bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucose feeds the TCA cycle via environmental ethanol in fermenting yeast
Authors: Xiao Tianxia , Khan Artem , Shen Yihui , Chen Li , Rabinowitz Joshua
Published: December 2021

Ethanol and lactate are typical waste products of glucose fermentation. In mammals, glucose is catabolized by glycolysis into circulating lactate, which is broadly used throughout the body as a carbohydrate fuel. Individual cells can both uptake and excrete lactate, uncoupling glycolysis from glucose oxidation. Here we show that similar uncoupling occurs in the yeast Saccharomyces cerevisiae. Even in fermenting yeast that are net releasing ethanol, media 13C-ethanol rapid enters and is oxidized to acetaldehyde and acetyl-CoA. This is evident in exogenous ethanol being a major source of both cytosolic and mitochondrial acetyl units. 2H-tracing reveals that ethanol is also a major source of both NADH and NADPH, and this role is augmented under oxidative stress conditions. Thus, uncoupling of glycolysis from the oxidation of glucose-derived carbon via rapid reversible reactions is an ancient and conserved feature of eukaryotic metabolism.
Bibliometric Analysis of Research Trends And Characteristics of Drug-Induced Gingival Overgrowth
Authors: Zhang Ruonan , Wu Jie , Wang Xiaoxiao , Song Jiangyuan
Published: December 2021

Objectives: Drug-induced gingival overgrowth (DIGO) is a common adverse drug reaction generally caused by the cyclosporine, phenytoin and nifedipine which belong to the category of immunosuppressant, anticonvulsant and calcium channel blocker respectively. The objective of the bibliometric analysis was to depict main citation characteristics and analyze research trend in the field of DIGO.Methods: An exhaustive search was performed in the Scopus database for the bibliometric list of DIGO in the syntax. The information related to the number of citations, drugs related to DIGO, study topic and design, authorship, year of publication, journal, contributing institution, country of origin and department was extracted.Results: A total of 399 papers on DIGO were retrieved. The total number of citations and that after removal of self-citations is 7814 and 7314, respectively. The mean number of citations is 19.6, with a range of 0 to 608. Article (76.9%) and review (19.5%) are the main paper types. A remarkable increasing trend in the number of citations is observed since 1994. Cyclosporine (45%) is the most common used drug which has close relation with DIGO, followed by nifedipine, phenytoin (both are 18%), amlodipine (7%). Review (28%) constitutes the most design in the study of DIGO. According to the top 20 keywords, the risk factors and pathogenesis of DIGO have been the hot area of research for several years.Conclusions: The bibliometric study is the first of its kind to identify the top-cited articles and their main characteristics and research trend of DIGO. Risk factors and pathogenesis is the hotspot of research in the field of DIGO. More high level of scientific evidence on DIGO, such as systematic reviews and randomized controlled trials, are encouraged to serve as good helper to reduce the incidence and severity of DIGO.
Climate Suitable Conditions Index and Autochthonous Dengue Infections: an Early Warning Index
Authors: Lu Xinting , Bambrick Hilary , Frentiu Francesca D. , Huang Xiaodong , Davis Callan , Li Zhongjie , Yang Weizhong , Devine Gregor J. , Hu Wenbiao
Published: December 2021

Background: Aedes aegypti is the primary vector of dengue and contributes to most major epidemics of this virus worldwide. Aedes albopictus is also blamed for certain epidemics, as the 2014 Guangdong dengue outbreak. In Guangdong province, Ae. albopictus is thought to be the dominant vector species, with Ae. aegypti absent from most areas. Whether or not primary mosquito vectors are present, optimal climatic conditions for dengue vector species may play a substantial role in epidemics of the virus. We hypothesise that although vector species are required to initiate and establish an outbreak, favourable weather conditions may then grow and perpetuate the outbreak via complex effects on vector sympatry or interactions.Methods: Vector spices-specific suitable conditions index (SCI) and autochthonous dengue case data were fitted to negative binomial (NB) regression models. After accounting for potential confounders, we assessed the relationship between SCI and autochthonous dengue cases. We assumed SCI interaction was a proxy for vector species sympatry and SCI difference a proxy for interspecies competition. Finally, we explored the relationship between these assumed conditions and the autochthonous dengue case. Results: Autochthonous dengue cases are associated negatively with SCI for Ae.albopictus and positively with SCI for Ae.aegypti. According to the NB regression models, autochthonous dengue cases increased 4% (Incident Rate Ratio (IRR): 1.04, 95% CI: 1.02, 1.06) for every unit increase in SCI for Ae. aegypti, but decreased by 3% (IRR: 0.97, 95% CI: 0.96, 0.99) for Ae. albopictus SCI. There was also an interaction between two SCIs and a positive effect of the difference in SCIs on autochthonous dengue cases. These findings support the hypothesis that vector sympatry and interactions may influence the risk of a dengue outbreak.Conclusions: Our results confirm the hypothesis that the dengue virus is more transmissible in regions with warmer weather conditions (high SCI for Ae. aegypti). SCI of Ae. aegypti would be a valuable index to predict dengue transmission even in the absence of Ae. aegypti but with Ae. albopictus present. The results also support that the SCI is beneficial for evaluating dengue outbreak risk in terms of vector sympatry and interactions in the absence of entomology data in future research.
An integrative approach to clinical recovery for COVID-19 patients using an Ayurvedic formulation: A multicentric double-blind randomized control trial.
Authors: Bhardwaja Pankaj , Ganapathy Kalaiselvan , Pathania Monika , Naveen K H , Charan Jaykaran , Dutta Siddhartha , Gadepalli Ravisekhar , Sriniva Srikanth , Gupta Manoj Kumar , Goelj Akhil D , Midha Naresh , Kumar Bharat , Sharma Meenakshi , Sharma Praveen , Banerjee Mithu , Mitra Prasenjit , Misra Sanjeev , V. Vinayagamoorthy , Subramaniant Girija , R Praveen , Dhar Minakshi , Saxena Vartika , Dhamija Puneet , Singh Archana , Subramanian Saumya , Kanchibhotlaz Divya
Published: December 2021

