Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Immune-Modulatory Drugs on Regulatory T Cell

Abstract Immunosuppression strategies that selectively inhibit effector T cells while preserving and even enhancing CD4+FOXP3+ regulatory T cells (Treg) permit immune self-regulation and may allow minimization of immunosuppression and associated toxicities. Many immunosuppressive drugs were developed before the identity and function of Treg were appreciated. A good understanding of the interactions between Treg and immunosuppressive agents will be valuable to the effective design of more tolerable immunosuppression regimens. This review will discuss preclinical and clinical evidence regarding the influence of current and emerging immunosuppressive drugs on Treg homeostasis, stability, and function as a guideline for the selection and development of Treg-friendly immunosuppressive regimens.
Quantitative measurement of intracellular transport of nanocarriers by spatio-temporal image correlation spectroscopy

Spatio-temporal image correlation spectroscopy (STICS) is a powerful technique for assessing the nature of particle motion in complex systems although it has been rarely used to investigate the intracellular dynamics of nanocarriers so far. Here we introduce a method for characterizing the mode of motion of nanocarriers and for quantifying their transport parameters on different length scales from single-cell to subcellular level. Using this strategy we were able to study the mechanisms responsible for the intracellular transport of DOTAP–DOPC/DNA (DOTAP: 1,2-dioleoyl-3-trimethylammonium-propane; DOPC: dioleoylphosphocholine) and DC-Chol–DOPE/DNA (DC-Chol: 3β-[N-(N,N-dimethylaminoethane)-carbamoyl] cholesterol; DOPE: dioleoylphosphatidylethanolamine) lipoplexes in CHO-K1 (CHO: Chinese hamster ovary) live cells. Measurement of both diffusion coefficients and velocity vectors (magnitude and direction) averaged over regions of the cell revealed the presence of distinct modes of motion. Lipoplexes diffused slowly on the cell surface (diffusion coefficient: D ≈ 0.003 μm2 s−1). In the cytosol, the lipoplexes’ motion was characterized by active transport with average velocity v ≈ 0.03 μm2 s−1 and random motion. The method permitted us to generate an intracellular transport map showing several regions of concerted motion of lipoplexes.
When R  >  0.8R0: fluorescence anisotropy, non-additive intensity, and cluster size

Assembly and clustering feature in many biological processes and homo-FRET and fluorescence anisotropy can assist in estimating the aggregation state of a system. The distance dependence of resonance energy transfer is well described and tested. Similarly, assessment of cluster size using steady state anisotropy is well described for non-oriented systems when R < 0.8R0, however, these methods break down when R > 0.8R0. Fused trimeric DNA clusters labelled with fluorescein were engineered to provide inter-fluorophore distances from 0.7 to 1.6 R/R0 and intensity and anisotropy were measured. These constructs cover a range where anisotropy effects depend on distance. Analytical expressions were derived for fully labelled and fractionally labelled clusters and the experimental results analysed. The experimental results showed that: (1) the system underwent distance dependent quenching; (2) when incompletely labelled both doubly and triply labelled forms could be assessed to obtain distance dependent intensity factors; (3) the anisotropy behaviour of a multiply labelled cluster of a particular size depends on the behaviour of the fluorophores and their distance in a cluster. This work establishes that when emission intensity data are available the analytically useful range for investigating clusters does not have to be restricted to R < 0.8R0 and is applicable to cases where the anisotropy of a cluster of N fluorophores is not well approximated by r1/N.
Developing an Interactive Physical Activity Group in a Geriatric Psychiatry Facility

Abstract Recreational activities are part of patient treatment plans in geriatric psychiatry facilities. An interactive physical activity group was developed, implemented and evaluated in a geriatric psychiatry facility. Persons over age 65 with a primary diagnosis of dementia were randomly assigned to control and experimental groups. The Mini Mental Status Exam (MMSE), Psychogeriatric Dependency Rating Scale (PGDRS), and Patient Behavior Rating Sheet were used throughout the intervention. The most notable finding of the study was that patient disruptive behavior decreased drastically during the group sessions. The implementation of the intervention, research limitations, and implications for practice, research and policy are discussed.
Simple and cost-effective fluorescent labeling of 5-hydroxymethylcytosine

