Miracle-dz/UniFAR-FTUs huggingface dataset:
Animal models for glioma drug discovery

Introduction: High-grade gliomas are among the most deadly of all cancer types and are also the most common malignant primary tumors of the CNS. Large-scale studies that have analyzed the transcriptional and translational expression patterns of glioma have found that the majority of these tumors can be categorized based on specific genomic anomalies. Genetically engineered mouse models (GEMMs) that represent the molecular subgroups of the human disease harbor a variety of molecular alterations that have been proven to drive gliomagenesis. These models provide an opportunity to assess the effects of novel therapies in the presence of specific molecular defects. Research using GEMMs, which are associated with these subclasses, allow researchers to assess drug efficacy by subclass. Areas covered: In this review, the authors discuss the histological and molecular characteristics of malignant gliomas, the therapies used to treat them and the animal models that closely recapitulate them. Expert opinion: It is likely that GEMMs that recapitulate the molecular character of human tumors will provide a more accurate prediction of individuals who may be more or less likely to benefit from specific therapies. This knowledge can be then used to drive clinical trial design and this, in turn, could lead to better therapeutic outcomes.
Hemostasis Testing during Massive Blood Replacement A Study of 172 Cases

Abstract. A 24‐hour service was organized to study changes in the hemostatic system in surgical patients undergoing massive transfusion for excessive bleeding during operation or in the early postoperative period. Hemostasis tests gave normal results in only 12 (7%) of the 172 patients, while in the remaining 160 (93%) one or more tests gave abnormal results. The platelet count was the most frequently abnormal, followed by the prothrombin time and plasma fibrinogen. Well‐defined hemostatic disorders (such as DIC, heparinization and liver disease) were ascertained in 82 patients (48%). 78 patients (45%) had less specific laboratory abnormalities, with a particularly high incidence of thrombocytopenia and less pronounced alterations in the coagulation tests. Unlike the patients with defined disorders, the strong inverse correlation in this group between platelet count, prothrombin time, plasma fibrinogen, and the number of transfusions suggests that the laboratory abnormalities were induced by massive blood replacement. Standard schemas involving the administration of platelet concentrates and/or fresh‐frozen plasma without evaluation of hemostasis did not help to reduce the incidence of abnormalities. These measures also failed to decrease the requirements for whole blood and/or packed red cells. Therefore, indiscriminate administration in the massively transfused postoperative patient of blood components based on preestablished schemes appears to be unjustified. An approach based on hemostasis screening, identification of the underlying disorder, directed therapeutic intervention and laboratory monitoring is likely to be more effective.
INSTRUCTIONAL DESIGN AND ASSESSMENT An Interprofessional Learning Module on Asthma Health Promotion

Objective. To develop, implement, and evaluate a new interprofessional learning module that focused on asthma health promotion called Taking Action Together for Asthma. Design. Faculty members in medicine, nursing, and pharmacy courses recruited 10 students each to participate in a 3-day interprofessional learning module. Students received extensive materials including a workbook to document their expectations and experience; completed a 1-day interprofessional workshop; received training in the Triple A (Adolescent Asthma Action) program; and went into high schools and taught the Triple A program to students in interprofessional teams. Assessment. Before and after participating in the module, students completed a questionnaire consisting of 3 previously validated instruments: the Asthma Knowledge for Health Professionals Scale, Attitudes Toward Health Care Teams Scale, and Readiness for Interprofessional Learning Scale (RIPLS). Seventeen students completed both the pre- and post-module scales and significant changes were seen only in means scores for the Attitude Toward Healthcare Teams (81.0 6 4.7 to 85.2 6 5.9) and the Teamwork and Collaboration subscale of the RIPLS (41.4 6 2.7 to 43.2 6 2.7). Conclusion. Health promotion activities offer a viable mechanism for fostering interprofessional learning among health professions students.
Distinct Structural Features of Phospholipids Differentially Determine Ethanol Sensitivity and Basal Function of BK Channels

