Miracle-dz/UniFAR-FTUs huggingface dataset:
All-trans-retinoic acid generation is an antidotal clearance pathway for all-trans-retinal in the retina

The present study was designed to analyze the metabolites of all-frans-retinal (atRal) and compare the cytotoxicity of atRal versus its derivative all-frans-retinoic acid (atRA) in human retinal pigment epithelial (RPE) cells. We confirmed that atRA was produced in normal pig neural retina and RPE. The amount of all-trans-retinol (atROL) converted from atRal was about 2.7 times that of atRal-derived atRA after incubating RPE cells with 10 µmol/L atRal for 24 h, whereas atRA in medium supernatant is more plentiful (91 vs. 29 pmol/mL), suggesting that atRA conversion facilitates elimination of excess atRal in the retina. Moreover, we found that mRNA expression of retinoic acid-specific hydroxylase CYP26b1 was dose-dependently up-regulated by atRal exposure in RPE cells, indicating that atRA inactivation may be also initiated in atRal-accumulated RPE cells. Our data show that atRA-caused viability inhibition was evidently reduced compared with the equal concentration of its precursor atRal. Excess accumulation of atRal provoked intracellular reactive oxygen species (ROS) overproduction, heme oxygenase-1 (HO-1) expression, and increased cleaved poly(ADP-ribose) polymerase 1 (PARP1) expression in RPE cells. In contrast, comparable dosage of atRA-induced oxidative stress was much weaker, and it could not activate apoptosis in RPE cells. These results suggest that atRA generation is an antidotal metabolism pathway for atRal in the retina. Moreover, we found that in the eyes of ABCA4−/−RDH8−/− mice, a mouse model with atRal accumulation in the retina, the atRA content was almost the same as that in the wild type. It is possible that atRal accumulation simultaneously and equally promotes atRA synthesis and clearance in eyes of ABCA4−/−RDH8−/− mice, thus inhibiting the further increase of atRA in the retina. Our present study provides further insights into atRal clearance in the retina.
Reconstruction of hand, elbow and shoulder actual and imagined trajectories in 3D space using EEG slow cortical potentials

Objective. The ability to decode kinematics of imagined movement from neural activity is essential for the development of prosthetic devices that can aid motor-disabled persons. To date, non-invasive recording methods, including electroencephalogram (EEG) were used to decode actual and imagined hand trajectory to control neuromotor prostheses, commonly by applying multi-dimensional linear regression (mLR) models to adjust the two temporal signals—neural signal and limb kinematics. It is still debated, however, whether the EEG signal, in general, and slow cortical potentials (SCPs), in specific, hold motor neural correlates. Moreover, it has not yet been tested whether the trajectory of proximal arm joints, i.e. shoulder, can also be reconstructed and if decoding performance is dependent on movement speed and/or position variance. Approach. We predicted hand, elbow and shoulder trajectories in 3D space in time series of both movement types (actual and imagined) of seven subjects using an mLR model, commonly applied for motion trajectory prediction (MTP) and used source localization to detect and compare between brain areas activated during actual and imagined movements for each arm joint. Main results. For all arm joints and movement types, SCPs contributed the most to trajectory reconstruction, and decoding accuracy peaked using neural signals preceding kinematics by 120–210 ms. The average (across subjects) Pearson’s correlation coefficient between predicted and actual trajectories ranged 0.24–0.49, 0.41–0.48 and 0.18–0.40 for the hand, elbow and shoulder, respectively, and was significantly higher than chance level (p < 0.01) for all subjects. For the imagined movements, reconstruction accuracy ranged between 0.09–0.23, 0.20–0.27 and 0.11–0.18 for the hand, elbow and shoulder, respectively, and was significantly higher than chance level (p < 0.05) for all or some of the arm joints. The model performance was positively correlated with movement speed and negatively correlated with position variance. Source localization suggested that the neural circuits engaged in motor imagery are more diffuse and bilateral; motor imagery was, when compared to movement execution, more associated with recruiting premotor regions and a large area of the left parietal cortex. Significance. Our results demonstrate the feasibility of predicting 3D imagined trajectories of all arm joints from scalp EEG and imply the existence of movement related neural correlates in slow cortical potentials.
PREVALENCE AND PARASITE COMPOSITION OF GASTROINTESTINAL PARASITES IN THE ENDANGERED TIBETAN ANTELOPE (PANTHOLOPS HODGSONII) FROM THE CALVING GROUND OF HOH XIL NATURE WORLD HERITAGE SITE, QINGHAI, CHINA

