Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of L-Tryptophan Supplementation on Exercise Performance

The performance of strenuous physical exercise is associated with discomfort and pain, the tolerance for that being modulated by the activity of the endogenous opioid systems. As 5-hydroxy-tryptamine (5-HT) affects nociception through its effects on the enkephalin-endorphin system, we have analyzed the effects of a moderate supplementation with L-tryptophan, the immediate precursor of 5-HT, on endurance and sensation of effort. Twelve healthy sportsmen were subjected to a work load corresponding to 80% of their maximal oxygen uptake on two separate trials, after receiving a placebo and after receiving the same amount of L-tryptophan. The subjects ran on a treadmill until exhaustion. Total exercise time, perceived exertion rate, maximum heart rate, peak oxygen consumption, pulse recovery rate, and excess post-exercise oxygen consumption were determined during the two trials. The total exercise time was 49.4% greater after receiving L-tryptophan than after receiving the placebo. A lower rate of perceived exertion was exhibited by the group while on tryptophan although the differences from the control group were not statistically significant. No differences were observed in the other parameters between the two trials. The longer exercise time als well at the total work load performed could be due to an increased pain tolerance as a result of L-tryptophan ingestion.
Is reflective writing an effective peer assessment tool for students in Higher Education?

Today the ability to monitor and evaluate the performance of team members and identify their strengths and weaknesses is highly crucial in any organizational role. Higher Education Institutes (HEIs) are adopting different strategies in their teaching curricula and assessment methods to encourage the development of team management skills among graduates, one of which is peer assessment. It is an important component in the design of an effective learning environment in Higher Education (HE) and for promoting a strong participatory and collaborative culture among students. It provides students with a platform to not only engage with the HE learning process but also to learn from each other by receiving and giving critical feedback. Reflective writing in HE offers a flexible platform for students to discuss the contributions made by peers in teamwork however, not many researchers have looked at its potential as a peer assessment tool. This study addresses this gap by using the case study of the MSc Engineering Management (EM) programme at York (UK). Using the method of content analysis, this study looks at the quality of peer assessment and the skills gap analysis demonstrated in the reflective assignments students undertake in one of the modules. The findings show the viability and potential of this method for building peer assessment skills. It eliminates some of the limitations like bias among students usually encountered in other peer assessment tools. It also helps in skills gap analysis and for understanding group dynamics in teamwork. Students should therefore, be encouraged to seek the application of such tools for skills analysis, to build up confidence in peer assessment and boosting employability factors.
Characterization of an alcohol addiction‐prone phenotype in mice

Human studies indicate that high impulsivity, novelty seeking and anxiety predispose individuals to alcohol abuse. Unclear, however, is whether the same phenotypes can be observed in laboratory animals prone to uncontrolled alcohol drinking. To characterize a novelty‐seeking trait, anxiety, impulsivity, compulsivity and the motivation for natural rewards in mice, numerous tests were performed in the automated IntelliCage learning system. The same mice then had extended access to alcohol for 70 days, followed by the evaluation of addiction‐like behaviors, including (1) the motivation for alcohol in a progressive‐ratio schedule of reinforcement; (2) persistent and compulsive alcohol seeking and taking during signaled ‘no alcohol’ periods and (3) when subjected to punishment; and (4) the intensity of relapse after alcohol withdrawal. Our data suggest that high levels of anxiety‐related traits (i.e. low novelty seeking, low resistance to punishment and a high level of compulsive behaviors) and high impulsivity predict addiction‐like alcohol drinking in mice. Future studies are, however, warranted to create a valid model of alcohol addiction in mice in the IntelliCage system.
Cystatin C-based glomerular filtration rate associates more closely with mortality than creatinine-based or combined glomerular filtration rate equations in unselected patients

