Miracle-dz/UniFAR-FTUs huggingface dataset:
Berberine Delays Onset of Collagen-Induced Arthritis through T Cell Suppression

There is evidence that berberine (BBR), a clinically relevant plant compound, ameliorates clinically apparent collagen-induced arthritis (CIA) in vivo. However, to date, there are no studies involving the use of BBR which explore its prophylactic potential in this model of rheumatoid arthritis (RA). The aim of this study was to determine if prophylactic BBR use during the preclinical phase of collagen-induced arthritis would delay arthritic symptom onset, and to characterize the cellular mechanism underlying such an effect. DBA/1J mice were injected with an emulsion of bovine type II collagen (CII) and complete Freund’s adjuvant (day 0) and a booster injection of CII in incomplete Freund’s adjuvant (day 18) to induce arthritis. Mice were then given i.p. injections of 1 mg/kg/day of BBR or PBS (vehicle with 0.01% DMSO) from days 0 to 28, were left untreated (CIA control), or were in a non-arthritic control group (n = 15 per group). Incidence of arthritis in BBR-treated mice was 50%, compared to 90% in both the CIA and PBS controls. Populations of B and T cells from the spleens and draining lymph nodes of mice were examined on day 14 (n = 5 per group) and day 28 (n = 10 per group). BBR-treated mice had significantly reduced populations of CD4+Th and CD4+CXCR5+ Tfh cells, and an increased proportion of Foxp3+ Treg at days 14 and 28, as well as reduced expression of co-stimulatory molecules CD28 and CD154 at both endpoints. The effect seen on T cell populations and co-stimulatory molecule expression in BBR-treated mice was not mirrored in CD19+ B cells. Additionally, BBR-treated mice experienced reduced anti-CII IgG2a and anti-CII total IgG serum concentrations. These results indicate a potential role for BBR as a prophylactic supplement for RA, and that its effect may be mediated specifically through T cell suppression. However, the cellular effector involved raises concern for BBR prophylactic use in the context of vaccine efficacy and other primary adaptive immune responses.
A Static Friction Model for Unlubricated Contact of Random Rough Surfaces at Micro/Nano Scale

A novel static friction model for the unlubricated contact of random rough surfaces at micro/nano scale is presented. This model is based on the energy dissipation mechanism that states that changes in the potential of the surfaces in contact lead to friction. Furthermore, it employs the statistical theory of two nominally flat rough surfaces in contact, which assumes that the contact between the equivalent rough peaks and the rigid flat plane satisfies the condition of interfacial friction. Additionally, it proposes a statistical coefficient of positional correlation that represents the contact situation between the equivalent rough surface and the rigid plane. Finally, this model is compared with the static friction model established by Kogut and Etsion (KE model). The results of the proposed model agree well with those of the KE model in the fully elastic contact zone. For the calculation of dry static friction of rough surfaces in contact, previous models have mainly been based on classical contact mechanics; however, this model introduces the potential barrier theory and statistics to address this and provides a new way to calculate unlubricated friction for rough surfaces in contact.
Assessing Age-Related Gray Matter Differences in Young Adults with Voxel-Based Morphometry: The Effect of Field Strengths

Knowing the patterns of brain differences with age in the young population could lead to a better understanding of the causes of certain psychiatric disorders; however, relevant information is insufficient. Here, a pattern of regional gray matter (GM) that changed with age in a young cohort aged 20–30 years was provided. Extending from previous age studies, all participants were imaged at both 1.5 T and 3 T to address the question of how far the field strength influences results. Fifty-nine young participants aged 20–30 years were scanned at both 1.5 T and 3 T. Voxel-based morphometry (VBM) was used to estimate the GM volume. Some brain regions showed a significant field strength-dependent difference in GM volume. VBM uncovered a significantly age-related increase in the GM volume in the left visual-associated area at 3 T, which was not detected at 1.5 T. In addition, voxels at 1.5 T that revealed a significant age-related reduction in the GM volume were found in the right cerebellum. In conclusion, age-related differences in human brain morphology could even be detected in a young cohort aged 20–30 years; however, the results varied across field strengths. Thus, field strength should be considered an important factor when comparing age-specific brain differences across studies.
Psychological Impact of COVID-19 Pandemic and Related Variables: A Cross-Sectional Study in a Sample of Workers in a Spanish Tertiary Hospital

