bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of fluorescent lateral flow immunoassay for SARS-CoV-2-specific IgM and IgG based on aggregation-induced emission carbon dots
Authors: Ju Jian , Zhang Xinyu , Li Lin , Regmi Sagar , Yang Guoqiang , Tang Shixing 
Published: October 2022

Understanding the dynamic changes in antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for evaluating the effectiveness of the vaccine and the stage for the recovery of the COVID-19 disease. A rapid and accurate method for the detection of SARS-CoV-2-specific antibodies is still urgently needed. Here, we developed a novel fluorescent lateral flow immunoassay (LFA) platform for the detection of SARS-CoV-2-specific IgM and IgG by the aggregation-induced emission carbon dots conjugated with the SARS-CoV-2 spike protein (SSP). The aggregation-induced emission carbon dots (AIE-CDs) are one of the best prospect fluorescent probe materials for exhibiting high emission efficiency in both aggregate and solid states. The AIE-CDs were synthesized and displayed dual fluorescence emission, which provides a new perspective for the design of a high sensitivity testing system. In this work, the novel LFA platform adopted the AIE carbon dots, which are used to detect SARS-CoV-2-specific IgM and IgG conveniently. Furthermore, this sensor had a low LOD of 100 pg/ml. Therefore, this newly developed strategy has potential applications in the areas of public health for the advancement of clinical research.
New R2-CHA2DS2-VASc score predicts no-reflow phenomenon and long-term prognosis in patients with ST-segment elevation myocardial infarction after primary percutaneous coronary intervention
Authors: Zhang Qinyao , Hu Meirong , Ma Shumei , Niu Tiesheng 
Published: October 2022

AimsEvaluating the prognostic validity of new R2-CHA2DS2-VASc score for no-reflow phenomena and long-term prognosis in patients following primary percutaneous coronary intervention (PCI) with ST-elevation myocardial infarction (STEMI).Materials and methodsFrom January 2017 to December 2018, a total of 401 patients with STEMI were continuously enrolled. According to the cut-off value, the patients were separated into two groups: R2-CHA2DS2-VASc &lt; 3 group (n = 275) and R2-CHA2DS2-VASc ≥ 3 group (n = 126).ResultsWith a sensitivity of 52.6% and a specificity of 73.1%, the optimal cut-off value for predicting no-reflow is R2-CHA2DS2-VASc ≥ 3. R2-CHA2DS2-VASc ≥ 3 as the ideal cut-off value for predicting major adverse cardiovascular events (MACE) with an area under the curve (AUC) of 0.781 [95% Confidence interval (CI): 0.738–0.801, P 0.001], a sensitivity of 50%, and a specificity of 91.1%. The incidence of MACE, death from all causes, and worsening heart failure was greater in the R2-CHA2DS2-VASc ≥ 3 group, although there was no significant difference in the incidence of repeated revascularisation procedures following PCI between the two groups. R2-CHA2DS2-VASc ≥ 3 was also an independent predictor of MACE (hazard ratio = 2.48, 95% confidence interval CI: 1.33–4.62, P = 0.04). Moreover, this score has a greater sensitivity (66.7%) and specificity (88.7%) for predicting the progression of heart failure.ConclusionR2-CHA2DS2-VASc ≥ 3 was independently associated with no-reflow phenomenon and poor clinical outcomes for patients in STEMI after primary PCI.
Cardiovascular toxicity associated with angiogenesis inhibitors: A comprehensive pharmacovigilance analysis based on the FDA Adverse Event Reporting System database from 2014 to 2021
Authors: Wang YanFeng , Cui Chanjuan , Ren Xiayang , Dong Xinran , Cui Wei 
Published: October 2022

