bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor-Specific Catalysis-Mediated Enhanced Chemodynamic Therapy in Synergy with Mitophagy Inhibition Improves Therapeutic Efficacy in Endometrial Cancer
Authors: Gong Xiaodi , Wang Jing , Yang Linlin , Li Lijuan , Sun Xiao , Bai Jingfeng , Liu Jichang , Pu Xin , Wang Yudong
Published: December 2021

BackgroundChemodynamic therapy (CDT) relies on tumor microenvironment (e.g. high H2O2 level) responsive Fenton-like reactions to produce hydroxyl radicals (·OH) against tumors. However, endogenous H2O2 is insufficient for effective chemodynamic reactions.ResultsAn NAD(P)H: quinone oxidoreductase 1 (NQO1)highCatalase (CAT)low therapeutic window for the use of NQO1 bioactive drug β-lapachone (β-Lap) was firstly identified in endometrial cancer (EC). Accompanied by NADH depletion, β-Lap was catalyzed by NQO1 to produce excess H2O2 initiating oxidative stress, which selectively suppressed NQO1high EC cell proliferation, induced DNA double-strand breaks and promoted apoptosis. SiRNA-mediated NQO1 knockdown or dicoumarol rescued NQO1high EC cells from β-Lap-induced cytotoxicity. Arginine-glycine-aspartic acid (RGD)-functionalized iron-based metal organic frameworks-MOF(Fe) further promoted the conversion of accumulated H2O2 into highly oxidative ·OH, and in turn exacerbated the oxidative damage to RGD-positive target cells. Mitophagy inhibition by Mdivi-1 blocked a powerful antioxidant defense approach, ultimately ensuring the antitumor efficacy of stepwise amplified ROS signals. The tumor growth inhibition rate was about 85.92%.ConclusionsTumor specific chemotherapy in combination with CDT-triggered therapeutic modality presented unprecedented therapeutic advantages for the treatment of NQO1+ advanced type I or type II EC.
Evaluation of Plasma Nucleosome Concentrations In Healthy Dogs And Dogs With A Variety of Common Cancers.
Authors: Wilson-Robles Heather , Bygott Thomas , Kelly Theresa Kathleen , Miller Tasha , Miller Pamela , Matsushita Matthew , Terrell Jason , Bougoussa Mhammed , Butera Thomas
Published: December 2021

Background: Cell free DNA, in the form of nucleosomes, is released into circulation during apoptosis and necrosis in a variety of diseases. They are small fragments of chromosomes that are composed of DNA wrapped around a histone core made of four duplicate histone proteins forming an octamer. The nucleosome compartment is a relatively uninvestigated area of circulating tumor biomarkers in dogs. The objectives of this study were to quantify and better characterize nucleosomes in 528 dogs with various common malignancies and 134 healthy dogs. Results: The sensitivity of elevated circulating nucleosome concentrations for the detection of cancer in all dogs was 49.8% with a specificity of 97% with an area under the curve of 68.74%. The top 4 malignancies detected by the test included lymphoma, hemangiosarcoma, histiocytic sarcoma and malignant melanoma. The malignancies least likely to be detected were soft tissue sarcomas and mast cell tumors. Conclusions: A variety of tumor types may cause elevated nucleosome concentations in dogs. Tumors of hematopoietic origin are most likely to cause elevations and local tumors such as soft tissue sarcomas are least likely to cause elevations in plasma nucleosome concentrations.
Fluorescent Indolo[2,3-b]quinoxalin-2-yl)(Phenyl)methanone Dyes: Photophysical, Aie Activity, Electrochemical, and Theoretical Studies
Authors: Kanekar Deepali , Dhanawade Sudhakar , Jadhav Anand , Ghadiyali Mohmmed , Chacko Sajeev , Kamble Rajesh M
Published: December 2021

Herein, we have synthesized four indolo[2,3-b]quinoxalin-2-yl)(phenyl)methanone derivatives 1−4 by cyclocondensation. The photophysical studies of dyes in various solvents and neat solid film exhibit typical electronic spectra with inbuilt intramolecular charge transfer (ICT) (λmax: 397‒490 nm) confirming donor-acceptor architecture. Herein, dyes fluoresce in the blue-orange region (λEmax: 435–614) on excitation at their ICT maxima in toluene, ethyl acetate, chloroform, DMSO, and neat solid film. 1 and 2 which exhibit good emission intensity in all mediums, were studied for aggregation-induced emission (AIE) effect. Electrochemical studies indicate 1−4 possess relatively low lying LUMO (‒3.65 to ‒3.98 eV) comparable to reported n-type/electron-transporting materials. The HOMO and LUMO energy levels in 1−4 were evaluated by DFT and TD-DFT calculations. TGA analysis shows 1−4 exhibit good thermal stability. The characteristic optoelectronic properties and thermal stability signify these dyes are potential candidate for their application in optoelectronics.
Ultrahigh Permittivity, Ultralow Loss and Stability in (In0.5Ta0.5)0.1Ti0.9O2 Ceramics With Temperature Range From -100 to 235 °C
Authors: Xue Ying , Wang Zhuo , Li Yanxin , Yi Zhihui , Li Xin , Wu Dan
Published: December 2021

