bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and integrated analysis of CircRNA and miRNA of Radiation-Induced lung injury in a mice model
Authors: Yang Xi , Li Yida , Zou Liqing , Chu Li , Ye Luxi , Ni Jianjiao , Chu Xiao , Guo Tiantian , Zhu Zhengfei 
Published: August 2020

Abstract
Radiation-induced lung injury (RILI) is a main threat to patients received thoracic radiotherapy, it is of great importance to understand the molecular mechanism of RILI. Circular RNAs (CircRNAs) have been found to act as the regulator of multiple biological processes and circRNA-miRNA-mRNA axis could play an important role in signaling pathway of many human diseases including radiation injury, here, we first investigate the circRNA and miRNA of radiation-induced lung injury in a mice model. The mice received 12 Gy thoracic irradiation and the irradiated lung tissues at 48 hours after irradiation were analyzed by RNA Sequencing (RNA-seq) technique compared with normal lung tissues. We identified 21 significantly up-regulated while significantly 33 down-regulated miRNAs. Among 27 differentially expressed circRNAs, 10 were down-regulated and 17 were up-regulated. We then performed circRNAs GO analysis of the target mRNAs of these significantly differently expressed circRNAs. These differentially expressed miRNAs took part in series of cellular processes such as positive regulation of alpha-beta T cell proliferation, interstitial matrix, collagen fibril organization, chemokine receptor activity, cellular defense response, and B cell receptor signaling pathway. Through this study, we found that immune-related molecular pathways play an important role in the early response after radiotherapy. In the future, research on the target mechanism and early intervention of circRNAs with associated miRNAs will benefit the treatment of RILI.
Deciphering the state of immune silence in fatal COVID-19 patients
Authors: Amit Ido , Bost Pierre , De Sanctis Francesco , Canè Stefania , Stefano Ugel , Donadello Katia , Castellucci Monica , David Eyal , Fiore Alessandra , Anselmi Cristina , Barouni Roza , Trovato Rosalinda , Caligola Simone , Lamolinara Alessia , Iezzi Manuela , Facciotti Federica , Mazzariol Anna , Gibellini Davide , De Nardo Pasquale , Tacconelli Evelina , Gottin Leonardo , Polati Enrico , Schwikowski Benno , Bronte Vincenzo 
Published: August 2020

Abstract
Since the beginning of the SARS-CoV-2 pandemic, COVID-19 has appeared as a unique disease with unconventional tissue and systemic immune features. While COVID-19 severe forms share clinical and laboratory aspects with various pathologies such as hemophagocytic lymphohistiocyto-sis, sepsis or cytokine release syndrome, their exact nature remains unknown. This is severely imped-ing the ability to treat patients facing severe stages of the disease. To this aim, we performed an in-depth, single-cell RNA-seq analysis of more than 150.000 immune cells isolated from matched blood samples and broncho-alveolar lavage fluids of COVID-19 patients and healthy controls, and integrated it with clinical, immunological and functional ex vivo data. We unveiled an immune sig-nature of disease severity that correlated with the accumulation of naïve lymphoid cells in the lung and an expansion and activation of myeloid cells in the periphery. Moreover, we demonstrated that myeloid-driven immune suppression is a hallmark of COVID-19 evolution and arginase 1 expression is significantly associated with monocyte immune regulatory features. Noteworthy, we found mon-ocyte and neutrophil immune suppression loss associated with fatal clinical outcome in severe pa-tients. Additionally, our analysis discovered that the strongest association of the patients clinical outcome and immune phenotype is the lung T cell response. We found that patients with a robust CXCR6+ effector memory T cell response have better outcomes. This result is line with the rs11385942 COVID-19 risk allel, which is in proximity to the CXCR6 gene and suggest effector memory T cell are a primary feature in COVID-19 patients. By systemically quantifying the viral landscape in the lung of severe patients, we indeed identified Herpes-Simplex-Virus 1 (HSV-1) as a potential opportunistic virus in COVID-19 patients. Lastly, we observed an unexpectedly high SARS-CoV-2 viral load in an immuno-compromised patient, allowing us to study the SARS-CoV-2 in-vivo life cycle. The development of myeloid dysfunctions and the impairment of lymphoid arm establish a condition of immune paralysis that supports secondary bacteria and virus infection and can progress to “immune silence” in patients facing death.
Congenital Muscular Dystrophy-Associated Inflammatory Chemokines Provide Axes for Effective Recruitment of Therapeutic Adult Stem Cell into Muscles
Authors: Alexeev Vitali , Olavarria Jacquelyn , Bonaldo Paolo , Merlini Luciano , Igoucheva Olga 
Published: August 2020

