Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomized, multicenter phase III study of ranpirnase plus doxorubicin (DOX) versus DOX in patients with unresectable malignant mesothelioma (MM).

7507 Background: Ranpirnase (Onconase), a novel ribonuclease with preclinical activity against various tumors, has led to a median survival of 8.3 ms (one year survival: 42%) in a multicentre phase II trial in chemonaive and pretreated pts whom met the Cancer and Leukemia Group B (CALGB) prognostic criteria for group 1-4 (Mikulski, J Clin Oncol 20, 2001). METHODS This multicenter controlled phase III trial compared efficacy and safety of Dox (one of the most active single agents when the study was planned) with or without ranpirnase. Primary endpoint was overall survival (OS), secondary endpoints included progression-free survival, response rate, safety and disease related symptoms. Eligibility criteria: histologically proven unresectable MM; CALGB group 1-4, ECOG PS 0-1, adequate organ function. Stratification was performed according to CALGB group and histology (epitheloid vs. non-epitheloid). One line of prior therapy was permitted. Between 08/01 and 09/07 413 eligible pts were randomized to DOX 60 mg/m2 every 3 wks with or without ranpirnase 240 μg/m2 weekly (cycle 1) and 480 μg/m2 in subsequent cycles (maximum 6) if no severe toxicity had occurred. The study was designed to detect an increase of 4 ms (9 vs. 13) in median OS (MST) using a two-sided logrank test (α = 5%) with 90% power. RESULTS Both arms were well balanced (DOX + ranpirnase / DOX: 203/210 pts): Mean age 62.2/61.8 yrs; males 157/156; PS 0 52/60; PS 1 151/150; prior chemo 65/65 pts (pemetrexed 35/35; other chemo 30/30). CALGB groups 14/14 (1), 45/51 (2), 117/115 (3), 27/30 (4). In the intent to treat population (ITT) there was no significant difference in OS (MST: 11.1 vs 10.7 ms; HR 1.02, 95% CI 0.82-1.26) whilst in a preplanned analysis including 130 pretreated patients a significant advantage in survival in favor of DOX + ranpirnase was found (MST: 10.5 vs 9 ms; HR 1.49, 95% CI 1.02-2.17). The safety profile for both treatment arms was similar. Most frequent side effects reported for both treatment groups included nausea, fatigue and alopecia. CONCLUSIONS Combination of ranpirnase and DOX is a safe and feasible treatment in unresectable MM and showed a significant impact on survival of pretreated patients compared to DOX alone. [Table: see text].
Adjunctive Lipid Lowering Therapy in the Era of Surrogate Endpoints

Statins have been shown to reduce cardiovascular events. However, despite widespread use of statin therapy, residual cardiovascular risk remains, and this has left clinicians searching for an effective adjunctive therapy to optimize lipid profiles and reduce risk further. Given the cost and duration of large event driven trials, adjunctive lipid lowering therapy options have largely been evaluated through surrogate measures of atherosclerosis, making clinical practice decisions regarding combination therapy difficult. Two common approaches that have been evaluated almost entirely by surrogate outcome trials include the addition of ezetimibe or the addition of niacin. Our article attempts to place these surrogate end point trials in their proper context, providing clinicians with a practical approach to making clinical practice decisions regarding adjunctive therapy in the absence of clinical outcomes data. Although definitive changes to lipid lowering guidelines should be based on clinical outcomes trials, in the absence of clinical outcomes data, it is reasonable to make individualized clinical practice decisions on the basis of surrogate measures of disease as long as there is corroboration among the effect on atherosclerosis and lipid parameters as adjunctive therapy, and clinical outcomes as monotherapy. Given that niacin fits these criteria, it seems prudent to support the use of niacin as adjunctive therapy in combination with maximally tolerated dose of statin in patients with low high-density lipoprotein-cholesterol and known coronary artery disease. Three ongoing clinical outcomes trials evaluating niacin and ezetimibe in combination with statin will provide more definitive word regarding the safety and efficacy of these agents as adjunctive therapy.
'Frontal' cognitive function in patients with Parkinson's disease 'on' and 'off' levodopa.

