bluuebunny/crossref_metadata_2025_split huggingface dataset:
LAT1 Protein Content Increases Following 12 Weeks of Resistance Exercise Training in Human Skeletal Muscle
Authors: Roberson Paul A. , Mobley C. Brooks , Romero Matthew A. , Haun Cody T. , Osburn Shelby C. , Mumford Petey W. , Vann Christopher G. , Greer Rory A. , Ferrando Arny A. , Roberts Michael D. 
Published: January 2021

Introduction: Amino acid transporters are essential for cellular amino acid transport and promoting protein synthesis. While previous literature has demonstrated the association of amino acid transporters and protein synthesis following acute resistance exercise and amino acid supplementation, the chronic effect of resistance exercise and supplementation on amino acid transporters is unknown. The purpose herein was to determine if amino acid transporters and amino acid metabolic enzymes were related to skeletal muscle hypertrophy following resistance exercise training with different nutritional supplementation strategies.Methods: 43 college-aged males were separated into a maltodextrin placebo (PLA, n = 12), leucine (LEU, n = 14), or whey protein concentrate (WPC, n = 17) group and underwent 12 weeks of total-body resistance exercise training. Each group's supplement was standardized for total energy and fat, and LEU and WPC supplements were standardized for total leucine (6 g/d). Skeletal muscle biopsies were obtained prior to training and ~72 h following each subject's last training session.Results: All groups increased type I and II fiber cross-sectional area (fCSA) following training (p &lt; 0.050). LAT1 protein increased following training (p &lt; 0.001) and increased more in PLA than LEU and WPC (p &lt; 0.050). BCKDHα protein increased and ATF4 protein decreased following training (p &lt; 0.001). Immunohistochemistry indicated total LAT1/fiber, but not membrane LAT1/fiber, increased with training (p = 0.003). Utilizing all groups, the change in ATF4 protein, but no other marker, trended to correlate with the change in fCSA (r = 0.314; p = 0.055); however, when regression analysis was used to delineate groups, the change in ATF4 protein best predicted the change in fCSA only in LEU (r2 = 0.322; p = 0.043). In C2C12 myoblasts, LAT1 protein overexpression caused a paradoxical decrease in protein synthesis levels (p = 0.002) and decrease in BCKDHα protein (p = 0.001).Conclusions: Amino acid transporters and metabolic enzymes are affected by resistance exercise training, but do not appear to dictate muscle fiber hypertrophy. In fact, overexpression of LAT1 in vitro decreased protein synthesis.
Early Toxicities After High Dose Rate Proton Therapy in Cancer Treatments
Authors: Doyen Jérôme , Sunyach Marie-Pierre , Almairac Fabien , Bourg Véronique , Naghavi Arash O. , Duhil de Bénazé Gwenaëlle , Claren Audrey , Padovani Laetitia , Benezery Karen , Noël Georges , Hannoun-Lévi Jean-Michel , Guedea Ferran , Giralt Jordi , Vidal Marie , Baudin Guillaume , Opitz Lucas , Claude Line , Bondiau Pierre-Yves 
Published: January 2021

BackgroundThe conventional dose rate of radiation therapy is 0.01–0.05 Gy per second. According to preclinical studies, an increased dose rate may offer similar anti-tumoral effect while dramatically improving normal tissue protection. This study aims at evaluating the early toxicities for patients irradiated with high dose rate pulsed proton therapy (PT).Materials and MethodsA single institution retrospective chart review was performed for patients treated with high dose rate (10 Gy per second) pulsed proton therapy, from September 2016 to April 2020. This included both benign and malignant tumors with ≥3 months follow-up, evaluated for acute (≤2 months) and subacute (&gt;2 months) toxicity after the completion of PT.ResultsThere were 127 patients identified, with a median follow up of 14.8 months (3–42.9 months). The median age was 55 years (1.6–89). The cohort most commonly consisted of benign disease (55.1%), cranial targets (95.1%), and were treated with surgery prior to PT (56.7%). There was a median total PT dose of 56 Gy (30–74 Gy), dose per fraction of 2 Gy (1–3 Gy), and CTV size of 47.6 ml (5.6–2,106.1 ml). Maximum acute grade ≥2 toxicity were observed in 49 (38.6%) patients, of which 8 (6.3%) experienced grade 3 toxicity. No acute grade 4 or 5 toxicity was observed. Maximum subacute grade 2, 3, and 4 toxicity were discovered in 25 (19.7%), 12 (9.4%), and 1 (0.8%) patient(s), respectively.ConclusionIn this cohort, utilizing high dose rate proton therapy (10 Gy per second) did not result in a major decrease in acute and subacute toxicity. Longer follow-up and comparative studies with conventional dose rate are required to evaluate whether this approach offers a toxicity benefit.
Case Report: Management Approach and Use of Extracorporeal Membrane Oxygenation for Diffuse Alveolar Hemorrhage After Pediatric Hematopoietic Cell Transplant
Authors: Fan Kimberly , Hurley Caitlin , McNeil Michael J. , Agulnik Asya , Federico Sara , Qudeimat Amr , Saini Arun , McArthur Jennifer , Morrison Ronald Ray , Sandhu Hitesh , Shah Samir , Ghafoor Saad 
Published: January 2021

