bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of One-Stage Surgical Repair for Berry Syndrome in Neonates
Authors: Shi Xu-Cong , Weng Jian-Bin , Yu Jin , Ma Xiao-Hui , Pu Yi-Qing , Ying Li-Yang , Yu Jian-Gen
Published: January 2022

Background

Berry syndrome is a challenging disease for surgeons to make early diagnosis and successful surgical correction in the neonatal period. Here, we summarized the clinical features of three neonates with berry syndrome in our center to optimize the therapeutic effect in the future.

Methods

From January 2014 to December 2019, three neonates with berry syndrome underwent one-stage surgical repair in our center. We mainly used two different surgical techniques to repair it, and collected clinical data retrospectively from hospitalization history, outpatient records, and telephone follow-up.

Results

The age at operation was 28, 8, and 8 days and the body weight was 3.65, 3.86, and 3.0 kg, respectively. The morphology of the interrupted aortic arch (IAA) was type A in two patients and type B in one patient. The aortopulmonary window (APW) morphology was type IIa, III, and IIb, respectively. The phenotype of the IAA type B combined with APW type III in our second patient was reported for the first time so far. All patients survived and were followed up to date. The second patient using intra-aortic baffle experienced twice reoperation for right pulmonary artery (RPA) stenosis. All patients grew well so far.

Conclusion

Once diagnosed in the neonatal period, berry syndrome can be safely corrected by one-stage surgical repair in experienced cardiac centers. Considering the variability of the location where the RPA arises from the posterior wall of the aorta, it is difficult to find the best surgical method for each patient.
Paroxetine and Mortality in Heart Failure: A Retrospective Cohort Study
Authors: Xu Hongxuan , Meng Lingbing , Long Huanyu , Shi Yueping , Liu Yunqing , Wang Li , Liu Deping
Published: January 2022

Introduction

Paroxetine is a GRK2 inhibitor that has been widely used to treat depression and anxiety over the last few decades. The inhibition of GRK2 has been studied extensively in vivo; however, evidence of its impact on heart failure remains scarce.

Methods

To assess the association between paroxetine use and mortality in patients with heart failure. We conducted a retrospective longitudinal cohort study from 2008 to 2019, with a follow-up time of 28 days for all groups. This is a single-center study using the Medical Information Mart for Intensive Care IV database with 11,657 heart failure patients identified. We performed genetic matching to adjust for the covariates. Heart failure patients prescribed paroxetine for >24 h after hospital admission were categorized into the paroxetine group (77 patients), with remaining heart failure patients making up the matched control group (231 patients). The primary outcome was 28-day all-cause mortality from the date of hospital admission. Secondary outcomes included length of intensive care unit stay, length of hospital stay, and in-hospital mortality. The Kaplan–Meier survival estimator, logistic regression, Cox regression, and restricted mean survival time were used to detect the association between paroxetine therapy and outcomes.

Results

Patients who received paroxetine during one hospital admission lived, on average, 0.7 lesser days (95% CI −2.53 to 1.1, p = 0.46) than patients who did not use it in a 28-day truncation time point. Multivariable logistic regression, including all matched covariates, demonstrated that the adjusted odds ratio of 28-day mortality of the paroxetine administration group was 1.1 (95% CI 0.37–2.9, p = 0.90). Multivariable Cox regression of 28-day mortality presented an adjusted hazard ratio of 1.00 (95% CI 0.42–2.62, p = 0.92). Paroxetine was associated with an increased survival time at a 3,000-day truncation time point (203 days, 95% CI −305.69 to 817.8, p = 0.37).

Conclusions

In patients with heart failure, treatment with paroxetine did not significantly reduce 28-day all-cause mortality.
The Role of Multimodality Imaging in HIV-Associated Cardiomyopathy
Authors: Gambahaya Ellise T. , Rana Rimsha , Bagchi Shashwatee , Sharma Garima , Sarkar Sudipa , Goerlich Erin , Cupido Blanche , Mukherjee Monica , Hays Allison G.
Published: January 2022

Despite marked advances in therapeutics, HIV infection remains a leading cause of morbidity and mortality worldwide. HIV infection is associated with cardiovascular complications including myocardial dysfunction. The description of HIV-associated cardiomyopathy (HIVAC) has evolved over time from a predominantly dilated cardiomyopathy with systolic dysfunction to one of subclinical diastolic dysfunction. Multimodality cardiovascular imaging plays an integral role in our understanding of the etiology and pathogenesis of HIVAC. Such imaging is also essential in the evaluation of individuals with chronic HIV disease who present with cardiac symptoms, especially of heart failure. In the present review, we will highlight current evidence for the role of multimodality imaging in establishing the diagnosis, etiology and pathophysiology of HIVAC as well as guiding treatment and assessing prognosis.
Disturbance and Control of National Strategic Gas Storage Induced by Adjacent Tunnel Blasting
Authors: Ma Longhao , Lin Fei , Liu Rong , Liu Peng , Xia Guang , Chen Lichuan
Published: January 2022

