bluuebunny/crossref_metadata_2025_split huggingface dataset:
Key Molecules of Triglycerides Pathway Metabolism Are Disturbed in Patients With Systemic Lupus Erythematosus
Authors: Quevedo-Abeledo Juan Carlos , Martín-González Candelaria , Ferrer-Moure Carmen , de Armas-Rillo Laura , Hernandez-Hernandez Maria Vanesa , González-Gay Miguel Á. , Ferraz-Amaro Iván 
Published: May 2022

BackgroundElevated triglycerides or triglyceride-rich lipoproteins are an additional cause of cardiovascular (CV) disease. Given that patients with systemic lupus erythematosus (SLE) have a high prevalence of premature CV disease and show an altered lipid profile, our objective was to study whether three molecules that play a central role in the triglyceride metabolism: apolipoprotein C-III (ApoC3), angiopoietin-like protein 4 (ANGPLT4), and lipoprotein lipase (LPL) differ between SLE patients and controls, and how they are related to disease characteristics, including disease damage.MethodsCross-sectional study that included 347 women, 185 of them diagnosed with SLE and 162 age-matched controls. ANGPTL4, ApoC3 and LPL, and standard lipid profiles were analyzed in SLE patients and controls. A multivariable analysis was performed to assess whether ANGPTL4, ApoC3 and LPL molecules differ between patients and controls and to study their relationship with SLE disease damage.ResultsAfter fully multivariable analysis that included classic CV risk factors, and the modifications that the disease itself produces over the lipid profile, it was found that ApoC3 was significantly lower (beta coef. -1.2 [95%CI -1.6- -0.8) mg/dl, &lt;0.001), and ANGPTL4 (beta coef. 63 [95%CI 35-90] ng/ml, &lt;0.001) and LPL (beta coef. 79 [95%CI 30-128] ng/ml, p=0.002) significantly higher in patients with SLE compared to controls. Disease damage score was significantly and independently associated with higher serum levels of LPL (beta coef. 23 [95%CI 10-35] ng/ml, p=0.001). Mediation analysis suggested that the relationship between disease damage and LPL was direct and not mediated by ApoC3 or ANGPLT4.ConclusionThe ApoC3, ANGPLT4 and LPL axis is disrupted in patients with SLE. Disease damage explains this disturbance.
Hyperoxia Is Not Associated With 30-day Survival in Out-of-Hospital Cardiac Arrest Patients Who Undergo Extracorporeal Cardiopulmonary Resuscitation
Authors: Kobayashi Mioko , Kashiura Masahiro , Yasuda Hideto , Sugiyama Kazuhiro , Hamabe Yuichi , Moriya Takashi 
Published: May 2022

IntroductionThe appropriate arterial partial pressure of oxygen (PaO2) in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) remains unclear. The present study aimed to investigate the relationship between hyperoxia and 30-day survival in patients who underwent ECPR.Materials and MethodsThis single-center retrospective cohort study was conducted between January 2010 and December 2018. OHCA patients who underwent ECPR were included in the study. Exclusion criteria were (1) age &lt;18 years, (2) death within 24 h after admission, (3) return of spontaneous circulation at hospital arrival, and (4) hypoxia (PaO2 &lt; 60 mmHg) 24 h after admission. Based on PaO2 at 24 h after admission, patients were classified into normoxia (60 mmHg ≤ PaO2 ≤ 100 mmHg), mild hyperoxia (100 mmHg &lt; PaO2 ≤ 200 mmHg), and severe hyperoxia (PaO2 &gt; 200 mmHg) groups. The primary outcome was 30-day survival after cardiac arrest, while the secondary outcome was 30-day favorable neurological outcome. Multivariate logistic regression analysis for 30-day survival or 30-day favorable neurological outcome was performed using multiple propensity scores as explanatory variables. To estimate the multiple propensity score, we fitted a multinomial logistic regression model using the patients' demographic, pre-hospital, and in-hospital characteristics.ResultsOf the patients who underwent ECPR in the study center, 110 were eligible for the study. The normoxia group included 29 cases, mild hyperoxia group included 46 cases, and severe hyperoxia group included 35 cases. Mild hyperoxia was not significantly associated with survival, compared with normoxia as the reference (adjusted odds ratio, 1.06; 95% confidence interval: 0.30–3.68; p = 0.93). Severe hyperoxia was also not significantly associated with survival compared to normoxia (adjusted odds ratio, 1.05; 95% confidence interval: 0.27–4.12; p = 0.94). Furthermore, no association was observed between oxygenation and 30-day favorable neurological outcomes.ConclusionsThere was no significant association between hyperoxia at 24 h after admission and 30-day survival in OHCA patients who underwent ECPR.
A Porcine Sepsis Model With Numerical Scoring for Early Prediction of Severity
Authors: Rutai Attila , Zsikai Bettina , Tallósy Szabolcs Péter , Érces Dániel , Bizánc Lajos , Juhász László , Poles Marietta Zita , Sóki József , Baaity Zain , Fejes Roland , Varga Gabriella , Földesi Imre , Burián Katalin , Szabó Andrea , Boros Mihály , Kaszaki József 
Published: May 2022

