Miracle-dz/UniFAR-FTUs huggingface dataset:
Arthroscopic treatment of femoroacetabular impingement: early outcomes.

OBJECTIVE The aim of the study was to assess the early outcomes of the arthroscopic treatment of femoroacetabular impingement. METHODS Forty-two femoroacetabular impingement (FAI) patients (mean age: 35.1 years, range: 16 to 52 years) treated arthroscopically between 2006 and 2011 in our clinic were retrospectively analyzed. Twenty-five patients had Cam, 6 Pincer and 11 combined femoroacetabular impingement. Mean follow-up time was 28.2 (range: 10 to 72) months. Patients were assessed clinically and functionally using the Non-Arthritic Hip Score (NAHS), modified Harris Hip Score (mHHS), Oxford Hip Score, WOMAC score, and Visual Analogue Scale (VAS) pain scores preoperatively and at the final follow-up. RESULTS In clinical and functional assessments, there were increases of 24.8 points in mean NAHS, 23.3 in mHHS, 20.6 in WOMAC score and 9.6 in Oxford Hip Score. VAS pain score decreased by 4.9 points in comparison to the preoperative scores. There were no major complications. However, transient pudendal nerve neuropraxia was present in two patients, transient lateral femoral cutaneous nerve neuropraxia in one and asymptomatic heterotopic ossification in one patient. CONCLUSION Short-term clinical results of the arthroscopic treatment of the FAI appear to be satisfactory.
Novel GPCR Screening Approach: Indirect Identification of S1P Receptor Agonists in Antagonist Screening Using a Calcium Assay

To elucidate the physiological function of sphingosine 1-phosphate receptors 1–3 (S1P1−3) we aimed to identify selective ligands for these GPCRs. S1P2 and S1P3 are coupled to Gq, and are, therefore, linked to the phospholipase C/IP3/calcium pathway. S1P1 is solely coupled to Gi and was artificially linked to calcium signaling by coexpression of Gα 16. The three receptors desensitized on challenge of cells with an agonist (i.e., agonists appeared as antagonists in a second calcium measurement). We screened a compound library for inhibitors of S1P-stimulated calcium signals, and we could identify agonists and antagonists with a single measurement. Agonism and antagonism were confirmed by recording compound-and S1P-induced calcium signals from the same assay well. For the three receptors, we found a reciprocal correlation of agonism and “apparent” antagonism of agonists. In addition, agonists indirectly discovered by this approach do not promote calcium mobilization through endogenous GPCRs.
Are Shorter Courses of Filgrastim Prophylaxis Associated with Increased Risk of Hospitalization?

Background: In clinical trials in patients receiving myelosuppressive chemotherapy, 10–11 days of prophylaxis with filgrastim has been found to reduce the incidence of febrile neutropenia. In clinical practice, however, many patients receive shorter courses of therapy, even though the effectiveness of this regimen is unknown. Objective: To examine the relationship between duration of filgrastim prophylaxis and risk of hospitalization in patients receiving chemotherapy for non–Hodgkin's lymphoma (NHL), breast cancer, or lung cancer. Methods: Using a large, automated, US healthcare claims database, we identified all adults who received chemotherapy for NHL, breast cancer, or lung cancer between 1998 and 2002. For these patients, we identified their first course of chemotherapy and each unique cycle within that course, We then focused attention on all patient cycles in which filgrastim was administered on or before cycle day 5 (filgrastim prophylaxis). Pooling all such cycles, we examined the relationship between duration of filgrastim prophylaxis and risk of hospitalization for neutropenia or infection and risk of hospitalization for any reason, using generalized estimating equations. Results: Mean ± SD duration of filgrastim prophylaxis was 6.5 ± 3.1 days across 332 cycles for 133 NHL patients, 6.1 ± 2.9 days across 482 cycles for 205 breast cancer patients, and 4.3 ± 3.1 days across 522 cycles for 260 lung cancer patients. In multivariate analyses, risk of hospitalization for neutropenia or infection was found to decline with each additional day of filgrastim prophylaxis for patients with NHL (OR 0.81; p = 0.003), breast cancer (OR 0.77; p = 0.001), and lung cancer (OR 0.91; p = 0.084). Risk reductions with each additional day of prophylaxis ranged from 15% to 19% for patients with NHL, 17% to 23% for those with breast cancer, and 8% to 9% for those with lung cancer. Similar reductions in risk were noted for all-cause hospitalization. Conclusions: Among patients with NHL, breast cancer, or lung cancer, shorter courses of filgrastim prophylaxis may increase the risk of hospitalization.
Menopausal status modifies breast cancer risk associated with ESR1 PvuII and XbaI polymorphisms in Asian women: a HuGE review and meta-analysis.