Introduction:Diffuse alveolar hemorrhage (DAH) is an early pulmonary complication of hematopoietic cell transplantation (HCT) associated with severe hypoxemic respiratory failure and mortality. Extracorporeal membrane oxygenation (ECMO) support is often used for respiratory failure refractory to conventional interventions; however, its use has been limited in HCT patients with DAH due to potential for worsening alveolar hemorrhage and reported high mortality.Case Presentation:We report two cases of DAH following HCT who developed refractory hypoxemic respiratory failure despite cessation of bleeding and were successfully supported with ECMO.Conclusion:DAH after HCT should not automatically preclude ECMO support; rather, these patients must be evaluated individually for ECMO within the context of their overall clinical picture.
Dihydropyridine Calcium Channel Blockers Suppress the Transcription of PD-L1 by Inhibiting the Activation of STAT1
Authors: Pan Xiaohui , Li Run , Guo Hongjie , Zhang Wenxin , Xu Xiaqing , Chen Xi , Ding Ling 
Published: January 2021

Programmed death ligand 1 (PD-L1) which is upregulated in various epithelial tumors, plays a central role in the evasion of the immune system. In addition to monoclonal antibodies that blocking PD1/PD-L1 axis, finding small molecule compounds that can suppress PD-L1 expression might be another substitutable strategy for PD1/PD-L1 based therapy. Here, we found that dihydropyridine calcium channel blockers dose-dependently reduced the expression of PD-L1, both in the cytoplasm and cell surface. IFNγ induced PD-L1 transcription was consistently suppressed by Lercanidipine in 24 h, whereas, the half-life of PD-L1 protein was not significantly affected. IFNγ trigged significant STAT1 phosphorylation, which was eliminated by Lercanidipine. Similarly, STAT1 phosphorylation could also be abolished by extracellular calcium chelating agent EGTA and intracellular calcium chelator BAPTA-AM. Furthermore, Lercanidipine enhanced killing ability of T cells by down-regulating PD-L1. Taken together, our studies suggest that calcium signal is a crucial factor that mediates the transcription of PD-L1 and regulation of calcium can be used as a potential strategy for PD-L1 inhibition.
Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in Rats
Authors: Zhang Wenchao , Liu Jianwei , Fu Yang , Ji Huifang , Fang Zheyan , Zhou Wanming , Fan Huimin , Zhang Yingxuan , Liao Yan , Yang Ting , Wang Xiaolin , Yuan Wanwan , Chen Xiaoshu , Dong Yi-fei 
Published: January 2021

Previous studies have confirmed the clinical efficacy of sacubitril/valsartan (Sac/Val) for the treatment of heart failure with reduced ejection fraction (HFrEF). However, the role of Sac/Val in heart failure with preserved ejection fraction (HFpEF) remains unclear. Sac/Val is a combination therapeutic medicine comprising sacubitril and valsartan that acts as a first angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor (ARNI)). Here, we investigated the role of Sac/Val in high-salt diet-induced HFpEF coupled with vascular injury as well as the underlying mechanism. Rats were fed with high-salt feed, followed by intragastric administration of Sac/Val (68 mg/kg; i.g.). The results of functional tests revealed that a high-salt diet caused pathological injuries in the heart and vascular endothelium, which were significantly reversed by treatment with Sac/Val. Moreover, Sac/Val significantly decreased the levels of fibrotic factors, including type I collagen and type Ⅲ collagen, thus, reducing the ratio of MMP2/TIMP2 while increasing Smad7 levels. Further investigation suggested that Sac/Val probably reversed the effects of high-salt diet-induced HFpEF by inhibiting the activation of the TGF-β1/Smad3 signaling pathway. Thus, treatment with Sac/Val effectively alleviated the symptoms of high-salt diet-induced HFpEF, probably by inhibiting fibrosis via the TGF-β1/Smad3 signaling pathway, supporting the therapeutic potential of Sac/Val for the treatment of HFpEF.
CPEB4-Promoted Paclitaxel Resistance in Ovarian Cancer In Vitro Relies on Translational Regulation of CSAG2
Authors: Zhang Yaqing , Gan Hongyun , Zhao Fei , Ma Xiaomei , Xie Xiaofeng , Huang Rui , Zhao Jin 
Published: January 2021

