Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of Xenogeneic T-cell Proliferation by B7 and mTOR Blockade of T Cells and Porcine Endothelial Cells

Background. Activation of porcine endothelial cells (PECs) is the mechanistic centerpiece of xenograft rejection. This study sought to characterize the immuno-phenotype of human T cells in response to PECs and to explore the immuno-modulation of B7 and mammalian target of rapamycin blockade of T cells and/or PECs during xeno-responses. Methods. Rapid memory T-cell (TM) responses to PECs were assessed by an intracellular cytokine staining. T-cell proliferation to PEC with or without belatacept or rapamycin was evaluated by a mixed lymphocyte-endothelial cell reaction (MLER). Additionally, rapamycin-pretreated PECs were used in MLER. Cell phenotypes were analyzed by flow cytometry. Results. Tumor necrosis factor-α/interferon-γ producers were detected in CD8+ cells stimulated by human endothelium but not PECs. MLER showed proliferation of CD4+ and CD8+ cells with predominantly memory subsets. Purified memory and naive cells proliferated following PEC stimulation with an increased frequency of TM in PEC-stimulated naive cells. Proliferating cells upregulated programmed cell death-1 (PD-1) and CD2 expression. Belatacept partially inhibited T-cell proliferation with reduced CD2 expression and frequency of the CD8+CD2highCD28− subset. Rapamycin dramatically inhibited PEC-induced T-cell proliferation, and rapamycin-preconditioned PECs failed to induce T-cell proliferation. PD-1 blockade did not restore T-cell proliferation to rapamycin-preconditioned PECs. Conclusions. Humans lack rapid TM-mediated responses to PECs but induce T-cell proliferative responses characterized largely as TM with increasing CD2 and PD-1 expression. B7-CD28 and mammalian target of rapamycin blockade of T cells exhibit dramatic inhibitory effects in altering xeno-proliferating cells. Rapamycin alters PEC xeno-immunogenicity leading to inhibition of xeno-specific T-cell proliferation independent of PD-1–PD ligand interaction.
Internet-delivered interpretation training reduces worry and anxiety in individuals with generalized anxiety disorder: A randomized controlled experiment.

Objective: Generalized anxiety disorder (GAD) is a debilitating condition, characterized by negative interpretations about ambiguous situations. This study tested whether entirely internet-delivered interpretation training [cognitive bias modification (CBM)] versus control promotes positive interpretations and reduces worry and anxiety in individuals with GAD, with or without depression. Method: A two-arm (CBM; control) parallel-group randomized controlled experiment. Assessments were preintervention (T0), postintervention (T1), 1-month (T2) postintervention, and 3-month (T3) postintervention. Participants with GAD (with or without comorbid depression) were randomly allocated to either CBM (n = 115) or control (n = 115). Participants, but not researchers, were blind to allocated condition. Participants completed up to 10 online CBM or control sessions across 1 month. Interpretation bias [coprimary outcomes: scrambled sentence test (SST), recognition test (RT)], and number of negative thought intrusions during a breathing focus task were measured at T0 and T1. Self-reported levels of worry [Penn State Worry Questionnaire-trait (PSWQ trait); Penn State Worry Questionnaire-past week (PSWQ weekly)], anxiety [Generalized Anxiety Disorder scale (GAD-7)], depression [Patient Health Questionnaire (PHQ-9)], rumination [Ruminative Response Scale (RRS)], and repetitive negative thinking [RNT; Repetitive Thinking Questionnaire-trait (RTQ-trait)] were assessed at T0-T3. Results: The per-protocol analyses included N = 186 participants (CBM n = 94; control n = 92). As predicted, we found moderate-to-large training effects on the primary outcome of interpretation bias at T1. Secondary outcomes of negative thought intrusions at T1 and self-reported symptoms at T2 were all significantly lower in the CBM versus control condition. All but one effect (trait RNT) were sustained at T3. Conclusions: In this randomized controlled study, we found that fully online interpretation training ameliorated core features of GAD in individuals with or without comorbid depression up to 3 months posttraining. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
The effects of assisted and resisted plyometric training on jump height and sprint performance among physically active females

