Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic and structural basis for evolution of tropane alkaloid biosynthesis

Significance Plants produce structurally diverse and lineage-specific natural products through a coordination of serial enzymes to catalyze sequential reactions. Cocaine and hyoscyamine with similar tropane skeletons are distributed among different families. The independent recruitments of serial biosynthetic enzymes responsible for cocaine and hyoscyamine biosynthesis were revealed on the genomic and structural levels. This rare phenomenon reminds us that the discovery of biosynthetic enzymes based exclusively on enzyme homology or key conserved sites requires caution when investigating the biosynthesis of natural products with similar chemical structure in phylogenetically distant species.
Clinical benefits of vortioxetine 20 mg/day in patients with major depressive disorder

Abstract Background Vortioxetine has demonstrated dose-dependent efficacy in patients with major depressive disorder (MDD), with the greatest effect observed with vortioxetine 20 mg/day. This analysis further explored the clinical relevance of the more rapid and greater improvement in depressive symptoms observed with vortioxetine 20 mg/day vs 10 mg/day. Methods Analysis of pooled data from six short-term (8-week), randomized, placebo-controlled, fixed-dose studies of vortioxetine 20 mg/day in patients with MDD (N = 2620). Symptomatic response (≥50% decrease in Montgomery–Åsberg Depression Rating Scale [MADRS] total score), sustained symptomatic response, and remission (MADRS total score ≤10) were assessed by vortioxetine dosage (20 or 10 mg/day). Results After 8 weeks, 51.4% of patients receiving vortioxetine 20 mg/day had achieved symptomatic response vs 46.0% of those receiving vortioxetine 10 mg/day (P < .05). Significantly more patients achieved symptomatic response vs placebo from week 2 onwards for vortioxetine 20 mg/day and from week 6 onwards for vortioxetine 10 mg/day (both P ≤ .05). Sustained response was achieved from week 4 for 26.0% of patients receiving vortioxetine 20 mg/day vs 19.1% of those receiving vortioxetine 10 mg/day (P < .01), increasing to 36.0% and 29.8%, respectively, over the 8-week treatment period (P < .05). At week 8, 32.0% of patients receiving vortioxetine 20 mg/day were in remission vs 28.2% of those receiving vortioxetine 10 mg/day (P = .09). Rates of adverse events and treatment withdrawal were not increased during the week following vortioxetine dose up-titration to 20 mg/day. Conclusion Vortioxetine 20 mg/day provides more rapid and more sustained symptomatic response than vortioxetine 10 mg/day in patients with MDD, without compromising tolerability.
Bile acid alterations associated with indolent course of inflammatory bowel disease

Abstract Background The indolent course of treatment-naive patients with inflammatory bowel disease (IBD) is confirmed predictable based on clinical characteristics. Current evidences supported that bile acids (BAs) alteration might be promising biomarkers in the field of IBD. We aimed to analyze the alterations of BAs as the disease progresses and explore their predictive value for indolent course of IBD. Methods The indolent course of IBD was defined as a disease course without need for strict interventions throughout the entire follow-up. A targeted metabolomics method was used to detect the concentration of 27 BAs from serum sample in treatment-naive patients with IBD (Crohn’s disease [CD], n = 27; ulcerative colitis [UC], n = 50). Patients with CD and UC were individually divided into two groups for further study according to the median time of indolent course. The overall BAs profile and the clinical value of BAs in predicting indolent course of IBD were identified between different groups. Results For CD, the levels of deoxycholic acid, glycodeoxycholic acid, taurodeoxycholic acid, glycolithocholic acid-3-sulfate disodium salt and iso-lithocholic acid were significantly increased in patients with indolent course > 18 M (p < 0.05). These five BAs owned 83.5% accuracy for predicting indolent course over 18 months in CD. For UC, the concentration of deoxycholic acid and glycodeoxycholic acid were significantly higher, while dehydrocholic acid were lower in patients with indolent course > 48 M (p < 0.05). These three BAs predicted indolent course over 48 months of 69.8% accuracy in UC. Conclusion The specific BAs alterations might be potential biomarkers in predicting disease course of IBD patients.
Electrical performance of monolayer MoS2 transistor with MoS2 nanobelt metallic edges as electrodes

