Miracle-dz/UniFAR-FTUs huggingface dataset:
Hierarchical CRMP2 posttranslational modifications control NaV1.7 function

Significance The voltage-gated sodium channel NaV1.7 is important for electrogenesis in sensory neurons. Insertion within the membrane is required for function of NaV1.7. However, the mechanisms determining how NaV1.7 is trafficked to neuronal cell membranes are poorly understood. Here, we elucidate a signaling program involving a complex and intriguing posttranslational modification regime of collapsin response mediator protein 2 (CRMP2), an NaV1.7-binding protein. NaV1.7 surface localization and currents are controlled by CRMP2 modifications. Activity of NaV1.7 is thought to modulate neuronal excitability that codes for several sensory modalities, including chronic pain, as inferred from human pain disorders caused by mutations in NaV1.7 channels. Understanding the role of cross-talk between CRMP2 modifications in modulation of NaV1.7 activity opens routes to exploit this system for pain. Voltage-gated sodium channels are crucial determinants of neuronal excitability and signaling. Trafficking of the voltage-gated sodium channel NaV1.7 is dysregulated in neuropathic pain. We identify a trafficking program for NaV1.7 driven by hierarchical interactions with posttranslationally modified versions of the binding partner collapsin response mediator protein 2 (CRMP2). The binding described between CRMP2 and NaV1.7 was enhanced by conjugation of CRMP2 with small ubiquitin-like modifier (SUMO) and further controlled by the phosphorylation status of CRMP2. We determined that CRMP2 SUMOylation is enhanced by prior phosphorylation by cyclin-dependent kinase 5 and antagonized by Fyn phosphorylation. As a consequence of CRMP2 loss of SUMOylation and binding to NaV1.7, the channel displays decreased membrane localization and current density, and reduces neuronal excitability. Preventing CRMP2 SUMOylation with a SUMO-impaired CRMP2-K374A mutant triggered NaV1.7 internalization in a clathrin-dependent manner involving the E3 ubiquitin ligase Nedd4-2 (neural precursor cell expressed developmentally down-regulated protein 4) and endocytosis adaptor proteins Numb and epidermal growth factor receptor pathway substrate 15. Collectively, our work shows that diverse modifications of CRMP2 cross-talk to control NaV1.7 activity and illustrate a general principle for regulation of NaV1.7.
Night shift work and other determinants of estradiol, testosterone, and dehydroepiandrosterone sulfate among middle-aged nurses and midwives.

OBJECTIVES The aims of our study were to (i) investigate the association between rotating night shift work and blood concentrations of estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) and (2) evaluate the role of their non-occupational determinants. METHODS A cross-sectional study was conducted on 345 premenopausal and 187 postmenopausal nurses and midwives (263 women working rotating night shifts and 269 women working during days). Data from in-person interviews were used, anthropometric measurements were performed, and body mass index (BMI) and waist- to-hip ratio were calculated. Morning blood and spot urine samples were collected. Multiple linear regression models were fitted with hormone concentrations as dependent variables, and night shift work characteristics and demographic, reproductive, lifestyle and anthropometric determinants as independent variables. Modification of the effect by chronotype was examined. RESULTS Among postmenopausal women, we observed a statistically significant positive association between the total duration of night shift work >15 years and estradiol level (P<0.05 when compared to night work duration <5 years). Night shift work characteristics were significantly associated with estradiol among morning-type postmenopausal women. The well-established associations between hormones and their major determinants, such as age and BMI, were confirmed. CONCLUSIONS The findings of our study imply that prolonged night shift work may be associated with increased estradiol levels among postmenopausal women, especially among the morning-type postmenopausal women.
A molecular Bose-Einstein condensate emerges from a Fermi sea

