Miracle-dz/UniFAR-FTUs huggingface dataset:
Endothelial-Derived Extracellular Vesicles Induce Cerebrovascular Dysfunction in Inflammation

Blood–brain barrier (BBB) dysfunction is a key hallmark in the pathology of many neuroinflammatory disorders. Extracellular vesicles (EVs) are lipid membrane-enclosed carriers of molecular cargo that are involved in cell-to-cell communication. Circulating endothelial EVs are increased in the plasma of patients with neurological disorders, and immune cell-derived EVs are known to modulate cerebrovascular functions. However, little is known about whether brain endothelial cell (BEC)-derived EVs themselves contribute to BBB dysfunction. Human cerebral microvascular cells (hCMEC/D3) were treated with TNFα and IFNy, and the EVs were isolated and characterised. The effect of EVs on BBB transendothelial resistance (TEER) and leukocyte adhesion in hCMEC/D3 cells was measured by electric substrate cell-substrate impedance sensing and the flow-based T-cell adhesion assay. EV-induced molecular changes in recipient hCMEC/D3 cells were analysed by RT-qPCR and Western blotting. A stimulation of naïve hCMEC/D3 cells with small EVs (sEVs) reduced the TEER and increased the shear-resistant T-cell adhesion. The levels of microRNA-155, VCAM1 and ICAM1 were increased in sEV-treated hCMEC/D3 cells. Blocking the expression of VCAM1, but not of ICAM1, prevented sEV-mediated T-cell adhesion to brain endothelia. These results suggest that sEVs derived from inflamed BECs promote cerebrovascular dysfunction. These findings may provide new insights into the mechanisms involving neuroinflammatory disorders.
Prevalence of Musculoskeletal Disorder and its Relation to Stress Among Medical Student at Taif University, Saudi Arabia

Background: The purpose of this research is to determine the prevalence of musculoskeletal disorders and their association with psychological stress among medical students at Taif University, Saudi Arabia. Methods: A total of 640 medical students were selected by multistage cluster sampling. The data were collected by trained students using a standardized Nordic questionnaire and 10-k questionnaire. Statistical analysis was carried out using the statistical package (SPSS.21). Standardized Nordic questionnaire and 10-k questionnaire besides questionnaire assessing sociodemographic characteristics (age, gender, study year, weight, height, smoking, marital status, chronic disease, and educational degree) were used. Results: Among 640 medical students, 45.9% males and 54.1% females reported musculoskeletal pain, it was more prevalent among fourth - and sixth year students, in the last 7 days, neck pain was the highest site of complaint (33.4%) followed by low back pain (15.1%) and shoulder pain (12.8%). Prevention of work was highest due to neck pain (27.7%) and low back (25.1%) followed by knees (19.1%), the stress rate was highest in the second year (67.8%) and third year (67.3%) students followed by the sixth year (65.8%) students. Conclusions: Musculoskeletal disorders are a common health problem reported by more than half of medical students, with a significant association with females and preclinical students. Stress is a common psychological problem that affects two-thirds of medical students. However, we found a nonsignificant association between the onset of musculoskeletal disorders and the level of stress among medical students.
On the Common Journey of Neural Cells through Ischemic Brain Injury and Alzheimer’s Disease

Ischemic brain injury and Alzheimer’s disease (AD) both lead to cell death in the central nervous system (CNS) and thus negatively affect particularly the elderly population. Due to the lack of a definitive cure for brain ischemia and AD, it is advisable to carefully study, compare, and contrast the mechanisms that trigger, and are involved in, both neuropathologies. A deeper understanding of these mechanisms may help ameliorate, or even prevent, the destructive effects of neurodegenerative disorders. In this review, we deal with ischemic damage and AD, with the main emphasis on the common properties of these CNS disorders. Importantly, we discuss the Wnt signaling pathway as a significant factor in the cell fate determination and cell survival in the diseased adult CNS. Finally, we summarize the interesting findings that may improve or complement the current sparse and insufficient treatments for brain ischemia and AD, and we delineate prospective directions in regenerative medicine.
Immunosuppressant-Responsive Enteropathy and Non-Responsive Enteropathy in Dogs: Prognostic Factors, Short- and Long-Term Follow Up

