Miracle-dz/UniFAR-FTUs huggingface dataset:
Longitudinal effect of disease‐modifying therapy on left ventricular diastolic function in children with sickle cell anemia

Cardiac abnormalities seen in sickle cell anemia (SCA) include diastolic dysfunction, which has been shown to be associated with high morbidity and early mortality. The effect of disease‐modifying therapies (DMT) on diastolic dysfunction is poorly understood. We prospectively evaluated the effects of hydroxyurea and monthly erythrocyte transfusions on diastolic function parameters over 2 years. A total of 204 subjects with HbSS or HbSβ0‐thalassemia (mean age 11 ± 3.7 years), unselected for disease severity, had diastolic function assessed with surveillance echocardiograms twice, 2 years apart. During this 2‐year observation period, 112 participants received DMTs (hydroxyurea, n = 72, monthly erythrocyte transfusions, n = 40), 34 initiated hydroxyurea, and 58 did not receive any DMT. The entire cohort showed an increase in left atrial volume index (LAVi) of 3.40 ± 10.86 mL/m2, p = . 001 over 2 years. This increase in LAVi was independently associated with anemia, high baseline E/e′ or LV dilation. Individuals not exposed to DMT were younger (mean age 8.8 ± 2.9 years), but at baseline their prevalence of abnormal diastolic parameters was similar to that of the DMT‐exposed participants who were older (mean age 12 ± 3.8 years). Participants on DMTs saw no improvement in diastolic function over the study period. In fact, participants on hydroxyurea saw a possible worsening in diastolic parameters (14% increase in LAVi and ~5% decrease in septal e′) but also a ~9% decrease in fetal hemoglobin (HbF) levels. Further studies are needed to evaluate if exposure to DMT for a longer duration or achieving higher HbF might be beneficial in alleviating diastolic dysfunction.
Molecular detection of

Procyonids are reservoirs of many zoonotic infectious diseases, including tick-borne pathogens. The role of coatis (Nasua nasua) in the epidemiology of piroplasmids and Rickettsia has not been fully addressed in Brazil. To molecularly study these agents in coatis and associated ticks, animals were sampled in two urban areas in Midwestern Brazil. Blood (n = 163) and tick (n = 248) DNA samples were screened by PCR assays targeting the 18S rRNA and gltA genes of piroplasmids and Rickettsia spp. , respectively. Positive samples were further molecularly tested targeting cox-1, cox-3, β-tubulin, cytB, and hsp70 (piroplasmid) and ompA, ompB, and htrA 17-kDa (Rickettsia spp.) genes, sequenced and phylogenetically analyzed. All coatis’ blood samples were negative for piroplasmids, whereas five pools of ticks (2%) were positive for two different sequences of Babesia spp. The first from Amblyomma sculptum nymphs was close (i.e., ≥ 99% nucleotide identity) to a Babesia sp. previously found in capybaras (Hydrochoerus hydrochaeris); the second from Amblyomma dubitatum nymphs and Amblyomma spp. larvae was identical (100% nucleotide identity) to a Babesia sp. detected in opossums (Didelphis albiventris) and associated ticks. Four samples (0.8%) were positive by PCR to two different Rickettsia spp. sequences, being the first from Amblyomma sp. larva identical to Rickettsia belli and the second from A. dubitatum nymph identical to Rickettsia species from Spotted Fever Group (SFG). The detection of piroplasmids and SFG Rickettsia sp. highlights the importance of Amblyomma spp. in the maintenance of tick-borne agents in urban parks where humans and wild and domestic animals are living in sympatry.
A STUDY OF THE MIXED MODE I+III LOADING OF A NON- PLANAR CRACK USING INFINITESIMAL DISLOCATIONS