Underground gas storage are often subject to external dynamic loads, blast vibrations, and seismic disturbances, since they function as backup areas for the strategic national energy reserve, supply and demand dispatch, and gas and energy storage. Currently, the research on dynamic response characteristics, dynamic stability, and disturbance control of underground gas storages under dynamic loads is still incomplete and of great practical importance to ensure national strategic security. Therefore, this paper takes the blasting project of the Sansheng tunnel, which passes through the national strategic gas storage reservoir, as the engineering background. Based on the geological conditions and rock characteristics, the dynamic response characteristics of the rock surrounding the tunnel and gas storage are studied using the finite element method. The peak vibration velocity distribution of the surrounding rocks at different blasting source distances is analyzed and compared with the theoretical formula. Subsequently, an asymmetric uncoupled blasting vibration control technique is proposed and used for field blasting. The results show that the numerical results are consistent with the theoretical formula. The blasting vibration velocity decreases exponentially with an increase in the blasting source distance. Overall, the proposed technique significantly decreases the average peak vibration velocity by 22.64% compared to the original vibration velocity.
Metabolic Profiling Identified a Novel Biomarker Panel for Metabolic Syndrome-Positive Hepatocellular Cancer
Authors: Cao Lin-Lin , Han Yi , Wang Yuanxiao , Pei Lin , Yue Zhihong , Qin Li , Liu Boyu , Cui Jingwen , Jia Mei , Wang Hui
Published: January 2022

Metabolic syndrome (MetS) is an independent risk factor for hepatocellular cancer (HCC). Currently, there is no highly sensitive and specific biomarkers for HCC surveillance in MetS population. Metabolomics has been reported as a powerful technology for biomarker discovery. In the present study, we aimed to explore novel biomarkers with high sensitivity and specificity for MetS-positive [MetS(+)] HCC by metabolomic analysis. At first, many serum metabolites were found dysregulated in MetS(+) HCC individuals. Validation of the dysregulated metabolites by targeted metabolite analyses revealed that serum L-glutamic acid (L-glu), pipecolic acid (PA) and 7-methylguanine (7-mG) were increased in MetS(+) HCC compared to MetS group. Then a biomarker panel including L-glu, PA and alpha-fetoprotein (AFP) was identified as a novel biomarker for the diagnosis of MetS(+) HCC. Receiver operating characteristic (ROC) curve was drawn and the area under the ROC curve (AUC) was 0.87 for discriminating MetS(+) HCC from MetS group. The biomarker panel was capable of detecting small (AUC = 0.82) and early-stage (AUC = 0.78) tumors as well. Moreover, it exhibited great diagnostic performance (AUC = 0.93) for discriminating MetS(+) HCC from other MetS-associated cancers, including colorectal cancer and gastric cancer. Collectively, our study establishes a novel diagnostic tool for MetS(+) HCC.
Influence of Different Offset Angles of Inlet Guide Vanes on Flow Characteristics of Centrifugal Pump
Authors: Lin Peifeng , Yang Tao , Xu Wenbin , Zhu Zuchao
Published: January 2022

The efficiency of the impeller machinery can be improved by the inlet guide vanes, but the relationship between the external characteristics of the centrifugal pump and the internal flow state needs further study. In this paper, the flow characteristics of the centrifugal pump with different offset angles of inlet guide vanes (IGVs) are simulated based on the SST k-ω turbulence model. The influence of the offset angle of the IGV on the internal flow and energy dissipation of the centrifugal pump is analyzed by using the entropy generation theory and Q-criterion. The research results show that the increase of the offset angle is beneficial to reducing the intensity of vortex in the volute and impeller, while the energy loss is reduced by 21.12 and 17.82% at 0.6Qd and 0.8Qd, respectively. However, the excessive offset angle of the IGV tends to cause greater energy loss in the inlet pipe, thus reducing the head and efficiency of the centrifugal pump. In terms of external characteristics, the pump with 25° IGVs has the best head and efficiency improvement. Under three small operating points, the pump with 25° IGVs increased the head by 2.11, 0.95, and 0.73% and the efficiency by 2.51, 1.67, and 1.25%, respectively, compared with the pump with 0° IGVs. The research in this paper contributes to the performance improvement of centrifugal pumps operating at low flow conditions.
Carbon Emission Reduction Effects of Green Credit Policies: Empirical Evidence From China
Authors: Qin Jiahong , Cao Jianhua
Published: January 2022

This paper employs the Green Credit Guidelines as green financial policy to investigate whether the implementation of green credit has contributed to the low-carbon economic development. The difference-in-differences method (DID) is then applied to estimate the emission reduction effects. The paper found that green financial policy has effectively reduced pollution and energy consumption in high pollution and high energy consuming industries. As a means of verifying the reliability of the results, propensity score matching difference-in-differences (PSM-DID) applies the match kernels and radius method before the DID. Furthermore, this paper explored the regional and industry heterogeneity in incremental carbon emission reductions. This is the first paper to use Guidelines to measure green finance, in order to achieve indicator innovation and provide corresponding policy advice. To reduce carbon emissions, the government must strengthen the implementation of green credit policy and create a green financial environment tailored to local needs.
Seasonal Amplitude of Water Storage Variations of the Yangtze–Huai Plain Lake Group: Implicaion for Floodwater Storage Capacity
Authors: Song Lijuan , Song Chunqiao , Zhan Pengfei , Chen Tan , Liu Kai , Jing Haitao
Published: January 2022

