bluuebunny/crossref_metadata_2025 huggingface dataset:
HMGB1, NLRP3, IL-6 and ACE2 Levels Are Elevated in COVID-19 with Headache: A Window to the Infection-Related Headache Mechanism
Authors: Bolay Hayrunnisa , Karadaş Ömer , Öztürk Bilgin , Sonkaya Rıza , Taşdelen Bahar , Bulut Tuba DS , Gülbahar Özlem , Özge Aynur , Baykan Betül
Published: July 2021

BACKGROUND AND AIM: Pathogenesis of COVID-19 -related headache is unknown, though the induction ofthe trigeminal neurons throughinflammation is proposed. Weaimed to investigatekey systemic circulating inflammatory moleculesand their clinical relations in COVID-19 patients with headache. METHODS: Thiscross-sectional study enrolled 88COVID-19 patients,hospitalized on a regular ward during the second wave of the pandemic.Clinical characteristics of COVID-19 patients were recorded,and laboratory testswere studied.RESULTS: The mean agesof 48 COVID-19 patients with headache (47.71±10.8) and 40 COVID-19 patients without headache (45.70±12.72) were comparable. COVID-19 patients suffered from headache had significantly higher serum levels of HMGB1, NLRP3, ACE2, and IL-6 than COVID-19 patients without headache, whereasCGRP and IL-10 levels were similar in the groups. Angiotensin II level was significantly decreased in the headache group.COVID-19 patients with headache showedan increased frequency of pulmonary involvement and increased D- dimer levels. Furthermore, COVID-19 was more frequently associated with weight loss, nausea, and diarrhea in patients with headache. The frequency of anosmia and ageusia did not reach significant levelsbetween the two groups. Serum NLRP3 levels were correlated with headache duration and hospital stay, while headache response to paracetamol was negatively correlated with HMGB1 and positively associated with IL-10 levels. CONCLUSION: Stronger inflammatory response is associated with headache in hospitalized COVID-19 patients with moderate disease severity.Increased levels of the circulating inflammatory and/or nociceptive molecules like HMGB1, NLRP3, and IL-6 may play a role in the potential induction of the trigeminalsystem and manifestation of headache secondary to SARS-CoV-2 infection.
Catechol, a Natural Allelochemical Thwarts Virulent Dimorphism in Candida Albicans and Potentiates the Antifungal Efficacy of Azoles and Polyenes.
Authors: Ravi Jothi , Ravichellam Sangavi , Ponnuchamy Kumar , Shunmugiah Karutha Pandian , Shanmugaraj Gowrishankar
Published: July 2021

The present study was deliberately focused to explore the antivirulence efficacy of a plant allelochemical –catechol against Candida albicans, and attempts were made to elucidate the underlying mechanisms as well. Catechol at its sub-MIC concentrations (2 to 256 μg/mL) exhibited a dose dependent biofilm as well as hyphal inhibitory efficacies, which were ascertained through both light and fluorescence microscopic analyses. Further, sub-MICs of catechol displayed remarkable antivirulence efficacy, as it substantially inhibited C. albicans’ virulence enzymes i.e. secreted hydrolases. Notably, FTIR analysis divulged the potency of catechol in effective loosening of C. albicans’ exopolymeric matrix, which was further reinforced using EPS quantification assay. Although, catechol at BIC (256 μg/mL) did not disrupt the mature biofilms of C. albicans, their initial adherence was significantly impeded by reducing their hydrophobic nature. Besides, FTIR analysis also unveiled the ability of catechol in enhancing the production of farnesol -a metabolite of C. albicans, whose accumulation naturally blocks yeast-hyphal transition. The qPCR data showed significant down-regulation of candidate genes viz., RAS1, HWP1 and ALS3 which are responsible for the regulation of Ras-cAMP-PKA pathway -the pathway that contribute for C. albicans’ pathogenesis. Interestingly, the up-regulation of TUP1 (a gene responsible for farnesol-mediated hyphal inhibition) during catechol exposure strengthen the speculation of catechol triggered farnesol-mediated hyphal inhibition. Furthermore, catechol profusely enhanced the fungicidal efficacy of certain known antifungal agent’s viz., azoles (ketoconazole and miconazole) and polyenes (amphotericin-B and nystatin).
A Pollution Sensitive Fuzzy EPQ Model With Endogenous Reliability and Product Deterioration Under Lock Fuzzy Game Theoretic Approach
Authors: Bhattacharya Kousik , De Sujit Kumar
Published: July 2021

This article deals with a cost minimization objective function of an economic production quantity (EPQ) inventory model with production breakdown and deterioration. The process reliability and the environmental pollution due to over production have also been considered. The model has been split into two different scenarios according to the breaking time before and after the production period. In scenario 1, no machinery failure occurs during production run time and that of scenario 2 the failure occurs during production run time. We develop a deterministic cost minimization problem first then we fuzzify the model by considering the production rate, the demand rate and all the cost components as lock fuzzy numbers. We convert the fuzzy model into equivalent game problem by considering Gaussian normal strategic probabilities. The model has been solved with the help of different key vectors employed by the decision maker. We have shown that the value of the game might be changed with the change of different key vectors. A comparative study has been made with the numerical results of the general fuzzy and crisp models. Finally, graphical illustrations and sensitivity analysis have been done followed by a conclusion.
The Negative Contingency Illusion: A Cognitive Bias Leading to Misjudgement of Protection
Authors: Piech Richard M. , Crump Matthew J. C. , Zald David H.
Published: July 2021

