bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Method to Develop the Primate Model of Knee Osteoarthritis With Focal Cartilage Defect
Authors: Bi Xin , Li Tao , Li Min , Xiang Shutian , Li Junhong , Ling Bin , Wu Zhaoxiang , Chen Zhong 
Published: November 2021

Objective: Osteoarthritis (OA) is a common degenerative joint disease, and animal models have proven pivotal in investigating this disease. This study aimed to develop a primate model of OA that may be more relevant to research studies on OA in humans.Method: Twelve female rhesus macaques were randomly divided into three groups. Four animals were untreated (Control group); four were subjected to the modified Hulth method, involving cutting of the anterior and posterior cruciate ligaments, and transecting the meniscus (Hulth group); and four were subjected to the modified Hulth method combined with cartilage defect (MHCD group). Each primate was subjected to motor ability tests, and underwent arthroscopic, radiographic, morphological, and pathological observation of the knee joints at various times for up to 180 days.Results: Motor ability on Day 180 was significantly lower in the MHCD group than in the Control (p＜0.01) and Hulth (p＜0.05) groups. Radiographic and morphological examination showed that the severity of knee joint deformity and articular cartilage injury were greater in the MHCD group than in the other groups. Pathological examination showed that cartilage thickness was significantly lower in the MHCD group than in the other groups at the same time points. The Mankin score on Day 180 was markedly higher in the MHCD group than in the Hulth (p＜0.05) and Control (p＜0.001) groups.Conclusion: The MHCD model of OA closely resembles the pathophysiological processes of spontaneous knee OA in humans. The time required to develop knee OA is shorter using the MHCD model than using the Hulth method.
From Stoop to Squat: A Comprehensive Analysis of Lumbar Loading Among Different Lifting Styles
Authors: von Arx Michael , Liechti Melanie , Connolly Lukas , Bangerter Christian , Meier Michael L. , Schmid Stefan 
Published: November 2021

Lifting up objects from the floor has been identified as a risk factor for low back pain, whereby a flexed spine during lifting is often associated with producing higher loads in the lumbar spine. Even though recent biomechanical studies challenge these assumptions, conclusive evidence is still lacking. This study therefore aimed at comparing lumbar loads among different lifting styles using a comprehensive state-of-the-art motion capture-driven musculoskeletal modeling approach. Thirty healthy pain-free individuals were enrolled in this study and asked to repetitively lift a 15 kg-box by applying 1) a freestyle, 2) a squat and 3) a stoop lifting technique. Whole-body kinematics were recorded using a 16-camera optical motion capture system and used to drive a full-body musculoskeletal model including a detailed thoracolumbar spine. Continuous as well as peak compressive, anterior-posterior shear and total loads (resultant load vector of the compressive and shear load vectors) were calculated based on a static optimization approach and expressed as factor body weight (BW). In addition, lumbar lordosis angles and total lifting time were calculated. All parameters were compared among the lifting styles using a repeated measures design. For each lifting style, loads increased towards the caudal end of the lumbar spine. For all lumbar segments, stoop lifting showed significantly lower compressive and total loads (−0.3 to −1.0BW) when compared to freestyle and squat lifting. Stoop lifting produced higher shear loads (+0.1 to +0.8BW) in the segments T12/L1 to L4/L5, but lower loads in L5/S1 (−0.2 to −0.4BW). Peak compressive and total loads during squat lifting occurred approximately 30% earlier in the lifting cycle compared to stoop lifting. Stoop lifting showed larger lumbar lordosis range of motion (35.9 ± 10.1°) than freestyle (24.2 ± 7.3°) and squat (25.1 ± 8.2°) lifting. Lifting time differed significantly with freestyle being executed the fastest (4.6 ± 0.7 s), followed by squat (4.9 ± 0.7 s) and stoop (5.9 ± 1.1 s). Stoop lifting produced lower total and compressive lumbar loads than squat lifting. Shear loads were generally higher during stoop lifting, except for the L5/S1 segment, where anterior shear loads were higher during squat lifting. Lifting time was identified as another important factor, considering that slower speeds seem to result in lower loads.
USP25 Regulates the Proliferation and Apoptosis of Ovarian Granulosa Cells in Polycystic Ovary Syndrome by Modulating the PI3K/AKT Pathway via Deubiquitinating PTEN
Authors: Gao Yue , Chen Jiao , Ji Rui , Ding Jinli , Zhang Yan , Yang Jing 
Published: November 2021

