bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomic Profiling of Pregnancies With Polycystic Ovary Syndrome Identifies a Unique Metabolic Signature and Potential Predictive Biomarkers of Low Birth Weight
Authors: Diboun Ilhame , Ramanjaneya Manjunath , Ahmed Lina , Bashir Mohammed , Butler Alexandra E. , Albagha Omar , Abou-Samra Abdul Badi , Atkin Stephen L. , Mazloum Nayef A. , Elrayess Mohamed A. 
Published: June 2021

BackgroundPolycystic ovary syndrome (PCOS) is a complex syndrome with clinical features of an endocrine/metabolic disorder. Various metabolites show significant association with PCOS; however, studies comparing the metabolic profile of pregnant women with and without PCOS are lacking. In this study, metabolomics analysis of blood samples collected from PCOS women and age and BMI matched controls in the second trimester of pregnancy was performed to identify metabolic differences between the two groups and determine their association with pregnancy outcome.MethodsSixteen PCOS and fifty-two healthy women in their second trimester underwent targeted metabolomics of plasma samples using tandem mass spectrometry with the Biocrates MxP® Quant 500 Kit. Linear regression models were used to identify the metabolic alterations associated with PCOS, followed by enrichment and Receiver Operating Characteristic (ROC) analyses to determine the best indicators of pregnancy outcomes.ResultsPCOS women had lower birth weight babies compared to healthy controls. As a group, systolic blood pressure (SBP) at both second trimester and at delivery negatively correlated with birth weight. Regression models indicated significant increases in the triglycerides C20:4_C34:3 and C18:2_C38:6 in the PCOS group [false discovery rate (FDR) &lt;0.05]. Enrichment analysis revealed significant elevations in triglycerides containing arachidonic acid, linoleic acid and palmitic acid in the PCOS group. A number of indicators of baby birth weight were identified including SBP at delivery, hexosylceramide (d18:2/24:0), ceramide (d18.0/24.1) and serine, with an AUC for all predictors combined for low birth weight (≤2500grams) of 0.88 (95%CI: 0.75-1.005, p&lt;0.001).ConclusionsPCOS pregnancies resulted in babies with a lower birth weight, marked by a unique metabolic signature that was enriched with specific triglycerides and unsaturated fatty acids. The functional significance of these associations needs further investigation.
Cardiovascular Safety of Febuxostat and Allopurinol in Hyperuricemic Patients With or Without Gout: A Network Meta-Analysis
Authors: Zhang Shengzhao , Xu Ting , Shi Qingyang , Li Sheyu , Wang Ling , An Zhenmei , Su Na 
Published: June 2021

Background: Hyperuricemia is a common metabolic disease and has become a public health problem because of its increasing prevalence and association with comorbidities. Allopurinol and febuxostat are recommended as the first-line treatments for hyperuricemia and gout. But cardiovascular safety between febuxostat and allopurinol is still controversial. The purpose of this study is to compare the cardiovascular safety of XOIs and placebo in hyperuricemic patients with or without gout.Methods: PubMed, Embase via OVID, Cochrane Library, CNKI, Wanfang, and VIP were searched from their earliest records to February 8th 2021. ClinicalTrials.gov was also searched for unpublished data. The reference lists of included studies and relevant review articles investigating the cardiovascular safety of XOIs in hyperuricemia patients are screened for potentially eligible studies. Randomized controlled trials (RCTs) evaluating allopurinol (100~900 mg/d), febuxostat (20~120 mg/d), or placebo for hyperuricemia were included. The outcomes were incidence of MACE, non-fatal MI, non-fatal stroke, and cardiovascular death. We conducted a Bayesian random-effects network meta-analysis on the included randomized controlled trials using the Markov Chain Monte Carlo simulation method. The grading of recommendations assessment, development, and evaluation (GRADE) approach was used to assesses the certainty of the evidence.Results: Ten RCTs with 18,004 participants were included. The network estimates showed that there was no significant difference observed among febuxostat, allopurinol, and placebo regarding outcomes. The certainty of the evidence ranged from very low to moderate. The probabilities of rankings and SUCRA showed that compared to placebo, febuxostat, and allopurinol might prevent adverse cardiovascular events.Conclusion: Febuxostat is not associated with increasing risk of adverse cardiovascular events compared to allopurinol; and compared to placebo, whether febuxostat and allopurinol reduce the risk of adverse cardiovascular events remains uncertain.
Metabolomic Analysis of Hexagenid Mayflies Exposed to Sublethal Concentrations of Naphthenic Acid
Authors: Pomfret Sarah M. , Brua Robert B. , Milani Danielle , Yates Adam G. 
Published: June 2021

