bluuebunny/crossref_metadata_2025 huggingface dataset:
The Usefulness of C-Reactive Protein to Albumin Ratio in the Prediction of Adverse Cardiovascular Events in Coronary Chronic Total Occlusion Undergoing Percutaneous Coronary Intervention
Authors: Cheng Lele , Meng Zixuan , Wang Qi , Jian Zhijie , Fan Pengcheng , Feng Xinxin , Qiao Xiangrui , Yang Jian , Yuan Zuyi , Li Bolin , Wu Yue
Published: November 2021

Inflammation and nutrition as main factors can affect the prognosis of patients with chronic total coronary occlusion (CTO) undergoing percutaneous coronary intervention (PCI). The C-reactive protein to albumin ratio (CAR) can clarify the inflammation and nutrition status, which are highly related to clinical outcomes. This study aims to investigate the association between CAR and adverse cardiovascular events in patients with CTO undergoing PCI. For this study, 664 patients were divided into three groups based on the tertiles of CAR. The primary endpoint was all-cause mortality and the secondary endpoint was major adverse cardiovascular events (MACE). Over a median follow-up of 33.7 months, the primary endpoint occurred in 64 patients (9.6%) and the secondary endpoint occurred in 170 patients (25.6%). The patients with higher CAR represented a worse prognosis with all-cause death and cardiovascular death after the adjustment for the baseline risk factors. Adding the CAR values raised the predictive value for the incidence of the all-cause death and cardiovascular death but not MACE. The capacity of prognosis prediction was improved after the addition of the CAR value to the traditional prediction model.
Successful Prevention of Fetal Autoimmune-Mediated Heart Block by Combined Therapies With Hydroxychloroquine and Intravenous Immunoglobulin: A Case Report
Authors: Zhao Li , Zhou Yan , Wang Chuan , Li Yifei , Zhu Qi , Hua Yimin , Qiao Lina , Wu Jinlin , Zhou Kaiyu
Published: November 2021

A fetal autoimmune-mediated atrioventricular block is a passively acquired autoimmune disease in which maternal autoantibodies enter the fetal circulation via the placenta and subsequently cause inflammation and fibrosis of the atrioventricular node. Once fetal autoimmune-mediated atrioventricular block occurs, it only takes a short time to progress from first-degree atrioventricular block to complete atrioventricular block, meaning that the damage is often irreversible. Autoimmune—associated AVB, a rare but life—threatening disorder, occurs in 2–5% of pregnancies with positive anti—Ro/SSA (the most common one) and La/SSB antibodies. The perinatal mortality of neonates with AVB outlined in research is approximately 30%. Thus far, for autoimmune-associated AVB fetuses, currently used treatments include corticosteroids, hydroxychloroquine, intravenous immunoglobulin (IVIG), b—sympathomimetic agent, and even plasma exchange. Currently, approaches for preventing the progression and recurrence of a fetal atrioventricular block are still controversial. Here, we reported a baby of successful prevention from the fate of the fetal atrioventricular block by adopting prophylactic comprehensive prenatal therapy.
Characteristics and Long-Term Ablation Outcomes of Supraventricular Arrhythmias in Hypertrophic Cardiomyopathy: A 10-Year, Single-Center Experience
Authors: Zhang Hong-Da , Ding Lei , Weng Si-Xian , Zhou Bin , Ding Xiao-Tong , Hu Li-Xing , Qi Ying-Jie , Yu Feng-Yuan , Feng Tian-Jie , Zhang Jing-Tao , Fang Pi-Hua , Hua Wei , Zhang Shu , Tang Min
Published: November 2021

Background: A variety of supraventricular arrhythmias (SVAs) may occur in patients with hypertrophic cardiomyopathy (HCM). The characteristics and long-term ablation outcomes of different types of SVAs in HCM have not been comprehensively investigated.

Methods: We retrospectively enrolled 101 consecutive patients with HCM who were referred to the electrophysiology and arrhythmia service from May 2010 to October 2020. The clinical features and ablation outcomes were analyzed.

Results: Seventy-eight patients had SVAs, which comprised 50 (64.1%) cases of atrial fibrillation (AF), 16 (20.5%) of atrial flutter (AFL), 15 (19.2%) of atrioventricular reentrant tachycardia (AVRT), 11 (14.1%) of atrial arrhythmia (AT), and 3 (3.8%) of atrioventricular nodal reentrant tachycardia (AVNRT). Thirty-four patients underwent catheter ablation and were followed up for a median (interquartile range) of 58.5 (82.9) months. There was no recurrence in patients with non-AF SVAs. In patients with AF, the 1- and 7-year AF-free survival rates were 87.5 and 49.5%, respectively. A receiver operator characteristic analysis showed that a greater left ventricular end-diastolic dimension (LVEDD) was associated with a higher recurrence of AF, with an optimum cutoff value of 47 mm (c-statistic = 0.91, p = 0.011, sensitivity = 1.00, specificity = 0.82). In Kaplan–Meier analysis, patients with a LVEDD ≥ 47 mm had worse AF-free survival than those with a LVEDD <47 mm (log-rank p = 0.014).

Conclusions: In this unique population of HCM, AF was the most common SVA, followed in order by AFL, AVRT, AT, and AVNRT. The long-term catheter ablation outcome for non-AF SVAs in HCM is satisfactory. A greater LVEDD predicts AF recurrence after catheter ablation in patients with HCM.
Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers: Anti-arrhythmic Drug for Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Tu Bin , Wu Lingmin , Zheng Lihui , Liu Shangyu , Sheng Lishui , Liu Limin , Zhu Zhenghui , Yao Yan
Published: November 2021

Background: Current treatment guidelines for arrhythmogenic right ventricular cardiomyopathy (ARVC) mainly emphasize on prevention of ventricular arrhythmic events. Despite the progressive nature of ARVC, therapeutic options focusing on decelerating disease progression are scarce.

