Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Diversity via Tetrasubstituted Alkenes Containing a Barbiturate Motif: Synthesis and Biological Activity

The synthesis of a molecularly diverse library of tetrasubstituted alkenes containing a barbiturate motif is described. Base-induced condensation of N1-substituted pyrimidine-2,4,6(1H,3H,5H)-triones with 5-(bis(methylthio)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione gave 3-substituted 5-(methylthio)-2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-triones (‘pyranopyrimidinones’), regioselectively. A sequence of reactions involving ring-opening of the pyran moiety, displacement of the methylthio group with an amine, re-formation of the pyran ring, and after its final cleavage with an amine, gave tetrasubstituted alkenes (3-amino-3-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)propanamides) with a diversity of substituents. Cleavage of the pyranopyrimidinones with an aniline was facilitated in 2,2,2-trifluoroethanol under microwave irradiation. Compounds were tested against Escherichia coli, Staphylococcus aureus, the yeast Schizosaccharomyces pombe, and the pathogenic fungus Candida albicans. No compounds exhibited activity against E. coli, whilst one compound was weakly active against S. aureus. Three compounds were strongly active against S. pombe, but none was active against C. albicans.
Association between implementation of novel therapies and improved survival in patients starting haemodialysis: the Swedish Renal Registry 2006–15

Abstract Background The recent years have witnessed significant therapeutic advances for patients on haemodialysis (HD). We evaluated temporal changes in treatments practices and survival rates among incident HD patients. Methods This was an observational study of patients initiating HD in Sweden in 2006–15. Trends of HD-related practices, medications and routine laboratory biomarkers were evaluated. The incidence of death and major cardiovascular events (MACEs) across calendar years were compared against the age- and sex-matched general population. Via Cox regression, we explored whether adjustment for implementation of therapeutic advances modified observed survival and MACE risks. Results Among 6612 patients, age and sex were similar, but the burden of comorbidities increased over time. The proportion of patients receiving treatment by haemodiafiltration, ≥3 sessions/week, lower ultrafiltration rate and working fistulas increased progressively, as did use of non-calcium phosphate binders, cinacalcet and vitamin D3. The standardized 1-year mortality decreased from 13.2% in 2006–07 to 11.1% in 2014–15. The risk of death decreased by 6% [hazard ratio (HR) = 0.94, 95% confidence interval (CI) 0.90–0.99] every 2 years, and the risk of MACE by 4% (HR = 0.96, 95% CI 0.92–1.00). Adjustment for changes in treatment characteristics abrogated these associations (HR = 1.00, 95% CI 0.92–1.09 for death and 1.00, 0.94–1.06 for MACE). Compared with the general population, the risk of death declined from 6 times higher in 2006–07 [standardized incidence rate ratio (sIRR) = 6.0, 95% CI 5.3–6.9] to 5.6 higher in 2014–15 (sIRR = 5.57, 95% CI 4.8–6.4). Conclusions Gradual implementation of therapeutic advances over the last decade was associated with a parallel reduction in short-term risk of death and MACE among HD patients.
Malignant prolongation of the QTc interval due to severe vitamin D deficiency: an unusual presentation

Long QT syndrome with Torsades de Pointes (TdP) is a life-threatening polymorphic ventricular arrhythmia. The corrected QT (QTc) prolongation >500 milliseconds (ms) has been associated with TdP. Hypocalcaemia due to severe vitamin D deficiency is an uncommon cause of acquired long QT. We hereby present a case of a 40-year-old woman with sensorineural deafness and having symptoms of palpitations and presyncope. She had a QTc interval of 556 ms (reference range, QTc 451–470 ms in adult healthy woman) on 24-hour Holter analysis. Genetic analysis for congenital long QT syndrome was negative. She was diagnosed with severe hypocalcaemia secondary to severe vitamin D deficiency. After treatment with intravenous calcium gluconate, followed by oral vitamin D and calcium supplementation, the QTc became normalised and no further episode of palpitations or presyncope occurred. The causes of vitamin D deficiency was due to inadequate exposure to sunlight and a strict vegan diet.
Ni-Rich Layered Oxide with Preferred Orientation (110) Plane as a Stable Cathode Material for High-Energy Lithium-Ion Batteries