BACKGROUND Published data on the association between single nucleotide polymorphisms (SNPs) in the ESR1 gene and breast cancer susceptibility are inconclusive or controversial. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to derive a more precise estimation of this relationship. METHODS A literature search of Pubmed, Embase, Web of science and CBM databases was conducted from inception through September 1 th, 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. RESULTS A total of five studies including 1,678 breast cancer cases and 1,678 general population controls in Asian populations were involved in this meta-analysis. When all the eligible studies were pooled into the meta-analysis, the higher transcriptional activity variant allele T of ESR1 PvuII (C>T) (rs2234693) in pre-menopausal breast cancer women showed a significant relation to increased risk (OR = 1.13, 95%CI: 1.01-1.28, P = 0.040) in contrast to their post-menopausal counterparts which showed non-significant increased risk (OR = 1.01, 95%CI: 0.87-1.18, P = 0.858). Nevertheless, no significant association between ESR1 XbaI (A>G) (rs9340799) polymorphism and the risk of breast cancer was observed in pre-menopausal and post-menopausal individuals. CONCLUSION Based on a homogeneous Asian population, results from the current meta-analysis indicates that the ESR1 PvuII (C>T) polymorphism places pre-menopausal breast cancer women at risk for breast cancer, while ESR1 XbaI (A>G) polymorphism is not likely to predict the risk of breast cancer.
A Comparison and Critical Analysis of Preclinical Anticancer Vaccination Strategies

Anticancer vaccines have been extensively studied in animal models and in clinical trials. While vaccination can lead to tumor protection in numerous murine models, objective tumor regressions after anticancer vaccination in clinical trials have been rare. B16 is a poorly immunogenic murine melanoma that has been extensively used in anticancer vaccination experiments. Because B16 has been widely used, different vaccination strategies can be compared. We reviewed the results obtained when B16 was treated with five common vaccine types: recombinant viral vaccines, DNA vaccines, dendritic cell vaccines, whole-tumor vaccines, and peptide vaccines. We also reviewed the results obtained when B16 was treated with vaccines combined with adoptive transfer of tumor antigen–specific T cells. We found several characteristics of vaccination regimens that were associated with antitumor efficacy. Many vaccines that incorporated xenogeneic antigens exhibited more potent anticancer activity than vaccines that were identical except that they incorporated the syngeneic version of the same antigen. Interleukin-2 enhanced the antitumor efficacy of several vaccines. Finally, several effective regimens generated large numbers of tumor antigen–specific CD8+ T cells. Identification of vaccine characteristics that are associated with antitumor efficacy may aid in the development of more effective anticancer vaccination strategies.
Resistance, resilience, and redundancy in microbial communities

Although it is generally accepted that plant community composition is key for predicting rates of ecosystem processes in the face of global change, microbial community composition is often ignored in ecosystem modeling. To address this issue, we review recent experiments and assess whether microbial community composition is resistant, resilient, or functionally redundant in response to four different disturbances. We find that the composition of most microbial groups is sensitive and not immediately resilient to disturbance, regardless of taxonomic breadth of the group or the type of disturbance. Other studies demonstrate that changes in composition are often associated with changes in ecosystem process rates. Thus, changes in microbial communities due to disturbance may directly affect ecosystem processes. Based on these relationships, we propose a simple framework to incorporate microbial community composition into ecosystem process models. We conclude that this effort would benefit from more empirical data on the links among microbial phylogeny, physiological traits, and disturbance responses. These relationships will determine how readily microbial community composition can be used to predict the responses of ecosystem processes to global change.
Endothelium-Derived Nitric Oxide Supports Renin Cell Recruitment Through the Nitric Oxide–Sensitive Guanylate Cyclase Pathway

