Publications by authors named "Yupeng Li"

143 Publications

Impact of Operative Timing in Infective Endocarditis with Cerebral Embolism-The Risk of Intermediate Deterioration.

J Clin Med 2021 May 15;10(10). Epub 2021 May 15.

Department of Cardiac Surgery, University Hospital, LMU Munich, 81377 Munich, Germany.

Cerebral embolism due to infective endocarditis (IE) is associated with significant morbidity and mortality. The optimal time-interval between symptomatic stroke and cardiac surgery remains unclear. This study aimed to analyze the patients' outcomes and define the potential risk factors with regard to surgical timing for IE patients with preoperative symptomatic cerebral embolism (CE). A total of 119 IE patients with CE were identified and analyzed with regard to operative timing: early (1-7 days), intermediate (8-21 days), and late (>22 days). The preoperative patient data, comorbidities and previous cardiac surgical procedures were analyzed to identify potential predictors and independent risk factors for in-hospital mortality using univariate and multivariate regression analysis. Actuarial survival was estimated by the Kaplan-Meier method. In-hospital mortality for the entire study cohort was 15.1% ( = 18), and in comparison, between groups was found to be highest in the intermediate surgical group (25.7%). Univariate analysis identified preoperative mechanical ventilation dependent respiratory insufficiency ( = 0.006), preoperative renal insufficiency ( = 0.019), age ( = 0.002), large vegetations ( = 0.018) as well as intermediate ( = 0.026), and late ( = 0.041) surgery as predictors of in-hospital mortality. The presence of large vegetations (>8 mm) ( = 0.019) and increased age ( = 0.037)-but not operative timing-were identified as independent risk factors for in-hospital mortality. In the presence of large vegetations (>8 mm), cardiac surgery should be performed early and independently from the entity of cerebral embolic stroke. Postponing surgery to achieve clinical stabilization and better postoperative outcomes of IE patients with CE is reasonable, however, worsening of the disease process with deterioration and resulting heart failure during the first 3 weeks after CE results in a significantly higher in-hospital mortality and inferior long-term survival.
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http://dx.doi.org/10.3390/jcm10102136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156108PMC
May 2021

Preparing Membrane Proteins for Simulation Using CHARMM-GUI.

Methods Mol Biol 2021 ;2302:237-251

School of Physics, Georgia Institute of Technology, Atlanta, GA, USA.

Molecular dynamics simulations of membrane proteins have grown dramatically in the last 20 years. Running these simulations first requires embedding the protein's three-dimensional structure in a lipid bilayer of a suitable composition, one that resembles its native environment. This step is far from trivial, especially for modeling heterogeneous mixtures of lipids. CHARMM-GUI, a webserver for simulation system preparation greatly simplifies this step, allowing for the construction of complex heterogeneous and/or asymmetric membranes. Here, we demonstrate how to use CHARMM-GUI to build the membrane for the outer-membrane protein BamA.
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http://dx.doi.org/10.1007/978-1-0716-1394-8_13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158057PMC
January 2021

Deep vein thrombosis and pulmonary embolism among hospitalized coronavirus disease 2019-positive patients predicted for higher mortality and prolonged intensive care unit and hospital stays in a multisite healthcare system.

J Vasc Surg Venous Lymphat Disord 2021 Apr 6. Epub 2021 Apr 6.

Division of Vascular Medicine of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn.

Objective: We assessed the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in hospitalized patients with coronavirus disease 2019 (COVID-19) compared with that in a matched cohort with similar cardiovascular risk factors and the effects of DVT and PE on the hospital course.

Methods: We performed a retrospective review of prospectively collected data from COVID-19 patients who had been hospitalized from March 11, 2020 to September 4, 2020. The patients were randomly matched in a 1:1 ratio by age, sex, hospital of admission, smoking history, diabetes mellitus, and coronary artery disease with a cohort of patients without COVID-19. The primary endpoint was the incidence of DVT/PE and the odds of developing DVT/PE using a conditional logistic regression model. The secondary endpoint was the hospitalization outcomes for COVID-19 patients with and without DVT/PE, including mortality, intensive care unit (ICU) admission, ICU stay, and length of hospitalization (LOH). Multivariable regression analysis was performed to identify the variables associated with mortality, ICU admission, discharge disposition, ICU duration, and LOH.

Results: A total of 13,310 patients had tested positive for COVID-19, 915 of whom (6.9%) had been hospitalized across our multisite health care system. The mean age of the hospitalized patients was 60.8 ± 17.0 years, and 396 (43.3%) were women. Of the 915 patients, 82 (9.0%) had had a diagnosis of DVT/PE confirmed by ultrasound examination of the extremities and/or computed tomography angiography of the chest. The odds of presenting with DVT/PE in the setting of COVID-19 infection was greater than that without COVID-19 infection (0.6% [5 of 915] vs 9.0% [82 of 915]; odds ratio [OR], 18; 95% confidence interval [CI], 8.0-51.2; P < .001). The vascular risk factors were not different between the COVID-19 patients with and without DVT/PE. Mortality (P = .02), the need for ICU stay (P < .001), duration of ICU stay (P < .001), and LOH (P < .001) were greater in the DVT/PE cohort than in the cohort without DVT/PE. On multivariable logistic regression analysis, the hemoglobin (OR, 0.71; 95% CI, 0.46-0.95; P = .04) and D-dimer (OR, 1.0; 95% CI, 0.33-1.56; P = .03) levels were associated with higher mortality. Higher activated partial thromboplastin times (OR, 1.1; 95% CI, 1.00-1.12; P = .03) and higher interleukin-6 (IL-6) levels (OR, 1.0; 95% CI, 1.01-1.07; P = .05) were associated with a greater risk of ICU admission. IL-6 (OR, 1.0; 95% CI, 1.00-1.02; P = .05) was associated with a greater risk of rehabilitation placement after discharge. On multivariable gamma regression analysis, hemoglobin (coefficient, -3.0; 95% CI, 0.03-0.08; P = .005) was associated with a prolonged ICU stay, and the activated partial thromboplastin time (coefficient, 2.0; 95% CI, 0.003-0.006; P = .05), international normalized ratio (coefficient, -3.2; 95% CI, 0.06-0.19; P = .002) and IL-6 (coefficient, 2.4; 95% CI, 0.0011-0.0027; P = .02) were associated with a prolonged LOH.

Conclusions: A significantly greater incidence of DVT/PE occurred in hospitalized COVID-19-positive patients compared with a non-COVID-19 cohort matched for cardiovascular risk factors. Patients affected by DVT/PE were more likely to experience greater mortality, to require ICU admission, and experience prolonged ICU stays and LOH compared with COVID-19-positive patients without DVT/PE. Advancements in DVT/PE prevention are needed for patients hospitalized for COVID-19 infection.
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http://dx.doi.org/10.1016/j.jvsv.2021.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023789PMC
April 2021

Mercury as a cause of membranous nephropathy and Guillain-Barre syndrome: case report and literature review.