Background: Drug resistance is a major obstacle in chemotherapy for ovarian cancer, wherein the up regulation of drug-resistant genes plays an important role. The cytoplasmic polyadenylation element binding protein 4 (CPEB4) is an RNA binding protein that controls mRNA cytoplasmic polyadenylation and translation.Methods: The expression of CPEB4 in paclitaxel-resistant ovarian cancer cell lines and recurrent ovarian tumors relative to counterparts was determined by qRT-PCR, Western blotting and immunohistochemistry. The response to paclitaxel treatment was evaluated by cellular viability test and colony formation assay. RNA immunoprecipitation and poly(A) tail test were applied to examine the levels of RNA binding and cytoplasmic polyadenylation.Results: CPEB4 is elevated in paclitaxel-resistant ovarian cancer cells and recurrent ovarian tumors treated with paclitaxel-based chemotherapy. In addition, CPEB4 overexpression promotes paclitaxel resistance in ovarian cancer cells in vitro, and vice versa, CPEB4 knockdown restores paclitaxel sensitivity, indicating that CPEB4 confers paclitaxel resistance in ovarian cancer cells. Mechanistically, CPEB4 binds with the taxol (paclitaxel)-resistance-associated gene-3 (TRAG-3/CSAG2) mRNAs and induces its expression at a translational level. Moreover, CSAG2 expression is upregulated in paclitaxel-resistant ovarian carcinoma and cancer cell lines, and more importantly, siRNA-mediated CSAG2 knockdown overtly attenuates CPEB4-mediated paclitaxel resistance.Conclusion: This study suggests that the drug-resistant protein CSAG2 is translationally induced by CPEB4, which underlies CPEB4-promoted paclitaxel resistance in ovarian cancer in vitro. Thus, interfering CPEB4/CSAG2 axis might be of benefit to overcome paclitaxel-resistant ovarian cancer.
Time-Dependent Distribution of Hydroxychloroquine in Cynomolgus Macaques Using Population Pharmacokinetic Modeling Method
Authors: Liu Qi , Bi Guofang , Chen Guiying , Guo Xuan , Tu Siqi , Tong Xiaolin , Xu Man , Liu Mengjie , Wang Bei , Jiang Hongliang , Wang Jufeng , Li Haiyan , Wang Kun , Liu Dongyang , Song Chunli 
Published: January 2021

To evaluate the biodistribution of hydroxychloroquine (HCQ) in cynomolgus macaques and receive dynamic quantitative relationship between plasma, blood, and lung tissue concentration using the population pharmacokinetic modeling method, seventeen cynomolgus macaques were divided into six groups according to different HCQ dosing regimens over 5 days. The monkeys were euthanized, and blood, plasma, urine, feces and ten tissues were collected. All the samples were prepared by protein precipitation and analyzed by HPLC-MS/MS detection. The population pharmacokinetics of HCQ in the plasma, red blood cells, and lung tissue was conducted and simulated via ADAPT program. Results demonstrated that the maximum concentration (Cmax) of HCQ was 292.33 ng/mL in blood and 36.90 ng/mL in plasma after single dose of 3 mg/kg. The value of area under curve (AUC0–∞) was determined as 5,978.94 and 363.31 h* ng/mL for the blood and plasma, respectively. The descending order of the tissue-to-plasma concentration ratio was liver &gt; spleen &gt; kidney &gt; lung &gt; heart &gt; subcutaneous fat &gt; brain. The tissue-to-plasma concentration ratio and the tissue-to-blood concentration ratio for lung were found to be time-dependent with 267.38 and 5.55 at 120 h postdose, respectively. A five-compartment model with first-order oral absorption and elimination best described the plasma, blood, and lung tissue pharmacokinetics. The estimated elimination rate constant (ke) for a typical monkey was 0.236 h−1. The volume of distribution in central (Vc/F) and other two peripheral compartments (Vb/F and Vl/F) were 114, 2.68, and 5.55 L, respectively. Model-based simulation with PK parameters from cynomolgus macaques showed that the ratio of the blood or plasma to lung tissue was a dynamic change course, which suggested that the rate of HCQ concentration decrease in the blood or plasma was faster than that in the lung tissue. HCQ was found to be accumulated in tissues, especially in the liver, kidney, lung, and spleen. Also, the tissue-to-plasma concentration ratio increased over time. The population pharmacokinetic model developed could allow for the assessment of pharmacokinetics–pharmacodynamics relationships, especially relevant tissue concentration-response for HCQ. Determining appropriate treatment regimens in animals allows translation of these to clinical studies.
Determination and Pharmacokinetic Profiles of Four Active Components From Scrophularia ningpoensis Hemsl. in Rats
Authors: Luo Shunbin , Xie Lingping , Chen Jingjing , Tang Congrong , Xu Ren-ai 
Published: January 2021

