Miracle-dz/UniFAR-FTUs huggingface dataset:
Mean Arterial Pressure: Getting It Right.

e156 www.ccmjournal. org February 2020 • Volume 48 • Number 2 extracorporeal membrane oxygenation: Risk factors for mortality. Crit Care Med 2019; 47:926–933 3. Schmidt M, Burrell A, Roberts L, et al: Predicting survival after ECMO for refractory cardiogenic shock: The survival after veno-arterialECMO (SAVE)-score. Eur Heart J 2015; 36:2246–2256 by Rietdijk et al (1) must be addressed. Rather one would expect that ROSC would be beneficial for patient survival. In our study (2), absence of ROSC within the groups of survivors and nonsurvivors were 39% and 83%, respectively, compared with 67% and 55% in the study by Rietdijk et al (1). These differences between the studies resulted in absence of ROSC being significant in the univariate analysis in our study (2) (p < 0.001), whereas it was not in their study (p = 0.19). In the subsequent multivariable analysis, absence of ROSC was not found to be positively related to 90-day mortality in our study (2) (p = 0.262), whereas the forced entry of the nonsignificant variable absence of ROSC may have distorted the multivariable analysis by Rietdijk et al (1), leading to the negative relation between absence of ROSC and 90-day mortality. Third: Interestingly, arterial lactate was only borderline significant in their study (p = 0.06), whereas we found arterial lactate to be significantly related to 90-day mortality (p < 0.041). This discrepancy may partly be related to the limited number of patients as highlighted by Rietdijk et al (1). However, it may also be explained by a larger difference in the median arterial lactate levels between nonsurvivors and survivors (15.0–8.0 = 7.0 mmol/L) in our study (2) compared with (12.0–9.4 = 2.6 mmol/L) in their study. Fourth: We agree with Rietdijk et al (1) that external validation of data is essential. Nevertheless, a prerequisite to obtain generalizability is the use of meticulously defined variables especially in a very heterogeneous patient population such as patients with cardiac arrest of different etiologies selected for venoarterial ECMO. Finally: Beyond the importance of validation of data, the next step should be, after cooperation between centers to gain the necessary larger patient cohorts, to derive an additive risk score that considers the interaction between factors of survival, that is, a similar risk score model to the survival after venoarterial ECMO score, but containing specific factors associated with cardiac arrest, which are rapidly available in the selection process for venoarterial ECMO suitability in patients with cardiac arrest (3). The authors have disclosed that they do not have any potential conflicts of interest.
Extended Intake of Mulberry Leaf Extract Delayed Metformin Elimination via Inhibiting the Organic Cation Transporter 2

Diabetes mellitus (DM) has become a major health problem in most countries of the world. DM causes many complications, including hyperglycemia, diabetic ketoacidosis, and death. In Asia, mulberry has been used widely in the treatment of DM. Combination of drugs with herbal medicine may reduce the unwanted side effects caused by drugs. In this study, the influence of extended mulberry leaves extract (MLE) intake on metformin (Met) was evaluated in terms of pharmacokinetics and pharmacodynamics in DM-induced rats. Three week-treatment of MLE alone produced the anti-hyperglycemic effect (around 24%) if compared to the control. Interestingly, Met administration after MLE treatment for 3 weeks enhanced about 49% of the anti-hyperglycemic effect of Met. In addition, the extended intake of MLE potentiated the anti-hyperglycemic effect of Met on various concentrations. This potentiated anti-hyperglycemic effect of Met appears to be due to the pharmacokinetic change of Met. In this study, 3 week-treatment of MLE reduced the elimination of Met in DM-induced rats. In addition, MLE reduced the human organic cation transporter 2 (hOCT2) activity in a concentration-dependent manner. Thus, these findings suggest that MLE lowered the elimination of Met via inhibiting the hOCT2.
Alpha-Gal and Cross-Reactive Carbohydrate Determinants in the N-Glycans of Salivary Glands in the Lone Star Tick, Amblyomma americanum

