Miracle-dz/UniFAR-FTUs huggingface dataset:
18F-FPPRGD2 and 18F-FDG PET of Response to Abraxane Therapy

Abraxane (nanoparticle albumin-bound paclitaxel) is an anticancer drug approved by the Food and Drug Administration. However, the mechanism of action of Abraxane is complex, and no established biomarker is available to accurately monitor its treatment outcomes. The aim of this study was to investigate whether the integrin-specific PET tracer 18F-FPPRGD2 (investigational new drug 104150) can be used to monitor early response of tumors to Abraxane therapy. Methods: Orthotopic MDA-MB-435 breast cancer mice were treated with Abraxane (25 mg/kg every other day, 3 doses) or phosphate-buffered saline. Tumor volume was monitored by caliper measurement. PET scans were obtained before and at different times after the start of treatment (days 0, 3, 7, 14, and 21) using 18F-FPPRGD2 and 18F-FDG. The tumoricidal effect was also assessed ex vivo by immunohistochemistry. Results: Abraxane treatment inhibited the tumor growth, and a significant difference in tumor volume could be seen at day 5 after the initiation of treatment. The tumor uptake of 18F-FPPRGD2 in the Abraxane-treated group was significantly lower on days 3 and 7 than at baseline but returned to the baseline level at days 14 and 21, indicative of relapse of the tumors after the treatment was halted. Immunohistologic staining confirmed that the change of 18F-FPPRGD2 uptake correlated with the variation of integrin level in the tumor vasculature induced by Abraxane treatment. No significant change of tumor (rather than vascular) integrin expression was observed throughout the study. No significant decrease of 18F-FDG uptake was found between the treated and the control tumors on days 3, 14, and 21, although an increase in 18F-FDG tumor uptake of treated mice, as compared with the control mice, was found on day 7. The increase of 18F-FDG on day 7 was related to the inflammatory response during therapy. Conclusion: Abraxane-mediated downregulation of integrin αvβ3 expression on tumor endothelial cells can be quantitatively visualized by PET. The change of integrin expression precedes that of tumor size. Consequently, 18F-FPPRGD2 PET is superior to 18F-FDG PET in monitoring early response to treatment, favoring its potential clinical translation.
Accuracy of contrast-enhanced dual-energy MDCT for the assessment of iodine uptake in renal lesions.

OBJECTIVE The objective of our study was to assess the accuracy of iodine-related attenuation and iodine quantification as imaging biomarkers of iodine uptake in renal lesions on a single-phase nephrographic image with dual-energy MDCT. MATERIALS AND METHODS Fifty-nine patients (41 men, 18 women; age range, 28-84 years) with 80 renal lesions underwent contrast-enhanced dual-energy CT during the nephrographic phase of enhancement. Renal lesions were characterized as enhancing or nonenhancing on color-coded iodine overlay maps using iodine-related attenuation (in Hounsfield units) and iodine quantification (in milligrams per milliliter). For iodine-related attenuation the iodine uptake thresholds of 15 and 20 HU were tested; a threshold of 0.5 mg/mL was used for iodine quantification. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of iodine-related attenuation and iodine quantification were calculated from chi-square tests of contingency with histopathology or imaging follow-up as the reference standard. The 95% CIs were calculated from binomial expression. Differences in sensitivity and specificity were assessed by means of McNemar analysis. RESULTS A significant difference in sensitivity and specificity was found between iodine-related attenuation with the thresholds of 15 HU (sensitivity, 91.4%; specificity, 93.3%; PPV, 91.4%; NPV, 93.3%) and 20 HU (sensitivity, 77.1%; specificity, 100%; PPV, 100%; NPV, 84.9%) (p = 0.008) and between iodine quantification (sensitivity, 100%; specificity, 97.7%; PPV, 97.2%; NPV, 100%) and iodine-related attenuation with a threshold of 20 HU (p = 0.004). No significant difference in sensitivity and specificity was found between iodine quantification and iodine-related attenuation with a threshold of 15 HU. CONCLUSION Contrast-enhanced dual-energy MDCT with iodine-related attenuation and iodine quantification allows accurate evaluation of iodine uptake in renal lesions on a single-phase nephrographic image.
Phase I/II Randomized Trial Evaluating the Safety and Clinical Effects of Repifermin Administered to Reduce Mucositis in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

