Miracle-dz/UniFAR-FTUs huggingface dataset:
Myeloid differentiation factor 88 signaling in donor T cells accelerates graft-versus-host disease

Myeloid differentiation factor 88 (MyD88) signaling has a crucial role in activation of both innate and adoptive immunity. MyD88 transduces signals via Toll-like receptor and interleukin-1 receptor superfamily to the NFκB pathway and inflammasome by forming a molecular complex with interleukin-1 receptor-associated kinase 4. The MyD88/interleukin-1 receptor-associated kinase 4 pathway plays an important role, not only in innate immunity, but also T-cell immunity; however, its role in donor T cells on the pathophysiology of graft-versus-host disease (GvHD) remains to be elucidated. We addressed this issue by using MyD88-deficient T cells in a mouse model of allogeneic hematopoietic stem cell transplantation (allo-SCT). While MyD88-deficient and wild-type T cells proliferated equivalently after transplantation, MyD88-deficient T cells demonstrated impaired survival and differentiation toward Th1, Tc1, and Th17, and induced less severe GvHD compared to wild-type T cells. Administration of interleukin-1 receptor-associated kinase 4 inhibitor PF-06650833 significantly ameliorated GvHD after allo-SCT. These results thus demonstrate that donor T-cell MyD88/interleukin-1 receptor-associated kinase 4 pathway is a novel therapeutic target against GvHD after allo-SCT.
Infantile Fibrosarcoma—A Clinical and Histologic Mimicker of Vascular Malformations: Case Report and Review of the Literature

Infantile fibrosarcoma is a rare soft tissue tumor that usually presents either at birth or in the 1st year of life. Here we describe a case of a 4-month-old female who presented with a congenital right axillary mass. The initial clinical impression was benign vascular/lymphatic malformation. The core biopsy showed a spindle cell lesion with abundant vasculature represented by small vascular channels. However, immunohistochemical analysis did not support a diagnosis of vascular lesion/tumor. Polymerase chain reaction study for ETS Translocation Variant 6/neurotrophic tyrosine kinase receptor, type 3 fusion transcript was positive, and the diagnosis of infantile fibrosarcoma was established. The patient underwent resection of the axillary mass. Microscopic examination of the resection specimen showed numerous vascular channels. Intermixed there were also cellular areas composed of spindle cells similar to those seen in the biopsy material. Molecular studies were repeated and confirmed the diagnosis of infantile fibrosarcoma. Infantile fibrosarcoma has been previously reported in the literature to clinically masquerade as hemangioma. In addition, this case proves that infantile fibrosarcoma could also mimic vascular malformations on clinical, radiologic, and pathologic exams. In fact, the vascular component of the tumor is very unusual in our patient and represents a histologic feature that has not been described before. The case highlights the diagnostic challenges at clinical, radiologic, and pathologic levels in some cases of infantile fibrosarcoma and raises awareness among clinicians and pathologists related to another peculiar pattern that can be encountered in this disease.
Fabrication of Ag-doped ZnO by mechanochemical combustion method and their application into photocatalytic Famotidine degradation

Abstract Ag/ZnO nanocomposites are successfully synthesized at different Ag contents through simple, effective, high yield and low-cost mechanochemical combustion technique, with the addition of silver acetate to zinc acetate and oxalic acid mixture. The synthesized materials are characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron spectroscopy (SEM), BET surface area analysis, UV − visible diffuse reflectance spectroscopy (UV − DRS) and photoluminescence spectroscopy (PL). It is shown that the prepared nanocomposites are composed of metallic Ag0 and wurtzite ZnO. The photocatalytic performance of different composites is evaluated by the degradation of Famotidine (FMT) under UV irradiation. The results indicate it that the maximum photodegradation rate is obtained with 6 wt% metallic Ag-decorated ZnO, and it is 2.1 times better than that obtained with pure ZnO. The photocatalytic degradation of FMT with Ag/ZnO is affected by various parameters such as calcination temperature and time, doping concentrations and reusability. The Ag/ZnO demonstrates higher activity due to the reduction of electron − hole recombination and Ag0 metal catalyst. The possible photocatalytic degradation mechanism of FMT with Ag/ZnO is estimated from the scavenger test.
Quantifying Hepatic Enzyme Kinetics of (-)-∆9-Tetrahydrocannabinol (THC) and Its Psychoactive Metabolite, 11-OH-THC, through In Vitro Modeling

