bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial DNA leakage induces odontoblast inflammation via the cGAS-STING pathway
Authors: Zhou Lu , Zhang Yi-Fei , Yang Fu-Hua , Mao Han-Qing , Chen Zhi , Zhang Lu 
Published: May 2021

Abstract
Background
Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from damaged mitochondria into the cytosol. mtDNA stress may contribute to cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway activation in infectious diseases. Odontoblasts are the first cells challenged by cariogenic bacteria and involved in maintenance of the pulp immune and inflammatory responses to dentine-invading pathogens. In this study, we investigated that mtDNA as an important inflammatory driver participated in defending against bacterial invasion via cGAS-STING pathway in odontoblasts.

Methods
The normal tissues, caries tissues and pulpitis tissues were measured by western blotting and immunohistochemical staining. Pulpitis model was built in vitro to evaluated the effect of the cGAS-STING pathway in odontoblast-like cell line (mDPC6T) under inflammation. Western blot and real-time PCR were performed to detect the expression of cGAS-STING pathway and pro-inflammatory cytokines. The mitochondrial function was evaluated reactive oxygen species (ROS) generated by mitochondria using MitoSOX Red dye staining. Cytosolic DNA was assessed by immunofluorescent staining and real-time PCR in mDPC6T cells after LPS stimulation. Furthermore, mDPC6T cells were treated with ethidium bromide (EtBr) to deplete mtDNA or transfected with isolated mtDNA. The expression of cGAS-STING pathway and pro-inflammatory cytokines were measured.

Results
The high expression of cGAS and STING in caries and pulpitis tissues in patients, which was associated with inflammatory progression. The cGAS-STING pathway was activated in inflamed mDPC6T. STING knockdown inhibited the nuclear import of p65 and IRF3 and restricted the secretion of the inflammatory cytokines CXCL10 and IL-6 induced by LPS. LPS caused mitochondrial damage in mDPC6T, which promoted mtDNA leakage into the cytosol. Depletion of mtDNA inhibited the cGAS-STING pathway and nuclear translocation of p65 and IRF3. Moreover, repletion of mtDNA rescued the inflammatory response, which was inhibited by STING knockdown.

Conclusion
Our study systematically identified a novel mechanism of LPS-induced odontoblast inflammation, which involved mtDNA leakage from damaged mitochondria into the cytosol stimulating the cGAS-STING pathway and the inflammatory cytokines IL-6 and CXCL10 secretion. The mtDNA-cGAS-STING axis could be a potent therapeutic target to prevent severe bacterial inflammation in pulpitis.

Graphic abstract
Comparison of short-term outcomes between direct anterior approach (DAA) and SuperPATH in total hip replacement: a systematic review and network meta-analysis of randomized controlled trials
Authors: Ramadanov Nikolai , Bueschges Simon , Liu Kuiliang , Lazaru Philip , Marintschev Ivan 
Published: May 2021

Abstract
Background
Two minimally invasive approaches showed some advantages in outcomes compared to conventional approaches (CAs)—the direct anterior approach (DAA) and the supercapsular percutaneously assisted approach in THA (SuperPATH). To the best of our knowledge, DAA and SuperPATH have never been compared, neither in clinical studies, nor in a meta-analysis. To conduct a systematic review and network meta-analysis of randomized controlled trials comparing short-term outcomes of DAA and SuperPATH in total hip joint arthroplasty (THA).

Methods
A systematic literature search up to May 2020 was performed to identify randomized controlled trials (RCTs) comparing SuperPATH with CAs and DAA with CAs in THA. We measured surgical, functional, and radiological outcomes. A network meta-analysis, using frequentist methods, was performed to assess treatment effects between DAA and SuperPATH. Information was borrowed from the above-mentioned RCTs, using the CA group as a common comparator.

Results
A total of 16 RCTs involving 1392 patients met the inclusion criteria, three trials with a level I evidence, 13 trials with a level II evidence. The overall network meta-analysis showed that SuperPATH reduced operation time (fixed effect model: MD = 12.8, 95% CI 9.9 to 15.7), incision length (fixed effect model: MD = 4.3, 95% CI 4.0 to 4.5; random effect model: MD = 4.3, 95% CI 0.2 to 8.4), intraoperative blood loss (fixed effect model: MD = 58.6, 95% CI 40.4 to 76.8), and early pain intensity (VAS 1 day postoperatively with a fixed effect model: MD = 0.8, 95% CI 0.4 to 1.2). The two approaches did not differ in acetabular cup positioning angles and in functional outcome.

