Miracle-dz/UniFAR-FTUs huggingface dataset:
FOXP3+ regulatory T cells as biomarkers in human malignancies

Background: Regulatory T cells (Treg) expressing the FOXP3 forkhead transcription factor maintain immunological self-tolerance and can enable tumour cells to escape immunosurveillance. Objective: To provide an overview of studies using FOXP3 as a biomarker in human malignancies, particularly in the context of the antibodies used to detect FOXP3 protein expression, the cell populations selected for study, and the detection and scoring methodologies used. Methods: A personal selection of studies analysing FOXP3 as a marker of Treg cells in human malignancies are discussed. Results/conclusion: FOXP3 is a useful marker that can be used in routine clinical practise to provide both diagnostic and prognostic information in human malignancies. However, the methods and reagents used to detect FOXP3 can have a significant effect on the robustness of experimental findings and conclusions.
The Effect of Itraconazole Pretreatment in Lipopolysaccharide-Induced Acute Lung Injury in Rats

Background: Despite the fact that a randomized controlled trial did not support the use of ketoconazole for treatment of acute lung injury (ALI), there is evidence that pretreatment with ketoconazole might prevent ALI in critically ill patients. An in vitro study showed, however, that itraconazole was a more potent inhibitor of thromboxane and leukotriene formation than was ketoconazole. We investigated the effect of itraconazole pretreatment in lipopolysaccharide (LPS)-induced ALI in rats. Methods: Twenty-one pathogen free, male Sprague-Dawley rats were administered either saline or LPS (5 mg/kg of body weight) intratracheally, with or without intraperitoneal pretreatment of itraconazole (2.5 mg/kg). Six hours after saline or LPS treatment (7 h after itraconazole pretreatment), samples were obtained. Results: Compared with the saline group, LPS group had increased total cell count, polymorphonuclear leukocyte differential count, protein, lactate dehydrogenase (LDH) and cytokines in BAL fluid. Itraconazole pretreatment decreased polymrphonuclear leukocyte differential count, protein and LDH in BAL fluid compared with those of LPS-treated rats without itraconazole pretreatment. Itraconazole pretreatment also decreased the elevated BAL fluid levels of interleukin-1β (IL-1β) and cytokine-induced neutrophil chemoattractant (CINC) by LPS. There was, however, no difference in the BAL fluid tumor necrosis factor α (TNF-α) level in terms of itraconazole pretreatment in LPS-treated rats. Histopathologic features of LPS-induced ALI were attenuated by itraconazole pretreatment. Conclusions: These results suggest that itraconazole pretreatment attenuated LPS-induced ALI in rats. Decreases in levels of IL-1β and CINC would likely be associated with attenuation of LPS-induced ALI in rats by itraconazole pretreatment.
Current concepts on the theories of the mechanism of action of fluoride

The caries-preventive effect of fluoride is mainly attributed to the effects on demineralization/remineralization at the tooth oral fluids interface. Sub ppm levels of fluoride in saliva are effective in shifting the balance from demineralization, leading to caries, to remineralization. This is attributed to the fluoride-enhanced precipitation of calcium phosphates, and the formation of fluorhydroxyapatite in the dental tissues. Low fluoride levels are found in saliva after toothbrushing with fluoride containing dentifrices. Similar concentrations are ineffective in interfering with processes of growth and metabolism of bacteria, and also do not result in a significantly reduced dissolution of tooth mineral as a result of (firmly bound) fluoride incorporation. Comparative studies of fluoride efficacy have shown that higher concentrations in solution are needed in pH-cycling studies of dentine than in enamel to maintain the mineral balance or to induce remineralization. This is attributed to the greater solubility of the dentine and the smaller size of the dentine crystallites compared to enamel. Fluoride slow-release devices, in the form of fluoride-releasing restorative materials, may serve to increase the fluoride levels in saliva and plaque to levels at which caries can be prevented, also in high-risk patients. Research questions for the next millennium and future perspectives for fluoride applications should be found in the retention and slow release of fluoride after various combinations of fluoride treatment, the combination of fluoride and anti-microbial treatment, the individualization of caries prevention, and the combination of preventive schemes with new developments in caries diagnosis.
Eight Years Later, Are We Still Hurting Newborn Infants?