Abstract
Background: Congenital muscular dystrophies (CMD) are a clinically and genetically heterogeneous group of neuromuscular disorders characterized by muscle weakness. The two most prevalent forms of CMD, collagen VI-related myopathies (COL6RM) and laminin a2 deficient CMD type 1A (MDC1A), are both caused by deficiency or dysfunction of extracellular matrix proteins. Previously, we showed that an intramuscular transplantation of human adipose-derived stem cells (ADSC) into the muscle of the Col6a1-/- mice results in efficient stem cell engraftment, migration, long-term survival, and continuous production of the collagen VI protein, suggesting the feasibility of the systemic cellular therapy for COL6RM. In order for this therapeutic approach to work however, stem cells must be efficiently targeted to the entire body musculature. Thus, the main goal of this study is to test whether muscle homing of systemically transplanted ADSC can be enhanced by employing muscle-specific chemotactic signals originating from CMD-affected muscle tissue. Methods: Proteomic screens of chemotactic molecules were conducted in the skeletal muscles of COL6RM- and MDC1A-affected patients and CMD mouse models to define the inflammatory and immune activities, thus, providing potential markers of disease activity or treatment effect. Also using a pre-clinical animal model, recapitulating mild Ullrich congenital muscular dystrophy (UCMD), the therapeutic relevance of identified chemotactic pathways was investigated in vivo, providing a basis for future clinical investigations. Results: Comprehensive proteomic screens evaluating relevant human and mouse skeletal muscle biopsies offered chemotactic axes to enhance directional migration of systemically transplanted cells into CMD-affected muscles, including CCL5-CCR1/3/5, CCL2-CCR2, CXCL1/2-CXCR1,2 and CXCL7-CXCR2. Also, the specific populations of ADSC selected with an affinity for the chemokines being released by damaged muscle showed efficient migration to injured site and presented their therapeutic effect.Conclusions: Collectively, identified molecules provided insight into the mechanisms governing directional migration and intra-muscular trafficking of systemically infused stem cells, thus, permitting broad and effective application of the therapeutic adult stem cells for CMD treatment.
Uridine Diphosphate (UDP) Promotes Rheumatoid Arthritis Through P2Y6 Activation
Authors: Wang Hongxing , Wu Hui , Fang Kehua , Chang Xiaotian 
Published: August 2020

Abstract
Background: Uridine diphosphate (UDP) is an extracellular nucleotide signaling molecule implicated in diverse biological processes via specific activation of the metabotropic pyrimidine and purine nucleotide receptor pyrimidinergic receptor P2Y, G Protein-Coupled, 6 (P2Y6).Methods: This study used a quasi-targeted liquid chromatography-mass spectrometry (LC-MS) approach to investigate the unique expression of metabolites in rheumatoid arthritis (RA) synovial fluid (SF) (n=10) with samples from osteoarthritis (OA) as controls (n=10). RA fibroblast-like synoviocytes (FLSs) were collected from synovial tissues and cultured with UDP or MRS2578, P2Y6 antagonist, and FLSs from OA was used as controls. Rats with collagen-induced arthritis (CIA) were established and injected with UDP or MRS2578 or both. P2Y6 expression was examined using real-time PCR, Western blotting and Immunohistochemistry. Cell proliferation, apoptosis and migration of FLSs were measured using CCK-8 assay, real-time cell analysis, flow cytometry, the wound healing assay and transwell assay. The concentration of UDP in culture medium, synovial fluid and peripheral blood RA and CIA rats was measured using a Transcreener UDP Assay, IL-6 was measured using ELISA and flow assay, and other pro-inflammatory cytokines was measured using Th1/Th2 Subgroup Detection Kit. Results: LC-MS analysis showed that the UDP level is not only higher in RA SF than in OA SF but also positively correlated with anticyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) levels in RA. The increased UDP concentration was verified in the plasma and SF samples of RA patients (n=36) and healthy volunteers (n=36), and the levels were significantly correlated with RF and anti-CCP level in the samples. The study also found that UDP stimulated the cell proliferation, migration and interleukin-6 (IL-6) secretion of RA FLSs and inhibited their apoptosis in the culture. The P2Y6 antagonist MRS2578 inhibited this effect of UDP in the culture. UDP injection accelerated the development of collagen-induced arthritis (CIA) in a rat model and stimulated IL-6 production, but simultaneous injection of MRS2578 suppressed these effects and alleviated CIA. P2Y6 expression was increased in RA and CIA synovial tissues and was unaltered by UDP treatment. UDP treatment and P2Y6 activity didn’t change levels of other proinflammatory cytokines in cultured FLSs and CIA rats.Conclusion: These results suggest that UDP is highly expressed in RA and stimulates RA pathogenesis by promoting P2Y6 activities to increase IL-6 production.
Spatiotemporal&nbsp;Prediction of COVID-19 Mortality&nbsp;and Risk Assessment
Authors: Torres-Signes Antoni , Frías M. Pilar , D.Ruiz-Medina María 
Published: August 2020