BackgroundTraditional medicine systems such as Ayurveda contain a vast repository of naturally occurring herbs with strong antimicrobial potency. A multitude of complementary therapies have been explored for their therapeutic role to treat COVID-19 during the pandemic. There have been promising results reported from in silico, in vitro and in vivo studies that need to be further explored in humans.ObjectiveThe present randomized placebo control trial evaluates the clinical efficacy of an integrated approach including Ayurvedic polyherbal formulation, NOQ19 in the improvement of mild to moderate category of COVID-19 infected patients.Patients and methodsA multicentric, randomized, placebo control design was adopted for the study. A total of 76 patients with positive COVID-19 RT-PCR test were enrolled in the study; 39 in the NOQ19 arm and 37 in the placebo arm. Patients were randomized and blinded to their respective intervention, which was provided along with the standard of care treatment. Rate of recovery assessment was done on Day 3, 5 and 7 via RT-PCR test to measure the rate of recovery. Blood markers were analysed on Day 0 and Day 7.OutcomesThe patients were assessed for rate of recovery via RT-PCR and improvement in blood biomarkers. They were also monitored for any adverse events or side effects of the drug.ResultsThe present study demonstrated a significant early recovery in the patients who took the NOQ19 formulation. Patients who received NOQ19 with the standard care of treatment showed clinical improvement in terms of oxygen requirement, breathlessness and SpO2, though the difference was not statistically significant. Moreover, no side effects were observed with the use of NOQ19.ConclusionAn overall integrated approach of standard of care treatment with Ayurvedic formulation (NOQ19) results in early clinical outcome in the management of mild to moderate cases of COVID-19.
Heterosis and combining ability studies by Line × tester analysis for fruit biochemical, morpho-physiological, and yield traits governing shelf life in tomato (Solanum lycopersicum L.)
Authors: MP pavan , S Gangaprasad , M Dushyanthakumar B , Adivappar Nagrajappa
Published: December 2021

Improving tomatoes keeping quality is crucial for reducing post-harvest losses. Knowledge on heterosis, and combining ability is pre requisite for breeding high yielding and good shelf life heterotic hybrids. An investigation was undertaken with each of 3 lines, testers, and 9 hybrids to identify desirable parents and crosses for 20 fruit biochemical, morpho-physiological, and yield traits and to elucidate nature of gene action for shelf life and its contributing traits through Line × Tester analysis. The lines contributed to most of hybrids variability than testers and fruit quality traits had higher degree of SCA variance as compared to GCA variance. pH, ascorbic acid, fruit firmness, and plant height governed by additive gene action. Lycopene, titratable acidity, TSS, calcium, magnesium, pericarp thickness, pulp content, locule number, fruit length, diameter, weight, shelf life, number of branches, number of clusters, number of fruit/cluster, and yield/plant were under the control of non-additive gene action. All the lines and Arka Saurabh were best general combiners and IIHR 2349 × Arka Vikas, IIHR 2349 × Arka Saurabh, IIHR 2358 × Arka Ahuti and IIHR 2357 × Arka Ahuti were the best specific combiner in producing heterotic hybrids. IIHR 2349 × Arka Vikas and IIHR 2349 × Arka Saurabh were promising hybrids for high yield and shelf life. The crosses involved both parents with high, one parent with high and other with low and both parents with low good overall general combining ability status respectively indicated the additive, non-additive and epistatic gene action in fruit quality and yield traits inheritance.
Characterization and Corrosion Resistance Behavior of Pure Ni Coatings & Ni-V2O5 Nano composite Coatings Developed by DC & PC Methods of Electrodeposition
Authors: Mohanreddy R , Praveen B M , Alhadhrami A
Published: December 2021

Pure nickel (Ni) coating and nickel – vanadium pentoxide (Ni-V2O5) nanocomposite coatings have been developed on mild steel substrates by direct current (DC) & pulse current (PC) methods of electrodeposition using sulfamate electrolyte bath by optimizing all the suitable parameters. The surface morphology and texture characterization of pure Ni coating and Ni-V2O5nanocomposite coatings were analyzed by spectroscopic techniques such as Scanning Electron Microscopy (SEM) equipped with an attachment for Energy Dispersive Spectrometry (EDS) & X-ray Diffraction (XRD) spectroscopy analysis. The SEM study confirmed surface morphology of the pure Ni coating was changed by the incorporation of V2O5 nanoparticles in the nickel metal matrix and chemical composition of all the coatings was determined by EDS. XRD study proved highly corrosion resistant nanocomposites show preferred orientation towards (111) plane. The corrosion rate of all the coatings was investigated in 3.5% corrosive medium using electrochemical techniques such as Tafel extrapolation and AC impedance. The coatings developed by PC show enhanced corrosion resistance behavior compare to coatings developed by DC. The 0.125g/L Ni-V2O5nanocomposite coating obtained by PC show more widened semicircle with high Rp value and has more positive shift with high corrosion resistance during AC impedance and Tafel extrapolation analysis respectively. The coatings developed by PC showed improved micro hardness compare to coatings developed by DC during micro hardness testing of all the coatings.
Protective Potential of Adiponectin and Quercetin on Alleviating Bisphenol-A-Induced Toxicity in Muscle Cells Through the KEAP1/NRF2 Pathway
Authors: Mohammadi Davood , Jalali-Mashayekhi Farideh , Nedaei Keivan , Ghadimi Darya , Rasooli Zahra , Hemmati Mina
Published: December 2021