Conclusions
Our overall findings suggested that the short-term outcomes of THA through SuperPATH were superior to DAA. SuperPATH showed better results in decreasing operation time, incision length, intraoperative blood loss, and early pain intensity. DAA and SuperPATH were equal in functional outcome and acetabular cup positioning.
Attenuated serum vasoactive intestinal peptide concentrations are correlated with disease severity of non-traumatic osteonecrosis of femoral head
Authors: Liu Ming , Zhao Gan , Wei Biao-Fang 
Published: May 2021

Abstract
Background and objective
The neuropeptide vasoactive intestinal peptide is a 28-amino acid neuropeptide that has been shown to stimulate bone repair and angiogenesis. The purpose of this study was to explore the potential role of serum VIP concentration in osteonecrosis of femoral trauma (ONFH).

Methods
One hundred five patients diagnosed with non-traumatic ONFH and 103 healthy individuals were enrolled in our study. Serum VIP, tumor necrosis factor-α (TNF-α), interluekin-1 beta (IL-1β), and macrophage colony-stimulating factor (M-CSF) levels also were detected using the commercial ELISA kit. Radiographic progression was evaluated using FICAT classification. The clinical severity of ONFH was assessed by visual analog score (VAS) and Harris Hip Score (HHS). Receiver-operating characteristic (ROC) curve was performed to test the potential diagnostic value of VIP in radiographic progression.

Results
The serum VIP level of patients with non-traumatic ONFH was significantly lower than that of healthy controls. There was no significant difference between the alcohol group, the steroid-induction group, and the idiopathic group. Serum VIP levels were significantly higher in ONFH patients with femoral head pre-collapse stage than collapse stage. Serum VIP levels were significantly lower. FICAT 4 non-traumatic ONFH patients had significantly lower serum concentrations of VIP when compared with FICAT 3 and FICAT 2. Moreover, serum VIP levels were significantly lower in ONFH patients with FICAT 3 than FICAT 2. Serum VIP levels were negatively related to FICAT stage. In addition, serum VIP levels were negatively associated with VAS score and positively associated with HHS score. Last, we found serum VIP levels were negatively associated with serum TNF-α and IL-1β levels. ROC curve analysis indicated that decreased serum VIP could serve as a decent biomarker with regard to the diagnosis of radiographic progression.

Conclusion
Attenuated serum VIP concentrations are correlated with disease severity of non-traumatic ONFH. Decreased serum VIP may serve as a potential indicator of non-traumatic ONFH.
Cyclin-dependent kinase 9 (CDK9) predicts recurrence in Middle Eastern epithelial ovarian cancer
Authors: Parvathareddy Sandeep Kumar , Siraj Abdul K. , Masoodi Tariq , Annaiyappanaidu Padmanaban , Al-Badawi Ismail A. , Al-Dayel Fouad , Al-Kuraya Khawla S. 
Published: May 2021

AbstractBackgroundCyclin-dependent kinase 9 (CDK9) has been shown to play an important role in tumorigenesis of several malignancies. However, the expression of CDK9 in ovarian cancer from Middle Eastern ethnicity remains unknown.MethodsA tissue microarray of 441 epithelial ovarian cancer (EOC) samples was used to study the expression of CDK9 immunohistochemically and their clinico-pathological associations were determined. Cox proportional hazards regression model was used for univariate and multivariate analysis of recurrence-free survival.ResultsCDK9 over-expression was noted in 56.2 % (248/441) of EOCs and was associated with adverse clinico-pathological parameters such as distant metastasis (p < 0.0001), stage IV tumors (p < 0.0001), tumor recurrence (p = 0.0105) and high Ki-67 index (p < 0.0001). Importantly, CDK9 over-expression was an independent predictor of poor recurrence-free survival (Hazard ratio = 1.51; 95 % confidence interval = 1.15–1.98;p = 0.0030). We also found that CDK9 outperforms Ki-67 as a predictor of tumor recurrence in EOC.ConclusionsOur results show that CDK9 expression correlates with markers of advanced disease in Middle Eastern EOC and is also a prognostic marker. CDK9 overexpression also identifies a subset of patients with highest likelihood of recurrence across the patient cohort. These patients may benefit from additional alternative therapies targeting CKD9.
Outcomes of vitrectomy for retinal detachment in a patient with Ehlers–Danlos syndrome type IV: a case report
Authors: Lumi Xhevat , Bergant Gaber , Lumi Anila , Mahnic Mina 
Published: May 2021

