Miracle-dz/UniFAR-FTUs huggingface dataset:
Expanded characterization of in vitro polarized M0, M1, and M2 human monocyte-derived macrophages: Bioenergetic and secreted mediator profiles

Respiratory macrophage subpopulations exhibit unique phenotypes depending on their location within the respiratory tract, posing a challenge to in vitro macrophage model systems. Soluble mediator secretion, surface marker expression, gene signatures, and phagocytosis are among the characteristics that are typically independently measured to phenotype these cells. Bioenergetics is emerging as a key central regulator of macrophage function and phenotype but is often not included in the characterization of human monocyte-derived macrophage (hMDM) models. The objective of this study was to expand the phenotype characterization of naïve hMDMs, and their M1 and M2 subsets by measuring cellular bioenergetic outcomes and including an expanded cytokine profile. Known markers of M0, M1 and M2 phenotypes were also measured and integrated into the phenotype characterization. Peripheral blood monocytes from healthy volunteers were differentiated into hMDM and polarized with either IFN-γ + LPS (M1) or IL-4 (M2). As expected, our M0, M1, and M2 hMDMs exhibited cell surface marker, phagocytosis, and gene expression profiles indicative of their different phenotypes. M2 hMDMs however were uniquely characterized and different from M1 hMDMs by being preferentially dependent on oxidativte phosphorylation for their ATP generation and by secreting a distinct cluster of soluble mediators (MCP4, MDC, and TARC). In contrast, M1 hMDMs secreted prototypic pro-inflammatory cytokines (MCP1, eotaxin, eotaxin-3, IL12p70, IL-1α, IL15, TNF-β, IL-6, TNF-α, IL12p40, IL-13, and IL-2), but demonstrated a relatively constitutively heightened bioenergetic state, and relied on glycolysis for ATP generation. These data are similar to the bioenergetic profiles we previously observed in vivo in sputum (M1) and BAL (M2)-derived macrophages in healthy volunteers, supporting the notion that polarized hMDMs can provide an acceptable in vitro model to study specific human respiratory macrophage subtypes.
An FBN1 deep intronic variant is associated with pseudoexon formation and a variable Marfan phenotype in a five generation family

Exome sequencing of genes associated with heritable thoracic aortic disease (HTAD) failed to identify a pathogenic variant in a large family with Marfan syndrome (MFS). A genome‐wide linkage analysis for thoracic aortic disease identified a peak at 15q21.1, and genome sequencing identified a novel deep intronic FBN1 variant that segregated with thoracic aortic disease in the family (LOD score 2.7) and was predicted to alter splicing. RT‐PCR and bulk RNA sequencing of RNA harvested from fibroblasts explanted from the affected proband revealed an insertion of a pseudoexon between exons 13 and 14 of the FBN1 transcript, predicted to lead to nonsense mediated decay (NMD). Treating the fibroblasts with an NMD inhibitor, cycloheximide, greatly improved the detection of the pseudoexon‐containing transcript. Family members with the FBN1 variant had later onset aortic events and fewer MFS systemic features than typical for individuals with haploinsufficiency of FBN1. Variable penetrance of the phenotype and negative genetic testing in MFS families should raise the possibility of deep intronic FBN1 variants and the need for additional molecular studies.
Vascularized versus non-vascularized bone grafting for scaphoid nonunion without avascular necrosis: a randomized clinical trial

In this clinical trial, patients were randomized to receive a pedicled vascularized bone graft, based on the 1,2-intercompartmental supraretinacular artery, or a non-vascularized iliac crest graft. Fixation was done with K-wires. Union and time to union were assessed using CT scans at regular intervals. Twenty-three patients received a vascularized graft, and 22 received a non-vascularized graft. Thirty-eight patients were available for union assessment and 23 for clinical measurements. There were no significant differences in union incidence, time to union, incidence of complications, patient-reported outcome scores, or wrist mobility and grip strength at final follow-up between the treatment groups. Smokers were 60% less likely to achieve union, independent of graft type. When controlling for smoking, patients receiving a vascularized graft were 72% more likely to achieve union. Given our small sample size, results should be interpreted with caution. Level of evidence: I
Gated transformations from egocentric to allocentric reference frames involving retrosplenial cortex, entorhinal cortex, and hippocampus