Background: Bisphenol A (BPA) is a toxic environmental estrogenic compound which exerts its detrimental effects by increasing oxidative stress and decreasing levels of antioxidants. This study aimed to evaluate beneficial effect of adiponectin and quercetin in reducing BPA-induced oxidative stress by assessing the Prooxidant-antioxidant balance (PAB) assay, catalase activity and KEAP1/NRF2 expression in muscle cells.Methods and Results: L6 rat muscle cells were exposed to BPA (50 an100 μM) with and without treatment with different concentrations of adiponectin (10 and 100 ng/ml) and quercetin (10 and 25 ng/ml) for 24 and 48 hours. Cell viability was assessed using MTT assay, and the PAB was evaluated with the ELISA at 540 nm. Catalase level was also evaluated in all groups. Furtheremore, the expression of KEAP1/Nrf2 genes was assessed using qRT-PCR. The results showed a significant reduction in L6 cells survival after being treated with 100 μM BPA. Adiponectin and quercetin treatment also increased cell survival compared to BPA-treated cells. It was also found that PAB increased with BPA exposure, and quercetin treatment significantly reduced it compared to BPA treatment. The catalase activity was reduced in BPA-treated cells, which was significantly increased by treatment with adiponectin and quercetin. A significant decrease in Nrf2 gene expression was observed in BPA-treated cells compared to the control group. It was further found that cell treatment with quercetin and adiponectin significantly increased the expression of Nrf2 gene compared to the control group.Conclusions: Taking together, our results implied that adiponectin and quercetin could modulate BPA-induced oxidative stress in muscle cells through KEAP1/Nrf2 pathway. Accordingly, it can be concluded that adiponectin in low dose and quercetin, may have significant impact in reducing toxicity due to BPA.
Toddalolactone Protects Against Osteoarthritis by Ameliorating Chondrocyte Inflammation and Suppressing Osteoclastogenesis
Authors: Xu Yiming , Xue Song , Zhang Tian , Jin Xinmeng , Wang Cong , Lu Haiming , Zhong Yiming , Chen Hongjie , Zhu Libo , Ma Jinzhong , Sang weilin
Published: December 2021

Background: Osteoarthritis (OA) is widely recognized as the most common chronic joint disease accompanied by progressive cartilage and subchondral bone damage. Toddalolactone (TOD), a natural compound extracted from Toddalia asiatica (L.) Lam., has been widely used in the treatment of stroke, rheumatoid arthritis, and oedema. Nevertheless, what TOD acts as in the pathogenesis and progression of OA hasn’t been reported. In this investigation, we have aimed to determine how TOD affects OA in vitro and in vivo.Methods: LPS (10μg/ml) was employed to induce chondrocyte inflammation or RANKL to induce osteoclast differentiation in bone marrow derived macrophages (BMMs); Meanwhile, the effects of TOD on chondrocyte inflammation and osteoclast differentiation were evaluated. Anterior cruciate ligament transection (ACLT) was performed to develop an OA animal model and study the effects of TOD.Results: We found that TOD inhibited the expression of inflammatory and catabolic mediators ( IL-6, IL-8, TNF-α, MMP2, MMP9, and MMP13) in LPS-treated chondrocytes in vitro. Furthermore, TOD was proven to inhibit RANKL-induced-osteoclastogenesis and inhibit the expression of marker genes (NFATc1 and c-fos). Our data also confirmed that TOD suppressed the destruction of articular cartilage and osteoclastogenesis by inhibiting the activation of the NF-κB and MAPK signalling pathways. In the ACLT mouse model, we found that TOD attenuated the ACLT-induced cartilage erosion and inhibited bone resorption.Conclusions: These results showed that TOD can be adopted as a potential therapeutic agent for OA.
Maternal Childbirth Experience and Time in Labor - A Population-Based Cohort Study
Authors: Carlhäll Sara , Nelson Marie , Svenvik Maria , Axelsson Daniel , Blomberg Marie
Published: December 2021

A negative childbirth experience may have long term negative effects on maternal health. New international guidelines allow a slower progress of labor in the early active phase, however a longer time in labor may influence the childbirth experience. In this population-based cohort study including 26,429 women, who gave birth between Jan 2016 to March 2020, the association between duration of the different phases of active labor and childbirth experience was studied. The women assessed their childbirth experience by visual analogue scale (VAS) score. Data including VAS score and labor time estimates were obtained from electronic medical records and adjusted odds ratios (aOR) were calculated.The prevalence of negative childbirth experience (VAS 1-3) was 4,9%. A significant association between longer duration of all phases of active labor and a negative childbirth experience (VAS 1-3) was found for primi- and multipara. The aOR for negative childbirth experience and longer time in active labor in primipara was 1.88, 95% CI (1.59-2.22) and for multipara aOR 1.90, 95% CI (1.59-2.28).It is of great importance to identify and optimize the clinical care of women with prolonged labor to reduce the risk of negative childbirth experience and associated adverse long-term effects.
Process Evaluation of Recombinant Chitin Deacetylase Expression in E. Coli Rosetta pLysS Cells using Statistical Design of Experiments
Authors: Pawaskar Goutam Mohan , Raval Ritu , S Subbalaxmi
Published: December 2021

