Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase Equilibria and Interdiffusion in Bimodal High-Density Polyethylene (HDPE) and Linear Low-Density Polyethylene (LLDPE) Based Compositions

The compositions based on bimodal high-density polyethylene (HDPE, copolymer of ethylene with hexene-1) and in mixture with monomodal tercopolymer of ethylene with butene-1/hexene-1 (LLDPE, low-density polyethylene) have been studied. Phase equilibrium, thermodynamic parameters of interdiffusion in a wide range of temperatures and ratios of co-components were identified by refractometry, differential scanning calorimetry, optical laser interferometry, X-ray phase analysis. The phase state diagrams of the HDPE—LLDPE systems were constructed. It has been established that they belong to the class of state diagrams of “solid crystal solutions with unrestricted mixing of components”. The paired parameters of the components interaction and their temperature dependences were calculated. Thermodynamic compatibility of α-olefins in the region of melts and crystallization of one of the components has been shown. The kinetics of formation of interphase boundaries during crystallization of α-olefins has been analyzed. The morphology of crystallized gradient diffusion zones has been analyzed by optical polarization microscopy. The sizes of spherulites in different areas of concentration profiles and values of interdiffusion coefficients were determined.
The Moderate Correlation Between 25(OH)D Serum and Saliva in Healthy People with Low Vitamin D Intake

Purpose The routine examination of vitamin D levels is carried out by checking serum 25(OH)D levels, while serum 1.25(OH)D levels are less frequently utilized. The proposition that testing for salivary vitamin D can show a correlation with serum levels in healthy people is questionable, especially with low vitamin D intake. This study aimed to find the correlation between vitamin D levels, which were assessed as 25(OH)D and 1.25(OH)D in saliva, and serum 25(OH)D and 1.25(OH)D levels in people with low vitamin D intake. Patients and Methods This study is a cross-sectional study involving healthy men and women, aged 18–60 years, carried out from August to November, 2020, in North Sumatra Province, Indonesia. The parameters studied were the 25(OH)D and 1.25(OH)D levels in saliva and serum, and vitamin D intake. The statistical analysis used was the Spearman correlation test, performed to determine the correlation between each parameter. Results This study involved 56 study subjects, who were rural adults (male or female) with a 78.6% deficiency in 25(OH)D found by examining saliva, and a 76.8% deficiency found by examining the serum. All of the subjects were categorized as having low vitamin D intake (less than 15 micrograms per day). The analysis showed a moderate correlation between levels of saliva 25(OH)D and serum 25(OH)D (p = 0.424), and a weak correlation between levels of saliva 1.25(OH)D and serum 25(OH)D (p = 0.339). Conclusion In people with low vitamin D intake, there was a moderate correlation between serum 25(OH)D and saliva, but a weak correlation was found in the 1.25(OH)D assay. The use of saliva 25(OH)D levels to detect 25(OH)D in the circulation is a possible non-invasive alternative to serum testing.
Laparoscopic Pectopexy—CUSUM Learning Curve and Perioperative Complications Analysis

The study aimed to examine the learning curve and perioperative complications for laparoscopic pectopexy (LP). A total of 60 women with stage II–IV apical prolapse who underwent LP were dichotomized into groups: LSH(+) with concomitant laparoscopic supracervical hysterectomy (LSH), LSH(−) after previous supracervical/total hysterectomy. Operative time, estimated blood loss and hospitalization length were evaluated with cumulative sum (CUSUM) analysis and the Kwiatkowski–Phillips–Schmidt–Shin (KPSS) test, separately for two surgeons (A and B). Intraoperative and perioperative complications according to the Clavien–Dindo (C–D) classification were analyzed. Mean operative time, change in hemoglobin level, and postoperative hospital stay were 143.5 ± 23.1 min—1.5 ± 0.5g/dL and 2.5 ± 0.9 days, respectively. LSH during pectopexy was associated with longer operative time (p = 0.01) but not with higher intraoperative bleeding or prolonged hospital stay. Severe complications rate was low (1.7%) with one bowel injury in LSH(−) (C–D grade IIIb). No C–D grade II, IV and V complications were found. Conversion to open pectopexy, return to the operating room or blood transfusion were not required. The KPSS test showed that a steady operative time for Surgeon A was achieved after 28 procedures. A proficiency for laparoscopic pectopexy based on CUSUM analysis was observed after 38–40 procedures.
An Evaluation of Executive Control Function and Its Relationship with Driving Performance