The realization of fermionic superfluidity in a dilute gas of atoms, analogous to superconductivity in metals, is a long-standing goal of ultracold gas research. Beyond being a new example of this fascinating quantum phenomenon, fermionic superfluidity in an atomic gas holds the promise of adjustable interactions and the ability to tune continuously from BCS-type superfluidity to Bose-Einstein condensation (BEC). This crossover between BCS superfluidity of correlated atom pairs in momentum space and BEC of local pairs has long been of theoretical interest, motivated in part by the discovery of high Tc superconductors. In atomic Fermi gas experiments superfluidity has not yet been demonstrated; however recent experiments have made remarkable progress toward this goal. Starting from an ultracold Fermi gas experimenters have used Feshbach resonances to reversibly create molecules, i.e. composite bosons consisting of local fermion pairs. Furthermore, the experiments have shown that the resulting diatomic molecules can have surprisingly long lifetimes. Here we report the conversion of a Fermi sea of atoms into a molecular BEC. In addition to being the first molecular condensate in thermal equilibrium, this BEC represents one extreme of the predicted BCS-BEC continuum.
Effects of a low salt diet on isolated systolic hypertension

Abstract Evidence has shown that long-term sodium reduction can not only reduce blood pressure, but also provide cardiovascular benefits. To date, there is little evidence related to the effects of salt reduction on isolated systolic hypertension (ISH). A total of 126 hypertensive patients were divided into an ISH group (n = 51) and a non-ISH (NISH) group (n = 75). The members of each group were then randomly assigned to low sodium salt (LSSalt) or normal salt (NSalt) diets for 6 months. Their blood pressure was measured every 2 months. Serum plasma renin-angiotensin activity, blood biochemical assays and urinary measurements were determined at the baseline and at the end of the 6 months. At the end of the study, the mean systolic blood pressure (SBP) of the ISH LSSalt group had significantly decreased by 10.18 mm Hg (95% confidence interval (CI): 3.13 to 17.2, P = . 006) compared with that of the ISH NSalt group, while the mean SBP only decreased by 5.10 mm Hg (95% CI: −2.02 to 12.2, P = .158) in the NISH LSSalt group compared with that of the NISH NSalt group. The mean diastolic blood pressure (DBP) had no significant differences in the ISH and NISH groups. No obvious renin angiotensin system activation was found after LSSalt intervention. Regarding the urinary excretion of electrolytes and blood biochemical assays, the LSSalt treatment had the same effects on the ISH group as on the NISH group. The present study showed that the SBP of ISH patients was significantly decreased with the LSSalt intervention, while neither the SBP of the NISH patients nor the DBP of either group were similarly decreased, which indicated that ISH patients were more sensitive to salt restriction.
Protective effect of cinnamic acid in endotoxin‐poisoned mice

In this work, we aimed to evaluate the protective effect of cinnamic acid (CD) on lipopolysaccharide (LPS; Escherichia coli 055:B5)‐induced endotoxin‐poisoned mice and clarify the underlying mechanisms. The mice were administrated CD 5 d before 15 mg/kg LPS challenge. 12 hr later, thymus was separated for determination of thymus indexes. Lung and spleen tissues were collected for histologic examination and the wet/dry weight ratio of lung was calculated, and serum was acquired for tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐18, and IL‐1β measurement. Moreover, the expression of NOD‐like receptor (NLR) family, pyrin domain‐containing 3 (NLRP3) inflammasome was determined in lung. CD increased the thymus indexes and decreased lung wet/dry weight ratio. In addition, CD improved the lung and spleen histopathological changes induced by LPS and decreased the number of neutrophils in lung tissues. CD also inhibited the pro‐inflammatory cytokines (TNF‐α, IL‐18, and IL‐1β) production in serum. Furthermore, CD suppressed the LPS‐induced NLRP3, Caspase‐1, and IL‐1β mRNA expression in lung, as well as the expression of NLRP3 and Caspase‐1 (p20) protein. CD may have protective effects in endotoxin‐poisoned mice via inhibiting the activation of NLRP3 inflammasome, and can be considered as a potential therapeutic candidate for diseases involved in endotoxin poisoning such as sepsis.
Cost-effectiveness of cladribine tablets, alemtuzumab, and natalizumab in the treatment of relapsing-remitting multiple sclerosis with high disease activity in England