Background Decreased glomerular filtration rate (GFR) is an important cardiovascular risk factor, but estimated GFR (eGFR) may differ depending on whether it is based on creatinine or cystatin C. A combined creatinine/cystatin C equation has recently been shown to best estimate GFR; however, the benefits of using the combined equation for risk prediction in routine clinical care have been less studied. This study compares mortality risk prediction by eGFR using the combined creatinine/cystatin C equation (CKD-EPI), a sole creatinine equation (CKD-EPI) and a sole cystatin C equation (CAPA), respectively, using assays that are traceable to international calibrators. Methods and results All patients analysed for both creatinine and cystatin C from the same blood sample tube (n = 13,054) during 2005–2007 in Uppsala University Hospital Laboratory were divided into eGFR risk categories>60, 30–60 and <30 mL/min/1.73 m2 by each eGFR equation. During follow-up (median 4.6 years), 4398 participants died, of which 1396 deaths were due to cardiovascular causes. Reduced eGFR was significantly associated with death as assessed by all eGFR equations. The net reclassification improvement (NRI) for the combination equation compared with the sole creatinine equation was 0.10 (p < 0.001) for all-cause mortality and 0.08 (p < 0.001) for cardiovascular mortality, indicating improved reclassification. In contrast, NRI for the combination equation, compared with the sole cystatin C equation, was –0.06 (p < 0.001) for all-cause mortality and –0.02 (p = 0.032) for cardiovascular mortality, indicating a worsened reclassification. Conclusions In routine clinical care, cystatin C-based eGFR was more closely associated with mortality compared with both creatinine-based eGFR and creatinine/cystatin C-based eGFR.
Developmental Regulation of an Adhesin Gene during Cellular Morphogenesis in the Fungal Pathogen Candida albicans

ABSTRACT Candida albicans expresses specific virulence traits that promote disease establishment and progression. These traits include morphological transitions between yeast and hyphal growth forms that are thought to contribute to dissemination and invasion and cell surface adhesins that promote attachment to the host. Here, we describe the regulation of the adhesin gene ALS3, which is expressed specifically during hyphal development in C. albicans. Using a combination of reporter constructs and regulatory mutants, we show that this regulation is mediated by multiple factors at the transcriptional level. The analysis of ALS3 promoter deletions revealed that this promoter contains two activation regions: one is essential for activation during hyphal development, while the second increases the amplitude of this activation. Further deletion analyses using the Renilla reniformis luciferase reporter delineate the essential activation region between positions −471 and −321 of the promoter. Further 5′ or 3′ deletions block activation. ALS3 transcription is repressed mainly by Nrg1 and Tup1, but Rfg1 contributes to this repression. Efg1, Tec1, and Bcr1 are essential for the transcriptional activation of ALS3, with Tec1 mediating its effects indirectly through Bcr1 rather than through the putative Tec1 sites in the ALS3 promoter. ALS3 transcription is not affected by Cph2, but Cph1 contributes to full ALS3 activation. The data suggest that multiple morphogenetic signaling pathways operate through the promoter of this adhesin gene to mediate its developmental regulation in this major fungal pathogen.
Risk for Incident Atrial Fibrillation in Patients Who Receive Antihypertensive Drugs

BACKGROUND Different antihypertensive drug classes may alter risk for atrial fibrillation. Some studies suggest that drugs that interfere with the renin-angiotensin system may be favorable because of their effect on atrial remodeling. OBJECTIVE To assess and compare the relative risk for incident atrial fibrillation among hypertensive patients who receive antihypertensive drugs from different classes. DESIGN Nested case-control analysis. SETTING The United Kingdom-based General Practice Research Database, a well-validated primary care database comprising approximately 5 million patient records. PATIENTS 4661 patients with atrial fibrillation and 18,642 matched control participants from a population of 682,993 patients treated for hypertension. MEASUREMENTS A comparison of the risk for atrial fibrillation among hypertensive users of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II-receptor blockers (ARBs), or beta-blockers with the reference group of users of calcium-channel blockers. Patients with clinical risk factors for atrial fibrillation were excluded. RESULTS Current exclusive long-term therapy with ACE inhibitors (odds ratio [OR], 0.75 [95% CI, 0.65 to 0.87]), ARBs (OR, 0.71 [CI, 0.57 to 0.89]), or beta-blockers (OR, 0.78 [CI, 0.67 to 0.92]) was associated with a lower risk for atrial fibrillation than current exclusive therapy with calcium-channel blockers. LIMITATION Blood pressure changes during treatment courses could not be evaluated, and risk for bias by indication cannot be fully excluded in an observational study. CONCLUSION In hypertensive patients, long-term receipt of ACE inhibitors, ARBs, or beta-blockers reduces the risk for atrial fibrillation compared with receipt of calcium-channel blockers. PRIMARY FUNDING SOURCE None.
Two Related Biosynthetic Pathways of Mugineic Acids in Gramineous Plants