BackgroundThe profiles of cardiovascular toxicity associated with angiogenesis inhibitors, including intravenous monoclonal antibodies (mAbs) and oral tyrosine kinase inhibitors (TKIs), targeting vascular endothelial growth factor (VEGF) remain poorly elucidated in real-world settings. This pharmacovigilance analysis aimed to comprehensively investigate the frequency, spectrum, timing, and outcomes of cardiovascular toxicities associated with angiogenesis inhibitors and to explore the differences in such patterns between mAbs and TKIs.MethodsDisproportionality analysis was performed by leveraging reports from the FDA Adverse Event Reporting System (FAERS) database from 2014 to 2021. Cardiovascular adverse events (AEs) were grouped into nine narrow categories using the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs). Reporting odds ratio (ROR) and information components (ICs) were calculated with statistical shrinkage transformation formulas and a lower limit of 95% confidence interval (CI) for ROR (ROR025) &gt; 1 or IC (IC025) &gt; 0, with at least three reports being considered statistically significant.ResultsA total of 757,577 reports of angiogenesis inhibitors and 70,668 (9.3%) reports of cardiovascular AEs were extracted. Significant disproportionality was detected in angiogenesis inhibitors for cardiovascular AEs (IC025/ROR025 = 0.35/1.27). Bevacizumab (31.8%), a mAb, presented the largest number of reports, followed by sunitinib (12.4%), a TKI. Hypertension (SMQ) was detected with the strongest signal value (IC025/ROR025 = 1.73/3.33), followed by embolic and thrombotic events (SMQ) (IC025/ROR025 = 0.32/1.26). Hypertension showed the shortest time to onset with a median (interquartile range) value of 23 (8, 69) days, while embolic and thrombotic events had the longest value of 51 (16, 153) days. Notably, hypertension presented the lowest proportions of death and life-threatening events (10.9%), whereas embolic and thrombotic events posed the highest (29.3%). Furthermore, both mAbs (IC025/ROR025 = 0.47/1.39) and TKIs (IC025/ROR025 = 0.30/1.23) showed increased cardiovascular AEs. Hypertension was detected in both agents (IC025/ROR025 = 1.53/2.90 for mAbs and IC025/ROR025 = 1.83/3.56 for TKIs) with a shorter time to onset of 17 (6, 48) days for TKIs than mAbs of 42 (14, 131) days. By contrast, embolic and thrombotic events were detected for mAbs (IC025/ROR025 = 0.90/1.87) without TKI (IC025/ROR025 = −0.08/0.95).ConclusionAngiogenesis inhibitors were associated with increased cardiovascular toxicity with a discrepancy between intravenous mAbs and oral TKIs, deserving distinct monitoring and appropriate management.
Dairy farm roadway surface materials as a P-source within the nutrient transfer continuum framework
Authors: Fenton Owen , Rice Paul , Murnane John. G. , Tuohy Patrick , Daly Karen 
Published: October 2022

Internal farm roadways are connectors within agricultural landscapes, which act as sub-components of the nutrient transfer continuum (NTC). On dairy farms, roadway surface runoff dissolved and particulate phosphorus (P) sources stem from a combination of cow excreta deposited at locations that impede animal flow, soil deposited from cow hooves or machinery tyres, run-on from up-gradient fields, public roadways or farmyards and incidental spill of organic/inorganic fertilizers. The present study investigates the storage and potential release of P from the underlying roadway material (i.e. composite of soil and stone aggregates) as this source component is not considered in the NTC framework or documented in the literature. Herein, farm roadway materials were sampled (to 1 cm depth) at 17 locations avoiding fresh cow excreta. Multiple location types were selected e.g. straight roadway sections, roadway junctions, before and adjacent standoff areas associated with cattle underpasses, with all locations varying in distance from the farmyard. Roadway samples were analysed for phosphorus (P) and metals (Al, B, Ca, Co, Cu, Fe, K, Mg, and Mn) content. Results showed that the soil component of roadway materials are significant P legacy sources and are in themselves a P-storage component that merits inclusion in the NTC framework. All sampled locations, when compared with fresh roadway stone aggregates or surrounding fields, had highly elevated P with plant available Morgans P &gt; 8 mg L-1 (Index 4, ranging from 10 – 110 mg L-1). Sampling points within 100 m of the farmyard together with roadway junctions and underpasses beyond this distance had highest P concentrations. Critical source areas, where source, mobilisation and transport of P to waters coincided, formed at three locations. Possible mitigation measures are a) divert roadway runoff into fields using low-cost surface water breaks, b) disconnect cattle underpass tanks from receiving waters and c) change roadway infrastructure to improve cow flow and minimise source build-up. Future research should examine P loads in runoff from roadway sections across farm typologies and roadway material types.
Analysis on heterogeneity of hepatocellular carcinoma immune cells and a molecular risk model by integration of scRNA-seq and bulk RNA-seq
Authors: Liu Xiaorui , Li Jingjing , Wang Qingxiang , Bai Lu , Xing Jiyuan , Hu Xiaobo , Li Shuang , Li Qinggang 
Published: October 2022

