Miracle-dz/UniFAR-FTUs huggingface dataset:
Trough Plasma Imatinib Concentrations Are Associated with Both Cytogenetic and Molecular Responses to Standard-Dose Imatinib in Chronic Myeloid Leukemia.

BACKGROUND Variable responses to imatinib, in the treatment of chronic myeloid leukemia (CML), are incompletely understood. Previous studies focused on cellular mechanisms of resistance to imatinib. Another hypothesis for variable response lies in pharmacokinetic variability that may reduce drug exposure in patients receiving imatinib. METHODS Using high-performance liquid chromatography-tandem mass spectrometry, we assessed trough plasma imatinib concentrations in CML patients who responded or not to standard-dose imatinib, after at least one year’s treatment. Complete cytogenetic response (CCR) was defined as 0 percent Philadelphia-chromosome-positive cells in bone marrow. Major molecular response (MMR) was defined as a 3 logarithm reduction of BCR-ABL transcripts, quantified from peripheral blood using real-time quantitative reverse-transcriptase polymerase chain reaction. RESULTS Sixty-eight patients were included. Mean trough plasma imatinib concentrations were significantly higher in the group with CCR (56 patients) than in the group without (P=0.02). Mean (±SD) trough plasma imatinib concentrations were significantly higher in the group with MMR (34 patients) than in the group without (1452.1±649.1 ng per milliliter vs. 869.3±427.5 ng per milliliter, P<0.001) whereas there was no difference in the imatinib daily dose. For trough plasma imatinib concentrations and their discrimination potential for MMR, the area under receiver-operating characteristic curve was 0.775, with best sensitivity (76.5 percent) and specificity (70.6 percent) at a plasma threshold of 1002 ng per milliliter. CONCLUSIONS Monitoring of plasma imatinib concentrations may become part of standard management of CML patients, or should at the very least be checked in the case of treatment failure or suboptimal response.
Institutions, banking structure and the cost of debt: new international evidence

This paper analyses the effect of institutions and the structure of the banking system on the cost of debt for a sample of firms from 37 countries. The cost of debt decreases with the rule of law, the protection of creditors’ rights, and the weight of banks in the economy. The bank financing and bank concentration have a positive differential effect on the cost of debt in those countries where the financial difficulties of banks are greater. Legal enforcement, the protection of creditors’ rights and the weight of bank financing have a greater influence in countries with a lower degree of economic development.
Furosemide terminates generalised seizure status epilepticus in a woman with inter-ictal focal seizures

tatus Epilepticus is an additional and life-threatening burden for patients living with epilepsy and their families. Extra precautionary measures attend the use of present medications available to treat the disorder. In this report, a 55-year old woman who presented with recurrent generalised tonic-clonic seizures and loss of consciousness between seizures had her attacks abated with 40mg of intravenously-administered furosemide. Her vital signs remained unperturbed and she regained consciousness in less than 30 minutes of the furosemide administration indicating that there was no evolution to subtle status epilepticus; after which there was post-ictal sleep which lasted about two hours. Also in this report, the mechanism of action of furosemide responsible for its seizure-terminating effects is discussed. The use of furosemide with its therapeutic efficacy, low cost and safety profile may stand to be a welcome addition to the armamentarium available to deal with status epilepticus.
Iron Deficiency in Menstruating Adult Women: Much More than Anemia