Purpose: To evaluate the safety of repifermin (keratinocyte growth factor-2) administered before and after autologous hematopoietic stem cell transplantation (auto-HSCT). A preliminary analysis of the ability of keratinocyte growth factor-2 to prevent mucositis was also done. Experimental Design: Forty-two patients received intravenous repifermin (25 μg/kg or 50 μg/kg) or placebo for 3 days before their auto-HSCT conditioning regimen and for up to 10 days after auto-HSCT. Within each dose level, 14 patients were randomized to repifermin and 7 patients to placebo. Clinical evaluations of mucositis were scheduled before auto-HSCT conditioning regimen, on the day of transplant, and three times per week until mucositis resolved. Results: In general, the incidence of adverse events was similar for patients treated with repifermin and placebo. No clinically meaningful differences were noted among treatment groups for clinical laboratory variables. Treatment groups experienced similar time to engraftment. The frequency of Grade 2 to 4 mucositis was 100% for patients in the placebo group, 64% for patients in the 25 μg/kg group (P = 0.041 versus placebo), and 50% for patients in the 50 μg/kg group (P = 0.006 versus placebo). Results of other endpoints, including pain on swallowing and use of pain medication specifically for mucositis, suggested a better outcome for patients in the 50 μg/kg group compared with the placebo and 25 μg/kg groups. Conclusions: Repifermin was well tolerated. Repifermin given before and after auto-HSCT seems to be active in reducing mucositis, but a larger trial will be necessary to determine the efficacy of repifermin with this dose schedule.
The diagnosis and treatment of myotonic disorders

Myotonia is a defining clinical symptom and sign common to a relatively small group of muscle diseases, including the myotonic dystrophies and the nondystrophic myotonic disorders. Myotonia can be observed on clinical examination, as can its electrical correlate, myotonic discharges, on electrodiagnostic testing. Research interest in the myotonic disorders continues to expand rapidly, which justifies a review of the scientific bases, clinical manifestations, and numerous therapeutic approaches associated with these disorders. We review the pathomechanisms of myotonia, the clinical features of the dystrophic and nondystrophic myotonic disorders, and the diagnostic approach and treatment options for patients with symptomatic myotonia. Muscle Nerve 47: 632–648, 2013
Plasma catecholamine and lactate relationship during graded exercise in men with spinal cord injury.

Catecholamine and lactate responses to incremental exercise were examined in individuals with spinal cord injury (SCI). Three men with high-level (HINJ) and four with low-level (LINJ) SCI performed VO2peak exercise tests on an arm ergometer. Forearm venous blood samples taken at rest and at the end of each work stage were analyzed for norepinephrine (NE), epinephrine (EPI), and lactate (LA) content. Mann-Whitney tests revealed that peak LA, NE, and EPI responses were greater in LINJ compared with HINJ subjects (LA = 7.1 +/- 0.5 vs 3.2 +/- 0.4 mM; NE = 3.1 +/- 1.0 vs 0.4 +/- 0.1 ng.ml-1; EPI = 0.5 +/- 0.2 vs 0.1 +/- 0.01 ng.ml-1). Spearman rank correlations for LINJ and HINJ groups were NE-EPI, rs = 0.85 vs rs = 0.17; NE-LA, rs = 0.83 vs rs = 0.31; and EPI-LA, rs = 0.73 vs rs = 0.41. The strong relationships between NE, EPI, and LA in the LINJ group were similar to those previously reported in able-bodied athletes. However, the relatively weak association between these factors in the HINJ group indicates that, while some function exits, the sympathoadrenal response to exercise is significantly impaired in these individuals. These results suggest that mechanisms other than catecholamines are primarily responsible for muscle lactate production during incremental exercise in individuals with HINJ.
On the Pleistocene Antiquity of Monte Verde, Southern Chile

The potential importance of the Monte Verde site for the peopling of the New World prompted a detailed examination of the collections from that locality, as well as a site visit in January 1997 by a group of Paleoindian specialists. It is the consensus of that group that the MV-II occupation at the site is both archaeological and 12,500 years old, as T. Dillehay has argued. The status of the potentially even older material at the site (MV-1, ∼ 33,000 B.P.) remains unresolved.
Electrocoagulation and curettage for carcinoma involving the skin of the face, nose, eyelids, and ears

