bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunosuppressed Miniswine as a Model for Testing Cell Therapy Success: Experience With Implants of Human Salivary Stem/Progenitor Cell Constructs
Authors: Wu Danielle , Lombaert Isabelle M. A. , DeLeon Maximilien , Pradhan-Bhatt Swati , Witt Robert L , Harrington Daniel Anton , Trombetta Mark G , Passineau Michael J , Farach-Carson Mary C. 
Published: September 2021

An urgent need exists to develop large animal models for preclinical testing of new cell therapies designed to replace lost or damaged tissues. Patients receiving irradiation for treatment of head and neck cancers frequently develop xerostomia/dry mouth, a condition that could one day be treated by cell therapy to repopulate functional saliva-producing cells. Using immunosuppression protocols developed for patients receiving whole face transplants, we successfully used immunosuppressed miniswine as a suitable host animal to evaluate the long-term stability, biocompatibility, and fate of matrix-modified hyaluronate (HA) hydrogel/bioscaffold materials containing encapsulated salivary human stem/progenitor cells (hS/PCs). An initial biocompatibility test was conducted in parotids of untreated miniswine. Subsequent experiments using hS/PC-laden hydrogels were performed in animals, beginning an immunosuppression regimen on the day of surgery. Implant sites included the kidney capsule for viability testing and the parotid gland for biointegration time periods up to eight weeks. No transplant rejection was seen in any animal assessed by analysis of the tissues near the site of the implants. First-generation implants containing only cells in hydrogel proved difficult to handle in the surgical suite and were modified to adhere to a porcine small intestinal submucosa (SIS) membrane for improved handling and could be delivered through the da Vinci surgical system. Several different surgical techniques were assessed using the second-generation 3D-salivary tissue (3D-ST) for ease and stability both on the kidney capsule and in the capsule-less parotid gland. For the kidney, sliding the implant under the capsule membrane and quick stitching proved superior to other methods. For the parotid gland, creation of a tissue “pocket” for placement and immediate multilayer tissue closure were well tolerated with minimal tissue damage. Surgical clips were placed as fiduciary markers for tissue harvest. Some implant experiments were conducted with miniswine 90 days post-irradiation when salivation decreased significantly. Sufficient parotid tissue remained to allow implant placement, and animals tolerated immunosuppression. In all experiments, viability of implanted hS/PCs was high with clear signs of both vascular and nervous system integration in the parotid implants. We thus conclude that the immunosuppressed miniswine is a high-value emerging model for testing human implants prior to first-in-human trials.
Correlation Between Serum Concentrations of Menaquinone-4 and Developmental Quotients in Children With Autism Spectrum Disorder
Authors: Dong Hanyu , Wang Bing , Feng Junyan , Yue Xiaojing , Jia Feiyong 
Published: September 2021

Objective: The vitamin K family has a wide range of effects in the body, including the central nervous system. Menaquinone-4 (MK-4), a form of vitamin K2, is converted from phylloquinone (PK), which is the main source of dietary vitamin K and is the main form of vitamin K in the brain. We conducted this study to investigate the serum concentration of MK-4 and the correlations between MK-4 and developmental quotients in children with autism spectrum disorder (ASD).Methods: We selected 731 children with ASD who were diagnosed for the first time. During the same period, 332 neurotypical children who underwent regular physical examinations in our outpatient department were selected as the TD group. We investigated the general situation of children, including gender and age. Children in ASD group were assessed for autistic symptoms and development quotients, including Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), ADOS-2, and Griffiths Development Scales-Chinese Language Edition (GDS-C). Both groups of children were tested for serum menaquinone-4. We compared serum menaquinone-4 levels of ASD group and TD group. We then conducted a correlation analysis between the level of menaquinone-4 and the developmental quotient of children with ASD.Results: The results of this study indicate that the serum concentration of MK-4 in children with ASD is lower than that in children with typical development (t = −2.702, P = 0.007). The serum concentration of MK-4 is related to the developmental quotients of several subscales in ASD children, and this correlation is more obvious in males.Conclusion: we conclude that MK-4 is present in lower concentrations in children with ASD, which may affect cognition and developmental quotients. The role of MK-4 in ASD needs to be further explored.
The Balance Between the Effectiveness and Safety for Chemotherapy-Induced Nausea and Vomiting of Different Doses of Olanzapine (10 mg Versus 5 mg): A Systematic Review and Meta-Analysis
Authors: Wang Dong-Yang , Chen Yi , Zhang You , Shen Ying-Qiang 
Published: September 2021