Abstract
This paper presents a multivariate functional data statistical approach, for spatiotemporal prediction of COVID-19 mortality counts. Specifically, spatial heterogeneous nonlinear parametric functional regression trend model fitting is first implemented. Classical and Bayesian infinite-dimensional log-Gaussian linear residual correlation analysis is then applied. The nonlinear regression predictor of the mortality risk is combined with the plug-in predictor of the multiplicative error term. An empirical model ranking, based on random K-fold validation, is established for COVID-19 mortality risk forecasting and assessment, involving Machine Learning (ML) models, and the adopted Classical and Bayesian semilinear estimation approach. This empirical analysis also determines the ML models favored by the spatial multivariate Functional Data Analysis (FDA) framework. The results could be extrapolated to other countries.
Estimation of drug-likeness properties of GC-MS separated bioactive compounds in rare medicinal Pleione maculata using molecular docking technique and SwissADME insilico tools
Authors: SYMPLI HAKANI D 
Published: August 2020

Abstract
The main aim of present paper is to determine bioactive compounds in Pleione maculata extracts using Gas chromatographic technique and to investigate their drug-likeness potential using molecular docking algorithm and ADME studies on the recent intractable disease for example; SARS-CoV-2. P. maculata sample was prepared for GC-MS analysis. The peak components are identified based on NIST Library. Molecular docking was performed using PatchDock and energy refinement was carried out using FireDock algorithm followed by drug-likeness analysis using Swiss ADME tool. Mass spectrum revealed various pharmacologically important compounds and novel compounds 8-oxatetracyclo{5.2.1.1(2,6). 1(4,10)}Dodecane, 7-tert-Butyl-1,9,9-Trimeth, Cholesterol Isocaproate, Docosane, 2,4-Dimethyl, 7.dehydrocholesterol isocaproate, Kryptogenin 2,4-dinitrophenyl hydrazine, N-decyl-Alpha,D-2-Deoxyglycoside, pyrimidine-2,4,6(1H,3H,5H)-Trione-1-octadecyl) which are reported for the first time. Molecular docking using PatchDock illustrates GC-MS compounds Nor-diazepam,3-{N-hydroxymethyl}aminocarbonyloxy a good docking and high binding affinity with Atomic contact energy -10.95 kcal/mol against SARS-CoV-2 Spike protein S2 subunit. ADME analysis predict Nor-diazepam,3-{N-hydroxymethyl}aminocarbonyloxy and andrographolide showed very high drug-likeness parameters with no metabolism disturbances. The random control anti-viral drug arabidiol revealed a lower binding energy and lower solubility compared to bioactive compounds of P. maculata. The study depicts the first and novel report on various pharmaceutical important GC-MS bioactive compounds and molecular docking study of Pleione maculata having potential against various intractable diseases.
Impact of Lockdown during COVID-19 on Annual Effective Dose Equivalent values of Natural Gamma Radiation
Authors: Jindal Manoj Kumar , Sar Santosh Kumar 
Published: August 2020

Abstract
The study aimed to find the impact of COVID-19 on values of Annual Effective Dose Equivalent of the natural Gamma dose rate from Balod, Durg and Bemetara districts of Chhattisgarh (India). COVID-19 is a severe problem for many countries and to control and prevent the spread of this problem implemented the lockdown approach in many countries, including India. In this lockdown situation, almost all people are staying at home for 24 hours. Due to the present status of COVID-19, the Indian government also fixed the 67 days lockdown and one day was already successfully done as Janta Curfew, which worked the same as a lockdown. The value of indoor gamma dose rates was reported higher in most places as compared to the outdoor gamma dose rate, but in this pandemic situation, occupancy factor values are not applicable as recommended by UNSCEAR for calculation of Annual Effective Dose Equivalent (AEDE). Therefore, the present study introduces the new equations, which can measure the extra AEDE value during the lockdown for adults, children and infants.
Artificial intelligence-based patient positioning for faster, more accurate and efficient CT imaging for COVID-19 patients
Authors: Gang Yadong , Chen Xiongfeng , Li Huan , Wang Hanlun , Li Jianying , Guo Ying , Zeng Junjie , Hu Qiang , Hu Jinxiang , Xu Haibo 
Published: August 2020