Humans possess a highly adaptive ability to draw inferences about the world by recognizing meaningful links between stimuli and events: making contingency judgements. We describe a systematic bias in contingency judgements that we label the negative contingency illusion in which individuals falsely judge a cue to be protective against an outcome. We demonstrate that the illusion arises when outcome probability is low and occurs when there is no actual relationship between cue and outcome and even when there is a modest positive relationship between cue and outcome. Such misjudgements may lead individuals to superstitious beliefs and could have major public health implications if they lead to the belief in and promotion of treatments that are ineffective or deleterious to the prevention and treatment of illness.
Three-Dimensional Simulator: Training for the Novices in Embolization With Liquid Agents
Authors: Matyjas Michal , Sauerbrey Marius , Scheel Michael
Published: July 2021

Background: To design the simulator for novices without prior experience in embolization with liquid agents such as n-Butyl cyanoacrylate (n-BCA) and to evaluate the simulator using surveys and post hoc video analysis. Materials and Methods: The simulator was created using computer-aided design software and three-dimensionally printed. Before an embolization, trainees had filled the questionnaires regarding their level of expertise and self-reported confidence level. The participants were divided into the novice or the expert groups, were shown an instruction video, and each performed four embolizations. Subsequently, they completed the surveys on self-reported confidence level and assessed the simulator’s face and content validities.Results: 5 experts and 12 novices trained on the simulator. The experts were radiology fellows with at least five years of work experience. The novices were medical students and radiology residents in postgraduate years one and three, without any previous experience with embolization. Based on the surveys, the experts assessed the simulator as very useful for embolization training. Performance, e.g. mean duration embolization between experts (mean ± standard deviation = 189 ± 42 seconds) and novices (mean ± standard deviation = 235 ± 66 seconds) were significantly different (p = .001). The embolization, simulated complications, and educational capabilities of the simulator were evaluated positively. The self-reported confidence level rose by a mean of over two points, using the 5-point Lickert scale, in the novice group (p < .001).Conclusion: The liquid embolization simulator is an educational tool, mimicking embolization. It reduces the duration of embolization and improves the confidence level of the novices significantly.
Network Pharmacology-Based Prediction of Active Ingredients and Mechanisms of Tongxinluo Against Acute Myocardial Infarction
Authors: Hu Meng-Jin , Chen Gui-Hao , Yang Yue-Jin
Published: July 2021

Purpose: The aim of this network pharmacology was to explore the potential active ingredients and mechanisms of Tongxinluo (TXL) against acute myocardial infarction (AMI).Methods: We selected active ingredients and targets of TXL according to TCMSP database and converted protein targets into gene symbol by UniProt database. Therapeutic gene targets on AMI were collected from DisGeNET and GeneCards databases. The overlapping genes between ingredients and AMI were identified using Venn diagram. Then, the interaction network between ingredients and overlapping genes was constructed, visualized, and analyzed by Cytoscape software. Protein-protein interaction (PPI) was analyzed by String database. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of overlapping genes were carried out by metascape platform.Results: A total of 111 active ingredients, 184 ingredient-related genes, and 1020 AMI-related genes were retrieved using public databases. Eventually, 79 overlapping genes between TXL and AMI were identified. Cytoscape and PPI results suggested that the active ingredients and genes of TXL against AMI consisted of 66 active ingredients and 79 genes, among them beta-sitosterol and IL-6 were the uppermost active ingredient and hub gene, respectively. Metascape results exhibited that the key mechanism of TXL against AMI might be reducing oxidative stress in cell membrane by inactivating pathways in cancer.Conclusion: This network pharmacology study reveals potential mechanisms of multi-target and multi-component TXL in the treatment of AMI, providing scientific evidence for further expounding the active ingredients and mechanisms of TXL against AMI.
Temperature Variation on Coal Gangue Dumps under the Action of Heat Pipe: Case Study on Yinying Coal Mine in China
Authors: Zhao Na , Zhang Yongbo , Niu Jinrong , Gao Tong , Wang Zhigang , Shi Hong
Published: July 2021

Coal gangue in long-term accumulation will often appear spontaneous combustion phenomenon. Generally, the disaster caused by it has always been one of the serious problems threatening the health of residents in the mining area. Master the regularity of deep temperature distribution and eliminate the internal heat is an effective method to control the spontaneous combustion. In this study, using the self-developed heat pipe (HP) and intelligent cloud monitoring software, three groups of single pipe experiments were carried out in different temperature areas of the coal gangue dump in Yinying Coal Mine, to analyze the internal temperature variation under the action of HP. The results show that the temperature is obviously restrained by the HP, and the average cooling range reaches 21.44% within 700h. However, the temperature of the control group without HP continued to rise by 8%. In the three groups of experiments, the effective control radius of single HP is 3m. When the depth of gangue is 1 ~ 4m and the temperature between 90 ℃ ~ 450 ℃, the cooling effect is the best. It revealed that the HP had a substantial effect on thermal removal and inhibited spontaneous coal gangue combustion. In addition, this paper provides a theoretical basis for the HP treatment of spontaneous combustion coal gangue dumps technology.
The Bradyrhizobium Sp. LmicA16 Type VI Secretion System is Required for Efficient Nodulation of Lupinus Spp.
Authors: L. Tighilt , F. Boulila , BFS De Sousa , E Giraud , T Ruiz-Argüeso , JM Palacios , J Imperial , L Rey
Published: July 2021