Chitin is a natural polymer with N-acetylglucosamine units, extracted from seafood waste as a major source. It remains an underexplored polymer due to its crystalline structure. The commercial applicability can be improved if we could make it soluble. One of the routes employed to decrease this crystallinity is the conversion of chitin to chitosan via deacetylation. The industrial production of chitosan uses chemical methods, which leaves the process footprint on the environment. The greener alternative approach to producing chitosan is using chitin deacetylases (CDA). The enzymatically converted chitosan with known characteristics has a wide range of applications, importantly in the biomedical field. In the present paper, we report heterologous expression of CDA from a marine moneran; Bacillus aryabhattai B8W22. The process and the nutritional conditions were optimized for the submerged fermentation condition of E. coli Rosetta pLysS expressing the recombinant CDA using the design of experiment tools. The employment of central composite design (CCD) resulted in a ~2.39 fold increase in the total activity of expressed CDA with the process conditions of induction temperature at 22 ºC, agitation at 120 rpm, and 30 h of fermentation. The nutritional conditions required for the optimized expression were 0.061% glucose concentration and 1% lactose in media. The employment of these optimal growth conditions could result in cost-effective large-scale production of the lesser-explored moneran deacetylase, embarking on the greener route to produce biomedical grade chitosan.
3DFAACTS-SNP: Using Regulatory T Cell-specific Epigenomics Data to Uncover Candidate Mechanisms of Type-1 Diabetes (T1D) risk
Authors: Liu Ning , Sadlon Timothy , Wong Ying Ying , Pederson Stephen Martin , Breen James , Barry Simon
Published: December 2021

BackgroundGenome-wide association studies (GWAS) have enabled the discovery of single nucleotide polymorphisms (SNPs) that are significantly associated with many autoimmune diseases including type 1 diabetes (T1D). However, many of the identified variants lie in non-coding regions, limiting the identification of mechanisms that contribute to autoimmune disease progression. To address this problem, we developed a variant filtering workflow called 3DFAACTS-SNP to link genetic variants to target genes in a cell specific manner. Here we use 3DFAACTS-SNP to identify candidate SNPs and target genes associated with the loss of immune tolerance in regulatory T cells (Treg) in T1D. ResultsUsing 3DFAACTS-SNP we identified from a list of 1,228 previously fine-mapped variants, 36 SNPs with plausible Treg-specific mechanisms of action. The integration of cell-type specific chromosome conformation capture data in 3DFAACTS-SNP, identified 119 regulatory regions and 51 candidate target genes that interact with these variant-containing regions in Treg cells. We further demonstrated the utility of the workflow by applying it to three other SNP autoimmune datasets, identifying 17 Treg-centric candidate variants and 35 interacting genes. Finally, we demonstrate the broad utility of 3DFAACTS-SNP for functional annotation of all known common (>10% allele frequency) variants from the Genome Aggregation Database (gnomAD). We identified 7,900 candidate variants and 3,245 candidate target genes, generating a list of potential sites for future T1D or autoimmune research. ConclusionsWe demonstrate that it is possible to further prioritise variants that contribute to T1D based on regulatory function and illustrate the power of using cell type specific multi-omics datasets to determine disease mechanisms. Our workflow can be customised to any cell type for which the individual datasets for functional annotation have been generated, giving broad applicability and utility.
Global Assessment of Spatiotemporal Variability of Wet, Normal and Dry Conditions using Multiscale Entropy-based Approach
Authors: Sreeparva Vijay , Srini V.V
Published: December 2021

In recent decades, human-induced climate change has caused a worldwide increase in the frequency/intensity/duration of extreme events, resulting in enormous disruptions to life and property. Hence, a comprehensive understanding of global-scale spatiotemporal trends and variability of extreme events at different intensity levels (e.g., moderate/severe/extreme) and durations (e.g., short-term/long-term) of normal, dry and wet conditions is essential in predicting/forecasting/mitigating future extreme events. This article analyses these aspects using estimates of a non-stationary standardized precipitation evapotranspiration index corresponding to different accumulation periods for 0.5˚ CRU resolution grids at globe-scale. Results are analyzed with respect to changes in land-use/landcover and location/geographic (latitude, longitude, elevation) indicators at different time scales (decadal/annual/seasonal/monthly) for each continent. The analysis showed an (i) increasing trend in the frequency/count of both dry and wet conditions and variability of dry conditions, and (ii) contrasting (decreasing) trend in the variability of wet conditions, possibly due to climate change-induced variations in atmospheric circulations. Globally, the highest variability in the wet and dry conditions is found during the Northern hemisphere's winter season. The decadal-scale analysis showed that change in variability in dry and wet conditions has been predominant from the 1930s and 1950s, respectively and is found to be increasing in recent decades.
Steinernema Feltiae- Xenorhabdus Bovienii: More Information about this Bactohelminthic Complex from Iran
Authors: Kuhestani Kimia , Karimi Javad , Makhdomi Ali
Published: December 2021

