Miracle-dz/UniFAR-FTUs huggingface dataset:
Adipokines and Insulin Resistance According to Characteristics of Pregnant Women with Gestational Diabetes Mellitus

Background The aim of this study was to evaluate adipokines concentration and insulin resistance according to maternal age or obesity at pregnancy and weight change at diagnosed gestational diabetes mellitus (GDM) in pregnant women with GDM. Methods This study included 57 pregnant women who were diagnosed with GDM at 24 to 28 weeks of gestation. The subjects were classified into two or three groups according to pre-pregnancy body mass index (BMI, <25 kg/m2 vs. ≥25 kg/m2), maternal age at pregnancy (<35 years old vs. ≥35 years old), and weight change during pregnancy at screening for GDM (weight change below, within, and in excess of the recommended range). They were respectively compared in each group. Results Leptin, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA2-%B were increased in the group with pre-pregnancy BMI ≥25 kg/m2. Leptin and HOMA-IR were positively correlated with BMI both before pregnancy and at screening for GDM. There were no significant correlations between HOMA-IR and adipokines. HOMA-IR showed positive correlation with HOMA2-%B and negative correlation with HOMA2-%S. Conclusion Leptin and HOMA-IR at diagnosed GDM were increased in the GDM patients with obesity before pregnancy. They were positively correlated with BMI both before pregnancy and at screening for GDM. The effect of maternal age at pregnancy and weight change during pregnancy at GDM screening on adipokines and insulin resistance might be less pronounced than the effect of maternal obesity.
Computation of Ground States of the Gross-Pitaevskii Functional via Riemannian Optimization

In this paper we combine concepts from Riemannian Optimization and the theory of Sobolev gradients to derive a new conjugate gradient method for direct minimization of the Gross-Pitaevskii energy functional with rotation. The conservation of the number of particles constrains the minimizers to lie on a manifold corresponding to the unit $L^2$ norm. The idea developed here is to transform the original constrained optimization problem to an unconstrained problem on this (spherical) Riemannian manifold, so that fast minimization algorithms can be applied as alternatives to more standard constrained formulations. First, we obtain Sobolev gradients using an equivalent definition of an $H^1$ inner product which takes into account rotation. Then, the Riemannian gradient (RG) steepest descent method is derived based on projected gradients and retraction of an intermediate solution back to the constraint manifold. Finally, we use the concept of the Riemannian vector transport to propose a Riemannian conjugate gradient (RCG) method for this problem. It is derived at the continuous level based on the "optimize-then-discretize" paradigm instead of the usual "discretize-then-optimize" approach, as this ensures robustness of the method when adaptive mesh refinement is performed in computations. We evaluate various design choices inherent in the formulation of the method and conclude with recommendations concerning selection of the best options. Numerical tests demonstrate that the proposed RCG method outperforms the simple gradient descent (RG) method in terms of rate of convergence. While on simple problems a Newton-type method implemented in the {\tt Ipopt} library exhibits a faster convergence than the (RCG) approach, the two methods perform similarly on more complex problems requiring the use of mesh adaptation. At the same time the (RCG) approach has far fewer tunable parameters.
Transmission Potential of Chikungunya Virus and Control Measures: The Case of Italy

During summer 2007 Italy has experienced an epidemic caused by Chikungunya virus – the first large outbreak documented in a temperate climate country – with approximately 161 laboratory confirmed cases concentrated in two bordering villages in North–Eastern Italy comprising 3,968 inhabitants. The seroprevalence was recently estimated to be 10.2%. In this work we provide estimates of the transmission potential of the virus and we assess the efficacy of the measures undertaken by public health authorities to control the epidemic spread. To such aim, we developed a model describing the temporal dynamics of the competent vector, known as Aedes albopictus, explicitly depending on climatic factors, coupled to an epidemic transmission model describing the spread of the epidemic in both humans and mosquitoes. The cumulative number of notified cases predicted by the model was 185 on average (95% CI 117–278), in good agreement with observed data. The probability of observing a major outbreak after the introduction of an infective human case was estimated to be in the range of 32%–76%. We found that the basic reproduction number was in the range of 1.8–6 but it could have been even larger, depending on the density of mosquitoes, which in turn depends on seasonal meteorological effects, besides other local abiotic factors. These results confirm the increasing risk of tropical vector–borne diseases in temperate climate countries, as a consequence of globalization. However, our results show that an epidemic can be controlled by performing a timely intervention, even if the transmission potential of Chikungunya virus is sensibly high.
Unraveling the role of motoneuron autophagy in ALS