Electrocoagulation and curettage has been criticized as inadequate therapy for skin carcinoma. This series of patients demonstrates the effectiveness of electrocoagulation and curettage in the treatment of carcinoma involving the skin of the head and face. From 1964 through 1968, 90 private patients with 128 skin cancers of the head and face were treated by electrocoagulation and curettage. Approximately 50% of these patients were more than 70 years old; 93% of the lesions were basal cell carcinomas and 39% involved the skin of the nose, eyelids, or ears. Forty‐four per cent were at least 1 cm or greater in transverse diameter. Only one patient required hospitalization for this therapy, and all lesions were destroyed under local anesthesia. The average healing time was 5.1 weeks. There was neither morbidity nor mortality related to this therapy. All patients were personally followed from 2‐7 years. Complete cure was observed in 93% of these lesions. The recurrence rate for 123 primary (previously untreated) skin cancers was 6.5%. Recurrence is first noticed on the scar created by the initial coagulation and is easily recoagulated. These data emphasize the simplicity and adequacy of this treatment modality. In addition, electrocoagulation and curettage is convenient, expeditious, and economical, important assets in these times of burgeoning hospital costs. It is well tolerated by cartilage, and cartilage necrosis has not been observed. Electrocoagulation is tissue‐sparing—of great importance in the nose, eye, and ear areas. It avoids anesthetic risks, extensive surgical procedures, prolonged hospitalization, and multiple treatment visits. These considerations justify its use as the preferred therapy of skin cancer of the head and face.
An analysis of undergraduate and graduate student nurses’ moral sensitivity

This study describes the level of moral sensitivity among nursing students enrolled in a traditional baccalaureate nursing program and a master’s nursing program. Survey responses to the Modified Moral Sensitivity Questionnaire for Student Nurses from 250 junior, senior, and graduate students from one nursing school were analyzed. It was not possible to draw conclusions based on the tool. Moral category analysis showed students ranked the category structuring moral meaning highest and interpersonal orientation second. The moral issue ranking highest was honesty, respect for the patient second, and third was responsibility to know the patient’s situation. Seniors agreed more often about the need to focus on patient safety. As students progress through the baccalaureate program and into the graduate program, their perspectives increasingly recognize the contextuality of moral issues. The results show a need to further develop a tool to measure moral sensitivity, using student understanding and perceptions of moral issues.
Purification and characterization of the main laccase produced by the white‐rot fungus Pleurotus pulmonarius on wheat bran solid state medium

The wood‐degrading fungus Pleurotus pulmonarius produces at least two laccase isoforms, Lcc1 and Lcc2, when grown on wheat bran solid state medium. The main laccase, Lcc2, was purified to apparent electrophoretic homogeneity by using acetone precipitation, anion‐exchange chromatography and gel filtration. Lcc2 had been purified 5.9‐fold with a yield of 49%. A specific activity of 19,750 U/mg protein was found using syringaldazine as a substrate under standard assay conditions. The enzyme is a homodimeric glycoprotein containing 44% glycosilation and an apparent molecular mass of 46 kDa. Type I and type III Cu2+ centers were identified by spectrophotometry. The laccase showed optimal activity at pH 6.2–6.5, 4.0–5.5, and 6.0–8.0 with syringaldazine, ABTS and guaiacol as substrates, respectively. For all substrates, the highest oxidation rates were obtained at 50 °C. The enzyme was stable over a large range of pH (4.5–8.0) and at temperatures up to 50 °C. Under standard assay conditions, the apparent KM values were 12, 210 and 550 μM for syringaldazine, ABTS and guaiacol, respectively. Purified Lcc2 was strongly inhibited by sodium azide, 2‐mercaptoethanol and Hg2+, and slightly inhibited by Mn+2 and the chelant agents, EDTA and EGTA. The enzyme was activated by Cu2+ and it retained a high percentage of its activity in the presence of organic solvents, such as acetonitrile and acetone.
The inferior mesenteric ganglion.