Abstract: Our objective was to provide baseline information on the gastrointestinal parasites of the female Tibetan antelope (Pantholops hodgsonii) on its calving ground at the Zhuonai Lake region, in the Hoh Xil Nature World Heritage site, Qinghai, China. On 3 July 2018, 238 freshly deposited fecal samples were collected from the calving grounds and analyzed by flotation technique to recover eggs, oocysts, and nematode larvae. All fecal samples demonstrated the presence of gastrointestinal parasites: 93% (221/238) had nematodes, 36% (86/238) had cestodes, and 99% (235/238) had coccidian oocysts. For each Tibetan antelope, mean (SD) parasite species richness was 3.4 (1.3). Coinfections with five parasite genera were found in 19% (45/238) of fecal samples. These results showed that prevalence of Trichostrongylus, Marshallagia, and Eimeria infections in these Tibetan antelopes were sufficiently high to suggest long-term monitoring be implemented because the climate there is becoming warmer and moisture is increasing, both presumably due to the influence of global warming which, in turn, may be contributing to increased infection risks with these parasites.
Germ cell cysts, a fetal feature in mammals, are constitutively present in the adult armadillo

Formation and subsequent break down of ovarian germ cell (GC) cysts is a key and an evolutionary‐conserved developmental event, described in phylogenetically diverse species of invertebrates and vertebrates. In mammals, cyst break down (CBD) ends at the time of, or soon after, birth with the formation of primordial follicles enclosing single oocytes, which constitute the sole reservoir of gametes available through the whole female's reproductive life. In this study, we challenge this paradigm demonstrating the constitutive presence of a large number of cysts, enclosing two‐thirty GCs, in the ovary of the adult armadillo Chaetophractus villosus, belonging to the superorder Xenarthra, one of the earliest offshoots among placentals. We also describe that (a) GCs enclosed within cysts are connected by intercellular bridges—intercellular bridges—markers of their clonal origin; (b) CBD occurs through four main phases, ending with primordial follicles containing single oocytes; (c) GCs encompass meiotic prophase I stages, from leptotene to diplotene; (d) seasonal variations in the number of GCs enclosed within cysts, suggesting the presence of a GC multiplying activity. The armadillo C. villosus''s ovary emerges as an extraordinary resource to investigate folliculogenesis and to explore the evolutionary past of the mammalian ovary.
Long-Term Efficacy and Toxicity of Cholinesterase Inhibitors in the Treatment of Alzheimer Disease

Though the symptoms of Alzheimer disease go on for years, the phase 3 trials of the cholinesterase inhibitors (ChEIs), the current mainstay of symptomatic pharmacotherapy for this condition, were typically of only 3- to 6-months' duration. We have limited data on long-term (that is, a year or more) therapy with these agents. In this review, we explore the available information on the biological and clinical effects of long-term ChEI therapy, what happens when these agents are discontinued, and examine what others have recommended. An individualized approach to deciding on whether to carry on with a ChEI should be taken. If continued, treatment goals should be clarified and patients monitored over time, for both drug-related benefits and adverse effects.
Isfahan Attitude of Citizens towards Local Radio