Large conductance Ca2+-activated K+ (BK) channel activity and its potentiation by ethanol are both critically modulated by bilayer phosphatidylserine (PS), a phospholipid involved in membrane-bound signaling. Whether PS is uniquely required for ethanol to modify channel activity is unknown. Furthermore, the structural determinants in membrane phospholipid molecules that control alcohol action remain to be elucidated. We addressed these questions by reconstituting BK channels from human brain (hslo) into bilayers that contained phospholipids differing in headgroup size, charge, and acyl chain saturation. Data demonstrate that ethanol potentiation of hslo channels is blunted by conical phospholipids but favored by cylindrical phospholipids, independently of phospholipid charge. As found with ethanol action, basal channel activity is higher in bilayers containing cylindrical phospholipids. Basal activity and its ethanol potentiation in bilayers containing phosphatidylcholine, however, are not as robust as in those containing PS. These results are best interpreted as resulting from the relief of bilayer stress caused by inclusion of cylindrical phospholipids, with this relief being synergistically evoked by molecular shape and negative headgroup charge. Present findings suggest that hslo gating structures targeted by ethanol are accessible to sense changes in bilayer stress. In contrast, hslo unitary conductance is significantly higher in bilayers that contain negatively charged phospholipids independently of molecular shape, a result that is likely to be dependent on an interaction between anionic phospholipids and deep channel residues coupled to the selectivity filter.
CD40 engagement induces monocyte procoagulant activity through an interleukin‐10 resistant pathway

Interactions between membrane‐bound molecules were previously shown to be involved in the induction of tissue factor‐dependent monocyte procoagulant activity (PCA) by activated T cells. To investigate the potential role of the CD40/CD40 ligand (CD40L) pathway in this process, we first determined the effects of blocking anti‐CD40 or anti‐CD40L monoclonal antibodies (mAb) on the development of monocyte PCA during mixed lymphocyte reaction (MLR) between allogeneic peripheral blood mononuclear cells (PBMC). The strong inhibitory effect exerted by both mAb (mean percentages of inhibition: 88 and 91% for anti‐CD40 and anti‐CD40L mAb, respectively) indicates that CD40/CD40L interactions are required for the induction of PCA in MLR. These data led us to measure monocyte PCA after incubation of PBMC or purified monocytes with a stimulating anti‐CD40 mAb (BL‐C4) or with 3T6 fibroblasts transfected with the gene encoding CD40L. In both systems, we found that CD40 engagement strongly induced monocyte PCA which was related to tissue factor expression as shown by flow cytometric analysis. Finally, we observed that recombinant interleukin (IL)‐10, which inhibits lipopolysaccharide‐induced PCA, did not significantly influence CD40‐dependent PCA. We conclude that CD40 engagement on monocytes induces tissue factor‐dependent PCA through an IL‐10‐resistant pathway. These findings have implications for the control of coagulation events triggered by interactions between T cells and monocytes.
Prevalence of cardiovascular risk factors in patients with psoriasis.

OBJECTIVES The main goal of the study was to describe the demographic, epidemiological, clinical and laboratory characteristics of a monitored group of patients with psoriasis to assess the prevalence of cardiovascular comorbidities and to define the cardiovascular risk profile. METHODS One hundred and ninety outpatients aged over 18 were included in the prospective observational cross-sectional study. Demographic and clinical data were obtained from patients. The severity of psoriasis was evaluated using the Psoriasis Area and Severity Index (PASI) and the Dermatology Life Quality Index (DLQI). The results of laboratory testing were identified based on patient health records. RESULTS Based on an evaluation of psoriasis phenotypes, 150 patients (78.95%) suffered from plaque psoriasis, 18 (9.5%) from palmoplantar psoriasis, 11 (5.8%) from guttate psoriasis, 6 (3.2%) from generalized pustular psoriasis, and 5 (2.6%) from erythrodermic psoriasis. The personal medical history discovered the occurrence of arterial hypertension in 83 patients (43.7%), the occurrence of depression in 49 patients (25.8%), type 2 diabetes in 29 patients (15.3%), and dyslipidaemia in 48 patients (25.3%). CONCLUSION It is noteworthy that psoriasis may be demonstrated as a multi-system disease which does not only affect the skin and its adnexa. The association of psoriasis with comorbidities may significantly increase morbidity and total mortality as well as the demands for health care provision.
Hybrid parallel-slant hole collimators for SPECT imaging