Background: Iron deficiency anemia (IDA) is highly prevalent in women of child-bearing age. However, their nonhematological symptoms have been overlooked. This study aims to analyze the nonhematological features and symptoms of IDA in a group of women of reproductive age and the changes occurred during iron therapy. Materials and Methods: IDA women underwent dietary, physical activity, menstrual blood loss, and cognitive function assessment at baseline. Hematological and biochemical parameters were analyzed. Executive attention was tested by the flanker task and working memory by the 2-back task. Oral iron therapy (ferrous sulfate) was given to 35 women for 8 weeks and the changes in iron status, biochemical markers, cognitive function, and nonhematological symptoms were evaluated. Results: Patients presented nonhematological symptoms: pica, 32.4%; cheilitis, 20.6%; restless legs syndrome (RLS), 20.6%; diffuse hair loss, 55.9%; and ungual alterations, 38.2%. Two or more symptoms were present in 58.8% of women. Serum iron and working memory were correlated at baseline. Multivariate analyses show associations (odds ratio [OR], 95% confidence interval [CI]) between pica and reaction time in the working memory test (OR 2.14, 95% CI 1.19–3.87, p = 0.012); RLS with total serum protein (OR 0.08, 95% CI 0.06–0.92, p = 0.043); and cheilitis with mean corpuscular hemoglobin (OR 0.388, 95% CI 0.189–0.799, p = 0.01). Pica, cheilitis, and RLS completely resolved with iron therapy, and ungual alterations and hair loss improved in 92.3% and 84.2% of women, respectively. Better performance in executive attention and working memory was observed after iron therapy. Conclusions: More attention should be given to the nonhematological manifestations of IDA to improve the quality of life of menstruating women.
Exchange Rate Effects on Agricultural Exports: Transaction‐Level Evidence from Pakistan

This article examines the effects of domestic currency depreciation on agricultural exports from Pakistan including the responses of price and quantity margins. It uses highly disaggregated firm‐level data that contains the exchange rates of the actual currencies of invoicing at the transaction level. The study finds that the currency depreciation positively affects both intensive and extensive margins. The intensive margin increase in agricultural exports operates mainly through prices, whereas the response of quantities is relatively smaller. Moreover, depreciation improves the extensive margins of firms and products and expands the client base in existing markets. These responses vary widely across firms' exporting experience, trade orientation, sectoral and spatial distribution, exchange rate regimes, and invoicing currencies.
The a-isoform of VEGFA165 is a Significantly Stronger Activator of Human Retinal Endothelial Cells compared to the b-isoform

Purpose: Studies show that the b-isoform of Vascular Endothelial Growth Factor-A-165 (VEGFA165b) is predominant in normal human vitreous, switching to the a-isoform (VEGFA165a) in the vitreous of eyes with active diabetic retinopathy or ROP. The potential of this isoform-switching to impact the retinal vasculature is not clear, particularly in primary human retinal endothelial cells, which are important targets of VEGFA. We do not know how these two isoforms compare in their ability to activate key intracellular signalling pathways (MAPK, AKT) or alter VEGFA-target gene expression in primary human endothelial cells from the neural retina. Methods: Effects of saturating amounts of both VEGFA165 isoforms (a/b) on the rat retinal vasculature were compared using intravitreal injection, fluorescein-angiography and Optical Coherence Tomography to monitor primary vein dilation and retinal edema. Full dose-response curves for the activation of MAPK (ERK1/2), AKT and VEGFR2 were determined using direct in-cell western assays of primary Human Retinal Microvascular Endothelial Cells (HRMECs). Differences in dose-response effects on gene expression markers related to endothelial cell / leukocyte adhesion (ICAM1, VCAM1 and SELE ) and tight-junctions (CLDN5 and OCLN ) were tested by quantitative-PCR. Results: In rats, dilation of primary retinal veins and edema could be induced within 24 hours by intravitreal injection of a saturating dose of either isoform. In HRMECs, activation dose-response analysis revealed much stronger activation of MAPK, AKT and VEGFR2 by the a-isoform at lower doses. While similar maximum activation of VEGFR2 and MAPK could be achieved by both isoforms at higher doses, maximum activation of AKT by the b-isoform was only half that observed for the a-isoform. At the level of gene expression, VEGFA165a was also more effective at increasing expression of ICAM1, VCAM1 and SELE and decreasing expression of CLDN5 and OCLN at intermediate and high doses in primary HRMECs. Conclusions: VEGFA165a maximally activated MAPK and AKT in HRMECs at lower concentrations where VEGFA165b had little effect. The timing for maximal activation of MAPK was similar for both isoforms in HRMECs, which is different from non-retinal endothelial cells. While the dose-responses for VEGFR2 and MAPK activation had similar maximums with both isoforms, there were large differences between the isoforms in their effects on endothelial cell gene expression even at a high dose. The shifts of VEGFA165 expression from mostly b-isoform to mostly a-isoform, as reported in some human retinal vascular diseases, could potentially impact the activation of intracellular signalling and VEGFA target gene expression in endothelial cells of the human neural retina.
Severe periodontitis associated with Marfan syndrome- an existence or a co-existence.

