Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of ischemia-reperfusion damage during coronary angioplasty. Electrocardiographic assessment and biochemical modifications in blood from the coronary sinus.

BACKGROUND Percutaneous transluminal coronary angioplasty (PTCA) constitutes a clinical model of reperfusion following a short period of ischemia connected to balloon inflation during the procedure. During the procedure some ischemic damage and oxidative injury related to free radical attack might occur. In the present study we investigated the extent of ischemic damage and some biochemical indexes of reperfusion damage in patients undergoing PTCA. METHODS Twenty-five patients who underwent PTCA because of angiographically detected occlusion of the coronary artery were enrolled. Balloon inflation lasted from 30 to 60 s. ECG changes were monitored throughout the procedure and blood samples were taken from the coronary artery and coronary sinus before balloon inflation, and again from coronary sinus at the peak of ischemia, 2 and 10 min after reperfusion. RESULTS During PTCA procedure angina pectoris appeared in 62.7% of patients, whereas ST-segment elevation was present in 87% of patients, regressing completely after balloon deflation. Plasma malonyldialdehyde, an index of lipid peroxidation, did not change; coenzyme Q10 (in its oxidized and reduced forms), vitamin E and beta-carotene were also unchanged. Total antioxidant capacity and uric acid decreased upon reperfusion. CONCLUSIONS Myocardial ischemia occurring during balloon inflation is brief and regresses completely after balloon deflation. Reperfusion following a short period of acute ischemia such as in PTCA does not constitute an oxidative event detectable through a common marker of lipid peroxidation nor does it alter the concentration of lipophilic antioxidants. It only lowers hydrosoluble antioxidants therefore representing a mild oxidative insult.
Management of substernal goiter

Objective: To analyze the presentation, evaluation and treatment of patients with large substernal goiters, with emphasis on the radiographic evaluation and the results of treatment. Study Design: A retrospective chart review of 150 patients undergoing thyroidectomy at the Vanderbilt University Department of Otolaryngology—Head and Neck Surgery. Methods: Charts of patients undergoing thyroidectomy were reviewed. Those with substernal goiter, defined as a major portion of the goiter within the mediastinum, were included in the study. When available, the radiographic studies were reviewed by a staff neuroradiologist. Results: Twenty‐three patients (15.3%) presented with substernal extension of the goiter. Characteristics of these patients included mean age of 59 years, 78% female, symptoms of compression such as dyspnea, choking, and dysphagia (65%), hoarseness (43%), and previous thyroid surgery (30%). Seventeen percent were asymptomatic. Preoperative radiographs demonstrated tracheal compression (73%), tracheal deviation (77%), esophageal compression (27%), and major vessel displacement (50%). Histology revealed multinodular goiter (16/23, 70%), thyroiditis (3/23, 13%), and malignancy (4/23, 17%). The average size of the resected specimen in greatest dimension was 8.0 cm (range, 3.0–14.0 cm) and weighed 148 g (range, 39–426 g). All were successfully approached through a transcervical incision without the need for sternotomy, and total thyroidectomy was performed in 83% of the cases. No major complications have been documented, and no evidence of tracheomalacia was encountered. Conclusion: Despite the large size of these goiters and the significant involvement of the major mediastinal structures, all were approached through the transcervical incision. Further, despite significant tracheal involvement, there were no cases of tracheomalacia or major complications. For intraoperative planning, the authors advocate the routine use of preoperative computed tomography scanning. Laryngoscope, 108:1611–1617, 1998
A clinical model to estimate the pretest probability of lung cancer in patients with solitary pulmonary nodules.