The driver’s attentional state is a significant human factor in traffic safety. The executive control process is a crucial sub-function of attention. To explore the relationship between the driver’s driving performance and executive control function, a total of 35 healthy subjects were invited to take part in a simulated driving experiment and a task-cuing experiment. The subjects were divided into three groups according to their driving performance (aberrant driving behaviors, including lapses and errors) by the clustering method. Then the performance efficiency and electroencephalogram (EEG) data acquired in the task-cuing experiment were compared among the three groups. The effect of group, task transition types and cue-stimulus intervals (CSIs) were statistically analyzed by using the repeated measures analysis of variance (ANOVA) and the post hoc simple effect analysis. The subjects with lower driving error rates had better executive control efficiency as indicated by the reaction time (RT) and error rate in the task-cuing experiment, which was related with their better capability to allocate the available attentional resources, to express the external stimuli and to process the information in the nervous system, especially the fronto-parietal network. The activation degree of the frontal area fluctuated, and of the parietal area gradually increased along with the increase of CSI, which implied the role of the frontal area in task setting reconstruction and working memory maintaining, and of the parietal area in stimulus–Response (S–R) mapping expression. This research presented evidence of the close relationship between executive control functions and driving performance.
The “Hitchhiker’s Guide to the Galaxy” of Endothelial Dysfunction Markers in Human Fertility

Endothelial dysfunction is an early event in the pathogenesis of atherosclerosis and represents the first step in the pathogenesis of cardiovascular diseases. The evaluation of endothelial health is fundamental in clinical practice and several direct and indirect markers have been suggested so far to identify any alterations in endothelial homeostasis. Alongside the known endothelial role on vascular health, several pieces of evidence have demonstrated that proper endothelial functioning plays a key role in human fertility and reproduction. Therefore, this state-of-the-art review updates the endothelial health markers discriminating between those available for clinical practice or for research purposes and their application in human fertility. Moreover, new molecules potentially helpful to clarify the link between endothelial and reproductive health are evaluated herein.
Screening of Key Genes of Sepsis and Septic Shock Using Bioinformatics Analysis

Objective Sepsis is a disease associated with high mortality. We performed bioinformatic analysis to identify key biomarkers associated with sepsis and septic shock. Methods The top 20% of genes showing the greatest variance between sepsis and controls in the GSE13904 dataset (children) were screened by co-expression network analysis. The differentially expressed genes (DEGs) were identified through analyzing differential gene expression between sepsis patients and control in the GSE13904 (children) and GSE154918 (adult) data sets. Intersection analysis of module genes and DEGs was performed to identify common DEGs for enrichment analysis, protein-protein interaction network (PPI network) analysis, and Short Time-series Expression Miner (STEM) analysis. The PPI network genes were ranked by degree of connectivity, and the top 100 sepsis-associated genes were identified based on the area under the receiver operating characteristic curve (AUC). In addition, we evaluated differences in immune cell infiltration between sepsis patients and controls in children (GSE13904, GSE25504) and adults (GSE9960, GSE154918). Finally, we analyzed differences in DNA methylation levels between sepsis patients and controls in GSE138074 (adults). Results The common genes were associated mainly with up-regulated inflammatory and metabolic responses, as well as down-regulated immune responses. Sepsis patients showed lower infiltration by most types of immune cells. Genes in the PPI network with AUC values greater than 0.9 in both GSE13904 (children) and GSE154918 (adults) were screened as key genes for diagnosis. These key genes (MAPK14, FGR, RHOG, LAT, PRKACB, UBE2Q2, ITK, IL2RB, and CD247) were also identified in STEM analysis to be progressively dysregulated across controls, sepsis patients and patients with septic shock. In addition, the expression of MAPK14, FGR, and CD247 was modified by methylation. Conclusion This study identified several potential diagnostic genes and inflammatory and metabolic responses mechanisms associated with the development of sepsis.
Functional States in Tumor-Initiating Cell Differentiation in Human Colorectal Cancer