We propose a new collimator geometry, the hybrid parallel-slant hole geometry (HPS), to improve sensitivity for SPECT imaging with large field of view (LFOV) gamma cameras. A HPS collimator has one segment with parallel holes and one or more segments with slant holes. The collimator can be mounted on a conventional SPECT LFOV system that uses parallel-beam collimators, and no additional detector or collimator motion is required for data acquisition. The parallel segment of the collimator allows for the acquisition of a complete data set of the organs-of-interest and the slant segments provide additional data. In this work, simulation studies of an MCAT phantom were performed with an HPS collimator with one slant segment. The slant direction points from patient head to patient feet with a slant angle of 30/spl deg/. We simulated 64 projection views over 180/spl deg/, and we modeled nonuniform attenuation effect. Images were reconstructed using an OSEM algorithm that incorporated the hybrid geometry. Sensitivity to the cardiac region of the phantom was increased by approximately 50% when using the HPS collimator compared with a parallel-hole collimator. No visible artifacts were observed in the reconstructed images and the signal-to- noise ratio (SNR) of the cardiac walls was improved. Compared with collimators with other geometries, using a HPS collimator has the following advantages: (a) significant sensitivity increase, (b) a complete data set obtained from the parallel segment that allows for artifact-free image reconstruction, and (c) no additional collimator or detector motion. This work demonstrates the potential value of hybrid geometry in collimator design for LFOV SPECT imaging.
Understanding of suspension DC plasma spraying of finely structured coatings for SOFC

Suspension plasma spraying was used to achieve a dense and thin (/spl sim/30 /spl mu/m) yttria stabilized zirconia (YSZ) coating for the electrolyte of solid oxide fuel cells (SOFCs). A suspension of YSZ powder (d/sub 50//spl sim/1 /spl mu/m) was mechanically injected in direct current (dc) plasma jets. The plasma jet acted as an atomizer and the suspension drops (d/spl sim/200 /spl mu/m) were sheared, long before they started vaporizing, into many droplets (d/spl sim/2 /spl mu/m). The solvent of the latters was then very rapidly (a few microseconds) evaporated and decomposed by the plasma jet. The solid particles enclosed in each droplet were then accelerated and melted before impacting on the substrate where they formed splats. The thermal inertia of particles with sizes below 1 /spl mu/m being low, the standoff distance was much shorter than in conventional plasma spraying (40-60 against 100-120 mm). Thus, the heat flux from the plasma to the coating reached 20 MW/spl middot/m/sup -2/ when spraying YSZ suspensions with Ar-H/sub 2/ or Ar-H/sub 2/-He plasma jets. It allowed keeping the whole pass (about 0.8-/spl mu/m-thick) completely molten resulting after its solidification, for YSZ, in a fully dense coating (20-30-/spl mu/m-thick) with a granular microstructure.
A global meta-analysis of soil phosphorus dynamics after afforestation.

Afforestation significantly affects soil chemistry and biota, but its effects on the potentially growth-limiting nutrient phosphorus (P) had not to our knowledge been analyzed globally. We conducted a comprehensive meta-analysis of 220 independent sampling sites from 108 articles to evaluate global patterns and controls of soil P change following afforestation. Overall, total P concentration decreased by 11% and total P stock by 12% in the top 20 cm of mineral soil following afforestation, with no change in available P. Time since afforestation had no consistent effect on total P, while available P tended to increase with time. Prior land cover was the most influential factor for soil P change after afforestation, with available P increasing on native vegetation but decreasing on cropland. Afforestation increased available P by 22% without decreasing total P on formerly 'degraded' land, but depleted total P by 15% at nondegraded sites. Climate also influenced soil P response to afforestation, with larger P loss in the tropics. Afforestation did not appear to directly induce P limitation, as available P only decreased on cropland. However, substantial declines in total P may drive tropical plantations toward greater P limitation as the capacity to replenish available P decreases.
Why blacks do not take part in HIV vaccine trials.