ABSTRACT The aim of the present study was to compare the effects of assisted and resisted plyometric jump training on jump height, sprint performance (acceleration (0–20m), maximum speed (30–40m) and 40m sprint time) among physically active females. Fifty-six participants (age: 21.1 ± 1.7 years; body mass: 64.2 ± 7.0 kg; height: 168.0 ± 5.6 cm) were randomly allocated to either an assisted (n = 16) or resisted training group (n = 17), or a control group (n = 14). Nine participants dropped out during the intervention. The training sessions consisted of three different plyometric jump exercises over an eight-week period, while the control group continued their normal training routine. The results revealed a significant between-group difference in jump height and maximal speed. The resisted training group achieved a significantly greater improvement in jump height compared to the active control group (p = .04, ES=1.06), and a significantly greater improvement in maximal speed (p = .02, ES = 0.93) when compared to the assisted training group. No other group differences were observed for jump height, acceleration or in maximal speed (p = .31–.53). The resisted training group improved jump height (p = .01, ES = 0.62) and maximum speed (p = .03, ES = 0.48) from pre- to post-test, while the control group improved maximal speed (p = .04, ES = 0.37) and acceleration (p = .01, ES = 0.68). All three groups improved their 40m sprint time from pre- to post-test (p = .01–.04, ES = 0.38–0.45). In conclusion, resisted plyometric training was more effective than assisted plyometric training for improving the maximal speed and more effective than the active control condition for increasing jump height.
Inhibition Profiles of Some Symmetric Sulfamides Derived from Phenethylamines on Human Carbonic Anhydrase I, and II Isoenzymes

In this work, the inhibitory effect of some symmetric sulfamides derived from phenethylamines were determined against human carbonic anhydrase (hCA) I, and II isoenzymes, and compared with standard compound acetazolamide. IC50 values were obtained from the Enzyme activity (%)‐[Symmetric sulfamides] graphs. Also, Ki values were calculated from the Lineweaver‐Burk graphs. Some symmetric sulfamides compounds (11–18) demonstrated excellent inhibition effects against hCA I, and II isoenzymes. These compounds demonstrated effective inhibitory profiles with IC50 values in ranging from 21.66–28.88 nM against hCA I, 14.44–30.13 nM against hCA II. Among these compounds, the best Ki value for hCA I (Ki: 8.34±1.60 nM) and hCA II (Ki: 16.40±1.00 nM) is compound number 11. Besides, the IC50 value of acetazolamide used as a standard was determined as hCA I, hCA II 57.75 nM, 49.50 nM, respectively. Moreover, in silico ADME‐Tox study showed that all synthesized compounds (11–18) had good oral bioavailability in light of Jorgensen's rule of three, and of Lipinski's rule of five.
Urinary Metabolite Biomarkers for the Detection of Synthetic Cannabinoid ADB-BUTINACA Abuse.

BACKGROUND (S)-N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-butyl-1H-indazole-3carboxamide (ADB-BUTINACA) is an emerging synthetic cannabinoid that was first identified in Europe in 2019 and entered Singapore's drug scene in January 2020. Due to the unavailable toxicological and metabolic data, there is a need to establish urinary metabolite biomarkers for detection of ADB-BUTINACA consumption and elucidate its biotransformation pathways for rationalizing its toxicological implications. METHODS We characterized the metabolites of ADB-BUTINACA in human liver microsomes using liquid chromatography Orbitrap mass spectrometry analysis. Enzyme-specific inhibitors and recombinant enzymes were adopted for the reaction phenotyping of ADB-BUTINACA. We further used recombinant enzymes to generate a pool of key metabolites in situ and determined their metabolic stability. By coupling in vitro metabolism and authentic urine analyses, a panel of urinary metabolite biomarkers of ADB-BUTINACA was curated. RESULTS Fifteen metabolites of ADB-BUTINACA were identified with key biotransformations being hydroxylation, N-debutylation, dihydrodiol formation, and oxidative deamination. Reaction phenotyping established that ADB-BUTINACA was rapidly eliminated via CYP2C19-, CYP3A4-, and CYP3A5-mediated metabolism. Three major monohydroxylated metabolites (M6, M12, and M14) were generated in situ, which demonstrated greater metabolic stability compared to ADB-BUTINACA. Coupling metabolite profiling with urinary analysis, we identified four urinary biomarker metabolites of ADB-BUTINACA: 3 hydroxylated metabolites (M6, M11, and M14) and 1 oxidative deaminated metabolite (M15). CONCLUSIONS Our data support a panel of four urinary metabolite biomarkers for diagnosing the consumption of ADB-BUTINACA.
Aztreonam/avibactam effect on pharmacodynamic indices for mutant selection of Escherichia coli and Klebsiella pneumoniae harbouring serine- and New Delhi metallo-β-lactamases.