Objective: To study whether new pharmacological and nonpharmacological guidelines lowered numbers of painful procedures in neonates and changed the amount and frequency of analgesic therapy as compared to the results of our previous study in 2001. Design: A prospective observational study. Setting: Level III NICU of the Erasmus MC-Sophia Children's Hospital, Rotterdam. Participants: Neonates admitted at postnatal ages less than 3 days with length of stay at least 72 h. Main Outcome Measures: Number of all potentially painful procedures and analgesic therapy recorded at the bedside during the first 14 days of NICU stay. Results: A total number of 21,076 procedures were performed in the 175 neonates studied during 1,730 patient-days (mean 12.2). The mean number of painful procedures per neonate per day was 11.4 (SD 5.7), significantly lower than the number of 14.3 (SD 4.0) in 2001 (p < 0.001). The use of analgesics was 36.6% compared to 60.3% in 2001. Sixty-three percent of all peripheral arterial line insertions failed versus 37.5% in 2001 and 9.1% venipunctures failed versus 21% in 2001. Conclusions: The mean number of painful procedures per NICU patient per day declined. Nonpharmacological pain- or stress-reducing strategies like NIDCAP and sucrose were fully embedded in our pain management. As further reduction of the number of painful procedures is unlikely, we should apply more nonpharmacological interventions and explore newer pharmacological agents.
CTLA4-Ig fusion proteins: promise for improved therapy of transplant rejection and autoimmune diseases

T-cell activation is critically involved in the pathogenesis of both transplant rejection and autoimmunity, making its modulation a promising approach for immunotherapy. One attractive target for that purpose is provided by the CD28/B7 costimulatory pathway which is composed of the T-cell-associated CD28 molecule and its B7 ligands (CD80 and CD86) on antigen-presenting cells. This pathway is pivotal in complementing, in a non-antigenspecific manner, the antigen-specific signals of T-cell activation that are delivered upon triggering of the T-cell receptor. In the absence of CD28-mediated costimulation, T-cells activated through their T-cell receptor may acquire a state of antigen-specific unresponsiveness or undergo apoptotic cell death, leading to an abortive immune response. A competitive inhibitor of the CD28/B7 pathway has therefore been designed for use as a selective immunosuppressant. This reagent, called CTLA4–immunoglobulin (Ig), is a soluble fusion protein that binds B7 molecules with greater affinity than CD28. Extensive studies in animal models of allograft rejection and autoimmune diseases demonstrated that CTLA4–Ig exerts immunosuppressive effects without major toxicity. Over the past few years, the development of CTLA4–Ig and several analogs further proceeded to enter clinical trials in kidney transplantation, psoriasis and rheumatoid arthritis, with encouraging results. The present article will discuss the therapeutic potential of CTLA4–Ig molecules in the light of these new data.
Similarity degrees and uncertainty measures in intuitionistic fuzzy decision tables

Recently, making decisions and analyzing data are getting more and more attention by taking advantage of rough set and intuitionistic fuzzy set theories. Additionally, it can be found that many works have been developed about intuitionistic fuzzy rough set approaches from different viewpoints. In this article, we introduce similarity degrees and four kinds of uncertainty measurement, called θ-conditional entropies, θ-similarity intuitionistic fuzzy accuracies, θ-similarity intuitionistic fuzzy roughness and θ-rough decision entropies in intuitionistic fuzzy decision tables. Also, we provide a novel method for classifying the objects’ intuitionistic fuzzy decision table. Moreover, we carefully discuss the lower approximation and upper approximation of a given set and classify their important properties based on the novel classes in the intuitionistic fuzzy decision table. Furthermore, an illustrated example is employed to demonstrate the conceptual arguments of these measurements based on different similarity degrees and similarity rates. From this, it can be found that the new measures are superior to the classical accuracy and roughness, and the method is valuable and useful in real life situations.
Left Ventricular Diastolic Function

