bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardial Work Efficiency, A Novel Measure of Myocardial Dysfunction, Is Reduced in COVID-19 Patients and Associated With In-Hospital Mortality
Authors: Minhas Anum S. , Gilotra Nisha A. , Goerlich Erin , Metkus Thomas , Garibaldi Brian T. , Sharma Garima , Bavaro Nicole , Phillip Susan , Michos Erin D. , Hays Allison G. 
Published: June 2021

Background: Although troponin elevation is common in COVID-19, the extent of myocardial dysfunction and its contributors to dysfunction are less well-characterized. We aimed to determine the prevalence of subclinical myocardial dysfunction and its association with mortality using speckle tracking echocardiography (STE), specifically global longitudinal strain (GLS) and myocardial work efficiency (MWE). We also tested the hypothesis that reduced myocardial function was associated with increased systemic inflammation in COVID-19.Methods and Results: We conducted a retrospective study of hospitalized COVID-19 patients undergoing echocardiography (n = 136), of whom 83 and 75 had GLS (abnormal &gt;−16%) and MWE (abnormal &lt;95%) assessed, respectively. We performed adjusted logistic regression to examine associations of GLS and MWE with in-hospital mortality. Patients were mean 62 ± 14 years old (58% men). While 81% had normal left ventricular ejection fraction (LVEF), prevalence of myocardial dysfunction was high by STE; [39/83 (47%) had abnormal GLS; 59/75 (79%) had abnormal MWE]. Higher MWE was associated with lower in-hospital mortality in unadjusted [OR 0.92 (95% CI 0.85–0.99); p = 0.048] and adjusted models [aOR 0.87 (95% CI 0.78–0.97); p = 0.009]. In addition, increased systemic inflammation measured by interleukin-6 level was associated with reduced MWE.Conclusions: Subclinical myocardial dysfunction is common in COVID-19 patients with clinical echocardiograms, even in those with normal LVEF. Reduced MWE is associated with higher interleukin-6 levels and increased in-hospital mortality. Non-invasive STE represents a readily available method to rapidly evaluate myocardial dysfunction in COVID-19 patients and can play an important role in risk stratification.
Sediment Metal Contamination, Bioavailability, and Oxidative Stress Response in Mangrove Avicennia marina in Central Red Sea
Authors: Alhassan Abdullahi Bala , Aljahdali Mohammed Othman 
Published: June 2021

Anthropogenic activities have been on the increase in the urban environment and have led to contamination of the environment with toxic metals. However, mangrove plants’ response to heavy metal stress due to anthropogenic activities explains the metal bioavailability and its potential ecotoxicological effect. We carried out a multi-approach study to investigate i) if the concentrations of metals (Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Mo, Cd, Pb, Sr, and V) in mangroves at the central Red Sea are due to the anthropogenic influence and are above the sediment quality guidelines and ii) if an increase in metal concentration influences height and antioxidant enzyme (catalase, CAT; glutathione S-transferase, GST; and superoxide dismutase, SOD) activities in Avicennia marina. There were significant variations (p &lt; 0.05) in metal concentrations and antioxidants across the six mangrove ecosystems with higher concentrations at Al Lith (LT) and south Jeddah (SJ). Even though the concentrations of metals in mangrove leaves are slightly higher in LT than SJ, principal component analysis showed that higher concentrations of Cr, Co, Zn, Cd, and Pb in mangrove leaves from SJ influence higher antioxidant enzyme activities and the lowest average mangrove height (2.01 m). This suggests that higher metal concentrations be factors for the biggest stress in these mangrove ecosystems. However, among the 13 metals, Cr (82.07 mg/kg), Cu (41.29 mg/kg), and As (10.30 mg/kg) in sediments have values within the ERL range of probable effect, while Ni (53.09 mg/kg) was above the ERM threshold. Hence, there is need to focus on monitoring these metals in mangrove sediments and their anthropogenic sources.
Spatio-Temporal Variations of the PM2.5/PM10 Ratios and Its Application to Air Pollution Type Classification in China
Authors: Fan Hao , Zhao Chuanfeng , Yang Yikun , Yang Xingchuan 
Published: June 2021

