Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I/II study of the combination of sorafenib and temsirolimus in patients with metastatic melanoma.

9026 Background: Inhibition of Signal transduction pathways at multiple levels may be a more effective therapeutic cancer strategy for advanced cancer patients. Sorafenib, a multikinase inhibitor and temsirolimus, an inhibitor of critical survival pathways, are targeted compounds with single agent anti-tumor activity in several solid tumors. Inhibition of mutant B-Raf and the AKT signaling pathway has been effective in vitro with melanoma cell lines. Therefore, we designed a phase I/II study of the combination of sorafenib and temsirolimus to inhibit multiple pathways for greater clinical efficacy. METHODS Patients (pts) with stage IV or unresectable or recurrent stage III melanoma and ECOG performance status of 0 to 1 were eligible. Pts with treated brain metastases were eligible if they had not progressed for 3 months. Sorafenib was given orally twice daily and temsirolimus was given intravenously once a week, both starting on day 1, with a 4-week cycle. Responses were assessed every 2 cycles per RECIST. RESULTS To date, 22 pts have been enrolled and treated. Median age was 56.5, and 17 were male. Median ECOG PS was 1. The MTD doses were sorafenib 400 mg in AM / 200 mg in PM daily and temsirolimus 25 mg IV weekly. The dose-limiting toxicity (DLT) included thrombocytopenia, hand-foot syndrome (HFS), serum transaminase elevation and hypertriglyceridemia. Other common adverse events were dry skin, fatigue, taste alteration, anorexia, flatulence, diarrhea, skin rash, insomnia, neuropathy, myalgia, and headaches, anemia, hypercholesterolemia, hyperglycemia and hypophosphatemia. There were 9 pts with stable disease among 21 evaluable pts for response. CONCLUSIONS Sorafenib and temsirolimus can be administered concomitantly although with significant toxicity at higher dose levels. Currently, pts are enrolled in a dose expansion cohort. Pharmacokinetic data will be presented. Supported in part by NCI grant UO1 CA062461 and N01 CM17003. [Table: see text] No significant financial relationships to disclose.
Combination of anisotropic diffusion and non-subsampled shearlet transform for image denoising

In this work, a non-subsampled shearlet transform (NSST) based anisotropic diffusion method is proposed. In the proposed method, the NSST transform is firstly applied to the noisy image to provide several scale and directional components. Then, the NSST coefficients are classified into textured regions and noise-related ones by using Sparse Un-mixing by the variable Splitting and Augmented Lagrangian (SUnSAL) classifier. Subsequently, an energy function is formed by the noise-related coefficients to be minimized by diffusion equations. The noisy free image is approximated from the denoised coefficients obtained by the anisotropic diffusion method and textured coefficients which are remained unchanged. Visual and quantitative assessments demonstrate that the proposed method outperforms the state-of-art denoising methods in terms of noise removal and detail preservation.
Two novel mutations in the NR5A1 gene as a cause of disorders of sex development in a Pakistani cohort of 46,XY patients

NR5A1 plays a central role in gonadal development and regulation by transcriptional regulation of key modulators involved in steroidogenesis. Mutations in human NR5A1 are frequently associated with 46,XY disorders of sex development (DSD). We analysed a Pakistani cohort of patients with 46,XY DSD, presenting with variable degrees of gonadal dysgenesis, for NR5A1 mutations. The study identified three mutations (p.Tyr03X, p.Glu07X and p.Gln299HisfsX386), of which two are novel, in these patients with 46,XY DSD. The mutations, p.Tyr03X and novel p.Glu07X, are located in the coding region of the gene, corresponding to DNA‐binding domain of the predicted protein. In silico analysis for the novel homozygous p.Gln299HisfsX386 mutation in ligand‐binding domain of NR5A1 revealed subtle changes in overall tertiary conformation which is predicted to affect the normal physiology of this mutant protein. This study reveals two novel mutations with altered NR5A1 protein in twenty patients with 46,XY DSD, highlighting the critical role of NR5A1 protein in gonadal development and differentiation. In conclusion, the current and previous studies suggest that the NR5A1 mutations are present in around 8–15% of patients with 46,XY DSD presenting with gonadal dysgenesis. For the clinical utility of NR5A1 gene mutations, more comprehensive studies with large 46,XY DSD patient series in different populations are suggested.
Short-Term Rat Inhalation Study With Aerosols of Acrylic Ester-Based Polymer Dispersions Containing a Fraction of Nanoparticles

