bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Efficacy of Adding Dapagliflozin to Furosemide in Type 2 Diabetic Patients With Decompensated Heart Failure and Reduced Ejection Fraction
Authors: Ibrahim Ayman , Ghaleb Ramadan , Mansour Hossam , Hanafy Amr , Mahmoud Naggeh M. , Abdelfatah Elsharef Mohamed , Kamal Salama Mohamed , Elsaughier Saud M. , Abdel-Wahid Lobna , Embarek Mohamed Mona , Ibrahim Ahmed K. , Abdel-Galeel Ahmed
Published: December 2020

Background:Heart failure is the most common cause of hospitalization in elderly patients. It is likely that many of the mechanisms that contribute to reductions in systolic and diastolic function, seen in diabetic patients, place them at an increased risk of heart failure. Diuretic therapy, especially loop diuretics, is the usual way of managing congestion, particularly in volume-overloaded patients. Little is known about the beneficial effect of dapagliflozin when added to loop diuretics in managing patients with decompensated heart failure.

Aim:To assess the effect of the addition of dapagliflozin to furosemide in managing decompensated patient with heart failure and reduced left ventricular ejection fraction in terms of weight loss and dyspnea improvement.

Patients and Methods:The study included 100 type 2 diabetic patients who were admitted with decompensated heart failure. The study population was randomly divided into two arms. Serum electrolytes and kidney functions were followed up during their hospital stay.

Results:With dapagliflozin, there was a statistically significant difference between the two groups regarding the change in body weight and body mass index. The diuresis parameters including urine output, total fluid loss, and fluid balance also showed a statistically significant difference in favor of the use of dapagliflozin, with no significant change in serum potassium or kidney functions. There was significant improvement in patient-reported dyspnea scores with the use of dapagliflozin.

Conclusions:Dapagliflozin may provide a new drug option in the treatment of heart failure especially among vulnerable group of diabetics. It had no remarkable effects on serum potassium level and kidney functions.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04385589.
The Use of Synthetic Electronic Health Record Data and Deep Learning to Improve Timing of High-Risk Heart Failure Surgical Intervention by Predicting Proximity to Catastrophic Decompensation
Authors: Guo Aixia , Foraker Randi E. , MacGregor Robert M. , Masood Faraz M. , Cupps Brian P. , Pasque Michael K.
Published: December 2020

Objective: Although many clinical metrics are associated with proximity to decompensation in heart failure (HF), none are individually accurate enough to risk-stratify HF patients on a patient-by-patient basis. The dire consequences of this inaccuracy in risk stratification have profoundly lowered the clinical threshold for application of high-risk surgical intervention, such as ventricular assist device placement. Machine learning can detect non-intuitive classifier patterns that allow for innovative combination of patient feature predictive capability. A machine learning-based clinical tool to identify proximity to catastrophic HF deterioration on a patient-specific basis would enable more efficient direction of high-risk surgical intervention to those patients who have the most to gain from it, while sparing others. Synthetic electronic health record (EHR) data are statistically indistinguishable from the original protected health information, and can be analyzed as if they were original data but without any privacy concerns. We demonstrate that synthetic EHR data can be easily accessed and analyzed and are amenable to machine learning analyses.

Methods: We developed synthetic data from EHR data of 26,575 HF patients admitted to a single institution during the decade ending on 12/31/2018. Twenty-seven clinically-relevant features were synthesized and utilized in supervised deep learning and machine learning algorithms (i.e., deep neural networks [DNN], random forest [RF], and logistic regression [LR]) to explore their ability to predict 1-year mortality by five-fold cross validation methods. We conducted analyses leveraging features from prior to/at and after/at the time of HF diagnosis.

Results: The area under the receiver operating curve (AUC) was used to evaluate the performance of the three models: the mean AUC was 0.80 for DNN, 0.72 for RF, and 0.74 for LR. Age, creatinine, body mass index, and blood pressure levels were especially important features in predicting death within 1-year among HF patients.

Conclusions: Machine learning models have considerable potential to improve accuracy in mortality prediction, such that high-risk surgical intervention can be applied only in those patients who stand to benefit from it. Access to EHR-based synthetic data derivatives eliminates risk of exposure of EHR data, speeds time-to-insight, and facilitates data sharing. As more clinical, imaging, and contractile features with proven predictive capability are added to these models, the development of a clinical tool to assist in timing of intervention in surgical candidates may be possible.
Instrument Bias Correction With Machine Learning Algorithms: Application to Field-Portable Mass Spectrometry
Authors: Loose B. , Short R. T. , Toler S.
Published: December 2020

In situ sensors for environmental chemistry promise more thorough observations, which are necessary for high confidence predictions in earth systems science. However, these can be a challenge to interpret because the sensors are strongly influenced by temperature, humidity, pressure, or other secondary environmental conditions that are not of direct interest. We present a comparison of two statistical learning methods—a generalized additive model and a long short-term memory neural network model for bias correction of in situ sensor data. We discuss their performance and tradeoffs when the two bias correction methods are applied to data from submersible and shipboard mass spectrometers. Both instruments measure the most abundant gases dissolved in water and can be used to reconstruct biochemical metabolisms, including those that regulate atmospheric carbon dioxide. Both models demonstrate a high degree of skill at correcting for instrument bias using correlated environmental measurements; the difference in their respective performance is less than 1% in terms of root mean squared error. Overall, the long short-term memory bias correction produced an error of 5% for O2 and 8.5% for CO2 when compared against independent membrane DO and laser spectrometer instruments. This represents a predictive accuracy of 92–95% for both gases. It is apparent that the most important factor in a skillful bias correction is the measurement of the secondary environmental conditions that are likely to correlate with the instrument bias. These statistical learning methods are extremely flexible and permit the inclusion of nearly an infinite number of correlates in finding the best bias correction solution.
Thyroid Hormone Changes in Early Pregnancy Along With the COVID-19 Pandemic
Authors: Lin Ting-Ting , Zhang Chen , Zhang Han-Qiu , Wang Yu , Chen Lei , Dennis Cindy-Lee , Huang Hefeng , Wu Yan-Ting
Published: December 2020