The nucleobase 5-hydroxymethylcytosine (5-hmC), a modified form of cytosine, is an important epigenetic mark related to regulation of gene expression. 5-hmC levels are highly dynamic during early development and are modulated during the progression of neurodegenerative disease and cancer. We describe a spectroscopic method for the global quantification of 5-hmC in genomic DNA. This method relies on the enzymatic glucosylation of 5-hmC, followed by a glucose oxidation step that results in the formation of aldehyde moieties that are covalently linked to a fluorescent reporter by oxime ligation. The fluorescence intensity of the labeled sample is directly proportional to its 5-hmC content. We show that this simple and cost-effective technique is suitable for quantification of 5-hmC content in different mouse tissues.
Effects of aqueous extracts of Hibiscus sabdariffa calyces and ocimun gratissimum leaves on interstinal transit in rats

The effects of aqueous extracts of the leaves of Ocimum gratissimum and calyces of Hibiscus sabdariffa on intestinal transit were determined in experimental rats The leaves of Ocimum gratissimum were oven dried and then pulverized. The dried calyces of Hibiscus sabdariffa were also pulverized. 10% extracts of both powders were made and administered orally to rats at varying doses. Test rats were given the 10% extracts of Ocimum gratissimum and Hibiscus sabdariffa at 0.5/100g, 1ml/100g, 2ml/100g body weight. Control rats received saline instead of extracts. After 30 minutes, each animal was then given 1.5 ml of a dye solution orally. 1 hour after administering the dye each rat was sacrificed and the intestine carefully dissected out. The length of the intestine and the transit point of the orally administered dye were then measured. The transit point was calculated as a percentage of the total length of the intestine. The extracts of both Ocimum gratissimum and Hibiscus sabdariffa caused a reduction in the transit points of the dye. The extract of Hibiscus sabdariffa was more effective. The reduction in transit point, and hence the increase in transit time by both extracts indicates that the plants could be useful at appropriate doses in the control of diarrhea. Hibiscus sabdariffa would be more effective in this regard.
“Model for Early Allograft Function” Outperforms “Early Allograft Dysfunction” as a Predictor of Transplant Survival

Background The Model of Early Allograft Function (MEAF) grades the severity of liver graft dysfunction. Unlike the categorical early allograft dysfunction (EAD) classification, MEAF is a continuous score, based on bilirubin, international normalized ratio, and alanine aminotransferase within 3 days posttransplant. Methods Multivariable regression models were used to validate the MEAF score in 660 liver-only transplants performed between 2000 and 2014. MEAF performance for prediction of transplant survival was compared with that of EAD in univariable and multivariable models by means of Harrell’s c-indices, integrated discrimination improvement, and net reclassification improvement. Results Median donor and recipient age was 52 years (interquartile range [IQR], 41-62 years) and 58 years (IQR, 50-64 years), respectively. Model for End-Stage Liver Disease score was 15 (IQR, 11-21); cold ischemia time, 8.0 hours (IQR, 6.4-9.7 hours); MEAF, 4 (IQR, 3-6). EAD occurred in 182 (27.6%) cases. Transplant survival was 93%, 90%, and 88% at 3, 6, and 12 months. Both MEAF and EAD were independent predictors of transplant survival within 3, 6, and 12 months. MEAF outperformed EAD as predictor of transplant survival, either when used as a standalone parameter or when corrected for additional independent predictors of transplant survival. Conclusions MEAF is a more accurate predictor of transplant loss than the commonly used EAD classification. As a continuous score grading graft dysfunction, MEAF provides additional, granulated information that could be used both clinically and as a surrogate endpoint of transplant survival in clinical trials.
From lab to bedside: emerging clinical applications of thymosin α1