The oil sands region in northeastern Alberta, Canada contain approximately 165 billion barrels of oil making it the third largest oil reserves in the world. However, processing of extracted bitumen generates vast amounts of toxic byproduct known as oil sands process waters. Naphthenic acids and associated sodium naphthenate salts are considered the primary toxic component of oil sands process waters. Although a significant body of work has been conducted on naphthenic acid toxicity at levels comparable to what is observed in current oil sands process waters, it is also important to understand any impacts of exposure to sublethal concentrations. We conducted a microcosm study using the mayflyHexageniaspp.to identify sublethal impacts of naphthenic acid exposure on the survival, growth, and metabolome across a concentration gradient (0–100 μg L−1) of sodium naphthenate. Nuclear magnetic resonance-based metabolomic analyses were completed on both the polar and lipophilic extracted fractions of whole organism tissue. We observed a positive relationship between sodium naphthenate concentration and mean principal component score of the first axis of the polar metabolome indicating a shift in the metabolome with increasing naphthenic acid exposure. Eleven metabolites correlated with increased naphthenic acid concentration and included those involved in energy metabolism and apoptosis regulation. Survival and growth were both high and did not differ among concentrations, with the exception of a slight increase in mortality observed at the highest concentration. Although lethal concentrations of naphthenic acids in other studies are higher (150–56,200 μg L−1), our findings suggest that physiological changes in aquatic invertebrates may begin at substantially lower concentrations. These results have important implications for the release of naphthenic acids into surface waters in the Alberta oil sands region as an addition of even small volumes of oil sands process waters could initiate chronic effects in aquatic organisms. Results of this research will assist in the determination of appropriate discharge thresholds should oil sands process waters be considered for environmental release.
Exclusion of the Possibility of “False Ripples” From Ripple Band High-Frequency Oscillations Recorded From Scalp Electroencephalogram in Children With Epilepsy
Authors: Kobayashi Katsuhiro , Shibata Takashi , Tsuchiya Hiroki , Akiyama Tomoyuki 
Published: June 2021

AimRipple-band epileptic high-frequency oscillations (HFOs) can be recorded by scalp electroencephalography (EEG), and tend to be associated with epileptic spikes. However, there is a concern that the filtration of steep waveforms such as spikes may cause spurious oscillations or “false ripples.” We excluded such possibility from at least some ripples by EEG differentiation, which, in theory, enhances high-frequency signals and does not generate spurious oscillations or ringing.MethodsThe subjects were 50 pediatric patients, and ten consecutive spikes during sleep were selected for each patient. Five hundred spike data segments were initially reviewed by two experienced electroencephalographers using consensus to identify the presence or absence of ripples in the ordinary filtered EEG and an associated spectral blob in time-frequency analysis (Session A). These EEG data were subjected to numerical differentiation (the second derivative was denoted as EEG″). The EEG″ trace of each spike data segment was shown to two other electroencephalographers who judged independently whether there were clear ripple oscillations or uncertain ripple oscillations or an absence of oscillations (Session B).ResultsIn Session A, ripples were identified in 57 spike data segments (Group A-R), but not in the other 443 data segments (Group A-N). In Session B, both reviewers identified clear ripples (strict criterion) in 11 spike data segments, all of which were in Group A-R (p &lt; 0.0001 by Fisher’s exact test). When the extended criterion that included clear and/or uncertain ripples was used in Session B, both reviewers identified 25 spike data segments that fulfilled the criterion: 24 of these were in Group A-R (p &lt; 0.0001).DiscussionWe have demonstrated that real ripples over scalp spikes exist in a certain proportion of patients. Ripples that were visualized consistently using both ordinary filters and the EEG″ method should be true, but failure to clarify ripples using the EEG″ method does not mean that true ripples are absent.ConclusionThe numerical differentiation of EEG data provides convincing evidence that HFOs were detected in terms of the presence of such unusually fast oscillations over the scalp and the importance of this electrophysiological phenomenon.
The Prognostic Value of Pre-treatment Hemoglobin (Hb) in Patients With Advanced or Metastatic Gastric Cancer Treated With Immunotherapy
Authors: Gou Miaomiao , Zhang Yong , Liu Tiee , Qu Tongtong , Si Haiyan , Wang Zhikuan , Yan Huan , Qian Niansong , Dai Guanghai 
Published: June 2021

