bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cobalamin is present in cells of non-tuberculous mycobacteria, but not in Mycobacterium tuberculosis
Authors: Minias Alina , Gąsior Filip , Brzostek Anna , Jagielski Tomasz , Dziadek Jarosław 
Published: June 2021

AbstractCobalamin (vitamin B12) is a structurally complex molecule that acts as a cofactor for enzymes and regulates gene expression through so-called riboswitches. The existing literature on the vitamin B12 synthesis capacity in Mycobacterium tuberculosis is ambiguous, while in non-tuberculous mycobacteria (NTM) is rather marginal. Here we present the results of our investigation into the occurrence of vitamin B12 in mycobacteria. For detection purposes, immunoassay methods were applied to cell lysates of NTM and M. tuberculosis clinical and laboratory strains grown under different conditions. We show that whereas vitamin B12 is present in cells of various NTM species, it cannot be evidenced in strains of differently cultured M. tuberculosis, even though the genes responsible for vitamin B12 synthesis are actively expressed based on RNA-Seq data. In summary, we conclude that the production of vitamin B12 does occur in mycobacteria, with the likely exception of M. tuberculosis. Our results provide direct evidence of vitamin B12 synthesis in a clinically important group of bacteria.
Automated home-cage for the evaluation of innate non-reflexive pain behaviors in a mouse model of inflammatory pain
Authors: Hasriadi  , Wasana Peththa Wadu Dasuni , Vajragupta Opa , Rojsitthisak Pornchai , Towiwat Pasarapa 
Published: June 2021

AbstractThe failure to develop analgesic drugs is attributed not only to the complex and diverse pathophysiology of pain in humans but also to the poor experimental design and poor preclinical assessment of pain. Although considerable efforts have been devoted to overcoming the relevant problems, many features of the behavioral pain assessment remain to be characterized. For example, a decreased locomotor activity as a common presentation of pain-like behavior has yet to be described. Studies on mice experimentally induced with carrageenan have provided opportunities to explore pain-related behaviors in automated home-cage monitoring. Through this approach, the locomotor activities of mice with carrageenan-induced inflammatory pain can be precisely and objectively captured. Here, we found that the mobile behaviors of mice reduced, and their immobility increased, indicating that carrageenan induction in mice caused a significant decrease in locomotor activity. These non-reflexive pain behaviors were strongly correlated with the reflexive pain behaviors measured via von Frey and plantar tests. Furthermore, the pharmacological intervention using indomethacin improved the locomotor activity of mice with carrageenan-induced pain. Thus, the analysis of the locomotor activity in automated home-cage monitoring is useful for studying the behavioral analgesia and the pharmacological screening of analgesic drugs. The combined evaluation of reflexive and non-reflexive pain behaviors enhances the translational utility of preclinical pain research in rodents.
Host specific endophytic microbiome diversity and associated functions in three varieties of scented black rice are dependent on growth stage
Authors: Singha K. Malabika , Singh Brahmanand , Pandey Piyush 
Published: June 2021

AbstractThe compositional and functional role of the endophytic bacterial community, associated with black scented rice, in correlation with its antioxidant property has been elucidated. Community dissimilarity analysis confirmed the overlapping of community in shoot and root tissues at the young stage, but not in mature plants. Proteobacteria was the most abundant phylum, in which Agrobacterium, Pleomorphomonas, Bradyrhizobium, Novasphingobium, Caulobacter were the most abundant genera, followed by Cyanobacteria and Planctomycetes in all three different varieties of the black rice. The antioxidant activity of mature plants was found to be higher in comparison to young plants. Intrinsically, the relative abundance of Pleomorphomonas and Streptomyces was positively correlated with total phenol content, while Gemmata, unclassified Pirellulaceae, unclassified Stramenopiles positively correlated with total flavonoid content and negatively correlated with Free radical scavenging activity. Accordingly, functional metagenome analysis of the endophytic microbiome revealed that naringenin -3-dioxygenase and anthocyanidin 3-O-glucosyltransferase for phenylpropanoid (flavonoid and anthocyanin) synthesis were abundant in the endophytic microbiome of mature plants. Specific enrichment of the antioxidant producing genes in the mature plant endophytic microbiome was assigned to some bacteria such as Streptomyces, Pantoea which might have contributed to the common pathway of flavonoid synthesis. The genomes of endophytic isolates Kluyvera sp.PO2S7, Bacillus subtilis AMR1 and Enterobacter sp. SES19 were sequenced and annotated, and were found to have genes for phenylpropanoid synthesis in their genomes.
Mechanistic insights into TNFR1/MADD death domains in Alzheimer’s disease through conformational molecular dynamic analysis
Authors: Hassan Mubashir , Zahid Sara , Alashwal Hany , Kloczkowski Andrzej , Moustafa Ahmed A. 
Published: June 2021

