bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug repurposing for ligand-induced rearrangement of Sirt2 active site-based inhibitors via molecular modeling and quantum mechanics calculations
Authors: Bharadwaj Shiv , Dubey Amit , Kamboj Nitin Kumar , Sahoo Amaresh Kumar , Kang Sang Gu , Yadava Umesh 
Published: May 2021

AbstractSirtuin 2 (Sirt2) nicotinamide adenine dinucleotide-dependent deacetylase enzyme has been reported to alter diverse biological functions in the cells and onset of diseases, including cancer, aging, and neurodegenerative diseases, which implicate the regulation of Sirt2 function as a potential drug target. Available Sirt2 inhibitors or modulators exhibit insufficient specificity and potency, and even partially contradictory Sirt2 effects were described for the available inhibitors. Herein, we applied computational screening and evaluation of FDA-approved drugs for highly selective modulation of Sirt2 activity via a unique inhibitory mechanism as reported earlier for SirReal2 inhibitor. Application of stringent molecular docking results in the identification of 48 FDA-approved drugs as selective putative inhibitors of Sirt2, but only top 10 drugs with docking scores > − 11 kcal/mol were considered in reference to SirReal2 inhibitor for computational analysis. The molecular dynamics simulations and post-simulation analysis of Sirt2-drug complexes revealed substantial stability for Fluphenazine and Nintedanib with Sirt2. Additionally, developed 3D-QSAR-models also support the inhibitory potential of drugs, which exclusively revealed highest activities for Nintedanib (pIC50 ≥ 5.90 µM). Conclusively, screened FDA-approved drugs were advocated as promising agents for Sirt2 inhibition and required in vitro investigation for Sirt2 targeted drug development.
Validation of reference genes for use in untreated bovine fibroblasts
Authors: Toorani T. , Mackie P. M. , Mastromonaco G. F. 
Published: May 2021

AbstractProper normalization of RT-qPCR data is pivotal to the interpretation of results and accuracy of scientific conclusions. Though different approaches may be taken, normalization against multiple reference genes is now standard practice. Genes traditionally used and deemed constitutively expressed have demonstrated variability in expression under different experimental conditions, necessitating the proper validation of reference genes prior to utilization. Considering the wide use of fibroblasts in research and scientific applications, it is imperative that suitable reference genes for fibroblasts of different animal origins and conditions be elucidated. Previous studies on bovine fibroblasts have tested limited genes and/or samples. Herein, we present an extensive study investigating the expression stability of 16 candidate reference genes across 7 untreated bovine fibroblast cell lines subjected to controlled conditions. Data were analysed using various statistical tools and algorithms, including geNorm, NormFinder, BestKeeper, and RefFinder. A combined use ofGUSBandRPL13Awas determined to be the best approach for data normalization in untreated bovine fibroblasts.
Refinery wastewater treatment via a multistage enhanced biochemical process
Authors: Wang Chunhua , Chen Zijian , Li Yuanhua , Feng Kejun , Peng Zhongli , Zhu Yongjuan , Yang Xiaofang 
Published: May 2021

AbstractPetroleum refinery wastewater (PRWW) that contains recalcitrant components as the major portion of constituents is difficult to treat by conventional biological processes. An effective and economical biological treatment process was established to treat industrial PRWW with an influent COD of over 2500 mg L−1 in this research. This process is mainly composed of internal circulation biological aerated filter (ICBAF), hydrolysis acidfication (HA), two anaerobic–aerobic (A/O) units, a membrane biological reactor (MBR), and ozone-activated carbon (O3-AC) units. The results showed that, overall, this system removed over 94% of the COD, BOD5, ammonia nitrogen (NH4+-N) and phosphorus in the influent, with the ICBAF unit accounting for 54.6% of COD removal and 83.6% of BOD5 removal, and the two A/O units accounting for 33.3% of COD removal and 9.4% of BOD5 removal. The degradation processes of eight organic pollutants and their removal via treatment were also analyzed. Furthermore, 26 bacteria were identified in this system, with Proteobacteria and Acidobacteria being the most dominant. Ultimately, the treatment process exhibited good performance in degrading complex organic pollutants in the PRWW.
Off-training physical activity and training responses as determinants of sleep quality in young soccer players
Authors: Mateus Nuno , Exel Juliana , Gonçalves Bruno , Weldon Anthony , Sampaio Jaime 
Published: May 2021