J Int Med Res 2021 Mar;49(3):300060521999756

Chu Hsien-I Memorial Hospital, Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.

Secondary renal involvement in chronic exposure to metallic mercury is well known. Mercury also causes central nervous system damage and demyelinating polyneuropathy. Here, we describe a case of a patient with daily exposure to mercury in skin lightening cream and hair dyes who was diagnosed with Guillain-Barre syndrome and then developed nephrotic syndrome because of membranous neuropathy. By reviewing the literature describing mercury-associated diseases, we found that mercury components have an immunomodulatory activity, which is also involved in both peripheral neuropathy and glomerulonephritis.
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http://dx.doi.org/10.1177/0300060521999756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168032PMC
March 2021

Investigation of 2'-Deoxyadenosine-Derived Adducts Specifically Formed in Rat Liver and Lung DNA by '-Nitrosonornicotine Metabolism.

Chem Res Toxicol 2021 Apr 15;34(4):1004-1015. Epub 2021 Mar 15.

Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, United States.

The International Agency for Research on Cancer has classified the tobacco-specific nitrosamines '-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as "carcinogenic to humans" (Group 1). To exert its carcinogenicity, NNN requires metabolic activation to form reactive intermediates which alkylate DNA. Previous studies have identified cytochrome P450-catalyzed 2'-hydroxylation and 5'-hydroxylation of NNN as major metabolic pathways, with preferential activation through the 5'-hydroxylation pathway in some cultured human tissues and patas monkeys. So far, the only DNA adducts identified from NNN 5'-hydroxylation in rat tissues are 2-[2-(3-pyridyl)--pyrrolidinyl]-2'-deoxyinosine (Py-Py-dI), 6-[2-(3-pyridyl)--pyrrolidinyl]-2'-deoxynebularine (Py-Py-dN), and -[4-hydroxy-1-(pyridine-3-yl)butyl]-2'-deoxyadenosine (-HPB-dAdo) after reduction. To expand the DNA adduct panel formed by NNN 5'-hydroxylation and identify possible activation biomarkers of NNN metabolism, we investigated the formation of dAdo-derived adducts using a new highly sensitive and specific liquid chromatography-nanoelectrospray ionization-high-resolution tandem mass spectrometry method. Two types of NNN-specific dAdo-derived adducts, -[5-(3-pyridyl)tetrahydrofuran-2-yl]-2'-deoxyadenosine (-Py-THF-dAdo) and 6-[2-(3-pyridyl)--pyrrolidinyl-5-hydroxy]-2'-deoxynebularine (Py-Py(OH)-dN), were observed for the first time in calf thymus DNA incubated with 5'-acetoxyNNN. More importantly, Py-Py(OH)-dN was also observed in relatively high abundance in the liver and lung DNA of rats treated with racemic NNN in the drinking water for 3 weeks. These new adducts were characterized using authentic synthesized standards. Both NMR and MS data agreed well with the proposed structures of -Py-THF-dAdo and Py-Py(OH)-dN. Reduction of Py-Py(OH)-dN by NaBHCN led to the formation of Py-Py-dN both and , which was confirmed by its isotopically labeled internal standard [pyridine-]Py-Py-dN. The NNN-specific dAdo adducts Py-THF-dAdo and Py-Py(OH)-dN formed by NNN 5'-hydroxylation provide a more comprehensive understanding of the mechanism of DNA adduct formation by NNN.
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http://dx.doi.org/10.1021/acs.chemrestox.1c00012DOI Listing
April 2021

Identification of an -Nitrosonornicotine-Specific Deoxyadenosine Adduct in Rat Liver and Lung DNA.

Chem Res Toxicol 2021 Apr 11;34(4):992-1003. Epub 2021 Mar 11.

Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, United States.

The tobacco-specific nitrosamines '-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are considered to be two of the most important carcinogens in unburned tobacco and its smoke. They readily cause tumors in laboratory animals and are classified as "carcinogenic to humans" by the International Agency for Research on Cancer. DNA adduct formation by these two carcinogens is believed to play a critical role in tobacco carcinogenesis. Among all the DNA adducts formed by NNN and NNK, 2'-deoxyadenosine (dAdo)-derived adducts have not been fully characterized. In the study reported here, we characterized the formation of -[4-(3-pyridyl)-4-oxo-1-butyl]-2'-deoxyadenosine (-POB-dAdo) and its reduced form -PHB-dAdo formed by NNN 2'-hydroxylation in rat liver and lung DNA. More importantly, we characterized a new dAdo adduct -[4-hydroxy-1-(pyridine-3-yl)butyl]-2'-deoxyadenosine (-HPB-dAdo) formed after NaBHCN or NaBH reduction both in calf thymus DNA reacted with 5'-acetoxy-'-nitrosonornicotine and in rat liver and lung upon treatment with NNN. This adduct was specifically formed by NNN 5'-hydroxylation. Chemical standards of -HPB-dAdo and the corresponding isotopically labeled internal standard [pyridine-]-HPB-dAdo were synthesized using a four-step method. Both NMR and high-resolution mass spectrometry data agreed well with the proposed structure of -HPB-dAdo. The new adduct coeluted with the synthesized internal standard under various LC conditions. Its product ion patterns of MS and MS transitions were also consistent with the proposed fragmentation patterns. Chromatographic resolution of the two diastereomers of -HPB-dAdo was successfully achieved. Quantitation suggested a dose-dependent response of the levels of this new adduct in the liver and lung of rats treated with NNN. However, its level was lower than that of 2-[2-(3-pyridyl)--pyrrolidinyl]-2'-deoxyinosine, a previously reported dGuo adduct that is also formed from NNN 5'-hydroxylation. The identification of -HPB-dAdo in this study leads to new insights pertinent to the mechanism of carcinogenesis by NNN and to the development of biomarkers of NNN metabolic activation.
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http://dx.doi.org/10.1021/acs.chemrestox.1c00013DOI Listing
April 2021

Reply to Nezic and Tomsic and Klautz.

Eur J Cardiothorac Surg 2021 Feb 15. Epub 2021 Feb 15.

Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Cologne, Germany.

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http://dx.doi.org/10.1093/ejcts/ezab076DOI Listing
February 2021

Women have similar mortality but higher morbidity than men after elective endovascular abdominal aortic aneurysm repair.

J Vasc Surg 2021 Feb 4. Epub 2021 Feb 4.

Division of Vascular and Endovascular Surgery, Mayo Clinic, Jacksonville, Fla.

Objective: Sex disparities regarding outcomes for women after open and endovascular abdominal aortic aneurysm repair have been well-documented. The purpose of this study was to review whether these disparities were also present at our institution for elective endovascular aneurysm repair (EVAR) and whether specific factors predispose female patients to negative outcomes.