The prevalence of cannabis use and the concentrations of the psychoactive cannabinoid in cannabis, (-)-∆9-tetrahydrocannabinol (THC), are rising. Physiologically based pharmacokinetic modeling and simulations (PBPK M&S) can mechanistically predict exposure of THC and its major and active metabolite, 11-hydroxy-THC (11-OH-THC). To build a THC/11-OH-THC PBPK model, mechanistic information about the disposition of these compounds is necessary, including the drug-metabolizing enzymes (DMEs) involved and the fraction metabolized (fm) and metabolic kinetic parameters (intrinsic clearance, maximal formation rate, and Km) via the identified enzymes. We previously identified and quantified the fm of DMEs involved in hepatic depletion of THC and 11-OH-THC. In this study, we extend this work to characterize the enzyme kinetics of THC and 11-OH-THC by monitoring their depletion and formation of some of their metabolites in pooled human liver microsomes. A P450 and UDP-glucuronosyltransferase (UGT) kinetic model was fitted to the concentration–time depletion/formation profiles to establish the contribution and kinetics of the individual DME pathways. CYP2C9 pathway was the major pathway for depletion of THC (fm = 0.91, Km,u = 3 nM) and formation of 11-OH-THC. The remaining THC depletion pathway was attributed to CYP2D6. 11-OH-THC was depleted by UGTs (fm = 0.67 and Km,u = 39 nM), CYP3A4 (fm = 0.18, Km,u = 824 nM), and CYP2C9 (fm = 0.15, Km,u = 33 nM). These mechanistic in vitro data can be used to predict the exposure of THC and 11-OH-THC in healthy and special populations, including in the presence of drug–drug interactions, via PBPK M&S.
CUMULANTS IN NONCOMMUTATIVE PROBABILITY THEORY III: CREATION AND ANNIHILATION OPERATORS ON FOCK SPACES

Exchangeability systems arising from Fock space constructions are considered and the corresponding cumulants are computed for generalized Toeplitz operators and similar noncommutative random variables. In particular, simplified calculations are given for the two known examples of q-cumulants. In the second half of the paper we consider in detail the Fock states associated to characters of the infinite symmetric group recently constructed by Bozejko and Guta. We express moments of multidimensional Dyck words in terms of the so-called cycle indicator polynomials of certain digraphs.
Dietary Patterns Are Associated with Predicted 10-Year Risk of Cardiovascular Disease Among Ghanaian Populations: the Research on Obesity and Diabetes in African Migrants (RODAM) Study

ABSTRACT Background Sub-Saharan African populations are disproportionately affected by cardiovascular disease (CVD). Although diet is an important lifestyle factor associated with CVD, evidence on the relation between dietary patterns (DPs) and CVD risk among sub-Saharan African populations is limited. Objective We assessed the associations of DPs with estimated 10-y atherosclerotic cardiovascular disease (ASCVD) risk in Ghanaian adults in Ghana and Europe. Methods Three DPs (‘mixed’; ‘rice, pasta, meat, and fish’; and ‘roots, tubers, and plantain’) were derived by principal component analysis (PCA) based on intake frequencies obtained by a self-administered Food Propensity Questionnaire in the multi-center, cross-sectional RODAM (Research on Obesity and Diabetes among African Migrants) study. The 10-y ASCVD risk was estimated using the Pooled Cohort Equations (PCE) for 2976 subjects, aged 40–70 y; a risk score ≥7.5% was defined as ‘elevated’ ASCVD risk. The associations of DPs with 10-y ASCVD risk were determined using Poisson regression with robust variance. Results Stronger adherence to a ‘mixed’ DP was associated with a lower predicted 10-y ASCVD in urban and rural Ghana and a higher 10-y ASCVD in Europe. The observed associations were attenuated after adjustment for possible confounders with the exception of urban Ghana (prevalence ratio [PR] for Quintile 5 compared with 1: 0.70; 95% CI: 0.53, 0.93, P-trend = 0.013). The ‘rice, pasta, meat, and fish’ DP was inversely associated with 10-y ASCVD across all study sites, with the adjusted effect being significant only in urban Ghana. A ‘roots, tubers, and plantain’ DP was directly associated with increased 10-y ASCVD risk. Conclusions Adherence to ‘mixed’ and ‘rice, pasta, meat, and fish’ DPs appears to reduce predicted 10-y ASCVD risk in adults in urban Ghana. Further investigations are needed to understand the underlying contextual-level mechanisms that influence dietary habits and to support context-specific dietary recommendations for CVD prevention among sub-Saharan African populations.
Genetic heterogeneity of residual variance of hatch weight in Mazandaran native chicken

