Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Systematic EGFR and KRAS Mutation Evaluation on Progression-Free Survival and Overall Survival in Patients with Advanced Non–Small-Cell Lung Cancer Treated by Erlotinib in a French Prospective Cohort (ERMETIC Project—Part 2)

Background: Epidermal growth factor and v-Ki-ras2 Kirsten ras sarcoma (KRAS) mutation status, although associated with EGFR- tyrosine kinase inhibitor (TKI) efficacy, has not been used in clinical practice until recently. The prospective Evaluation of the EGFR Mutation status for the administration of EGFR-TKIs in non small cell lung Carcinoma (ERMETIC) study aimed to implement these biomarkers in France. Methods: Between March 2007 and April 2008, EGFR and KRAS were studied by sequencing DNA tumor specimens from 522 consecutive advanced non–small-cell lung cancer patients treated with EGFR-TKI, mostly in second- or third-line settings. Cox models were used to investigate the impact of patient characteristics and mutations on progression-free survival (PFS) and overall survival (OS). Added value from mutation status was evaluated using likelihood ratio (LR) tests. Classification and regression tree analysis aimed to identify homogeneous groups in terms of survival. Results: Among the 522 patients, 87% were white, 32% were women, and 18% were never-smokers, with 65% presenting with adenocarcinoma. Biological data were available for 307 patients, showing 44 EGFR mutations (14%) and 42 KRAS (14%) mutations. Median PFS was 2.4 months (interquartile range, 1.4–4.6) and median OS 5.6 months (interquartile range, 2.2–14.0). Factors independently associated with PFS were performance status 1 or 2 to 3 (hazards ratio [HR] = 1.5, 95% confidence interval [CI] 1.1–1.9; and HR = 2.3, CI 1.7–3.1, respectively; p < 0.001); former or current smoker status (HR = 1.8, CI 1.4–2.4 and 2.0,CI 1.4–2.8, respectively; p < 0.001); nonadenocarcinoma histology (squamous cell: HR = 0.9 CI 0.7–1.2]; others: HR = 1.6, 1.3–2.1; p < 0.001); at least two metastatic sites (HR = 1.3, CI 1.1–1.6 and 1.6, CI 1.3–2.1, respectively; p < 0.001); prior taxane-based chemotherapy (HR = 1.3, CI 1.0–1.3, p = 0.01); non-white (HR = 0.7, CI 0.5–0.9, p = 0.009). Similar results were found for OS. In addition, EGFR and KRAS mutations were significantly associated with PFS (HR = 0.5, CI 0.3–0.7 and HR = 1.2, CI 0.8–1.8, respectively, versus no mutation; LR p = 0.001). In the OS model, adjusted HR was 0.7 (0.4–1.0) for EGFR mutation and 1.7 (1.1–2.4) for KRAS (LR p = 0.004). Classification and regression tree analysis revealed EGFR mutation to be the primary factor for identifying homogeneous patient subgroups in terms of PFS. Conclusions: EGFR and KRAS status independently impacts outcomes in advanced non–small-cell lung cancer patients treated with EGFR-TKI. However, EGFR status impacts both PFS and OS whereas KRAS only impacts OS. These findings support the nationwide use of EGFR status for patient selection before EGFR-TKI therapy. The role of KRAS mutations remains to be elucidated.
Ribonuclease and deoxyribonuclease activites in experimental and human tumors by the histochemical substrate film method.

Summary The ribonuclease and deoxyribonuclease activities of 65 experimental and human tumors (32 different types) have been examined by histochemical substrate film methods. A same general pattern was obtained for the distribution of both nucleases in the various types of experimental and human tumors. The connective tissue stroma and the necrotic regions of the tumor masses showed various levels of nuclease activity, whereas the neoplastic cells showed no demonstrable activity. It appears that deficiencies in ribonuclease and deoxyribonuclease activities represent general properties of cancer cells. The possible significance of the losses of nuclease activities in carcinogenesis is discussed.
Can we bottle psychosocial treatments for addiction? The role of oxytocin.