Dielectric materials with excellent dielectric properties are being promoted in requirements of microelectronic devices. In this study, (In0.5Ta0.5)0.1Ti0.9O2 ceramics were achieved by a solid-state reaction with reducing atmosphere of N2. Also, dense microstructure, ultrahigh permittivity (εr = 1.18 × 105) and ultralow dielectric loss (tanδ = 0.0072) were demonstrated at1 kHz. Interestingly enough, the temperature coefficient of permittivity which satisfies X9D (-100 °C - 235 °C, Δεr/ε25°C < ± 3.3 %) maintained stability at 1 kHz, and the dielectric mechanism could be connected to the electron-pinned defect dipoles (EPDD), which has favourable potential applications in electronic devices.
Reproducible and Opposing Microbiome Signatures Distinguish Autoimmune Diseases and Cancers: A Systematic Review and Meta-Analysis
Authors: Islam Md Zohorul , Tran Melissa , Xu Tao , Tierney Braden T. , Patel Chirag , Kostic Aleksandar David
Published: December 2021

Background: The gut microbiome promotes specific immune responses, and in turn the immune system has a hand in shaping the microbiome. Cancer and autoimmune diseases are two major disease families that result from the contrasting manifestations of immune dysfunction. We hypothesized that the opposing immunological profiles between cancer and autoimmunity yield analogously inverted gut microbiome signatures. To test this, we conducted a systematic review and meta-analysis on gut microbiome signatures and their directionality in cancers and autoimmune conditionsMethodology: We searched PubMed, Web of Science, and EMBAS to identify relevant articles to be included in this study. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements and PRISMA 2009 checklist. Study estimates were pooled by a generic inverse variance random-effects meta-analysis model. The relative abundance of microbiome features was converted to log fold-change and the standard error was calculated from the p-values, sample size and fold-change. Results: We screened 3,874 potentially relevant publications. A total of 82 eligible studies comprising 37 autoimmune and 45 cancer studies with 4,208 healthy human controls and 5,957 disease cases from 27 countries were included in this study. We identified a set of microbiome features that show consistent, opposite directionality between cancers and autoimmune diseases in multiple studies. Fusobacterium and Peptostreptococcus were the most consistently increased genera among the cancer cases which were found to be associated in a remarkable 13 (+0.54 log fold-change in 5 studies) and 11 studies (+3.75 log fold-change in 5 studies), respectively. Conversely, Bacteroides was the most prominent genus, which was found to be increased in 12 autoimmune studies (+0.24 log fold-change in 6 studies) and decreased in six cancer studies (-0.32 log fold-change in 4 studies). Sulfur-metabolism pathways were found to be the most frequent pathways among the member of cancer-increased genus and species.Conclusions: The surprising reproducibility of these associations across studies and geographies suggests a shared underlying mechanism shaping the microbiome across cancers and autoimmune diseases.
Preparation and Methylene Blue Adsorption Capacity of HDPE/PVA Foaming Composites
Authors: Li Fenghong , Wang Zhe , Li Pengzhen , Da Wei , Lv Weisi , Guo Keyun , Huang Feihong
Published: December 2021

High density polyethylene (HDPE) and polyvinyl alcohol (PVA) are blended with maleic anhydride grafted amorphous-alpha olefin copolymer as the compatibilizer. The effects of different raw material ratio and the content of compatibilizer and foaming agent on the mechanical properties of the material are studied. It is found that the increasing content of PVA added to HDPE has a negative effect on the properties of the composites. The compatibility and mechanical properties are improved after adding MAH-g-APAO and the most appropriate addition amount is 4%. Foaming agent can make the material lightweight but will decrease the mechanical properties of the material. The composites have a good effect on the removal of methylene blue (MB). Through the experiment, it is found that the initial concentration of MB and adsorption time will also influence the adsorption. The experiment to explore the influence of pH value and temperature of solution on the removal efficiency shows that alkaline environment and high temperature can promote the removal of MB. At 343.15 K, the adsorption capacity (qe) reaches 2.08 mg·g-1. Using the composites to remove dye has the advantages of environmental protection, simple operation and easy recycling. It has broad application prospects in the field of dye wastewater treatment.
Top of Basilar Artery Infarction: A Case Series from Sudan
Authors: Daoud Mahmoud Hussien Salih , Ahmed.E.Abushama Ejlal , Mahmmoud Abdallah.H , Eljack Moh.Mah.Fadelallah , Hussein Khabab Abbashar , Haroun Mazin S. , Elsheikh Duaa Baderaldeen Ibraheem , Abdelkareim.G.Mohammed Sulieman , Eltayeb.O.Eltayeb Ahmed , Allah Yusif Abduelmagid.M.Naiem , Ahmed Al ameen Ahmed Alameen , Yusif Mohamed Yusif Mohamed , Mokhtar Asmaa Esam Abbas , Awadalbari Sarra Nasreldeen Ibrahim , Eltayeb Rowda Babikir Osman
Published: December 2021

The posterior circulation represents 20% of blood supply of the brain and its occlusion commonly by embolism cause brainstem, cerebellar and lower cerebral infarction. The clinical presentation varies from mild innocent symptoms leading to sever neurological deficit or death. Time of intervention is vital commonly with antithrombatic drugs or through intervention. Here, we report two Sudanese patients who had a complicated medical sequence over months ended as top of basilar artery occlusion received anticoagulants and supportive therapy according to their condition showed a variable recovery over weeks.
Motherhood Modulates Cognitive Biases Toward Family Members: the Maternal Self-concept Re-examined Through Categorization Tasks
Authors: Jiang Mengyin , Sui Jie
Published: December 2021

