bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycemic Control is Associated with Heart Failure with Recovered Ejection Fraction in Diabetic Patients
Authors: Yang Chen Die , Aihemaiti Muladili , Ding Feng Hua , Yang Zhen Kun , Hu Jian , Shen Wei Feng , Lu Lin , Zhang Rui Yan , Wang Xiao Qun 
Published: October 2021

Abstract
Background: Due to advances in medical treatments, a substantial proportion of heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF, HFrEF) have experienced partial or complete recovery of LVEF, termed HFrecEF, and markedly improved clinical outcomes. In the present study, we sought to investigate the relationship between glycemic control and the incidence of HFrecEF in patients with type 2 diabetes mellitus (T2DM).Methods: A total of 310 age- and sex-matched T2DM patients with HFrecEF and persistent HFrEF were retrospectively enrolled based on 12-month repeat echocardiograms. HFrecEF was defined as follow-up LVEF > 40% and absolute LVEF improvement ≥ 10% compared to the baseline. The relationship between HFrecEF and HbA1c levels was analyzed. Results: During the 12-month follow-up, LVEF recovered from 35.93% ± 5.62% to 51.11% ± 8.53% in the HFrecEF group (P<0.001), while remained reduced (33.08% ± 6.40% to 33.63% ± 6.10%, P=0.238) in the HFrEF group. T2DM patients with HFrecEF had significantly lower HbA1c level than those with persistent HFrEF (6.4% [IQR 5.8%~7.1%] vs. 6.8% [IQR 6.3%~7.4%], P<0.001), irrespective of HF etiology. After multivariate adjustment, every 1% increase in HbA1c conferred a 20.8% [OR: 0.792, 95% CI 0.642~0.967] lower likelihood of HFrecEF. When dividing HbA1c into tertiles, patients with HbA1c ≥ 7.1% corresponded to a 60.9% [OR: 0.391, 95% CI 0.201~0.750] decreased likelihood of HFrecEF as compared to those with HbA1c < 6.2%. Conclusions: This study demonstrates that HFrEF patients with T2DM are more likely to develop HFrecEF under optimal glycemic control valued by lower HbA1c level.
The SGLT2i Dapagliflozin Reduces RV Hypertrophy Independent of Changes in RV Pressure Induced by Pulmonary Artery Banding
Authors: Connelly Kim A , Wu Ellen , Visram BSc Aylin , Friedberg Mark K. , Batchu Sri Nagarjun , Yeera Veera Ganesh , Thai Kerri , Nghiem Linda , Zhang Yanling , Kabir Golam , Desjardins JF , Advani Andrew , Gilbert Richard E 
Published: October 2021

Abstract
Background— Sodium glucose linked transporter 2 (SGLT2) inhibition not only reduces morbidity and mortality in patients with diagnosed heart failure but also prevents the development of heart failure hospitalization in those at risk. While studies to date have focused on the role of SGLT2 inhibition in left ventricular failure, whether this drug class might be similarly efficacious in the treatment and prevention of right heart failure has not been unexplored.Hypothesis: We hypothesized that SGLT2 inhibition would reduce the structural, functional and molecular responses to pressure overload of the right ventricle.Methods: Thirteen-week-old Fischer F344 rats underwent pulmonary artery banding (PAB) or sham surgery prior to being randomized to receive either the SGLT2 inhibitor: dapagliflozin (1.5mg/kg/day) or vehicle by oral gavage. After six weeks of treatment, animals underwent transthoracic echocardiography and invasive hemodynamic studies. Animals were then terminated, and their hearts harvested for structural and molecular analyses.Results: PAB induced features consistent with a compensatory response to increased right ventricular (RV) afterload with elevated mass, end systolic pressure, collagen content and alteration in calcium handling protein expression (all p<0.05 when compared to sham + vehicle). Dapagliflozin reduced RV mass, including both wet and dry weight as well as normalizing the protein expression of SERCA 2A, AMPkinase and LC3I/II ratio expression (all p<0.05).Significance: Dapagliflozin reduces the structural, functional, and molecular manifestations of right ventricular pressure overload. Whether amelioration of these early changes in the RV may ultimately lead to a reduction in RV failure remains to be determined.
Preclinical Study on the Ameliorating Effect of L-Ascorbic Acid for the Oxidative Stress of Caused by Chronic Administration of Organic Nitrates in Cardiovascular Diseases
Authors: Hamdan Ahmed M , Mohammedsaleh Zuhair M. , Aboelnour Aalaa , Elkhannishi Sherif M.H. 
Published: October 2021