The contact electrodes have great influence on the performance of monolayer MoS2 devices. In this paper, monolayer MoS2 and MoS2 nanobelts were synthesized on SiO2/Si substrates via the chemical vapor deposition method. By using wet and dry transfer process, MoS2 nanobelt metallic edges were designed as the source/drain contact electrodes of monolayer MoS2 field effect transistor. The ‘nanobelt metallic edges’ refers to the top surface of the nanobelt being metallic. Because the base planes of MoS2 nanobelt vertically stand on the substrate, which makes the layer edges form the top surface of the nanobelt. The nonlinear I ds–V ds characteristics of the device indicates that the contact between the monolayer MoS2 and MoS2 metallic edges displays a Schottky-like behavior. The back-gated transfer characteristics indicate that monolayer MoS2 device with MoS2 nanobelt metallic edges as electrodes shows an n-type behavior with a mobility of ∼0.44 cm2 V−1·s−1, a carrier concentration of ∼7.31 × 1011 cm−2, and an on/off ratio of ∼103. The results enrich the electrode materials of two-dimensional material devices and exhibit potential for future application of MoS2 metallic edges in electronic devices.
Quality of anticoagulant control and patient experience associated with long-term warfarin in Canadian patients with non-valvular atrial fibrillation: A multicentre, prospective study

Background Despite the fact that direct oral anticoagulants (DOACs) are favoured over warfarin for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), physicians need to maintain competence in using and monitoring warfarin since many patients have contraindications or other barriers to using DOACs. Unlike DOACs, warfarin therapy requires regular blood testing to ensure that it is within a target range to ensure efficacy and safety. There is limited real-world data on the adequacy of warfarin control and the cost and burden of monitoring warfarin therapy in Canadian NVAF patients. Objectives In a large cohort of Canadian patients with NVAF on warfarin we assessed time in therapeutic range (TTR), determinants of TTR, process of care, direct costs, health related quality of life and loss of work time and productivity related to warfarin therapy. Methods Five hundred and fifty one patients with NVAF, either newly initiated or stable on warfarin were prospectively enrolled across 9 Canadian provinces from primary care practices and anticoagulant clinics. Participating physicians provided baseline demographic and medical information. Patients completed diaries for 48 weeks, capturing information about International Normalized Ratio (INR) test results, test locations, process of INR monitoring, direct costs of travel, health-related quality of life and work productivity measures. TTR was estimated using linear interpolation of INR results and linear regression used to investigate associations between TTR and factors (defined a priori). Results Four hundred and eighty (87.1%) patients had complete follow-up with an overall TTR of 74.4% based on 7,175 physician-reported INR values from 501 patients. 88% of this cohort were monitored through routine medical care (RMC). The average number of INRs per patient during the 48-week period was 14.1 (standard deviation (SD) = 8.3) tests with a mean duration of 23.8 (SD = 11.1) days between tests. We did not find a relationship between TTR and age, sex, presence of major comorbidities, patient’s province of residence or rural vs. urban residence. 12% of patients monitored through anticoagulant clinics had significantly better TTR than patients monitored through RMC (82% vs. 74%; 95% confidence interval: -13.8, -1.2; p = 0.02). Health related quality of life utility values were high and remained consistent throughout the study. The majority of patients reported no impact on either work productivity or impairment of regular activities due to being on long-term warfarin treatment. Conclusions We showed excellent overall TTR in an observed Canadian cohort, with monitoring through a dedicated anticoagulant clinic being associated with a statistically and clinically significant improvement in TTR. The burden of warfarin therapy on patients’ health related quality of life or daily work and activities was low.
Numerical simulation and analysis of flow control using electromagnetic forcing

