Miracle-dz/UniFAR-FTUs huggingface dataset:
Enteric infection coupled with chronic Notch pathway inhibition alters colonic mucus composition leading to dysbiosis, barrier disruption and colitis

Intestinal mucus layer disruption and gut microflora modification in conjunction with tight junction (TJ) changes can increase colonic permeability that allows bacterial dissemination and intestinal and systemic disease. We showed previously that Citrobacter rodentium (CR)-induced colonic crypt hyperplasia and/or colitis is regulated by a functional cross-talk between the Notch and Wnt/β-catenin pathways. In the current study, mucus analysis in the colons of CR-infected (108 CFUs) and Notch blocker Dibenzazepine (DBZ, i.p.; 10μmol/Kg b.w.)-treated mice revealed significant alterations in the composition of trace O-glycans and complex type and hybrid N-glycans, compared to CR-infected mice alone that preceded/accompanied alterations in 16S rDNA microbial community structure and elevated EUB338 staining. While mucin-degrading bacterium, Akkermansia muciniphila (A. muciniphila) along with Enterobacteriaceae belonging to Proteobacteria phyla increased in the feces, antimicrobial peptides Angiogenin-4, Intelectin-1 and Intelectin-2, and ISC marker Dclk1, exhibited dramatic decreases in the colons of CR-infected/DBZ-treated mice. Also evident was a loss of TJ and adherens junction protein immuno-staining within the colonic crypts that negatively impacted paracellular barrier. These changes coincided with the loss of Notch signaling and exacerbation of mucosal injury. In response to a cocktail of antibiotics (Metronidazole/ciprofloxacin) for 10 days, there was increased survival that coincided with: i) decreased levels of Proteobacteria, ii) elevated Dclk1 levels in the crypt and, iii) reduced paracellular permeability. Thus, enteric infections that interfere with Notch activity may promote mucosal dysbiosis that is preceded by changes in mucus composition. Controlled use of antibiotics seems to alleviate gut dysbiosis but may be insufficient to promote colonic crypt regeneration.
Epidemiological data of anaphylaxis in french emergency departments.

BACKGROUND Although anaphylaxis has been pointed as a high priority public health issue in the allergy world community, morbidity and mortality epidemiological data are still not optimal. This first multi-centric epidemiological study performed in 7 French emergency departments for one year intended to map the key issues to substantiate the need for changes and support ongoing national and international efforts for better diagnosis, management and prevention of anaphylaxis. METHODS This is a descriptive study using data routinely reported to French institutional administrative databases reported from 7 French public health institutions of the Lorraine region from January to December 2015, based on International Classification of Diseases (ICD)-10 pre-selected anaphylaxis-related codes and clinically validated as anaphylaxis cases. RESULTS From the 202,079 ED admissions, 4,817 had ICD-10 anaphylaxis-related codes, 323 of those have been clinically validated as anaphylaxis cases. Although 45.8% presented severity criteria, adrenaline has been prescribed only in 32.4% of these cases. Overall 323 cases, 57.9% were subsequently referred to allergy work-up or evaluation (after or during hospitalization) and 17.3% received a prescription of auto-injectable adrenaline. CONCLUSION Taken the results of this study, there is an urgent and pressing need for improved public health initiatives regarding anaphylaxis recognition and treatment. Timely, we strongly believe that this document flags key problems, which may be managed in the forthcoming years by implementing national and international actions.
Towards Modelling Future Trends of Quebec's Boreal Birds' Species Distribution under Climate Change

Adaptation to climate change requires prediction of its impacts, especially on ecosystems. In this work we simulated the change in bird species richness in the boreal forest of Quebec, Canada, under climate change scenarios. To do so, we first analyzed which geographical and bioclimatic variables were the strongest predictors for the spatial distribution of the current resident bird species. Based on canonical redundancy analysis and analysis of variance, we found that annual temperature range, average temperature of the cold season, seasonality of precipitation, precipitation in the wettest season, elevation, and local percentage of wet area had the strongest influence on the species’ distributions. We used these variables with Random Forests, Multivariate Adaptive Regression Splines and Maximum Entropy models to explain spatial variations in species abundance. Future species distributions were calculated by replacing present climatic variables with projections under different climate change pathways. Subsequently, maps of species richness change were produced. The results showed a northward expansion of areas of highest species richness towards the center of the province. Species are also likely to appear near James Bay and Ungava Bay, where rapid climate change is expected.
Anti-EGFR anchored paclitaxel loaded PLGA nanoparticles for the treatment of triple negative breast cancer. In-vitro and in-vivo anticancer activities