Abstract
PurposeThe therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. The principal objective of our research is to explain the ameliorating effect of L-ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs. MethodsWe studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered ISMN. Afterwards, we evaluated the role of L-ascorbic acid against these biochemical changes. ResultsChronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in myocardium muscles in a dose dependent manner. Meanwhile, such exposure caused decline in the enzymatic effect of superoxide dismutase (SOD), glutathione (GSH) and catalase activity (CAT) accompanied with a decrease of in the level of mitochondrial oxidative stress marker (nrf2) in myocardium muscles and decrease in the serum iron and total iron binding capacity (TIBC) in a dose dependent manner. Concomitant treatment with L-ascorbic acid significantly diminished these changes for all examined parameters.ConclusionChronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to generation of reactive oxygen species. Using vitamin C can effectively ameliorate such intoxication to overcome the nitrate tolerance.
Comparison of Percutaneous Cortical Bone Trajectory Screw Fixation Vs. Traditional Percutaneous Pedicle Screw Fixation for Traumatic Type a Lumbar Fractures Without Neurological Deficits
Authors: Zheng Zhangan , Zhang Li , Zhu Yu , Chen Jun , Yan Zheng , Zhang Pengpeng , Liu Chunhong , Zhang Yinshun , Xu Hongguang , Wang Bing , Gui Zhaoliu , Xue Shuangtao , Yin Zongsheng 
Published: October 2021

Abstract
Objective: The purposes of this study were to examine the clinical and radiological outcomes after percutaneous cortical bone trajectory screw fixation (PCBT) for traumatic type A lumbar fractures without neurological deficits and to compare these outcomes with those after traditional percutaneous pedicle screw fixation (PPSF) technique.Methods: The study included 22 consecutively treated patients who underwent PCBT technique (PCBT group) and a historical control group of 24 consecutively treated patients who underwent traditional PPSF surgery (PPSF group). Clinical outcomes (including Visual analogue scores (VAS), Oswestry disability index (ODI) scores) and radiographic assessments including Vertebral wedge angle (VWA) and Sagittal index were recorded and compared between the two groups.Results: Incision length and hospital stay in the PCBT group were significantly better than the PPSF group (p < 0.05). There were no significant differences between the two groups in clinical and radiographic outcomes, including blood loss, X-ray exposure, surgery time, VAS, ODI scores, VWA and sagittal index (p > 0.05 each). However, after multiply adjustment, PCBT group had better postoperative restoration in terms of VWA than the PPSF group (p < 0.05).Conclusions: The present study showed that PCBT is a safe and feasible method for the treatment of lumbar fractures without neurological deficits. It resulted in smaller incisions and shorter period of hospital stay, yet yielded equivalent or superior clinical and radiographic outcomes compared to the traditional PPSF.
Translational Imaging of the Fibroblast Activation Protein (FAP) Using the New Ligand [68Ga]Ga-OncoFAP-DOTAGA
Authors: Backhaus Philipp , Gierse Florian , Burg M.C. , Büther Florian , Asmus Inga , Dorten Paulina Marie , Cufe Juela , Roll Wolfgang , Neri Dario , Cazzamalli Samuele , Millul Jacopo , Mock Jacqueline , Galbiati Andrea , Zana Aureliano , Schäfers Klaus P. , Hermann Sven , Weckesser Matthias , Tio Joke , Wagner Stefan , Breyholz Hans-Jörg , Schäfers Michael 
Published: October 2021