Purpose

COVID-19 (Coronavirus Disease 2019) was first reported in December 2019 and quickly swept across China and around the world. Levels of anxiety and depression were increased among pregnant women during this infectious pandemic. Thyroid function is altered during stressful experiences, and any abnormality during early pregnancy may significantly affect fetal development and pregnancy outcomes. This study aimed to determine whether the COVID-19 pandemic induces thyroid hormone changes in early pregnant women.

Methods

This study comprised two groups of pregnant women in Shanghai in their first trimester – those pregnant women before the COVID-19 outbreak from January 20, 2019, to March 31, 2019 (Group 1) and those pregnant during the COVID-19 outbreak from January 20, 2020, to March 31, 2020 (Group 2). All women were included if they had early pregnancy thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), and total thyroxine (TT4) concentrations, thyroid peroxidase (TPO) antibody or thyroglobulin antibody (TgAb) available and did not have a history of thyroid diseases or received thyroid treatment before or during pregnancy. We used propensity score matching to form a cohort in which patients had similar baseline characteristics.

Results

Among 3338 eligible pregnant women, 727 women in Group 1 and 727 in Group 2 had similar propensity scores and were included in the analyses. Pregnant women in Group 2 had significantly higher FT3 (5.7 vs. 5.2 pmol/L, P<0.001) and lower FT4 (12.8 vs. 13.2 pmol/L, P<0.001) concentrations compared with those in Group 1. Pregnant women in Group 2 were more likely to develop isolated hypothyroxinemia (11.6% vs. 6.9%, OR, 1.75 [95% CI, 1.20–2.53], P=0.003) than those in Group 1 but had a significantly lower risk of TgAb positivity (12.0% vs. 19.0%, OR, 0.58 [95% CI, 0.43–0.78], P<0.001).

Conclusion

Pregnant women in their first trimester in Shanghai during the COVID-19 outbreak were at an increased risk of having higher FT3 concentrations, lower FT4 concentrations, and isolated hypothyroxinemia. The association between thyroid hormones, pregnancy outcomes, and the COVID-19 outbreak should be explored further.
Biomonitoring Studies in Geothermal Areas: A Review
Authors: Lattanzi Pierfranco , Benesperi Renato , Morelli Guia , Rimondi Valentina , Ruggieri Giovanni
Published: December 2020

Biomonitoring is a widely employed approach to track changes in the environment. Its use to assess the impact of geothermal energy exploitation for power production is comparatively minor, and largely referred to Tuscany, Italy, geothermal fields. Most examples describe impacts on vegetation, particularly lichens. Biomonitoring proved useful as a tool to reveal the distribution of specific contaminants (e.g., mercury and H2S), and as an overall indicator of the impact on ecosystems. In consideration of the comparatively low cost/benefit ratio, the use of biomonitoring should be encouraged. In particular, it could prove useful to establish the natural background prior to development of geothermal exploitation, and to document any subsequent change.
GapB Is Involved in Biofilm Formation Dependent on LrgAB but Not the SinI/R System in Bacillus cereus 0-9
Authors: Zhang Juanmei , Meng Li , Zhang Yubing , Sang Lidan , Liu Qing , Zhao Linlin , Liu Fengying , Wang Gang
Published: December 2020

Bacillus cereus 0-9, a Gram-positive endospore-forming bacterium isolated from healthy wheat roots, has biological control capacity against several soil-borne plant diseases of wheat such as sharp eyespot and take-all. The bacterium can produce various biofilms that differ in their architecture and formation mechanisms, possibly for adapting to different environments. The gapB gene, encoding a glyceraldehyde-3-phosphate dehydrogenase (GAPDH), plays a key role in B. cereus 0-9 biofilm formation. We studied the function of GapB and the mechanism of its involvement in regulating B. cereus 0-9 biofilm formation. GapB has GAPDH activities for both NAD+- and NADP+-dependent dehydrogenases and is a key enzyme in gluconeogenesis. Biofilm yield of the ΔgapB strain decreased by 78.5% compared with that of wild-type B. cereus 0-9 in lysogeny broth supplemented with some mineral salts (LBS), and the ΔgapB::gapB mutants were recovered with gapB gene supplementation. Interestingly, supplementing the LBS medium with 0.1–0.5% glycerol restored the biofilm formation capacity of the ΔgapB mutants. Therefore, GapB regulates biofilm formation relative to its function in gluconeogenesis. To illustrate how GapB is involved in regulating biofilm formation through gluconeogenesis, we carried out further research. The results indicate that the GapB regulated the B. cereus 0-9 biofilm formation independently of the exopolysaccharides and regulatory proteins in the typical SinI/R system, likely owing to the release of extracellular DNA in the matrix. Transcriptome analysis showed that the gapB deletion caused changes in the expression levels of only 18 genes, among which, lrgAB was the most significantly increased by 6.17-fold. We confirmed this hypothesis by counting the dead and living cells in the biofilms and found the number of living cells in the biofilm formed by the ΔgapB strain was nearly 7.5 times than that of wild-type B. cereus 0-9. Therefore, we concluded that the GapB is involved in the extracellular DNA release and biofilm formation by regulating the expression or activities of LrgAB. These results provide a new insight into the regulatory mechanism of bacterial biofilm formation and a new foundation for further studying the stress resistance of B. cereus.
The Role of Chronic Inflammatory Bone and Joint Disorders in the Pathogenesis and Progression of Alzheimer's Disease
Authors: Culibrk Robert A. , Hahn Mariah S.
Published: December 2020