Simple Summary Chronic intestinal inflammation in dogs is a challenging disease to manage. Most studies about prognostic factors and follow-up data are only available for small populations or with short-term follow-up. The aim of this study of 165 dogs with chronic intestinal inflammation was to identify clinical and haematological factors associated with mortality, clinical response and relapse, with long-term follow-up. Nine per cent of dogs did not respond to therapy at 1 month follow-up. Most dogs with chronic intestinal inflammation had a good clinical course in most cases, and the non-response or relapse rate was 9–11%. A reduction of body condition (loss of weight), lower serum albumin concentration and presence of lacteal dilatation on intestinal histology at diagnosis were identified as factors associated with a decreased response rate, higher mortality and lower chance of achieving long-term remission. Abstract A multicentre prospective study was performed to assess whether clinical, hematobiochemical, endoscopic and histopathological parameters were associated with mortality, clinical response and relapse of disease in short- and long-term follow-up of a total of 165 dogs with chronic inflammatory enteropathy, of which 150 had immunosuppressant responsive enteropathy (IRE), and 15 had non-responsive enteropathy (NRE) dogs. Clinical severity (CCECAI) was evaluated from presentation (T0) to 18 months (T18) from diagnosis. T0 body condition score (BCS), selected haematological parameters and endoscopic and histopathological scores were evaluated. Presence/absence of histopathological duodenal lesions was recorded. Responders were evaluated using CCECAI at T1. Relapse was evaluated from T3 to T18. Long-term responders included dogs who responded at T1 and showed no relapse. Dogs were divided into responders/non-responders, survivors/non-survivors and relapsed/non-relapsed. At T1, 15/165 dogs (9%) were considered NRE. Sixteen dogs (11%) were considered relapsed at T3, 8% at T6 and 10% at T12, and none of 96 dogs relapsed at T18. NREs showed significantly lower BCS than IREs. Non-survivors showed a significantly lower serum albumin concentration and BCS than survivors. Non-responders, relapsed or non-survivors had higher presence of lacteal dilatation compared to long-term responders. Dogs with IRE showed a good clinical course with a low relapse rate, with only a few dogs in the NRE group. Reduction of BCS, albumin and lacteal dilatation at diagnosis may be considered negative prognostic factors for response, mortality and long-term disease remission.
Systematic Review and Meta-Analysis on the Effects of Astaxanthin on Human Skin Ageing

Context: Astaxanthin (ASX), a xanthophyll carotenoid derived from microalgae Haematococcus pluvialis, mitigating skin photoaging and age-related skin diseases by its antioxidant and anti-inflammatory effects in animal studies. Objective: The aim was to systematically evaluate if ASX applications have anti-ageing effects in humans. Methods: A comprehensive search of PubMed, Scopus and Web of Science found a total of eleven studies. Nine randomised, controlled human studies assessed oral ASX effects and two open-label, prospective studies evaluated topical, oral-topical ASX effects on skin ageing. GetData Graph Digitizer was used to extract mean values and standard deviations of baseline and endpoint, and Cochrane Collaboration’s tool assessed RoB for all included studies. Review Manager 5.4 was used to conduct meta-analysis of RCTs; the results were reported as effect size ± 95% confidence interval. Results: Oral ASX supplementation significantly restored moisture content (SMD = 0.53; 95% CI = 0.05, 1.01; I2 = 52%; p = 0.03) and improved elasticity (SMD = 0.77; 95% CI = 0.19, 1.35; I2 = 75%; p = 0.009) but did not significantly decrease wrinkle depth (SMD = −0.26; 95% CI = −0.58, 0.06; I2 = 0%; p = 0.11) compared to placebo. Open-label, prospective studies suggested slightly protective effects of topical and oral-topical ASX applications on skin ageing. Conclusions: Ingestion and/or topical usages of ASX may be effective in reducing skin ageing and have promising cosmetical potential, as it improves moisture content and elasticity and reduces wrinkles.
Use of Multiple Low Cost Carbon Dioxide Sensors to Measure Exhaled Breath Distribution with Face Mask Type and Wearing Behaviour