Introduction: We intend to objectify the psychological impact of the COVID-19 pandemic on the workers of a tertiary hospital. Methods: All the workers were invited to an online survey. In total, 657 workers were recruited, including 536 healthcare workers (HCWs) and 121 non-healthcare workers (nHCWs). General Health Questionnaire-12 items (GHQ-12) was used as a screening tool. Sociodemographic data, working environmental conditions, and health behaviors were also analyzed. Results: inadequate sleep, poor nutritional and social interaction habits, misuse of psychotropics, female gender, COVID-19 clinical diagnosis, and losing a relative by COVID-19 were variables associated with higher probability of GHQ-12 positive screening. Significant differences between “frontline workers” and the rest were not found, nor was higher the probability of psychological distress in healthcare workers compared to non-healthcare workers. After 3 months from the peak of the pandemic, 63.6% of participants screening positive in GHQ-12 reported remaining “the same or worse. ” Limitations: Causal inferences cannot be established. Retrieval and selection biases must be considered as the survey was not conducted during the peak of the outbreak. Conclusions: psychological impact of COVID-19 has been broad, heavy, and persistent in our institution. Proper assessment and treatment must be offered to all hospital workers.
Distinct miRNA Signatures and Networks Discern Fetal from Adult Erythroid Differentiation and Primary from Immortalized Erythroid Cells

MicroRNAs (miRNAs) are small non-coding RNAs crucial for post-transcriptional and translational regulation of cellular and developmental pathways. The study of miRNAs in erythropoiesis elucidates underlying regulatory mechanisms and facilitates related diagnostic and therapy development. Here, we used DNA Nanoball (DNB) small RNA sequencing to comprehensively characterize miRNAs in human erythroid cell cultures. Based on primary human peripheral-blood-derived CD34+ (hCD34+) cells and two influential erythroid cell lines with adult and fetal hemoglobin expression patterns, HUDEP-2 and HUDEP-1, respectively, our study links differential miRNA expression to erythroid differentiation, cell type, and hemoglobin expression profile. Sequencing results validated by reverse-transcription quantitative PCR (RT-qPCR) of selected miRNAs indicate shared differentiation signatures in primary and immortalized cells, characterized by reduced overall miRNA expression and reciprocal expression increases for individual lineage-specific miRNAs in late-stage erythropoiesis. Despite the high similarity of same-stage hCD34+ and HUDEP-2 cells, differential expression of several miRNAs highlighted informative discrepancies between both cell types. Moreover, a comparison between HUDEP-2 and HUDEP-1 cells displayed changes in miRNAs, transcription factors (TFs), target genes, and pathways associated with globin switching. In resulting TF-miRNA co-regulatory networks, major therapeutically relevant regulators of globin expression were targeted by many co-expressed miRNAs, outlining intricate combinatorial miRNA regulation of globin expression in erythroid cells.
Field Performances of Rapid Diagnostic Tests Detecting Human Plasmodium Species: A Systematic Review and Meta-Analysis in India, 1990–2020

Rapid diagnostic tests (RDTs) have become a mainstay of malaria diagnosis in endemic countries since their implementation in the 1990s. We conducted a 30-year systematic review and meta-analysis on malaria RDTs performance in India. Outcomes of interest were sensitivity (Se), specificity (Sp), positive/negative likelihood ratio (PLR/NLR), and diagnostic odd ratio (DOR). Among the 75 studies included, most of the studies were cross-sectional (65.3%), hospital-based (77.3%), and targeted febrile patients (90.6%). Nearly half of RDTs were designed for detecting Plasmodium falciparum only (47.5%) while the rest were for P. falciparum and P. vivax (11.9%), and P. falciparum/Pan-Plasmodium except for P. knowlesi (32.3%). When compared to light microscopy (gold standard), pooled estimates of performances were: Se = 97.0%, Sp = 96.0%, PLR = 22.4, NLR = 0.02 and DOR = 1080. In comparison to polymerase chain reaction, the RDTs showed Se = 89.0% and Sp = 99.0%. Performance outcomes (Se and Sp) were similar for RDT targeting P. falciparum only, but decreased for mixed and non-falciparum infections. Performances of malaria RDTs are still high India. However, there is a need for developing RDTs with regard to targeting minor malarial species, individuals carrying only mature gametocytes, and pfhrp2-deleted parasites.
Two-photon, two-color in vivo flow cytometry to noninvasively monitor multiple circulating cell lines

