Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanical Stress Induce PG-E2 in Murine Synovial Fibroblasts Originating from the Temporomandibular Joint

Genetic predisposition, traumatic events, or excessive mechanical exposure provoke arthritic changes in the temporomandibular joint (TMJ). We analysed the impact of mechanical stress that might be involved in the development and progression of TMJ osteoarthritis (OA) on murine synovial fibroblasts (SFs) of temporomandibular origin. SFs were subjected to different protocols of mechanical stress, either to a high-frequency tensile strain for 4 h or to a tensile strain of varying magnitude for 48 h. The TMJ OA induction was evaluated based on the gene and protein secretion of inflammatory factors (Icam-1, Cxcl-1, Cxcl-2, Il-1ß, Il-1ra, Il-6, Ptgs-2, PG-E2), subchondral bone remodelling (Rankl, Opg), and extracellular matrix components (Col1a2, Has-1, collagen and hyaluronic acid deposition) using RT-qPCR, ELISA, and HPLC. A short high-frequency tensile strain had only minor effects on inflammatory factors and no effects on the subchondral bone remodelling induction or matrix constituent production. A prolonged tensile strain of moderate and advanced magnitude increased the expression of inflammatory factors. An advanced tensile strain enhanced the Ptgs-2 and PG-E2 expression, while the expression of further inflammatory factors were decreased. The tensile strain protocols had no effects on the RANKL/OPG expression, while the advanced tensile strain significantly reduced the deposition of matrix constituent contents of collagen and hyaluronic acid. The data indicates that the application of prolonged advanced mechanical stress on SFs promote PG-E2 protein secretion, while the deposition of extracellular matrix components is decreased.
Inhibition of glioma by adenovirus KGHV500 encoding anti-p21Ras scFv and carried by cytokine-induced killer cells

Ras gene mutation or overexpression can lead to tumorigenesis in multiple kinds of cancer, including glioma. However, no drugs targeting Ras or its expression products have been approved for clinical application thus far. Adenoviral gene therapy is a promising method for the treatment of glioma. In this study, the human glioma cell line U251 was co-cultured with recombinant adenovirus KGHV500, and the anti-tumor effects of KGHV500 were determined by MTT, scratch test, Transwell invasion, and apoptosis assays. Then, KGHV500 was delivered via the intravenous injection of CIK cells into glioma xenografts. Tumor volume, ki67 proliferation index, apoptosis levels, and anti-p21Ras scFv expression were tested to evaluate targeting ability, anti-tumor efficacy, and safety. We found that the KGHV500 exhibited anti-tumor activity in U251 cells and increased the intracellular expression of anti-p21Ras scFv compared with that in the control groups. CIK cells delivered KGHV500 to U251 glioma cell xenografts and enhanced anti-tumor activity against glioma xenografts compared to that produced by the control treatment. In conclusion, targeting Ras is a useful therapeutic strategy for gliomas and other Ras-driven cancers, and the delivery of anti-p21Ras scFv by recombinant adenovirus and CIK cells may play an essential role in the therapy of Ras-driven cancers.
Validation of the International Classification of Functioning, Disability and Health (ICF) core sets from 2001 to 2019 – a scoping review

Abstract Objective: To investigate and summarize the literature on the validation of International Classification of Functioning, Disability and Health (ICF) core sets from 2001 to 2019 and explore what research methods have been used when validating ICF core sets. Methods: The current study is a scoping review using a structured literature search. Results: In total, 66 scientific articles were included, of which 23 ICF core sets were validated. Most validation studies were conducted in Europe using a quantitative methodology and were validated from the perspective of patients. Analysis methods differed considerably between the studies, and most ICF core sets were validated only once for a single target population or from a single perspective. The comprehensive core sets were validated more often than the brief core sets, and core sets for stroke and low back pain were validated most often. Conclusion: The results of the current study show that only 66% of the existing ICF core sets are validated. Many of the validation studies are conducted in a European context and from a single perspective. More validation studies of ICF core sets from the perspective of both patients and professionals are needed. Implications for rehabilitation ICF core sets aim to facilitate assessments in clinical settings and research. Validation studies indicate in general that the ICF core sets are valid and relevant for patients and professionals in the specific areas explored and thus can be used in rehabilitation settings. To improve the quality of ICF core sets, more validation studies are needed for ICF core sets not yet tested and for ICF core sets that have been validated only in one study or for one specific population or target group.
Synthesis and Antileishmanial Evaluation of Arylimidamide-Azole Hybrids Containing a Phenoxyalkyl Linker.

