Miracle-dz/UniFAR-FTUs huggingface dataset:
Dopamine Precursor Depletion in Healthy Volunteers Impairs Processing of Duration but Not Temporal Order

Abstract Studies in animals and humans have implicated the neurotransmitter dopamine in duration processing. However, very few studies have examined dopamine's involvement in other forms of temporal processing such as temporal order judgments. In a randomized within-subject placebo-controlled design, we used acute phenylalanine/tyrosine depletion (APTD) to reduce availability of the dopamine precursors tyrosine and phenylalanine in healthy human volunteers. As compared to a nutritionally balanced drink, APTD significantly impaired the ability to accurately reproduce interval duration in a temporal reproduction task. In addition, and confirming previous findings, the direction of error differed as a function of individual differences in underlying dopamine function. Specifically, APTD caused participants with low baseline dopamine precursor availability to overestimate the elapse of time, whereas those with high dopamine availability underestimated time. In contrast to these effects on duration processing, there were no significant effects of APTD on the accuracy of discriminating the temporal order of visual stimuli. This pattern of results does not simply represent an effect of APTD on motor, rather than perceptual, measures of timing because APTD had no effect on participants' ability to use temporal cues to speed RT. Our results demonstrate, for the first time in healthy volunteers, a dopaminergic dissociation in judging metrical (duration) versus ordinal (temporal order) aspects of time.
Amniotic membrane‐mesenchymal stromal cells secreted factors and extracellular vesicle‐miRNAs: Anti‐inflammatory and regenerative features for musculoskeletal tissues

Human amniotic membrane‐derived mesenchymal stromal cells (hAMSCs) are easily obtained in large quantities and free from ethical concerns. Promising therapeutic results for both hAMSCs and their secreted factors (secretome) were described by several in vitro and preclinical studies, often for treatment of orthopedic disorders such as osteoarthritis (OA) and tendinopathy. For clinical translation of the hAMSC secretome as cell‐free therapy, a detailed characterization of hAMSC‐secreted factors is mandatory. Herein, we tested the presence of 200 secreted factors and 754 miRNAs in extracellular vesicles (EVs). Thirty‐seven cytokines/chemokines were identified at varying abundance, some of which involved in both chemotaxis and homeostasis of inflammatory cells and in positive remodeling of extracellular matrix, often damaged in tendinopathy and OA. We also found 336 EV‐miRNAs, 51 of which accounted for more than 95% of the genetic message. A focused analysis based on miRNAs related to OA and tendinopathy showed that most abundant EV‐miRNAs are teno‐ and chondro‐protective, able to induce M2 macrophage polarization, inhibit inflammatory T cells, and promote Treg. Functional analysis on IL‐1β treated tenocytes and chondrocytes resulted in downregulation of inflammation‐associated genes. Overall, presence of key regulatory molecules and miRNAs explain the promising therapeutic results of hAMSCs and their secretome for treatment of musculoskeletal conditions and are a groundwork for similar studies in other pathologies. Furthermore, identified molecules will pave the way for future studies aimed at more sharply predicting disease‐targeted clinical efficacy, as well as setting up potency and release assays to fingerprint clinical‐grade batches of whole secretome or purified components.
Treatments for NAFLD: State of Art

Non-alcoholic fatty liver disease (NAFLD) is to date the most common chronic liver disease in clinical practice and, consequently, a major health problem worldwide. It affects approximately 30% of adults in the general population and up to 70% of patients with type 2 diabetes (T2DM). Despite the current knowledge of the epidemiology, pathogenesis, and natural history of NAFLD, no specific pharmacological therapies are until now approved for this disease and, consequently, general strategies have been proposed to manage it. They include: (a) lifestyle change in order to promote weight loss by diet and physical activity, (b) control of the main cardiometabolic risk factors, (c) correction of all modifiable risk factors leading the development and progression of advanced forms of NAFLD, and (d) prevention of hepatic and extra-hepatic complications. In the last decade, several potential agents have been widely investigated for the treatment of NAFLD and its advanced forms—shedding some light but casting a few shadows. They include some glucose-lowering drugs (such as pioglitazone, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose co-transporter-2 (SGLT-2) inhibitors), antioxidants (such as vitamin E), statins or other lipid lowering agents, bile and non-bile acid farnesoid X activated receptor (FXR) agonists, and others. This narrative review discusses in detail the different available approaches with the potential to prevent and treat NAFLD and its advanced forms.
Safety and Efficacy of B-Cell Depletion with Rituximab for the Treatment of Systemic Sclerosis Associated Pulmonary Arterial Hypertension: A Multi-center, Double-blind, Randomized, Placebo-controlled Trial.