The cathode, a crucial constituent part of Li-ion batteries, determines the output voltage and integral energy density of batteries to a great extent. Among them, Ni-rich LiNixCoyMnzO2 (x + y + z = 1, x ≥ 0.6) layered transition metal oxides possess a higher capacity and lower cost as compared to LiCoO2, which have stimulated widespread interests. However, the wide application of Ni-rich cathodes is seriously hampered by their poor diffusion dynamics and severe voltage drops. To moderate these problems, a nanobrick Ni-rich layered LiNi0.6Co0. 2Mn0.2O2 cathode with a preferred orientation (110) facet was designed and successfully synthesized via a modified co-precipitation route. The galvanostatic intermittent titration technique (GITT) and electrochemical impedance spectroscopy (EIS) analysis of LiNi0.6Co0. 2Mn0.2O2 reveal its superior kinetic performance endowing outstanding rate performance and long-term cycle stability, especially the voltage drop being as small as 67.7 mV at a current density of 0.5 C for 200 cycles. Due to its unique architecture, dramatically shortened ion/electron diffusion distance, and more unimpeded Li-ion transmission pathways, the current nanostructured LiNi0.6Co0. 2Mn0.2O2 cathode enhances the Li-ion diffusion dynamics and suppresses the voltage drop, thus resulting in superior electrochemical performance.
Isolation and Antitrypanosomal Characterization of Furoquinoline and Oxylipin from Zanthoxylum zanthoxyloides

In the absence of vaccines, there is a need for alternative sources of effective chemotherapy for African trypanosomiasis (AT). The increasing rate of resistance and toxicity of commercially available antitrypanosomal drugs also necessitates an investigation into the mode of action of new antitrypanosomals for AT. In this study, furoquinoline 4, 7, 8-trimethoxyfuro (2, 3-b) quinoline (compound 1) and oxylipin 9-oxo-10, 12-octadecadienoic acid (compound 2) were isolated from the plant species Zanthoxylum zanthoxyloides (Lam) Zepern and Timler (root), and their in vitro efficacy and mechanisms of action investigated in Trypanosoma brucei (T. brucei), the species responsible for AT. Both compounds resulted in a selectively significant growth inhibition of T. brucei (compound 1, half-maximal effective concentration EC50 = 1.7 μM, selectivity indices SI = 74.9; compound 2, EC50 = 1.2 μM, SI = 107.3). With regards to effect on the cell cycle phases of T. brucei, only compound 1 significantly arrested the second growth-mitotic (G2-M) phase progression even though G2-M and DNA replication (S) phase arrest resulted in the overall reduction of T. brucei cells in G0-G1 for both compounds. Moreover, both compounds resulted in the aggregation and distortion of the elongated slender morphology of T. brucei. Analysis of antioxidant potential revealed that at their minimum and maximum concentrations, the compounds exhibited significant oxidative activities in T. brucei (compound 1, 22.7 μM Trolox equivalent (TE), 221.2 μM TE; compound 2, 15.0 μM TE, 297.7 μM TE). Analysis of growth kinetics also showed that compound 1 exhibited a relatively consistent growth inhibition of T. brucei at different concentrations as compared to compound 2. The results suggest that compounds 1 and 2 are promising antitrypanosomals with the potential for further development into novel AT chemotherapy.
Decoration of SiO2 and Fe3O4 Nanoparticles onto the Surface of MWCNT-Grafted Glass Fibers: A Simple Approach for the Creation of Binary Nanoparticle Hierarchical and Multifunctional Composite Interphases

We report on a versatile method for chemically grafting multiwalled carbon nanotubes (MWCNTs) onto the surface of conventional glass fibers (GFs), as well as depositing further silica (SiO2) or superparamagnetic (SPM) magnetite (Fe3O4) nanoparticles (NPs) creating novel hierarchical reinforcements. The CNT-grafted GFs (GF-CNT) were utilized further as the support to decorate nano-sized SiO2 or Fe3O4 via electrostatic interactions, resulting finally into double hierarchy reinforcements. SiO2 NPs were first used as model nano-particulate objects to investigate the interfacial adhesion properties of binary coated GFs (denoted as GF-CNT/SiO2) in epoxy matrix via single fiber pull-out (SFPO) tests. The results indicated that the apparent interfacial shear strength (IFSS or τapp) was significantly increased compared to the GF-CNT. Fe3O4 NPs were assembled also onto CNT-grafted GFs resulting into GF-CNT/Fe3O4. The fibers exhibited a magnetic response upon being exposed to an external magnet. Scanning electron microscopy (SEM) revealed the surface morphologies of the different hierarchical fibers fabricated in this work. The interphase microstructure of GF-CNT and GF-CNT/SiO2 embedded in epoxy was investigated by transmission electron microscopy (TEM). The hybrid and hierarchical GFs are promising multifunctional reinforcements with appr. 85% increase of the IFSS as compared to typical amino-silane modified GFs. It could be envisaged that, among other purposes, GF-CNT/Fe3O4 could be potentially recyclable reinforcements, especially when embedded in thermoplastic polymer matrices.
Diagnostic indexes of a rapid immunoglobulin G/immunoglobulin M combined antibody test for severe acute respiratory syndrome coronavirus 2

Detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a supplemental option for reverse transcription polymerase chain reaction (RT-PCR) detection, regardless of whether it is immunoglobulin M (IgM), immunoglobulin G (IgG) or combined detection. However, there are inadequate data on the sensitivity and specificity of IgM/IgG detection, which is of paramount importance for the decision of whether, when, and how to use IgM/IgG antibody detection. The aim of this study was to evaluate the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of IgM/IgG antibody detection, especially the anti-interference ability and kappa coefficient compared with the SARS-CoV-2 RT-PCR, which was defined as a standard diagnosis in this study.
The transcription factor Shox2 shapes thalamocortical neuron firing and synaptic properties

Thalamocortical neurons (TCNs) transmit information about sensory stimuli from the thalamus to the cortex. In response to different physiological states and demands TCNs can fire in tonic and/or phasic burst modes. These firing properties of TCNs are supported by precisely timed inhibitory synaptic inputs from the thalamic reticular nucleus and intrinsic currents, including T-type Ca2+ and HCN currents. These intrinsic currents are mediated by Cav3.1 and HCN channel subunits, and alterations in expression or modulation of these channels can have dramatic implications on thalamus function. The factors that regulate these currents controlling the firing patterns important for integration of the sensory stimuli and the consequences resulting from the disruption of these firing patterns are not well understood. Shox2 is a transcription factor known to be important for pacemaker activity in the heart. We show here that Shox2 is also expressed in adult mouse thalamus. We hypothesized that genes regulated by Shox2’s transcriptional activity may be important for physiological properties of TCNs. In this study, we used RNA sequencing on control and Shox2 knockout mice to determine Shox2-affected genes and revealed a network of ion channel genes important for neuronal firing properties. Quantitative PCR confirmed that expression of Hcn2, 4 and Cav3.1 genes were affected by Shox2 KO. Western blotting showed expression of the proteins for these channels was decreased in the thalamus, and electrophysiological recordings showed that Shox2 KO impacted the firing and synaptic properties of TCNs. Finally, behavioral studies revealed that Shox2 expression in TCNs play a role in somatosensory function and object recognition memory. Overall, these results reveal Shox2 as a transcription factor important for TCN firing properties and thalamic function.
Buffer selection for HP treatment of biomaterials and its consequences for enzyme inactivation studies

Biochemical systems are best studied under buffered conditions and it is, therefore, necessary to have good knowledge on the pressure-induced changes in buffer pH. For experiments conducted at a set temperature, it is possible to use a relatively stable pressure buffer. However, when experiments have to be performed in a relatively large window of both pressure and temperature, it is not possible to find a buffer that is both pressure and temperature independent. An example of such an experiment is the measurement of pressure and temperature stability of enzymes. Here, we present the pressure dependence of pH of several buffers. We show that the pH of MES buffer pH 6.0 in a P–T plane from 0.1 to 1000 MPa and 10–90 °C has a pH range from 5.5 to 6.5. The effect of pH changes on enzyme inactivation is illustrated by an inactivation experiment with the β-glycosidase from the hyperthermophile Pyrococcus furiosus. Within the measured range, a decrease in pH of 0.5 units causes the enzyme inactivation constant to increase by an additional factor 2–3.
Characterization of α-Glucosidase Inhibitors from Psychotria malayana Jack Leaves Extract Using LC-MS-Based Multivariate Data Analysis and In-Silico Molecular Docking