The self-bias is a robust effect where self-related information is processed with greater priority than other-related information. Interestingly, the advantages of self-bias can be extended to close others – faster and more accurate responses for one’s mother and best friend have been observed compared to strangers – suggesting that significant others play an important role in the formation of one’s self-concept. Moreover, important life experiences such as childbirth can also impact the self-concept. Motherhood is a major transformation for women as one prepares to become a mother while maintaining the integrity of the pre-pregnant self-concept to achieve an ideal maternal self. The current study explored how the transition into motherhood changes the self-concept and subsequently impact the categorization of information for family members in postpartum mothers. In two experiments, results consistently revealed biases towards the self and close kin (one’s baby and mother) regardless of stimulus type (names in Experiment 1, faces in Experiment 2) and response category (self/other, family/non-family, familiar/non-familiar). A family bias (for baby and mother) over friend was observed in the family/non-family but not in the familiar/non-familiar categorization task, suggesting that motherhood may enhance the boundary between family and non-family to facilitate the processing of family-related information.
The extensive intergenerational molecular effects of ocean acidification on the olfactory epithelium transcriptome of a marine fish are associated with a better viral resistance
Authors: Cohen-Rengifo Mishal , Danion Morgane , Gonzalez Anne-Alicia , Bégout Marie-Laure , Madec Lauriane , Cormier Alexandre , Noël Cyril , Cabon Joëlle , Vitré Thomas , Mark Felix C. , Mazurais David
Published: December 2021

Background

Progressive climate-induced ocean acidification (OA) impacts marine life in ways that are difficult to predict but are likely to become exacerbated over generations. Although marine fishes can balance internal acid-base homeostasis efficiently, indirect ionic regulation effects that alter neurosensory systems can result in behavioural abnormalities. In marine invertebrates, OA can also affect immune system function, but whether this is the case in marine fishes of ecological and commercial importance is not yet understood. Farmed fish are highly susceptible to disease outbreak yet strategies for overcoming such threats in the wake of OA are wanting. Here, we exposed two generations of the European sea bass (Dicentrarchus labrax) to end-of-century predicted CO2 levels (IPCC RCP8.5), with parents being exposed for four years and their offspring for two years. Our design included a transcriptomic analysis of the olfactory rosette (collected from the F1 offspring) and a viral challenge (exposing F1 offspring to betanodavirus) where we assessed survival rates.
Results

We discovered long-term intergenerational molecular trade-offs in both sensory and immune systems. Specifically, RNA-Seq analysis of the olfactory rosette, the peripheral olfactory organ, from two-year-old F1 offspring revealed extensive regulation in genes involved in ion transport and neuronal signalling, including GABAergic signalling. We also detected extensive OA-induced intergenerational up-regulation of genes associated with odour transduction, synaptic plasticity, neuron excitability and wiring and down-regulation of genes involved in energy metabolism. In addition, intergenerational exposure to OA induced up-regulation of genes involved in innate antiviral immunity (pathogen recognition receptors and interferon-stimulated genes) in combination with down-regulation of the protein biosynthetic machinery. Consistently, OA-exposed F1 fish challenged with betanodavirus, which causes damage to the nervous system of marine fish, had acquired improved resistance.
Conclusion

F1 exposed to OA-intergenerational acclimation showed superior viral resistance, though as their metabolic and odour transduction programs were altered, odour-mediated behaviours might be consequently altered. Our results reveal that trade-offs in adaptive plastic responses is a core feature of the olfactory epithelium transcriptome in OA-exposed fish, suggesting that intergenerational plasticity propagate with progressive exposure to OA and will have important consequences for how cultured and wild fish interacts with its environment.
Knowledge, Attitude and Acceptance of a COVID-19 Vaccine in Indian Population : a Cross Sectional Study
Authors: Soni Aditya , Tripathi Devanshi , Bhaskar Manju , Modi Rujul
Published: December 2021

INTRODUCTION: The COVID-19 pandemic keeping on to devastate the world. A vaccine provides the best hope to control the pandemic. Understanding vaccine acceptance is important, because there is relatively high vaccine hesitancy for existing vaccines and relatively low vaccination coverage. MATERIALS AND METHODS: Participants included are adults between the age group of 18-29 years (n=100). This is a cross-sectional, web based observational study conducted over a period of 1 month. An online survey is carried out through distribution of questionnaire via social network with snow ball effect. RESULTS: A total 100 participants were included in the study. Almost more than half (55%) of the young adults aged between 18 and 29 years were oblivious about the COVID-19 vaccine availability, followed by 22% person aged between 30-39 years and 22% of the persons aged between 40- 59 years and around 1% of more than 60 years were oblivious about the vaccine availability. Among the study participants, nearly 40% were willing to take COVID-19 vaccine when it is available for use and only 30% did not want the vaccination. CONCLUSION: The most dominant factor for vaccine hesitancy is because of adverse effects following immunization. Vaccine acceptability may be increased once additional information about vaccine safety and efficacy is available in the public domain, preferably from a trusted, centralized source of information.
Prediction modeling of isoscapes for stable isotopes in China’s rice based on environmental similarity
Authors: Sheng Meiling , Zhang Weixing , Nie Jing , Li Chunlin , Zhu A-Xing , Hu Hao , Lou Weidong , Deng Xunfei , Lyu Xiaonan , Ren Zhouqiao , Rogers Karyne M. , Zhang Yongzhi , YUAN Yuwei
Published: December 2021