Lakes are of significant importance in regulating floods and providing water sources. The seasonal water storage variations for the plain lake group in the Yangtze–Huai River Basin (YHRB) are significant for alleviating flood pressure and regulating runoff. However, to date, the seasonal amplitude of lake water storage variations and its capacity of buffering floodwater in the YHRB is not quantified well and remains to be investigated comprehensively. To advance the understanding of such a critical scientific issue, the water level data of the plain lake group (area>100 km2, 29 lakes) in the YHRB is collected from multi-source data between 1990 and 2020. Using lake inundation area obtained from Global Surface Water and water level variations, water storage dynamics for the plain lake group are quantified. Furthermore, this study also uses the Gravity Recovery and Climate Experiment (GRACE) products to analyze the terrestrial water storage anomalies (TWSA) in the whole basin. The results indicate that the seasonal amplitude of water level change and water storage variation of the plain lake group are 2.80 ± 0.71 m and 37.38 ± 14.19 Gt, respectively. Poyang and Dongting Lakes, two lakes that maintain the natural connection with the Yangtze River, have the most substantial seasonal amplitude in the hydrological situation. The amplitude in water level and water storage in Poyang Lake is 9.53 ± 2.02 m and 14.13 ± 5.54 Gt respectively, and that in Dongting Lake is 7.39 ± 1.29 m and 7.31 ± 3.42 Gt respectively. The contribution of seasonal variation of water storage for large plain lakes to TWSA in the YHRB is approximately 33.25%, fully reflecting these lake’s imperative position in the YHRB. This study is expected to enhance the scientific understanding of the seasonal hydrologic regime for the large lakes in the YHRB and contribute to the management of flood risks and water resources in East China.
Circular RNA CDR1as Alleviates Cisplatin-Based Chemoresistance by Suppressing MiR-1299 in Ovarian Cancer
Authors: Wu Han , Zhao Xibo , Wang Jing , Jiang Xinyan , Cheng Yan , He Yanan , Sun Liyuan , Zhang Guangmei
Published: January 2022

Cisplatin (CDDP) chemoresistance seriously affects the prognosis and survival of patients with ovarian cancer (OC). Previous research has shown that circular RNA CDR1as is biologically associated with a large number of cancers. However, the molecular mechanism underlying the role of CDR1as in CDDP chemoresistance in OC remains unclear. Here, we investigated the mechanism of CDR1as in CDDP-resistant OC. First, we employed bioinformatics analysis and quantitative real-time PCR (qRT-PCR) to determine the expression of CDR1as and related RNAs in CDDP-sensitive and -resistant OC tissues and cells. Then, functional experiments were used to determine cell proliferation, invasion, migration, and apoptosis in CDDP chemoresistance and parent OC cells in vitro. The effect of CDR1as in CDDP chemoresistance OC progression was tested in nude mice in vivo. Moreover, dual-luciferase assays and RNA immunoprecipitation (RIP) were performed to confirm the interactions of CDR1as and related RNAs. Finally, we used Western blotting to determine protein expression levels. Our findings interpret the underlying mechanisms of the CDR1as/miR-1299/PPP1R12B axis and shed light on the clinical applications for CDDP-chemoresistant OC.
Case Report: Altered NK Cell Compartment and Reduced CXCR4 Chemotactic Response of B Lymphocytes in an Immunodeficient Patient With HPV-Related Disease
Authors: Doria Margherita , Moscato Giusella M. F. , Di Cesare Silvia , Di Matteo Gigliola , Sgrulletti Mayla , Bachelerie Françoise , Marin-Esteban Viviana , Moschese Viviana
Published: January 2022

The study of inborn errors of immunity (IEI) provides unique opportunities to elucidate the microbiome and pathogenic mechanisms related to severe viral infection. Several immunological and genetic anomalies may contribute to the susceptibility to develop Human Papillomavirus (HPV) pathogenesis. They include different acquired immunodeficiencies, EVER1-2 or CIB1 mutations underlying epidermodysplasia verruciformis (EV) syndrome and multiple IEI. Whereas EV syndrome patients are specifically unable to control infections with beta HPV, individuals with IEI show broader infectious and immune phenotypes. The WHIM (warts, hypogammaglobulinemia, infection, and myelokathexis) syndrome caused by gain-of-CXCR4-function mutation manifests by HPV-induced extensive cutaneous warts but also anogenital lesions that eventually progress to dysplasia. Here we report alterations of B and NK cells in a female patient suffering from cutaneous and mucosal HPV-induced lesions due to an as-yet unidentified genetic defect. Despite no detected mutations in CXCR4, B but not NK cells displayed a defective CXCR4-dependent chemotactic response toward CXCL12. In addition, NK cells showed an abnormal distribution with an expanded CD56bright cell subset and defective cytotoxicity of CD56dim cells. Our observations extend the clinical and immunological spectrum of IEI associated with selective susceptibility toward HPV pathogenesis, thus providing new insight on the immune control of HPV infection and potential host susceptibility factors.
SARS-CoV-2 Spike-Specific CD4+ T Cell Response Is Conserved Against Variants of Concern, Including Omicron
Authors: Mazzoni Alessio , Vanni Anna , Spinicci Michele , Capone Manuela , Lamacchia Giulia , Salvati Lorenzo , Coppi Marco , Antonelli Alberto , Carnasciali Alberto , Farahvachi Parham , Giovacchini Nicla , Aiezza Noemi , Malentacchi Francesca , Zammarchi Lorenzo , Liotta Francesco , Rossolini Gian Maria , Bartoloni Alessandro , Cosmi Lorenzo , Maggi Laura , Annunziato Francesco
Published: January 2022

Although accumulating data have investigated the effect of SARS-CoV-2 mutations on antibody neutralizing activity, less is known about T cell immunity. In this work, we found that the ancestral (Wuhan strain) Spike protein can efficaciously reactivate CD4+ T cell memory in subjects with previous Alpha variant infection. This finding has practical implications, as in many countries only one vaccine dose is currently administered to individuals with previous COVID-19, independently of which SARS-CoV-2 variant was responsible of the infection. We also found that only a minority of Spike-specific CD4+ T cells targets regions mutated in Alpha, Beta and Delta variants, both after natural infection and vaccination. Finally, we found that the vast majority of Spike-specific CD4+ T cell memory response induced by natural infection or mRNA vaccination is conserved also against Omicron variant. This is of importance, as this newly emerged strain is responsible for a sudden rise in COVID-19 cases worldwide due to its increased transmissibility and ability to evade antibody neutralization. Collectively, these observations suggest that most of the memory CD4+ T cell response is conserved against SARS-CoV-2 variants of concern, providing an efficacious line of defense that can protect from the development of severe forms of COVID-19.
Self-Tolerance of Vascular Tissues Is Broken Down by Vascular Dendritic Cells in Response to Systemic Inflammation to Initiate Regional Autoinflammation
Authors: Sun Li , Zhang Wenjie , Zhao Lin , Zhao Yanfang , Wang Fengge , Lew Andrew M. , Xu Yuekang
Published: January 2022