Psychotria malayana Jack has traditionally been used to treat diabetes. Despite its potential, the scientific proof in relation to this plant is still lacking. Thus, the present study aimed to investigate the α-glucosidase inhibitors in P. malayana leaf extracts using a metabolomics approach and to elucidate the ligand–protein interactions through in silico techniques. The plant leaves were extracted with methanol and water at five various ratios (100, 75, 50, 25 and 0% v/v; water–methanol). Each extract was tested for α-glucosidase inhibition, followed by analysis using liquid chromatography tandem to mass spectrometry. The data were further subjected to multivariate data analysis by means of an orthogonal partial least square in order to correlate the chemical profile and the bioactivity. The loading plots revealed that the m/z signals correspond to the activity of α-glucosidase inhibitors, which led to the identification of three putative bioactive compounds, namely 5′-hydroxymethyl-1′-(1, 2, 3, 9-tetrahydro-pyrrolo (2, 1-b) quinazolin-1-yl)-heptan-1′-one (1), α-terpinyl-β-glucoside (2), and machaeridiol-A (3). Molecular docking of the identified inhibitors was performed using Auto Dock Vina software against the crystal structure of Saccharomyces cerevisiae isomaltase (Protein Data Bank code: 3A4A). Four hydrogen bonds were detected in the docked complex, involving several residues, namely ASP352, ARG213, ARG442, GLU277, GLN279, HIE280, and GLU411. Compound 1, 2, and 3 showed binding affinity values of −8.3, −7.6, and −10.0 kcal/mol, respectively, which indicate the good binding ability of the compounds towards the enzyme when compared to that of quercetin, a known α-glucosidase inhibitor. The three identified compounds that showed potential binding affinity towards the enzymatic protein in molecular docking interactions could be the bioactive compounds associated with the traditional use of this plant.
Aerobic Exercise Improves Postprandial Inflammatory and Hemostatic Markers After a High-Fat Meal: A Randomized Cross-Over Study.

Exercise intensity modulates postprandial lipemia. It is still unknown, however, its effect on hemostatic and pro- and anti-inflammatory markers in the postprandial state. Eleven young males perform a 2-day trial on different conditions: (i) REST: rest for 45 min; (ii) MIE: moderate-intensity exercise; and (iii) HIE: heavy-intensity exercise. Experimental conditions were performed in the evening. On the following morning, blood samples were taken in the fasted state (0 h) and at 1, 3, and 5 h after the consumption of a high-fat meal (HFM). Interleukin-10 (IL-10) levels were higher in the HIE vs. MIE trial at 0 and 1 h (p < 0.033) and IL-10 iAUC was greater in the MIE (p = 0.027) and HIE (p = 0.045) vs. REST. Lower levels of anti-coagulation factor VII (FVII) were observed at 1 h in the MIE condition vs. REST (p = 0.043). In comparison with REST, MIE improved hemostatic (FVII) and anti-inflammatory markers (IL-10 iAUC) whereas HIE enhanced IL-10 in the postprandial state. Regardless of the exercise intensity, aerobic exercise mitigates the deleterious consequences of an HFM. Novelty Bullets: • Prior aerobic exercise at moderate-intensity attenuates next day's postprandial FVII and IL-10 levels whereas exercise performed at heavy-intensity increases IL-10 levels. • Moderate-intensity exercise may be more beneficial to improve hemostatic (FVII) and anti-inflammatory (IL-10) responses while heavy-intensity exercise may improve anti-inflammatory (IL-10) levels only.
Misincorporation of Galactose by Chondroitin Synthase of Escherichia coli K4: From Traces to Synthesis of Chondbiuronan, a Novel Chondroitin-Like Polysaccharide

Chondroitin synthase KfoC is a bifunctional enzyme which polymerizes the capsular chondroitin backbone of Escherichia coli K4, composed of repeated β3N-acetylgalactosamine (GalNAc)-β4-glucuronic acid (GlcA) units. Sugar donors UDP-GalNAc and UDP-GlcA are the natural precursors of bacterial chondroitin synthesis. We have expressed KfoC in a recombinant strain of Escherichia coli deprived of 4-epimerase activity, thus incapable of supplying UDP-GalNAc in the bacterial cytoplasm. The strain was also co-expressing mammal galactose β-glucuronyltransferase, providing glucuronyl-lactose from exogenously added lactose, serving as a primer of polymerization. We show by the mean of NMR analyses that in those conditions, KfoC incorporates galactose, forming a chondroitin-like polymer composed of the repeated β3-galactose (Gal)-β4-glucuronic acid units. We also show that when UDP-GlcNAc 4-epimerase KfoA, encoded by the K4-operon, was co-expressed and produced UDP-GalNAc, a small proportion of galactose was still incorporated into the growing chain of chondroitin.
Developing Virtual Reality Trauma Training Experiences Using 360-Degree Video: Tutorial