Methods: All elective EVARs were identified from our three sites (Florida, Minnesota, and Arizona) from 2000 to 2018. The primary outcome was in-hospital mortality and three-year mortality. Secondary outcomes included complications requiring return to the operating room, length of hospitalization (LOH), intensive care unit (ICU) days, and location of discharge after hospitalization. Multivariable logistic regression models were used to assess for the risk of complications.

Results: There were 1986 EVARs; 1754 (88.3%) were performed in male and 232 (11.7%) in female patients. Female patients were older (79 years [interquartile range (IQR), 72-83 years] vs 76 years [IQR, 70-81 years]; P < .001), had a lower body mass index (median, 26.1 kg/m [IQR, 22.1-31.0 kg/m] vs 28.3 kg/m [IQR, 25.3-31.6 kg/m]; P < .001 and hematocrit (median, 37.6% [IQR, 33.4%-40.6%] vs 39.4% [IQR, 35.6%-42.6%]; P < .001) and had higher glomerular filtration rate (median, 84.4 mL/min per 1.73m [IQR, 62.3-103 mL/min/1.73 m] vs 51.1 mL/min/1.73 m [IQR, 41.8-60.8 mL/min/1.73 m]; P < .001. Female patients were also more likely to be active smokers (15.3% vs 13.1%; P < .001) and have chronic obstructive pulmonary disease (24.7% vs 15.3%; P = .001). They were less likely to have coronary artery disease (31.6% vs 45.6%; P < .001). Aneurysms in women were slightly smaller in size (median, 54 mm [IQR, 50.0-58.0 mm] vs 55 mm [IQR, 51.0-60.0 mm]; P = .004). In-hospital mortality and mortality at the 3-year follow-up was not significant between female and male patients (0.86% vs 0.17%; P = .11 and 38.4% vs 36.2%; P = .57). However, female patients returned to the operating room with a greater frequency than male patients (3.9% vs 1.4%; P = .011). LOH (mean, 3.4 ± 3.8 days vs 2.5 ± 2.4 days; P < .001) and ICU days (mean, 0.3 ± 2.0 days vs 0.1 ± 0.5 days; P < .001) were longer for female patients. After hospitalization, female patients were discharged to rehabilitation facilities in greater proportion (12.7% vs 3.1%; P < .001) than their male counterparts. On multivariable analysis, female sex was associated with a return to the operating room (odds ratio, 6.4; 95% confidence interval [CI], 1.4-3.5; P = .02), longer LOH (Coef 4.0; 95% CI, 1.0-2.5; P = .00007), more ICU days (Coef 2.8; 95% CI, 1.1-3.0; P = .005), and a greater likelihood of posthospitalization rehabilitation facility placement (odds ratio, 5.8; 95% CI, 1.5-2.4; P = .0001).

Conclusions: Our three-site, single-institution data support sex disparities to the detriment of female patients regarding return to the operating room after EVAR, LOH, ICU days, and discharge to rehabilitation facility. However, we found no differences for in-hospital or 3-year mortality.
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http://dx.doi.org/10.1016/j.jvs.2020.12.095DOI Listing
February 2021

Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response.

Cell Host Microbe 2021 03 29;29(3):489-502.e8. Epub 2021 Jan 29.

Department of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, China; Department of Laboratory Medicine and Department of Pediatric Infectious Diseases, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (Δ500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-β levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-β responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.
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http://dx.doi.org/10.1016/j.chom.2021.01.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846228PMC
March 2021

, a Potential Probiotic to Improve the Health of LPS-Challenged Piglet Intestine by Alleviating Inflammation as Well as Oxidative Stress in a Dose-Dependent Manner During Weaning Transition.

Front Vet Sci 2020 16;7:547425. Epub 2020 Dec 16.

Tianjin Key Laboratory of Conservation and Utilization of Animal Diversity, College of Life Sciences, Tianjin Normal University, Tianjin, China.

Intestinal health is a critical issue for piglets during their weaning transition period. Previous reports have emphasized the promise of distinct probiotics in improving the enteric health. Here in this research, a newly isolated strain was pretreated to Lipopolysaccharide (LPS)-challenged piglets and its association with integrity of the intestinal barrier coupled with effective dosage were expected to be signified. In the present study, 72 piglets (Landrace × Yorkshiere × Duroc) were randomly allotted to four groups, each group with six replicates. The subjects in the control group were provided with basal diet while those in other tested groups with extra 0.05, 0.1, and 0.2% , respectively. Fourteen days later, LPS was intraperitoneally injected and sodium pentobarbital was then delivered to euthanize those LPS-challenged piglets. An increase of average daily gain and body weight along with an apparent decline of diarrhea rate were observed in -treated groups. Both 0.1 and 0.2% supplement in total diet had the capability to markedly elevate levels of CAT, GSH-Px, SOD, anti-inflammatory cytokine from the serum as well as tight junction proteins (Claudin-1, Occludin, and ZO-1) extracted from intestine in LPS-challenged piglets. These changes were accompanied by the obvious downregulation of D-lactic acid, DAO, MDA and pro-inflammatory mediators in the serum, including IL-1β, IL-6, IFN-γ, and TNF-α. Meanwhile, the expression levels of TLR2 and TLR4 in spleen and mesenteric lymph nodes were significantly lower whereas the oxidation-related gene, was up-regulated with administration. Our findings suggested that relatively high dose (0.1-0.2%) could regulate the progression of inflammatory response and oxidative stress when individuals were exposed to LPS, thus probably offering valuable assistance in restoring barrier function and improving overall performance.
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http://dx.doi.org/10.3389/fvets.2020.547425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772421PMC
December 2020

Evaluation of the GERAADA score for prediction of 30-day mortality in patients with acute type A aortic dissection.

Eur J Cardiothorac Surg 2021 May;59(5):1109-1114

Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Cologne, Germany.

:

Objectives: The German Registry of Acute Aortic Dissection Type A (GERAADA) score to predict 30-day mortality in patients suffering from acute aortic dissection type A (AADA) was recently introduced. The aim of this study was to evaluate if the GERAADA score's prediction corresponds with the authors' institutional results.

Methods: All consecutive AADA patients between 2010 and 2020 were included. Retrospective data collection comprised 11 preoperative parameters: age, sex, previous cardiac surgery, inotropic support at referral, resuscitation before surgery, aortic regurgitation, preoperative hemiparesis, intubation/ventilation at referral, preoperative organ malperfusion, extension of aortic dissection and location of primary entry site. Calculations of the GERAADA score were individually performed by a cardiac surgeon blinded to the study for all patients via a web-based application (https://www.dgthg.de/de/GERAADA_Score).

Results: A total of 371 AADA patients were operated at the authors' institution. The mean age was 62.7 ± 13.5 years and 233 (63%) were males. Prediction of 30-day mortality was accurate for the entire study cohort (actual vs predicted 30-day mortality: 15.1% vs 15.7%; P = 0.776) as well as for all 26 subgroups. In addition, preoperative resuscitation (P < 0.001), advanced age (P = 0.042) and other/unknown malperfusion (P = 0.032) were identified as independent risk factors.