Ticks are important ectoparasites and vectors of numerous human and animal pathogens. Ticks secrete saliva that contains various bioactive materials to evade the host defense system, and often facilitates the pathogen transmission. In addition, the Lone star tick saliva is thought to be the sensitizer in red meat allergy that is characterized by an allergic reaction to glycan moieties carrying terminal galactose-alpha-1,3-galactose (aGal). To assess N-glycome of Amblyomma americanum, we examined the N-glycan structures in male and female salivary glands at three different feeding stages and in carcasses of partially fed lone star ticks. We also surveyed the genes involved in the N-glycosylation in the tick species. The aGal epitopes and cross-reactive carbohydrate determinants (CCD) increases over time after the onset of blood feeding in both male and female A. americanum. These CCDs include xylosylation of the core mannose, 1,3-mono and 1,3- and 1,6-difucosylations of the basal GlcNac and mono- or diantennary aGal. Combinations of both xylosylation and aGal and fucosylation and aGal were also found on the N-glycan structures. While the enzymes required for the early steps of the N-glycosylation pathway are quite conserved, the enzymes involved in the later stages of N-glycan maturation in the Golgi apparatus are highly diverged from those of insects. Most of all, we propose that the aGal serves as a molecular mimicry of bioactive proteins during tick feedings on mammalian hosts, while it contributes as a sensitizer of allergy in atypical host human.
Role of Sulfonylurea Receptor 1 and Glibenclamide in Traumatic Brain Injury: A Review of the Evidence

Cerebral edema and contusion expansion are major determinants of morbidity and mortality after TBI. Current treatment options are reactive, suboptimal and associated with significant side effects. First discovered in models of focal cerebral ischemia, there is increasing evidence that the sulfonylurea receptor 1 (SUR1)—Transient receptor potential melastatin 4 (TRPM4) channel plays a key role in these critical secondary injury processes after TBI. Targeted SUR1-TRPM4 channel inhibition with glibenclamide has been shown to reduce edema and progression of hemorrhage, particularly in preclinical models of contusional TBI. Results from small clinical trials evaluating glibenclamide in TBI have been encouraging. A Phase-2 study evaluating the safety and efficacy of intravenous glibenclamide (BIIB093) in brain contusion is actively enrolling subjects. In this comprehensive narrative review, we summarize the molecular basis of SUR1-TRPM4 related pathology and discuss TBI-specific expression patterns, biomarker potential, genetic variation, preclinical experiments, and clinical studies evaluating the utility of treatment with glibenclamide in this disease.
Serum visfatin and vaspin levels in hepatocellular carcinoma (HCC)

Hepatocellular carcinoma (HCC) is the most common liver cancer, accountable for 90% cases. Visfatin and vaspin are adipocytokines with various suggested functions and proven significant correlations between BMI and percentage of body fat. The aim was to assess visfatin and vaspin serum levels in HCC patients and controls, compare their levels in patients with different cancer etiology and grade assessed according to the Barcelona-Clinic Liver Cancer (BCLC) staging system. The additional aim was to analyze relationship between analyzed adipokines and metabolic abnormalities and liver disfunction severity. The study was performed on 69 cirrhotic patients (54 males/15 females) with HCC, aged 59.0 ± 12.1 years, and with BMI 29.0 ± 4.5 kg/m2 compared to 20 healthy volunteers. Serum visfatin and vaspin concentrations were significantly increased in HCC patients compared to controls (p = 0.01 and p = 0.02, respectively). Serum vaspin was significantly higher in HCC patients with viral compared to those with non-viral etiology (p = 0.02), with more evident increase in chronic hepatitis C patients (CHC). Serum visfatin levels were significantly higher in patients with higher insulin resistance (p = 0.04) and with platelets count > 100 000/mm3 (p<0.001). Patients with BMI >30 kg/m2 had markedly up-regulated vaspin levels (p = 0.04). There was no difference in vaspin and visfatin serum levels with respect to liver dysfunction and BCLC classification. In conclusion, our study revealed serum vaspin and visfatin to be significantly increased in HCC patients independently of cancer etiology compared to controls. Additionally, serum vaspin was elevated in viral disease, especially in CHC. Vaspin up-regulation can be a compensatory mechanism against IR in HCC patients. Serum visfatin and vaspin, although up-regulated, seem not to be associated with cancer grade and cirrhosis severity.
Comparison of seizure outcomes and safety between anterior temporal lobotomy and lobectomy in patients with temporal lobe epilepsy