AbstractThis study aimed to quantify and assess the relationship of young soccer players' off-training physical activity (PA) and training responses on sleep quality. Eleven adolescent soccer players (13 ± 0.5 years old) were monitored during weekdays for four consecutive weeks, throughout soccer practice days. Off-training PA and sleep quality were assessed using 100 Hz tri-axial accelerometers and training responses analyzed using 20 Hz global positioning measurement units. A cluster analysis classified all cases into three different dimensions, (1) off-training PA, (2) training responses and (3) sleep quality. For each dimension, the most important variables for classifying the cases into clusters were sedentary PA and moderate-to-vigorous PA; total distance covered and impacts; and sleep onset latency and sleep fragmentation index, respectively. Afterwards, a correspondence analysis was used to identify whether off-training PA and training responses affected sleep quality. Results exposed that high to medium off-training PA combined with medium to high training responses may have decreased sleep quality. Conversely, no correspondence was observed between off-training PA and training responses, with higher sleep quality. This study emphasizes the importance of sports organizations adopting a holistic approach to youth soccer players’ development, that appropriately considers the inter-relationship between lifestyle, performance and health-related information.
Ratio of venous-to-arterial PCO2 to arteriovenous oxygen content difference during regional ischemic or hypoxic hypoxia
Authors: Mallat Jihad , Vallet Benoit 
Published: May 2021

AbstractThe purpose of the study was to evaluate the behavior of the venous-to-arterial CO2 tension difference (ΔPCO2) over the arterial-to-venous oxygen content difference (ΔO2) ratio (ΔPCO2/ΔO2) and the difference between venous-to-arterial CO2 content calculated with the Douglas’ equation (ΔCCO2D) over ΔO2 ratio (ΔCCO2D/ΔO2) and their abilities to reflect the occurrence of anaerobic metabolism in two experimental models of tissue hypoxia: ischemic hypoxia (IH) and hypoxic hypoxia (HH). We also aimed to assess the influence of metabolic acidosis and Haldane effects on the PCO2/CO2 content relationship. In a vascularly isolated, innervated dog hindlimb perfused with a pump-membrane oxygenator system, the oxygen delivery (DO2) was lowered in a stepwise manner to decrease it beyond critical DO2 (DO2crit) by lowering either arterial PO2 (HH-model) or flow (IH-model). Twelve anesthetized and mechanically ventilated dogs were studied, 6 in each model. Limb DO2, oxygen consumption ($${\dot{\text{V}}\text{O}}_{2}$$

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), ΔPCO2/ΔO2, and ΔCCO2D/ΔO2 were obtained every 15 min. Beyond DO2crit, $${\dot{\text{V}}\text{O}}_{2}$$

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decreased, indicating dysoxia. ΔPCO2/ΔO2, and ΔCCO2D/ΔO2 increased significantly only after reaching DO2crit in both models. At DO2crit, ΔPCO2/ΔO2 was significantly higher in the HH-model than in the IH-model (1.82 ± 0.09 vs. 1.39 ± 0.06, p = 0.002). At DO2crit, ΔCCO2D/ΔO2 was not significantly different between the two groups (0.87 ± 0.05 for IH vs. 1.01 ± 0.06 for HH, p = 0.09). Below DO2crit, we observed a discrepancy between the behavior of the two indices. In both models, ΔPCO2/ΔO2 continued to increase significantly (higher in the HH-model), whereas ΔCCO2D/ΔO2 tended to decrease to become not significantly different from its baseline in the IH-model. Metabolic acidosis significantly influenced the PCO2/CO2 content relationship, but not the Haldane effect. ΔPCO2/ΔO2 was able to depict the occurrence of anaerobic metabolism in both tissue hypoxia models. However, at very low DO2 values, ΔPCO2/ΔO2 did not only reflect the ongoing anaerobic metabolism; it was confounded by the effects of metabolic acidosis on the CO2–hemoglobin dissociation curve, and then it should be interpreted with caution.
Detection of Plasmodium falciparum in laboratory-reared and naturally infected wild mosquitoes using near-infrared spectroscopy
Authors: Da Dari F. , McCabe Ruth , Somé Bernard M. , Esperança Pedro M. , Sala Katarzyna A. , Blight Josua , Blagborough Andrew M. , Dowell Floyd , Yerbanga Serge R. , Lefèvre Thierry , Mouline Karine , Dabiré Roch K. , Churcher Thomas S. 
Published: May 2021