The correlation of infections with vascular autoinflammatory diseases such as vasculitis and atherosclerosis has been long recognized, and progressive inflammation with the formation of tertiary lymphoid organs in arterial adventitia intensively studied, the immunological basis of the nondiseased vasculatures that predispose to subsequent vascular autoimmunity during inflammation, however, is not well characterized. Here, we investigated the vascular immunity in situ of steady-state C57BL/6 mice and found that healthy vascular tissues contained a comprehensive set of immune cells with relatively higher proportion of innate components than lymphoid organs. Notably, a complete set of dendritic cell (DC) subsets was observed with monocyte-derived DCs (moDCs) constituting a major proportion; this is in contrast to moDCs being considered rare in the steady state. Interestingly, these vascular DCs constitutively expressed more suppressive factors with cDC1 for PD-L1 and moDCs for IL-10; this is concordant with the inhibitive phenotype of T cells in normal vascular tissues. The immunotolerant state of the vascular tissues, however, was readily eroded by systemic inflammation, demonstrated by the upregulation of proinflammatory cytokines and enhanced antigen presentation by vascular DCs to activate both cellular and humoral immunity in situ, which ultimately led to vascular destruction. Different vascular DC subsets elicited selective effects: moDCs were potent cytokine producers and B-cell activators, whereas cDCs, particularly, cDC1, were efficient at presenting antigens to stimulate T cells. Together, we unveil regional immunological features of vascular tissues to explain their dual facets under physiological versus pathological conditions for the better understanding and treatment of cardiovascular autoinflammation.
Accurate MHC Motif Deconvolution of Immunopeptidomics Data Reveals a Significant Contribution of DRB3, 4 and 5 to the Total DR Immunopeptidome
Authors: Kaabinejadian Saghar , Barra Carolina , Alvarez Bruno , Yari Hooman , Hildebrand William H. , Nielsen Morten
Published: January 2022

Mass spectrometry (MS) based immunopeptidomics is used in several biomedical applications including neo-epitope discovery in oncology, next-generation vaccine development and protein-drug immunogenicity assessment. Immunopeptidome data are highly complex given the expression of multiple HLA alleles on the cell membrane and presence of co-immunoprecipitated contaminants. The absence of tools that deal with these challenges effectively and guide the analysis and interpretation of this complex type of data is currently a major bottleneck for the large-scale application of this technique. To resolve this, we here present the MHCMotifDecon that benefits from state-of-the-art HLA class-I and class-II predictions to accurately deconvolute immunopeptidome datasets and assign individual ligands to the most likely HLA molecule, allowing to identify and characterize HLA binding motifs while discarding co-purified contaminants. We have benchmarked the tool against other state-of-the-art methods and illustrated its application on experimental datasets for HLA-DR demonstrating a previously underappreciated role for HLA-DRB3/4/5 molecules in defining HLA class II immune repertoires. With its ease of use, MHCMotifDecon can efficiently guide interpretation of immunopeptidome datasets, serving the discovery of novel T cell targets. MHCMotifDecon is available athttps://services.healthtech.dtu.dk/service.php?MHCMotifDecon-1.0.
BRD4 Inhibition Attenuates Inflammatory Pain by Ameliorating NLRP3 Inflammasome-Induced Pyroptosis
Authors: Hua Tong , Wang Haowei , Fan Xiaoyi , An Ni , Li Jian , Song Honghao , Kong Erliang , Li Yongchang , Yuan Hongbin
Published: January 2022

Chronic pain, such as persistent inflammatory pain, remains a public health problem that has no effective treatment at present. Bromodomain-containing protein 4 (BRD4) inhibition, induced by JQ1 injection or BRD4 knockdown, has been used to attenuate inflammatory pain; However, it remains elusive whether BRD4 aggravates inflammatory pain by regulating inflammasome. Western blot and immunofluorescence staining showed that BRD4 expression increased after administration of complete Freund’s adjuvant (CFA) and reached its peak on day 3. Immunofluorescence staining showed that BRD4 was mainly colocalized with NeuN-positive neurons in the spinal cord, which was accompanied by upregulation of inflammasome component proteins, such as NLRP3, gasdermin D, and caspase-1. JQ1 was intrathecally injected into mice 1 h before CFA administration, and the mechanical and thermal hyperalgesia levels were measured on days 1, 3, and 7 after CFA administration. CFA-induced inflammatory pain, paw inflammation, and swelling were attenuated by pre-treatment with JQ1. To our knowledge, this study was the first to prove that NLRP3 inflammasome-induced neuronal pyroptosis participates in inflammatory pain. BRD4 inhibition decreased the expression of pyroptosis-related proteins by inhibiting the activation of NF-κB signaling pathway, both in vivo and in vitro. Taken together, BRD4 inhibition exerted analgesic and anti-inflammatory effects against inflammatory pain by inhibiting NF-κB and inflammasome activation, which protected neural cells from pyroptosis.
Durability of Concrete With Coal Gasification Slag and Coal Gangue Powder
Authors: Zhu Xiaoliang , Guo Zhaoheng , Yang Wen , Song Wenjing
Published: January 2022

