Miracle-dz/UniFAR-FTUs huggingface dataset:
Low-dose radioimmunotherapy ((90)Y-PAM4) combined with gemcitabine for the treatment of experimental pancreatic cancer.

PURPOSE Monoclonal antibody PAM4 is reactive with the MUC1 mucin as expressed by >85% of human pancreatic cancers. Significant antitumor effects have been demonstrated using radiolabeled PAM4 for radioimmunotherapy (RAIT) of experimental pancreatic cancer. The goal of the present study was to determine whether the addition of low-dose (90)Y-PAM4 RAIT to a clinically relevant regimen of gemcitabine chemotherapy would provide enhanced antitumor efficacy over that observed by chemotherapy alone without the addition of significant toxicity to normal tissues. EXPERIMENTAL DESIGN Mice bearing human pancreatic tumor xenografts (CaPan1) were administered three cycles of gemcitabine chemotherapy (1000 mg/m(2)/week for 3 weeks with 1 week off) concomitant with (90)Y-labeled PAM4 RAIT (25 micro Ci; 10% of the single agent MTD) given at weeks 0, 4, and 7. Control groups of mice received chemotherapy alone, (90)Y-PAM4 RAIT alone, or an equidose of (90)Y-labeled nontargeting control antibody with and without gemcitabine. RESULTS Mice that received (90)Y-PAM4 RAIT with gemcitabine had tumors that were significantly smaller in size than all of the other treatment groups (P < 0.005). A median survival of 24 weeks was achieved in mice that received the combined treatment versus 10 weeks for mice that received only gemcitabine (P < 0.001) and 16 weeks for mice that received only (90)Y-PAM4 RAIT (P < 0.040). The combined treatment regimen was well tolerated. CONCLUSIONS A combined chemoimmunotherapy and RAIT approach using gemcitabine and low-dose (90)Y-PAM4 provided significantly increased antitumor efficacy than was observed for each treatment arm given alone. Importantly, the enhanced antitumor efficacy was achieved with minimal toxicity to normal tissues. These studies provide justification for clinical trials using the combined modality treatment for patients with pancreatic cancer.
SimMed: combining simulation and interactive tabletops for medical education

A large body of work asserts that interactive tabletops are well suited for group work, and numerous studies have examined these devices in educational contexts. However, few of the described systems support simulations for collaborative learning, and none of them explicitly address immersion. We present SimMed, a system allowing medical students to collaboratively diagnose and treat a virtual patient using an interactive tabletop. The hybrid user interface combines elements of virtual reality with multitouch input. The paper delineates the development process of the system and rationale behind a range of interface design decisions. Thereby, the role of realism in gaining procedural knowledge is discussed - in particular, the interplay between realism, immersion and training goals. We implemented several medical test cases and evaluated our approach with a user study that suggests the great potential of the system. Results show a high level of immersion, cooperation and engagement by the students.
Insulin Analogs and Cancer

Today, insulin analogs are used in millions of diabetic patients. Insulin analogs have been developed to achieve more physiological insulin replacement in terms of time-course of the effect. Modifications in the amino acid sequence of the insulin molecule change the pharmacokinetics and pharmacodynamics of the analogs in respect to human insulin. However, these changes can also modify the molecular and biological effects of the analogs. The rapid-acting insulin analogs, lispro, aspart, and glulisine, have a rapid onset and shorter duration of action. The long-acting insulin analogs glargine and detemir have a protracted duration of action and a relatively smooth serum concentration profile. Insulin and its analogs may function as growth factors and therefore have a theoretical potential to promote tumor proliferation. A major question is whether analogs have an increased mitogenic activity in respect to insulin. These ligands can promote cell proliferation through many mechanisms like the prolonged stimulation of the insulin receptor, stimulation of the IGF-1 receptor (IGF-1R), prevalent activation of the extracellular-signaling-regulated kinase (ERK) rather than the protein kinase B (PKB/AKT) intracellular post-receptor pathways. Studies on in vitro models indicate that short-acting analogs elicit molecular and biological effects that are similar to those of insulin. In contrast, long-acting analogs behave differently. Although not all data are homogeneous, both glargine and detemir have been found to have a decreased binding to receptors for insulin but an increased binding to IGF-1R, a prevalent activation of the ERK pathway, and an increased mitogenic effect in respect to insulin. Recent retrospective epidemiological clinical studies have suggested that treatment with long-acting analogs (specifically glargine) may increase the relative risk for cancer. Results are controversial and methodologically weak. Therefore prospective clinical studies are needed to evaluate the possible tumor growth-promoting effects of these insulin analogs.
A Source Transfer Domain Decomposition Method for Helmholtz Equations in Unbounded Domain

