bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering Centimeter-Scale Microbial Biogeographic Patterns and Community Assembly Processes From A 3D Perspective
Authors: Xue Ran , Zhao Kankan , Yu Xiuling , Stirling Erinne , Liu Shan , Ye Shudi , Ma Bin , Xu Jianming 
Published: July 2020

Abstract
Background: Revealing the effects of multi-dimensional spatial distribution on microorganisms is crucial for the further understanding of microbial diversity, turnover and ecological processes. However, microbial community assembly and the factors that shape it are still unknown from a three dimensional (3D) perspective. Here, a 3D model was created by performing an exhaustive sampling strategy to a 4x4x4 soil matrix. We examined the dynamics of microbial diversity, biogeographic patterns and microbial assembly processes when transfroming sampling scheme from 2D to 3D.Results: Our results indicated that dispersion of microbial community and significance of distance decay relationship was higher in the 3D compared with 2D sampling scheme, suggesting increased microbial turnover when transforming the model from 2D to 3D. Only a small fraction of community variation can be explained by environmental, spatial factors and spatial canonical axes, possibly due to unmeasured environmental variables. The assembly of microbial community was dominated by deterministic processes that shifted from homogeneous selection to variable selection as we transformed the model from 2D to 3D. The importance of stochasticity increased when homogeneous and variable selection processes were well balanced. However, heterogeneity of existing environmental and spatial variables failed to explain the dynamics of community assembly.Conclusions: Our study revealed significant dynamics of microbial diversity and assembly processes when assessed from 2D and 3D perspectives. As microorganisms are spatially distributed in soil, this spatial dependent diversity and assembly suggests that microbial ecological questions need to be considered in more dimensions than they usually are. Further, new models that integrate all data sets are still needed to disengle the microbial processes in multiple dimensions.
Identification of TIMP2 and RAX as key regulators in chemosensitive osteosarcoma
Authors: Wang HuaBin , Liu Yuanxiang , Zeng Haitao 
Published: July 2020

Abstract
Background This study is trying to investigate the regulation mechanism of chemosensitive osteosarcoma. mRNA and miRNA profiles were explored between chemosensitive and chemoresistant osteosarcoma patients based on GSE39058 dataset. IPA was used for pathway and function enrichment. Another dataset GSE21257 with clinical characteristics was used for survival analysis, and 68 new enrolled osteosarcoma patients with chemotherapy responses were used for RT-PCR validation. Finally, lentiviruses infected U-2 OS cells were subjected to cell counting and real-time cell analyzer.Results A total of 567 differentially expressed genes and 34 differentially expressed miRNAs were screened out. These genes mainly involved in the biology functions of cell survival and cell proliferation, and enriched in the pathways of VEGF signaling, Paxillin signaling, and Inhibition of matrix matalloproteases. In 53 validation osteosarcoma patients from GSE21257, high-expression of TIMP2 and BAX, two common genes among the enriched biology functions, have favorable prognosis with p-values 0.052 and 0.027 respectively. In the 68 new enrolled patients, both TIMP2 and BAX were RT-PCR validated to be high-expressed in chemosensitive group with p-values 0.04 and 0.003 respectively. In addition, cell count and cell index either in TIMP2 or BAX infected U-2 OS cells were smaller compared with control cells within four consecutive days.Conclusions In summary, the biology functions of cell survival and cell proliferation were identified to be mainly inhibited in chemosensitive osteosarcoma patients. Two up-regulated genes, TIMP2 and BAX, were validated to be important regulators of cell proliferation and cell apoptosis in chemosensitive group. Further experimental evidences are still needed to consolidate this results.
Impact of Nonsteroidal Anti-Inflammatory Drug Administration for 12 Months on Renal Function
Authors: Hayashi Kazuhiro , Miki Kenji , Kajiyama Hiroshi , Ikemoto Tatsunori , Yukioka Masao 
Published: July 2020