A wide range of cognitive impairments can be observed in patients with Parkinson's disease. A close parallel exists between these deficits and those found following damage to prefrontal cortex. Anatomical evidence is reviewed which reveals a complex pattern of neuronal circuits connecting the frontal cortex and basal ganglia. All these circuits are in some way dependent upon dopamine, suggesting that changes in the levels of dopamine stimulation may alter performance on 'frontal' tests. To test this hypothesis, a group of patients with Parkinson's disease were assessed both on and off levodopa treatment, on a range of tests selected from the human and animal experimental literature as being sensitive to disruption of prefrontal cortex. A variable pattern of results was obtained. On one test, a measure of verbal fluency, patients were impaired, compared with normal controls, only when off levodopa. On two measures, associative conditional learning and subject-ordered pointing, patients were impaired only when on levodopa, while on the final measures, the Wisconsin Card Sorting Test, patients were impaired both on and off levodopa. Two mechanisms are discussed to explain these results, one based on the effects of dopamine depletion, and the other based on the adverse effects of dopamine overstimulation. The results suggest that different areas of prefrontal cortex are involved in the tasks employed, and that functional levels of dopamine in separate areas of cortex and caudate may differ crucially in Parkinson's disease.
Origins of positive cloud‐to‐ground lightning flashes in the stratiform region of a mesoscale convective system

The origins of positive cloud‐to‐ground (+CG) lightning in the stratiform region of a leading‐line, trailing‐stratiform mesoscale convective system (MCS) are investigated. Platforms include radars, NLDN data, and a VHF 3‐D lightning mapping system. This study examines a small asymmetric MCS that occurred near the Colorado‐Kansas border in June 2000. In this storm 39 of the 269 +CGs produced over a nearly 5‐hour period came to ground within the stratiform region. Of these, 30 initiated in the leading convective line and propagated rearward before coming to ground. Nine other +CGs originated within the stratiform region. Stratiform +CGs were observed to propagate mostly horizontally through vertically thin layers. The observations suggest that stratiform charge is a conduit for +CG lightning from the convective line, and can initiate +CGs as well.
Heterogeneity of Specific CD4+ and CD8+ T Cells Stimulated by CMV pp65 and IE1 Antigens

Characterization of human cytomegalovirus-specific T cells (CMV-T) is of critical importance for their potential use in adoptive immunotherapy after allogeneic hematopoietic stem cell transplantation. Background frequencies of CMV-T in peripheral blood mononuclear cells (PBMCs) of CMV-seropositive healthy subjects are usually very low, hence the requirement for prolonged culture time and multiple stimulations to expand them. The evaluation of the end-culture specificity and composition has sometimes been neglected or difficult to assess in these settings. We explored the identity and the functionality of pp65-specific and IE1-specific T cells, enriched in short-term cultures from PBMCs. Antigen-specific T cells were further isolated by IFN-&ggr; capture system and/or CD154 microbeads. Frequency of IE1-specific cytotoxic T cells in PBMCs secreting IFN-&ggr; was higher compared with the pp65-specific one, whereas the latter cell types showed a higher median CD107a degranulation. Cell viability, rate of CMV-T increase, and multicytokine secretion profile after epitope-specific short-term cultures were heterogenous. T cells were mainly of late effector stages but they significantly dropped off upon CMV rechallenge with peptide pools. In parallel, CMV-T expansion was accompanied by a significant increase of cytotoxic naive/memory stem cells (CTLs), whereas the CD4+ counterpart significantly increased only upon stimulation with IE1. Outcome was variable and showed donor and epitope dependency. Differences in human leukocyte antigen and epitope dominance and variability in the relative number of CD3+ effector cells and IFN-&ggr;/CD154 expression among healthy donors could reflect the observed individual CMV-specific cellular immunity. This heterogeneity raises points to be considered when approaching adoptive immunotherapy.
Comparison of breath and in-mouth collection for the measurement of oral malodorous compounds by gas chromatography using sulfur chemiluminescence detection