We propose and study a domain decomposition method for solving the truncated perfectly matched layer (PML) approximation in bounded domain of Helmholtz scattering problems. The method is based on the decomposition of the domain into nonoverlapping layers and the idea of source transfer which transfers the sources equivalently layer by layer so that the solution in the final layer can be solved using a PML method defined locally outside the last two layers. The convergence of the method is proved for the case of constant wave number based on the analysis of the fundamental solution of the PML equation. The method can be used as an efficient preconditioner in the preconditioned GMRES method for solving discrete Helmholtz equations with constant and heterogeneous wave numbers. Numerical examples are included.
Numerical Analysis of the Transient Behaviour of a Variable Speed Pump-Turbine during a Pumping Power Reduction Scenario

To achieve the carbon free electricity generation target for 2050, the penetration of renewable energy sources should further increase. To address the impacts of their unpredictable and intermittent characteristics on the future electricity grid, Pumped Hydro Energy Storage (PHES) plants should enhance their regulation capability by extending their continuous operating range far beyond the optimal normal working range. However, for the time being, the regulation capability of the new generation of PHES, equipped with reversible pump-turbines due to their cost-effectiveness, is limited at part load by instability problems. The aim of this paper is to analyse, during a pumping power reduction scenario, the onset and development of unsteady phenomena leading to unstable behaviour. A 3D transient numerical simulation was carried out on the first stage of a variable-speed two-stage pump-turbine from full load to the unstable operating zone by progressively reducing the speed from 100% to 88% rpm corresponding to a power reduction from full load to about 60% with a ramp rate of 1.5% per s. Two three-dimensional unsteady flow structures affecting the return channel and the wicket gates at the end of the first stage were identified and their evolution in the power regulation scenario was fluid-dynamically and spectrally characterized to determine the fluid-dynamical conditions causing the head drop in the hump zone.
Relationship of Surgical Approach to Neurodevelopmental Outcomes in Hypoplastic Left Heart Syndrome

OBJECTIVE. Two strategies for surgical management are used for infants with hypoplastic left heart syndrome (HLHS), primary heart transplantation and the Norwood procedure. We sought to determine how these 2 surgical approaches influence neurodevelopmental outcomes at school age. METHODS. A multicenter, cross-sectional study of neurodevelopmental outcomes among school-aged children (>8 years of age) with HLHS was undertaken between July 2003 and September 2004. Four centers enrolled 48 subjects, of whom 47 completed neuropsychologic testing. Twenty-six subjects (55%) had undergone the Norwood procedure and 21 (45%) had undergone transplantation, with an intention-to-treat analysis. The mean age at testing was 12.4 ± 2.5 years. Evaluations included the Wechsler Abbreviated Scale of Intelligence, Clinical Evaluation of Language Fundamentals, Wechsler Individual Achievement Test, and Beery-Buktenica Developmental Test of Visual-Motor Integration. RESULTS. The mean neurocognitive test results were significantly below population normative values. The mean full-scale IQ for the entire cohort was 86 ± 14. In a multivariate model, there was no association of surgical strategy with any measure of developmental outcome. A longer hospital stay, however, was associated significantly with lower verbal, performance, and full-scale IQ scores. Aortic valve atresia was associated with lower math achievement test scores. CONCLUSIONS. Neurodevelopmental deficits are prevalent among school-aged children with HLHS, regardless of surgical approach. Complications that result in prolonged hospitalization at the time of the initial operation are associated with neurodevelopmental status at school age.
Synaptic Control of Spiking in Cerebellar Purkinje Cells: Dynamic Current Clamp Based on Model Conductances