Abstract
PurposeThe fibroblast activation protein (FAP) is an emerging target for molecular imaging and therapy in cancer. OncoFAP is a novel small organic ligand for FAP with very high affinity. In this translational study, we establish [68Ga]Ga-OncoFAP-DOTAGA (68Ga-OncoFAP) radiolabeling, benchmark its properties in preclinical imaging and evaluate its application in clinical PET scanning.Methods68Ga-OncoFAP was synthesized in a cassette-based fully automated labelling module. Lipophilicity, affinity, and serum stability of 68Ga-OncoFAP were assessed by determining logD7.4, IC50 values and radiochemical purity. 68Ga-OncoFAP tumor uptake and imaging properties were assessed in preclinical dynamic PET/MRI in murine subcutaneous tumor models. Finally, biodistribution and uptake in a variety of tumor types were analyzed in 12 patients based on individual clinical indications that received 163 ± 50 MBq 68Ga-OncoFAP combined with PET/CT and PET/MRI.Results68Ga-OncoFAP radiosynthesis was accomplished with high radiochemical yields. Affinity for FAP, lipophilicity and stability of 68Ga-OncoFAP measured are ideally suited for PET imaging. PET and gamma counting-based biodistribution demonstrated beneficial tracer kinetics and high uptake in murine FAP expressing tumor models with high tumor-to-blood ratios of 8.6 ± 5.1 at 1 h and 38.1 ± 33.1 at 3 h p.i. Clinical 68Ga-OncoFAP PET/CT and PET/MRI demonstrated favorable biodistribution and kinetics with high and reliable uptake in primary cancers (SUVmax 12.3 ± 2.3), lymph nodes (SUVmax 9.7 ± 8.3) and distant metastases (SUVmax up to 20.0).ConclusionExcellent preclinical and clinical imaging characteristics validate 68Ga-OncoFAP as a powerful alternative to currently available FAP tracers.
Crosstalk between SUMOylated PPARγ1 and FOXO1 Exerts a Positive-feedback Effect on Vascular Endothelial Insulin Resistance
Authors: Kong Ying , Niu Ailin , Yuan Wanwan , Xia Min , Xiong Xiaowei , Lu Yanli , Yin Tingting , Zhang Yanan , Chen Sheng , Huang Qianqian , Zeng Guohua , Huang Qiren 
Published: October 2021