This study focuses on the response of a boundary layer to perturbation by periodic electromagnetic forces in sea water. Both laminar and turbulent flows are simulated. The time-dependent NavierStokes equations are solved coupled with unsteady Lorentz force actuators. An electromagnetic solver provides the spatial variation of the electric and magnetic fields, which are then cycled in time. This simulation work provides significant insight into the phenomenology that would be difficult to gain experimentally. The simulations capture many essential features of the perturbed flowfield that have been experimentally observed, including rotational flow structures, frequency dependence, reductions in local skin friction, and effect of magnet orientation.
Inhibitory effect of natural compounds on Dihydropteroate synthase of Mycobacterium leprae: Molecular dynamic study

Abstract Leprosy is a chronic infectious disease caused by a bacillus, Mycobacterium leprae. According to official data from 139 countries in the 6 WHO Regions, there were 127558 new leprosy cases worldwide in 2020. Leprosy mainly affects the skin, the peripheral nerves, mucosa of the upper respiratory tract, and the eyes. If this disease is left untreated, can harm the skin, nerves, limbs, eyes, and skin permanently. The disease is curable with multidrug therapy. Over a period of time Mycobacterium leprae has become resistant to these drugs. Therefore, new therapeutic molecules are warranted. This study was aimed to carry out the in-silico analysis to determine the inhibitory effect of natural compounds on Dihydropteroate synthase (DHPS) of Mycobacterium leprae. The DHPS is a key enzyme in the folate biosynthesis pathway in M. leprae and acts as a competitive inhibitor of PABA. The 3D structure of DHPS protein was modeled using homology modeling and was validated. Molecular docking and simulation along with other in-silico methods were employed to determine the inhibitory effect of ligand molecules towards DHPS target protein. Results revealed ZINC03830554 molecule as a potential inhibitor of DHPS. Binding experiments and bioassays utilizing this strong inhibitor molecule against purified DHPS protein are necessary to validate these early findings. Communicated by Ramaswamy H. Sarma
On the Approximation and Smoothed Complexity of

We show that the problem of finding an �-approximate Nash equilibrium of an n× n two-person games can be reduced to the computation of an (�/n) 2 -approximate market equilibrium of a Leontief economy. Together with a recent result of Chen, Deng and Teng, this polynomial reduction implies that the Leontief market exchange problem does not have a fully polynomial-time approximation scheme, that is, there is no algorithm that can compute an �-approximate market equilibrium in time polynomial �
International performance level in adult ice hockey: The role of the talent environment in youth

ABSTRACT Despite a growing interest in conducive talent development environments (TDE), the relationship between TDEs and the performance level in adulthood remains unclear. Therefore, this study examined the relationship of the micro-environment of former Swiss junior national team ice hockey players with their performance level in adulthood. With quantitative, retrospective data from n = 106 players born between 1984 and 1994, patterns of four factors club, family, peer, and school were built for early (13–15 years old) and late (16–19 years old) youth. The results revealed four structurally and mainly individually stable clusters for both developmental stages in youth. The cluster of the moderately above-average supported players between 16–19 years old demonstrated above-average values in all factors of the micro-environment and are more likely to reach international playing level in adulthood, whereas the structurally weak supported players are linked to a later regional playing level. These results indicate that simultaneous support across all four factors of the micro-environment in youth (club, family, peers, and school) is important to reach an international playing level, while low support in one or more area reduces the chance thereof. Thus, creating supportive environments across the board should be considered for a successful talent development.
Quantitative 1H Nuclear Magnetic Resonance Assay for the Rapid Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis from Sputum Samples