Marfan syndrome is the most common dominant autosomal genetic disorder of connective tissue origin. Over the years various diagnostic criteria have been developed for this entity, the earliest among them is the Berlin Nosology, which classifies this condition mainly based on its physical characteristics.Oral manifestations associated with this condition are poorly documented and periodontitis associated with Marfan syndrome is still a controversy. This article report a case of Marfan syndrome with periodontal involvement, the patient was successfully managed with nonsurgical periodontal therapy. Keywords: Connective tissue disorders, Marfan’s syndrome,Dolichocephalia,Fibrillin.
A Phase I Humanized Anti-CD40 Monoclonal Antibody (SGN-40) in Patients with Multiple Myeloma.

SGN-40, a humanized anti-CD40 monoclonal antibody, is being evaluated in a phase I dose escalation study for patients with relapsed and/or refractory multiple myeloma. This single-arm trial is designed to evaluate safety, pharmacokinetics, immunogenicity, antitumor activity, and the maximum tolerated dose. SGN-40 has demonstrated potent in vitro and in vivo efficacy against cell lines expressing CD40, a member of the tumor necrosis factor receptor family. CD40 is widely expressed on tumors of B-cell origin, including myeloma, non-Hodgkin’s lymphoma, Hodgkin’s disease, and chronic lymphocytic lymphoma. The original protocol called for cohorts of patients to be treated with four weekly infusions of 0.5, 1.0, 2.0, 4.0, 8.0, or 16.0 mg/kg. Sixteen patients were treated at doses ranging from 0.5 – 4.0 mg/kg/wk for four weeks. Enrollment of new patients was temporarily halted after two of three patients developed severe headaches and aseptic meningitis following the first dose at 4 mg/kg. Grade 1 headaches were seen after the first dose in three of six patients receiving 2 mg/kg, but no patients at lower doses reported headaches. We have determined that this drug-related event is a first-dose effect, and was not seen clinically after second or subsequent infusions of SGN-40. SGN-40 appears to trigger cytokine release, and TNF-alpha levels in the plasma are elevated following the first infusion only. Initial pharmacokinetic data in humans demonstrate that the half-life of SGN-40 depends on the dose given: mean values after the first and third infusions were 0.9 and 1.3 days, respectively, at 0.5 mg/kg; 1.7 and 2.6 days at 1.0 mg/kg; and 2.9 and 4.2 days at 2.0 mg/kg. This is consistent with results in non-human primates, in which the half-life was relatively short at low doses. These data suggest that there is a rapid elimination pathway and/or redistribution volume that has not been saturated at the doses used to date. Although human anti-human antibodies (HAHA) have not yet been measured, the preliminary analysis suggests that if antibodies were formed, they did not significantly affect pharmacokinetics. Even at the low doses tested thus far, there is preliminary evidence for antitumor activity; four of sixteen patients had declining serum and/or urine M-protein during treatment. Of note, these four individuals also demonstrated the most profound B-cell depletion during therapy, an expected consequence of SGN-40 activity. This protocol has been amended to include a drug-loading period that should eliminate first-dose cytokine release syndrome. Dose escalation is ongoing under the revised protocol, and no headaches have been seen in the first cohort at a peak dose of 3 mg/kg. In conclusion, SGN-40 demonstrated an apparent first-dose cytokine release reaction that required a modification in the dosing strategy. Pharmacokinetic data suggest that higher doses are required to saturate the elimination pathway, and preliminary antitumor activity is encouraging.
Environmental Infractions and Fines Imposed for Illegal Fishing in the State of Pará, Amazon, Brazil

