Miracle-dz/UniFAR-FTUs huggingface dataset:
Temsirolimus in the treatment of mantle cell lymphoma: frequency and management of adverse effects

Purpose of review Temsirolimus (Torisel) is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL). The recommended dosage in this indication (175mg once weekly for 3 weeks and then 75 mg once weekly as maintenance) is higher than that for renal cell carcinoma; thus, the safety profile is quite different in the two indications. The aim of this review is to examine safety data for temsirolimus in MCL and provide guidance on the incidence and management of adverse events. Medline and EMBASE searches using the search terms ‘temsirolimus’ and ‘mantle cell lymphoma’ Findings Four main published phase II–III clinical studies of temsirolimus in MCL were identified. Many adverse events are class-effect toxicities of mTOR inhibitors but, for others, often an accurate relationship with temsirolimus is difficult to assess with certainty. Haematological adverse events are the most frequently reported, but these are generally successfully managed by dose reductions or treatment delay. Gastrointestinal toxicity, especially diarrhoea, is a frequent and common adverse effect, but the incidence of grade 3–4 events is low. Other nonhaematological toxicities include stomatological/dermatological and endocrinological adverse events. Incidence of these adverse events can be reduced by careful management and/or prevention. Grade 3 or higher pneumonitis, a known mTOR inhibitor-associated toxicity, was rarely reported in this indication, but the incidence was higher when temsirolimus was administered in combination with rituximab. Other adverse events include fatigue/asthenia, infection, hypersensitivity and extravasation. Sexual disorders, foetal malformations and psychiatric disorders are rarely reported. Summary Most temsirolimus-associated adverse events in patients with relapsed/refractory MCL are manageable, often without impacting administration of temsirolimus.
THE IMPACT OF TRANSFORMATIONAL AND TRANSACTIONAL LEADERSHIP STYLES ON THE MOTIVATION OF EMPLOYEES IN PAKISTAN

The role of leadership is very important in building a sustainable business and community organization. The purpose of this study is to find out the association of transformational and transactional leadership with the motivation of employees. The study uses a data consisted of the employees of all private and public banking sector of Pakistan. These banking employees have been randomly selected for ensuring the involvement of various demographic variables. The results of the study show positive and significant relationship between the independent variables transformational and transactional leadership with the dependent variable motivation.
Understanding Indirect Causal Relationships in Node‐Link Graphs

To find correlations and cause and effect relationships in multivariate data sets is central in many data analysis problems. A common way of representing causal relations among variables is to use node‐link diagrams, where nodes depict variables and edges show relationships between them. When performing a causal analysis, analysts may be biased by the position of collected evidences, especially when they are at the top of a list. This is of crucial importance since finding a root cause or a derived effect, and searching for causal chains of inferences are essential analytic tasks when investigating causal relationships. In this paper, we examine whether sequential ordering influences understanding of indirect causal relationships and whether it improves readability of multi‐attribute causal diagrams. Moreover, we see how people reason to identify a root cause or a derived effect. The results of our design study show that sequential ordering does not play a crucial role when analyzing causal relationships, but many connections from/to a variable and higher strength/certainty values may influence the process of finding a root cause and a derived effect.
Administration of adenosine during reperfusion reduces injury of vascular endothelium and death of myocytes.