Abstract
Background: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of renal complications. Resolution of renal side effects following NSAID administration has been observed following short-term use. Thus, the aim of the present study was to investigate whether switching from long-term NSAID administration to tramadol hydrochloride/acetaminophen (TA) combination tablets results in reversal of renal side effects.Methods: This was a longitudinal retrospective study of 99 patients with chronic musculoskeletal pain. The patients were administrated NSAIDs daily during the first 12 months followed by daily TA combination tablets for 12 months. Estimated glomerular filtration rate (eGFR) and serum levels of aspartate aminotransferase and alanine transaminase were measured at baseline, after NSAIDs administration, and after TA administration.Results: eGFR was significantly reduced following 12-month NSAIDs administration (median, from 84.0 mL/min/1.73 m2 to 72.8 mL/min/1.73 m2), and further reduction was prevented following the subsequent 12-month TA administration. Reduction in eGFR was less in patients who received celecoxib (median, -1.8 mL/min/1.73 m2) during the first 12 months. There was no significant difference in aspartate aminotransferase and alanine transaminase in each period.Conclusions: Thus, patients receiving NSAIDs for 12 months displayed both reversible and irreversible reduction of eGFR upon cessation of NSAIDs and switching to TA. Our data highlights the potential safety benefit of utilizing multimodal analgesic therapies to minimize the chronic administration of NSAIDs.
Neonatal SARS-CoV-2 infections: systematic review, synthesis and meta-analysis of reported cases
Authors: Raschetti Roberto , Vivanti Alexandre , Vauloup Christelle , Loi Barbara , Benachi Alexandra , De Luca Daniele 
Published: July 2020

Abstract
It is unclear if COVID-19 affects neonates. Some cases of neonatal SARS-CoV-2 infections have been reported but not systematically analysed. We aim to clarify the main transmission route, clinical features and outcomes of neonatal SARS-CoV-2 infections and we performed an individual patient data meta-analysis, following PRISMA guidelines, of neonates infected by SARS-CoV-2 (demonstrated by: at least one positive nasopharyngeal swab and/or the presence of specific IgM). We analysed 117 infected neonates. 68% and 32% of infections were due to environmental and vertical transmission, respectively. Approximately 55% of infected neonates developed clinically evident COVID-19. Commonest clinical features were fever (50%), gastrointestinal (43.7%), respiratory (42.2%) and neurological manifestations (20.3%). Lung imaging was abnormal in 59.4%. The lack of mother-neonate separation from birth was associated with the incidence of late SARS-CoV-2 infection (OR 5.1 (95% CI: 1.6-18); p=0.003), while breastfeeding was not (OR 0.49 (95% CI: 0.12-1.94); p=0.35).
Cryo-EM Structures of Respiratory bc1-cbb3 type CIII2CIV Supercomplex and Electronic Communication Between the Complexes
Authors: Steimle Stefan , Eeuwen Trevor Van , Ozturk Yavuz , Kim Hee Jong , Braitbard Merav , Selamoglu Nur , Garcia Benjamin , Schneitman-Duhovny Dina , Murakami Kenji , Daldal Fevzi 
Published: July 2020

Abstract
Respiratory electron transport complexes are organized as individual entities or combined as large super-complexes (SC). The Gram-negative bacteria deploy a mitochondrial-like cytochrome (cyt) bc1 (Complex III, CIII2), and may have specific cbb3-type cyt c oxidases (Complex IV, CIV) instead of the canonical aa3-type CIV. Electron transfer between these complexes is mediated by soluble (c2) and membrane-anchored (cy) cyts. Here, we report the first structure of a bc1-cbb3 type SC (CIII2CIV, 5.2Å resolution) and three conformers of native CIII2 (3.3Å resolution) of functional relevance. The SC contains all catalytic subunits and cofactors as well as two extra transmembrane helices attributed to cyt cy and the assembly factor CcoH. The cyt cy is integral to SC, its cyt domain is mobile and conveys electrons to CIV differently than cyt c2. For the first time, this work establishes the structural characteristics of membrane-confined and membrane-external electron transport pathways of SCs in Gram-negative bacteria.
Expression of Long-Chain Noncoding RNA GAS5 in Osteoarthritis And Its Effect on Apoptosis And Autophagy of Osteoarthritis Chondrocytes
Authors: Ji Qinghui , Qiao Xiaofeng , Liu Yongxiang , Wang Dawei , Yan Jinglong 
Published: July 2020