Volatile sulfur compounds (VSCs), specifically hydrogen sulfide, methyl mercaptan and dimethyl sulfide, are generally considered to be the primary volatiles responsible for ‘morning’ malodors in breath. To date, the ‘gold standard’ for detecting VSC concentrations in breath is the use of gas chromatography coupled with sulfur chemiluminescence detection. Breath gas is often collected in a polypropylene syringe and then aliquots are injected into a gas chromatograph for analysis. The objective of this work was to compare the Twister™ bar in-mouth extraction methodology for measurement of VSCs with the gas syringe breath-sampling collection technique. The Twister bar technology captures malodorous compounds in the mouth as opposed to breath gas. Using these techniques, comparable results were obtained in studies demonstrating the efficacy of a proprietary oral malodor counteraction system.
Quality of life and related risk factors in a Taiwanese Village population 21 months after an earthquake.

OBJECTIVE To investigate quality of life and related risk factors of Taiwanese earthquake survivors with different psychiatric disorders 21 months after the earthquake. METHOD This was a population survey. Trained assistants used the Medical Outcomes Study Short Form-36 (MOS SF-36) and questionnaires to interview 461 respondents (209 males and 252 females) 16 years or older who were equally exposed to the earthquake. Psychiatrists interviewed the same respondents using the Mini-International Neuropsychiatric Interview (MINI), with an adjusted response rate of 79.9%. RESULTS The prevalence of varied psychiatric disorders in earthquake survivors ranged from 3.3% to 18%. However, there was almost a positive trend in quality of life in survivors among the following groups: posttraumatic stress disorder combined with major depressive episode; major depressive episode; posttraumatic stress disorder; other psychiatric diseases; and healthy mentality groups on the physical aspect or mental aspect of the MOS SF-36. When survivors were elderly or female and had experienced prominent financial loss immediately after the earthquake, social network change, and mental impairment, their quality of life tended to be worse. CONCLUSION The earthquake survivors had a higher percentage of psychiatric disorders. The risk factors that affected quality of life in survivors were age, female sex, financial loss, social network change, and mental impairment.
Angular Dependence of Low-Frequency Noise in Al$_{2}$ O$_{3}$ -Based Magnetic Tunnel Junction Sensors With Conetic Alloy

We demonstrated the noise performances of Al2O3-based magnetic tunnel junction sensors (MTJs) in the low-frequency regimes. Conetic alloy Ni77Fe14Cu5Mo4 was deposited as both the MTJ pinned layer and free layer because of its superb magnetically soft properties. A rotating magnetic field was employed to investigate the angular dependence of the MTJ low-frequency noise. Hooge parameter was applied for parameterizing the low-frequency noise. The measurement results demonstrate that the Hooge parameters are angular-dependent and they exhibit a linear relation with respect to the angular magnetoresistive susceptibility. It can be also observed that the Hooge parameters possess a higher value when the Conetic MTJs are in the region of antiparallel state. These results indicate that the magnetic fluctuations in the ferromagnetic layers contribute to the low-frequency noise level in Conetic MTJ sensors.
Bilingualism advantage in handwritten character recognition: A deep learning investigation on Persian and Latin scripts

In this study, we investigated the effects of mastering multiple scripts in handwritten character recognition by means of computational simulations. In particular, we trained a set of deep neural networks on two different datasets of handwritten characters: the HODA dataset, which is a collection of images of handwritten Persian digits, and the MNIST dataset, which contains Latin handwritten digits. We simulated native language individuals (trained on a single dataset) as well as bilingual individuals (trained on both datasets), and compared their performance in a recognition task performed under different noisy conditions. Our results show the superior performance of bilingual networks in handwritten digit recognition in comparison to the monolingual networks, thereby suggesting that mastering multiple languages might facilitate knowledge transfer across similar domains.
Overexpression of HuD Accelerates Neurite Outgrowth and Increases GAP-43 mRNA Expression in Cortical Neurons and Retinoic Acid-Induced Embryonic Stem Cells in Vitro


