bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic Accuracy of the HAS-BLED Bleeding Score in VKA- or DOAC-Treated Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis
Authors: Gao Xinxing , Cai Xingming , Yang Yunyao , Zhou Yue , Zhu Wengen
Published: November 2021

Background: Several bleeding risk assessment models have been developed in atrial fibrillation (AF) patients with oral anticoagulants, but the most appropriate tool for predicting bleeding remains uncertain. Therefore, we aimed to assess the diagnostic accuracy of the Hypertension, Abnormal liver/renal function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly, Drugs/alcohol concomitantly (HAS-BLED) score compared with other risk scores in anticoagulated patients with AF.

Methods: We comprehensively searched the PubMed and Embase databases until July 2021 to identify relevant pieces of literature. The predictive abilities of risk scores were fully assessed by the C-statistic, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) values, calibration data, and decision curve analyses.

Results: A total of 39 studies met the inclusion criteria. The C-statistic of the HAS-BLED score for predicting major bleeding was 0.63 (0.61–0.65) in anticoagulated patients regardless of vitamin k antagonists [0.63 (0.61–0.65)] and direct oral anticoagulants [0.63 (0.59–0.67)]. The HAS-BLED had the similar C-statistic to the Hepatic or renal disease, Ethanol abuse, Malignancy, Older, Reduced platelet count or function, Re-bleeding risk, Hypertension (uncontrolled), Anemia, Genetic factors, Excessive fall risk, Stroke (HEMORR2HAGES), the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA), the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT), the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF), or the Age, Biomarkers, Clinical History (ABC) scores, but significantly higher C-statistic than the Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke/transient ischemic attack history (CHADS2) or the Congestive heart failure/left ventricular ejection fraction ≤ 40%, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke/transient ischemic attack/thromboembolism history, Vascular disease, Age 65–74 years, Sex (female) (CHA2DS2-VASc) scores. NRI and IDI values suggested that the HAS-BLED score performed better than the CHADS2 or the CHA2DS2-VASc scores and had similar or superior predictive ability compared with the HEMORR2HAGES, the ATRIA, the ORBIT, or the GARFIELD-AF scores. Calibration and decision curve analyses of the HAS-BLED score compared with other scores required further assessment due to the limited evidence.

Conclusion: The HAS-BLED score has moderate predictive abilities for bleeding risks in patients with AF regardless of type of oral anticoagulants. Current evidence support that the HAS-BLED score is at least non-inferior to the HEMORR2HAGES, the ATRIA, the ORBIT, the GARFIELD-AF, the CHADS2, the CHA2DS2-VASc, or the ABC scores.
Prevalence of Healed Plaque and Factors Influencing Its Characteristics Under Optical Coherence Tomography in Patients With Coronary Artery Disease: A Systematic Review, Meta-Analysis, and Meta-Regression
Authors: Feng Xunxun , Liu Yang , Yang Jiaqi , Zhai Guangyao , Zhou Yujie , Guo Qianyun
Published: November 2021

Aim: The purpose of this study was to determine the prevalence of healed plaque and its characteristics under optical coherence tomography (OCT) through a formal systematic review, meta-analysis, and meta-regression.

Methods and Results: Thirteen studies were selected from MEDLINE, EMBASE, Cochrane, and online databases. The overall incidence of healed plaques was 40% (95% CI: 39–42), with 37% (95% CI: 35–39) in patients with acute coronary syndrome (ACS) and with 46% (95% CI: 43–49) in patients with stable angina pectoris (SAP). The incidence of healed plaque among culprit plaques (48%, 95% CI: 46–50) was nearly two times higher than that among non-culprit plaques (24%, 95% CI: 21–27). The incidence of thin cap fibroatheroma (TCFA), plaque rupture, microvessel, macrophage accumulation, and calcification was significantly higher in the healed plaque group. Meta-regression revealed an association between smoking (P = 0.033) and healed plaque rupture. Gender (P = 0.047) was independently associated with macrophage accumulation, and mean low-density lipoprotein cholesterol (LDL-C) was independently associated with microvessel.

Conclusions: In summary, with a total incidence of 40%, the incidence of healed plaques under OCT was higher in SAP than in ACS, and higher in culprit plaques than in non-culprit plaques. Higher incidence of TCFA, plaque rupture, microvessel, macrophage accumulation, and calcification was found in the healed-plaque group. Smoking, gender, and mean LDL-C level were associated with healed-plaque characteristics.
Numerical and Experimental Analysis of Influence of Impeller Structures on Slurry Pump Performance
Authors: Peng Guangjie , Du Jialin , Chang Hao , Chen Qiang , Li Jiahu , Pan Chengxiang , Yang Yongfei
Published: November 2021

Slurry pump as an important equipment for transporting coal, which are widely used in power plants, mines and other fossil energy field. Therefore, the improvement of slurry pump performance can effectively reduce the energy loss of fossil energy industry. In this paper, a novel impeller with splitter blade structure was proposed, and the internal flow field of slurry pumps with different impeller structures was analyzed. Meanwhile, according to the shape and structure of the vortex in slurry pump, the vortex can be divided into leading edge vortex, trailing edge vortex and gap leakage vortex by employing the Q criterion, and the generation mechanism of each vortex and relationship between vortex strength and flow condition were analyzed. What is more, the entropy generation theory was employed to study the energy loss of slurry pump. The pressure distribution and wear characteristics of different impeller structures under two-phase flow conditions are studied. The result shows that the energy loss caused by entropy production in the slurry pump can be declined by employing the splitter blades, which can restrain the flow separation at the impeller outlet. Thus, the impeller with splitter blades not only can reduce the energy loss of the slurry pump, but also enhance the wear characteristics of impeller under two-phase flow conditions. Finally, the result can provide the guidelines for the design optimization of slurry pump.
Quasi-Unidirectional Transport Bilayer Two-Dimensional Nanopores for Highly-Efficient Molecular Sieving
Authors: Sun Chengzhen , Liu Cheng , Luo Kailin , Bai Bofeng
Published: November 2021