ABSTRACT In recent years, the role of autophagy in the pathogenesis of most neurodegenerative diseases has transitioned into a limbo of protective or detrimental effects. Genetic evidence indicates that mutations in autophagy-regulatory genes can result in the occurrence of amyotrophic lateral sclerosis (ALS), suggesting a physiological role of the pathway to motoneuron function. However, experimental manipulation of autophagy in ALS models led to conflicting results depending on the intervention strategy and the disease model used. A recent work by the Maniatis group systematically explored the role of cell-specific autophagy in motoneurons at different disease stages, revealing surprising and unexpected findings. Autophagy activity at early stages may contribute to maintaining the structure and function of neuromuscular junctions, whereas at later steps of the disease it has a pathogenic activity possibly involving cell-nonautonomous mechanisms related to glial activation. This new study adds a new layer of complexity in the field, suggesting an intricate interplay between proteostasis alterations, the time-differential function of autophagy in neurons, and muscle innervation in ALS.
Efficacy and safety of nilotinib in patients with KIT-mutated metastatic or inoperable melanoma: final results from the global, single-arm, phase II TEAM trial

Background The single-arm, phase II Tasigna Efficacy in Advanced Melanoma (TEAM) trial evaluated the KIT-selective tyrosine kinase inhibitor nilotinib in patients with KIT-mutated advanced melanoma without prior KIT inhibitor treatment. Patients and methods Forty-two patients with KIT-mutated advanced melanoma were enrolled and treated with nilotinib 400 mg twice daily. TEAM originally included a comparator arm of dacarbazine (DTIC)-treated patients; the design was amended to a single-arm trial due to an observed low number of KIT-mutated melanomas. Thirteen patients were randomized to DTIC before the protocol amendment removing this study arm. The primary endpoint was objective response rate (ORR), determined according to Response Evaluation Criteria In Solid Tumors. Results ORR was 26.2% (n = 11/42; 95% CI, 13.9%–42.0%), sufficient to reject the null hypothesis (ORR ≤10%). All observed responses were partial responses (PRs; median response duration, 7.1 months). Twenty patients (47.6%) had stable disease and 10 (23.8%) had progressive disease; 1 (2.4%) response was unknown. Ten of the 11 responding patients had exon 11 mutations, four with an L576P mutation. The median progression-free survival and overall survival were 4.2 and 18.0 months, respectively. Three of the 13 patients on DTIC achieved a PR, and another patient had a PR following switch to nilotinib. Conclusion Nilotinib activity in patients with advanced KIT-mutated melanoma was similar to historical data from imatinib-treated patients. DTIC treatment showed potential activity, although the low patient number limits interpretation. Similar to previously reported results with imatinib, nilotinib showed greater activity among patients with an exon 11 mutation, including L576P, suggesting that nilotinib may be an effective treatment option for patients with specific KIT mutations. Clinical Trial Registration ClinicalTrials.gov, NCT01028222.
Blastomycosis in Children: An Analysis of Clinical, Epidemiologic, and Genetic Features