The biosynthesis of mugineic acids was studied by feeding 2H- or 13C-labeled compounds to water-cultured roots in several gramineous plants. The fate of labeled compounds was monitored by using 2H- and 13C-nuclear magnetic resonance. On investigating the proton changes during biosynthesis by feeding D,L-[3,3,4,4-d4]-methionine (98.6% 2H), 2H-labeled 2[prime]-deoxymugineic, mugineic, and 3-epihydroxymugineic acids were isolated from root washings of wheat (Triticum aestivum L. cv Minori), barley (Hordeum vulgare L. cv Minorimugi), and beer barley (Hordeum vulgare L. cv AM Nijo Tochigi), respectively. The 2H-nuclear magnetic resonance study indicated that 12 deuteriums were incorporated into the labeled 2[prime]-deoxymugineic acid, suggesting that three molecules of L-[3,3,4,4-d4]methionine were combined. In comparison, one of the deuteriums at C-2[prime] position in the mugineic acid, and one each of the deuteriums at C-2[prime] and C-3 positions in the 3-epihydroxymugineic acid, were lost. However, all other deuteriums were incorporated in a manner similar to that of the labeled 2[prime]-deoxymugineic acid. When [1,4[prime],4″-13C3]2[prime]-deoxymugineic acid (20% 13C) was fed to oat roots (Avena sativa L. cv Amuri II), avenic acid A, which was 13C enriched at the corresponding positions, was obtained. These results revealed that L-methionine was the precursor for all these mugineic acids and that cleavage of the azetidine ring or hydroxylation of the 2[prime]-deoxymugineic acid produced two related biosynthetic pathways in different gramineous plant species: L-methionine -> 2[prime]-deoxymugineic acid -> avenic acid A in oat; and L-methionine -> 2[prime]-deoxymugineic acid -> mugineic acid -> 3-epihydroxymugineic acid in barley and beer barley.
MicroRNA-148b and microRNA-152 reactivate tumor suppressor genes through suppression of DNA methyltransferase-1 gene in pancreatic cancer cell lines

Overexpression of DNA methyltransferase 1 (DNMT-1) is observed mostly in pancreatic cancer and it can cause tumor suppressor genes silencing in this disease. Recent studies suggest that abnormal expressions of microRNAs (miRs) are involved in pathogenesis of different types of human cancers including pancreatic cancer. In this study we aimed to investigate the effect of miR-148b and -152 on reverting the tumorigenic phenotype of pancreatic cancer cell lines. In order to investigate whether miR-148b and -152 are involved in the regulation of DNMT-1, luciferase reporter assay was used and confirmed that the DNMT-1 mRNA could be a target for miR-148b and miR-152. Furthermore, overexpression of miR-148b and -152 in pancreatic cancer cell lines (MIA PaCa-2 and AsPC-1) decreased DNMT-1 expression (53% and 59% respectively), returned DNA methylation to normal patterns and induced re-expression of tumor suppressor genes, like BNIP3 (4.7- and 3.8-fold) and SPARC (5.3- and 2.9-fold) for miR-148b and -152 respectively. Moreover, the introduced miR-148b and -152 could inhibit the proliferation of MIA PaCa-2 (35% and 37% respectively) and AsPC-1 (39% and 40% respectively) cell lines. The apoptosis rates of MIA PaCa-1 after treatment with miR-148b and -152 were 10% and 8% respectively; while these rates in AsPC-1 were 16% and 11% respectively. Conclusively these findings mean that miRs that are targeting DNMT-1 and modifying methylation status of tumor suppressor genes such as BNIP3 and SPARC can be applied in killing the pancreatic cancer cells and decreasing the tumorigenicity of these cells.
Measures of abstinence in clinical trials: issues and recommendations.