Background: Polycystic ovarian syndrome (PCOS) is an endocrine-related disease related to abnormal folliculogenesis and is a leading cause of infertility worldwide. Inhibition of granulosa cells (GCs) proliferation and increased GCs apoptosis have been identified as the major factors in aberrant follicle maturation.Methods: USP25 and PTEN expression in GCs from women with and without PCOS was analyzed using Western blotting. A PCOS-like mouse model was constructed using USP25 knockout and wild-type mice to explore the role of USP25 in PCOS. The human granular cell line KGN was cultured for proliferation and apoptosis assays, and the effect of USP25 on PTEN was investigated after transfection with shRNA-USP25 lentivirus.Results: USP25 expression was found to be elevated in patients and mice with PCOS. With mouse model, we observed a reduction in PCOS symptoms in mice after USP25 deletion. Increased proliferation, reduced apoptosis, activation of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and decreased PTEN expression were found in KGN cells after USP25 knockdown. Finally, we verified that USP25 could deubiquitinate PTEN in KGN cells.Conclusions: In this study, we investigated that USP25 can regulate the PI3K/AKT signaling pathway by deubiquitinating PTEN, thus affecting the proliferation and apoptosis of GCs and contributing to the pathogenesis of PCOS.
A Homogeneous Label-Free Electrochemical microRNA Biosensor Coupling With G-Triplex/Methylene Blue Complex and λ-Exonuclease-Assisted Recycling Amplification
Authors: Meng Yao , Chen Fangming , Jiang Mingrui , Guo Qin , Wang Yaqiong , Wang Jian , Zhang De-Wen 
Published: November 2021

A novel homogeneous label-free electrochemical biosensor using G-triplex/methylene blue (G3/MB) complex as the signal generator together with an amplification assisted by the λ-exonuclease (λ-Exo) has been successfully constructed for ultrasensitive microRNA (miRNA) detection. An integrated microelectrode was designed to realize the miniaturization of the homogeneous electrochemical assay. Taking advantage of G3, that can specifically bind with MB and decrease its diffusion current, a single-stranded functional DNA hairpin structure was designed as the bio-recognition probe. The probe consisted of G3, eight bases to block G3, and the complementary sequences of the target miRNA. Here we chose miRNA141—a potentially diagnostic biomarker of prostate cancer as the model target. The presence of miRNA141 could hybridize with the probe DNA to form a double-stranded structure with a 5′-phosphorylated terminus. Then λ-Exo was adopted to digest mononucleotides from the 5′-end, leading to the release of G3 part and miRNA141. The released miRNA could hybridize with another probe to trigger the cycling process, while the released G3 could therefore interact with MB to cause a detectable decrease of diffusion current. The proposed strategy showed a low detection limit of 16 fM and an excellent specificity to discriminate single-base mismatches. Furthermore, this sensor was applied to detect miRNA141 from diluted human serum samples, indicating that it has great potential in the application of nucleic acid detection in real samples.
Optical Coherence Tomography-Derived Changes in Plaque Structural Stress Over the Cardiac Cycle: A New Method for Plaque Biomechanical Assessment
Authors: Huang Jiayue , Yang Fan , Gutiérrez-Chico Juan Luis , Xu Tianxiao , Wu Jigang , Wang Liang , Lv Rui , Lai Yan , Liu Xuebo , Onuma Yoshinobu , Tang Dalin , Serruys Patrick W. , Wijns William , Tu Shengxian 
Published: November 2021