IntroductionThe aim of this study is to rigorously review the efficacy and safety of olanzapine in chemotherapy-induced nausea and vomiting (CINV) settings including (1) at 5- and 10-mg doses, and (2) the setting of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).MethodsEmbase, Pubmed, and Cochrane Library were searched from the establishment of the database through April 18, 2021. The primary efficacy endpoints were the rate of complete response (CR; no emesis and no rescue), in the acute (0–24 h post-chemotherapy), delayed (24–120 h post-chemotherapy), and overall (0–120 h post-chemotherapy) phases. The secondary efficacy endpoints were the rates of complete control (CC, no nausea, and no emesis), for each phase. Safety endpoints were the rate of somnolence, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) criteria. The Mantel–Haenszel, random, or fixed-effect analysis model was used to compute risk ratios and accompanying 95% confidence intervals for each endpoint. For endpoints that statistically favored one arm, absolute risk differences were computed to assess whether there is a 10% or greater difference, used as the threshold for clinical significance by MASCC/ESMO.ResultNine studies reported the use of 10 mg olanzapine to prevent CINV; three studies reported the use of 5 mg olanzapine to prevent CINV. When olanzapine was administered at 10 mg for HEC patients, the six endpoints were statistically and clinically better than the control group. For MEC patients, four out of six endpoints were better than the control group. When olanzapine is administered at 5 mg for MEC patients, four endpoints have statistical and clinical advantages. The sedative effects of 10 and 5 mg olanzapine were statistically more significant than those of the control group. The sedative effect of the 10-mg olanzapine group was more significant than that of the 5-mg olanzapine group, both statistically and clinically.Conclusion5 mg olanzapine may be as effective as 10 mg olanzapine for patients with HEC and MEC, and its sedative effect is lower than 10 mg olanzapine. Fewer studies on 5 mg olanzapine have led to uncertain data. In the future, more randomized controlled trials of 5 mg olanzapine are needed to study the balance between the effectiveness and safety of olanzapine.
68Ga-Labeled GX1 Dimer: A Novel Probe for PET/Cerenkov Imaging Targeting Gastric Cancer
Authors: Yin Jipeng , Xin Bo , Zhang Mingru , Hui Xiaoli , Chai Na , Hu Hao , Xu Bing , Wang Jing , Nie Yongzhan , Zhou Guangqing , Wang Guanliang , Lu Hongbing , Yao Liping , Chen Liusheng , Wu Kaichun 
Published: September 2021

PurposeTo synthesize the dimer of GX1 and identify whether its affinity and targeting are better than those of GX1. To prepare 68Ga-DOTA-KEK-(GX1)2 and to apply it to PET and Cerenkov imaging of gastric cancer.Methods68Ga-DOTA-KEK-(GX1)2 was prepared, and the labeling yield and stability were determined. Its specificity and affinity were verified using an in vitro cell binding assay and competitive inhibition test, cell immunofluorescence, and cell uptake and efflux study. Its tumor-targeting ability was determined by nano PET/CT and Cerenkov imaging, standardized uptake value (SUV), signal-to-background ratio (SBR) quantification, and a biodistribution study in tumor-bearing nude mice.Results68Ga-DOTA-KEK-(GX1)2 was successfully prepared, and the labeling yield was more than 97%. It existed stably for 90 min in serum. The binding of 68Ga-DOTA-KEK-(GX1)2 to cocultured HUVECs (Co-HUVECs) was higher than that to human umbilical vein endothelial cells (HUVECs), BGC823 cells, and GES cells. It was also higher than that of 68Ga-DOTA-GX1, indicating that the dimer did improve the specificity and affinity of GX1. The binding of KEK-(GX1)2 to Co-HUVECs was significantly higher than that of GX1. Additionally, the uptake of 68Ga-DOTA-KEK-(GX1)2 by Co-HUVECs was higher than that of 68Ga-DOTA-GX1 and reached a maximum at 60 min. Nano PET/CT and Cerenkov imaging showed that the tumor imaging of the nude mice injected with 68Ga-DOTA-KEK-(GX1)2 was clear, and the SUV and SBR value of the tumor sites were significantly higher than those of the nude mice injected with 68Ga-DOTA-GX1, indicating that the probe had better targeting in vivo. Finally, the biodistribution showed quantitatively that when organs such as the kidney and liver metabolized rapidly, the radioactivity of the tumor site of the nude mice injected with 68Ga-DOTA-KEK-(GX1)2 decreased relatively slowly. At the same time, the percentage of injected dose per gram (%ID/g) of the tumor site was higher than that of other normal organs except the liver and kidney at 60 min, which indicated that the tumor had good absorption of the probe.ConclusionGX1 was modified successfully, and the in vivo and in vitro properties of the GX1 dimer were significantly better than those of GX1. The imaging probe, 68Ga-DOTA-KEK-(GX1)2, was successfully prepared, which provides a candidate probe for PET and Cerenkov diagnosis of gastric cancer.
Decreased Incidence of Intraventricular Hemorrhage in Extremely Low Birth Weight Infants Using Customized Circulatory Management to Evaluate the Hemodynamic Change of Patent Ductus Arteriosus
Authors: Huang Wan-Heng , Li De-Ming , Hsu Chung-Ting , Lin Yi-Hsuan , Hsu Ya-Chi , Wang Teh-Ming , Lin Ming-Chih 
Published: September 2021