A workgroup formed by the Society for Research on Nicotine and Tobacco reviewed the literature on abstinence measures used in trials of smoking cessation interventions. We recommend that trials report multiple measures of abstinence. However, at a minimum we recommend that trial: (a) report prolonged abstinence (i.e., sustained abstinence after an initial period in which smoking is not counted as a failure) as the preferred measure, plus point prevalence as a secondary measure; (b) use 7 consecutive days of smoking or smoking on > or = 1 day of 2 consecutive weeks to define treatment failure; (c) include non-cigarette tobacco use, but not nicotine medications in definitions of failure; and (d) report results from survival analysis to describe outcomes more fully. Trials of smokers willing to set a quit date should tie all follow-ups to the quit date and report 6- and/or 12-month abstinence rates. For these trials, we recommend an initial 2-week grace period for prolonged abstinence definitions; however, the period may vary, depending on the presumed mechanism of the treatment. Trials of smokers who may not be currently trying to quit should tie follow-up to the initiation of the intervention and should report a prolonged abstinence measure of > or = 6-month duration and point prevalence rates at 6- and 12-month follow-ups. The grace period for these trials will depend on the time necessary for treatment dissemination, which will vary depending on the treatment, setting, and population. Trials that use short-term follow-ups (< or = 3 months) to demonstrate possible efficacy should report a prolonged abstinence measure of > or = 4 weeks. We again recommend a 2-week grace period; however, that period can vary.
Theoretical Research into Anticancer Activity of Diterpenes Isolated from the Paraiban Flora

Many studies of the scientific literature discuss the anticancer activity of diterpenes inhibiting the Akt/IKK/NF-κB pro-survival signaling cascade, mainly by the activation of serine/threonine phosphatase PP2A. The aim of this work was to evaluate and compare the anticancer potential of three atisane, three kaurane and three trachylobane diterpenes extracted from the roots of Xylopia langsdorffiana. Thus, we investigated the reactivity (H-LGAP parameter), HOMO atmosphere favorable to neutralize the radical reactivity, and the docking of compounds with PP2A. With all approaches, this theoretical study showed that atisane diterpenes have favorable characteristics for antitumor activity, like electron donating ability and greater hydrophilic interactions with the enzyme, by inhibition of Akt/IKK/NF-κB, and activation of PP2A.
Ankle Dorsiflexion Arthrodesis to Salvage Chopart’s Amputation With Anterior Skin Insufficiency

Background: In Chopart-level amputations the heel often deviates into equinus and varus when, due to the lack of healthy anterior soft tissue, rebalancing tendon transfers to the talar head are not possible. Consequently, anterior and lateral wound dehiscence and ulceration may occur requiring higher-level amputation to achieve wound closure, with considerable loss of function for the patients. Methods: Twenty-four consecutive patients (15 diabetes, 6 trauma, and 3 tumor) had Chopart’s amputation and simultaneous or delayed additional ankle dorsiflexion arthrodesis to allow for tension-free wound closure or soft tissue reconstruction, or to treat secondary recurrent ulcerations. Percutaneous Achilles tendon lengthening and subtalar arthrodesis were added as needed. Wound healing problems, time to fusion and full weight-bearing in the prosthesis, complications in the prosthesis, and the ambulatory status were assessed. Satisfaction and function were evaluated by the AmpuPro score and the validated Prosthesis Evaluation Questionnaire scale. Results: Five patients had successful soft tissue healing and fusions but died of their underlying disease 2 to 46 months after the operation. Two diabetic patients required a transtibial amputation. The other 17 patients were followed for 27 months (range, 13-63). The average age of the 4 women and 13 men was 53.9 years (range, 16-87). Postoperative complications included minor wound healing problems in 8 patients, wound breakdown requiring revision in 4, phantom pain in 3, residual equinus in 1, and adjacent scar carcinoma in 1 patient. The time to full weight-bearing in the prosthesis ranged from 6 to 24 weeks (mean 10). The mean AmpuPro score was 107 points (of 120), and the mean Prosthesis Evaluation Questionnaire scale was 147 points (of 200). No complications occurred with the prosthesis. Twelve patients lost 1 to 2 mobility classes (mean 0.9). The arthrodeses all healed within 2.5 months (range, 1.5 to 5 months). Conclusion: Adding an ankle arthrodesis to a Chopart’s amputation either immediately or in a delayed fashion to treat anterior soft tissue complications was a successful salvage in most patients at this amputation level. It enabled the patients to preserve the advantages of a full-length limb with terminal weight-bearing. Level of Evidence: Level IV, retrospective case series.
Graftskin Treatment of Difficult to Heal Diabetic Foot Ulcers: One Center's Experience