Historically, medical trainees were educated in the hospital on real patients. Over the last decade, there has been a shift to practicing skills through simulations with mannequins or patient actors. Virtual reality (VR), and in particular, the use of 360-degree video and audio (cineVR), is the next-generation advancement in medical simulation that has novel applications to augment clinical skill practice, empathy building, and team training. In this paper, we describe methods to design and develop a cineVR medical education curriculum for trauma care training using real patient care scenarios at an urban, safety-net hospital and Level 1 trauma center. The purpose of this publication is to detail the process of finding a cineVR production partner; choosing the camera perspectives; maintaining patient, provider, and staff privacy; ensuring data security; executing the cineVR production process; and building the curriculum.
Helicobacter pylori Infection and the Patterns of Gastric Mucin Expression in Children

Background: The updated model for the mechanism of gastric carcinogenesis demonstrates that Helicobacter pylori (H. pylori) is a risk factor in every step of the process. The expression of certain gastric mucins is altered by H. pylori infection in adult patients. The aim of our research was to assess the impact of H. pylori infection on the expression of secretory mucins in the pediatric antral mucosa. Methods: Slides were stained with monoclonal antibodies for MUC5AC, MUC6 and MUC2, digitalized and scored using both a semiquantitative and a quantitative approach. Results: The expression of MUC5AC was significantly lower in infected children. Also, MUC2 expression was more pronounced in infected children. MUC6 expression did not differentiate between infected and noninfected children. Additionally, the presence of chronic inflammation significantly altered the expression of MUC6 and MUC2. The expression of MUC6 was significantly higher in patients with gastric atrophy. Conclusion: The minor differences in mucin expression at distinct ages might stem from different H. pylori exposure periods. Further research is needed to determine the particular patterns of expression according to age and to evaluate the effects of the interaction between H. pylori and mucins in the progression of the gastric carcinogenesis cascade.
Nomograms based on pre-operative parametric for prediction of short-term mortality in acute myocardial infarction patients treated invasively

Objective Our aim was to develop and independently validate nomograms to predict short-term mortality in acute myocardial infarction (AMI) patients. Results There were 1229 AMI patients enrolled in this study. In the training cohort (n=534), 69 deaths occurred during a median follow-up period of 375 days. The C-index for 1-year mortality in the training group and the validation cohort was 0.826 (95%CI: 0.780 - 0.872) and 0.775 (95%CI: 0.695 - 0.855), respectively. Integrated Discrimination Improvement (IDI) and net reclassification improvement (NRI) also showed a significant improvement in the accuracy of the new model compared with the Global Registry of Acute Coronary Events (GRACE) risk score. Furthermore, C-index of the prospective cohort (n=309) achieved 0.817 (95%CI: 0.754 - 0.880) for 30-day mortality and 0.790 (95%CI: 0.718 - 0.863) for 1-year mortality. Conclusions Collectively, our simple-to-use nomogram effectively predicts short-term mortality in AMI patients. Methods AMI patients who had undergone invasive intervention between January 2013 and Jan 2018 were enrolled. Cox regression analysis was used on the training cohort to develop nomograms for predicting 30-day and 1-year mortality. Model performance was then evaluated in the validation cohort and another independent prospective cohort.
Alterins Produced by Oyster-Associated Pseudoalteromonas Are Antibacterial Cyclolipopeptides with LPS-Binding Activity

Discovery after discovery, host-associated microbiota reveal a growing list of positive effects on host homeostasis by contributing to host nutrition, improving hosts’ immune systems and protecting hosts against pathogens. In that context, a collection of oyster associated bacteria producing antibacterial compounds have been established to evaluate their role in non-host-derived immunity. Here, we described alterins; potent anti-Gram negative compounds produced by Pseudoalteromonas hCg-6 and hCg-42 isolated from different healthy oyster hemolymph. The strains hCg-6 and hCg-42 produce a set of at least seven antibacterial compounds, ranging from 926 to 982 Da structurally characterized as cyclolipopeptides (CLPs). Alterins share the same cationic heptapeptidic cycle connected via an amido bond to different hydrophobic hydrocarbon tails. Their MICs disclosed a potent antibacterial activity directed against Gram-negative bacteria including oyster and human pathogens that may confer a beneficial defense mechanism to the host but also represents an untapped source of new antibiotics. The alterins’ mechanisms of action have been deciphered: after binding to lipopolysaccharides (LPS), alterins provoke a membrane depolarization and permeabilization leading to bacterial lysis. As hCg-6 and hCg-42 produced a set of natural derivatives, the structure/activity relationship linked to the carbon tail is clarified. We showed that the hydrocarbon tail determines the LPS-binding properties of alterins and consequently their antibacterial activities. Its length and saturation seem to play a major role in this interaction.