Conclusions: The GERAADA score prediction of 30-day mortality after surgery is accurate, easily accessible due to its web-based platform and can be calculated with very basic preoperative clinical parameters. A prospective clinical trial is required to further evaluate the new GERAADA score as a useful tool to allow for improved decision-making in the emergency setting of AADA.
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http://dx.doi.org/10.1093/ejcts/ezaa455DOI Listing
May 2021

Higher Risk for Reintervention in Patients after Stenting for Radiation-Induced Internal Carotid Artery Stenosis: A Single-Center Analysis and Systematic Review.

Ann Vasc Surg 2021 May 26;73:1-14. Epub 2020 Dec 26.

Department of Neurology, Mayo Clinic, Jacksonville, FL.

Background: This study aimed to review short- and long-term outcomes of all carotid artery stenting (CAS) in patients with radiation-induced (RI) internal carotid artery (ICA) stenosis compared with patients with atherosclerotic stenosis (AS).

Methods: We performed a single-center, multisite case-control study of transfemoral carotid artery intervention in patients stented for RI or AS. Cases of stented RI carotid arteries were identified using a CAS database covering January 2000 to December 2019. These patients were randomly matched 2:1 with stented patients because of AS by age, sex, and year of CAS. A conditional logistic regression model was performed to estimate the odds of reintervention in the RI group. Finally, a systematic review was performed to assess the outcomes of RI stenosis treated with CAS.

Results: There were 120 CAS in 113 patients because of RI ICA stenosis. Eighty-nine patients (78.8%) were male, and 68 patients (60.2%) were symptomatic. The reasons for radiation included most commonly treatment for diverse malignancies of the head and neck in 109 patients (96.5%). The mean radiation dose was 58.9 ± 15.6 Gy, and the time from radiation to CAS was 175.3 ± 140.4 months. Symptoms included 31 transient ischemic attacks (TIAs), 21 strokes (7 acute and 14 subacute), and 17 amaurosis fugax. The mean National Institutes of Health Stroke Scale in acute strokes was 8.7 ± 11.2. In asymptomatic patients, the indication for CAS was high-grade stenosis determined by duplex ultrasound. All CAS were successfully completed. Reinterventions were more frequent in the RI ICA stenosis cohort compared with the AS cohort (10.1% vs. 1.4%). Reinterventions occurred in 14 vessels, and causes for reintervention were restenosis in 12 followed by TIA/stroke in two vessels. On conditional regression modeling, patients with RI ICA stenosis were at a higher risk for reintervention (odds ratio = 7.1, 95% confidence interval = 2.1-32.8; P = 0.004). The mean follow-up was 33.7 ± 36.9 months, and the mortality across groups was no different (P = 0.12).

Conclusions: In our single-center, multisite cohort study, patients who underwent CAS for RI ICA stenosis experienced a higher rate of restenosis and a higher number of reinterventions compared with CAS for AS. Although CAS is safe and effective for this RI ICA stenosis cohort, further data are needed to reduce the risk of restenosis, and close patient surveillance is warranted. In our systematic review, CAS was considered an excellent alternative option for the treatment of patients with RI ICA stenosis. However, careful patient selection is warranted because of the increased risk of restenosis on long-term follow-up.
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http://dx.doi.org/10.1016/j.avsg.2020.11.027DOI Listing
May 2021

Is Aortic Z-score an Appropriate Index of Beneficial Drug Effect in Clinical Trials in Aortic Aneurysm Disease?

Am J Cardiol 2021 03 9;143:145-153. Epub 2021 Jan 9.

Aortic Institute at Yale-New Haven Hospital, Yale University School of Medicine, New Haven, Connecticut. Electronic address:

Aortic Z-score (Z-score) is utilized in clinical trials to monitor the effect of medications on aortic dilation rate in Marfan (MFS) patients. Z-scores are reported in relation to body surface area and therefore are a function of height and weight. However, an information void exists regarding natural, non-pharmacological changes in Z-scores as children age. We had concerns that Z-score decrease attributed to "therapeutic" effects of investigational drugs for Marfan disease connective tissue diseases might simply reflect normal changes ("filling out" of body contour) as children age. This investigation studies natural changes with age in Z-score in normal and untreated MFS children, teasing out normal effects that might erroneously be attributed to drug benefit. (1) We first compared body mass index (BMI) and Z-scores (Boston Children's Hospital calculator) in 361 children with "normal" single echo exams in four age ranges (0 to 1, 5 to 7, 10 to 12, 15 to 18 years). Regression analysis revealed that aging itself decreases ascending Z-score, but not root Z-score, and that increase in BMI with aging underlies the decreased Z-scores. (2) Next, we examined Z-score findings in both "normal" and Marfan children (all pharmacologically untreated) as determined on sequential echo exams over time. Of 27 children without aortic disease with sequential echos, 19 (70%) showed a natural decrease in root Z-score and 24 (89%) showed a natural decrease in ascending Z- score, over time. Of 25 untreated MFS children with sequential echos, 12 (40%) showed a natural decrease in root Z-score and 10 (33%) showed a natural decrease in ascending Z-score. Thus, Z-score is over time affected by natural factors even in the absence of any aneurysmal pathology or medical intervention. Specifically, Z-score decreases spontaneously as a natural phenomenon as children age and with fill out their BMI. Untreated Marfan patients often showed a spontaneous decrease in Z-score. In clinical drug trials in aneurysm disease, decreasing Z-score has been interpreted as a sign of beneficial drug effect. These data put such conclusions into doubt.
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http://dx.doi.org/10.1016/j.amjcard.2020.12.025DOI Listing
March 2021

ILDGDB: a manually curated database of genomics, transcriptomics, proteomics and drug information for interstitial lung diseases.

BMC Pulm Med 2020 Dec 11;20(1):323. Epub 2020 Dec 11.

Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.

Background: Interstitial lung diseases (ILDs), a diverse group of diffuse lung diseases, mainly affect the lung parenchyma. The low-throughput 'omics' technologies (genomics, transcriptomics, proteomics) and relative drug information have begun to reshaped our understanding of ILDs, whereas, these data are scattered among massive references and are difficult to be fully exploited. Therefore, we manually mined and summarized these data at a database (ILDGDB, http://ildgdb.org/ ) and will continue to update it in the future.

Main Body: The current version of ILDGDB incorporates 2018 entries representing 20 ILDs and over 600 genes obtained from over 3000 articles in four species. Each entry contains detailed information, including species, disease type, detailed description of gene (e.g. official symbol of gene), and the original reference etc. ILDGDB is free, and provides a user-friendly web page. Users can easily search for genes of interest, view their expression pattern and detailed information, manage genes sets and submit novel ILDs-gene association.