Background:In extremely low birth weight (ELBW) infants, the patent ductus arteriosus (PDA) with left-to-right shunt and an increase in systemic artery resistance may cause increasing preload and afterload of the left ventricle. The immature myocardium in ELBW infants has a limited ability to respond to the change, which leads to hemorrhagic complications. In this study, we detected the hemodynamic change of cardiac performance and applied a clinical strategy to prevent PDA-associated hemorrhagic complications in ELBW infants.Methods:We enrolled ELBW infants at a single medical center in Taiwan. The customized circulatory management was performed by echocardiography after birth until the PDA closed. Inotropic agents were administrated according to the requirements of hemodynamic parameters or clinical conditions. The primary outcomes were hemorrhagic complications including pulmonary hemorrhage and intraventricular hemorrhage (IVH) greater than grade II. The secondary outcomes were the rate of surgical ligation of PDA, mortality, necrotizing enterocolitis, and bronchopulmonary dysplasia.Results:A total of 20 ELBW infants were evaluated by customized circulatory management from 2019 to 2020. We reviewed 35 ELBW infants born between 2017 and 2018 in our hospital, who served as the non-management group. The management group had a significantly lower incidence rate of IVH greater than grade 2 (p= 0.02). Other outcomes showed no significant differences. Dobutamine was prescribed in 8 cases in the management group, and end-systolic wall stress (ESWS) was significantly decreased after Dobutamine administration (p= 0.017).Conclusion:The incidence rate of IVH greater than grade II in ELBW infants decreased after use of customized circulatory management in our study. The strategy of customized circulatory management might be an effective “early target therapy” for hemodynamically significant PDA in high-risk ELBW infants. Inotropic therapy with Dobutamine could be a useful medical choice for improving cardiac function to prevent hemorrhagic complications.
Parental Stress, Depression, and Participation in Care Before and During the COVID-19 Pandemic: A Prospective Observational Study in an Italian Neonatal Intensive Care Unit
Authors: Bua Jenny , Mariani Ilaria , Girardelli Martina , Tomadin Murphy , Tripani Antonella , Travan Laura , Lazzerini Marzia 
Published: September 2021