The literature on the hedonic properties of drugs of abuse has been our major source of information about the neurobiology of reward. … It seems likely that these pathways and genes evolved not for drug abuse but for mediating the motivational aspects of social interaction. parallels exist between and addiction, and often been compared in philosophy, and throughout history. completely we will briefly identify some of the key neurobiological parallels that exist between social attachment and addiction. We will also outline the advancement of knowledge related to the novel antiaddiction properties of oxytocin and future directions for its development as a potential adjunct to addiction treatment.
Expression of cytotoxic molecule TIA‐1 in malignant lymphomas mimicking fulminant hepatitis

Involvement of malignant lymphoma in the liver inducing fuiminant hepatic failure has rarely been reported. There fore, a close association between some lymphoma types with severe liver damage and the mechanism underlying the liver damage is intriguing. Three malignant lymphoma cases, which were clinically diagnosed as fulminant hepatitis, were collected from the autopsy records of Kawasaki Medical School (Kurashiki, Japan). All three cases were characterized by the presence of hepatosplenomegaly without superficial lymph node swelling, high elevation of transaminase and lactate dehydrogenase (LDH; especially LDH‐2), and a quite aggressive clinical course. Immuno‐histochemlcally, the tumor cells in all three cases were positive for T cell intracellular antlgen VIA‐l), which is a cytolytic protein in cytotoxic T and natural klller (NK) cells. The lymphomas were CD8+ perlpheral T cell lymphoma (case l), CD56+ T/NK cell lymphoma (case 2), and T cell lymphoma in a patient with mosquito hypersensitivity (case 3). Epstein‐Barr virus infection was demonstrated on the tumor cells of cases 2 and 3 using an in situ hybridization method and those cases showed high titers of serum interferon‐γ and Fas. Frequent apoptosis of liver cells, where the lymphoma cells had infiltrated, was revealed by a terminal deoxyribosyl transferase‐mediated deoxyuridine nick end‐labeling (TUNEL) method. The findings in this study suggest that fulminant hepatic injury is closely associated with cytotoxic molecule TIA‐1 expression of the lymphoma cells and that some specific mechanism may be involved In liver damage.
Common Profile for Instant Messaging (CPIM)

At the time this document was written, numerous instant messaging protocols were in use, and little interoperability between services based on these protocols has been achieved. This specification defines common semantics and data formats for instant messaging to facilitate the creation of gateways between instant messaging services. [STANDARDS-TRACK]
Persistence of retinal indocyanine green dye following vitreous surgery.

BACKGROUND AND OBJECTIVE To investigate the duration of postoperative persistence of indocyanine green (ICG) dye used during vitreous surgery. PATIENTS AND METHODS Thirty-three patients (34 eyes) underwent macular surgery with removal of the internal limiting membrane (ILM) or epiretinal membrane using ICG dye to stain the membrane for better visualization. Infrared fundus photographs were taken postoperatively until infrared fluorescence had completely disappeared. The time for residual ICG dye to fade from the retina was studied for eyes with full-thickness macular hole, epiretinal membrane, and macular edema for comparison. served at sites where macular hole was present, sites of normal ILM that had not been removed, and the optic disc. ICG dye faded at an average of 7.3 months for patients with macular hole and 3.4 months for patients with other macular diseases (P< .01). CONCLUSIONS ICG dye used during macular surgery can persist in the macular region for up to 7 months following surgery, and seems to remain for a longer period of time in cases with macular hole than in cases with other diseases. Caution is required regarding light exposure by postoperative fundus examinations, daylight, and other natural light.
Intervention to decrease emergency department crowding: does it have an effect on return visits and hospital readmissions?

STUDY OBJECTIVES We evaluate the effect of a multifaceted intervention to decrease emergency department crowding on the incidence of return visits to the ED or a hospital ward. The intervention included increased emergency physician coverage, the designation of physician coordinators, and new hospital policies regarding laboratory, consultation, and admission procedures. METHODS The incidence of return visits within 7 days of discharge was estimated in samples from 2 populations (ie, patients discharged from the ED and patients discharged from the hospital) and during a 12-month period before and a 12-month period after the implementation of the intervention. Return visits were categorized into the following groups: (1) scheduled or not and (2) related or not to initial visit. Logistic regression was used in subsamples to assess the effect of the intervention while controlling for potential confounders. By using information from the provincial medical services database, variation between the periods before and after implementation of the intervention in the incidence of return visits to any ED was compared between the study hospital and 2 external control hospitals. RESULTS No difference was found in the incidence of return visits between the periods before and after implementation of the intervention, either for patients discharged from the ED (all returns: 11.0% versus 12.4%, 95% confidence interval on difference [CID] -1.5% to 4.3%; unscheduled-related returns: 6.5% versus 5.8%, 95% CID -2.8% to 1.6%) or the hospital (all returns: 6.8% versus 6.6%, 95% CID -2.5% to 2.1%; unscheduled-related returns: 4.2% versus 4.0%, 95% CID -2.0% to 1.7%). This lack of effect remained even after controlling for potential confounders. Variation between the periods before and after implementation of the intervention in the incidence of return to any ED was similar in the 3 hospitals examined. CONCLUSION Our successful hospital intervention to decrease crowding reduced the mean length of stay for patients discharged from the ED from 13.8 to 5.9 hours, without resulting in increased return visits to the ED or hospital readmission.
Novel Trifunctional Xylanolytic Enzyme Axy43A from Paenibacillus curdlanolyticus Strain B-6 Exhibiting Endo-Xylanase, β-d-Xylosidase, and Arabinoxylan Arabinofuranohydrolase Activities

