bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-World Use of Clopidogrel and Ticagrelor in Patients With Myocardial Infarction With Nonobstructive Coronary Arteries: Patient Characteristics and Long-Term Outcomes
Authors: Gao Side , Xu Haobo , Huang Sizhuang , Yuan Jiansong , Yu Mengyue 
Published: December 2021

Background: Current guidelines recommend ticagrelor as the preferred P2Y12 inhibitor on top of aspirin in patients after an acute coronary syndrome. Yet, the efficacy and safety of ticagrelor vs. clopidogrel in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) remain uncertain.Methods: A total of 1,091 patients with MINOCA who received dual antiplatelet therapy were enrolled and divided into the clopidogrel (n = 878) and ticagrelor (n = 213) groups. The primary efficacy endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, stroke, revascularization, and hospitalization for unstable angina or heart failure. The safety endpoint referred to bleeding events. The Kaplan-Meier, propensity score matching (PSM), and Cox regression analyses were performed.Results: The incidence of MACE was similar for clopidogrel- and ticagrelor-treated patients over the median follow-up of 41.7 months (14.3 vs. 15.0%; p = 0.802). The use of ticagrelor was not associated with a reduced risk of MACE compared with clopidogrel after multivariable adjustment in overall (HR = 1.25, 95% CI: 0.84–1.86, p = 0.262) and in subgroups of MINOCA patients. Further, there was no significant difference in the risk of bleeding between two groups (HR = 1.67, 95% CI: 0.83–3.36, p = 0.149). After PSM, 206 matched pairs were identified, and the differences between clopidogrel and ticagrelor for ischemic endpoints and bleeding events remained nonsignificant (all p &gt; 0.05).Conclusions: In this observational analysis of MINOCA patients, ticagrelor was not superior to clopidogrel in reducing ischemic events and did not cause a significant increase in bleeding, indicating a similar efficacy and safety between clopidogrel and ticagrelor. A randomized study of ticagrelor vs. clopidogrel in this specific population is needed.
Mid-Miocene Lake Level Fluctuations in the Lunpola Basin, Central Tibetan Plateau
Authors: Liang Yu , Quan Cheng , Li Yongxiang , Liu Weiguo , Liu Zhonghui 
Published: December 2021

Knowledge of paleolake evolution is highly important for understanding the past hydroclimate regime on the Tibetan Plateau and associated forcing mechanisms. However, the hydrological history of paleolakes on the central plateau, the core region of the plateau, remains largely inconclusive. Here we present new biomarker records from lacustrine deposits of the Lunpori section in the Lunpola Basin to reconstruct detailed lake-level fluctuations during the mid-Miocene. A set of n-alkane indexes, including the proportion of aquatic macrophytes (Paq), average chain length and carbon preference index as well as the content of n-alkanes, vary substantially and consistently throughout the studied interval. Our results altogether show relatively low lake level at ∼16.3–15.5 Ma and high lake level before and after the interval, which is in line with the lithological observations in the section. Further comparison with existing regional and global temperature records suggests that lake level fluctuations can be largely linked to global climatic conditions during the mid-Miocene, with lake expansion during relatively warm periods and vice versa. Therefore, we infer that global climatic changes might have controlled the lake-level fluctuations in this region during the mid-Miocene, whereas the tectonic uplift likely played a subordinate role on this timescale.
Altered Tim-1 and IL-10 Expression in Regulatory B Cell Subsets in Type 1 Diabetes
Authors: Liu Yikai , Chen Zhiying , Qiu Junlin , Chen Hongzhi , Zhou Zhiguang 
Published: December 2021

