bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitomycin-Treated Endothelial and Smooth Muscle Cells Suitable for Safe Tissue Engineering Approaches
Authors: Zakharova Irina , Saaya Shoraan , Shevchenko Alexander , Stupnikova Alena , Zhiven' Maria , Laktionov Pavel , Stepanova Alena , Romashchenko Alexander , Yanshole Lyudmila , Chernonosov Alexander , Volkov Alexander , Kizilova Elena , Zavjalov Evgenii , Chernyavsky Alexander , Romanov Alexander , Karpenko Andrey , Zakian Suren 
Published: March 2022

In our previous study, we showed that discarded cardiac tissue from the right atrial appendage and right ventricular myocardium is an available source of functional endothelial and smooth muscle cells for regenerative medicine and tissue engineering. In the study, we aimed to find out what benefits are given by vascular cells from cardiac explants used for seeding on vascular patches engrafted to repair vascular defects in vivo. Additionally, to make the application of these cells safer in regenerative medicine we tested an in vitro approach that arrested mitotic division to avoid the potential tumorigenic effect of dividing cells. A tissue-engineered construction in the form of a patch based on a polycaprolactone-gelatin scaffold and seeded with endothelial and smooth muscle cells was implanted into the abdominal aorta of immunodeficient SCID mice. Aortic patency was assessed using ultrasound, MRI, immunohistochemical and histological staining. Endothelial and smooth muscle cells were treated with mitomycin C at a therapeutic concentration of 10 μg/ml for 2 h with subsequent analysis of cell proliferation and function. The absence of the tumorigenic effect of mitomycin C-treated cells, as well as their angiogenic potential, was examined by injecting them into immunodeficient mice. Cell-containing patches engrafted in the abdominal aorta of immunodeficient mice form the vessel wall loaded with the appropriate cells and extracellular matrix, and do not interfere with normal patency. Endothelial and smooth muscle cells treated with mitomycin C show no tumorigenic effect in the SCID immunodeficient mouse model. During in vitro experiments, we have shown that treatment with mitomycin C does not lead to a decrease in cell viability. Despite the absence of proliferation, mitomycin C-treated vascular cells retain specific cell markers, produce specific extracellular matrix, and demonstrate the ability to stimulate angiogenesis in vivo. We pioneered an approach to arresting cell division with mitomycin C in endothelial and smooth muscle cells from cardiac explant, which prevents the risk of malignancy from dividing cells in vascular surgery. We believe that this approach to the fabrication of tissue-engineered constructs based on mitotically inactivated cells from waste postoperative material may be valuable to bring closer the development of safe cell products for regenerative medicine.
Relationship Between the Choice of Clinical Treatment, Gait Functionality and Kinetics in Patients With Comparable Knee Osteoarthritis
Authors: Tassani Simone , Tio Laura , Castro-Domínguez Francisco , Monfort Jordi , Monllau Juan Carlos , González Ballester Miguel Angel , Noailly Jérôme 
Published: March 2022

Objective: The objective of this study was to investigate the relationship between the choice of clinical treatment, gait functionality, and kinetics in patients with comparable knee osteoarthritis.Design: This was an observational case-control study.Setting: The study was conducted in a university biomechanics laboratory.Participants: Knee osteoarthritis patients were stratified into the following groups: clinical treatment (conservative/total knee replacement (TKR) planned), sex (male/female), age (60–67/68–75), and body mass index (BMI) (&lt;30/≥30). All patients had a Kellgren–Lawrence score of 2 or 3 (N = 87).Main Outcome Measures: All patients underwent gait analysis, and two groups of dependent variables were extracted:• Spatiotemporal gait variables: gait velocity, stride time, and double-support time, which are associated with patient functionality.• Kinetic gait variables: vertical, anterior–posterior, and mediolateral ground reaction forces, vertical free moment, joint forces, and moments at the ankle, knee, and hip. Multifactorial and multivariate analyses of variance were performed.Results: Functionality relates to treatment decisions, with patients in the conservative group walking 25% faster and spending 24% less time in the double-support phase. However, these differences vary with age and are reduced in older subjects. Patients who planned to undergo TKR did not present higher knee forces, and different joint moments between clinical treatments depended on the age and BMI of the subjects.Conclusions: Knee osteoarthritis is a multifactorial disease, with age and BMI being confounding factors. The differences in gait between the two groups were mitigated by confounding factors and risk factors, such as being a woman, elderly, and obese, reducing the variability of the gait compression loads. These factors should always be considered in gait studies of patients with knee osteoarthritis to control for confounding effects.
The Influence of Oncogenic RAS on Chemotherapy and Radiotherapy Resistance Through DNA Repair Pathways
Authors: Cáceres-Gutiérrez Rodrigo E. , Alfaro-Mora Yair , Andonegui Marco A. , Díaz-Chávez José , Herrera Luis A. 
Published: March 2022

