Miracle-dz/UniFAR-FTUs huggingface dataset:
Feature, Function, and Information of Drug Transporter–Related Databases

With the rapid progress in pharmaceutical experiments and clinical investigations, extensive knowledge of drug transporters (DTs) has accumulated, which is valuable data for the understanding of drug metabolism and disposition. However, such data are largely dispersed in the literature, which hampers its utility and significantly limits its possibility for comprehensive analysis. A variety of databases have, therefore, been constructed to provide DT-related data, and they were reviewed in this study. First, several knowledge bases providing data regarding clinically important drugs and their corresponding transporters were discussed, which constituted the most important resources of DT-centered data. Second, some databases describing the general transporters and their functional families were reviewed. Third, various databases offering transporter information as part of their entire data collection were described. Finally, customized database functions that are available to facilitate DT-related research were discussed. This review provided an overview of the whole collection of DT-related databases, which might facilitate research on precision medicine and rational drug use. SIGNIFICANCE STATEMENT A collection of well established databases related to drug transporters were comprehensively reviewed, which were organized according to their importance in drug absorption, distribution, metabolism, and excretion research. These databases could collectively contribute to the research on rational drug use.
Moths sense but do not learn flower odors with their proboscis during flower investigation

ABSTRACT Insect pollinators, such as the tobacco hawkmoth Manduca sexta, are known for locating flowers and learning floral odors by using their antennae. A recent study revealed, however, that the tobacco hawkmoth additionally possesses olfactory sensilla at the tip of its proboscis. Here, we asked whether this second ‘nose’ of the hawkmoth is involved in odor learning, similar to the antennae. We first show that M. sexta foraging efficiency at Nicotiana attenuata flowers increases with experience. This raises the question whether olfactory learning with the proboscis plays a role during flower handling. By rewarding the moths at an artificial flower, we show that, although moths learn an odor easily when they perceive it with their antennae, experiencing the odor just with the proboscis is not sufficient for odor learning. Furthermore, experiencing the odor with the antennae during training does not affect the behavior of the moths when they later detect the learned odor with the proboscis only. Therefore, there seems to be no cross-talk between the antennae and proboscis, and information learnt by the antennae cannot be retrieved by the proboscis.
Can emotional expressivity and writing content predict beneficial effects of expressive writing among breast cancer patients receiving chemotherapy? A secondary analysis of randomized controlled trial data from China

Abstract Background To explore whether emotional expressivity and the patterns of language use could predict benefits from expressive writing (EW) of breast cancer (BC) patients in a culture that strongly discourages emotional disclosure. Methods Data were obtained from a recent trial in which we compared the health outcomes between a prolonged EW group (12 sessions) and a standard EW group (four sessions) (n = 56 per group) of BC patients receiving chemotherapy. The Chinese texts were tokenized using the THU Lexical Analyser for Chinese. Then, LIWC2015 was used to quantify positive and negative affect word use. Results Our first hypothesis that BC patients with higher levels of emotional expressivity tended to use higher levels of positive and negative affect words in texts was not supported (r = 0.067, p = 0.549 and r = 0.065, p = 0.559, respectively). The level of emotional expressivity has a significant effect on the quality of life (QOL), and those who used more positive or fewer negative affective words in texts had a better QOL (all p < 0.05). However, no significant difference was identified in physical and psychological well-being (all p > 0.05). Furthermore, the patterns of affective word use during EW did not mediate the effects of emotional expressivity on health outcomes (all p > 0.05). Conclusions Our findings suggest that the level of emotional expressivity and the pattern of affective word use could be factors that may moderate the effects of EW on QOL, which may help clinicians identify the individuals most likely to benefit from such writing exercises in China.
Short- and long-term exposure to air pollution increases the risk of stroke