We have developed a new two-photon system for in vivo flow cytometry, thereby allowing us to simultaneously quantify different circulating populations in a single animal. The instrument was able to resolve minute-by-minute depletion dynamics of injected fluorescent microspheres at finer time scales than conventional flow cytometry. Also observed were the circulation dynamics of human MCF-7 and MDA-MB-435 breast cancer cells, which have low and high metastatic potential, respectively. After co-injection of both cell types into mice, markedly greater numbers of MCF-7 cells were present in the circulation at early time points. While low metastatic MCF-7 cells were cleared from the vascular system within 24 hours, detectable numbers of metastatic MDA-MB- 435 cells in the circulation remained constant over time. When we replace the commercial (80-MHz) NIR excitation laser with a reduced-repetition-rate (20-MHz) mode-locked oscillator, the signal is enhanced four-fold, enabling superior detection in blood of cell lines expressing fluorescent proteins tdTomato and mPlum (crosslabeled with DiI and DiD). Detection sensitivity versus incident laser power is understood in terms of detected event photon count distribution, which can be predicted with simple fluorophore distribution assumptions. The technique of two-color, two-photon flow cytometry greatly enhances the capabilities of ex vivo flow cytometry to investigate dynamics of circulating cells in cancer and other important diseases.
Aerobic Exercise and Stretching as Add-On to Inpatient Treatment for Depression Have No Differential Effects on Stress-Axis Activity, Serum-BDNF, TNF-Alpha and Objective Sleep Measures

(1) Background: While the antidepressant effects of aerobic exercise (AE) are well documented, fewer studies have examined impact of AE as an add-on treatment. Moreover, various effects on neurobiological variables have been suggested. This study examines effects of AE on Cortisol Awakening Reaction (CAR), serum Brain Derived Neurotrophic Factor (sBDNF), Tumor Necrosis Factor alpha (TNF-alpha) and sleep. (2) Methods: Inpatients with moderate-to-severe depression (N = 43) were randomly assigned to the AE or stretching condition (active control) taking place 3x/week for 6 weeks. CAR, sBDNF and TNF-alpha were assessed at baseline, after 2 weeks and post-intervention. The 17-item Hamilton Depression Rating Scale (HDRS17), subjective sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG) were obtained at baseline and post-intervention. (3) Results: Stress axis activity decreased in both groups from baseline to post-intervention. sBDNF showed a significant increase over time, whereas the number of awakenings significantly decreased. No significant time by group interactions were detected for any of the study variables. Correlational analyses showed that higher improvements in maximum oxygen capacity (VO2max) from baseline to post-intervention were associated with reduced scores on the HDRS17, PSQI and REM-latency post-intervention. (4) Conclusions: While some neurobiological variables improved during inpatient treatment (CAR, sBDNF), no evidence was found for differential effects between AE and an active control condition (stretching). However, patients in which cardiorespiratory fitness increased showed higher improvements in depression severity and depression-related sleep-parameters.
The Characteristics of Natural Rubber Composites with Klason Lignin as a Green Reinforcing Filler: Thermal Stability, Mechanical and Dynamical Properties