This study was conducted to assess the attitudes of listeners Center. This study was a descriptive - survey (cross). Of population, the Isfahan city had a population of 1/745/428 and using stratified sampling - random, 600 were selected345 people who listen to the radio programs of Isfahan and major review and assessment was based on the number of. For gather information from the questionnaire, which included demographic information and questions based on likert spectrum was used to test hypotheses.Cronbach's alpha was calculated for the questionnaire, 0.941 and reliability of the questionnaire was approved. In a radio program, the highest percentage of radio listeners, Province News (78.3%) and home and family was the most satisfying of the program (mean 4.05). Comparison test showed that the attitude of people towards educational guidance programs with an average of 3.59, Average educational information programs 3.41, Fun entertainment programs averaged 37/3And programs related to public officials, averaging 3.44, was above average. Educational guidance Friedman ranking test components, respectively (mean 2.93) between people and officials (mean 2.49), Educational data (mean 2.33) Is an
In vitro and in vivo biocompatibility study on acellular sheep periosteum for guided bone regeneration

This study addresses the fabrication of an extracellular matrix material of the acellular sheep periosteum and the systematic evaluation of its biocompatibility to explore its potential application in guided bone regeneration. Sheep periosteum was harvested and decellularized by a combined decellularization protocol. The effectiveness of cell removal was proved and residual α-Gal antigen was also quantitatively detected. Then, mouse MC3T3-E1 cells were seeded onto the acellular periosteum. A scanning electron microscope (SEM) was used to record the whole process of cell adhesion. The CCK-8 assay suggested that the acellular periosteum not only had zero toxic effect on pre-osteoblasts, but played a positive role in cell proliferation. We also tested whether the acellular periosteum possesses favorable osteogenesis induction activity using an alkaline phosphatase (ALP) assay and a quantitative real-time PCR (Col I, Runx2, OCN) assay. An in vivo study of a subcutaneous implantation test using Sprague Dawley (SD) rats was performed to detect the changes in IL-2, IFN-γ and IL-4 in serum and elucidate the host’s local response to acellular periosteum through hematoxylin and eosin (HE) and immunohistochemical staining. The results show that acellular sheep periosteum did not elicit a severe immunogenic response via the Th1 pathway, unlike fresh sheep periosteum. In conclusion, acellular sheep periosteum possesses favorable biocompatibility to be employed for guided bone regeneration.
The biology of pulmonary exacerbations in bronchiectasis

Bronchiectasis is a heterogeneous chronic disease. Heterogeneity characterises bronchiectasis not only in the stable state but also during exacerbations, despite evidence on clinical and biological aspects of bronchiectasis, exacerbations still remain poorly understood. Although the scientific community recognises that bacterial infection is a cornerstone in the development of bronchiectasis, there is a lack of data regarding other trigger factors for exacerbations. In addition, a huge amount of data suggest a primary role of neutrophils in the stable state and exacerbation of bronchiectasis, but the inflammatory reaction involves many other additional pathways. Cole's vicious cycle hypothesis illustrates how airway dysfunction, airway inflammation, infection and structural damage are linked. The introduction of the concept of a “vicious vortex” stresses the complexity of the relationships between the components of the cycle. In this model of disease, exacerbations work as a catalyst, accelerating the progression of disease. The roles of microbiology and inflammation need to be considered as closely linked and will need to be investigated in different ways to collect samples. Clinical and translational research is of paramount importance to achieve a better comprehension of the pathophysiology of bronchiectasis, microbiology and inflammation both in the stable state and during exacerbations. “The hardest thing of all is to find a black cat in a dark room, especially if there is no cat. ” There is a lack of knowledge about exacerbation of bronchiectasis. Future efforts are required to better define the biology of exacerbations. http://bit.ly/2XgjaHG
Frequency of Interaction between Advisors and Adult Learners during Mentoring and Academic Advising in Universities

The study intended to find out the frequency of interaction between Advisors/lecturers and adult learners. The objectives were to find out: the regularity of adult learners talking to an advisor, factors that contributed to the regularity of meeting and how readily they accessed advisors. The study was significance in that faculty members realized that frequent interaction with adult learners was more strongly related to satisfaction than any other type of involvement. The respondents included fourteen academic advisors and three hundred and twenty students sampled in one of Kenya’s public university. Stratified and systematic random sampling technique was used. Data were collected using questionnaires, interviews, focus group discussions and analyzed qualitatively and quantitatively. The study established that a high percentage of adult learners rarely talked to advisers and 167 (69.0%) considered availability of advisers as scarce and not available. The study recommended that university students should be allocated academic advisors.
The Lumbar Ligamentum Flavum Does Not Have Two Layers and Is Confluent with the Interspinous Ligament

