Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Radiosterilized Glyercerolated Amniotic Membranes as a Substrate for Cultured Human Epithelial Cells

ABSTRACT Human amniotic membrane (HAM) is a biomaterial with biological properties beneficial to tissue repair, serving as a substrate for cell cultivation. Irradiation is used for tissue sterilization, but can damage the HAM structure. The objective of this paper was to construct a skin substitute, composed of human keratinocytes cultured on glycerolated HAMs, and to evaluate the influence radiation on subsequent cell culture growth. Four batches of HAMs were glycerolated, and half of them were radio-sterilzed with 25 kGy. Non-irradiated glycerolated HAM (ni-HAM) and irradiated glycerolated HAM (i-HAM) samples were then de-epithelized and analyzed using optical microscopy (Picrossirius staining), immunofluorescence and electron microscopy. Subsequently, keratinocytes were cultured on ni- and i-HAMs, and either immersed or positioned at the air-liquid interface. The basement membranes of the ni-HAM group remained intact following de-epithelialization, whereas the i-HAM group displayed no evidence or remnant presence of these membranes. Concerning the keratinocyte cultures, the ni-HAM substrate promoted the growth of multi-layered and differentiated epithelia. Keratinocytes cultured on i-HAM formed epithelium composed of three layers of stratification and discrete cell differentiation. The glycerolated HAM was compatible with cultured epithelia, demonstrating its potential as a skin substitute. Irradiation at 25 kGy caused structural damage to the amnion.
Therapeutic landscape for NAFLD in 2020.

Lifestyle modifications focused on healthy eating and regular exercise are the primary recommendations for patients with NASH. However, for multiple societal, psychological, physical, genetic, and epigenetic reasons, the ability of people to adopt and sustain such changes is challenging and typically not successful. To end the epidemic of NASH and prevent its complications including cirrhosis and hepatocellular carcinoma, pharmacological interventions are now being evaluated in clinical trials. Treatments include drugs targeting energy intake, energy disposal, lipotoxic liver injury, and the resulting inflammation and fibrogenesis that lead to cirrhosis. It is likely that patients develop the phenotype of NASH by multiple mechanisms and thus the optimal treatments of NASH will likely evolve to personalized therapy once we understand the mechanistic underpinnings of NASH in each patient. Reviewed here is the treatment landscape in this rapidly evolving field with an emphasis on drugs in Phase 2 and Phase 3 trials.
Leisure-time Physical Activity and Fruit and Vegetable Intake of Young Adult Millennials

This study aimed to identify the prevalence of leisure-time physical activity (LTPA) and fruit and vegetable intake (FVI) behaviors and to examine relationships between biological, sociocultural, and psychological personal factors and these behaviors among young adult Millennials aged 20 years to 32 years. Descriptive and inferential statistics were performed on data from the 2013–2014 National Health and Nutrition Examination Survey. Of the 1,137 respondents, 47% met the recommendations for LTPA, and only 13% and 17% met the recommendations for intake of fruits and vegetables, respectively. Engagement in LTPA was associated with being male, race/ethnicity, and increased education and income. Obesity, measured by body mass index, and poor perceived health status were associated with not meeting the recommendations for LTPA. Increased education was associated with meeting the recommendations for vegetable intake. No other regression models were significant. These findings suggest contemporary young adults would benefit from health promotion efforts.
Association of religiosity with mental health and quality of life in women with chronic pelvic pain

Objective This study evaluated religiosity and its association with mental health, quality of life, and the intensity of pelvic pain in women with chronic pelvic pain. Methods A cross-sectional study was conducted with 100 women with chronic pelvic pain. Religiosity was investigated using the Duke University Religion Index. Quality of life was evaluated using the abbreviated version of the World Health Organization’s quality of life instrument. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale, while pain intensity was evaluated using a visual analog scale. Results Almost half the participants attended religious services at least once a week and 62% prayed, meditated, or studied the Bible at least once a day. There was no association between religiosity and anxiety or depression. The intrinsic religiosity score was lower for women with mixed anxiety-depressive disorder compared to those without mixed anxiety-depressive disorder. There was a positive association between intrinsic religiosity and the psychological health domain of the quality of life instrument. There was no association between religiosity and pain intensity. Conclusions Women with chronic pelvic pain were strongly religious. Women with mixed anxiety-depressive disorder had lower levels of intrinsic religiosity. On the other hand, intrinsic religiosity was positively associated with quality of life in women with chronic pelvic pain. Religiosity was not associated with the intensity of pelvic pain. These data suggest that health-care professionals should take religiosity into account when treating women with chronic pelvic pain.
The bucket handle meniscal tear. A technique using two incisions.