Late-onset Alzheimer's Disease (LOAD) is a devastating neurodegenerative disorder that causes significant cognitive debilitation in tens of millions of patients worldwide. Throughout disease progression, abnormal secretase activity results in the aberrant cleavage and subsequent aggregation of neurotoxic Aβ plaques in the cerebral extracellular space and hyperphosphorylation and destabilization of structural tau proteins surrounding neuronal microtubules. Both pathologies ultimately incite the propagation of a disease-associated subset of microglia—the principle immune cells of the brain—characterized by preferentially pro-inflammatory cytokine secretion and inhibited AD substrate uptake capacity, which further contribute to neuronal degeneration. For decades, chronic neuroinflammation has been identified as one of the cardinal pathophysiological driving features of AD; however, despite a number of works postulating the underlying mechanisms of inflammation-mediated neurodegeneration, its pathogenesis and relation to the inception of cognitive impairment remain obscure. Moreover, the limited clinical success of treatments targeting specific pathological features in the central nervous system (CNS) illustrates the need to investigate alternative, more holistic approaches for ameliorating AD outcomes. Accumulating evidence suggests significant interplay between peripheral immune activity and blood-brain barrier permeability, microglial activation and proliferation, and AD-related cognitive decline. In this work, we review a narrow but significant subset of chronic peripheral inflammatory conditions, describe how these pathologies are associated with the preponderance of neuroinflammation, and posit that we may exploit peripheral immune processes to design interventional, preventative therapies for LOAD. We then provide a comprehensive overview of notable treatment paradigms that have demonstrated considerable merit toward treating these disorders.
Early Dendritic Dystrophy in Human Brains With Primary Age-Related Tauopathy
Authors: Shi Yan-Bin , Tu Tian , Jiang Juan , Zhang Qi-Lei , Ai Jia-Qi , Pan Aihua , Manavis Jim , Tu Ewen , Yan Xiao-Xin
Published: December 2020

Dystrophic neurites (DNs) are found in many neurological conditions such as traumatic brain injury and age-related neurodegenerative diseases. In Alzheimer’s disease (AD) specifically, senile plaques containing silver-stained DNs were already described in the original literature defining this disease. These DNs could be both axonal and dendritic in origin, while axonal dystrophy relative to plaque formation has been more extensively studied. Here, we demonstrate an early occurrence of dendritic dystrophy in the hippocampal CA1 and subicular regions in human brains (n = 23) with primary age-related tauopathy (PART), with neurofibrillary tangle (NFT) burden ranging from Braak stages I to III in the absence of cerebral β-amyloid (Aβ) deposition. In Bielschowsky’s silver stain, segmented fusiform swellings on the apical dendrites of hippocampal and subicular pyramidal neurons were observed in all the cases, primarily over the stratum radiatum (s.r.). The numbers of silver-stained neuronal somata and dendritic swellings counted over CA1 to subiculum were positively correlated among the cases. Swollen dendritic processes were also detected in sections immunolabeled for phosphorylated tau (pTau) and sortilin. In aged and AD brains with both Aβ and pTau pathologies, silver- and immunolabeled dystrophic-like dendritic profiles occurred around and within individual neuritic plaques. These findings implicate that dendritic dystrophy can occur among hippocampal pyramidal neurons in human brains with PART. Therefore, as with the case of axonal dystrophy reported in literature, dendritic dystrophy can develop prior to Alzheimer-type plaque and tangle formation in the human brain.
Quality of Stroke Patient Information Applied in Randomized Controlled Trials—Literature Review
Authors: Alegiani Anna C. , Rahn Anne C. , Steckelberg Anke , Thomalla Götz , Heesen Christoph , Köpke Sascha
Published: December 2020

Background: Strokes have a huge impact on patients' quality of life. Although there are potentially effective secondary preventions and treatment options for stroke patients, adherence is mostly low. Low disease and treatment-related knowledge and, consequently, a lack of informed decision-making in stroke patients may contribute to this problem. However, stroke patient information did not seem to have relevant effects on patients' knowledge in randomized controlled trials. One contributing factor may be the lack of thoroughly developed patient information materials.

Methods: We aimed to evaluate the quality of patient information materials for stroke patients by using randomized controlled trials, applying quality criteria for evidence-based patient information (EBPI). We conducted a literature search (MEDLINE, Embase, CINAHL, PsycINFO, and CENTRAL). To be included in the review, research had to be randomized controlled trials that provided stroke patient information, were published in English, and had knowledge assessed as the primary endpoint. Authors of primary studies were contacted and asked for information materials applied.