This paper reviews the recent experimental finding that neurons in behaving rodents show egocentric coding of the environment in a number of structures associated with the hippocampus. Many animals generating behavior on the basis of sensory input must deal with the transformation of coordinates from the egocentric position of sensory input relative to the animal, into an allocentric framework concerning the position of multiple goals and objects relative to each other in the environment. Neurons in retrosplenial cortex show egocentric coding of the position of boundaries in relation to an animal. These neuronal responses are discussed in relation to existing models of the transformation from egocentric to allocentric coordinates using gain fields and a new model proposing transformations of phase coding that differ from current models. The same type of transformations could allow hierarchical representations of complex scenes. The responses in rodents are also discussed in comparison to work on coordinate transformations in humans and non‐human primates.
Comprehensive Metabolic Tracing Reveals the Origin and Catabolism of Cysteine in Mammalian Tissues and Tumors

Abstract Cysteine plays critical roles in cellular biosynthesis, enzyme catalysis, and redox metabolism. The intracellular cysteine pool can be sustained by cystine uptake or de novo synthesis from serine and homocysteine. Demand for cysteine is increased during tumorigenesis for generating glutathione to deal with oxidative stress. While cultured cells have been shown to be highly dependent on exogenous cystine for proliferation and survival, how diverse tissues obtain and use cysteine in vivo has not been characterized. We comprehensively interrogated cysteine metabolism in normal murine tissues and cancers that arise from them using stable isotope 13C1-serine and 13C6-cystine tracing. De novo cysteine synthesis was highest in normal liver and pancreas and absent in lung tissue, while cysteine synthesis was either inactive or downregulated during tumorigenesis. In contrast, cystine uptake and metabolism to downstream metabolites was a universal feature of normal tissues and tumors. However, differences in glutathione labeling from cysteine were evident across tumor types. Thus, cystine is a major contributor to the cysteine pool in tumors, and glutathione metabolism is differentially active across tumor types. Significance: Stable isotope 13C1-serine and 13C6-cystine tracing characterizes cysteine metabolism in normal murine tissues and its rewiring in tumors using genetically engineered mouse models of liver, pancreas, and lung cancers.
Myeloid‐specific deletion of activating transcription factor 6 alpha increases CD11b+ macrophage subpopulations and aggravates lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung disease of unknown etiology. The accumulation of macrophages is associated with disease pathogenesis. The unfolded protein response (UPR) has been linked to macrophage activation in pulmonary fibrosis. To date, the impact of activating transcription factor 6 alpha (ATF6α), one of the UPR mediators, on the composition and function of pulmonary macrophage subpopulations during lung injury and fibrogenesis is not fully understood. We began by examining the expression of Atf6α in IPF patients’ lung single‐cell RNA sequencing dataset, archived surgical lung specimens, and CD14+ circulating monocytes. To assess the impact of ATF6α on pulmonary macrophage composition and pro‐fibrotic function during tissue remodeling, we conducted an in vivo myeloid‐specific deletion of Atf6α. Flow cytometric assessments of pulmonary macrophages were carried out in C57BL/6 and myeloid specific ATF6α‐deficient mice in the context of bleomycin‐induced lung injury. Our results demonstrated that Atf6α mRNA was expressed in pro‐fibrotic macrophages found in the lung of a patient with IPF and in CD14+ circulating monocytes obtained from blood of a patient with IPF. After bleomycin administration, the myeloid‐specific deletion of Atf6α altered the pulmonary macrophage composition, expanding CD11b+ subpopulations with dual polarized CD38+CD206+ expressing macrophages. Compositional changes were associated with an aggravation of fibrogenesis including increased myofibroblast and collagen deposition. A further mechanistic ex vivo investigation revealed that ATF6α was required for CHOP induction and the death of bone marrow‐derived macrophages. Overall, our findings suggest a detrimental role for the ATF6α‐deficient CD11b+ macrophages which had altered function during lung injury and fibrosis.
NONPARAMETRIC ESTIMATION OF REGRESSION FUNCTIONS WITH DISCRETE REGRESSORS