RAS oncogenes are chief tumorigenic drivers, and their mutation constitutes a universal predictor of poor outcome and treatment resistance. Despite more than 30 years of intensive research since the identification of the first RAS mutation, most attempts to therapeutically target RAS mutants have failed to reach the clinic. In fact, the first mutant RAS inhibitor, Sotorasib, was only approved by the FDA until 2021. However, since Sotorasib targets the KRAS G12C mutant with high specificity, relatively few patients will benefit from this therapy. On the other hand, indirect approaches to inhibit the RAS pathway have revealed very intricate cascades involving feedback loops impossible to overcome with currently available therapies. Some of these mechanisms play different roles along the multistep carcinogenic process. For instance, although mutant RAS increases replicative, metabolic and oxidative stress, adaptive responses alleviate these conditions to preserve cellular survival and avoid the onset of oncogene-induced senescence during tumorigenesis. The resulting rewiring of cellular mechanisms involves the DNA damage response and pathways associated with oxidative stress, which are co-opted by cancer cells to promote survival, proliferation, and chemo- and radioresistance. Nonetheless, these systems become so crucial to cancer cells that they can be exploited as specific tumor vulnerabilities. Here, we discuss key aspects of RAS biology and detail some of the mechanisms that mediate chemo- and radiotherapy resistance of mutant RAS cancers through the DNA repair pathways. We also discuss recent progress in therapeutic RAS targeting and propose future directions for the field.
Meta-Analysis and Systematic Review of Coagulation Disbalances in COVID-19: 41 Studies and 17,601 Patients
Authors: Len Polina , Iskakova Gaukhar , Sautbayeva Zarina , Kussanova Aigul , Tauekelova Ainur T. , Sugralimova Madina M. , Dautbaeva Anar S. , Abdieva Meruert M. , Ponomarev Eugene D. , Tikhonov Alexander , Bekbossynova Makhabbat S. , Barteneva Natasha S. 
Published: March 2022

IntroductionCoagulation parameters are important determinants for COVID-19 infection. We conducted meta-analysis to assess the association between early hemostatic parameters and infection severity.MethodsElectronic search was made for papers that addressed clinical characteristics of COVID-19 patients and disease severity. Results were filtered using exclusion and inclusion criteria and then pooled into a meta-analysis to estimate the standardized mean difference (SMD) with 95% confidence interval (CI) for D-dimers, fibrinogen, prothrombin time, platelet count (PLT), activated partial thromboplastin time. To explore the heterogeneity and robustness of our fundings, sensitivity and subgroup analyses were conducted. Publication bias was assessed with contour-enhanced funnel plots and Egger's test by linear regression. Coagulation parameters data from retrospective cohort study of 451 patients with COVID-19 at National Research Center for Cardiac Surgery were included in meta-analysis of published studies.ResultsOverall, 41 original studies (17,601 patients) on SARS-CoV-2 were included. For the two groups of patients, stratified by severity, we identified that D-dimers, fibrinogen, activated partial thromboplastin time, and prothrombin time were significantly higher in the severe group [SMD 0.6985 with 95%CI (0.5155; 0.8815); SMD 0.661 with 95%CI (0.3387; 0.9833); SMD 0.2683 with 95%CI (0.1357; 0.4009); SMD 0.284 with 95%CI (0.1472; 0.4208)]. In contrast, PLT was significantly lower in patients with more severe cases of COVID-19 [SMD −0.1684 with 95%CI (−0.2826; −0.0542)]. Neither the analysis by the leave-one-out method nor the influence diagnostic have identified studies that solely cause significant change in the effect size estimates. Subgroup analysis showed no significant difference between articles originated from different countries but revealed that severity assessment criteria might have influence over estimated effect sizes for platelets and D-dimers. Contour-enhanced funnel plots and the Egger's test for D-dimers and fibrinogen revealed significant asymmetry that might be a sign of publication bias.ConclusionsThe hemostatic laboratory parameters, with exception of platelets, are significantly elevated in patients with severe COVID-19. The two variables with strongest association to disease severity were D-dimers and fibrinogen levels. Future research should aim outside conventional coagulation tests and include analysis of clotting formation and platelet/platelet progenitors characteristics.
Non-Dissecting Distal Aortic and Peripheral Arterial Aneurysms in Patients With Marfan Syndrome
Authors: Pellenc Quentin , Boitet Auréline , Roussel Arnaud , Milleron Olivier , Mordant Pierre , Senemaud Jean , Cerceau Pierre , Jondeau Guillaume , Castier Yves 
Published: March 2022