Two-dimensional nanopores are very promising for high-permeance molecular sieving, but the molecular backflow from permeate-side to feed-side is not beneficial for improving molecular permeance. We study the quasi-unidirectional molecular transport through a graphene-hexagonal boron nitride bilayer nanopore, aiming to realize a high-permeance molecular sieving. Molecular dynamics simulations of CO2/CH4 separations show that the bilayer pore presents 3.7 times higher selectivity comparing to the single-layer graphene nanopore with the same size. The quasi-unidirectional molecular transport is attributed to the distinctive adsorption abilities of gas molecules on the two sides of bilayer nanopores and the inhibited molecular backflow from permeate-side to feed-side. This work provides a promising way to realize the ultra-permeable porous membranes with molecular permeance even higher than the single-layer atomic-thickness membranes.
Spatio-Temporal Evolution and Correlation Analysis of Urban Land Use Patterns and Air Quality in Pearl River Delta, China
Authors: Hong Kai-rong , Qiu Lin-shu , Yang Dong-xiao , Jiang Minxing
Published: November 2021

Urban air quality, which is related to the health of local residents of the Pearl River Delta Region, China, (PRD) has been a hot topic among the masses and academic circles. In addition to economic growth, China’s rapidly increasing urbanization rate has also brought great pressure on urban air quality, in the Region, where due to its huge economic size and population, urban air quality has become the focus of local residents. This study first analyzed the spatio-temporal trends and correlation of land use and PM2.5 average annual concentration, which represents air quality in the PRD from 2000 to 2018, and according to Moran index, PM2.5 concentration in this area has spatial correlation in the study time. Secondly, the spatial error model of the PRD was constructed by using spatial effect, spatial modeling theory and spatial model estimation. The spatial-temporal evolution and influencing factors of PM2.5 concentration were discussed in fixed overall effect. The results showed that the area of cultivated land in the PRD decreased and the area of artificial surface increased year by year, while the PM2.5 concentration increased first and then decreased. In addition, the area of cultivated land and forestland were negatively correlated, while the area of grassland and water body were positively correlated with PM2.5 concentration. The conclusion of this study has a certain theoretical reference for urban land use planning and air quality assurance.
Estimation of Genetic Parameters of Type Traits in First Parity Cows of the Autochthonous Cika Cattle in Slovenia
Authors: Simčič Mojca , Luštrek Barbara , Štepec Miran , Logar Betka , Potočnik Klemen
Published: November 2021

The aim of this study was to estimate genetic parameters of 26 individual and four composite type traits in first parity Cika cows. An analysis of variance was performed with the generalized linear model procedure of the SAS/STAT statistical package, where the fixed effects of year of recording, cow’s age at recording and days after calving as a linear regression were included in the model. The variance components for the direct additive genetic effect and the herd effect in all type traits were estimated using the REML method in the VCE-6 software package. The estimated heritabilities ranged from 0.42 to 0.67 for the measured body frame traits, from 0.36 to 0.80 for the scored autochthonous traits, from 0.11 to 0.61 for the scored body frame traits, and from 0.20 to 0.47 for the scored udder traits. The estimated heritabilities for the composite traits called “autochthonous characteristics”, “muscularity”, “body frame” and “udder” were 0.55, 0.19, 0.19, and 0.26, respectively. The estimated genetic correlations among the measured body frame traits were positive and high, while the majority of them among the scored body frame traits were low to moderate. The estimated proportions of variance explained by the herd effect for the composite traits “autochthonous characteristics,” “muscularity,” “body frame” and “udder” were 0.09, 0.28, 0.14, and 0.10, respectively. The estimated heritabilities for the type traits of first parity Cika cows were similar to those reported for other breeds where breeding values have been routinely predicted for a long time. All estimated genetic parameters are already used for breeding value prediction in the Cika cattle population.
A Mutation-Related Long Noncoding RNA Signature of Genome Instability Predicts Immune Infiltration and Hepatocellular Carcinoma Prognosis
Authors: Wu Jianhua , Ren Xueting , Wang Nan , Zhou Ruina , Chen Mengsha , Cai Yifan , Lin Shuai , Zhang Hao , Xie Xin , Dang Chengxue , Zhang Shuqun , Zhou Zhangjian
Published: November 2021

Background: Long noncoding RNAs (lncRNAs) have been discovered to play a regulatory role in genomic instability (GI), which participates in the carcinogenesis of various cancers, including hepatocellular carcinoma (HCC). We endeavored to establish a GI-derived lncRNA signature (GILncSig) as a potential biomarker and explore its impact on immune infiltration and prognostic significance.