Lack and quality decrease of supplementary cementing materials (SCMs) such as fly ash and granulated blast-furnace slag is increasingly prominent in China. Thus, the use of coal gangue (CG) and coal gasification slag (CGS) as SCMs in concrete attracted more researcher’s attention. This paper investigated the mechanical strength, porosity, and durability of CG-and CGS-added concrete. Experimental results showed that the activity of the treated CG and CGS is better than that of ordinary mineral SCMs, indicating that CG and CGS concrete can satisfy the requirements of ordinary construction under reasonable processing technology. Both CG-added and CGS-added concrete illustrated better chloride penetration resistance. The aluminum element contained in CG and CGS causes the C3S hydration to generate ettringite which is an erosion product under sulfate erosion, and it will intensify the damage of sulfate erosion. After 125th freeze-thaw cycles, the CGS-added concrete has no obvious failure which indicates that CGS-added concrete has great capacity in the frost resistance.
Green–Light–Driven Poly(N-isopropylacrylamide-acrylamide)/Fe3O4 Nanocomposite Hydrogel Actuators
Authors: Cao Ying , Li Wenjiao , Quan Fengyu , Xia Yanzhi , Xiong Zhong
Published: January 2022

Light-responsive hydrogel actuators show attractive biomedical applications for in vivo drug delivery tool, surgical tissue repair operation, and vascular cleaning due to its non-contact, rapid, precise, and remote spatial control of light. Conventional visible–light–responsive hydrogels contain special chemical structure or groups, and the difficulty in synthesis results in that few can be applied to fabricate visible–light–driven hydrogel actuators. In this study, based on photothermal effect, surface-modified Fe3O4 nanoparticles were incorporated into poly(N-isopropylacrylamide-acrylamide) hydrogel by UV photopolymerization, which revealed excellent green–light–responsive volume change. Under a laser irradiation of 200 mW at 520 nm, the bending angle deformation of hydrogel strips with 2.62 wt% Fe3O4 reached 107.8°. Strip-shaped hydrogel actuators could be applied to transport tiny objects. Furthermore, a boomerang-like hydrogel actuator was designed and fabricated to drive floating foam on water. By 12 cycles of continuous laser on–off irradiation to a hydrogel actuator underwater, a circular returning movement of the float was accomplished. The study on driving a float using visible–light–triggered hydrogel actuators provides a new idea for the design of light-driven biomedical devices and soft robots.
Clinical Application of Noninvasive Prenatal Testing for Sex Chromosome Aneuploidies in Central China
Authors: Zhao Ganye , Dai Peng , Wang Conghui , Liu Lina , Zhao Xuechao , Kong Xiangdong
Published: January 2022

Background

The relatively high incidence and the clinical symptoms of sex chromosome aneuploidies (SCAs) make prenatal screening of SCAs an attractive option for pregnant women. However, limited studies have assessed the clinical performance of noninvasive prenatal testing (NIPT) for screening SCAs. This study was performed to evaluate the clinical performance of NIPT for SCAs in singleton pregnancies in central China.

Methods

Noninvasive prenatal testing was performed using next-generation sequencing. Standard Z-score analysis was used to identify fetal SCAs. NIPT-positive results were confirmed by invasive prenatal diagnosis (IPD).

Results

A total of 42,164 pregnant women with singleton pregnancies were recruited in this study. They were divided into the following five groups with different clinical indications: with ultrasound soft index abnormalities (9.23%, 3,892/42,164); with advanced maternal age (22.14%, 9,336/42,164); with high risk for maternal serum screening (MSS) (18.35%, 7,738/42,164); with an intermediate risk for MSS (26.6%, 11,215/42,164); and with low risk (23.68%, 9,983/42,164). In all, 223 women had a high risk for SCAs by NIPT with a positive rate of 0.53%. There was no significant difference associated with the five groups in the positive rate. Of all of the positive results, 89 were 45,X (39.91%), 38 were 47,XXX (17.04%), 31 were 46,XY,del(X) (13.90%), 50 were 47,XXY (22.42%,), and 15 were 47,XYY (6.73%). Finally, 147 participants (65.92%) chose to undergo IPD, and 47 cases were confirmed. The combined positive predictive value (PPV) of NIPT for SCA was 31.97% (47/147). PPV was high for 47,XYY (100%, 11/11), moderate for 47,XXX (42.86%, 9/21) and 47,XXY (45.45%, 15/33), but low for 45,X (16.13%, 10/62) and 46,XY,del(X) (10%, 2/20). The termination rates of Turner syndrome and 47,XXY syndrome were higher than 47,XXX and 47,XYY syndromes.

Conclusion

In this relatively large cohort, we evaluated the value of NIPT for SCAs. Our data showed that with informed consent and subsequent professional genetical consulting, NIPT can be a useful method to screen SCAs.
The Glomerulus According to the Mesangium
Authors: Ebefors Kerstin , Bergwall Lovisa , Nyström Jenny
Published: January 2022

The glomerulus is the functional unit for filtration of blood and formation of primary urine. This intricate structure is composed of the endothelium with its glycocalyx facing the blood, the glomerular basement membrane and the podocytes facing the urinary space of Bowman's capsule. The mesangial cells are the central hub connecting and supporting all these structures. The components as a unit ensure a high permselectivity hindering large plasma proteins from passing into the urine while readily filtering water and small solutes. There has been a long-standing interest and discussion regarding the functional contribution of the different cellular components but the mesangial cells have been somewhat overlooked in this context. The mesangium is situated in close proximity to all other cellular components of the glomerulus and should be considered important in pathophysiological events leading to glomerular disease. This review will highlight the role of the mesangium in both glomerular function and intra-glomerular crosstalk. It also aims to explain the role of the mesangium as a central component involved in disease onset and progression as well as signaling to maintain the functions of other glomerular cells to uphold permselectivity and glomerular health.
Diagnostic Performance of Deep Learning Classifiers in Measuring Peripheral Anterior Synechia Based on Swept Source Optical Coherence Tomography Images
Authors: Yang Yangfan , Wu Yanyan , Guo Chong , Han Ying , Deng Mingjie , Lin Haotian , Yu Minbin
Published: January 2022

Purpose

To develop deep learning classifiers and evaluate their diagnostic performance in detecting the static gonioscopic angle closure and peripheral anterior synechia (PAS) based on swept source optical coherence tomography (SS-OCT) images.