The neuron-specific RNA-binding protein HuD binds to a U-rich regulatory element of the 3' untranslated region (3' UTR) of the GAP-43 mRNA and stabilizes the mRNA. We have previously shown that overexpression of HuD in PC12 cells increases GAP-43 protein expression and induces the spontaneous formation of multiple neurites (K. D. Anderson et al. 2000. J. Neurochem. 75: 1103-1114). In this study, we examined the effects of HuD overexpression on the initial stages of neurite outgrowth and on GAP-43 gene expression using two in vitro systems: E19 rat cortical neurons and retinoic acid (RA)-induced embryonic stem (ES) cells. Normal neurite outgrowth of cortical neurons in vitro occurs over a 3-day period with a concomitant increase in GAP-43 and HuD expression. Cortical cells were infected with a replication-deficient HSV-1 vector containing the HuD cDNA in the sense orientation (HSV-HuD). Overexpression of HuD accelerated the formation of neurites. Immunocytochemical analysis showed that excess HuD resulted in a threefold increase in the number of GAP-43-positive cells undergoing morphological differentiation after 24 h of treatment. Using in situ hybridization, we found that the increased HuD expression resulted in a twofold increase in the levels of GAP-43 mRNA. Similarly, overexpression of HuD in RA-induced embryonic stem cells was found to increase the number of GAP-43-positive cells undergoing process outgrowth. In conclusion, our results demonstrate that HuD functions in the initiation of neurite outgrowth in a manner due, at least in part, to its regulation of GAP-43 expression.
Software Defect Prediction using Bayesian Networks and Kernel Methods

There are lots of different software metrics discovered and used for defect prediction in the literature. Instead of dealing with so many metrics, it would be practical and easy if we could determine the set of metrics that are most important and focus on them more to predict defectiveness. In this book, we use Bayesian modeling to determine the influential relationships among software metrics and defect proneness. Furthermore, we propose a novel technique for defect prediction that uses plagiarism detection tools. We use kernel programming to model the relationship between source code similarity and defectiveness and suggest that source code similarity is a good means of predicting both defectiveness and the number of defects in software systems.
Experience with bortezomib for the treatment of patients with relapsed classical Hodgkin lymphoma.

The proteasome inhibitor bortezomib has been successfully used to treat patients with multiple myeloma and non-Hodgkin lymphoma. [1][1]-[3][2] We have recently reported that bortezomib can induce cell cycle arrest and apoptosis in a variety of Hodgkin lymphoma (HL)-derived cell lines in vitro. [4][3]
Medical versus Fiscal Gatekeeping: Navigating Professional Contingencies at the Pharmacy Counter

Commercialization of medicine is a growing trend that threatens to undermine physicians’ commitments to patient care in favor of personal financial interests. Bemoaned by Arnold Relman as early as 1980, growing for-profit sectors of health care have been reshaping medicine from a profession into a business, forming the foundation of what he terms a “medical-industrial complex” that threatens to undermine professional identity and reshape health care funding. Commercialization poses new ethical challenges for health care providers who have a financial stake in their health care decisions and may undermine their fiduciary duties to patients. Certainly, commercialization has brought about new trends in medicine — one need only to look as far as the rise in for-profit hospitals, diagnostic laboratories, and proprietary nursing homes to see how opportunities for financial gain reposition physicians’ orientations vis-à-vis patients.
Septic Cardiomyopathy

Myocardial depression without structural changes in patients with sepsis is termed “septic cardiomyopathy. ” Calvin et al in 1981 demonstrated myocardial dysfunction in volume-resuscitated septic patients, who had decreased ejection fraction and increased enddiastolic volume index. Subsequently, using pulmonary artery catheters (PAC) with serial radionuclide imaging, Parker et al furthered these observations with the 2 major findings that (a) survivors of septic shock had increased end-diastolic volume index and decreased ejection fraction, whereas nonsurvivors typically maintained normal cardiac volumes; and (b) these acute changes in end-diastolic volume index and ejection fraction, although sustained for several days, were reversible. More recently, echocardiographic studies have demonstrated impaired left ventricular systolic and diastolic function in septic patients. Overall, septic cardiomyopathy can be characterized by sudden (1) depression of cardiac output despite elevated levels of catecholamines; (2) decreased blood pressure response to fluid boluses; (3) reversible reduction in ejection fraction; and (4) biventricular dilation. Patients may also have profoundly reduced stroke volumes and left ventricular ejection fractions of <30% despite exhibiting normal left ventricular end-diastolic volumes. Septic cardiomyopathy was believed to occur late in the sepsis continuum; however, it has been also demonstrated early in the disease state and impairs both ventricles. Preclinical and clinical data suggest that myocardial depression occurs in the presence of elevated levels of proinflammatory cytokines.
Parthenogenetic development of bovine oocytes matured in vitro for 24 hr and activated by ethanol and cycloheximide