Methods and Results: This retrospective observational cohort study included 311 patients [age, 39.1 ± 14.4 years; male, 233 (74.9%)] with a definite diagnosis of ARVC as determined by the 2010 Task Force Diagnostic Criteria. Among them, 113 patients (36.3%) received ACEI/ARB treatment. Disease progression was evaluated according to repeat transthoracic echocardiograms with a linear mixed model. Patients receiving ACEI/ARB treatment were associated with slower disease progression reflected by a gradual decrease in tricuspid annular plane systolic excursion than those not receiving ACEI/ARB treatment (0.37 vs. 0.61 mm per year decrease, P < 0.001) and slower dilation of right ventricular outflow tract (0.57 vs. 1.06 mm per year increased, P = 0.003). Cox proportional hazard regression models were used to evaluate the association between life-threatening ventricular tachycardia events and ACEI/ARB treatment. A reduced risk of life-threatening ventricular arrhythmia was associated with ACEI/ARB treatment compared to that without ACEI/ARB treatment (adjusted HR: 0.71, 95% CI: 0.52–0.96, P = 0.031).

Conclusions: ACEI/ARB treatment is associated with slower disease progression and lower risk of life-threatening ventricular arrhythmia in patients with ARVC. Delaying disease progression may pave way for reducing life-threatening ventricular arrhythmia risk.
Mapping Relation of Leakage Currents of Polluted Insulators and Discharge Arc Area
Authors: Fang Chunhua , Tao Yuning , Wang Jianguo , Ding Can , Huang Li , Zhou Mi , Gu Yi , Wang Yali
Published: November 2021

A fundamental parameter of polluted insulator online monitoring is the leakage current, which has already been shown to be well-related to the pollution discharge of insulators. In this article, in an effort to quantitatively reflect the discharge intensity and the discharge status by the leakage current, we carried out an experimental study on artificial pollution discharge of insulators. A high-speed photographic apparatus was utilized to capture the entire process of local arcs on a porcelain insulator surface, including the arc generation, the arc development, and the flashover, for which the associated leakage current of insulators was synchronously digitized. A comparative analysis of the relation between the two-dimensional discharge image and the leakage current waveform in the process of arc generation and development shows that if the arc area on the insulator surface is relatively small and the leakage current passes through zero, the arc might completely become extinct, whereas this phenomena will not occur if the arc area is larger. In addition, the amplitude of the discharge arc area is found to be roughly proportional to the square of leakage current over the range of leakage current amplitude from 0 to 150 mA. Our results can provide an important guidance for judgment of the discharge status and the discharge intensity on insulator surfaces using the leakage current of insulators.
Flow Regimes and Transitions for Two-Phase Flow of R152a During Condensation in a Circular Minichannel
Authors: Liu Na , Zhao Qian , Lan Zhixiang
Published: November 2021

Two-phase flow regimes were experimentally investigated during the entire condensation process of refrigerant R152a in a circular glass minichannel. The inner and outer diameters of the test minichannel were 0.75 and 1.50 mm. The channel was 500 mm long to allow observation of all the two-phase flow regimes during the condensation process. The experiments used saturation temperatures from 30 to 50°C, a mass flux of 150 kg/(m2·s) and vapor qualities from 0 to 1. The annular, intermittent and bubbly flow regimes were observed for the experimental conditions in the study. The absence of the stratified flow regime shows that the gravitational effect is no longer dominant in the minichannel for these conditions. Vapor-liquid interfacial waves, liquid bridge formation and vapor core breakage were observed in the minichannel. Quantitative measurements of flow regime transition locations were carried out in the present study. The experiments also showed the effects of the saturation temperature and the cooling water mass flow rate on flow regime transitions. The results show that the annular flow range decreases and the intermittent and bubbly flow ranges change little with increasing saturation temperature. The cooling water mass flow rate ranging from 38.3 kg/h to 113.8 kg/h had little effect on the flow regime transitions.
Responses of Functional Traits of Macrobenthic Communities to Human Activities in Daya Bay (A Subtropical Semi-Enclosed Bay), China
Authors: Rao Yiyong , Cai Lizhe , Chen Xinwei , Zhou Xiping , Fu Sujing , Huang Honghui
Published: November 2021

The biological trait analysis (BTA) is regarded as a promising approach to unravel how ecosystem functions respond to human-induced disturbances. This study considered the four sampling locations associated with different human activities in Daya Bay, that is, the domestic and industrial sewage discharge area (SED), mariculture area (MRC), nuclear power plants thermal discharge area (NTD), and an area with relatively low human disturbance as a reference (REF). Thirty modalities of nine traits were selected in BTA. Our results showed a clear shift in the functional structure of macrobenthic communities between the sampling locations, except for the case between NTD and REF. The trait composition in the communities did not highlight any seasonal patterns. Bioturbation, longevity, tolerance, body size, feeding habit, and environmental position were the key traits to characterize the functional structure of macrobenthic communities and demonstrated predictable responses along the environmental gradients. Water depth, DO, Chl-a, NH4+, and petroleum contaminants in sediments were the main variables influencing the trait composition. In addition, the taxonomic index (H′) and functional diversity index (Rao’s Q) showed clear differences among the sampling locations. Although there were no significant differences between NTD and REF in terms of the trait composition and functional diversity, a potential function loss in NTD still can be detected through the integrated analysis with taxonomic diversity. We suggest that the traits (except for fragility, larval development, and living habits) selected and the diversity indices (H′ and Rao’s Q) could serve as promising indicators of ecological conditions in Daya Bay.
Assessing the Role of Environmental Expenditures and Green Transport in Emissions Released by Transport: An Application of ARDL Approach
Authors: Hussain Zahid , Miao Cuifen , Zhang Weitu , Khan Muhammad Kaleem , Xia Zhiqing
Published: November 2021