Abstract Aims: Cladribine tablets were the first oral short-course treatment approved for highly active relapsing multiple sclerosis (MS). The Association of British Neurologists guidelines currently recommend two infusion therapies, alemtuzumab and natalizumab, to treat high disease activity relapsing remitting MS (HDA-RRMS). This analysis assessed the cost-effectiveness of cladribine tablets in HDA-RRMS compared with alemtuzumab and natalizumab, from the perspective of the National Health Service (NHS) in England. Materials and methods: A cohort-based Markov model with 11 health states (10 Expanded Disability Status Scale [EDSS] plus death) was developed. Transition matrices from the British Columbia registry were used to model the natural history of EDSS. The treatment effect on EDSS was modelled using hazard ratios for 6-month confirmed disability progression from an indirect treatment comparison (ITC). Relapses and drug-related adverse events were modeled via annualized relapse rates and event probabilities, with associated costs and quality-adjusted life year (QALY) losses. Utilities were derived from trials and the literature, and costs from NHS and literature sources. Uncertainty was assessed via probabilistic and deterministic sensitivity analyses. Results: Cladribine tablets were dominant (i.e., less costly and more effective) vs alemtuzumab and natalizumab in pairwise comparisons, and the dominant strategy in fully incremental analyses. Incremental cost was driven largely by drug acquisition and administration costs, and incremental QALY gain largely by differences in delayed EDSS progression. Cladribine tablets had a 93% probability of being cost-effective at a threshold of GBP 30,000 per QALY gained, and remained dominant across the scenario analyses tested. The greatest influence on results was the treatment effect on disability progression derived from the ITC. Limitations: Uncertainty over the efficacy of DMT beyond trial durations. In line with other comparative effectiveness analyses, the network meta-analysis informing this cost-effectiveness analysis was associated with a degree of uncertainty. No treatment switching analyses were undertaken. Conclusions: Cladribine tablets are a cost-effective alternative to alemtuzumab and natalizumab in the treatment of HDA-RRMS from the perspective of the NHS in England.
Effect of iron-fortified foods on hematologic and biological outcomes: systematic review of randomized controlled trials.

BACKGROUND The utility of iron fortification of food to improve iron deficiency, anemia, and biological outcomes is not proven unequivocally. OBJECTIVES The objectives were to evaluate 1) the effect of iron fortification on hemoglobin and serum ferritin and the prevalence of iron deficiency and anemia, 2) the possible predictors of a positive hemoglobin response, 3) the effect of iron fortification on zinc and iron status, and 4) the effect of iron-fortified foods on mental and motor development, anthropometric measures, and infections. DESIGN Randomized and pseudorandomized controlled trials that included food fortification or biofortification with iron were included. RESULTS Data from 60 trials showed that iron fortification of foods resulted in a significant increase in hemoglobin (0.42 g/dL; 95% CI: 0.28, 0.56; P < 0.001) and serum ferritin (1.36 μg/L; 95% CI: 1.23, 1.52; P < 0.001), a reduced risk of anemia (RR: 0.59; 95% CI: 0.48, 0.71; P < 0.001) and iron deficiency (RR: 0.48; 95% CI: 0.38, 0.62; P < 0.001), improvement in other indicators of iron nutriture, and no effect on serum zinc concentrations, infections, physical growth, and mental and motor development. Significant heterogeneity was observed for most of the evaluated outcomes. Sensitivity analyses and meta-regression for hemoglobin suggested a higher response with lower trial quality (suboptimal allocation concealment and blinding), use of condiments, and sodium iron edetate and a lower response when adults were included. CONCLUSION Consumption of iron-fortified foods results in an improvement in hemoglobin, serum ferritin, and iron nutriture and a reduced risk of remaining anemic and iron deficient.
Hypoglycemic and antioxidant effect of Tai chi exercise training in older adults with metabolic syndrome

