Miracle-dz/UniFAR-FTUs huggingface dataset:
Electric and thermal field effects in tissue around radiofrequency electrodes.

OBJECTIVE A study is carried out of the spatial distribution and time dependence of electric and thermal fields in the tissue around a radiofrequency (RF) electrode used in pain therapy. Finite-element calculation of the fields is performed, and results are compared with ex vivo tissue data. Field predictions are made for continuous and for pulsed RF applications. DESIGN A special RF cannula electrode is constructed with both macro and micro thermocouple sensors to measure both average and rapid, transitory temperature effects. Temperatures and impedances are recorded in liver and egg-white models using signal outputs from a commercially available RF lesion generator. These data are compared with the results of finite-element calculations using electric field equations and the bio-heat equation. RESULTS Average and pulsatory temperatures at the RF electrode are measured. Rapid temperature spikes during pulsed RF bursts are observed. These data compared well with theoretical calculations using known electrical and thermal tissue parameters. CONCLUSION Continuous RF lesioning causes heat destruction of neurons. Pulsed RF lesioning (PRFL) produces heat bursts with temperatures in the range associated with destructive heat lesions. PRFL also produces very high electric fields that may be capable of disrupting neuronal membranes and function. Finite-element calculations agree substantially with the measured data, giving confidence to their predictions of fields around the RF electrode.
Direct Binding of Cell Polarity Protein PAR-3 to Cell-Cell Adhesion Molecule Nectin at Neuroepithelial Cells of Developing Mouse*

PAR-3 is a cell polarity protein that localizes at tight junctions (TJs) by direct binding to an immunoglobulin (Ig)-like cell-cell adhesion molecule JAM-1 in mammalian epithelial cells. Another Ig-like cell-cell adhesion molecule nectin plays a role in the localization of JAM-1 at TJs in epithelial cells. Nectin furthermore plays a role in the organization of adherens junctions (AJs) and TJs. Nectin comprises a family of four members, nectin-1, -2, -3, and -4. Nectins are associated with the actin cytoskeleton through afadin, of which the PDZ domain binds to nectins through their C-terminal four amino acids. We show here that PAR-3 binds to nectin-1 and -3 in neuroepithelial cells of the embryonic telencephalon, which are equipped with AJs, but not with typical TJs. Nectin-1, -2, -3, and afadin, but not JAM-1, were concentrated at AJs in neuroepithelial cells of the embryonic telencephalon at E13.5 and PAR-3 co-localized with nectins. PAR-3 was co-immunoprecipitated with nectin-1 and -3, but not with nectin-2 or JAM-1, from the mouse whole brain at E13.5. Recombinant PAR-3 stoichiometrically bound to recombinant nectin-1 and -3. The first one of the three PDZ domains of PAR-3 bound to the C-terminal four amino acids of nectin-1 and -3. The affinities of PAR-3 and afadin for nectin-1 and -3 were similar. Cadherin-deficient L cells expressing nectin-1 and -3 formed nectin-1- and -3-based cell-cell junctions, respectively, where PAR-3 as well as afadin was recruited. These results indicate that nectin-1 and -3 are involved in the localization of PAR-3 at AJs in the neuroepithelial cells of the embryonic telencephalon.
Treatment and survival in children with pulmonary arterial hypertension: the UK Pulmonary Hypertension Service for Children 2001–2006