ABSTRACT Objectives: To compare the efficacy and safety of anterior temporal lobotomy (ATLo) and anterior temporal lobectomy (ATLe) in drug-resistant temporal lobe epilepsy. Methods: Patients diagnosed with pharmacoresistant temporal lobe epilepsy who underwent anterior temporal lobotomy (ATLo) or anterior temporal lobectomy (ATLe) performed by a single surgeon were retrospectively included. Every patient was followed up annually after surgery. The postoperative seizure outcome evaluation was based on the Engel and ILAE classifications. We compared postoperative complications and 2-year follow-up seizure outcomes between the ATLo group and the ATL group. Results: A total of 42 individuals (21 ATLo and 20 ATLe) were included. At the two-year follow-up, more patients in the ATLo group than the ATLe group had reached Engel class I (20 versus 14) and ILAE I (19 versus 13). However, these differences were not significant. One patient in the ATLo group had intraparenchymal hematoma and fully recovered. The two groups had similar incidences of other short-term complications, and no patients died or had any permanent complications. Discussion: ATLo is not inferior to ATLe for patients with drug-resistant temporal epilepsy. There was no significant difference in seizure outcomes or the rate of postoperative complications between the two groups. A large sample randomized control study is needed.
Imaging of Colorectal Liver Metastases: New Developments and Pending Issues

Computed tomography (CT), magnetic resonance imaging (MRI), and 18-fluorideoxyglucose positron emission tomography (18FDG-PET) are historically the most accurate imaging techniques for diagnosing liver metastases. Recently, the combination of diffusion-weighted imaging and hepatospecific contrast media, such as gadoxetic acid in MRI, have been demonstrated to have the highest diagnostic accuracy, sensitivity, and specificity for detecting liver metastases. Various recent meta-analyses have confirmed the diagnostic superiority of this combination (diffusion-weighted imaging and gadoxetic acid-enhanced MRI), especially in terms of per lesion sensitivity, as compared with CT and 18FDG-PET, even for smaller lesions (≤1 cm). However, none of the oncological guidelines have suggested the use of MRI as a first-line technique for liver metastasis detection during the staging process of oncological patients. This review analyzes the history of the principal imaging techniques for the diagnosis of liver metastases, in particular of colorectal liver metastases, focusing on the most accurate method (diffusion-weighted imaging combined with gadoxetic acid-enhanced MRI), possible reasons for the lack of its diffusion in the guidelines, and possible future scenarios.
Heat Transfer Through Insulating Glass Units Subjected to Climatic Loads

One of the structural elements used in the construction of insulating glass units (IGUs) are tight gaps filled with gas, the purpose of which is to improve the thermal properties of glazing in buildings. Natural changes in weather parameters: atmospheric pressure, temperature, and wind influence the gas pressure changes in the gaps and, consequently, the resultant loads and deflections of the component glass panes of a unit. In low temperature conditions and when the atmospheric pressure increases, the component glass panes may have a concave form of deflection, so that the thickness of the gaps in such loaded glazing may be less than its nominal thickness. The paper analyses the effect of reducing this thickness in winter conditions on the design heat loss through insulating glass units. For this purpose, deflections of glass in sample units were determined and on this basis the thickness of the gaps under operating conditions was estimated. Next, the thermal transmittance and density of heat-flow rate determined for gaps of nominal thickness and of thickness reduced under load were compared. It was shown that taking into account the influence of climatic loads may, under certain conditions, result in an increase in the calculated heat loss through IGUs. This happens when the gaps do not transfer heat by convection, i.e., in a linear range of changes in thermal transmittance. For example, for currently manufactured triple-glazed IGUs in conditions of “mild winter”, the calculated heat losses can increase to 5%, and for double-glazed IGUs with 10–14 mm gaps this ratio is about 4.6%. In other cases—e.g., large thickness of the gaps in a unit, large reduction in outside temperature—convention appears in the gaps. Then reducing the thickness of the gaps does not worsen the thermal insulation of the glazing. This effect should be taken into account when designing IGUs. It was also found that the wind load does not significantly affect the thickness of the gaps.
Roles of TrkC Signaling in the Regulation of Tumorigenicity and Metastasis of Cancer

