bluuebunny/crossref_metadata_2025_split huggingface dataset:
AstraZeneca COVID-19 vaccine induces robust broadly cross-reactive antibody responses in Malawian adults previously infected with SARS-CoV-2
Authors: Chibwana Marah G. , Moyo-Gwete Thandeka , Kwatra Gaurav , Mandolo Jonathan , Hermanaus Tandile , Motlou Thopisang , Mzindle Nonkululeko , Ayres Frances , Chaponda Mphatso , Tembo Godwin , Mwenechanya Percy , Mitole Ndaona , Jassi Chisomo , Kamng’ona Raphael , Afran Louise , Mzinza David , Mwandumba Henry C. , Gordon Stephen B. , Jere Khuzwayo , Madhi Shabir , Moore Penny L. , Heyderman Robert S. , Jambo Kondwani C. 
Published: March 2022

AbstractBackgroundBinding and neutralising anti-Spike antibodies play a key role in immune defence against SARS-CoV-2 infection. Since it is known that antibodies wane with time and new immune-evasive variants are emerging, we aimed to assess the dynamics of anti-Spike antibodies in an African adult population with prior SARS-CoV-2 infection and to determine the effect of subsequent COVID-19 vaccination.MethodsUsing a prospective cohort design, we recruited adults with prior laboratory-confirmed mild/moderate COVID-19 in Blantyre, Malawi, and followed them up for 270 days (n = 52). A subset of whom subsequently received a single dose of the AstraZeneca COVID-19 vaccine (ChAdOx nCov-19) (n = 12). We measured the serum concentrations of anti-Spike and receptor-binding domain (RBD) IgG antibodies using a Luminex-based assay. Anti-RBD antibody cross-reactivity across SARS-CoV-2 variants of concern (VOC) was measured using a haemagglutination test. A pseudovirus neutralisation assay was used to measure neutralisation titres across VOCs. Ordinary or repeated measures one-way ANOVA was used to compare log10 transformed data, withpvalue adjusted for multiple comparison using Šídák's or Holm-Šídák's test.ResultsWe show that neutralising antibodies wane within 6 months post mild/moderate SARS-CoV-2 infection (30–60 days vs. 210–270 days; Log ID506.8 vs. 5.3,p = 0.0093). High levels of binding anti-Spike or anti-RBD antibodies in convalescent serum were associated with potent neutralisation activity against the homologous infecting strain (p < 0.0001). A single dose of the AstraZeneca COVID-19 vaccine following mild/moderate SARS-CoV-2 infection induced a 2 to 3-fold increase in anti-Spike and -RBD IgG levels 30 days post-vaccination (both,p < 0.0001). The anti-RBD IgG antibodies from these vaccinated individuals were broadly cross-reactive against multiple VOCs and had neutralisation potency against original D614G, beta, and delta variants.ConclusionsThese findings show that the AstraZeneca COVID-19 vaccine is an effective booster for waning cross-variant antibody immunity after initial priming with SARS-CoV-2 infection. The potency of hybrid immunity and its potential to maximise the benefits of COVID-19 vaccines needs to be taken into consideration when formulating vaccination policies in sub-Saharan Africa, where there is still limited access to vaccine doses.
Retrospective analysis of radiographic signs in feline pleural effusions to predict disease aetiology
Authors: Hung Lily , Hopper Belinda Judith , Lenard Zoe 
Published: March 2022

Abstract
Background
The objectives of the study were to determine the prevalence of underlying conditions causing pleural effusion in cats and to calculate the positive predictive values, negative predictive values, sensitivity and specificity of radiographic signs to predict aetiology of the pleural fluid.

Methods
Data from 148 cats with pleural effusion and diagnosed with known aetiologies were retrospectively analysed. Sixty one cats had thoracic radiographs evaluated by consensus through pre-defined radiographic signs by two radiologists blinded to the diagnoses.

Results
Congestive heart failure (53.4%) was the most common diagnosis, followed by neoplasia (20.3%), pyothorax (10.8%), idiopathic chylous effusion (5.4%), feline infectious peritonitis (1.4%) and "other" or cats with multiple diagnoses (total 8.8%). Cats with an enlarged cardiac silhouette had a high positive predictive value of congestive heart failure (90%). Mediastinal masses (100%)and pulmonary masses (100%) were highly predictive of neoplastic disease. Pulmonary nodules (50%) were poorly predictive of neoplastic disease. The remainder of the radiographic variables were not informative predictors of underlying disease.