Rice quality is directly related to human health, so it is important to have traceability systems that can trace inferior or contaminated rice back to its geographical origin. This ensures farming practices in substandard regions become better regulated to improve rice quality, origin labelling and consumer trust. However, tracing the origin of rice on the marketplace requires an accurate database benchmarking the isotope distribution over areas of rice production. Large stable isotope data sets can be used to determine the geographical origin of rice through predictive isoscape models. This study presents the first rice isoscape based on environmental similarity to predict the geospatial distribution of δ13C, δ2H and δ18O values of Chinese rice and provides uncertainty at every location such prediction is made. For this study, 794 rice samples were collected in 2017 from primary rice production regions of China. An independent verification shows that the predicted isotope distribution from this new approach is of high accuracy, with a root mean squared error (RMSE) of 0.51‰, 7.09‰ and 2.06‰ for δ13C, δ2H and δ18O values respectively. In addition, uncertainty in the spatial distribution of isotopes can be used to indicate the prediction accuracy and to guide future sampling. Our results indicate that an isoscape prediction method based on environmental similarity is effective to predict the spatial distribution of stable isotope in rice, and is an effective tool for building isotope distribution in rice over large areas with complex environment. This method could also be used to predict potential isotopic variations in future years due to climate change.
Comparative efficacy of tocilizumab and baricitinib in COVID-19 treatment: a retrospective cohort study
Authors: Kojima Yuichi , Nakakubo Sho , Takei Nozomu , Kamada Keisuke , Yamashita Yu , Nakamura Junichi , Matsumoto Munehiro , Horii Hiroshi , Sato Kazuki , Shima Hideki , Suzuki Masaru , Konno Satoshi
Published: December 2021

Background

Although the biological agents tocilizumab and baricitinib have been shown to improve the outcomes of patients with COVID-19, a comparative evaluation has not been performed. The aim of our study was to evaluate the comparative effect of the use of tocilizumab and baricitinib on patient outcomes in COVID-19.
Methods

A retrospective, single-center study was conducted using the data of patients with COVID-19 admitted to Hokkaido University hospital between April 2020 and September 2021 and were treated with tocilizumab or baricitinib. The clinical characteristics of the patients who received each drug were compared. Univariate and multivariate logistic regression analyses were performed against the outcomes of all-cause mortality and the improvement in respiratory status. The development of secondary infection events was analyzed using the Kaplan–Meier method and the log-rank test.
Results

Among the 459 patients hospitalized with COVID-19 during the study, 64 received tocilizumab and 34 received baricitinib, and they were included in the study. Most patients were treated with concomitant steroids, and the severity of the disease at the time of initiation of biological agents was similar. The use of tocilizumab or baricitinib was not associated with all-cause mortality or the improvement in respiratory status within 28 days of drug administration. Age, chronic renal disease, and comorbid respiratory disease were independent prognostic factors for all-cause mortality, whereas anti-viral drug use and severity of COVID-19 at baseline were associated with the improvement in respiratory status. There was no significant difference in the infection-free survival rate between patients treated with tocilizumab and those with baricitinib.
Conclusion

There were no differences in efficacy and safety between tocilizumab and baricitinib in the treatment of COVID-19. Both these biological agents are expected to be equally safe and clinically effective.
Combinatorial Assembly and Optimisation of Designer Cellulosomes - A Galactomannan Case Study
Authors: Vanderstraeten Julie , Fonseca Maria João Maurício da , De Groote Philippe , Grimon Dennis , Gerstmans Hans , Kahn Amaranta , Moraïs Sarah , Bayer Edward A. , Briers Yves
Published: December 2021

Background: Designer cellulosomes are self-assembled chimeric enzyme complexes that can be used to improve lignocellulosic biomass degradation. They are composed of a synthetic multimodular backbone protein, termed the scaffoldin, and a range of different chimeric docking enzymes that degrade polysaccharides. Over the years, several functional designer cellulosomes have been constructed. Since many parameters influence the efficiency of these multi-enzyme complexes, there is a need to optimise designer cellulosome architecture by testing combinatorial arrangements of docking enzyme and scaffoldin variants. However, the modular cloning procedures are tedious and cumbersome. Results: VersaTile is a combinatorial DNA assembly method, allowing the rapid construction and thus comparison of a range of modular proteins. Here, we present the extension of the VersaTile platform to facilitate the construction of designer cellulosomes. We have constructed a tile repository, composed of dockerins, cohesins, linkers, tags and enzymatically active modules. The developed toolbox allows us to efficiently create and optimise designer cellulosomes at an unprecedented speed. As a proof of concept, a trivalent designer cellulosome able to degrade the specific hemicellulose substrate, galactomannan, was constructed and optimised. The main factors influencing cellulosome efficiency were found to be the selected dockerins and linkers and the docking enzyme ratio on the scaffoldin. The optimised designer cellulosome was able to hydrolyse the galactomannan polysaccharide and release mannose and galactose monomers. Conclusion: We have eliminated one of the main technical hurdles in the designer cellulosome field and anticipate the VersaTile platform to be a starting point in the development of more elaborate multi-enzyme complexes.
NLRP3 is Highly Expressed in Stomach Adenocarcinoma and May Serve as a Novel Prognostic Biomarker
Authors: Yuan Chenxi , Wang Qingwei , Song Yipeng , Yu Jinming
Published: December 2021