The existence of an inferior mesenteric ganglion in man is either not mentioned or is disputed in some standard anatomical text-books, and apparently very few workers have attempted to prove or disprove its presence by macroscopic and microscopic studies. It is shown by Schafer & Thane (1895) in a diagram in the 10th edition of Quain's Elements of Anatomy, but is not described in the text. Petit-Dutaillis & Flandrin (1928) found a single ganglion on the left side of the inferior mesenteric artery in five out of thirteen subjects; Hovelacque (1927) reported an inferior mesenteric ganglion in 50% of cases, and in these it was always placed to the right of the median plane. Kuntz (1940) described the histology of such a ganglion. Mitchell (1958) stated that a ganglion may exist just above the origin of the inferior mesenteric artery, or more often minute discrete ganglia are found both above and below the root of the artery or scattered in the proximal part of the plexus. Kuntz & Jacob (1955) described minute ganglia in the inferior mesenteric plexus. Clearly there is no unanimity about the ganglion or ganglia so it was decided to re-investigate the problem.
Lack of Predictive Value of Tachypnea in the Diagnosis of Pneumonia in Children

Background: The World Health Organization (WHO) recommends the use of tachypnea as a proxy to the diagnosis of pneumonia in resource poor settings. Objective: To assess the relation between tachypnea and radiographic pneumonia among children evaluated in a pediatric emergency department (ED). Methods: Prospective study of children less than 5 years of age undergoing chest radiography (CXR) for possible pneumonia was conducted in an academic pediatric ED. Tachypnea was defined using 3 different measurements: (1) mean triage respiratory rate (RR) by age group, (2) age-defined tachypnea based on WHO guidelines (<2 months [RR ≥60/min], 2 to 12 months [RR ≥50], 1 to 5 years [RR ≥40]), and (3) physician-assessed tachypnea based on clinical impression assessed before CXR. The presence of pneumonia on CXR was determined by an attending radiologist. Results: A total of 1622 patients were studied, of whom, 235 (14.5%) had radiographic pneumonia. Mean triage RR among children with pneumonia (RR = 39/min) did not differ from children without pneumonia (RR = 38/min). Twenty percent of children with tachypnea as defined by WHO age-specific cut-points had pneumonia, compared with 12% of children without tachypnea (P < 0.001). Seventeen percent of children who were assessed to be tachypneic by the treating physician had pneumonia, compared with 13% of children without tachypnea (P = 0.07). Conclusion: Among an ED population of children who have a CXR performed to assess for pneumonia, RR alone, and subjective clinical impression of tachypnea did not discriminate children with and without radiographic pneumonia. However, children with tachypnea as defined by WHO RR thresholds were more likely to have pneumonia than children without tachypnea.
Using video‐tracking to assess sublethal effects of pesticides on honey bees (Apis mellifera L.)

Concern about the role of pesticides in honey bee decline has highlighted the need to examine the effects of sublethal exposure on bee behaviors. The video‐tracking system EthoVisionXT (Noldus Information Technologies) was used to measure the effects of sublethal exposure to tau‐fluvalinate and imidacloprid on honey bee locomotion, interactions, and time spent near a food source over a 24‐h observation period. Bees were either treated topically with 0.3, 1.5, and 3 µg tau‐fluvalinate or exposed to 0.05, 0.5, 5.0, 50, and 500 ppb imidacloprid in a sugar agar cube. Tau‐fluvalinate caused a significant reduction in distance moved at all dose levels (p < 0.05), as did 50 and 500 ppb imidacloprid (p < 0.001). Bees exposed to 50 and 500 ppb spent significantly more time near the food source than control bees (p < 0.05). Interaction time decreased as time in the food zone increased for both chemicals. This study documents that video‐tracking of bee behavior can enhance current protocols for measuring the effects of pesticides on honey bees at sublethal levels. It may provide a means of identifying problematic compounds for further testing. Environ. Toxicol. Chem. 2012;31:1349–1354. © 2012 SETAC
The Rice Cyclin-Dependent Kinase –Activating Kinase R2 Regulates S-Phase Progression Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.010386.