Objective: A retrospective study of the UK Pulmonary Hypertension Service for Children for the first 5-year period of its existence. Design and patients: Records of 216 children with idiopathic pulmonary arterial hypertension (IPAH) and associated pulmonary arterial hypertension (APAH) were reviewed. Kaplan-Meier survival curves were constructed for different diagnostic groups and for different therapies. Results: At cardiac catheterisation only 7.4% of those with IPAH and 6% of those with APAH responded positively to vasodilator testing and so were treated with nifedipine. Others needing treatment were given continuous intravenous epoprostenol, bosentan or sildenafil singly or in combination. For IPAH survival rates were 85.6%, 79.9% and 71.9% at 1, 3 and 5 years, respectively, compared with a survival time of less than a year in historical untreated controls. A combination of intravenous epoprostenol with either bosentan or sildenafil, or both, appeared to achieve the best outcome. Six children underwent lung transplantation. In APAH survival rates were 92.3%, 83.8% and 56.9% at 1, 3 and 5 years, respectively, postoperative congenital heart disease with severe pulmonary hypertension having the worst outcome. Conclusion: New pulmonary hypertension-specific medicines have improved survival in children as in adults. Outcome in this series compares favourably with international outcome data.
Optimal surgical management of Stage I non-small-cell lung cancer in an increasingly aging population: challenges and recent progress

Lung cancer remains the main cause of cancer deaths in the USA. The dismal prognosis for non-small-cell lung cancer (NSCLC) despite current advances in chemotherapy is disappointing. In an increasingly aging population, computed tomography screening allows the detection of very early Stage I NSCLC lesions. Although many retrospective trials have indicated better prognosis for those undergoing lobectomy versus sublobar resection (anatomical segmentectomy or wedge resection), the issue remains equivocal. This is particularly true for patients with significant comorbid cardiorespiratory disease compromising postoperative recovery. This review will describe landmark retrospective studies related to the topic, in an attempt to highlight the difficulties associated with surgical decision making. Key factors in the characteristics of the lesions will be examined equally with the ultimate objective of allowing the decision of lobectomy versus sublobar resection to be centered around the need of the individual patient per se. This review article will also provide an insight into ongoing randomized, prospective clinical trials on the subject, investigating into some of the emerging technologies from the laboratory and the clinic that will hopefully enable the provision of a solidly acceptable treatment plan for the Stage I NSCLC patient, with maximum survival rates and low disease recurrence.
Minimal residual disease detection defined as the malignant fraction of the total primitive stem cell compartment offers additional prognostic information in acute myeloid leukaemia

Introduction: Immunophenotypic detection of minimal residual disease (MRD) in bone marrow (BM) of acute myeloid leukaemia (AML) patients is of high prognostic relevance. Standard MRD percentage is assessed as a percentage of total white blood cells (WBCs) and is therefore highly dependent on WBC count. Peripheral blood (PB) contains more than five times lower MRD percentages. Therefore, PB in BM aspirates cause dilution of the MRD cells, possibly leading to false‐negative results for BM MRD. The latter is avoided when relating the fraction of malignant primitive cells, identified by aberrant marker expression [aberrant primitive cells (aPC)], to the total population of primitive cells. Such a fraction may in addition reflect an important biological parameter.
Role of Extracellular DNA in Initial Bacterial Adhesion and Surface Aggregation

ABSTRACT Extracellular DNA (eDNA) is an important component of the biofilm matrix. We show that removal of eDNA from Gram-positive bacteria reduces initial adhesion to and aggregation of bacteria on surfaces. Thermodynamic analyses indicated that eDNA introduces favorable acid-base interactions, explaining the effect of eDNA on aggregation and adhesion to the surface.
IN VITRO AND IN VIVO CORRELATION OF HEPATIC TRANSPORTER EFFECTS ON ERYTHROMYCIN METABOLISM: CHARACTERIZING THE IMPORTANCE OF TRANSPORTER-ENZYME INTERPLAY