Materials and Methods

Subjects were recruited from the Glaucoma Service at Zhongshan Ophthalmic Center of Sun Yat-sun University, Guangzhou, China. Each subject underwent a complete ocular examination, such as gonioscopy and SS-OCT imaging. Two deep learning classifiers, using convolutional neural networks (CNNs), were developed to diagnose the static gonioscopic angle closure and to differentiate appositional from synechial angle closure based on SS-OCT images. Area under the receiver operating characteristic (ROC) curve (AUC) was used as outcome measure to evaluate the diagnostic performance of two deep learning systems.

Results

A total of 439 eyes of 278 Chinese patients, which contained 175 eyes of positive PAS, were recruited to develop diagnostic models. For the diagnosis of static gonioscopic angle closure, the first deep learning classifier achieved an AUC of 0.963 (95% CI, 0.954–0.972) with a sensitivity of 0.929 and a specificity of 0.877. The AUC of the second deep learning classifier distinguishing appositional from synechial angle closure was 0.873 (95% CI, 0.864–0.882) with a sensitivity of 0.846 and a specificity of 0.764.

Conclusion

Deep learning systems based on SS-OCT images showed good diagnostic performance for gonioscopic angle closure and moderate performance in the detection of PAS.
Endotyping Seasonal Allergic Rhinitis in Children: A Cluster Analysis
Authors: Malizia Velia , Ferrante Giuliana , Cilluffo Giovanna , Gagliardo Rosalia , Landi Massimo , Montalbano Laura , Fasola Salvatore , Profita Mirella , Licari Amelia , Marseglia Gian Luigi , La Grutta Stefania
Published: January 2022

Background

Seasonal Allergic Rhinitis (SAR) is a heterogeneous inflammatory disease. We hypothesized that a cluster analysis based on the evaluation of cytokines in nasal lavage (NL) could characterize distinctive SAR endotypes in children.

Methods

This cross-sectional study enrolled 88 children with SAR. Detailed medical history was obtained by well-trained physicians. Quality of life and sleep quality were assessed through standardized questionnaires [Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and Pittsburgh Sleep Quality Index (PSQI) respectively]. Children were grouped through K-means clustering using Interleukin (IL)-5, IL-17, IL-23, and Interferon (INF)-γ in NL.

Results

Out of the 88 patients enrolled, 80 were included in the cluster analysis, which revealed three SAR endotypes. Cluster 1 showed lower levels of IL-5 and IL-17 and intermediate levels of IL-23 and IFN-γ; Cluster 2 had higher levels of IL-5 and intermediate levels of IL-17, IL-23, and IFN-γ; Cluster 3 showed higher levels of IL-17, IL-23, and IFN-γ and intermediate levels of IL-5. Cluster 1 showed intermediate values of nasal pH and nasal nitric oxide (nNO), and a lower percentage of neutrophils at nasal cytology than Clusters 2 and 3. Cluster 2 had a lower level of nasal pH, a higher nNO, higher scores in the ocular domain of PRQLQ, and worse sleep quality than Clusters 1 and 3. Cluster 3 showed a higher percentage of neutrophils at nasal cytology than Clusters 1 and 2.

Conclusions

Our study identified three endotypes based on the evaluation of cytokines in NL, highlighting that childhood SAR is characterized by heterogeneous inflammatory cytokines.
The Involvement of the csy1 Gene in the Antimicrobial Resistance of Acinetobacter baumannii
Authors: Guo Tingting , Sun Xiaoli , Li Mengying , Wang Yuhang , Jiao Hongmei , Li Guocai
Published: January 2022

Acinetobacter baumannii is an important, opportunistic nosocomial pathogen that causes a variety of nosocomial infections, and whose drug resistance rate has increased in recent years. The CRISPR-Cas system exists in several bacteria, providing adaptive immunity to foreign nucleic acid invasion. This study explores whether CRISPR-Cas is related to drug resistance. Antibiotics were used to treat strains ATCC19606 and AB43, and the expression of CRISPR-related genes was found to be changed. The Csy proteins (Csy1–4) were previously detected to promote target recognition; however, the potential function of csy1 gene is still unknown. Thus, the RecAb homologous recombination system was utilized to knock out the csy1 gene from A. baumannii AB43, which carries the Type I-Fb CRISPR-Cas system, and to observe the drug resistance changes in wild-type and csy1-deleted strains. The AB43Δcsy1 mutant strain was found to become resistant to antibiotics, while the wild-type strain was sensitive to antibiotics. Moreover, transcriptome analysis revealed that the csy1 gene regulates genes encoding CRISPR-Cas-related proteins, drug-resistant efflux pumps, membrane proteins, and oxidative phosphorylation-related proteins, inhibiting antimicrobial resistance in A. baumannii. The in vitro resistance development assay revealed that the complete CRISPR-Cas system could inhibit the development of bacterial resistance. Our findings expand our understanding of the role of CRISPR-Cas csy1 gene in A. baumannii and link the CRISPR-Cas system to the biogenesis of bacterial drug-resistant structures.
Field Site-Specific Effects of an Azospirillum Seed Inoculant on Key Microbial Functional Groups in the Rhizosphere
Authors: Renoud Sébastien , Vacheron Jordan , Abrouk Danis , Prigent-Combaret Claire , Legendre Laurent , Muller Daniel , Moënne-Loccoz Yvan
Published: January 2022