This paper investigates the mixed mode I+III loadin g of a non-planar crack that fluctuates about an average fracture 3 1x x plane in an infinitely extended isotropic elastic medium. The crack is a continuous array of long non-straight dislocations with infinitesimal Burgers vectors. The dislocations are perpendicular to the 1 x direction of fracture propagation, have an arbitrar y periodic small shape ) ( 3 x ξ ξ = spreading in the 3 2 x x plane and their portions may be arbitrarily inclined with respect to the 3 x direction. The dislocation distribution contains two types of dislocation: dis locations 1 have an edge average character and respond to mode I loading; di slocations 2 have a screw average character and respond to mode III. The disp lacement and stress fields of two dislocations, with arbitrary shape and average character of edge or screw type, are first given. Expressions for the stress a bout the crack front and crack extension force G per unit length of the crack front are also given. Formula for > < G is maximum conform to
Examining the potential for resource‐dependent female reproductive fluid‐sperm interactive effects in a livebearing fish

Sexually selected traits can be costly to produce and maintain. The amount of resources available to an individual is therefore expected to influence investment in costly sexual traits. While resource‐dependent expression of sexually selected traits has traditionally been examined in males, resource limitation can also influence how sexual selection operates in females. Female reproductive fluids are thought to be costly to produce and may play an important role in shaping the outcome of postcopulatory sexual selection by influencing sperm performance. However, we know surprisingly little about whether and how female reproductive fluids are influenced by resource limitation. Here, we examine if resource restriction influences female reproductive fluid‐sperm interactive effects in the pygmy halfbeak (Dermogenys collettei), a small internally fertilizing freshwater fish where females store sperm. After experimentally altering female diets (high vs. restricted diets), we compared how female reproductive fluids influence two key metrics of sperm quality: sperm viability and velocity. While female reproductive fluids enhanced sperm viability and velocity, we found no evidence that female diet influenced the interactive effect between female reproductive fluids and sperm viability or velocity. Our findings build on the growing evidence that female reproductive fluids influence sperm performance and call for further attention to be devoted to understanding how resource quantity and quality influence how female reproductive fluids affect sperm performance.
Non-obese or lean nonalcoholic fatty liver disease matters, but is it preventable or inevitable in light of its risk factors?

Copyright © 2023 by Korean Association for the Study of the Liver This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Corresponding author : Won Kim Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 07061, Korea Tel: +82-2-870-2233, Fax: +82-2-831-2826, E-mail: drwon1@snu.ac. kr https://orcid.org/0000-0002-2926-1007 pISSN 2287-2728 eISSN 2287-285X
Comparing measurement properties of EQ-5D and SF-6D in East and South-East Asian populations: a scoping review

ABSTRACT Introduction Euro-Qol-5 Dimension (EQ-5D) and Short-Form 6-Dimension (SF-6D) are the most commonly used generic multi-attribute utility instruments (MAUI) to calculate quality-adjusted life-years (QALYs) in East and South-East Asia. This study aims to systematically review and summarize current evidence on comparing measurement properties of EQ-5D and SF-6D in East and South-East Asian populations. Areas covered Guided by the PRISMA systematic review and meta-analysis guidelines, a systematic literature search was conducted in databases of PubMed, Web of Science, MEDLINE, EMBASE and CINAHL (until June 2022) to obtain studies which compared measurement properties (feasibility, reliability, validity, responsiveness, and sensitivity) and agreement of EQ-5D and SF-6D in the populations. Expert opinion In general, both EQ-5D and SF-6D had good measurement properties in East and South-East Asian populations; but their utility scores cannot be used interchangeably. Compared to the 3-level EQ-5D, SF-6D had better sensitivity and lower ceiling effects, but the comparison results between the 5-level EQ-5D and SF-6D were inconsistent across populations. This scoping review found that most studies did not consider order effects, did not specify the versions of SF-6D, and ignored certain measurement properties (reliability, content validity, and responsiveness). These aspects need to be further explored in future studies.
Critical reflection and abyssal trapping of near-inertial waves on a β-plane

