bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review- The periodontal pathogen Treponema denticola: an atherosclerosis risk factor
Authors: Santos Pâmela Beatriz do Rosário Estevam dos , Lima Patrícia Michelle Nagai de , Palma Ana Luiza do Rosário , Hasna Amjad Abu , Rossoni Rodnei Dennis , Junqueira Juliana Campos , Oliveira Luciane Dias de 
Published: January 2021

Objective: Treponema denticola “T. denticola” is a pathogen associated with periodontal diseases that exhibits capacity for adherence, invasion, and colonization of host tissues, which allows alternating its location and damage in different sites of human body. This review aimed to discuss different studies that detected T. denticola in atherosclerotic plaques, demonstrating the importance of periodontal disease on the systemic health and the necessity of exploring the outcome of this colonization apart from the oral cavity. Methodology: Fifty-five studies were identified and gathered in this review according to the following topics: Periodontal disease, atherosclerosis and T. denticola. In vitro and in vivo studies published between 2002 and 2020 were searched on PubMed, raising relevant insights about the role of T. denticola and its association with the systemic disease, atherosclerosis, focusing on the bacterial tissue invasion and development of atherosclerosis. Results: After bibliographic review, it was possible to identify studies demonstrating the presence of T. denticola and other oral pathogens in cardiac or vascular tissues and in blood serum, as well, there is research in which other evidence of a relationship with atherosclerosis is shown. Conclusion: The invasion of periodontal pathogens and its toxins associated to the host’s immune and inflammatory response may contribute to the development of atherosclerosis.
Curcumin-Induced Global Profiling of Transcriptomes in Small Cell Lung Cancer Cells
Authors: Mo Fei , Xiao Yinan , Zeng Hao , Fan Dian , Song Jinen , Liu Xiaobei , Luo Meng , Ma Xuelei 
Published: January 2021

BackgroundCurcumin, one of the promising candidates for supplementary therapy in cancer treatment, has been demonstrated by numerous preclinical and clinical evidence to be beneficial in treating various cancers. Apart from the critical role in a deluge of pathological processes, some mRNAs, in particular, microRNAs (miRNAs), are also involved in the anti-tumor activity. Therefore, our research focused on the possible effects of curcumin on small cell lung cancer (SCLC) cells and drew a comprehensive transcriptomes profile by high throughput sequencing to understand the molecular mechanism of curcumin as an anti-tumor agent.MethodsFirst, we calculated the apoptosis rate of H446 cells (a human SCLC cell line) cultured with curcumin. The high output sequencing uncovered the altered expression profile of genes and miRNAs. KEGG analysis selected the potential signal pathway associated with the antiproliferative property of curcumin. Finally, miRNAs significantly changed, as well as the regulatory roles of those miRNAs in cell apoptosis were determined.ResultThe apoptosis rate of H446 cells increased under the elevated concentration of curcumin treatment. And cell cycle-related genes downregulated in the curcumin-treated cells. Besides, miRNA-548ah-5p of a high level acted as a negative role in the anticarcinogenic activity of curcumin.ConclusionOur findings not only enriched the understanding of anti-tumor activity initiated by curcumin through figuring out the downregulated cell cycle-related pathways but also shed light on its novel therapeutic application.
New High-Resolution Modeling of the 2018 Palu Tsunami, Based on Supershear Earthquake Mechanisms and Mapped Coastal Landslides, Supports a Dual Source
Authors: Schambach Lauren , Grilli Stephan T. , Tappin David R. 
Published: January 2021