: The bucket handle tear is a common meniscal tear in both the medial and lateral menisci, occurring in a relatively young age group, and with a high incidence of associated intra-articular pathology. Treatment of the tear consists of removal of the mobile fragment leaving a remaining meniscal rim that is both stable and smoothly contoured. This can be accomplished percutaneously under arthroscopic visualization. Numerous different methods for arthroscopic removal of the bucket handle fragment have been described and often in any particular situation, one method works slightly better than another. It is therefore important for a surgeon who routinely performs arthroscopic meniscal surgery to be comfortable with a wide variety of techniques and approaches. THe seven step technique that has been described is presently the easiest, most accurate, and most reliable technique in my experience. Progress, both in the development of new methods and in the development of better instrumentation, is extremely rapid in this field and therefore this technique must be considered in this context of rapid change.
Photodegradation of ibuprofen and four other pharmaceutical pollutants on natural pigments sensitized TiO2 nanoparticles

Pharmaceuticals and personal care products (PPCPs) in water system have drawn increasing concerns in recent years. TiO2‐based photodegradation has shown great potential as a low‐cost and sustainable technology in water treatment, however, can only use the UV light range of solar radiation which makes the system less efficient. Dyes have been studied to improve the TiO2 system light‐harvesting range, but studies on environmental friendly natural dyes are rare. In this study, a screening method using UV‐Vis spectra analysis was carried out on a group of 22 different tropical natural plants for the potential applications on dye‐sensitized TiO2 in PPCP treatment. As a result, Begonia “Martin's Mystery” significantly increased TiO2 photodegradation efficiency toward ibuprofen treatments which is first time reported in literature as our best knowledge. Moreover, the promising discovery of Begonia application in ibuprofen treatment has been successfully applied to warfarin and famotidine treatment. Similar results were expanded to many other Begonia species which indicate that Begonia extracts could be excellent sensitizers for TiO2‐based photodegradation of PPCPs. Our discovery suggested that the screening process may potentially open a brand‐new way for future TiO2 photodegradation studies before the complex and time‐consuming detailed mechanism studies.
Estimating total small solute clearance in patients treated with continuous ambulatory peritoneal dialysis without urine and dialysate collection

Background: International Society for Peritoneal Dialysis guidelines recommend to routinely monitor the total measured clearance (mCl) of small solutes such as creatinine; however, collection of 24-h urine and peritoneal dialysis (PD) fluid is burdensome to patients and prone to errors. We hypothesized that equations could be developed to estimate mCl (estimated clearance (eCl)) using endogenous filtration markers. Methods: In the Guangzhou PD Study (n = 980), we developed eCl equations using linear regression in two-third and validated them in the remaining one-third. Reference tests were mCl for urea nitrogen (UN) (mClUN, ml/min) and average mCl for UN and creatinine (mClUN-cr, ml/min/1.73 m2). Index tests were various eCl equations using UN, creatinine, low-molecular-weight proteins (LMWPs) (beta-trace protein (BTP), beta-2 microglobulin (B2M), and cystatin C), demographic variables, and body size. After reexpression of the equations in the combined data set, we analyzed accuracy (eCl within ± 2.0 units of mCl) and the predictive value of eCl to detect a weekly total standard Kt/V (weekly mClUN indexed for total body water) > 1.7 using receiver operating characteristic curve. Results: Mean age of the cohort was 50 ± 15 years, 53% were male; mClUN was 6.9 ± 1.8 and mClUN-cr was 7.5 ± 2.8. Creatinine but not UN contributed to eCl for both mCl. LMWP did not improve accuracy for mClUN (range 88–89%). BTP and B2M improved the accuracy for mClUN-cr (82% vs. 80%); however, differences were small. The area under the curve for predicting a weekly Kt/V > 1.7 was similar for all equations (range 0.79–0.80). Conclusions: Total small solute clearance can be estimated moderately well in continuous ambulatory PD patients using serum creatinine and demographic variables without urine and dialysate collection.
Designing novel teduglutide analogues with improved binding affinity: An in silico peptide engineering approach.