Many bacteria of the genus Bradyrhizobium are capable of inducing nodules in legumes. In this work, the importance of a type VI secretion system (T6SS) in a symbiotic strain of the genus Bradyrhizobium is described. T6SS of Bradyrhizobium sp. LmicA16 (A16) is necessary for efficient nodulation with Lupinus micranthus and L. angustifolius . A mutant in the gene vgrG, coding for a component of the T6SS nanostructure, induced less nodules and smaller plants than the wild type strain (wt) and was less competitive when co-inoculated with the wt strain. A16 T6SS genes are organized in a 26 kb DNA region in two divergent gene clusters of nine genes each. One of these genes codes for a protein (Tsb1) of unknown function but containing a methyltransferase domain. A tsb1 mutant showed an intermediate symbiotic phenotype regarding vgrG mutant and higher mucoidy and motility than the wt strain in free living conditions. T6SS promoter fusions to the lacZ reporter indicate expression in nodules but not in free living cells grown in different media and conditions. The analysis of nodule structure revealed that the level of nodule colonization was significantly reduced in the mutants with respect to the wt strain.
Economic Burden Attributable to Healthcare-Associated Infections in Tertiary Public Hospitals of Central China: A Multi-Center Case-Control Study
Authors: Li Peng , Li Yan , Zhang Youjian , Bao Junzhe , Yuan Ruixia , Lan Hongwen , Sun Mingjie
Published: July 2021

BackgroundHealthcare-associated infection (HAI) is a major cause of morbidity, mortality and cost, which vary widely by region and hospital. We aimed to calculate losses attributable to HAI in central China.MethodsWe performed a three-stage random sampling and employed a 1:1 matched case-control study in tertiary public hospitals of Central China. The direct medical cost attributable to HAIs was calculated, and then compared among different types of HAIs by employing a subgroup analysis.ResultsA total of 2976 patients in 10 hospitals were enrolled, and the incidence rate of HAI (range, 0.88%-4.15%) was significantly, but negatively associated with the cost per 1000 beds of its prevention (range, $24929.76-$53146.41; r=-0.76). The per capita economic loss attributable to HAIs was $2047.07 (interquartile range, $327.63-$6429.17), mainly from the pharmaceutical cost (median, $1044.39). The HAIs, which occurred in patients with commercial medical insurance, affected the hematologic system and caused by A. baumannii, contributed most to the losses (median, $3881.55, $4734.20 and $9882.75, respectively), and a significant correlation existed between the economic loss and age (r=0.26). Furthermore, the economic losses attributable to device-associated infections and hospital-acquired multi-drug resistant bacteria were 2 to 4 times those of the controls.ConclusionsThe economic burden attributable to HAI in central China is heavy, and opportunities for easing this burden exist in several areas, including that strengthening antibiotic stewardship and practicing effective bundle of HAI prevention for patients carrying high risk factors, for example, elders or those with catheterizations in healthcare institutions, and accelerating the medical insurance payment system reform based on Diagnosis Related Groups (DRGs) by policy-making departments.
An Automatic Detection Model of Microaneurysms Based on Improved FC-Densenet
Authors: Wang Zhenhua , Yao Mudi , Li Xiaokai , Jiang Qing , Yan Biao
Published: July 2021

Diabetic retinopathy (DR) is a common eye disease, which leads cause of blindness all around the world. Microaneurysms (MAs) is one of the early symptoms of DR. Accurate and effective MAs detection and segmentation is an important step for the diagnosis and treatment of DR. In this paper, we propose an automatic model for detection of MAs in fluorescein fundus angiography (FFA) images. The model mainly consists of two steps. The first step is pre-processing of FFA images, where the quality of FFA images is improved by Histogram Stretching and Gaussian Filtering algorithm. The second step is to detect MAs regions, where the MAs regions are detected by improved FC-DenseNet. We compare the proposed model with traditional FC-DenseNet model and other previously published models. The experimental result shows that our proposed model has the highest scores on evaluation metrics of pixel accuracy (PA), mean pixel accuracy (MPA), precision (Pre), recall (Re), F1-score (F1) and mean intersection over union (MIoU), which are 99.97%, 94.19%, 88.40%, 89.70%, 88.98% and 90.14%, respectively. The result suggests that the performance of our proposed model is closer to the ground truth of MAs detection. Our proposed model would be helpful for ophthalmologists to find the symptoms more quickly and to take better treatment measures in the screening process of diabetic retinopathy.
Uses of radio emission spectroscopy for non-contact and in situ diagnostics of low pressure radio frequency plasma processing
Authors: Vijayaraghavan Rajani K. , Kelly Sean , Coates David , Gaman Cezar , MacGearailt Niall , McNally Patrick
Published: July 2021

We demonstrate that a passive non-contact diagnostic technique, radio emission spectroscopy (RES), provides a sensitive monitor of currents in a low pressure radio frequency (RF) plasma. A near field magnetic loop antenna was used to capture RF emissions from the plasma without perturbing it. The analysis was implemented for a capacitively coupled RF plasma with an RF supply at a frequency of 13.56 MHz. Real-time measurements are captured in scenarios relevant to contemporary challenges faced during semiconductor fabrication (e.g. window coating and wall disturbance). Exploration of the technique for key equipment parameters including applied RF power, chamber pressure, RF bias frequencies and chamber wall cleanliness shows sensitive and repeatable function. In particular, the induced RES signal was found to vary sensitively to pressure changes and we were able to detect pressure and power variations as low as ~2.5 %/mtorr and ~3.5 %/watt, respectively, during the plasma processing during a trial generic plasma process. Finally, we explored the ability of RES to monitor the operation of a multiple frequency low-pressure RF plasma system (f1 = 2 MHz, f2 = 162 MHz) and intermixing products which suggests strongly that the plasma sheaths are the primary source of this non-linear diode mixing effect.
Do we swallow the waste from our brain?
Authors: Leaston Joshua , Kulkarni Praveen , Gharagouzloo Codi , Qiao Ju , Bens Nicole , Ferris Craig
Published: July 2021

