Miracle-dz/UniFAR-FTUs huggingface dataset:
A Phase II Study of Halichondrin B Analog Eribulin Mesylate (E7389) in Patients with Advanced Non-small Cell Lung Cancer Previously Treated with a Taxane: A California Cancer Consortium Trial

Introduction: Eribulin mesylate (E7389) is an analog of halichondrin B with a unique mechanism of microtubule binding. The activity and toxicity of eribulin were assessed in patients with advanced non-small cell lung cancer (NSCLC) previously treated with a taxane. Methods: An open-label phase II study included patients with NSCLC previously treated with platinum and taxane-based therapy, with up to two prior cytotoxic regimens, given for metastatic disease or as adjuvant therapy. Patients were stratified by taxane-sensitivity: taxane-sensitive (TS, progression >90 days after taxane) or taxane-resistant (TR, progression ⩽90 days after taxane). Patients received an intravenous infusion of eribulin at 1.4 mg/m2 on days 1 and 8 every 21 days. The primary end point was objective response rate and secondary end points included progression-free survival and overall survival. Results: Sixty-six patients were accrued. The objective response rate was 5% with a median duration of response of 7.8 months. In the TS arm, 3 of 45 patients (7%) achieved a partial response and another 11 of 45 (24%) achieved stable disease for at least 3 months, whereas in the TR arm, no patients achieved a partial response and 4 of 21 (19%) achieved stable disease for at least 3 months. Median progression-free survival was 2.9 months in the TS subgroup and 1.2 months in the TR subgroup. The median overall survival was 12.6 months in the TS subgroup and 8.9 months in the TR subgroup. Toxicities were primarily hematologic; only two patients developed grade 3 neuropathy. Conclusions: Eribulin mesylate is well tolerated and demonstrates activity in pretreated, TS NSCLC.
Adenosine triphosphatase and active cation transport in red blood cell membranes.

Most cells are capable of active transport of sodium and potassium across the cell membrane. The human red blood cell is one of the best studied systems with regard to the characteristics and mechanism of active cation transport. A membrane-associated enzyme, adenosine triphosphatase activated by Na and K (Na,K-ATPase), appears to be identical with the Na-K pump. The evidence includes similar kinetic properties and responses to cardiac glycosides of the pump and Na,-K-ATPase, the spatial asymmetry of activation of both pump and enzyme by K and Na, and synthesis of ATP mediated by the pump working in reverse. The energy-dependent transfer of Na and K through the membrane appears to be associated with the following reactions of Na,-K-ATPase: Na-dependent phosphorylation of the enzyme; conversion to a second form of phosphorylated enzyme; and K-dependent release of phosphate.
Attenuation of Ischemia/Reperfusion-Induced Ovarian Damage in Rats: Does Edaravone Offer Protection?

Aim: The aim of this study was to investigate whether prophylactic treatment with edaravone prevents ischemia/reperfusion (I/R)-induced ovarian damage during pneumoperitoneum in an experimental rat model. Methods: Twenty-eight female Sprague Dawley rats were allocated randomly to 4 groups. The sham group (group 1) was only subjected to catheter insertion, not to pneumoperitoneum. Group 2 received a 1 mg/kg dose of 0.9% sodium chloride by the intraperitoneal route for 10 min before pneumoperitoneum. Groups 3 and 4 received 6 and 12 mg/kg edaravone, respectively, by the intraperitoneal route for 10 min before pneumoperitoneum. After 60 min of pneumoperitoneum, the gas was deflated. Immediately after the reperfusion period, both ovaries were excised for histological scoring, caspase-3 immunohistochemistry and biochemical evaluation including glutathione (GSH) and malondialdehyde (MDA) levels. Also, total antioxidant capacity (TAC) was measured in plasma samples to evaluate the antioxidant effect of edaravone. Results: Ovarian sections in the saline group revealed higher scores for follicular degeneration and edema (p < 0.0001) when compared with the sham group. Administration of different doses of edaravone in rats significantly prevented degenerative changes in the ovary (p < 0.0001). Caspase-3 expression was only detected in the ovarian surface epithelium in all groups, and there was a significant difference between the treatment groups and the saline group (p < 0.0001). Treatment of rats with edaravone reduced caspase-3 expression in a dose-dependent manner. Moreover, biochemical measurements of oxidative stress markers (MDA, GSH and TAC) revealed that prophylactic edaravone treatment attenuated oxidative stress induced by I/R injury. Conclusion: These results indicate that prophylactic treatment with edaravone prevents I/R-induced ovarian damage during pneumoperitoneum in an experimental rat model.
Comparison of the Books of the New Testament (English Translation) in Terms of Emotion and Word Use