We consider the problem of estimating a nonparametric regression model containing categorical regressors only. We investigate the theoretical properties of least squares cross-validated smoothing parameter selection, establish the rate of convergence (to zero) of the smoothing parameters for relevant regressors, and show that there is a high probability that the smoothing parameters for irrelevant regressors converge to their upper bound values, thereby automatically smoothing out the irrelevant regressors. A small-scale simulation study shows that the proposed cross-validation-based estimator performs well in finite-sample settings.
DECOMPOSITION OF STOCHASTIC FLOWS AND ROTATION MATRIX

We provide geometrical conditions on the manifold for the existence of the Liao's factorization of stochastic flows [10]. If M is simply connected and has constant curvature, then this decomposition holds for any stochastic flow, conversely, if every flow on M has this decomposition, then M has constant curvature. Under certain conditions, it is possible to go further on the factorization: φt = ξt°Ψt° Θt, where ξt and Ψt have the same properties of Liao's decomposition and (ξt°Ψt) are affine transformations on M. We study the asymptotic behaviour of the isometric component ξt via rotation matrix, providing a Furstenberg–Khasminskii formula for this skew-symmetric matrix.
Millimeter-wave passive components of correlation radiometers for polarization measurements

In this paper the millimeter-wave passive components developed for the Ka-band Bar-SPOrt (Balloon-borne Radiometer for Sky Polarization Observatory) correlation radiometer are described. Comparison between numerical and experimental results are reported for all the building blocks of the radiometer: marker injector, polarizer, ortho-mode transducer, filtering sections and correlation unit. Due to the very low level of the polarized sky emission to be measured, all the components were designed and manufactured in order to achieve a very high level of sensitivity.
Physician empathy in Korean clinical contexts: developing a conceptual framework and exploring influencing factors

Purpose Despite its well-known clinical importance, physician empathy (PE) has been variably defined and its concepts among cultures are yet to be studied. This study aimed to develop a conceptual framework of PE and explore influencing factors on physicians’ empathetic behavior in the Korean clinical context. Methods Forty-two faculty members and 67 residents participated in the two-round Delphi survey to arrive at a consensus regarding the conceptual framework of PE in 2019. To explore individual and external factors affecting physicians’ empathetic behavior, a Likert scale questionnaire based on an initial free-text response was administered to the same participants. Results The conceptual framework of PE among Korean doctors consisted of basic communication skills and attitudes, cognitively understanding of patients’ thoughts and emotions, and communicating the doctors’ understandings to patients. Individual attributes and system- and patient-factors were revealed as influencing factors for PE in real practice. The former included communication ability, self-awareness and management, humanism, clinical competence, and good personality traits. Excessive workload, time constraints, aggressive attitudes, and negative preconceptions towards doctors were perceived as inhibiting or hindering empathy in patient care. Conclusion PE in the Korean clinical context comprised behavioral and cognitive components. Individual attributes, as well as external factors including system- and patient-factors were identified to affect PE in clinical settings. Further studies are needed to enhance the conceptual clarity of PE and identify how to promote doctors’ empathetic practice even in less favorable healthcare environments.
Instabilities of two-layer shallow-water flows with vertical shear in the rotating annulus

Being motivated by the recent experiments on instabilities of the two-layer flows in the rotating annulus with super-rotating top, we perform a full stability analysis for such system in the shallow-water approximation. We use the collocation method which is benchmarked by comparison with analytically solvable one-layer shallow-water equations linearized about a state of cyclogeostrophic equilibrium. We describe different kinds of instabilities of the cyclogeostrophically balanced state of solid-body rotation of each layer (baroclinic, Rossby–Kelvin (RK) and Kelvin–Helmholtz (KH) instabilities), and give the corresponding growth rates and the structure of the unstable modes. We obtain the full stability diagram in the space of parameters of the problem and demonstrate the existence of crossover regions where baroclinic and RK, and RK and KH instabilities, respectively, compete having similar growth rates.
Incidence and Types of Fetal Chromosomal Abnormalities in First Trimester of Thai Pregnant Women between Miscarriages and Intrauterine Survivals