Results: We screened 15,507 hits and identified 30 eligible studies. Information materials were available for only eight studies. Analyses revealed that all available materials had important shortcomings concerning EBPI quality criteria [concerning, for example, structural information (e.g., reporting conflicts of interest), content information (e.g., reporting sources of information), or comprehensive descriptions of treatment effects and side effects]. Frequently, treatment effects were reported only narratively without providing absolute numbers, values, or frequencies.

Conclusion: Quality of materials differed, but none sufficiently fulfilled EBPI quality criteria. Unsatisfactory trial results concerning patient knowledge and patient involvement in decision-making may at least partially be explained by limitations of the provided materials. Future patient information should consider EBPI quality criteria.
Nocebo-Hypothesis Cognitive Behavioral Therapy (NH-CBT) for Persons With Functional Neurological Symptoms (Motor Type): Design and Implementation of a Randomized Active-Controlled Trial
Authors: Richardson Matt , Kleinstäuber Maria , Wong Dana
Published: December 2020

Introduction: Functional Neurological Symptom Disorders (FNSD) are associated with high levels of disability and immense direct and indirect health costs. An innovative interdisciplinary rehabilitation approach for individuals with functional neurological symptoms of motor type–Nocebo-Hypothesis Cognitive Behavioral Therapy (NH-CBT)—combines CBT and movement retraining with video feedback embedded in a comprehensive explanatory model of the etiology of FNSD.

Methods: This protocol describes the development and implementation of a phase II, parallel group, randomized controlled trial with blinded outcome assessors to compare the efficacy of NH-CBT with an active control condition (supportive counseling and movement retraining). Individuals meeting diagnostic criteria of an FNSD or psychogenic movement disorder will be randomly assigned to one of the 8-week interventions. Self-report scales of motor and other physical symptoms, symptom-related psychological variables, and assessor ratings of participants' mobility will be administered at baseline, and at 8- and 16-week follow-up. Adverse events will be monitored across all sessions and therapeutic alliance will be measured at the end of therapy. The primary statistical analysis will test the hypothesis that NH-CBT is more effective than the control intervention at the 8-week follow-up.

Discussion: The therapeutic strategies of NH-CBT are theory-driven by assumptions of the predictive coding model of the etiology of FNSD. Strengths and limitations of this trial will be discussed.

Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR; identifier: ACTRN12620000550909).
The Blood Component Iron Causes Neuronal Apoptosis Following Intracerebral Hemorrhage via the PERK Pathway
Authors: Wu Muyao , Gao Rong , Dang Baoqi , Chen Gang
Published: December 2020

PERK signaling pathway plays an important role in neuronal apoptosis after Intracerebral hemorrhage (ICH). ICH can cause the release of blood components into the brain. However, which component in the blood plays a major role still unclear. This study was designed to investigate the activation of the PERK pathway in different blood components after ICH and explore which components have major relationships with neuronal apoptosis. Eighty-five Sprague–Dawley rats were used to establish an ICH model. Western blot (WB) and immunofluorescence (IF) were used to evaluate the expression of the PERK pathway. TUNEL staining, FJC staining and neurological score were used to evaluate neuronal apoptosis and necrosis after ICH. The results showed that protein levels of p-PERK and p-eIF2α were upregulated following ICH with the injection of Fe3+ and Fe2+ after 48 h. Then, deferoxamine (DFX) was used to study the roles of Fe3+ in ICH through the PERK signaling pathway. The results showed that injection of DFX reversed increasing protein levels and prevented neuronal apoptosis. Thus, iron plays an important role in ICH through the PERK signaling pathway. Furthermore, the reduction of iron demonstrates neuroprotective effects in ICH. This suggests that targeting intervention of the iron and PERK pathway could be an effective treatment strategy to improve ICH prognosis.
Testing the Specificity of Predictors of Reading, Spelling and Maths: A New Model of the Association Among Learning Skills Based on Competence, Performance and Acquisition
Authors: Zoccolotti Pierluigi , De Luca Maria , Marinelli Chiara Valeria , Spinelli Donatella
Published: December 2020

In a previous study (Zoccolotti et al., 2020) we examined reading, spelling, and maths skills in an unselected group of 129 Italian children attending fifth grade by testing various cognitive predictors; results showed a high degree of predictors’ selectivity for each of these three behaviors. In the present study, we focused on the specificity of the predictors by performing cross-analyses on the same dataset; i.e., we predicted spelling and maths skills based on reading predictors, reading based on maths predictors and so on. Results indicated that some predictors, such as the Orthographic Decision and the Arithmetic Facts tests, predicted reading, spelling and maths skills in similar ways, while others predicted different behaviors but only for a specific parameter, such as fluency but not accuracy (as in the case of RAN), and still others were specific for a single behavior (e.g., Visual-auditory Pseudo-word Matching test predicted only spelling skills). To interpret these results, we propose a novel model of learning skills separately considering factors in terms of competence, performance and acquisition (automatization). Reading, spelling and calculation skills would depend on the development of discrete and different abstract competences (accounting for the partial dissociations among learning disorders reported in the literature). By contrast, overlap among behaviors would be accounted for by defective acquisition in automatized responses to individual “instances”; this latter skill is item specific but domain independent. Finally, performance factors implied in task’s characteristics (such as time pressure) may contribute to the partial association among learning skills. It is proposed that this new model may provide a useful base for interpreting the diffuse presence of comorbidities among learning disorders.
Hippocampal Neurotransmitter Inhibition Suppressed During Gaming Explained by Skill Rather Than Gamer Status
Authors: Prena Kelsey , Cheng Hu , Newman Sharlene D.
Published: December 2020