BACKGROUND AIDS is still a major cause of death. To combat this disease, researchers are developing a vaccine. Although blacks account for most new infections in the United States, they account for a low percent of experimental vaccine recipients. This study, conducted in a mid-sized U.S. city where vaccine trials are held, seeks to learn why. METHODS We conducted 11 in-depth ethnographic interviews. Two groups were targeted: blacks who had not participated in HIV vaccine trials and blacks who had. RESULTS Overall, three major causes of nonparticipation were identified: misinformation, fear/mistrust and stigma. Factors that favored participation included having close friends with HIV and being homosexual. CONCLUSIONS HIV is considered by many blacks to be a gay, white disease. Steps to increase participation must include efforts to destigmatize the condition and disseminate accurate information. Efforts to address historical causes of mistrust through "education" alone are insufficient. Trust needs to be earned through long-term relationships with black communities.
Patient and staff radiation dosimetry during cardiac electrophysiology studies and catheter ablation procedures: a comprehensive analysis.

AIMS To perform a comprehensive analysis of all aspects of patient and in-room personnel radiation dosimetry in interventional electrophysiology. METHODS AND RESULTS Measurements were performed during 19 diagnostic electrophysiology studies and 24 catheter ablations. Kerma-area product and exposure time values were 48.7 (6.4-230) Gy cm2 and 25.5 (4.4-79.2) min for ablation, and 12.5 (4.5-117.2) Gy cm2 and 4.5 (1.2-31) min for diagnostic studies, respectively. Patient effective doses were 15.2 (2.1-59.6) mSv for ablation and 3.2 (1.3-23.9) mSv for diagnostic procedures. Radiation risk to the patient was estimated to be up to eight cases of fatal cancer in 10,000 procedures. The risk of development of fatal cancer was less than 3x10(-6) per procedure to the primary operator. The risk for the nurse and technician was much lower. The dose per procedure for the primary operator was 7.1 microGy at the eyes, 0.79 microGy at the chest under the lead apron, 13.68 microGy at the chest over the apron, 3.82 microGy at the thyroid, 17.76 microGy at the left hand, and 12.11 microGy at the left knee. CONCLUSION As far as radiation exposure is concerned, electrophysiology studies followed by radiofrequency ablation are safe procedures for both patient and personnel when performed in catheterization laboratories with modern equipment, experienced operators, and standard safety precautions.
HIGH FREQUENCY OF APOPTOSIS IN INFANTILE CAPILLARY HAEMANGIOMA

Infantile capillary haemangioma (ICH) is a well‐established clinicopathological entity which often regresses spontaneously. To elucidate the cause of spontaneous involution of ICH, the apoptotic and proliferative activities in seven cases of ICH were compared with those in five cases of lobular capillary haemangioma (LCH), using formalin‐fixed paraffin‐embedded tissue sections. The number of apoptotic cells detected by the modified in situ end‐labelling method was significantly higher in ICH than in LCH, while the proliferative activities evaluated with mitosis and Ki‐67 antigen expression did not differ significantly. Lewisy (Ley) antigen, an apoptosis‐associated marker, was expressed in all cases of ICH but in none of LCH, while labelling for p53 protein and bcl‐2 protein was almost completely negative in both tumours. These findings clearly demonstrate a much higher apoptotic activity in ICH than in LCH and suggest that apoptosis might be a cause of the spontaneous involution of ICH.
P Glycoprotein: A New Mechanism to Control Drug-Induced Nephrotoxicity