BACKGROUND Estimating the clinical probability of malignancy in patients with a solitary pulmonary nodule (SPN) can facilitate the selection and interpretation of subsequent diagnostic tests. METHODS We used multiple logistic regression analysis to identify independent clinical predictors of malignancy and to develop a parsimonious clinical prediction model to estimate the pretest probability of malignancy in a geographically diverse sample of 375 veterans with SPNs. We used data from Department of Veterans Affairs (VA) administrative databases and a recently completed VA Cooperative Study that evaluated the accuracy of positron emission tomography (PET) scans for the diagnosis of SPNs. RESULTS The mean (+/- SD) age of subjects in the sample was 65.9 +/- 10.7 years. The prevalence of malignant SPNs was 54%. Most participants were either current smokers (n = 177) or former smokers (n = 177). Independent predictors of malignant SPNs included a positive smoking history (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.6 to 23.6), older age (OR, 2.2 per 10-year increment; 95% CI, 1.7 to 2.8), larger nodule diameter (OR, 1.1 per 1-mm increment; 95% CI, 1.1 to 1.2), and time since quitting smoking (OR, 0.6 per 10-year increment; 95% CI, 0.5 to 0.7). Model accuracy was very good (area under the curve of the receiver operating characteristic, 0.79; 95% CI, 0.74 to 0.84), and there was excellent agreement between the predicted probability and the observed frequency of malignant SPNs. CONCLUSIONS Our prediction rule can be used to estimate the pretest probability of malignancy in patients with SPNs, and thereby facilitate clinical decision making when selecting and interpreting the results of diagnostic tests such as PET imaging.
Translocation and clustering of endosomes and lysosomes depends on microtubules

Indirect immunofluorescence labeling of normal rat kidney (NRK) cells with antibodies recognizing a lysosomal glycoprotein (LGP 120; Lewis, V., S.A. Green, M. Marsh, P. Vihko, A. Helenius, and I. Mellman, 1985, J. Cell Biol., 100:1839-1847) reveals that lysosomes accumulate in the region around the microtubule-organizing center (MTOC). This clustering of lysosomes depends on microtubules. When the interphase microtubules are depolymerized by treatment of the cells with nocodazole or during mitosis, the lysosomes disperse throughout the cytoplasm. Lysosomes recluster rapidly (within 30-60 min) in the region of the centrosomes either upon removal of the drug, or, in telophase, when repolymerization of interphase microtubules has occurred. During this translocation process the lysosomes can be found aligned along centrosomal microtubules. Endosomes and lysosomes can be visualized by incubating living cells with acridine orange. We have analyzed the movement of these labeled endocytic organelles in vivo by video- enhanced fluorescence microscopy. Translocation of endosomes and lysosomes occurs along linear tracks (up to 10 microns long) by discontinuous saltations (with velocities of up to 2.5 microns/s). Organelles move bidirectionally with respect to the MTOC. This movement ceases when microtubules are depolymerized by treatment of the cells with nocodazole. After nocodazole washout and microtubule repolymerization, the translocation and reclustering of fluorescent organelles predominantly occurs in a unidirectional manner towards the area of the MTOC. Organelle movement remains unaffected when cells are treated with cytochalasin D, or when the collapse of intermediate filaments is induced by microinjected monoclonal antivimentin antibodies. It can be concluded that translocation of endosomes and lysosomes occurs along microtubules and is independent of the intermediate filament and microfilament networks.
Evolutionary foundations of human prosocial sentiments

A growing body of evidence shows that humans are remarkably altruistic primates. Food sharing and division of labor play an important role in all human societies, and cooperation extends beyond the bounds of close kinship and networks of reciprocating partners. In humans, altruism is motivated at least in part by empathy and concern for the welfare of others. Although altruistic behavior is well-documented in other primates, the range of altruistic behaviors in other primate species, including the great apes, is much more limited than it is in humans. Moreover, when altruism does occur among other primates, it is typically limited to familiar group members—close kin, mates, and reciprocating partners. This suggests that there may be fundamental differences in the social preferences that motivate altruism across the primate order, and there is currently considerable interest in how we came to be such unusual apes. A body of experimental studies designed to examine the phylogenetic range of prosocial sentiments and behavior is beginning to shed some light on this issue. In experimental settings, chimpanzees and tamarins do not consistently take advantage of opportunities to deliver food rewards to others, although capuchins and marmosets do deliver food rewards to others in similar kinds of tasks. Although chimpanzees do not satisfy experimental criteria for prosociality in food delivery tasks, they help others complete tasks to obtain a goal. Differences in performance across species and differences in performance across tasks are not yet fully understood and raise new questions for further study.
Stevens–Johnson syndrome and toxic epidermal necrolysis: a review of treatment options