Introduction: Cyclic plaque structural stress has been hypothesized as a mechanism for plaque fatigue and eventually plaque rupture. A novel approach to derive cyclic plaque stress in vivo from optical coherence tomography (OCT) is hereby developed.Materials and Methods: All intermediate lesions from a previous OCT study were enrolled. OCT cross-sections at representative positions within each lesion were selected for plaque stress analysis. Detailed plaque morphology, including plaque composition, lumen and internal elastic lamina contours, were automatically delineated. OCT-derived vessel and plaque morphology were included in a 2-dimensional finite element analysis, loaded with patient-specific intracoronary pressure tracing data, to calculate the changes in plaque structural stress (ΔPSS) on vessel wall over the cardiac cycle.Results: A total of 50 lesions from 41 vessels were analyzed. A significant ΔPSS gradient was observed across the plaque, being maximal at the proximal shoulder (45.7 [32.3, 78.6] kPa), intermediate at minimal lumen area (MLA) (39.0 [30.8, 69.1] kPa) and minimal at the distal shoulder (35.1 [28.2, 72.3] kPa; p = 0.046). The presence of lipidic plaques were observed in 82% of the diseased segments. Larger relative lumen deformation and ΔPSS were observed in diseased segments, compared with normal segments (percent diameter change: 8.2 ± 4.2% vs. 6.3 ± 2.3%, p = 0.04; ΔPSS: 59.3 ± 48.2 kPa vs. 27.5 ± 8.2 kPa, p &lt; 0.001). ΔPSS was positively correlated with plaque burden (r = 0.37, p &lt; 0.001) and negatively correlated with fibrous cap thickness (r = −0.25, p = 0.004).Conclusions: ΔPSS provides a feasible method for assessing plaque biomechanics in vivo from OCT images, consistent with previous biomechanical and clinical studies based on different methodologies. Larger ΔPSS at proximal shoulder and MLA indicates the critical sites for future biomechanical assessment.
Extracellular Vesicles Are Associated With Outcome in Veno-Arterial Extracorporeal Membrane Oxygenation and Myocardial Infarction
Authors: Siegel Patrick M. , Bender Ileana , Chalupsky Julia , Heger Lukas A. , Rieder Marina , Trummer Georg , Wengenmayer Tobias , Duerschmied Daniel , Bode Christoph , Diehl Philipp 
Published: November 2021

Background:Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is being increasingly applied in patients with circulatory failure, but mortality remains high. An inflammatory response syndrome initiated by activation of blood components in the extracorporeal circuit may be an important contributing factor. Patients with ST-elevation myocardial infarction (STEMI) may also experience a systemic inflammatory response syndrome and are at risk of developing cardiogenic shock and cardiac arrest, both indications for VA-ECMO. Extracellular vesicles (EV) are released by activated cells as mediators of intercellular communication and may serve as prognostic biomarkers. Cardiomyocyte EV, released upon myocardial ischemia, hold strong potential for this purpose. The aim of this study was to assess the EV-profile in VA-ECMO and STEMI patients and the association with outcome.Methods:In this prospective observational study, blood was sampled on day 1 after VA-ECMO initiation or myocardial reperfusion (STEMI patients). EV were isolated by differential centrifugation. Leukocyte, platelet, endothelial, erythrocyte and cardiomyocyte (caveolin-3+) Annexin V+EV were identified by flow cytometry. EV were assessed in survivors vs. non-survivors of VA-ECMO and in STEMI patients with normal-lightly vs. moderately-severely reduced left ventricular function. Logistic regression was conducted to determine the predictive accuracy of EV. Pearson correlation analysis of EV with clinical parameters was performed.Results:Eighteen VA-ECMO and 19 STEMI patients were recruited. Total Annexin V+, cardiomyocyte and erythrocyte EV concentrations were lower (p≤ 0.005) while the percentage of platelet EV was increased in VA-ECMO compared to STEMI patients (p= 0.002). Total Annexin V+EV were increased in non-survivors of VA-ECMO (p= 0.01), and higher levels were predictive of mortality (AUC = 0.79,p= 0.05). Cardiomyocyte EV were increased in STEMI patients with moderately-severely reduced left ventricular function (p= 0.03), correlated with CK-MBmax(r= 0.57,p= 0.02) and time from reperfusion to blood sampling (r= 0.58,p= 0.01). Leukocyte EV correlated with the number of coronary stents placed (r= 0.60,p= 0.02).Conclusions:Elevated total Annexin V+EV on day 1 of VA-ECMO are predictive of mortality. Increased cardiomyocyte EV on day 1 after STEMI correlate with infarct size and are associated with poor outcome. These EV may aid in the early identification of patients at risk of poor outcome, helping to guide clinical management.
Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial Infarction
Authors: Wu Xun , Wang Di , Qin Kele , Iroegbu Chukwuemeka Daniel , Xiang Kun , Zhou Yuanjing , Guan Qing , Tang Weijie , Peng Jun , Guo Jianjun , Yang Jinfu , Fan Chengming 
Published: November 2021