Background: Entomopathogenic nematodes (EPNs) of the families Steinernematidae and Heterorhabditidae that are symbiotically associated with Xenorhabdus and Photorhabdus bacteria are one of the effective biological control agents of insect pests. Native isolates can probably be more efficacious to control insect pests than exotic ones due to their adaptability to indigenous environmental conditions. Results: In this study, Steinernema feltiae isolate FUM221 was recovered from soil samples collected from the Fandoghloo pasture, Ardabil province, Iran. Morphological investigations of the first and second-generation adults, infective juveniles, and molecular characterizations were given based on ITS and 18S rDNA genes. Besides, molecular analysis based on the 16S rRNA region and phenetic data recognized Xenorhabdus bovienii as its symbiont bacterium. The scanning electron microscopy (SEM) images verified the identification of this isolate.Conclusion: The molecular characterization using two loci and phylogenetic analyses provided more evidence for the classification of this steinernematid and its difference of the same species from other countries. Moreover, molecular and phenetic characterizations of its symbiotic bacterium were provided with low variations compared to other isolates. Herein, the comprehensive taxonomic data of this steinernematid from Iran is presented.
Health Problems Among Forcibly Displaced Myanmar Nationals (FDMNs) Admitted To The Medicine Ward of Cox’s Bazar Medical College Hospital
Authors: Ismail Mohammad , Hussain Mohammad Farhad , Hasan Mohammad Abdullah Al , Kamal AHM Mustafa , Rahman Monjur , Hassan Mohammad Jahid
Published: December 2021

Background
Forcibly displaced Myanmar nationals (FDMNs) or Rohingya refugees are one of the vulnerable groups suffering from different kinds of health problems but have been less reported yet. Therefore, the study was designed to delineate the health problems among FDMNs admitted to Cox’s Bazar Medical College Hospital.
Methods
This hospital-based cross-sectional study was conducted at the Medicine ward, Cox’s Bazar Medical College Hospital, for a six-month period following approval. Rohingya refugees who were admitted during the study period were approached for inclusion. Informed written consent was ensured prior to participation. A structured questionnaire was used during data collection. Collected information was recorded in case record form. A total of 290 subjects were interviewed. Analysis was performed using the statistical package for social science (SPSS) version 20.
Results
The mean age of the participants was 48.76±18.67 years (range: 16-91), with a clear male predominance (60.7%). Family size ranged 6-8. All of the participants reported at least one of the illnesses. Of all, 29.66% patients reported disease of the respiratory system, and 26.9% reported disease of the gastrointestinal disease and hepatobiliary system. Accidental injury or injury due to electrocution or thin falls or snake bites was present in 10.4% of the cases. Among the single most common diseases, COPD (20%) was the most frequently observed, and the rest of them were chronic liver disease (13.1%), pulmonary TB (5.5%), ischemic stroke (5.5%), CAP (4.1%), acute coronary syndrome (3.4%), thalassaemia (3.4%) and hepatocellular carcinoma (3.4%). Among the top 6 reported diseases, PTB was more common in elderly individuals (p=0.29). The disease pattern was similar across the sexes among the refugees except community acquisition pneumonia (CAP), which was commonly observed among males (p=.004). Considering different age groups, genitourinary problems were more common in males aged >60 years, and rheumatology and musculoskeletal problems were equally affected in females aged between 40-60 years.
Conclusion
COPD, CLD and CAP were the most prevalent diseases in FDMN patients who attended the medicine ward of Cox’s Bazar Medical College Hospital. Further exploration is warranted before any policy making and comprehensive plan.
Metformin Combined with Local Irradiation Provokes Abscopal Effects in a Murine Rectal Cancer Model
Authors: Tojo Mineyuki , Miyato Hedeyo , Koinuma Koji , Horie Hisanaga , Tsukui Hidenori , Kimura Yuki , Kaneko Yuki , Ohzawa Hideyuki , Yamaguchi Hironori , Yoshimura Kotaro , Lefor Alan Kawarai , Sata Naohiro , Kitayama Joji
Published: December 2021

BackgroundAlthough preoperative chemoradiation therapy can down-stage locally advanced rectal cancer (LARC), it has little effect on distant metastases. Metformin exerts an anti-cancer effect partly through the activation of host immunity. MethodLuM1, a highly lung metastatic subclone of colon 26, was injected subcutaneously in BALB/c mice and treated with metformin and/or local radiation (RT). Lung metastases and the primary tumor were evaluated and the phenotypes of immune cells in the spleen and lung metastases were examined with flowcytometry and immunohistochemistry.ResultsLocal RT, but not metformin, partially delayed the growth of sc tumor which was augmented with metformin. Lung metastases was unchanged in metformin or RT alone, but significantly reduce in the combined therapy. The ratios of splenic T cells tended to be low in the RT group, which were increased by the addition of metformin. IFN-gamma production of the splenic CD4(+) and CD8(+) T cells was enhanced and CD49b (+) CD335(+) activated NK cells was increased after combined treatment group. Density of NK cells infiltrating in lung metastases was increased after combination treatment. ConclusionMetformin effectively enhances local and abscopal effects of RT though the activation of cell-mediated immunity and might be clinically useful for LARC.
Impact of Post Traumatic Stress Disorder on Employee Job Performance: Moderating Role of Spirituality
Authors: Baloch Qadar Bakhsh , Baloch Verdah Qadar , Maher Sourath , Iqbal Nadeem , Shah Syed Naseeb , Hussain Mujahid
Published: December 2021