Goal-directed spatial decision making video games combine spatial mapping, memory, and reward; all of which can involve hippocampal excitation through suppression of an inhibitory neurotransmitter, γ-aminobutyric acid (GABA). In this study, GABA was measured before and after 30 min of video game play within a voxel around the hippocampus. It was predicted that all participants would experience a decrease in GABA during gaming as a result of in-game rewards; and, those who were most competitive with the goal-directed spatial decision making game would display lower hippocampal GABA concentrations after gaming. Those who were not competitive, because they were too skilled or not skilled enough, would demonstrate higher hippocampal GABA concentrations after gaming. While there were no significant differences in hippocampal GABA before and after gaming for gamers and non-gamers alike, there was a significant quadratic regression between performance on a spatial working memory task and post-gaming hippocampal GABA concentrations.
Amino Acid Profiling and Chemometric Relations of Black Dwarf Honey and Bee Pollen
Authors: Sommano Sarana Rose , Bhat Farhan M. , Wongkeaw Malaiporn , Sriwichai Trid , Sunanta Piyachat , Chuttong Bajaree , Burgett Michael
Published: December 2020

This research reports the characterization of bee pollen of Apis andreniformis colonies on the basis of morphology, proximate composition, the amino acid, and nutritive patterns in relation with their honey. The pollen gains of the sampling colonies revealed variations in their structure, symmetry, and sculpture. The exile surfaces of the pollens showed psilate, scabrate, clavate, and echinate types of morphology. Total amino acid content of black dwarf honeybee collected pollen (150 mg/g) was found significantly higher than that of honey (15 mg/g) from the same colony. Threonine, phenylalanine, and leucine were among the highest essential amino acid types found in the analyzed pollen and honey samples. The proline content in both products was found the lowest comparing to other amino acid types. The moisture content of the honey samples were found to exceed the limit as prescribed by Codex Alimentarius Commission (<20%). The ash content of the analyzed samples was mostly within the limits (<0.6%) prescribed by international norms. The fat content of the pollens varied from 5.01 to 5.05%, and the honey showed zero fat content. The carbohydrate content in the honey samples was found to differ significantly from each other with a maximum content (73.16%), and the lowest carbohydrate content was 67.80%. The pollen and honey samples were found to have positive effect on in vitro digestibility of proteins.
Circulating Long Noncoding RNAs Act as Diagnostic Biomarkers in Non-Small Cell Lung Cancer
Authors: Yuan Shuai , Xiang Ying , Guo Xiaoping , Zhang Yao , Li Chengying , Xie Weijia , Wu Na , Wu Long , Cai Tongjian , Ma Xiangyu , Yu Zubin , Bai Li , Li Yafei
Published: December 2020

Identification of novel effective early diagnostic biomarkers may provide alternative strategies to reduce the mortality for non-small cell lung cancer (NSCLC) patients. Circulating long non-coding RNAs (lncRNAs) have emerged as a new class of promising cancer biomarkers. Our study aimed to identify circulating lncRNAs for diagnosing NSCLC. A total 528 plasma samples were continuously collected and allocated to four progressive phases: discovery, training, verification, and expansion phases. The expression of candidate lung cancer related lncRNAs were detected using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). We identified a 4-lncRNA panel (RMRP, NEAT1, TUG1, and MALAT1) that provided a high diagnostic value in NSCLC (AUC = 0.86 and 0.89 for training and verification phase, respectively). Subgroup analyses showed that the 4-lncRNA panel had a sensitivity of 78.95% [95% confidence interval (CI) = 62.22%–89.86%] in stage I-II patients and 75.00% (95% CI = 52.95%–89.40%) in patients with small tumor size (≤3cm). Notably, the sensitivity of 4-lncRNA panel was significantly higher than that of routine protein panels in adenocarcinoma (CEA, CA125, and CYFRA21-1, 86.30% vs. 73.96%). Adding 4-lncRNA to protein markers significantly improved the diagnostic capacity in both adenocarcinoma (AUC=0.85, 95% CI = 0.78–0.91) and squamous cell carcinoma (AUC=0.93, 95% CI = 0.86–0.97). In conclusion, we identified a plasma 4-lncRNA panel that has considerable clinical value in diagnosing NSCLC. The 4-lncRNA panel could improve the diagnostic values of routine tumor protein markers in diagnosing NSCLC. Circulating lncRNAs could be used as promising candidates for NSCLC diagnosis.
A Prognostic Microenvironment-Related Immune Signature via ESTIMATE (PROMISE Model) Predicts Overall Survival of Patients With Glioma
Authors: Qiu Huaide , Li Yongqiang , Cheng Shupeng , Li Jiahui , He Chuan , Li Jianan
Published: December 2020

Objective

In the development of immunotherapies in gliomas, the tumor microenvironment (TME) needs to be investigated. We aimed to construct a prognostic microenvironment-related immune signature via ESTIMATE (PROMISE model) for glioma.