The 27 books of the New Testament (English Translation) were scored using the Dictionary of Affect in Language. Books were compared with one another in terms of Activation, Pleasantness, and Imagery scores, and in terms of word length, use of the word “love,” and mentions of Jesus. Significant differences among books were evident for all variables. A table of means and standard errors is provided. Measures of the books were related to one another, e.g., Pleasantness score and the use of the word “love” (ρ = .80) and to descriptors of the books, e.g., longer books tended to score lower on Pleasantness (ρ = -.79).
Stereological Characteristics of the Equine Accessory Nerve

Stereological techniques have been increasingly employed for assessment and characterization of neuromuscular diseases in humans and animals. As an adjunct to histopathology, morphometrical algorithms provide quantitative evidence of the peripheral nerve composition, thereby shedding light on its fibre characteristics and basic electrophysiological properties. In the horse, stereological investigations already have focussed on the recurrent laryngeal, deep peroneal and lateral palmar nerves (LPN). Of these, only the latter is suitable for taking biopsies in clinical settings, however, it does not contain any motor fibres and Ia‐afferents. On account of its virtually mixed fibre qualities, most researchers today recommend the cervical branch of the equine accessory nerve (AN) for harvesting diagnostic samples. Thus, the present study was carried out to gain morphometrical proof of the AN composition and to obtain stereological base values in healthy individuals using state‐of‐the‐art technology. All parameters were compared to the common peroneal nerve (CPN), known to harbour all myelinated fibre classes. As this second biopsy site is located farther distally to the neuro‐axis, attention was paid to possible length‐dependent features.
Application for VTE stratification and risk assessment

Venous thromboembolism is a pathology that is responsible for high rates of morbidity and mortality in hospitals. An adequate thromboprophylaxis may contribute to an effective improvement of the well-being and safety of patients. One of the important factors for the prescription of a thromboprophylaxis is the determination of the risk of thromboembolism, which can be implemented in several ways, using different methodologies, namely by using risk scales. In this work, developed in the Hospital Center of Trás-os-Montes and Alto Douro, Portugal, we describe the development and implementation of an application with two scales for the assessment and stratification of the risk of thromboembolism, to be applied in hospitalized patients (Caprini scale) and in patients in ambulatory surgery (scale recommended by the Portuguese Ambulatory Surgery Association). The application was integrated into the hospital electronic health record system (SClínico).
Mutations of the cationic trypsinogen in hereditary pancreatitis

Hereditary pancreatitis (OMIM 167800) is thought to be associated with a mutation of the exon 3 of cationic trypsinogen (Nature Genet (1996): 14:141–145). This paper reports sequence data of two independent families suffering from this disease. PCR amplificates from leukocyte or buccal swab DNA showed no mutation of exon 3 of cationic trypsinogen. Instead, in exon 2, an A‐to‐T tranversion was found that led to the substitution of Asn by Ile in the sixth amino acid of the active trypsin. In exons 4 and 5, silent mutations were found. In the other expressed trypsinogens, several homozygous alterations not associated to hereditary pancreatitis were identified. As a model of pathogenesis, we hypothesize that mutation of trypsinogen in exon 2 could lead to premature cleavage of the activation peptide of trypsinogen or to altered intracellular transport. Hum Mutat 12:39–43, 1998. © 1998 Wiley‐Liss, Inc.
Structure and Organization of the Living Mitotic Spindle of Haemanthus Endosperm