IntroductionSepsis can lead to organ dysfunctions with disturbed oxygen dynamics and life-threatening consequences. Since the results of organ-protective treatments cannot always be transferred from laboratory models into human therapies, increasing the translational potential of preclinical settings is an important goal. Our aim was to develop a standardized research protocol, where the progression of sepsis-related events can be characterized reproducibly in model experiments within clinically-relevant time frames.MethodsPeritonitis was induced in anesthetized minipigs injected intraperitoneally with autofeces inoculum (n = 27) or with saline (sham operation; n = 9). The microbial colony-forming units (CFUs) in the inoculum were retrospectively determined. After awakening, clinically relevant supportive therapies were conducted. Nineteen inoculated animals developed sepsis without a fulminant reaction. Sixteen hours later, these animals were re-anesthetized for invasive monitoring. Blood samples were taken to detect plasma TNF-α, IL-10, big endothelin (bET), high mobility group box protein1 (HMGB1) levels and blood gases, and sublingual microcirculatory measurements were conducted. Hemodynamic, respiratory, coagulation, liver and kidney dysfunctions were detected to characterize the septic status with a pig-specific Sequential Organ Failure Assessment (pSOFA) score and its simplified version (respiratory, cardiovascular and renal failure) between 16 and 24 h of the experiments.ResultsDespite the standardized sepsis induction, the animals could be clustered into two distinct levels of severity: a sepsis (n = 10; median pSOFA score = 2) and a septic shock (n = 9; median pSOFA score = 8) subgroup at 18 h of the experiments, when the decreased systemic vascular resistance, increased DO2 and VO2, and markedly increased ExO2 demonstrated a compensated hyperdynamic state. Septic animals showed severity-dependent scores for organ failure with reduced microcirculation despite the adequate oxygen dynamics. Sepsis severity characterized later with pSOFA scores was in correlation with the germ count in the induction inoculum (r = 0.664) and CFUs in hemocultures (r = 0.876). Early changes in plasma levels of TNF-α, bET and HMGB1 were all related to the late-onset organ dysfunctions characterized by pSOFA scores.ConclusionsThis microbiologically-monitored, large animal model of intraabdominal sepsis is suitable for clinically-relevant investigations. The methodology combines the advantages of conscious and anesthetized studies, and mimics human sepsis and septic shock closely with the possibility of numerical quantification of host responses.
SPECT Imaging of Acute Disc Herniation by Targeting Integrin α5β1 in Rat Models
Authors: Guan Jian , Yuan Chenghua , Tian Xin , Cheng Lei , Gao Hannan , Yao Qingyu , Wang Xinyu , Wu Hao , Chen Zan , Jian Fengzeng 
Published: May 2022

ObjectiveTraditional morphological imaging of intervertebral disc herniation (IVDH) is challenging in early disease diagnosis. Aiming at the early diagnosis of IVD by non-invasive molecular imaging targeting of integrin α5β1, we performed novel imaging in rats with acute IVDH for the first time.MethodsAnimal models were prepared by conducting an established needle puncture procedure through the normal intervertebral disc (IVD). The disc-injured rats underwent SPECT/CT imaging of the 99mTc-3PisoDGR2 peptide at 1 day to 2 months postinjury. The expression change of integrin α5β1 was determined by anti-integrin α5 and anti-integrin α5β1 immunohistochemistry (IHC). Magnetic resonance imaging (MRI) was performed for comparison during disease progression. The morphological changes of the disc were determined by safranin-O staining.ResultsRats with acute IVDH showed gradually increased disc uptake of 99mTc-3PisoDGR2 from 1 to 7 days posttreatment, which was a significantly higher level than that of the normal disks in degenerative diseases. IHC results showed the expression of integrin α5β1 on the surface of annulus fibrosus (AF) cells and nucleus pulposus (NP) cells, which agreed with the uptake data. MRI showed a progressively decreased T2 density and MRI index throughout the investigation. Hematoxylin and eosin (HE) staining and safranin-O staining revealed a disorganized structure of the IVD as well as loss of proteoglycans after puncture.ConclusionsThe present study demonstrated a good correlation between integrin α5β1 expression and acute disc herniation. The SPECT/CT imaging of 99mTc-3PisoDGR2 targeting integrin α5β1 may diagnose IVDH in an acute phase for early disease management.
The Impact of Endovascular Rescue Therapy on the Clinical and Radiological Outcome After Aneurysmal Subarachnoid Hemorrhage: A Safe and Effective Treatment Option for Hemodynamically Relevant Vasospasm?
Authors: Mielke Dorothee , Döring Katja , Behme Daniel , Psychogios Marios Nikos , Rohde Veit , Malinova Vesna 
Published: May 2022