BackgroundBiomarkers such as prevailing PD-L1 expression and TMB have been proposed as a way of predicting the outcome of immunotherapy in patients with advanced gastric cancer (AGC) and metastatic gastric cancer (MGC). Our study aims to investigate whether there is a link between pretreatment hemoglobin (Hb) levels and survival to immunotherapy in patients with AGC and MGC.MethodsWe retrospectively reviewed patients with AGC or MGC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor. The Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) and overall survival (OS) was analyzed among different Hb level (normal Hb group and decreased Hb group). Objective response rate (ORR), disease control rate (DCR) were also analyzed. Univariate analysis and multivariate analysis were performed further to validate the prognostic value of Hb level.ResultsWe included 137 patients with AGC and MGC who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) in this study. After PSM matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 7.8 months in the normal Hb level group and 4.3 months in the decreased Hb group (HR 95% CI 0.5(0.31, 0.81), P=0.004). The OS was 14.4 months with normal Hb level as compared with 8.2 months with decreased Hb level(HR 95% CI 0.59(0.37, 0.94), P=0.024). The ORR was 40.7% and DCR was 83.0% in the normal Hb group, while the ORR was 25.5% and DCR was 85.1% in the decreased Hb group. No significant differences were found in the ORR and DCR between the two groups (P=0.127, P=0.779). Univariate analysis and multivariate analysis showed that Hb level was only independent predictor for PFS and baseline Hb level was significant prognostic factor influencing the OS. Only when patients had normal Hb level, anti-pd-1 monotherapy or combined with chemotherapy was superior to anti-pd-1 plus anti-angiogenic therapy with respect to PFS (10.3 m vs 2.8 m, HR 95% CI 0.37(0.15, 0.95), P=0.031) and OS(15 m vs 5.7 m, HR 95% CI 0.21 (0.08, 0.58), P=0.001).ConclusionsOur study have demonstrated that pretreatment Hb level was an independent prognostic biomarker in term of PFS and OS with immunotherapy for AGC and MGC patients. Correction of anemia for GC patients as immunotherapy would be a strategy to improve the survival. More data was warranted to further influence this finding.
Outstanding Response in a Patient With ROS1-Rearranged Inflammatory Myofibroblastic Tumor of Soft Tissues Treated With Crizotinib: Case Report
Authors: Comandini Danila , Catalano Fabio , Grassi Massimiliano , Pesola Guido , Bertulli Rossella , Guadagno Antonio , Spina Bruno , Mascherini Matteo , De Cian Franco , Pistoia Federico , Rebuzzi Sara Elena 
Published: June 2021

Inflammatory myofibroblastic tumor (IMT) is a very rare subtype of sarcoma, which frequently harbor chromosomal rearrangements, including anaplastic lymphoma kinase (ALK) rearrangements (almost 50% of the IMTs) and other kinase fusions such as ROS1. ROS1 fusions are present in about 10% of IMT, almost half of the ALK-negative IMT patients. Apart from radical surgery for resectable tumors, there is no standard-of-care therapy for advanced IMTs. Nonetheless, the use of tyrosine kinase inhibitors has shown promising efficacy in IMT patients with targetable genomic alterations. We report the case of a 24-year-old patient with chemotherapy-refractory metastatic IMT harboring ROS1 kinase fusion, who experienced a significant clinical and pathological response to crizotinib. This clinical case highlights the need to assess all patients with unresectable IMTs for chromosomal abnormalities and gene mutations and address them to targeted agents as well as clinical trials.
Prospective Assessment of Early Proton Therapy-Induced Optic Neuropathy in Patients With Intracranial, Orbital or Sinonasal Tumors: Impact of A Standardized Ophthalmological Follow Up
Authors: Lecornu Marie , Lesueur Paul , Salleron Julia , Balosso Jacques , Stefan Dinu , Kao William , Plouhinec Tiphaine , Vela Anthony , Dutheil Pauline , Bouter Jordan , Marty Pierre-Alban , Thariat Juliette , Quintyn Jean-Claude 
Published: June 2021