We congratulate Iwanaga and colleagues (Iwanaga et al., 2019) including Ms. Yoshino on the recent publication of their descriptive report regarding the anatomy of the lumbar ligamentum flavum. We are particularly impressed by the preservation of anatomical relationships within the embedded tissue and the resulting histological sections. Many authors have either commented on or published images with fractures or folds affecting the quality of the sections (Okuda et al., 2004; Ramsey, 1966; Rissanen, 1960; Scapinelli et al., 2006; Yahia et al., 1989). This arises from the difficulty that this tissue presents for histological processing. To have three serial sections presented in reasonable condition is laudable and highlights the quality of data at hand. Our group is currently exploring the effect of obesity upon the interspinous ligament in a combined MRI/dissection study funded by the Australia and New Zealand College of Anesthetists. We hypothesize that islands of adipose tissue may populate an anterior midline gap in the ligament, which is associated with the ligamentum flavum divergence. The results published by Iwanaga and colleagues (Iwanaga et al., 2019) are consistent with progress we have made regarding the detailed anatomy of the lumbar interspinous ligaments. Our hypothesis is at least partially supported by the comment that “The interspinous ligament split into right and left parts at the junction with ligamentum flavum”. Although Rissanen (1960) and Heylings (1978) also made this observation, we have not noted the inclusion of this feature in an anatomical textbook before 2005 (Lawrence et al., 2017). Even today, it is not part of the standard anatomical descriptions of the interspinous ligament. As part of his study, Rissanen (1960)) examined 114 individuals less than 11 years of age. He described dense deposits of adipose tissue in this anterior split of the interspinous ligament. This would be expected to leave a legacy of adipocytes. Having shared the clinical experience of difficult epidural analgesia in severely morbidly obese individuals (Saravanakumar et al., 2006), we postulate that adipose tissue in the interspinous ligament may be an additional but unexplored factor (Hameed et al., 2012). The gross dissection portion of our study included small serial sections (<0.5 mm) through the interspinous ligament and ligamentum flavum at the level of the interspinous portion of the ligamentum flavum to measure and document the nature of these structures. At all times, these small sections from embalmed body donors remained as one unit, reinforcing the understanding of the ligamentum flavum as a single layer that is confluent with the interspinous ligament. The histological techniques used by Iwanaga and colleagues would prevent direct staining for lipids. It would offer new insights though, if the authors could comment on the nature of tissue and cells in the area of interspinous ligament splitting that was described.
Immunogenicity: Its Impact on ADME of Therapeutic Biologics

The immunogenicity of therapeutic biologics is an intensively studied feature shared by almost all biologics that have been developed. This chapter addresses essentially three aspects: which factors are key in initiating and orchestrating an anti-drug antibody (ADA) response; the impact of ADA (both neutralizing and nonneutralizing) on the absorption, distribution, and clearance of biologics, such as monoclonal antibodies (mAbs) and other protein drugs; and how to deal with ADA responses in nonclinical and clinical studies in the establishment of a pharmacokinetic/pharmacodynamic (PK/PD) relationship. The impact of ADA on absorption, distribution, and clearance are discussed mainly based on nonclinical data. To establish a causal relationship between unexpected PK/ PD profiles and unwanted immune responses, PK/PD sampling needs to be accompanied by sampling for immunogenicity/ ADA testing and vice versa-in both nonclinical and clinical studies. Keywords: ADME; anti-drug antibodies; immunogenicity; monoclonal antibodies; pharmacodynamics; pharmacokinetics; therapeutic biologics; unwanted immune responses
Prevalence and Risk Factors of Insomnia in Community-Dwelling Chinese Elderly: A Taiwanese Urban Area Survey