ObjectiveCerebral vasospasm (CVS) represents one of the multiple contributors to delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH). Especially the management of CVS, refractory to medical treatment, is a challenging task during the acute phase after aSAH. Endovascular rescue therapies (ERT), such as medical and mechanical dilation, are possible treatment options on an individual basis. However, data about the influence on the patients' functional outcomes are limited. This study aims to assess the impact of ERT on the long-term functional outcome in aSAH-patients with refractory CVS.MethodsWe performed a retrospective analysis of aSAH patients treated between 2012 and 2018. CVS was considered refractory, if it persisted despite oral/intravenous nimodipine application and induced hypertension. The decision to perform ETR was made on an individual basis, according to the detection of “tissue at risk” on computed tomography perfusion (CTP) scans and CVS on computed tomography angiography (CTA) or digital subtraction angiography (DSA). The functional outcome was assessed according to the modified Rankin scale (mRS) 3 months after the ictus, whereas an mRS ≤ 2 was considered as a good outcome.ResultsA total of 268 patients were included. Out of these, 205 patients (76.5%) were treated without ERT (group 1) and 63 patients (23.5%) with ERT (group 2). In 20 patients (31.8%) balloon dilatation was performed, in 23 patients (36.5%) intra-arterial nimodipine injection alone, and in 20 patients (31.8%) both procedures were combined. Considering only the patient group with DCI, the patients who were treated with ERT had a significantly better outcome compared to the patients without ERT (Mann–Whitney test, p = 0.02).ConclusionEndovascular rescue therapies resulted in a significantly better functional outcome in patients with DCI compared to the patient group treated without ETR. CTP and CTA-based identification of “tissue at risk” might be a reliable tool for patient selection for performing ERT.
Safety, Adherence and Persistence in a Real-World Cohort of German MS Patients Newly Treated With Ocrelizumab: First Insights From the CONFIDENCE Study
Authors: Weber Martin S. , Buttmann Mathias , Meuth Sven G. , Dirks Petra , Muros-Le Rouzic Erwan , Eggebrecht Julius C. , Hieke-Schulz Stefanie , Leemhuis Jost , Ziemssen Tjalf 
Published: May 2022

BackgroundReal-world relapsing multiple sclerosis (RMS) and primary progressive MS (PPMS) populations may be more diverse than in clinical trials. Here, we present a first analysis of safety, adherence and persistence data from a real-world cohort of patients newly treated with ocrelizumab.MethodsCONFIDENCE (ML39632, EUPAS22951) is an ongoing multicenter, non-interventional post authorization safety study assessing patients with RMS or PPMS newly treated with ocrelizumab or other disease-modifying therapies for up to 10 years. For this analysis, patients newly treated with ocrelizumab were analyzed in subgroups by MS phenotype and age over a mean ~1 year of exposure totaling 2,329 patient years [PY]).ResultsAt data cutoff (14 October 2020), 1,702 patients with RMS and 398 patients with PPMS were treated with ≥1 dose of ocrelizumab. At baseline, the mean ages (SD) of patients with RMS and PPMS were 41.59 (11.24) and 50.95 (9.88) years and the mean EDSS (Expanded Disability Status Scale) was 3.18 (1.87) and 4.41 (1.59), respectively. The most common adverse events (AEs) and serious AEs across both phenotypes were infections and infestations, with infection SAE rates of 2.8 events/100 PY and 1.5 events/100 PY in patients with RMS and PPMS, respectively. Across all phenotypes, ocrelizumab persistence was 92% at 24 months; median time between doses was ~6 months.ConclusionsThe ocrelizumab safety profile observed in the CONFIDENCE real-world MS population was consistent to the one observed in pivotal clinical trials. High treatment persistence and adherence were observed.Trial RegistrationML39632, EUPAS22951
Multifocal Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIA/DIG): An Institutional Series Report and a Clinical Summary of This Rare Tumor
Authors: Wang Qiguang , Meng Jinli , Cheng Jian , Zhang Si , Hui Xuhui , Li Qiang , Liu Wenke , Ju Yan , Sun Lin 
Published: May 2022