Particulate Matter (PM) is an important indicator of the degree of air pollution. The PM type and the ratio of coarse and fine PM particles determine the ability to affect human health and atmospheric processes. Using the observation data across the country from 2015 to 2018, this study investigates the distribution and proportion of PM2.5 and PM10 at different temporal and spatial scales in mainland China; clarifies the PM2.5, PM10 and PM2.5/PM10 ratios interrelation; and classifies the dust, mixed, and anthropogenic type aerosol. It shows that the annual average concentration of PM2.5 and PM10 decreased by 10.55 and 8.78 μg m−3 in 4 years. PM2.5, PM10, and PM2.5/PM10 ratios show obvious while different seasonal variations. PM2.5 is high in winter and low in summer, while PM10 is high in winter and spring, and low in summer and autumn. Differently, the PM2.5/PM10 ratios are the highest in winter, and the lowest in spring. PM2.5/PM10 ratios show strong independence on PM2.5 and PM10, implying that it can provide extra information about the aerosol pollution such as aerosol type. A classification method about air pollution types is then further proposed based on probability distribution function (PDF) morphology of PM2.5/PM10 ratios. The results show that dust type mainly lies in the west of Hu-Line, mixed type pollution distributes near Hu-Line, and the anthropogenic type dominates over North China Plain and cities in southern China. The results provide insights into China’s future clean air policy making and environmental research.
Investigation of a Hypoxia-Immune-Related Microenvironment Gene Signature and Prediction Model for Idiopathic Pulmonary Fibrosis
Authors: Li Xinyu , Cai Haozheng , Cai Yufeng , Zhang Quyan , Ding Yinghe , Zhuang Quan 
Published: June 2021

BackgroundThere is growing evidence found that the role of hypoxia and immune status in idiopathic pulmonary fibrosis (IPF). However, there are few studies about the role of hypoxia and immune status in the lung milieu in the prognosis of IPF. This study aimed to develop a hypoxia-immune-related prediction model for the prognosis of IPF.MethodsHypoxia and immune status were estimated with microarray data of a discovery cohort from the GEO database using UMAP and ESTIMATE algorithms respectively. The Cox regression model with the LASSO method was used for identifying prognostic genes and developing hypoxia-immune-related genes. Cibersort was used to evaluate the difference of 22 kinds of immune cell infiltration. Three independent validation cohorts from GEO database were used for external validation. Peripheral blood mononuclear cell (PBMC) and bronchoalveolar lavage fluid (BALF) were collected to be tested by Quantitative reverse transcriptase-PCR (qRT-PCR) and flow cytometry from 22 clinical samples, including 13 healthy controls, six patients with non-fibrotic pneumonia and three patients with pulmonary fibrosis.ResultsHypoxia and immune status were significantly associated with the prognosis of IPF patients. High hypoxia and high immune status were identified as risk factors for overall survival. CD8+ T cell, activated CD4+ memory T cell, NK cell, activated mast cell, M1 and M0 macrophages were identified as key immune cells in hypoxia-immune-related microenvironment. A prediction model for IPF prognosis was established based on the hypoxia-immune-related one protective and nine risk DEGs. In the independent validation cohorts, the prognostic prediction model performed the significant applicability in peripheral whole blood, peripheral blood mononuclear cell, and lung tissue of IPF patients. The preliminary clinical specimen validation suggested the reliability of most conclusions.ConclusionsThe hypoxia-immune-based prediction model for the prognosis of IPF provides a new idea for prognosis and treatment.
Distinct Patterns of Myeloid Cell Infiltration in Patients With hrHPV-Positive and hrHPV-Negative Penile Squamous Cell Carcinoma: The Importance of Assessing Myeloid Cell Densities Within the Spatial Context of the Tumor
Authors: Rafael Tynisha S. , de Vries Hielke M. , Ottenhof Sarah R. , Hofland Ingrid , Broeks Annegien , de Jong Jeroen , Bekers Elise , Horenblas Simon , de Menezes Renée X. , Jordanova Ekaterina S. , Brouwer Oscar R. 
Published: June 2021