This study investigates the effects of transport and environmental factors on transport carbon dioxide emissions (TCO2). It employs cross-sectional autoregressive distributed lags for the estimation in the short and long runs and examines the panel time-series data from 2000 to 2020 in the OECD countries. This method allows heterogeneity in the dependencies and slope parameters across the countries. The results demonstrate that road and railway traffic movements increase the amount of TCO2in the short and long runs. In addition, transport energy consumption is the driving factor in releasing TCO2in the long run. Moreover, the joint effect of locomotives and transport energy consumption significantly reduces TCO2in the short run. By contrast, the findings support the argument that environmental expenditures and green transport mitigate TCO2in the long run. The findings also show an inverted u-shaped relationship between TCO2and transport energy consumption. With the empirical findings as a basis, we suggest that the OECD countries should reduce traffic movements and enhance the environmental expenditures so that they may produce green transport vehicles to combat environmental issues.
Recent Nitrogen Storage and Accumulation Rates in Mangrove Soils Exceed Historic Rates in the Urbanized San Juan Bay Estuary (Puerto Rico, United States)
Authors: Wigand Cathleen , Oczkowski Autumn J. , Branoff Benjamin L. , Eagle Meagan , Hanson Alana , Martin Rose M. , Balogh Stephen , Miller Kenneth M. , Huertas Evelyn , Loffredo Joseph , Watson Elizabeth B.
Published: November 2021

Tropical mangrove forests have been described as “coastal kidneys,” promoting sediment deposition and filtering contaminants, including excess nutrients. Coastal areas throughout the world are experiencing increased human activities, resulting in altered geomorphology, hydrology, and nutrient inputs. To effectively manage and sustain coastal mangroves, it is important to understand nitrogen (N) storage and accumulation in systems where human activities are causing rapid changes in N inputs and cycling. We examined N storage and accumulation rates in recent (1970 – 2016) and historic (1930 – 1970) decades in the context of urbanization in the San Juan Bay Estuary (SJBE, Puerto Rico), using mangrove soil cores that were radiometrically dated. Local anthropogenic stressors can alter N storage rates in peri-urban mangrove systems either directly by increasing N soil fertility or indirectly by altering hydrology (e.g., dredging, filling, and canalization). Nitrogen accumulation rates were greater in recent decades than historic decades at Piñones Forest and Martin Peña East. Martin Peña East was characterized by high urbanization, and Piñones, by the least urbanization in the SJBE. The mangrove forest at Martin Peña East fringed a poorly drained canal and often received raw sewage inputs, with N accumulation rates ranging from 17.7 to 37.9 g m–2 y–1 in recent decades. The Piñones Forest was isolated and had low flushing, possibly exacerbated by river damming, with N accumulation rates ranging from 18.6 to 24.2 g m–2 y–1 in recent decades. Nearly all (96.3%) of the estuary-wide mangrove N (9.4 Mg ha–1) was stored in the soils with 7.1 Mg ha–1 sequestered during 1970–2017 (0–18 cm) and 2.3 Mg ha–1 during 1930–1970 (19–28 cm). Estuary-wide mangrove soil N accumulation rates were over twice as great in recent decades (0.18 ± 0.002 Mg ha–1y–1) than historically (0.08 ± 0.001 Mg ha–1y–1). Nitrogen accumulation rates in SJBE mangrove soils in recent times were twofold larger than the rate of human-consumed food N that is exported as wastewater (0.08 Mg ha–1 y–1), suggesting the potential for mangroves to sequester human-derived N. Conservation and effective management of mangrove forests and their surrounding watersheds in the Anthropocene are important for maintaining water quality in coastal communities throughout tropical regions.
miR-224-5p and miR-545-5p Levels Relate to Exacerbations and Lung Function in a Pilot Study of X-Linked MicroRNA Expression in Cystic Fibrosis Monocytes
Authors: McKiernan Paul J. , Molloy Kevin P. , Glasgow Arlene M. A. , McElvaney Noel G. , Greene Catherine M.
Published: November 2021

Altered microRNA expression patterns in bronchial brushings from people with versus without cystic fibrosis (CF) relate to functional changes and disease pathophysiology. The expression of microRNAs encoded on the X chromosome is also altered in peripheral blood monocytes of p. Phe508del homozygous versus non-CF individuals. Here we investigate whether levels of the top seven X-linked microRNAs (miR-224-5p, miR-452-5p, miR-450b-5p, miR-542-3p, miR-450a-5p, miR-424-5p, and miR-545-5p) that are significantly increased over 1.5 fold in CF versus non-CF monocytes correlate with lung function. CD14+ monocytes were isolated from males and females with (n = 12) and without cystic fibrosis (n = 12) and examined for the expression of X-linked microRNAs by qRT-PCR array. MicroRNA target mRNA levels were quantified using qRT-PCR. Clinical correlations with lung function data were analysed in the CF cohort. Increasing levels of miR-545-5p correlated moderately with FEV1% predicted (r = -0.4553, p > 0.05) and strongly with exacerbation rate (r = 0.5858, p = 0.0483). miR-224-5p levels were significantly higher in the severe (FEV1 <40%) versus mild (FEV1 ≥80%, p = 0.0377) or moderate (FEV1 40–79%, p = 0.0350) groups. MiR-224-5p expression inversely correlated with lung function (FEV1%: r = -0.5944, p = 0.0457) and positively correlated with exacerbation rates (r = 0.6139, p = 0.0370). These data show that peripheral blood monocyte miR-545-5p and miR-224-5p levels correlate with exacerbation rate, whilst miR-224-5p levels also correlate with lung function in cystic fibrosis.
Rare CYLD Variants in Chinese Patients With Amyotrophic Lateral Sclerosis
Authors: Gu Xiaojing , Chen Yongping , Wei Qianqian , Hou Yanbing , Cao Bei , Zhang Lingyu , Ou Ruwei , Lin Junyu , Liu Kuncheng , Zhao Bi , Shang Huifang
Published: November 2021

Background: CYLD Lysine 63 Deubiquitinase gene (CYLD) was recently identified to be a novel causative gene for frontal temporal dementia (FTD)-amyotrophic lateral sclerosis (ALS). In the current study, we aimed to (1) systematically screen the mutations of CYLD in a large cohort of Chinese ALS patients, (2) study the genotype–phenotype correlation, and (3) explore the role of CYLD in ALS via rare variants burden analysis.