Methods: Combining expression and somatic mutation profiles from The Cancer Genome Atlas database, we identified GI-related lncRNAs and conducted functional analyses on co-expressed genes. Based on Cox regression analysis, a GILncSig was established in the training cohort (n = 187), and an independent testing patient cohort (n = 183) was used to validate its predictive ability. Kaplan-Meier method and receiver operating characteristic curves were adopted to evaluate the performance. The correlation between GI and immune infiltration status was investigated based on the CIBERSORT algorithm and single sample gene set enrichment analysis. In addition, a comprehensive nomogram integrating the GILncSig and clinicopathological variables was constructed to efficiently assess HCC patient prognosis in clinical applications.

Results: A total of 88 GI-related lncRNAs were screened out and the functional analyses indicated diversified effects on HCC progression. The GILncSig was established using four independent lncRNAs (AC116351.1, ZFPM2-AS1, AC145343.1, and MIR210HG) with significant prognostic value (p < 0.05). Following evaluation with the GILncSig, low-risk patients had significantly better clinical outcomes than high-risk patients in the training cohort (p < 0.001), which was subsequently validated in the independent testing cohort. High-risk group exhibited more immunocyte infiltration including B cells memory, macrophages M0 and neutrophils and higher expression of HLA gene set and immune checkpoint genes. Compared to existing HCC signatures, the GILncSig showed better prognosis predictive performance [area under the curve (AUC) = 0.709]. Furthermore, an integrated nomogram was constructed and validated to efficiently and reliably evaluate HCC patient prognosis (3-years survival AUC = 0.710 and 5-years survival AUC = 0.707).

Conclusion: The GILncSig measuring GI and impacting immune infiltration serves as a potential biomarker and independent predictor of HCC patient prognosis. Our results highlight further investigation of GI and HCC molecular mechanisms.
The Role of GM-CSF Autoantibodies in Infection and Autoimmune Pulmonary Alveolar Proteinosis: A Concise Review
Authors: Ataya Ali , Knight Vijaya , Carey Brenna C. , Lee Elinor , Tarling Elizabeth J. , Wang Tisha
Published: November 2021

Autoantibodies to multiple cytokines have been identified and some, including antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), have been associated with increased susceptibility to infection. High levels of GM-CSF autoantibodies that neutralize signaling cause autoimmune pulmonary alveolar proteinosis (aPAP), an ultrarare autoimmune disease characterized by accumulation of excess surfactant in the alveoli, leading to pulmonary insufficiency. Defective GM-CSF signaling leads to functional deficits in multiple cell types, including macrophages and neutrophils, with impaired phagocytosis and host immune responses against pulmonary and systemic infections. In this article, we review the role of GM-CSF in aPAP pathogenesis and pulmonary homeostasis along with the increased incidence of infections (particularly opportunistic infections). Therefore, recombinant human GM-CSF products may have potential for treatment of aPAP and possibly other infectious and pulmonary diseases due to its pleotropic immunomodulatory actions.
Reactive Oxygen Species: Do They Play a Role in Adaptive Immunity?
Authors: Bassoy Esen Yonca , Walch Michael , Martinvalet Denis
Published: November 2021

The immune system protects the host from a plethora of microorganisms and toxins through its unique ability to distinguish self from non-self. To perform this delicate but essential task, the immune system relies on two lines of defense. The innate immune system, which is by nature fast acting, represents the first line of defense. It involves anatomical barriers, physiological factors as well as a subset of haematopoietically-derived cells generically call leukocytes. Activation of the innate immune response leads to a state of inflammation that serves to both warn about and combat the ongoing infection and delivers the antigenic information of the invading pathogens to initiate the slower but highly potent and specific second line of defense, the adaptive immune system. The adaptive immune response calls on T lymphocytes as well as the B lymphocytes essential for the elimination of pathogens and the establishment of the immunological memory. Reactive oxygen species (ROS) have been implicated in many aspects of the immune responses to pathogens, mostly in innate immune functions, such as the respiratory burst and inflammasome activation. Here in this mini review, we focus on the role of ROS in adaptive immunity. We examine how ROS contribute to T-cell biology and discuss whether this activity can be extrapolated to B cells.
CD247, a Potential T Cell–Derived Disease Severity and Prognostic Biomarker in Patients With Idiopathic Pulmonary Fibrosis
Authors: Li Yupeng , Chen Shibin , Li Xincheng , Wang Xue , Li Huiwen , Ning Shangwei , Chen Hong
Published: November 2021

Background

Idiopathic pulmonary fibrosis (IPF) has high mortality worldwide. The CD247 molecule (CD247, as known as T-cell surface glycoprotein CD3 zeta chain) has been reported as a susceptibility locus in systemic sclerosis, but its correlation with IPF remains unclear.

Methods

Datasets were acquired by researching the Gene Expression Omnibus (GEO). CD247 was identified as the hub gene associated with percent predicted diffusion capacity of the lung for carbon monoxide (Dlco% predicted) and prognosis according to Pearson correlation, logistic regression, and survival analysis.

Results

CD247 is significantly downregulated in patients with IPF compared with controls in both blood and lung tissue samples. Moreover, CD247 is significantly positively associated with Dlco% predicted in blood and lung tissue samples. Patients with low-expression CD247 had shorter transplant-free survival (TFS) time and more composite end-point events (CEP, death, or decline in FVC >10% over a 6-month period) compared with patients with high-expression CD247 (blood). Moreover, in the follow-up 1st, 3rd, 6th, and 12th months, low expression of CD247 was still the risk factor of CEP in the GSE93606 dataset (blood). Thirteen genes were found to interact with CD247 according to the protein–protein interaction network, and the 14 genes including CD247 were associated with the functions of T cells and natural killer (NK) cells such as PD-L1 expression and PD-1 checkpoint pathway and NK cell-mediated cytotoxicity. Furthermore, we also found that a low expression of CD247 might be associated with a lower activity of TIL (tumor-infiltrating lymphocytes), checkpoint, and cytolytic activity and a higher activity of macrophages and neutrophils.