Ferumoxytol an iron oxide nanoparticle was infused into the lateral cerebroventricle of awake rats to follow its movement and clearance from the brain using magnetic resonance imaging. Within minutes the contrast agent could be observed accumulating on the soft palate at the back of the throat. In a subsequent study fluorescent quantum dots were infused into the brain of rats and within 15 min could be observed in the esophagus using microscopy. These imaging studies clearly show the gut is helping to clear waste from the brain.
Characterization of Heavy Metals in Typical River Sediments on the West Bank of Taihu Lake, China
Authors: Wang Fei , Ren Xiaoming , Qiu Yang , Cheng Jiade , Chen Yan , Wang Lingling , Zhang Limin , Zhao Shanshan , Wang Xiaoping
Published: July 2021

In this study, nine heavy metals (Cd, Cr, As, Hg, Pb, Cu, Ni, Be, Sb) in typical river sediments of Wujin and Yixing, two cities on the west bank of Taihu Lake, were determined. Variety of statistical methods were applied to analyze the distribution, sources, pollution status and the potential ecological risk of these metals. The results showed that the mean concentrations for most of the heavy metals in sediments exceeded their local background values, except for Hg and Be. Geoaccumulation index (Igeo) and potential ecological risk index (RI) analysis showed the partially serious contaminated status and strong potential ecological risk for Cd in most sites. The highest contamination level was observed in the estuary of Taihu Lake and most of the sediment samples were polluted and under risk. Principal component analysis (PCA), Cluster analysis (CA) and correlation analysis demonstrated that Ni, Sb, Cr and Cu were controlled by industrial sources, whereas the other metals appeared to be influenced by complex origins including industrial, agricultural and natural sources.
Evaluation of Rockfall Hazard Based On UAV Technology And 3D Rockfall Simulations
Authors: Utlu Mustafa , ÖZTÜRK Muhammed Zeynel , Şimşek Mesut
Published: July 2021

In this study, the rockfall hazard in Hacıabdullah village located in the Central Anatolia region of Turkey was assessed with three-dimensional (3D) rockfall analyses based on unmanned aerial vehicle (UAV) technology. With several rockfall disasters experienced in the village, the final event occurred as severe rockfall in 2008 and several houses were evacuated due to rockfall risk after this event. In order for the rockfall hazard to be assessed close to reality in the study area, rocks with falling potential identified in the field were assessed using high-resolution digital surface model (DSM) data produced from images obtained with UAV. During field studies, 17 rocks with fall hazard were identified and dimensional measurements were performed. According to dimensional values, the geometric and volumetric features of each rock were assessed close to reality with the RAMMS 3D rockfall modelling program. As a result of modelling, the kinetic energies of the rocks were identified to reach up to 3476 kJ, with velocities of up to 23.1 m/s and bounce heights of up to 14.57 m. On steep slopes rocks do not travel very long distances; however, in gentle slopes, they were identified to be able to roll very long distances. Rocks that do not move very far from the source are; in other words, where the fall process is dominant, may create damage on roads mainly. However, those with the feature of rolling, in other words, blocks which can travel long distances from the source area, have the potential to cause great damage to settlement areas, roads and trees. According to the hazard map, modelling of rock blocks numbered R6, R12, R13, R14, R15, R16 and R17 showed settlement units were within the high and moderate risk areas.
Formulating Intuitionistic Fuzzy Regression Models: A Mathematical Programming Approach
Authors: Nien Sheng-Hsing , Chen Liang-Hsuan
Published: July 2021

This study develops a mathematical programming approach to establish intuitionistic fuzzy regression models (IFRMs) by considering the randomness and fuzziness of intuitionistic fuzzy observations. In contrast to existing approaches, the IFRMs are established in terms of five ordinary regression models representing the components of the estimated triangular intuitionistic fuzzy response variable. The optimal parameters of the five ordinary regression models are determined by solving the proposed mathematical programming problem, which is linearized to make the resolution process efficient. Based on the concepts of randomness and fuzziness in the formulation processes, the proposed approach can improve on existing approaches’ weaknesses with establishing IFRMs, such as the limitation of symmetrical triangular membership (or non-membership) functions, the determination of parameter signs in the model, and the wide spread of the estimated responses. In addition, some numerical explanatory variables included in the intuitionistic fuzzy observations are also allowed in the proposed approach, even though it was developed for intuitionistic fuzzy observations. In contrast to existing approaches, the proposed approach is general and flexible in applications. Comparisons show that the proposed approach outperforms existing approaches in terms of similarity and distance measures.
Increasing Rate of a Positive Family History of Inflammatory Bowel Disease (IBD) in Pediatric IBD Patients
Authors: Ruban Maya , Slavick Adam , Amir Achiya , Ben-Tov Amir , Moran-Lev Hadar , Weintraub Yael , Anafy Adi , Cohen Shlomi , Yerushalmy-Feler Anat
Published: July 2021