Acteoside, angoroside C, harpagoside, and cinnamic acid, which are the main bioactive ingredients of Scrophularia ningpoensis Hemsl., have wide clinical use with various biological effects. A new and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established with taxifolin as the internal standard (IS) in this study and was successfully used to study the pharmacokinetic profiles of four active components from S. ningpoensis Hemsl. in rats after sublingual intravenous administration. After protein precipitation with acetonitrile, the mobile phase (consisting of acetonitrile and 0.1% formic acid) was used to separate the analytes on an Acquity UPLC BEH C18 chromatography column (2.1 × 50 mm, 1.7 μm) under gradient elution. The precursor-to-product ion transitions of 623.4 → 161.3 m/z for acteoside, 783.5 → 175.0 m/z for angoroside C, 493.3 → 345.2 m/z for harpagoside and 147.2 → 103.4 m/z for cinnamic acid were monitored by mass spectrometry with negative electrospray ionization in the multiple reaction monitoring (MRM) mode. The concentration range of 10–1,000 ng/ml could be detected by this method with a lower limit of quantification (LLOQ) of 10 ng/ml for each analyte. The intra- and inter-day precision (RSD%) of the method ranged from 2.6 to 9.9% and 2.7–11.5%, respectively. Meanwhile, the accuracy (RE%) was −9.6–10.7% in this developed method. The mean recoveries of four active components from S. ningpoensis Hemsl. were more than 76.7% with negligible matrix effects. The four active components from S. ningpoensis Hemsl. were stable under multiple storage and process conditions. A new, sensitive and simple analytical method had been established and was successfully applied to the pharmacokinetic profiles of four active components from S. ningpoensis Hemsl. in rats after sublingual intravenous administration.
Deep Learning Assisted Zonal Adaptive Aberration Correction
Authors: Zhang Biwei , Zhu Jiazhu , Si Ke , Gong Wei 
Published: January 2021

Deep learning (DL) has been recently applied to adaptive optics (AO) to correct optical aberrations rapidly in biomedical imaging. Here we propose a DL assisted zonal adaptive correction method to perform corrections of high degrees of freedom while maintaining the fast speed. With a trained DL neural network, the pattern on the correction device which is divided into multiple zone phase elements can be directly inferred from the aberration distorted point-spread function image in this method. The inference can be completed in 12.6 ms with the average mean square error 0.88 when 224 zones are used. The results show a good performance on aberrations of different complexities. Since no extra device is required, this method has potentials in deep tissue imaging and large volume imaging.
An Investigation of the Coherence of Oral Narratives: Associations With Mental Health, Social Support and the Coherence of Written Narratives
Authors: Vanaken Lauranne , Bijttebier Patricia , Hermans Dirk 
Published: January 2021

Research QuestionsIn a first research question, we examined whether the relations that are generally observed between the coherence of written autobiographical narratives and outcomes of mental health and social support, can be replicated for the coherence of oral narratives. Second, we studied whether the coherence of oral narratives is related to the coherence of written narratives.MethodsPearson correlations and t-tests were calculated on data of two separate studies to examine the research questions.ResultsFirst, only thematic coherence of oral narratives was significantly, although moderately, negatively associated to symptoms of depression, anxiety and negative social interactions. Second, the coherence of oral narratives was higher than the coherence of written narratives. Only the thematic coherence of oral narratives was positively associated with thematic and total coherence of written narratives. Furthermore, correlations between written and oral narratives were stronger for negative narratives as compared to positive narratives.DiscussionThe ability to elaborate emotionally and make meaning out of important life events in oral narratives is, to a certain extent, related to better mental health and more social support. Furthermore, thematic coherence may be a relatively stable feature of individuals’ narrative styles that is reflected in narratives of different modalities. Nonetheless, these topics need to be further researched to overcome present limitations.
Current Addiction in Youth: Online Sports Betting
Authors: Aragay Núria , Pijuan Laia , Cabestany Àngela , Ramos-Grille Irene , Garrido Gemma , Vallès Vicenç , Jovell-Fernández Esther 
Published: January 2021