Background Blastomyces spp. are endemic in regions of the United States and result in blastomycosis, a serious and potentially fatal infection. Little is known about the presentation, clinic course, epidemiology, and genetics of blastomycosis in children. Methods A retrospective review of children with blastomycosis confirmed by culture or cytopathology between 1999 and 2014 was completed. Blastomyces sp. isolates were genotyped by using microsatellite typing, and species were typed by sequencing of internal transcribed spacer 2 (its2). Results Of the 114 children with blastomycosis identified, 79% had isolated pulmonary involvement and 21% had extrapulmonary disease. There were more systemic findings, including fever (P = .01), poor intake (P = .01), elevated white blood cell count (P < .01), and elevated C-reactive protein level (P < .01), in children with isolated pulmonary disease than in children with extrapulmonary disease. Children with extrapulmonary disease had more surgeries (P = .01) and delays in diagnosis (P < .01) than those with isolated pulmonary infection. Of 52 samples genotyped, 48 (92%) were Blastomyces gilchristii and 4 (8%) were Blastomyces dermatitidis. Conclusion This is the first large-scale study of the clinical, epidemiologic, and genetic features of blastomycosis in children. The majority of the children had isolated pulmonary disease with systemic findings. Patients with extrapulmonary disease were less likely to have systemic symptoms or additional laboratory evidence of infection, which made delays in diagnosis more common. More than 90% of the pediatric cases were caused by B gilchristii.
Improved Image Captioning via Policy Gradient optimization of SPIDEr

Current image captioning methods are usually trained via maximum likelihood estimation. However, the log-likelihood score of a caption does not correlate well with human assessments of quality. Standard syntactic evaluation metrics, such as BLEU, METEOR and ROUGE, are also not well correlated. The newer SPICE and CIDEr metrics are better correlated, but have traditionally been hard to optimize for. In this paper, we show how to use a policy gradient (PG) method to directly optimize a linear combination of SPICE and CIDEr (a combination we call SPIDEr): the SPICE score ensures our captions are semantically faithful to the image, while CIDEr score ensures our captions are syntactically fluent. The PG method we propose improves on the prior MIXER approach, by using Monte Carlo rollouts instead of mixing MLE training with PG. We show empirically that our algorithm leads to easier optimization and improved results compared to MIXER. Finally, we show that using our PG method we can optimize any of the metrics, including the proposed SPIDEr metric which results in image captions that are strongly preferred by human raters compared to captions generated by the same model but trained to optimize MLE or the COCO metrics.
The Allometry of Prey Preferences

The distribution of weak and strong non-linear feeding interactions (i.e., functional responses) across the links of complex food webs is critically important for their stability. While empirical advances have unravelled constraints on single-prey functional responses, their validity in the context of complex food webs where most predators have multiple prey remain uncertain. In this study, we present conceptual evidence for the invalidity of strictly density-dependent consumption as the null model in multi-prey experiments. Instead, we employ two-prey functional responses parameterised with allometric scaling relationships of the functional response parameters that were derived from a previous single-prey functional response study as novel null models. Our experiments included predators of different sizes from two taxonomical groups (wolf spiders and ground beetles) simultaneously preying on one small and one large prey species. We define compliance with the null model predictions (based on two independent single-prey functional responses) as passive preferences or passive switching, and deviations from the null model as active preferences or active switching. Our results indicate active and passive preferences for the larger prey by predators that are at least twice the size of the larger prey. Moreover, our approach revealed that active preferences increased significantly with the predator-prey body-mass ratio. Together with prior allometric scaling relationships of functional response parameters, this preference allometry may allow estimating the distribution of functional response parameters across the myriads of interactions in natural ecosystems.
Smart grids and households: how are household consumers represented in experimental projects?

ABSTRACT This study contributes a comparative analysis of 11 Danish smart grid experimental projects with household involvement. The analysis describes the scripts for the future smart grid interaction investigated in the examined projects, the approaches to user representation, and the project findings concerning consumers and smart grids. Three main dimensions of the scripts are identified and discussed: economic incentives, automation, and information/visualisation. The methods employed for the development of user representations are primarily technical and techno-economic. While our analysis confirms previous findings that economic rationales and automation are central elements of smart grid scripts, the analysis also shows that there is considerable variation in the details of the scripts investigated. Our findings suggest that it may be useful for future smart grid projects to be more systematic and explicit in the analysis of household user perspectives and may consider a broader set of methods in this regard.
An Exploratory Study of Radiation Dermatitis in Breast Cancer Patients.