Abstract
Background
The Ehlers–Danlos syndrome (EDS) is a group of connective tissue disorders characterized by fragile blood vessels and an increased tendency for bleeding and scarring. Here, we report the outcome of a pars plana vitrectomy for the treatment of rhegmatogenous retinal detachment in a patient with EDS type IV (vascular type).

Case presentation
A 40-year-old Slovenian man with high myopia, unilateral bullous retinal detachment, and vitreous hemorrhage was referred for surgery. The patient had a history of colon perforation, muscle and arterial rupture in both lower limbs, and recurrent shoulder joint luxations. Genetic testing revealed a pathogenic mutation in the COL3A1 gene. The patient underwent a 25-gauge three-port pars plana vitrectomy. The tendency for bleeding during surgery was prevented by endodiathermy applied to the edges of the retinal breaks. Endolaser photocoagulation was performed under air. The surgical procedure was completed with the injection of gas tamponade, followed by the patient remaining for a few days in a face-down position. Mild postoperative vitreous hemorrhage was resorbed in first week after the surgery. Postoperative extensive pigment dispersion on the posterior lens face persisted for several weeks. After the gas tamponade had resorbed, the retina was flat and remained attached during the follow-up period. Eight months after the surgery, visual acuity continued to improve from a preoperative 6/38 to 6/6.6 (Snellen chart) at the last checkup.

Conclusion
A small-gauge pars plana vitrectomy with gas tamponade and laser photocoagulation under air may successfully achieve reattachment of the retina in patients with high myopia with EDS type IV and restore visual acuity.
Lipid and lipoprotein predictors of functional outcomes and long-term mortality after surgical sepsis
Authors: Guirgis Faheem W. , Leeuwenburgh Christiaan , Moldawer Lyle , Ghita Gabriela , Black Lauren Page , Henson Morgan , DeVos Elizabeth , Holden David , Efron Phil , Reddy Srinivasa T. , Moore Frederick A. 
Published: May 2021

Abstract
Rationale
Sepsis is a life-threatening, dysregulated response to infection. Lipid biomarkers including cholesterol are dynamically regulated during sepsis and predict short-term outcomes. In this study, we investigated the predictive ability of lipid biomarkers for physical function and long-term mortality after sepsis.

Methods
Prospective cohort study of sepsis patients admitted to a surgical intensive-care unit (ICU) within 24 h of sepsis bundle initiation. Samples were obtained at enrollment for lipid biomarkers. Multivariate regression models determined independent risk factors predictive of poor performance status (Zubrod score of 3/4/5) or survival at 1-year follow-up.

Measurements and main results
The study included 104 patients with surgical sepsis. Enrollment total cholesterol and high-density lipoprotein (HDL-C) levels were lower, and myeloperoxidase (MPO) levels were higher for patients with poor performance status at 1 year. A similar trend was seen in comparisons based on 1-year mortality, with HDL-C and ApoA-I levels being lower and MPO levels being higher in non-survivors. However, multivariable logistic regression only identified baseline Zubrod and initial SOFA score as significant independent predictors of poor performance status at 1 year. Multivariable Cox regression modeling for 1-year survival identified high Charlson comorbidity score, low ApoA-I levels, and longer vasopressor duration as predictors of mortality over 1-year post-sepsis.