OBJECTIVES Ceftazidime/avibactam is not active against MBL-producing bacteria. Combining ceftazidime/avibactam or avibactam with aztreonam can counter the resistance of MBL-producing Enterobacterales. The aim of this study was to evaluate whether the addition of avibactam could reduce or close the mutant selection window (MSW) of aztreonam in Escherichia coli and Klebsiella pneumoniae harbouring MBLs; MSW is a pharmacodynamic (PD) parameter for the selection of emergent resistant mutants. METHODS In vitro susceptibility of 19 clinical isolates to ceftazidime/avibactam, aztreonam alone, and in co-administration (aztreonam/ceftazidime/avibactam and aztreonam/avibactam) was determined, as well as the mutant prevention concentration (MPC). The fraction of time within 24 h that the free drug concentration was within the MSW (fTMSW) and the fraction of time that the free drug concentration was above the MPC (fT>MPC) in both plasma and epithelial lining fluid (ELF) were determined from simulations of 10 000 profiles. The joint PTA was used to derive a joint cumulative fraction of response (CFR). RESULTS All isolates were resistant to ceftazidime/avibactam or aztreonam. Combining aztreonam and avibactam or ceftazidime/avibactam resulted in synergistic bactericidal activities against all isolates. Synergism was primarily due to the aztreonam/avibactam combination. For aztreonam/avibactam dosing regimens evaluated in clinical trials, fT>MPC values were >90% and >80%, whereas fTMSW measures were <10% and <20% in plasma and ELF, respectively. The CFR was 100% for aztreonam/avibactam against the collection of clinical isolates. CONCLUSIONS Effective antimicrobial combination optimized the PD parameters measuring selection for emergent mutants by increasing fT>MPC and reducing fTMSW.
Deaths in Children and Adolescents Associated With COVID-19 and MIS-C in the United States

OBJECTIVES To describe the demographics, clinical characteristics, and hospital course among persons <21 years of age with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–associated death. METHODS We conducted a retrospective case series of suspected SARS-CoV-2-associated deaths in the United States in persons <21 years of age during February 12 to July 31, 2020. All states and territories were invited to participate. We abstracted demographic and clinical data, including laboratory and treatment details, from medical records. RESULTS We included 112 SARS-CoV-2-associated deaths from 25 participating jurisdictions. The median age was 17 years (IQR 8.5–19 years). Most decedents were male (71, 63%), 31 (28%) were Black (non-Hispanic) persons, and 52 (46%) were Hispanic persons. Ninety-six decedents (86%) had at least 1 underlying condition; obesity (42%), asthma (29%), and developmental disorders (22%) were most commonly documented. Among 69 hospitalized decedents, common complications included mechanical ventilation (75%) and acute respiratory failure (82%). The sixteen (14%) decedents who met multisystem inflammatory syndrome in children (MIS-C) criteria were similar in age, sex, and race and/or ethnicity to decedents without MIS-C; 11 of 16 (69%) had at least 1 underlying condition. CONCLUSIONS SARS-CoV-2-associated deaths among persons <21 years of age occurred predominantly among Black (non-Hispanic) and Hispanic persons, male patients, and older adolescents. The most commonly reported underlying conditions were obesity, asthma, and developmental disorders. Decedents with coronavirus disease 2019 were more likely than those with MIS-C to have underlying medical conditions.
Recommendations for Virtual Qualitative Health Research During a Pandemic