BackgroundStudies have shown that hepatocellular carcinoma (HCC) heterogeneity is a main cause leading to failure of treatment. Technology of single-cell sequencing (scRNA) could more accurately reveal the essential characteristics of tumor genetics.MethodsFrom the Gene Expression Omnibus (GEO) database, HCC scRNA-seq data were extracted. The FindCluster function was applied to analyze cell clusters. Autophagy-related genes were acquired from the MSigDB database. The ConsensusClusterPlus package was used to identify molecular subtypes. A prognostic risk model was built with the Least Absolute Shrinkage and Selection Operator (LASSO)–Cox algorithm. A nomogram including a prognostic risk model and multiple clinicopathological factors was constructed.ResultsEleven cell clusters labeled as various cell types by immune cell markers were obtained from the combined scRNA-seq GSE149614 dataset. ssGSEA revealed that autophagy-related pathways were more enriched in malignant tumors. Two autophagy-related clusters (C1 and C2) were identified, in which C1 predicted a better survival, enhanced immune infiltration, and a higher immunotherapy response. LASSO–Cox regression established an eight-gene signature. Next, the HCCDB18, GSA14520, and GSE76427 datasets confirmed a strong risk prediction ability of the signature. Moreover, the low-risk group had enhanced immune infiltration and higher immunotherapy response. A nomogram which consisted of RiskScore and clinical features had better prediction ability.ConclusionTo precisely assess the prognostic risk, an eight-gene prognostic stratification signature was developed based on the heterogeneity of HCC immune cells.
Neoadjuvant sintilimab and chemotherapy in patients with resectable esophageal squamous cell carcinoma: A prospective, single-arm, phase 2 trial
Authors: Zhang Zhi , Ye Jinjun , Li Hui , Gu Dayong , Du Mingyu , Ai Dashan , Chen Wei , Fang Ying , Xu Xinyu , Bai Chenguang , Zhao Kuaile , Zhou Guoren 
Published: October 2022

BackgroundImmunotherapy (Programmed cell death 1 blockade) has entered the ranks of advanced esophageal cancer first-line treatment; however, little is known about the efficacy of PD-1 inhibitor as neoadjuvant therapy in resectable esophageal squamous cell carcinoma (ESCC). We aim to evaluate the activity and safety of the neoadjuvant sintilimab combined with chemotherapy in the treatment of resectable thoracic ESCC.MethodsThe enrolled patients with resectable (clinical stage II to IVA) ESCC received neoadjuvant sintilimab injection (200 mg/time, day 1), paclitaxel liposomes (135 mg/m2, day 1), and carboplatin (area under curve of 5 mg/mL/min, day 1) every 21 days for 2 cycles, and esophagectomy was performed within 3-6 weeks after the 2 cycles of treatment. The primary endpoint of the study was the pathological complete response (PCR) rate.ResultsFrom July 2019 to March 2021, a total of 47 patients were enrolled, of which 33 patients (70.2%) had clinical stage III disease. All patients completed the full two-cycle treatment and forty-five patients received radical surgery, including 44 (97.8%) R0 resections. Ten (22.2%) of 45 patients had a PCR, and the major pathological response (MPR) rate was 44.4% (20/45). The grade 3–4 treatment-related adverse events (TRAEs) were mainly neutropenia (6 of 47,12.8%) and leucopenia (8 of 47,17.0%). One (2.1%) patient occurred postoperative immune-associated encephalitis. No delays in surgery were observed.Conclusionssintilimab combined with paclitaxel liposome and carboplatin, as demonstrated in this phase II trial to exhibit a relatively high PCR rate and acceptable safety, warrants additional investigation in resectable ESCC.Trial Registrationhttp://www.chictr.org.cn/, ChiCTR1900026593.
Examining attachment, cortisol secretion, and cognitive neurodevelopment in preschoolers and its predictive value for telomere length at age seven
Authors: de Mendonça Filho Euclides José , Frechette Ariane , Pokhvisneva Irina , Arcego Danusa Mar , Barth Barbara , Tejada Camila-Andrea Valle , Sassi Roberto , Wazana Ashley , Atkinson Leslie , Meaney Michael J. , Silveira Patricia P. 
Published: October 2022

