 μg/mL), and
24 (IC50 = 6.7 ± 0.3 μg/mL) exhibited enhanced activity as compared to the standard ibuprofen
(IC50 = 11.2 ± 1.9 μg/mL). Compounds 20 (IC50 = 25.5 ± 0.7 μg/mL), 50 (IC50 = 42.9 ± 5.6 μg/mL),
and 8 (IC50 = 53.9 ± 3.1 μg/mL) were moderately active, however, rest of the compounds were
found to be inactive.

Conclusion:

The sulfonamide and sulfonate derivatives of quinoline were found to have promising
anti-inflammatory activity. Further studies on the modification of these molecules may lead to the
discovery of new and potential anti-inflammatory agents.
Epidemiology of Ischemic Heart Disease and Diabetes in South Asia: An Overview of the Twin Epidemic
Authors: Gupta Rajeev , Gaur Kiran
Published: October 2020

Background & Objective:

Ischemic heart disease (IHD) is one of the most important causes of death and disability in the world and diabetes is an important risk factor. This review was performed to describe the mortality and morbidity burden from this twin epidemic in South Asian countries.

Methods:

Country-level data on the epidemiology of IHD and diabetes were obtained from the Global Burden of Disease (GBD) study. Sub-national data were available only for India. We also retrieved epidemiological studies from published reviews on IHD and diabetes in India. These were supplemented with MEDLINE search.

Results:

GBD study and regional epidemiological studies have reported that there are significant regional variations in IHD mortality and disease burden within South Asian countries. IHD burden has increased significantly from 2000 to 2017. Prospective Urban Rural Epidemiology study has reported that diabetes is an important IHD risk factor in the South Asian region. GBD Study and International Diabetes Federation have reported increasing diabetes-related mortality and disease burden in South Asian countries, especially India. There are regional variations in diabetes-related mortality, disease burden, and prevalence in South Asia. At the macrolevel, rapid food and nutrition transition along with increasing physical inactivity is responsible for this twin epidemic.

Conclusions:

Increasing trends in IHD and diabetes-related mortality and disease burden with regional variations are observed in South Asian countries.
Predicting the Intention to Preconception Care on the Basis of Planning Behavior Theory in Women Referred to the Marriage Counseling Centers in Asadabad in 2015
Authors: Khorsandi Mahboobeh , Aziz Maryam Valayi , Ranjbaran Mehdi , Vakilian Katayon
Published: October 2020

Background and Objective:

Maternal health is one of the main factors influencing pregnancy
outcomes. Women at childbearing age with poor health are at higher risks. In this context,
preconception planning and receiving care services are of great importance for early identification
and diagnosis of risk factors for pregnancy. The present study assessed the theoretical structures of
planned behavior for the intention of preconception care.

Materials and Methods:

This cross-sectional analytical study was performed on 200 women selected
using a simple random sampling method in Asadabad, located in the west of Iran, in 2015.
The tool used for collecting data was a researcher-made questionnaire containing the theoretical construct
of planning behavior. It included the constructs of attitude, subjective norms, perceived behavior
control, and behavioral and functional intentions. The validity and reliability of the questionnaire
were examined before conducting the research. SPSS 16 using multiple logistic regression and Pearson
correlation coefficient test was used to analyze data.

Results:

The mean and standard deviation of the knowledge were 6.39 ± 3.31, attitude (37.37 ±
4.21), subjective norms (21.12 ± 3.25), perceived behavior control (9.6 ± 2.23), and behavioral intention
(26.7 ± 4.06). There was a direct and significant correlation between the construct of subjective
norms and intention (p=0.039, r=0.146). The construct of attitude and subjective norms were the
most important predictor variables of changes in women's intention of preconception care. Moreover,
no statistically significant relationship was observed between intention and the person's age,
spouse's education, the person's occupation, and women's education (p>0.05).