RATIONALE Systemic sclerosis-pulmonary arterial hypertension (SSc-PAH) is one of the most prevalent and deadly forms of PAH. B cells may contribute to SSc pathogenesis. OBJECTIVE We investigated the safety and efficacy of B-cell depletion for SSc-PAH. METHODS AND MEASUREMENTS In an NIH-sponsored, multi-center, double-blinded, randomized, placebo-controlled, proof-of-concept trial, 57 SSc-PAH patients on stable-dose standard medical therapy received two infusions of 1000 mg of rituximab or placebo administered two weeks apart. The primary outcome measure was the change in six-minute walk distance (6MWD) at 24 weeks. Secondary endpoints included safety and invasive hemodynamics. We applied a machine learning approach to predict drug-responsiveness. MAIN RESULTS We randomized 57 subjects from 2010-2018. In the primary analysis, using data through week 24, the adjusted mean change in 6MWD at 24 weeks favored the treatment arm but did not reach statistical significance (23.6±11.1m vs. 0.5±9.7m, p=0.12). While a negative study, when data through week 48 were also considered, the estimated change in 6MWD at week 24 was 25.5±8.8m for rituximab and 0.4±7.4m for placebo (p=0.03). Rituximab treatment appeared to be safe and well tolerated. Low levels of rheumatoid factor (RF), IL-12, and IL-17 were sensitive and specific as favorable predictors of a rituximab response as measured by an improved 6MWD (ROC AUC 0.88-0.95). CONCLUSIONS B cell depletion therapy is a potentially effective and safe adjuvant treatment for SSc-PAH. Future studies in these patients can confirm whether the identified biomarkers predict rituximab-responsiveness. Clinical trial registration available at www.clinicaltrials. gov, ID: NCT01086540.
On Convection Currents in High Pressure Mercury Arcs

Convection speeds in commercial high pressure Hg vapor lamps are measured by photographing on a moving film, the tracks of incandescent particles of CaO and MgO. A deep red filter and panchromatic film are used. The convection system is found to consist of a laminar flow of hot gas upward in the center and of cold gas downward near the walls. For the 400 watt lamp (p≅1 atmosphere, m = mass of Hg per cm of tube length = 11.5 mg cm−1) an upward speed of about 40 cm sec. −1 is found at the axis in the mid‐section of the lamp. The speed is somewhat greater near the bottom, this effect increasing with m. Speeds are found to increase somewhat less rapidly than in proportion to m as predicted. An approximate theory of these currents is presented, based largely on the work of Elenbaas, which accounts sufficiently well for the order of magnitude of the observed speeds. For similar discharges, speeds do not depend on the tube diameter but simply on m; for such discharges the watts lost by convection are proportional.
Comprehensive Identification of Glycosphingolipids in Human Plasma Using Hydrophilic Interaction Liquid Chromatography—Electrospray Ionization Mass Spectrometry

Glycosphingolipids (GSL) represent a highly heterogeneous class of lipids with many cellular functions, implicated in a wide spectrum of human diseases. Their isolation, detection, and comprehensive structural analysis is a challenging task due to the structural diversity of GSL molecules. In this work, GSL subclasses are isolated from human plasma using an optimized monophasic ethanol–water solvent system capable to recover a broad range of GSL species. Obtained deproteinized plasma is subsequently purified and concentrated by C18-based solid-phase extraction (SPE). The hydrophilic interaction liquid chromatography coupled to electrospray ionization linear ion trap tandem mass spectrometry (HILIC-ESI-LIT-MS/MS) is used for GSL analysis in the human plasma extract. Our results provide an in-depth profiling and structural characterization of glycosphingolipid and some phospholipid subclasses identified in the human plasma based on their retention times and the interpretation of tandem mass spectra. The structural composition of particular lipid species is readily characterized based on the detailed interpretation of mass spectrometry (MS) and tandem mass spectrometry (MS/MS) spectra and further confirmed by specific fragmentation behavior following predictable patterns, which yields to the unambiguous identification of 154 GSL species within 7 lipid subclasses and 77 phospholipids representing the highest number of GSL species ever reported in the human plasma. The developed HILIC-ESI-MS/MS method can be used for further clinical and biological research of GSL in the human blood or other biological samples.
Using Tertiary Sulci to Map the “Cognitive Globe” of Prefrontal Cortex

