Miracle-dz/UniFAR-FTUs huggingface dataset:
TNF-Producing Th1 Cells Are Selectively Expanded in Liver Infiltrates of Patients with Autoimmune Hepatitis

Key Points TNF-producing CD4+ T cells in patients with AIH are significantly expanded. Most TNF-producing T cells also produce IFN-γ and have an inflammatory phenotype. Autoantigen-specific stimulation results in expansion of these inflammatory T cells. Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that is believed to be driven by a CD4+ T cell response to liver Ags. However, the pathogenic function of CD4+ effector T cells in AIH is not fully understood. To characterize liver-infiltrating lymphocytes in AIH, we determined the cytokine production of infiltrating cells obtained from biopsy material by quantitative RT-PCR and flow cytometry. A cytokine quantitiative RT-PCR array of AIH specimens revealed that TNF was the most strongly upregulated cytokine, as compared with control livers. To confirm this finding, we determined the frequencies of TNF-producing CD4+ T cells in peripheral blood and in liver biopsy specimens in comparison with those of CD4+ T cells producing IFN-γ or IL-17. In AIH, TNF-producing CD4+ T cells were significantly expanded, both in blood and liver, whereas IL-17–producing CD4+ T cells were not. However, the majority of the TNF-producing CD4+ T cells in AIH also produced IFN-γ, suggesting that TNF producers might represent a pathogenic activation state of Th1 cells. Ag-specific stimulation of PBMC from AIH patients with the AIH-associated autoantigen SEPSECS resulted in significant TNF production only in patients manifesting SLA/LP autoantibodies targeting SEPSEC but not in healthy individuals who do not manifest this reactivity. Taken together, our findings indicated that TNF-producing CD4+ T cells are expanded in AIH, both in blood and in liver. TNF-producing CD4+ T cells in AIH seem to be aberrantly activated Th1 cells. Our findings provide a rationale for therapeutic efforts using TNF blockade in AIH.
Sex differences in thigh muscle volumes, sprint performance and mechanical properties in national-level sprinters

The purpose of this study was to determine and compare thigh muscle volumes (MVs), and sprint mechanical properties and performance between male and female national-level sprinters. We also studied possible relationships between thigh MVs and sprint performance. Nine male and eight female national-level sprinters participated in the study. T1-weighted magnetic resonance images of the thighs were obtained to determine MVs of quadriceps, hamstrings and adductors. Sprint performance was measured as the time to cover 40 and 80 m. Instantaneous sprint velocity was measured by radar to obtain theoretical maximum force (F0), theoretical maximum velocity (V0) and maximum power (Pmax). When MVs were normalized by height–mass, males showed larger hamstrings (13.5%, ES = 1.26, P < 0.05) compared with females, while quadriceps and adductors showed no statistically significant differences. Males were extremely faster than females in 40 m (14%, ES = 6.68, P < 0.001) and in 80 m (15%, ES = 5.01, P < 0.001. Males also showed increased sprint mechanical properties, with larger F0 (19%, ES = 1.98, P < 0.01), much larger Pmax (46%, ES = 3.76, P < 0.001), and extremely larger V0 (23%, ES = 6.97, P < 0.001). With the pooled data, hamstring and adductor MVs correlated strongly (r = -0.685, P < 0.01) and moderately (r = -0.530, P < 0.05), respectively, with sprint performance; while quadriceps showed no association. The sex-stratified analysis showed weaker associations compared with pooled data, most likely due to small sample size. In conclusion, males were faster than females and showed larger MVs, especially in hamstrings. Moreover, regarding the thigh muscles, hamstrings MV seems the most related with sprint performance as previously proposed.
Managerial functions of organizing and leading people in MLM organizations and their manifestations in historical schools of managerial thinking