AbstractProteins are tiny players involved in the activation and deactivation of multiple signaling cascades through interactions in cells. The TNFR1 and MADD interact with each other and mediate downstream protein signaling pathways which cause neuronal cell death and Alzheimer’s disease. In the current study, a molecular docking approach was employed to explore the interactive behavior of TNFR1 and MADD proteins and their role in the activation of downstream signaling pathways. The computational sequential and structural conformational results revealed that Asp400, Arg58, Arg59 were common residues of TNFR1 and MADD which are involved in the activation of downstream signaling pathways. Aspartic acid in negatively charged residues is involved in the biosynthesis of protein. However, arginine is a positively charged residue with the potential to interact with oppositely charged amino acids. Furthermore, our molecular dynamic simulation results also ensured the stability of the backbone of TNFR1 and MADD death domains (DDs) in binding interactions. This DDs interaction mediates some conformational changes in TNFR1 which leads to the activation of mediators proteins in the cellular signaling pathways. Taken together, a better understanding of TNFR1 and MADD receptors and their activated signaling cascade may help treat Alzheimer’s disease. The death domains of TNFR1 and MADD could be used as a novel pharmacological target for the treatment of Alzheimer’s disease by inhibiting the MAPK pathway.
Residual limb volume fluctuations in transfemoral amputees
Authors: Paternò Linda , Ibrahimi Michele , Rosini Elisa , Menfi Giuseppe , Monaco Vito , Gruppioni Emanuele , Ricotti Leonardo , Menciassi Arianna 
Published: June 2021

AbstractThis study constitutes the first attempt to systematically quantify residual limb volume fluctuations in transfemoral amputees. The study was carried out on 24 amputees to investigate variations due to prosthesis doffing, physical activity, and testing time. A proper experimental set-up was designed, including a 3D optical scanner to improve precision and acceptability by amputees. The first test session aimed at measuring residual limb volume at 7 time-points, with 10 min intervals, after prosthesis doffing. This allowed for evaluating the time required for volume stabilization after prosthesis removal, for each amputee. In subsequent sessions, 16 residual limb scans in a day for each amputee were captured to evaluate volume fluctuations due to prosthesis removal and physical activity, in two times per day (morning and afternoon). These measurements were repeated in three different days, a week apart from each other, for a total of 48 scans for each amputee. Volume fluctuations over time after prosthesis doffing showed a two-term decay exponential trend (R2 = 0.97), with the highest variation in the initial 10 min and an average stabilization time of 30 min. A statistically significant increase in residual limb volume following both prosthesis removal and physical activity was verified. No differences were observed between measures collected in the morning and in the afternoon.Clinical Trials.gov ID: NCT04709367.
Results of the IROCA international clinical audit in prostate cancer radiotherapy at six comprehensive cancer centres
Authors: Lopes de Castro Carla , Fundowicz Magdalena , Roselló Alvar , Jové Josep , Deantonio Letizia , Aguiar Artur , Pisani Carla , Villà Salvador , Boladeras Anna , Konstanty Ewelina , Kruszyna-Mochalska Marta , Milecki Piotr , Jurado-Bruggeman Diego , Lencart Joana , Modolell Ignasi , Muñoz-Montplet Carles , Aliste Luisa , Torras Maria Gloria , Puigdemont Montserrat , Carvalho Luísa , Krengli Marco , Guedea Ferran , Malicki Julian 
Published: June 2021