Aqueous polymer dispersions are important raw materials used in a variety of industrial processes. They may contain particles with diameters ranging from 10 to 1500 nm. Polymer exposure alone may cause pulmonary lesions after inhalation exposure. Polymer dispersions with increased proportions of nano-sized particles are being developed for improved material characteristics, and this may pose even increased pulmonary hazards upon potential inhalation exposure. In a 5-day screening study, male rats were nose-only exposed to aerosols generated from 2 dispersions of acrylic ester polymers with identical chemical composition but different nano-sized particle proportions at particle concentrations of 3 and 10 mg/m3. Immediately and 19 days after the end of inhalation, necropsies were conducted with major emphasis on respiratory tract histopathology. Three and 23 days after the end of inhalation, bronchoalveolar lavage was performed to screen for early pulmonary injury and inflammation. In contrast to the adverse effects known for other materials in short-term inhalation studies, none of the tested preparations of acrylic ester polymers elicited any adverse effect at the end of the inhalation or postinhalation periods. No shift in toxicity could be observed by the increased proportion of nano-sized polymer particles. Under the conditions of this study, the no observable adverse effect levels for both preparations were >10 mg/m3, that is 2- to 3-fold beyond current nuisance dust threshold limit values.
CT evaluation of bone dehiscence of the superior semicircular canal as a cause of sound- and/or pressure-induced vertigo.

PURPOSE To describe the computed tomographic (CT) findings at different collimation widths associated with superior semicircular canal (SSC) dehiscence syndrome and to determine the frequency of these findings in a control population. MATERIALS AND METHODS Temporal bone CT scans with 1.0-mm and/or 0.5-mm collimation were obtained in 50 patients with sound- and/or pressure-induced vestibular symptoms. The control population consisted of 50 patients undergoing CT at 1.0-mm collimation and 57 patients undergoing CT at 0.5-mm collimation for other reasons. RESULTS SSC dehiscence was documented on CT scans in all 36 patients with the clinical syndrome, with bilateral findings in six patients. Six other patients without specific clinical signs appeared to have dehiscence on 1.0-mm-collimated scans. Intact bone overlaying the SSC was subsequently identified with 0.5-mm-collimated CT in each case. On the 1.0-mm-collimated scans in 50 control patients, an area judged as possible or definite dehiscence was identified in 18 of 100 ears. The bone overlaying the SSC was intact in each of the 114 control ears evaluated with 0.5-mm-collimated CT. CT findings from the patients with vestibular symptoms combined with those in the control population indicated that the positive predictive value of an apparent dehiscence in the diagnosis of SSC dehiscence syndrome improved from 50% with 1.0-mm-collimated CT with transverse and coronal images to 93% with 0.5-mm-collimated CT with reformation in the plane of the SSC. CONCLUSION The positive predictive value of CT in identification of SSC dehiscence syndrome improves with 0.5-mm-collimated helical CT and reformation in the SSC plane.
Alterations in the Fhit gene in pancreatic duct adenocarcinomas induced by N‐nitrosobis(2‐oxopropyl)amine in hamsters

Alteration of the Fhit gene was investigated in pancreatic duct adenocarcinomas induced by N‐nitrosobis(2‐oxopropyl)amine (BOP) in Syrian golden hamsters. The animals received 70 mg/kg BOP, followed by repeated exposure to an augmentation pressure regimen consisting of a choline‐deficient diet combined with DL‐ethionine and then L‐methionine and administration of 20 mg/kg BOP. A total of 15 pancreatic duct adenocarcinomas were obtained 10 wk after the beginning of the experiment, and total RNAs were extracted from each for assessment of aberrant transcription of the Fhit gene by reverse transcription–polymerase chain reaction analysis. Aberrant transcripts lacking nucleotides in the regions of nt −75 to 348, nt −15 to 348, or nt −75 to 178 were detected in 11 adenocarcinomas (73.3%). Southern blot analysis of eight tumors did not show any evidence of gross rearrangement or deletion. These results indicated that changes in the Fhit gene occurred frequently and thus may have played a role in the development of pancreatic duct adenocarcinomas induced by BOP in hamsters. © 2003 Wiley‐Liss, Inc.
Diagnosis of gestational diabetes mellitus by use of the homeostasis model assessment–insulin resistance index in the first trimester