The beneficial effects of plant growth–promoting Rhizobacteria (PGPR) entail several interaction mechanisms with the plant or with other root-associated microorganisms. These microbial functions are carried out by multiple taxa within functional groups and contribute to rhizosphere functioning. It is likely that the inoculation of additional PGPR cells will modify the ecology of these functional groups. We also hypothesized that the inoculation effects on functional groups are site specific, similarly as the PGPR phytostimulation effects themselves. To test this, we assessed in the rhizosphere of field-grown maize the effect of seed inoculation with the phytostimulatory PGPR Azospirillum lipoferum CRT1 on the size and/or diversity of selected microbial functional groups important for plant growth, using quantitative polymerase chain reaction and/or Illumina MiSeq metabarcoding. The functional groups included bacteria able to fix nitrogen (a key nutrient for plant growth), producers of 1-aminocyclopropane-1-carboxylate (ACC) deaminase (which modulate ethylene metabolism in plant and stimulate root growth), and producers of 2,4-diacetylphloroglucinol (an auxinic signal enhancing root branching). To test the hypothesis that such ecological effects were site-specific, the functional groups were monitored at three different field sites, with four sampling times over two consecutive years. Despite poor inoculant survival, inoculation enhanced maize growth. It also increased the size of functional groups in the three field sites, at the maize six-leaf and flowering stages for diazotrophs and only at flowering stage for ACC deaminase and 2,4-diacetylphloroglucinol producers. Sequencing done in the second year revealed that inoculation modified the composition of diazotrophs (and of the total bacterial community) and to a lesser extent of ACC deaminase producers. This study revealed an ecological impact that was field specific (even though a few taxa were impacted in all fields) and of unexpected magnitude with the phytostimulatory Azospirillum inoculant, when considering microbial functional groups. Further methodological developments are needed to monitor additional functional groups important for soil functioning and plant growth under optimal or stress conditions.
Effects of Multispecies Probiotic on Intestinal Microbiota and Mucosal Barrier Function of Neonatal Calves Infected With E. coli K99
Authors: Wu Yanyan , Nie Cunxi , Luo Ruiqing , Qi Fenghua , Bai Xue , Chen Hongli , Niu Junli , Chen Chen , Zhang Wenju
Published: January 2022

Altered gut microbiota are implicated in inflammatory neonatal calf diarrhea caused by E. coli K99. Beneficial probiotics are used to modulate gut microbiota. However, factors that mediate host-microbe interactions remain unclear. We evaluated the effects of a combination of multispecies probiotics (MSP) on growth, intestinal epithelial development, intestinal immune function and microbiota of neonatal calves infected with E. coli K99. Twelve newborn calves were randomly assigned as follows: C (control, without MSP); D (E. coli O78:K99 + gentamycin); and P (E. coli O78:K99 + supplemental MSP). All groups were studied for 21 d. MSP supplementation significantly (i) changed fungal Chao1 and Shannon indices of the intestine compared with group D; (ii) reduced the relative abundance of Bacteroides and Actinobacteria, while increasing Bifidobacteria, Ascomycetes, and Saccharomyces, compared with groups C and D; (iii) improved duodenal and jejunal mucosal SIgA and total Short Chain Fatty Acids (SCFA) concentrations compared with group D; (iv) increased relative ZO-1 and occludin mRNA expression in jejunal mucosa compared with group D; and (v) enhanced intestinal energy metabolism and defense mechanisms of calves by reducing HSP90 expression in E. coli K99, thereby alleviating the inflammatory response and promoting recovery of mucosal function. Our research may provide direct theoretical support for future applications of MSP in ruminant production.
Role of Extracellular Trap Release During Bacterial and Viral Infection
Authors: Schultz Bárbara M. , Acevedo Orlando A. , Kalergis Alexis M. , Bueno Susan M.
Published: January 2022

Neutrophils are innate immune cells that play an essential role during the clearance of pathogens that can release chromatin structures coated by several cytoplasmatic and granular antibacterial proteins, called neutrophil extracellular traps (NETs). These supra-molecular structures are produced to kill or immobilize several types of microorganisms, including bacteria and viruses. The contribution of the NET release process (or NETosis) to acute inflammation or the prevention of pathogen spreading depends on the specific microorganism involved in triggering this response. Furthermore, studies highlight the role of innate cells different from neutrophils in triggering the release of extracellular traps during bacterial infection. This review summarizes the contribution of NETs during bacterial and viral infections, explaining the molecular mechanisms involved in their formation and the relationship with different components of such pathogens.
Experimental Evolution Expands the Breadth of Adaptation to an Environmental Gradient Correlated With Genome Reduction
Authors: Kurokawa Masaomi , Nishimura Issei , Ying Bei-Wen
Published: January 2022