Methods: A total of 978 Chinese sporadic ALS (sALS) patients and 46 familial ALS (fALS) patients were sequenced with whole-exome sequencing and analyzed rare variants in CYLD with minor allele frequency <0.1%.

Results: In total, seven rare missense variants in CYLD have been identified in 7 (0.72%) patients among 978 sALS patients. Two (4.3%) rare missense variants were identified among the 46 fALS cases, in which one patient was diagnosed as having comorbidity of ALS and progressive supranuclear palsy (PSP). Moreover, the burden analysis indicated no enrichment of rare variants in CYLD among patients with ALS.

Conclusion: In conclusion, our study extended the genotype and phenotype of CYLD in ALS, but the pathogenicity of these variants needs to be further verified. Moreover, burden analysis argued against the role of CYLD in the pathogenesis of ALS. More studies from different ethnicities would be needed.
A Novel Loss-of-Function Mutation in the NPRL3 Gene Identified in Chinese Familial Focal Epilepsy with Variable Foci
Authors: Li Youzhi , Zhao Xu , Wang Shanshan , Xu Ke , Zhao Xin , Huang Shanshan , Zhu Suiqiang
Published: November 2021

Familial focal epilepsy with variable foci is an autosomal dominant disorder characterized by partial epilepsy with variable foci. In this study, we report a six-generation with segregation of the mutation present in four generations Chinese family presenting with focal epilepsy with variable foci. Whole exome sequencing confirms a novel pathogenic mutation in the NPRL3 gene (c316C>T; p. Q106*). PCR, Western blotting, and immunohistochemistry were conducted to analyze the gene transcription, protein expression, and subcellular localization of NPRL3 and related signaling molecules in peripheral blood cells from family members. As compared with healthy family members, both mRNA level and protein expression of NPRL3 are decreased in peripheral blood cells of the mutation carrier. In addition, the expression of downstream molecular Phospho-p70 S6 kinase (P-s6k) are increased consequently. Our findings expand the genotypic and phenotypic spectrum of the NPRL3-associated epilepsy and reveal the mechanisms of mTOR pathway signaling and GATOR1 pathogenesis in focal epilepsies, providing exciting potential for future diagnostic and therapeutic interventions. However, further in vitro and animal experiments are still needed to evaluate the role of NPRL3 loss-of-function mutation in epileptogensis.
Identification of Genetic Predisposition in Noncirrhotic Portal Hypertension Patients With Multiple Renal Cysts by Integrated Analysis of Whole-Genome and Single-Cell RNA Sequencing
Authors: Wu Yanjing , Wu Yongle , Liu Kun , Liu Hui , Wang Shanshan , Huang Jian , Ding Huiguo
Published: November 2021

Background and Aims: The multiple renal cysts (MRC) occur in some patients with noncirrhotic portal hypertension (NCPH) could be a subset of ciliopathy. However, the potential genetic influencers and/or determinants in NCPH with MRC are largely unknown. The aim of this study was to explore the potential candidate variants/genes associated with those patients.

Methods: 8,295 cirrhotic patients with portal hypertension were enrolled in cohort 1 and 267 patients affected with NCPH were included in cohort 2. MRC was defined as at least two cysts in both kidneys within a patient detected by ultrasonography or computed tomography. Whole-genome sequencing (WGS) was performed in nine patients (four from cohort 1 and five from cohort 2). Then we integrated WGS and publicly available single-cell RNA sequencing (scRNA-seq) to prioritize potential candidate genes. Genes co-expressed with known pathogenic genes within same cell types were likely associated NCPH with MRC.

Results: The prevalence of MRC in NCPH patients (19.5%, 52/267) was significantly higher than cirrhotic patients (6.2%, 513/8,295). Further, the clinical characteristics of NCPH patients with MRC were distinguishable from cirrhotic patients, including late-onset, more prominent portal hypertension however having preserved liver functions. In the nine whole genome sequenced patients, we identified three patients with early onset harboring compound rare putative pathogenic variants in the known disease gene PKHD1. For the remaining patients, by assessing cilia genes profile in kidney and liver scRNA-seq data, we identified CRB3 was the most co-expressed gene with PKHD1 that highly expressed in ureteric bud cell, kidney stromal cell and hepatoblasts. Moreover, we found a homozygous variant, CRB3 p.P114L, that caused conformational changes in the evolutional conserved domain, which may associate with NCPH with MRC.