Background: Thymosin α1 (Tα1), a synthetic version of a thymic-derived biological response modifier was the first of the thymosins in clinical use. Tα1 is approved in over 35 countries for the treatment of hepatitis B and C, and as an immune stimulant and adjuvant. Tα1 is also in late-stage clinical testing in the United States and Europe for hepatitis C and stage IV melanoma. Objective/methods: Novel applications and other recently completed trials point to much broader clinical applications of Tα1 in the treatment of life-threatening and chronic diseases, and are the subject of this review. Result/conclusions: The most recent reports of clinical trials with Tα1 are pointing to important, hitherto unrecognized, applications in a number of diseases and disorders, including septic shock, acute respiratory distress syndrome, peritonitis, acute cytomegalovirus infection, TB, severe acute respiratory syndrome, and lung infections in critically ill patients. It is also emerging as a promising chemoprotection agent in patients undergoing chemotherapy.
Comparison of oxidative status of mouse pre‐antral follicles derived from vitrified whole ovarian tissue and vitrified pre‐antral follicles in the presence of alpha lipoic acid

The main goal of this study was to compare developmental competence and oxidative status of vitrified‐warmed pre‐antral follicles (VPF) with pre‐antral follicles derived from vitrified‐warmed ovarian tissue (VOF) in the presence of alpha lipoic acid (ALA).
Two By Two in Cyberspace: Getting Together and Connecting Online

From qualitative research of the last 2 years on 40 couples who met online between 1992 and 1999, I have selected two for further study: a couple in their 40s who split up after courting online for 4 months and meeting once offline at a southwestern resort town and a married couple in their 30s from different countries who managed to communicate, visit, and commit to each other, though each was married to another person at the time they met online. Data was collected from E-mail questionnaires asking about the progress of the relationship and, for the first case, from ongoing letters and a follow-up telephone interview with each party. More information will be sought by phone on the second case; the husband has already agreed to provide more detail. By examining the case histories, some factors of success in developing online relationships may begin to emerge. Processes of communication and situational circumstances are compared between the two couples and to others in the research on online couples.
Contemporary Policies Regarding Alcohol and Marijuana Use Among Liver Transplant Programs in the United States

Background Alcoholic liver disease is a common indication for orthotopic liver transplantation (OLT). Although OLT has been shown to confer survival benefit to patients with acute alcoholic hepatitis (AAH), historically most programs require a 6-month abstinence period before OLT which excludes patients with AAH. Marijuana has become legal in more than half the states in the United States. This survey of liver transplant programs was conducted to evaluate current policies regarding alcohol, marijuana and methadone use. Methods A questionnaire was distributed to 100 United Network for Organ Sharing–approved liver transplant programs in North America that have performed at least 30 liver transplants/year in the last 5 years. Results Forty-nine programs responded. Only 43% of the programs required a specific period of abstinence before transplant for alcoholic liver disease and only 26% enforced 6-month abstinence policy. For patients with AAH, 71% programs waived the 6-month abstinence requirement and considered psychosocial factors, such as family support, patient’s motivation, or commitment to rehabilitate. Few programs used validated instruments to assess risk of relapse in AAH patients. Fourteen percent of programs transplant patients actively using marijuana and an additional 28% of programs listed patients using marijuana provided they discontinue by the time of OLT. Active methadone users were accepted in 45% of the programs. Conclusions Policies regarding alcohol use have become more flexible particularly toward patients with AAH. Marijuana use is also more accepted. Although policies regarding alcohol and marijuana have changed significantly in the last decade, they remain highly variable among programs.
Contemporary Outcomes of Combined Heart-Liver Transplant in Patients With Congenital Heart Disease