Two-dimensional echocafdiography has gained widespread acceptance I as the procedure of choice to evaluate left ventricular function. In the last decade, the importance of diastolic function in the overall performance of the left ventricle has received much attention. Recent evidence suggests that diastolic dysfunction may contribute to symptoms of left heart failure in many patients, including those with normal sys tolic function. Alterations in transmitral Dop pler flow velocity patterns have been used to assess changes in left ventricular diastolic func tion. This article reviews the concept and clin ical signincance of diastolic function and the assessment of diastolic function by Doppler echocardiography.
Comparative assessment of right, left, and biventricular pacing in patients with permanent atrial fibrillation

Aims Left ventricular (LV) and biventricular (BiV) pacing are potentially superior to right ventricular (RV) apical pacing in patients undergoing atrioventricular (AV) junction ablation and pacing for permanent atrial fibrillation. Methods and results Prospective randomized, single-blind, 3-month crossover comparison between RV and LV pacing (phase 1) and between RV and BiV pacing (phase 2) performed in 56 patients (70±8 years, 34 males) affected by severely symptomatic permanent atrial fibrillation, uncontrolled ventricular rate, or heart failure. Primary endpoints were quality of life and exercise capacity. Compared with RV pacing, the Minnesota Living with Heart Failure Questionnaire (LHFQ) score improved by 2 and 10% with LV and BiV pacing, respectively, the effort dyspnoea item of the Specific Symptom Scale (SSS) changed by 0 and 2%, the Karolinska score by 6 and 14% ( P <0.05 for BiV), the New York Heart Association (NYHA) class by 5 and 11% ( P <0.05 for BiV), the 6-min walked distance by 12 (+4%) and 4 m (+1%), and the ejection fraction by 5 and 5% ( P <0.05 for both). BiV pacing but not LV pacing was slightly better than RV pacing in the subgroup of patients with preserved systolic function and absence of native left bundle branch block. Compared with pre-ablation measures, the Minnesota LHFQ score improved by 37, 39, and 49% during RV, LV, and BiV pacing, respectively, the effort dyspnoea item of the SSS by 25, 25, and 39%, the Karolinska score by 39, 42, and 54%, the NYHA class by 21, 25, and 30%, the 6-min walking distance by 35 (12%), 47 (16%), and 51 m (19%) and the ejection fraction by 5, 10, and 10% (all differences P <0.05). Conclusions Rhythm regularization achieved with AV-junction ablation improved quality of life and exercise capacity with all modes of pacing. LV and BiV pacing provided modest or no additional favourable effect compared with RV pacing.
Single Versus Multiple Item Questions on Occupational Physical Activity

Background: In 2002, the National Physical Activity and Weight Loss Survey asked two sets of questions on occupational physical activity—one question from the Behavioral Risk Factor Surveillance System (BRFSS) and eight detailed questions from the occupational physical activity questionnaire (OPAQ). This study compares the responses. Methods: On the basis of percentage of occupational physical activity reported on OPAQ, 5847 respondents were classified by three levels (sitting or standing, walking, and heavy labor). Kappa, MET-min per day, and median hours worked at the three levels were calculated to compare the two sets of questions. Results: Levels of occupational physical activity reported on the BRFSS question agreed with OPAQ (kappa = 0.56). Hours of heavy labor per day reported on OPAQ increased among the three activity levels on BRFSS. Conclusions: The BRFSS question and OPAQ classify respondents similarly by occupational physical activity. The BRFSS question is useful for overview and OPAQ, for m.
Rare disease landscape: will the blockbuster model be replaced?