The Mw 7.5 earthquake that struck Central Sulawesi, Indonesia, on September 28, 2018, was rapidly followed by coastal landslides and destructive tsunami waves within Palu Bay. Here, we present new tsunami modeling that supports a dual source mechanism from the supershear strike-slip earthquake and coastal landslides. Up until now the tsunami mechanism: earthquake, coastal landslides, or a combination of both, has remained controversial, because published research has been inconclusive; with some studies explaining most observations from the earthquake and others the landslides. Major challenges are the numerous different earthquake source models used in tsunami modeling, and that landslide mechanisms have been hypothetical. Here, we simulate tsunami generation using three published earthquake models, alone and in combination with seven coastal landslides identified in earlier work and confirmed by field and bathymetric evidence which, from video evidence, produced significant waves. To generate and propagate the tsunamis, we use a combination of two wave models, the 3D non-hydrostatic model NHWAVE and the 2D Boussinesq model FUNWAVE-TVD. Both models are nonlinear and address the physics of wave frequency dispersion critical in modeling tsunamis from landslides, which here, in NHWAVE are modeled as granular material. Our combined, earthquake and coastal landslide, simulations recreate all observed tsunami runups, except those in the southeast of Palu Bay where they were most elevated (10.5 m), as well as observations made in video recordings and at the Pantoloan Port tide gauge located within Palu Bay. With regard to the timing of tsunami impact on the coast, results from the dual landslide/earthquake sources, particularly those using the supershear earthquake models are in good agreement with reconstructed time series at most locations. Our new work shows that an additional tsunami mechanism is also necessary to explain the elevated tsunami observations in the southeast of Palu Bay. Using partial information from bathymetric surveys in this area we show that an additional, submarine landslide here, when simulated with the other coastal slides, and the supershear earthquake mechanism better explains the observations. This supports the need for future marine geology work in this area.
Drift Characteristics of DONET Pressure Sensors Determined From In-Situ and Experimental Measurements
Authors: Matsumoto Hiroyuki , Araki Eiichiro 
Published: January 2021

DONET, the dense ocean-floor network system for earthquakes and tsunamis, began operations in the Nankai Trough, SW Japan, in 2010. The present study focuses on pressure sensors that are being used as tsunami meters to measure changes in hydraulic pressure. Pressure sensors typically show a drift in their readings over their operational lifespan. DONET pressure sensors can act as geodetic sensors measuring vertical crustal deformation change over time if the sensor drift can be accurately corrected. Monitoring crustal deformation before the occurrence of megathrust earthquakes is performed by discriminating between the vertical crustal deformation and the sensor drift of the pressure sensors. Therefore, in this study, we evaluated the sensor drift shown by the DONET pressure sensors since their deployment into the deep-sea, by removing the tidal component and confirming the occurrence of sensor drift. We evaluated the initial behavior of pressure sensors before deep-sea deployment using our own high-accuracy pressure standard. Our experiment involved 20-MPa pressurization for the pressure sensors under an ambient temperature of 2°C for a duration of 1 month. Some sensor drifts in our experiment correspond in rate and direction to those from the in-situ measurements determined to be in the initial stage. Our experiment suggests that the pre-deployment pressurization of pressure sensors can be an effective procedure to determine the sensor drift after sensor deployment into the deep-sea.
Opportunistic Osteoporosis Screening Reveals Low Bone Density in Patients With Screw Loosening After Lumbar Semi-Rigid Instrumentation: A Case-Control Study
Authors: Löffler Maximilian T. , Sollmann Nico , Burian Egon , Bayat Amirhossein , Aftahy Kaywan , Baum Thomas , Meyer Bernhard , Ryang Yu-Mi , Kirschke Jan S. 
Published: January 2021

ObjectiveDecreased bone mineral density (BMD) impairs screw purchase in trabecular bone and can cause screw loosening following spinal instrumentation. Existing computed tomography (CT) scans could be used for opportunistic osteoporosis screening for decreased BMD. Purpose of this case-control study was to investigate the association of opportunistically assessed BMD with the outcome after spinal surgery with semi-rigid instrumentation for lumbar degenerative instability.MethodsWe reviewed consecutive patients that had primary surgery with semi-rigid instrumentation in our hospital. Patients that showed screw loosening in follow-up imaging qualified as cases. Patients that did not show screw loosening or—if no follow-up imaging was available (n = 8)—reported benefit from surgery ≥ 6 months after primary surgery qualified as controls. Matching criteria were sex, age, and surgical construct. Opportunistic BMD screening was performed at L1 to L4 in perioperative CT scans by automatic spine segmentation and using asynchronous calibration. Processing steps of this deep learning-driven approach can be reproduced using the freely available online-tool Anduin (https://anduin.bonescreen.de). Area under the curve (AUC) was calculated for BMD as a predictor of screw loosening.ResultsForty-six elderly patients (69.9 ± 9.1 years)—23 cases and 23 controls—were included. The majority of surgeries involved three spinal motion segments (n = 34). Twenty patients had low bone mass and 13 had osteoporotic BMD. Cases had significantly lower mean BMD (86.5 ± 29.5 mg/cm³) compared to controls (118.2 ± 32.9 mg/cm³, p = 0.001), i.e. patients with screw loosening showed reduced BMD. Screw loosening was best predicted by a BMD &lt; 81.8 mg/cm³ (sensitivity = 91.3%, specificity = 56.5%, AUC = 0.769, p = 0.002).ConclusionPrevalence of osteoporosis or low bone mass (BMD ≤ 120 mg/cm³) was relatively high in this group of elderly patients undergoing spinal surgery. Screw loosening was associated with BMD close to the threshold for osteoporosis (&lt; 80 mg/cm³). Opportunistic BMD screening is feasible using the presented approach and can guide the surgeon to take measures to prevent screw loosening and to increase favorable outcomes.
Deregulation of a Cis-Acting lncRNA in Non-small Cell Lung Cancer May Control HMGA1 Expression
Authors: Stewart Greg L. , Sage Adam P. , Enfield Katey S. S. , Marshall Erin A. , Cohn David E. , Lam Wan L. 
Published: January 2021

