bluuebunny/crossref_metadata_2025_split huggingface dataset:
EGFR-Mutated Squamous Cell Lung Cancer and Its Association With Outcomes
Authors: Jin Rui , Peng Ling , Shou Jiawei , Wang Jin , Jin Yin , Liang Fei , Zhao Jing , Wu Mengmeng , Li Qin , Zhang Bin , Wu Xiaoying , Lan Fen , Xia Lixia , Yan Junrong , Shao Yang , Stebbing Justin , Shen Huahao , Li Wen , Xia Yang 
Published: June 2021

BackgroundThe therapeutic efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced EGFR-mutant lung squamous cell carcinoma (SCC) patients remains uncertain. Furthermore, the factors underlying the responsiveness have not been fully investigated. We therefore investigated the link between genomic profiles and EGFR-TKI efficacy.Material and MethodsWe consecutively enrolled stage IV, EGFR-mutant, and EGFR-TKI–treated patients with SCC. Patients with EGFR wild-type lung SCC and EGFR-mutant lung adenocarcinoma were consecutively enrolled as controls, and next-generation sequencing (NGS) was performed.ResultsIn total, 28 EGFR-mutant lung SCC, 41 EGFR-mutant lung adenocarcinoma, and 40 EGFR wild-type lung SCC patients were included. Among the patients with EGFR mutations, shorter progression-free survival (PFS) was observed in SCC compared to adenocarcinoma (4.6 vs. 11.0 months, P&lt;0.001). Comparison of the genomic profiles revealed that EGFR-mutant SCC patients had similar mutation characteristics to EGFR-mutant adenocarcinoma patients, but differed from those with EGFR wild-type SCC. Further exploration of EGFR-mutant SCC revealed that mutations in CREBBP (P = 0.005), ZNF217 (P = 0.016), and the Wnt (P = 0.027) pathway were negatively associated with PFS. Mutations in GRM8 (P = 0.025) were associated with improved PFS.ConclusionsEGFR-mutant lung SCC has a worse prognosis than EGFR-mutant adenocarcinoma. Mutations in other genes, such as CREBBP, ZNF217, GRM8, or Wnt that had implications on PFS raise the possibility of understanding mechanisms of resistance to EGFR-TKI in lung SCC, which will aid identification of potential beneficial subgroups of patients with EGFR-mutant SCCs receiving EGFR-TKIs.
An Analysis of Cardiac Disorders Associated With Chimeric Antigen Receptor T Cell Therapy in 126 Patients: A Single-Centre Retrospective Study
Authors: Qi Kunming , Yan Zhiling , Cheng Hai , Chen Wei , Wang Ying , Wang Xue , Cao Jiang , Zhang Huanxin , Sang Wei , Zhu Feng , Sun Haiying , Li Depeng , Wu Qingyun , Qiao Jianlin , Fu Chunling , Zeng Lingyu , Li Zhenyu , Zheng Junnian , Xu Kailin 
Published: June 2021

IntroductionChimeric antigen receptor T (CAR-T) cells are effective in treating hematological malignancies. However, in patients receiving CAR-T therapy, data characterizing cardiac disorders are limited.Methods126 patients with hematologic malignancies receiving CAR-T cell therapy were analyzed to determine the impact of CAR-T therapy on occurrence of cardiac disorders, including heart failure, arrhythmias, myocardial infarction, which were defined by the Common Terminology Criteria for Adverse Events (CTCAE). Parameters related to cardiac disorders were detected including myocardial enzyme, NT-proBNP and ejection fraction (EF). Cardiovascular (CV) events included decompensated heart failure (HF), clinically significant arrhythmias and CV death.ResultsThe median age of patients was 56 years (6 to 72 years). 58% patients were male, 62% had multiple myeloma, 20% had lymphoma and 18% had ALL. 33 (26%) patients had cardiac disorders, most of which were grade 1-2. 13 patients (10%) were observed with cardiac disorders grade 3-5, which comprised 5(4%) patients with new-onset HF, 2 (2%) patients with new-onset arrhythmias, 4 (3%) patients with the acute coronary syndrome, 1(1%) patient with myocardial infarction and 1(1%) patient with left ventricular systolic dysfunction. There were 9 CV events (7%) including 6 decompensated heart failure, 1 clinically significant arrhythmias and 2 CV deaths. Among the 33 patients with cardiac disorders, the patients with cardiac disorders CTCAE grade 3-5 had higher grade CRS (grade ≥ 3) than those with cardiac disorders CTCAE grade ≤ 2 (P &lt;0.001). More patients with cardiac disorders CTCAE grade 3-5 were observed in the cohort who did not receive corticosteroids and/or tocilizumab therapy timely comparing with those who received corticosteroids and/or tocilizumab therapy timely (P =0.0004).ConclusionsCardiac disorders CAR-T cell therapy were common and associated with occurrence of CRS. However, most cases were mild. For patients with CRS grade 3-5, timely administration of corticosteroids and/or tocilizumab can effectively prevent the occurrence and progression of cardiac disorders.
Comparing Robot-Assisted Laparoscopic Pyeloplasty vs. Laparoscopic Pyeloplasty in Infants Aged 12 Months or Less
Authors: Wong Yuenshan Sammi , Pang Kristine Kit Yi , Tam Yuk Him 
Published: June 2021