INTRODUCTION Short bowel syndrome (SBS) is a disabling condition which occurs following the loss of substantial portions of intestine leading to inadequate absorption of nutrients and fluids. Teduglutide is the only drug which has been FDA-approved for long-term treatment of SBS. This medicine exerts its biological effects through binding to the GLP-2 receptor. METHODS The current study aimed to use computational mutagenesis approaches to design novel potent analogues of teduglutide. To this end, the constructed teduglutide-GLP2R 3D model was subjected to the alanine scanning mutagenesis where ARG20, PHE22, ILE23, LEU26, ILE27 and LYS30 were identified as the key amino acids involved in ligand-receptor interaction. In order to design potent teduglutide analogues, using MAESTROweb machine learning method, the residues of teduglutide were virtually mutated into all naturally occurring amino acids and the affinity improving mutations were selected for further analysis using PDBePISA methodology which interactively investigates the interactions established at the interfaces of macromolecules. RESULT The calculations resulted in D15I, D15L, D15M and N24M mutations which can improve the binding ability of ligand to receptor. Final evaluation of identified mutations was performed by molecular dynamics simulations indicating that D15I and D15M are the most reliable mutations to increase teduglutide affinity towards its receptor. CONCLUSION The findings in the current study may facilitate designing more potent teduglutide analogues leading to the development of novel treatments in short bowel syndrome.
Association of Gene Variations in Ionotropic Glutamate Receptor and Attention-Deficit/Hyperactivity Disorder in the Chinese Population: A Two-Stage Case–Control Study

Objective: The aim of this study was to comprehensively explore the relationship between genetic variations within GRIN2A, GRIN2B, GRIK1, GRIK4, GRID2, and ADHD. Method: Genotyping was performed with the Sequenom MassARRAY system in a two-stage case–control study. ADHD symptoms were assessed using the Swanson, Nolan, and Pelham version IV scale and the Integrated Visual and Auditory Continuous Performance Test. In silico analysis was performed with website resources. Results: GRID2 rs1385405 showed a significant association with ADHD risk in the codominant model (OR = 2.208, 95% CI = [1.387, 3.515]) in the first stage and in the codominant model (OR = 1.874, 95% CI = [1.225, 2.869]) and recessive model (OR = 1.906, 95% CI = [1.265, 2.873]) in the second stage and related to inattention and hyperactivity symptom. In addition, rs1385405 disturbed the activity of exonic splicing enhancer and mediated GRID2 gene expression in the frontal cortex. Conclusion: our data provided evidence for the participation of GRID2 variants in conferring the risk of ADHD.
Comparison of the efficacy of cyclosporine and leflunomide in treating inflammatory colorectal polyps in miniature dachshunds

Inflammatory colorectal polyps (ICRPs) are frequently observed in miniature dachshunds in Japan and treated by prednisolone and immunosuppressive drugs such as cyclosporine and leflunomide. The purpose of this retrospective study was to compare the treatment efficacy, such as response rate, response interval, recurrence rate, and adverse events between cyclosporine and leflunomide. While the response rates were significantly higher in dogs treated with leflunomide, no significant differences were observed in the response interval or recurrence rate. Two of the 11 dogs treated with leflunomide showed hematological or gastrointestinal adverse events, while no dog treated with cyclosporine showed any adverse events. A case-controlled prospective study to compare the treatment efficacy of leflunomide with that of cyclosporine should be conducted.
Anti-genotoxic and anti-mutagenic effects of melatonin supplementation in a mouse model of melanoma