Abstract
Objective: To investigate the expression of long chain non-coding RNA GAS5 in osteoarthritis(OA) and the effect on autophagy and apoptosis of chondrocytes. Method: OA rat model was constructed and the expressions of GAS5 in articular cartilage tissues at 4 weeks(early OA) and 12 weeks(late OA) after modeling were detected. The chondrocytes of OA rat were isolated, cultured and transfected with si-GAS5 to silence the GAS5. Then the change of apoptosis and autophagy levels of OA chondrocytes were detected. The microRNA binding to GAS5 and the competitive target gene were analyzed and verified. Results: The expression of GAS5 in cartilage tissue of OA rats was higher than that of control, which was higher in late OA than that in early OA. After silencing the GAS5, the autophagy ability of OA chondrocytes was increased and the apoptosis rate was decreased. GAS5 could bind with miR-144 competitively and regulate mTOR positively. The mTOR inhibitor GDC-0349 could reverse the inhibition of GAS5 on cell autophagy but could not reverse the promotion on apoptosis. Conclusion: GAS5 expression was high and increased with the progression of OA. GAS5 could inhibit the autophagy and promote the apoptosis of OA chondrocytes, and the effect on autophagy may be related to the regulation on mTOR.
A Qualitative Evaluation of the Usability of a Hospital-Wide Electronic Medication Management System in the Oncology setting using the Unified Theory and Use of Technology Framework
Authors: dabliz racha , Poon Simon K. , Ritchie Angus , Burke Rosemary , Penm Jonathan 
Published: July 2020

Abstract
Background: In light of the complexity of the medication process and the difficultly of examining it in isolation from other interrelated processes and contextual factors, this qualitative research aims to fill the gap in the literature by cohesively determining the usability of a hospital-wide Electronic Medication Management System in a specialised oncology unit by bringing in the perspective of three key user groups. Furthermore, it demonstrates how the UTAUT can be used to guide qualitative evaluation studies in evaluating the usability of an integrated EMMS. Methods: This was a qualitative study conducted in a 12-bed hospital outpatient Oncology unit in a major teaching hospital. In-depth semi-structured interviews were performed with the doctors, nurses and pharmacists to identify user’s requirements. Data were analysed by using the UTAUT framework for analysis. Results: The UTAUT framework facilitated the evaluation of interrelated aspects and provided a structured summary of user experience usability factors. The direct cross comparison between user groups illustrated that doctors and pharmacists were generally satisfied with the facilitating conditions (hardware and training), but had varying perceptions of performance (automation, standardised protocols and communication and documented) and effort (mental and temporal demand). On the other hand, nurses were generally satisfied across all constructs. It also illustrated the key role that ‘previous system experience’ plays in developing user’s system frustrations and acted as a moderator for these constructs. Conclusion: Considering the complexity of the medication process and the difficultly of examining it in isolation from other interrelated processes and contextual factors, this study cohesively demonstrated the need to explore perceptions of usability across user groups. It illustrated that doctors and pharmacists were satisfied with the EMMS if it provided desirable utility to their practice, and nurses when the EMMS was easy to use in the nursing processes using the UTAUT framework. As multidisciplinary teams are involved in cancer care, all potential users and their requirements should be considered.
Early Surgical Intervention for Active Thoracic Spinal Tuberculosis with Paraplegia
Authors: Li Weiwei , Liu Zheng , Xiao Xiao , Xu Zhenchao , Sun Zhicheng , Zhang Zhen , Wang Xiyang 
Published: July 2020