Due to the limitations of existing medications, there is a critical need for new drugs to treat visceral leishmaniasis. Since arylimidamides and antifungal azoles both show oral activity in murine visceral leishmaniasis models, a molecular hybridization approach was employed where arylimidamide and azole groups were separated by phenoxyalkyl linkers in an attempt to capitalize on the favorable antileishmanial properties of both series. Among the target compounds synthesized, a greater antileishmanial potency against intracellular Leishmania donovani was observed as the linker length increased from two to eight carbons and when an imidazole ring was employed as the terminal group compared to a 1,2,4-triazole group. Compound 24c (N-(4-((8-(1H-imidazol-1-yl)octyl)oxy)-2-isopropoxyphenyl) picolinimidamide) displayed activity against L. donovani intracellular amastigotes with an IC50 value of 0.53 μM. When tested in a murine visceral leishmaniasis model, compound 24c at a dose of 75 mg/kg/day p.o. for five consecutive days resulted in a modest 33% decrease in liver parasitemia compared to the control group, indicating that further optimization of these molecules is needed. While potent hybrid compounds bearing an imidazole terminal group were also strong inhibitors of recombinant CYP51 from L. donovani, as assessed by a fluorescence-based assay, additional targets are likely to play an important role in the antileishmanial action of these compounds.
Bayesian inference: The comprehensive approach to analyzing single-molecule experiments

Biophysics experiments performed at single-molecule resolution contain exceptional insight into the structural details and dynamic behavior of biological systems. However, extracting this information from the corresponding experimental data unequivocally requires applying a biophysical model. Here, we discuss how to use probability theory to apply these models to single-molecule data. Many current single-molecule data analysis methods apply parts of probability theory, sometimes unknowingly, and thus miss out on the full set of benefits provided by this self-consistent framework. The full application of probability theory involves a process called Bayesian inference that fully accounts for the uncertainties inherent to single-molecule experiments. Additionally, using Bayesian inference provides a scientifically rigorous manner to incorporate information from multiple experiments into a single analysis and to find the best biophysical model for an experiment without the risk of overfitting the data. These benefits make the Bayesian approach ideal for analyzing any type of single-molecule experiment.
Temporal Relationships between Pain, Mood and Urinary Symptoms in Urological Chronic Pelvic Pain Syndrome: A MAPP Network Study

Purpose: We sought to determine the time-lagged, bidirectional relationships among clinical variables of pelvic pain, urinary symptoms, negative mood, nonpelvic pain and quality of life in men and women with urological chronic pelvic pain syndrome, incorporating interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. Materials and Methods: A total of 204 female and 166 male patients were assessed up to 24 times over a 48-week period on the 5 primary outcomes. A lagged autoregressive analysis was applied to determine the directional relationship of one variable to another 2 weeks later, beyond that of the concurrent relationships at each time point and autocorrelations and trends over time. Results: The results show clear evidence for a bidirectional positive relationship between changes in pelvic pain severity and urinary symptom severity. Increases in either variable predicted significant increases in the other 2 weeks later, beyond that explained by their concurrent relationship at each time point. Pelvic pain and to a lesser degree urinary frequency also showed similar bidirectional relationships with negative mood and decreased quality of life. Interestingly, neither pelvic pain or urinary symptom severity showed lagged relationships with nonpelvic pain severity. Conclusions: Results document for the first time specific short-term positive feedback between pelvic pain and urinary symptoms, and between symptoms of urological chronic pelvic pain syndrome, mood and quality of life. The feedforward aspects of these relationships can facilitate a downward spiral of increased symptoms and worsening psychosocial function, and suggest the need for multifaceted treatments and assessment to address this possibility in individual patients.
Relative tidal volume and respiratory airflow estimation using tracheal sound and movement during sleep

Airflow is the reference signal to assess sleep respiratory disorders, such as sleep apnea. Previous studies estimated airflow using tracheal sounds in short segments with specific airflow rates, while requiring calibration or a few breaths for tuning the relationship between sound energy and airflow. Airflow−sound relationship can change by posture, sleep stage and airflow rate or tidal volume. We investigated the possibility of estimating surrogates of tidal volume without calibration in the adult sleep apnea population using tracheal sounds and movements. Two surrogates of tidal volume: thoracoabdominal range of sum movement and airflow level were estimated. Linear regression was used to estimate thoracoabdominal range of sum movement from sound energy and the range of movements. The sound energy lower envelope was found to correlate with airflow level. The agreement between reference and estimated signals was assessed by repeated‐measure correlation analysis. The estimated tidal volumes were used to estimate the airflow signal. Sixty‐one participants (30 females, age: 51 ± 16 years, body mass index: 29.5 ± 6.4 kg m−2, and apnoea−hypopnea index: 20.2 ± 21.2) were included. Reference and estimated thoracoabdominal range of sum movement of whole night data were significantly correlated with the reference signal extracted from polysomnography (r = 0.5 ± 0.06). Similarly, significant correlations (r = 0.3 ± 0.05) were found for airflow level. Significant differences in estimated surrogates of tidal volume were found between normal breathing and apnea/hypopnea. Surrogate of airflow can be extracted from tracheal sounds and movements, which can be used for assessing the severity of sleep apnea and even phenotyping sleep apnea patients based on the estimated airflow shape.
Does the bowfin gas bladder represent an intermediate stage during the lung‐to‐gas bladder evolutionary transition?