Abstract
Background: PPARγ and FOXO1 are key regulators of transcription factors that mediate insulin sensitivity. We previously showed that a small ubiquitin-related modifier of PPARγ1 at K77 (SUMOylation) favors endothelial insulin resistance (IR) induced by high-fat/high-glucose (HF/HG) administration. However, whether and how the crosstalk between SUMOylated PPARγ1 and FOXO1 mediates the development of IR remains unclear. Here, we place emphasis on elucidating how PPARγ1-K77 SUMOylation interacts with FOXO1 and participates in the development of endothelial IR.Methods: Adenovirus or adeno-associated virus carrying a truncated PPARγ1 containing AF1 and DBD domains fused with SUMO-1 (PPARγ1[1-182 aa]-SUMO-1 fusion protein) was utilized to simulate PPARγ1-K77 SUMOylation. Furthermore, we carried out PPARγ1-K77 SUMOylation imitating-IR and worsening-IR experiments in vitro and in vivo. The vascular diastolic function and levels of p-IKK, IKK, p-PI3K, PI3K, p-Akt, Akt, p-eNOS, and eNOS were measured. To elucidate the underlying mechanism, the interaction of PPARγ1-K77 SUMOylation and FOXO1 was examined by co-immunoprecipitation. The recruitment of PPARγ1 or FOXO1 to PPRE was analyzed by chromatin immunoprecipitation, followed by measuring the PPARγ1 transcriptional activity and translocation of FOXO1.Results: Our results show that like HF/HG, PPARγ1-K77 SUMOylation imitates endothelial IR and dysfunction, presenting decreased NO levels and elevated ET-1 levels, with PI3K/Akt/eNOS pathway inhibited, and endothelium-dependent vasodilation function impaired. Moreover, combination of HF/HG and PPARγ1-K77 SUMOylation exhibits a synergistic worsening effect on endothelial IR. Mechanistically, the results reveal that PPARγ1-K77 SUMOylation readily interacts with FOXO1, and the PPRE binding site of PI3K is competitively blocked by FOXO1, which represses PPARγ1 transcriptional activity and downregulates the PI3K-Akt pathway. Inhibition of the PI3K-Akt pathway promotes the nuclear accumulation of FOXO1, which interacts with SUMOylated PPARγ1 in the nucleus, exerting a positive feedback effect on IR pathogenesis.Conclusion: These results reveal a novel association between PPARγ1-K77 SUMOylation and FOXO1, which inhibits PPARγ1 transcriptional activity and contributes to vascular endothelial IR. These findings will be beneficial for better understanding the pathogenesis of endothelial IR and providing novel pharmacological targets for diabetic angiopathy.
Impaired JAK-STAT Pathway Signaling in Leukocytes of Frail Elderly
Authors: Samson Leonard Daniël , Engelfriet Peter , Verschuren W. M. Monique , Picavet H. Susan J. , Ferreira José A. , de Zeeuw-Brouwer Mary-lène , Buisman Anne-Marie , Boots A. Mieke H. 
Published: October 2021

Abstract
Background: Elderly often show reduced immune functioning and develop chronic low-grade inflammation. Why some elderly are more prone to become frail is unknown. We investigated whether frailty is associated with differences in cytokine signaling through the JAK-STAT pathway in leukocytes of 34 individuals aged 65-77 years. In addition, we investigated how this relation is affected by chronic low-grade inflammation during the previous 20 years. Cytokine signaling was quantified by measuring intracellular STAT1, STAT3, and STAT5 phosphorylation in monocytes, B cells, CD4+ T cells and CD8+ T cells upon stimulation with IL-2, IL-6, IL-10, IFNα and IFNγ, using phospho-flow cytometry. Plasma inflammatory markers had been measured repeatedly in the same individuals over the previous 20 years. Frailty was assessed as a score on a frailty index. Results: We found that lower cytokine-induced pSTAT responsiveness in the various cell subsets was seen with higher frailty scores in both men and women, indicative of dysfunctional pSTAT responses in frailer individuals. Associations differed between men and women, with frailer women showing lower pSTAT1 responses in monocytes and frailer men showing lower pSTAT5 responses in CD4+ and CD8+ T cells. Notably, lower IL-10-induced pSTAT3 responses in men were related to both higher frailty scores and higher CRP levels over the past 20 years. This might indicate poor resolution of low-grade inflammation due to defective regulatory pSTAT signaling in older men. Conclusions: Our results emphasize the importance of preserved JAK-STAT pathway signaling in healthy aging and reveal cellular pSTAT levels as a candidate biomarker of frailty.
Duchenne Muscular Dystrophy and Bone Mineral Density
Authors: Lima Luana da Costa , Grilo Evellyn Câmara , Cunha Thais Alves , de Araújo Bárbara Gurgel Magalhães , Brandão-Neto José , Vale Sancha Helena de Lima 
Published: October 2021