Conclusions
In our sample of cats, congestive heart failure was the most common cause of pleural effusion. Radiographically enlarged cardiac silhouette and presence of a mediastinal mass may be useful predictors of aetiology, however there are limitations to the use of radiography alone as a diagnostic tool.
NADPH oxidase 4 signaling in a ventilator-induced lung injury mouse model
Authors: Lee Sang Hoon , Shin Mi Hwa , Leem Ah Young , Lee Su Hwan , Chung Kyung Soo , Kim Young Sam , Park Moo Suk 
Published: March 2022

Abstract
Background
For patients with acute respiratory distress syndrome, a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. In this study, we investigated the role of NOX4 using NOX4 knockout (KO) mice and NOX4 inhibitors in a ventilator-induced lung injury (VILI) model.

Methods
Wild-type (WT) male C57BL/6J mice and NOX4 knockout (KO) male mice were divided into five groups: (1) control group; (2) high tidal ventilation (HTV) group: WT mice + HTV ± DMSO; (3) NOX4 KO group; (4) NOX4 KO with HTV group; (5) NOX4 inhibitor group: WT mice + HTV + NOX4 inhibitor. In the VILI model, the supine position was maintained at 24 mL/kg volume, 0 cm H2O PEEP, 100/min respiratory rate, and 0.21 inspired oxygen fraction. In the NOX4 inhibitor group, 50 μL anti-GKT 137831 inhibitor was injected intraperitoneally, 2 h after ventilator use. After 5 h of HTV, mice in the ventilator group were euthanized, and their lung tissues were obtained for further analysis. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 and EphA2 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined.

Results
Cell counts from BALFs were significantly lower in the NOX4 KO with HTV group (p < 0.01) and EphA2 KO with HTV group (p < 0.001) compared to that in the HTV group. In the NOX4 inhibitor group, cell counts and protein concentrations from BALF were significantly lower than those in the HTV group (both, p < 0.001). In the NOX4 KO group and the NOX4 inhibitor group, EphA2 levels were significantly lower than those in the HTV group (p < 0.001). In patients with respiratory disease, NOX4 and EphA2 levels were significantly higher in patients with pneumonia and patients who received ventilator treatment in the intensive care unit.

Conclusion
In the VILI model with high tidal volume, NOX4 KO, EphA2 KO or monoclonal antibodies attenuated the VILI. NOX4 and EphA2 levels were significantly higher in patients with pneumonia and especially in mechanical ventilated in the ICU. Inhibition of Nox4 is a potential therapeutic target for the prevention and reduction of VILI.
Pulmonary 99mTc-HMDP uptake correlates with restrictive ventilatory defects and abnormal lung reactance in transthyretin cardiac amyloidosis patients
Authors: Monfort Astrid , Rivas Alexia , Banydeen Rishika , Inamo Jocelyn , Farid Karim , Neviere Remi 
Published: March 2022

Abstract
Background
Pulmonary involvement in individuals with transthyretin cardiac amyloidosis is unclear. The aim of this study was to quantify 99mTc-hydroxy methylene diphosphonate (HMDP) lung retention in hereditary transthyretin (ATTRv) cardiac amyloidosis patients and to relate tracer uptake intensity to pulmonary function and aerobic capacity.

Methods
We prospectively enrolled 20 patients with biopsy-proven ATTRv cardiac amyloidosis and 20 control subjects. Cardiac involvement was confirmed by echocardiography and nuclear imaging using 99mTc-HMDP. Semi-quantitative analysis of the heart, rib and lung retention was assessed using a simple region of interest technique. Pulmonary function was evaluation by the means of whole-body plethysmography, diffusing capacity of the lung for carbon monoxide, forced oscillation technique and cardiopulmonary exercise testing.

Results
Pulmonary tracer uptake estimated by lung to rib retention ratio was higher in ATTRv amyloidosis patients compared with control subjects: median 0.62 (0.55–0.69) vs 0.51 (0.46–0.60); p = 0.014. Analysis of relation between lung 99mTc-HMDP retention and pulmonary function parameters shown statistically significant correlations with total lung volume (% predicted), lung reactance (Xrs 5 Hz) and peak VO2, suggesting total lung capacity restriction impaired elastic properties of the lung and poor aerobic capacity.