Simple Summary Different types of cells with tumor-initiating cell (TIC) activity contribute to colorectal cancer (CRC) progression and resistance to anti-cancer treatment. In this study, we aimed to understand whether different cell types exist within a patient-derived tumor culture, distinguishable by different patterns of their gene expression. By mRNA sequencing of patient-derived CRC cultures at the single-cell level, we defined expression programs that closely resemble differentiated cell populations of the normal intestine. Here, cell type-associated subpopulations showed differences in functional properties such as cell growth and energy metabolism. Subsequent functional analyses in vitro and in vivo demonstrated that metabolic states are linked to TIC activity in primary CRC cultures. We also show that TIC activity is dependent on oxidative phosphorylation, which may therefore represent a target for novel therapies. Abstract Intra-tumor heterogeneity of tumor-initiating cell (TIC) activity drives colorectal cancer (CRC) progression and therapy resistance. Here, we used single-cell RNA-sequencing of patient-derived CRC models to decipher distinct cell subpopulations based on their transcriptional profiles. Cell type-specific expression modules of stem-like, transit amplifying-like, and differentiated CRC cells resemble differentiation states of normal intestinal epithelial cells. Strikingly, identified subpopulations differ in proliferative activity and metabolic state. In summary, we here show at single-cell resolution that transcriptional heterogeneity identifies functional states during TIC differentiation. Furthermore, identified expression signatures are linked to patient prognosis. Targeting transcriptional states associated to cancer cell differentiation might unravel novel vulnerabilities in human CRC.
The CXCL2/IL8/CXCR2 Pathway Is Relevant for Brain Tumor Malignancy and Endothelial Cell Function

We aimed to evaluate the angiogenic capacity of CXCL2 and IL8 affecting human endothelial cells to clarify their potential role in glioblastoma (GBM) angiogenesis. Human GBM samples and controls were stained for proangiogenic factors. Survival curves and molecule correlations were obtained from the TCGA (The Cancer Genome Atlas) database. Moreover, proliferative, migratory and angiogenic activity of peripheral (HUVEC) and brain specific (HBMEC) primary human endothelial cells were investigated including blockage of CXCR2 signaling with SB225502. Gene expression analyses of angiogenic molecules from endothelial cells were performed. Overexpression of VEGF and CXCL2 was observed in GBM patients and associated with a survival disadvantage. Molecules of the VEGF pathway correlated but no relation for CXCR1/2 and CXCL2/IL8 was found. Interestingly, receptors of endothelial cells were not induced by addition of proangiogenic factors in vitro. Proliferation and migration of HUVEC were increased by VEGF, CXCL2 as well as IL8. Their sprouting was enhanced through VEGF and CXCL2, while IL8 showed no effect. In contrast, brain endothelial cells reacted to all proangiogenic molecules. Additionally, treatment with a CXCR2 antagonist led to reduced chemokinesis and sprouting of endothelial cells. We demonstrate the impact of CXCR2 signaling on endothelial cells supporting an impact of this pathway in angiogenesis of glioblastoma.
NFAT5 Deficiency Alleviates Formalin-Induced Inflammatory Pain Through mTOR

Nuclear factor of activated T cells (NFAT5) is a well-known transcription factor that regulates the expression of genes involved in osmotic stress. However, the role of NFAT5 in inflammatory pain remains unknown. Here, we studied the function of NFAT5 in inflammatory pain using NFAT5-heterozygous (Het) mice. To study inflammatory pain, we injected 10 µL of 2% formalin into the right hind paws of mice and monitored pain behaviors, such as licking, lifting, and flinching, for 60 min. After the first 15 min (phase I), there were no significant differences in pain behaviors between wild-type (WT) and NFAT5-Het mice. However, from 15–60 min (phase II), NFAT5-Het mice displayed significantly fewer pain behaviors compared to WT mice. Further, the expression levels of inflammatory-pain-related factors, including c-Fos, phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated n-methyl-D-aspartate receptor subunit 2B (p-NR2B), were significantly elevated in the spinal dorsal neurons of formalin-treated WT mice but was not elevated in NFAT5-Het mice. Similarly, c-Fos, p-ERK, and p-NR2B levels were significantly higher in glutamate-treated PC12 neuronal cells but were not affected by Nfat5 silencing in glutamate-treated PC12 cells. Altogether, our findings suggest that NFAT5 deficiency may mitigate formalin-induced inflammatory pain by upregulating mammalian target of rapamycin (mTOR) expression and downregulating its downstream factors in spinal dorsal neurons. Therefore, NFAT5 is a potential therapeutic target for the treatment of inflammatory pain.
Extracellular vesicles from recombinant cell factories improve the activity and efficacy of enzymes defective in lysosomal storage disorders