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous reactions that are medication‐induced in most instances. While the clinical manifestations of SJS and TEN are well‐defined, the optimal treatment for these disorders is not. Case reports have shown benefit with the use of a variety of agents including tumor necrosis factor‐alpha inhibitors and cyclophosphamide, whereas thalidomide was associated with an increased mortality. Plasmapheresis and cyclosporine have also demonstrated efficacy anecdotally, albeit with an even smaller number of cases in the literature. Most of the reporting has focused on the use of systemic corticosteroids and intravenous immunoglobulin (IVIG) for these severe reactions. The majority of studies analyzing the use of IVIG in the treatment of SJS/TEN show a benefit, though more recent series cast doubt upon this conclusion. The results of these studies are summarized in this present review study.
Reduction in Primary Nonfunction of Syngeneic Islet Transplants with Nordihydroguaiaretic Acid, a Lipoxygenase Inhibitor

To study the effectiveness of a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), in the reduction of primary nonfunction, an insufficient number of syngeneic islets were transplanted underneath the renal capsule with NDGA administered daily for 4 weeks. After transplantation of the 150 islets, the decrement of blood glucose levels was significantly faster in the mice that had received NDGA than in the mice that had received no drug at all or dimethyl sulfoxide (DMSO) (p < 0.005, p < 0.05). The mean duration of temporary posttransplant hyperglycemia was 22.3 ± 3.2 (n = 10), 35.9 ± 2.3 (n = 14), and 33.7 ± 4.1 (n = 6) days for the respective groups. The diabetic mice that received 300 islets had their blood glucose levels decrease faster than those that received 150 islets (19.7 ± 1.6 vs. 35.9 ± 2.3 days, n = 14, p < 0.0001). There was no significant difference in the blood glucose reducing effect between the mice that received 150 islets with NDGA and the mice that received 300 islets [22.3 ± 3.2 (n = 10) vs. 19.7 ± 1.6 (n = 14) days, p > 0.05]. The insulin content of the graft from the mice treated with 150 islets and NDGA (3.02 ± 0.24 μg, n = 4) was higher than that from the mice that received 150 islets but no treatment (1.10 ± 0.26 μg, n = 15, p < 0.005) or that had been treated with DMSO (1.21 ± 0.30 μg, n = 4, p < 0.05). The insulin content of the pancreas remnant had no significant differences among the three groups. The net glucose-stimulated insulin secretion was 0.82 ± 0.14 vs. 0.20 ± 0.10 μIU/islet × 60 min (n = 8, p < 0.005) and 0.59 ± 0.08 vs. 0.04 ± 0.02 μIU/islet × 60 min (n = 8, p < 0.0001) for islets cultured without NDGA vs. with NDGA at 1 and 2 weeks, respectively. However, the insulin content of the cultured islets was similar between the two groups for up to 2 weeks of incubation (at 1 week: 0.71 ± 0.01 vs. 0.67 ± 0.04 ng/islet, n = 8, p > 0.05; at 2 weeks: 0.71 ± 0.02 vs. 0.80 ± 0.07 ng/islet, n = 8, p > 0.05). Serum leukotriene B4 (LTB4) concentrations before and between the fifth and seventh days after transplantation were determined. For diabetic mice that received 150 islets, serum LTB4 levels were 25,835 ± 3,335 and 27,631 ± 3,136 pg/ml (n = 4, p > 0.05). For diabetic mice that received 150 islets and NDGA, the corresponding figures were 22,401 ± 2,706 pg/ml and 27,530 ± 2,190 pg/ml (n = 8, p > 0.05). The graft histology revealed viable islet cells and networks of close vascular structures around the islets and did not reveal microscopic differences among the samples of all four groups. In conclusion, our data revealed that daily administration of NDGA for 4 weeks enhanced isoislet engraftment and preserved three times more mass of the islet beta cells in the isografts. This result indicates that NDGA reduces primary nonfunction of islet syngeneic grafts in diabetic mice.
The results of amniotic membrane transplantation for symptomatic bullous keratopathy.