Objective Many epidemiological studies have observed the association of air pollutant exposure with the onset, progression, and mortality of stroke. The aim of this study was to investigate the associations of air pollutants, including SO2, NO2, O3, CO, and PM10, with stroke according to exposure duration. Methods Data from the Korean National Health Insurance Service-Health Screening Cohort from 2002 to 2015 were obtained. The 21,240 patients who were admitted for or died due to stroke were 1:4 matched for age, sex, income, and region of residence with 84,960 control participants. The meteorological factors of mean, highest, and lowest temperatures; relative humidity; ambient atmospheric pressure; and air pollutant concentrations (SO2, NO2, O3, CO, and PM10) were analyzed to determine their associations with stroke. The odds ratios for stroke after exposure to each meteorological factor and air pollutant at 7 and 30 days were calculated in the stroke and control groups. Subgroup analyses were conducted according to age, sex, income, and region of residence. Results The odds ratio associated with seven days of exposure to CO was 1.16 (95% CI = 1.04–1.31) in stroke patients. For 30 days of exposure, the odds ratio associated with CO was 1.16 (95% CI = 1.02–1.32) in stroke patients. Seven and 30 days of NO2 exposure were inversely associated with stroke. The odds ratio associated with seven days of exposure to O3 was 1.16 (95% CI = 1.01–1.32) in ischemic stroke patients. Both ischemic and hemorrhagic stroke had negative associations with 7 and 30 days of NO2 exposure. Conclusion Both short- and long-term exposure to CO were related to stroke.
Causes and Consequences of Purifying Selection on SARS-CoV-2

Abstract Owing to a lag between a deleterious mutation’s appearance and its selective removal, gold-standard methods for mutation rate estimation assume no meaningful loss of mutations between parents and offspring. Indeed, from analysis of closely related lineages, in SARS-CoV-2, the Ka/Ks ratio was previously estimated as 1.008, suggesting no within-host selection. By contrast, we find a higher number of observed SNPs at 4-fold degenerate sites than elsewhere and, allowing for the virus’s complex mutational and compositional biases, estimate that the mutation rate is at least 49–67% higher than would be estimated based on the rate of appearance of variants in sampled genomes. Given the high Ka/Ks one might assume that the majority of such intrahost selection is the purging of nonsense mutations. However, we estimate that selection against nonsense mutations accounts for only ∼10% of all the “missing” mutations. Instead, classical protein-level selective filters (against chemically disparate amino acids and those predicted to disrupt protein functionality) account for many missing mutations. It is less obvious why for an intracellular parasite, amino acid cost parameters, notably amino acid decay rate, is also significant. Perhaps most surprisingly, we also find evidence for real-time selection against synonymous mutations that move codon usage away from that of humans. We conclude that there is common intrahost selection on SARS-CoV-2 that acts on nonsense, missense, and possibly synonymous mutations. This has implications for methods of mutation rate estimation, for determining times to common ancestry and the potential for intrahost evolution including vaccine escape.
Evaluation of the effect of high-intensity interval training on macular microcirculation via swept-source optical coherence tomography angiography in young football players

Purpose: This study was conducted to evaluate the effect of high intensity interval training (HIIT) on macular microcirculation, measured by swept source optical coherence tomography angiography (ss OCTA) in young football players. Methods: Football players between 18–20 years old were included. After a detailed ophthalmological examination, physiological parameters, including height, body weight, body fat, systemic blood pressure, hematocrit values, oxygen saturation, and heart rate, were recorded. Intraocular pressure and ss OCTA parameters were measured one day before and the day after the high intensity interval training program using DRI OCT Triton (Topcon, Tokyo, Japan) between 11:00 am and 1:00 pm. Results: Fifteen participants completed the study. All were males with a mean age of 18.1 ± 0.4 years. Systolic and diastolic blood pressure and oxygen saturation did not change significantly (P > 0.05), while hematocrit levels increased remarkably (P = 0.049) after the HIIT program. Heart rates and intraocular pressure decreased (P = 0.003, P = 0.017, respectively). There was a significant increase in the central vessel density in deep capillary plexus (before: 18.7 ± 3.8%, after: 21.1 ± 4.5%) and central vessel density in choriocapillaris (before: 54.5 ± 2.8%, after 56.9 ± 2.2%) (P = 0.02, P = 0.02, respectively), although no changes were observed in other ss OCTA or in the central macular thickness and subfoveal choroidal thickness. Conclusion: A 6 week, high intensity interval training program with three exercise sessions per week seems not to alter mean superficial vascular densities, deep foveal avascular zone, and superficial foveal avascular zones, central macular thickness, or subfoveal choroidal thickness, while the central deep vascular density and central choriocapillaris vascular density increased remarkably among ss OCTA parameters.
Contribution of Nε-lysine Acetylation towards Regulation of Bacterial Pathogenesis