Qualitative health research has been uniquely affected by the COVID-19 pandemic. Various public health directives will likely remain in place until this pandemic is fully controlled, creating long-lasting impacts on the design and conduct of qualitative health research. Virtual qualitative research provides an alternative to traditional interviews or focus groups and can help researchers adhere to public health directives. In this commentary, we respond to methodological needs created by the COVID-19 pandemic. Specifically, we explore unique elements of, and recommendations for, the design and conduct of obtrusive virtual qualitative research (online interviews, online focus groups, and email interviews) and demonstrate crucial ethical, recruitment, analytical, and interpretive considerations. Researchers are currently faced with an ethical imperative to advance virtual qualitative research methods and ensure that rigorous qualitative health research continues during this pandemic and beyond. Our discussions provide a starting point for researchers to explore the potential of virtual qualitative research.
Air pollution and COVID-19: clearing the air and charting a post-pandemic course: a joint workshop report of ERS, ISEE, HEI and WHO

Air pollution is now recognised by governments, international institutions and civil society as a major global public health risk factor. The health burden of air pollution is large: 509 000 premature deaths every year in Europe [1] and serious aggravations of heart and lung diseases that affect millions of patients, both children and adults. The European Environmental Agency estimated that in 2018 there were 417 000 premature deaths attributable to particulate matter with diameter <2.5 µm (PM2.5), 55 000 to NO2, and 20 600 to O3 in Europe (table 10.1 in EEA Report 9/2020 [2]). In addition, 4 805 800 years of life lost could be attributed to PM2.5, 623 600 to NO2, and 246 700 to O3 (table 10.2 in [2]). This “silent killer” is one the most important determinants of health, surpassed only by high blood pressure, tobacco use and poor diet. The coronavirus disease 2019 (COVID-19) pandemic has raised concerns about whether air pollution can increase the severity of disease and risk of death after infection, as well as facilitate the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Chronic lung disease patients are in the epicentre of the current crisis, as they are more vulnerable to both the adverse effects of a SARS-CoV-2 infection and air pollution exposure, as well as their possible interactions. At the same time, the lockdown measures to control the spread of COVID-19 brought historical short-term reductions in air pollution levels around the globe, and increasing general public interest and demand for clean air policies [3]. The COVID-19 pandemic, an emerging infectious disease probably caused by a spill over from animals, and its possible interactions with air pollution, is an existential reminder that we are a part of a larger ecosystem, and that human health is closely connected with the health of our environment and planet. Here we provide a short summary on the potential role of air pollution in the spread and worsening of health impacts of COVID-19, and on the influence of the pandemic on air pollution levels in Europe. Moreover, we outline the major lessons learned to chart a healthy post-pandemic course. This work summarises the key messages from a workshop that took place on 2 December, 2020, organised by the European Respiratory Society (ERS), the International Society for Environmental Epidemiology (ISEE) and the Health Effects Institute (HEI), endorsed by the World Health Organization (WHO), and hosted by the European Parliament Lung Health Group and the European Commission (table 1). The potential role of air pollution in the worsening of health impacts of COVID-19, and the influence of the pandemic on air pollution levels in Europe is explored. This editorial outlines the major lessons learned to chart a healthy post-pandemic course. https://bit.ly/3hmbaya
Measles virus exits human airway epithelia within dislodged metabolically active infectious centers