Background: Recent studies reported, during the COVID-19 pandemic, increased mental distress among the general population and among women around the childbirth period. COVID-19 pandemic may undermine the vulnerable well-being of parents in Neonatal Intensive Care Units (NICUs).Objective: Our study aimed to explore whether parental stress, depression, and participation in care in an Italian NICU changed significantly over three periods: pre-pandemic (T0), low (T1), and high COVID-19 incidence (T2).Methods: Enrolled parents were assessed with the Parental Stressor Scale in the NICU (PSS:NICU), Edinburgh Postnatal Depression Scale (EPDS), and Index of Parental Participation (IPP). Stress was the study primary outcome. A sample of 108 parents, 34 for each time period, was estimated to be adequate to detect a difference in PSS:NICU stress occurrence level score (SOL) of 1.25 points between time periods. To estimate score differences among the three study periods a non-parametric analysis was performed. Correlation among scores was assessed with Spearman rank coefficient.Results: Overall, 152 parents were included in the study (62 in T0, 56 in T1, and 34 in T2). No significant differences in the median PSS:NICU, EPDS, and IPP scores were observed over the three periods, except for a slight increase in the PSS:NICU parental role sub-score in T2 (T0 3.3 [2.3–4.1] vs. T2 3.9 [3.1–4.3]; p = 0.038). In particular, the question regarding the separation from the infant resulted the most stressful aspect during T2 (T0 4.0 [4.0–5.0] vs. T2 5.0 [4.0–5.0], p = 0.008). The correlation between participation and stress scores (r = 0.19–022), and between participation and depression scores (r = 0.27) were weak, while among depression and stress, a moderate positive correlation was found (r = 0.45–0.48).Conclusions: This study suggests that parental stress and depression may be contained during the COVID-19 pandemic, while participation may be ensured.
Eicosanoid Metabolomic Profile of Remdesivir Treatment in Rat Plasma by High-Performance Liquid Chromatography Mass Spectrometry
Authors: Du Ping , Wang Guo-yong , Zhao Rui , An Zhuo-ling , Liu Li-hong 
Published: September 2021

Remdesivir, a nucleotide analog prodrug, has displayed pharmacological activity against SARS-CoV-2. Recently, eicosanoids are widely involved in regulating immunity and inflammation for COVID-19 patients. Rats were intravenously administered remdesivir at a dose of 5 mg/kg, and series of blood samples were collected before and after treatment. Targeted metabolomics regarding the eicosanoid profile were investigated and quantitated simultaneously using the previously reported reliable HPLC-MS/MS method. Additionally, interplay relationship between metabolomics and pharmacokinetic parameters was performed using the Pearson correlation analysis and PLS model. For the longitudinal metabolomics of remdesivir, metabolic profiles of the same rat were comparatively substantial at discrete sampling points. The metabolic fingerprints generated by individual discrepancy of rats were larger than metabolic disturbance caused by remdesivir. As for the transversal metabolomics, the prominent metabolic profile variation was observed between the baseline and treatment status. Except for TXB2, the inflammatory- and immunology-related eicosanoids of resolvin D2, 5-HEPE, 5-HETE, and DHA were significantly disturbed and reduced after single administration of remdesivir (p &lt; 0.05, p &lt; 0.001). Moreover, the metabolite of PGE2 correlated with GS-441524 (active metabolite of remdesivir) concentration and pharmacokinetic parameters of Cmax, AUC0-t, AUC0-infinity, and CL significantly. Eicosanoid metabolic profiles of remdesivir at both longitudinal and transversal levels were first revealed using the robust HPLC-MS/MS method. This initial observational eicosanoid metabolomics may lighten the therapy for fighting COVID-19 and further provide mechanistic insights of SARS-CoV-2 virus infection.
Protease-Activated Receptor-1 Antagonist Protects Against Lung Ischemia/Reperfusion Injury
Authors: Chu Shi-Jye , Tang Shih-En , Pao Hsin-Ping , Wu Shu-Yu , Liao Wen-I 
Published: September 2021