Abstract Melanoma, an aggressive skin cancer originating from melanocytes, can metastasize to the lungs, liver, cortex, femur, and spinal cord, ultimately resulting in DNA mutagenic effects. Melatonin is an endogenous hormone and free radical scavenger that possesses the ability to protect the DNA and to exert anti-proliferative effects in melanoma cells. The aim of this study was to evaluate the effects of B16F10 melanoma cells and the effects of melatonin supplementation on genotoxic parameters in murine melanoma models. Thirty-two male C57Bl/6 mice were divided in the following four groups: PBS + vehicle (n = 6), melanoma + vehicle (n = 10), PBS + melatonin (n = 6), and melanoma + melatonin (n = 10). The melanoma groups received a B16F10 cell injection, and melatonin was administered during 60 days. After treatment, tumor sizes were evaluated. DNA damage within the peripheral blood, lungs, liver, cortex, and spinal cord was determined using comet assay, and the mutagenicity within the bone marrow was determined using the micronucleus test. B16F10 cells effectively induced DNA damage in all tissues, and melatonin supplementation decreased DNA damage in the blood, liver, cortex, and spinal cord. This hormone exerts anti-tumor activity via its anti-proliferative, antioxidative, and pro-apoptotic effects. As this result was not observed within the lungs, we hypothesized that melatonin can induce apoptosis in cancer cells, and this was not evaluated by comet assay. This study provides evidence that melatonin can reduce the genotoxicity and mutagenicity caused by B16F10 cells.
Dietary protein-bound or free amino acids differently affect intestinal morphology, gene expression of amino acid transporters, and serum amino acids of pigs exposed to heat stress.

Pigs exposed to heat stress (HS) increase body temperature in which can damage the intestinal epithelia and affect the absorption and availability of AA. Protein digestion and metabolism further increase body temperature. An experiment was conducted with 6 pairs of pigs (of 47.3 ± 1.3 kg initial BW) exposed to natural HS to assess the effect of substituting dietary protein-bound AA by free AA on morphology and gene expression of intestinal epithelial, and serum concentration (SC) of free AA. Treatments were: high protein, 21.9% CP diet (HShp); and low protein, 13.5% CP diet supplemented with crystalline Lys, Thr, Met, Trp, His, Ile, Leu, Phe, and Val (HSaa). The HShp diet met or exceeded all AA requirements. The HSaa diet was formulated on the basis of ideal protein. Pigs were fed the same amount at 0700 and 1900 h during the 21-d study. Blood samples were collected at 1700 h (2.0 h before the evening meal), 2030 h, and 2130 h (1.5 and 2.5 h after the evening meal). At the end, all pigs were sacrificed to collect intestinal mucosa and a 5-cm section from each segment of small intestine from each pig. Villi measures, expression of AA transporters (y+L and B0) in mucosa, and SC of AA were analyzed. Ambient temperature fluctuated daily from 24.5 to 42.6 °C. Weight gain and G.F were not affected by dietary treatment. Villi height tended to be larger (P ≤ 0.10) and the villi height:crypt depth ratio was higher in duodenum and jejunum of pigs fed the HSaa diet (P < 0.05). Gene expression of transporter y+L in jejunum tended to be lower (P < 0.10) and transporter B0 in ileum was lower (P < 0.05) in HSaa pigs. Preprandial (1700 h) SC of Arg, His, Ile, Leu, Thr, Trp, Val was higher (P < 0.05), and Phe tended to be higher (P < 0.10) in HShp pigs. At 2030 h (1.5 h postprandial), serum Lys, Met, and Thr was higher in the HSaa pigs (P < 0.05). At 2130 h (2.5 h), Arg, His, Ile, Phe, and Trp was lower (P < 0.05), Met was higher (P < 0.05), and Lys tended to be higher (P < 0.10) in HSaa pigs. In conclusion, feeding HS pigs with low protein diets supplemented with free AA reduces the damage of the intestinal epithelia and seems to improve its absorption capacity, in comparison with HS pigs fed diets containing solely protein-bound AA. This information is useful to formulate diets that correct the reduced AA consumption associated with the decreased voluntary feed intake of pigs under HS.
Using Process Improvement and Systems Redesign to Improve Rheumatology Care Quality in a Safety Net Clinic