Background: Stomach adenocarcinoma (STAD) is a common cancer type around the world. The prognosis in advanced patients is poor. Since NLRP3 was not extensively studied in the field of tumor, so we aimed to identify the impact of NLRP3 on STAD by bioinformatics analyses and in vitro experiments. Methods: TCGA , kaplan-Meier Plotter and TIMER database were utilized in this study. We compared the expression of NLRP3 in different cancers and evaluated its influence on survival of gastric carcinoma patients. The correlations between clinical information and NLRP3 expression were analyzed using logistic regression. Clinicopathologic characteristics associated with overall survival in were analyzed by Cox regression. In addition, we explored the correlation between NLRP3 and immune infiltrates. GSEA and co-expressed gene with NLRP3 were also done in this study. Finally, we verified the NLRP3 expression in paired gastric cancer tissues and adjacent normal tissues by western blot and q-PCR. We also constructed NLRP3 overexpression model in gastric cancer cell line and observed cell proliferation ability.Results: NLRP3 expressed disparately in gastric tumor tissues and normal tissues. Cox regression analysis indicated that up-regulated NLRP3 was an independent prognostic factor for bad prognosis in STAD. Logistic regression analysis showed increased NLRP3 expression was significantly correlated with unfavorable clinicopathologic parameters such as higher T stage, higher histologic grade and worse survival outcome. Specifically, a positive correlation between increased NLRP3 expression and immune infiltrating level of various immune cells was observed. Conclusion: Together with all these findings, increased NLRP3 expression correlates with poor prognosis, unfavorable clinicopathologic parameters and increased proportion of immune cells in STAD. In vitro analysis revealed that cell proliferation ability was enhanced in gastric cancer cells trasnfected with NLRP3 overexpression. These conclusions indicate that NLRP3 has great potential to serve as a biomarker for evaluating prognosis in patients diagnosed with gastric carcinoma.
A Novel Prognostic Signature Based on Cell-In-Cell-Related Genes for Predicting Survival and Tumor Microenvironment in Pancreatic Cancer
Authors: Song Jianlu , Ruze Rexiati , Chen Yuan , Xu Ruiyuan , Yin Xinpeng , Wang Chengcheng , Zhao Yupei
Published: December 2021

Background: Pancreatic cancer (PC) is a highly malignant tumor featured with high intra-tumoral heterogeneity and poor prognosis. Cell-in-cell (CIC) structures have been reported in multiple tumor types, and their presence is thought to promote clonal selection and tumor evolution. Here, we aimed to establish a CIC-related gene signature for predicting the prognosis and evaluating immune microenvironment in PC. Methods: In this study, the gene expression data, as well as corresponding clinicopathological data of PC and normal pancreatic tissues were collected from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) databases. Differential gene expression analysis, random forest screening, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis were performed on 101 CIC-related genes to construct a prognostic gene signature. The effectiveness and robustness of the prognostic gene signature were evaluated by receiver operating characteristic (ROC) curves, Kaplan-Meier survival analysis and establishing the nomogram model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to annotate the biological functions of the differentially expressed genes (DEGs). Quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry (IHC) staining were validated the core gene expression in both mRNA and protein levels. Results: A 4-gene signature was constructed to stratify patients into the low-risk and high-risk groups with distinct survival outcomes, somatic mutation profiles and immune features. The high-risk group had poorer prognosis than did the low-risk group. This signature was found to be an independent prognostic factor for PC patients with favorable predictive efficiency. Functional enrichment analyses showed that numerous terms and pathways associated with invasion and metastasis were enriched in the high-risk group. Moreover, the high-risk group had a higher tumor mutation burdens and lower immune cell infiltrations. KRT7, as the most important risk gene, was significantly associated with the worse prognosis of PC. CIC formation assay performing in PC cell lines indicated that KRT7 expression was correlated with CIC frequency. Conclusions: The signature based on four CIC-related genes could be applicable for predicting the prognosis of PC, and targeting CIC processes may be a potential therapeutic option. Further studies are needed to reveal the underlying molecular mechanisms and biological implications of CIC in PC progression.
Comparison of the Characteristics and Outcomes of SARS-COV 2 Critically Ill Patients After Emergence of the Variant of Concern 20H/501Y.V2: A Comparative Cohort Study
Authors: ARIES Philippe , HUET Olivier , BALICCHI Julien , MATHAIS Quentin , ESTAGNASIE Camille , MARTIN-LECAMP Gonzague , MORVAN Anne-Cécile , SIMON Olivier , PUECH Bérénice , SUBIROS Marion , BLONDE Renaud , BOUE Yvonnick
Published: December 2021

BackgroundThere are currently no data regarding characteristics of critically ill patients with SARS-CoV-2 Variant of Concern (VOC) 20H/501Y.V2. We therefore aimed to describe changes of characteristics in critically ill patients with Covid-19 between the first and the second wave when viral genome sequencing indicated that VOC was largely dominant in Mayotte Island (Indian Ocean).MethodsConsecutive patients with Covid-19 and over 18 years admitted in the unique Intensive Care Unit (ICU) of Mayotte during wave 2 were compared with an historical cohort of patients admitted during wave 1. We performed a Logistic Regression (LR) comparing wave 1 and wave 2 as outcomes. To complete analysis of changes in characteristics and outcomes, we built a Random Forest model (RF) -i.e., a machine learning classification tool- using the same variable set as that of the LR.ResultsWe included 156 patients, 41 (26.3%) and 115 (73.7%) belonging to the first and second waves respectively. Univariate analysis did not find difference in demographic data or in mortality. Our multivariate LR found that patients in wave 2 had less fever (absence of fever aOR 5.23, 95% CI 1.89 – 14.48, p=0.001) and a lower SAPS II (aOR 0.95, 95% CI 0.91 – 0.99, p=0.007) at admission; at 24 hours, the need of invasive mechanical ventilation was higher (aOR 3.49, 95% CI 0.98 – 12.51, p=0.055) and pO2/FiO2 ratio was lower (aOR 0.99, 95 % CI 0.98-0.99, p=0.03). Patients in wave 2 had also an increased risk of VAP (aOR 4.64, 95% CI 1.54-13.93, p=0.006). Occurrence of VAP was also a key variable to classify patients between wave 1 and wave 2 in the variable importance plot of the RF model.ConclusionOur data suggested that VOC 20H/501Y.V2 could be associated with a higher severity of respiratory failure at admission and a higher risk for developing VAP. We hypothesized that the expected gain in survival brought by recent improvements in critical care management could have been mitigated by increased transmissibility of the new lineage leading to admission of more severe patients. The immunological role of VOC 20H/501Y.V2 in the propensity for VAP requires further investigations.
Inducer-Free Cellulase Production System Based on the Constitutive Expression of Mutated Xyr1 and Ace3 in the Industrial Fungus Trichoderma Reesei
Authors: Arai Toshiharu , Ichinose Sakurako , Shibata Nozomu , Kakeshita Hiroshi , Kodama Hiroshi , Igarashi Kazuaki , Takimura Yasushi
Published: December 2021