Methods

Stromal score (SS) and immune score (IS) were calculated via ESTIMATE for each glioma sample in the cancer genome atlas (TCGA), and differentially expressed genes (DEGs) were identified between high-score and low-score groups. Prognostic DEGs were selected via univariate Cox regression analysis. Using the lower-grcade glioma (LGG) data set in TCGA, we performed LASSO regression based on the prognostic DEGs and constructed a PROMISE model for glioma. The model was validated with survival analysis and the receiver operating characteristic (ROC) in TCGA glioma data sets (LGG, glioblastoma multiforme [GBM] and LGG+GBM) and Chinese glioma genome atlas (CGGA). A nomogram was developed to predict individual survival chances. Further, we explored the underlying mechanisms using gene set enrichment analysis (GSEA) and Cibersort analysis of tumor-infiltrating immune cells between risk groups as defined by the PROMISE model.

Results

We obtained 220 upregulated DEGs and 42 downregulated DEGs in both high-IS and high-SS groups. The Cox regression highlighted 155 prognostic DEGs, out of which we selected 4 genes (CD86, ANXA1, C5AR1, and CD5) to construct a PROMISE model. The model stratifies glioma patients in TCGA as well as in CGGA with distinct survival outcome (P<0.05, Hazard ratio [HR]>1) and acceptable predictive accuracy (AUCs>0.6). With the nomogram, an individualized survival chance could be predicted intuitively with specific age, tumor grade, Isocitrate dehydrogenase (IDH) status, and the PROMISE risk score. ROC showed significant discrimination with the area under curves (AUCs) of 0.917 and 0.817 in TCGA and CGGA, respectively. GSEA between risk groups in both data sets were significantly enriched in multiple immune-related pathways. The Cibersort analysis highlighted four immune cells, i.e., CD 8 T cells, neutrophils, follicular helper T (Tfh) cells, and Natural killer (NK) cells.

Conclusions

The PROMISE model can further stratify both LGG and GBM patients with distinct survival outcomes.These findings may help further our understanding of TME in gliomas and shed light on immunotherapies.
Apatinib Mesylate Inhibits the Proliferation and Metastasis of Epithelioid Malignant Peritoneal Mesothelioma In Vitro and In Vivo
Authors: Yang Zhi-Ran , Chen Zhi-Gao , Du Xue-Mei , Li Yan
Published: December 2020

Objective

Malignant peritoneal mesothelioma (MPM) is a rare malignancy with few effective molecular therapies. In this study, we evaluated the anti-tumor activity and safety of apatinib, a vascular endothelial growth factor receptor 2 inhibitor, in MPM in vitro and in vivo.

Methods

We established several patient-derived xenograft (PDX) models and primary cell lines of MPM. The cell lines were used to study the effects of apatinib on proliferation, cell cycle, migration, and apoptosis by CCK8, flow cytometry, wound-healing, Transwell, DAPI staining, and caspase-3 assays, respectively. For in vivo study, apatinib was delivered by gastric gavage into PDX models, and then efficacy and toxicity were determined by experimental peritoneal cancer index (ePCI) score and pathological examinations.

Results

Our results showed that apatinib significantly inhibited the proliferation and migration of MPM cells in vitro and induced cell cycle arrest. Studies on PDX models concurred that apatinib effectively suppressed subphrenic and liver invasions of nude mice. Moreover, histopathological analysis found that lymphocyte infiltration, coagulation necrosis and eosinophilic cell fragments were detected in tumor tissues after apatinib treatment. Apatinib showed no obvious effects on body mass of models and did not affect function of important organs, except for occasional focal lymphoid infiltration of liver (16.7%) and cardiac muscle (16.7%).

Conclusions

We successfully established MPM PDX models and primary cell lines, and confirmed that apatinib effectively inhibited proliferation and metastasis of MPM in vitro and in vivo study.
Paclitaxel Plus Platinum Neoadjuvant Chemotherapy Followed by Surgery Versus Primary Surgery in Locally Advanced Cervical Cancer—A Propensity Score Matching Analysis
Authors: Zhang Yanan , Li Bin , Wang Yating , Liu Shuanghuan , Wang Haibo
Published: December 2020

Objective

To compare the efficacy and safety of neoadjuvant chemotherapy followed by surgery (NACTS) and primary surgery (PS) in locally advanced cervical cancer (LACC).

Methods

LACC (stage IB2/IIA2, FIGO 2009) patients who accepted NACTS or PS in the Cancer Hospital of the Chinese Academy of Medical Sciences from 2007 to 2017 were enrolled, and a database was established. A 1:1 ratio propensity score matching (PSM) was performed for the NACTS group and PS group according to pretreatment characteristics. After PSM, the clinicopathological features and prognosis between the matched groups were compared.

Results

Of 802 cases in the database, 639 met the inclusion criteria, with 428 received paclitaxel plus platinum NACTS, and 211 received PS. After PSM, the two groups had comparable pretreatment characteristics, with 190 cases in each group. In the NACTS group, the operation parameters were similar to the PS group except for the longer operation time (median 255 min vs. 239 min, P = 0.007); pathological intermediate-risk factors including tumor diameter (P < 0.001) and LVSI(+) (P < 0.001) were significantly decreased; fewer patients were with ≥2 intermediate-risk factors (10.5 vs. 53.2%, P < 0.001) so that the rate of adjuvant radiotherapy was reduced (54.2 vs. 70.0%, P = 0.002). DFS and OS were similar between the NACTS group and PS group (P > 0.05). However, for patients with tumor diameter ≥5 cm or SCC ≥5 ng/ml, DFS of the NACTS group was significantly prolonged (P = 0.016, P = 0.007).