The role of a positive family history in pediatric inflammatory bowel disease (IBD) in the era of biologic therapy has not been elucidated. We retrospectively reviewed the medical records of children with IBD and retrieved demographic and clinical characteristics, including the presence of a positive family history of IBD, IBD phenotype, disease course, and therapy. Overall, 325 children (age range at diagnosis 11-15 years) were included, of whom 82 (25.2%) had a positive family history. Children diagnosed during 2016-2020 had a higher frequency of positive family history compared to those diagnosed during 2010-2015 (31.8% versus 20.7%, respectively, p = 0.024). Children with a positive family history had a higher risk for a stricturing phenotype than those with a negative family history (11.3% versus 2.8%, respectively, p = 0.052). They more often received nutritional therapy (53.7% versus 36.6%, p = 0.007) and less often received corticosteroids (36.6% versus 52.7%, p = 0.012). More children with a negative family history needed intensification of biologic therapy (p = 0.041). Conclusion: The rate of a positive family history of IBD in the pediatric IBD population is increasing. A positive family history may have some impact upon IBD phenotype but none on IBD outcome.
Organochlorine Pesticides Occurrence In Fish Muscle And Their Public Health Risks In Northwest Ethiopia
Authors: Agmas Birhan , Adugna Marshet
Published: July 2021

Pesticides are the parent compounds, their metabolites, and associated impurities of agricultural and health chemical inputs. If they are found concentration level higher than the standard limits, they have potential negative impacts on ecosystem in general and in fish and humans in particular. This study investigates organochlorine pesticides (OCPs) residue occurrences in fish muscle and assesses their public health potential risks, in North West Ethiopia. The concentration of OCPs residue under GC-ECD detected in 37.84% fish muscle samples. The mean amount detected were Endosalfan I, 341.50 ± 32.19 μg/kg; Endosalfan II, 36.01 ± 2.3μg/kg; Endosalfan sulfate, 5.43 ± 4.06 μg/kg; 4,4, DDE, 64.01 ± 9.08μg /kg; 4, 4, DDD, 5.65 ± 3.12μg /kg; and 4,4, DDT, 1.58 ± 0.30μg/kg. The mean concentration of Endosalfan I tested fish muscle sample was higher than that of permissible limit of different international standards. However, due to low per capital consumption rate of fish origin food in Ethiopia, health risk index (HRI) ranges from 0.002-0.1275 which shows there is no public health risk. This study highlights the possibilities of chemical residues occurrence in fish food products and hence pesticide use regulations and monitoring concentration level should be implemented regularly to avoid human and environmental health risks.
Self-Amplification of Oxidative Stress with Tumor Microenvironment-Activatable Iron-Doped Nanoplatform for Targeting Hepatocellular Carcinoma Synergistic Cascade Therapy and Diagnosis
Authors: Zhou Qiao-Mei , Lu Yuan-Fei , Zhou Jia-Ping , Yang Xiao-Yan , Wang Xiao-Jie , Yu Jie-Ni , Du Yong-Zhong , Yu Ri-Sheng
Published: July 2021

Background

The rapid development of hepatocellular carcinoma (HCC) treatment resistance has become a technical bottleneck for clinical treatment. Conventional chemotherapy has long been regarded as ineffective against HCC because of the insensitivity to chemotherapy drugs. Ferroptosis is a form of programmed cell death with a definite Fenton reaction mechanism that converts endogenous hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (·OH). Therefore, we have developed an ultrasensitive iron-doped magnetic mesoporous silica nanoplatform (DOX@Fe-HMON-Tf NPs) for HCC-targeted synergistic cascade therapy and diagnosis.
Results

This organic/inorganic nanoplatform consists of a silica shell doped with iron and bis[3-(triethoxysilyl)propyl]tetrasulfide (BTES) and the etched core loaded DOX that generate H2O2 in situ to enhance the ferroptosis effect. DOX@Fe-HMON-Tf NPs can efectively internalized into hepatoma cells by precise delivery through the transferrin grafted with polyethylene glycol (PEG) outside the shell. The resulting nanoplatform can be activated by the tumor microenvironment (TME) in which the glutathione (GSH)-responsive biodegradability could synergize with the therapeutic interaction between DOX and iron and induce tumor cells death through complementary ferroptosis and apoptosis mechanisms. At the same time, the nanoplatform has a superparamagnetic framework that can be used for treatment guidance and monitoring under the guidance of T2-weighted magnetic resonance imaging (MRI).
Conclusion

The rationally designed nanoplatform provides a new strategy for anti-tumor effects with self-amplified synergistic chemotherapy and chemodynamic therapy (CDT) based on ferroptosis, and magnetic resonance imaging that realizes the integration of diagnosis, treatment and monitoring.
Intestinal Microsporidiosis Among HIV/AIDS Patients Receiving Antiretroviral Therapy in Sana’a City, Yemen: First Report on Prevalence and Predictors
Authors: Al-Barhami Kwkab A. R. , Abdul-Ghani Rashad , Al-Qobati Salah A.
Published: July 2021