Introduction The antioxidant and anti-inflammatory effects of Tai chi (TC) exercise training in healthy older adults has been demonstrated. However, there are no studies on this effect in older adults with metabolic syndrome (MetS). Purpose The aim of this study was to determine the effect of TC exercise on oxidative stress and inflammatory markers in older adults with MetS. Methods A quasi-experimental study was carried out with a sample of 110 older sedentary volunteers with clinical diagnoses of MetS: (i) a control group, n = 50, of individuals who do not participate in physical exercise, of which 37 fulfilled the entire study protocol, and (ii) an experimental group, n = 60, of subjects enrolled in a TC exercise training program (eight-form easy), 5 days a week for 6 months, in sessions of 50 min, under the supervision of a qualified instructor, of which 48 fulfilled the entire study protocol. We measured in both groups (pre- and post-intervention) the following cardiovascular parameters: resting heart rate (RHR), diastolic and systolic blood pressure (DBP and SBP), mean arterial pressure (MAP), RHR-SBP product, RHR-MAP product; glycosylated hemoglobin (HbA1c); oxidative stress markers (superoxide dismutase, total antioxidant status, thiobarbituric acid reacting substances, and oxidative stress score); and inflammation markers (TNF-α, IL-6, IL-8, and IL-10). Results A statistically significant decrease in HbA1c concentration was observed in the TC group compared with the control group (p < 0.05). This group also showed a statistically significant increase in TAS and a decrease in the oxidative stress score (p < 0.05). We did not observe changes in the cardiovascular parameters (RHR, DBP, SBP, MAP, RHR-SBP product, and RHR-MAP product) in the TC experimental group compared to the control group. Conclusion Our findings suggest that the practice of TC exercise has an antioxidative and hypoglycemic effect in the elderly with MetS.
Anti-Colitic Effect of Purple Carrot on Dextran Sulfate Sodium (DSS)-Induced Colitis in C57BL/6J Mice

The anti-colitic effect of purple carrot (PC) on 2% dextran sulfate sodium (DSS)-induced colitis in C57BL6/J mice was compared with those of yellow carrot (YC), beet (BT), and red cabbage (RC). Component analysis showed that PC contained cyanidin-3-xyloglucoside, cyanidin-3-xylosyl(sinapoly-glucosyl)galactoside, cyanidin-3-xylosyl(feruloylglucosyl) galactoside, and cyanidin-3-O-(6-O-glycosyl-2-O-xylosylgalactoside). PC diet (5% in AIN 93G diet) strongly reduced DSS-induced colon shortening and inflammatory cell infiltration in mice, followed by RC, BT, and YC diets. Treatment with PC reduced serum levels of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-6 as well as reduced mRNA expression in colon tissue of colitis mice in comparison with other treatments. In addition, PC treatment inhibited colonic mRNA expression of inflammatory factors such as inducible nitric oxide synthase and cyclooxygenase-2 in mice. These results suggest that PC can attenuate the inflammatory reaction in mice with DSS-induced colitis, probably due to the anthocyanins in PC.
A practical tool for maximal information coefficient analysis

Background The ability of finding complex associations in large omics datasets, assessing their significance, and prioritizing them according to their strength can be of great help in the data exploration phase. Mutual Information based measures of association are particularly promising, in particular after the recent introduction of the TICe and MICe estimators, which combine computational efficiency with good bias/variance properties. Despite that, a complete software implementation of these two measures and of a statistical procedure to test the significance of each association is still missing. Findings In this paper we present MICtools, a comprehensive and effective pipeline which combines TICe and MICe into a multi-step procedure that allows the identification of relationships of various degrees of complexity. MICtools calculates their strength assessing statistical significance using a permutation-based strategy. The performances of the proposed approach are assessed by an extensive investigation in synthetic datasets and an example of a potential application on a metagenomic dataset is also illustrated. Conclusions We show that MICtools, combining TICe and MICe, is able to highlight associations that would not be captured by conventional strategies. MICtools is implemented in Python, and is available for download at https://github.com/minepy/mictools.
The compatibility of concurrent high intensity interval training and resistance training for muscular strength and hypertrophy: a systematic review and meta-analysis

ABSTRACT The purpose of this systematic review and meta-analysis is to assess the effect of concurrent high intensity interval training (HIIT) and resistance training (RT) on strength and hypertrophy. Five electronic databases were searched using terms related to HIIT, RT, and concurrent training. Effect size (ES), calculated as standardised differences in the means, were used to examine the effect of concurrent HIIT and RT compared to RT alone on muscle strength and hypertrophy. Sub-analyses were performed to assess region-specific strength and hypertrophy, HIIT modality (cycling versus running), and inter-modal rest responses. Compared to RT alone, concurrent HIIT and RT led to similar changes in muscle hypertrophy and upper body strength. Concurrent HIIT and RT resulted in a lower increase in lower body strength compared to RT alone (ES = −0.248, p = 0.049). Sub analyses showed a trend for lower body strength to be negatively affected by cycling HIIT (ES = −0.377, p = 0.074) and not running (ES = −0.176, p = 0.261). Data suggests concurrent HIIT and RT does not negatively impact hypertrophy or upper body strength, and that any possible negative effect on lower body strength may be ameliorated by incorporating running based HIIT and longer inter-modal rest periods.
Incidence of gallstone disease in Italy: results from a multicenter, population-based Italian study (the MICOL project).