BackgroundType 1 diabetes (T1D) is an autoimmune disease with a complex aetiology. B cells play an important role in the pathogenesis of T1D. Regulatory B cells (Bregs) are a subset of B cells that produce and secrete the inhibitory factor interleukin-10 (IL-10), thereby exerting an anti-inflammatory effect. It was recently discovered that T-cell immunoglobulin mucin domain 1 (Tim-1) is essential for maintaining Bregs function related to immune tolerance. However, the detailed understanding of Tim-1+Bregs and IL-10+Bregs in T1D patients is lacking. This study aimed to characterize the profile of B cell subsets in T1D patients compared with that in controls and determine whether Tim-1+Bregs and IL-10+Bregs play roles in T1D.Materials and MethodsA total of 47 patients with T1D, 30 patients with type 2 diabetes (T2D) and 24 healthy controls were recruited in this study. Flow cytometry was used to measure the levels of different B cell subsets (including B cells, plasmablasts, and Bregs) in the peripheral blood. Radiobinding assays were performed to detect the antibody titres of T1D patients. In addition, the correlations between different B cell subsets and patient parameters were investigated.ResultsCompared with healthy controls, differences in frequency of Tim-1+Bregs were significantly decreased in patients with T1D (36.53 ± 6.51vs. 42.25 ± 6.83,P=0.02*), and frequency of IL-10+Bregs were lower than healthy controls (17.64 ± 7.21vs. 24.52 ± 11.69,P=0.009**), the frequency of total Bregs in PBMC was also decreased in patients with T1D (1.42 ± 0.53vs. 1.99 ± 0.93,P=0.002.**). We analyzed whether these alterations in B cells subsets were associated with clinical features. The frequencies of Tim-1+Bregs and IL-10+Bregs were negatively related to fasting blood glucose (FBG) (r=-0.25 and -0.22;P=0.01*and 0.03*,respectively). The frequencies of Tim-1+Bregs and IL-10+Bregs are positively correlated with fast C-peptide (FCP) (r=0.23 and 0.37;P=0.02*and 0.0001***, respectively). In addition, the frequency of IL-10+Breg was also negatively related to glycosylated haemoglobin (HbA1c) (r=-0.20,P=0.04*). The frequencies of Tim-1+Bregs, IL-10+Bregs and Bregs in T2D patients were reduced, but no statistically significant difference was found between other groups. Interestingly, there was positive correlation between the frequencies of Tim-1+Bregs and IL-10+Bregs in T1D (r=0.37,P=0.01*). Of note, it is worth noting that our study did not observe any correlations between B cell subsets and autoantibody titres.ConclusionsOur study showed altered Tim-1 and IL-10 expression in regulatory B cell in T1D patients. Tim-1, as suggested by the present study, is associated with islet function and blood glucose levels. These findings indicate that Tim-1+Bregs and IL-10+Bregs were involved in the pathogenesis of T1D.
Effects of Transient Thermal Shock on the Microstructure and Mechanical Properties of CoCrFeNiMn High-Entropy Alloy Coatings
Authors: Liu Jing-Tong , Liu Si-Wei , Zheng Hai-Lan , Huang Wen-Jing , Zhao Wei , Liao Wei-Bing 
Published: December 2021

CoCrFeNiMn high-entropy alloy (HEA) has great potential for engineering application due to its good ductility and high fracture toughness at low temperature. It can be deposited on components as coatings to take advantage of its excellent properties and reduce the cost. In this study, CoCrFeNiMn HEA coatings were deposited on 316L stainless steel substrates by atmospheric plasma spraying (APS) technique, and a series of transient thermal shock tests were performed. It was found that the coatings contained two main phases: a face-centered cubic (FCC) solid solution phase and a flocculent oxides phase. The elemental contents of Co, Cr, Fe, and Ni were close to equal atomic percentage in the coating, while Mn was reduced significantly. The oxygen was mainly distributed in the dark flocculent oxides phase. After transient thermal shock tests, these two phases remained stable, but some tiny cracks appeared on the surface. Meanwhile, the microhardness of the coating after transient thermal shock tests also showed stable, ∼ 420 HV. Weibull statistics were used to analyze the reliability of the microhardness, and the Weibull modulus m was distributed from 9 to 15. The CoCrFeNiMn HEA coating exhibited high phase stability and excellent properties under transient thermal shock, making it have service advantages in extreme environments, especially in the fields of the development of future nuclear and aerospace structural materials.
Ultrastructural Analysis of Rehydrated Human Donor Corneas After Air-Drying and Dissection by Femtosecond Laser
Authors: Pedrotti Emilio , Bonacci Erika , Fasolo Adriano , De Rossi Arianna , Camposampiero Davide , Jones Gary L. A. , Bernardi Paolo , Merigo Flavia , Ponzin Diego , Marchini Giorgio , Sbarbati Andrea 
Published: December 2021