The use of cloth face coverings and face masks has become widespread in light of the COVID-19 pandemic. This paper presents a method of using low cost wirelessly connected carbon dioxide (CO2) sensors to measure the effects of properly and improperly worn face masks on the concentration distribution of exhaled breath around the face. Four types of face masks are used in two indoor environment scenarios. CO2 as a proxy for exhaled breath is being measured with the Sensirion SCD30 CO2 sensor, and data are being transferred wirelessly to a base station. The exhaled CO2 is measured in four directions at various distances from the head of the subject, and interpolated to create spatial heat maps of CO2 concentration. Statistical analysis using the Friedman’s analysis of variance (ANOVA) test is carried out to determine the validity of the null hypotheses (i.e., distribution of the CO2 is same) between different experiment conditions. Results suggest CO2 concentrations vary little with the type of mask used; however, improper use of the face mask results in statistically different CO2 spatial distribution of concentration. The use of low cost sensors with a visual interpolation tool could provide an effective method of demonstrating the importance of proper mask wearing to the public.
New Molecular Targets for Antidepressant Drugs

Major depressive disorder (MDD) is a common and severe mental disorder that is usually recurrent and has a high risk of suicide. This disorder manifests not only with psychological symptoms but also multiple changes throughout the body, including increased risks of obesity, diabetes, and cardiovascular disease. Peripheral markers of oxidative stress and inflammation are elevated. MDD is therefore best described as a multisystem whole-body disease. Pharmacological treatment with antidepressants usually requires several weeks before the desired effects manifest. Previous theories of depression, such as the monoamine or neurogenesis hypotheses, do not explain these characteristics well. In recent years, new mechanisms of action have been discovered for long-standing antidepressants that also shed new light on depression, including the sphingolipid system and the receptor for brain-derived neurotrophic factor (BDNF).
Efficacy and safety of chemotherapy combined with bevacizumab in Chinese patients with metastatic colorectal cancer: A prospective, multicenter, observational, non-interventional phase IV trial

Objective Bevacizumab has an important and evolving role in improving outcomes in patients with metastatic colorectal cancer (mCRC) worldwide and was approved in China in 2010. However, there are limited real-world data on the efficacy and safety of chemotherapy regimens combined with bevacizumab in Chinese patients with mCRC. This observational, phase IV trial study aimed to obtain more experience on the efficacy and safety of bevacizumab combined with chemotherapy in Chinese mCRC patients. Methods Between September 2013 and November 2016, patients with histologically confirmed mCRC were enrolled in a prospective, multicenter, observational, non-interventional phase IV trial at 26 centers across China. Eligible patients received different chemotherapeutic regimens combined with bevacizumab. The efficacy and safety data in the intention-to-treat study population were analyzed. Results A total of 611 patients were included in the efficacy analysis. The median overall survival and median progression-free survival was 18.00 and 10.05 months, respectively. The objective response rate was 21.00% and disease control rate was 89.40%. In subgroup analyses, the survival differences were observed according to metastatic status, duration of treatment and elevation in blood pressure. A total of 613 patients were evaluable for safety assessments. And 569 (92.82%) patients reported at least one adverse event (AE), and 151 (24.63%) experienced grade 3 or higher AEs. The incidence of bevacizumab-associated AEs of special interest was reported in 31 (5.06%) patients with hypertension (n=12), abscesses and fistulae (n=7), bleeding (n=6), proteinuria (n=3), gastrointestinal perforation (n=2) and venous thrombotic events (n=1). Conclusions This observational phase IV trial broadens our experience and knowledge of bevacizumab in the Chinese population and provides a good indication of its overall efficacy and safety. Bevacizumab in combination with chemotherapy offers clinical benefits to Chinese patients with mCRC and has an acceptable and manageable safety profile.
Comprehensive Insight into Chemical Stability of Important Antidiabetic Drug Vildagliptin Using Chromatography (LC-UV and UHPLC-DAD-MS) and Spectroscopy (Mid-IR and NIR with PCA)