Comprehensive analysis of tumor infiltrating myeloid cells in the tumor microenvironment of penile squamous cell carcinoma (PSCC) is lacking. In this retrospective study, for the first time, PSCC resection specimens (N = 103) were annotated into the following compartments: intratumoral tumor (IT Tumor), intratumoral stroma (IT Stroma), peritumoral tumor (PT Tumor) and peritumoral stroma (PT Stroma) compartments. We then quantified CD14+, CD68+ and CD163+ myeloid cells within these compartments using an image analysis software and assessed their association with various clinical parameters, including high-risk human papillomavirus (hrHPV) status. In the total cohort, hrHPV status, grade of differentiation, age and tumor size were associated with myeloid cell densities. hrHPV+ tumors had higher infiltration rates of CD14+, CD68+ and CD163+ myeloid cells in the IT tumor compartment (p &lt; 0.001, for all) compared to hrHPV− tumors. Furthermore, when examining the association between compartment-specific infiltration and differentiation grade, increased myeloid cell densities in the IT tumor compartment were associated with a more advanced histological grade (p &lt; 0.001, for all). This association remained significant when the hrHPV− cohort (N = 60) was analyzed (CD14+ p = 0.001; CD68+ p &lt; 0.001; CD163+ p = 0.004). Subgroup analysis in the hrHPV+ group (N = 43) showed that high infiltration rates of CD68+ and CD163+ cells in the PT tumor compartment were associated with lymph node (LN) metastasis (p = 0.031 and p = 0.026, respectively). Regarding the association between myeloid cell densities and disease-specific survival, the risk of death was found to decrease slightly as the number of myeloid cells in the IT tumor compartment increased (CD14+ p = 0.04; CD68+ p = 0.05; CD163+ p = 0.02). However, after adjusting for hrHPV, no independent association between myeloid densities and disease-specific survival were found. Altogether, these findings demonstrate the importance of assessing myeloid cell densities within the spatial context of the tumor. Further studies are needed to unravel the specific phenotype of myeloid cells residing in the different compartments, their effect on clinical parameters and the impact of hrHPV on the recruitment of myeloid cell populations in PSCC.
Rationale and Design of Assessing the Effectiveness of Short-Term Low-Dose Lithium Therapy in Averting Cardiac Surgery-Associated Acute Kidney Injury: A Randomized, Double Blinded, Placebo Controlled Pilot Trial
Authors: Sharif Sairah , Chen Bohan , Brewster Pamela , Chen Tian , Dworkin Lance , Gong Rujun 
Published: June 2021

Background: Burgeoning pre-clinical evidence suggests that therapeutic targeting of glycogen synthase kinase 3β (GSK3β), a convergence point of multiple cellular protective signaling pathways, confers a beneficial effect on acute kidney injury (AKI) in experimental models. However, it remains unknown if GSK3β inhibition likewise mitigates AKI in humans. Cardiac surgery associated acute kidney injury (CSA-AKI) poses a significant challenge for clinicians and currently the only treatment available is general supportive measures. Lithium, an FDA approved mood stabilizer, is the best-known GSK3β inhibitor and has been safely used for over half a century as the first line regimen to treat bipolar affective disorders. This study attempts to examine the effectiveness of short term low dose lithium on CSA-AKI in human patients.Methods/Design: This is a single center, prospective, randomized, double blinded, placebo controlled pilot study on patients undergoing cardiac surgery with cardiopulmonary bypass. Patients will be randomized to receive a small dose of lithium or placebo treatment for three consecutive days. Renal function will be measured via creatinine as well as novel AKI biomarkers. The primary outcome is incidence of AKI according to Acute Kidney Injury Network (AKIN) criteria, and secondary outcomes include receipt of new dialysis, days on dialysis, days on mechanical ventilation, infections within 1 month of surgery, and death within 90 days of surgery.Discussion: As a standard selective inhibitor of GSK3β, lithium has been shown to exert a beneficial effect on tissue repair and regeneration upon acute injury in multiple organ systems, including the central nervous system and hematopoietic system. In experimental AKI, lithium at small doses is able to ameliorate AKI and promote kidney repair. Successful completion of this study will help to assess the effectiveness of lithium in CSA-AKI and could potentially pave the way for large-scale randomized trials to thoroughly evaluate the efficacy of this novel regimen for preventing AKI after cardiac surgery.Trial Registration: This study was registered prospectively on the 17th February 2017 at ClinicalTrials.gov (NCT03056248, https://clinicaltrials.gov/ct2/show/NCT03056248?term=NCT03056248&amp;draw=2&amp;rank=1).
Methylprednisolone Pulses Plus Tacrolimus in Addition to Standard of Care vs. Standard of Care Alone in Patients With Severe COVID-19. A Randomized Controlled Trial
Authors: Solanich Xavier , Antolí Arnau , Rocamora-Blanch Gemma , Padullés Núria , Fanlo-Maresma Marta , Iriarte Adriana , Mitjavila Francesca , Capdevila Olga , Riera-Mestre Antoni , Bas Jordi , Vicens-Zygmunt Vanesa , Niubó Jordi , Calvo Nahum , Bolivar Santiago , Rigo-Bonnin Raúl , Mensa-Vilaró Anna , Arregui Laura , Tebe Cristian , Videla Sebastià , Hereu Pilar , Corbella Xavier 
Published: June 2021