Abortion is a common pregnancy complication. Fetuses with several types of chromosomal abnormalities are aborted during the first trimester, while others have a better chance of surviving. This research aims to study and compare the incidence and types of fetal chromosomal abnormalities during the first trimester of Thai pregnant women between miscarriages and intrauterine survivals. Cytogenetic and BACs-on-Beads™ assays were assessed from 2010 to 2020 in Ramathibodi Hospital using first trimester samples of 265 chorionic villi as a retrospective study. Chromosomal abnormalities were observed in 135 cases (50.94%) including 38.11% miscarriages and 12.83% intrauterine survivals. In total, 75.56% single autosomal trisomies, 18.52% sex chromosome aneuploidies, 5.19% double aneuploidies, and 0.74% structural abnormalities were detected. In miscarriages, all chromosomes were involved in abnormalities except chromosomes 1, 5, 8, 9, 11, and 17, while survivals had only trisomy 13, 18, 21, and sex chromosome aneuploidy. Trisomy 16 and 18 were the most common abnormalities in miscarriages and intrauterine survivals, respectively. The highest rate of chromosomal aberrations was demonstrated in 8–9+6 and 12–13+6 weeks of gestation in miscarriages and intrauterine survivals, respectively. Correlation between chromosomal abnormalities and maternal age <35 years and ≥35 years was significant (p < 0.05) in intrauterine survival and first trimester groups.
A Class of Simple Methods for Exploratory Structural Analysis

Simple modifications of principal component methods are described that have distinct advantages for structural analysis of relations among educational and psychological variables. Advantages include the provision for the incorporation of prior beliefs about errors in the variables, computational efficiency, tractability for large battery analysis, and the availability of hypothesis testing procedures. The methods are contrasted theoretically and empirically with conventional principal component methods and with maximum likelihood factor analysis.
In silico investigation of binding propensity of hematoxylin derivative and damnacanthal for their potential inhibitory effect on HIV-1 Vpr from different subtypes

Abstract HIV-1, the causative agent of AIDS leads to many deaths worldwide though few options are available as therapeutics. To deal with the continuous mutation in the virus genome, requirement of new drugs is always there. Subtype variation plays a crucial role in case of HIV-1 therapeutics development. In this study, we want to investigate some pre examined molecules that can be effective for HIV-1 VPR. Inhibition of several protein–protein interactions with the small molecules will lead to identify some molecules as therapeutics other than the conventional drugs. We retrieved the sequences of different subtypes from the database and representative sequences were identified. Representative structures were modelled and validated using MD simulations. Forty molecules, showing anti Vpr activity in vitro were identified from literature survey and those were docked with each subtype representative structures. Two molecules a stable Hematoxylin Derivative (SHD) and Damnacanthal (D3), these were shown to be bind more effectively for all the subtypes. The stability of the protein and those two small molecule complexes were identified again with MD simulation followed by the binding energy calculation. Thus, these molecules can be thought as any option other than the conventional drug targeting HIV-1 Vpr. Communicated by Ramaswamy H. Sarma
Schottky‐barrier field‐effect transistors of 3C‐SiC

Schottky‐barrier field‐effect transistors have been fabricated first from 3C‐type SiC. Al‐doped p‐type and nondoped n‐type 3C‐SiC epilayers were successively grown on p‐type Si substrates by chemical vapor deposition. Au and Al electrodes were used for Schottky‐barrier gate contacts and ohmic (source and drain) contacts for n‐type SiC. Transistor operation was observed for the first time for the field‐effect transistors of 3C‐SiC.
Model for the high-energy emission from blazars