Conclusion: The main principle behind ILDGDB's design is to provide an exploratory platform, with minimum filtering and interpretation, while making the presentation of the data very accessible, which will provide great help for researchers to decipher gene mechanisms and improve the prevention, diagnosis and therapy of ILDs.
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http://dx.doi.org/10.1186/s12890-020-01350-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731518PMC
December 2020

Factors Associated with a Positive Severe Acute Respiratory Syndrome Coronavirus 2 Testing in Suspected Cases Presenting with Pneumonia: A Retrospective Cohort Study in a Single Medical Center.

Respiration 2020 18;99(9):739-747. Epub 2020 Nov 18.

Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, China,

Background: Coronavirus disease 2019 (COVID-19) has become a global emerging infectious disease.

Objectives: To analyze the initial clinical characteristics of COVID-19 suspected and confirmed patients on admission in order to find out which kinds may be more likely to get positive nucleic acid testing results, and to explore the risk factors associated with all-cause death.

Methods: Medical records from 309 highly suspected cases with pneumonia were collected from February 13, 2020, to March 14, 2020, in a COVID-19-designated hospital of Wuhan. The majority of the clinical data were collected on the first day of hospital admission.

Results: Of 309 patients with median age 64 years (interquartile ranges [IQR], 53-72 years), 111 patients (35.9%) were confirmed by nucleic acid testing (median age 64 years, IQR: 56-71 years; 48 males). Of those 111 patients, 13 (11.7%) patients died. In multivariate analysis, factors associated with positive testing included fatigue (odds ratios [OR] = 3.14; 95% confidence interval [CI]: 1.88-5.24, p < 0.001), cough (OR = 0.55; 95% CI: 0.32-0.95, p = 0.032), no less than 1 comorbidity (OR = 1.77; 95% CI: 1.06-2.98, p = 0.030), and severe pneumonia (OR = 2.67; 95% CI: 1.20-5.97, p = 0.016). Furthermore, age, dyspnea, noneffective antibiotic treatment, white blood cell, lymphocyte, platelets, and organ dysfunction (e.g., higher lactate dehydrogenase) were significantly associated with all-cause in-hospital death in patients with COVID-19.

Conclusion: Patients with severe forms of this disease were more likely to get positive results. Age and organ dysfunction were associated with a greater risk of death.
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http://dx.doi.org/10.1159/000508398DOI Listing
January 2021

A multi-institutional review of endovenous thermal ablation of the saphenous vein finds male sex and use of anticoagulation are predictors of long-term failure.

Phlebology 2021 May 11;36(4):283-289. Epub 2020 Nov 11.

Division of Vascular and Endovascular Surgery, Mayo Clinic, Jacksonville, FL, USA.

Background: To review long-term outcomes and saphenous vein (SV) occlusion rate after endovenous ablation (EVA) for symptomatic varicose veins.

Methods: A review of our EVA database (1998-2018) with at least 3-years of clinical and sonographic follow-up. The primary end point was SV closure rate.

Results: 542 limbs were evaluated. 358 limbs had radiofrequency and 323 limbs had laser ablations; 542 great saphenous veins (GSV), 106 small saphenous veins (SSV) and 33 anterior accessory saphenous veins (AASV) were treated. Follow-up was 5.6 ± 2.3 years; 508 (74.6%) veins were occluded, 53 (7.8%) partially occluded and 120 (17.6%) were patent. On multivariable Cox regression analysis, male sex (HR 1.6, 95% CI [0.46-018], p = 0.012) and use anticoagulation (HR 2.0, 95% CI [0.69-0.34], p = 0.044) were predictors of long-term failure. On Kaplan-Meier curve, we had an 86.3% occlusion rate.

Conclusion: Our experience revealed a 5-year closure rate of 86.3%. Ablations have satisfactory occlusion rate.
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http://dx.doi.org/10.1177/0268355520972923DOI Listing
May 2021

A comprehensive update on early gastric cancer: defining terms, etiology, and alarming risk factors.

Expert Rev Gastroenterol Hepatol 2021 Mar 9;15(3):255-273. Epub 2020 Nov 9.

Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital , Tianjin, PR, China.

Introduction: Early gastric cancer (EGC) is a well-defined gastric malignancy that is limited to the mucosa or submucosa, irrespective of lymph node metastasis. At an early stage, gastric cancer often does not cause symptoms until it becomes advanced, and it is a heterogeneous disease and usually encountered in its late stages.

Area Covered: This comprehensive review will provide a novel insight into the evaluation of EGC epidemiology, defining terms, extensive etiology and risk factors, and timely diagnosis since prevention is an essential approach for controlling this cancer and reducing its morbidity and mortality.

Expert Opinion: The causative manner of EGC is complex and multifactorial. In recent years, researchers have made significant contributions to understanding the etiology and pathogenesis of EGC, and standardization in the evaluation of disease activity. Though the incidence of this cancer is steadily declining in some advanced societies owing to appropriate interventions, there remains a serious threat to health in developing nations. Early detection of resectable gastric cancer is crucial for better patient outcomes.
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http://dx.doi.org/10.1080/17474124.2021.1845140DOI Listing
March 2021

Increased Virulence of Descending Thoracic and Thoracoabdominal Aortic Aneurysms in Women.

Ann Thorac Surg 2020 Oct 17. Epub 2020 Oct 17.

Aortic Institute at Yale-New Haven Hospital, Yale University School of Medicine, New Haven, Connecticut. Electronic address:

Background: This study evaluates sex differences in the natural history of descending thoracic and thoracoabdominal aortic aneurysms (DTTAAs).

Methods: In all, 907 patients with descending thoracic and thoracoabdominal aortic sizes greater than 3 cm were retrospectively reviewed. Growth rate estimates were performed utilizing an instrumental variables approach. Yearly complication rates as a function of aortic size were computed.

Results: There were 615 men (67.8%) and 292 women (32.2%) treated between 1990 and 2018, with mean aortic diameters of 4.1 ± 1.4 cm and 4.8 ± 1.6 cm, respectively (P < .001). The mean growth rate of DTTAAs was 0.17 cm per year in men and 0.25 cm per year in women (P < .001), increasing with increasing aneurysm size. Dissection, rupture, or aortic death or the combination of the three occurred at double the rate for women compared with men (5.8% vs 2.3% per year for the combined endpoint). Diameter of DTTAA greater than 5 cm was associated with 26.3% (male) and 33.1% (female) average yearly rates of the composite endpoint of rupture, dissection, and death (P < .05). The probability of fatal complications (rupture and death) increased sharply at 5.75 cm in both sexes. Between 4.5 and 5.75 cm, there was another hinge-point of higher probability of fatal complications among women.