INTRODUCTION To test the hypothesis that administration of adenosine during reperfusion attenuates endothelial dysfunction and extension of infarct size by inhibiting polymorphonuclear neutrophil (PMN)-mediated events and apoptosis. METHODS Anesthetized dogs were subjected to 1 h coronary artery occlusion and 6 h of reperfusion with infusion of saline (vehicle, n = 8) or 140 micrograms/kg per min adenosine, n = 8) continuously into the left atrium starting 5 min before reperfusion and continuing for 2 h. RESULTS There was no intergroup difference in collateral myocardial blood flow measured by using colored microspheres in the area at risk during ischemia. Infusion of adenosine transiently improved segmental shortening (4.1 +/- 3.1% versus -2.5 +/- 2.3%, P < 0.05) and segmental work (41.4 +/- 22 versus 15 +/- 13 mmHg/mm, P < 0.05) after 4 h of reperfusion. Infusion of adenosine reduced size of infarct (determined by staining with triphenyltetrazolium chloride) from 27 +/- 2% with vehicle to 14 +/- 1%, (P < 0.05). This was confirmed by measuring that it lowered activity of plasma creatine kinase (from 19 +/- 2 versus 8 +/- 1 IU/g protein, P < 0.05). It also reduced the proportion of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei in the perinecrotic zone from 17.3 +/- 1.6 to 10.3 +/- 1.0% (P < 0.05) and reduced the appearance of DNA ladders in gel electrophoresis. In addition, it significantly decreased accumulation of PMN in the ischemic area (determined by immunohistochemistry with anti-CD18 antibody) and activity of cardiac myeloperoxidase compared with vehicle (439 +/- 52 versus 183 +/- 20 PMN/mm2 myocardium and 1.1 +/- 0.1 versus 2.4 +/- 0.2 U/100 mg tissue, P < 0.05, respectively). Furthermore, infusion of adenosine during reperfusion preserved vascular endothelial function expressed in terms of a decrease in adherence of PMN to postischemic coronary artery endothelium (63 +/- 3 versus 36 +/- 4 PMN/mm2 endothelium, P < 0.05, basal function) and agonist (acetylcholine)-induced endothelium-dependent relaxation (negative logarithm to base 10 of concentration (mol/l) for half-maximal effect 7.7 +/- 0.1 versus 7.2 +/- 0.1, P < 0.05, stimulated function). Infusion of adenosine directly inhibited generation of superoxide radical from canine PMN in vitro dose dependently from 27.8 +/- 6.3 to 5.8 +/- 2.1 nmol/l/5 x 10(6) PMN (P < 0.05). CONCLUSION Intra-atrial infusion of adenosine during reperfusion reduced accumulation of PMN in area at risk, preserved vascular endothelial function after ischemia-reperfusion by inhibiting interaction between PMN and endothelial cells, and decreased extension of infarct, possibly by limiting apoptosis.
The Philosophy of Animal Minds: Invertebrate concepts confront the generality constraint (and win)

What does it take to possess a concept? Do any non-human animals have concepts? One crucial constraint on the concept concept is that concepts are the building blocks of thought. Hence no creature could count as a conceptuser that wasn’t capable of thinking. This mightn’t seem like a significant additional restriction, but actually it has some teeth, ruling out some otherwise concept-like phenomena. Consider the Australian digger wasp (Gould and Gould [1994]). The female builds a tower-and-bell structure above the hole in which she lays her eggs, to protect them from another species of parasitic wasp. At various points during construction she uses her own body as a yardstick. For example, she stops building the tower and begins on the bell once the former is three of her own body lengths high. Does she, then, have the concept, three body lengths (or some sufficiently close analog)? She does at least possess a sort of recognitional capacity which she deploys to end one phase of her activity and initiate another. (And likewise she must be capable of recognizing the materials that she collects for the construction of the tower, as well as recognizing that one side of the tower that she is constructing is higher than the other, and so forth.) But does the wasp believe that the tower is now three body lengths high, and is that why she moves on to the next activity (the construction of the bell)? There are multiple reasons for denying that she does. The most fundamental derives from the fact that the overall pattern of her behavior is rigid (albeit displaying flexibility of detail – collecting mud from here rather than there, placing the mud on this side rather than that side, and so on). For example, if an experimenter progressively buries the tower in sand
Communication about depression during rheumatoid arthritis patient visits.