Abstract
Duchenne muscular dystrophy (DMD) patients are at risk of developing conditions that can compromise their bone health, such as fractures and walking impairment. We aimed to assess bone mineral density as a function of the age of DMD patients. The cross-sectional study included 48 patients distributed into four groups by age: G1 (5.1-9.2 years), G2 (9.3-10.7 years), G3 (11.2-15.9 years), and G4 (18-24.7 years). Lumbar spine and total body bone mineral density (BMD) measurements were performed with dual-energy X-ray absorptiometry. There was a moderate negative correlation between age and the lumbar spine BMD z-score (p = 0.001; r = -0.45) and a strong negative correlation between age and the total body BMD z-score (p = 0.001; r = -0.79). The lumbar spine BMD z-scores in G3 and G4 were significantly lower than those in G1 and G2 (p < 0.05). The total body BMD z-score in G3 was lower than those in G1 and G2 (p < 0.05), and in G4 was lower ​​than those in the other groups (p < 0.05). Conclusion: The older patients had lower lumbar spine and total body BMD z-score values than younger patients. Moreover, these values ​​were negatively correlated with the age of the patients.
Low-Dose 68 Ga-PSMA Prostate PET/MRI Imaging Using Deep Learning Based On MR Priors
Authors: Deng Fuquan , Li Xiaoyuan , Yang Fengjiao , Sun Hongwei , Yuan Jianmin , He Qiang , Xu Weifeng , Yang YongFeng , Liang Dong , Liu Xin , Zheng Hairong , hu zhanli 
Published: October 2021

Abstract
Purpose: 68 Ga-prostate-specific membrane antigen (PSMA) PET/MRI has become an effective imaging method for prostate cancer. The purpose of this study was to use deep learning methods to perform low-dose image restoration on PSMA PET/MRI and to evaluate the effect of synthesis on the images and the medical diagnosis of patients at risk of prostate cancer.Methods: We reviewed the 68 Ga-PSMA PET/MRI data of 41 patients. The low-dose PET images of these patients were restored to full-dose PET images through a deep learning method based on MR priors. The synthesized images were evaluated according to quantitative scores from nuclear medicine doctors and multiple imaging indicators, such as peak-signal noise ratio (PSNR), structural similarity (SSIM), normalization mean square error (NMSE), and relative contrast-to-noise ratio (RCNR).Results: The scores of the full images synthesized from 25%- and 50%-dose images based on MR priors were 3.84±0.36 and 4.03±0.17, respectively, which were higher than the scores of the target images. Correspondingly, the PSNR, SSIM, NMSE, and RCNR values of the full-dose images synthesized from 25%-dose PET images based on MR priors were 37.86±4.16, 0.916±0.063, 0.015±0.012, and 1.004±0.126, respectively.Conclusion: According to a combination of quantitative scores from nuclear medicine doctors and evaluations with multiple image indicators, the synthesis of full-dose images based on MR priors using 25%- and 50%-dose PET images did not affect the clinical diagnosis of prostate cancer. Prostate cancer patients can undergo 68 Ga-PSMA prostate PET/MRI scans with radiation doses reduced by up to 75% through the use of deep learning methods to synthesize full-dose images.
Soybean Meal Extract Preserves Memory Ability By Increasing Presynaptic Function and Modulating Gut Microbiota in Rats
Authors: Yeh Kun-Chieh , Hung Chi-Feng , Lee Hui-Ling , Hsieh Ting-Yang , Wang Su-Jane 
Published: October 2021

Abstract
Age-related degenerative brain diseases frequently manifest as memory deficits. Dietary interventions or nutraceuticals may provide efficacious treatments through prevention and cure. Soybean meal, a byproduct of soy oil refining, has health benefits, but its effect on memory function is unknown. Therefore, we evaluated the effect of the oral administration of soybean meal extract (SME) for 2 weeks on memory function using the Morris water maze (MWM) test in healthy rats and investigated the possible underlying mechanisms. First, analysis of the composition revealed that SME is rich in isoflavones; SME did not exhibit hepatotoxicity or renal toxicity at the different doses tested. The MWM results revealed that the escape latency and movement distance of rats were significantly shorter in the SME group than in the control group, indicating that SME can help in memory preservation. In addition, SME increased the levels of presynaptic proteins such as synaptophysin, synaptobrevin, synaptotagmin, syntaxin, synapsin I, and 25-kDa synaptosome-associated protein as well as protein kinases and their phosphorylated expression, including extracellular signal-regulated kinases 1 and 2 (ERK1/2), protein kinase C (PKC), and Ca2+/calmodulin-dependent protein kinase II (CaMKII)] in the hippocampal nerve terminals (synaptosomes). Transmission electron microscopy also indicated that SME increased the number of synaptic vesicles in hippocampal synaptosomes. Furthermore, SME rats exhibited increased gut microbiota diversity and altered microbiota composition compared with control rats. Therefore, our data suggest that SME can increase presynaptic function and modulate gut microbiota, thus aiding in memory preservation in rats.
Influence of Discharge Gap On Material Removal and Melt Pool Movement in EDM Discharge Process
Authors: Yue Xiaoming , Fan Ji , Li Qi , Yang Xiaodong , Xu Zuoke , Chen Zhiyuan 
Published: October 2021