Chronic challenge of renin–angiotensin causes recruitment of renin-producing cells in the kidney along the media layer of afferent arterioles and hypertrophy of cells in the juxtaglomerular apparatus. This study aimed to define the role of nitric oxide (NO) with regard to the recruitment pattern of renin-producing cells and to the possible pathways along which NO could act. We considered the hypothesis that endothelium-derived NO acts via NO-sensitive guanylate cyclase. Mice were treated with low-salt diet in combination with the angiotensin I–converting enzyme inhibitor enalapril for 3 weeks, which led to a 13-fold increase in renin expression associated with marked recruitment of renin cells in afferent arterioles and hypertrophy of the juxtaglomerular apparatus in wild-type mice. In wild-type mice additionally treated with the nonselective NO synthase inhibitor L-NAME, the recruitment of renin-expressing cells along the afferent arterioles was absent and juxtaglomerular hypertrophy was diminished. An almost identical attenuation of renin cell recruitment as with L-NAME treatment in wild-type mice was found in mice lacking the endothelial isoform of NO synthase. Treatment of mice lacking NO-sensitive guanylate cyclase in renin-expressing cells and preglomerular smooth muscle cells with low-salt diet in combination with the angiotensin I–converting enzyme inhibitor enalapril for 3 weeks produced juxtaglomerular hypertrophy like in wild-type mice, but no recruitment in afferent arterioles. These findings suggest that endothelium-derived NO and concomitant formation of cGMP in preglomerular renin cell precursors supports recruitment of renin-expressing cells along preglomerular vessels, but not in the juxtaglomerular apparatus.
Fluorescent labeling of proteins in living cells using the FKBP12 (F36V) tag

Over the past decade live cell imaging has become a key technology to monitor and understand the dynamic behavior of proteins in the physiological context of living cells. The visualization of a protein of interest is most commonly achieved by genetically fusing it to green fluorescent protein (GFP) or one of it variants. Considerable effort has been made to develop alternative methods of protein labeling to overcome the intrinsic limitations of fluorescent proteins. In this report we show the optimization of a live cell labeling technology based on the use of a mutant form of FKBP12 (FKBP12(F36V)) in combination with a synthetic high affinity ligand (SLF') that specifically binds to this mutant. It had been previously shown that the use of a fluorescein‐conjugated form of SLF' (5′‐fluorescein‐SLF') allowed the labeling of proteins genetically fused to FKBP‐F36V in living cells. Here we describe the identification of novel fluorescent SLF'dye conjugates that allow specific labeling of FKBP12(F36V) fusion proteins in living cells. To further increase the versatility of this technology we developed a number of technical improvements. We implemented the use of pluronics during the labeling process to facilitate the uptake of the SLF'‐dye conjugates and the use suppression dyes to reduce background signal. Furthermore, the time and dose dependency of labeling was investigated in order to determine optimal labeling conditions. Finally, the specificity of the FKBP12(F36V) labeling technology was extensively validated by morphological analysis using a diverse set of FKBP12(F36V) fusions proteins. In addition we show a number of different application examples, such as translocation assays, the generation of biosensors, and multiplex labeling in combination with different labeling technologies, such as FlAsH or GFP. In summary we show that the FKBP12(F36V)/SLF' labeling technology has a broad range of applications and should prove useful for the study of protein function in living cells. © 2008 International Society for Advancement of Cytometry
Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma.