Abstract In the present study the use of extracellular vesicles (EVs) as vehicles for therapeutic enzymes in lysosomal storage disorders was explored. EVs were isolated from mammalian cells overexpressing alpha‐galactosidase A (GLA) or N‐sulfoglucosamine sulfohydrolase (SGSH) enzymes, defective in Fabry and Sanfilippo A diseases, respectively. Direct purification of EVs from cell supernatants was found to be a simple and efficient method to obtain highly active GLA and SGSH proteins, even after EV lyophilization. Likewise, EVs carrying GLA (EV‐GLA) were rapidly uptaken and reached the lysosomes in cellular models of Fabry disease, restoring lysosomal functionality much more efficiently than the recombinant enzyme in clinical use. In vivo, EVs were well tolerated and distributed among all main organs, including the brain. DiR‐labelled EVs were localized in brain parenchyma 1 h after intra‐arterial (internal carotid artery) or intravenous (tail vein) administrations. Moreover, a single intravenous administration of EV‐GLA was able to reduce globotriaosylceramide (Gb3) substrate levels in clinically relevant tissues, such kidneys and brain. Overall, our results demonstrate that EVs from cells overexpressing lysosomal enzymes act as natural protein delivery systems, improving the activity and the efficacy of the recombinant proteins and facilitating their access to organs neglected by conventional enzyme replacement therapies.
Peri-Implantitis: A Clinical Update on Prevalence and Surgical Treatment Outcomes

Dental implants may be considered a reliable routine procedure in clinical practice for the replacement of missing teeth. Results from long-term studies indicate that implant-supported dental prostheses constitute a predictable treatment method for the management of fully and partially edentulous patients. Implants and their restorations, however, are not free from biological complications. In fact, peri-implantitis, defined as progressive bone loss associated to clinical inflammation, is not a rare finding nowadays. This constitutes a concern for clinicians and patients given the negative impact on the quality of life and the sequelae originated by peri-implantitis lesions. The purpose of this narrative review is to report on the prevalence of peri-implantitis and to overview the indications, contraindications, complexity, predictability and effectiveness of the different surgical therapeutic modalities to manage this disorder.
Prediction of Neurologically Intact Survival in Cardiac Arrest Patients without Pre-Hospital Return of Spontaneous Circulation: Machine Learning Approach

Current multimodal approaches for the prognostication of out-of-hospital cardiac arrest (OHCA) are based mainly on the prediction of poor neurological outcomes; however, it is challenging to identify patients expected to have a favorable outcome, especially before the return of spontaneous circulation (ROSC). We developed and validated a machine learning-based system to predict good outcome in OHCA patients before ROSC. This prospective, multicenter, registry-based study analyzed non-traumatic OHCA data collected between October 2015 and June 2017. We used information available before ROSC as predictor variables, and the primary outcome was neurologically intact survival at discharge, defined as cerebral performance category 1 or 2. The developed models’ robustness were evaluated and compared with various score metrics to confirm their performance. The model using a voting classifier had the best performance in predicting good neurological outcome (area under the curve = 0.926). We confirmed that the six top-weighted variables predicting neurological outcomes, such as several duration variables after the instant of OHCA and several electrocardiogram variables in the voting classifier model, showed significant differences between the two neurological outcome groups. These findings demonstrate the potential utility of a machine learning model to predict good neurological outcome of OHCA patients before ROSC.
Antistaphylococcal Penicillin vs Cefazolin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Spinal Epidural Abscesses