Abstract
Objective: To analyze and compare the imaging workflow, radiation dose and image quality for COVID-19 patients examined using either the conventional manual positioning method or an AI-based positioning method. Materials and Methods: 127 adult COVID-19 patients underwent chest CT scans on a CT scanner using the same scan protocol except with the manual positioning (MP group) for the initial scan and an AI-based positioning method (AP group) for the follow-up scan. Radiation dose, patient off-center distance, examination and positioning time of the two groups were recorded and compared. Image noise and signal-to-noise ratio (SNR) were assessed by three experienced radiologists and were compared between the two groups.Results: The AP group reduced the total positioning time and examination time by 28% and 8%, respectively compared with the MP group. Compared with the MP group, AP group had significantly less patient off-center distance (AP:1.56cm ± 0.83 vs. MP: 4.05cm ± 2.40, p<0.001) and higher proportion of positioning accuracy (AP: 99% vs. MP: 92%), resulted in 16% radiation dose reduction (AP: 6.1mSv ± 1.3 vs. MP: 7.3mSv ± 1.2, p<0.001) and 9% image noise reduction in erector spinae and lower noise and higher SNR for lesions in the pulmonary peripheral areas.Conclusion: The AI-based positioning and centering in CT imaging is a promising new technique for reducing radiation dose, optimizing imaging workflow and image quality in imaging the chest. This technique has important added clinical value in imaging COVID-19 patients to reduce the cross-infection risks.
Allergen Fragrance Molecules: A Potential Relief for COVID-19
Authors: Aydın Aslı Deniz , Altınel Faruk , Erdoğmuş Hüseyin , Son Cagdas Devrim 
Published: August 2020

Abstract
Background: The latest coronavirus SARS-CoV-2, discovered in China and rapidly spread Worldwide. COVID-19 affected millions of people and killed hundreds of thousands worldwide. There are many ongoing studies investigating drug(s) suitable for preventing and/or treating this pandemic; however, there are no specific drugs or vaccines available to treat or prevent SARS-CoV-2 as of today.Methods: 58 fragrance materials, which are classified as allergen fragrance molecules, were selected and used in this study. Docking simulations were carried out using four functional proteins; the Covid19 Main Protase (Mpro), Receptor binding domain (RBD) of spike protein, Nucleocapsid, and host Bromodomain protein (BRD2), as target macromolecules. Three different software, AutoDock, AutoDock Vina (Vina), and Molegro Virtual Docker (MVD), running a total of four different docking protocol with optimized energy functions were used. Results were compared with the five molecules reported in the literature as potential drugs against COVID-19. Virtual screening was carried out using Vina, molecules satisfying our cut-off (-6.5 kcal/mol) binding affinity was confirmed by MVD. Selected molecules were analyzed using the flexible docking protocol of Vina and AutoDock default settings. Results: Ten out of 58 allergen fragrance molecules were selected for further docking studies. Mpro and BRD2 are potential targets for the tested allergen fragrance molecules, while RBD and Nucleocapsid showed weak binding energies. According to AutoDock results, three molecules, Benzyl Cinnamate, Dihydroambrettolide, and Galaxolide, had good binding affinities to BRD2. While Dihydroambrettolide and Galaxolide showed the potential to bind to Mpro, Sclareol and Vertofix had the best calculated binding affinities to this target. When the flexible docking results analyzed, all the molecules tested had better calculated binding affinities as expected. Benzyl Benzoate and Benzyl Salicylate showed good binding affinities to BRD2. In the case of Mpro, Sclareol had the lowest binding affinity among all the tested allergen fragrance molecules. Conclusion: Allergen fragrance molecules are readily available, cost-efficient, and shown to be safe for human use. Results showed that several of these molecules had comparable binding affinities as the potential drug molecules reported in the literature to target proteins. Thus, these allergen molecules at correct doses could have significant health benefits.
Personal Protection with PBO-Pyrethroid Synergist Treated Nets After Two Years of Household Use Against Pyrethroid-Resistant Anopheles in Tanzania
Authors: Martin Jackline , Mosha Franklin W , Lukole Eliud , Rowland Mark , Todd Jim , Charlwood Jacques D , Mosha Jacklin F , Protopopoff Natacha 
Published: August 2020