Conclusions
In this surgical sepsis study, lipoproteins were not found to predict poor performance status at 1 year. ApoA-I levels, Charlson comorbidity scores, and duration of vasopressor use predicted 1 year survival. These data implicate cholesterol and lipoproteins as contributors to the underlying pathobiology of sepsis.
“Real-world” radiomics from multi-vendor MRI: an original retrospective study on the prediction of nodal status and disease survival in breast cancer, as an exemplar to promote discussion of the wider issues
Authors: Doran Simon J. , Kumar Santosh , Orton Matthew , d’Arcy James , Kwaks Fenna , O’Flynn Elizabeth , Ahmed Zaki , Downey Kate , Dowsett Mitch , Turner Nicholas , Messiou Christina , Koh Dow-Mu 
Published: May 2021

AbstractBackgroundMost MRI radiomics studies to date, even multi-centre ones, have used “pure” datasets deliberately accrued from single-vendor, single-field-strength scanners. This does not reflect aspirations for the ultimate generalisability of AI models. We therefore investigated the development of a radiomics signature from heterogeneous data originating on six different imaging platforms, for a breast cancer exemplar, in order to provide input into future discussions of the viability of radiomics in “real-world” scenarios where image data are not controlled by specific trial protocols but reflective of routine clinical practice.MethodsOne hundred fifty-six patients with pathologically proven breast cancer underwent multi-contrast MRI prior to neoadjuvant chemotherapy and/or surgery. From these, 92 patients were identified for whom T2-weighted, diffusion-weighted and contrast-enhanced T1-weighted sequences were available, as well as key clinicopathological variables. Regions-of-interest were drawn on the above image types and, from these, semantic and calculated radiomics features were derived. Classification models using a variety of methods, both with and without recursive feature elimination, were developed to predict pathological nodal status. Separately, we applied the same methods to analyse the information carried by the radiomic features regarding the originating scanner type and field strength. Repeated, ten-fold cross-validation was employed to verify the results. In parallel work, survival modelling was performed using random survival forests.ResultsPrediction of nodal status yielded mean cross-validated AUC values of 0.735 ± 0.15 (SD) for clinical variables alone, 0.673 ± 0.16 (SD) for radiomic features only, and 0.764 ± 0.16 (SD) for radiomics and clinical features together. Prediction of scanner platform from the radiomics features yielded extremely high values of AUC between 0.91 and 1 for the different classes examined indicating the presence of confounding features for the nodal status classification task. Survival analysis, gave out-of-bag prediction errors of 19.3% (clinical features only), 36.9–51.8% (radiomic features from different combinations of image contrasts), and 26.7–35.6% (clinical plus radiomics features).ConclusionsRadiomic classification models whose predictive ability was consistent with previous single-vendor, single-field strength studies have been obtained from multi-vendor, multi-field-strength data, despite clear confounding information being present. However, our sample size was too small to obtain useful survival modelling results.
Parameterization of physical properties of layered body structure into equivalent circuit model
Authors: Lee Jiho , Park Sung-Min 
Published: May 2021

AbstractBackgroundThis study presents a novel technique to develop an equivalent circuit model (ECM) for analyzing the responses of the layered body structure to transcutaneous electrical nerve stimulation (TENS) by parameterizing electrical and geometrical properties.Many classical ECMs are non-parametric because of the difficulty in projecting intrapersonal variability in the physical properties into ECM. However, not considering the intrapersonal variability hampers patient-specifically analyzing the body response to TENS and personal optimization of TENS parameter design. To overcome this limitation, we propose a tissue property-based (TPB) approach for the direct parameterization of the physical properties in the layered body structure and thus enable to quantify the effects of intrapersonal variability.ResultsThe proposed method was first validated through in vitro phantom studies and then was applied in-vivo to analyze the TENS on the forearm. The TPB-ECM calculated the impedance network in the forearm and corresponding responses to TENS. In addition, the modelled impedance was in good agreement with well-known impedance properties that have been achieved empirically.ConclusionsThe TPB approach uses the parameterized circuit components compared to non-parametric conventional ECMs, thus overcoming the intrapersonal variability problem of the conventional ECMs. Therefore, the TPB-ECM has a potential for widely-applicable TENS analysis and could provide impactful guidance in the TENS parameter design.
Nasal airflow of patient with septal deviation and allergy rhinitis
Authors: Lim Zi Fen , Rajendran Parvathy , Musa Muhamad Yusri , Lee Chih Fang 
Published: May 2021