PurposeProton therapy (PT) can be a good option to achieve tumor control while reducing the probability of radiation induced toxicities compared to X-ray-based radiotherapy. However, there are still uncertainties about the effects of PT on the organs in direct contact with the irradiated volume. The aim of this prospective series was to report 6-month follow-up of clinical and functional optic neuropathy rates of patients treated by proton therapy using a standardized comprehensive optic examination.Methods and MaterialsStandardized ophthalmological examinations were performed to analyze subclinical anomalies in a systematic way before treatment and 6 months after the end of proton therapy with: Automatic visual field, Visual evoked potential (VEP) and optic coherence of tomography (OCT).ResultsFrom October 2018 to July 2020 we analyzed 81 eyes. No significant differences were found in the analysis of the clinical examination of visual functions by the radiation oncologist. However, considering VEP, the impairment was statistically significant for both fibers explored at 30’angle (p:0.007) and 60’angle (p &lt;0.001). In patients with toxicity, the distance of the target volume from the optical pathways was more important with a p-value for 30’VEP at 0.035 and for 60’VEP at 0.039.ConclusionsThese results confirm uncertainties concerning relative biological effectiveness of proton therapy, linear energy transfer appears to be more inhomogeneous especially in areas close to the target volumes. The follow-up of patients after proton therapy is not an easy process to set up but it is necessary to improve our knowledges about the biological effects of proton therapy in real life. Our study which will continue during the coming years, suggests that follow-up with in-depth examinations such as VEP as a biomarker could improve the detection of early abnormalities.
Osteoking Decelerates Cartilage Degeneration in DMM-Induced Osteoarthritic Mice Model Through TGF-β/smad-dependent Manner
Authors: Ling Houfu , Zeng Qinghe , Ge Qinwen , Chen Jiali , Yuan Wenhua , Xu Rui , Shi Zhenyu , Xia Hanting , Hu Songfeng , Jin Hongting , Wang Pinger , Tong Peijian 
Published: June 2021

Osteoarthritis (OA) is a common disease characterized by cartilage degeneration. In recent years much attention has been paid to Traditional Chinese Medicine (TCM) since its treatments have shown efficacy for ameliorating cartilage degradation with mild side effects. Osteoking is a TCM prescription that has long been used in OA treatment. However, the exact mechanism of Osteoking are not fully elucidated. In the current study, destabilization of the medial meniscus (DMM)-induced OA mice was introduced as a wild type animal model. After 8 weeks of administration of Osteoking, histomorphometry, OARSI scoring, gait analysis, micro-CT, and immunohistochemical staining for Col2, MMP-13, TGFβRII and pSmad-2 were conducted to evaluate the chondroprotective effects of Osteoking in vivo. Further in vitro experiments were then performed to detect the effect of Osteoking on chondrocytes. TGFβRIICol2ER transgenic mice were constructed and introduced in the current study to validate whether Osteoking exerts its anti-OA effects via the TGF-β signaling pathway. Results demonstrated that in wild type DMM mice, Osteoking ameliorated OA-phenotype including cartilage degradation, subchondral bone sclerosis, and gait abnormality. Col2, TGFβRII, and pSmad-2 expressions were also found to be up-regulated after Osteoking treatment, while MMP-13 was down-regulated. In vitro, the mRNA expression of MMP-13 and ADAMTS5 decreased and the mRNA expression of Aggrecan, COL2, and TGFβRII were up-regulated after the treatment of Osteoking in IL-1β treated chondrocytes. The additional treatment of SB505124 counteracted the positive impact of Osteoking on primary chondrocytes. In TGFβRIICol2ER mice, spontaneous OA-liked phenotype was observed and treatment of Osteoking failed to reverse the OA spontaneous progression. In conclusion, Osteoking ameliorates OA progression by decelerating cartilage degradation and alleviating subchondral bone sclerosis partly via the TGF-β signaling pathway.
Retrospective Study on the Influencing Factors and Prediction of Hospitalization Expenses for Chronic Renal Failure in China Based on Random Forest and LASSO Regression
Authors: Dai Pingping , Chang Weifu , Xin Zirui , Cheng Haiwei , Ouyang Wei , Luo Aijing 
Published: June 2021