Background: Intestinal microsporidiosis is an opportunistic infection associated with persistent diarrhea among HIV/AIDS patients. In Yemen, however, its epidemiology is unknown. Therefore, this study determined its prevalence and predictors among HIV/AIDS patients receiving antiretroviral therapy (ART) in Sana'a city, Yemen.Methods: This cross-sectional study included 402 patients receiving ART at Al-Jomhori Educational Hospital in Sana'a from November 2019 to December 2020. Data about demographics, clinical characteristics and risk factors were collected using a pre-designed questionnaire. Stool samples were collected and examined for microsporidian spores using the Gram-chromotrope Kinyoun staining. Blood samples were also collected and used for CD4 cell counting by flow cytometry. Univariate analysis was used to test the association of patients’ characteristics and risk factors with intestinal microsporidiosis. Multivariable logistic regression was then used to identify the independent predictors of infection. Statistical significance was considered at P-values <0.05. Results: Intestinal microsporidiosis was prevalent among 14.2% (57/402) of HIV/AIDS patients but was not significantly associated with any of the studied demographics, source of drinking water, bathing and/or swimming outdoors, contact with soil, presence of domestic animals or indiscriminate defecation. However, it was significantly associated with diarrhea (OR=3.4, 95% CI: 1.7–6.6; P=0.001) and <200 CD4 cells/µl (OR=2.7, 95% CI: 1.5–5.0; P=0.001). The significant independent predictors of infection were <200 CD4 cells/µl (AOR=3.2, 95% CI: 1.5–6.9; P=0.003), not washing hands after contacting soil (AOR=2.5, 95% CI: 1.1–5.4; P=0.026) and before eating (AOR=3.1, 95% CI: 1.5–6.4; P=0.003), eating unwashed raw produce (AOR=2.5, 95% CI: 1.2–5.3; P=0.017) and absence of indoor latrines (AOR=6.2, 95% CI: 1.5–25.9; P=0.012).Conclusions: The prevalence of intestinal microsporidiosis among HIV/AIDS patients in Sana'a is high and comparable to that several other countries, being prevalent among approximately 14.0% of patients and significantly associated with diarrhea. It could be predicted among patients who have <200 CD4 cells/µl, poor hand hygiene after contacting soil and before eating, usually eat unwashed raw produce and do not possess indoor latrines. Large-scale studies on its epidemiology and predictors among HIV/AIDS patients across the country are warranted.
Recurrent Uterine Tumor Resembling Ovarian Sex Cord Tumor: A Case report and Clinicopathological and Immunohistochemical Analysis
Authors: Wei Xiao-qiang , Tang Meng , Liu Lili , Zhao Shu-ping
Published: July 2021

Background: Uterine tumor resembling ovarian sex-cord tumor (UTROSCT) is a considerably rare gynecological tumor which has undetermined pathogenesis but with distinct polyphenotypic immunohistochemical expressions. According to the limited cases and follow-up information in the relevant literature, most of the tumors exhibit indolent or low malignant clinical course and the outcomes of the patients with the tumors generally have a good ending. But for the subset of UTROSCT with aggressive characters, the outcomes of the patients with recurrent neoplasm were not always satisfactory.Case presentation: In this case report, the recurrence of neoplasm was reported in the pelvic cavity after 53 months of surgery and irregular follow-up. The recurrent neoplasm grew in an invasive manner, and the arrangement of the recurrent neoplasm cells was closer, the nucleus atypia is more pronounced, and the cells demonstrated a more briskly mitotic activity (10 mitotic figures/10 HPF). The Ki67 index increased significantly and the expression of P53 was positive. For the recurrent tumor, both the clinical characteristics and the histological morphology of the recurrent neoplastic cells showed a more malignant behavior. The patient received a palliative resection of pelvic mass and bilateral oophorectomy, and she died of intestinal obstruction caused by the recurrent disease 9 months postoperatively.Conclusions: UTROSCT should be recognized as a definite malignant potential neoplasm. Based on the clinicopathological, immunohistochemistry parameters and the reviewed previous literature, we speculated that significant mitotic activity and large tumors (≥10 cm) were of value for the aggressive characters of the tumor, and the recurrence of the tumor might lead to a poor prognosis.
Endothelin B Receptor Mutant Exhibits Craniofacial Dysmorphology Resembling Domestication Syndrome
Authors: Chen Ko-Chin , Gee Allison , Croaker Geoffrey
Published: July 2021

Background: ETB-/- mutation is a major cause of HSCR, a neurocristopathy known for its enteric nervous system failure. Other than regulating ENCC migration, ETB mediates ET-1 clearance. Consequently, ETB may indirectly affect ET-1/ETA signaling, which controls CNCC migration and craniofacial development. Interestingly, it was hypothesized that “domestication syndrome” arise from changes in neural crest determining genes, including ETA and ETB. While ETA-/- animals are known to suffer severe dysmorphology resembling CATCH22 syndrome, we hypothesize that sl/sl rat, an ETB-/- HSCR model animal, may exhibit subtle craniofacial changes through indirect control. These features may share resemblance to those of domestication syndrome. Methods: Ten rat pups with an average age of 88 hours were anaesthetized with 5% isoflurane and culled via exsanguination. Tail tips were removed for genotyping. Head tissue were stained in 1.5% iodine for two weeks prior to micro-CT scanning. In vivo micro-CT scanning of cranial specimen was performed followed by ex vivo micro-CT scanning of 2 samples for image quality control. 3D visualization and analyses were performed using open-source program, Drishti. Cephalometric measurements were made based on selected craniofacial landmarks. Comparisons were made between sl/sl rats and the control group, which consisted of wild-type and heterozygotes. Results: Subtle reductions in facial measurements were seen in sl/sl rats when compared with the control group, ranging from 1.4% to 15%. These changes were observed in cranial, maxillary and mandibular parameters: total skull length, nasal length, nasal width, nasal cavity width, interorbital width, interlens distance, inner and outer canthal distance, maximal skull height, cranial length, intracranial length and width, interorbital width, and interzygomatic width. Consistently, craniofacial ratio indices showed sl/sl rat has a flatter cranium (skull height/skull length: 0.393 vs 0.413) and a shorter but broader nose (nasal-width/nasal-length: 0.794 vs 0.874). Additionally, subtle dystopia canthorum may be presented in sl/sl rat based on increased W index. While there was no discrepancy in dental number and morphology between the control and sl/sl groups, dimensional difference was detected. Conclusions: This study demonstrated subtle craniofacial changes are presented in ETB-/- HSCR model, supporting the idea that ETB regulates CNCC migration. The findings also implicate HSCR patient may have predisposing risks for conditions such as obstructive sleep apnea, cleft palate, or dental malocclusion. Lastly, these changes share resemblance with described domestication syndrome, supporting NCC-determining gene, ETB, may play a role in the formation of domestication.
TK/gI/gE/11K Genes Is Not Involved in the Virulence Enhancement of Highly Virulent Pseudorabies Virus
Authors: Tan Feifei , Guo Linghua , Zhang Chaoling , Yan Shijun , Wang Yuzhou , Xiao Yan , Wang Tongyan , Huang Baicheng , Tian Kegong
Published: July 2021