Objective: We investigated the potency of cardiac repair based on echocardiography-guided multiple percutaneous left ventricular intramyocardial injection of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) after myocardial infarction (MI).Methods: Mice with surgically induced MI were randomly divided into three groups (n = 8 in each group) and subjected to echocardiography-guided percutaneous left ventricular infarcted border injection of hiPSC-CMs (single dose; 10 μl 3 × 105 cells) or repeated injections of hiPSC-CMs at post-MI weeks 1 and 2 (multiple doses). The sham group of animals underwent all surgical procedures necessary for MI induction except for ligation. Then 4 weeks after MI, heart function was measured with transthoracic echocardiography. Engraftment was evaluated through the detection of human-specific cardiac troponin T. Infarct size and collagen volume were calculated with Sirius Red/Fast Green staining. Angiogenesis was evaluated with isolectin B4 staining. Cardiac remodeling was evaluated from the cardiomyocyte minimal fiber diameter in the infarcted border zone. Apoptosis was detected via TdT-mediated dUTP Nick-End Labeling (TUNEL) staining in cardiomyocytes from the infarcted border zone.Results: No mice died after echocardiography-guided percutaneous left ventricular intramyocardial injection. hiPSC-CMs were about nine-fold higher in the multiple-dose group at week 4 compared to the single-dose group. Multiple-dose transplantation was associated with significant improvement in left ventricular function, infarct size, angiogenesis, cardiac remodeling, and cardiomyocyte apoptosis.Conclusion: Echocardiography-guided multiple percutaneous left ventricular intramyocardial injection is a feasible, satisfactory, repeatable, relatively less invasive, and effective method of delivering cell therapy. The delivery of hiPSC-CMs indicates a novel therapy for MI.
Optimization of a Low Volume Extraction Method to Determine Polycyclic Aromatic Hydrocarbons in Aerosol Samples
Authors: Scaramboni Caroline , Neris Jordan Brizi , do Nascimento Rita de Kássia Silva , Chiaranda da Rosa Natasha Leandra , Carvalho Jonatas Schadeck , Grosseli Guilherme Martins , Campos Maria Lucia Arruda Moura , Fadini Pedro Sérgio , Urban Roberta Cerasi 
Published: November 2021

This work describes the optimization of an extraction method for the determination of polycyclic aromatic hydrocarbons (PAHs) and their nitro- and oxy-PAH derivatives in atmospheric particulate matter (PM) samples, and demonstrates that this method is also effective for the determination of levoglucosan. The optimization of the extraction solvents was performed using a three-component mixture design with the solvents dichloromethane, methanol, and acetonitrile. The number of extractions, volume of solvent, and duration of extraction in an ultrasonic bath were optimized using a full factorial design followed by a central composite design. The analyses were performed by gas chromatography coupled with mass spectrometry. The optimized conditions of the method were three extractions using 4.0 ml of acetonitrile, with ultrasonication for 34 min. The proposed method presented good linearity (r &gt; 0.990) and acceptable precision for low (100 ng ml−1, RSD: 1–16%), medium (300 ng ml−1, RSD: 1–19%), and high (500 ng ml−1, RSD: 2–16%) concentrations of PAHs. The limits of quantification for different PAHs ranged from 10 to 50 ng ml−1, which were suitable for atmospheric PM. Assessment of the method using sample matrix spiking/recovery assays, as well as use of a reference method, showed good recoveries for levoglucosan and for most of the PAHs and their derivatives, except for the most volatile compounds, which were lost during the evaporation of the solvent. The results for PM samples extracted by the optimized method and the reference method were in good agreement. The proposed method required 97% less solvent than the reference method, shortened the analysis time by 85%, and proved to be accurate and precise for the determination of at least 27 PAHs and their derivatives present in PM samples collected with a low-volume sampler.
The Relative Early Decrease in Platelet Count Is Associated With Mortality in Post-cardiotomy Patients Undergoing Venoarterial Extracorporeal Membrane Oxygenation
Authors: Wang Liangshan , Shao Juanjuan , Shao Chengcheng , Wang Hong , Jia Ming , Hou Xiaotong 
Published: November 2021