The aim of this paper was to determine the correlation amid post-traumatic stress disorder (PTSD) and employee job performance with moderating role of spirituality among Police officials who experienced during the war on terror. Ninety seven personnel from Pakistan Security Forces, hospitalized as result of injuries in war against terror, were selected as study respondents and personally administered with the seventeen items questionnaire to measure PTSD symptoms. All the instruments administered to measure PTSD symptoms, employees’ performance and spiritualty were adopted. Andrew F. Hayes Process model was used to test the hypotheses derived from the study’s conceptual model as it was identical with the Andrew model (Hayes 2013) in which moderation is tested with one moderator that is spirituality. Correlation and Regression analysis were carried out by using SPSS. Moderation analysis checked the moderating effect of spirituality upon the relationship between PTSD and employees performance. The research concluded that PTSD negatively affects the job performance, however, spirituality reduces the negative outcomes of PTSD. The research found that the spirituality contributes positively to the psychological well-being of a person, thereby making one’s self more robust to tremor and harrowing engagement and subsiding the negative impacts of PTSD. Managerial implications and future direction were also discussed.
Recognizing relationship between groundwater level and hydrological time series (Case study: Ardabil plain)
Authors: Vousoughi Farnaz Daneshvar
Published: December 2021

Two approaches to identify the relation between hydrological time series (rainfall and runoff) and groundwater level (GWL) were used in the Ardabil plain. In this way, Wavelet-entropy measure (WEM) and wavelet transform coherence (WTC) as two approaches of wavelet transform (WT) were used. WEM have been considered as a criterion for the degree of time series fluctuations and WTC present common time-frequency space. In WEM calculation, monthly rainfall, runoff and GWL time series were divided into three different time periods and decomposed to multiple frequent time series and then, the energies of wavelet were calculated for each sub-series. The result showed WEM reduction in rainfall, runoff and GWL. The reduction of WEM presents the natural fluctuations decrease of time series. The reduction of entropy for runoff, rainfall and GWL time series were about 1.58, 1.36 and 29% respectively, it is concluded that fluctuation reduction of hydrological time series has relatively not more effect on the oscillation patterns of GWL signal. In this regard, it could be concluded that the human activities such as water driving from wells can be played main role in the reduction of GWL in Ardabil plain. WTC findings showed that runoff had most coherence (0.9-1) among the hydrological variables with GWL time series in the frequency bands of 4-8 and 8-16 months.
Evaluation of the Virulence Factor Profile of Avian Pathogenic Escherichia Coli in Clinical Isolates of Avian Samples in Caloto, Cauca, Colombia
Authors: Durango Harold , Morales Hernando , Murillo Enderson , Echeverri Laura , Quiroz Natalia , Villarreal Rafael
Published: December 2021

Avian pathogenic E. coli (APEC), produces an extraintestinal infection in chickens, turkeys, and other types of birds, called colibacillosis, and is considered one of the main causes of economic losses due to morbidity, mortality, and the disposal of poultry carcasses. The objective of the present study was to characterize the genetic profile of the virulence factors of different isolates of avian E. coli in Caloto, Cauca, Colombia. Materials and methods: E. coli was isolated and identified by biochemical tests, from 47 clinical isolates. Subsequently, the DNA was extracted using Chelex. Three multiplex PCRs were designed to amplify 13 virulence factors (iroN, hlyF, iss, iutA, frz, vat, sitA, KpsM, sitD, fimH, pstB, sopB, and uvrY), using primers previously reported for each. The amplification products were verified on agarose gels. Each isolate was classified according to the number of virulence factors: group A (between 10 and 13), group B (between 5 and 9), and group C (4 or less). Conclusion: we were able to identify the presence of a group of virulence factors in clinical isolates of APEC, which allows us to demonstrate that both the frequency and the profile of virulence factors in the isolated strains showed a different profile than the reported by other authors. The virulence genes pstB and fimH were detected in all of our samples, and the iss gene was the one with the lowest frequency. And according to the number of virulence factors, the group A was the most frequent.
The Biological Behavior of High-Grade Glioma in H3K27M Mutant Circumscribed Midline Gliomas
Authors: Li Hainan , Tan Jieyun , Lai Mingyao , Chen Wendan , Liu Minting , Zhou Zhaoming , Deng Dabiao , Cheng Baijie , Fan Chongzuo , Cai Linbo , Li Zhi
Published: December 2021

Purpose Due to the prognosis of circumscribed middle gliomas（CMGs）with H3K27M mutation is still unclear. This study explored the prognostic stratification of （CMGs） with H3K27M mutation.Methods: One hundred and sixty middle gliomas（MGs）were identified over 10 years. Immunohistochemistry was done for H3K27M, ATRX, IDH1, and P53, and Sanger sequencing performed for IDH and H3 genes. The clinicopathological characteristics were reviewed and survival analysis performed.Results: 1. H3K27M mutation was associated with a poor prognosis (p = 0.00017) for brainstem gliomas, but not for thalamic gliomas (p = 0.3). In the elder adults (≥40 years), there was no correlation between H3K27M mutation and the prognosis for MGs (p = 0.49).2. For H3K27M mutant MGs, there was no difference in prognosis between diffuse midline gliomas (DMGs) and CMGs (p = 0.211), also between the CNS WHO grades.3. The prognosis of H3K27M mutant CMGs of CNS WHO grade 1 was worse than that of H3K27M wild-type CMGs (p = 0.0024), even worse than of DMGs without H3K27M mutation of CNS WHO grade 2(p = 0.0066). There was no significant difference in prognosis from DMGs with histological grades CNS WHO grade 3 and 4 (p = 0.46).Conclusions: The weight value of H3K27M affecting prognosis is affected by location and age. CMGs with H3K27M mutation have biological behavior similar to high-grade gliomas. It is recommended that Treatment management was referenced to high-grade glioma for CMGs with H3K27 mutation.
The Mammalian Kalrn Locus Gives Rise to Several Novel Long Non-coding RNAs
Authors: Pal Muneesh , Chaubey Divya , Tanwar Mohit , Pillai Beena
Published: December 2021