Previous simulations using a realistic model of a cerebellar Purkinje cell suggested that synaptic control of somatic spiking in this cell type is mediated by voltage-gated intrinsic conductances and that inhibitory rather than excitatory synaptic inputs are more influential in controlling spike timing. In this paper, we have tested these predictions physiologically using dynamic current clamping to apply model-derived synaptic conductances to Purkinje cells in vitro. As predicted by the model, this input transformed thein vitro pattern of spiking into a different spike pattern typically observed in vivo. A net inhibitory synaptic current was required to achieve such spiking, indicating the presence of strong intrinsic depolarizing currents. Spike-triggered averaging confirmed that the length of individual intervals between spikes was correlated to the amplitude of the inhibitory conductance but was not influenced by excitatory inputs. Through repeated presentation of identical stimuli, we determined that the output spike rate was very sensitive to the relative balance of excitation and inhibition in the input conductances. In contrast, the accuracy of spike timing was dependent on input amplitude and was independent of spike rate. Thus, information could be encoded in Purkinje cell spiking in a precise spike time code and a rate code at the same time. We conclude that Purkinje cell responses to synaptic input are strongly dependent on active somatic and dendritic properties and that theories of cerebellar function likely need to incorporate single-cell dynamics to a greater degree than is customary.
Increase in Serum Amyloid A Evoked by Dietary Cholesterol Is Associated With Increased Atherosclerosis in Mice

Background—Elevated serum amyloid A (SAA) levels are associated with increased cardiovascular risk. SAA levels can be increased by dietary fat and cholesterol. Moreover, SAA can cause lipoproteins to bind extracellular vascular proteoglycans, a process that is critical in atherogenesis. Therefore, we hypothesized that diet-induced increases in SAA would increase atherosclerosis independent of their effect on plasma cholesterol levels. Methods and Results—Female LDL-receptor–null (LDLR−/−) mice were fed high–saturated fat diets (21%, wt/wt), with or without added cholesterol (0.15%, wt/wt), for 10 weeks. Compared with chow-fed controls, the high-fat diets increased plasma SAA levels. Addition of cholesterol further increased SAA levels 2-fold (P<0.05) without further increasing plasma cholesterol levels. Addition of dietary cholesterol also increased atherosclerosis (P<0.05). Four lines of evidence suggest that SAA actually might cause atherosclerosis: (1) SAA levels when mice were euthanized correlated with the extent of atherosclerosis (r=0.49; P<0.02); (2) SAA levels after 5 weeks of diet correlated with the extent of atherosclerosis at 10 weeks (r=0.66; P<0.01); (3) binding of HDL from these animals to proteoglycans in vitro was related to the HDL-SAA content (r=0.65; P<0.01); and (4) immunoreactive SAA was present in lesion areas enriched with both proteoglycans and apolipoprotein A-I, the major HDL apolipoprotein. Conclusions—Addition of cholesterol to a high-fat diet increased plasma SAA levels and atherosclerosis independent of an adverse effect on plasma lipoproteins, consistent with the hypothesis that SAA may promote atherosclerosis directly by mediating retention of SAA-enriched HDL to vascular proteoglycans.
Distributed Stochastic Search for Constraint Satisfaction and Optimization: Parallelism, Phase Transitions and Performance

Many distributed problems can be captured as distributed constraint satisfaction problems (CSPs) and constraint optimization problems (COPs). In this research, we study an existing distributed search method, called distributed stochastic algorithm (DSA), and its variations for solving distributed CSPs and COPs. We analyze the relationship between the degree of parallel executions of distributed processes and DSAs’ performance, including solution quality and communication cost. Our experimental results show that DSAs’ performance exhibits phase-transition patterns. When the degree of parallel executions increases beyond some critical level, DSAs’ performance degrades abruptly and dramatically, changing from near optimal solutions to solutions even worse than random solutions. Our experimental results also show that DSAs are generally more effective and efficient than distributed breakout algorithm on many network structures, particularly on over-constrained structures, finding better solutions and having lower communication cost.
Polyaperturate pollen types and ratios of heteromorphism in the monocot genus Conostylis (Haemodoraceae)