Objective. Gestational diabetes mellitus (GDM) affects 2–10% of all pregnant women, causing increased morbidity and mortality, and is tested for in the second trimester of pregnancy. The purpose of the present study was to predict GDM in the first trimester. Design and methods. The study included 271 patients who were between the 10th and 14th week of gestation. Fasting glucose and insulin were measured in the first trimester and the homeostasis model assessment–insulin resistance index (HOMA-IR) was calculated for each patient. These values were compared with the results of the second-trimester glucose tolerance test. Results. HOMA-IR values were higher in women with GDM. A cut-off value of 2.60 for HOMA-IR was calculated at the end of the study. Conclusion. Accepting patients whose HOMA-IR value is higher than 2.60 in the first trimester seems to be a good method to predict GDM.
Activating mutations of STAT 5 B and STAT 3 in lymphomas derived from gdT or NK cells

Can Küçük1,*, Bei Jiang1,*, Xiaozhou Hu1, Wenyan Zhang2, John K.C. Chan3, Wenming Xiao4, Nathan Lack5, Can Alkan6, John C. Williams7, Kendra N. Avery7, Pınar Kavak8, Anna Scuto1, Emel Sen5, Philippe Gaulard9, Lou Staudt10, Javeed Iqbal11, Weiwei Zhang11, Adam Cornish12, Qiang Gong13, Qunpei Yang2, Hong Sun2, Francesco d’Amore14, Sirpa Leppä15, Weiping Liu2, Kai Fu2, Laurence de Leval16, Timothy McKeithan1 & Wing C. Chan1
Clopidogrel pharmacogenetics: metabolism and drug interactions

Abstract The thienopyridine, clopidogrel bisulfate (clopidogrel), is the most widely prescribed antiplatelet therapy in the world. Clopidogrel, alone or in conjunction with aspirin as part of a dual antiplatelet therapy regimen, is the standard of care for reducing ischemic events in patients with acute coronary syndrome, recent myocardial infarction, recent stroke, or established peripheral artery disease. Initially approved for use in 1997, the label was updated by both the USA Food and Drug Administration and the European Medicines Agency in 2009 to include information regarding cytochrome P450 (CYP) genotype status and concomitant proton pump inhibitor use. Labeling warns of reduced effectiveness in those with impaired CYP2C19 function and to avoid concomitant clopidogrel use with drugs that are strong or moderate CYP2C19 inhibitors, such as omeprazole. The interpretation of this warning and the implementation in clinical practice is not without controversy. The following review provides a summary of the published evidence regarding CYP2C19 function, both genotype status and drug inhibition from concomitant proton pump inhibitors use, and response to clopidogrel.
Polarization diversity improves RSSI based location estimation for wireless sensor networks

Signal strength based wireless location estimation suffers accuracy in indoor environments since the distance to RSSI (received signal strength indicator) function is not monotonic and gives multiple distance estimates for a specific signal strength value. In this paper an advancement of the existing estimation techniques is proposed by establishing the use of polarization diversity in getting robust location estimation. The measurements done in indoor environment clearly bring to fore the need to compute the signal strengths on different polarization vectors of radiated E-field, for prediction of location of wireless communication nodes with a better accuracy. Experiments conducted for both line-of sight and non-line of sight cases show that an optimal weighted sum of the respective signal strengths for different polarizations lead to a monotonic path loss expression which can be used for predicting the locations even with minimal initial training sequence. This novel approach enables precision indoor localization with a minimal set of measurements by exploiting the easily available RSSI information
The Impact of an Embodied Agent's Emotional Expressions Over Multiple Interactions

The impact of simulated embodied agent emotion has been explored in short-term studies, but no work to date has examined its impact in longer interactions that involve multiple interactions with agents. We present an embodied agent (Rachael) that simulates a health professional and attempts to help people improve their fruit and vegetable consumption. Emotional and unemotional versions of the agent were developed to examine how user perceptions of the agent changed over an intervention period of 49 days and in turn how this influenced fruit and vegetable consumption. Results found that whilst participants consumed more daily portions of fruit and vegetables over the intervention period and reduced their consumption gains post-intervention, there was no significant difference in consumption gains over time between those who interacted with the emotional or unemotional agents. Qualitative feedback, however, highlighted a strong preference for the emotional agent. A novelty effect was also observed where the agents were perceived more positively initially and less so over time.
Orbital Injury in Endoscopic Sinus Surgery for Sinonasal Inflammatory Disorders: Juntendo’s Ten-Year Experience