Background: Trichoderma reesei (Hypocrea jecorina) is a filamentous fungus that can produce extremely high levels of protein; consequently, it is utilized as a host for the production of cellulase and hemicellulase cocktails for lignocellulosic biomass degradation. Several hyper-producer strains of T. reesei have been bred for use in industrial production, but they generally require inducers to achieve high production capacities. The most commonly used inducers are soluble sugars produced by the degradation of cellulose; however, the dependence on cellulose degradation is problematic because cellulose is insoluble and has poor handling properties as a carbon source. Furthermore, once cellulose is decomposed, little cellulase is produced, making it difficult to produce the enzyme continuously and efficiently. The aim of this study was to establish a simple, inducer-free, cellulase production system using glucose as the sole carbon source.Results: Here, we focused on transcription factors that regulate both cellulase and hemicellulase genes. First, we verified that the previously reported Xylanase regulator 1 (Xyr1) mutation had a glucose-blind phenotype in T. reesei, and confirmed that constitutive expression of the V821F mutation in Xyr1 produced high levels of proteins, especially hemicellulase and cellulase, even in inducer-free conditions. However, the majority of proteins were hemicellulases. To reproduce cellulase/hemicellulase production similar to those observed under induced conditions, an activator of cellulase expression 3 (Ace3) was expressed in Xyr1V821F expressed strain additionally. As a result, the T. reesei strain constitutively expressing Xyr1V821F and Ace3 exhibited a 1.5-fold increase than Xyr1V821F expressed only in protein productivity under inducer-free conditions. Notably, the enzyme composition significantly improved for cellulases ratio and similar to that induced by cellulose. Furthermore, the enzymes exhibited a high saccharification efficiency when compared to that of produced by the strain expressing only the mutated Xyr1.Conclusions: This work shows that the constitutive expression of mutated Xyr1 and Ace3 can increase cellulase and hemicellulase production in T. reesei without inducers. This inducer-free enzyme production method could provide an effective system to reduce costs and simplify production processes, and is expected to be applied in the production of various proteins.
New Data and New Features of the FunRiceGenes (Functionally Characterized Rice Genes) Database: 2021 Update
Authors: Huang Fangfang , Jiang Yingru , Chen Tiantian , Li Haoran , Fu Mengjia , Wang Yazhou , Xu Yufang , Li Yang , Zhou Zhengfu , Jia Lihua , Ouyang Yidan , Yao Wen
Published: December 2021

As a major food crop and model organism, rice has been mostly studied with the largest number of functionally characterized genes among all crops. We previously built the funRiceGenes database including ∼2800 functionally characterized rice genes and ∼5000 members of different gene families. Since being published, the funRiceGenes database has been accessed by more than 49,000 users with over 490,000 page views. The funRiceGenes database has been continuously updated with newly cloned rice genes and newly published literature, based on the progress of rice functional genomics studies. Up to Nov 2021, ≥4100 functionally characterized rice genes and ∼6000 members of different gene families were collected in funRiceGenes, accounting for 22.3% of the 39,045 annotated protein-coding genes in the rice genome. Here, we summarized the update of the funRiceGenes database with new data and new features in the last five years.
Preimplantation Genetic Testing for Thalassemia Through Next- Generation Sequencing of Affected-embryos
Authors: Ou Zhanhui , Deng Yu , Liang Yunhao , Chen Zhiheng , Sun Ling
Published: December 2021

Background: To evaluate the ability of next-generation sequencing (NGS) to conduct preimplantation genetic testing (PGT) for thalassemia using affected embryos. Methods: This study included data from 36 couples who underwent PGT for thalassemia without proband and relative pedigrees. NGS results were compared with prenatal diagnosis results.Results: Thirty-six couples (29 α-thalassemia and 7 β-thalassemia) underwent 41 PGT cycles (31 α-thalassemia and 10 β-thalassemia). All biopsied blastocysts received conclusive results from NGS analysis (100%, 217/217). One hundred and sixty (73.7%, 160/217) were determined to be unaffected by thalassemia. PGT-A (PGT for aneuploidy) results showed that 112 (70.0%, 112/160) were euploid. Thirty-four couples were transferred with a single blastocyst (53 frozen embryo transfer (FET) cycles). Thirty-two cycles resulted in clinical pregnancies, and the clinical pregnancy rate was 60.1% (32/53) per FET cycle. Twenty-two cycles (22 couples) resulted in 23 live births and the live birth rate was 43.4% (23/53, 3 cycles were ongoing pregnancy). All 25 cycles’ prenatal diagnosis results and/or thalassemia gene analysis after the delivery were concordant with the NGS-PGT results. Seven cycles were miscarried before 12 weeks’ gestation, and the abortion villus in four cycles showed a normal karyotype and thalassemia results consistent with the NGS-PGT results. Aborted fetus samples from 3 cycles were not available because the pregnancy was less than 5 weeks.Conclusion: NGS can be used to conduct PGT for thalassemia using affected embryos as a reference.Trial registration: Retrospectively registered.
Structure and Properties of Mixed Former Aluminum Borate Glasses Modified With Silver Oxide
Authors: El-Damrawi Gomaa , Salah H
Published: December 2021