Introduction: Severe lung injury is triggered by both the SARS-CoV-2 infection and the subsequent host-immune response in some COVID-19 patients.Methods: We conducted a randomized, single-center, open-label, phase II trial with the aim to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) vs. SoC alone, in hospitalized patients with severe COVID-19. The primary outcome was time to clinical stability within 56 days after randomization.Results: From April 1 to May 2, 2020, 55 patients were prospectively included for subsequent randomization; 27 were assigned to the experimental group and 28 to the control group. The experimental treatment was not associated with a difference in time to clinical stability (hazard ratio 0.73 [95% CI 0.39–1.37]) nor most secondary outcomes. Median methylprednisolone cumulative doses were significantly lower (360 mg [IQR 360–842] vs. 870 mg [IQR 364–1451]; p = 0.007), and administered for a shorter time (median of 4.00 days [3.00–17.5] vs. 18.5 days [3.00–53.2]; p = 0.011) in the experimental group than in the control group. Although not statistically significant, those receiving the experimental therapy showed a numerically lower all-cause mortality than those receiving SoC, especially at day 10 [2 (7.41%) vs. 5 (17.9%); OR 0.39 (95% CI 0.05–2.1); p = 0.282]. The total number of non-serious adverse events was 42 in each the two groups. Those receiving experimental treatment had a numerically higher rate of non-serious infectious adverse events [16 (38%) vs. 10 (24%)] and serious infectious adverse events [7 (35%) vs. 3 (23%)] than those receiving SoC.Conclusions: The combined use of methylprednisolone pulses plus tacrolimus, in addition to the SoC, did not significantly improve the time to clinical stability or other secondary outcomes compared with the SoC alone in severe COVID-19. Although not statistically significant, patients receiving the experimental therapy had numerically lower all-cause mortality than those receiving SoC, supporting recent non-randomized studies with calcineurin inhibitors. It is noteworthy that the present trial had a limited sample size and several other limitations. Therefore, further RCTs should be done to assess the efficacy and safety of tacrolimus to tackle the inflammatory stages of COVID-19.Clinical Trial Registration: Identifier [NCT04341038/EudraCT: 2020-001445-39].
Exploring the Key Genes and Identification of Potential Diagnosis Biomarkers in Alzheimer’s Disease Using Bioinformatics Analysis
Authors: Yu Wuhan , Yu Weihua , Yang Yan , Lü Yang 
Published: June 2021

BackgroundAlzheimer’s disease (AD) is one of the major threats of the twenty-first century and lacks available therapy. Identification of novel molecular markers for diagnosis and treatment of AD is urgently demanded, and genetic biomarkers show potential prospects.MethodWe identify and intersected differentially expressed genes (DEGs) from five microarray datasets to detect consensus DEGs. Based on these DEGs, we conducted Gene Ontology (GO), performed the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, constructed a protein—protein interaction (PPI) network, and utilized Cytoscape to identify hub genes. The least absolute shrinkage and selection operator (LASSO) logistic regression was applied to identify potential diagnostic biomarkers. Gene set enrichment analysis (GSEA) was performed to investigate the biological functions of the key genes.ResultWe identified 608 consensus DEGs, several dysregulated pathways, and 18 hub genes. Sixteen hub genes dysregulated as AD progressed. The diagnostic model of 35 genes was constructed, which has a high area under the curve (AUC) value in both the validation dataset and combined dataset (AUC = 0.992 and AUC = 0.985, respectively). The model can also differentiate mild cognitive impairment and AD patients from controls in two blood datasets. Brain-derived neurotrophic factor (BDNF) and WW domain-containing transcription regulator protein 1 (WWTR1), which are associated with the Braak stage, Aβ 42 levels, and β-secretase activity, were identified as critical genes of AD.ConclusionOur study identified 16 hub genes correlated to the neuropathological stage and 35 potential biomarkers for the diagnosis of AD. WWTR1 were identified as candidate genes for future studies. This study deepens our understanding of the transcriptomic and functional features and provides new potential diagnostic biomarkers and therapeutic targets for AD.
Implications of Habitual Alcohol Intake With the Prognostic Significance of Mean Corpuscular Volume in Stage II-III Colorectal Cancer
Authors: Liu Qi , Yang Yufei , Li Xinxiang , Zhang Sheng 
Published: June 2021