Purpose: To evaluate the efficiency of femtosecond laser (FSL) incision of rehydrated human donor corneas after air-drying and its effects on corneal structure.Methods: We compared the rehydrated and fresh-preserved corneas by microscopy following Victus-Tecnolas FSL treatment for straight-edge anterior lamellar keratoplasty (ALK). The corneas were dehydrated at room temperature under a laminar-flow hood.Results: To obtain the horizontal cut in rehydrated corneas, we increased the FSL pulse energy to 1.2 μJ from 0.80 μJ applied for the fresh corneas and obtained a clear-cut separation of the lamellar lenticule cap from the corneal bed. Light microscopy showed regular arrangement of stromal collagen lamellae, with spaces in between the fibers in the corneal stroma in the fresh and the rehydrated corneas, but the uppermost epithelial layers in the rehydrated corneas were lost. Transmission electron microscopy (TEM) revealed no signs of thermal or mechanical damage to the corneal structure. The epithelial basal membrane and Bowman's layer maintained their integrity. The epithelial basal layer and cells were separated by large spaces due to junction alteration in the rehydrated corneas. There were gaps between the lamellar layers in the stroma, especially in the rehydrated corneas. Keratocytes displayed normal structure in the fresh corneas but were devoid of microorganules in the rehydrated corneas. Minor irregularities were observed in the vertical incision and the horizontal stroma appeared smooth on scanning electron microscopy.Conclusion: The corneal stroma of rehydrated corneas maintained morphology and integrity, while corneal cellular components were generally altered. When corneas are intended for FSL-assisted ALK, effective stromal bed incision is best achieved at a laser power higher than that currently adopted for fresh corneas.
miRNA Combinatorics and its Role in Cell State Control—A Probabilistic Approach
Authors: Mahlab-Aviv Shelly , Linial Nathan , Linial Michal 
Published: December 2021

A hallmark of cancer evolution is that the tumor may change its cell identity and improve its survival and fitness. Drastic change in microRNA (miRNA) composition and quantities accompany such dynamic processes. Cancer samples are composed of cells’ mixtures of varying stages of cancerous progress. Therefore, cell-specific molecular profiling represents cellular averaging. In this study, we consider the degree to which altering miRNAs composition shifts cell behavior. We used COMICS, an iterative framework that simulates the stochastic events of miRNA-mRNA pairing, using a probabilistic approach. COMICS simulates the likelihood that cells change their transcriptome following many iterations (100 k). Results of COMICS from the human cell line (HeLa) confirmed that most genes are resistant to miRNA regulation. However, COMICS results suggest that the composition of the abundant miRNAs dictates the nature of the cells (across three cell lines) regardless of its actual mRNA steady-state. In silico perturbations of cell lines (i.e., by overexpressing miRNAs) allowed to classify genes according to their sensitivity and resilience to any combination of miRNA perturbations. Our results expose an overlooked quantitative dimension for a set of genes and miRNA regulation in living cells. The immediate implication is that even relatively modest overexpression of specific miRNAs may shift cell identity and impact cancer evolution.
Iron Rims in Patients With Multiple Sclerosis as Neurodegenerative Marker? A 7-Tesla Magnetic Resonance Study
Authors: Dal-Bianco A. , Schranzer R. , Grabner G. , Lanzinger M. , Kolbrink S. , Pusswald G. , Altmann P. , Ponleitner M. , Weber M. , Kornek B. , Zebenholzer K. , Schmied C. , Berger T. , Lassmann H. , Trattnig S. , Hametner S. , Leutmezer F. , Rommer P. 
Published: December 2021