Conclusion: ScRNA-seq enables unravelling cell heterogeneity with cell specific gene expression across multiple tissues. With the boosting public accessible scRNA-seq data, we believe our proposed analytical strategy would effectively help disease risk gene identification.
A High-Density Genetic Linkage Map and Fine Mapping of QTL For Feed Conversion Efficiency in Common Carp (Cyprinus carpio)
Authors: Zhang Xiaofeng , Luan Peixian , Cao Dingchen , Hu Guo
Published: November 2021

Feed conversion efficiency (FCE) is an economically crucial trait in fish, however, little progress has been made in genetics and genomics for this trait because phenotypes of the trait are difficult to measure. In this study, we constructed a high-density and high-resolution genetic linkage map with 28,416 SNP markers for common carp (Cyprinus carpio) based on high throughput genotyping with the carp 250K single nucleotide polymorphism (SNP) array in a full-sib F1 family of mirror carp (Cyprinus carpio) consisting of 141 progenies. The linkage map contained 11,983 distinct loci and spanned 3,590.09 cM with an average locus interval of 0.33 cM. A total of 17 QTL for the FCE trait were detected on four LGs (LG9, LG20, LG28, and LG32), explaining 8.9–15.9% of the phenotypic variations. One major cluster containing eight QTL (qFCE1-28, qFCE2-28, qFCE3-28, qFCE4-28, qFCE5-28, qFCE6-28, qFCE7-28, and qFCE8-28) was detected on LG28. Two clusters consisting of four QTL (qFCE1-32, qFCE2-32, qFCE3-32, and qFCE4-32) and three QTL (qFCE1-20, qFCE2-20, and qFCE3-20) were detected on LG32 and LG20, respectively. Nine candidate genes (ACACA, SCAF4, SLC2A5, TNMD, PCDH1, FOXO, AGO1, FFAR3, and ARID1A) underlying the feed efficiency trait were also identified, the biological functions of which may be involved in lipid metabolism, carbohydrate metabolism, energy deposition, fat accumulation, digestion, growth regulation, and cell proliferation and differentiation according to GO (Gene Ontology). As an important tool, high-density and high-resolution genetic linkage maps play a crucial role in the QTL fine mapping of economically important traits. Our novel findings provided new insights that elucidate the genetic basis and molecular mechanism of feed efficiency and the subsequent marker-assisted selection breeding in common carp.
Diagnostic Model for Discrimination Between Tuberculous Meningitis and Bacterial Meningitis
Authors: Luo Ying , Xue Ying , Lin Qun , Mao Liyan , Tang Guoxing , Song Huijuan , Liu Wei , Wu Shiji , Liu Weiyong , Zhou Yu , Xu Lingqing , Xiong Zhigang , Wang Ting , Yuan Xu , Gan Yong , Sun Ziyong , Wang Feng
Published: November 2021

Background

The differential diagnosis between tuberculous meningitis (TBM) and bacterial meningitis (BM) remains challenging in clinical practice. This study aimed to establish a diagnostic model that could accurately distinguish TBM from BM.

Methods

Patients with TBM or BM were recruited between January 2017 and January 2021 at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort). The detection for indicators involved in cerebrospinal fluid (CSF) and T-SPOT assay were performed simultaneously. Multivariate logistic regression was used to create a diagnostic model.

Results

A total of 174 patients (76 TBM and 98 BM) and another 105 cases (39 TBM and 66 BM) were enrolled from Qiaokou cohort and Caidian cohort, respectively. Significantly higher level of CSF lymphocyte proportion while significantly lower levels of CSF chlorine, nucleated cell count, and neutrophil proportion were observed in TBM group when comparing with those in BM group. However, receiver operating characteristic (ROC) curve analysis showed that the areas under the ROC curve (AUCs) produced by these indicators were all under 0.8. Meanwhile, tuberculosis-specific antigen/phytohemagglutinin (TBAg/PHA) ratio yielded an AUC of 0.889 (95% CI, 0.840–0.938) in distinguishing TBM from BM, with a sensitivity of 68.42% (95% CI, 57.30%–77.77%) and a specificity of 92.86% (95% CI, 85.98%–96.50%) when a cutoff value of 0.163 was used. Consequently, we successfully established a diagnostic model based on the combination of TBAg/PHA ratio, CSF chlorine, CSF nucleated cell count, and CSF lymphocyte proportion for discrimination between TBM and BM. The established model showed good performance in differentiating TBM from BM (AUC: 0.949; 95% CI, 0.921–0.978), with 81.58% (95% CI, 71.42%–88.70%) sensitivity and 91.84% (95% CI, 84.71%–95.81%) specificity. The performance of the diagnostic model obtained in Qiaokou cohort was further validated in Caidian cohort. The diagnostic model in Caidian cohort produced an AUC of 0.923 (95% CI, 0.867–0.980) with 79.49% (95% CI, 64.47%–89.22%) sensitivity and 90.91% (95% CI, 81.55%–95.77%) specificity.

Conclusions

The diagnostic model established based on the combination of four indicators had excellent utility in the discrimination between TBM and BM.
A Bioactive Extract Rich in Triterpenic Acid and Polyphenols from Olea europaea Promotes Systemic Immunity and Protects Atlantic Salmon Smolts Against Furunculosis
Authors: Salomón Ricardo , Furones M. Dolors , Reyes-López Felipe E. , Tort Lluis , Firmino Joana P. , Esteban M. Angeles , Espinosa Ruíz Cristóbal , Quintela José C. , Pinilla-Rosas José M. , Vallejos-Vidal Eva , Gisbert Enric
Published: November 2021