Objective: To investigate the outcomes of minimally invasive approach to infants with ureteropelvic junction (UPJ) obstruction by comparing the two surgical modalities of robot-assisted laparoscopic pyeloplasty (RALP) and laparoscopic pyeloplasty (LP).Methods: We conducted a retrospective review of all consecutive infants aged ≤12 months who underwent either LP or RALP in a single institution over the period of 2008–Jul 2020. We included primary pyeloplasty cases that were performed by or under the supervision of the same surgeon.Results: Forty-six infants (LP = 22; RALP = 24) were included with medians of age and body weight at 6 months (2–12months) and 8.0 kg (5.4–10 kg), respectively. There was no difference between the two groups in the patients' demographics and pre-operative characteristics. All infants underwent LP or RALP successfully without conversion to open surgery. None had intraoperative complications. Operative time (OT) was 242 min (SD = 59) in LP, compared with 225 min (SD = 39) of RALP (p = 0.25). Linear regression analysis showed a significant trend of decrease in OT with increasing case experience of RALP(p = 0.005). No difference was noted in the post-operative analgesic requirement. RALP was associated with a shorter hospital length of stay than LP (3 vs. 3.8 days; p = 0.009). 4/22(18%) LP and 3/24(13%) RALP developed post-operative complications (p = 0.59), mostly minor and stent-related. The success rates were 20/22 (91%) in LP and 23/24 (96%) in RALP (p = 0.49).Conclusions: Pyeloplasty by minimally invasive approach is safe and effective in the infant population. RALP may have superiority over LP in infants with its faster recovery and a more manageable learning curve to acquire the skills.
sVEGFR1 Is Enriched in Hepatic Vein Blood—Evidence for a Provisional Hepatic Factor Candidate?
Authors: Spearman Andrew D. , Gupta Ankan , Pan Amy Y. , Gudausky Todd M. , Foerster Susan R. , Konduri G. Ganesh , Ramchandran Ramani 
Published: June 2021

Background: Pulmonary arteriovenous malformations (PAVMs) are common sequelae of palliated univentricular congenital heart disease, yet their pathogenesis remain poorly defined. In this preliminary study, we used paired patient blood samples to identify potential hepatic factor candidates enriched in hepatic vein blood.Methods: Paired venous blood samples were collected from the hepatic vein (HV) and superior vena cava (SVC) from children 0 to 10 years with univentricular and biventricular congenital heart disease (n = 40). We used three independent protein analyses to identify proteomic differences between HV and SVC blood. Subsequently, we investigated the relevance of our quantified protein differences with human lung microvascular endothelial assays.Results: Two independent protein arrays (semi-quantitative immunoblot and quantitative array) identified that soluble vascular endothelial growth factor receptor 1 (sVEGFR1) is significantly elevated in HV serum compared to SVC serum. Using ELISA, we confirmed the previous findings that sVEGFR1 is enriched in HV serum (n = 24, p &lt; 0.0001). Finally, we studied the quantified HV and SVC serum levels of sVEGFR1 in vitro. HV levels of sVEGFR1 decreased tip cell selection (p = 0.0482) and tube formation (fewer tubes [p = 0.0246], shorter tube length [p = 0.0300]) in vitro compared to SVC levels of sVEGFR1.Conclusions: Based on a small heterogenous cohort, sVEGFR1 is elevated in HV serum compared to paired SVC samples, and the mean sVEGFR1 concentrations in these two systemic veins cause pulmonary endothelial phenotypic differences in vitro. Further research is needed to determine whether sVEGFR1 has a direct role in pulmonary microvascular remodeling and PAVMs in patients with palliated univentricular congenital heart disease.
Predictive Indicators for Necrotizing Enterocolitis With the Presence of Portal Venous Gas and Outcomes of Surgical Interventions
Authors: Lin Xin , Zeng Hui-Ping , Fang Yi-Fan , Lin Ying-Ying , Yang Chang-Yi 
Published: June 2021