The large-scale outbreaks of Pseudorabies in china since 2011 in vaccine-immunized pig farms were caused by the highly virulent Pseudorabies virus (PRV). To investigate the factors involved in the virulence enhancement of the variant PRV, four recombinant viruses with the virulence gene’s replacement, gI/gE/11K and TK/gI/gE/11K, between the variant strain HN1201 and the classical strain Fa were constructed based on bacterial artificial chromosome infectious clones. Compared with their parental strain, the viral titers of the recombinant PRV strains are not strongly influenced by the replacement of TK/gI/gE/11K, while as previously reported, the strain HN1201 and its derived viruses showed the higher mortality, the severer clinical symptoms and tissues damage than that of strain Fa and its derived strains. In summary, the TK/gI/gE/11K genes of variant strain HN1201 showed no contribute to its virulence enhancement compares with the classical strain.
Features of Cerebral Demyelination and Clinical Relevance in Systemic Lupus Erythematosus
Authors: Guo Qian , He Yang , Liu Xia , Gao Xu guang , Xu Jing , Li Xue , Sun Yue , Xiang Yajuan , Li Ru , Li Zhanguo
Published: July 2021

We aimed to explore the clinical features and cerebral magnetic resonance imaging (MRI) changes of central nervous system demyelination in systemic lupus erythematosus (SLE) patients. Based on a consecutive cohort of 1191 SLE patients, 273 patients with cerebral MRI were enrolled to assess cerebral demyelination. Patients were divided into two groups, ie. complicated with or without demyelination. The MRI findings of the cerebral demyelination were divided into three categories: type A, periventricular white matter (WM) lesions; type B, subcortical WM lesions; type C, multiple discrete WM lesions. Among the 273 SLE patients with cerebral MRI, 35.9% (98/273) had demyelinating changes. The incidences of type A, B and C were 54.1% (53/98), 11.2% (11/98) and 92.9% (91/98), respectively. Fifty-one percent of the patients were with overlap of 2 or 3 types. Type C was the most common subgroup combined with other types. Compared with those without demyelination, the patients with demyelination were more likely to develop neuropsychiatric systemic lupus erythematosus (NPSLE), lupus nephritis (LN), hypertension and hyperuricemia (p < 0.05). Significantly higher rates of polyserous effusions and cardiac involvement were found in the patients with demyelination (p < 0.05). In addition, the patients with demyelination had higher frequency of proteinuria and higher levels of CD8+ T cells (p < 0.05). In multivariate logistic analysis, hyperuricemia and higher CD8+ T cells were significantly correlated with demyelination in SLE patients (p < 0.05). The data suggest that demyelination is a common complication in SLE patients and strongly associated with systemic involvements, including NPSLE, LN, polyserous effusions and cardiac involvement. Hyperuricemia and higher CD8+ T cells were independent risk factors for demyelination in SLE.
QAEmap: A Novel Local Quality Assessment Method for Protein Crystal Structures Using Machine Learning
Authors: Miyaguchi Ikuko , Sato Miwa , Kashima Akiko , Nakagawa Hiroyuki , Kokabu Yuichi , Ma Biao , Matsumoto Shigeyuki , Tokuhisa Atsushi , Ohta Masateru , Ikeguchi Mitsunori
Published: July 2021

Low-resolution electron density maps can pose a major obstacle in the determination and use of protein structures. Herein, we describe a novel method, quality assessment based on an electron density map (QAEmap), that evaluates local protein structures determined by X-ray crystallography and corrects structural errors using low-resolution maps. QAEmap uses a three-dimensional deep convolutional neural network with electron density maps and their corresponding coordinates as input and predicts the correlation between the local structure and the putative high-resolution experimental electron density map. This estimates how well the structure fits the high-resolution map. Further, we propose that this method may be applied to evaluate ligand binding, which can be difficult to determine at low resolution.
Methyloradius Palustris Gen. Nov., Sp. Nov., a Methanol-oxidizing Bacterium Isolated From Snow
Authors: Miyadera Takeshi , Kojima Hisaya , Fukui Manabu
Published: July 2021

