bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Dysfunctions of Intestinal Fatty Acids and Tryptophan Reveal Immuno-Inflammatory Response Activation in IgA Nephropathy
Authors: Wu Hongwei , Tang Donge , Yun Manhua , Liu Haiping , Huang Shaoxing , Yun Chen , Hocher Berthold , Zhang Xinzhou , Liu Fanna , Yin Lianghong , Dai Yong 
Published: February 2022

BackgroundImmunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis. Although an important link between intestinal metabolites and immune activity is widely established, the metabolic profile of IgAN is still poorly understood, which severely limits the mechanistic studies and therapy of IgAN.MethodsThe diversity of intestinal flora and relative abundance of metabolites in IgAN patients and healthy subjects were measured by 16s ribosomal RNA gene sequencing combined with liquid chromatography tandem-mass spectrometry. The levels of serum Gd-IgA1, IL-6, IL-10, IL-22, and TNF-a were tested by ELISA. We employed the tryptophan-targeted UHPLC-MRM-MS approach to assess the content of tryptophan metabolites quantitatively.ResultsIntestinal fatty acid levels, mainly unsaturated fatty acids, were observed to be dramatically decreased in IgAN patients. Disorders in linoleic acid and arachidonic acid metabolism, metabolic imbalances of anti-/pro- inflammatory fatty acid metabolites, and intestinal AhR signaling deficiency might reflect the damage of the intestinal mucosal barrier in IgAN patients. In addition, we found that high levels of Gd-IgA1, IL-22, and TNF-α were associated with the activity of the tryptophan-kynurenine metabolic pathway, as well as lower levels of 3-indolepropionic acid. 3-indolepropionic acid, kynurenine, and indoleacrylic acid had synergistic effects on regulating immuno-inflammatory responses in IgAN patients.ConclusionsThe metabolic characteristic of fatty acids and tryptophan in the intestinal system is disturbed in IgAN patients, leading to active immune-inflammatory reactions.
Effects of Exercise on Patients Important Outcomes in Older People With Sarcopenia: An Umbrella Review of Meta-Analyses of Randomized Controlled Trials
Authors: Shen Yanjiao , Liu Dan , Li Sheyu , He Yazhou , Tan Fucha , Sun Xuelian , Li Daiping , Xia Xin , Hao Qiukui 
Published: February 2022

BackgroundMany clinical practice guidelines strongly recommend exercise as an intervention for patients with sarcopenia. However, the significance of exercise on patient-important outcomes in older adults with sarcopenia is inconsistent when considering available minimal important differences. To synthesize current systematic review and meta-analyses evidence on the efficacy of exercise on patient-important outcomes in the treatment of sarcopenia in older adults.MethodsWe searched MEDLINE, EMBASE, Cochrane Library (Cochrane database of systematic review, CDSR) via OvidSP and Web of science until April 2021 and reference lists. Two independent investigators performed abstracted and title screening, assessed the full text and quality of evidence. This umbrella review included systematic reviews and meta-analyses of randomized controlled trials (RCTs). Eligible reviews aim to evaluate the effect of exercise on patient-important sarcopenic outcomes (muscle or physical function, mortality, and quality of life) in treating sarcopenia in older people. We used the minimally important differences (MIDs) of these outcomes to assess if the effects of exercise matter to patients.ResultsThis umbrella review provided a broad overview of the existing evidence and evaluated the systematic reviews' methodological quality and evidence for all these associations. In older patients with sarcopenia, moderate- to high-quality evidence showed that exercise intervention probably increases walking speed and improved physical performance (measured by TUG test); exercise may increase the muscle strength (grip strength, keen extension strength); but the effect size for grip strength probably too small to achieve patients important changes. Evidence for older people with sarcopenic obesity is limited, and we found the consistent effect of exercise interventions on grip strength and usual walking speed.ConclusionExercise has a positive and important effect on physical performance for older adults with sarcopenia, which supports leaving the current recommendations unchanged. New systematic reviews to summarize the effect of exercise on the quality of life are warranted to fill the current evidence gap.
Prediction of Moderate to Severe Obstructive Sleep Apnea Using Neck Computed Tomography With Computational Fluid Dynamics Study
Authors: Chung Wei-Sheng , Chung Sunny 
Published: February 2022