AbstractThere is an urgent need for high throughput, affordable methods of detecting pathogens inside insect vectors to facilitate surveillance. Near-infrared spectroscopy (NIRS) has shown promise to detect arbovirus and malaria in the laboratory but has not been evaluated in field conditions. Here we investigate the ability of NIRS to identify Plasmodium falciparum in Anopheles coluzzii mosquitoes. NIRS models trained on laboratory-reared mosquitoes infected with wild malaria parasites can detect the parasite in comparable mosquitoes with moderate accuracy though fails to detect oocysts or sporozoites in naturally infected field caught mosquitoes. Models trained on field mosquitoes were unable to predict the infection status of other field mosquitoes. Restricting analyses to mosquitoes of uninfectious and highly-infectious status did improve predictions suggesting sensitivity and specificity may be better in mosquitoes with higher numbers of parasites. Detection of infection appears restricted to homogenous groups of mosquitoes diminishing NIRS utility for detecting malaria within mosquitoes.
LSD1-mediated demethylation of OCT4 safeguards pluripotent stem cells by maintaining the transcription of PORE-motif-containing genes
Authors: Dan Songsong , Song Yuelin , Duan Xiaotao , Pan Xiao , Chen Cheng , She Shiqi , Su Tong , Li Jingchao , Chen Xinyu , Zhou Yanwen , Chen Wenjie , Zhang Xiaobing , Pan Xiaoyun , Wang Ying-Jie , Kang Bo 
Published: May 2021

AbstractReversible lysine methylation is essential for regulating histones and emerges to critically regulate non-histone proteins as well. Here we show that the master transcription factor OCT4 in pluripotent stem cells (PSCs) was methylated at multiple lysine residues. LSD1 that is highly expressed in PSCs can directly interact with and demethylate OCT4 at lysine 222 (K222) in the flexible linker region. Reduced LSD1 activity led to the methylation of OCT4-K222 that diminished the differentiation potential of PSCs while facilitating proteasome-independent degradation of OCT4 proteins. Furthermore, site-specifically replacing K222 with phenylalanine to mimic the constitutively methylated lysine promoted the ‘locked-in’ mode engagement of the OCT4 PORE-homodimers that tightly bind to and block the transcription of multiple PORE-motif-containing target genes regulating cell fate determination and cell junction organization, and thereby reducing the pluripotency of PSCs. Thus, LSD1-mediated demethylation of OCT4 plays a crucial role in restricting the ‘locked-in’ mode binding of OCT4 PORE-homodimers to the PORE-motif-containing genes and thereby maintaining their transcription to safeguard the pluripotency of PSCs.
Divergent nucleic acid allocation in juvenile insects of different metamorphosis modes
Authors: Villar-Argaiz Manuel , López-Rodríguez Manuel J. , Tierno de Figueroa J. Manuel 
Published: May 2021

AbstractNucleic acids help clarify variation in species richness of insects having different metamorphosis modes, a biological conundrum. Here we analyse nucleic acid contents of 639 specimens of aquatic insects collected from four high mountain streams of Sierra Nevada in southern Spain to test whether the allocation to RNA or DNA content differs during ontogeny between juvenile insects undergoing direct (hemimetabolous) or indirect (holometabolous) metamorphosis. The results show that RNA content as a function of body mass was negatively correlated to insect body length in four out of six and three out of six of the holometabolan and hemimetabolan taxa, respectively. Although no significant differences in RNA content were found between holometabolans and hemimetabolans, the significant interaction between body length and metamorphosis mode for RNA and RNA:DNA indicates a strong ontogenetic component to RNA allocation. In addition, our finding of lower DNA content in holometabolans relative to hemimetabolans agree with the analysis of empirical genome data in aquatic and terrestrial insects, and extend to this class of arthropods the “growth rate-genome size-nutrient limitation” hypothesis that differences in allocation between RNA and DNA may reflect fundamental evolutionary trade-off of life-history strategies associated with high growth rates (and RNA content) in holometabolans at the expense of diminished genome sizes.
Predicting sex from retinal fundus photographs using automated deep learning
Authors: Korot Edward , Pontikos Nikolas , Liu Xiaoxuan , Wagner Siegfried K. , Faes Livia , Huemer Josef , Balaskas Konstantinos , Denniston Alastair K. , Khawaja Anthony , Keane Pearse A. 
Published: May 2021