BACKGROUND Combined BRAF and MEK inhibition, as compared with BRAF inhibition alone, delays the emergence of resistance and reduces toxic effects in patients who have melanoma with BRAF V600E or V600K mutations. METHODS In this phase 3 trial, we randomly assigned 423 previously untreated patients who had unresectable stage IIIC or stage IV melanoma with a BRAF V600E or V600K mutation to receive a combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily) or dabrafenib and placebo. The primary end point was progression-free survival. Secondary end points included overall survival, response rate, response duration, and safety. A preplanned interim overall survival analysis was conducted. RESULTS The median progression-free survival was 9.3 months in the dabrafenib-trametinib group and 8.8 months in the dabrafenib-only group (hazard ratio for progression or death in the dabrafenib-trametinib group, 0.75; 95% confidence interval [CI], 0.57 to 0.99; P=0.03). The overall response rate was 67% in the dabrafenib-trametinib group and 51% in the dabrafenib-only group (P=0.002). At 6 months, the interim overall survival rate was 93% with dabrafenib-trametinib and 85% with dabrafenib alone (hazard ratio for death, 0.63; 95% CI, 0.42 to 0.94; P=0.02). However, a specified efficacy-stopping boundary (two-sided P=0.00028) was not crossed. Rates of adverse events were similar in the two groups, although more dose modifications occurred in the dabrafenib-trametinib group. The rate of cutaneous squamous-cell carcinoma was lower in the dabrafenib-trametinib group than in the dabrafenib-only group (2% vs. 9%), whereas pyrexia occurred in more patients (51% vs. 28%) and was more often severe (grade 3, 6% vs. 2%) in the dabrafenib-trametinib group. CONCLUSIONS A combination of dabrafenib and trametinib, as compared with dabrafenib alone, improved the rate of progression-free survival in previously untreated patients who had metastatic melanoma with BRAF V600E or V600K mutations. (Funded by GlaxoSmithKline; Clinical Trials.gov number, NCT01584648.).
Effects of a cross-training exercise program in persons with osteoarthritis of the knee a randomized controlled trial.

This study was designed to evaluate, by means of a randomized controlled trial, the effects of a physical activity program incorporating aerobic, strength, and stretching exercises in individuals with osteoarthritis of the knee. We randomly assigned 137 volunteers ages >/=50 to an experimental group or a control group. The experimental group participated in three 1-hour sessions of supervised exercises per week over a 3-month period. The control participants were instructed to continue their usual daily activities, and they attended 1-hour education sessions twice a month. The effectiveness of the program was evaluated using repeated measurements of parameters related to self-reported health status, physical capacity, and joint tenderness.After 3 months, significantly greater improvements were observed in the experimental group than the control group in terms of: arthritis pain (p = 0.02), ability to walk and bend (p = 0.03), aerobic capacity (p < 0.0001), hamstring and low back flexibility (p = 0.003), quadriceps and hamstring strength (p <0.01), and the perception of changes relating to osteoarthritis of the knee and general condition (p < 0.0001). However, no significant differences were observed between the groups in isokinetic strength of the quadriceps (all p's >== 0.05), joint tenderness (p = 0.18), and health perception (p = 0.7). The overall results suggest that this program is effective for older persons with osteoarthritis of the knee and that it could contribute to maintaining their independence and improving their quality of life.
Monopolar versus bipolar device: safety, feasibility, limits and perioperative complications in performing hysteroscopic myomectomy.

PURPOSE OF INVESTIGATION The authors' aim is to compare surgical outcome of hysteroscopic G1 and G2 submucous myomectomy using bipolar resectoscope to those performed by monopolar device. MATERIALS AND METHODS a multicenter-observational-case-control study was conducted on premenopausal women affected by menorrhagia, pelvic pain or infertility because of submucous uterine myoma. The authors considered eligible: single G1 or G2 submucous uterine myoma, at least 0.5 cm ultrasound 'myometrial-free-margin' and two months GnRH pre-surgical treatment (myoma > three cm). Goup A patients were treated b y bipolar resectoscope and Group B by monopolar resectoscope. Primary endpoint was to compare the groups in term of complete or incomplete myomas resection ("second-step-procedure" rate). Secondary endpoint was to compare two treatments in term of surgical time and intraoperative complications rate. RESULTS Group A (60 patients) and Group B (216 patients) were homogeneous for general features and myomas location but they differed for G2 type prevalence (73.3% vs 50.5%), mean myomas diameter (33.17 +/- 11.93 vs 29.45 +/- 9.63), and surgical time (29.43 +/- 12.6 vs 23.2 +/- 8.2 minutes). In Group A patients both G1 and G2 myomas were completely removed in single step without intraoperative/postoperative complications; in Group B surgical outcomes of G1 myomas were similar to those of Group A, while G2 myomas required procedure termination in 12% of cases because of light electrolyte disturbance (22 cases) and severe iponatremia in four cases. All intraoperative complications occurred when procedure time exceeded 30 minutes and when myomas diameter was greater than 37.5 millimeters. CONCLUSION in the era ofmini-invasive surgery, hysteroscopic approach by bipolar device should be considered as a useful, safe, and large scale feasible procedure for submucosal myoma treatment, particularly when G2.
Evaluation of two graphical approaches for regional analysis and parametric mapping of dynamic [18F]FDDNP PET studies