Measles virus (MeV) is the most contagious human virus. Unlike most respiratory viruses, MeV does not directly infect epithelial cells upon entry in a new host. MeV traverses the epithelium within immune cells that carry it to lymphatic organs where amplification occurs. Infected immune cells then synchronously deliver large amounts of virus to the airways. However, our understanding of MeV replication in airway epithelia is limited. To model it, we use well-differentiated primary cultures of human airway epithelial cells (HAE) from lung donors. In HAE, MeV spreads directly cell-to-cell forming infectious centers that grow for ~3–5 days, are stable for a few days, and then disappear. Transepithelial electrical resistance remains intact during the entire course of HAE infection, thus we hypothesized that MeV infectious centers may dislodge while epithelial function is preserved. After documenting by confocal microscopy that infectious centers progressively detach from HAE, we recovered apical washes and separated cell-associated from cell-free virus by centrifugation. Virus titers were about 10 times higher in the cell-associated fraction than in the supernatant. In dislodged infectious centers, ciliary beating persisted, and apoptotic markers were not readily detected, suggesting that they retain functional metabolism. Cell-associated MeV infected primary human monocyte-derived macrophages, which models the first stage of infection in a new host. Single-cell RNA sequencing identified wound healing, cell growth, and cell differentiation as biological processes relevant for infectious center dislodging. 5-ethynyl-2’-deoxyuridine (EdU) staining located proliferating cells underneath infectious centers. Thus, cells located below infectious centers divide and differentiate to repair the dislodged infected epithelial patch. As an extension of these studies, we postulate that expulsion of infectious centers through coughing and sneezing could contribute to MeV’s strikingly high reproductive number by allowing the virus to survive longer in the environment and by delivering a high infectious dose to the next host.
Phenolic extract of Libidibia ferrea inhibits dentin endogenous enzymatic activity depending on the adhesive system strategy

This study evaluated the influence of Libidibia ferrea (Lf) extract used as dentin pretreatment on the resin–dentin bond strength stability and dentin endogenous enzymatic activity. The phytochemical profile (PP) of the Lf extract was evaluated by liquid chromatography; particle size, polydispersity index (PdI), and zeta potential (ZP) were evaluated by dynamic light scattering. The tested groups were ER—Scotchbond Universal (SBU) in the etch‐and‐rinse (ER) mode; ERLf—SBU in the ER mode + Lf after etching; SE— SBU in the self‐etch (SE) mode; and LfSE—Lf before SBU in the SE mode. Sticks were obtained for microtensile bond strength tests and failure mode (24 hr and 12 months). The hybrid layer was evaluated using scanning electron microscopy. The endogenous enzymatic activity of the underlying dentin was analyzed by in situ zymography with the same treatments. The PP showed the presence of quercetin (2.6% w/w). Lf particles were considered large after the analysis of the PdI. The ZP remained stable over time. The ER and ERLf groups had lower bond strength after 12 months, but SE and LfSE remained stable. The predominant failure mode was adhesive for both times. ER and ERLf had longer resin tags and a thicker hybrid layer. The ER and LfSE groups showed higher enzymatic activity than the ERLf and SE groups after 12 months. The Lf extract may contribute to inhibit the dentin endogenous enzymatic activity when associated with an adhesive system in the ER mode.
Shared understanding of color among sighted and blind adults

Significance We learn in a variety of ways: through direct sensory experience, by talking with others, and by thinking. Disentangling how these sources contribute to what we know is challenging. A wedge into this puzzle was suggested by empiricist philosophers, who hypothesized that people born blind would lack deep knowledge of “visual” phenomena such as color. We find that, contrary to this prediction, congenitally blind and sighted individuals share in-depth understanding of object color. Blind and sighted people share similar intuitions about which objects will have consistent colors, make similar predictions for novel objects, and give similar explanations. Living among people who talk about color is sufficient for color understanding, highlighting the efficiency of linguistic communication as a source of knowledge. Empiricist philosophers such as Locke famously argued that people born blind might learn arbitrary color facts (e.g., marigolds are yellow) but would lack color understanding. Contrary to this intuition, we find that blind and sighted adults share causal understanding of color, despite not always agreeing about arbitrary color facts. Relative to sighted people, blind individuals are less likely to generate “yellow” for banana and “red” for stop sign but make similar generative inferences about real and novel objects’ colors, and provide similar causal explanations. For example, people infer that two natural kinds (e.g., bananas) and two artifacts with functional colors (e.g., stop signs) are more likely to have the same color than two artifacts with nonfunctional colors (e.g., cars). People develop intuitive and inferentially rich “theories” of color regardless of visual experience. Linguistic communication is more effective at aligning intuitive theories than knowledge of arbitrary facts.