Objective To develop and evaluate interventions to improve quality of care in 4 priority areas in an urban safety net adult rheumatology clinic serving a racially/ethnically and socioeconomically diverse patient population. Methods The Institute for Healthcare Improvement’s Model for Improvement was used to redesign clinical processes to achieve prespecified benchmarks in the following areas from 2015 to 2017: 13-valent pneumococcal conjugate vaccine (PCV13) administration among immunocompromised patients; disease activity monitoring with the Clinical Disease Activity Index (CDAI) for patients with rheumatoid arthritis; latent tuberculosis infection (LTBI) screening for new biologic users with RA; and reproductive health counseling among women receiving potentially teratogenic medications. We measured performance for each using standardized metrics, defined as the proportion of eligible patients receiving recommended care. Results There were 1205 patients seen in the clinic between 2015 and 2017. Regarding demographics, 71% were women, 88% identified as racial/ethnic minorities, and 45% were eligible for at least 1 of the quality measures. Shewart charts for the PCV13 and CDAI measures showed evidence of improved healthcare delivery over time. Benchmarks were achieved for the CDAI and LTBI measures with 93% and 91% performance, respectively. Performance for the PCV13 and reproductive health counseling measures was 78% and 46%, respectively, but did not meet prespecified improvement targets. Conclusion Through an interprofessional approach, we were able to achieve durable improvements in key rheumatology quality measures largely by enhancing workflow, engaging nonphysician providers, and managing practice variation.
Probabilistic Learning in Children With Attention-Deficit/Hyperactivity Disorder

Objective: The current study examined instrumental learning in ADHD. Method: A total of 58 children with ADHD and 58 typically developing (TD) children performed a probabilistic learning task using three reward probability conditions (100%, 85%, 70% reward). After a learning phase, application of what was learned was assessed in a test phase. Results: Results showed that children with ADHD performed less accurate compared with TD children during the learning phase, particularly in the 100% and 85% reward probability conditions. These findings were accompanied by a blunted learning rate in the first few task trials. Furthermore, children with ADHD showed poorer application of what was learned. Conclusion: To conclude, children with ADHD show initial learning problems, but increased performance in a similar manner as TD children independent of the probability of reward, although they fail to apply their knowledge. Findings are of clinical relevance as the application of knowledge is important to successfully adapt to daily challenges in life.
Cross‐sectional and longitudinal associations between probable rapid eye movement sleep behavior disorder and impulse control disorders in Parkinson’s disease

The aim was to investigate whether probable rapid eye movement sleep behavior disorder (pRBD) is associated with impulse control disorders (ICDs) in drug‐naïve patients with Parkinson’s disease (PD) and whether baseline pRBD is associated with a higher incidence of ICDs during follow‐up.
Predictors of outcome in childhood Plasmodium falciparum malaria

ABSTRACT Plasmodium falciparum malaria is classified as either uncomplicated or severe, determining clinical management and providing a framework for understanding pathogenesis. Severe malaria in children is defined by the presence of one or more features associated with adverse outcome, but there is wide variation in the predictive value of these features. Here we review the evidence for the usefulness of these features, alone and in combination, to predict death and other adverse outcomes, and we consider the role that molecular biomarkers may play in augmenting this prediction. We also examine whether a more personalized approach to predicting outcome for specific presenting syndromes of severe malaria, particularly cerebral malaria, has the potential to be more accurate. We note a general need for better external validation in studies of outcome predictors and for the demonstration that predictors can be used to guide clinical management in a way that improves survival and long-term health.
EDEM2 stably disulfide-bonded to TXNDC11 catalyzes the first mannose trimming step in mammalian glycoprotein ERAD

Sequential mannose trimming of N-glycan (Man9GlcNAc2 -> Man8GlcNAc2 -> Man7GlcNAc2) facilitates endoplasmic reticulum-associated degradation of misfolded glycoproteins (gpERAD). Our gene knockout experiments in human HCT116 cells have revealed that EDEM2 is required for the first step. However, it was previously shown that purified EDEM2 exhibited no α1,2-mannosidase activity toward Man9GlcNAc2 in vitro. Here, we found that EDEM2 was stably disulfide-bonded to TXNDC11, an endoplasmic reticulum protein containing five thioredoxin (Trx)-like domains. C558 present outside of the mannosidase homology domain of EDEM2 was linked to C692 in Trx5, which solely contains the CXXC motif in TXNDC11. This covalent bonding was essential for mannose trimming and subsequent gpERAD in HCT116 cells. Furthermore, EDEM2-TXNDC11 complex purified from transfected HCT116 cells converted Man9GlcNAc2 to Man8GlcNAc2(isomerB) in vitro. Our results establish the role of EDEM2 as an initiator of gpERAD, and represent the first clear demonstration of in vitro mannosidase activity of EDEM family proteins.