BackgroundModerate to severe obstructive sleep apnea (OSA) is associated with cardiovascular disease. Polysomnography is time intensive and difficult to access for diagnosis of OSA. Neck computed tomography (CT) provides upper airway delineation but not diagnostic criteria for moderate to severe OSA. We explored neck CT with computational fluid dynamics (CFD) study for airway pressure and airflow velocity to predict moderate to severe OSA.MethodsEnrolled from February 1, 2020, to June 30, 2021, patients with OSA with overnight oxygen desaturation (sPO2 &lt;90%) received awake neck CT with a CFD study of their airway pressure and airflow velocity. CTL12 and CTL34 were defined as airflow velocity &lt;3 and ≥3 m/s, respectively, and airway pressure &lt;10 and ≥10 pa, respectively, in the narrowest upper airway.ResultsSixty-two patients (42 male and 20 female; mean age: 50.4 ± 14.6 years) were included; 12 and 50 patients had mild OSA and moderate to severe OSA, respectively. The minimum sPO2 in the supine position was 80.7 ± 9.1%. The total time of sPO2 &lt;90% at overnight oximetry was 29.3 ± 51.1 min. Most (85.5%) neck CT examinations with CFD study presented CTL34. Patients with CTL34 had a lower minimum sPO2 in the supine position (78.4 vs. 88.1%, P = 0.004) and longer duration of sPO2 &lt;90% at overnight oximetry (33.9 vs. 1.9 min, P = 0.001) than those with CTL12. The values of the area under the receiver operating characteristic curves of airway pressure and of airflow velocity at the narrowest upper airway were 0.788 and 0.733, respectively.ConclusionNeck CT with CFD study of airway pressure and airflow velocity may provide a quick prediction of moderate to severe OSA.
Erythrocytic α-Synuclein Species for Parkinson’s Disease Diagnosis and the Correlations With Clinical Characteristics
Authors: Yu Zhenwei , Liu Genliang , Li Yang , Arkin Ehsan , Zheng Yuanchu , Feng Tao 
Published: February 2022

BackgroundErythrocytes contain most of the peripheral α-synuclein (α-syn), which is the key pathological molecular of α-synucleinopathies including Parkinson’s disease (PD). Our objectives were to assess the efficiency of erythrocytic total and oligomeric α-syn levels as PD diagnostic biomarkers, and to identify the correlations between erythrocytic α-syn levels and physiological/psychiatrical assessment scales.MethodsHome-brewed electrochemiluminescence assays were applied to assess the concentrations of erythrocytic total and oligomeric α-syn levels in a cohort including 124 patients with PD and 79 healthy controls (HCs). The correlations between erythrocytic α-syn levels and clinical measurements were assessed using Spearman’s rank test.ResultsBoth the erythrocytic total and oligomeric α-syn levels were significantly higher in PD patients than HCs. The biomarkers adjusted for age and sex discriminated PDs from HCs well with 80% sensitivity, 89% specificity and 79% sensitivity, 83% specificity, respectively. Combining erythrocytic total and oligomeric α-syn levels by using binary logistic regression analysis with the controlling of age and sex generated a factor discriminates PDs from HCs with 88% sensitivity and 85% specificity. The erythrocytic total but not oligomeric α-syn levels adjusted for age and sex significantly correlated with anxiety scales and the MDS-UPDRS III scales in PD patients, respectively.ConclusionWe showed the usefulness of erythrocytic total and oligomeric α-syn levels as biomarkers for PD. Our results also suggest the capability of erythrocytic α-syn as a potential pathological factor and therapeutic target for psychiatric symptoms in PD patients.
Daily Remote Ischemic Conditioning Can Improve Cerebral Perfusion and Slow Arterial Progression of Adult Moyamoya Disease—A Randomized Controlled Study
Authors: Xu Jiali , Zhang Qian , Rajah Gary B. , Zhao Wenbo , Wu Fang , Ding Yuchuan , Zhang Bowei , Guo Wenting , Yang Qi , Xing Xiurong , Li Sijie , Ji Xunming 
Published: February 2022