AimMultifocal desmoplastic infantile ganglioglioma/astrocytoma (DIA/DIG) has rarely been reported. Here, two cases have been presented, reviewing the literature and proposed treatment algorithms for this rare tumor.Patients and MethodsWe report two patients diagnosed with multifocal DIA/DIGs in West China Hospital. In addition, a literature review was performed, in October 2019, on case reports of DIA/DIGs with multifocal lesions. The clinical and radiological features, treatment, and outcome of this rare disease were discussed.ResultsDIA/DIGs with multifocal locations were rare, and only thirteen cases (including ours) had been reported. This series included 8 males and 5 females with a mean age of 31.4 ± 45.7 months (range, 3-144 months). The supratentorial hemisphere, suprasellar region, posterior cranial fossa, and spinal cord were frequently involved. Ten patients (76.9%) received surgical resection for the symptomatic lesions and three patients (23.1%) underwent biopsy. Seven patients received chemotherapy postoperatively. Six individuals had tumor recurrences during the follow-up period, while three patients had tumors that spontaneously regressed. Finally, two patients died of tumor progression and one patient died of respiratory insufficiency and hypothalamic dysfunction.ConclusionsMultifocal DIA/DIGs have more aggressive clinical behavior and poor outcome despite benign histology. DIA/DIGs should be included in the differential diagnosis of multifocal brain tumors in children. The mainstay of treatment is surgical resection; adjuvant treatment with chemotherapeutic drugs is unknown and requires additional research.
A Crucial Angiogenesis-Associated Gene MEOX2 Could Be a Promising Biomarker Candidate for Breast Cancer
Authors: Wang Huxia , Tang Yanan , Yang Xiaomin , Wang Weiyi , Han Pihua , Zhao Jing , He Sai , Liu Peijun 
Published: May 2022

BackgroundAngiogenesis plays a critical role in the growth and metastasis of breast cancer and angiogenesis inhibition has become an effective strategy for cancer therapy. Our study aimed to clarify the key candidate genes and pathways related to breast cancer angiogenesis.MethodsDifferentially expressed genes (DEGs) in the raw breast cancer (BRCA) gene dataset from the Cancer Genome Atlas (TCGA) database were identified and gene ontology analysis of the DEGs was performed. Hub genes were subsequently determined using the Gene Expression Omnibus database. The expression of the mesenchyme homeobox 2 (MEOX2) in breast cancer cells and tissues was assessed by quantification real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), respectively. The prognostic value of the MEOX2 gene in breast cancer tissue was evaluated with the Kaplan-Meier plotter.ResultsA total of 61 angiogenesis-related DEGs were identified in the TCGA dataset, among which the gene MEOX2 was significantly down-regulated. GO functional annotation and pathway enrichment analyses showed that MEOX2 was significantly enriched in the regulation of vasculature development. The IHC results confirmed that MEOX2 expression was repressed in breast cancer tissues and the relatively low level indicated the tissue was densely vascularized. Moreover, MEOX2 expression was significantly elevated in breast cancer cells after treatment with cisplatin (DDP) and epirubicin (EPI). Finally, the Kaplan-Meier plotter confirmed that higher expression levels of MEOX2 were related to better overall survival.ConclusionOur study revealed that the angiogenesis-associated gene MEOX2 can be used as a novel biomarker for breast cancer diagnosis and clinical therapy.
Are Children Suffering From Congenital Pseudarthrosis of the Tibia Associated With Decreased Bone Strength?
Authors: Yang Ge , Xu Siyu , Mei Haibo , Zhu Guanghui , Liu Yaoxi , Tan Qian , Yu Hui 
Published: May 2022