Conclusions: Women diagnosed with DTTAA fare worse. Faster aneurysm growth and higher rates of dissection, rupture, and aortic death are apparent among women. Current guidelines recommend surgical intervention at 5.5 to 6 cm for DTTAAs without sex considerations. Our findings suggest that increased virulence of DTTAA in women may indicate surgery at a somewhat smaller diameter.
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http://dx.doi.org/10.1016/j.athoracsur.2020.08.026DOI Listing
October 2020

Recent fall Eurasian cooling linked to North Pacific sea surface temperatures and a strengthening Siberian high.

Nat Commun 2020 10 15;11(1):5202. Epub 2020 Oct 15.

Department of Geography, Dartmouth College, Hanover, NH, 03755, USA.

Winter Eurasian cooling after the mid-1990s has been verified by numerous studies, although in recent decades, the mid-latitudes of the Northern Hemisphere have been rapidly warming globally. Because the cooling is not uniform at different spatial and temporal scales, over time, this change may not truly reflect the nature of climate fluctuations. Here, by using three types of data (reanalysis, weather station, and remote sensing image data) to assess variations in Eurasian seasonal cooling, we examine the causes of these changes. During a 30-year climatology (1989-2018), we show that a significant (P < 0.05) abrupt change in the autumn Eurasian air temperature trend occurred in 2003. Our results suggest that from 2004-2018, the autumn Eurasian temperature reveals a significant cooling trend (P < 0.05). We demonstrate that the autumn cooling in Eurasia is likely influenced by the Pacific Decadal Oscillation (PDO) and Siberian high (SH). Since 2004, the strengthening of the PDO and SH explains approximately 54% and 18% of the autumn cooling in Eurasia, respectively. We also find that the cooling in autumn is stronger than that in winter.
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http://dx.doi.org/10.1038/s41467-020-19014-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567785PMC
October 2020

Single Cell RNA Expression Analysis Using Flow Cytometry Based on Specific Probe Ligation and Rolling Circle Amplification.

ACS Sens 2020 10 24;5(10):3031-3036. Epub 2020 Sep 24.

School of Biomedical Sciences and School of Medicine, Huaqiao University, Quanzhou 362021, China.

Conventional flow cytometry has been widely used for high-throughput single-cell gene expression analysis using specific antibody staining. However, this is limited by the availability of high-quality antibodies. We developed a novel flow cytometry RNA detection technique termed RCA-Flow for single-cell RNA expression analysis. We showed that it is able to analyze not only mRNAs but also microRNAs and circular RNAs that are otherwise difficult to analyze by other flow cytometry techniques. The versatility for high-throughput analysis of different types of RNA molecules makes our method possess great potential for both biomedical and clinical applications.
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http://dx.doi.org/10.1021/acssensors.0c01569DOI Listing
October 2020

Ratios of neutrophil-to-lymphocyte and platelet-to-lymphocyte predict all-cause mortality in inpatients with coronavirus disease 2019 (COVID-19): a retrospective cohort study in a single medical centre.

Epidemiol Infect 2020 09 9;148:e211. Epub 2020 Sep 9.

Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.

The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern. The current study aims to explore whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with the development of death in patients with COVID-19. A total of 131 patients diagnosed with COVID-19 from 13 February 2020 to 14 March 2020 in a hospital in Wuhan designated for treating COVID-19 were enrolled in the current study. These 131 patients had a median age of 64 years old (interquartile range: 56-71 years old). Furthermore, among these patients, 111 (91.8%) patients were discharged and 12 (9.2%) patients died in the hospital. The pooled analysis revealed that the NLR at admission was significantly elevated for non-survivors, when compared to survivors (P < 0.001). The NLR of 3.338 was associated with all-cause mortality, with a sensitivity of 100.0% and a specificity of 84.0% (area under the curve (AUC): 0.963, 95% confidence interval (CI) 0.911-1.000; P < 0.001). In view of the small number of deaths (n = 12) in the current study, NLR of 2.306 might have potential value for helping clinicians to identify patients with severe COVID-19, with a sensitivity of 100.0% and a specificity of 56.7% (AUC: 0.729, 95% CI 0.563-0.892; P = 0.063). The NLR was significantly associated with the development of death in patients with COVID-19. Hence, NLR is a useful biomarker to predict the all-cause mortality of COVID-19.
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http://dx.doi.org/10.1017/S0950268820002071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506174PMC
September 2020

Nonusefulness of Antithrombotic Therapy After Surgical Bioprosthetic Aortic Valve Replacement.

Am J Cardiol 2020 08 18;129:71-78. Epub 2020 May 18.

Aortic Institute at Yale-New Haven Hospital, Yale University School of Medicine, New Haven, Connecticut. Electronic address:

Controversy persists regarding the advisability of anticoagulation for the early period after biological surgical aortic valve replacement (AVR). We aim to examine the impact of various antithrombotic regimens on outcomes in a large cohort of biological AVR patients. Records of 1,111 consecutive adult patients who underwent surgical biological AVR at our institution between 2013 and 2017 were reviewed. Outcomes included stroke, bleeding, and death at 3 and 12 months. Treatment regimens included (1) no therapy, (2) anticoagulants (warfarin or Factor Xa inhibitors), (2) antiplateles (various), and (4) anticoagulants + antiplatelets. Kaplan-Meier analysis was used to track outcomes, and Cox-proportional hazards regression models were conducted to analyze effects of different therapies on adverse events. At 3 months, thromboembolic events were low and not significantly different between the no therapy group (2.2%) and anticoagulation (2.8%) or anticoagulation + antiplatelet (3.6%) or all groups (3.7%). The antiplatelet group was just significantly lower, at 2.2%. However, this was driven by non-stroke cardiovascular events in patients with coronary artery disease. The incidence of death at 3 months was low and not significantly different between all groups. At 12 months, there were no thromboembolic benefits between groups, but bleeding events were significantly higher in the anticoagulation group (no therapy (1.4%), anticoagulation (8.4%), antiplatelet (4.5%), anticoagulation + antiplatelet (7.9%)). In conclusion, none of the antithrombotic regimens showed benefits in stroke or survival at 3 or 12 months after biological AVR. Anticoagulation increased bleeding events. Routine anticoagulation after biological AVR appears to be unnecessary and potentially harmful.
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http://dx.doi.org/10.1016/j.amjcard.2020.05.018DOI Listing
August 2020

Proton and photon radiosensitization effects of niraparib, a PARP-1/-2 inhibitor, on human head and neck cancer cells.

Head Neck 2020 09 23;42(9):2244-2256. Epub 2020 Apr 23.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Background: Combining photon or proton radiotherapy with targeted therapy shows promise for head and neck cancer (HNSCC). The poly (adenosine diphosphate [ADP]-ribose) polymerase-1/2 inhibitor niraparib targets DNA damage repair (DDR). We evaluated the effects of niraparib in combination with photons or protons, and its effects on the relative biological effectiveness (RBE) of protons, in human HNSCC cell lines.

Methods: Radiosensitivity was assessed and RBE was calculated with clonogenic survival assays; unrepaired DNA double-strand breaks were evaluated using immunocytochemical analysis of 53BP1 foci.