During forced degradation, the intrinsic stability of active pharmaceutical ingredients (APIs) could be determined and possible impurities that would occur during the shelf life of the drug substance or the drug product could be estimated. Vildagliptin belongs to relatively new oral antidiabetic drugs named gliptins, inhibiting dipeptidyl peptidase 4 (DPP-4) and prolonging the activities of the endogenous incretin hormones. At the same time, some gliptins were shown as prone to degradation under specific pH and temperature conditions, as well as in the presence of some reactive excipients. Thus, forced degradation of vildagliptin was performed at high temperature in extreme pH and oxidative conditions. Then, selective LC-UV was used for quantitative determination of non-degraded vildagliptin in the presence of its degradation products and for degradation kinetics. Finally, identification of degradation products of vildagliptin was performed using an UHPLC-DAD-MS with positive ESI. Stability of vildagliptin was also examined in the presence of pharmaceutical excipients, using mid-IR and NIR with principal component analysis (PCA). At 70 °C almost complete disintegration of vildagliptin occurred in acidic, basic, and oxidative media. What is more, high degradation of vildagliptin following the pseudo first-order kinetics was observed at room temperature with calculated k values 4.76 × 10−4 s−1, 3.11 × 10−4 s−1, and 1.73 × 10−4 s−1 for oxidative, basic and acidic conditions, respectively. Next, new degradation products of vildagliptin were detected using UHPLC-DAD-MS and their molecular structures were proposed. Three degradants were formed under basic and acidic conditions, and were identified as [(3-hydroxytricyclo- [3.3.1.13,7]decan-1-yl)amino]acetic acid, 1-{[(3-hydroxytricyclo[3.3.1.13,7]decan-1-yl)amino]acetyl}-pyrrolidine-2-carboxylic acid and its O-methyl ester. The fourth degradant was formed in basic, acidic, and oxidative conditions, and was identified as 1-{[(3-hydroxytricyclo[3.3.1.13,7]-decan-1-yl)amino]acetyl}pyrrolidine-2-carboxamide. When stability of vildagliptin was examined in the presence of four excipients under high temperature and humidity, a visible impact of lactose, mannitol, magnesium stearate, and polyvinylpirrolidone was observed, affecting-NH- and CO groups of the drug. The obtained results (kinetic parameters, interactions with excipients) may serve pharmaceutical industry to prevent chemical changes in final pharmaceutical products containing vildagliptin. Other results (e.g., identification of new degradation products) may serve as a starting point for qualifying new degradants of vildagliptin as it is related to substances in pharmacopoeias.
The Input of Structural Vaccinology in the Search for Vaccines against Bunyaviruses

A significant increase in the number of viruses causing unexpected illnesses and epidemics among humans, wildlife and livestock has been observed in recent years. These new or re-emerging viruses have often caught the scientific community off-guard, without sufficient knowledge to combat them, as shown by the current coronavirus pandemic. The bunyaviruses, together with the flaviviruses and filoviruses, are the major etiological agents of viral hemorrhagic fever, and several of them have been listed as priority pathogens by the World Health Organization for which insufficient countermeasures exist. Based on new techniques allowing rapid analysis of the repertoire of protective antibodies induced during infection, combined with atomic-level structural information on viral surface proteins, structural vaccinology is now instrumental in the combat against newly emerging threats, as it allows rapid rational design of novel vaccine antigens. Here, we discuss the contribution of structural vaccinology and the current challenges that remain in the search for an efficient vaccine against some of the deadliest bunyaviruses.
Doxycycline in the Coronavirus Disease 2019 Therapy