Nε-lysine acetylation is an important, dynamic regulatory posttranslational modification (PTM) that is common in bacteria. Protein acetylomes have been characterized for more than 30 different species, and it is known that acetylation plays important regulatory roles in many essential biological processes. ABSTRACT Nε-lysine acetylation is an important, dynamic regulatory posttranslational modification (PTM) that is common in bacteria. Protein acetylomes have been characterized for more than 30 different species, and it is known that acetylation plays important regulatory roles in many essential biological processes. The levels of acetylation are enzymatically controlled by the opposing actions of lysine acetyltransferases and deacetylases. In bacteria, a second mechanism of acetylation exists and occurs via an enzyme-independent manner using the secondary metabolite acetyl-phosphate. Nonenzymatic acetylation accounts for global low levels of acetylation. Recently, studies concerning the role of protein acetylation in bacterial virulence have begun. Acetylated virulence factors have been identified and further characterized. The roles of the enzymes that acetylate and deacetylate proteins in the establishment of infection and biofilm formation have also been investigated. In this review, we discuss the acetylomes of human bacterial pathogens. We highlight examples of known acetylated virulence proteins and examine how they affect survival in the host. Finally, we discuss how acetylation might influence host-pathogen interactions and look at the contribution of acetylation to antimicrobial resistance.
Volumetric, acoustic, optical and spectroscopic studies of binary mixtures of the ionic liquid, 1-butyl-3-methyl imidazolium bis(trifluoromethylsulfonyl)imide and diethyl carbonate

ABSTRACT The properties, density, speed of sound and refractive index of ‘IL’ [Bmim][NTf2], diethyl carbonate and their binary mixtures are measured over the whole composition range as a function of temperature between 303.15 and 323.15 K at atm. pressure. These values are used to calculate the excess molar volumes, excess partial molar volumes, partial molar volumes at infinite dilution, excess isentropic compressibility, free length, speeds of sound and isobaric thermal expansion coefficient for the mixture. Various rules were used to predict the refractive indices and the data have been compared with the experimental results. These excess properties are fitted to the Redlich–Kister type equation to obtain the binary coefficients and the standard deviations. A qualitative analysis of these parameters indicates strong intermolecular interactions and the interaction increases with the increase in temperature. This was further supported by IR spectroscopy. In addition, analysis of data of the mixture was done through the Prigogine–Flory–Patterson theory.
Identification and functional analysis of the mitochondrial cysteine synthase TtCsa2 from Tetrahymena thermophila

Cysteine is a crucial component for all organisms and plays a critical role in the structure, stability, and catalytic functions of many proteins. Tetrahymena has reverse transsulfuration and de novo pathways for cysteine biosynthesis. Cysteine synthase is involved in the de novo cysteine biosynthesis and catalyzes the production of cysteine from O‐acetylserine. The novel cysteine synthase TtCSA2 was identified from Tetrahymena thermophila. The TtCSA2 showed high expression levels at the log‐phase and the sexual development stage. The TtCsa2 was localized on the outer mitochondrial membrane throughout different developmental stages. However, the truncated N‐terminal signal peptide mutant TtCsa2‐ΔN23 was localized into the mitochondria. His‐TtCsa2 was expressed in Escherichia coli and purified using affinity chromatography. The His‐TtCsa2 showed O‐acetylserine sulfhydrylase and serine sulfhydrylase activities. Cysteine and glutathione contents decreased in the csa2KD mutant. Furthermore, mutant cells were sensitive to cadmium and copper stresses. This study indicated that the TtCSA2 was involved in the cysteine synthesis in mitochondria and related to heavy metal stresses resistance in Tetrahymena.
Cutaneous Bacteria of Confiscated Telmatobius culeus in Lima, Peru