BackgroundLong non-coding RNAs (lncRNAs) have long been implicated in cancer-associated phenotypes. Recently, a class of lncRNAs, known as cis-acting, have been shown to regulate the expression of neighboring protein-coding genes and may represent undiscovered therapeutic action points. The chromatin architecture modification gene HMGA1 has recently been described to be aberrantly expressed in lung adenocarcinoma (LUAD). However, the mechanisms mediating the expression of HMGA1 in LUAD remain unknown. Here we investigate the deregulation of a putative cis-acting lncRNA in LUAD, and its effect on the oncogene HMGA1.MethodsLncRNA expression was determined from RNA-sequencing data of tumor and matched non-malignant tissues from 36 LUAD patients. Transcripts with significantly deregulated expression were identified and validated in a secondary LUAD RNA-seq dataset (TCGA). SiRNA-mediated knockdown of a candidate cis-acting lncRNA was performed in BEAS-2B cells. Quantitative real-time PCR was used to observe the effects of lncRNA knockdown on the expression of HMGA1.ResultsWe identified the lncRNA RP11.513I15.6, which we refer to as HMGA1-lnc, neighboring HMGA1 to be significantly downregulated in both LUAD cohorts. Conversely, we found HMGA1 significantly overexpressed in LUAD and anticorrelated with HMGA1-lnc. In vitro experiments demonstrated siRNA-mediated inhibition of HMGA1-lnc in immortalized non-malignant lung epithelial cells resulted in a significant increase in HMGA1 gene expression.ConclusionOur results suggest that HMGA1-lnc is a novel cis-acting lncRNA that negatively regulates HMGA1 gene expression in lung cells. Further characterization of this regulatory mechanism may advance our understanding of the maintenance of lung cancer phenotypes and uncover a novel therapeutic intervention point for tumors driven by HMGA1.
Isoflurane-Induced Burst Suppression Is a Thalamus-Modulated, Focal-Onset Rhythm With Persistent Local Asynchrony and Variable Propagation Patterns in Rats
Authors: Ming Qianwen , Liou Jyun-You , Yang Fan , Li Jing , Chu Chaojia , Zhou Qingchen , Wu Dan , Xu Shujia , Luo Peijuan , Liang Jianmin , Li Dan , Pryor Kane O. , Lin Weihong , Schwartz Theodore H. , Ma Hongtao 
Published: January 2021

Background: Inhalational anesthetic-induced burst suppression (BS) is classically considered a bilaterally synchronous rhythm. However, local asynchrony has been predicted in theoretical studies and reported in patients with pre-existing focal pathology.Method: We used high-speed widefield calcium imaging to study the spatiotemporal dynamics of isoflurane-induced BS in rats.Results: We found that isoflurane-induced BS is not a globally synchronous rhythm. In the neocortex, neural activity first emerged in a spatially shifting, variably localized focus. Subsequent propagation across the whole cortex was rapid, typically within &lt;100 milliseconds, giving the superficial resemblance to global synchrony. Neural activity remained locally asynchronous during the bursts, forming complex recurrent propagating waves. Despite propagation variability, spatial sequences of burst propagation were largely preserved between the hemispheres, and neural activity was highly correlated between the homotopic areas. The critical role of the thalamus in cortical burst initiation was demonstrated by using unilateral thalamic tetrodotoxin injection.Conclusion: The classical impression that anesthetics-induced BS is a state of global brain synchrony is inaccurate. Bursts are a series of shifting local cortical events facilitated by thalamic projection that unfold as rapid, bilaterally asynchronous propagating waves.
Efficacy and Safety of PD-1/PD-L1 Inhibitors Plus Chemotherapy Versus PD-1/PD-L1 Inhibitors in Advanced Non-Small Cell Lung Cancer: A Network Analysis of Randomized Controlled Trials
Authors: Li Xiang , Yan Shi , Yang Jichun , Wang Yaqi , Lv Chao , Li Shaolei , Zhao Jun , Yang Yue , Zhuo Minglei , Wu Nan 
Published: January 2021