The article looks into managerial functions of organizing and leading in multilevel marketing (MLM) organizations, focusing on the creation of organizational structures and the style of leadership. Paper is trying to identify what historical trends of managerial thinking these functions are derived from and what other trends influenced them. The functions are studied in a concrete MLM organization in which the organizational structure and the style of leading people are defined. The article determines specifics typical for MLM organizations in the sphere of organizing and leading. Also, it identifies the activities of the manager including the overlapping of individual managerial functions. On the basis of comparison it is then possible to find theoretical assumptions that are applied in the practice of MLM organizations.
Non-Typical Fluorescence Effects and Biological Activity in Selected 1,3,4-thiadiazole Derivatives: Spectroscopic and Theoretical Studies on Substituent, Molecular Aggregation, and pH Effects

The below article presents the results of spectroscopic research, theoretical (time-dependent density functional theory (TD-DFT)), microbiological, and antioxidative calculations for three compounds from the group of 1,3,4-thiadiazoles: 2-amino-5-phenyl-1,3,4-thiadiazole (TB), 2-amino-5-(2-hydroxyphenyl)-1,3,4-thiadiazole (TS), 2-amino-5-(2-hydroxy-5-sulfobenzoyl)-1,3,4-thiadiazole (TSF). In the fluorescence emission spectra (TS) of solutions with varying concentrations of hydrogen ions, a particularly interesting effect of dual fluorescence was observed. The aforementioned effect was observed even more clearly in the environment of butan-1-ol, relative to the compound’s concentration. Depending on the modification of the resorcylic substituent (TS and TSF), we observed the emergence of two separate, partially overlapping, fluorescence emission spectra or a single emission spectrum. Interpretation of the obtained spectra using stationary and time-resolved spectroscopy allowed the correlation of the effect’s emergence with the phenomenon of molecular aggregation (of a particular type) as well as, above all, the structure of the substituent system. The overlap of said effects most likely induces the processes related to the phenomenon of charge transfer (in TS) and is responsible for the observed fluorescence effects. Also, the position of the –OH group (in the resorcylic ring) is significant and can facilitate the charge transfer (CT). The determinations of the changes in the dipole moment and TD-DFT calculations further corroborate the above assumption. The following paper presents the analysis (the first for this particular group of analogues) of the fluorescence effects relative to the changes in the structure of the resorcylic group combined with pH effects. The results of biological studies also indicate the highest pharmacological potential of the analogue in the case where the effects of dual fluorescence emission are observed, which predisposes this particular group of fluorophores as effective fluorescence probes or potential pharmaceuticals with antimycotic properties.
A survey for variable young stars with small telescopes: First results from HOYS-CAPS

Variability in Young Stellar Objects (YSOs) is one of their primary characteristics. Long-term, multi-filter, high-cadence monitoring of large YSO samples is the key to understand the partly unusual light-curves that many of these objects show. Here we introduce and present the first results of the HOYS-CAPS citizen science project which aims to perform such monitoring for nearby (d<kpc) and young (age<10Myr) clusters and star forming regions, visible from the northern hemisphere, with small telescopes. We have identified and characterised 466 variable (413 confirmed young) stars in 8 young, nearby clusters. All sources vary by at least 0.2mag in V, have been observed at least 15 times in V, R and I in the same night over a period of about 2yrs and have a Stetson index of larger than 1. This is one of the largest samples of variable YSOs observed over such a time-span and cadence in multiple filters. About two thirds of our sample are classical T-Tauri stars, while the rest are objects with depleted or transition disks. Objects characterised as bursters show by far the highest variability. Dippers and objects whose variability is dominated by occultations from normal interstellar dust or dust with larger grains (or opaque material) have smaller amplitudes. We have established a hierarchical clustering algorithm based on the light-curve properties which allows the identification of the YSOs with the most unusual behaviour, and to group sources with similar properties. We discuss in detail the light-curves of the unusual objects V2492Cyg, V350Cep and 2MASSJ21383981+5708470.
Tuber yield prognosis model and agronomic nitrogen use efficiency of potato cultivars