ABSTRACT The axy43A gene encoding the intracellular trifunctional xylanolytic enzyme from Paenibacillus curdlanolyticus B-6 was cloned and expressed in Escherichia coli. Recombinant PcAxy43A consisting of a glycoside hydrolase family 43 and a family 6 carbohydrate-binding module exhibited endo-xylanase, β-xylosidase, and arabinoxylan arabinofuranohydrolase activities. PcAxy43A hydrolyzed xylohexaose and birch wood xylan to release a series of xylooligosaccharides, indicating that PcAxy43A contained endo-xylanase activity. PcAxy43A exhibited β-xylosidase activity toward a chromogenic substrate, p-nitrophenyl-β-d-xylopyranoside, and xylobiose, while it preferred to hydrolyze long-chain xylooligosaccharides rather than xylobiose. In addition, surprisingly, PcAxy43A showed arabinoxylan arabinofuranohydrolase activity; that is, it released arabinose from both singly and doubly arabinosylated xylose, α-l-Araf-(1→2)-d-Xylp or α-l-Araf-(1→3)-d-Xylp and α-l-Araf-(1→2)-[α-l-Araf-(1→3)]-β-d-Xylp. Moreover, the combination of PcAxy43A and P. curdlanolyticus B-6 endo-xylanase Xyn10C greatly improved the efficiency of xylose and arabinose production from the highly substituted rye arabinoxylan, suggesting that these two enzymes function synergistically to depolymerize arabinoxylan. Therefore, PcAxy43A has the potential for the saccharification of arabinoxylan into simple sugars for many applications. IMPORTANCE In this study, the glycoside hydrolase 43 (GH43) intracellular multifunctional endo-xylanase, β-xylosidase, and arabinoxylan arabinofuranohydrolase (AXH) from P. curdlanolyticus B-6 were characterized. Interestingly, PcAxy43A AXH showed a new property that acted on both the C(O)-2 and C(O)-3 positions of xylose residues doubly substituted with arabinosyl, which usually obstruct the action of xylanolytic enzymes. Furthermore, the studies here show interesting properties for the processing of xylans from cereal grains, particularly rye arabinoxylan, and show a novel relationship between PcAxy43A and endo-xylanase Xyn10C from strain B-6, providing novel metabolic potential for processing arabinoxylans into xylose and arabinose.
Evidence that high-dosage zidovudine at time of retrovirus exposure reduces antiviral efficacy

The antiviral efficacy of prophylactic 3'-azido-3'-deoxythymidine (AZT) therapy administered by continuous infusion or intermittent injection was compared in pediatric cats infected with feline leukemia virus. A 4-week treatment regimen of AZT was initiated at -48, 8, or 96 h postinfection (p.i.). For AZT therapy begun at -48 h p.i. , significant efficacy was attained when therapy was given by continuous infusion but not by intermittent injection. However, when AZT therapy was delayed until 96 h p.i. , both continuous infusion and intermittent injection gave complete protection. The results suggest that intermittent AZT administration is less efficacious than continuous infusion. Higher peak AZT concentrations in plasma associated with intermittent injection compared with those associated with continuous infusion may be immunotoxic, thus reducing the drug-induced vaccine effect. Furthermore, AZT toxicity seemed to be restricted to a window of sensitivity close to the time of virus challenge because delaying the start of AZT therapy until 96 h p.i. was highly efficacious, regardless of the method of administration.
Effect of chelating agents on heavy metal extraction from contaminated soils