OBJECTIVE To examine whether rheumatologists and rheumatoid arthritis (RA) patients with depressive symptoms communicate about depression. METHODS The data used in this study came from a randomized controlled trial to improve provider-patient communication about patients' agendas. The current secondary analysis used data collected at baseline, before any intervention occurred. A total of 200 RA patients from 4 rheumatology clinics participated in the study. Patient medical visits were audiotape recorded and patients were interviewed after their medical visits. Physicians recorded patients' American College of Rheumatology (ACR) functional status after their visits. RESULTS Twenty-one (11%) patients were scored as having moderately severe to severe symptoms of depression. Patients who were rated by their physicians as having worse ACR functional status were more than twice as likely to have moderately severe to severe symptoms of depression (odds ratio 2.23, 95% confidence interval 1.1-4.6). Only 4 (19%) of the 21 patients who were scored as having moderately severe to severe symptoms of depression discussed depression during their medical visits, and patients initiated the discussion each time. CONCLUSION Rheumatologists should consider assessing depressive symptoms among their patients, especially among those with worse functional status.
Prognostic factors in the surgical treatment of medically intractable epilepsy associated with mesial temporal sclerosis

Objectives– To assess the prognostic factors determining seizure remission after temporal lobectomy for intractable epilepsy associated with mesial temporal sclerosis (MTS) at pathology. Methods– The clinical and investigative features of 116 consecutive patients who had temporal lobe surgery for drug‐resistant epilepsy and MTS at pathology were assessed using actuarial statistics and logistic regression analysis. Results– At a median follow‐up of 63 months the probability of achieving at least a 1‐year period of continuous seizure freedom was 67%. Factors contributing to a favourable outcome were interictal EEG localization to the operated lobe and the absence of secondarily generalized seizures. These were also selected in the multivariate analysis, although at lower statistical significance (P=0.08 and 0.09, respectively). Perinatal complications were associated with a significantly worse outcome but overall, complicated febrile convulsions and congruent neuropsychological deficits were not significantly predictive variables. Conclusions– The present findings may aid in the non‐invasive presurgical assessment of patients with intractable TLE and clinical and neuroimaging evidence of MTS.
SEASONAL DISPERSAL PATTERNS OF SYLVAN DEER MICE (PEROMYSCUS MANICULATUS) WITHIN MONTANA RANGELANDS

We examined seasonal dispersal patterns and timing of new infections of Sin Nombre virus (SNV), as determined by recent acquisition of antibodies (seroconversion), in deer mice (Peromyscus maniculatus) at two Montana rangeland study sites over three years, 2004–2007. One study site was located in grassland habitat, and the other was located in shrub-steppe. In Montana, both of these habitats are commonly associated with peridomestic environments (in and around buildings). Peridomestic environments are where most reported human cases of hantavirus pulmonary syndrome (HPS) likely originate. Furthermore, deer mice dispersing from sylvan habitats colonize peridomestic environments. Thus, a thorough understanding of deer mouse dispersal is needed to help predict when humans are most at risk for exposure to SNV. We trapped mice at each study site twice a month, accumulating 85,200 trap nights of effort and capturing 6,185 individual deer mice a total of 22,654 times. We documented 980 dispersing individuals over 3 yr. We found positive correlations between the number of dispersing mice and number captured at each site, but there were no statistically significant seasonal differences in the number of dispersing mice. However, we did find a spring/summer bias in mice that seroconverted and dispersed, suggesting that recently infected deer mice are most likely to enter settings where humans may be exposed to SNV during spring and summer.
Low-Operating-Voltage Operation and Improvement in Sensitivity With Passivated OFET Sensors for Determining Total Dose Radiation

Using high-k material in a gate dielectric stack, low-operating-voltage organic semiconducting material sensors for determining total dose radiation are proposed. To improve the stability of organic semiconducting layer in the atmospheric conditions, a thin silicon nitride layer deposited by hot-wire CVD process was used as a passivation layer. Furthermore, in order to achieve higher sensitivity, a parallel connection of organic field-effect transistors (OFETs) is explored in this letter. These sensors are exposed to ionizing radiation using a cobalt-60 radiation source for different total dose values. A three-times improvement in sensitivity was observed in the off current with a three-OFET array.
The in fl uence of rebate programs on the demand for water heaters : The case of New South Wales ☆