The effects of hepatic uptake and efflux transporters on erythromycin (ERY) disposition and metabolism were examined by comparing results from rat hepatic microsomes, freshly isolated hepatocytes, and in vivo studies. Uptake studies carried out in freshly isolated rat hepatocytes showed that ERY and its metabolite (N-demethyl-ERY) are substrates of Oatp1a4 and Oatp1b2. Whereas rifampin and GG918 [GF120918: N-{4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)-ethyl]-phenyl}-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamine] exerted minimal effects on metabolism in microsomes, rifampin (2.5 μM) and GG918 (0.5 μM) significantly decreased and increased ERY metabolism in hepatocytes, respectively. Concentration-time course studies further demonstrated that, compared with the intracellular N-demethyl-ERY control area under the curve (AUC) (0.795 ± 0.057 μM · min), a decreased AUC (0.513 ± 0.028 μM · min, p < 0.005) was observed when ERY was coincubated with rifampin, and an increased AUC (2.14 ± 0.21 μM · min, p < 0.05) was found when GG918 was present. The results of the i.v. bolus studies showed that, compared with the ERY clearance of the controls (47.2 ± 12.5 ml/min/kg for the rifampin group and 42.1 ± 5.7 for the GG918 group), a decreased blood clearance, 29.8 ± 6.1 ml/min/kg (p < 0.05) and 21.7 ± 9.0 ml/min/kg (p < 0.01), was observed when rifampin or GG918, respectively, was coadministered. When either inhibitor was codosed with ERY, volume of distribution at steady state was unchanged, but t1/2 and mean residence time significantly increased compared with the controls. Hepatic uptake and efflux transporters modulate intracellular concentrations of ERY, thereby affecting metabolism. The interplay of transporters and enzymes must be considered in evaluating potential drug-drug interactions.
Maintaining Neutral Sagittal Cervical Alignment After Football Helmet Removal During Emergency Spine Injury Management

Study Design. Descriptive laboratory study. Objective. To determine whether the placement of padding beneath the occiput after helmet removal is an effective intervention to maintain neutral sagittal cervical spine alignment in a position comparable with the helmeted condition. Summary of Background Data. Current on-field recommendations for managing football athletes with suspected cervical spine injuries call for face mask removal, rather than helmet removal, because the combination of helmet and shoulder pads has been shown to maintain neutral cervical alignment. Therefore, in cases when helmet removal is required, recommendations also call for shoulder pad removal. Because removal of equipment causes motion, any technique that postpones the need to remove the shoulder pads would reduce prehospital motion. Methods. Four lateral radiographs of 20 male participants were obtained (age = 23.6 ± 2.7 years). Radiographs of participants wearing shoulder pads and helmet were first obtained. The helmet was removed and radiographs of participants with occipital padding were obtained immediately and 20 minutes later and finally without occipital padding. Cobb angle measurements for C2–C6 vertebral segments were determined by an orthopedic spine surgeon blinded to the study's purpose. Intraobserver reliability was determined using intraclass coefficient analysis. Measurements were analyzed using a 1×4 repeated-measures analysis of variance and post hoc pairwise comparisons with Bonferroni correction. Results. Intraobserver analysis showed excellent reliability (intraclass correlation = 1.0; 95% confidence interval [CI], 0.999–1.0). Repeated-measures analysis of variance detected significant differences (F3,17 = 13.34; P < 0.001). Pairwise comparisons revealed no differences in cervical alignment (all measurements reported reflect lordosis) when comparing the baseline helmeted condition (10.1° ± 8.7°; 95% CI, 6.0–14.1) with the padded conditions. Measurements taken after removal of occipital padding (14.4° ± 8.1°; 95% CI, 10.6–18.2) demonstrated a significant increase in cervical lordosis compared with the immediate padded measurement (9.5° ± 6.9°; 95% CI, 6.3–12.7; P = 0.011) and the 20-minute padded measurement (6.5° ± 6.8°; 95% CI, 3.4–9.7; P < 0.001). Conclusion. Although face mask removal remains the standard, if it becomes necessary to remove the football helmet in the field, occipital padding (along with full body/head immobilization techniques) may be used to limit cervical lordosis, allowing safe delay of shoulder pad removal.
Memory strength affects reporting of misinformation.