In the present study shacking and incubation experiment were carried out in order to evaluate the changes in heavy metal solubility in the studied soils by addition of different concentration of Ethylene dinitrilo tetra acetic acid (EDTA), Diethylene triamine penta acetic acid (DTPA), and Nitrilo tri acetic acid (NTA). The effects of EDTA, DTPA and NTA application on solubility of copper(Cu), lead(Pb), cadmium(Cd) and chromium(Cr) in soil was evaluated. In shacking experiment, maximum Cu, Pb, Cd and Cr were solubilized by DTPA extractant. It was found that with increasing chelating agent doses metals availability was increased and 5.0 mM doses of EDTA, DTPA and NTA was noticed the best optimum dose for further experiments. For shacking time significant results were achieved at 120 hours by applying EDTA and NTA where as DTPA behaved well at 24 hours. In incubation experiments more Cu and Cd was extracted by DTPA 6.65 and 6.67 ppm respectively. EDTA was proved good extracting solution for Pb which has solubilized maximum concentration of Pb (22.816 ppm). Maximum concentration of Cr (1.335 ppm) was solubilized by NTA as compared to EDTA and DTPA. For incubation experiment day 20-30 were more suitable for solubilzation of metals. Chelats has potential for the remediation of heavy metal-contaminated soils either as on-site soil washing agents or for in situ remediation. These findings could be used to develop a predictive tool for the target metals contaminants and for assessing chelation remediation efficiency based on chelates dose and contact time test results.
Fuels or microclimate? Understanding the drivers of fire feedbacks at savanna–forest boundaries

The higher flammability of tropical savanna, compared with forest, plays a critical role in mediating vegetation-environment feedbacks, alternate stable states, and ultimately, the distribution of these two biomes. Multiple factors contribute to this difference in flammability, including microclimate, fuel amount and fuel type. To understand this transition in flammability, we studied fuel characteristics and microclimate across eight savanna–forest boundaries in south-central Brazil. At each boundary, the environment was monitored for one week with automated measurements of near-surface wind speed, air temperature, relative humidity and presence of dew. Manual measurements were performed to quantify fuel amounts and fuel moisture. These data were used to parameterize the fire behaviour model BehavePlus5 in order to simulate fire behaviour over the savanna–forest boundary. There were strong gradients across the boundary in all variables with the exception of total fuel load. During the day, savannas had higher wind speed and air temperature, and lower relative humidity and fuel moisture than forests. Although fuel loads were similar in savanna and forest, savanna was characterized by lower fuel bulk density, largely because of the presence of grasses. Based on these measurements, the fire behaviour model predicted savanna fires to be faster, more intense, and with greater flame lengths, relative to forest. A sensitivity analysis indicated that the primary cause of these differences was the low fuel bulk density characteristic of grassy fuels, with lesser contributions from wind speed, fuel moisture and total fuel load. These results indicate that the dominance of grassy fuels is the primary cause of the high flammability of savanna.
AN EXPERIMENTAL MODEL FOR ASSESSMENT OF RENAL RECOVERY FROM WARM ISCHEMIA

A study was made of the acute and chronic (15 days) functional and morphologic effects on the rat kidney of warm ischemia and contralateral nephrectomy, in order to define a suitable animal model for testing renal transplant preservation techniques when warm ischemia is a contributing factor. Spontaneous recovery from 30-min warm ischemia was complete, and the model was consequently unsuitable; the high mortality from 90 min was unacceptable. Warm ischemia of 60 minutes produced severe renal tubular necrosis, an acceptable mortality, residual morphologic damage, and impairment of isolated kidney perfusion parameters at 15 days. Renal function in vivo was normal in many of these animals, despite appreciable residual morphologic changes, and it is evident that functional data alone are not sufficient for assessment of preservation regimens.
Large Intervening Non-Coding RNA HOTAIR is Associated with Hepatocellular Carcinoma Progression