Whether phenotypic evolution occurs gradually through time has prompted the search for intermediate forms between the ancestral and derived states of morphological features, especially when there appears to be a discontinuous origin. The gas bladder, a derived character of the Actinopteri, is a modification of lungs, which characterize the common ancestor of bony vertebrates. While gas bladders and lungs are similar in many ways, the key morphological difference between these organs is the direction of budding from the foregut during development; essentially, the gas bladder buds dorsally and the lungs bud ventrally from the foregut. Did the shift from ventral lungs to dorsal gas bladder transition through a lateral‐budding stage? To answer this question, the precise location of budding during gas bladder development in bowfin, representing the sister lineage to teleosts, has been debated. In the early 20th‐century, it was suggested that the bowfin gas bladder buds laterally from the right wall of the foregut. We used nano‐CT scanning to visualize the early development of the bowfin gas bladder to verify the historical studies of gas bladder developmental morphology and determine whether the direction of gas bladder budding in bowfin could be intermediate between ventrally budding lungs and dorsally budding gas bladders. We found that the bowfin gas bladder buds dorsally from the anterior foregut; however, during early development, the posterior gas bladder twists right. As development progresses, the posterior, right‐hand twist becomes shallower, and the gas bladder itself shifts toward a mid‐dorsal position. The budding site is definitively dorsal, despite the temporary lateral twist of the posterior gas bladder.
Pancreastatin Reduces Alternatively Activated Macrophages, Disrupts the Epithelial Homeostasis and Aggravates Colonic Inflammation. A Descriptive Analysis

Ulcerative colitis (UC) is characterized by modifying alternatively activated macrophages (AAM) and epithelial homeostasis. Chromogranin-A (CHGA), released by enterochromaffin cells, is elevated in UC and is implicated in inflammation progression. CHGA can be cleaved into several derived peptides, including pancreastatin (PST), which is involved in proinflammatory mechanisms. Previously, we showed that the deletion of Chga decreased the onset and severity of colitis correlated with an increase in AAM and epithelial cells’ functions. Here, we investigated PST activity in colonic biopsies of participants with active UC and investigated PST treatment in dextran sulfate sodium (DSS)-induced colitis using Chga−/− mice, macrophages, and a human colonic epithelial cells line. We found that the colonic protein expression of PST correlated negatively with mRNA expression of AAM markers and tight junction (TJ) proteins and positively with mRNA expression of interleukin (IL)-8, IL18, and collagen in human. In a preclinical setting, intra-rectal administration of PST aggravated DSS-induced colitis by decreasing AAM’s functions, enhancing colonic collagen deposition and disrupting epithelial homeostasis in Chga+/+ and Chga−/− mice. This effect was associated with a significant reduction in AAM markers, increased colonic IL-18 release, and decreased TJ proteins’ gene expression. In vitro, PST reduced Chga+/+ and Chga−/− AAM polarization and decreased anti-inflammatory mediators’ production. Conditioned medium harvested from PST-treated Chga+/+ and Chga−/− AAM reduced Caco-2 cell migration, viability, proliferation, and mRNA levels of TJ proteins and increased oxidative stress-induced apoptosis and proinflammatory cytokines release. In conclusion, PST is a CHGA proinflammatory peptide that enhances the severity of colitis and the inflammatory process via decreasing AAM functions and disrupting epithelial homeostasis.
Artificial Intelligence: the "Trait D'Union" in Different Analysis Approaches of Autism Spectrum Disorder Studies.

Autistic Spectrum Disorder (ASD) is a neurodevelopmental condition affecting approximately 1 out of 70 (range 1:59 - 1:89) children worldwide. It is characterized by a delay in cognitive capabilities, repetitive and restricted behaviors and deficit in communication and social interaction. Several factors seem to be associated with ASD development; its heterogeneous nature makes the diagnosis difficult and slow since it is essentially based on screening tools focused on stereotypical and repetitive behaviors, gait, facial emotion expression and speech assessments. Recently, artificial intelligence (AI) has been widely used to investigate ASD with the overall goal of simplifying and speeding up the diagnostic process as well as making earlier access to therapies possible. The aim of this review is to provide an overview of the state-of-the-art research in the ASD field identifying and describing machine learning (ML) approaches in ASD literature that could be used by clinicians to improve diagnostic capability and treatment efficiency. A systematic search was conducted and the resulting articles were subdivided into several categories reflecting the different fields of study associated with ASD research. The existing literature has widely demonstrated the potential of ML in several types of ASD study analyses: behavior, gait, speech, facial emotion expression, neuroimaging, genetics, and metabolomics. Therefore, AI techniques are becoming increasingly implemented and accepted, so highlighting the power of ML approaches to extract and obtain knowledge from a large volume of data. This makes ML a promising tool for future ASD research and clinical endeavors suggesting possible avenues for improving ASD screening, diagnostic and therapeutic tools.
Contaminant Transport in Nonisothermal Fractured Porous Media