AbstractDeep learning may transform health care, but model development has largely been dependent on availability of advanced technical expertise. Herein we present the development of a deep learning model by clinicians without coding, which predicts reported sex from retinal fundus photographs. A model was trained on 84,743 retinal fundus photos from the UK Biobank dataset. External validation was performed on 252 fundus photos from a tertiary ophthalmic referral center. For internal validation, the area under the receiver operating characteristic curve (AUROC) of the code free deep learning (CFDL) model was 0.93. Sensitivity, specificity, positive predictive value (PPV) and accuracy (ACC) were 88.8%, 83.6%, 87.3% and 86.5%, and for external validation were 83.9%, 72.2%, 78.2% and 78.6% respectively. Clinicians are currently unaware of distinct retinal feature variations between males and females, highlighting the importance of model explainability for this task. The model performed significantly worse when foveal pathology was present in the external validation dataset, ACC: 69.4%, compared to 85.4% in healthy eyes, suggesting the fovea is a salient region for model performance OR (95% CI): 0.36 (0.19, 0.70) p = 0.0022. Automated machine learning (AutoML) may enable clinician-driven automated discovery of novel insights and disease biomarkers.
Novel computational analysis of large transcriptome datasets identifies sets of genes distinguishing chronic obstructive pulmonary disease from healthy lung samples
Authors: Roessler Fabienne K. , Benedikter Birke J. , Schmeck Bernd , Bar Nadav 
Published: May 2021

AbstractChronic obstructive pulmonary disease (COPD) kills over three million people worldwide every year. Despite its high global impact, the knowledge about the underlying molecular mechanisms is still limited. In this study, we aimed to extend the available knowledge by identifying a small set of COPD-associated genes. We analysed different publicly available gene expression datasets containing whole lung tissue (WLT) and airway epithelium (AE) samples from over 400 human subjects for differentially expressed genes (DEGs). We reduced the resulting sets of 436 and 663 DEGs using a novel computational approach that utilises a random depth-first search to identify genes which improve the distinction between COPD patients and controls along the first principle component of the data. Our method identified small sets of 10 and 15 genes in the WLT and AE, respectively. These sets of genes significantly (p < 10–20) distinguish COPD patients from controls with high fidelity. The final sets revealed novel genes like cysteine rich protein 1 (CRIP1) or secretoglobin family 3A member 2 (SCGB3A2) that may underlie fundamental molecular mechanisms of COPD in these tissues.
Comparison of different techniques for the management of venous steno-occlusive lesions during placement of peripherally inserted central catheter
Authors: Yang Woo Jin , Kang Danbee , Shin Ji Hoon , Jang Eun Ho , Noh Seung Yeon , Park Suyoung , Chu Hee Ho , Kim Jong Woo 
Published: May 2021

AbstractThe purpose of this study is to investigate strategies for peripherally inserted central catheter (PICC) placement in patients with venous steno-occlusive lesion (VSOL). We performed a retrospective cohort study in adults with central or peripheral VSOL who underwent PICC placement procedures from January 2015 to December 2018. Four different strategies [selecting alternative pathway/over the wire (SAP/OTW), percutaneous transluminal angioplasty (PTA), re-puncture in ipsilateral arm (RIA), and catheter placement in the contralateral arm (CICA)] were analyzed and we compared the clinical outcomes by strategy and compared the strategy between central and peripheral VSOLs. During 4 years, 258 PICC procedures performed in patients with VSOLs, 100 PICC were included in the analysis. The overall technical success rate of initial attempt with SAP/OTW was 32.2%. As a second-line technique, PTA was most frequently used in both central (100%) and peripheral (68.2%) VSOL groups. The clinical success rates within 2 months of SAP/OTW, PTA, RIA, CICA were 55.2%, 43.2%, 14.3%, and 33.3%, respectively (P = 0.24). In conclusion, when the SAP/OTW failed, the PTA can be preferred as a second-line technique for both central and peripheral VSOLs. When guidewire passage fails, the operator could adopt the RIA or CICA technique as an alternative method.
Detection and quantification of bovine papillomavirus DNA by digital droplet PCR in sheep blood
Authors: Roperto Sante , Cutarelli Anna , Corrado Federica , De Falco Francesca , Buonavoglia Canio 
Published: May 2021