BackgroundIn Marfan syndrome (MFS), an aortic or peripheral arterial dilatation is usually the consequence of aortic dissection. Non-dissecting distal aortic and peripheral aneurysms (DAPA) are barely described. We sought to determine the incidence and prognostic impact of non-dissecting DAPA, requiring a surgical repair in a large population of patients with MFS.MethodsThe patients referred to the French MFS reference center were included in a prospective database, and the patients treated for a non-dissecting DAPA between 2013 and 2020 were retrospectively reviewed. The first-line therapy was open surgery. The patients unfit for open repair or experiencing life-threatening complications underwent endovascular repair.ResultsAmong 1,575 patients with MFS, 19 (1.2%) were operated for 25 non-dissecting DAPA. The mean age was 42.4 ± 11.5 years. Non-dissecting DAPA involved the subclavian or axillary artery (n = 12), the descending or thoracoabdominal aorta (n = 6), the abdominal aorta andiliac arteries (n = 6), and the popliteal artery (n = 1). Open and endovascular repairs were performed in 22 and three cases, respectively. After a median follow-up of 54.2 months, no local recurrence was noticed and no secondary procedure was performed. Eight patients presented a new aortic event, including two aortic dissections and seven new aortic surgeries. Compared to the overall MFS population, the non-dissecting DAPA group presented a significantly higher risk of an aortic event (100 vs. 28%, p &lt; 0.0001), a higher risk of aortic dissection (53 vs. 8%, p &lt; 0.0001), and a higher rate of pejorative genetic mutations (68 vs. 40%, p = 0.011).ConclusionAmong the patients with MFS, the diagnosis of non-dissecting DAPA is infrequent but is associated with a significant adverse outcome, thus, advocating for a specific follow-up.
Low Molecular Weight Apolipoprotein(a) Phenotype Rather Than Lipoprotein(a) Is Associated With Coronary Atherosclerosis and Myocardial Infarction
Authors: Afanasieva Olga I. , Ezhov Marat V. , Tmoyan Narek A. , Razova Oksana A. , Afanasieva Marina I. , Matchin Yuri G. , Pokrovsky Sergei N. 
Published: March 2022

Background and AimsCurrent evidence suggests that lipoprotein(a) [Lp(a)] level above 50 mg/dL is associated with increased cardiovascular risk. Our study aim was to determine the relationship of apolipoprotein(a) [apo(a)] phenotypes and Lp(a) concentration below and above 50 mg/dL with coronary atherosclerosis severity and myocardial infarction (MI).Material and MethodsThe study population consisted of 540 patients (mean age 54.0 ± 8.8 years, 82% men) who passed through coronary angiography. The number of diseased major coronary arteries assessed atherosclerosis severity. Lipids, glucose, Lp(a) levels and apo(a) phenotypes were determined in all patients. All patients were divided into four groups: with Lp(a) &lt;50 mg/dL [ “normal” Lp(a)] or ≥50 mg/dL [hyperLp(a)], and with low-molecular (LMW) or high-molecular weight (HMW) apo(a) phenotypes.ResultsBaseline clinical and biochemical characteristics were similar between the groups. In groups with LMW apo(a) phenotypes, the odds ratio (OR; 95% confidence interval) of multivessel disease was higher [10.1; 3.1–33.5, p &lt; 0.005 for hyperLp(a) and 2.2; 1.0–4.9, p = 0.056 for normal Lp(a)], but not in the group with HMW apo(a) and hyperLp(a) [1.1; 0.3–3.3, p = 0.92] compared with the reference group with HMW apo(a) and normal Lp(a). Similarly, MI was observed more often in patients with LMW apo(a) phenotype and hyperLp(a) and normal Lp(a) than in groups with HMW apo(a) phenotype.ConclusionThe LMW apo(a) phenotype is associated with the severity of coronary atherosclerosis and MI even when Lp(a) level is below 50 mg/dL. The combination of Lp(a) level above 50 mg/dL and LMW apo(a) phenotype increases the risk of severe coronary atherosclerosis, regardless of other risk factors.
Immunotherapy-Associated Hypothyroidism: Comparison of the Pre-Existing With De-Novo Hypothyroidism
Authors: Kristan Megan M. , Toro-Tobon David , Francis Nnenia , Desale Sameer , Bikas Athanasios , Jonklaas Jacqueline , Goyal Rachna M. 
Published: March 2022