Conclusion

These results imply that CD247 may be a potential T cell-derived disease severity and prognostic biomarker for IPF.
Exposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines
Authors: Zuiderwijk-Sick Ella A. , van der Putten Céline , Timmerman Raissa , Veth Jennifer , Pasini Erica M. , van Straalen Linda , van der Valk Paul , Amor Sandra , Bajramovic Jeffrey J.
Published: November 2021

Interleukin (IL)-4 is a cytokine that affects both adaptive and innate immune responses. In the central nervous system, microglia express IL-4 receptors and it has been described that IL-4-exposed microglia acquire anti-inflammatory properties. We here demonstrate that IL-4 exposure induces changes in the cell surface protein expression profile of primary rhesus macaque microglia and enhances their potential to induce proliferation of T cells with a regulatory signature. Moreover, we show that Toll like receptor (TLR)-induced cytokine production is broadly impaired in IL-4-exposed microglia at the transcriptional level. IL-4 type 2 receptor-mediated signaling is shown to be crucial for the inhibition of microglial innate immune responses. TLR-induced nuclear translocalization of NF-κB appeared intact, and we found no evidence for epigenetic modulation of target genes. By contrast, nuclear extracts from IL-4-exposed microglia contained significantly less NF-κB capable of binding to its DNA consensus site. Further identification of the molecular mechanisms that underlie the inhibition of TLR-induced responses in IL-4-exposed microglia may aid the design of strategies that aim to modulate innate immune responses in the brain, for example in gliomas.
Intrinsic and Wind-Driven Decadal Variability of the Kuroshio Extension in Altimeter Observations
Authors: Zhou Guidi , Li Zhuhua , Cheng Xuhua
Published: November 2021

In this work we use satellite altimeter observations to study the mechanism of decadal variability of the Kuroshio Extension (KE), with special attention on jet-eddy energy transfer, and on the relationship between the wind-driven sea surface height anomalies (SSHAs) and those directly driven by intrinsic oceanic processes including jet and eddies. It is shown that energy feedback between the jet and mesoscale eddies can maintain the decadal oscillation of the KE. The wind-driven SSHAs are broad-scale and very weak compared to the intrinsic variability. Physically they can potentially trigger delayed responses of the latter by modulating vorticity advection from upstream but the statistical significance is low. KE perturbations resulting from the intrinsic variability, on the other hand, could feedback onto the wind-driven SSHAs by inducing anomalous basin-scale wind stress. The KE jet is thus an integrated system involving the jet and the eddies, possibly feeding back to, and paced by, wind stress anomalies.
Short 2-[18F]Fluoro-2-Deoxy-D-Glucose PET Dynamic Acquisition Protocol to Evaluate the Influx Rate Constant by Regional Patlak Graphical Analysis in Patients With Non-Small-Cell Lung Cancer
Authors: Indovina Luca , Scolozzi Valentina , Capotosti Amedeo , Sestini Stelvio , Taralli Silvia , Cusumano Davide , Giancipoli Romina Grazia , Ciasca Gabriele , Cardillo Giuseppe , Calcagni Maria Lucia
Published: November 2021

Purpose: To test a short 2-[18F]Fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET dynamic acquisition protocol to calculate Ki using regional Patlak graphical analysis in patients with non-small-cell lung cancer (NSCLC).

Methods: 24 patients with NSCLC who underwent standard dynamic 2-[18F]FDG acquisitions (60 min) were randomly divided into two groups. In group 1 (n = 10), a population-based image-derived input function (pIDIF) was built using a monoexponential trend (10–60 min), and a leave-one-out cross-validation (LOOCV) method was performed to validate the pIDIF model. In group 2 (n = 14), Ki was obtained by standard regional Patlak plot analysis using IDIF (0–60 min) and tissue response (10–60 min) curves from the volume of interests (VOIs) placed on descending thoracic aorta and tumor tissue, respectively. Moreover, with our method, the Patlak analysis was performed to obtain Ki,s using IDIFFitted curve obtained from PET counts (0–10 min) followed by monoexponential coefficients of pIDIF (10–60 min) and tissue response curve obtained from PET counts at 10 min and between 40 and 60 min, simulating two short dynamic acquisitions. Both IDIF and IDIFFitted curves were modeled to assume the value of 2-[18F]FDG plasma activity measured in the venous blood sampling performed at 45 min in each patient. Spearman's rank correlation, coefficient of determination, and Passing–Bablok regression were used for the comparison between Ki and Ki,s. Finally, Ki,s was obtained with our method in a separate group of patients (group 3, n = 8) that perform two short dynamic acquisitions.

Results: Population-based image-derived input function (10–60 min) was modeled with a monoexponential curve with the following fitted parameters obtained in group 1: a = 9.684, b = 16.410, and c = 0.068 min−1. The LOOCV error was 0.4%. In patients of group 2, the mean values of Ki and Ki,s were 0.0442 ± 0.0302 and 0.33 ± 0.0298, respectively (R2 = 0.9970). The Passing–Bablok regression for comparison between Ki and Ki,s showed a slope of 0.992 (95% CI: 0.94–1.06) and intercept value of −0.0003 (95% CI: −0.0033–0.0011).