In the present study, the modulation of the transcriptional immune response (microarray analysis) in the head kidney (HK) of the anadromous fish Atlantic salmon (Salmo salar) fed a diet supplemented with an olive fruit extract (AQUOLIVE®) was evaluated. At the end of the trial (133 days), in order to investigate the immunomodulatory properties of the phytogenic tested against a bacterial infection, an in vivo challenge with Aeromonas salmonicida was performed. A total number of 1,027 differentially expressed genes (DEGs) (805 up- and 222 downregulated) were found when comparing the transcriptomic profiling of the HK from fish fed the control and AQUOLIVE® diets. The HK transcripteractome revealed an expression profile that mainly favored biological processes related to immunity. Particularly, the signaling of i-kappa B kinase/NF-kappa and the activation of leukocytes, such as granulocytes and neutrophils degranulation, were suggested to be the primary actors of the innate immune response promoted by the tested functional feed additive in the HK. Moreover, the bacterial challenge with A. salmonicida that lasted 12 days showed that the cumulative survival was higher in fish fed the AQUOLIVE® diet (96.9 ± 6.4%) than the control group (60.7 ± 13.5%). These results indicate that the dietary supplementation of AQUOLIVE® at the level of 0.15% enhanced the systemic immune response and reduced the A. salmonicida cumulative mortality in Atlantic salmon smolts.
Impairment of Multiple Mitochondrial Energy Metabolism Pathways in the Heart of Chagas Disease Cardiomyopathy Patients
Authors: Teixeira Priscila Camillo , Ducret Axel , Langen Hanno , Nogoceke Everson , Santos Ronaldo Honorato Barros , Silva Nunes João Paulo , Benvenuti Luiz , Levy Debora , Bydlowski Sergio Paulo , Bocchi Edimar Alcides , Kuramoto Takara Andréia , Fiorelli Alfredo Inácio , Stolf Noedir Antonio , Pomeranzeff Pablo , Chevillard Christophe , Kalil Jorge , Cunha-Neto Edecio
Published: November 2021

Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy occurring in 30% of the 6 million infected with the protozoan Trypanosoma cruzi in Latin America. Survival is significantly lower in CCC than ischemic (IC) and idiopathic dilated cardiomyopathy (DCM). Previous studies disclosed a selective decrease in mitochondrial ATP synthase alpha expression and creatine kinase activity in CCC myocardium as compared to IDC and IC, as well as decreased in vivo myocardial ATP production. Aiming to identify additional constraints in energy metabolism specific to CCC, we performed a proteomic study in myocardial tissue samples from CCC, IC and DCM obtained at transplantation, in comparison with control myocardial tissue samples from organ donors. Left ventricle free wall myocardial samples were subject to two-dimensional electrophoresis with fluorescent labeling (2D-DIGE) and protein identification by mass spectrometry. We found altered expression of proteins related to mitochondrial energy metabolism, cardiac remodeling, and oxidative stress in the 3 patient groups. Pathways analysis of proteins differentially expressed in CCC disclosed mitochondrial dysfunction, fatty acid metabolism and transmembrane potential of mitochondria. CCC patients’ myocardium displayed reduced expression of 22 mitochondrial proteins belonging to energy metabolism pathways, as compared to 17 in DCM and 3 in IC. Significantly, 6 beta-oxidation enzymes were reduced in CCC, while only 2 of them were down-regulated in DCM and 1 in IC. We also observed that the cytokine IFN-gamma, previously described with increased levels in CCC, reduces mitochondrial membrane potential in cardiomyocytes. Results suggest a major reduction of mitochondrial energy metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gamma. This may partially explain the worse prognosis of CCC as compared to DCM or IC.
Case Report: Evolution of a Severe Vascular Refractory Form of ECD Requiring Liver Transplantation Correlated With the Change in the Monocyte Subset Analysis
Authors: Razanamahery Jérôme , Roggy Anne , Emile Jean-François , Malakhia Alexandre , Lakkis Zaher , Garnache-Ottou Francine , Soumagne Thibaud , Cohen-Aubart Fleur , Haroche Julien , Bonnotte Bernard
Published: November 2021

Erdheim–Chester disease is a rare histiocytosis characterized by iconic features associated with compatible histology. Most patients have somatic mutations in the MAP-kinase pathway gene, and the mutations occur in CD14+ monocytes. Differentiation of the myeloid lineage plays a central role in the pathogenesis of histiocytosis. Monocytes are myeloid-derived white blood cells, divided into three subsets, but only the CD14++CD16− “classical monocyte” can differentiate into dendritic cells and tissue macrophages. Since most mutations occur in CD14+ cells and since ECD patients have a particular monocytic phenotype resembling CMML, we studied the correlation between disease activity and monocytic subset distribution during the course of a severe vascular form of ECD requiring liver transplantation. During early follow-up, increased CD14++CD16− “classical monocyte” associated with decreased CD14lowCD16++ “non-classical monocyte” correlated with disease activity. Further studies are needed to confirm the use of monocyte as a marker of disease activity in patients with ECD.
Clinical and Immunological Features of Human BCL10 Deficiency
Authors: Garcia-Solis Blanca , Van Den Rym Ana , Pérez-Caraballo Jareb J. , Al–Ayoubi Abdulwahab , Alazami Anas M. , Lorenzo Lazaro , Cubillos-Zapata Carolina , López-Collazo Eduardo , Pérez-Martínez Antonio , Allende Luis M. , Markle Janet , Fernández-Arquero Miguel , Sánchez-Ramón Silvia , Recio Maria J. , Casanova Jean-Laurent , Mohammed Reem , Martinez-Barricarte Rubén , Pérez de Diego Rebeca
Published: November 2021

The CARD-BCL10-MALT1 (CBM) complex is critical for the proper assembly of human immune responses. The clinical and immunological consequences of deficiencies in some of its components such as CARD9, CARD11, and MALT1 have been elucidated in detail. However, the scarcity of BCL10 deficient patients has prevented gaining detailed knowledge about this genetic disease. Only two patients with BCL10 deficiency have been reported to date. Here we provide an in-depth description of an additional patient with autosomal recessive complete BCL10 deficiency caused by a nonsense mutation that leads to a loss of expression (K63X). Using mass cytometry coupled with unsupervised clustering and machine learning computational methods, we obtained a thorough characterization of the consequences of BCL10 deficiency in different populations of leukocytes. We showed that in addition to the near absence of memory B and T cells previously reported, this patient displays a reduction in NK, γδT, Tregs, and TFH cells. The patient had recurrent respiratory infections since early childhood, and showed a family history of lethal severe infectious diseases. Fortunately, hematopoietic stem-cell transplantation (HSCT) cured her. Overall, this report highlights the importance of early genetic diagnosis for the management of BCL10 deficient patients and HSCT as the recommended treatment to cure this disease.
Microvascular Structure Changes After Intravitreal Ranibizumab Injection in Retinal Vein Occlusion Patients With and Without Macular Ischemia
Authors: Zhu Ziyi , Meng Yongan , Kozak Igor , Xie Manyun , Liang Youling , Yan Bin , Zhou Liang , Ouyang Pingbo , Yao Xiaoxi , Luo Jing
Published: November 2021

Purpose: To investigate the changes in the macular microvascular structure after anti-vascular endothelial growth factor (anti-VEGF) treatment in retinal vein occlusion (RVO) patients with and without macular ischemia.