New details of mitotic spindle structures in the endosperm of Haemanthus katherinae (Bak) have been demonstrated by differential interference microscopy. Spindle fibers are clearly seen in the living spindle extending from the kinetochores to the polar region. Individual spindle fibers consist of a bundle of smaller filaments which diverge slightly from the kinetochore and intermingle with filaments from other spindle fibers as they approach the polar region. The degree of intermingling increases during metaphase and anaphase. The chromosomes stop moving when the spindle fibers are still 5 to 10microns long; then the fibers disappear. These observations explain some aspects of spindle movements which were difficult to reconcile with earlier concepts of spindle organization.
SUPPRESSION OF THE WRAPPING EFFECT BY TAYLOR MODEL-BASED VERIFIED INTEGRATORS : LONG-TERM STABILIZATION BY SHRINK WRAPPING

The verified integration of ranges of initial conditons through ODEs faces two major challenges, namely the precise representation of the flow over the short term, and the avoidance of unfavorable buildup of errors in the long term. We discuss the method of shrink wrapping for meeting the second of these challenges within the framework of Taylor model methods. Illustrative examples of the performance of the method and comparisons to other approaches are given. AMS Subject Classification: 65L05, 65G20, 34-04, 41A58
Models of confabulation: A critical review and a new framework

Confabulation can be defined as statements or actions that involve distortions of memories. This paper reviews current theories of confabulation focusing on source monitoring, temporal-context, and retrieval theories. The attributes and criticisms of these three models are discussed. From this review, a three-factor cognitive-neuropsychological framework is proposed, which can be used to explain the variable symptoms of confabulation. The framework takes its basis from the Langdon and Coltheart (2000a, 2000b) cognitive model of delusional belief formation. The model suggests that two deficits are likely in most cases of confabulation—an executive control retrieval deficit and an evaluation deficit. It also takes into consideration how the general organization of the autobiographical memory store and a person's individual emotional/motivational biases can influence confabulatory symptoms and content. This is an overarching framework that can be used to model confabulations, and it builds upon links between delusions and confabulation.
Synthesis of Paullones with Aminoalkyl Side Chains

Paullones 3 and 4 with aminoalkyl side chains in 2‐ or 3‐position were synthesized as derivatives of kenpaullone 1. Both 3 and 4 showed the characteristic CDK1‐inhibitory activity of the paullones and a modest antiproliferative activity on cultured human tumor cell lines. Hence, 3 and 4 appear to be suitable tools for affinity studies directed to find additional intracellular paullone targets.
Structural Uncertainty and Optimal Pollution Control

We relax the economic literature’s usual assumption that the structural relationship between emissions and ambient levels of pollution is known with certainty. We find that uncertainty over this relationship can manifest as a unique form of multiplicative uncertainty in the marginal damages from emissions. We show how the optimal stringency of environmental regulation depends on this structural uncertainty. We also show how new information, like the discovery of previously unapportioned emission sources, can counterintuitively lead to increases in both optimal emissions and ambient pollution levels.
The application of logistic regression in modeling of survival chances of HIV-positive patients under highly active antiretroviral therapy ( HAART ) : A Case of Nyakach District , Kenya

In Kenya the number of persons requiring antiretroviral Therapy (ART) in 2012 was over 90,000 while globally more than 1.4 million were under ART in the year 2012. Though ART treatment has decreased mortality of HIV associated deaths, there is still need for funding of ART services by donors and Ministry of health so as to prevent the loss caused by AIDS related deaths in the society. This study modeled using logistic regression the survival chances of the HIV positive patients under ART treatment in within Nyakach district. The study outlined the various socio-economic factors affecting the survival or death of the patients using logistic regression model. The sample of 320 patients was considered from patients from Katito health center from Nyakach district for a period of six months. The analysis of the data showed that risk factors consisting TB infection, kind of drug regimen, distance from the health facility, access to tap and portable water, the kind of marital status of patients and counselling session attendance by patients on ART affected their survival. Thus, the survival of patients under ART programs can be improved if we improve the access to socioeconomic factors like access to water, setting up many health facilities too provide health services at close distance to the affected and also we can bring behavioral change among HIV patients to attend counselling session and get pieces of advices on correct health measures and be-haviours.
The Contrasting Responses of Splanchnic and Renal Glucose Output to Gluconeogenic Substrates and to Hypoglucagonemia in 60-h-fasted Humans