BackgroundImmunotherapy has revolutionized the treatment of solid malignancies, but is associated with endocrine-related adverse events. This study aims to dissect the natural course of immunotherapy-induced hypothyroidism and provide guidance regarding diagnosis and management in patients with and without pre-existing hypothyroidism.MethodsA retrospective analysis was conducted using patients who received immunotherapy between 2010‐2019 within a multicenter hospital system. Participants were separated in three groups—those with pre-existing hypothyroidism, those who developed primary hypothyroidism and those with hypophysitis within a year of their first immunotherapy. Serial effects of immunotherapy on thyroid function tests (TFTs) and levothyroxine dosing were evaluated.Results822 patients were screened, with 85 determined to have pre-existing hypothyroidism, 48 de-novo primary hypothyroidism and 12 de-novo hypophysitis. All groups displayed fluctuations in TFTs around weeks 6‐8 of treatment. In the pre-existing hypothyroidism group, the levothyroxine dose was higher at 54 weeks than at baseline with the difference showing a trend towards statistical significance (p=0.06). The observed mean levothyroxine dose was significantly lower than the mean calculated weight-based dose for all groups. This finding was most clinically significant for the de-novo hypophysitis group (mean difference: -58.3 mcg, p&lt;0.0001). The mean 0.9 mcg/kg levothyroxine dose at week 54 for the de-novo hypophysitis group was statistically lower than the other groups (p=0.009).ConclusionIt is reasonable to screen with TFTs every 4 weeks, and space out TFTs surveillance to every 12 weeks after week 20. Our findings suggest a more conservative approach for levothyroxine dosing in those developing de-novo hypothyroidism, especially hypophysitis, such as initiating at 0.9-1.2 mcg/kg.
Variability in Global DNA Methylation Rate Across Tissues and Over Time in Sheep
Authors: Drouilhet Laurence , Moreno Carole , Plisson-Petit Florence , Marcon Didier , Fabre Stéphane , Hazard Dominique 
Published: March 2022

Recent studies highlighted the influence of epigenetic marks in the variability of many complex traits, both in plants and animals. These studied focused only on specific sites of the genome having differentially methylated profiles among individuals and/or tissues. In contrast, we recently used the methylation rate of the entire genome as a unique measure considered as a novel quantitative phenotype in sheep. This phenotype named global DNA methylation rate (GDMR), measured by luminometric assay, integrates the methylation level of each CpG dinucleotide within the 6 million of CCGG sites along the ovine genome. GDMR measured in blood previously showed moderate heritability of 0.20 and provided evidence for a genetic determinism. The main objective of the present study was to better characterize the GDMR phenotype in various tissues and investigate its variability in several breeds of sheep reared in the same environment. GDMR was measured on blood samples collected monthly from 59 growing male and female lambs (24 Romane, 23 Blackbelly and 12 Charollais), between birth and 4 months of age. Blood GDMR was on average around 80% and was influenced by the sampling date (p &lt; 0.001), the breed (p = 0.002) and the sex (p = 0.002). In addition, GDMR was determined in 12 somatic (frontal lobe, pituitary gland, heart, lung, sub cutaneous and perirenal adipose tissue, skeletal muscle, liver, spleen, adrenal gland, medulla and cortical kidney) and 6 reproductive tissues (ovary, oviduct, uterus, testis, epididymis and seminal vesicle). GDMR was on average 70% in somatic tissues but marked variation was observed depending on the tissue. The GDMR measured in blood was higher than that measured in other somatic tissues, and is not a good proxy of less accessible tissues. Female reproductive tissues had a 10% higher GDMR than male reproductive tissues. We demonstrated a significant influence of the breed on blood GDMR, certainly reflecting the influence of different genetic backgrounds. The effect of the breed on GDMR may be related to their specific abilities to adapt to and live in different conditions.
Tribological Performance Optimization of Mg-WC Nanocomposites in Dry Sliding: A Statistical Approach
Authors: Banerjee Sudip , Sahoo Prasanta , Davim J. Paulo 
Published: March 2022