Whether and how adaptive evolution adjusts the breadth of adaptation in coordination with the genome are essential issues for connecting evolution with ecology. To address these questions, experimental evolution in five Escherichia coli strains carrying either the wild-type genome or a reduced genome was performed in a defined minimal medium (C0). The ancestral and evolved populations were subsequently subjected to fitness and chemical niche analyses across an environmental gradient with 29 combinations of eight chemical components of the minimal medium. The results showed that adaptation was achieved not only specific to the evolutionary condition (C0), but also generally, to the environmental gradient; that is, the breadth of adaptation to the eight chemical niches was expanded. The magnitudes of the adaptive improvement and the breadth increase were both correlated with genome reduction and were highly significant in two out of eight niches (i.e., glucose and sulfate). The direct adaptation-induced correlated adaptation to the environmental gradient was determined by only a few genome mutations. An additive increase in fitness associated with the stepwise fixation of mutations was consistently observed in the reduced genomes. In summary, this preliminary survey demonstrated that evolution finely tuned the breadth of adaptation correlated with genome reduction.
Endothelial Progenitor Cells and Vascular Alterations in Alzheimer’s Disease
Authors: Custodia Antía , Ouro Alberto , Romaus-Sanjurjo Daniel , Pías-Peleteiro Juan Manuel , de Vries Helga E. , Castillo José , Sobrino Tomás
Published: January 2022

Alzheimer’s disease (AD) is a neurodegenerative disease representing the most common type of dementia worldwide. The early diagnosis of AD is very difficult to achieve due to its complexity and the practically unknown etiology. Therefore, this is one of the greatest challenges in the field in order to develop an accurate therapy. Within the different etiological hypotheses proposed for AD, we will focus on the two-hit vascular hypothesis and vascular alterations occurring in the disease. According to this hypothesis, the accumulation of β-amyloid protein in the brain starts as a consequence of damage in the cerebral vasculature. Given that there are several vascular and angiogenic alterations in AD, and that endothelial progenitor cells (EPCs) play a key role in endothelial repair processes, the study of EPCs in AD may be relevant to the disease etiology and perhaps a biomarker and/or therapeutic target. This review focuses on the involvement of endothelial dysfunction in the onset and progression of AD with special emphasis on EPCs as a biomarker and potential therapeutic target.
Residual Renal Function – How Fast Does the Residual Urine Output Function Decline in the First Year of Haemodialysis? – A Scoping Review
Authors: Steinwandel Ulrich , Kheirkhah Homa , Davies Hugh
Published: January 2022

Background

Haemodialysis is the most common treatment method in Australia for individuals requiring renal replacement therapy. Although it is known that the residual renal function in these patients has many advantages for their overall health outcomes and that the residual urine volume production is also declining over time, it is unknown how fast this functional decline occurs when patients are embarking on their first year on haemodialysis.

Aim

This scoping review sought to determine if the functional decline in renal residual function in the first year of haemodialysis has been previously investigated, documented or quantified.

Method

The scoping review was performed using variety of nursing and medical databases comprising MEDLINE, Embase, Web of Science and CINAHL Plus with Full Text.

Results

The decline of renal residual function in patients on Peritoneal dialysis over the first year of treatment has previously been described, but not in detail for patients receiving haemodialysis. There is a paucity of knowledge how fast residual urine production can decline in patients receiving haemodialysis during their first year of treatment. A PRISMA checklist has been used to validate the results of this scoping review.

Conclusions

The extended preservation of renal residual function in patients on haemodialysis is crucial for their survival and may have a positive impact on their quality of life. An observational study is needed to examine how fast the functional decrease of the residual urine production function within patients receiving haemodialysis generally occurs. This information could prove to be useful in the context of treatment goals and could inform clinical practice.
Serum Vitamin D Levels Are Associated With Increased COVID-19 Severity and Mortality Independent of Whole-Body and Visceral Adiposity
Authors: Vanegas-Cedillo Pablo Esteban , Bello-Chavolla Omar Yaxmehen , Ramírez-Pedraza Natalia , Rodríguez Encinas Bethsabel , Pérez Carrión Carolina Isabel , Jasso-Ávila María Isabel , Valladares-García Jorge Carlos , Hernández-Juárez Diana , Vargas-Vázquez Arsenio , Antonio-Villa Neftali Eduardo , Chapa-Ibarguengoitia Monica , Ponce de Leon Alfredo , Sifuentes-Osornio José , Aguilar-Salinas Carlos A. , Mehta Roopa
Published: January 2022

Introduction

Coronavirus disease (COVID-19) is a global pandemic. Vitamin D deficiency has been associated with susceptibility to infectious disease. In this study, the association between COVID-19 outcomes and vitamin D levels in patients attending a COVID-19 reference center in Mexico City are examined.

Methods

Consecutive patients with confirmed COVID-19 were evaluated. All patients underwent clinical evaluation and follow-up, laboratory measurements and a thoracic computerized tomography, including the measurement of epicardial fat thickness. Low vitamin D was defined as levels <20 ng/ml (<50nmol/L) and deficient Vitamin D as a level ≤12 ng/ml (<30 nmol/L).

Results

Of the 551 patients included, low vitamin D levels were present in 45.6% and deficient levels in 10.9%. Deficient Vitamin D levels were associated with mortality (HR 2.11, 95%CI 1.24–3.58, p = 0.006) but not with critical COVID-19, adjusted for age, sex, body-mass index and epicardial fat. Using model-based causal mediation analyses the increased risk of COVID-19 mortality conferred by low vitamin D levels was partly mediated by its effect on D-dimer and cardiac ultrasensitive troponins. Notably, increased risk of COVID-19 mortality conferred by low vitamin D levels was independent of BMI and epicardial fat.

Conclusion

Vitamin D deficiency (≤12 ng/ml or <30 nmol/L), is independently associated with COVID-19 mortality after adjustment for visceral fat (epicardial fat thickness). Low vitamin D may contribute to a pro-inflammatory and pro-thrombotic state, increasing the risk for adverse COVID-19 outcomes.