Background: Gambling landscape has changed in recent years with the emergence of online gambling (OG). Greater accessibility and availability of this betting modality can increase the risk of developing a gambling disorder (GD). Online sports betting (OSB) is currently the most common type of OG, but little is known about the clinical characteristics of OSB compared to slot-machine (SM) gamblers, the most common offline gambling disorder.Methods: This was a prospective study conducted between October 2005 and September 2019, and included outpatients diagnosed with GD seen in a Pathological Gambling and Behavioral Addictions referral unit. Only patients with OSB and SM disorders were included. The main objective was to assess the clinical profile of OSB compared to SM gamblers, and to define clinical predictors for developing OSB gambling disorder. Logistic regression was performed to determine the effects of variables on the likelihood of this disorder.Results: Among 1,186 patients attended in our Unit during the study period, 873 patients were included; 32 (3.7%) were OSB gamblers and 841 (96.3%) were SM gamblers. Overall, mean age was 45 ± 13 years and 94.3% were men. Compared to SM patients, OSB patients were younger (34.9 ± 9.5 vs. 45.3 ±13), more frequently single (43.8 vs. 20.6%) and had a university education level (43.8 vs. 4.5%); they were also more frequently non-smokers (18.7 vs. 66.7%) and had fewer psychiatric comorbidities (12.5 vs. 29.4%) than SM gamblers. GD duration before treatment initiation was shorter in OSB patients than in SM gamblers, most of them (81.3 vs. 42.4%) with ≤ 5 years of GD duration. OSB gamblers showed significant differences in weekly gambling expenditure, spending higher amounts than SM patients. Younger age (OR: 0.919; 95% CI: 0.874–0.966), university education level (OR: 10.658; 95% CI: 3.330–34.119), weekly expenditure &gt;100€ (OR: 5.811; 95% CI:1.544–21.869), and being a non-smoker (OR:13.248; 95% CI:4.332–40.517) were associated with an increased likelihood of OSB gambling behavior.Conclusions: We identified different profiles for OSB and SM gamblers. Younger age, university education level, higher weekly expenditure, and non-smoking habit were associated with OSB compared to SM disorders. Prevention strategies should help young people become aware of the severe risks of OSB.
Effects of a Trans-Theoretical Model-Based Health Education Program on the Management of Cognitive Dysfunction in Older Adults With Mild Cognitive Impairment: Study Rationale and Protocol Design for a Randomized Controlled Trial
Authors: Liu Xiaoshen , Wang Lina , Tao Hong , Ge Chenxi , Zhen Xueting , Sun Xue , Wang Simeng , Su Liming 
Published: January 2021

Introduction: Recent studies have confirmed that the management of cognitive dysfunction produces considerable positive effects in individuals with mild cognitive impairment (MCI), however, compliance with participation in various cognitive dysfunction management strategies remains scant in older adults with MCI. Health education programs can improve the level of knowledge of the disease effectively, though it remains unclear as to whether health education programs are sufficient to promote behavior changes of older adults with MCI in the community.Objective: The study aims to provide insight into the effect of a trans-theoretical Model (TTM)-based health education program on increasing knowledge about mild cognitive impairment (MCI), compliance in cognitive dysfunction management, and other cognition-related health outcomes (general cognitive function, sleep quality, depression symptoms, apathy symptoms) for older adults with MCI.Methods: This study is a single-blinded, randomized, prospective clinical trial. We will recruit 132 participants with MCI who will be randomly assigned to a TTM-based health education group and a standard health education group in a ratio of 1:1. The intervention group will receive a TTM-based health education program (1 session/week, 4–560 min/session for 8 weeks), while the control group will receive standard health education. Assessors blinded to participant allocation will conduct baseline, post-intervention, and 3-month follow-up assessments. Statistical analyses will consist of the Wilcoxon test, the Chi-square test, the T-test, and 2 (group) × 3 (time) ANOVA with a 5% cut-off for significance.Discussion: Supposing the TTM-based health education program will provide validated community-based cognitive dysfunction management strategies for older adults with MCI, this would be a feasible approach to improve the compliance of participation in cognitive dysfunction management and the cognition-related health outcomes.Clinical Trial Registration: ChiCTR1900028351. Registered on December 19, 2019. http://www.chictr.org.cn/edit.aspx?pid=47223&amp;htm=4.