Introduction: Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system, characterized by inflammatory-driven demyelination. Symptoms in MS manifest as both physical and neuropsychological deficits. With time, inflammation is accompanied by neurodegeneration, indicated by brain volume loss on an MRI. Here, we combined clinical, imaging, and serum biomarkers in patients with iron rim lesions (IRLs), which lead to severe tissue destruction and thus contribute to the accumulation of clinical disability.Objectives: Subcortical atrophy and ventricular enlargement using an automatic segmentation pipeline for 7 Tesla (T) MRI, serum neurofilament light chain (sNfL) levels, and neuropsychological performance in patients with MS with IRLs and non-IRLs were assessed.Methods: In total 29 patients with MS [15 women, 24 relapsing-remitting multiple sclerosis (RRMS), and five secondary-progressive multiple sclerosis (SPMS)] aged 38 (22–69) years with an Expanded Disability Status Score of 2 (0–8) and a disease duration of 11 (5–40) years underwent neurological and neuropsychological examinations. Volumes of lesions, subcortical structures, and lateral ventricles on 7-T MRI (SWI, FLAIR, and MP2RAGE, 3D Segmentation Software) and sNfL concentrations using the Simoa SR-X Analyzer in IRL and non-IRL patients were assessed.Results: (1) Iron rim lesions patients had a higher FLAIR lesion count (p = 0.047). Patients with higher MP2Rage lesion volume exhibited more IRLs (p &lt;0.014) and showed poorer performance in the information processing speed tested within 1 year using the Symbol Digit Modalities Test (SDMT) (p &lt;0.047). (2) Within 3 years, patients showed atrophy of the thalamus (p = 0.021) and putamen (p = 0.043) and enlargement of the lateral ventricles (p = 0.012). At baseline and after 3 years, thalamic volumes were lower in IRLs than in non-IRL patients (p = 0.045). (3) At baseline, IRL patients had higher sNfL concentrations (p = 0.028). Higher sNfL concentrations were associated with poorer SDMT (p = 0.004), regardless of IRL presence. (4) IRL and non-IRL patients showed no significant difference in the neuropsychological performance within 1 year.Conclusions: Compared with non-IRL patients, IRL patients had higher FLAIR lesion counts, smaller thalamic volumes, and higher sNfL concentrations. Our pilot study combines IRL and sNfL, two biomarkers considered indicative for neurodegenerative processes. Our preliminary data underscore the reported destructive nature of IRLs.
Group-Level Ranking-Based Hubness Analysis of Human Brain Connectome Reveals Significant Interhemispheric Asymmetry and Intraparcel Heterogeneities
Authors: Hanalioglu Sahin , Bahadir Siyar , Isikay Ilkay , Celtikci Pinar , Celtikci Emrah , Yeh Fang-Cheng , Oguz Kader Karli , Khaniyev Taghi 
Published: December 2021

Objective: Graph theory applications are commonly used in connectomics research to better understand connectivity architecture and characterize its role in cognition, behavior and disease conditions. One of the numerous open questions in the field is how to represent inter-individual differences with graph theoretical methods to make inferences for the population. Here, we proposed and tested a simple intuitive method that is based on finding the correlation between the rank-ordering of nodes within each connectome with respect to a given metric to quantify the differences/similarities between different connectomes.Methods: We used the diffusion imaging data of the entire HCP-1065 dataset of the Human Connectome Project (HCP) (n = 1,065 subjects). A customized cortical subparcellation of HCP-MMP atlas (360 parcels) (yielding a total of 1,598 ROIs) was used to generate connectivity matrices. Six graph measures including degree, strength, coreness, betweenness, closeness, and an overall “hubness” measure combining all five were studied. Group-level ranking-based aggregation method (“measure-then-aggregate”) was used to investigate network properties on population level.Results: Measure-then-aggregate technique was shown to represent population better than commonly used aggregate-then-measure technique (overall rs: 0.7 vs 0.5). Hubness measure was shown to highly correlate with all five graph measures (rs: 0.88–0.99). Minimum sample size required for optimal representation of population was found to be 50 to 100 subjects. Network analysis revealed a widely distributed set of cortical hubs on both hemispheres. Although highly-connected hub clusters had similar distribution between two hemispheres, average ranking values of homologous parcels of two hemispheres were significantly different in 71% of all cortical parcels on group-level.Conclusion: In this study, we provided experimental evidence for the robustness, limits and applicability of a novel group-level ranking-based hubness analysis technique. Graph-based analysis of large HCP dataset using this new technique revealed striking hemispheric asymmetry and intraparcel heterogeneities in the structural connectivity of the human brain.
Insufficient Post-operative Energy Intake Is Associated With Failure of Enhanced Recovery Programs After Laparoscopic Colorectal Cancer Surgery: A Prospective Cohort Study
Authors: Liu Shuang , Zhang Sheng , Li Zike , Li Meng , Zhang Yujie , He Min , Jin Chengcheng , Gao Chun , Gong Jianping 
Published: December 2021