OBJECTIVES To evaluate the outcomes of amniotic membrane transplantation for symptomatic relief in patients with bullous keratopathy. MATERIAL AND METHOD This retrospective study included 17 eyes (17 patients) with bullous keratopathy presenting with intractable pain or discomfort. The patients were enrolled from January 2000 to December 2004. Amniotic membrane transplantation was performed. Symptomatic relief epithelial healing, and visual changes were analyzed. RESULTS During the follow up period of 14.1 +/- 11.9 months (range 1-36 months) after amniotic membrane transplantation, 14 eyes of 17 eyes (82.4%) with intolerable pain preoperatively had pain relief postoperatively. Corneal epithelial healing was complete in all except 2 eyes one of which had evisceration because of severe corneal ulcer, and the other underwent penetrating keratoplasty soon after amniotic membrane transplantation. CONCLUSION Amniotic membrane transplantation is a safe and effective treatment modality for pain relief associated with chronic bullous keratopathy. It can be an alternative to conjunctival flap, with better cosmetic appearance for the management of patients with bullous keratopathy.
Up-Regulation of UDP-Glucuronosyltransferase (UGT) 1A4 by 17β-Estradiol: A Potential Mechanism of Increased Lamotrigine Elimination in Pregnancy

Oral clearance of lamotrigine, an antiepileptic drug commonly used in pregnant women, is increased in pregnancy by unknown mechanisms. In this study, we show that 17β-estradiol (E2) up-regulates expression of UDP glucuronosyltransferase (UGT) 1A4, the major enzyme responsible for elimination of lamotrigine. Endogenous mRNA expression levels of UGT1A4 in estrogen receptor (ER) α-negative HepG2 cells were induced 2.3-fold by E2 treatment in the presence of ERα expression. E2 enhanced transcriptional activity of UGT1A4 in a concentration-dependent manner in HepG2 cells when ERα was cotransfected. Induction of UGT1A4 transcriptional activity by E2 was also observed in ERα-positive MCF7 cells, which was abrogated by pretreatment with the antiestrogen fulvestrant (ICI 182,780). Analysis of UGT1A4 upstream regions using luciferase reporter assays identified a putative specificity protein-1 (Sp1) binding site (–1906 to –1901 base pairs) that is critical for the induction of UGT1A4 transcriptional activity by E2. Deletion of the Sp1 binding sequence abolished the UGT1A4 up-regulation by E2, and Sp1 bound to the putative Sp1 binding site as determined by a electrophoretic mobility shift assay. Analysis of ERα domains using ERα mutants revealed that the activation function (AF) 1 and AF2 domains but not the DNA binding domain of ERα are required for UGT1A4 induction by E2 in HepG2 cells. Finally, E2 treatment increased lamotrigine glucuronidation in ERα-transfected HepG2 cells. Together, our data indicate that up-regulation of UGT1A4 expression by E2 is mediated by both ERα and Sp1 and is a potential mechanism contributing to the enhanced elimination of lamotrigine in pregnancy.
Testing the genomic control parameter

In genome-wide case-control association studies, the genomic control factor, λ, is generally computed to estimate the inflation of chi-square statistics due to population heterogeneity. For a given estimated λ value, all chi-square values are then divided by λ before their associated significance level is computed. We hypothesize that in some studies λ may not be significantly larger than 1, in which case division by λ leads to decreased power. Thus, we treat λ as a test statistic and evaluate the p=value associated with the null hypothesis, H<inf>0</inf>: λ = 1, versus the one-sided alternative, H<inf>1</inf>: λ > 1. Our analyses of published disease data show that, owing to the large number of SNPs generally used, observed λ values are in most cases significantly larger than 1.
Demystifying a Dark Art: Understanding Real-World Machine Learning Model Development