Conclusions: Despite several practical limitations, like the need to position the patient twice and to perform two CT scans, our method contemplates two short 2-[18F]FDG dynamic acquisitions, a population-based input function model, and a late venous blood sample to obtain robust and personalized input function and tissue response curves and to provide reliable regional Ki estimation.
Comparative Efficacy and Safety of Four Different Spontaneous Breathing Trials for Weaning From Mechanical Ventilation: A Systematic Review and Network Meta-Analysis
Authors: Yi Li-Juan , Tian Xu , Chen Min , Lei Jin-Mei , Xiao Na , Jiménez-Herrera Maria F.
Published: November 2021

Background: Spontaneous breathing trial (SBT) has been used to predict the optimal time of weaning from ventilator. However, it remains controversial which trial should be preferentially selected. We aimed to compare and rank four common SBT modes including automatic tube compensation (ATC), pressure support ventilation (PSV), continuous positive airway pressure (CPAP), and T-piece among critically ill patients receiving mechanical ventilation (MV).

Methods: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify studies that investigated the comparative efficacy and safety of at least two SBT strategies among critically ill patients up to May 17, 2020. We estimated the surface under the cumulative ranking curve (SUCRA) to rank SBT techniques, and determined the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation method. Primary outcome was weaning success. Secondary outcomes were reintubation, SBT success, duration of acute care, and intensive care unit (ICU) mortality. Statistical analysis was conducted by using RevMan 5.4, Stata, and R software.

Results: We enrolled 24 trials finally. Extubation success rate was significantly higher in ATC than that in T-piece (OR, 0.28; 95% CI, 0.13–0.64) or PSV (OR, 0.53; 95% CI, 0.32–0.88). For SBT success, ATC was better than other SBT techniques, with a pooled OR ranging from 0.17 to 0.42. For reintubation rate, CPAP was worse than T-piece (OR, 2.76; 95% CI, 1.08 to 7.06). No significant difference was detected between SBT modes for the length of stay in ICU or long-term weaning unit (LWU). Similar result was also found for ICU mortality between PSV and T-piece. Majority direct results were confirmed by network meta-analysis. Besides, ATC ranks at the first, first, and fourth place with a SUCRA of 91.7, 99.7, and 39.9%, respectively in increasing weaning success and SBT success and in prolonging ICU or LWU length of stay among four SBT strategies. The confidences in evidences were rated as low for most comparisons.

Conclusion: ATC seems to be the optimal choice of predicting successful weaning from ventilator among critically ill patients. However, randomized controlled trials (RCTs) with high quality are needed to further establish these findings.
Case Report: Infantile Bullous Pemphigoid: Triggering by COVID-19 Is Speculative
Authors: Rosińska-Więckowicz Anna , Jałowska Magdalena , Bowszyc-Dmochowska Monika , Dmochowski Marian
Published: November 2021

Bullous pemphigoid (BP) is a cutaneous disease triggered by numerous stimuli, where genetic milieu-influenced autoimmunity to hemidesmosomal proteins, namely, BP180 and/or BP230 initiate an inflammation leading to dermal-epidermal junction (DEJ) enzymatic pathological remodelling. Here, to the best of our knowledge, we present the first case of an infantile BP apparently triggered by COVID-19. BP should be included in differential diagnosis of infantile rashes showing blisters or vesicles or both as well as their prodromal and evolutionary lesions. Possible triggers, such as coronavirus disease 2019 (COVID-19), of BP in infancy should be identified and properly dealt with.
Clinical Risk Score for Invasive Pulmonary Aspergillosis in Patients With Liver Failure: A Retrospective Study in Zhejiang
Authors: Zhang Xuan , Shen Sijia , Dai Xiahong , Bi Yunjiao , Zhang Junjie , Wu Yuhao , Shi Yishang , Wei Runan , Gao Hainv
Published: November 2021

Purpose: The mortality of invasive pulmonary aspergillosis (IPA) in patients with liver failure was high. However, the prophylactic treatment in those patients with a high-risk factor in IPA has not been researched.

Patients and methods: A multicenter, retrospective study was conducted in patients with liver failure. The study cohort of liver failure was randomly split into a training set for model development and the other served as the testing set for model verification. Multivariate analysis was performed to identify the risk factors of IPA. A weighted risk score for IPA was established. Anti-fungal treatment was prophylactically used in patients with medium and high IPA risk to evaluate the effect.

Results: In total, 1,722 patients with liver failure were enrolled. Fifty-seven patients who received prophylactic treatment were excluded from the risk factor system study. About 1,665 patients were randomly split at a ratio of 2:1 into two datasets. Diabetes, glucocorticoids, plasma exchange, and hepatorenal syndrome (HRS) were risk factors in IPA in patients with liver failure, with weighted risk scores of 4, 7, 2, and 3, respectively. In the validation set and test set, the patients with risk scores of ≤ 3 presented low incidences of IPA at 4 and 2.7%. Patients with risk scores of 4–5 had an IPA incidence of 7.6% and 10.1%, and could be considered as a medium-risk group (p < 0.01 vs. the group with scores of ≤ 3), whereas those with risk scores of >5 manifested a significantly higher IPA incidence of 21.2 and 12.7%, who were considered a high-risk group (p < 0.01 vs. the groups with scores of 4–5 and >5, respectively). The IPA risk scores in the training set and the testing set were also analyzed by the ROC with an area under the ROC of 0.7152 and 0.6912. In this study, 57 patients received antifungal prophylaxis; the incidence of IPA was 1.8%, which was significantly lower after prophylactic antifungal therapy (p < 0.001).