BackgroundSecure attachment reflects caregiver-child relationship in which the caregiver is responsive when support and comforting are needed by the child. This pattern of bond has an important buffering role in the response to stress by the reduction of the negative experience and its associated physiological response. Disruption of the physiological stress system is thought to be a central mechanism by which early care impacts children. Early life stress causes cellular and molecular changes in brain regions associated with cognitive functions that are fundamental for early learning.MethodsThe association between attachment, cortisol response before and after the Strange Situation Experiment, and neurodevelopment was examined in a sample of 107 preschoolers at age three. Also, the predictive effect of cortisol reactivity and attachment on telomere length at age seven was investigated in a followed-up sample of 77 children.ResultsChildren with insecure attachment had higher cortisol secretion and poorer neurodevelopmental skills at age three. A significant cortisol change was observed across the experiment with non-significant interaction with attachment. The attachment and neurodevelopment association was not mediated by cortisol secretion. Preschoolers’ attachment and cortisol did not associate nor interacted to predict telomere length at age seven.ConclusionThese findings add evidence to the detrimental effects of insecure attachment as an aggravator of the physiological response to stress and poorer neurodevelopment during the preschool period. Although attachment and cortisol were not predictive of telomere length, intervention policies that promote secure attachment are more likely to positively echo on several health domains.
Systems biology analyses reveal enhanced chronic morphine distortion of gut-brain interrelationships in simian human immunodeficiency virus infected rhesus macaques
Authors: Olwenyi Omalla A. , Johnson Samuel D. , Bidokhti Mehdi , Thakur Vandana , Pandey Kabita , Thurman Michellie , Acharya Arpan , Uppada Srijayaprakash , Callen Shannon , Giavedoni Luis , Ranga Udaykumar , Buch Shilpa J. , Byrareddy Siddappa N. 
Published: October 2022

BackgroundCommonly used opioids, such as morphine have been implicated in augmented SIV/HIV persistence within the central nervous system (CNS). However, the extent of myeloid cell polarization and viral persistence in different brain regions remains unclear. Additionally, the additive effects of morphine on SIV/HIV dysregulation of gut-brain crosstalk remain underexplored. Therefore, studies focused on understanding how drugs of abuse such as morphine affect immune dynamics, viral persistence and gut-brain interrelationships are warranted.Materials and methodsFor a total of 9 weeks, rhesus macaques were ramped-up, and twice daily injections of either morphine (n = 4) or saline (n = 4) administered. This was later followed with infection with SHIVAD8EO variants. At necropsy, mononuclear cells were isolated from diverse brain [frontal lobe, cerebellum, medulla, putamen, hippocampus (HIP) and subventricular zone (SVZ)] and gut [lamina propria (LP) and muscularis (MUSC) of ascending colon, duodenum, and ileum] regions. Multiparametric flow cytometry was used to were profile for myeloid cell polarity/activation and results corroborated with indirect immunofluorescence assays. Simian human immunodeficiency virus (SHIV) DNA levels were measured with aid of the digital droplet polymerase chain reaction (PCR) assay. Luminex assays were then used to evaluate soluble plasma/CSF biomarker levels. Finally, changes in the fecal microbiome were evaluated using 16S rRNA on the Illumina NovaSeq platform.ResultsFlow Cytometry-based semi-supervised analysis revealed that morphine exposure led to exacerbated M1 (CD14/CD16)/M2 (CD163/CD206) polarization in activated microglia that spanned across diverse brain regions. This was accompanied by elevated SHIV DNA within the sites of neurogenesis–HIP and SVZ. HIP/SVZ CD16+ activated microglia positively correlated with SHIV DNA levels in the brain (r = 0.548, p = 0.042). Simultaneously, morphine dependence depleted butyrate-producing bacteria, including Ruminococcus (p = 0.05), Lachnospira (p = 0.068) genera and Roseburia_sp_831b (p = 0.068). Finally, morphine also altered the regulation of CNS inflammation by reducing the levels of IL1 Receptor antagonist (IL1Ra).ConclusionThese findings are suggestive that morphine promotes CNS inflammation by altering receptor modulation, increasing myeloid brain activation, distorting gut-brain crosstalk, and causing selective enhancement of SHIV persistence in sites of neurogenesis.
Electrophysiological correlates of mindfulness in patients with major depressive disorder
Authors: Sarlon Jan , Brühl Annette B. , Lang Undine E. , Kordon Andreas 
Published: October 2022