Background and PurposeMoyamoya disease (MMD) is a complicated cerebrovascular disease with recurrent ischemic or hemorrhagic events. This study aimed to prove the safety and efficacy of remote ischemic conditioning (RIC) on MMD.MethodsIn total, 34 patients with MMD participated in this pilot, prospective randomized controlled study for 1 year. 18 patients were allocated into the RIC group, and 16 patients accepted routine medical treatment only. RIC-related adverse events were recorded. The primary outcome was the improvement ratio of mean cerebral blood flow (mCBF) in middle cerebral artery territory measured by multidelay pseudocontinuous arterial spin labeling, and the secondary outcomes were the cumulative incidence of major adverse cerebrovascular events (MACEs), the prevalence of stenotic-occlusive progression, and periventricular anastomosis at 1-year follow-up.ResultsIn total, 30 of the 34 patients with MMD completed the final follow-up (17 in the RIC group and 13 in the control group). No adverse events of RIC were observed. The mCBF improvement ratio of the RIC group was distinctively higher compared with the control group (mCBF−whole-brain: 0.16 ± 0.15 vs. −0.03 ± 0.13, p = 0.001). Stenotic-occlusive progression occurred in 11.8% hemispheres in the RIC group and 38.5% in the control group (p = 0.021). The incidence of MACE was 5.9% in the RIC group and 30.8% in the control group (hazard ratio with RIC, 0.174; 95% CI, 0.019–1.557; p = 0.118). No statistical difference was documented in the periventricular anastomosis between the two groups after treatment.ConclusionsRemote ischemic conditioning has the potential to be a safe and effective adjunctive therapy for patients with MMD largely due to improving cerebral blood flow and slowing the arterial progression of the stenotic-occlusive lesions. These findings warrant future studies in larger trials.
Prevention of Oxaliplatin-Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis
Authors: Peng Siyu , Ying Ariel Fangting , Chan Nicholas Jian Hao , Sundar Raghav , Soon Yu Yang , Bandla Aishwarya 
Published: February 2022

BackgroundOxaliplatin-induced peripheral neuropathy (OIPN) has significant clinical impact on the quality of life for cancer patients and is a dose limiting toxicity. Trials studying preventive measures have been inconclusive. A systematic review and meta-analysis were conducted to evaluate the existing pharmacological and non-pharmacological interventions to prevent chronic OIPN.MethodsLiterature databases PubMed-MEDLINE, Embase and Scopus, were searched from 1 Jan 2005 to 08 Aug 2020 and major conferences’ abstracts were reviewed for randomized controlled trials that examined the efficacy of any preventive measure for OIPN. The primary outcome measure was the incidence of chronic OIPN with a preventive intervention as compared to placebo or no intervention. The pooled risk ratio and its 95% confidence interval were calculated using a random effects model. A network meta-analysis was conducted to derive indirect evidence of any preventive effect of an intervention against placebo when original trials compared one intervention against another.ResultsForty-four trials were analyzed describing 29 chemoprotective interventions, including combinations, and 1 non-pharmacological intervention. Ratings were assessed via a combination of outcomes with quality assessment using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Of the 30 interventions examined, there were six interventions supporting potential efficacy, 11 interventions with insufficient evidence and 13 interventions not recommended.ConclusionCurrently, there is insufficient certainty to support any intervention as effective in preventing OIPN. Of note is that most of these studies have focused on pharmacological interventions; non-pharmacological interventions are underexplored. Further research on ways to limit OIPN is needed.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=225095, Prospero Registration Number: CRD42021225095.
Development and Validation of a Prognostic Nomogram for Predicting Cancer-Specific Survival in Patients With Lymph Node Positive Bladder Cancer: A Study Based on SEER Database
Authors: Zhan Xiangpeng , Jiang Ming , Deng Wen , Liu Xiaoqiang , Chen Luyao , Fu Bin 
Published: February 2022