Tropomyosin receptor kinase (Trk) C contributes to the clinicopathology of a variety of human cancers, and new chimeric oncoproteins containing the tyrosine kinase domain of TrkC occur after fusion to the partner genes. Overexpression of TrkC and TrkC fusion proteins was observed in patients with a variety of cancers, including mesenchymal, hematopoietic, and those of epithelial cell lineage. Both microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) were involved in the regulation of TrkC expression through transcriptional and posttranscriptional alteration. Aberrant activation of TrkC and TrkC fusion proteins markedly induces the epithelial-mesenchymal transition (EMT) program, growth rate, tumorigenic capacity via constitutive activation of Ras-MAP kinase (MAPK), PI3K-AKT, and the JAK2-STAT3 pathway. The clinical trial of TrkC or TrkC fusion-positive cancers with newly developed Trk inhibitors demonstrated that Trk inhibitors were highly effective in inducing tumor regression in patients who do not harbor mutations in the kinase domain. Recently, there has been a progressive accumulation of mutations in TrkC or the TrkC fusion protein detected in the clinic and its related cancer cell lines caused by high-throughput DNA sequencing. Despite given the high overall response rate against Trk or Trk fusion proteins-positive solid tumors, acquired drug resistance was observed in patients with various cancers caused by mutations in the Trk kinase domain. To overcome acquired resistance caused by kinase domain mutation, next-generation Trk inhibitors have been developed, and these inhibitors are currently under investigation in clinical trials.
Diabetic retinopathy screening uptake after health education with or without retinal imaging within the facility in two AYUSH hospitals in Hyderabad, India: A nonrandomized pilot study

Purpose: In India, people with diabetes (PwDM) often seek care in the government-approved alternative medicine system, AYUSH (Ayurveda, Yoga and naturopathy, Unani, Siddha and Homeopathy). The purpose of this pilot study was to assess whether health education plus retinal imaging for diabetic retinopathy (DR) within an AYUSH hospital increased the uptake of screening for DR compared with health education and referral. Methods: The study was a nonrandomized pilot conducted in two AYUSH hospitals. Both hospitals received intervention on educating the AYUSH practitioners about DR screening and distributing health education materials to diabetic patients. In one hospital in addition to education, retinal imaging by a trained technician with remote grading by an ophthalmologist was provided, while in another hospital PwDM were referred to nearby eye hospitals for screening. The uptake of screening was assessed through registers and phone calls. Results: At baseline, only 10.7% of 178 PwDM were aware of DR and only 8% had undergone DR screening. After the intervention, in the hospital where screening was provided, all (100%) eligible patients (101) underwent digital imaging, whereas in the other hospital only 25% of 77 eligible patients underwent screening in eye hospitals (P < 0.001). Conclusion: AYUSH hospitals could provide a feasible and acceptable location for providing DR screening services. Further studies are required to assess scale-up of such intervention.
Sickness Presence among Health Care Professionals: A Cross Sectional Study of Health Care Professionals in Slovenia

Background and objectives: Presenteeism is a relatively new phenomenon that people, despite complaints and ill health that should prompt them to rest and take sick leave, go to work in any case. The highest sickness presence is largely to be found in the care and welfare and educational sectors. The aim of the study is to investigate the relations between different factors and sickness presence among health care professionals. Materials and Methods: A cross-sectional study was conducted at the largest hospital in Slovenia involving 5865 health care professionals employed at the University Medical Centre Ljubljana in the period between 1 January 2010 and 31 December 2010. Logistic regression methods were used to assess the associations between risk factors and their interactions and sickness presence. Results: Besides high odds for sickness presence in multivariate modelling for acute (OR = 359.7; 95%CI = 89.1–1452.8) and chronic disease (OR = 722.5; 95%CI = 178.5–2924.5) the highest odds were calculated for poor self-related health (OR = 3.0; 95%CI = 1.9–4.8), no possibility of replacement (OR = 1.9; 95%CI = 1.5–2.3), sickness absence > two times a year (OR = 1.6; 95%CI = 1.2–2.1), disabled workers (OR = 1.6; 95%CI = 1.0–2.5), and lower salary when on sick leave (OR = 1.5; 95%CI = 120–1.9). Risk factors interactions were not found to be associated with sickness presence among health care workers. Conclusions: The pre-requisite for higher sickness presence is workers’ bad health. The results indicate that sickness presence was associated with psycho social risk factors at work and their economic consequences. Continued sickness presence might have negative rather than positive consequences on work and health care professionals’ health in the future. Sickness presence needs to be taken into account for health care organizers.
Biocompatible Organic Coatings Based on Bisphosphonic Acid RGD-Derivatives for PEO-Modified Titanium Implants