Background: The relationship between the magnitude of platelet count decrease and mortality in post-cardiotomy cardiogenic shock (PCS) patients undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO) has not been well-reported. This study was designed to evaluate the association between the relative decrease in platelet count (RelΔplatelet) at day 1 from VA-ECMO initiation and in-hospital mortality in PCS patients.Methods: Patients (n = 178) who received VA-ECMO for refractory PCS between January 2016 and December 2018 at the Beijing Anzhen Hospital were reviewed retrospectively. Multivariable logistic regression analyses were performed to assess the association between RelΔplatelet and in-hospital mortality.Results: One hundred and sixteen patients (65%) were weaned from VA-ECMO, and 84 patients (47%) survived to hospital discharge. The median [interquartile range (IQR)] time on VA-ECMO support was 5 (3–6) days. The median (IQR) RelΔ platelet was 41% (26–59%). Patients with a RelΔ platelet ≥ 50% had an increased mortality compared to those with a RelΔ platelet &lt; 50% (57 vs. 37%; p &lt; 0.001). A large RelΔplatelet (≥50%) was independently associated with in-hospital mortality after controlling for potential confounders (OR 8.93; 95% CI 4.22–18.89; p &lt; 0.001). The area under the receiver operating characteristic curve for RelΔ platelet was 0.78 (95% CI, 0.71–0.85), which was better than that of platelet count at day 1 (0.69; 95% CI, 0.61–0.77).Conclusions: In patients receiving VA-ECMO for post-cardiotomy cardiogenic shock, a large relative decrease in platelet count in the first day after ECMO initiation is independently associated with an increased in-hospital mortality.
Development of a Structured Query Language and Natural Language Processing Algorithm to Identify Lung Nodules in a Cancer Centre
Authors: Hunter Benjamin , Reis Sara , Campbell Des , Matharu Sheila , Ratnakumar Prashanthi , Mercuri Luca , Hindocha Sumeet , Kalsi Hardeep , Mayer Erik , Glampson Ben , Robinson Emily J. , Al-Lazikani Bisan , Scerri Lisa , Bloch Susannah , Lee Richard 
Published: November 2021

Importance: The stratification of indeterminate lung nodules is a growing problem, but the burden of lung nodules on healthcare services is not well-described. Manual service evaluation and research cohort curation can be time-consuming and potentially improved by automation.Objective: To automate lung nodule identification in a tertiary cancer centre.Methods: This retrospective cohort study used Electronic Healthcare Records to identify CT reports generated between 31st October 2011 and 24th July 2020. A structured query language/natural language processing tool was developed to classify reports according to lung nodule status. Performance was externally validated. Sentences were used to train machine-learning classifiers to predict concerning nodule features in 2,000 patients.Results: 14,586 patients with lung nodules were identified. The cancer types most commonly associated with lung nodules were lung (39%), neuro-endocrine (38%), skin (35%), colorectal (33%) and sarcoma (33%). Lung nodule patients had a greater proportion of metastatic diagnoses (45 vs. 23%, p &lt; 0.001), a higher mean post-baseline scan number (6.56 vs. 1.93, p &lt; 0.001), and a shorter mean scan interval (4.1 vs. 5.9 months, p &lt; 0.001) than those without nodules. Inter-observer agreement for sentence classification was 0.94 internally and 0.98 externally. Sensitivity and specificity for nodule identification were 93 and 99% internally, and 100 and 100% at external validation, respectively. A linear-support vector machine model predicted concerning sentence features with 94% accuracy.Conclusion: We have developed and validated an accurate tool for automated lung nodule identification that is valuable for service evaluation and research data acquisition.
The VITAAL Stepping Exergame Prototype for Older Adults With Major Neurocognitive Disorder: A Usability Study
Authors: Swinnen Nathalie , de Bruin Eling D. , Dumoulin Chantal , Thalmann Melanie , Guimarães Vânia , De Jong Jacqueline , Vandenbulcke Mathieu , Vancampfort Davy 
Published: November 2021

Purpose:This study investigates the usability of a stepping exergame in older adults with major neurocognitive disorder (MNCD) residing in a long-term care facility.Materials and Methods:A mixed methods study was conducted. Participants played exergames for 30 min on one try-out session. During the exergames, the think aloud method was used, and field notes were taken by the facilitator. Following the exergames, participants completed the System Usability Scale (SUS) and a semi-structured in-depth interview about usability including their personal experiences. Audio files were transcribed and a thematic content analysis of the think aloud data, field notes and interviews were performed using NVivo 12.Results:Twenty-two participants with MNCD were included [mean age = 84.3 ± 5.5 (70–95) years; 81.8% women; Short Physical Performance Battery score = 7.5 ± 3.2 (1–12), Montreal Cognitive Assessment score = 11.9 ± 4.4 (2–19)]. System usability was rated “ok to good” with a mean SUS score of 57.8 (SD= 12.3) with scores ranging from 37.5 to 90.0. Five main themes emerged from the thematic content analysis: (1) perceived user friendliness and acceptability of the exergames; (2) interactional experience; (3) motivational factors; (4) training modalities; and (5) risks. There were no adverse events nor dropouts.Conclusion:Participants evaluated the usability of the exergames positively. The results indicate that the stepping exergame is usable in older adults with MNCD.