The Kalrn gene encodes several multi-domain protein isoforms that localise to neuronal synapses, and play dynamic roles in shaping axonal outgrowth, dendrite morphology and dendritic spine re-modelling. The genomic locus is implicated in several neurodevelopmental and neuropsychiatric diseases including autism, schizophrenia and bipolar disease. Mutations in the coding regions, inherited in a classical Mendelian manner, have also been implicated in certain forms of autism and intellectual disability. At the molecular level, the protein isoforms, encoded by reported transcript isoforms, share some core domains arising from the central exons, while other domains, especially towards the C terminal may be selectively incorporated. This heterogeneity seems to confer the ability to grow and retract dendritic spines, thus making Kalirin a critical and dynamic player in dendritogenesis. We have previously shown that in the zebrafish genome, a novel brain specific non-coding RNA arising from the 5’ end of the Kalirin gene, durga regulates neuronal morphology. In search of the mammalian equivalent, we characterized the mammalian Kalrn loci in detail, annotating multiple novel non-coding RNAs, including linear and circular variants, through analysis of transcriptomics data and experimental approaches. By comparing the mouse and human loci and studying the expression of the novel lncRNAs arising from the locus during differentiation of primary cortical neurons in culture, we show that certain non-coding RNAs arising from the locus show a temporal expression profile that coincides with a subset of Kalirin protein coding isoforms. In humans, mouse and zebrafish the 5’end of the Kalrn locus gives rise to a chromatin associated lncRNA that is present in adult ovaries besides being expressed during brain development and in certain regions of the adult brain. Besides correcting some of the annotations available in public databases, we propose that this lncRNA arising from the 5’end of the Kalrn locus is the mammalian ortholog of zebrafish lncRNA durga.
Long-term Changes In Aberrant DNA Methylation And Gastritis After Helicobacter Pylori Eradication Focused On Metachronous Gastric Cancer
Authors: Tanaka Ikko , Ono Shoko , Watanabe Yoshiyuki , Yamamoto Hiroyuki , Oikawa Ritsuko , Matsumoto Shogo , Kubo Marina , Nishimura Yusuke , Shimoda Yoshihiko , Ono Masayoshi , Yamamoto Keiko , Sakamoto Naoya
Published: December 2021

BackgroundA persistently high methylation level in gastric mucosa after Helicobacter pylori (H. pylori) eradication is presumed to be a risk for metachronous gastric cancer (MGC); however, long-term changes in aberrant DNA methylation and histological gastritis have been unclear. Our aim was to examine changes in DNA methylation and histological gastritis according to the occurrence of MGC.MethodsSubjects were classified into 3 groups: 25 patients in whom metachronous gastric cancers occurred after the initial endoscopic resection (ER) for early gastric cancer and H. pylori eradication (MGC group), 17 patients in whom MGC did not occur for more than 5 years after initial ER and H. pylori eradication (non-MGC group) and 29 patients without a history of gastric cancer who succeeded in eradication more than 5 years ago (HP group). Aberrance of DNA methylation in 3 genes (miR-124a-3, EMX1, NKX6-1) and histological score of atrophy and intestinal metaplasia (IM) were evaluated using biopsy samples before and more than a mean of 5 years after H. pylori eradication.ResultsThe methylation level of miR-124a-3 in the HP group and non-MGC group and that of EMX1 in the HP group significantly decreased in the long term after eradication. In the MGC group, H. pylori eradication did not improve aberrant methylation, and the Z-score significantly increased. There were significant positive correlations between methylation levels in miR-124a-3 and EMX1 and histological findings after eradication.ConclusionsA persistently high methylation level after H. pylori eradication reflected precancerous mucosal conditions and led to long-term MGC.
Compare the Similarity between Two Quantum Images
Authors: Liu You-hang , Qi Zai-dong , Liu Qiang
Published: December 2021

Comparing the similarity between digital images is an important subroutine in various image processing algorithms. In this study, we present three quantum algorithms for comparing the similarity between two quantum images. These algorithms apply to binary, grey and color images respectively. Without considering the image preparation, the proposed algorithms achieve exponential acceleration than the existing quantum and classical methods in complexity. At the end of this paper, an experiment based on the real quantum computer of IBMQ and simulations verify the effectiveness of the algorithms.
Knockdown of CDC20 Promotes Adipogenesis of Bone Marrow-derived Stem Cells
Authors: Du Yangge , Liu Yunsong , Zhou Yongsheng , Zhang Ping
Published: December 2021