ABSTRACT 1. In current breeding programmes, uniformity of end products and producing animals that are robust to environmental challenges are desirable. Several studies have provided evidence of the presence of genetic heterogeneity of residual variance and proposed that it could be possible to increase uniformity of livestock productions by selection. The present study aimed to define the micro environmental sensitivity of dual-purpose chickens for body weight at hatch. 2. The data set consisted of 24,321 female and 21,547 male chickens’ records of hatch weight from 19 consecutive generations of Mazandaran fowl. The statistical analysis was carried out in a two-step approach: first, an animal model was fitted to the data and then, the impact of additive genetic effects on the residual variance of the studied trait was investigated. 3. The estimate of heritability for body weight at hatch was in the range of 0.23–0.25 for female and 0.14–0.16 for male offspring, respectively. The proportion of maternal environmental variance to phenotypic variance ranged from 0.24 to 0.27 for female and 0.17 to 0.24 for male offspring. Heritabilities in females were higher than males. Estimates of the heritability of residual variance ranged between 0.067 and 0.090. The genetic coefficients of variation were high ranging between 0.83 and 0.86. Genetic correlations between hatch weight and its residual variance estimates from bivariate analysis were −0.39 and −0.44 in females and males, respectively. 4. The results suggest that there is an opportunity to simultaneously improve body weight and the uniformity of body weight by selecting for lower residual variance in native chickens.
Overexpression of VOZ2 confers biotic stress tolerance but decreases abiotic stress resistance in Arabidopsis

VOZ (vascular plant one zinc-finger protein) is a plant specific one-zinc finger type transcriptional activator, which is highly conserved through land plant evolution. We have previously shown that loss-of-function mutations in VOZ1 and VOZ2 showed increased cold and drought stress tolerances whereas decreased biotic stress resistance in Arabidopsis. Here, we demonstrate that transgenic plants overexpressing VOZ2 impairs freezing and drought stress tolerances but increases resistance to a fungal pathogen, Colletoricum higginsianum. Consistent with changes in the tolerance to biotic and abiotic stresses, the expression of marker genes for these stresses is significantly altered compared with those of the wild-type plant. These results indicate that a overexpression of VOZ2 confers biotic stress tolerance but impairs abiotic stress tolerances in Arabidopsis.
Words as Invitations to Form Categories: Evidence from 12- to 13-Month-Old Infants

Recent research has documented specific linkages between language and conceptual organization in the developing child. However, most of the evidence for these linkages derives from children who have made significant linguistic and conceptual advances. We therefore focus on the emergence of one particular linkage--the noun-category linkage--in infants at the early stages of lexical acquisition. We propose that when infants embark upon the process of lexical acquisition, they are initially biased to interpret a word applied to an object as referring to that object and to other members of its kind. We further propose that this initial expectation will become increasingly specific over development, as infants begin to distinguish among the grammatical categories as they are marked in their native language and assign them more specific types of meaning. To test this hypothesis, we conducted three experiments using a modified novelty-preference paradigm to reveal whether and how novel words influence object categorization in 12- to 13-month old infants. The data reveal that a linkage between words and object categories emerges early enough to serve as a guide in infants' efforts to map words to meanings. Both nouns and adjectives focused infants' attention on object categories, particularly at the superordinate level. Further, infants' progress in early word learning was associated with their appreciation of this linkage between words and object categories. These results are interpreted within a developmental and cross-linguistic account of the emergence of linkages between linguistic and conceptual organization.
Early-Stage Waves in the Retinal Network Emerge Close to a Critical State Transition between Local and Global Functional Connectivity