A novel methylotrophic bacterium, strain Zm11 T , was isolated from reddish brown snow collected in a moor in Japan. Cells of the isolate were Gram-stain-negative, motile and rod-shaped (0.6-0.7×1.2-2.7 μm). Growth was observed at 5–32°C with an optimum growth temperature of 25–28°C. The pH range for growth was 5.4–7.8 with an optimum pH of 6.8. The strain utilized only methanol as carbon and energy sources for aerobic growth. The major cellular fatty acids (>40% of total) were summed feature 3 (C 16:1 ω 7 c and/or C 16:1 ω 6 c ) and C 16 : 0 . The predominant quinone was Q-8. The complete genome of strain Zm11 T is composed of a circular chromosome (2,800,413 bp), with G + C content of 46.4 mol%. Phylogenetic analyses were conducted based on the 16S rRNA gene sequence and conserved proteins encoded in the genome. The results of analyses indicate that strain Zm11 T is a member of the family Methylophilaceae but does not belong to any existing genus. On the basis of its genomic and phenotypic properties, strain Zm11 T (= DSM111909 T = NBRC114766 T ) is proposed as the type strain of a new species in a new genus, Methyloradius palustris gen. nov., sp. nov.
Spatiotemporal Change Analysis of Long Time Series Inland Water in Sri Lanka Based on Remote Sensing Cloud Computing
Authors: Li Jianfeng , Wang Jiawei , Yang Liangyan , Ye Huping
Published: July 2021

Sri Lanka is an important hub connecting Asia-Africa-Europe maritime routes, with abundant rainfall but uneven spatiotemporal distribution, and obvious seasonal water shortage. Monitoring water area change in its inland lakes and reservoirs plays an important role in guiding the development and utilization of water resources. In this study, a rapid extraction model of surface water based on Google Earth Engine remote sensing cloud computing platform was constructed. On the basis of evaluating the optimal spectral water index method, the spatiotemporal variation of typical reservoir and inland lakes and reservoirs in Sri Lanka were analyzed. The results showed that AWEIsh can accurately identify the water boundary, with an overall accuracy of 99.14%, which was suitable for the extraction of surface water in Sri Lanka. The area of Maduru Oya Reservoir showed an overall increasing trend on the basis of small fluctuations from 1988 to 2018, and the monthly area of reservoir fluctuated greatly in 2017, thus water resources management in dry zone should pay more attention to seasonal regulation and control. From 1995 to 2015, the number and area of lakes and reservoirs in Sri Lanka increased in different degrees, mainly concentrated in arid provinces such as Northern Province, North Central Province, Western Province, etc., and the amount of surface water resources increased as a whole.
Specific expression of lactate dehydrogenases in glioblastoma controls intercellular lactate transfer to promote tumor growth and invasion
Authors: Guyon Joris , Fernandez-Moncada Ignacio , Larrieu Claire , Bouchez Cyrielle , Chouleur Tiffanie , Espedal Heidi , Røsland Gro , Daher Boutaina , Barre Aurelien , Dartigues Benjamin , Coffe Aurelien , Rudewicz Justine , Romero-Garmendia Irati , Klink Barbara , Grützmann Konrad , Derieppe Marie-Alix , Molinié Thibaut , Obad Nina , Leon Céline , Miletic Hrvoje , Marsicano Giovanni , Nikolski Macha , Bjerkvig Rolf , Bikfalvi Andreas , DAUBON Thomas
Published: July 2021

Lactate is a central metabolite in brain physiology, involved in the astrocyte-neuron lactate shuttle, but also contributes to tumor development. Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults, recognized by angiogenic and invasive growth, in addition to its altered metabolism. By adapting their glycolytic or oxidative metabolism, GBM stem-like cells are able to resist chemo- and radiotherapy. We show herein that lactate fuels GBM anaplerosis by replenishing the TCA cycle in absence of glucose. Lactate dehydrogenases (LDH) catalyze the interconversion of pyruvate and lactate. Deletion of either LDHA or LDHB did not alter significantly GBM growth and invasion. However, ablation of both LDH isoforms led to a reduction of tumor growth, and, consequently, to an increase in mouse survival. Comparative transcriptomics and metabolomics revealed metabolic rewiring involving high oxidative phosphorylation (OxPhos) in the double LDHA/B KO group which sensitized tumors to cranial irradiation, massively improving mouse survival. Survival was also increased when control mice were treated with the antiangiogenic treatment, bevacizumab, and the antiepileptic drug, stiripentol which targets LDH activity. Taken together, this highlights the complex metabolic network in which both LDH A and B are integrated and underscores that combined inhibition of LDHA and B is necessary to impact tumor development. Targeting of these enzymes in combination with anti-angiogenic and repurposed drugs may be of therapeutic benefit, especially when associated with radiotherapy.
Bioimpedance Measurement of Knee Injuries using Bipolar Electrode Configuration
Authors: Ye Xuanjie , Wu Lexi , Mao Kaining , Feng Yiwei , Lin Xianfeng , Chen Jie
Published: July 2021

Currently, there is no suitable solution for the point-of-care of knee injuries. A potential portable and low-cost technique for accessing and monitoring knee injuries is bioimpedance measurement. This study validated the feasibility of the bipolar electrode configuration for knee bioimpedance measurements with two electrodes placed on a fixed pair of knee acupuncture locations called Xiyan. Then, the study collected 82 valid samples to investigate the relationship between bioimpedance and knee injuries, among whom 45 patients, each with one healthy knee and one injured knee, and 37 individuals all with healthy knees. The self-contrast results indicated that knee injuries caused a reduction of bioimpedance of the knee by about 5% on average, which was detectable at around 100 kHz (p ≈ 0.001). Furthermore, the results analyzed by principal component analysis and support vector machines show that the detection sensitivity can reach 91.11% using the leave-one-out cross-validation.