Background: Bone is a rigid organ that provides support and physical protection to vital organs of the body. Several bone loss disorders are commonly associated with increased bone marrow adipose tissue. Bone marrow mesenchymal stromal/stem cells (BMSCs) are multipotent progenitors differentiating into osteoblasts, adipocytes, and chondrocytes. CDC20 is a co-activator of APC/C, required for full ubiquitin ligase activity. In our previous study, CDC20 promoted the osteogenic commitment of BMSCs and Cdc20 conditional knockout mice suggested a decline in bone mass. In this study, we investigated the function of CDC20 in the adipogenic differentiation of BMSCs and provided a new clue between adipogenesis and osteogenesis. Methods: Lentivirus containing CDC20 shRNA was used for CDC20 knockdown in hBMSCs. Primary mBMSCs were isolated from Cdc20f/f and Sp7-Cre;Cdc20f/f mice. Adipogenesis was examined by qRT-PCR and western blot analysis of adipogenic regulators, Oil Red O staining and transplantation into nude mice. The CDC20 knockout efficiency was determined through immunochemistry, qRT-PCR and western blot of bone marrow. Accumulation of adiposity was measured through histology and staining of bone sections. Results: CDC20 expression in hBMSCs was significantly decreased during adipogenic differentiation. Knockdown of CDC20 enhanced adipogenic differentiation of hBMSCs in vitro. CDC20-knockdown hBMSCs showed more adipose tissue–like constructs in H&E staining and Oil Red O staining. Sp7-Cre;Cdc20f/f mice presented increased adipocytes in bone marrow compared with control mice. mBMSCs from Sp7-Cre;Cdc20f/f mice exerted upregulated adipogenic differentiation. Conclusions: Our findings showed that knockdown of CDC20 enhanced adipogenesis of h(m)BMSCs in vitro and in vivo. Overall, CDC20 regulated both adipogenesis and osteogenesis of BMSCs, and may lead to the development of new therapeutic target for “fatty bone” and osteoporosis.
Activation of TRESK background potassium channels by cloxyquin exerts protective effects against excitotoxic-induced brain injury and neuroinflammation in neonatal rats
Authors: Dilek Mustafa , Kilinc Yasemin Baranoglu , Kilinc Erkan , Torun Ibrahim Ethem , Saylan Aslihan , Duzcu Selma Erdogan
Published: December 2021

The excitotoxicity is a common pathological mechanism of perinatal brain injuries (PBI), however neuroinflammation resulting in PBI is both a cause and a consequence of excitotoxicity. TRESK background potassium channels are an important regulator of neuronal excitability. We therefore investigated effects of activation of TRESK channels by selective activator cloxyquin on excitotoxic-induced brain injury and neuroinflammation involving brain mast cells and inflammatory cytokines in neonatal rats. An excitotoxic model mimicking human perinatal brain lesions was established via intracerebral injection of the glutamatergic agonist ibotenate to into newborn rats. P5 rat pups were intraperitoneally pretreated with vehicle, three different doses of cloxyquin (0.2, 1 and 5 mg/kg), or NMDA receptor antagonist MK-801 (positive control) 30 minutes prior to intracerebral injection of 10 µg ibotenate. Rat pups were sacrificed one or five days after the injury. Coronal brain sections were stained with cresyl-violet for histopathological examinations, and with toluidine-blue for brain mast cells assessments. Concentrations of activin A, IL-1β, IL-6 and IL-10 in brain homogenates were measured using ELISA. Cloxyquin dose-dependently ameliorated ibotenate-induced impairments in the cortical and white matter, and suppressed ibotenate-induced activation and number of brain mast cells. Moreover, cloxyquin dose-dependently reduced concentrations of activin A, IL-1β and IL-6 in the brain tissue induced by ibotenate while it elevated IL-10 level. Our findings reveal for the first time that cloxyquin, a selective activator of TRESK channels, dose-dependently exerted protective effects against excitotoxic-induced neonatal brain injury and neuroinflammation. TRESK channels may be a promising new target for the treatment of PBIs.
Identification of HOX Signatures Contributing to Oral Cancer Phenotype
Authors: Padam Kanaka , Morgan Richard , Hunter Keith , Chakrabarty Sanjiban , Kumar Naveena , Radhakrishnan Raghu
Published: December 2021

Purpose: Evolutionarily conserved homeobox-containing HOX genes as transcriptional regulators in the developmental specification of organisms is well known. The contribution of HOX genes involvement in oral cancer phenotype has yet to be fully ascertained.Methods: GEO datasets (GSE72627, GSE30784, GSE37991) were accessed and analyzed using GEO2R. TCGA-HNSC HTSeq-counts and clinical data were retrieved from the GDC portal for oral cavity neoplasms. Differential HOX gene expression was profiled using the DESeq2 R package with a log2 fold change cut-off (-1 and +1) and Benjamini-Hochberg p-adjusted value at <0.01. Gene set over-representation analysis and semantic analysis associated with the disease ontology were performed using ClusterProfiler R package and pathway over-representation analysis was performed using IMPaLa. HOX protein interaction network was constructed using the Pathfind R package. HOX phenotype associations were performed using Mammalian Phenotype Ontology, Human Phenotype Ontology, PhenGenI associations, Jensen tissues, and OMIM entries. Drug connectivity mapping was carried out with Dr. Insight R Package.Results: HOXB2 and HOXA5 genes were upregulated in oral dysplasia but silenced during tumor progression. Loss of HOXB2 expression was consistent through potentially malignant dysplastic oral lesions (PMOL) to primary tumor formation. HOXA10, HOXB7, HOXC6, HOXC10 and HOXD10 showed consistent upregulation from premalignancy to malignancy and were notably associated with risk factors. Overrepresentation analysis suggested HOXA10 was involved in the transcriptional misregulation leading to oral cancer phenotype. HOX subnetwork analysis showed crucial interactions with cell cycle regulators, growth responsive elements, and proto-oncogenes.Conclusion: Phenotype associations specific to the oral region involving HOX genes provide intrinsic cues to tumor development. The 5’ HOX genes were aberrantly deregulated which reflects their posterior prevalence during oral carcinogenesis.