Background As more patients survive into adulthood with repaired congenital heart disease (CHD), transplant centers now have patients presenting with both end-stage cardiac and hepatic failure. An understanding of the contemporary outcomes with combined heart liver transplantation (CHLT) in patients with CHD is needed. Methods A retrospective review of the outcomes of CHLT in CHD was conducted from October 1, 1987, to June 30, 2015, from the United Network of Organ Sharing (UNOS) database. Propensity score matched cohorts were formed for the assessment of posttransplant outcome: CHLT with CHD, CHLT without CHD, and isolated heart transplant for CHD (HT-CHD). Cohorts were matched based on age, body mass index, inotrope use, and ventilator support at the time of transplant. We assessed 30-day, 1-, 5-, and 10-year posttransplant survivals. Results There were 61 437 heart transplants during the study period, of which 190 (0.3%) were CHLT. Among CHLT, 41(22%) patients had CHD. In 26 (63%) of these, the indication for CHLT was hepatic congestion/cirrhosis of cardiac origin. In the matched cohorts, the overall survival for CHLT with CHD at 30 days, 1, 5, and 10 years was 95%, 86%, 83%, and 83%, respectively; for CHLT without CHD, it was 100%, 92%, 92%, and 63%, respectively (vs CHLT with CHD: P = 0.49); and for HT-CHD, it was 90%, 84%, 63%, and 39% (vs CHLT with CHD: P = 0.03), respectively. Conclusions The posttransplant outcome of CHLT, with and without CHD, is comparable. However, there is a trend toward better survival for CHLT for CHD compared with isolated heart transplant for CHD.
Immersive Virtual Environments in Cue Exposure

Cue reactivity to drug-related stimuli is a frequently observed phenomenon in drug addiction. Cue reactivity refers to a classical conditioned response pattern that occurs when an addicted subject is exposed to drug-related stimuli. This response consists of physiological and cognitive reactions. Craving, a subjective desire to use the drug of choice, is believed to play an important role in the occurrence of relapse in the natural setting. Besides craving, other subjective cue-elicited reactions have been reported, including withdrawal symptoms, drug-agonistic effects, and mood swings. Physiological reactions that have been investigated include skin conductance, heart rate, salivation, and body temperature. Conditioned reactivity to cues is an important factor in addiction to alcohol, nicotine, opiates, and cocaine. Cue exposure treatment (CET) refers to a manualized, repeated exposure to drug-related cues, aimed at the reduction of cue reactivity by extinction. In CET, different stimuli are presented, for example, slides, video tapes, pictures, or paraphernalia in nonrealistic, experimental settings. Most often assessments consist in subjective ratings by craving scales. Our pilot study will show that immersive virtual reality (IVR) is as good or even better in eliciting subjective and physiological craving symptoms as classical devices.
Intraoperative Management of Liver Transplant Patients Without the Routine Use of Renal Replacement Therapy

Background Renal failure is common among patients undergoing liver transplantation. Liver allocation based on the model for end-stage liver disease score has increased the number of recipients who require perioperative renal replacement therapy (RRT). Although RRT can be continued intraoperatively, the risks and benefits of intraoperative RRT are not well defined. The aim of this study is to report the intraoperative management of patients with pretransplant renal failure at a transplant center with extremely infrequent utilization of intraoperative RRT. Materials and Methods We performed a retrospective analysis of all adult patients undergoing orthotopic liver or simultaneous liver-kidney (SLK) transplantation between June 2009 and December 2015. Patients were divided into 2 groups based on their need for pretransplant RRT. Results A total of 785 patients underwent liver or SLK transplant during the study period. One hundred and seventy-four patients (22.2%) required preoperative dialysis. Only 2 patients required intraoperative RRT. There was no difference in the incidence of acidosis or hyperkalemia between patients who required preoperative dialysis and those who did not. Conclusions We describe the successful management of patients undergoing liver or SLK transplantation almost entirely without the need for intraoperative RRT.
Sodiation as a tool for enhancing the diagnostic value of MALDI-TOF/TOF-MS spectra of complex astaxanthin ester mixtures from Haematococcus pluvialis.