Alternative formulations of the analytical modeling for contaminant transport in nonisothermal fractured porous media are presented. Transient and steady heat flows are coupled with solute transport, either implicitly as natural convection incorporating the effect of thermal flux on the variation of concentration gradients, or explicitly as a Soret effect, where the divergence of the thermal flux acts as an additional source term affecting the change of solute concentration. The effect of solid deformation due to temperature changes and subsequent impact on the variation of solute concentrations are identified. The proposition of using function transformation within Laplace space may be of significance for numerical implementation in solving advection-dispersion equations. Two different dual-porosity conceptualizations of fractured porous media are proposed based on alternative assumptions of matrix flow. The concept of matrix replenishment in relation to the traditional matrix diffusion is presented, which may have practical significance in the evaluation of contaminant transport in fractured porous media. The solutions are applicable for modeling the process using thermal sweeping to remediate contaminated areas.
Factor XIII-A in Diseases: Role Beyond Blood Coagulation

Multidisciplinary research from the last few decades has revealed that Factor XIII subunit A (FXIII-A) is not only involved in blood coagulation, but may have roles in various diseases. Here, we aim to summarize data from studies involving patients with mutations in the F13A1 gene, performed in FXIII-A knock-out mice models, clinical and histological studies assessing correlations between diseases severity and FXIII-A levels, as well as from in vitro experiments. By providing a complex overview on its possible role in wound healing, chronic inflammatory bowel diseases, athe-rosclerosis, rheumatoid arthritis, chronic inflammatory lung diseases, chronic rhinosinusitis, solid tumors, hematological malignancies, and obesity, we also demonstrate how the field evolved from using FXIII-A as a marker to accept and understand its active role in inflammatory and malignant diseases.
A Qualitative Analysis of Concussion-Reporting Behavior in Collegiate Student-Athletes With a History of Sport-Related Concussion.

CONTEXT Many survey-based methods have been used to explore concussion-reporting behavior. However, because the decision to report or conceal a concussion is likely multifactorial, this may narrow the findings, as the surveys were largely designed by the researchers. OBJECTIVE To explore student-athletes' perspectives regarding factors that may influence the reporting of sport-related concussion. DESIGN Qualitative study. SETTING National Collegiate Athletic Association Division I athletics. PATIENTS OR OTHER PARTICIPANTS We conducted 17 semistructured interviews with student-athletes who had sustained 1 or more concussions while attending a large university (men = 4, women = 13, age = 20.9 ± 1.3 years). DATA COLLECTION AND ANALYSIS After data saturation and member checks, a 5-cycle analytic process was completed: topical review, literature review, data collection and summarizing using a codebook developed by a 3-person research team, linking of findings to current research, and final interpretations. RESULTS We discovered 3 themes. Participants discussed concussion perceptions by describing their understanding of a concussion, their own injury experiences, and their perceptions of symptom severity and duration. Regarding reporting behavior, participants described an order of individuals with whom they would speak, symptoms present in order to report (eg, feeling different from normal), immediate reactions, and influential factors for mitigating short- and long-term consequences. Lastly, participants discussed the value of support systems, such as how coaches can both positively and negatively influence reporting and athletic trainer involvement. CONCLUSIONS Participants often drew from their own concussion experiences in naming common concussion signs and symptoms. Additionally, they indicated that both short- and long-term health consequences influenced and deterred their seeking care and that their support systems, including coaches and athletic trainers, played a role in their concussion experience. Research is needed to determine if using student-athletes' own words to describe a concussion and incorporating student-athletes' support systems, especially coaches and athletic trainers, is effective in increasing concussion reporting.
Cuparene‐Derived Sesquiterpenes from the Chinese Red Alga Laurencia okamurai Yamada

Four new cuparene-derived sesquiterpenes, laureperoxide (1), 10-bromoisoaplysin (2), isodebromolaurinterol (3), and 10-hydroxyisolaurene (4), together with seven known, related sesquiterpenes, 5–11, have been isolated from the red alga Laurencia okamurai. Their structures were determined on the basis of detailed spectroscopic analyses and comparison with known compounds. Compounds 8–11 were shown for the first time to represent true natural products, and the full 1H- and 13C-NMR assignments of 5 are reported for the first time.