Pollen aperture heteromorphism (variation of aperture number in pollen grains within each flower and in all plantsofataxon)isdescribedinthediversemonocotgenusConostylisR.Br. (Haemodoraceae)andthatofrelatedgenera,all endemictoWesternAustralia.Wereportresultsofpollenobservationsfrom153specimens. InConostylis,aperturenumber varies greatly, with biporate, triporate, tetraporate and polyporate pollen present, features considered rare and possibly developmentallysignificantformonocots.Pollenaperturetypesandtheirratiosinthisgenusarestableandconsistentwithin species and subspecies groupings and phylogenetically informative.
Identifying News from Tweets

Informal genres such as tweets provide large quantities of data in real time, which can be exploited to obtain, through ranking and clas-siﬁcation, a succinct summary of the events that occurred. Previous work on tweet ranking and classiﬁcation mainly focused on salience and social network features or rely on web documents such as online news articles. In this paper, we exploit language independent journalism and content based features to identify news from tweets. We propose a novel newsworthiness classiﬁer trained through active learning and investigate human assessment and automatic methods to encode it on both the tweet and trending topic levels. Our ﬁndings show that content and journalism based features proved to be effective for ranking and classifying content on Twitter.
Adjuvant Ozonetherapy in Advanced Head and Neck Tumors: A Comparative Study

Advanced head and neck (H&N) tumors have a poor prognosis, and this is worsened by the occurrence of hypoxia and ischemia in the tumors. Ozonetherapy has proved useful in the treatment of ischemic syndromes, and several studies have described a potential increase of oxygenation in tissues and tumors. The aim of this prospective study was to evaluate the clinical effect of ozonetherapy in patients with advanced H&N cancer in the course of their scheduled radiotherapy. Over a period of 3 years, 19 patients with advanced H&N tumors who were undergoing treatment in our department with non-standard fractionated radiotherapy plus oral tegafur. A group of 12 patients was additionally treated with intravenous chemotherapy before and/or during radiotherapy. In the other group of seven patients, systemic ozonetherapy was administered twice weekly during radiotherapy. The ozonetherapy group was older (64 versus 54 years old, P = 0.006), with a higher percentage of lymph node involvement (71% versus 8%, P = 0.019) and with a trend to more unfavorable tumor stage (57% versus 8% IVb + IVc stages, P = 0.073). However, there was no significant difference in overall survival between the chemotherapy (median 6 months) and ozonetherapy (8 months) groups. Although these results have to be viewed with caution because of the limited number of patients, they suggest that ozonetherapy could have had some positive effect during the treatment of our patients with advanced H&N tumors. The adjuvant administration of ozonetherapy during the chemo–radiotherapy for these tumors merits further research.
Association between Kidney Function and Framingham Global Cardiovascular Disease Risk Score: A Chinese Longitudinal Study

Background Chronic kidney disease (CKD) is generally considered an independent risk factor for cardiovascular disease (CVD) development, but rates in individuals with estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m2 are uncertain. The Framingham global CVD risk score (FRS) equation is a widely accepted tool used to predict CVD risk in the general population. The purpose of the present study was to examine whether an association exists between eGFR and FRS in a Chinese population with no CKD or CVD. Methods A total of 333 participants were divided into three groups based on FRS. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and CKD-EPI equation for Asians (CKD-EPI-ASIA) were used to measure eGFR. Results A significant inverse association between eGFR and FRS was confirmed with Pearson correlation coefficients of –0.669, –0.698 (eGFRCKD-EPI, P<0.01) and –0.658, –0.690 (eGFRCKD-EPI-ASIA, P<0.01). This association gradually diminished with progression from the low- to high-risk groups (eGFRCKD-EPI, r = –0.615, –0.282, –0.197, P<0.01, P<0.01, P>0.05; similar results according to the CKD-EPI-ASIA equation). In the low- or moderate-risk new-groups, this association became stronger with increased FRS (eGFRCKD-EPI-ASIA, r = –0557, –0.622 or –0.326, –0.329, P<0.01). In contrast to the results from 2008, eGFR was independently associated with FRS following adjustment for traditional cardiovascular risk factors (P<0.05). Conclusion Renal function has multiple influences on predicting CVD risk in various populations. With increasing FRS and decreasing eGFR, it is also independently associated with CVD, even in individuals with eGFR >60 ml/min/1.73 m2.
Mutations in AtPS1 (Arabidopsis thaliana Parallel Spindle 1) Lead to the Production of Diploid Pollen Grains