The microalga Haematococcus pluvialis produces the pigment astaxanthin mainly in esterified form with a multitude of fatty acids, which results in a complex mixture of carotenol mono- and diesters. For rapid fingerprinting of these esters, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS) might be an alternative to traditional chromatographic separation combined with MS. Investigation of ionization and fragmentation of astaxanthin mono- and diester palmitate standards in MALDI-TOF/TOF-MS showed that sodium adduct parent masses [M + Na](+) gave much simpler MS(2) spectra than radical / protonated [M](+●) / [M + H](+) parents. [M + Na](+) fragments yielded diagnostic polyene-specific eliminations and fatty acid neutral losses, whereas [M](+●) / [M + H](+) fragmentation resulted in a multitude of non-diagnostic daughters. For diesters, a benzonium fragment, formed by polyene elimination, was required for identification of the second fatty acid attached to the astaxanthin backbone. Parents were forced into [M + Na](+) ionization by addition of sodium acetate, and best signal-to-noise ratios were obtained in the 0.1 to 1.0 mM range. This method was applied to fingerprinting astaxanthin esters in a crude H. pluvialis extract. Prior to MALDI-TOF/TOF-MS, the extract was fractionated by normal phase Flash chromatography to obtain fractions enriched in mono- and diesters and to remove pheophytin a, which compromised monoester signals. All 12 types of all-trans esterified esters found in LC were identified with MALDI-TOF/TOF-MS, with the exception of two minor monoesters.
Doing Play: Competency, Control, and Expression

This qualitative study investigated the personal experiences of children with cerebral palsy engaging in a virtual reality play intervention program. The study involved in-depth, focused interviews that were conducted with 19 participants aged 8-13 who had a diagnosis of cerebral palsy. A constant comparative inductive method of analysis was used, and several themes emerged. Findings were interpreted using the theory of flow, the theory of self-efficacy, and the model of playfulness in virtual reality computer interactions. The three themes uncovered in the data include (a) doing play, (b) it's my way that matters, and (c) how I see me. The sub-theme safety also emerged. Findings from this study showed that children with physical disabilities are often limited in their play experience compared to their peers without physical disabilities. Children perceived engagement in a virtual reality play intervention program as an enjoyable experience which increased their self-competence and self-efficacy. Participants experienced a sense of control and mastery over the virtual environment and were provided a safe way to explore and challenge their abilities. Participants perceived experiencing flow and reported perceived physical changes and increased social acceptance from both peers and family. These findings provide evidence that virtual reality continues to show promise as a pediatric rehabilitation play intervention tool.
Internet Gambling and Social Responsibility: An Exploratory Study

Within the last few years, we have seen a substantial increase in the amount of gambling opportunities offered on the Internet. Many concerns have been raised about the activity, including the potential for excessive gambling, and the lack of safeguards for vulnerable populations such as adolescents and problem gamblers. Given these concerns, a representative selection of 30 U.K.-owned Internet gambling sites were studied to examine what safeguards were in place to encourage social responsibility of Internet gamblers. It was found that very few sites were engaged in socially responsible practice and that much more could be done to protect vulnerable groups. The findings from this study were then used to compile a list of recommendations for good practice among Internet gambling operators.
Photolysis and photocatalysis of ibuprofen in aqueous medium: characterization of by-products via liquid chromatography coupled to high-resolution mass spectrometry and assessment of their toxicities against Artemia salina.

The degradation of the pharmaceutical compound ibuprofen (IBP) in aqueous solution induced by direct photolysis (UV-A and UV-C radiation) and photocatalysis (TiO2 /UV-A and TiO2 /UV-C systems) was evaluated. Initially, we observed that whereas photocatalysis (both systems) and direct photolysis with UV-C radiation were able to cause an almost complete removal of IBP, the mineralization rates achieved for all the photodegradation processes were much smaller (the highest value being obtained for the TiO2 /UV-C system: 37.7%), even after an exposure time as long as 120 min. Chemical structures for the by-products formed under these oxidative conditions (11 of them were detected) were proposed based on the data from liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) analyses. Taking into account these results, an unprecedented route for the photodegradation of IBP could thus be proposed. Moreover, a fortunate result was achieved herein: tests against Artemia salina showed that the degradation products had no higher ecotoxicities than IBP, which possibly indicates that the photocatalytic (TiO2 /UV-A and TiO2 /UV-C systems) and photolytic (UV-C radiation) processes can be conveniently employed to deplete IBP in aqueous media.