The current study focuses on glass preparation and characterization in the xAl2O3 (35-x) Ag2O.65B2O3 system (0≤x≤35 mol%), where Ag2O is replaced with Al2O3. To examine a wide range of both structure and morphology of the produced glasses, nuclear magnetic resonance (NMR) of 27Al nuclei, X-ray diffraction (XRD) spectroscopy, and transmission electron microscopy (TEM) are used. Changing the Al2O3 and Ag2O molar ratios reveals a substantial change in material structure. In Al2O3-rich glass, the well-formed AlO6, AlO5, and AlO4 structured groups are the well-formed units. In samples of (20 and 30 mol % Al2O3), tetrahedral AlO4 and traces from AlO6 units may be detected. At lower concentrations of Al2O3 (10 mol%), the dominant unit is only AlO4 groups containing non-bridging oxygen bonds (NBO). The XRD and EDP spectra confirm the amorphous nature of the glasses of Al2O3 ˂ 20 mol%. Glasses of higher Al2O3 concentrations contain crystalline Ag2Al2B2O7 which are formed due to the higher oxygen packaging of the mixed AlO5 and AlO4 compared with that of glasses containing only AlO4 species. The amount of higher coordinated Al species AlO5 and AlO6 are gradually increased in response to an increase in the ratios of Al2O3/Ag2O. The morphology of crystalline units is confirmed from TEM to differ from that of an amorphous composition. The conductivity decreases and the activation energy for ionic conduction increase with increasing Al2O3. The hardness number of the studied glasses is highly increased with increasing Al2O3 content. The increase of activation energy and the hardness number of the glasses led to an increase in the durability of the investigated glasses.
Quality Assessment of Some Alcohol-Based Hand Sanitizers Circulating in the Federal Capital Territory, Abuja. Nigeria
Authors: Adigwe Obi , John Judith , Isimi Christianah , Oloye Simisola , Onavbavba Godspower , Emeje Martins
Published: December 2021

Background

The emergence of corona virus disease caused by SARS-COV-2 (Covid-19) and the subsequent recommendation by the World Health Organization (WHO) on the use of non-pharmaceutical measures led to an upsurge in the production and sale of hand sanitizers across the globe including Nigeria. It is important that product regulation schemes are designed in such a way as to ensure the continual quality of the products to potential clients. Hence, this paper provides an understanding of the quality of alcohol based hand sanitizers in Abuja, Nigeria.
Methods

A total of fifty (50) different brands of alcohol-based hand sanitizers were purchased from different pharmacies, supermarkets, and stores, within Abuja. In the laboratory, samples were checked for their label claims, NAFDAC registration number, batch number, manufacturing and expiration dates. The information was recorded in the laboratory notebook in accordance with ISO 17025 requirement, then samples were coded as SAN1 to SAN50 and assessed for pH values and Alcohol Content.
Results

About 40% of the circulating hand sanitizers in the market did not go through regulatory vetting, 34% of the products did not have information on the country of manufacture, 32% of the sanitizers had pH values within acceptable range, while 78% of the products contained less than 60% alcohol.
Conclusion

This study gives an insight into the quality of alcohol-based hand sanitizers and we suggest an urgent need for the regulatory authorities of developing countries to enhance their surveillance and control of these substandard products in the society.
Prevalence of Kidney Stones Among Patients Presenting to Orotta Medical Surgical National Referral Hospital
Authors: Teklehaimanot Selomie Zemicael , Bahta Bernandos , Baye Nardos Tareke , Gebremichael Eyob , Gebrezgi Tsegezeab , Saleh Biniam , Tesfagiorgis Andemariam , Osman Abdu , Angesom Haileab , Mohammed Omer , Berhe Yonas
Published: December 2021

Background

Nephrolithiasis is a condition of having stones in the kidneys, which progressively lead to loss of renal function if untreated properly.1 The prevalence and incidence of kidney stones is increasing across the world.2
Methods

A retrospectively collected data of kidney stone disease was reviewed on patients who visited the outpatient department of Orotta Medical Surgical National Referral Hospital from January 2012 to December 2012.
Results

Out of 30,335 patients 173 were confirmed to have stones making them 0.5%. Generally results show male predominance with male to female ratio of 2.46:1. Results also show prevalence decreases as age increases with the highest among the age group 15-25 making a prevalence rate of 27.7% with observed significance of 0.002. Out of those patients who visited the outpatient department patients from Zoba Maekel were the highest in number (59.9%) followed by Debub (19.1%) while the southern Red Sea Zone had the lowest prevalence (2.3%). Majority of the stones were found on the kidney comprising about 80.3%, followed by ureter 16.8% of patients and 2.9% stones were located on the bladder. When data was reviewed for associated co morbidity only one patient had associated Diabetes mellitus and Hypertension, three had ectopic kidney(1.7%), one had renal cyst (0.6%) and 12 (6.9%) patients were complicated with hydronephrosis. (P=0.548)
Conclusions