A model of long-term retention was used to examine whether and how the strength of original information (differences in learning and testing time) and the strength of misleading information (differences in timing and frequency) influence 3- to 5-year-olds' memory for an event. In three experiments, preschoolers viewed a slide presentation depicting an event, some of them were asked misleading questions, and memory for event details was tested. There was little evidence of memory impairment, but exposure to misleading information encouraged reporting of this information. Differences in learning influenced reporting in that children exposed to the event once reported more misled details than those who saw the event multiple times. Furthermore, preschoolers who saw the event once were just as susceptible to misleading information whether exposed to misinformation once or three times; however, preschoolers who had seen the event multiple times were susceptible only to repeated presentations of misinformation. Given that the reporting of misinformation is determined by the degree of integrity of both the original and misleading information, it is important to control for differences in trace strength for both types of information in future research.
Double-Stator Switched Reluctance Machines (DSSRM): Fundamentals and Magnetic Force Analysis

In this paper, a new switched reluctance machine with a double-stator configuration (DSSRM) is introduced. The proposed design is based on optimization of the motional forces, which leads to a high-grade electromechanical energy conversion process. A local examination of the force densities within and throughout a conventional switched reluctance machine (SRM) shows that the majority of the force produced is in the radial direction and does not contribute to motion. If the normal forces happen to be in the direction of motion, a larger motional force profile for SRM is yield. Based on these guidelines, a new SRM (DSSRM) is proposed. To compare energy conversion efficiency of DSSRM with that of the conventional SRM, a finite element model is constructed. An experimental prototype of the proposed machine is developed, and the phase inductance is measured. The results of our investigations indicate that the proposed geometry offers superior performance in terms of higher power density and higher percentage of the motional forces.
Expert consensus on blood pressure management of diabetic patients in China (中国糖尿病患者血压管理专家共识)

This Expert Consensus proposed by the Chinese Society of Endocrinology (CSE) updates concepts on hypertension management in patients with diabetes. It focuses on clinical outcomes literature published within the past 5 years and currently in press, and incorporates these new observations into modifications of established guidelines. Complications and mortality in diabetic patients are increased when hypertension is present. The present update focuses on questions such as what to do when a diabetic patient has an elevated blood pressure level when therapy is initiated and whether combinations of agents should be used as soon as possible. Although the strategies and principles of treatment remain unchanged, approaches to specific patient‐related issues influencing cardiovascular outcomes in people with diabetes have changed. Finally, an updated integrated management of multiple cardiovascular risk factors is provided and is suggested as a starting point to achieve blood pressure goals. In addition to controlling blood pressure, the CSE suggests that individualized strategies are equally important and that attention should be paid to other factors, including safety (which is the most important), feasibility, and health economic evaluation.
Translational Regulation of the JunD Messenger RNA*

JunD, a member of the Jun family of nuclear transcription proteins, dimerizes with Fos family members or other Jun proteins (c-Jun or JunB) to form the activator protein 1 (AP-1) transcription factor. The junD gene contains no introns and generates a single mRNA. Here we show that two predominant JunD isoforms are generated by alternative initiation of translation, a 39-kDa full-length JunD protein (JunD-FL) by initiation at the first AUG codon downstream of the mRNA 5′ cap and a shorter, 34-kDa JunD protein (ΔJunD) by initiation at a second in-frame AUG codon. The JunD mRNA contains a long, G/C-rich 5′-untranslated region that is predicted to be highly structured and is important for regulating the ratio of JunD-FL and ΔJunD protein expression. A third functional out-of-frame AUG directs translation from a short open reading frame positioned between the JunD-FL and ΔJunD start sites. In addition, three non-AUG codons also support translation, an ACG codon (in-frame with JunD) and a CUG are positioned in the 5′-untranslated region, and a CUG codon (also in-frame with JunD) is located downstream of the short open reading frame . Mutation of these start sites individually had no affect on ΔJunD protein levels, but mutation of multiple upstream start sites led to an increase in ΔJunD protein levels, indicating that these codons can function cumulatively to suppress ΔJunD translation. Finally, we show that the JunD mRNA does not possess an internal ribosome entry site and is translated in a cap-dependent manner.
Get Your Paws off of My Pixels: Personal Identity and Avatars as Self