Abstract
Background: The spread of pyrethroid resistance in malaria vectors threatens the effectiveness of standard long-lasting insecticidal nets (LLIN). Synergist nets combine pyrethroid (Py) and piperonyl-butoxide (PBO) to enhance potency against resistance mediated by mono-oxygenase mechanisms. Our project assessed personal protection of WHO first-in-class PBO-Py treated nets (Olyset Plus) versus standard LLIN (Olyset net) against pyrethroid resistant Anopheles gambiae and An. funestus in North West Tanzania after 20 months of household use.Methods: From household survey, 39 standard Olyset net and 39 Olyset Plus houses were selected, physical integrity and hole index (HI) of nets assessed, resting mosquitoes collected from inside nets and from room walls, indoor abundance estimated using CDC light traps and species identified using PCR. Residual bio-efficacy of PBO and standard LLINs was assessed using 30 min cylinder bioassays.Results: Of 2397 Anopheles collected, 8.9% (n=213) were resting inside standard Olyset nets while none were found inside Olyset Plus PBO-Py nets of any HI category. Resting density of blood fed mosquitoes was higher on walls of sleeping rooms with Olyset net compared to Olyset Plus (0.62 vs 0.10, density ratio: 0.03, 95% CI: 0.01-0.13, p<0.001). Mosquitoes were found inside Olyset nets of all WHO HI categories but more were collected inside the more damaged (HI≥ 643) nets than in less damaged (HI 0-64) nets (DR: 6.4, 95% CI: 1.1-36.0, p=0.037). In residual bioassay, mortality of An. gambiae s.l was higher with Olyset Plus than with Olyset net for new nets (76.8% vs 27.5%) and 20 months’ nets (56.8% vs 12.8%); similar trends were observed with An. funestus. Conclusion: The PBO-Py treated net provided improved protection after 20 months of household use, as demonstrated by the higher bioassay mortality and absence of pyrethroid resistant An. gambiae s.s. and An. funestus collected from inside Olyset Plus, irrespective of hole index category, as compared to Olyset nets.
Developmental Delay and Its Predictors Among Under-Five Uncomplicated Severe Acute Malnourished Children: a Cross-Sectional Study in Rural Areas of Pakistan
Authors: Saleem Javeria , Zakar Rubeena , Bukhari Gul Mehar Javaid , Fatima Aneela , Fischer Florian 
Published: August 2020

Abstract
Background: In developing countries, malnutrition in children and developmental delays are two major challenges for public health. To achieve the vision of the Sustainable Development Goals in the broader perspective of child health, an early identification of developmental delays and timely intervention is crucial. The aim of this study is to assess the prevalence of suspected developmental delay and their predictors in under-five uncomplicated severe acute malnourished children in rural areas of Pakistan.Methods: A multicentre cross-sectional study has been conducted among 185 uncomplicated severe acute malnourished children. We screened 6–59 months aged children for their nutritional status and clinical complications. Children fulfilling the inclusion criteria underwent the Denver Development Screening Tool II (DDSTII). The global developmental profile of children was calculated according to established protocols of DDSTII based on four important domains of development: personal and social behaviour, language, gross motor adaptive and fine motor adaptive skills. A pretested structured questionnaire on socio-demographic and nutritional factors was used for assessing predictors of developmental delay, which were analysed in a multivariate logistic regression model.Results: Out of 177 severe acute malnourished children, 69 (38.9%) had normal global development and 108 (61.1%) had delayed global development. Significant associations with global development delay were found for lower aged children (6-24 months vs. 25-59 month; AOR=4.53, 95% CI: 1.56–13.10, p<0.01), not exclusively breastfeed children (AOR=3.07, 95% CI: 1.24–7.56, p=0.01), and a history of contact with tuberculosis smear positive adult (AOR=2.67, 95% CI: 1.30–5.49, p<0.01). Conclusion: With about two thirds of study participants showing delayed or unstable global development, there is a high prevalence of suspected developmental delay among under-five uncomplicated severe acute malnourished children in rural areas Pakistan. Particularly children in their first two years of life with insufficient breastfeeding are at high risk. This emphasizes the need for providing adequate infrastructure and information to parents in remote areas.