Objectives: Portal venous gas (PVG) was an important clinical sign in stage II or III necrotizing enterocolitis (NEC) in preterm neonates. Not a proper predictive indicator was found to predict the diseases (NEC with the presence of PVG) up to now. There is a need to put forward predictive indicators and compare the predictive effects among them.Methods: We conducted a retrospective study of preterm neonates with NEC-PVG (n = 61) or NEC-non PVG (n = 62) from 2014 to 2021. Predictive indicators were put forward and determined by receiver operating characteristic curve analysis. An analysis of the surgical interventions and their outcomes was performed.Results: The incidence rate of NEC among preterm neonates was 4.99%; surgical and conservative interventions accounted for 20.47 and 75.07%, and the mortality rate was 0.03%. The composition ratio of shock in the NEC-PVG group increased 13.2% (P = 0.029). C-reactive protein, fibrinogen degradation product, and blood glucose had better predictive effects in the predictive indicators (P &lt; 0.05). Intestinal necrosis and subependymal hemorrhage in the outcomes of surgical interventions had a strong relationship with the presence of PVG in NEC II/III (P &lt; 0.05).Conclusion: Early and reasonable use of antibiotics, improvement of coagulation function, rectification of acidosis, and decreased blood glucose could cut down the occurrence of the disease (NEC with the presence of PVG). Except for subependymal hemorrhage and intestinal necrosis, NEC with the presence of PVG did not increase the occurrence of other outcomes after surgery.
Continuous Renal Replacement Therapy in Critically Ill Children in the Pediatric Intensive Care Unit: A Retrospective Analysis of Real-Life Prescriptions, Complications, and Outcomes
Authors: Buccione Emanuele , Guzzi Francesco , Colosimo Denise , Tedesco Brigida , Romagnoli Stefano , Ricci Zaccaria , L'Erario Manuela , Villa Gianluca 
Published: June 2021

Introduction: Severe acute kidney injury is a common finding in the Pediatric Intensive Care Unit (PICU), however, Continuous Renal Replacement Therapy (CRRT) is rarely applied in this setting. This study aims to describe our experience in the rate of application of CRRT, patients' clinical characteristics at admission and CRRT initiation, CRRT prescription, predictors of circuit clotting, short- and long-term outcomes.Methods: A 6-year single center retrospective study in a tertiary PICU.Results: Twenty-eight critically ill patients aged 0 to 18 years received CRRT between January 2012 and December 2017 (1.4% of all patients admitted to PICU). Complete clinical and CRRT technical information were available for 23/28 patients for a total of 101 CRRT sessions. CRRT was started, on average, 40 h (20–160) after PICU admission, mostly because of fluid overload. Continuous veno-venous hemodiafiltration and systemic heparinization were applied in 83.2 and 71.3% of sessions, respectively. Fifty-nine sessions (58.4%) were complicated by circuit clotting. At multivariate Cox-regression analysis, vascular access caliber larger than 8 Fr [HR 0.37 (0.19–0.72), p = 0.004] and regional citrate anticoagulation strategy [HR 0.14 (0.03–0.60), p = 0.008] were independent protective factors for clotting. PICU mortality rate was 42.8%, and six survivors developed chronic kidney disease (CKD), within an average follow up of 3.5 years.Conclusions: CRRT is uncommonly applied in our PICU, mostly within 2 days after admission and because of fluid overload. Larger vascular access and citrate anticoagulation are independent protective factors for circuit clotting. Patients' PICU mortality rate is high and survival often complicated by CKD development.
Pioglitazone Inhibits Diabetes-Induced Atrial Mitochondrial Oxidative Stress and Improves Mitochondrial Biogenesis, Dynamics, and Function Through the PPAR-γ/PGC-1α Signaling Pathway
Authors: Zhang Zhiwei , Zhang Xiaowei , Meng Lei , Gong Mengqi , Li Jian , Shi Wen , Qiu Jiuchun , Yang Yajuan , Zhao Jianping , Suo Ya , Liang Xue , Wang Xinghua , Tse Gary , Jiang Ning , Li Guangping , Zhao Yungang , Liu Tong 
Published: June 2021