Background:Congenital pseudarthrosis of the tibia (CPT) is a rare and difficult-to-treat congenital disease in neonates. Our previous study found that exosomes derived from serum of children with CPT inhibit bone formation. In this study, we used ultrasound bone densitometry to detect the bone strength differences between hospitalized children with CPT and with non-metabolic diseases to determine the bone strength of children with CPT.MethodsA total of 37 children with CPT with a mean age of 3.14 ± 1.81 years and 40 hospitalized children with a mean age of 3.32 ± 2.66 years with supracondylar fracture of the humerus and without a bone metabolic disease (control group) were recruited in our hospital. The ultrasonic bone densitometer was used to examine the bilateral calcaneus of the subjects. We collected the broadband ultrasonic attenuation (BUA), speed of sound (SOS), quantitative ultrasound index (QUI), bone strength index (STI) and bone mineral density estimation (BMDe) values. Multivariable regression was used to examine the associations between quantitative ultrasound measurement differences and age, body mass index (BMI), neurofibromatosis type 1 (NF1) and CPT Crawford type. Intra-class correlation coefficient (ICC) was calculated to estimate intra- and inter-rater agreements.Results74 calcaneus scans were taken from CPT patients (23 boys and 14 girls) and 80 calcaneus scans were taken from the control (24 boys and 16 girls). The CPT patients exhibited significantly lower SOS (1,368.75 ± 136.78 m/s), STI (7.2319 ± 38.6525), QUI (8.2532 ± 56.1720), and BMDe (−0.0241 ± 0.3552 g/cm3) than the control (SOS: 1,416.02 ± 66.15 m/s, STI: 7.96 ± 16.884, QUI: 28.8299 ± 25.461, BMDe: 0.0180 ± 0.1610 g/cm3). Multiple regression revealed that SOS, STI and QUI were statistically significant and negatively correlated with CPT Crawford classification.ConclusionsWe found the incidence of decreased bone strength in CPT group was higher than that in the non-bone metabolic disease group. This phenomenon was not related to NF1 but related to CPT Crawford classification, which suggested that the higher the grade of the CPT Crawford classification, the lower the bone strength and the higher the risk of fracture.
Effects of Chang-Kang-Fang Formula on the Microbiota-Gut-Brain Axis in Rats With Irritable Bowel Syndrome
Authors: Ling Xiwen , Peng Siyuan , Zhong Jingbin , Guo Lirong , Xu Yaqin , Jin Xiaobao , Chu Fujiang 
Published: May 2022

Chang-Kang-Fang formula (CKF), a multi-herb traditional Chinese medicine, has been used in clinical settings to treat irritable bowel syndrome (IBS). Recent studies show that 5.0 g/kg/d CKF can alleviate the symptoms of IBS rats by modulating the brain-gut axis through the production of brain-gut peptides (BGPs), thus relieving pain, and reversing the effects of intestinal propulsion disorders. However, the exact mechanisms underlying the therapeutic effects of CKF in IBS remain unclear. The microbiota-gut-brain axis (MGBA) is central to the pathogenesis of IBS, regulating BGPs, depression-like behaviors, and gut microbiota. Given that CKF ameliorates IBS via the MGBA, we performed metabolomic analyses, evaluated the gut microbiota, and system pharmacology to elucidate the mechanisms of action of CKF. The results of intestinal tract motility, abdominal withdrawal reflex (AWR), sucrose preference test (SPT), and the forced swimming test (FST) showed that the male Sprague–Dawley rats subjected to chronic acute combining stress (CACS) for 22 days exhibited altered intestinal motility, visceral hypersensitivity, and depression-like behaviors. Treatment of IBS rats with CKF normalized dysfunctions of CACS-induced central and peripheral nervous system. CKF regulated BDNF and 5-HT levels in the colon and hippocampus as well as the expressions of the related BGP pathway genes. Moreover, the system pharmacology assays were used to assess the physiological targets involved in the action of CKF, with results suggesting that CKF putatively functioned through the 5-HT-PKA-CREB-BDNF pathway. LC-MS-based metabolomics identified the significantly altered 5-HT pathway-related metabolites in the CKF treatment group, and thus, the CKF-related signaling pathways were further examined. After pyrosequencing-based analysis of bacterial 16S rRNA (V3 + V4 region) using rat feces, the Lefse analysis of gut microbiota suggested that CKF treatment could induce structural changes in the gut microbiota, thereby regulating it by decreasing Clostridiales, and the F-B ratio while increasing the levels of Lactobacillus. Furthermore, the integrated analysis showed a correlation of CKF-associated microbes with metabolites. These findings showed that CKF effectively alleviated IBS, which was associated with the altered features of the metabolite profiles and the gut microbiota through a bidirectional communication along the microbiota-gut-brain axis.