Magnesium nanocomposites reinforced with ceramic reinforcements have emerged as a superior structural material for automotive applications due to their excellent specific properties. In this context, the current study aims to scrutinize the performance of Mg-WC nanocomposites in tribological applications. The effect of various input parameters (wt.% of reinforcement, load, and speed) on output responses (wear and coefficient of friction) is scrutinized using response surface methodology. Mg-WC nanocomposites having varying weight percentages of WC are synthesized using ultrasonic treatment associated the stir-casting technique. Typical characterizations of as-cast nanocomposites are done using scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). SEM micrographs confirm homogeneous dissemination of fortified particles in the base matrix while EDS confirms elemental composition. Analysis of variance (ANOVA) study is conducted to discover significant parameters affecting tribological performance. Surface plots and contour plots for tribological responses are also examined to observe interaction effects. ANOVA on wear confirms that wt.% of WC and speed are the most significant parameters while the interaction between wt.% of WC and speed has a significant influence. For the coefficient of friction, all the input parameters are significant, and interaction between wt.% of WC and load is of utmost significance. Regression equations for response parameters are also developed. Additionally, a desirability approach is considered to investigate both single- and multiple-objective-optimization criterions of output parameters. The desirability function for both single- and multi-optimization remains 0.9778, suggesting the presence of all input parameters within the working limit. Predicted and experimental values of the optimal setting possess a close fit for the current study. Minimum wear is achieved when wt.% of WC is 1.73%, load is 40 N, and speed is 100 rpm. Minimum friction is obtained when wt.% of WC is 1.78%, load is 40 N, and speed is 100 rpm. The multi-optimization result shows that the minimum value of wear and friction is achievable when wt.% of WC is 1.73%, load is 40 N, and speed is 100 rpm. Finally, the worn surface of samples is examined to observe possible wear mechanisms.
Breathing-Focused Yoga Intervention on Respiratory Decline in Chronically Pesticide-Exposed Farmers: A Randomized Controlled Trial
Authors: Dhansoia Vipin , Majumdar Vijaya , Manjunath N. K. , Singh Gaharwar Usha , Singh Deepeshwar 
Published: March 2022

BackgroundOccupational exposure to pesticides has been associated with lung and cognitive function exacerbations. In the present study, we tested the effectiveness of breathing focused yoga intervention on alleviation of adverse respiratory and cognitive effects associated with chronic pesticide exposure in farmers.MethodsWe undertook a parallel, two-armed randomized controlled trial with blinded outcome assessors on a chronically pesticide-exposed farming population. The study was conducted at district Panipat, State Haryana located in the Northern part of India from November 2019 to August 2020. A total of 634 farmers were screened, and 140 farmers were randomized to breathing-focused yoga intervention (BFY, n = 70) and waitlist control arms (n = 65). BFY was delivered weekly in 45-min group sessions over 12 weeks followed by home-based practice. The primary outcome was the change in spirometry-based markers of pulmonary function from baseline expressed as raw values, Global Lung Initiative (GLI) percent predicted (pp), and GLI z-scores after 24 weeks of intervention. Secondary variables were Trail making tests (TMT A and B), Digit symbol substitution (DSST), and WHO Quality of life-BREF (WHOQOL-Bref). Analysis was by intention-to-treat. Mediation analysis was done considering oxidative stress markers as potential mediators.ResultsAt the end of 6 months of intervention, the overall follow-up in the participants was 87.85% (n = 123); 90% (n = 63) in the control group, and 85.71% in the yoga group (n = 60). The mean age of the study cohort (n = 140) was 38.75 (SD = 7.50) years. Compared with the control group, at 24 weeks post-intervention, the BFY group had significantly improved status of the raw sand z scores markers of airway obstruction, after adjusting for confounders, FEV1, FVC, FEF25-75 [z score-adjusted mean differences (95% CI); 1.66 (1.10–2.21) 1.88 (1.21–2.55), and 6.85 (5.12–8.57), respectively. A fraction of FEF25-75 change (mediation percentage 23.95%) was explained by glutathione augmentation. There were also significant improvements in cognitive scores of DSST, TMT-A and TMT-B, and WHOQOL-Bref.ConclusionIn conclusion, regular practice of BFY could improve the exacerbations in the markers of airway obstruction in chronically pesticide-exposed farmers and cognitive variables. A significant mediating effect of glutathione augmentation was also observed concerning the effect of the intervention on FEF25-75. These findings provide an important piece of beneficial evidence of the breathing-based yoga intervention that needs validation across different farming ethnicities.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: CTRI/2019/11/021989.