Background: Oxidative stress contributes to adverse atrial remodeling in diabetes mellitus. This remodeling can be prevented by the PPAR-γ agonist pioglitazone via its antioxidant and anti-inflammatory effects. In this study, we examined the molecular mechanisms underlying the protective effects of pioglitazone on atrial remodeling in a rabbit model of diabetes.Methods: Rabbits were randomly divided into control, diabetic, and pioglitazone-treated diabetic groups. Echocardiographic, hemodynamic, and electrophysiological parameters were measured. Serum PPAR-γ levels, serum and tissue oxidative stress and inflammatory markers, mitochondrial morphology, reactive oxygen species (ROS) production rate, respiratory function, and mitochondrial membrane potential (MMP) levels were measured. Protein expression of the pro-fibrotic marker TGF-β1, the PPAR-γ coactivator-1α (PGC-1α), and the mitochondrial proteins (biogenesis-, fusion-, and fission-related proteins) was measured. HL-1 cells were transfected with PGC-1α small interfering RNA (siRNA) to determine the underlying mechanisms of pioglitazone improvement of mitochondrial function under oxidative stress.Results: The diabetic group demonstrated a larger left atrial diameter and fibrosis area than the controls, which were associated with a higher incidence of inducible atrial fibrillation (AF). The lower serum PPAR-γ level was associated with lower PGC-1α and higher NF-κB and TGF-β1 expression. Lower mitochondrial biogenesis (PGC-1α, NRF1, and TFAM)-, fusion (Opa1 and Mfn1)-, and fission (Drp1)-related proteins were detected. Mitochondrial swelling, higher mitochondrial ROS, lower respiratory control rate, and lower MMP were observed. The pioglitazone group showed a reversal of structural remodeling and a lower incidence of inducible AF, which were associated with higher PPAR-γ and PGC-1α. The pioglitazone group had lower NF-κB and TGF-β1 expression levels, whereas biogenesis-, fusion-, and fission-related protein expression was higher. Further, mitochondrial structure and function were improved. In HL-1 cells, PGC-1α siRNA transfection blunted the effect of pioglitazone on Mn-SOD protein expression and MMP collapse in H2O2-treated cells.Conclusion: Diabetes mellitus induces adverse atrial structural, electrophysiological remodeling, and mitochondrial damage and dysfunction. Pioglitazone prevented these abnormalities through the PPAR-γ/PGC-1α pathway.
Dendrobium Officinale Polysaccharide Attenuates Insulin Resistance and Abnormal Lipid Metabolism in Obese Mice
Authors: Qu Jian , Tan Shengyu , Xie Xinyan , Wu Wenqiang , Zhu Haihong , Li Hang , Liao Xiaobo , Wang Jiaojiao , Zhou Zhi-Ang , Huang Song , Lu Qiong 
Published: June 2021

Objectives: Dendrobium officinale polysaccharide (DOP) is the main active ingredient in a valuable traditional Chinese medicine, which exerts several pharmacological activities including hepatoprotection and hypoglycemic effects. However, the effects of DOP on obesity-associated insulin resistance (IR) and lipid metabolism remain unknown. This study aimed to investigate the role of DOP in IR and abnormal lipid metabolism in obese mice.Methods: IR models were established using 3T3-L1 adipocytes, C2C12 myocytes, and primary cultured hepatocytes exposed to palmitate acid. After treatment with DOP, insulin-stimulated glucose uptake, glucose release, and AKT phosphorylation was detected. Fasting blood glucose, fasting serum insulin, the glucose tolerance test (GTT), and the insulin tolerance test (ITT) were measured to evaluate IR of obese mice. Lipid analysis was conducted to evaluate the effects of DOP on lipid metabolism in obese mice.Results:In vitro, DOP treatment ameliorated palmitic acid-induced IR in adipocytes, myocytes, and hepatocytes. DOP regulated cellular insulin sensitivity via the peroxisome proliferator-activated receptor-γ (PPAR-γ). Furthermore, administration of DOP significantly reduced the IR and visceral adipose tissue (VAT) inflammation of diet-induced obese (DIO) and the genetically-induced obesity mice (ob/ob) mouse models. In addition, DOP treatment attenuated the high-fat diet (HFD)-induced liver lipid accumulation by reducing liver triglycerides (TG), plasma free fatty acid (FFA), serum cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels, while increasing HDL-C levels.Conclusion: DOP could improve obesity-associated IR and abnormal lipid metabolism through its activities on PPAR-γ, and may serve as a potential therapeutic agent for obesity-associated insulin resistance and lipid metabolism disorder.
Melatonin Attenuates Intervertebral Disk Degeneration via Maintaining Cartilaginous Endplate Integrity in Rats
Authors: Wu Xiexing , Liu Yijie , Du Jiacheng , Li Xiaoping , Lin Jiayi , Ni Li , Zhu Pengfei , Zhou Hong , Kong Fanchen , Yang Huilin , Geng Dechun , Mao Haiqing 
Published: June 2021