BACKGROUND/AIM Radiation dermatitis is observed in 95% of breast cancer patients receiving radiotherapy. The aim of this study was to explore the correlation between protein expression in tumor cells and the risk of developing radiation dermatitis. PATIENTS AND METHODS Breast cancer patients receiving postoperative radiotherapy were included in this study. Tumor specimens from 122 patients were examined by immunohistochemistry for the expression of Ki67, ataxia telangiectasia mutated (ATM) kinase, hypoxia-inducible factor-1-alpha (HIF-1a), inducible nitric oxide synthase (iNOS), and a-glucosidase (aGluc). The findings were correlated with the occurrence and severity of radiation dermatitis (Radiation therapy oncology group-RTOG grading scale), taking into consideration body weight and skin type (Fitzpatrick system). Data were explored further via pathway and network analyses. RESULTS Correlation of radiation dermatitis (RTOG scale) with the observed increased expression of Ki67, ATM, iNOS, HIF-1a and aGluc, failed to reach statistical significance when skin type and/or body weight were considered. Network interactions of proteins involved in tumor growth (Ki67, ATM) and/or affect the oxidation state of the cell (HIF-1a, iNOS, aGluc) were revealed, that may contribute to the risk of developing acute radiation dermatitis. CONCLUSION Correlation of the increased expression of the studied proteins and the occurrence and severity of radiation dermatitis in women undergoing postoperative radiotherapy, failed to reach statistical significance. Pathway and network analyses predicted that vasodilation and angiogenesis may contribute to radiation-induced dermatitis via mechanisms that need to be further explored. Our strategy serves as a paradigm for coupling histopathological data to molecular findings and network analyses for risk assessment in the clinic.
Pomalidomide plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma and moderate renal impairment: a pooled analysis of three clinical trials

Abstract Renal impairment (RI) is a major comorbidity in patients with multiple myeloma (MM). Here we present the pooled safety and efficacy analysis of three clinical trials (MM-002, MM-003, and MM-010) of pomalidomide + low-dose dexamethasone (POM + LoDEX) in patients with moderate RI (creatinine clearance [CrCl] ≥ 30 to <60 mL/min) and without RI (≥ 60 mL/min). Trial protocols were approved by the institutional review board of each site involved. Patients with RI were older than patients without RI, although other baseline characteristics were similar. The dosing and safety profile of POM + LoDEX was similar across RI subgroups. Median overall response rate, progression-free survival, time to progression, and duration of response were not significantly different between RI subgroups. However, patients with vs. without RI had significantly shorter median overall survival (10.5 vs. 14.0 months, respectively; p = .004). This analysis demonstrates that POM + LoDEX is a safe and effective treatment for patients with moderate RI. The trials were registered at ClinicalTrials.gov as NCT00833833 (MM-002), NCT01311687 (MM-003), and NCT01712789 (MM-010) and at EudraCT as 2010-019820-30 (MM-003) and 2012-001888-78 (MM-010).
The cost of avoiding freezing in stems: trade-off between xylem resistance to cavitation and supercooling capacity in woody plants

Stems and leaves of Olea europaea L. (olive) avoid freezing damage by substantial supercooling during the winter season. Physiological changes during acclimation to low temperatures were studied in five olive cultivars. Water relations and hydraulic traits, ice nucleation temperature (INT) and temperatures resulting in 50% damage (LT50) were determined. All cultivars showed a gradual decrease in INT and LT50 from the dry and warm summer to the wet and cold winter in Patagonia, Argentina. During acclimation to low temperatures there was an increase in leaf cell wall rigidity and stomatal conductance (gs), as well as a decrease in leaf apoplastic water content, leaf water potential (Ψ), sap flow and stem hydraulic conductivity (ks). More negative Ψ as a consequence of high gs and detrimental effects of low temperatures on root activity resulted in a substantial loss of ks due to embolism formation. Seasonal stem INT decrease from summer to winter was directly related to the xylem resistance to cavitation, determined by the loss of ks across cultivars. Thus the loss of freezable water in xylem vessels by embolisms increased stem supercooling capacity and delayed ice propagation from stems to the leaves. For the first time, a trade-off between xylem resistance to cavitation and stem and leaf supercooling capacity was observed in plants that avoid extracellular freezing by permanent supercooling. The substantial loss of hydraulic function in olive cultivar stems by embolism formation with their high repair costs are compensated by avoiding plant damage at very low subzero temperatures.
On Ranks of Regular Polygons