Introduction: The pharmaceutical industry entered the 21st century buoyed by a series of mega hits that carried it through the nineties on a wave of promise. More recently, the perceived wisdom came that the age of the mega-selling, mass-marketed drug was over; no more Prozacs, Lipitors or Viagras. With the ‘blockbuster bubble’ seemingly burst and patent protection giving way to huge rises in generic competition, the pharmaceutical industry would now seek to sustain itself by focusing on niche markets; high-value drugs for rare diseases of low prevalence, but for which a rich return on investment could be reaped. Is this picture correct? Areas covered: This analysis looks across the rare diseases to determine the top disease targets, the most active drug developers and density by drug development phase, using data from a proprietary pipeline drug database. Examples of different development strategies (orphan expansion to other orphan designations; mainstream disease to orphan; orphan expansion to mainstream) are also highlighted. Expert opinion: The growing trend in orphan drug designations and approvals of drugs to treat the rare diseases is likely unsustainable, largely due to pressure on health care bodies and governments to reduce costs at a time of widespread austerity. As more targeted therapies are developed along with companion diagnostics, diseases will become more segmented – to the point where a once prevalent disease meets the rare disease designation. Cancer drug development is already demonstrating this trend.
Metabolic Implications of Peritoneal Dialysis in Patients with Acute Kidney Injury

♦ Background: Peritoneal dialysis (PD) is a treatment for selected acute kidney injury patients (AKI), but little is known about its metabolic implications. The aim of the present study was to evaluate the metabolic implications of glucose absorption, sodium removal, protein loss into the dialysate, and catabolism in AKI patients undergoing high-volume PD and to identify risk factors associated with those metabolic effects. ♦ Methods: A prospective cohort study over 18 consecutive months evaluated 208 sessions of high-volume PD performed in 31 AKI patients. One session of high-volume PD lasted 24 hours. Repeated-measures analysis was performed, and correlations were calculated using the Spearman test for continuous variables and generalized linear models for categorical variables. ♦ Results: Glucose absorption remained at approximately 35.3% ± 10.5% per session. Protein loss measured 4.2 ± 6.1 g daily, with higher values initially, which declined significantly after 2 sessions. Nitrogen balance (NB) was initially negative, but stabilized at approximately zero after 3 sessions. Glucose uptake was positively correlated with the Acute Tubular Necrosis Individual Severity Score [ATNISS (r = 0.21, p = 0.0036)], C-reactive protein (r = 0.26, p = 0.0167), protein loss (r = 0.36, p < 0.0001), and sodium removal (r = 0.24, p = 0.002). Protein loss was positively correlated with sodium removal (r = 0.22, p = 0.0085) and gastrointestinal disease (p = 0.0004). Sodium removal was positively correlated with serum sodium (r = 0.21, p = 0.0064), ATNISS (r = 0.15, p = 0.0411), urea nitrogen appearance [UNA (r = 0.24, p = 0.0019)], and fluid overload as an indication for dialysis (p < 0.0001). Urea nitrogen appearance was positively correlated with the indication for dialysis (electrolyte disturbances: p = 0.0287) and negatively correlated with nephrotoxic AKI (p < 0.0001). Nitrogen balance was negatively correlated with UNA (r = -0.389, p < 0.0001) and ischemic AKI (p = 0.0047). ♦ Conclusions: High-volume PD did not increase hypercatabolism in AKI patients, and protein loss and glucose uptake remained constant during treatment. Those parameters were influenced by the clinical condition of the patients, including the cause of AKI, inflammation, and comorbidities—factors that should be known before the prescription of dialysis and nutrition, thus avoiding metabolic complications such as hyperglycemia, hypernatremia, and worsening catabolism.
Delirium and acute stroke: the occurrence of delirium and its association with long term outcomes for patients post-stroke