Increasing evidence suggests that large intervening non-coding RNAs (lincRNAs) regulate key pathways in cancer invasion and metastasis. In this observational retrospective study, the expression of the oncogenic lincRNA HOX transcript antisense RNA (HOTAIR) gene was measured in 63 patients with hepatocellular carcinoma (HCC) following hepatic resection. The HOTAIR gene was significantly overexpressed in HCC tissues compared with adjacent non-tumour tissues. Patients with high HOTAIR gene expression in their tumours had an increased risk of recurrence after hepatectomy. There was also a significant correlation between HOTAIR expression and lymph node metastasis. In vitro assays in the HCC cell line Bel7402 demonstrated that knockdown of HOTAIR lincRNA reduced cell proliferation and was associated with reductions in levels of matrix metalloproteinase-9 and vascular endothelial growth factor protein, which are important for cell motility and metastasis. In conclusion, HOTAIR lincRNA might be a potential biomarker for the existence of lymph node metastasis in HCC.
Oxidative Stress and Cardiovascular Disease in Dialyzed Patients

Background/Aim: Oxidative damage has been suggested to play a key role in accelerated atherosclerosis and to be involved in cardiovascular disease (CVD) of dialyzed patients who are at risk of increased oxidative stress. The purpose of the present study was to examine the relationship between the severity of CVD and some markers of oxidative stress and antioxidant activity in our hemodialyzed (HD) and peritoneal dialysis (PD) patients. Methods: Plasma reactive oxygen metabolites, malondialdehyde and 4-hydroxynonenal (MDA-4HNE), thiols, α-tocopherol, and total antioxidant status (TAS) were measured in 55 HD and in 16 PD patients. CVD was considered as the result of variably combined cardiac, cerebral, and vascular pathologies which were scored and grouped in a single CVD index and analyzed with respect to the markers of the oxidative status. 16 normal subjects served as controls. Results: All patients showed evidence of increased oxidative stress which was more severe in HD than in PD patients and which was exacerbated by HD. When cardiac, cerebral, and vascular diseases were analyzed separately, plasma MDA-4HNE and TAS were significantly higher in more severely affected HD patients, but not in PD patients. In HD patients the CVD index was directly correlated with both MDA-4HNE and TAS (r = 0.42, p < 0.01; r = 0.39, p < 0.01) and inversely correlated with α-tocopherol (r = –0.32, p < 0.05). MDA-4HNE and TAS were directly correlated in HD patients and inversely correlated in control subjects. Conclusions: Our data show that, in spite of increased antioxidant defense, there is a relationship between the degree of lipid peroxidation and the severity of CVD in HD patients. Moreover, these data underscore the utility of MDA-4HNE, α-tocopherol, and TAS in the evaluation of cardiovascular disease.
An evaluation of the interactions between freshwater pulmonate snail hosts of human schistosomes and macrophytes.

An account is given of a laboratory investigation designed to evaluate the extent to which the freshwater pulmonate snail Biomphalaria glabrata (Say) can utilize various species of aquatic plants, mainly macrophytes, when presented in the following forms over different time scales: normal plants; dried plant material; homogenized plant material in calcium alginate matrices; water-soluble filtrates of plant homogenates in the medium. The following propositions, derived from the theory of phased coevolution of components of the module consisting of the epiphytic bacteria, algae, snails and macrophytes, are evaluated on the basis of the present results and others including those obtained in this laboratory. That as the snails had become specialized to exploit surface communities of epiphytic algae, decaying plant material and dissolved organic matter (DOM) early in their evolutionary history they would continue to exploit these resources when they later become associated with aquatic macrophytes. That pulmonate snails would tend to be feeding generalists capable of adapting to food of varying chemical composition, given sufficient time, provided it was sufficiently small or flaccid. That although macrophytes and snails show a strong positive relationship, the living macrophyte tissue would be little used by the snails. That the hard outer envelope, inherited from their terrestrial ancestors, would remain as the major defence mechanism of aquatic macrophytes against attack by snails and other aquatic invertebrates. That aquatic macrophytes would invest little in the nutrient deficiency strategy to reduce attack by invertebrates such as snails. That truly aquatic submerged macrophytes would not possess secondary plant compounds (SPC) that would be molluscicidal. Emergent parts of subaquatic or aquatic plants might be expected to be better sources of SPC with molluscicidal factors than submerged aquatic plants. Species of epiphytic or planktonic algae might be better sources of SPC with molluscicidal effects than aquatic macrophytes. That the strategies developed by pulmonate snails for obtaining their energy supplies would not be conducive to rapid speciation. The analysis of the present and other related results supports these propositions. Predictions based on the theory of mutualism involving the snails, macrophytes and other components of the module also receive some support from an analysis of the present results. The additional empirical work that could be undertaken to test this theory is briefly discussed. (ABSTRACT TRUNCATED AT 400 WORDS)