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the 10 leading killer diseases in the world. At least one-quarter of the population has been infected, and there are 1.3 million deaths annually. ABSTRACT Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the 10 leading killer diseases in the world. At least one-quarter of the population has been infected, and there are 1.3 million deaths annually. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains challenges TB treatments. One of the drugs widely used in first- and second-line regimens is pyrazinamide (PZA). Statistically, 50% of MDR and 90% of XDR clinical strains are resistant to PZA, and recent studies have shown that its use in patients with PZA-resistant strains is associated with higher mortality rates. Therefore, the is an urgent need for the development of an accurate and efficient PZA susceptibility assay. PZA crosses the M. tuberculosis membrane and is hydrolyzed to its active form, pyrazinoic acid (POA), by a nicotinamidase encoded by the pncA gene. Up to 99% of clinical PZA-resistant strains have mutations in this gene, suggesting that this is the most likely mechanism of resistance. However, not all pncA mutations confer PZA resistance, only the ones that lead to limited POA production. Therefore, susceptibility to PZA may be addressed simply by its ability to form, or not, POA. Here, we present a nuclear magnetic resonance method to accurately quantify POA directly in the supernatant of sputum cultures collected from TB patients. The ability of the clinical sputum culture to hydrolyze PZA was determined, and the results were correlated with the results of other biochemical and molecular PZA drug susceptibility assays. The excellent sensitivity and specificity values attained suggest that this method could become the new gold standard for the determination of PZA susceptibility.
Complete Genome Sequence of Klebsiella pneumoniae Bacteriophage KpS110, Encoding Five Tail-Associated Proteins with Putative Polysaccharide Depolymerase Domains

We report the genome sequence of bacteriophage KpS110, which infects Klebsiella pneumoniae, a multidrug-resistant encapsulated bacterium that causes severe community-acquired and hospital-acquired infections. The phage genome is 156,801 bp, with 201 open reading frames. KpS110 is most closely related to phages of the family Ackermannviridae at the genome and proteome levels. ABSTRACT We report the genome sequence of bacteriophage KpS110, which infects Klebsiella pneumoniae, a multidrug-resistant encapsulated bacterium that causes severe community-acquired and hospital-acquired infections. The phage genome is 156,801 bp, with 201 open reading frames. KpS110 is most closely related to phages of the family Ackermannviridae at the genome and proteome levels.
The Effects of Uniform and Nonuniform Magnetic Fields in Plant Growth: A Meta‐Analysis Approach

Magnetic field (MF) effects have been reported in plants' growth, seed germination, gene expression, and water consumption. Accordingly, magnetic treatments have been proposed as a sustainable alternative to improve yields. Nevertheless, a comprehensive quantitative assessment is needed to understand whether their effects are general, species‐specific, or dependent on the experimental setting. We conducted a multilevel meta‐analysis of 45 articles that studied 29 different plant species. A positive and neutral effect of a nonuniform MF was found on fresh weight and germination rate, respectively. A significant association was found between a uniform MF and germination. These results suggest that MFs improve plant growth. However, the effects are highly dependent on the experimental setting. This opens exciting questions about the biophysical mechanisms underlying the perception and transduction of this environmental cue and about the possible translation to agricultural practices. © 2023 Bioelectromagnetics Society.
A hybrid three-dimensional electromagnetic modeling scheme

We present an efficient numerical method for computing electromagnetic (EM) scattering of arbitrary three‐dimensional (3-D) local inhomogeneities buried in a uniform or two‐layered earth. In this scheme the inhomogeneity is enclosed by a volume whose conductivity is discretized by a finite‐element mesh and whose boundary is only a slight distance away from the inhomogeneity. The scheme uses two sets of independent equations. The first is a set of finite‐element equations derived from a variational integral, and the second is a mathematical expression for the fields at the boundany in terms of electric fields inside the boundary. The Green’s function is used to derive the second set of equations. An iterative algorithm has been developed to solve these two sets of equations. The solutions are the electric fields at nodes inside the finite‐element mesh. The scattered fields anywhere may then be obtained by performing volume integrations over the inhomogeneous region. The scheme is used for modeling 3-D inho.
What Factors Explain Family Quality of Life in Neurodegenerative Diseases?