Conclusions: A weighted risk score for patients with liver failure, complicated with IPA, was established and confirmed in the testing cohort. Voriconazole prophylactic treatment to patients with liver failure with medium and high IPA risk can effectively prevent Aspergillus infection.
Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates—Chennai, India, 2013–2016
Authors: Tamilzhalagan Sembulingam , Shanmugam Sivakumar , Selvaraj Ashok , Suba Sakthi , Suganthi Chittibabu , Moonan Patrick K. , Surie Diya , Sathyanarayanan Mukesh Kumar , Gomathi Narayanan Shivaram , Jayabal Lavanya , Sachdeva Kuldeep Singh , Selvaraju Sriram , Swaminathan Soumya , Tripathy Srikanth Prasad , Hall Patricia J. , Ranganathan Uma Devi
Published: November 2021

India has a high burden of drug-resistant tuberculosis (DR TB) and many cases go undetected by current drug susceptibility tests (DSTs). This study was conducted to identify rifampicin (RIF) and isoniazid (INH) resistance associated genetic mutations undetected by current clinical diagnostics amongst persons with DR TB in Chennai, India. Retrospectively stored 166 DR TB isolates during 2013–2016 were retrieved and cultured in Löwenstein-Jensen medium. Whole genome sequencing (WGS) and MGIT DST for RIF and INH were performed. Discordant genotypic and phenotypic sensitivity results were repeated for confirmation and the discrepant results considered final. Further, drug resistance-conferring mutations identified through WGS were analyzed for their presence as targets in current WHO-recommended molecular diagnostics. WGS detected additional mutations for rifampicin and isoniazid resistance than WHO-endorsed line probe assays. For RIF, WGS was able to identify an additional 10% (15/146) of rpoB mutant isolates associated with borderline rifampicin resistance compared to MGIT DST. WGS could detect additional DR TB cases than commercially available and WHO-endorsed molecular DST tests. WGS results reiterate the importance of the recent WHO revised critical concentrations of current MGIT DST to detect low-level resistance to rifampicin. WGS may help inform effective treatment selection for persons at risk of, or diagnosed with, DR TB.
Effects of Phytic Acid-Degrading Bacteria on Mineral Element Content in Mice
Authors: Zhou Diao , Zhao Ying , Li Jing , Ravichandran Vinothkannan , Wang Leli , Huang Qiuyun , Chen Cang , Ni Hengjia , Yin Jia
Published: November 2021

Trace minerals are extremely important for balanced nutrition, growth, and development in animals and humans. Phytic acid chelation promotes the use of probiotics in nutrition. The phytic acid-degrading strain Lactococcus lactis psm16 was obtained from swine milk by enrichment culture and direct plate methods. In this study, we evaluated the effect of the strain psm16 on mineral element content in a mouse model. Mice were divided into four groups: basal diet, 1% phytic acid, 1% phytic acid + psm16, 1% phytic acid + 500 U/kg commercial phytase. Concentrations of acetic acid, propionic acid, butyric acid, and total short-chain fatty acids were significantly increased in the strain psm16 group compared to the phytic acid group. The concentrations of copper (p = 0.021) and zinc (p = 0.017) in liver, calcium (p = 0.000), manganese (p = 0.000), and zinc (p = 0.000) in plasma and manganese (p = 0.010) and zinc (p = 0.022) in kidney were significantly increased in psm16 group, while copper (p = 0.007) and magnesium (p = 0.001) were significantly reduced. In conclusion, the addition of phytic acid-degrading bacteria psm16 into a diet including phytic acid can affect the content of trace elements in the liver, kidney, and plasma of mice, counteracting the harmful effects of phytic acid.
The Relationship of Malnutrition With Cognitive Function in the Older Chinese Population: Evidence From the Chinese Longitudinal Healthy Longevity Survey Study
Authors: Sun Boran , Zhao Yihao , Lu Wenli , Chen Yongjie
Published: November 2021

Background and Objective: Few studies have explored the relationship between malnutrition measured by the Geriatric Nutritional Risk Index (GNRI) and cognitive performance. This study aimed to investigate the association of malnutrition with cognitive function in the Chinese population.

Methods: It was a prospective longitudinal study and used three waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) data in 2011–2012, 2014, and 2017–2018. Participants aged 60 years or older without mental illness and cerebrovascular diseases were eligible. The GNRI was used to assess nutritional status as follows: normal nutrition (a GNRI > 98), mild malnutrition (92 ≤ a GNRI ≤ 98), and moderate-to-severe malnutrition (a GNRI < 92). Cognitive performance was evaluated by the Mini-Mental State Examination (MMSE) scores. The relationship between the GNRI and cognitive function was analyzed using a linear mixed-effects model.

Results: A total of 1,632 subjects were analyzed, including 741 males and 891 females. Of these, 65.0, 19.4, and 15.6% of subjects were at normal nutritional status, mild, and moderate-to-severe malnutrition, respectively. After adjusting for potential confounders, participants under mild and moderate-to-severe malnutrition status have a lower MMSE score [β (95% CI): –0.95 (–1.60, –0.25) and –1.39 (–2.21, –0.57), respectively], compared with those having normal nutrition. Also, there was a linear trend in the association of malnutrition risk with cognitive function in the total population [β (95% CI): –0.74 (–1.13, –0.35)]. However, a significant association of malnutrition with cognitive function was observed only among illiterate females aged above 90 years.