Abstract: The Lake Titicaca frog is endangered due to threats such as water pollution, introduced species, and overharversting for markets, where people consume them as frog juice. This study, conducted June to November 2012, aimed to determinate the bacteria microflora living on the skin of frogs confiscated from the La Parada market, Lima, Peru, and housed individually in the Laboratory of Wildlife at the Faculty of Veterinary Medicine and Zootechnic of the Universidad Peruana Cayetano Heredia in Lima, Peru. Samples collected with sterile swabs and cultured on blood, tryptic soy, and MacConkey agars were investigated using commercially available test kits, to investigate the commonly encountered bacterial and potentially zoonotic microorganisms associated with their consumption. We found three species of zoonotic concern in the genus Vibro: Vibrio alginolyticus, Vibro cholerae, and Vibro fluvialis. Other Gram-negative species cultured included two different colonies of Aeromonas hydrophila, or Aeromonas caviae or Aeromonas sobria; Pseudomona luteola; one example of Weeksella virosa or Empedobacter brevis; and Citrobacter freundii. Gram-positive bacteria detected were Staphylococcus spp. , Micrococcus spp. , and Erysipelothrix rhusiopathiae. We recommend against the consumption of this frog due to the pathogens it may carry that could cause serious illness among consumers and in vendors who handle animals.
Role of spectral domain optical coherence tomography in the diagnosis and prognosis of papilledema

Purpose: The study of papilledema with a novel noninvasive technique such as spectral domain-optical coherence tomography (SD-OCT) provides minute and detailed cross-sectional changes thus giving an insight into the application of biomechanical principles and pathophysiology of disc edema. Methods: We measured average retinal nerve fiber layer (RNFL) thickness and the retinal pigment epithelium/Bruch's membrane (RPE/BM) angle at the temporal and nasal borders of the neural canal opening (NCO) in 30 eyes with papilledema, 30 eyes with papillitis, and 80 control eyes. The inward angulation was considered as positive and the outward as negative. Follow-up was done at 1, 2, 3, and 6 months. The main outcome measures are the average RNFL thickness and the RPE/BM angle. Results: 29 eyes (96.6%) with papilledema had a positive RPE/BM angle (+8.11 ± 3.13). 29 eyes (96.6%) with papillitis had a negative RPE/BM angle (−1.04 ± 3.27). On follow-up at 1 month, both RNFL thickness (P = 0.01) and RPE-BM angle (P = 0.001) reduced significantly in eyes with papilledema; in eyes with papillitis, there was a significant reduction in the RNFL thickness (P = 0.02), but not in the RPE-BM angle (P > 0.05). RNFL thickness in papilledema cases normalized at 3 months whereas RPE/BM normalized at 6 months of follow-up. To detect papilledema, OCT has a sensitivity of 96.66% and specificity of 99.09% on both nasal and temporal sides. Conclusion: After appropriate treatment, the RPE/BM angle in papilledema decreased much later than the RNFL thickness. Hence, the RPE/BM angle in papilledema (positive) can be used to differentiate it from papillitis (negative) and also to monitor the activity of the disease.
Cohort study: “Outcomes of kidney transplantation in patients with prosthetic heart valves”