BACKGROUND Chronic diabetes-related foot ulcers result from predisposition, tissue injury, and inadequate reparative mechanisms. Standard care for diabetes-related foot ulcers includes weight off-loading, pressure-relieving footwear, aggressive surgical debridement, and frequent dressing changes. Graftskin is a recently developed living skin construct. OBJECTIVE To compare Graftskin and standardized wound care to standardized wound care alone in the treatment of difficult to heal diabetes-related neuropathic foot ulcers, and to assess the handling and application characteristics of Graftskin. METHODS A university dermatology clinic was part of a 24-center prospective, randomized, controlled, parallel group comparative trial of Graftskin for the treatment of difficult to heal neuropathic diabetes-related foot ulcers. Patients were randomly assigned to treatment with Graftskin with aggressive debridement and standardized wound care, or aggressive debridement and standardized wound care alone. Blinding was not feasible due to device visibility during application. RESULTS Five of nine patients (56%) treated with Graftskin therapy had complete healing. Three of eight control patients (37%) had complete healing. CONCLUSION Graftskin as an adjunct to aggressive debridement and standardized wound care appears to be a valuable treatment adjunct in patients with difficult to heal diabetes-related neuropathic foot ulcers. The application learning curve was steep and the ease of application exceptional.
Correlation Networks to Measure the Systemic Implications of Banks Resolution

We propose a market-based, early warning measure of credit risk able to enhance the observed CDS spreads with a risk premium that derives from contagion by means of a correlation network model. We then combine the proposed measure with balance-sheet information and liabilities composition, in order to investigate the systemic contagion that arises from the resolution of a failing financial institution within the context of the European single resolution framework. To this aim we consider three alternative scenarios: liquidation, private recapitalisation or a bail-in resolution action. The application of our methodology reveals that, from the system’s viewpoint, a private intervention and a bail-in resolution minimise losses with respect to the liquidation alternative. In addition, the bail-in resolution slightly reduces contagion effects with respect to a private intervention. Our empirical findings show that the proposed measure is quite effective to help the decision making process, from both an individual bank’s perspective and an overall regulatory viewpoint.
TCRs Genetically Linked to CD28 and CD3ε Do Not Mispair with Endogenous TCR Chains and Mediate Enhanced T Cell Persistence and Anti-Melanoma Activity

Adoptive transfer of T cells that are gene engineered to express a defined TCR represents a feasible and promising therapy for patients with tumors. However, TCR gene therapy is hindered by the transient presence and effectiveness of transferred T cells, which are anticipated to be improved by adequate T cell costimulation. In this article, we report the identification and characterization of a novel two-chain TCR linked to CD28 and CD3ε (i.e., TCR:28ε). This modified TCR demonstrates enhanced binding of peptide–MHC and mediates enhanced T cell function following stimulation with peptide compared with wild-type TCR. Surface expression of TCR:28ε depends on the transmembrane domain of CD28, whereas T cell functions depend on the intracellular domains of both CD28 and CD3ε, with IL-2 production showing dependency on CD28:LCK binding. TCR:28ε, but not wild-type TCR, induces detectable immune synapses in primary human T cells, and such immune synapses show significantly enhanced accumulation of TCR transgenes and markers of early TCR signaling, such as phosphorylated LCK and ERK. Importantly, TCR:28ε does not show signs of off-target recognition, as evidenced by lack of TCR mispairing, as well as preserved specificity. Notably, when testing TCR:28ε in immune-competent mice, we observed a drastic increase in T cell survival, which was accompanied by regression of large melanomas with limited recurrence. Our data argue that TCR transgenes that contain CD28, and, thereby, may provide T cell costimulation in an immune-suppressive environment, represent candidate receptors to treat patients with tumors.