Methods: A total of 39 patients were divided into the macular ischemia group (n = 22) and the nonischemia group (n = 17) at baseline. All the patients received an intravitreal injection of ranibizumab with a 3+ pro re nata (PRN) regimen. The foveal avascular zone (FAZ) areas, macular vessel density (VD), and macular ischemic index (ISI) were evaluated at baseline and 3 and 6 months after treatment.

Results: After treatment, some patients in the macular ischemia group achieved obvious reperfusion in macular nonperfusion areas. The VD and macular ISI improved in RVO patients, but the changes in VD and macular ISI were different in the two groups. The improvement of best corrected visual acuity (BCVA) was positively correlated with the improvement of macular perfusion status. Macular perfusion remained stable in most patients in RVO and only one patient had macular ischemia aggravation.

Conclusion: The macular microvascular structures were stable in most RVO patients after anti-VEGF treatment. At the same time, some patients with macular ischemia presented reperfusion in macular nonperfusion areas, and still a few patients presented aggravated macular ischemia. Macular ISI is a good way to evaluate macular perfusion status in RVO compared to VD.
Differentiation of Brain Abscess From Cystic Glioma Using Conventional MRI Based on Deep Transfer Learning Features and Hand-Crafted Radiomics Features
Authors: Bo Linlin , Zhang Zijian , Jiang Zekun , Yang Chao , Huang Pu , Chen Tingyin , Wang Yifan , Yu Gang , Tan Xiao , Cheng Quan , Li Dengwang , Liu Zhixiong
Published: November 2021

Objectives: To develop and validate the model for distinguishing brain abscess from cystic glioma by combining deep transfer learning (DTL) features and hand-crafted radiomics (HCR) features in conventional T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI).

Methods: This single-center retrospective analysis involved 188 patients with pathologically proven brain abscess (102) or cystic glioma (86). One thousand DTL and 105 HCR features were extracted from the T1WI and T2WI of the patients. Three feature selection methods and four classifiers, such as k-nearest neighbors (KNN), random forest classifier (RFC), logistic regression (LR), and support vector machine (SVM), for distinguishing brain abscess from cystic glioma were compared. The best feature combination and classifier were chosen according to the quantitative metrics including area under the curve (AUC), Youden Index, and accuracy.

Results: In most cases, deep learning-based radiomics (DLR) features, i.e., DTL features combined with HCR features, contributed to a higher accuracy than HCR and DTL features alone for distinguishing brain abscesses from cystic gliomas. The AUC values of the model established, based on the DLR features in T2WI, were 0.86 (95% CI: 0.81, 0.91) in the training cohort and 0.85 (95% CI: 0.75, 0.95) in the test cohort, respectively.

Conclusions: The model established with the DLR features can distinguish brain abscess from cystic glioma efficiently, providing a useful, inexpensive, convenient, and non-invasive method for differential diagnosis. This is the first time that conventional MRI radiomics is applied to identify these diseases. Also, the combination of HCR and DTL features can lead to get impressive performance.
Identification of Galectin-3 as Potential Biomarkers for Renal Fibrosis by RNA-Sequencing and Clinicopathologic Findings of Kidney Biopsy
Authors: Ou Shuo-Ming , Tsai Ming-Tsun , Chen Huan-Yuan , Li Fu-An , Tseng Wei-Cheng , Lee Kuo-Hua , Chang Fu-Pang , Lin Yao-Ping , Yang Ruey-Bing , Tarng Der-Cherng
Published: November 2021

Background: Galectin-3 (Gal-3) is a multifunctional glycan-binding protein shown to be linked to chronic inflammation and fibrogenesis. Plasma Gal-3 is associated with proteinuria and renal dysfunction, but its role has never been confirmed with kidney biopsy results. In our study, we aimed to explore the expression of Gal-3 in biopsy-proven patients, and we tested the hypothesis that chronic kidney disease (CKD) leads to upregulation of plasma Gal-3 expression in corresponding biopsy findings and RNA sequencing analysis.

Method: In 249 patients (male/female: 155/94, age: 57.2 ± 16.3 years) who underwent kidney biopsy, plasma levels of Gal-3 were measured to estimate the association of renal fibrosis. Relationships between plasma Gal-3 levels, estimated glomerular filtration rate (eGFR) and renal histology findings were also assessed. We further examined the gene expression of Gal-3 in RNA-sequencing analysis in biopsy-proven patients.

Results: Compared to patients without CKD, CKD patients had higher levels of plasma Gal-3 (1,016.3 ± 628.1 pg/mL vs. 811.6 ± 369.6 pg/ml; P = 0.010). Plasma Gal-3 was inversely correlated with eGFR (P = 0.005) but not with proteinuria. Higher Gal-3 levels were associated with interstitial fibrosis, tubular atrophy and vascular intimal fibrosis. RNA-sequencing analysis showed the upregulation of Gal-3 in fibrotic kidney biopsy samples, and the differentially expressed genes were mainly enhanced in immune cell activation and the regulation of cell-cell adhesion.