Cyclin-dependent kinases (CDKs) are the central components of eukaryotic cell cycle regulation. Phosphorylation of CDKs at a conserved threonine residue is required for their full activity and is mediated by a CDK-activating kinase (CAK). The CAK R2 from rice belongs to those CAKs that phosphorylate not only CDKs but also the C-terminal domain (CTD) of RNA polymerase II. We showed that R2 is a nuclear protein with increased expression and increased CTD kinase activity in S-phase. Increasing R2 abundance through a transgenic approach accelerated S-phase progression and overall growth rate in suspension cells. In planta, the CTD kinase activity of R2 was induced by a growth-promoting signal. R2 regulation, therefore, may constitute a plant-specific adaptive mechanism that is used to adjust the rate of cell proliferation in response to a changing environment.
INFLUENCEOF TEMPERATURE ONSEASONALABUNDANCE OF Ectomyelois ceratoniae Zeller,1839 (LEPIDOPTERA, PYRALIDAE) IN TOLGA PALM GROVE

Le but de ce travail est l’etude de l’impact de la temperature sur l'abondance saisonniere des populations de la pyrale des dattes Ectomyelois ceratoniae Zeller dans la palmeraie de Tolga (Biskra) durant l’annee 2010. Le suivi de la fluctuation du vol des adultes de la pyrale a l’aide des pieges a pheromones nous a permis de constater la presence de deux generations successives et non chevauchantes durant l’annee. Nos resultats montrent aussi que les releves des temperatures minimales sont significativement et positivement correlees aux releves des individus pieges en hiver et en automne, alors qu’elle a un effet negative et significatif faible en ete (R2=0,428 ; P< 0,015)et une action non significative au printemps (R2= 0,274 ;P< 0,066). Tandis que les temperatures maximale et moyenne ont un effet positivement significatif pendant la periode hivernale et automnale, mais elles ont une influence significative et negative en ete et au printemps. En outre, l’action combinee des temperatures maximale et minimale a revele un effet significatif sur le vol des adultes de la pyrale des dattes durant toute l’annee.
Intracranial pressure in patients with dementia and communicating hydrocephalus.

✓ Intracranial pressure (ICP) was monitored continuously for 48 to 72 hours in 12 patients with dementia and communicating hydrocephalus, to see if this would help determine which patients might benefit from surgical shunting of CSF, since not all such patients respond to treatment. Patients who showed variability of ICP improved following surgery, while patients with consistently flat ICP tracings did not. It is suggested that continuous monitoring of ICP may help identify cases suitable for surgery.
The Transmembrane Domain of the E5 Oncoprotein Contains Functionally Discrete Helical Faces*

The E5 protein of bovine papillomavirus is a 44-amino acid, Golgi-resident, type II transmembrane protein that efficiently transforms immortalized mouse fibroblasts. The transmembrane (TM) domain of E5 is not only critical for biological activity, it also regulates interactions with cellular targets including the platelet derived growth factor receptor (PDGF-R) and the 16-kDa subunit of the vacuolar proton ATPase (V-ATPase). In order to define the specific TM amino acids essential for E5 biological and biochemical activity, we performed scanning alanine mutagenesis on 25 of the 30 potential TM residues and genetically mapped discrete α-helical domains which separately regulated the ability of E5 to bind PDGF-R, activate PDGF-R, and to form oligomers. Alanine substitutions at positions 17, 21, and 24 (which lie on the same helical face) greatly inhibited E5 association with the PDGF-R, suggesting that this region comprises the receptor binding site. PDGF-R activation also mapped to a specific but broader domain in E5; mutant proteins with alanines on one helical face (positions 8, 9, 11, 16, 19, 22, and 23) continued to induce PDGF-R tyrosine phosphorylation, whereas mutant proteins with alanines on the opposite helical face (positions 7, 10, 13, 17, 18, 21, 24, and 25) did not, indicating that the latter helical face was critical for mediating receptor transphosphorylation. Interestingly, these “activation-defective” mutants segregated into two classes: 1) those that were unable to form dimers but that could still form higher order oligomers and transform cells, and 2) those that were defective for PDGF-R binding and were transformation-incompetent. These findings suggest that the ability of E5 to dimerize and to bind PDGF-R is important for receptor activation. However, since several transformation-competent E5 mutants were defective for binding and/or activating PDGF-R, it is apparent that E5 must have additional activities to mediate cell transformation. Finally, alanine substitutions also defined two separate helical faces critical for E5/E5 interactions (homodimer formation). Thus, our data identify distinct E5 helical faces that regulate homologous and heterologous intramembrane interactions and define two new classes of biologically active TM mutants.