ObjectiveTo elucidate the prognostic significance of mean corpuscular volume (MCV), with implications of habitual alcohol intake in stage II-III colorectal cancer (CRC).BackgroundMCV had the potential to become an ideal prognostic biomarker and be put into clinical application. Few studies, however, have explored whether habitual alcohol intake which greatly increased the value of MCV would affect the prognostic role of MCV.MethodsEligible patients were identified from the CRC database of Fudan University Shanghai Cancer Center (FUSCC) between January 2012 and December 2013. Survival analyses were constructed using the Kaplan–Meier method to evaluate the survival time distribution, and the log-rank test was used to determine the survival differences. Univariate and multivariate Cox proportional hazard models were built to calculate the hazard ratios of different prognostic factors.ResultsA total of 694 patients diagnosed with stage II-III CRC between January 2012 and December 2013 were identified from FUSCC. Low pretreatment MCV was independently associated with 72.0% increased risk of overall mortality compared with normal MCV (HR = 1.720, 95%CI =1.028-2.876, P =0.039, using normal MCV as the reference). In patients with habitual alcohol intake, however, pretreatment MCV positively correlated with the mortality (P = 0.02) and tumor recurrence (P = 0.002) after adjusting for other known prognostic factors.ConclusionsIn CRC patients without habitual alcohol intake, low (&lt;80 fL) level of pretreatment MCV was a predictor of poor prognosis. In patients with habitual alcohol intake, however, pretreatment MCV showed the opposite prognostic role, which would elicit many fundamental studies to elucidate the mechanisms behind.
Safety and Success of Lumbar Puncture in Young Infants: A Prospective Observational Study
Authors: Bedetti Luca , Lugli Licia , Marrozzini Lucia , Baraldi Alessandro , Leone Federica , Baroni Lorenza , Lucaccioni Laura , Rossi Cecilia , Roversi Maria F. , D'Amico Roberto , Iughetti Lorenzo , Berardi Alberto 
Published: June 2021

Objective:This study aims to evaluate safety and success rates of lumbar puncture (LP) and to identify factors associated with adverse events or failure of LP in infants.Methods:This two-center prospective observational study investigated infants younger than 90 days of age who underwent LP. Need for resuscitation oxygen desaturation (SpO2&lt; 90%), bradycardia and intraventricular hemorrhage were considered adverse events. LP failed if cerebrospinal spinal fluid was not collected or had traces of blood. Logistic regression analysis was used to evaluate whether corrected gestational age (GA), body weight at LP, position, and any respiratory support during LP affected SpO2desaturation or failure of LP.Results:Among 204 LPs, 134 were performed in full-term and 70 in pre-term born infants. SpO2desaturations occurred during 45 (22.4%) LPs. At multivariate analysis, lower GA at LP (p&lt; 0.001), non-invasive respiratory support (p0.007) and mechanical ventilation (p0.004) were associated with SpO2desaturations. Transient, self-resolving bradycardia occurred in 7 (3.4%) infants. Two infants had intraventricular hemorrhage detected within 72 h of LP. No further adverse events were registered. Failure of LP occurred in 38.2% of cases and was not associated with any of the factors evaluated.Conclusions:LP was safe in most infants. Body weight or GA at LP did not affect LP failure. These data are useful to clinicians, providing information on the safety of the procedure.