Conclusions: Plasma Gal-3 levels are inverse correlated with eGFR but positively correlated with renal fibrosis, which may be involved in the immune response and associated pathways. These findings support the role of Gal-3 as a predictive marker of renal fibrosis.
Effect of Whole or Ground Flaxseed Supplementation on Fatty Acid Profile, Fermentation, and Bacterial Composition in Rumen of Dairy Cows
Authors: Huang Guoxin , Guo Liya , Chang Xiaofeng , Liu Kaizhen , Tang Wenhao , Zheng Nan , Zhao Shengguo , Zhang Yangdong , Wang Jiaqi
Published: November 2021

Flaxseed is rich in α-linolenic acid (ALA) and can increase omega-3 polyunsaturated fatty acid in the milk of dairy cows. However, the response of rumen fermentation to different forms of flaxseed supplementation is unknown. This study aimed to investigate the effect of different forms of flaxseed on the fatty acid profile, fermentation, and composition of bacteria in the rumen of dairy cows. In total, 30 Holstein dairy cows were selected and randomly assigned into three groups (10/group). Cows were fed a basal diet (control check; CK) or basal diets supplemented with either 1,500 g per day whole flaxseed (WF) or 1,500 g per day ground flaxseed (GF). The WF group had the highest ALA content in rumen fluid, whereas no difference was found between the CK and GF groups. However, the molar proportion of acetate increased in the WF and GF groups and was the highest in the GF group, and a similar trend was shown by propionate, isobutyrate, butyrate, isovalerate, and valerate (CK < WF < GF). The abundance of Ruminococcaceae_NK4A214_group, Christensenellaceae_R-7_group, and Eubacterium_coprostanoligenes_group also showed the same trend (CK < WF < GF). Different forms of flaxseed release ALA by different mechanisms in the rumen, and the molar proportions of volatile fatty acids and the bacterial composition were potentially influenced mainly by the amount of ALA released into the rumen.
Predicting Delayed Neurocognitive Recovery After Non-cardiac Surgery Using Resting-State Brain Network Patterns Combined With Machine Learning
Authors: Jiang Zhaoshun , Cai Yuxi , Zhang Xixue , Lv Yating , Zhang Mengting , Li Shihong , Lin Guangwu , Bao Zhijun , Liu Songbin , Gu Weidong
Published: November 2021

Delayed neurocognitive recovery (DNR) is a common subtype of postoperative neurocognitive disorders. An objective approach for identifying subjects at high risk of DNR is yet lacking. The present study aimed to predict DNR using the machine learning method based on multiple cognitive-related brain network features. A total of 74 elderly patients (≥ 60-years-old) undergoing non-cardiac surgery were subjected to resting-state functional magnetic resonance imaging (rs-fMRI) before the surgery. Seed-based whole-brain functional connectivity (FC) was analyzed with 18 regions of interest (ROIs) located in the default mode network (DMN), limbic network, salience network (SN), and central executive network (CEN). Multiple machine learning models (support vector machine, decision tree, and random forest) were constructed to recognize the DNR based on FC network features. The experiment has three parts, including performance comparison, feature screening, and parameter adjustment. Then, the model with the best predictive efficacy for DNR was identified. Finally, independent testing was conducted to validate the established predictive model. Compared to the non-DNR group, the DNR group exhibited aberrant whole-brain FC in seven ROIs, including the right posterior cingulate cortex, right medial prefrontal cortex, and left lateral parietal cortex in the DMN, the right insula in the SN, the left anterior prefrontal cortex in the CEN, and the left ventral hippocampus and left amygdala in the limbic network. The machine learning experimental results identified a random forest model combined with FC features of DMN and CEN as the best prediction model. The area under the curve was 0.958 (accuracy = 0.935, precision = 0.899, recall = 0.900, F1 = 0.890) on the test set. Thus, the current study indicated that the random forest machine learning model based on rs-FC features of DMN and CEN predicts the DNR following non-cardiac surgery, which could be beneficial to the early prevention of DNR.

Clinical Trial Registration: The study was registered at the Chinese Clinical Trial Registry (Identification number: ChiCTR-DCD-15006096).
Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice
Authors: Ebert Tim , Heinz Daniel E. , Almeida-Corrêa Suellen , Cruz Renata , Dethloff Frederik , Stark Tibor , Bajaj Thomas , Maurel Oriana M. , Ribeiro Fabiola M. , Calcagnini Silvio , Hafner Kathrin , Gassen Nils C. , Turck Christoph W. , Boulat Benoit , Czisch Michael , Wotjak Carsten T.
Published: November 2021

Dementia is a devastating age-related disorder. Its therapy would largely benefit from the identification of susceptible subjects at early, prodromal stages of the disease. To search for such prognostic markers of cognitive impairment, we studied spatial navigation in male BALBc vs. B6N mice in combination with in vivo magnetic resonance spectroscopy (1H-MRS). BALBc mice consistently showed higher escape latencies than B6N mice, both in the Water Cross Maze (WCM) and the Morris water maze (MWM). These performance deficits coincided with higher levels of myo-inositol (mIns) in the dorsal hippocampus before and after training. Subsequent biochemical analyses of hippocampal specimens by capillary immunodetection and liquid chromatography mass spectrometry-based (LC/MS) metabolomics revealed a higher abundance of glial markers (IBA-1, S100B, and GFAP) as well as distinct alterations in metabolites including a decrease in vitamins (pantothenic acid and nicotinamide), neurotransmitters (acetylcholine), their metabolites (glutamine), and acetyl-L-carnitine. Supplementation of low abundant acetyl-L-carnitine via the drinking water, however, failed to revert the behavioral deficits shown by BALBc mice. Based on our data we suggest (i) BALBc mice as an animal model and (ii) hippocampal mIns levels as a prognostic marker of mild cognitive impairment (MCI), due to (iii) local changes in microglia and astrocyte activity, which may (iv) result in decreased concentrations of promnesic molecules.