Environmental regulation and the implementation of formal sanctions, including fines, are part of the environmental policy of almost all nations, including Brazil. The BrazilianÂ Institute of the Environment and Renewable Natural Resources (IBAMA) is the main environmental body responsible for the supervision of fishing in Brazil. This study aimed to characterize environmental infringements and fines related to illegal fishing in the state of ParAi between 2009 and 2016 by means of data interpretation, using the Corporate System of Registration, Collection, and Monitoring of IBAMA, which contains management information on environmental monitoring. A total of 886 notices of infringement against illegal fishing were recorded in ParAi, with 2009 having the highest (198) and 2015 the lowest number of notices (42). The main infractions against fishing in the state were for fishing in an unauthorized season or zone and fishing without prior registration, inscription, authorization, license, permit or registration of the competent body, or contrary to obtained permit. Â According to the notices conducted by IBAMA, fisheries resources have been exploited illegally in estuarine and coastal environments in the state of ParAi.
A Rate-scalable Perceptual Wavelet-based Vibrotactile Codec

For a fully immersive virtual reality experience, humans have to be presented with high quality haptic stimuli in addition to audio and video. However, delivering haptic stimuli with high level of realism is still challenging. An important component of haptic stimulation is based on vibrotactile signals. They are emitted when sliding a tooltip or a finger over a textured surface and carry a large amount of information about the surface material properties. Vibrotactile signals have received considerable attention so far, though as the number of interaction points to be displayed will start to increase soon, it is vital that data rates are kept low. This calls for an efficient codec that is able to compress these signals while maintaining perceptual transparency. The IEEE P1918.1. 1 standardization group has issued a call for contributions for such a codec. In this work, we present our contribution to this standardization effort. We have developed a highly efficient codec which employs a discrete wavelet transform, human tactile perceptual modeling, quantization, and lossless coding to achieve high compression, while maintaining perceptual signal quality. The proposed vibrotactile codec compresses the signals at least by a factor of 10 with practically no perceptual impairment for most signals. Thus, our approach significantly outperforms the current state-of-the-art.
Settling disks in a linearly stratified fluid

We consider the unbounded settling dynamics of a circular disk of diameter $d$ and finite thickness $h$ evolving with a vertical speed $U$ in a linearly stratified fluid of kinematic viscosity $\unicode[STIX]{x1D708}$ and diffusivity $\unicode[STIX]{x1D705}$ of the stratifying agent, at moderate Reynolds numbers ($Re=Ud/\unicode[STIX]{x1D708}$). The influence of the disk geometry (diameter $d$ and aspect ratio $\unicode[STIX]{x1D712}=d/h$) and of the stratified environment (buoyancy frequency $N$, viscosity and diffusivity) are experimentally and numerically investigated. Three regimes for the settling dynamics have been identified for a disk reaching its gravitational equilibrium level. The disk first falls broadside-on, experiencing an enhanced drag force that can be linked to the stratification. A second regime corresponds to a change of stability for the disk orientation, from broadside-on to edgewise settling. This occurs when the non-dimensional velocity $U/\sqrt{\unicode[STIX]{x1D708}N}$ becomes smaller than some threshold value. Uncertainties in identifying the threshold value is discussed in terms of disk quality. It differs from the same problem in a homogeneous fluid which is associated with a fixed orientation (at its initial value) in the Stokes regime and a broadside-on settling orientation at low, but finite Reynolds numbers. Finally, the third regime corresponds to the disk returning to its broadside orientation after stopping at its neutrally buoyant level.
Predictors of attitudes and performance in U.S. Army recruiters: Does personality matter?