The prevalence of kidney stone in Orotta Medical Surgical National Referral hospital from January to December 2012 is 0.5%, with higher predominance in men than in women with a ratio of 2.46:1.
Safety and Immunogenicity of Combination of Vaccines – Covishield and Covaxin – a Pilot Study
Authors: Attunuru Bhanu Prakash Reddy , Reddy Podduturi Naveenchander , Mitnala Sasikala , Deepika Gujjarlapudi , Veturi Sadhana Yelamanchili , Reddy Duvvur Nageshwar
Published: December 2021

This single-center prospective observational study was conducted to assess the safety and immunogenicity of combination vaccines AstraZeneca’s ChAdOx1-nCov-19 (Covishield in India) and inactivated whole virion BBV152 (Covaxin). A total of 330 unvaccinated healthy volunteers were screened for SARS-COV2 seropositivity. RT PCR tests were conducted for seronegative volunteers (n =44). They were randomly assigned to four groups and given either same or mixed vaccines at an interval of 4 weeks between the two doses. Mix and match of vaccines did not evoke any adverse events. Combination of vaccines elicited similar immune responses in 4 groups. In Conclusion, Combination vaccines are safe and immunogenic.
Treatment of COVID-19 pneumonia and acute respiratory distress with ramatroban, a thromboxane A2 and prostaglandin D2 receptor antagonist: A 4-Patient Case Series Report
Authors: Ogletree Martin L. , Chiang Kate Chander , Kulshreshta Rashmi , Agarwal Aditya , Agarwal Ashutosh , Gupta Ajay
Published: December 2021

COVID-19 associated pneumonia and acute respiratory distress syndrome are accompanied by a massive and sustained increase in lung and systemic thromboxane (Tx) A2. TxA2 is a short-lived, potent vasoconstrictor of pulmonary veins > arteries, and thereby selectively increases pulmonary venous resistance, promoting an increase in pulmonary capillary pressure. TxA2 also increases vascular permeability which, in the lungs, exaggerates pressure-mediated transudation into the alveolar space, causing pulmonary edema and ARDS. Also relevant to COVID-19 pathophysiology, TxA2 contracts bronchial smooth muscle, triggers and amplifies platelet activation, mediates apoptosis of immature thymocytes, and promotes a procoagulant state, all of which are mediated by TxA2 receptor (TPr) activation. The stable TxA2 metabolite, 11-dehydro-TxB2, is elevated in direct proportion to COVID-19 severity. Though inactive at TPr, 11-dehydro-TxB2 activates PGD2 / DP2 receptors (DPr2) which promote a Th2 immune response that is atypical for viral infections and inhibits antiviral defense by suppressing interferon λ expression. Ramatroban is an orally bioavailable, potent, dual antagonist of TPr and DPr2 receptors. We report use of ramatroban (Baynas®, Bayer Yakuhin Ltd., Japan) in 4 COVID-19 outpatients, 22 to 87 years of age, with acute onset / worsening of respiratory distress and hypoxemia. All four patients experienced a decrease in respiratory distress and increase in SpO2, within hours of the first dose of ramatroban and, thereby, avoided hospitalization. By the 5th day all 4 patients had complete resolution of respiratory distress and hypoxemia. Ramatroban has an established safety profile, having been indicated in Japan for the treatment of allergic rhinitis for over 20 years. As an anti-vasospastic, broncho-relaxant, anti-thrombotic and immunomodulator, ramatroban addresses the fundamental host response mechanisms underlying respiratory and critical organ failure in COVID-19, and merits urgent clinical trials that might impact the ongoing pandemic.
Prevalence of nephropathy among type two diabetes patients in Eastern Mediterranean Region: A systematic review and meta-analysis
Authors: Zeighami Shahryar , Shaabani Sonia , Moheb Mohammad , Pakfetrat Maryam , Azarchehry Seyede Pegah , Dehghankhalili Saeid , Mirahmadizadeh Alireza , Heiran Alireza
Published: December 2021

Objectives: The global epidemic of Diabetes Mellitus exerts a substantial burden on health services. This high prevalence of diabetes leads to an increase in diabetic complications, especially diabetic nephropathy, a leading cause of end stage renal disease and renal replacement therapies. Due to its’ the high prevalence reported by Individual studies in EMR, we conducted a meta-analysis of relevant studies to estimate diabetic retinopathy in EMR.Method: We searched for the relevant keywords in title and abstract of Medline/PubMed, Scopus, Embase, Web of knowledge, and Gray literature from Jan 1st, 2000 to December 13, 2019. The two-step screening was carried out by two independent researchers and relevant data were extracted. Estimation of summary proportions, subgroup analysis, meta-regressions, and publication bias assessment were performed. Results: Out of 3,225 identified citations, 38 articles were entered into meta-analysis, involving 112,235 patients. The prevalence of nephropathy in type two diabetes was 26.34% (95% confidence interval (CI)= 21.04, 32%); and it was 30.42% (95% CI= 23.38, 37.94%) in males and 22.1% (95% CI= 16.05, 28.79%) in females. The meta-regression analysis showed that HDI, publication year, mean duration of diabetes, mean age, and diagnostic test were not significant moderators (p = .332, .725, .280, .220, and .468, respectively).Conclusions: Diabetic nephropathy high prevalence in EMR implicates the importance of diabetes screening, periodic examinations, diabetes care, and risk factor controls. Large-scale longitudinal studies should be conducted in EMR.