Conclusion:

According to the results, it is suggested to emphasize creating positive attitudes and
subjective norms while designing educational interventions in order to increase the coverage of preconception
care.
Antimicrobial and Antifungal Properties of Leaves to Root Extracts and Saponin Fractions of Chlorophytum borivilianum
Authors: Sharma Pallavi , Singh Vineeta , Maurya Sanjeev K. , Kamal Mohammad A. , Poddar Nitesh K.
Published: October 2020

Objective:

The study was conducted to examine the antimicrobial activity of methanolic
crude extract from different parts of the Chlorophytum borivilianum plant against pathogenic microorganisms
and toassess antimicrobial activity by MIC and structural characterization of purified
saponin of Chlorophytum borivilianum by using spectrophotometric and NMR analysis.

Methods:

The antimicrobial analysis of the extracts of leaves, roots and stems of C. borivilianum is
based on the agar well diffusion method and Minimum Inhibitory Concentration (MIC). The phytochemical
screening and characterization of saponin on the basis of structural and antimicrobial activity
present in C. borivilianum were analyzed by different spectrophotometric methods such as
HPLC, UV-visible, IR, NMR, LC-ESI-MS and pharmacophore modeling.

Results:

The results revealed that the methanolic leaf, stem and root extracts have inhibitory potential
against the growth of K. pneumonia, B. subtilis, M. tuberculosis, E coli and S. aureus in case of
bacteria and C. albicans, A. fumigatus and Tricoderma in case of fungus. The MIC values of leaf,
stem and root extracts were found in the range of 1 mg/ml to 0.125 mg/ml. Moreover, the purified
saponins indicated MIC in the range of 0.5 mg/ml to 0.0625 mg/ml against the selected microbial
pathogens. Saponins act as one of the major phytocomponents present in C. borivilianum. The antimicrobial
and structural analysis of purified saponins of C. borivilianum was also performed using
different spectral analysis methods.

Conclusion:

The anti-microbial results showed that the extract from the leaf and stems had higher
anti-pathogenic activity as compared to the roots. The MIC results showed that the purified
saponin also possessed the anti-microbial activity and oleanolic acid content, as detected by spectral
analysis the fundamental structure of the extracted saponin.
A Review on Pharmacokinetics Properties of Antiretroviral Drugs to
Treat HIV-1 Infections
Authors: Khan Mohd. Aqueel , Gupta Krishna Kant , Singh Sanjeev Kumar
Published: October 2020

Background:

The HIV-1 pandemic is undoubtedly the major public-health crisis of our time. The extensive
research on HIV has deepened our understanding of its pathogenesis and transmission dynamics. Some new entity
molecules have been approved by the FDA for HIV treatment but till now protective vaccine remains elusive. Scientists
are targeting many important proteins of HIV-1; gp41, gp120, CCR5 coreceptor, integrase, reverse transcriptase and
protease. Few compounds are used as nucleotide analogues to stop HIV replication. Altogether, these compounds and
their derivatives specifically block HIV entry and DNA replication. Using ADMET studies, people are working on these
compounds to reduce toxicity and increase potency.

Objective:

Our main aim is to discuss the Pharmacokinetics properties of 23 important FDA antiretroviral drugs used for
the treatment of HIV-1 infections.

Methods:

We have searched literature related to pharmacokinetics properties in PubMed, Google Scholar search engine.

Conclusion:

Here, we have reviewed the pharmacokinetic properties such as absorption, bioavailability, distribution,
metabolism, and excretion, of important 23 FDA approved drugs. The drugs namely Fuzeon, Selzentry, Complera, Epivir,
Retrovir, Emtriva, Ziagen, Edurant, Intelence, Pifeltro, Sustiva, Viramune, Isentress, Genvoya, Tivicay, Reyataz, Prezista,
Lexiva, Invirase, Aptivus etc. are classified into five major classes: fusion inhibitors, Nucleoside/Nucleotide Reverse
Transcriptase Inhibitors (NRTIs), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), Integrase Strand transfer
inhibitors (INSTIs) and Protease inhibitors (PIs). This Review may helpful for the future development of potent
antiretroviral drugs with improved pharmacokinetic properties.