The role of P glycoprotein (P-gp) in kidney is now being explored, and under physiological conditions, this protein is thought to be an excretory pump of cationic xenobiotics and metabolites. Functionally, two different types of P-gp have been described, but only the class I has been related to drug transport, and its overexpression confers the multidrug resistance phenotype in tumoral cells. It has been proposed that P-gp is involved in the energy-dependent transport of substrates through the cell membrane (toxic metabolites, toxins, nutrients, ions, peptides, etc.) – like a ‘hydrophobic molecule vacuum cleaner’. Several physiological functions have been attributed to P-gp: defense against xenobiotic aggression and transmembrane transport of prenylcysteine methyl esters, removing these cytotoxic metabolites from cells. A variety of substrates ranging from chemotherapeutics to steroid hormones, antibiotics, and calcium channel blockers can be transported by P-gp, suggesting the possible involvement of this protein in other unknown functions. Results from our group and others have suggested that overexpression of P-gp in renal tubular and mesangial cells prevents pharmacological nephrotoxicity by cyclosporin A (CsA). On the other hand CsA, a substrate of the pump, could act as a blocker in tubular cells by competitive inhibition. One relevant aspect in kidney is the possible relationship between P-gp and protein kinase C. Several reports suggest that protein kinase C may play a role in inducing the P-gp overexpression in cells under xenobiotic pressure, through activation of the ras oncoprotein family. This could be mediated directly by angiotensin II as a ras activator. This way, the detoxicant function of P-gp against products of the ras catabolism could mediate their accumulation when the ‘vacuum cleaner’ function is blocked by CsA or tacrolimus, contributing to the initial development of fibroblastic activation that leads to interstitial fibrosis associated with nephrotoxicity by these immunosuppressor drugs. In conclusion, P-gp expression could be an important component of a complex detoxifying system in kidney against xenobiotics or regulating the traffic of endogenous metabolites responsible for the susceptibility of subjects to the development of nephrotoxicity against different drugs.
Tracking Alcohol Consumption Over Time

Researchers are tracking long-term changes in alcohol consumption and related behaviors or outcomes in order to detect trends in the entire population or certain subgroups, test models of alcohol-related outcomes, and understand the consequences of interventions. Such analyses must consider the complexity of typical lifetime consumption patterns. Major approaches to measuring alcohol consumption over time include aggregate measures of consumption (e.g., sales data), cross-sectional surveys, and longitudinal or panel surveys. When analyzing the data, researchers must try to ensure the comparability of measurements over time. The stability of various measures and the potential for combining different types of data are also important considerations when tracking alcohol consumption over time. If these requirements are met, the regular collection of data on aspects of alcohol consumption will greatly increase researchers’ understanding of the forces influencing a population’s alcohol consumption and its consequences.
Systematic psychosocial screening in a paediatric cardiology clinic: clinical utility of the Pediatric Symptom Checklist 17

Abstract Objective To examine the clinical utility of the Pediatric Symptom Checklist 17 for identifying psychosocial concerns and improving access to psychology services within a paediatric cardiology clinic. Method Parents of 561 children (aged 4–17 years) presenting for follow-up of CHD, acquired heart disease, or arrhythmia completed the Pediatric Symptom Checklist 17 as part of routine care; three items assessing parental (1) concern for learning/development, (2) questions about adjustment to cardiac diagnosis, and (3) interest in discussing concerns with a behavioural healthcare specialist were added to the questionnaire. A psychologist contacted the parents by phone if they indicated interest in speaking with a behavioural healthcare specialist. Results Percentages of children scoring above clinical cut-offs for externalising (10.5%), attention (8.7%), and total (9.3%) problems were similar to a “normative” primary-care sample, whereas fewer children in this study scored above the cut-off for internalising problems (7.8%; p<0.01). Sociodemographic, but not clinical, characteristics were associated with Pediatric Symptom Checklist 17 scores. 17% of the parents endorsed concerns about learning/development, and 20% endorsed questions about adjustment to diagnosis. History of cardiac surgery was associated with increased concern about learning/development (p<0.01). Only 37% of the parents expressing psychosocial concerns reported interest in speaking with a psychologist. Conclusions The Pediatric Symptom Checklist 17 may not be sensitive to specific difficulties experienced by this patient population. A questionnaire with greater focus on learning/development and adjustment to diagnosis may yield improved utility. Psychology integration in clinics serving high-risk cardiac patients may decrease barriers to behavioural healthcare services.