This research was undertaken to improve development of parthenogenetic embryos following various combined treatments of ethanol and cycloheximide. In Experiment 1 in vitro matured oocytes (IVM, 24 hr) were treated with 7% ethanol for 5 min followed by incubation in 10 μg/ml cycloheximide in Medium 199 for 0 (control), 5, 10, and 20 hr. Development to 2–8 cells following culture for 3 days was similar among treated groups (32–41%; P > 0.05), which was higher than that of controls (6%; P < 0.05). Experiment 2 compared pre‐ethanol exposures for 0, 1, 2.5, and 5 min, followed by 5 hr cycloheximide treatment on activation development. One‐ to 5‐min groups resulted in 42–44% cleavage contrasted to 1–12% for controls (P < 0.05). Experiment 3 examined the effect on oocyte development of ethanol and different concentrations of cycloheximide (0, 1, 5, and 10 μg/ml). Cleavage to 2–8 cells was similar among the 5 and 10 μg/ml cycloheximide groups (36% and 42%, P > 0.05) but lower (P < 0.05) for the 1 μg/ml group (24%) and the controls (2–13%). When 5 μg/ml cycloheximide was used (Experiment 4), pre‐exposure to ethanol (1, 2.5, and 5 min) resulted in more oocytes cleaved (38–41%) than in the cycloheximide alone group (0%) or the control (0%, P < 0.05). Experiment 5 tested blastocyst development of the activated oocytes with or without cytochalasin B treatment. Oocytes developed to blastocyts were 0%, 14%, 3%, and 3% (P < 0.05), respectively, for control, treatment with ethanol and cycloheximide in the presence, or absence of cytochalasin B, or electrical pulse plus cycloheximide. In conclusion, the combined ethanol and cycloheximide treatment supported high rates of parthenogenetic development using 24 hr IVM bovine oocytes. Blastocyst rate was significantly higher when cytochalasin B was added to the combined activation regimen. © 1994 Wiley‐Liss, Inc.
Isoflavonoids, flavonoids, phenolic acids profiles and antioxidant activity of soybean seeds as affected by organic and bioorganic fertilization

3 Abstract: Soybean intake is inversely correlated with risks of several chronic diseases in human. Phytochemicals and in particular phenolic acids, flavonoids and isoflavonoids compounds present in soybean seeds may be partially responsible for these health benefits through their antioxidants activity. In a pot experiment, soybean plants was grown in sandy media and irrigated with Hoagland solution as inorganic treatment or grown under one of the three levels of compost i.e. 25, 50 and 75% alone or in a mixture with multi- bioorganic. Individual phenolic acids, quercetin, genistein and daidzein in seeds were quantified by HPLC. Changes in the levels of individual phenolics and less value of quercetin under various compost levels resulting in insignificant lower values of total phenolics and total flavonoids as compared with inorganic grown seeds. Adding multi-bioorganic to 50 or 75% compost treatments produce great enhancement effects on total phenolics, total flavonoids, protocatechuic acid, p-hydroxybenzoic acid, chlorogenic acid, caffeic acid, quercetin, genistein and daidzein contents as compared with other treatments. The most enhancement effect was exhibited phenolic acids, quercetin and genistein. Addition of multi-bioorganic to 50% compost treatments resulted in 68 and 40% increases in quercetin and genistein, respectively, as compare with inorganic treatment, as well as 90 and 47% increases, respectively, as compare with 50% compost alone. The highest values of antioxidant activity was determined in soybean seeds grown under 50 and 75% compost, especially when mixed with bioorganic. Using either 50 or 75%, compost in a mixture with bioorganic caused increases in antioxidant activity ranged between 25 and 60% when compared with other inorganic and compost alone treatments. These results indicate that bioorganic fertilizers play a role in determining antioxidant activity and phenolic metabolites of soybean seeds.