☆ Thefirst authorwould like to acknowledge research su Council grant DP 0774142 and UTS Faculty of Business Re University of Technology Sydney. Jordan Louviere provide mental design, Yen-Ching Sung provided assistance on in and Edward Wei provided invaluable assistance in Panpiemras and participants at several conference and s helpful comments on earlier versions of the paper. ⁎ Corresponding author. Tel. : +1 734 936 0324; fax: + E-mail address: nwasi@umich.edu (N. Wasi). 1 http://www.climatechange. gov.au/government/p hot-water.aspx.
Deblurring and Denoising of Images by Nonlocal Functionals

This paper investigates the use of regularization functionals with nonlocal correlation terms for the problem of image denoising and image deblurring. These functionals are expressed as integrals over the Cartesian product of the pixel space. We show that the class of neighborhood filters can be described in this framework. Using these functionals we can consider the functional analytic properties of some of these neighborhood filters and show how they can be seen as regularization terms using a smoothed version of the Prokhorov metric. Moreover, we define a nonlocal variant of the well-known bounded variation regularization, which does not suffer from the staircase effect. We show existence of a minimizer of the corresponding regularization functional for the denoising and deblurring problem, and we present some numerical examples comparing the nonlocal version to the bounded variation regularization and the nonlocal mean filter.
Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With Different Susceptibility to Experimental Autoimmune Prostatitis

Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate‐specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).
A Predictive Coexpression Network Identifies Novel Genes Controlling the Seed-to-Seedling Phase Transition in Arabidopsis thaliana1[OPEN]

A seed-to-seedling gene coexpression network reveals homeodomain leucine zipper I transcription factor AtHB13 as a novel key regulator affecting primary root length during late seedling establishment. The transition from a quiescent dry seed to an actively growing photoautotrophic seedling is a complex and crucial trait for plant propagation. This study provides a detailed description of global gene expression in seven successive developmental stages of seedling establishment in Arabidopsis (Arabidopsis thaliana). Using the transcriptome signature from these developmental stages, we obtained a coexpression gene network that highlights interactions between known regulators of the seed-to-seedling transition and predicts the functions of uncharacterized genes in seedling establishment. The coexpressed gene data sets together with the transcriptional module indicate biological functions related to seedling establishment. Characterization of the homeodomain leucine zipper I transcription factor AtHB13, which is expressed during the seed-to-seedling transition, demonstrated that this gene regulates some of the network nodes and affects late seedling establishment. Knockout mutants for athb13 showed increased primary root length as compared with wild-type (Columbia-0) seedlings, suggesting that this transcription factor is a negative regulator of early root growth, possibly repressing cell division and/or cell elongation or the length of time that cells elongate. The signal transduction pathways present during the early phases of the seed-to-seedling transition anticipate the control of important events for a vigorous seedling, such as root growth. This study demonstrates that a gene coexpression network together with transcriptional modules can provide insights that are not derived from comparative transcript profiling alone.
Effect of BM-573 [N-Terbutyl-N′-[2-(4′-methylphenylamino)-5-nitro-benzenesulfonyl]urea], a Dual Thromboxane Synthase Inhibitor and Thromboxane Receptor Antagonist, in a Porcine Model of Acute Pulmonary Embolism

The aim of this study was to evaluate the effect of BM-573 [N-terbutyl-N′-[2-(4′-methylphenylamino)-5-nitro-benzenesulfonyl]urea], a dual thromboxane A2 synthase inhibitor and receptor antagonist, on the hemodynamic response to acute pulmonary embolism. Six anesthetized pigs were infused with placebo (placebo group) and compared with six other pigs receiving a continuous infusion of BM-573 (BM group). Pulmonary embolization with 0.3 g/kg autologous blood clots was carried out 30 min after the start of the infusion. Right ventricular pressure-volume loops were recorded using a conductance catheter, and end-systolic ventricular elastance was periodically assessed by varying right ventricular preload. Pulmonary vascular properties were studied by use of a four-element windkessel model. Hemodynamic data, including assessment of right ventricular-arterial coupling, were collected at baseline and every 30 min for 4 h. Blood samples were collected to assess gas exchange, thromboxane A2, and prostacyclin plasma levels and to evaluate platelet aggregation. Mean pulmonary arterial pressure in the placebo group increased significantly more than in the BM group, mainly because of an additional increase in pulmonary vascular resistance. Arterial and end-systolic ventricular elastances increased also more in the placebo group, whereas right ventricular efficiency decreased. BM-573 prevented both platelet aggregation induced by U-46619 (9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α) or by arachidonic acid, and thromboxane A2 overproduction, whereas prostacyclin liberation was preserved. Oxygenation, however, was not significantly improved. We conclude that in this animal model of acute pulmonary embolism, infusion of BM-573 reduced pulmonary vasoconstriction. As a result, right ventricular-vascular coupling values were maintained at a maximal efficiency level.
ARDS as Presenting Symptom in an Infant with CD40L Deficiency (Hyper-IgM Syndrome Type 1)