A novel, biophysically realistic model for early-stage, acetylcholine-mediated retinal waves is presented. In this model, neural excitability is regulated through a slow after-hyperpolarization (sAHP) operating on two different temporal scales. As a result, the simulated network exhibits competition between a desynchronizing effect of spontaneous, cell-intrinsic bursts, and the synchronizing effect of synaptic transmission during retinal waves. Cell-intrinsic bursts decouple the retinal network through activation of the sAHP current, and we show that the network is capable of operating at a transition point between purely local and global functional connectedness, which corresponds to a percolation phase transition. Multielectrode array recordings show that, at this point, the properties of retinal waves are reliably predicted by the model. These results indicate that early spontaneous activity in the developing retina is regulated according to a very specific principle, which maximizes randomness and variability in the resulting activity patterns.
Pathomechanisms of immune-mediated alopecia.

The hair follicle (HF) is a complex mini-organ that constantly undergoes dynamic cycles of growth and regression throughout life. While proper progression of the hair cycle requires homeostatic interplay between the HF and its immune microenvironment, specific parts of the HF, such as the bulge throughout the hair cycle and the bulb in the anagen phase, maintain relative immune privilege. When this immune privilege collapses, inflammatory infiltrates that aggregate around the bulge and bulb launch an immune attack on the HF, resulting in hair loss or alopecia. Alopecia areata (AA) and primary cicatrical alopecia (PCA) are two common forms of immune-mediated alopecias, and recent advancements in understanding their disease mechanisms have accelerated the discovery of novel treatments for immune-mediated alopecias, specifically AA. In this review, we highlight the pathomechanisms involved in both AA and CA in hopes that a deeper understanding of their underlying disease pathogenesis will encourage the development of more-effective treatments that can target distinct disease pathways with greater specificity while minimizing adverse effects.
Alleviating Social Pain: A Double-Blind, Randomized, Placebo-Controlled Trial of Forgiveness and Acetaminophen.

BACKGROUND Research has suggested that physical pain (e.g., caused by injury) and social pain (e.g., caused by social rejection) are modulated by some of the same biological systems. Consequently, it is possible that acetaminophen, which is commonly used to alleviate physical pain through neurochemical pathways, may have social pain-relieving effects that interact with forgiveness, which reduces social pain through psychological pathways. To date, however, only a few studies have examined how experiences of social pain change over time, and none have examined how acetaminophen and forgiveness interact to influence these effects. PURPOSE We addressed these issues by investigating how acetaminophen administration and daily forgiveness are associated with experiences of social pain over 21 days. We hypothesized that acetaminophen-related reductions in social pain across the 21-day study period would be greatest on days following high levels of forgiveness. METHOD To test this hypothesis, we conducted a double-blind, randomized, placebo-controlled trial in which we randomly assigned 42 healthy young adults to an acetaminophen condition (1,000 mg of acetaminophen daily), placebo-control condition (400 mg of potassium daily), or empty-control (no pill) condition. We then assessed their levels of forgiveness and social pain for 20 consecutive days. RESULTS As hypothesized, acetaminophen reduced participants' social pain levels over time but only for those exhibiting high levels of forgiveness (i.e., 18.5% reduction in social pain over 20 days). CONCLUSIONS These data are the first to show that forgiveness and acetaminophen have interactive effects on experiences of social pain, which is one of the most common and impactful of all human experiences.
A comparison of socio-behavioral risk factors between HIV-infected and non-infected older adults in Northern Thailand

ABSTRACT There is a shift in the demographic profile of people living with HIV toward older age groups. The current study compares alcohol use, smoking, and physical exercise between HIV-infected and non-infected older adults recruited in 12 community hospitals in Chiang Mai Province, Northern Thailand. Participants in the two groups were 50 years and above, matched by age and gender. The sample included 364 participants in each of the groups. Older adults living with HIV were less likely to report drinking alcohol in the past year (AOR, 0.55; CI, 0.34–0.89, P = 0.015) and more likely to report being currently engaged in physical activities (AOR, 2.58; CI, 1.77–3.76, P < 0.001). There was no difference between the two groups in terms of “current smoking status”. Older adults living with HIV were healthier than their non-infected counterparts in terms of the socio-behavioral risks.
TiO_2-promoted mineralization of organic sunscreens in water suspension and sodium dodecyl sulfate micelles