Conclusion

Paclitaxel plus platinum neoadjuvant chemotherapy can reduce adjuvant radiotherapy by decreasing pathological risk factors. Patients with tumor diameter ≥5 cm or SCC ≥5 ng/ml may obtain survival benefits.
Prevalence of Therapeutic use of Opioids in Chronic non-Cancer Pain Patients and Associated Factors: A Systematic Review and Meta-Analysis
Authors: De Sola Helena , Dueñas María , Salazar Alejandro , Ortega-Jiménez Patricia , Failde Inmaculada
Published: December 2020

Objectives:To determine the prevalence and factors associated with the use of opioids among patients with chronic non-cancer pain (CNCP).

Methods:A systematic review and meta-analysis. Comprehensive literature searches in Medline-PubMed, Embase and SCOPUS databases. Original studies published between 2009 and 2019 with a cross-sectional design were included. The quality of the studies was assessed with Critical Appraisal Checklist for Studies Reporting Prevalence Data from the Joanna Briggs Institute. Protocol registered in the International Prospective Register of Systematic Reviews with reference number: CRD42019137990.

Results:Out of the 1,310 potential studies found, 25 studies fulfilled the inclusion criteria. Most of the studies were of high quality. High levels of heterogeneity were found in the studies included. In the general population, the prevalence of long-term opioid use was 2.3% (95% CI: 1.5–3.6%), the prevalence of short-term opioid use was 8.1% (95% CI: 5.6–11.6%), and among people with chronic low back pain it was 5.8% (95% CI: 0.5–45.5%). The prevalence of opioid use among patients from the health records or medical surveys was 41% (95% CI: 23.3–61.3%). Finally, in patients with musculoskeletal pain, the prevalence was 20.5% (95% CI: 12.9–30.9%) and in patients with fibromyalgia, 24.5% (95% CI: 22.9–26.2%). A higher prevalence of opioid use was observed among men, younger people, patients receiving prescriptions of different types of drugs, smokers and patients without insurance or with noncommercial insurance. In addition, non-white and Asian patients were less likely to receive opioids than non-Hispanic white patients.

Conclusions:The prevalence of opioid use among patients with CNCP was higher in subjects with short or occasional use compared to those with long-term use. Men, younger people, more chronic pain conditions, and patients without insurance or with noncommercial insurance were most related to opioid use. However, non-white and Asian patients, and those treated by a physician trained in complementary medicine were less likely to use opioids.
Capsular Polysaccharide From Bacteroides fragilis Protects Against Ulcerative Colitis in an Undegraded Form
Authors: Zheng Lijun , Luo Meihua , Kuang Gaobo , Liu Yangyang , Liang Debao , Huang Haiqing , Yi Xiaomin , Wang Congfeng , Wang Ye , Xie Qiuling , Zhi Fachao
Published: December 2020

The prominent human symbiont Bacteroides fragilis protects animals from intestinal diseases, such as ulcerative colitis, and its capsular polysaccharide plays a key role in reducing inflammation. B. fragilis strain ZY-312 was isolated from the feces of a healthy breast-fed infant, and the zwitterionic capsular polysaccharide zwitterionic polysaccharide, TP2, was extracted. In rats with 2,4-dinitrobenzenesulfonic acid (DNBS)-induced enteritis, TP2 at an optimal dose of 2.5 mg/kg could significantly alleviate enteritis and reduced the degree of intestinal adhesions, the intestinal ulcer area, and the incidence of ulcers in rats. To understand the underlying mechanism, TP2 was labeled with Fluorescein isothiocyanate and orally administered at a dose of 2.5 mg/kg in rats. TP2 was mainly distributed in the cecum and colorectum, but it was not detected in the blood and other organs except that a compound with a molecular weight greater than that of TP2-FITC was found in liver tissue. During the absorption, distribution, metabolism, and excretion, TP2 was indigestible. These results were further confirmed by investigation in the simulated gastric, intestinal fluid, and colonic fluid with fecal microbiota in vitro, where TP2 remained unaltered at different time points. Furthermore, flora composition was analyzed in simulated colonic fluid with TP2 added and it was found that TP2 increased the abundance of Faecalibacterium, Enterococcus romboutsia, and Ruminococcaceae, whereas the abundance of the phylum Proteobacteria represented by Sutterella, Desulfovibrio, and Enterobacteriaceae was decreased. However, the amount of short-chain fatty acids in the simulated colonic fluid was not changed by intestinal flora post-TP2 addition. In conclusion, these findings confirmed that TP2, a capsular polysaccharide of B. fragilis, protects against ulcerative colitis in an undegraded form.
Hydroxychloroquine in COVID-19 Patients: Pros and Cons
Authors: Younis Nour K. , Zareef Rana O. , Al Hassan Sally N. , Bitar Fadi , Eid Ali H. , Arabi Mariam
Published: December 2020