Aim: With the improvement in people's living standards, the incidence of chronic renal failure (CRF) is increasing annually. The increase in the number of patients with CRF has significantly increased pressure on China's medical budget. Predicting hospitalization expenses for CRF can provide guidance for effective allocation and control of medical costs. The purpose of this study was to use the random forest (RF) method and least absolute shrinkage and selection operator (LASSO) regression to predict personal hospitalization expenses of hospitalized patients with CRF and to evaluate related influencing factors.Methods: The data set was collected from the first page of data of the medical records of three tertiary first-class hospitals for the whole year of 2016. Factors influencing hospitalization expenses for CRF were analyzed. Random forest and least absolute shrinkage and selection operator regression models were used to establish a prediction model for the hospitalization expenses of patients with CRF, and comparisons and evaluations were carried out.Results: For CRF inpatients, statistically significant differences in hospitalization expenses were found for major procedures, medical payment method, hospitalization frequency, length of stay, number of other diagnoses, and number of procedures. The R2 of LASSO regression model and RF regression model are 0.6992 and 0.7946, respectively. The mean absolute error (MAE) and root mean square error (RMSE) of the LASSO regression model were 0.0268 and 0.043, respectively, and the MAE and RMSE of the RF prediction model were 0.0171 and 0.0355, respectively. In the RF model, and the weight of length of stay was the highest (0.730).Conclusions: The hospitalization expenses of patients with CRF are most affected by length of stay. The RF prediction model is superior to the LASSO regression model and can be used to predict the hospitalization expenses of patients with CRF. Health administration departments may consider formulating accurate individualized hospitalization expense reimbursement mechanisms accordingly.
Assessment of Platelet and Plasma Serotonin in Canine Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease
Authors: Tangmahakul Nattawan , Makoom Pussadee , Surachetpong Sirilak Disatian 
Published: June 2021

Background: Pulmonary hypertension (PH) is a common complication of degenerative mitral valve disease (DMVD), the most common cardiovascular disease in dogs. Serotonin has been suspected to play a role in the pathogenesis of PH, so this study aimed to investigate the differences in platelet and plasma serotonin between normal, DMVD and DMVD with PH (DMVD+PH) dogs.Materials and Methods: Sixty-two small-breed dogs were enrolled to the study and divided into the normal (n = 22), DMVD (n = 20), and DMVD+PH (n = 20) groups. The platelet and plasma serotonin concentrations were measured by the competitive ELISA.Results: The Kruskal–Wallis revealed the difference among the four groups of normal (179.73 [102.37–352.24] ng/109 platelets), DMVD (325.99 [96.84–407.66] ng/109 platelets), DMVD with intermediate probability of PH (291.11 [106.69–400.84] ng/109 platelets) and DMVD with high probability of PH (35.82 [2.69–126.35] ng/109 platelets) (p = 0.014). The Dunn's post-hoc test showed a decrease in the platelet serotonin concentration of the DMVD dogs with high probability of PH compared to the DMVD group (p = 0.008). The plasma serotonin concentration was not different between normal, DMVD, and DMVD+PH dogs.Conclusion: In conclusion, a decrease in platelet serotonin concentration, which is associated with a degree of PH probability was found in DMVD dogs with PH. Further studies investigating roles of platelet serotonin in PH secondary to DMVD should be performed.