AbstractHighly pathogenic bovine papillomaviruses (BPVs) were detected and quantified for the first time using digital droplet polymerase chain reaction (ddPCR) by liquid biopsy in 103 clinically healthy sheep. Overall, ddPCR detected BPVs in 68 blood samples (66%). BPV infection by a single genotype was revealed in 61.8% of the blood samples, and BPV coinfection by double, triple or quadruple genotypes was observed in 38.2% of liquid biopsies. The BPV-2 genotype was most frequently seen in sheep, whereas BPV-1 was the least common. Furthermore, ddPCR was very useful for detection and quantification; the BPV-14 genotype was observed for the first time in ovine species, displaying the highest prevalence in some geographical areas (Apulia). In 42 of the positive samples (61.8%), a single BPV infection was observed, 26 of which were caused by BPV-2 (61.9%) and 7 by BPV-13 (16.7%). BPV-14 was responsible for 7 single infections (16.7%) and BPV-1 for 2 single infections (4.7%). Multiple BPV coinfections were observed in the remaining 26 positive samples (38.2%), with dual BPV-2/BPV-13 infection being the most prevalent (84.6%). BPV infection by triple and quadruple genotypes was also observed in 11.5% and 3.8% of cases, respectively. The present study showed that ddPCR, a biotechnological refinement of conventional PCR, is by far the most sensitive and accurate assay for BPV detection compared to conventional qPCR. Therefore, ddPCR displayed an essential diagnostic and epidemiological value very useful for the identification of otherwise undetectable BPV genotypes as well as their geographical distributions and suggesting that animal husbandry practices contribute to cross-species transmission of BPVs.
Quantitative trait locus mapping identifies the Gpnmb gene as a modifier of mouse macrophage lysosome function
Authors: Robinet Peggy , Ritchey Brian , Lorkowski Shuhui Wang , Alzayed Alexander M. , DeGeorgia Sophia , Schodowski Eve , Traughber C. Alicia , Smith Jonathan D. 
Published: May 2021

AbstractWe have previously shown that the DBA/2J versus AKR/J mouse strain is associated with decreased autophagy-mediated lysosomal hydrolysis of cholesterol esters. Our objective was to determine differences in lysosome function in AKR/J and DBA/2J macrophages, and identify the responsible genes. Using a novel dual-labeled indicator of lysosome function, DBA/2J versus AKR/J bone marrow derived macrophages had significantly decreased lysosome function. We performed quantitative trait loci mapping of lysosome function in bone marrow macrophages from an AKR/J × DBA/2J strain intercross. Four distinct lysosome function loci were identified, which we named macrophage lysosome function modifier (Mlfm) Mlfm1 through Mlfm4. The strongest locus Mlfm1 harbors the Gpnmb gene, which has been shown to recruit autophagy protein light chain 3 to autophagosomes for lysosome fusion. The parental DBA/2J strain has a nonsense variant in Gpnmb. siRNA knockdown of Gpnmb in AKR/J macrophages decreased lysosome function, and Gpnmb deletion through CRISP/Cas9 editing in RAW 264.7 mouse macrophages also demonstrated a similar result. Furthermore, a DBA/2 substrain, called DBA/2J-Gpnmb+/SjJ, contains the wildtype Gpnmb gene, and macrophages from this Gpnmb-preserved DBA/2 substrain exhibited recovered lysosome function. In conclusion, we identified Gpnmb as a causal modifier gene of lysosome function in this strain pair.
Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients
Authors: Bando Silvia Yumi , Bertonha Fernanda Bernardi , Pimentel-Silva Luciana Ramalho , de Oliveira João Gabriel Mansano , Carneiro Marco Antonio Duarte , Oku Mariana Hiromi Manoel , Wen Hung-Tzu , Castro Luiz Henrique Martins , Moreira-Filho Carlos Alberto 
Published: May 2021

AbstractIn about a third of the patients with epilepsy the seizures are not drug-controlled. The current limitation of the antiepileptic drug therapy derives from an insufficient understanding of epilepsy pathophysiology. In order to overcome this situation, it is necessary to consider epilepsy as a disturbed network of interactions, instead of just looking for changes in single molecular components. Here, we studied CA3 transcriptional signatures and dentate gyrus histopathologic alterations in hippocampal explants surgically obtained from 57 RMTLE patients submitted to corticoamygdalohippocampectomy. By adopting a systems biology approach, integrating clinical, histopathological, and transcriptomic data (weighted gene co-expression network analysis), we were able to identify transcriptional modules highly correlated with age of disease onset, cognitive dysfunctions, and granule cell alterations. The enrichment analysis of transcriptional modules and the functional characterization of the highly connected genes in each trait-correlated module allowed us to unveil the modules’ main biological functions, paving the way for further investigations on their roles in RMTLE pathophysiology. Moreover, we found 15 genes with high gene significance values which have the potential to become novel biomarkers and/or therapeutic targets in RMTLE.