Conclusion
Our study suggests that some grade of pulmonary retention of 99mTc-HMDP may occur in patients with cardiac ATTRv amyloidosis, which can elicit deleterious effects on patient’s lung function and aerobic capacity.
Biosensor-driven, model-based optimization of the orthogonally expressed naringenin biosynthesis pathway
Authors: Van Brempt Maarten , Peeters Andries Ivo , Duchi Dries , De Wannemaeker Lien , Maertens Jo , De Paepe Brecht , De Mey Marjan 
Published: March 2022

Abstract
Background
The rapidly expanding synthetic biology toolbox allows engineers to develop smarter strategies to tackle the optimization of complex biosynthetic pathways. In such a strategy, multi-gene pathways are subdivided in several modules which are each dynamically controlled to fine-tune their expression in response to a changing cellular environment. To fine-tune separate modules without interference between modules or from the host regulatory machinery, a sigma factor (σ) toolbox was developed in previous work for tunable orthogonal gene expression. Here, this toolbox is implemented in E. coli to orthogonally express and fine-tune a pathway for the heterologous biosynthesis of the industrially relevant plant metabolite, naringenin. To optimize the production of this pathway, a practical workflow is still imperative to balance all steps of the pathway. This is tackled here by the biosensor-driven screening, subsequent genotyping of combinatorially engineered libraries and finally the training of three different computer models to predict the optimal pathway configuration.

Results
The efficiency and knowledge gained through this workflow is demonstrated here by improving the naringenin production titer by 32% with respect to a random pathway library screen. Our best strain was cultured in a batch bioreactor experiment and was able to produce 286 mg/L naringenin from glycerol in approximately 26 h. This is the highest reported naringenin production titer in E. coli without the supplementation of pathway precursors to the medium or any precursor pathway engineering. In addition, valuable pathway configuration preferences were identified in the statistical learning process, such as specific enzyme variant preferences and significant correlations between promoter strength at specific steps in the pathway and titer.

Conclusions
An efficient strategy, powered by orthogonal expression, was applied to successfully optimize a biosynthetic pathway for microbial production of flavonoids in E. coli up to high, competitive levels. Within this strategy, statistical learning techniques were combined with combinatorial pathway optimization techniques and an in vivo high-throughput screening method to efficiently determine the optimal operon configuration of the pathway. This “pathway architecture designer” workflow can be applied for the fast and efficient development of new microbial cell factories for different types of molecules of interest while also providing additional insights into the underlying pathway characteristics.
Dietary oxalate to calcium ratio and incident cardiovascular events: a 10-year follow-up among an Asian population
Authors: Bahadoran Zahra , Mirmiran Parvin , Azizi Fereidoun 
Published: March 2022

Abstract
Background and aim
The potential cardiovascular impact of usual intakes of oxalate (Ox) is uninvestigated. We evaluated the effect of dietary Ox and its interaction with dietary calcium (Ca) on incident cardiovascular disease (CVD).

Methods
We included 2966 adult men and women aged 19–84 y without known CVD during baseline enrollment (2006–2008) of the Tehran Lipid and Glucose Study. Dietary intakes were assessed using a validated FFQ, and incident CVD (i.e., coronary heart disease, stroke, and CVD mortality) were documented through March 2018.

Results
A 7.1% incident of CVD occurred during a median follow-up of 10.6 y. After multivariable adjustment for traditional risk factors and key dietary nutrients, including total fat and fiber, Ox intakes ≥220 mg/d increased incident CVD (HR T3 vs. T1 = 1.47, 95% CI = 1.02–2.12). This association was potentiated (HR T3 vs. T1 = 2.42, 95% CI = 1.19–4.89) in subjects who had a lower intake of Ca (< 981 mg/d); in a low-Ca diet, an even lower amount of dietary Ox (second tertile, 148–220 mg/d) was related to increased CVD events by 92% (HR = 1.92, 95% CI = 1.00–3.70). No association was observed between dietary Ox and CVD events in the presence of medium- and high levels of Ca intakes. The critical cut-off point of Ox-to-Ca for predicting CVD events was 0.14, which was related to an increased risk of CVD by 37% (HR = 1.37, 95% CI = 1.02–1.84).