Orbital injury and complications are commonly encountered in endoscopic sinus surgery (ESS) despite advances in techniques and instrumentation. For the recent 10 years, we summarized the experience of the rhinology unit of our department regarding orbital injury and complications of ESS for sinonasal inflammatory disorders. One thousand seventy-three patients (1869 sides) from January 1, 2003 to December 31, 2012 undergoing ESS for sinonasal inflammatory diseases were enrolled in the present study. The age of the patients ranged from 8 to 81 years, mean age 49 years. Orbital injury and complications were observed in 13 patients (13 sides), which corresponded to 0.7% of the operated sides and 1.2% of the patients. Eight patients showed herniation of orbital fat alone through the injury of the lamina papyracea. The protruding orbital fat was snipped and cut using forceps in 2 patients. Removal of exposed orbital fat using powered instruments was performed in 3 patients, two of whom transiently showed periorbital edema postoperatively. No permanent complications were observed. Meticulous preoperative and perioperative planning is critical to prevent orbital complications. Especially, exposure of the periorbit and herniation of orbital fat after lamina injury with powered instrumentation dramatically increases the potential for more severe complications.
Dobutamine echocardiography and quantitative rest-redistribution 201Tl tomography in myocardial hibernation. Relation of contractile reserve to 201Tl uptake and comparative prediction of recovery of function.

BACKGROUND The purposes of this study were to evaluate the comparative accuracy of dobutamine echocardiography and quantitative rest-redistribution 201Tl tomography in the prediction of recovery of function after revascularization and to assess the relation of contractile reserve to thallium uptake. METHODS AND RESULTS Thirty-four patients with stable coronary disease and regional dysfunction underwent dobutamine echocardiography (2.5 up to 40 micrograms.kg-1.min-1) and rest-redistribution 201Tl tomography 1 day before revascularization. Resting echocardiography and scintigraphy were repeated at > or = 6 weeks. Before revascularization, resting 201Tl uptake was similar in segments demonstrating biphasic or sustained improvement and was higher than in those exhibiting no change or worsening function during dobutamine. After revascularization, 201Tl uptake increased only in segments that showed a biphasic response (from 66 +/- 12% to 78 +/- 13%; P < .05). Biphasic response had a sensitivity of 74% and specificity of 89% for prediction of recovery. The use of biphasic or sustained improvement responses increased the sensitivity to 86% with a decrease in specificity to 68%. Qualitative thallium assessment provided a high sensitivity (98%) but poor specificity (27%). Quantification of thallium uptake, however, improved its accuracy: a maximal uptake (at rest or redistribution) of > or = 60% yielded a 90% sensitivity and a 56% specificity. CONCLUSIONS In patients with myocardial hibernation, biphasic response during dobutamine is less sensitive but more specific for recovery of function, whereas indexes of 201Tl scintigraphy are in general more sensitive and less specific, the least accurate being a qualitative assessment of thallium uptake. The sensitivity and specificity of both methods, however, can be altered depending on the quantitative criteria of thallium uptake or combination of responses of the myocardium to dobutamine.
Heritability of Fitness Components in a Wild Bird Population

Consistently with the prediction that selection should deplete additive genetic variance (VA) in fitness, traits closely associated to fitness have been shown to exhibit low heritabilities (h2 = VA/(VA + VR )). However, empirical data from the wild indicate that this is in fact due to increased residual variance (VR), rather than due to decreased additive genetic variance, but the studies in this topic are still rare. We investigated relationships between trait heritabilities, additive genetic variances, and traits' contribution to lifetime reproductive success (≈fitness) in a red-billed gull (Larus novaehollandiae) population making use of animal model analyses as applied to 15 female and 13 male traits. We found that the traits closely associated with fitness tended to have lower heritabilities than traits less closely associated with fitness. However, in contrast with the results of earlier studies in the wild, the low heritability of the fitness-related traits was not only due to their high residual variance, but also due to their low additive genetic variance. Permanent environment effects—integrating environmental effects experienced in early life as well as nonadditive genetic effects—on many traits were large, but unrelated to traits' importance for fitness.
Weak, but Complex Pulsed Magnetic Fields May Reduce Depression following Traumatic Brain Injury