The number of kidney transplant candidates with prosthetic heart valves (PHVs) is increasing. Yet, outcomes of kidney transplantation in these patients are still unclear. This is the first report of post‐transplant outcomes in patients with PHVs at time of kidney transplantation. We conducted a matched cohort study among recipients from the multicentric and prospective DIVAT cohort to compare the outcomes in patients with left‐sided PHVs at time of transplantation and a group of recipients without PHV matched according to age, dialysis time, initial disease, pretransplant DSA, diabetes, and cardiovascular events. Of 23 018 patients, 92 patients with PHVs were included and compared to 276 patients without PHV. Delayed graft function and postoperative bleeding occurred more frequently in patients with PHVs. Kidney graft survival was similar between groups. 5‐year overall survival was 68.5% in patients with PHV vs. 87.9% in patients without PHV [HR, 2.72 (1.57–4.70), P = 0.0004]. Deaths from infection, endocarditis, and bleeding were more frequent in patients with PHV. Mechanical valves, but not bioprosthetic valves, were independent risk factors for mortality [HR, 2.89 (1.68–4.97), P = 0.0001]. Patients with PHV have high mortality rates after kidney transplantation. These data suggest that mechanical valves, but not biological valves, increase risks of post‐transplant mortality.
Foxm1 regulates neural progenitor fate during spinal cord regeneration

Xenopus tadpoles have the ability to regenerate their tails upon amputation. Although some of the molecular and cellular mechanisms that globally regulate tail regeneration have been characterised, tissue‐specific response to injury remains poorly understood. Using a combination of bulk and single‐cell RNA sequencing on isolated spinal cords before and after amputation, we identify a number of genes specifically expressed in the spinal cord during regeneration. We show that Foxm1, a transcription factor known to promote proliferation, is essential for spinal cord regeneration. Surprisingly, Foxm1 does not control the cell cycle length of neural progenitors but regulates their fate after division. In foxm1−/− tadpoles, we observe a reduction in the number of neurons in the regenerating spinal cord, suggesting that neuronal differentiation is necessary for the regenerative process. Altogether, our data uncover a spinal cord‐specific response to injury and reveal a new role for neuronal differentiation during regeneration.
Musculoskeletal Pain in Patients with Psoriasis and its Influence on Health-related Quality of Life: Results from a Danish Populationbased Survey

A nationwide e-based survey of patients with psoriasis was preformed to assess the pattern of musculoskeletal pain and its influence on patient-reported outcomes, including health-related quality of life and disability. A total of 561 respondents (56% of the screened psoriasis patients) reported physician- diagnosed psoriasis and completed the questionnaire. Respondents were grouped based on the presence of musculoskeletal pain and/or diagnosed psoriatic arthritis: 81% had psoriasis without arthritis (29% pain now, 23% pain previously, 39% no pain ever), and 19% had psoriatic arthritis. Patients with psoriasis with pain now had poorer quality of life compared with patients without pain and, importantly, similar to that of patients with arthritis. Furthermore, patients with pain now/previously reported higher self-assessed severity of psoriasis and lower satisfaction with current treatment than patients without pain. Two-thirds of patients with psoriasis with pain now/previously and one-third of patients with arthritis had never been examined by a rheumatologist, demonstrating an unmet need for adequate evaluation of such patients.
Effect of the surface charge density of nanoparticles on their translocation across pulmonary surfactant monolayer: a molecular dynamics simulation

Abstract Interaction between nanoparticles (NPs) and pulmonary surfactant monolayer plays a very significant role in nanoparticle-based pulmonary drug delivery system. Previous researches have indicated that different properties of nanoparticles can affect their translocation across pulmonary surfactant monolayer. Here we performed coarse-grained molecular dynamics simulation aimed at nanoparticles’ surface charge density effect on their penetration behaviours. Several hydrophilic nanoparticles with different surface charge densities were modelled in the simulations. The results show that NPs’ surface charge density affects their translocation capability: the higher the surface charge densities of NPs are, the worse their translocation capability is. It will cause the structural changes of pulmonary surfactant monolayer, and inhibit the normal phase transition of the monolayer during the compression process. Besides, charged NPs can be adsorbed on the surface of the monolayer after translocation as a stable state, and the adsorption capability of NPs increases generally with the increase of surface charge densities. Our simulation results suggest that the study of nanoparticle-based pulmonary drug delivery system should consider the nanoparticles’ surface charge density effect in order to avoid biological toxicity and improve efficacy.