AbstractTo assess adherence to standard clinical practice for the diagnosis and treatment of patients undergoing prostate cancer (PCa) radiotherapy in four European countries using clinical audits as part of the international IROCA project. Multi-institutional, retrospective cohort study of 240 randomly-selected patients treated for PCa (n = 40/centre) in the year 2015 at six European hospitals. Clinical indicators applicable to general and PCa-specific radiotherapy processes were evaluated. All data were obtained directly from medical records. The audits were performed in the year 2017. Adherence to clinical protocols and practices was satisfactory, but with substantial inter-centre variability in numerous variables, as follows: staging MRI (range 27.5–87.5% of cases); presentation to multidisciplinary tumour board (2.5–100%); time elapsed between initial visit to the radiation oncology department and treatment initiation (42–102.5 days); number of treatment interruptions ≥ 1 day (7.5–97.5%). The most common deviation from standard clinical practice was inconsistent data registration, mainly failure to report data related to diagnosis, treatment, and/or adverse events. This clinical audit detected substantial inter-centre variability in adherence to standard clinical practice, most notably inconsistent record keeping. These findings confirm the value of performing clinical audits to detect deviations from standard clinical practices and procedures.
Insulin resistance is linked to a specific profile of immune activation in human subjects
Authors: Cezar Renaud , Desigaud Delphine , Pastore Manuela , Kundura Lucy , Dupuy Anne-Marie , Cognot Chantal , Vincent Thierry , Reynes Christelle , Sabatier Robert , Maggia Elisabeth , Corbeau Pierre 
Published: June 2021

AbstractWe tested the hypothesis that a particular immune activation profile might be correlated with insulin resistance in a general population. By measuring 43 markers of immune, endothelial, and coagulation activation, we have previously shown that five different immune activation profiles may be distinguished in 150 volunteers. One of these profiles, Profile 2, characterized by CD4+ T cell senescence, inflammation, monocyte, B cell, and endothelial activation, presented elevated insulinemia, glycemia, triglyceridemia, and γ-glutamyl transferase, a marker of liver injury, in comparison with other profiles. Our data are compatible with a model in which a particular immune activation profile might favor the development of insulin resistance and metabolic syndrome. In this hypothesis, identification of this profile, that is feasible with only 3 markers with an error rate of 5%, might allow to personalize the screening and prevention of metabolic syndrome-driven morbidities as liver steatosis.
Heparanase inhibition preserves the endothelial glycocalyx in lung grafts and improves lung preservation and transplant outcomes
Authors: Noda Kentaro , Philips Brian J. , Snyder Mark E. , Phillippi Julie A. , Sullivan Mara , Stolz Donna B. , Ren Xi , Luketich James D. , Sanchez Pablo G. 
Published: June 2021

AbstractThe endothelial glycocalyx (eGC) is considered a key regulator of several mechanisms that prevent vascular injury and disease. Degradation of this macromolecular layer may be associated with post-transplant graft dysfunction. In this study, we aimed to demonstrate the benefits of eGC protection via heparanase inhibition on graft quality. We established rat models of lung grafts with damaged or preserved eGC using ischemic insult and transplanted the grafts into recipients. Lung grafts were also subjected to normothermic ex vivo lung perfusion for detailed assessment under isolated conditions. Physiologic parameters and eGC-associated cellular events were assessed in grafts before and after reperfusion. Structurally degraded eGC and highly activated heparanase were confirmed in lungs with ischemic insult. After transplant, lungs with damaged eGC exhibited impaired graft function, inflammation, edema, and inflammatory cell migration. Increased eGC shedding was evident in the lungs after reperfusion both in vivo and ex vivo. These reperfusion-related deficiencies were significantly attenuated in lungs with preserved eGC following heparanase inhibition. Our studies demonstrated that eGC plays a key role in maintaining lung graft quality and function. Heparanase inhibition may serve as a potential therapeutic to preserve eGC integrity, leading to improved post-transplant outcomes.
Extracellular vesicle-shuttled miRNAs as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients
Authors: Ueta Eijiro , Tsutsumi Koichiro , Kato Hironari , Matsushita Hiroshi , Shiraha Hidenori , Fujii Masakuni , Matsumoto Kazuyuki , Horiguchi Shigeru , Okada Hiroyuki 
Published: June 2021