Immune checkpoint inhibitors (ICIs) are recommended as first-line treatment for late-stage non-small cell lung cancer (NSCLC), either as monotherapy or in combination with chemotherapy. However, efficacy and safety comparisons between ICIs as monotherapy and ICIs with chemotherapy are lacking. We searched PubMed, Embase, and Cochrane Library for randomized controlled trials published before February 29th, 2020, with the search terms “immunotherapy” and “chemotherapy”. 10 eligible trials were identified with a total of 5,956 patients. Of these patients, 3,204 received immune therapy and 2,752 received chemotherapy. PD-1 inhibitors with chemotherapy improved OS (HR 0.84, 0.77–0.92), PFS (HR 0.80, 0.75–0.85), and objective response rate (ORR) (odds ratio (OR) 2.55, 1.20–5.28) compared to PD-1 inhibitors as monotherapy. In contrast, PD-L1 inhibitors plus chemotherapy showed no significant differences in OS, PFS, or ORR compared with PD-L1 inhibitors as monotherapy. When patients were stratified according to PD-L1 expression level, patients with high PD-L1 expression (≥ 50%) receiving PD-1 inhibitors plus chemotherapy had improved PFS, but not other outcomes, compared to PD-1 inhibitors as monotherapy. In these patients, PD-L1 inhibitors plus chemotherapy showed no significant difference in survival compared with PD-L1 inhibitors. In the low PD-L1 expression group (1%–49%), PD-1 inhibitors plus chemotherapy improved OS and PFS, but no advantage was observed in PD-L1 inhibitors plus chemotherapy in OS, PFS, or ORR compared with PD-L1 inhibitor monotherapy. When comparing PD-1/PD-L1 inhibitors plus chemotherapy with PD-1/PD-L1 inhibitors monotherapy, no significant differences were observed in the rate of immune-related adverse events (AEs). In summary, for treating patients with late-stage NSCLC, PD-1 inhibitors plus chemotherapy have improved efficacy compared with PD-1 inhibitor monotherapy, but PD-L1 inhibitors plus chemotherapy have similar efficacy as PD-L1 monotherapy. Survival benefits of PD-1/PD-L1 inhibitors combined with chemotherapy were particularly significant in patients with low PD-L1 expression levels.Systematic Review RegistrationPROSPERO, identifier CRD42020166678 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=166678).
Efficacy and Safety of Daprodustat for Anemia Therapy in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis
Authors: Zheng Qiyan , Wang Yahui , Yang Huisheng , Sun Luying , Fu Xinwen , Wei Ruojun , Liu Yu Ning , Liu Wei Jing 
Published: January 2021