Approximate formulae for the instantaneous scattered radiation spectra are derived in the Thomson and Klein-Nishina regimes, assuming that the relativistic electrons are described by an isotropic angular and power-law energy distribution in the outflowing fluid frame. The soft photon source is assumed to be axially symmetric. We find that the Thomson-limit luminosity enhancement in the direction that the scattered radiation is most intense varies as Γ 6 for photons entering from the side and as Γ 2 for photons entering directly from behind, where Γ is the bulk Lorentz factor of the outflowing plasma cloud. Energy loss and flow are treated in a model where energetic electrons are instantaneously injected with a power-law energy distribution at some height above a point or disk photon source, and instantaneous and time-average spectra are calculated
Shunted bicrystal Josephson junctions arrays for voltage standards

Series arrays of 365 shunted YBa2Cu3O7−x Josephson junctions on yttria‐stabilized zirconia bicrystals were investigated under microwave irradiation in the K‐band. Sub‐arrays of up to 39 junctions were synchronized to the external microwave power at a temperature of 15 K. Although there was a considerable spread in the critical currents of the junctions and in the microwave bias current distribution, a first Shapiro step with a height of 30% of the total critical current of the sub‐array was obtained by using an external shunt resistor, thus reducing the spread in normal resistances to 5%. Such high‐Tc cryoelectronic circuits are applicable for voltage standards and precision digital‐analog converters.
Self-ordering of nanoparticles in magneto-organic composite films

A combination of polarized neutron reflectometry and grazing incidence small-angle neutron scattering has been employed to deduce the structural and magnetic parameters of cobalt-oleyl amine nanocomplexes in thin films. It is demonstrated that inside the film the nanoparticles are self-organized into a three-dimensional paracrystallinelike lattice with the positional order well defined over a few interparticle spacings. Joint evaluation of the data elucidates the size of the saturated Co core and the CoO shell of the nanoparticles.
Recent Advancements in Technologies to Detect Enterohaemorrhagic Escherichia coli Shiga Toxins

Shiga toxin (Stxs)-producing enterohaemorrhagic Escherichia coli (EHEC) and Shigella dysenteriae serotype 1 are major causative agents of severe bloody diarrhea (known as hemorrhagic colitis) and hemolytic uremic syndrome (HUS) associated with extraintestinal complications such as acute renal failure and neurologic impairment in infected patients under 9 years of age. Extreme nephrotoxicity of Stxs in HUS patients is associated with severe outcomes, highlighting the need to develop technologies to detect low levels of the toxin in environmental or food samples. Currently, the conventional polymerase chain reaction (PCR) or immunoassay is the most broadly used assay to detect the toxin. However, these assays are laborious, time-consuming, and costly. More recently, numerous studies have described novel, highly sensitive, and portable methods for detecting Stxs from EHEC. To contextualize newly emerging Stxs detection methods, we briefly explain the basic principles of these methods, including lateral flow assays, optical detection, and electrical detection. We subsequently describe existing and newly emerging rapid detection technologies to identify and measure Stxs.
Accreditation standards items of post-2nd cycle related to the decision of accreditation of medical schools by the Korean Institute of Medical Education and Evaluation

Purpose The purpose of this study is to analyze the accreditation standards items related to the decision of accreditation of medical schools by the Korea Institute of Medical Education and Evaluation (KIMEE). Methods The subjects are medical schools in Korea that have received post-2nd cycle accreditation from the KIMEE between 2012 and 2016. Analyses were conducted for differences in accreditation decisions according to the characteristics of medical schools, sufficient ratios of basic standards items, and correlation between standards items related to accreditation decisions. Results After examining differences in accreditation decisions by the medical school’s characteristics, there were no significant correlations between accreditation standard items and accreditation decisions. Second, according to the number of schools that sufficiently or insufficiently met each standard item, from the total of 97 standard items, 20 (20.6%) were sufficiently fulfilled by all medical schools. Standard item 2-5-2 demonstrated the highest insufficiency ratio. Third, with respect to the standard item that had an effect on accreditation decisions, standard item 1-5-1 showed the highest correlation with the sufficiency rate. Conclusion The validity of accreditation standards items was assured as this study evaluated the post-2nd cycle accreditation standards items regardless of each medical school’s characteristics. The accreditation standards items were found to have a meaningful impact on the development of medical schools and qualitative improvement in medical education. The findings are expected to contribute to guaranteeing the validity and reliability of accreditation decisions and raising the quality of accreditation.