Abstract We consider near-inertial waves continuously excited by a localized source and their subsequent radiation and evolution on a two-dimensional $\ensuremath{\beta} $-plane. Numerical simulations are used to quantify the wave propagation and the energy flux in a realistically stratified ocean basin. We focus on the dynamics near and poleward of the inertial latitude where the local value of the Coriolis parameter $f$ matches the forcing frequency $\sigma $, contrasting the behaviour of waves under the traditional approximation (TA), where only the component of the Earth’s rotation aligned with gravity is retained in the dynamics, with that obtained under the non-traditional approach (non-TA) in which the horizontal component of rotation is retained. Under the TA, assuming inviscid linear wave propagation in the WKB limit, all energy radiated from the source eventually propagates toward the equator, with the initially poleward propagation being internally reflected at the inertial latitude. Under the non-TA however, these waves propagate sub-inertially beyond their inertial latitude, exhibiting multiple reflections between internal turning points that lie poleward of the inertial latitude and the bottom. The numerical experiments complement and extend existing theory by relaxing the linearity and WKB approximations, and by illustrating the time development of the steadily forced flow and the spatial patterns of energy flux and flux divergence. The flux divergence of the flow at both the forcing frequency and its first harmonic reveal the spatial patterns of nonlinear energy transfer and highlight the importance of nonlinearity in the vicinity of near-critical bottom reflection at the inertial latitude of the forced waves.
Computational Methods for Molecular Understanding of the Antibiotic‐Aminoacyl tRNA Synthetase Interaction

Developing an understanding of the interactions between an antibiotic and its binding site in a pathogen cell is the key to antibiotic design—an important cost‐saving methodology compared to the costly and time‐consuming random trial‐and‐error approach. The rapid development of antibiotic resistance provides an impetus for such studies. Recent years have witnessed the beginning of the use of combined computational techniques, including computer simulations and quantum mechanical computations, to understand how antibiotics bind at the active site of aminoacyl tRNA synthetases (aaRSs) from pathogens. Such computational protocols assist the knowledge‐based design of antibiotics targeting aaRSs, which are their validated targets. After the ideas behind the protocols and their strategic planning are discussed, the protocols are described along with their major outcomes. This is followed by an integration of results from the different basic protocols. © 2023 Wiley Periodicals LLC.
Toxic heavy metal/oxyanion tolerance in haloarchaea from some saline and hypersaline ecosystems

Toxic heavy metal/oxyanion contamination has increased severely through the last decades. In this study, 169 native haloarchaeal strains were isolated from different saline and hypersaline econiches of Iran. After providing pure culture and performing morphological, physiological, and biochemical tests, haloarchaea resistance toward arsenate, selenite, chromate, cadmium, zinc, lead, copper, and mercury were surveyed using an agar dilution method. On the basis of minimum inhibitory concentrations (MICs), the least toxicities were found with selenite and arsenate, while the haloarchaeal strains revealed the highest sensitivity for mercury. On the other hand, the majority of haloarchaeal strains exhibited similar responses to chromate and zinc, whereas the resistance level of the isolates to lead, cadmium, and copper was very heterogeneous. 16 S ribosomal RNA (rRNA) gene sequence analysis revealed that most haloarchaeal strains belong to the Halorubrum and Natrinema genera. The obtained results from this study showed that among the identified isolates, Halococcus morrhuae strain 498 had an exceptional resistance toward selenite and cadmium (64 and 16 mM, respectively). Also, Halovarius luteus strain DA5 exhibited a remarkable tolerance against copper (32 mM). Moreover, strain Salt5, identified as Haloarcula sp. , was the only strain that could tolerate all eight tested heavy metals/oxyanions and had a significant tolerance of mercury (1.5 mM).
In silico and in vitro analyses of a novel FoxO1 agonist reducing Aβ levels via downregulation of BACE1

Abstract Aims FoxO1 is an important target in the treatment of Alzheimer's disease (AD). However, FoxO1‐specific agonists and their effects on AD have not yet been reported. This study aimed to identify small molecules that upregulate the activity of FoxO1 to attenuate the symptoms of AD. Methods FoxO1 agonists were identified by in silico screening and molecular dynamics simulation. Western blotting and reverse transcription‐quantitative polymerase chain reaction assays were used to assess protein and gene expression levels of P21, BIM, and PPARγ downstream of FoxO1 in SH‐SY5Y cells, respectively. Western blotting and enzyme‐linked immunoassays were performed to explore the effect of FoxO1 agonists on APP metabolism. Results N‐(3‐methylisothiazol‐5‐yl)‐2‐(2‐oxobenzo[d]oxazol‐3(2H)‐yl) acetamide (compound D) had the highest affinity for FoxO1. Compound D activated FoxO1 and regulated the expression of its downstream target genes, P21, BIM, and PPARγ. In SH‐SY5Y cells treated with compound D, BACE1 expression levels were downregulated, and the levels of Aβ1‐40 and Aβ1‐42 were also reduced. Conclusions We present a novel small‐molecule FoxO1 agonist with good anti‐AD effects. This study highlights a promising strategy for new drug discovery for AD.
Fibrin gel enhanced trilayer structure in cell‐cultured constructs