Objective: Daprodustat is a novel oral agent in treating anemia of chronic kidney disease (CKD), and several clinical trials have been conducted to compare daprodustat with recombinant human erythropoietin (rhEPO) or placebo. Our systematic review aimed to investigate the efficacy and safety of daprodustat for anemia treatment in both dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients.Methods: Six databases were searched for randomized controlled trials (RCTs) reporting daprodustat vs. rhEPO or placebo for anemia patients in CKD. The outcome indicators were focused on hemoglobin (Hb), ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), vascular endothelial growth factor (VEGF), and serious adverse events (SAEs).Results: Eight eligible studies with 1,516 participants were included. For both NDD and DD patients, changes in Hb levels from baseline were significantly higher in daprodustat group than that in the placebo (mean difference (MD) = 1.73, [95% confidence interval (CI), 0.34 to 3.12], p = 0.01; MD = 1.88, [95% CI, 0.68 to 3.09], p = 0.002; respectively), and there was no significant difference between daprodustat and rhEPO group (MD = 0.05, [95% CI, −0.49 to 0.59], p = 0.86; MD = 0.12, [95% CI, −0.28 to 0.52], p = 0.55; respectively). The indexes of iron metabolism were improved significantly in the daprodustat group compared to placebo- or rhEPO-treated patients, while there was no similar change in terms of TSAT for DD patients. Furthermore, no trend of increasing plasma VEGF was observed in daprodustat-treated subjects. As for safety, there was no significant difference in the incidence of SAEs between daprodustat and placebo treatment, while the incidence of SAEs in the daprodustat group was significantly lower than that in the rhEPO group.Conclusion: Daprodustat was efficacious and well tolerated for anemia in both NDD and DD patients in the short term based on current RCTs. And daprodustat may become an effective alternative for treatment of anemia with CKD. Since the application of daprodustat is still under exploration, future researches should consider the limitations of our study to evaluate the value of daprodustat.
SGLT1 Inhibition Attenuates Apoptosis in Diabetic Cardiomyopathy via the JNK and p38 Pathway
Authors: Lin Na , Lin Hui , Yang Qi , Lu Wenqiang , Sun Zhenzhu , Sun Shimin , Meng Liping , Chi Jufang , Guo Hangyuan 
Published: January 2021

Background: Recent studies have revealed that a novel selective sodium-glucose cotransporter 1 (SGLT1) inhibiton has shown beneficial effects in cardiovascular diseases. However, the question of whether SGLT1 inhibition influences diabetic cardiomyopathy (DCM) remains unanswered. In this study, we investigated the influence and underlying mechanism of SGLTI inhibition on DCM.Methods: SGLT1 levels were measured in diabetic patients with similar conditions who visited our hospital from January to December 2019. Wistar male rats (n = 50) were divided into five groups: control, diabetes induced by streptozotocin infusion, and diabetes treated with 0.5, 1.0, or 1.5 mg/kg mizagliflozin via stomach gavage for 12 weeks. H9C2 cardiomyocytes were treated with mizagliflozin and then exposed to a high glucose concentration (30 mmol/L). TUNEL assays were performed, and bcl2, bax, p-p38, p-Erk, p-JNK and caspase-3 levels were measured. We used siRNA and an SGLT1 overexpression plasmid to detect the effects of SGLT1.Results: SGLT1 levels were significantly elevated in DCM patients, and receiver operating characteristic (ROC) curve analysis identified SGLT1 as influencing DCM. The area under the curve (AUC) was 0.705 (p &lt; 0.05), with 65.8% sensitivity, and 62.2% specificity. SGLT1 inhibition appeared to attenuate apoptosis in DCM via the JNK and p38 pathway.Conclusion: SGLT1 can be used as a marker for the diagnosis of DCM, and SGLT1 inhibition can attenuate apoptosis, thereby suppressing DCM development via the JNK and p38 pathway.
Influence of Multiple Animal Scanning on Image Quality for the Sedecal SuperArgus2R Preclinical PET Scanner
Authors: Efthimiou Nikos , Wright John D. , Clayton Luke , Renard Isaline , Zagni Federico , Caribé Paulo R.R.V. , Archibald Stephen J. , Cawthorne Christopher J. 
Published: January 2021

Background: Increased throughput in small animal preclinical studies using positron emission tomography leads to reduced costs and improved efficiency of experimental design, however the presence of multiple off-centre subjects, as opposed to a single centered one, may affect image quality in several ways.Methods: We evaluated the count rate performance using a NEMA scatter phantom. A Monte Carlo simulation of the system was validated against this dataset and used to simulate the count rate performance for dual scatter phantoms. NEMA NU4 image quality phantoms were then scanned in the central and offset positions, as well as in the offset position next to a uniform activity phantom. Uniformity, recovery coefficients and spillover ratios were then compared, as were two time frames for acquisition.Results: Count rate performance assessed with a single NEMA scatter phantom was in line with previous literature, with simulated data in good agreement. Simulation of dual scatter phantoms showed an increase in scatter fraction. For the NEMA Image Quality phantom, uniformity and Recovery coefficients were degraded in the offset, and dual phantom cases, while spillover ratios were increased, notably when the chamber was placed nearest the gantry. Image quality metrics were comparable between the 20- and 10 min timeframes.Conclusion: Dual animal scanning results in some loss of image quality on the Sedecal Argus PET scanner; however, this degradation is within acceptable limits.