The pandemic of COVID-19, caused by SARS-CoV-2, has recently overwhelmed medical centers and paralyzed economies. The unparalleled public distress caused by this pandemic mandated an urgent quest for an effective approach to manage or treat this disease. Due to their well-established anti-infectious and anti-inflammatory properties, quinine derivatives have been sought as potential therapies for COVID-19. Indeed, these molecules were originally employed in the treatment and prophylaxis of malaria, and later in the management of various autoimmune rheumatic and dermatologic diseases. Initially, some promising results for the use of hydroxychloroquine (HCQ) in treating COVID-19 patients were reported by a fewin vitroandin vivostudies. However, current evidence is not yet sufficiently solid to warrant its use as a therapy for this disease. Additionally, the therapeutic effects of HCQ are not without many side effects, which range from mild gastrointestinal effects to life-threatening cardiovascular and neurological effects. In this review, we explore the controversy associated with the repurposing of HCQ to manage or treat COVID-19, and we discuss the cellular and molecular mechanisms of action of HCQ.
Coming Back to Physiology: Extra Hepatic Functions of Proprotein Convertase Subtilisin/Kexin Type 9
Authors: Schlüter Klaus-Dieter , Wolf Annemarie , Schreckenberg Rolf
Published: December 2020

Neuronal apoptosis regulated convertase-1 (NARC-1), now mostly known as proprotein convertase subtilisin/kexin type 9 (PCSK9), has received a lot of attention due to the fact that it is a key regulator of the low-density lipoprotein (LDL) receptor (LDL-R) and is therefore involved in hepatic LDL clearance. Within a few years, therapies targeting PCSK9 have reached clinical practice and they offer an additional tool to reduce blood cholesterol concentrations. However, PCSK9 is almost ubiquitously expressed in the body but has less well-understood functions and target proteins in extra hepatic tissues. As such, PCSK9 is involved in the regulation of neuronal survival and protein degradation, it affects the expression of the epithelial sodium channel (ENaC) in the kidney, it interacts with white blood cells and with cells of the vascular wall, and it modifies contractile activity of cardiomyocytes, and contributes to the regulation of cholesterol uptake in the intestine. Moreover, under stress conditions, signals from the kidney and heart can affect hepatic expression and thereby the plasma concentration of PCSK9 which then in turn can affect other target organs. Therefore, there is an intense relationship between the local (autocrine) and systemic (endocrine) effects of PCSK9. Although, PCSK9 has been recognized as a ubiquitously expressed modifier of cellular function and signaling molecules, its physiological role in different organs is not well-understood. The current review summarizes these findings.
Programmed Cell Death in Stigmatic Papilla Cells Is Associated With Senescence-Induced Self-Incompatibility Breakdown in Chinese Cabbage and Radish
Authors: Huang Jiabao , Su Shiqi , Dai Huamin , Liu Chen , Wei Xiaochun , Zhao Yanyan , Wang Zhiyong , Zhang Xiaowei , Yuan Yuxiang , Yu Xiaolin , Zhang Changwei , Li Ying , Zeng Weiqing , Wu Hen-Ming , Cheung Alice Y. , Wang Shufen , Duan Qiaohong
Published: December 2020

Self-incompatibility (SI) is a genetic mechanism flowering plants adopted to reject self-pollen and promote outcrossing. In the Brassicaceae family plants, the stigma tissue plays a key role in self-pollen recognition and rejection. We reported earlier in Chinese cabbage (Brassica rapa) that stigma tissue showed upregulated ethylene responses and programmed cell death (PCD) upon compatible pollination, but not in SI responses. Here, we show that SI is significantly compromised or completely lost in senescent flowers and young flowers of senescent plants. Senescence upregulates senescence-associated genes in B. rapa. Suppressing their expression in young stigmas by antisense oligodeoxyribonucleotide abolishes compatible pollination-triggered PCD and inhibits the growth of compatible pollen tubes. Furthermore, ethylene biosynthesis genes and response genes are upregulated in senescent stigmas, and increasing the level of ethylene or inhibiting its response increases or decreases the expression of senescence-associated genes, respectively. Our results show that senescence causes PCD in stigmatic papilla cells and is associated with the breakdown of SI in Chinese cabbage and in radish.
Use of Stroop Test for Sports Psychology Study: Cross-Over Design Research
Authors: Takahashi Shinji , Grove Philip M.
Published: December 2020

Background:In sports psychology research, the Stroop test and its derivations are commonly used to investigate the benefits of exercise on cognitive function. The measures of the Stroop test and the computed interference often have different interclass correlation coefficients (ICC). However, the ICC is never reported in cross-over designs involving multiple variances associated with individual differences.

Objective:We investigated the ICC of the Stroop neutral and incongruent tests and interference (neutral test—incongruent test), and reverse Stroop task using the linear mixed model.

Methods:Forty-eight young adults participated in a cross-over design experiment composed of 2 factors: exercise mode (walking, resistance exercise, badminton, and seated rest as control) and time (pre- and post-tests). Before and after each intervention, participants completed the Stroop neutral and incongruent, and the reverse-Stroop neutral and incongruent tests. We analyzed for each test performance and interference and calculated ICC using the linear mixed model.

Results:The linear mixed model found a significant interaction of exercise mode and time for both the Stroop and reverse-Stroop tasks, suggesting that exercise mode influences the effect of acute exercise on inhibitory function. On the other hand, there was no significant effect of exercise mode for both the Stroop and reverse-Stroop interference. The results also revealed that calculating both the Stroop and reverse-Stroop interference resulted in smaller ICCs than the ICCs of the neutral and incongruent tests for both the Stroop and reverse-Stroop tasks.

Conclusion:The Stroop and reverse-Stroop interferences are known as valid measures of the inhibitory function for cross-sectional research design. However, to understand the benefits of acute exercise on inhibitory function comprehensively by cross-over design, comparing the incongruent test with the neutral test also seems superior because these tests have high reliability and statistical power.