Positron emission tomography (PET) with 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malo-nonitrile ([18F]FDDNP) has been used for in vivo imaging of β-amyloid plaques and neurofibrillary tangles, the neuropathological hallmarks of Alzheimer's disease (AD). Due to its simplicity as compared to other reference tissue modeling methods, Logan graphical analysis with cerebellum as reference region has been primarily used to estimate the distribution volume ratio (DVR) of [18F]FDDNP as a measure of amyloid burden and tau deposition in human brain. However, it sometimes produces spurious parametric DVR images when the noise level is high and the total scan duration is shortened. The purpose of this study was to characterize a new graphical analysis method against the Logan analysis for the estimation of the DVR estimates at regional and voxel-wise levels, using the cerebellum as the reference region. Effects on regional (frontal and medial temporal) DVR estimates and parametric DVR images obtained by the Logan and the new approaches using data in different time intervals and total scan durations (35–125 min, 65–125 min, 85–125 min, and 45–65 min) were investigated and compared to the reference values derived by the Logan analysis for the time interval 35–125 min. For regional analyses, with the exception of DVR estimates of medial temporal in ADs obtained by the Logan analysis for the interval 85–125 min, no significant difference was observed for all paired comparisons with the reference values. Logan DVR images generated using shortened time intervals (85–125 min and 45–65 min) were extremely noisy. In contrast, the new method produced DVR images comparable to the reference images even when shortened time intervals were used. The new method provides more reliable regional DVR estimates and less noisy parametric images, indicating that it is an improvement over the Logan graphical analysis for analyzing [18F]FDDNP PET data.
Intravascular Enhancement With Identical Iodine Delivery Rate Using Different Iodine Contrast Media in a Circulation Phantom

PurposeBoth iodine delivery rate (IDR) and iodine concentration are decisive factors for vascular enhancement in computed tomographic angiography. It is unclear, however, whether the use of high–iodine concentration contrast media is beneficial to lower iodine concentrations when IDR is kept identical. This study evaluates the effect of using different iodine concentrations on intravascular attenuation in a circulation phantom while maintaining a constant IDR. Materials and MethodsA circulation phantom with a low-pressure venous compartment and a high-pressure arterial compartment simulating physiological circulation parameters was used (heart rate, 60 beats per minute; stroke volume, 60 mL; blood pressure, 120/80 mm Hg). Maintaining a constant IDR (2.0 g/s) and a constant total iodine load (20 g), prewarmed (37°C) contrast media with differing iodine concentrations (240–400 mg/mL) were injected into the phantom using a double-headed power injector. Serial computed tomographic scans at the level of the ascending aorta (AA), the descending aorta (DA), and the left main coronary artery (LM) were obtained. Total amount of contrast volume (milliliters), iodine delivery (grams of iodine), peak flow rate (milliliter per second), and intravascular pressure (pounds per square inch) were monitored using a dedicated data acquisition program. Attenuation values in the AA, the DA, and the LM were constantly measured (Hounsfield unit [HU]). In addition, time-enhancement curves, aortic peak enhancement, and time to peak were determined. ResultsAll contrast injection protocols resulted in similar attenuation values: the AA (516 [11] to 531 [37] HU), the DA (514 [17] to 531 [32] HU), and the LM (490 [10] to 507 [17] HU). No significant differences were found between the AA, the DA, and the LM for either peak enhancement (all P > 0.05) or mean time to peak (AA, 19.4 [0.58] to 20.1 [1.05] seconds; DA, 21.1 [1.0] to 21.4 [1.15] seconds; LM, 19.8 [0.58] to 20.1 [1.05] seconds). ConclusionsThis phantom study demonstrates that constant injection parameters (IDR, overall iodine load) lead to robust enhancement patterns, regardless of the contrast material used. Higher iodine concentration itself does not lead to higher attenuation levels. These results may stimulate a shift in paradigm toward clinical usage of contrast media with lower iodine concentrations (eg, 240 mg iodine/mL) in individual tailored contrast protocols. The use of low–iodine concentration contrast media is desirable because of the lower viscosity and the resulting lower injection pressure.