Adjusting nitrogen (N) fertilization rates to crop requirements optimizes N efficiency and reduces environmental pollution. In accordance with such precision agriculture, methods facilitating rapid and simple real-time crop yield prognostication are desirable. The aims of this study are to establish a prognostic model for tuber yield; early characterization of a properly N-nourished plant and to determine the N use efficiency by the Asterix and Atlantic potato cultivars. In two separate experiments, on for each cultivar, five pre-planting N fertilization rates (0, 50, 100, 200, and 300 kg ha -1 ) were evaluated. A randomized complete block design with four replicates per experiment was utilized. Variable chosen for early evaluation, 21 days after emergence, were categorized into four named groups. Group one, linked to chlorophyll (SPAD index and total fourth leaf chlorophyll concentration). Group two, concerning with physiological indexes (leaf, fourth leaf, stem, and shoot dry matter; fourth- and whole-plant leaf area; fourth leaf and plant specific leaf area; and leaf area ratio). The third group linked to fourth leaf N indexes (N concentration per unit dry matter and per unit leaf area, and total N content). The fourth group referring to N use efficiency (fourth leaf N use efficiency and agronomic N use efficiency). For both cultivars, there are a significant positive correlation between tuber yield and physiologic and N indexes, while there is a significant negative correlation between tuber yield and N use efficiency. Regression models utilising the SPAD index as an independent variable are effective in predicting the marketable tuber yield of potato plants, and have the added advantage of real-time determination of the SPAD index in relationship a another methods.
e-Cigarette Use Among Youth in the United States, 2019.

Importance The prevalence of e-cigarette use among US youth increased from 2011 to 2018. Continued monitoring of the prevalence of e-cigarette and other tobacco product use among youth is important to inform public health policy, planning, and regulatory efforts. Objective To estimate the prevalence of e-cigarette use among US high school and middle school students in 2019 including frequency of use, brands used, and use of flavored products. Design, Setting, and Participants Cross-sectional analyses of a school-based nationally representative sample of 19 018 US students in grades 6 to 12 participating in the 2019 National Youth Tobacco Survey. The survey was conducted from February 15, 2019, to May 24, 2019. Main Outcomes and Measures Self-reported current (past 30-day) e-cigarette use estimates among high school and middle school students; frequent use (≥20 days in the past 30 days) and usual e-cigarette brand among current e-cigarette users; and use of flavored e-cigarettes and flavor types among current exclusive e-cigarette users (no use of other tobacco products) by school level and usual brand. Prevalence estimates were weighted to account for the complex sampling design. Results The survey included 10 097 high school students (mean [SD] age, 16.1 [3.0] years; 47.5% female) and 8837 middle school students (mean [SD] age, 12.7 [2.8] years; 48.7% female). The response rate was 66.3%. An estimated 27.5% (95% CI, 25.3%-29.7%) of high school students and 10.5% (95% CI, 9.4%-11.8%) of middle school students reported current e-cigarette use. Among current e-cigarette users, an estimated 34.2% (95% CI, 31.2%-37.3%) of high school students and 18.0% (95% CI, 15.2%-21.2%) of middle school students reported frequent use, and an estimated 63.6% (95% CI, 59.3%-67.8%) of high school students and 65.4% (95% CI, 60.6%-69.9%) of middle school students reported exclusive use of e-cigarettes. Among current e-cigarette users, an estimated 59.1% (95% CI, 54.8%-63.2%) of high school students and 54.1% (95% CI, 49.1%-59.0%) of middle school students reported JUUL as their usual e-cigarette brand in the past 30 days; among current e-cigarette users, 13.8% (95% CI, 12.0%-15.9%) of high school students and 16.8% (95% CI, 13.6%-20.7%) of middle school students reported not having a usual e-cigarette brand. Among current exclusive e-cigarette users, an estimated 72.2% (95% CI, 69.1%-75.1%) of high school students and 59.2% (95% CI, 54.8%-63.4%) of middle school students used flavored e-cigarettes, with fruit, menthol or mint, and candy, desserts, or other sweets being the most commonly reported flavors. Conclusions and Relevance In 2019, the prevalence of self-reported e-cigarette use was high among high school and middle school students, with many current e-cigarette users reporting frequent use and most of the exclusive e-cigarette users reporting use of flavored e-cigarettes.
Geographical scale and the role of firm migration in spatial economic dynamics