Abstract
Background: To explore the therapeutic effect of early surgical interventions for patients of active thoracic spinal tuberculosis (TB) with paraplegia. Methods: Data of 118 patients with active thoracic spinal TB and paraplegia who had undergone surgeries at an early stage (within three weeks of paraplegia) from January 2008 to December 2014 were retrospectively analyzed. The operation duration, blood loss, perioperative complication rate, VAS score, ASIA grade of neurological status, Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), kyphotic Cobb’s angle, and duration of bone graft fusion were analyzed to evaluate the therapeutic effects. Results: Mean operation time was 194.2 minutes, mean blood loss was 871.2 ml. The perioperative complication rate was 5.1%. Mean preoperative VAS score was 5.3, significantly decreased to 3.2 after operation, and continued decreasing to 1.1 at the follow up (P＜0.05). All cases achieved at least one grade elevation after operation, specifically, 2 cases of ASIA grade A rose to grade B, 10 cases of ASIA grade A rose to grade C, 2 cases of ASIA grade A rose to grade E; 9 cases of ASIA grade B rose to grade D, 38 cases of ASIA grade B rose to grade E; all 57 cases of ASIA grade C rose to ASIA grade E. The rate of full neurological recovery for complete paraplegia patients was 14.3%, significantly lower than the rate (91.3%) for incomplete paraplegia patients. Mean preoperative ESR and CRP were 73.1 mm /h and 82.4 mg/L, insignificantly increased after operation (P＞0.05), then gradually decreased to 11.5 ± 1.8 mm /h and 2.6 ± 0.82 mg/L at the final follow up, respectively (P＜0.05). The mean preoperative kyphotic Cobb’s angle was 21.9º, significantly decreased to 6.5º after operation (P＜0.05) and the kyphotic correction had not lost during the follow up (P＞0.05). Mean duration of bone graft fusion was 8.6±1.3 months Conclusion: Early surgical intervention may be beneficial for patients with active thoracic spinal TB with and paraplegia, with surgical intervention being more beneficial for incomplete paraplegic recovery compared with that of complete paraplegia.
Partnering with Patients to Get Better Outcomes with Chimeric Antigen Receptor T-cell Therapy: Towards Meaningful Patient Engagement in Early Phase Trials
Authors: Foster Madison , Fergusson Dean , Hawrysh Terry , Presseau Justin , Kekre Natasha , Schwartz Stuart , Castillo Gisell , Asad Sarah , Fox Grace , Atkins Harold , Thavorn Kednapa , Montroy Joshua , Holt Robert , Monfaredi Zarah , Lalu Manoj 
Published: July 2020

Abstract
Aim: Though patient engagement in clinical research is growing, recent reports suggest few clinical trials report on such activities. To address this gap, we describe our approach to patient engagement in the development of a clinical trial protocol for a new immunotherapy for blood cancer (chimeric antigen receptor T-cell therapy, CAR-T cell therapy). Methods: Our team developed a clinical trial protocol by working with patient partners from inception. Two patient partners with lived blood cancer experience were identified through referrals from our team’s professional network and patient organization contacts. Our patient partners were onboarded to the team and engaged in several studies conducted to develop the clinical trial protocol, including a systematic review of the existing literature on the therapy, patient interviews and a survey to obtain perspectives on barriers and enablers to participating in the trial, an early economic analysis, and a retrospective cohort study. Results: Engaging patient partners enhanced our research in ways that would not have otherwise occurred. By selecting patient important outcomes for data collection, our partners helped flag that quality of life and health utility measures have not been reported in previous CAR-T cell therapy trials for blood cancer. Our partners also co-developed a non-technical summary of the systematic review that summarized results in an accessible manner. Our patient partners reviewed interview and survey questions, to improve the language and appropriateness; provided recruitment suggestions; and provided a patient perspective on the results, thereby confirming the importance of findings. Input was also obtained on costs for the early economic analysis. Our patient partners identified costs that may be a burden to both patients and caregivers during a trial and helped to confirm that the overall structure of the economic model reflected the patient care pathway. Our patient partners also shared their diagnosis and treatment stories, which helped to provide the research team with insight into this experience.Conclusions: Contributions by our patient partners were invaluable to each component study, as well as the overall development of the trial protocol. We plan to use this approach in the future, to meaningfully engage patients in the development of other clinical trials; we also hope that by reporting our methods this will help other research teams to do the same. Trial Registration: Affiliated with the development of NCT03765177
MiR-221-5p Is Involved in the Regulation of Inflammatory Responses in Acute Gouty Arthritis by Targeting IL-1β
Authors: Li Guangwen , Zhang Huihui , Ma Hong , Qu Shiping , Xing Qian , Wang Ge 
Published: July 2020