Introduction: Delirium is an acute generalised impairment of brain function and a common complication of illness in older people. However it is commonly overlooked or misdiagnosed in clinical practice. Previous studies have found that delirium is linked to longer hospital stays, an increased need for institutionalisation and future complications e.g. increased risk of dementia and mortality. Delirium onset may be associated with an acute stroke, although few studies have investigated this association. The aims of this study were to identify delirium incidence in stroke, compare long term patient outcomes and identify confounding variables that may affect delirium onset. Methods: Based on the findings from the systematic review, a UK based prospective cohort study with a one year follow up period was designed to recruit stroke patients with and without delirium. Additional assessments were administered within 72 hours of admission to assess physical function, mood, risk of dementia and cognitive impairment. These assessments were repeated six months post-stroke as well as monitoring outcomes such as mortality, length of stay and discharge destination. Results: A total of 298 patients were recruited from the stroke unit at the Leeds Teaching Hospitals Trust, with a delirium incidence of 32.9%. Patients with delirium were associated with longer hospital stays, higher mortality rates at one and six months and an increased need for institutionalisation, as well as positive associations with a number of predisposing factors. Delirium patients also had lower assessment scores for physical function and dementia risk at six months. Conclusion: The results of this study show that delirium has a significant effect on outcomes for stroke patients. Increased emphasis and awareness of delirium on the stroke units could help increase detection rates of delirium. Suggestions for the implementation of better education programmes and screening protocols may aid delirium management and these require further research.
Utilidad en la combinación de oligonucleótidos universales para la detección del virus del papiloma humano en cáncer cervicouterino y lesiones premalignas

Objective. To determine the prevalence of human papillomavirus (HPV) infection at different stages of the natural history of cervical cancer. Also, to optimize its detection by means of different sets of general primers. Material and Methods. A descriptive, cross-sectional study was conducted between January and December 1999. Samples were processed and analyzed at the Instituto Nacional de Cancerologia (National Cancerology Institute) in Mexico City. A comparative analysis was performed using Student’s t for continuous values and the chi-squared test for proportions. A contingency analysis was made between biopsy and cervical exudates with the Kappa statistic. HPV detection was done by PCR with general primers which recognize different regions of the L1 gene (MY09/11; GP5/6; L1C1/2) and with HPV16- and HPV18- specific primers, as well as direct sequencing of PCR products. Results. In total, 154 samples were analyzed: 65 (42.2%) of them showed normal cytology; 45 (29.2%) high and low grade lesions; and 44 (28.6%) invasive cervical cancer. HPV was detected in 95.5% of invasive cervical cancers, in 91.6% of high grade lesions, in 66.7% of low grade lesions, and in 23.1% of normal smears, by PCR with at least one set of oligonucleotide primers. HPV detection was more efficient in biopsy specimens than in cervical scrapes. The total percentage of HPV detection us
Desidratação e recomendações para a reposição hídrica em crianças fisicamente ativas

Objective: The practice of physical exercises leads to dehydration due to heat production. Most studies that address the risks of dehydration and provide recommendations for restoring water are directed to adults living in temperate climate regions, but little is known about the needs of restoring water to physically active children in tropical regions. This review discusses the recommendations for this population and the risks of sports practice in tropical climate areas. Data source: Systematic analysis of the national (SciELO) and international (Medline) literature from 1972 to 2009, with the following keywords, alone or in combination, in Portuguese and English: hydration, children, dehydration and water replacement. Data synthesis: There are risks related to dehydration and possible development of hyperthermia especially in adverse
Wireless Sensor Network and RFID Fusion Approach for Mobile Robot Navigation

There are numerous applications for mobile robots that require relatively high levels of speed and precision. For many systems, these two properties are a tradeoff, as oftentimes increasing the movement speed can mean failing to detect some sensors. This research attempts to create a useful and practical system by combining a wireless sensor network with a passive radio frequency identification system. The sensor network provides fast general navigation in open areas and the radio frequency identification system provides precision navigation near static obstacles. By fusing the data from both systems, we are able to provide fast and accurate navigation for a mobile robot. Additionally, with WSN nodes and passive RFID tag mats, the system infrastructure can be easily installed in existing environments.