Conclusion: This study suggested that there was a significant relationship between the GNRI and cognitive function in the Chinese elderly. Furthermore, subjects with more serious malnutrition have a worse cognitive function, especially in the oldest illiterate females. Clinicians should put more emphasis on assessing the nutritional and cognitive status of the elderly to timely intervene and prevent cognitive impairment.
Genetic Variants of Fatty Acid Amide Hydrolase Modulate Acute Inflammatory Responses to Colitis in Adult Male Mice
Authors: Vecchiarelli Haley A. , Aukema Robert J. , Hume Catherine , Chiang Vincent , Morena Maria , Keenan Catherine M. , Nastase Andrei S. , Lee Francis S. , Pittman Quentin J. , Sharkey Keith A. , Hill Matthew N.
Published: November 2021

Cannabinoids, includingcannabisderived phytocannabinoids and endogenous cannabinoids (endocannabinoids), are typically considered anti-inflammatory. One such endocannabinoid isN-arachidonoylethanolamine (anandamide, AEA), which is metabolized by fatty acid amide hydrolase (FAAH). In humans, there is a loss of function single nucleotide polymorphism (SNP) in the FAAH gene (C385A, rs324420), that leads to increases in the levels of AEA. Using a mouse model with this SNP, we investigated how this SNP affects inflammation in a model of inflammatory bowel disease. We administered 2,4,6-trinitrobenzene sulfonic acid (TNBS) intracolonically, to adult male FAAH SNP mice and examined colonic macroscopic tissue damage and myeloperoxidase activity, as well as levels of plasma and amygdalar cytokines and chemokines 3 days after administration, at the peak of colitis. We found that mice possessing the loss of function alleles (AC and AA), displayed no differences in colonic damage or myeloperoxidase activity compared to mice with wild type alleles (CC). In contrast, in plasma, colitis-induced increases in interleukin (IL)-2, leukemia inhibitory factor (LIF), monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF) were reduced in animals with an A allele. A similar pattern was observed in the amygdala for granulocyte colony stimulating factor (G-CSF) and MCP-1. In the amygdala, the mutant A allele led to lower levels of IL-1α, IL-9, macrophage inflammatory protein (MIP)-1β, and MIP-2 independent of colitis—providing additional understanding of how FAAH may serve as a regulator of inflammatory responses in the brain. Together, these data provide insights into how FAAH regulates inflammatory processes in disease.
Gradient Decomposition Methods for Training Neural Networks With Non-ideal Synaptic Devices
Authors: Zhao Junyun , Huang Siyuan , Yousuf Osama , Gao Yutong , Hoskins Brian D. , Adam Gina C.
Published: November 2021

While promising for high-capacity machine learning accelerators, memristor devices have non-idealities that prevent software-equivalent accuracies when used for online training. This work uses a combination of Mini-Batch Gradient Descent (MBGD) to average gradients, stochastic rounding to avoid vanishing weight updates, and decomposition methods to keep the memory overhead low during mini-batch training. Since the weight update has to be transferred to the memristor matrices efficiently, we also investigate the impact of reconstructing the gradient matrixes both internally (rank-seq) and externally (rank-sum) to the memristor array. Our results show that streaming batch principal component analysis (streaming batch PCA) and non-negative matrix factorization (NMF) decomposition algorithms can achieve near MBGD accuracy in a memristor-based multi-layer perceptron trained on the MNIST (Modified National Institute of Standards and Technology) database with only 3 to 10 ranks at significant memory savings. Moreover, NMF rank-seq outperforms streaming batch PCA rank-seq at low-ranks making it more suitable for hardware implementation in future memristor-based accelerators.
Ultrastructural Analysis of Neuroimplant-Parenchyma Interfaces Uncover Remarkable Neuroregeneration Along-With Barriers That Limit the Implant Electrophysiological Functions
Authors: Sharon Aviv , Shmoel Nava , Erez Hadas , Jankowski Maciej M. , Friedmann Yael , Spira Micha E.
Published: November 2021

Despite increasing use of in vivo multielectrode array (MEA) implants for basic research and medical applications, the critical structural interfaces formed between the implants and the brain parenchyma, remain elusive. Prevailing view assumes that formation of multicellular inflammatory encapsulating-scar around the implants [the foreign body response (FBR)] degrades the implant electrophysiological functions. Using gold mushroom shaped microelectrodes (gMμEs) based perforated polyimide MEA platforms (PPMPs) that in contrast to standard probes can be thin sectioned along with the interfacing parenchyma; we examined here for the first time the interfaces formed between brains parenchyma and implanted 3D vertical microelectrode platforms at the ultrastructural level. Our study demonstrates remarkable regenerative processes including neuritogenesis, axon myelination, synapse formation and capillaries regrowth in contact and around the implant. In parallel, we document that individual microglia adhere tightly and engulf the gMμEs. Modeling of the formed microglia-electrode junctions suggest that this configuration suffice to account for the low and deteriorating recording qualities of in vivo MEA implants. These observations help define the anticipated hurdles to adapting the advantageous 3D in vitro vertical-electrode technologies to in vivo settings, and suggest that improving the recording qualities and durability of planar or 3D in vivo electrode implants will require developing approaches to eliminate the insulating microglia junctions.
Nr4a2 Transcription Factor in Hippocampal Synaptic Plasticity, Memory and Cognitive Dysfunction: A Perspective Review
Authors: Català-Solsona Judit , Miñano-Molina Alfredo J. , Rodríguez-Álvarez José
Published: November 2021