Spatial economic change can be decomposed in it's demographic constituents firm formation, closure, relocation and growth. This paper focusses on the role of relocation in the balancing equation of spatial economic dynamics: Total Change(zone i) = New firms(i)-Closures(i)+ Growth(i)-Decline(i)+ Inmoves(i)-Outmoves(i). Whereas the other components are scale invariant (i.e. a firm birth is a birth whether measured at the local or the regional level) for firm relocation the geographical scale is very important. The larger the size of the region, the smaller the number of border crossing relocations. The question about the role of firm migration in regional economic change can therefore only be answered taking into account the geographical scale. In this paper we will answer this question for various geographical scales. The data that we use are from the longitudinal business register of the province of Gelderland, in the east of the Netherlands, covering the period 1988-2002.
Recent advances in molecular imaging with gold nanoparticles.

Gold nanoparticles (AuNP) have been extensively developed as contrast agents, theranostic platforms and probes for molecular imaging. This popularity has yielded a large number of AuNP designs that vary in size, shape, surface functionalization and assembly, to match very closely to the requirements for various imaging applications. Hence, AuNP based probes for molecular imaging allow the use of computed tomography (CT), fluorescence and other forms of optical imaging, photoacoustic imaging (PAI) and magnetic resonance imaging (MRI), and other newer techniques. The unique physico-chemical properties, biocompatibility and highly developed chemistry of AuNP have facilitated breakthroughs in molecular imaging that allow the detection and imaging of physiological processes with a high sensitivity and spatial resolution. In this review, we summarize the recent advances in molecular imaging achieved using novel AuNP structures, cell tracking using AuNP, targeted AuNP for cancer imaging, and activatable AuNP probes. Finally, the perspectives and current limitations for the clinical translation of AuNP based probes are discussed.
White matter hypointensities and hyperintensities have equivalent correlations with age and CSF β‐amyloid in the nondemented elderly

T1‐ and T2‐weighted sequences from MRI often provide useful complementary information about tissue properties. Leukoaraiosis results in signal abnormalities on T1‐weighted images, which are automatically quantified by FreeSurfer, but this marker is poorly characterized and is rarely used. We evaluated associations between white matter hyperintensity (WM‐hyper) volume from FLAIR and white matter hypointensity (WM‐hypo) volume from T1‐weighted images and compared their associations with age and cerebrospinal fluid (CSF) β‐amyloid and tau.
Learning Large Scale Ordinary Differential Equation Systems

Learning large scale nonlinear ordinary differential equation (ODE) systems from data is known to be computationally and statistically challenging. We present a framework together with the adaptive integral matching (AIM) algorithm for learning polynomial or rational ODE systems with a sparse network structure. The framework allows for time course data sampled from multiple environments representing e.g. different interventions or perturbations of the system. The algorithm AIM combines an initial penalised integral matching step with an adapted least squares step based on solving the ODE numerically. The R package episode implements AIM together with several other algorithms and is available from CRAN. It is shown that AIM achieves state-of-the-art network recovery for the in silico phosphoprotein abundance data from the eighth DREAM challenge with an AUROC of 0.74, and it is demonstrated via a range of numerical examples that AIM has good statistical properties while being computationally feasible even for large systems.
Genetic Variations of Ultraconserved Elements in the Human Genome.