The objective of this work was to investigate the influences of Klason lignin as a filler on the thermal stability and properties of natural rubber composites. The modulus and tensile strength of stabilized vulcanizates were measured before and after thermo-oxidative aging. It was determined that lignin filled natural rubber had significantly enhanced thermo-oxidative aging and mechanical properties compared to those of controlled samples. The reinforcement effect of lignin increased stress with lignin loading but it decreased at 20 phr, suggesting that the reinforcement mechanism of lignin was via strain-induced crystallization. The composite samples with 10 phr filler loading had the highest mechanical properties as well as thermo-oxidative degradation resistance. Such a finding could be due to interactions between the Klason lignin filler and natural rubber matrix. Based on the findings in this work, the degradation temperature of Klason lignin occurred at 420 °C. The absorption peaks at wavenumbers 1192 and 1374 cm−1 indicated that C–O stretching vibrations of the syringyl and guaiacyl rings of hardwood lignin existed. It was also found that the Klason lignin–rubber composite containing 10 phr had the highest stress–strain, 100% modulus, and tensile strength, while lignin showed increasing aging resistance of the composite comparable with commercial antioxidant at 1.5 phr. It appears that Klason lignin from rubberwood could be used as a green antioxidant and alternative reinforcing filler and for high performance eco-friendly natural rubber biocomposites.
Molecular Analysis of Polymyxin Resistance among Carbapenemase-Producing Klebsiella pneumoniae in Colombia

Polymyxin resistance in Klebsiella pneumoniae has been attributed to mutations in mgrB, phoPQ, pmrAB, and crrAB and to the presence of mcr plasmid-mediated genes. Herein, we describe the molecular characteristics of 24 polymyxin- and carbapenem-resistant K. pneumoniae isolates recovered from six Colombian cities between 2009 and 2019. Minimum inhibitory concentrations (MICs) to polymyxin were confirmed by broth microdilution, and whole-genome sequencing was performed to determine sequence type, resistome, and mutations in the genes related to polymyxin resistance, as well the presence of mcr. The results showed high-level resistance to polymyxin (MICs ≥ 4 μg/mL). blaKPC-3 was present in the majority of isolates (17/24; 71%), followed by blaKPC-2 (6/24; 25%) and blaNDM-1 (1/24; 4%). Most isolates belonged to the CG258 (17/24; 71%) and presented amino acid substitutions in PmrB (22/24; 92%) and CrrB (15/24; 63%); mutations in mgrB occurred in only five isolates (21%). Additional mutations in pmrA, crrA, and phoPQ nor any of the mcr resistance genes were identified. In conclusion, we found clonal dissemination of polymyxin and carbapenem-resistant K. pneumoniae isolates in Colombia, mainly associated with CG258 and blaKPC-3. Surveillance of this multidrug-resistant clone is warranted due to the limited therapeutic options for the treatment of carbapenem-resistant K. pneumoniae infections.
Multidimensional Diffusion Magnetic Resonance Imaging for Characterization of Tissue Microstructure in Breast Cancer Patients: A Prospective Pilot Study

Simple Summary In this prospective pilot study, we investigated the potential of clinical multidimensional diffusion magnetic resonance imaging (MDD MRI) for the microstructural characterization of breast cancers and normal fibroglandular breast tissue. The method relies on advanced gradient waveforms to encode the signal with information about cell densities, shapes, and orientations, and to quantify tissue composition as a probability distribution of diffusion tensors in a space with dimensions analogous to those on a cellular level. Sixteen patients with breast cancer underwent MDD MRI within a clinically feasible scan time of approximately 4 min, providing voxel-resolved distributions and parameter maps with microstructural information that is not accessible with conventional methods. Abstract Diffusion-weighted imaging is a non-invasive functional imaging modality for breast tumor characterization through apparent diffusion coefficients. Yet, it has so far been unable to intuitively inform on tissue microstructure. In this IRB-approved prospective study, we applied novel multidimensional diffusion (MDD) encoding across 16 patients with suspected breast cancer to evaluate its potential for tissue characterization in the clinical setting. Data acquired via custom MDD sequences was processed using an algorithm estimating non-parametric diffusion tensor distributions. The statistical descriptors of these distributions allow us to quantify tissue composition in terms of metrics informing on cell densities, shapes, and orientations. Additionally, signal fractions from specific cell types, such as elongated cells (bin1), isotropic cells (bin2), and free water (bin3), were teased apart. Histogram analysis in cancers and healthy breast tissue showed that cancers exhibited lower mean values of “size” (1.43 ± 0.54 × 10−3 mm2/s) and higher mean values of “shape” (0.47 ± 0.15) corresponding to bin1, while FGT (fibroglandular breast tissue) presented higher mean values of “size” (2.33 ± 0.22 × 10−3 mm2/s) and lower mean values of “shape” (0.27 ± 0.11) corresponding to bin3 (p < 0.001). Invasive carcinomas showed significant differences in mean signal fractions from bin1 (0.64 ± 0.13 vs. 0.4 ± 0.25) and bin3 (0.18 ± 0.08 vs. 0.42 ± 0.21) compared to ductal carcinomas in situ (DCIS) and invasive carcinomas with associated DCIS (p = 0.03). MDD enabled qualitative and quantitative evaluation of the composition of breast cancers and healthy glands.
Palestinian Refugee Youth in Jordan: Parental Practices, Neighborhood Cohesion and Assistance, and Adolescent Wellbeing