SUMMARY Arterial concentrations and splanchnic as well as renal exchange of glucose, lactate, pyruvate, glycerol, and alanine were studied in the basal state and during intravenous infusion of alanine or glycerol in healthy subjects who had fasted for 60 h. After 45 min of infusion of alanine or glycerol, somatostatin administration (SRIF, 9 μg/min) was added to induce hypoglucagonemia. Alanine infusion, at a rate of 1 mmol/min, was accompanied by an 80% rise in splanchnic glucose output (SGO) and a small (16%) rise in arterial glucose. Splanchnic alanine uptake, which rose fivefold to sixfold above basal, could account for the entire rise in SGO. Intravenous administration of glycerol (1 mmol/min) resulted in an elevation of blood glucose (+ 9%) but no significant change in SGO, even though glycerol uptake by the splanchnic tissues rose eightfold above basal levels. Measurements of renal exchange of glucose indicated a small but statistically significant release of glucose from the kidney (0.04 ± 0.01 mmol/min) in the basal state, which accounted for 10% of total (renal plus splanchnic) glucose production. Administration of glycerol at a rate of 2 mmol/min resulted in a rise in renal glucose output to 0.16 ± 0.03 mmol/min, which could be accounted for in its entirety by renal glycerol uptake. In contrast, infusion of alanine (2 mmol/min), did not alter the renal glucose exchange. Infusion of SRIF was accompanied by a significant fall in the arterial glucagon level in all studies. Concomitante, large decreases in arterial glucose and SGO were observed during both alanine and glycerol administration. However, splanchnic uptake of gluconeogenic precursors was not influenced by SRIF administration. The elevated renal glucose output seen during glycerol administration was not altered by SRIF infusion. It is concluded that, in 60-h-fasted man, (a) renal glucose output contributes significantly to total glucose production, (b) administration of glycerol stimulates renal glucose production, (c) alanine infusion increases splanchnic but may not affect renal glucose output, and (d) hypoglucagonemia inhibits splanchnic but not renal glucose output. These data indicate that hepatic and renal gluconeogeneses respond differently with respect to stimulation by specific substrates and to their dependence on basal glucagon levels.
Key Structural Determinants in the Agonist Binding Loops of Human β2 and β4 Nicotinic Acetylcholine Receptor Subunits Contribute to α3β4 Subtype Selectivity of α-Conotoxins*

α-Conotoxins represent a large group of pharmacologically active peptides that antagonize nicotinic acetylcholine receptors (nAChRs). The α3β4 nAChR, a predominant subtype in the peripheral nervous system, has been implicated in various pathophysiological conditions. As many α-conotoxins have multiple pharmacological targets, compounds specifically targeting individual nAChR subtypes are needed. In this study, we performed mutational analyses to evaluate the key structural components of human β2 and β4 nAChR subunits that determine α-conotoxin selectivity for α3β4 nAChR. α-Conotoxin RegIIA was used to evaluate the impact of non-conserved human β2 and β4 residues on peptide affinity. Two mutations, α3β2[T59K] and α3β2[S113R], strongly enhanced RegIIA affinity compared with wild-type α3β2, as seen by substantially increased inhibitory potency and slower off-rate kinetics. Opposite point mutations in α3β4 had the contrary effect, emphasizing the importance of loop D residue 59 and loop E residue 113 as determinants for RegIIA affinity. Molecular dynamics simulation revealed the side chains of β4 Lys59 and β4 Arg113 formed hydrogen bonds with RegIIA loop 2 atoms, whereas the β2 Thr59 and β2 Ser113 side chains were not long enough to form such interactions. Residue β4 Arg113 has been identified for the first time as a crucial component facilitating antagonist binding. Another α-conotoxin, AuIB, exhibited low activity at human α3β2 and α3β4 nAChRs. Molecular dynamics simulation indicated the key interactions with the β subunit are different to RegIIA. Taken together, these data elucidate the interactions with specific individual β subunit residues that critically determine affinity and pharmacological activity of α-conotoxins RegIIA and AuIB at human nAChRs.
Laplace–Beltrami Operator on Point Clouds Based on Anisotropic Voronoi Diagram