Ultraconserved elements (UCEs) are among the most popular DNA markers for phylogenomic analysis. In at least three of five placental mammalian genomes (human, dog, cow, mouse, and rat), 2189 UCEs of at least 200 bp in length that are identical have been identified. Most of these regions have not yet been functionally annotated, and their associations with diseases remain largely unknown. This is an important knowledge gap in human genomics with regard to UCE roles in physiologically critical functions, and by extension, their relevance for shared susceptibilities to common complex diseases across several mammalian organisms in the event of their polymorphic variations. In the present study, we remapped the genomic locations of these UCEs to the latest human genome assembly, and examined them for documented polymorphisms in sequenced human genomes. We identified 29,983 polymorphisms within analyzed UCEs, but revealed that a vast majority exhibits very low minor allele frequencies. Notably, only 112 of the identified polymorphisms are associated with a phenotype in the Ensembl genome browser. Through literature analyses, we confirmed associations of 37 (i.e., out of the 112) polymorphisms within 23 UCEs with 25 diseases and phenotypic traits, including, muscular dystrophies, eye diseases, and cancers (e.g., familial adenomatous polyposis). Most reports of UCE polymorphism-disease associations appeared to be not cognizant that their candidate polymorphisms were actually within UCEs. The present study offers strategic directions and knowledge gaps for future computational and experimental work so as to better understand the thus far intriguing and puzzling role(s) of UCEs in mammalian genomes.
Time perception deficits and its dose-dependent effect in methamphetamine dependents with short-term abstinence

Dose-dependent effect of time perception deficits in methamphetamine addicts is associated with drug use history and task setting. Intake of addictive substances acutely modifies dopaminergic transmission in the striatum and prefrontal cortex, which is the neural substrate underlying time processing. However, the persistent effects of methamphetamine (meth) abuse (e.g., during abstinence) on temporal processing have not been fully elucidated. Here, we recruited different samples in two experiments. We first compared the potential differences in motor timing between healthy controls and meth dependents with varied length of abstinence and then examined the ability of perceptual timing between the healthy subjects and the meth group at short abstinence. We found that motor timing, but not perceptual timing, was altered in meth dependents, which persisted for at least 3 months of abstinence. Dose-dependent effects on time perception were only observed when short-term abstinent meth abusers processed long time intervals. We conclude that time perception alteration in meth dependents is task specific and dose dependent.
A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody–Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

Purpose: ADCT-402 (loncastuximab tesirine) is an antibody–drug conjugate comprising a CD19-targeting antibody and pyrrolobenzodiazepine dimers. A first-in-human study evaluated the safety and preliminary clinical activity of loncastuximab tesirine in patients with B-cell non-Hodgkin lymphoma (NHL). Patients and Methods: A multicenter, phase I, dose-escalation and dose-expansion study enrolled patients ages ≥18 years with relapsed/refractory (R/R) B-cell NHL. Patients received loncastuximab tesirine every 3 weeks at doses assigned by a 3+3 dose-escalation design. Dose escalation was used to assess the safety and tolerability of loncastuximab tesirine to determine the dose for expansion. Secondary objectives evaluated clinical activity, characterized the pharmacokinetic profile, and evaluated antidrug antibodies. Results: During dose escalation, 88 patients with R/R B-cell NHL were treated with loncastuximab tesirine at doses 15 to 200 μg/kg. Treatment-emergent adverse events (TEAEs) were experienced by 87/88 (98.9%) patients. Most common TEAEs (≥20% of patients) were hematologic abnormalities, fatigue, edema, liver test abnormalities, nausea, rash, and dyspnea. Grade ≥3 TEAEs (≥5% of patients) included hematologic abnormalities, liver test abnormalities, fatigue, and dyspnea. Overall response rate at doses ≥120 μg/kg was 59.4% (41 of 69 patients; 40.6% complete response; 18.8% partial response). Median duration of response, progression-free survival, and overall survival (all doses) were 4.8, 5.5, and 11.6 months, respectively. Drug exposure increased with increasing dose, showing moderate accumulation with multiple doses ≥150 μg/kg. There was no evidence of immunogenicity. Conclusions: Loncastuximab tesirine had promising activity with acceptable safety in this dose-escalation study. A phase II study with initial dosing at 150 μg/kg has been initiated based on these results.
Pathway‐based meta‐analysis for partially paired transcriptomics analysis

Pathway‐based differential expression analysis allows the incorporation of biological domain knowledge into transcriptomics analysis to enhance our understanding of disease mechanisms. To integrate information among multiple studies at the pathway level, pathway‐based meta‐analysis can be performed. Paired or partially paired samples are common in biomedical research. However, there are currently no existing pathway‐based meta‐analysis methods appropriate for paired or partially paired study designs.