AbstractA numerical simulation of a patient’s nasal airflow was developed via computational fluid dynamics. Accordingly, computerized tomography scans of a patient with septal deviation and allergic rhinitis were obtained. The three-dimensional (3D) nasal model was designed using InVesalius 3.0, which was then imported to (computer aided 3D interactive application) CATIA V5 for modification, and finally to analysis system (ANSYS) flow oriented logistics upgrade for enterprise networks (FLUENT) to obtain the numerical solution. The velocity contours of the cross-sectional area were analyzed on four main surfaces: the vestibule, nasal valve, middle turbinate, and nasopharynx. The pressure and velocity characteristics were assessed at both laminar and turbulent mass flow rates for both the standardized and the patient’s model nasal cavity. The developed model of the patient is approximately half the size of the standardized model; hence, its velocity was approximately two times more than that of the standardized model.
Cervical and ocular vestibular evoked myogenic potentials in epileptic patients
Authors: Kabel Abd El Mageed Hassan , Afifi Khaled Hatem , ElFakhrany Samar Mohammed , Moaty Asmaa Salah 
Published: May 2021

Abstract
Background
Vertigo and dizziness are very common complaints that may be related to epilepsy. The purpose of this study was to assess vestibulo-spinal and linear vestibulo-ocular function in epileptic patients in the inter ictal period. The current observational study was carried out in audio-vestibular unit Menoufia University. Subjects in the current study were divided into two groups: The control group included 30 normal individuals not complaining from any dizzy symptoms and the epileptic cases group included 30 epileptic patients. All subjects in the study were submitted to cervical and ocular vestibular evoked myogenic potential.

Results
There was no significant difference between the control and epileptic group regarding the age and sex distribution. Sixty-seven percent of epileptic cases had dizzy symptoms. There was statistically significant difference in the latency and amplitude of c and o VEMP between the control and the epileptic group, 39/60 ears (65%) in the study group had cVEMP abnormalities, 32/60 ears (53%) had oVEMP abnormalities. Abnormal c and o VEMP were reported in 28/60 ears (46.7%). There was statistically significant relationship between VEMP abnormalities and duration of seizures, frequency of epileptic attacks, and type of therapy.

Conclusion
Vestibular abnormalities were frequently reported in epileptic patients in the current study which may be related to the severity and control of epilepsy.
Systems Modeling to Quantify Safety Risks in Early Drug Development: Using Bifurcation Analysis and Agent-Based Modeling as Examples
Authors: Pin Carmen , Collins Teresa , Gibbs Megan , Kimko Holly 
Published: May 2021

AbstractQuantitative Systems Toxicology (QST) models, recapitulating pharmacokinetics and mechanism of action together with the organic response at multiple levels of biological organization, can provide predictions on the magnitude of injury and recovery dynamics to support study design and decision-making during drug development. Here, we highlight the application of QST models to predict toxicities of cancer treatments, such as cytopenia(s) and gastrointestinal adverse effects, where narrow therapeutic indexes need to be actively managed. The importance of bifurcation analysis is demonstrated in QST models of hematologic toxicity to understand how different regions of the parameter space generate different behaviors following cancer treatment, which results in asymptotically stable predictions, yet highly irregular for specific schedules, or oscillating predictions of blood cell levels. In addition, an agent-based model of the intestinal crypt was used to simulate how the spatial location of the injury within the crypt affects the villus disruption severity. We discuss the value of QST modeling approaches to support drug development and how they align with technological advances impacting trial design including patient selection, dose/regimen selection, and ultimately patient safety.
Blast waves in a paraxial fluid of light
(a)
Authors: Abuzarli M. , Bienaimé T. , Giacobino E. , Bramati A. , Glorieux Q. 
Published: May 2021

Abstract
We study experimentally blast wave dynamics on a weakly interacting fluid of light. The fluid density and velocity are measured in 1D and 2D geometries. Using a state equation arising from the analogy between optical propagation in the paraxial approximation and the hydrodynamic Euler's equation, we access the fluid hydrostatic and dynamic pressure. In the 2D configuration, we observe a negative differential hydrostatic pressure after the fast expansion of a localized over-density, which is a typical signature of a blast wave for compressible gases. Our experimental results are compared to the Friedlander waveform hydrodynamical model (Friedlander F. G., Proc. R. Soc. A: Math. Phys. Sci., 186 (1946) 322). Velocity measurements are presented in 1D and 2D configurations and compared to the local speed of sound, to identify the supersonic region of the fluid. Our findings show an unprecedented control over hydrodynamic quantities in a paraxial fluid of light.