Abstract Stuss considered the human PFC as a “cognitive globe” [Stuss, D. T. , & Benson, D. F. Neuropsychological studies of the frontal lobes. Psychological Bulletin, 95, 3–28, 1984] on which functions of the frontal lobe could be mapped. Here, we discuss classic and recent findings regarding the evolution, development, function, and cognitive role of shallow indentations or tertiary sulci in PFC, with the goal of using tertiary sulci to map the “cognitive globe” of PFC. First, we discuss lateral PFC (LPFC) tertiary sulci in classical anatomy and modern neuroimaging, as well as their development, with a focus on those within the middle frontal gyrus. Second, we discuss tertiary sulci in comparative neuroanatomy, focusing on primates. Third, we summarize recent findings showing the utility of tertiary sulci for understanding structural–functional relationships with functional network insights in ventromedial PFC and LPFC. Fourth, we revisit and update unresolved theoretical perspectives considered by C. Vogt and O. Vogt (Allgemeinere ergebnisse unserer hirnforschung. Journal für Psychologie und Neurologie, 25, 279–462, 1919) and F. Sanides (Structure and function of the human frontal lobe. Neuropsychologia, 2, 209–219, 1964) that tertiary sulci serve as landmarks for cortical gradients. Together, the consideration of these classic and recent findings indicate that tertiary sulci are situated in a unique position within the complexity of the “cognitive globe” of PFC: They are the smallest and shallowest of sulci in PFC, yet can offer insights that bridge spatial scales (microns to networks), modalities (functional connectivity to behavior), and species. As such, the map of tertiary sulci within each individual participant serves as a coordinate system specific to that individual on which functions may be further mapped. We conclude with new theoretical and methodological questions that, if answered in future research, will likely lead to mechanistic insight regarding the structure and function of human LPFC.
Injury Trends in Irish Amateur Rugby: An Epidemiological Comparison of Men and Women

Background: Rugby union is a physically demanding sport that carries an inherent risk of injury. Despite being a popular and widely played team sport, little is known about injuries occurring across the male and female amateur game. Purpose: To establish and compare injury incidence, nature, and severity in male and female Irish amateur rugby union. Study Design: Prospective cohort study. Level of Evidence: Level 3. Methods: Data were collected prospectively from 25 male teams (959 players) and 8 female teams (234 players) over 2 full seasons. Both time-loss (24-hour time-loss injury definition) and non-time-loss match injury reports were collected, alongside match exposure data. Results: Time-loss match injury incidence rates were 49.1/1000 and 35.6/1000 player-hours for male and female players, respectively. Concussion and ankle ligament sprains were the most common diagnoses for male (5.6/1000 and 4.4/1000 player-hours, respectively) and female players (5.5/1000 and 3.9/1000 player-hours, respectively). Anterior cruciate ligament injuries presented the highest injury burden for male and female players with 200.3 and 307.2 days of absence per 1000 player-hours, respectively. In female players, 83% of noncontact injuries occurred in the fourth quarter of match play. Conclusion: While female players had a lower overall injury incidence rate compared with male players, concussion and ankle ligament injuries were the most common injuries in both cohorts. In female players, a high rate of noncontact injuries in the second half points to the need for strength and conditioning training programs to reduce fatigue-related injuries. Clinical Relevance: Establishing the incidence and burden of rugby-related injuries is an essential step in minimizing injury risk. This epidemiological information will aid the development of future reduction strategies, including education and coaching strategies and strength and conditioning programs, informed by the most common injuries observed and the mechanism of injury.
Cytotoxicity and Apoptosis Effects of Curcumin Analogue (2E,6E)-2,6-Bis(2,3-Dimethoxybenzylidine) Cyclohexanone (DMCH) on Human Colon Cancer Cells HT29 and SW620 In Vitro

Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. According to the Malaysian National Cancer Registry Report 2012–2016, colorectal cancer was the second most common cancer in Malaysia after breast cancer. Recent treatments for colon cancer cases have caused side effects and recurrence in patients. One of the alternative ways to fight cancer is by using natural products. Curcumin is a compound of the rhizomes of Curcuma longa that possesses a broad range of pharmacological activities. Curcumin has been studied for decades but due to its low bioavailability, its usage as a therapeutic agent has been compromised. This has led to the development of a chemically synthesized curcuminoid analogue, (2E,6E)-2,6-bis(2,3-dimethoxybenzylidine) cyclohexanone (DMCH), to overcome the drawbacks. This study aims to examine the potential of DMCH for cytotoxicity, apoptosis induction, and activation of apoptosis-related proteins on the colon cancer cell lines HT29 and SW620. The cytotoxic activity of DMCH was evaluated using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) cell viability assay on both of the cell lines, HT29 and SW620. To determine the mode of cell death, an acridine orange/propidium iodide (AO/PI) assay was conducted, followed by Annexin V/FITC, cell cycle analysis, and JC-1 assay using a flow cytometer. A proteome profiler angiogenesis assay was conducted to determine the protein expression. The inhibitory concentration (IC50) of DMCH in SW620 and HT29 was 7.50 ± 1.19 and 9.80 ± 0.55 µg/mL, respectively. The treated cells displayed morphological features characteristic of apoptosis. The flow cytometry analysis confirmed that DMCH induced apoptosis as shown by an increase in the sub-G0/G1 population and an increase in the early apoptosis and late apoptosis populations compared with untreated cells. A higher number of apoptotic cells were observed on treated SW620 cells as compared to HT29 cells. Human apoptosis proteome profiler analysis revealed upregulation of Bax and Bad proteins and downregulation of Livin proteins in both the HT29 and SW620 cell lines. Collectively, DMCH induced cell death via apoptosis, and the effect was more pronounced on SW620 metastatic colon cancer cells, suggesting its potential effects as an antimetastatic agent targeting colon cancer cells.
Determination of Pesticides in the Rhizome of Traditional Chinese Medicines by Gas Chromatography with Electron Capture Detection