Abstract Acute respiratory syndrome, associated with coronavirus 2 (SARS-CoV-2), is the most important medical and epidemic problem of today. The biggest challenge is to find an effective treatment and to reduce the need for hospitalisation. In the article, the patients with mild to moderate coronavirus disease 2019 (COVID-19) treated with doxycycline with significant improvement have been discussed. Doxycycline is a known antibiotic, but also an anti-inflammatory and immunomodulatory drug, so it seems to be ideal for the treatment of COVID-19. Doxycycline, as an easily available and low-cost medication, should be considered as a COVID-19 therapy in all patients in the first days of the symptoms of a SARS-CoV-2 infection. Due to its immunomodulatory, anti-inflammatory, cardioprotective and antiviral effects, it seems to be an ideal drug for patients with mild, moderate and severe disease. A large multicentre study is needed to evaluate the effects of this medication.
Where Is Ethology Heading? An Invitation for Collective Metadisciplinary Discussion

Simple Summary I analyzed the current state of Ethology (i.e., the study of animal behavior and cognition) from the researchers’ perspective through an online questionnaire that was responded to by almost a hundred participants. Despite that the number of the respondents was small, it is interesting to highlight some of the results, since they align with some published analyses. First, not many basic concepts of the discipline, nor its denomination, reached homogeneous consensus. This is alarming because researchers need common vocabulary to communicate effectively between them. Second, despite the enormous biodiversity existent, the researchers seem to be biased towards studying primates, our own family species. Also, the apparatuses employed in the studies are not always adapted to the species’ specific characteristics, so our conclusions about their behavior or cognition might be biased. Fortunately, the technology needed to conduct further studies already exists. However, there is not enough funding or collaboration with engineers to make it real. Establishing big scale networking, adopting some research principles such as transparency, and broadening gender and ethnic diversity in research teams may help in adopting new endeavors. Abstract Many factors can impact the advancement of scientific disciplines. In the study of animal behavior and cognition (i.e., Ethology), a lack of consensus about definitions or the emergence of some current events and inventions, among other aspects, may challenge the discipline’s grounds within the next decades. A collective metadisciplinary discussion may help in envisioning the future to come. For that purpose, I elaborated an online questionnaire about the level of consensus and the researchers’ ways of doing in seven areas: Discipline name and concepts, species, Umwelt, technology, data, networking, and the impact of sociocultural and ecological factors. I recruited the opinion of almost a hundred of colleagues worldwide (N = 98), both junior and seniors, working both in the wild and in the lab. While the results were pitted against the literature, general conclusions should be taken with caution and considered as a first attempt in exploring the state of the discipline from the researchers’ perspective: There is no unanimity for the discipline’s name; 71.4% of the researchers reported there is limited consensus in the definition of relevant concepts (i.e., culture, cognition); primate species still predominate in publications whereas the species selection criteria is sometimes based on fascination, chance, or funding opportunities rather than on biocentric questions; 56.1% of the apparatuses employed do not resemble species’ ecological problems, and current tech needs would be solved by fostering collaboration with engineers. Finally, embracing the Open Science paradigm, supporting networking efforts, and promoting diversity in research teams may help in gathering further knowledge in the area. Some suggestions are proposed to overcome the aforementioned problems in this contemporary analysis of our discipline.
A Structural Perspective of the Role of IP6 in Immature and Mature Retroviral Assembly

The small cellular molecule inositol hexakisphosphate (IP6) has been known for ~20 years to promote the in vitro assembly of HIV-1 into immature virus-like particles. However, the molecular details underlying this effect have been determined only recently, with the identification of the IP6 binding site in the immature Gag lattice. IP6 also promotes formation of the mature capsid protein (CA) lattice via a second IP6 binding site, and enhances core stability, creating a favorable environment for reverse transcription. IP6 also enhances assembly of other retroviruses, from both the Lentivirus and the Alpharetrovirus genera. These findings suggest that IP6 may have a conserved function throughout the family Retroviridae. Here, we discuss the different steps in the viral life cycle that are influenced by IP6, and describe in detail how IP6 interacts with the immature and mature lattices of different retroviruses.