Abstract Cefazolin is commonly used as an alternative to antistaphylococcal penicillins (ASPs) in treating methicillin-susceptible Staphylococcus aureus (MSSA) infections; however, no study has compared these agents in MSSA spinal epidural abscess (SEA). We describe our experience in managing MSSA SEA and compare the clinical efficacy of cefazolin with ASPs. This retrospective multicenter study reviewed 79 adult patients diagnosed with SEA between January 2006 and July 2020 using data collected from electronic health records and clinical microbiology laboratory databases. Forty-five patients received cefazolin, while 34 received ASPs. The total antibiotic duration was longer in the ASPs group but not statistically significant. There were no significant differences in treatment failure at week 6 vs week 12, 30-day vs overall mortality, or in 90-day recurrence rates between the treatment groups. Cefazolin was equally as effective as ASPs, and our findings suggest that it can be an alternative to ASPs in the treatment of MSSA SEA.
An Estimation Method of Continuous Non-Invasive Arterial Blood Pressure Waveform Using Photoplethysmography: A U-Net Architecture-Based Approach

Blood pressure (BP) monitoring has significant importance in the treatment of hypertension and different cardiovascular health diseases. As photoplethysmogram (PPG) signals can be recorded non-invasively, research has been highly conducted to measure BP using PPG recently. In this paper, we propose a U-net deep learning architecture that uses fingertip PPG signal as input to estimate arterial BP (ABP) waveform non-invasively. From this waveform, we have also measured systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP). The proposed method was evaluated on a subset of 100 subjects from two publicly available databases: MIMIC and MIMIC-III. The predicted ABP waveforms correlated highly with the reference waveforms and we have obtained an average Pearson’s correlation coefficient of 0.993. The mean absolute error is 3.68 ± 4.42 mmHg for SBP, 1.97 ± 2.92 mmHg for DBP, and 2.17 ± 3.06 mmHg for MAP which satisfy the requirements of the Association for the Advancement of Medical Instrumentation (AAMI) standard and obtain grade A according to the British Hypertension Society (BHS) standard. The results show that the proposed method is an efficient process to estimate ABP waveform directly using fingertip PPG.
Trends in the magnitude of chronic conditions in patients hospitalized with a first acute myocardial infarction

Background: Among adults with heart disease, there is a high prevalence of concomitant chronic medical conditions. We studied patients with a first acute myocardial infarction to describe: sample population characteristics; trends of the most prevalent pairs of chronic conditions; and differences in hospital management according to burden of these morbidities. Methods and Results: Patients (n = 1,564) hospitalized with an incident AMI at the 3 major medical centers in central Massachusetts during 2005, 2011, and 2015 comprised the study population. Hospital medical records were reviewed to identify 11 more prevalent chronic conditions. The median age of this population was 68 years and 56% were men. The median number of previously diagnosed chronic conditions was 2. Patients hospitalized during 2015 were more likely to be younger than those hospitalized in the earliest study cohorts. The most common pairs of chronic conditions for those hospitalized in 2005 were: anemia-chronic kidney disease (31%), chronic kidney disease-heart failure (30%), and stroke-atrial fibrillation (27%). Among patients hospitalized during 2011, chronic kidney disease-heart failure (29%), hypertension-hyperlipidemia (27%), and hypertension-diabetes (27%) were the most common pairs whereas hypertension-hyperlipidemia (43%), diabetes-heart failure (30%), and chronic kidney disease-diabetes (23%) were the most frequent pairs recorded in 2015. There was a significant decrease in the odds of undergoing cardiac catheterization and a percutaneous coronary intervention in those with higher chronic disease burden in the most recent as compared to earliest study years. Conclusions: Our findings highlight the magnitude of chronic conditions in patients with AMI and the challenges of caring for this vulnerable population.
Celiac Disease as a Rare Cause of Membranous Nephropathy: A Case Report

Membranous nephropathy is the most common cause of nephrotic syndrome in adults. A non-negligible number of cases are associated with systemic conditions. We report a case of a 50-year-old man who presented with nephrotic syndrome six months after being diagnosed with celiac disease. Although the patient showed disappearance of circulating immunoglobulin A (IgA) anti-tissue transglutaminase antibodies following a gluten-free diet, he had a sudden onset of nephrotic syndrome presenting with severe hypoalbuminemia. Other secondary causes were promptly excluded leading to the assumption of celiac disease-associated membranous nephropathy with remission after treatment with angiotensin system blockade and a gluten-free diet. The goal of this case report is to alert the clinic towards this rare association aiming for an early diagnosis and adequate selection of long-term therapy.