PurposeTo construct a prognostic model to predict the cancer-specific survival (CSS) for bladder cancer patients with lymph node-positive.Patients and MethodsWe enrolled 2,050 patients diagnosed with lymph node-positive bladder cancer from the Surveillance Epidemiology and End Results (SEER) database (2004–2015). All patients were randomly split into development cohort (n = 1,438) and validation cohort (n = 612) at a ratio of 7:3. The univariate and multivariate Cox regression analysis were performed to identify prognostic factors. A nomogram predicting CSS was established based on the results of multivariate Cox analysis. Its performance was evaluated by calibration curves, the receiver operating characteristic (ROC) curves, and the concordance index (C-index). Internal verification was performed in the validation cohort. The Kaplan–Meier method with the log-rank test was applied in the different risk groups.ResultsThe nomogram incorporated summary stage, tumor size, chemotherapy, regional nodes examined and positive lymph nodes. The C-index of the nomogram in the development cohort was 0.716 (0.707–0.725), while the value of the C-index was 0.691 (0.689–0.693) in the validation cohort. The AUC of the nomogram was 0.803 for 3-year and 0.854 for 5-year in the development cohort, while was 0.773 for 3-year and 0.809 for 5-year in the validation cohort. Calibration plots for 3-year and 5-year CSS showed good concordance. Significant differences were observed between high, medium, and low risk groups (P &lt;0.001).ConclusionsWe have established a prognostic nomogram providing an accurate individualized probability of cancer-specific survival in bladder cancer patients with lymph node-positive. The nomogram could contribute to patient counseling, follow-up scheduling, and selection of treatment.
18F-DCFPyL PET/CT in Newly Diagnosed Prostate Cancer: Diagnostic Value of Intraprostatic PSMA Uptake in Risk Classification of Prostate Cancer
Authors: Zhou Shuoming , Liu Tiantian , Zhu Ziqiang , Zhang Lin , Qian Subo , Fu Hongliang , Cao Qifeng , Kang Jian 
Published: February 2022

Purpose18F-DCFPyL prostate-specific membrane antigen (PSMA) PET/CT is commonly applied to locate lesions of prostate cancer (PCa), but its diagnostic function of quantitative parameters is ignored. Our study evaluates the parameters of intraprostatic PSMA uptake in patients newly diagnosed with PCa and explores their predictive value in risk classification, which is similar to D’Amico criteria.Materials and MethodsWe quantified the maximal standardized uptake value (SUVmax), mean SUV (SUVmean), total lesion (TL)-PSMA, prostate/muscle (P/M) ratio of the primary tumor, and PSMA-derived tumor volume (PSMA-TV) from 62 patients with histologically proven PCa. Patients newly diagnosed with PCa were allocated into risk groups (at low, intermediate, and high risk, respectively) in accordance with D’Amico criteria. Afterwards, the five parameters mentioned above among three different risk groups were compared, and their predictive values in the risk classification of PCa were explored.ResultsSignificantly decreased levels of SUVmax, SUVmean, TL-PSMA, and P/M ratio were observed in the risk groups of low or intermediate or both, compared with the high-risk group. However, only the P/M ratio significantly elevated in patients with intermediate risk [mean ± SD (median): 46.58 ± 9.74 (45.27), P = 0.042] or high risk [98.95 ± 38.83 (97.52), P &lt; 0.001], compared with low-risk patients [12.33 ± 5.93 (9.81)]. When P/M ratio was used to distinguish between low-risk and intermediate-risk patients, its c-statistics was 0.660. On the other hand, when distinguishing between intermediate-risk and high-risk groups, the c-statistics of P/M ratio was 0.667. Finally, when P/M ratio was used to distinguish between low-risk and high-risk patients, the c-statistics was 0.969. P/M ratio had a positive correlation with prostate-specific antigen in all enrolled PCa patients.ConclusionThe quantitative parameters of 18F-DCFPyL PET/CT, including SUVmax, SUVmean, and P/M ratio, might assist in distinguishing low-risk or intermediate-risk groups from the high-risk group. Of these parameters, P/M ratio appears to be the better promising parameter for risk classification of prostate cancer than SUVmax.
Quantitative Parameters of Diffusion Spectrum Imaging: HER2 Status Prediction in Patients With Breast Cancer
Authors: Mao Chunping , Jiang Wei , Huang Jiayi , Wang Mengzhu , Yan Xu , Yang Zehong , Wang Dongye , Zhang Xiang , Shen Jun 
Published: February 2022