In this study, a total of 335 Palestinian refugees (M = 15.5 years, SD = 1.05, 49% males), recruited from four United Nations Relief and Work Agency (UNRWA) schools at the Al-Baqa’a and Jabal Al-Hussein refugee camps in Jordan, rated their neighborhood physical environment and neighborhood support and cohesion, separately rated their mothers’ and fathers’ parenting on several dimensions, and reported on their adjustment to these circumstances (internalizing symptoms, self-concept clarity, and norm breaking). Living in more dangerous physical environments was associated with higher levels of refugee youths’ internalizing symptoms and norm breaking, but effects were not significant when parenting was considered. Our study showed that higher levels of psychological control–disrespect (significantly for fathers and marginally for mothers) and marginally, higher levels of maternal harsh punishment were associated with more teen internalizing symptoms. In addition, fathers’ greater psychological control and lower levels of support had a marginally significant effect on teens’ greater norm breaking. For behavioral control, only mothers’ greater behavioral control was associated with refugee youths’ greater self-concept clarity but not with paternal behavioral control. Thus, fathers’ psychological control and mothers’ behavioral control had the biggest association with adolescent outcomes.
Part I: Relationship among Training Load Management, Salivary Immunoglobulin A, and Upper Respiratory Tract Infection in Team Sport: A Systematic Review

Immunoglobulin A (IgA), which is the first line of defense against upper respiratory tract viruses, has been related with training load management. This article aimed to systematically identify and summarize (1) the studies that have found a relationship between training load and salivary IgA in team sports, and (2) the studies that have highlighted a relationship between IgA and upper respiratory tract infection (URTI) in team sports. A systematic review of relevant articles was carried out using two electronic databases (PubMed and WoK) until 3 October 2020. From a total of 174 studies initially found, 24 were included in the qualitative synthesis. This systematic review confirmed that lower values of IgA occurred after greater training load (intensity/volume) and congested periods. In this scenario, a low level of IgA was correlated with higher URTI, which makes training load management mandatory to healthcare avoiding immunosuppression. Therefore, physical fitness and conditioning coaches should carefully manage training load progression, avoiding high-intensity sessions in two consecutive days. In addition, they should not program high-intensity training sessions during at least the two days following competition.
The mechanical strength of a covalent bond calculated by density functional theory

The rupture forces of covalent bonds in a polymer as a function of bond lifetime are calculated with an Arrhenius kinetics model based on high-level density functional theory calculations. Relaxed potential energy surface scans of small model molecules yield potential functions that account for the deformations and hybridizations caused by the application of force. Morse potentials chosen to exhibit the same well depth and maximum force are used as an analytic representation of an individual bond in an infinitely long one-dimensional polymer. Application of force deforms the potential, and the activation energy for the bond rupture event together with the frequency of an optical phonon in the one-dimensional polymer are the two Arrhenius parameters. Rupture forces of the bonds C–C, C–N, C–O, Si–C, Si–N, Si–O, and Si–Si are reported as a function of the lifetime of the bond.