ObjectiveThe aim of this study is to verify whether melatonin (Mel) could mitigate intervertebral disk degeneration (IVDD) in rats and to investigate the potential mechanism of it.MethodA rat acupuncture model of IVDD was established with intraperitoneal injection of Mel. The effect of Mel on IVDD was analyzed via radiologic and histological evaluations. The specific Mel receptors were investigated in both the nucleus pulposus (NP) and cartilaginous endplates (EPs). In vitro, EP cartilaginous cells (EPCs) were treated by different concentrations of Mel under lipopolysaccharide (LPS) and Luzindole conditions. In addition, LPS-induced inflammatory response and matrix degradation following nuclear factor kappa-B (NF-κB) pathway activation were investigated to confirm the potential mechanism of Mel on EPCs.ResultsThe percent disk height index (%DHI) and MRI signal decreased after initial puncture in the degeneration group compared with the control group, while Mel treatment protected disk height from decline and prevented the loss of water during the degeneration process. In the meantime, the histological staining of the Mel groups showed more integrity and well-ordered construction of the NP and EPs in both low and high concentration than that of the degeneration group. In addition, more deep-brown staining of type II collagen (Coll-II) was shown in the Mel groups compared with the degeneration group. Furthermore, in rat samples, immunohistochemical staining showed more positive cells of Mel receptors 1a and 1b in the EPs, instead of in the NP. Moreover, evident osteochondral lacuna formation was observed in rat EPs in the degeneration group; after Mel treatment, the osteochondral destruction alleviated accompanying fewer receptor activator for nuclear factor-κB ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP)-stained positive cells expressed in the EPs. In vitro, Mel could promote the proliferation of EPCs, which protected EPCs from degeneration under LPS treatment. What is more, Mel downregulated the inflammatory response and matrix degradation of EPCs activated by NF-κB pathway through binding to its specific receptors.ConclusionThese results indicate that Mel protects the integrity of the EPs and attenuates IVDD by binding to the Mel receptors in the EPs. It may alleviate the inflammatory response and matrix degradation of EPCs activated by NF-κB pathway.
The Prevalence of Generalised Anxiety Disorder Among Prisoners of the Penitentiary Institution in North-Eastern Poland
Authors: Stawinska-Witoszynska Barbara , Czechowska Katarzyna , Moryson Waclaw , Wieckowska Barbara 
Published: June 2021

Introduction: Generalised anxiety disorder (GAD) is one of the most common mental disorders. The psychosocial factors that may lead to generalised anxiety disorders include stress, traumatic events, conscious and unconscious internal conflicts, and low social and economic status. Imprisonment and forced isolation may favour the development of depression or anxiety disorders in inmates. Thus, this study aimed to analyse the prevalence of generalised anxiety disorder (GAD) in the population of inmates detained in one of the largest penitentiary units in north-eastern Poland.Materials and Methods: The data comes from 2017 and includes information on 635 male inmates incarcerated at the Czerwony Bór Prison. The information comes from the health records of individual inmates, kept by the prison outpatient clinician, and documented consultations with doctors of units outside the prison. The classification of generalised anxiety disorders (F41.1) was made in accordance with the 10th Revision of the International Statistical Classification of Diseases and Health Problems and the clinical diagnosis made by a psychiatrist. The Mann-Whitney test was used to compare quantitative data without normal distribution, chi-squared test or Fisher exact test for comparing qualitative data. A one-dimensional and multi-dimensional logistic regression model was used to examine the impact of the prison type on the prevalence of generalised anxiety disorder.Results: Generalised anxiety disorder was observed among 44 prisoners (6.9%), most often in the age range 30–39 years and among men younger than 30 years, respectively 40.9 and 31.8% of all diagnosed. The average age of patients was 34.6 years. The least number of prisoners with GAD was in the age group 50–59 (2.3%). Nearly 66% of patients were prisoners detained in a closed type prison; the chance of generalised anxiety disorder was three times higher than among the prisoners in a half-open and open type facility. Generalised anxiety disorder was diagnosed significantly more often with those currently serving a prison sentence than those before incarceration.Conclusions: In Polish conditions, the importance of the problem associated with GAD is evidenced by a significant increase in its prevalence in the prison environment and a three times higher chance of developing generalised anxiety disorder among prisoners in a closed type institution, which calls for highly organised psychiatric care and increased availability of psychological assistance for prisoners.