Long-lasting changes of synaptic efficacy are largely mediated by activity-induced gene transcription and are essential for neuronal plasticity and memory. In this scenario, transcription factors have emerged as pivotal players underlying synaptic plasticity and the modification of neural networks required for memory formation and consolidation. Hippocampal synaptic dysfunction is widely accepted to underlie the cognitive decline observed in some neurodegenerative disorders including Alzheimer’s disease. Therefore, understanding the molecular pathways regulating gene expression profiles may help to identify new synaptic therapeutic targets. The nuclear receptor 4A subfamily (Nr4a) of transcription factors has been involved in a variety of physiological processes within the hippocampus, ranging from inflammation to neuroprotection. Recent studies have also pointed out a role for the activity-dependent nuclear receptor subfamily 4, group A, member 2 (Nr4a2/Nurr1) in hippocampal synaptic plasticity and cognitive functions, although the underlying molecular mechanisms are still poorly understood. In this review, we highlight the specific effects of Nr4a2 in hippocampal synaptic plasticity and memory formation and we discuss whether the dysregulation of this transcription factor could contribute to hippocampal synaptic dysfunction, altogether suggesting the possibility that Nr4a2 may emerge as a novel synaptic therapeutic target in brain pathologies associated to cognitive dysfunctions.
Dietary Strategies to Improve Cardiovascular Health: Focus on Increasing High-Density Lipoprotein Functionality
Authors: Stadler Julia T. , Marsche Gunther
Published: November 2021

Cardiovascular disease is one of the leading causes of morbidity and mortality worldwide, with increasing incidence. A cornerstone of cardiovascular disease prevention is lifestyle modification through dietary changes to influence various risk factors such as obesity, hypertension and diabetes. The effects of diet on cardiovascular health are complex. Some dietary components and metabolites directly affect the composition and structure of high-density lipoproteins (HDL) and increase anti-inflammatory and vasoprotective properties. HDLs are composed of distinct subpopulations of particles of varying size and composition that have several dynamic and context-dependent functions. The identification of potential dietary components that improve HDL functionality is currently an important research goal. One of the best-studied diets for cardiovascular health is the Mediterranean diet, consisting of fish, olive oil, fruits, vegetables, whole grains, legumes/nuts, and moderate consumption of alcohol, most commonly red wine. The Mediterranean diet, especially when supplemented with extra virgin olive oil rich in phenolic compounds, has been shown to markedly improve metrics of HDL functionality and reduce the burden, or even prevent the development of cardiovascular disease. Particularly, the phenolic compounds of extra virgin olive oil seem to exert the significant positive effects on HDL function. Moreover, supplementation of anthocyanins as well as antioxidants such as lycopene or the omega−3 fatty acid eicosapentaenoic acid improve parameters of HDL function. In this review, we aim to highlight recent discoveries on beneficial dietary patterns as well as nutritional components and their effects on cardiovascular health, focusing on HDL function.
A Retrospective Analysis of the Effect of Irinotecan-Based Regimens in Patients With Metastatic Breast Cancer Previously Treated With Anthracyclines and Taxanes
Authors: Suo Jiaojiao , Zhong Xiaorong , He Ping , Zheng Hong , Tian Tinglun , Yan Xi , Luo Ting
Published: November 2021

Background

At present, patients with metastatic breast cancer (MBC) have few treatment options after receiving anthracyclines and taxanes. Studies have shown that irinotecan has modest systemic activity in some patients previously treated with anthracyclines and taxanes. This study aimed to evaluate the efficacy of irinotecan-based chemotherapy for breast cancer patients in a metastatic setting.

Methods

We retrospectively collected the clinical information and survival data of 51 patients with MBC who received irinotecan at West China Hospital of Sichuan University. The primary endpoints were the progression free survival (PFS) and overall survival (OS), and the secondary endpoint was the objective response rate (ORR). To minimize potential confounding factors, we matched 51 patients who received third-line chemotherapy without irinotecan through propensity score matching (PSM) based on age, hormone receptor (HR), and human epidermal growth factor receptor 2 (HER2), compared their OS and PFS rates to those treated with irinotecan.

Results

From July 2012 to October 2020, 51 patients were treated with an irinotecan-containing regimen. The median number of previous treatment lines was 4, and a median of two previous chemotherapy cycles (ranging from 1–14 cycles) were given in a salvage line setting. The ORR was 15.7%, and the disease control rate (DCR) was 37.3%. For the irinotecan group, the median PFS was 3.2 months (95% CI 2.7–3.7), while the median OS was 33.1 months (95% CI 27.9–38.3). Univariate analysis results suggested that irinotecan could improve PFS in patients with visceral metastasis (P=0.031), which was 0.7 months longer than patients without visceral metastasis (3.5 monthsvs.2.8 months). Compared to the patients who received third-line non-irinotecan chemotherapy, the irinotecan group showed a longer trend of PFS without statistical significance (3.2 monthsvs2.1 months, P = 0.052). Similarly, the OS of the irinotecan group was longer than the third-line survival without irinotecan, but it was not statistically significant (33.1 monthsvs18.0 months, P = 0.072).

Conclusions

For MBC patients who were previously treated with anthracyclines and/or taxanes, an irinotecan-containing regimen achieved moderate objective response and showed a trend of survival benefit, which deserves further study.