Conclusion
Higher dietary Ox intake appeared to be associated with a modestly elevated risk of incident CVD, especially in a diet with a lower amount of Ca.
Multifunctional nanoparticles co-loaded with Adriamycin and MDR-targeting siRNAs for treatment of chemotherapy-resistant esophageal cancer
Authors: Zhang Xiangyang , Wang Min , Feng Junyi , Qin Bin , Zhang Chenglin , Zhu Chengshen , Liu Wentao , Wang Yaohe , Liu Wei , Huang Lei , Lu Shuangshuang , Wang Zhimin 
Published: March 2022

AbstractThe development of multidrug resistance (MDR) during cancer chemotherapy is a major challenge in current cancer treatment strategies. Numerous molecular mechanisms, including increased drug efflux, evasion of drug-induced apoptosis, and activation of DNA repair mechanisms, can drive chemotherapy resistance. Here we have identified the major vault protein (MVP) and the B-cell lymphoma-2 (BCL2) gene as two potential factors driving MDR in esophageal squamous cell carcinoma (ESCC). We have designed a novel and versatile self-assembling nanoparticle (NP) platform on a multifunctional carboxymethyl chitosan base to simultaneously deliver Adriamycin, and siRNAs targeting MVP and BCL2 (CEAMB NPs), thus reducing drug efflux and promoting apoptosis of esophageal cancer cells. To achieve effective delivery to tumor tissues and inhibit tumor growth in vivo, carboxymethyl chitosan was engineered to contain multiple histidines for enhanced cytosol delivery, cholesterol for improved self-assembly, and epidermal growth factor receptor (EGFR) antibodies to target cancer cells. Our results indicate that these nanoparticles are efficiently synthesized with the desired chemical composition to self-assemble into cargo-containing NPs. Furthermore, we have shown that the synthesized NPs will successfully inhibit cancer cells growth and tumor development when delivered to cultured ESCC cells or to in vivo mouse xenograft models. Our engineered NPs offer a potential novel platform in treating various types of chemotherapy-resistant tumors.
Graphical Abstract
The Chinese version of the Quality of Life in Childhood Epilepsy Questionnaire-16-C (QOLCE-16-C): translation, validity, and reliability
Authors: Tang Ping , Lu Qunfeng , Wu Yinghui , Wang Lin , Tang Wenjuan , Jiang Yan , Yang Liling , Ji Jianlin , Sun Xiaomin , Sun Jingmin , Yang Jie 
Published: March 2022

AbstractBackgroundEpilepsy is one of the most common chronic neurological diseases that adversely impact the quality of life of patients and their families. The “Quality of Life of Childhood Epilepsy Questionnaire” (hereinafter referred to as “QOLCE-16”) is a 16-item measure that was designed to assess health-related quality of life (HRQOL) among children with epilepsy. The purpose of the study was to translate and evaluate the psychometric properties of the QOLCE-16.MethodsThe 10 steps of Principles of Good Practices for translation and cultural adaptation of measures were adopted to translate the QOLCE-16 into Chinese. After that, item analysis, floor effect and ceiling effect, internal consistency, test–retest reliabilities, content validity and construct validity were conducted to test its applicability in children with epilepsy in China. A total of 435 native Chinese-speaking parents with children who had epilepsy from one children’s hospital were invited to take part in the study, including a cognitive interview sample of 5 and a validation sample of 430.ResultsA total of 414 objects were enrolled in our study for psychometric testing. The results of the item analysis revealed QOLCE-16-C to have good discrimination, the floor effect and ceiling effect were 0.2% and 1.0% respectively, and each item was significantly related to the total scale (P < 0.001). The Cronbach’s α value was 0.938 and the test–retest reliability was 0.724. For validity, results showed that the QOLCE-16-C had good content validity. Exploratory factor analysis indicated it was reasonable that the QOLCE-16-C consists of four dimensions after rotation. Confirmatory factor analysis demonstrated good construct validity (χ2/df = 1.698, GFI = 0.913, CFI = 0.974, RMSEA = 0.058).ConclusionThe Chinese version of QOLCE-16-C appears to be a culturally appropriate, valid and reliable tool to assess the health-related quality of life of children with epilepsy in China.
Expression and prognostic analyses of the significance of STEAP1 and STEAP2 in lung cancer
Authors: Liu Tianshu , Niu Xiaoxin , Li Yanqing , Xu Zekun , Chen Jie , Xu Geng 
Published: March 2022

Abstract
Purpose
Lung cancer is the leading cause of cancer-related mortality. STEAP1 and STEAP2 are overexpressed in various cancers. The purpose of this study was to evaluate the expression and prognostic value of STEAP1 and STEAP2 in patients with lung cancer.