Results: Niraparib reduced colony formation in two of the four cell lines tested (P < .05), enhanced radiosensitivity in all four cell lines, delayed DDR (P < .05), and increased proton vs photon RBE.

Conclusion: Niraparib enhanced the sensitivity of four HNSCC cell lines to both photons and protons and increased the RBE of protons, possibly by inhibiting DDR. Niraparib may enhance the effectiveness of both photon and proton radiotherapy for patients with HNSCC.
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http://dx.doi.org/10.1002/hed.26155DOI Listing
September 2020

Dietary Clostridium butyricum supplementation modifies significantly the liver transcriptomic profile in weaned piglets.

J Anim Physiol Anim Nutr (Berl) 2020 Sep 24;104(5):1410-1423. Epub 2020 Mar 24.

Tianjin Institute of Animal Husbandry and Veterinary Medicine, Tianjin, China.

The addition of probiotics in swine nutrition is known to positively influence both health and growth. The current study investigates differences in the hepatic transcriptome profiles between weaned piglets supplemented with Clostridium butyricum (C. butyricum) and control animals that received no probiotic. The liver is an important metabolic organ that plays a critical role in oxidizing triglycerides for energy production, lipid synthesis and degradation, as well as immune regulation in animals. RNA-Seq analysis was carried out on total RNA harvested from the liver of piglets fed with (n = 3) or without (n = 3) 5 × 10 C. butyricum CFU/g. Compared to the control piglets, 588 of the genes examined (352 up-regulated and 236 down-regulated) were significantly differentially expressed at a fold change > 2 and p < .05 in animals fed with C. butyricum. Quantitative real-time reverse transcription PCR (qRT-PCR) analysis was further used to validate the microarray expression results for 28 genes tested. The functional annotation analyses revealed several genes, processes and pathways with putative involvement in piglet growth and performance. Feeding swine with 5 × 10 C. butyricum CFU/g appears to reinforce their immune status as well as foster the cell cycle and improve the metabolism of carbohydrates, lipids and amino acids. This study provides valuable information about the expression profiles of mRNAs in piglet liver and in-depth functional investigations of these mRNAs that could provide new insights into the molecular networks of growth, immune responses and nutrient metabolism in the porcine liver.
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http://dx.doi.org/10.1111/jpn.13326DOI Listing
September 2020

Design and Optimization of 3'-(Imidazo[1,2-]pyrazin-3-yl)-[1,1'-biphenyl]-3-carboxamides as Selective DDR1 Inhibitors.

ACS Med Chem Lett 2020 Mar 6;11(3):379-384. Epub 2020 Jan 6.

International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development, Ministry of Education (MOE) of PR China, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China.

DDR1 is considered as a promising target for cancer therapy, and selective inhibitors against DDR1 over other kinases may be considered as promising therapeutic agents. Herein, we have identified a series of 3'-(imidazo[1,2-]pyrazin-3-yl)-[1,1'-biphenyl]-3-carboxamides as novel selective DDR1 inhibitors. Among these, compound potently inhibited DDR1 with an IC of 23.8 nM, while it showed less inhibitory activity against DDR2 (IC = 1740 nM) and negligible activities against Bcr-Abl (IC > 10 μM) and c-Kit (IC > 10 μM). also exhibited excellent selectivity in a KINOMEscan screening platform with 468 kinases. This compound dose-dependently suppressed NSCLC cell tumorigenicity, migration, and invasion. Collectively, these studies support its potential application for treatment of NSCLC.
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http://dx.doi.org/10.1021/acsmedchemlett.9b00495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074218PMC
March 2020

Declining snowfall fraction in the alpine regions, Central Asia.

Sci Rep 2020 02 26;10(1):3476. Epub 2020 Feb 26.

College of Pratacultural and Environmental Sciences, Xinjiang Agricultural University, Urumqi, 830052, China.

In a warming climate, precipitation (P) is less likely to occur as snowfall (S). Change in the snowfall fraction (S/P) is currently assumed not only influences the accumulation and ablation of glaciers, but also influences the streamflow and water resources significantly in mountainous regions. However, until now, most studies have focused on precipitation magnitude and its frequency changes, while seasonal shifts in precipitation types have been mostly neglected. This paper employs the threshold temperature method in combination with multi-source dataset (APHRODITE, CPC and meteorological stations) analysis to determine snowfall proportions in precipitation in the Tienshan Mountains, Central Asia, during 1960-2017. The results indicated that temperature-induced precipitation shifting from snow to rain. The S/P experienced an overall declining trend, increasing at a rate of 0.6%/decade prior to the mid-1990s, followed by a downward trend at a rate of -0.5%/decade. The S/P decreased mainly at low and middle altitudes (between 1500 and 3500 m). At higher altitudes (over 3500 m), the magnitudes of the decreased S/P ratios were small or even increased due to the temperature always being below freezing. Decreases in S/P are always associated with decreases in annual streamflow in the glacier/snow melt recharged rivers.
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http://dx.doi.org/10.1038/s41598-020-60303-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044428PMC
February 2020

Higher Long-Term Mortality with Carotid Artery Stenting in Asymptomatic Male Compared with Female Patients in the Southeastern Vascular Study Group.

Ann Vasc Surg 2020 Jul 3;66:390-399. Epub 2020 Feb 3.

Division of Vascular and Endovascular Surgery, Mayo Clinic, Jacksonville, FL.

Background: To review the sex differences among symptomatic and asymptomatic patients treated with carotid endarterectomy (CEA) and carotid artery stenting (CAS) in the Southeastern Vascular Study Group (SEVSG), a regional quality group of the Vascular Quality Initiative (VQI).

Methods: All cases reported by the SEVSG members of symptomatic and asymptomatic patients were included in this retrospective review of CEA and CAS. Primary end point was 3-year survival difference between male and female patients. Secondary end points included in-hospital myocardial infarction (MI), transient ischemic attack (TIA)/stroke, and mortality differences between symptomatic and asymptomatic male and female patients. Cox proportional hazard regression was used to assess 3-year survival differences.

Results: There were 8,303 CEA and 1,876 CAS procedures performed in 29 centers from January 2011 to December 2018. From those, 4,650 (56.0%) and 938 (50.1%) were asymptomatic CEA and CAS, respectively. There were 2,760 (59.4%) male patients in the asymptomatic CEA and 597 (63.9%) in the asymptomatic CAS groups. After CEA, the rates of in-hospital MI (P = 0.034), TIA/stroke (P < 0.001), and death (P < 0.001) were significantly higher in symptomatic patients. MIs were more frequent in females with asymptomatic disease (P = 0.041). After CAS, the rate of TIA/stroke was higher in symptomatic patients (P = 0.030). There were no differences according to sex in the CAS group. On follow-up, asymptomatic male patients treated with CAS had a higher 3-year all-cause mortality compared with their female counterparts (7.0% vs. 1.8%; P = 0.015). On multivariable Cox regression analysis, male sex (HR = 2.63 [95% CI = 1.058-6.536]; P = 0.038) and lower hemoglobin levels (HR = 0.72 [95% CI = 0.597-0.857]; P < 0.001) were predictors of death in asymptomatic male patients treated with CAS.