Abstract
Background: Gout is caused by the accumulation of deposited sodium urate (MSU) crystals in the joints. Recent studies have shown that interleukin-1β (IL-1β) is a key inflammatory mediator of acute gouty arthritis(AGA), and its level is regulated by microRNAs (miRNAs). However, the molecular mechanism of its regulation is still unclear.Methods: 100 patients with AGA and 94 healthy individuals were recruited. The expression of serum miR-221-5p was determined by qRT-PCR. The receiver operating curve (ROC) was applied for diagnostic value analysis. A luciferase reporter assay was performed to confirm the interaction of miRNA and the 3'-untranslated region (UTR) of IL-1β. ELISA was used to detect serum and proinflammatory factors.Results: miR-221-5p was lower expressed in the serum of AGA patients. The AUC was 0.884, the sensitivity was 82.0%, and the specificity was 80.9%. Serum miR-221-5p was negatively correlated with the expression levels of VAS and IL-1β. Cell experiments showed that overexpression of miR-221-5p significantly inhibited the expression of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and IL-1β, while down-regulation of miR-221-5p was the opposite. Luciferase analysis showed that IL-1β was the target gene of miR-221-5p.Conclusions: This study confirmed that miR-221-5p regulates the production of inflammatory cytokines during the pathogenesis of AGA. These results suggest that miR-221-5p can be used as potential therapeutic targets for the treatment of AGA.
Plasma Fibrinogen, D-dimer, and Fibrin Degradation Product as Biomarkers of Rheumatoid Arthritis
Authors: Xue Li , Li Ming , Tao Li , Li Xueyi , Wang Wei , Wang Yan , Wang Biao , Zhang Yanping , Gao Ning , Dong Yanying , Zhou Ting , Liu Zeshi , Liu Hailong , He Juntao , Li Ke , Geng Yan 
Published: July 2020

Abstract
Objective: This study aimed to assess the role of coagulation-related indicators such as plasma ﬁbrinogen (FIB), D-dimer, and fibrin degradation product (FDP) in rheumatoid arthritis (RA) and their association with disease activity.Methods: Data from 105 RA patients and 102 age- and gender- matched healthy controls were collected in the retrospective study. Disease activity score in 28 joints based on C-reactive protein (DAS28-CRP) was used to divide the RA patients into inactive group (DAS28-CRP ≤ 2.7) and active group (DAS28-CRP > 2.7). The association between plasma FIB, D-dimer, and FDP and DAS28-CRP was evaluated by spearman correlation. Receiver operating characteristic (ROC) curve was applied to determine the area under curve (AUC) value. The prognostic value of plasma FIB, D-dimer, and FDP in the RA disease activity was tested by logistical regression analysis.Results: RA patients showed higher FAR levels of plasma FIB, D-dimer, and FDP than the controls (P < 0.01). Plasma FIB, D-dimer, and FDP were also increased in active group of RA patients than those in inactive group (P < 0.001). Spearman analysis showed that plasma FIB, D-dimer, and FDP were positively related with DAS28-CRP (P < 0.001) in RA patients. ROC curve analyses revealed that the AUC of D-dimer was higher than ESR and RF, and that of FDP was higher than RF in RA patients. In addition, the optimal cut-oﬀ value of plasma FIB, D-dimer, and FDP for RA diagnosis was 286 mg/dL, 470 μg/L, and 1.45 mg/L, respectively. Logistical regression analyses showed that D-dimer (odds ratio = 2.862, 95% conﬁdence interval: 1.851-4.426, P < 0.001) was a predictor for RA disease activity.Conclusions: FIB, D-dimer, and FDP were increased in RA patients and positively correlated with the disease activity of RA. D-dimer may act as a novel inﬂammatory parameter for predicting disease activity in RA patients.