AbstractCirculating microRNAs (miRNAs) in serum extracellular vesicles (EVs) are a promising biomarker in cancer. We aimed to elucidate the serum EVs miRNA biomarkers to identify patients with gallbladder cancer (GBC) and to clarify their potential roles. One hundred nineteen serum EVs from GBC and non-GBC individuals were isolated by pure-EVs-yieldable size-exclusion chromatography, and then were analyzed using a comprehensive miRNAs array and RT-qPCR-based validation. The functional roles of the identified miRNAs were also investigated using GBC cell lines. Serum EVs miR-1246 and miR-451a were significantly upregulated and downregulated, respectively in GBC patients (P = 0.005 and P = 0.001), in line with their expression levels in cancer tissue according to an in silico analysis. The combination of CEA and CA19-9 with miR-1246 showed the highest diagnostic power (AUC, 0.816; Sensitivity, 72.0%; Specificity, 90.8%), and miR-1246 was an independent prognostic marker of GBC (Hazard ratio, 3.05; P = 0.017) according to a Cox proportional hazards model. In vitro, miR-1246 promoted cell proliferation and invasion, while miR-451a inhibited cell proliferation and induced apoptosis with the targeting of MIF, PSMB8 and CDKN2D. Taken together, miR-1246 in serum EVs has potential application as a diagnostic and prognostic marker and miR-451a may be a novel therapeutic target in GBC.
Identifying molecular targets for reverse aging using integrated network analysis of transcriptomic and epigenomic changes during aging
Authors: Lee Hwang-Yeol , Jeon Yeonsu , Kim Yeon Kyung , Jang Jae Young , Cho Yun Sung , Bhak Jong , Cho Kwang-Hyun 
Published: June 2021

AbstractAging is associated with widespread physiological changes, including skeletal muscle weakening, neuron system degeneration, hair loss, and skin wrinkling. Previous studies have identified numerous molecular biomarkers involved in these changes, but their regulatory mechanisms and functional repercussions remain elusive. In this study, we conducted next-generation sequencing of DNA methylation and RNA sequencing of blood samples from 51 healthy adults between 20 and 74 years of age and identified aging-related epigenetic and transcriptomic biomarkers. We also identified candidate molecular targets that can reversely regulate the transcriptomic biomarkers of aging by reconstructing a gene regulatory network model and performing signal flow analysis. For validation, we screened public experimental data including gene expression profiles in response to thousands of chemical perturbagens. Despite insufficient data on the binding targets of perturbagens and their modes of action, curcumin, which reversely regulated the biomarkers in the experimental dataset, was found to bind and inhibit JUN, which was identified as a candidate target via signal flow analysis. Collectively, our results demonstrate the utility of a network model for integrative analysis of omics data, which can help elucidate inter-omics regulatory mechanisms and develop therapeutic strategies against aging.
Maternal periconceptional folic acid supplementation reduced risks of non-syndromic oral clefts in offspring
Authors: Xu Wenli , Yi Ling , Deng Changfei , Zhao Ziling , Ran Longrong , Ren Zhihong , Zhao Shunxia , Zhou Tianjin , Zhang Gang , Liu Hanmin , Dai Li 
Published: June 2021