ABSTRACT Neurodegenerative diseases (NDs) are a major cause of dependency among elderly and affect the entire family unit. However, the literature has paid little attention to Family Quality of Life (FQOL) and focused on the patient and the main caregiver. The aim was to analyze the FQOL of people with NDs from a systemic perspective and to identify associated factors. A sample of 300 family caregivers from the cross-border region of Spain-Portugal completed the FQOLS – ND, which collected FQOL global and domain-level scores in terms of attainment and satisfaction. The highest rates of FQOL were obtained for the domain Family relations and the lowest for Support from services. The level of perceived barriers to social-health services emerged as the strongest predictor of global FQOL in all models. It is essential to reduce the obstacles to access social-health services and provide the family with resources according to their needs, especially in rural areas.
Respiratory Adenovirus Quantification with a Droplet Digital Polymerase Chain Reaction (ddPCR) Assay

Measuring viral load using droplet digital PCR (ddPCR) is an absolute quantification approach that can facilitate comparability between different laboratories. This approach could prove valuable in studies that focus on the clinical utility of quantification. In this study, we evaluate a human adenovirus (HAdV) ddPCR assay and study the relationship between viral loads and outcomes after HAdV respiratory infections. ABSTRACT Human adenoviruses (HAdVs) are double-stranded DNA viruses that can cause a wide spectrum of disease, including respiratory infections. Little is known about the value of respiratory HAdV quantification and its correlation with disease severity. In this study, we developed a quantitative HAdV droplet digital PCR (ddPCR) assay to study the association between viral loads, circulating types, and clinical outcomes. Remnant respiratory specimens positive for HAdV after the standard of care testing were collected from December 2020 to April 2022. A total of 129 samples were tested by a ddPCR method. Typing was performed using Nanopore sequencing of the hexon gene hypervariable region. Clinical chart reviews were performed to correlate the viral loads with the disease severity. The ddPCR assay showed an analytical sensitivity and a lower limit of quantification below 100 copies/mL. Of 129 positive clinical samples, 100 were quantified by ddPCR, 7 were too concentrated to be quantified, and 22 were negative. Of the 22 false negatives, only 3 were successfully typed; however, 99 of the 107 positive samples had a characterized genotype. The main HAdV types identified in this cohort were C1 (49.5%) followed by C2 (34.3%). No significant difference in HAdV loads was noted between patients who were admitted, those who required supplemental oxygen, and outpatients or between different HAdV types. HAdV ddPCR is a reliable absolute quantification approach for HAdV from respiratory samples. HAdV loads at initial presentation does not appear to differ between patients who require hospitalization versus outpatients. IMPORTANCE Measuring viral load using droplet digital PCR (ddPCR) is an absolute quantification approach that can facilitate comparability between different laboratories. This approach could prove valuable in studies that focus on the clinical utility of quantification. In this study, we evaluate a human adenovirus (HAdV) ddPCR assay and study the relationship between viral loads and outcomes after HAdV respiratory infections.
LncRNA EPR regulates intestinal mucus production and protects against inflammation and tumorigenesis

Abstract The long non-coding RNA EPR is expressed in epithelial tissues, binds to chromatin and controls distinct biological activities in mouse mammary gland cells. Because of its high expression in the intestine, in this study we have generated a colon-specific conditional targeted deletion (EPR cKO) to evaluate EPR in vivo functions in mice. EPR cKO mice display epithelium hyperproliferation, impaired mucus production and secretion, as well as inflammatory infiltration in the proximal portion of the large intestine. RNA sequencing analysis reveals a rearrangement of the colon crypt transcriptome with strong reduction of goblet cell-specific factors including those involved in the synthesis, assembly, transport and control of mucus proteins. Further, colon mucosa integrity and permeability are impaired in EPR cKO mice, and this results in higher susceptibility to dextran sodium sulfate (DSS)-induced colitis and tumor formation. Human EPR is down-regulated in human cancer cell lines as well as in human cancers, and overexpression of EPR in a colon cancer cell line results in enhanced expression of pro-apoptotic genes. Mechanistically, we show that EPR directly interacts with select genes involved in mucus metabolism whose expression is reduced in EPR cKO mice and that EPR deletion causes tridimensional chromatin organization changes.