Currently, significant attention is attracted to the problem of the development of the specific architecture and composition of the surface layer in order to control the biocompatibility of implants made of titanium and its alloys. The titanium surface properties can be tuned both by creating an inorganic sublayer with the desired morphology and by organic top coating contributing to bioactivity. In this work, we developed a composite biologically active coatings based on hybrid molecules obtained by chemical cross-linking of amino acid bisphosphonates with a linear tripeptide RGD, in combination with inorganic porous sublayer created on titanium by plasma electrolytic oxidation (PEO). After the addition of organic molecules, the PEO coated surface gets nobler, but corrosion currents increase. In vitro studies on proliferation and viability of fibroblasts, mesenchymal stem cells and osteoblast-like cells showed the significant dependence of the molecule bioactivity on the structure of bisphosphonate anchor and the linker. Several RGD-modified bisphosphonates of β-alanine, γ-aminobutyric and ε-aminocaproic acids with BMPS or SMCC linkers can be recommended as promising candidates for further in vivo research.
Revealing the Usefulness of Aroma Networks to Explain Wine Aroma Properties: A Case Study of Portuguese Wines

Wine aroma is the result of complex interactions between volatile compounds and non-volatile ones and individual perception phenomenon. In this work, an aroma network approach, that links volatile composition (chromatographic data) with its corresponding aroma descriptors was used to explain the wine aroma properties. This concept was applied to six monovarietal wines from Bairrada Appellation (Portugal) and used as a case study. A comprehensive determination of the wines’ volatile composition was done (71 variables, i.e., volatile components), establishing a workflow that combines extraction techniques and gas chromatographic analysis. Then, a bipartite network-based approach consisting of two different nodes was built, one with 19 aroma descriptors, and the other with the corresponding volatile compound(s). To construct the aroma networks, the odor active values were calculated for each determined compound and combined with the bipartite network. Finally, the aroma network of each wine was compared with sensory descriptive analysis. The analysis of the specific aroma network of each wine revealed that Sauvignon Blanc and Arinto white wines present higher fruity (esters) and sweet notes (esters and C13 norisoprenoids) than Bical wine. Sauvignon Blanc also exhibits higher toasted aromas (thiols) while Arinto and Bical wines exhibit higher flowery (C13 norisoprenoids) and herbaceous notes (thiols), respectively. For red wines, sweet fruit aromas are the most abundant, especially for Touriga Nacional. Castelão and Touriga Nacional wines also present toasted aromas (thiols). Baga and Castelão wines also exhibit fusel/alcohol notes (alcohols). The proposed approach establishes a chemical aroma fingerprint (aroma ID) for each type of wine, which may be further used to estimate wine aroma characteristics by projection of the volatile composition on the aroma network.
TranCEP: Predicting the substrate class of transmembrane transport proteins using compositional, evolutionary, and positional information

Transporters mediate the movement of compounds across the membranes that separate the cell from its environment and across the inner membranes surrounding cellular compartments. It is estimated that one third of a proteome consists of membrane proteins, and many of these are transport proteins. Given the increase in the number of genomes being sequenced, there is a need for computational tools that predict the substrates that are transported by the transmembrane transport proteins. In this paper, we present TranCEP, a predictor of the type of substrate transported by a transmembrane transport protein. TranCEP combines the traditional use of the amino acid composition of the protein, with evolutionary information captured in a multiple sequence alignment (MSA), and restriction to important positions of the alignment that play a role in determining the specificity of the protein. Our experimental results show that TranCEP significantly outperforms the state-of-the-art predictors. The results quantify the contribution made by each type of information used.