In this paper we study various versions of extension complexity for polygons through the study of factorization ranks of their slack matrices. In particular, we develop a new asymptotic lower bound for their nonnegative rank, decreasing the gap between the current bounds, we introduce a new upper bound for their boolean rank, deriving some numerical evidence for the asymptotic equivalence of the boolean rank of $n$-gons and $\log_2(n)$, and we show the nonmonotonicity of the complex positive semidefinite rank of $n$-gons.
Recent Emergence of Dengue Virus Serotype 4 in French Polynesia Results from Multiple Introductions from Other South Pacific Islands

Background Infection by dengue virus (DENV) is a major public health concern in hundreds of tropical and subtropical countries. French Polynesia (FP) regularly experiences epidemics that initiate, or are consecutive to, DENV circulation in other South Pacific Island Countries (SPICs). In January 2009, after a decade of serotype 1 (DENV-1) circulation, the first cases of DENV-4 infection were reported in FP. Two months later a new epidemic emerged, occurring about 20 years after the previous circulation of DENV-4 in FP. In this study, we investigated the epidemiological and molecular characteristics of the introduction, spread and genetic microevolution of DENV-4 in FP. Methodology/Principal Findings Epidemiological data suggested that recent transmission of DENV-4 in FP started in the Leeward Islands and this serotype quickly displaced DENV-1 throughout FP. Phylogenetic analyses of the nucleotide sequences of the envelope (E) gene of 64 DENV-4 strains collected in FP in the 1980s and in 2009–2010, and some additional strains from other SPICs showed that DENV-4 strains from the SPICs were distributed into genotypes IIa and IIb. Recent FP strains were distributed into two clusters, each comprising viruses from other but distinct SPICs, suggesting that emergence of DENV-4 in FP in 2009 resulted from multiple introductions. Otherwise, we observed that almost all strains collected in the SPICs in the 1980s exhibit an amino acid (aa) substitution V287I within domain I of the E protein, and all recent South Pacific strains exhibit a T365I substitution within domain III. Conclusions/Significance This study confirmed the cyclic re-emergence and displacement of DENV serotypes in FP. Otherwise, our results showed that specific aa substitutions on the E protein were present on all DENV-4 strains circulating in SPICs. These substitutions probably acquired and subsequently conserved could reflect a founder effect to be associated with epidemiological, geographical, eco-biological and social specificities in SPICs.
Relative Rates of Amino Acid Import via the ABC Transporter GlnPQ Determine the Growth Performance of Lactococcus lactis

ABSTRACT The GlnPQ transporter from Lactococcus lactis has the remarkable feature of having two substrate-binding domains (SBDs) fused to the N terminus of the transmembrane domain (TMD), and thus four SBDs are present in the homodimeric complex. Although X-ray structures and ligand binding data are available for both SBDs, little is known of how different amino acids compete with each other for transport via GlnPQ. Here we show GlnPQ has a broader substrate specificity than previously thought, with the ability to take up asparagine, glutamine, and glutamic acid, albeit via different routes and with different affinities. Asparagine and glutamine compete with each other at the level of binding to SBD1 and SBD2 (with differences in dissociation constant), but at the same time SBD1 and SBD2 compete with each other at the level of interaction with the translocator domain (with differences in affinity constant and rate of transport). Although glutamine transport via SBD1 is outcompeted by physiological concentrations of asparagine, SBD2 ensures high rates of import of the essential amino acid glutamine. Taken together, this study demonstrates that even in the presence of competing asparagine concentrations, GlnPQ has a high capacity to transport glutamine, which matches the high needs of the cell for glutamine and glutamate. IMPORTANCE GlnPQ is an ATP-binding cassette (ABC) transporter for glutamine, glutamic acid, and asparagine. The system is essential in various Gram-positive bacteria, including L. lactis and several pathogens. Here we show how the amino acids compete with each other for binding to the multiple SBDs of GlnPQ and how these SBDs compete with each other for substrate delivery to the transporter. Overall, our results show that GlnPQ has evolved to transport diverse substrates via different paths and to optimally acquire the abundant and essential amino acid glutamine.