Polyploidy has had a considerable impact on the evolution of many eukaryotes, especially angiosperms. Indeed, most—if not all—angiosperms have experienced at least one round of polyploidy during the course of their evolution, and many important crop plants are current polyploids. The occurrence of 2n gametes (diplogametes) in diploid populations is widely recognised as the major source of polyploid formation. However, limited information is available on the genetic control of diplogamete production. Here, we describe the isolation and characterisation of the first gene, AtPS1 (Arabidopsis thaliana Parallel Spindle 1), implicated in the formation of a high frequency of diplogametes in plants. Atps1 mutants produce diploid male spores, diploid pollen grains, and spontaneous triploid plants in the next generation. Female meiosis is not affected in the mutant. We demonstrated that abnormal spindle orientation at male meiosis II leads to diplogamete formation. Most of the parent's heterozygosity is therefore conserved in the Atps1 diploid gametes, which is a key issue for plant breeding. The AtPS1 protein is conserved throughout the plant kingdom and carries domains suggestive of a regulatory function. The isolation of a gene involved in diplogamete production opens the way for new strategies in plant breeding programmes and progress in evolutionary studies.
RNA Recognition and Stress Granule Formation by TIA Proteins

Stress granule (SG) formation is a primary mechanism through which gene expression is rapidly modulated when the eukaryotic cell undergoes cellular stresses (including heat, oxidative, viral infection, starvation). In particular, the sequestration of specifically targeted translationally stalled mRNAs into SGs limits the expression of a subset of genes, but allows the expression of heatshock proteins that have a protective effect in the cell. The importance of SGs is seen in several disease states in which SG function is disrupted. Fundamental to SG formation are the T cell restricted intracellular antigen (TIA) proteins (TIA-1 and TIA-1 related protein (TIAR)), that both directly bind to target RNA and self-associate to seed the formation of SGs. Here a summary is provided of the current understanding of the way in which TIA proteins target specific mRNA, and how TIA self-association is triggered under conditions of cellular stress.
Assessment of the efficacy of combination therapy with folic acid and tadalafil for the management of erectile dysfunction in men with type 2 diabetes mellitus.

INTRODUCTION. : Phosphodiesterase type 5 inhibitors PDE5Is are less effective in diabetic men with erectile dysfunction (ED); however, the effect of combination therapy with folic acid and PDE5Is in these patients has not been investigated. AIM. : To evaluate the efficacy and safety of combination therapy with folic acid and tadalafil for the management of ED in men with type 2 diabetes mellitus. METHODS. : Eighty-three patients with type 2 diabetes mellitus and ED were included in this randomized double-blind clinical trial. They were randomly divided into two groups. Group A was treated with tadalafil 10 mg every other day plus folic acid 5 mg daily and group B received tadalafil 10 mg every other day plus placebo daily for 3 months. The mean International Index of Erectile Function (IIEF) scores before and after treatment in each groups were recorded. Men with diagnosis of psychological ED, spinal cord injury, or who used folic acid in the past 3 months and patients with any contradiction for use of PDE5Is were excluded. MAIN OUTCOMES MEASURES. : The cross tabulation and independent t-test were used to evaluate the difference between baseline characteristic of the patients in the two groups. Wilcoxon signed-ranks test and Mann-Whitney U-test were used to evaluate the IIEF score and also its changes before and after treatment in the two groups. RESULTS. : The mean IIEF scores before and after treatment were 11.65 ± 2.67 and 16.80 ± 4.03 in group A (P < 0.001) and 12.70 ± 2.31 and 14.37 ± 2.17 in group B (P < 0.001), respectively. The difference of mean IIEF score after treatment between the two groups was significant (16.80 ± 4.03 vs. 14.37 ± 2.17 in groups A and B, respectively) (P = 0.002). Also, the mean IIEF score was significantly increased in group A as compared with group B (5.14 ± 3.84 vs. 1.68 ± 0.99 in groups A and B, respectively) (P < 0.001). Both folic acid and tadalafil were well tolerated by all the patients. CONCLUSION. : Sexual function in diabetic patients with ED treated with the combination of tadalafil and folic acid improved significantly as compared with the placebo group. The use of folic acid and tadalafil is safe.