ObjectivesMindfulness-based interventions (MBI) can reduce both stress and depressive symptoms. However, the impact of mindfulness on stress level in depressed subjects remains unclear. This study aims to assess electrophysiological correlates of mindfulness in patients with major depressive disorder (MDD) at baseline, under stress exposure, and in relaxation following stress exposure.MethodsPerceived mindfulness was assessed with the Freiburger Mindfulness Inventory (FMI) in 89 inpatients (mean age 51) with MDD [mean Beck Depression Inventory (BDI) 30]. Electrophysiological parameters [resting heart rate (RHR), heart rate variability (HRV), respiration rate, skin conductance, and skin temperature] were recorded at 5-min baseline, 1-min stress exposure, and 5-min self-induced relaxation.ResultsFreiburger Mindfulness Inventory was strongly inversely correlated with symptom severity measured by BDI (r = –0.53, p &lt; 0.001). No correlations between FM score and electrophysiological parameters in any of the three conditions (baseline, stress exposure, relaxed state) could be found. The factor openness was associated with higher VLF (very low frequency of HRV) in the baseline condition. However, this correlation was no more significant after regression analysis when corrected for respiratory rate, age, and sex.ConclusionAutonomous nervous reactivity in depression was not associated with perceived mindfulness as measured by FMI score and presented electrophysiological parameters, despite the strong inverse correlation between state mindfulness and symptom severity.
A nomogram based on nutritional status and A2DS2 score for predicting stroke-associated pneumonia in acute ischemic stroke patients with type 2 diabetes mellitus: A retrospective study
Authors: Song Xiaodong , He Yang , Bai Jie , Zhang Jun 
Published: October 2022

BackgroundStroke-associated pneumonia (SAP) commonly complicates acute ischemic stroke (AIS) and significantly worsens outcomes. Type 2 diabetes mellitus (T2DM) may contribute to malnutrition, impair innate immunity function, and increase the probability of SAP occurrence in AIS patients. We aimed to determine early predictors of SAP in AIS patients with T2DM and to construct a nomogram specifically for predicting SAP in this population by combining the A2DS2 score with available nutrition-related parameters.MethodsA total of 1,330 consecutive AIS patients with T2DM were retrospectively recruited. The patients were randomly allocated to the training (n = 887) and validation groups (n = 443). Univariate and multivariate binary logistic regression analyses were applied to determine the predictors of SAP in the training group. A nomogram was established according to the identified predictors. The areas under the receiver operating characteristic curve (AUROC) and calibration plots were performed to access the predictive values of the nomogram. The decision curve was applied to evaluate the net benefits of the nomogram.ResultsThe incidence of SAP was 9% and 9.7% in the training and validation groups, respectively. The results revealed that the A2DS2 score, stroke classification, Geriatric Nutritional Risk Index, hemoglobin, and fast blood glucose were independent predictors for SAP. A novel nomogram, A2DS2-Nutrition, was constructed based on these five predictors. The AUROC for A2DS2-Nutrition (0.820, 95% CI: 0.794–0.845) was higher than the A2DS2 score (0.691, 95% CI: 0.660–0.722) in the training group. Similarly, it showed a better predictive performance than the A2DS2 score [AUROC = 0.864 (95% CI: 0.828–0.894) vs. AUROC = 0.763 (95% CI: 0.720–0.801)] in the validation group. These results were well calibrated in the two groups. Moreover, the decision curve revealed that the A2DS2-Nutrition provided an additional net benefit to the AIS patients with T2DM compared to the A2DS2 score in both groups.ConclusionThe A2DS2 score, stroke classification, Geriatric Nutritional Risk Index, hemoglobin, and fast blood glucose were independent predictors for SAP in AIS patients with T2DM. Thus, the proposed A2DS2-Nutrition may be a simple and reliable prediction model for SAP occurrence in AIS patients with T2DM.