AbstractMaternal periconceptional folic acid supplementation (FAS) has been documented to be associated with decreased risk of nonsyndromic oral clefts (NsOC). However, the results remain inconclusive. In this population-based case–control study of 807 singletons affected by NsOC and 8070 healthy neonates who were born between October 2010 and September 2015 in Chengdu, China, we examined the association of maternal FAS with the risk of nonsyndromic cleft lip with or without cleft palate (NsCL/P), and cleft palate (NsCP). Unconditional logistic regression analysis was used to estimate the crude and adjusted odds ratios (ORs) and 95% confidential intervals (CI). Significant associations were found between maternal periconceptional FAS and decreased risk of NsCL/P (aOR = 0.41, 95% CI 0.33–0.51). This protective effect was also detected for NsCL (aOR = 0.42, 95% CI 0.30–0.58) and NsCLP (aOR = 0.41, 95% CI 0.31–0.54). Both maternal FAS started before and after the last menstrual period (LMP) were inversely associated with NsCL/P (before LMP, aOR = 0.43, 95% CI 0.33–0.56; after LMP, aOR = 0.41, 95% CI 0.33–0.51). The association between NsCP and maternal FAS initiating before LMP was also found (aOR = 0.52, 95% CI 0.30–0.90). The findings suggest that maternal periconceptional FAS can reduce the risk of each subtype of NsCL/P in offspring, while the potential effect on NsCP needs further investigations.
HLA-B27 is associated with reduced disease activity in axial spondyloarthritis
Authors: Rosenbaum James T. , Weisman Michael H. , Hamilton Hedley , Shafer Cassie , Aslanyan Elin , Howard Richard A. , Ogle Kimberly , Reveille John D. , Winthrop Kevin L. , Choi Dongseok 
Published: June 2021

AbstractHLA-B27 is associated with increased susceptibility and disease activity of ankylosing spondylitis, but the effect of HLA-B27 on the activity of the broader category now called axial spondyloarthritis (AxSpA) is apparently the opposite. A modified Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to assess disease activity among 3435 patients with spondyloarthritis (SpA) who participated in a survey designed to assess the effect of their disease and its treatment on the susceptibility and severity of Covid-19. Chi square testing was used to compare BASDAI scores between HLA-B27 positive and negative subjects. 2836 survey respondents were HLA B27 positive. The average BASDAI for the HLA-B27 negative cohort was 4.92 compared to 4.34 for the HLA-B27 positive subjects. Based on linear regression, a subject’s sex could not fully account for the differing BASDAI score in HLA-B27 negative subjects compared to those who are HLA-B27 positive. The difference between B27 positive and negative subjects was skewed by those with a BASDAI score of one or two. HLA-B27 positive subjects were more than twice as likely to have a BASDAI score of 1 compared to HLA B27 negative subjects and about 60% more likely to have a BASDAI score of 2 (p < 0.0001). HLA-B27 positive subjects have less active spondyloarthritis compared to HLA-B27 negative subjects as measured by a BASDAI score. Our data indicate that patients with mild back pain and a diagnosis of AxSpA are disproportionately HLA-B27 positive. The HLA-B27 test facilitates the diagnosis of axial spondyloarthritis such that patients from a community survey with mild back pain may be disproportionately diagnosed as having AxSpA if they are HLA-B27 positive. The test result likely introduces a cognitive bias into medical decision making and could explain our observations.
Effect of freeze–thaw cycle on physical and mechanical properties and damage characteristics of sandstone
Authors: Chen Longxiao , Li Kesheng , Song Guilei , Zhang Deng , Liu Chuanxiao 
Published: June 2021

AbstractRock deterioration under freeze–thaw cycles is a concern for in-service tunnel in cold regions. Previous studies focused on the change of rock mechanical properties under unidirectional stress, but the natural rock mass is under three dimensional stresses. This paper investigates influences of the number of freeze–thaw cycle on sandstone under low confining pressure. Twelve sandstone samples were tested subjected to triaxial compression. Additionally, the damage characteristics of sandstone internal microstructure were obtained by using acoustic emission (AE) and mercury intrusion porosimetry. Results indicated that the mechanical properties of sandstone were significantly reduced by freeze–thaw effect. Sandstone’ peak strength and elastic modulus were 7.28–37.96% and 6.38–40.87% less than for the control, respectively. The proportion of super-large pore and large pore in sandstone increased by 19.53–81.19%. We attributed the reduced sandstone’ mechanical properties to the degenerated sandstone microstructure, which, in turn, was associated with increased sandstone macropores. The macroscopic failure pattern of sandstone changed from splitting failure to shear failure with an increasing of freeze–thaw cycles. Moreover, the activity of AE signal increased at each stage, and the cumulative ringing count also showed upward trend with the increase of freeze–thaw number.