ABSTRACT Given the interpersonal nature of recruiting and the validity of personality assessments for predicting performance in a broad range of civilian and military jobs, personality traits are likely to predict the performance of recruiters in the Army as well. However, much of the research on the characteristics of successful recruiters has been conducted in civilian samples and has not examined the effects of recruiters’ personality on their job-related attitudes and behaviors. Although some research has examined the prediction of recruiter performance in a military context, more research is needed to identify profiles of personality traits that will help recruiters to be successful on the job. We explored this relationship in a sample of experienced recruiters with at least six months of service in a recruiting duty assignment. Results indicated that composites of personality traits were substantial predictors of recruiter performance and attitudes. The implications of these results for the selection and assessment of recruiters in the U.S. Army will be discussed.
Intellectual Capital, Supply Chain Learning, and Adaptability: A Comparative Investigation in China and the United States

This article investigates the relationship between intellectual capital, supply chain learning, and supply chain adaptability. Specifically, relying on organizational learning theory, a research model is proposed linking intellectual capital (consisting of the trichotomy of human, organizational, and social capital), supply chain learning (consisting of supplier learning and customer learning) and supply chain adaptability. We scrutinize these relationships in two culturally-diverse contexts, China and USA, and develop hypotheses concerning the differences in the relative strengths of these relationships. Data from 300 Chinese and 229 USA manufacturers in high-tech industries are used to test these hypotheses. While the relationships are generally supported, especially insightful are the results where they differ between the two countries. While human capital is more important in influencing organizational capital in USA, social capital is more important in China. Social capital also plays a more significant role in influencing customer learning in China, while no statistical differences are detected in social capital's influence on supplier learning across the two countries. The divergence observed can be explained by the cultural differences between the two countries. Implications are provided for managers in both countries to improve supply chain adaptability.
A showdown between bilingual and mainstream education: the impact of language of instruction on learning subject content knowledge

ABSTRACT Bilingual education has become popular in many countries in the last two decades. It is generally acknowledged that learning a second language (L2) through subject content has a positive impact on students’ L2 learning, but there is less agreement on whether this also applies to learning subject content knowledge in and through L2. This cross-sectional study compared Dutch pre-university mainstream and bilingual education students in grades 7 and 9 on a history knowledge test, taking into consideration the language of instruction and testing. Students were also tested on their motivation to learn and affinity with history, because of the alleged higher motivation bilingual education students bring to the classroom. Multilevel analyses showed that bilingual education students in grade 7 lagged behind in the English part of the test but performed at the same level in the Dutch part. 9th bilingual education graders on the other hand performed significantly better on the knowledge test than 9th mainstream graders in both L2 and L1, thus providing evidence for the non-detrimental effect of bilingual education on the acquisition of subject content knowledge.
The Relationship Between Inflammation and Metabolic Syndrome (MetS)-A Matter of Gender?

ADELA VIVIANA SITAR TAUT1,2,#, OLGA ORASAN1,2,#, ADRIANA FODOR1,3#, ANCA DANIELA FARCAS1,4*, SIMINA TARMURE SARLEA1,2, GABRIELA DOGARU1,5, DUMITRU TUDOR ZDRENGHEA1,6, DANA POP1,6, ANGELA COZMA 1,2,# 1 Iuliu Hatieganu University of Medicine and Pharmacy, 8 Victor Babes Str. , 400012, Cluj Napoca, Romania 2 Department of Internal Medicine 4th Medical Clinic, 18 Republicii Str. , 400015, Cluj Napoca, Romania, 3 Clinical Center of Diabetes, Nutrition, Metabolic Diseases, 2-4 Clinicilor Str. , 400006, Cluj Napoca, Romania 4 Emergency Clinical County Hospital, Cardiology Department, 3-5 Clinicilor Str, 400006, Cluj Napoca, Romania 5 Clinical Rehabilitation Hospital, Department of Medical Rehabilitation, 46-50 Viilor Str. , 400437, Cluj Napoca, Romania 6 Clinical Rehabilitation Hospital, Department of Cardiology, 46-50 Viilor Str, 400437, Cluj Napoca Romania