AIM To evaluate gallstone incidence and risk factors in a large population-based study. METHODS Gallstone incidence and risk factors, were evaluated by structured questionnaire and physical examination, respectively, in 9611 of 11 109 (86.5%) subjects who were gallstone-free at the cross-sectional study. RESULTS Six centers throughout Italy enrolled 9611 subjects (5477 males, 4134 females, aged 30-79 years), 9517 of whom were included into analysis: 424 subjects (4.4%) had gallstones and 61 (0.6%) had been cholecystectomized yielding a cumulative incidence of 0.67% per year (0.66% in males, 0.81% in females). Increasing age, a high body mass index (BMI), a history of diabetes, peptic ulcer and angina, and low cholesterol and high triglyceride levels were identified as risk factors in men while, in females, the only risk factors were increasing age and a high BMI. Increasing age and pain in the right hypocondrium in men and increasing age in females were identified as predictors of gallstones. Pain in the epigastrium/right hypocondrium was the only symptom related to gallstones; furthermore, some characteristics of pain (forcing to rest, not relieved by bowel movements) were significantly associated with gallstones. No correlation was found between gallstone characteristics and clinical manifestations, while increasing age in men and increasing age and BMI in females were predictors of pain. CONCLUSION Increasing age and BMI represent true risk factors for gallstone disease (GD); pain in the right hypocondrium and/or epigastrium is confirmed as the only symptom related to gallstones.
Weakly Supervised Object Discovery by Generative Adversarial & Ranking Networks

The deep generative adversarial networks (GAN) recently have been shown to be promising for different computer vision applications, like image editing, synthesizing high resolution images, generating videos, etc. These networks and the corresponding learning scheme can handle various visual space mappings. We approach GANs with a novel training method and learning objective, to discover multiple object instances for three cases: 1) synthesizing a picture of a specific object within a cluttered scene; 2) localizing different categories in images for weakly supervised object detection; and 3) improving object discovery in object detection pipelines. A crucial advantage of our method is that it learns a new deep similarity metric, to distinguish multiple objects in one image. We demonstrate that the network can act as an encoder-decoder generating parts of an image which contain an object, or as a modified deep CNN to represent images for object detection in supervised and weakly supervised scheme. Our ranking GAN offers a novel way to search through images for object specific patterns. We have conducted experiments for different scenarios and demonstrate the method performance for object synthesizing and weakly supervised object detection and classification using the MS-COCO and PASCAL VOC datasets.
Deep Collective Classification in Heterogeneous Information Networks

Collective classification has attracted considerable attention in the last decade, where the labels within a group of instances are correlated and should be inferred collectively, instead of independently. Conventional approaches on collective classification mainly focus on exploiting simple relational features (such ascount andexists aggregators on neighboring nodes). However, many real-world applications involve complex dependencies among the instances, which are obscure/hidden in the networks. To capture these dependencies in collective classification, we need to go beyond simple relational features and extract deep dependencies between the instances. In this paper, we study the problem of deep collective classification inHeterogeneous Information Networks (HINs), which involves different types of autocorrelations, from simple to complex relations, among the instances. Different from conventional autocorrelations, which are given explicitly by the links in the network, complex autocorrelations are obscure/hidden in HINs, and should be inferred from existing links in a hierarchical order. This problem is highly challenging due to the multiple types of dependencies among the nodes and the complexity of the relational features. In this study, we proposed a deep convolutional collective classification method, called GraphInception to learn the deep relational features in HINs. The proposed method can automatically generate a hierarchy of relational features with different complexities. Extensive experiments on four real-world networks demonstrate that our approach can improve the collective classification performance by considering deep relational features in HINs.