ObjectiveTo explore the value of quantitative parameters derived from diffusion spectrum imaging (DSI) in preoperatively predicting human epidermal growth factor receptor 2 (HER2) status in patients with breast cancer.MethodsIn this prospective study, 114 and 56 female patients with invasive ductal carcinoma were consecutively included in a derivation cohort and an independent validation cohort, respectively. Each patient was categorized into HER2-positive or HER2-negative groups based on the pathologic result. All patients underwent DSI and conventional MRI including dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI). The tumor size, type of the time-signal intensity curve (TIC) from DCE-MRI, apparent diffusion coefficient (ADC) from DWI, and quantitative parameters derived from DSI, including diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), mean apparent propagator (MAP), and neurite orientation dispersion and density imaging (NODDI) of primary tumors, were measured and compared between the HER2-positive and HER2-negative groups in the derivation cohort. Univariable and multivariable logistic regression analyses were used to determine the potential independent predictors of HER2 status. The discriminative ability of quantitative parameters was assessed by receiver operating characteristic (ROC) curve analyses and validated in the independent cohort.ResultsIn the derivation cohort, the tumor size, TIC type, and ADC values did not differ between the HER2-positive and HER2-negative groups (p = 0.126–0.961). DSI quantitative parameters including axial kurtosis of DKI (DKI_AK), non-Gaussianity (MAP_NG), axial non-Gaussianity (MAP_NGAx), radial non-Gaussianity (MAP_NGRad), return-to-origin probability (MAP_RTOP), return-to-axis probability of MAP (MAP_RTAP), and intracellular volume fraction of NODDI (NODDI_ICVF) were lower in the HER2-positive group than in the HER2-negative group (p ≤ 0.001–0.035). DSI quantitative parameters including radial diffusivity (DTI_RD), mean diffusivity of DTI (DTI_MD), mean squared diffusion (MAP_MSD), and q-space inverse variance of MAP (MAP_QIV) were higher in the HER2-positive group than in the HER2-negative group (p = 0.016–0.049). The ROC analysis showed that the area under the curve (AUC) of ADC was 0.632 and 0.568, respectively, in the derivation and validation cohorts. The AUC values of DSI quantitative parameters ranged from 0.628 to 0.700 and from 0.673 to 0.721, respectively, in the derivation and validation cohorts. Logistic regression analysis showed that only NODDI_ICVF was an independent predictor of HER2 status (p = 0.001), with an AUC of 0.700 and 0.721, respectively, in the derivation and validation cohorts.ConclusionsDSI could be helpful for preoperative prediction of HER2, but DSI alone may not be sufficient in predicting HER2 status preoperatively in patients with breast cancer.
Fabrication of pH/Redox Dual-Responsive Mixed Polyprodrug Micelles for Improving Cancer Chemotherapy
Authors: Luo Ji , Zhang Shuguang , Zhu Peiyao , Liu Wenke , Du Jiang 
Published: February 2022