Abstract
In electrical discharge machining (EDM), gap control is the key to stable processing; the discharge gap plays a significant role in EDM. To determine the influence of the discharge gap on material removal and melt pool movement, which are two fundamental issues in EDM, high-speed photography and molecular dynamics (MD) simulations were used to study the discharge process. Research results demonstrate that the discharge gap has a significant influence on material removal during the discharge process. A smaller gap width produces more and larger removed materials. The influence mechanism of the gap width on material removal is explained as follows. A smaller gap width produces discharge plasma with a smaller diameter and greater heat flux. Discharge with a greater heat flux generates more material removed during the discharge process. In addition, a smaller gap width and greater heat flux produce a stronger interaction of metal vapor jets, generating a stronger shear force acting on the melt pool. The discharge gap also influences the movement of the melt pool and the final topography of the discharge crater through external pressure acting on the melt pool. Smaller gap width produces greater external pressure acting on the melt pool, generating a bowl-shaped melt pool and a discharge crater with a depression in the center and a bulge around the edge. A larger gap width produces less external pressure acting on the melt pool, generating a flat melt pool and a discharge crater with swelling in the center and a depression around the edge.
Photodynamic therapy using mannose-conjugated chlorin e6 stimulates tumor immunity by increasing cell surface calreticulin in cancer cells and promoting macrophage phagocytosis
Authors: Kimura Yuka , Aoki Hiromasa , Soyama Tatsuki , Sakuragi Akira , Otsuka Yuto , Nomoto Akihiro , Yano Shigenobu , Nishie Hirotada , Kataoka Hiromi , Aoyama Mineyoshi 
Published: October 2021

Abstract
Photodynamic therapy (PDT) damages cancer cells via photosensitization using harmless laser irradiation. We synthesized a new photosensitizer, mannose-conjugated-chlorin e6 (M-chlorin e6), which targets mannose receptors that are highly expressed on M2-like tumor-associated macrophages (M2-TAMs) and cancer cells. In our previous study, we demonstrated that M-chlorin e6 PDT reduces tumor volume and decreases the proportion of M2-TAMs. Whether M-chlorin e6 PDT–treated cancer cells activate tumor immunity remains unclear, although the decrease in M2-TAMs is thought to be a direct injurious effect of M-chlorin e6 PDT. Calreticulin (CRT) is exposed at the surface of the membrane of cancer cells in response to treatment with chemotherapeutic agents such as anthracycline and oxaliplatin. Surface-exposed CRT induces phagocytosis of CRT receptor–positive cells, including macrophages, resulting in antigen processing and the induction of T cell–mediated anticancer immune responses. In the present study, we found that M-chlorin e6 PDT increases CRT on the surface of cancer cells, leading to macrophage phagocytosis of cancer cells. Furthermore, M-chlorin e6 PDT increases CD80+CD86+ macrophages. These results suggest that M-chlorin e6 PDT stimulates T cell–mediated tumor immunity by enhancing the macrophage phagocytosis of cancer cells and the antigen-presenting capability of macrophages.