Background: Although enhanced recovery after surgery (ERAS) has been proven to be beneficial after laparoscopic colorectal surgery, some of the patients may fail to complete the ERAS program during hospitalization. This prospective study aims to evaluate the risk factors associated with ERAS failure after laparoscopic colorectal cancer surgery.Methods: This is a prospective study from a single tertiary referral hospital. Patients diagnosed with colorectal cancer who met the inclusion criteria were included in this study. Demographic and clinicopathological characteristics were collected. Post-operative activity time and 6-min walking distance (6MWD) were measured. Patients were divided into ERAS failure group and ERAS success according to decreased post-operative activity and 6MWD. Factors associated with ERAS failure were investigated by univariate and multivariate analysis.Results: A total of 91 patients with colorectal cancer were included. The incidence of ERAS failure is 28.6% among all patients. Patients in ERAS failure group experienced higher rate of post-operative ileus and prolonged hospital stay (p &lt; 0.001). Multivariate analysis revealed that older age (p = 0.006), body mass index ≥25.5 kg/m2 (p = 0.037), smoking (p = 0.002), operative time (p = 0.048), and post-operative energy intake &lt;18.5 kcal/kg•d (p = 0.045) were independent risk factors of ERAS failure after laparoscopic colorectal surgery.Conclusions: Our findings indicated that a proportion of patients may fail the ERAS program after laparoscopic colorectal surgery. We for the first time showed that post-operative energy intake was an independent risk factor for ERAS failure. This may provide evidence for further investigation on precise measurement of nutritional status and selected high-risk patients for enhanced nutrition support.
Priority Micronutrient Density of Foods for Complementary Feeding of Young Children (6–23 Months) in South and Southeast Asia
Authors: Ortenzi Flaminia , Beal Ty 
Published: December 2021

Background: Given their high nutrient requirements and limited gastric capacity, young children during the complementary feeding period (6–23 months) should be fed nutrient-dense foods. However, complementary feeding diets in low- and middle-income countries are often inadequate in one or more essential micronutrients. In South and Southeast Asia infants' and young children's diets are commonly lacking in iron, zinc, vitamin A, folate, vitamin B12, and calcium, hereafter referred to as priority micronutrients.Objective: This study aimed to identify the top food sources of priority micronutrients among minimally processed foods for complementary feeding of children (6–23 months) in South and Southeast Asia.Methods: An aggregated regional food composition database for South and Southeast Asia was built, and recommended nutrient intakes (RNIs) from complementary foods were calculated for children aged 6–23 months. An approach was developed to classify foods into one of four levels of priority micronutrient density based on the calories and grams required to provide one-third (for individual micronutrients) or an average of one-third (for the aggregate score) of RNIs from complementary foods.Results: We found that the top food sources of multiple priority micronutrients are organs, bivalves, crustaceans, fresh fish, goat, canned fish with bones, and eggs, closely followed by beef, lamb/mutton, dark green leafy vegetables, cow milk, yogurt, and cheese, and to a lesser extent, canned fish without bones.Conclusions: This analysis provided insights into which foods to prioritize to fill common micronutrient gaps and reduce undernutrition in children aged 6–23 months in South and Southeast Asia.