Methods
The mRNA expression and protein expression of STEAP1 and STEAP2 and their prognostic characteristics were examined using Oncomine, GEPIA, and Kaplan-Meier (KM) plotters. The correlation analysis of STEAP1 and STEAP2 gene and protein levels was conducted using GeneMANIA and STRING. KEGG pathway analysis was used to explore the related signal pathways of STEAP 1 and STEAP2. Immunohistochemical methods were used to compare the expression of STEAP2 in normal lung and non-small cell lung cancer (NSCLC) tissues. Real-time quantitative polymerase chain reaction, western blotting, and immunocytochemistry were used to evaluate the expression of STEAP1 and STEAP2 in three lung cancer cell lines and normal lung epithelial cell lines.

Results
Analysis of the Oncomine database and GEPIA showed that STEAP1 was upregulated and STEAP2 was downregulated in lung cancer tissue, and both expressions were related to the clinical stage of lung cancer. Immunohistochemical analysis showed that STEAP1 protein expression was significantly upregulated in lung cancer compared to that in adjacent tissues. The expression of STEAP1 was positively correlated with the migration and invasion abilities of lung cancer cells. Compared with paracancer tissues, the expression of STEAP2 protein in lung cancer was significantly downregulated and was correlated with the histological grade of squamous cell carcinoma, pathological classification of adenocarcinoma, tumor, lymph node, and metastasis clinical stage, and lymph node metastasis. The expression of STEAP2 was negatively correlated with the migration and invasion abilities of lung cancer cells. The KM curve showed that the downregulation of STEAP1 expression and upregulation of STEAP2 expression were related to a good lung cancer prognosis.

Conclusion
STEAP1 and STEAP2 are expected to be potential diagnostic and prognostic markers for lung cancer, which may provide more accurate prognostic indicators for lung cancer.
The role of health facility and individual level characteristics on medication adherence among PLHIV on second-line antiretroviral therapy in Northeast Ethiopia: use of multi-level model
Authors: Wedajo Shambel , Degu Getu , Deribew Amare , Ambaw Fentie 
Published: March 2022

Abstract
Background
Medication adherence plays a pivotal role in achieving the desired treatment outcomes. The proportion of HIV patients on second-line antiretroviral therapy is becoming a growing public health concern. However, to date, little attention has been given to second-line antiretroviral medication adherence. Moreover, the association between health facility characteristics and medication adherence has yet not been tested. Thus, this research was conducted to determine the magnitude of medication adherence and examine the role of facility-level determinants among HIV patients on second-line ART.

Methods
A cross-sectional study was conducted on 714 HIV patients on second-line therapy who were selected via systematic random sampling in twenty public health facilities. Medication adherence was measured using the six-item Simplified Medication Adherence Questionnaire (SMAQ) tool. Data were collected in a personal interview as well as document reviews. A multi-level binary logistic regression was used to uncover individual and facility-level determinants. The effect size was presented using an adjusted odds ratio (AOR), and statistical significance was declared at a P value less than 0.05.

Results
The magnitude of optimal medication adherence among HIV patients on second-line antiretroviral therapy was 69.5% (65.9–72.7%). Medication adherence was positively associated with the use of adherence reminder methods [AOR = 3.37, (95% CI 2.03–5.62)], having social support [AOR = 1.11, (95% CI 1.02–1.23)], and not having clinical depression [AOR = 3.19, (95% CI 1.93–5.27). The number of adherence counselors [AOR = 1.20, (95% CI 1.04–1.40)], teamwork for enhanced adherence support [AOR = 1.82, (95% CI 1.01–3.42)], and caseloads at ART clinics were all significantly correlated with ARV medication adherence at the facility level.

Conclusions
A large proportion of HIV patients on second-line antiretroviral therapy had adherence problems. Both facility-level and individual-level were linked with patient medication adherence. Thus, based on the identified factors, individual and system-level interventions should be targeted.