Efficient cell seeding and subsequent support from a substrate ensure optimal cell growth and neotissue development during tissue engineering, including heart valve tissue engineering. Fibrin gel as a cell carrier may provide high cell seeding efficiency and adhesion property, improved cellular interaction, and structural support to enhance cellular growth in trilayer polycaprolactone (PCL) substrates that mimic the structure of native heart valve leaflets. This cell carrier gel coupled with a trilayer PCL substrate may enable the production of native‐like cell‐cultured leaflet constructs suitable for heart valve tissue engineering. In this study, we seeded valvular interstitial cells onto trilayer PCL substrates with fibrin gel as a cell carrier and cultured them for 1 month in vitro to determine if this gel can improve cell proliferation and production of extracellular matrix within the trilayer cell‐cultured constructs. We observed that the fibrin gel enhanced cellular proliferation, their vimentin expression, and collagen and glycosaminoglycan production, leading to improved structure and mechanical properties of the developing PCL cell‐cultured constructs. Fibrin gel as a cell carrier significantly improved the orientations of the cells and their produced tissue materials within trilayer PCL substrates that mimic the structure of native heart valve leaflets and, thus, may be highly beneficial for developing functional tissue‐engineered leaflet constructs.
Design, molecular dynamics simulation, and investigation of the mechanical behavior of DNA origami nanotubes with auxetic and honeycomb structures

Abstract Numerous applications of DNA origami nanotubes for load-bearing purposes necessitate the improvement of properties and mechanical behavior of these types of structures, as well as the use of innovative structures such as metamaterials. To this end, the present study aims to investigate the design, molecular dynamics (MD) simulation, and mechanical behavior of DNA origami nanotube structures consisting of honeycomb and re-entrant auxetic cross-sections. The results revealed both structures kept their structural stability. In addition, DNA origami based-nanotube with auxetic cross-section exhibits negative Poisson’s ratio (NPR) under tensile loading. Furthermore, MD simulation results demonstrated that the values of stiffness, specific stiffness, energy absorption, and specific energy absorption in the structure with an auxetic cross-section are higher than that of a honeycomb cross-section, similar to their behavior in macro-scale structures. The finding of this study is to propose re-entrant auxetic structure as the next generation of DNA origami nanotubes. In addition, it can be utilized to aid scientists with the design and fabrication of novel auxetic DNA origami structures. Communicated by Ramaswamy H. Sarma
Di(2‐ethylhexyl) phthalate and microplastics cause necroptosis and apoptosis in hepatocytes of mice by inducing oxidative stress

Di(2‐ethylhexyl) phthalate (DEHP) is a plasticizer and an endocrine disruptor. Microplastics (MPs) are pathogenic small plastic particles and abundant in the aqueous environment. The problem of residual hazards of plastic products is worthy of study, especially the joint exposure of a variety of plastic‐related products to the toxic effect. We used 200 mg/kg DEHP and 10 mg/L MPs to establish exposure model in vivo and 2 mM DEHP and 200 μg/L MPs to establish AML12 cell exposure model in vitro. In vivo study results showed that compared with the control group (NC) group, DEHP and MPs significantly increased the contents of malondialdehyde and hydrogen peroxide, and significantly decreased the contents of glutathione and the activity of superoxide dismutase, total antioxidant capacity, catalase and glutathione peroxidase. The level of oxidative stress was further aggravated after combined exposure. The reactive oxygen species level of AML12 exposed to DEHP and MPs in vitro was significantly higher than NC group, and the combined exposure was significantly higher than the single exposure. The in vivo and in vitro also confirmed that DEHP and MPs could significantly increase the mRNA and protein levels of apoptosis markers and necroptosis markers and there was an additive effect. After N‐acetylcysteine treatment in vitro, the above‐mentioned oxidative stress level and cell damage decreased significantly. This study provided a reference for advocating the reduction of the mixed use of plastic products, and provided a basis for preventing the harm of plastic products residues.
Incidence and risk factors of myocarditis in hospitalized patients with COVID‐19