The photostability of the widely used UVB sunscreen agents 2′-ethylhexyl-2-cyano-3-phenylcinnamate (1), 2-hydroxy-4-methoxybenzophenone (2), octyl salicilate (3), and 2′-ethylhexyl-4-methoxycinnamate (4) has been investigated under UVA irradiation in the absence and presence of TiO_2, an inorganic filter commonly employed in combination with organic filters in sunscreen preparations. In the absence of TiO_2, 1-3 are photostable and 4 undergoes the expected E - Z isomerization; the presence of TiO_2 caused mineralization of the organic filters and, surprisingly, the process is noticeably faster in the presence of surfactant than in sunscreen and water suspensions. The results indicate that in water suspension, mineralization is likely to occur on or near the TiO_2 particle surface; when the organic sunscreens are segregated in the micelle core, reactive radicals, produced during TiO_2-promoted degradation of the micellar system, may participate in sunscreen degradation. In addition, a pre-fluorescent probe for carbon-centered radical detection, 4-(3-hydroxy-2-methyl-4-quinolineoxy)-2,2,6,6,-tetramethylpiperidine-1-oxyl free radical or QT (5), was employed to demonstrate that carbon-centered radicals are evolved during micelle degradation and may participate in the mineralization of sunscreens.
Patterns of Cerebrovascular Reactivity in Patients With Unilateral Asymptomatic Carotid Artery Stenosis

Background and Purpose Intracranial hemodynamic status varies in patients with unilateral significant carotid artery stenosis. It ranges from normal, because of sufficient collaterals, to poor, because of a severely reduced blood supply that puts the patient at an increased risk of stroke or cerebral ischemia. The present study examined patterns of abnormal cerebrovascular hemodynamics in patients with asymptomatic carotid artery stenosis. Methods The CO2 reactivity of the cerebral resistance index (CR1) and of mean blood flow velocity (vmean) was determined via transcranial Doppler sonography in 91 patients with unilateral high-grade to threadlike carotid artery stenosis and in 37 control subjects. The interhemispheric asymmetry of CR1 reactivity of the control group was used to differentiate between normal and abnormal findings. Results We found that 64.8% of the patients demonstrated normal CR1 asymmetry with comparable CR1 reactivity (ipsilateral, 4.42±0.44 %CR1/vol%CO2; contralateral, 4.51±0.39 %CR1/vol%CO2) and vmean reactivity (ipsilateral, 0.080±0.004 m/s per vol%CO2; contralateral, 0.079±0.005 m/s per vol%CO2) at both hemispheres. In 16.5% of the patients, CR1 reactivity was supranormal at the affected hemisphere. This phenomenon was due to an exaggerated dilatory response of the ipsilateral hemisphere and was combined with an absent CR1 reactivity of the contralateral hemisphere (ipsilateral, 6.63±1.03 %CR1/ vol%CO2; contralateral, −1.16±1.78 %CR,/vol%CO2). In contrast, hemispheric vmean reactivities were comparable (ipsilateral, 0.078±0.008 m/s per vol%CO2; contralateral, 0.077±0.008 m/s per vol%CO2). The remaining 18.7% showed severely diminished ipsilateral CR, reactivity (ipsilateral, 1.91±0.83 %CR1/ vol%CO2; contralateral, 8.48±1.00 %CR1/vol%CO2) and vmean reactivity (ipsilateral, 0.073±0.007 m/s per vol%CO2; contralateral, 0.108±0.012 m/s per vol%CO2; P<.01), compatible with a significantly reduced perfusion pressure at the poststenotic hemisphere. Conclusions Most asymptomatic patients do not suffer from severely abnormal hemodynamics at the poststenotic hemisphere. One small subgroup of patients presented with severely disturbed ipsilateral hemodynamics; another small subgroup demonstrated a steal phenomenon with secondary dilation of large cerebral vessels at the contralateral hemisphere. These subgroups require specific evaluation of proper treatment.