Conclusions: In our SEVSG region, postoperative MIs, TIA/stroke, and deaths were higher in symptomatic CEA patients. MIs were more frequent in asymptomatic CEA females. Postoperative TIA/stroke was more frequent in symptomatic CAS patients. After CAS, asymptomatic male patients had higher 3-year all-cause mortality than female patients. On multivariable Cox regression analysis, male sex and lower hemoglobin levels were predictors of death in these asymptomatic male patients treated with CAS. Long-term mortality risk in asymptomatic males should be considered before offering CAS. Further national VQI analysis of our asymptomatic and symptomatic male and female patients treated with CEA and CAS would be warranted.
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http://dx.doi.org/10.1016/j.avsg.2020.01.090DOI Listing
July 2020

Microwave Absorption Ability of Steel Slag and Road Performance of Asphalt Mixtures Incorporating Steel Slag.

Materials (Basel) 2020 Feb 2;13(3). Epub 2020 Feb 2.

School of Highway, Chang'an University, Xi'an 710064, China.

Excessive usage of non-renewable natural resources and massive construction wastes put pressure on the environment. Steel slags, the main waste material from the metal industry, are normally added in asphalt concrete to replace traditional aggregate. In addition, as a typical microwave absorber, steel slag has the potential to transfer microwave energy into heat, thus increasing the limited self-healing ability of asphalt mixture. This paper aims to investigate the microwave absorption potentials of steel slag and the effect of its addition on road performance. The magnetic parameters obtained from a microwave vector network analyzer were used to estimate the potential use of steel slag as microwave absorber to heal cracks. Meanwhile, the initial self-healing temperature was further discussed according to the frequency sweeping results. The obvious porous structure of steel slag observed using scanning electron microscopy (SEM) had important impacts on the road performance of asphalt mixtures. Steel slag presented a worse effect on low-temperature crack resistance and water stability, while high-temperature stability can be remarkably enhanced when the substitution of steel slag was 60% by volume with the particle size of 4.75-9.5 mm. Overall, the sustainability of asphalt mixtures incorporating steel slag can be promoted due to its excellent mechanical and microwave absorption properties.
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http://dx.doi.org/10.3390/ma13030663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040692PMC
February 2020

Natural history of descending thoracic and thoracoabdominal aortic aneurysms.

J Thorac Cardiovasc Surg 2021 02 11;161(2):498-511.e1. Epub 2019 Nov 11.

Aortic Institute at Yale-New Haven Hospital, Yale University School of Medicine, New Haven, Conn. Electronic address:

Objectives: Elucidating critical aortic diameters at which natural complications (rupture, dissection, and death) occur is of paramount importance to guide timely surgical intervention. Natural history knowledge for descending thoracic and thoracoabdominal aortic aneurysms is sparse. Our small early studies recommended repairing descending thoracic and thoracoabdominal aortic aneurysms before a critical diameter of 7.0 cm. We focus exclusively on a large number of descending thoracic and thoracoabdominal aortic aneurysms followed over time, enabling a more detailed analysis with greater granularity across aortic sizes.

Methods: Aortic diameters and long-term complications of 907 patients with descending thoracic and thoracoabdominal aortic aneurysms were reviewed. Growth rates (instrumental variables approach), yearly complication rates, 5-year event-free survival (Kaplan-Meier), and risk of complications as a function of aortic height index (aortic diameter [centimeters]/height [meters]) (competing-risks regression) were calculated.

Results: Estimated mean growth rate of descending thoracic and thoracoabdominal aortic aneurysms was 0.19 cm/year, increasing with increasing aortic size. Median size at acute type B dissection was 4.1 cm. Some 80% of dissections occurred below 5 cm, whereas 93% of ruptures occurred above 5 cm. Descending thoracic and thoracoabdominal aortic aneurysm diameter 6 cm or greater was associated with a 19% yearly rate of rupture, dissection, or death. Five-year complication-free survival progressively decreased with increasing aortic height index. Hazard of complications showed a 6-fold increase at an aortic height index of 4.2 or greater compared with an aortic height index of 3.0 to 3.5 (P < .05). The probability of fatal complications (aortic rupture or death) increased sharply at 2 hinge points: 6.0 and 6.5 cm.

Conclusions: Acute type B dissections occur frequently at small aortic sizes; thus, prophylactic size-based surgery may not afford a means for dissection protection. However, fatal complications increase dramatically at 6.0 cm, suggesting that preemptive intervention before that criterion can save lives.
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http://dx.doi.org/10.1016/j.jtcvs.2019.10.125DOI Listing
February 2021

Resolution and Quantitation of Mercapturic Acids Derived from Crotonaldehyde, Methacrolein, and Methyl Vinyl Ketone in the Urine of Smokers and Nonsmokers.

Chem Res Toxicol 2020 02 30;33(2):669-677. Epub 2020 Jan 30.

Masonic Cancer Center , University of Minnesota , 2231 Sixth Street SE , Minneapolis , Minnesota 55455 , United States.

Using improved HPLC analysis conditions, we report the separation of three isomers of mercapturic acid conjugates previously assigned in the literature only to 3-hydroxy-1-methylpropylmercapturic acid (HMPMA-1), a human urinary metabolite of crotonaldehyde. The new conditions, employing a biphenyl column cooled to 5 °C and eluted with a gradient of formic acid, acetonitrile, and methanol, allow the analysis of human urinary mercapturic acids derived not only from crotonaldehyde but also from its isomers methacrolein (3-hydroxy-2-methylpropyl mercapturic acid, HMPMA-2) and methyl vinyl ketone (3-hydroxy-3-methylpropyl mercapturic acid, HMPMA-3). The mercapturic acids were detected and quantified by LC-ESI-MS/MS using the corresponding stable isotope labeled mercapturic acids as internal standards. The analysis was validated for accuracy and precision and applied to urine samples collected from cigarette smokers and nonsmokers. Smokers had significantly higher levels of all three mercapturic acids than did nonsmokers. The results demonstrated that HMPMA-3 from methyl vinyl ketone comprised the major portion of the peaks previously ascribed in multiple studies to HMPMA-1. HMPMA-1 had concentrations intermediate between those of HMPMA-2 and HMPMA-3 in both smokers and nonsmokers. This study reports the first quantitation of HMPMA-2 and HMPMA-3 in human urine. The observation of higher levels of HMPMA-3 than in the other two mercapturic acids suggests a previously unrecognized potential significance of methyl vinyl ketone as a toxicant in smokers and nonsmokers.
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http://dx.doi.org/10.1021/acs.chemrestox.9b00491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193944PMC
February 2020