Myocarditis as cardiac involvement in coronavirus disease 2019 (COVID‐19)‐infection is well known. Real‐world data about incidence in hospitalized COVID‐19‐patients and risk factors for myocarditis in COVID‐19‐patients are sparse. We used the German nationwide inpatient sample to analyze all hospitalized patients with confirmed COVID‐19‐diagnosis in Germany in 2020 and stratified them for myocarditis. Overall, 176 137 hospitalizations (52.3% males, 53.6% aged ≥70 years) with confirmed COVID‐19‐infection were coded in Germany in 2020 and among them, 226 (0.01%) had myocarditis (incidence: 1.28 per 1000 hospitalization‐cases). Absolute numbers of myocarditis increased, while relative numbers decreased with age. COVID‐19‐patients with myocarditis were younger (64.0 [IQR: 43.0/78.0] vs. 71.0 [56.0/82.0], p < 0.001). In‐hospital case‐fatality was 1.3‐fold higher in COVID‐19‐patients with than without myocarditis (24.3% vs. 18.9%, p = 0.012). Myocarditis was independently associated with increased case‐fatality (OR: 1.89 [95% CI: 1.33−2.67], p < 0.001). Independent risk factors for myocarditis were age <70 years (OR: 2.36 [95% CI: 1.72−3.24], p < 0.001), male sex (1.68 [95% CI: 1.28−2.23], p < 0.001), pneumonia (OR: 1.77 [95% CI: 1.30−2.42], p < 0.001), and multisystemic inflammatory COVID‐19‐infection (OR: 10.73 [95% CI: 5.39−21.39], p < 0.001). The incidence of myocarditis in hospitalized COVID‐19‐patients in Germany was 1.28 cases per 1000 hospitalizations in 2020. Risk factors for myocarditis in COVID‐19 were young age, male sex, pneumonia, and multisystemic inflammatory COVID‐19‐infection. Myocarditis was independently associated with increased case‐fatality.
Multidrug-resistant Neisseria gonorrhoeae isolate SE690: mosaic penA-60.001 gene causing ceftriaxone resistance internationally has spread to the more antimicrobial-susceptible genomic lineage, Sweden, September 2022

We report a ceftriaxone-resistant, multidrug-resistant urogenital Neisseria gonorrhoeae in a female sex worker in Sweden, September 2022, who was treated with ceftriaxone 1 g, but did not return for test-of-cure. Whole genome sequencing of isolate SE690 identified MLST ST8130, NG-STAR CC1885 (new NG-STAR ST4859) and mosaic penA-60.001. The latter, causing ceftriaxone resistance in the internationally spreading FC428 clone, has now also spread to the more antimicrobial-susceptible genomic lineage B, showing that strains across the gonococcal phylogeny can develop ceftriaxone resistance.
Time spent on social media use and BMI z‐score: A cross‐sectional explanatory pathway analysis of 10798 14‐year‐old boys and girls

The association between adolescent time spent on social media use and body mass index z‐score (BMI z‐score) is unclear. Pathways of association and sex differences are also unclear. This study examined the association between time spent on social media use and BMI z‐score (primary objective) and potential explanatory pathways (secondary objective) for boys and girls.
Optimised plasma sample preparation and LC‐MS analysis to support large‐scale proteomic analysis of clinical trial specimens: Application to the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial

Robust, affordable plasma proteomic biomarker workflows are needed for large‐scale clinical studies. We evaluated aspects of sample preparation to allow liquid chromatography‐mass spectrometry (LC‐MS) analysis of more than 1500 samples from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial of adults with type 2 diabetes.