A simple and efficient gas chromatography method for the determination of 27 organochlorine and pyrethroid pesticides in traditional Chinese medicine was developed. Pesticide residues were extracted from the samples by oscillation and ultrasound, and purified by gel permeation chromatography and florisil solid phase extraction. The analysis was performed by gas chromatography with micro-electron capture detection. The purification conditions, such as the extraction and elution solvents, extraction methodology, and gel permeation chromatography conditions, were optimized. Traditional Chinese medicines were purified by different methods based on their composition. Under optimized conditions, the calibration graph was linear from 10 to 500 µg/L and the correlation coefficients varied from 0.9958 to 0.9997. The detection limits of these pesticides were between 0.09 and 1.82 µg/kg. The recovery of the pesticides spiked in various samples at four concentrations ranged from 73.2% to 106.4%, with relative standard deviations between 1.0% and 14.0%. This study indicates that the method is useful for determining pesticides in rhizome traditional Chinese medicines.
ATF3-Induced Mammary Tumors Exhibit Molecular Features of Human Basal-Like Breast Cancer

Basal-like breast cancer (BLBC) is an aggressive and deadly subtype of human breast cancer that is highly metastatic, displays stem-cell like features, and has limited treatment options. Therefore, developing and characterizing preclinical mouse models with tumors that resemble BLBC is important for human therapeutic development. ATF3 is a potent oncogene that is aberrantly expressed in most human breast cancers. In the BK5.ATF3 mouse model, overexpression of ATF3 in the basal epithelial cells of the mammary gland produces tumors that are characterized by activation of the Wnt/β-catenin signaling pathway. Here, we used RNA-Seq and microRNA (miRNA) microarrays to better define the molecular features of BK5.ATF3-derived mammary tumors. These analyses showed that these tumors share many characteristics of human BLBC including reduced expression of Rb1, Esr1, and Pgr and increased expression of Erbb2, Egfr, and the genes encoding keratins 5, 6, and 17. An analysis of miRNA expression revealed reduced levels of Mir145 and Mir143, leading to the upregulation of their target genes including both the pluripotency factors Klf4 and Sox2 as well as the cancer stem-cell-related gene Kras. Finally, we show through knock-down experiments that ATF3 may directly modulate MIR145/143 expression. Taken together, our results indicate that the ATF3 mouse mammary tumor model could provide a powerful model to define the molecular mechanisms leading to BLBC, identify the factors that contribute to its aggressiveness, and, ultimately, discover specific genes and gene networks for therapeutic targeting.
Intention to voluntary blood donation among private higher education students, Jimma town, Oromia, Ethiopia: Application of the theory of planned behaviour

Background Blood is an important and crucial component in the management of patients presenting with severe accident injuries, surgical conditions, malignancies, pregnancy-related complications, and other medical conditions. Objectives To assess intention to voluntary blood donation among private higher education students in Jimma Town, South West Ethiopia, 2019. Methods Institution-based cross-sectional study with quantitative methods was conducted in private higher education students in Jimma town. A multistage sampling technique was used to recruit study participants. First, a simple random sampling technique was used to select departments in each private higher education institution. Seven departments were included in the study and after proportionally allocated in each department, a total of 595 were participated in the study, producing a response rate of 98%. The data was collected using self-administered structured questioners with 3 trained data collectors. Multivariable linear regression analysis was done to assess association between the independent variables and dependent variable. Results The mean score for intention of the respondents to donate blood voluntarily was 15.41 out of 25 with standard deviation of 4.42. The TPB variables explained 61.3% of the variance of intention to donate blood. Direct perceived behavioral control (β = 0.745, P < 0.001), direct attitude (B = 0.295, P<0.001) and direct subjective norm (β = 0.131, P< 0.001) were significant predictors of the intention. Conclusion Respondents’ intentions are mainly determined by perceived barriers and, subjective norms, the attitude of respondents towards voluntary blood donation.