Protease-activated receptor (PAR)-1 is a thrombin-activated receptor that plays an essential role in ischemia/reperfusion (IR)-induced acute inflammation. PAR-1 antagonists have been shown to alleviate injuries in various IR models. However, the effect of PAR-1 antagonists on IR-induced acute lung injury (ALI) has not yet been elucidated. This study aimed to investigate whether PAR-1 inhibition could attenuate lung IR injury. Lung IR was induced in an isolated perfused rat lung model. Male rats were treated with the specific PAR-1 antagonist SCH530348 (vorapaxar) or vehicle, followed by ischemia for 40 min and reperfusion for 60 min. To examine the role of PAR-1 and the mechanism of SCH530348 in lung IR injury, western blotting and immunohistochemical analysis of lung tissue were performed. In vitro, mouse lung epithelial cells (MLE-12) were treated with SCH530348 or vehicle and subjected to hypoxia-reoxygenation (HR). We found that SCH530348 decreased lung edema and neutrophil infiltration, attenuated thrombin production, reduced inflammatory factors, including cytokine-induced neutrophil chemoattractant-1, interleukin-6 and tumor necrosis factor-α, mitigated lung cell apoptosis, and downregulated the phosphoinositide 3-kinase (PI3K), nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in IR-injured lungs. In addition, SCH530348 prevented HR-induced NF-κB activation and inflammatory chemokine production in MLE12 cells. Our results demonstrate that SCH530348 exerts protective effects by blocking PAR-1 expression and modulating the downstream PI3K, NF-κB and MAPK pathways. These findings indicate that the PAR-1 antagonist protects against IR-induced ALI and is a potential therapeutic candidate for lung protection following IR injury.
Actuators for MRE: New Perspectives With Flexible Electroactive Materials
Authors: Gnanago Jean-Lynce , Capsal Jean-Fabien , Gerges Tony , Lombard Philippe , Semet Vincent , Cottinet Pierre-Jean , Cabrera Michel , Lambert Simon Auguste 
Published: September 2021

Since 1995, Magnetic Resonance Elastography (MRE) has been constantly developed as a non-invasive diagnostic tool for quantitative mapping of mechanical properties of biological tissues. Indeed, mechanical properties of tissues vary over five orders of magnitude (the shear stiffness is ranging from 102 Pa for fat to 107 Pa for bones). Additionally, these properties depend on the physiological state which explains the granted benefit of MRE for staging liver fibrosis and its potential in numerous medical and biological domains. In comparison to the other modalities used to perform such measurement, Magnetic Resonance (MR) techniques offer the advantages of acquiring 3D high spatial resolution images at high penetration depth. However, performing MRE tissue characterization requires low frequency shear waves propagating in the tissue. Inducing them is the role of a mechanical actuator specifically designed to operate under Magnetic Resonance Imaging (MRI) specific restrictions in terms of electromagnetic compatibility. Facing these restrictions, many different solutions have been proposed while keeping a common structure: a vibration generator, a coupling device transmitting the vibration and a piston responsible for the mechanical coupling of the actuator with the tissue. The following review details the MRI constraints and how they are shaping the existing actuators. An emphasis is put on piezoelectric solutions as they solve the main issues encountered with other actuator technologies. Finally, flexible electroactive materials are reviewed as they could open great perspectives to build new type of mechanical actuators with better adaptability, greater ease-of-use and more compactness of dedicated actuators for MRE of small soft samples and superficial organs such as skin, muscles or breast.
Immersive Virtual Reality Influences Physiologic Responses to Submaximal Exercise: A Randomized, Crossover Trial
Authors: Rutkowski Sebastian , Szary Patryk , Sacha Jerzy , Casaburi Richard 
Published: September 2021

Objectives: This cross-sectional, randomly assigned study aimed to assess the influence of immersive virtual reality (VR) on exercise tolerance expressed as the duration of a submaximal exercise test (ET) on a cycle ergometer.Methods: The study enrolled 70 healthy volunteers aged 22–25years. Each participant performed an ET with and without VR. Time- and frequency-domain heart rate variability (HRV) parameters were analyzed for the first 3min (T1), the last 3min (T2), and the time at which the shorter of the two tests terminated (Tiso). In the time domain, a SD of R–R intervals (SDNN) and a root mean square of successive R–R interval differences (RMSSD) in milliseconds were computed. The following spectral components were considered: low frequency (LF), high frequency (HF), total power (TP), and LF/HF ratio. The study was registered in ClinicalTrials.gov (NCT04197024).Results: Compared to standard ET, tests in immersive VR lasted significantly longer (694 vs. 591s, p&lt;0.00001) and were associated with lower HR response across the range of corresponding exercise levels, averaging 5–8 beats/min. In the multiple regression analysis, the ET duration was positively determined by male sex, immersion in VR, and negatively determined by HRT1 and RMSSDT1.Conclusion: Exercising in VR is associated with lower HR which allowed subjects to exercise for a longer time before reaching target heart rate (HR). In addition, the increase in exercise duration was found to be related to an adjustment in autonomic nervous activity at a given work rate favoring parasympathetic predominance.