It is well-known that the process of developing machine learning (ML) workflows is a dark-art; even experts struggle to find an optimal workflow leading to a high accuracy model. Users currently rely on empirical trial-and-error to obtain their own set of battle-tested guidelines to inform their modeling decisions. In this study, we aim to demystify this dark art by understanding how people iterate on ML workflows in practice. We analyze over 475k user-generated workflows on OpenML, an open-source platform for tracking and sharing ML workflows. We find that users often adopt a manual, automated, or mixed approach when iterating on their workflows. We observe that manual approaches result in fewer wasted iterations compared to automated approaches. Yet, automated approaches often involve more preprocessing and hyperparameter options explored, resulting in higher performance overall--suggesting potential benefits for a human-in-the-loop ML system that appropriately recommends a clever combination of the two strategies.
Major bleeding rates after prophylaxis against venous thromboembolism: Systematic review, meta-analysis, and cost implications

Objectives: The frequency and consequences of major bleeding associated with anticoagulant prophylaxis for prevention of venous thromboembolism is examined. Methods: We conducted a systematic review and meta-analysis of controlled trials that reported rates of major bleeding after pharmaceutical thromboprophylaxis in patients undergoing major orthopedic surgery. Thromboprophylactic agents were divided into four groups:warfarin/other coumarin derivatives (WARF), unfractionated heparin (UFH), low molecular weight heparin (LMWH), and pentasaccharide (PS). Meta-analysis was conducted comparing LMWH with each of WARF, UFH, and PS. The frequency of re-operation due to major bleeding was reviewed and combined with published costs to estimate the mean cost of managing major bleeding events in these patients. Results: Twenty-one studies including 20,523 patients met inclusion criteria for the meta-analysis. No evidence of significant between-trial heterogeneity in risk ratios was found. Combined (fixed effects) relative risks (RR) of major bleeding compared with LMWH were WARF – RR 0.59 (95 percent confidence interval [CI], 0.44–0.80); UFH – RR 1.52 (95 percent CI, 1.04–2.23); PS – RR 1.52 (95 percent CI, 1.11–2.09). Seventy-one studies including 32,433 patients were included in the review of consequences of major bleeding. We estimated that the average cost of major bleeding is $113 per patient receiving thromboprophylaxis. Conclusions: LMWH results in fewer major bleeding episodes than UFH and PS but more than WARF. These events are costly and clinically important.
Understanding the Data-Action Cycle of Surveillance: A Qualitative Study of Federal and State Stakeholders

This qualitative study aims to understand how personnel in state and federal agencies view surveillance systems and the extent to which systematically collected data inform nutrition and physical activity policies and interventions addressing obesity. In-depth interviews were conducted with 17 respondents purposively sampled from state health departments, federal public health agencies, and prevention research centers. All informants acknowledged the importance of surveillance systems and influence of the data-action cycle for monitoring trends and increasing obesity awareness. However, state-level respondents believed surveillance systems should be designed for programmatic purposes, whereas federal participants thought they should be designed for monitoring. Respondents held differing opinions about the flexibility, timeliness, accessibility, and usefulness of existing national surveillance systems, highlighting significant differences in state and federal agencies’ perceptions and utilization of surveillance systems. Such discrepancies call for increased communication surrounding purposes and uses of surveillance data, enabling stronger partnerships between state and federal agencies.
Electronic tuning of a high frequency DC/AC inverter for inductive power transfer

The misalignment and displacement of the coupled coils in an inductive power transfer system reduce the power efficiency and limit the amount of power that can be transferred. Coil misalignment results in the primary coil driver to operate in an un-tuned state which causes non-optimum switching operation and results in an increase in switching losses. This paper presents a novel method to electronically tune a Class E inverter used as a primary coil driver in an inductive power transfer system to minimize the detrimental effects of misalignment between the inductively coupled coils which may occur during operation. The tuning method uses current controlled inductors (saturable reactors) and a variable switching frequency to achieve optimum switching conditions regardless of the misalignment. Mathematical analysis is performed on a Class E inverter based on a piecewise linear state-space model. Experimental results are presented to confirm the analysis approach and the suitability of the proposed tuning method.