The symmetrizable and converged Laplace–Beltrami operator ( ΔM ) is an indispensable tool for spectral geometrical analysis of point clouds. The ΔM , introduced by Liu et al. [LPG12] is guaranteed to be symmetrizable, but its convergence degrades when it is applied to models with sharp features. In this paper, we propose a novel ΔM , which is not only symmetrizable but also can handle the point‐sampled surface containing significant sharp features. By constructing the anisotropic Voronoi diagram in the local tangential space, the ΔM can be well constructed for any given point. To compute the area of anisotropic Voronoi cell, we introduce an efficient approximation by projecting the cell to the local tangent plane and have proved its convergence. We present numerical experiments that clearly demonstrate the robustness and efficiency of the proposed ΔM for point clouds that may contain noise, outliers, and non‐uniformities in thickness and spacing. Moreover, we can show that its spectrum is more accurate than the ones from existing ΔM for scan points or surfaces with sharp features.
Pyrosequencing-based screening for genetic polymorphisms in cytochrome P450 2B6 of potential clinical relevance.

OBJECTIVES Three exonic single nucleotide polymorphisms (SNPs) in the cytochrome P450 2B6 (CYP2B6) gene, 516G>T, 785A>G and 1459C>T, have been described to be associated with functional changes in the CYP2B6 catalytic activity or protein expression. They are therefore of potential clinical importance for drug efficacy and safety of CYP2B6 substrates, in particular of antiretroviral therapy regimes that include efavirenz. Therefore, we aimed at providing genetic screening assays for these three SNPs. METHODS Simplex Pyrosequencing assays were developed for the selected CYP2B6 SNPs. A total of 273 DNA samples from healthy volunteers of Caucasian ethnicity were genotyped. RESULTS The presently developed Pyrosequencing assays afford an accurate determination of the three SNPs in the 273 DNA samples. The assays were verified by routine implementation of control samples obtained by conventional sequencing. The frequencies for the variant alleles 516T, 785G and 1459T were 0.22, 0.24 and 0.13, respectively. All genotype frequencies were in agreement with the Hardy-Weinberg equilibrium. CYP2B6 alleles CYP2B6*5A (1459T), CYP2B6*6 (516T/785G) and *7B (516T/785G/1459T) were found at allelic frequencies of 0.12, 0.20 and 0.01. CONCLUSION The present reliable and quick Pyrosequencing assays afford facilitating future research on the importance of CYP2B6 pharmacogenetics for personalized drug therapy with CYP2B6 substrates.
Effect of 2, 4-Dichlorophenoxy acetic acid on nutrients and heavy metals accumulation in wheat (Triticum durum) root

The experiment was designed to determine the role played by the herbicidal auxin 2, 4D on accumulation of two micro, two macro-nutrients and two heavy metals in root of tetraploid wheat (T. durum). Three different doses of 2, 4-D 48, 96 and 240ppm were applied on wheat seed and allowed to germinate. Iron, Manganese, Magnesium, Calcium, Chromium and Lead content were analyzed by Flame Atomic Absorption Spectrometry (FAAS) in samples from different time interval (3, 5 and 7 days). Abnormal protuberance growth was observed at root of wheat plant in each concentration of the applied herbicide after three days of treatment. The herbicidal dose had significant inhibitory effect on uptake of micro nutrients, Iron and Manganese and macro nutrients, Calcium and Magnesium by the root of the tested plant. However, no inhibitory effect was observed on the uptake of heavy metals like Chromium and Lead. Incubation time had no effect on Chromium content but both dose and time had positive association with Lead content. It may be concluded that 2, 4–Dichlorophenoxy acetic acid impairs the nutrient uptake and increase the content of heavy metal in root of wheat.