Objective: To determine the prevalence of and risk factors for self-reported sleep complaints in the elderly. Method: A cross-sectional interview study was conducted in a total of 2045 noninstitutionalized older individuals aged 65 years or above of an urban community of Taiwan. Results: The prevalence of one-month insomnia was 6% overall with a higher rate in elderly women (8%) than men (4.5%). Frequent use of hypnotics over the past month was 8.4%. Among specific sleep complaints, poor sleep quality was the most commonly reported symptom, followed by difficulty falling asleep and difficulty maintaining sleep or early morning awakenings. Increasing age did not correlate with an increased rate of insomnia and female gender was not an independent risk factor. Factors associated with insomnia for both genders were nocturnal micturation (OR = 20.6) and regular use of hypnotics (OR = 3.2). Pulmonary disease (OR = 2.7), not married (OR = 2.3), excessive daytime sleepiness (OR = 2.4), and mental illness (OR = 8.6) were risk factors for men while lack of education (OR = 1.8) and body pain (OR = 2.6) were risk factors for women. Depression (OR = 2.2) was strongly associated with insomnia in the elderly women as well. Conclusions: There was a low insomnia prevalence rate in the urban elderly community. Identified insomniacs required treatment of physical and mental problems, particularly in gender-specific risk factors. For those who complained of putative poor sleep quality symptom, early intervention may halt their progress of sleep disturbance and avoid unnecessary benzodiazepine use. Future longitudinal studies to investigate causes of insomnia, as well as its detrimental effects on mood and health, are warranted.
Retrieved Cerebral Thrombi Studied By T2 and ADC Mapping: Preliminary Results

Abstract Background Recent advances in MRI technology makes it increasingly more competitive to CT also in the field of interventions. Multi-parametric MRI offers a significant amount of data relevant for characterization of human cerebral thrombi. Patients and methods Cerebral thrombi of 17 patients diagnosed with acute stroke were acquired by mechanical thrombectomy. The thrombi were subsequently scanned using a high spatial-resolution 3D T1-weighted MRI to obtain morphological characteristics of the thrombi and also by apparent diffusion coefficient (ADC) and transversal nuclear magnetic resonance (NMR) relaxation time (T2) mapping. The MRI results were analysed for possible correlations between thrombectomy procedure parameters (recanalization time and number of passes) and MR-measurable parameters (sample-mean ADC and T2, within-sample coefficient of variation of ADC and T2, and thrombus length). Results Both MRI mapping techniques enabled a good discrimination among thrombi regions of different water mobility and compaction. Within-sample coefficient of variation of ADC was found most sensitive for discrimination between the thrombi where thrombectomy procedure was performed in a single pass and those where is was performed in two or more passes (p = 0.03). Interestingly, negative correlation was found between the recanalization time and thrombus length (ρ = -0.22). Conclusions Preliminary results of presented study shows that pretreatment MRI assessment of thrombi in stroke patients could potentially ease stroke treatment planning. In this study it is shown that within-sample coefficient of variation of ADC could serve for prediction of possible complications during thrombectomy procedures.
Changes in Early Psychosis Service Provision: A File Audit

Objective: To measure change in services provided to young people with first-episode psychosis following the introduction of specialized early psychosis teams and staff training. Method: A standardized tool was developed to audit services provided to young people with first-episode psychosis. The tool initially comprised 27 clinical indicators measuring aspects of optimal care derived from the Australian clinical guidelines for early psychosis. The first 12 months of treatment, as documented in the case records, were audited for all young people receiving their first treatment for psychosis during a 6-month period prior to the introduction of these service developments (n = 47). These subjects were compared with those who received treatment after the implementation of service development strategies (n = 70). A comparison was also made within the second group, between those receiving some treatment from a specialized early psychosis team and those being exclusively treated by other services. Results: Inter-rater reliability was achieved for 24 of the 27 indicators. Improvements were found on 10 indicators which measured psychosocial interventions, prescribing practices, family interventions and continuity of care. There was no significant deterioration on any of the indicators. Clients who attended early psychosis teams were significantly more likely to receive psychoeducation. Conclusions: The services increased their provision of ‘guideline concordant’ care for early psychosis. The audit proved useful to monitor performance, to demonstrate improvements in care and to identify those areas of service provision and documentation in need of improvement.