Many patients who display psychological depression following a traumatic brain injury do not respond completely to antidepressant drugs. We hypothesized that this type of depression is strongly correlated with subclinical, complex partial seizure-activity within the hippocampal-amygdaloid region that continues for months to years after apparent neurological and behavioral “recovery. ” Four depressed patients who had sustained traumatic brain injuries and who exhibited mild to moderate brain impairment according to standardized tests received 30 min. of weak (1 μT) burst-firing magnetic fields across the temporal lobes once per week for 5 weeks. There was a significant improvement of depression and reduction of phobias while physical symptoms and other complaints were not changed.
A comparative study of cervical cancer screening methods in a rural community setting of North India.

CONTEXT Pap smear testing as a conventional cervical screening approach has limitations for implementation and aided visual cervical testing has varying results in different regions. AIMS The aim of this study is to demonstrate the performance of aided visual cervical screening tests as against conventional Pap smear testing in a rural community setting of North India. SETTINGS AND DESIGN This was a rural community based cross-sectional study. MATERIALS AND METHODS All 7603 ever married women of age 30-59 years surveyed in a pocket of Dadri Tehsil, Uttar Pradesh, India were targeted for screening by Pap, visual inspection of cervix using acetic acid (VIA) and visual inspection of cervix using Lugol's iodine (VILI) methods. Screen positives were referred to colposcopy and confirmation by histology. STATISTICAL ANALYSIS USED Detection of histological cervical intraepithelial neoplasia (CIN) II + and CIN III + assessed separately by sensitivity, specificity and likelihood ratio's and predictive values. Analysis of data was performed by using IBM SPSS statstics software version 16.0. RESULTS A total of 65.6%(4988/7604) eligible women of 30-59 years age group in the target population were screened. Out of 4988, further analysis was performed on 4148 after excluding those who did not complete all screenings, who lost to follow-up and had missing histology results. Screen positivity rates by Pap (ASCUS and above), VIA and VILI were 2.6%, 9.7% and 13.5% respectively. Sensitivity and specificity of detecting the CIN III+ lesions were 87.5 and 98.8% for Pap, 50.0% and 96.7% for VIA and 50.0% and 95.7% for VILI respectively. CONCLUSIONS VIA screening demonstrated as a feasible primary screening test for detecting high grade CIN and as to perform better when the Pap test is not feasible.
The Effect of the APPRISE Mandate on Use of Erythropoiesis-Stimulating Agents and Transfusion Rates in Patients With Ovarian Cancer Receiving Chemotherapy

Objective Erythropoiesis-stimulating agents (ESAs) support chemotherapy-induced anemia in patients with epithelial ovarian cancer (EOC). In response to research demonstrating that ESAs increase tumor growth and shorten survival, the Food and Drug Administration mandated the new APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe use of ESAs) guidelines for consenting patients before ESAs administration. We sought to quantify the change in ESA and red blood cell (RBC) transfusion use after the APPRISE mandate was instituted. Methods/Materials After institutional review board approval, a retrospective chart review compared patients with EOC undergoing chemotherapy before and after the APPRISE mandate. Abstracted data included patient demographics, chemotherapy treatment status and regimen, and number of patients requiring ESAs or RBCs. A cost savings analysis was also performed. Results Eighty-four patients who underwent 367 cycles of chemotherapy after the APPRISE guidelines were compared with a matched set of 88 patients receiving 613 cycles of chemotherapy before the APPRISE guidelines. There were no statistically significant differences between the groups. Most patients had advanced stage disease and received primary taxane-/platinum-based chemotherapy. Of 88 patients, 45 (51%) in the pre-APPRISE group received a total of 196 ESA injections compared with 0 patients in the post-APPRISE group. Red blood cell transfusion in the post-APPRISE group was similar to that in the pre-APPRISE group (8.3% vs 14.8%, P = 0.28). Omission of ESAs in the post-APPRISE group resulted in a roughly $700,000 savings in billable charges. Conclusions In our institution, the APPRISE guidelines have resulted in complete cessation of the use of ESAs in patients with primary or recurrent EOC, resulting in considerable cost savings. Importantly, RBC transfusion rates did not significantly increase after the guidelines were imposed.