We report on a 4 month old male infant with respiratory syncytial virus (RSV) infection leading to acute respiratory distress syndrome (ARDS). A diagnostic algorithm including extended infectiological and immunological work-up revealed absence of CD40-ligand. ARDS was treated successfully with a complex respiratory therapy plus intravenous immunoglobulin substitution. Molecular analysis detected mutations in the CD40L gene (Hyper-IgM syndrome Type 1). The case underlines the importance of an extended diagnostic work-up in an uncommonly severe course of respiratory infection in early infancy.
Ultrasound-guided laser thermal ablation for treatment of benign thyroid nodules.

OBJECTIVE To evaluate the efficacy of ultrasound (US)-guided laser thermal ablation (LTA) in reducing the volume of hypofunctioning benign thyroid lesions. METHODS The criteria for entry into the study were as follows: (1) presence of a hypofunctioning thyroid nodule with a volume exceeding 8 mL, (2) benign cytologic findings, (3) local compression symptoms or patient concern, and (4) refusal of or ineligibility for surgical treatment. Twenty patients (15 women and 5 men; mean age, 63.3 +/- 14.1 years) fulfilling the entry criteria were enrolled in the study. Under US monitoring, a 75-mm, 21-gauge spinal needle was inserted into the thyroid gland, and a flat-tipped 300-microm quartz fiberoptic guide was placed through the needle into the tissues. LTA was performed with use of a 1.064-microm continuous-wave neodymium yttrium-aluminum-garnet laser that had an output power of 3 W for 10 minutes. US scans were used to assess the decrease in nodule volume at 1 month and 6 months after LTA. RESULTS After LTA, mean nodule volume decreased from a baseline value of 24.1 +/- 15.0 mL to 13.3 +/- 7.7 mL at 1 month and to 9.6 +/- 6.6 mL at 6 months. Mean nodule volume reduction in comparison with baseline was 43.8 +/- 8.1% at 1 month and 63.8 +/- 8.9% at 6 months. LTA induced burning cervical pain, which rapidly decreased after the laser energy was turned off. Three patients (15%) required treatment with betamethasone for 48 hours. No patient had local bruising, cutaneous burning, or dysphonia. CONCLUSION LTA may be an effective procedure for the treatment of benign cold thyroid nodules that cause pressure symptoms in patients who are not candidates for surgical treatment or who refuse to undergo a surgical procedure.
Correlates of protection efficacy induced by vaccinia virus‐specific CD8+ T‐cell epitopes in the murine intranasal challenge model

The recent identification of a large array of different vaccinia virus‐derived CD8+ T‐cell epitopes offers a unique opportunity to systematically analyze the correlation between protective efficacy and variables such as kinetics of expression and function of viral proteins, binding affinity to MHC molecules, immunogenicity, and viral antigen processing/presentation. In the current study, 49 different H‐2b restricted epitopes were tested for their ability to protect peptide‐immunized C57Bl/6 mice from lethal i.n. challenge with vaccinia virus. The epitopes varied greatly in their ability to confer protection, ranging from complete protection with minimal disease to no protection at all. The function or kinetics of the viral antigen expression did not correlate with protective efficacy. However, binding affinity partially predicted protection efficacy and ultimately epitope immunogenicity and recognition of infected cells offered the best correlation.