In this work, we prepared pH/redox dual-responsive mixed polyprodrug micelles (MPPMs), which were co-assembled from two polyprodrugs, namely, poly(ethylene glycol) methyl ether-b-poly (β-amino esters) conjugated with doxorubicin (DOX) via redox-sensitive disulfide bonds (mPEG-b-PAE-ss-DOX) and poly(ethylene glycol) methyl ether-b-poly (β-amino esters) conjugated with DOX via pH-sensitive cis-aconityl bonds (mPEG-b-PAE-cis-DOX) for effective anticancer drug delivery with enhanced therapeutic efficacy. The particle size of MPPMs was about 125 nm with low polydispersity index, indicating the reasonable size and uniform dispersion. The particle size, zeta-potential, and critical micelle concentration (CMC) of MPPMs at different mass ratios of the two kinds of polyprodrugs were dependent on pH value and glutathione (GSH) level, suggesting the pH and redox responsiveness. The drug release profiles in vitro of MPPMs at different conditions were further studied, showing the pH—and redox-triggered drug release mechanism. Confocal microscopy study demonstrated that MPPMs can effectively deliver doxorubicin molecules into MDA-MB-231 cells. Cytotoxicity assay in vitro proved that MPPMs possessed high toxic effect against tumor cells including A549 and MDA-MB-231. The results of in vivo experiments demonstrated that MPPMs were able to effectively inhibit the tumor growth with reduced side effect, leading to enhanced survival rate of tumor-bearing mice. Taken together, these findings revealed that this pH/redox dual-responsive MPPMs could be a potential nanomedicine for cancer chemotherapy. Furthermore, it could be a straightforward way to fabricate the multifunctional system basing on single stimuli-responsive polyprodrugs.
A Cannabinoid 2-Selective Agonist Inhibits Allogeneic Skin Graft Rejection In Vivo
Authors: Jayarajan Senthil , Meissler Joseph J. , Adler Martin W. , Eisenstein Toby K. 
Published: February 2022

Previous work from our laboratory showed that a CB2 selective agonist, O-1966, blocked the proliferative response of C57BL/6 mouse spleen cells exposed to spleen cells of C3HeB/FeJ mice in vitro in the mixed lymphocyte reaction (MLR). The MLR is widely accepted as an in vitro correlate of in vivo grant rejection. Mechanisms of the immunosuppression induced by the cannabinoid were explored, and it was shown that O-1966 in this in vitro assay induced CD25+Foxp3+ Treg cells and IL-10, as well as down-regulated mRNA for CD40 and the nuclear form of the transcription factors NF-κB and NFAT in T-cells. The current studies tested the efficacy of O-1966 in prolonging skin grafts in vivo. Full thickness flank skin patches (1-cm2) from C3HeB/FeJ mice were grafted by suturing onto the back of C57BL/6 mice. O-1966 or vehicle was injected intraperitoneally into treated or control groups of animals beginning 1 h pre-op, and then every other day until 14 days post-op. Graft survival was scored based on necrosis and rejection. Treatment with 5 mg/kg of O-1966 prolonged mean graft survival time from 9 to 11 days. Spleens harvested from O-1966 treated mice were significantly smaller than those of vehicle control animals based on weight. Flow cytometry analysis of CD4+ spleen cells showed that O-1966 treated animals had almost a 3-fold increase in CD25+Foxp3+ Treg cells compared to controls. When dissociated spleen cells were placed in culture ex vivo and stimulated with C3HeB/FeJ cells in an MLR, the cells from the O-1966 treated mice were significantly suppressed in their proliferative response to the allogeneic cells. These results support CB2 selective agonists as a new class of compounds to prolong graft survival in transplant patients.