There is an astounding silence in the peer-reviewed literature regarding what rights a person ought to expect to retain when being represented by an avatar rather than a biological body. Before one can have meaningful ethical discussions about informed consent in virtual worlds, avatar bodily integrity, and so on, the status of avatars vis-à-vis the self must first be decided. We argue that as another manifestation of the individual, an individual’s avatar should have rights analogous to those of a biological body. Our strategy will be to show that (1) possessing a physical body is not a necessary condition for possessing rights; (2) rights are already extended to representations of a person to which no biological consciousness is attached; and (3) when imbued with intentionality, some prostheses become “self. ” We will then argue that avatars meet all of the conditions necessary to be protected by rights similar to those enjoyed by a biological body. The structure of our argument will take the form of a conditional. We will argue that if a user considers an avatar an extension of the self, then the avatar has rights analogous to the rights of the user. Finally, we will discuss and resolve some of the objections to our position including conflicts that may arise when more than one individual considers an avatar to be part of the self.
The effect of thymidine kinase transduction and ganciclovir therapy on tumor vasculature and growth of 9L gliomas in rats.

Eradication of malignant brain tumors by in situ intratumoral, retrovirally mediated transfer of the herpes simplex virus thymidine kinase (HSVtk) gene, which sensitizes the tumor cells to ganciclovir, has recently been demonstrated in animal models. The observation that tumors studied in vitro and in animals can be completely eliminated despite only partial transduction of the tumor suggests a bystander mechanism that affects nontransduced tumor cells. Such a bystander effect is not completely understood and may represent a combination of several factors that lead to tumor eradication. Endothelial cells of the tumor blood vessels were shown to occasionally integrate the retroviral vector and thus become sensitized to ganciclovir. In the presence of vector-producer cells, which continuously release infectious viral particles, diffuse multifocal hemorrhages occurred during ganciclovir administration. When the tumor was composed of cells that had been transduced with the thymidine kinase gene before inoculation, no infectious viral particles were present within the tumor, no transduction of endothelial cells occurred, and no hemorrhages were observed during ganciclovir therapy. These observations suggest that tumor regression may be due, in part, to destruction of in vivo HSVtk-transduced endothelial cells after exposure to ganciclovir, resulting in tumor ischemia as one possible bystander mechanism. The authors investigated this hypothesis using the subcutaneous 9L gliosarcoma tumor model in Fischer rats. The tumors were evaluated with Doppler color-flow and ultrasound imaging during the various phases of the study. Twenty rats received intratumoral injections of HSVtk retroviral vector-producer cells (6 x 10(7) cells/ml) 21 days after bilateral flank tumor inoculation. Ten rats were subsequently treated with intraperitoneal ganciclovir (15 mg/kg/ml twice a day) for 14 days starting on Day 7 after producer cell injection; 10 control rats received intraperitoneal saline injections (1 ml twice a day) instead of ganciclovir. Ultrasound and flow images were obtained before cell injection, before and during ganciclovir or saline administration, and after cessation of treatment. The number, location, and ultrasonographic appearance of tumor vessels and the tumor volumes were recorded. The number of blood vessels in the tumors increased over time in both groups before treatment. Intratumoral cell injection without ganciclovir administration did not influence tumor growth or intratumoral vasculature. However, tumor vasculature decreased after initiation of ganciclovir therapy in the HSVtk-transduced tumors (p < 0.05). Early patchy or diffuse necrotic changes associated with ultrasonographic evidence of scattered intratumoral hemorrhage occurred in tumors treated with ganciclovir. (ABSTRACT TRUNCATED AT 400 WORDS)