The aim of the present study is to analyze the viability of anti-EGFR anchored immunonanoparticle (INP) bearing Paclitaxel (PTX) to specifically bind the EGFR protein on the TNBC cells. The NP was prepared by nanoprecipitation and characterized the particle size, charge, entrapment of drug and release of it. The anti-EGFR anchored and the integrity was confirmed by SDS-PAGE. Cytotoxicity and NPs cellular uptake was analyzed with MDA-MB-468 type cancer cells and the EGFR expression was confirmed by PCR, qualitatively and quantitatively. The in-vivo antitumor activity of INP was determined by using athymic mice model and targeting efficiency was measured by calculating the PTX accumulation in the tumor plasma. The prepared INP with the size of 336.3 nm and the charge of -3.48 mV showed sustained drug release upto 48 h. The INP showed significant reduction of cancer cell viability of 10.6% for 48 h with 93 fold higher PTX accumulation in the tumor plasma compared with NPs. Based on these reports, we recommend that anti-EGFR anchored PTX loaded NP may have the ability to target the TNBC cells and improve the therapeutic action and subsidize the side effects of PTX for the treatment of TNBC.
Long Coronary Lesions Requiring Long Stents 20 mm. Analysis And Outcome In Patients Treated At Queen Alia Heart Institute

Objective: To determine the outcome after using long coronary stents >20 mm for long coronary lesions among patients treated at Queen Alia Heart Institute. Methods: This is a descriptive, and a retrospective non randomized study which was conducted at Queen Alia Heart Institute on 900 adult patients who underwent coronary angiography and intervention for either stable or unstable angina pectoris during the period between 2006 to 2011. Those patients had coronary intervention using a single long stent for each long lesion (>20 mm). Their follow up was analyzed and the outcome of these long stents was studied for in stent restenosis or in stent total occlusion in each specific coronary artery. A specially designed form was used to record the following data in the involved patients: age, gender, size and type of coronary stent (drug eluting or bare metal), the presence of diabetes mellitus, hypertension or hypercholesterolemia, and the status of the left ventricle. Results: The total number of patients who had long coronary stent intervention was 900 cases. Four hundred eighty patients (53.3%) had restudy cardiac catheterization within 6-8 months, which showed instent restenosis or instent total occlusion in 90 patients. Males constituted the majority (88.9%) of the affected patients. Smoking was the commonest (83.3%) factor associated with instent restenosis followed by Diabetes Mellitus (61.1%). About half the cases of long instent restenosis was found in left anterior descending artery, whereas right coronary artery and circumflex artery had almost equal ratios: 23.3% and 22.2% respectively. Long instent restenosis was commoner (33.3%) in ostial lesions and was the least (14.5%) in mid segment lesions. Bare metal stents were associated with the majority (77.8%) of cases of instent restenosis. About two thirds of the affected patients had small caliber stents (2.5 and 2.75 mm diameter). Conclusion: Instent restenosis or instent total occlusion in long coronary stents is a well recognized and not uncommon clinical entity. Men are more commonly affected than women. Ostial left anterior descending artery is more affected than other coronaries. Smoking, Diabetes Mellitus and the use of bare metal stents of small sized caliber (≤ 2.75 mm) were common in our study patient population and associated with increased incidence of long instent restenosis
Towards realistic walk path simulation of single subjects: presenting a probabilistic motion planning algorithm

Within the manufacturing industry, digital modelling activities and the simulation of human motion in particular, have emerged during the last decades. For the use-case of walk path planning, however, recent path planning approaches on the one hand reveal drawbacks in terms of realism and naturalness of motion. On the other hand, the generation of variant-rich travel routes by means of modeling the statistical nature of human motion has not been explored yet. In order to contribute to a better prediction quality of planning models, this paper therefore presents an approach for realistically simulating walk paths of single subjects. In order to take into consideration the variability of human locomotion, a statistical model describing human motion in a two-dimensional bird's eye view is presented. This model is generated from a comprehensive database (20 000 steps) of captured human motion and covers a wide range of gait variants. In order to obtain short and collision-free trajectories, this approach is combined with a path planning algorithm. The utilized hybrid A* path planner can be regarded as an orchestration-instance, stitching together succeeding left and right steps, which were drawn from the statistical motion model. Although being initially designed for industrial purposes, this method can be applied to a wide range of use-cases beyond automotive walk path planning. To underline the evident benefits of the proposed approach, the novel motion planner's technical performance is demonstrated in an evaluation.
Diagnostic Performance and Accuracy of the 3 Interpreting Methods of Breast Strain Elastography: A Systematic Review and Meta‐analysis

There are 3 methods of interpreting breast strain elastography: the elastographic–to–B‐mode length ratio (E/B), a 5‐point color scale (5P), and the strain ratio (SR). This meta‐analysis assessed which method is superior to the others. A systematic search of the medical literature was performed in July 2017. Studies were eligible for inclusion if they fulfilled the following criteria: (1) had biopsy‐proven or long‐term stability as the reference standard; (2) used either the E/B, 5P, or SR to interpret results; and (3) had at least 50 cases. A total of 220 records were retrieved; 60 full‐text articles were examined, and 46 were included in the meta‐analysis. Publication years ranged from 2007 and 2017. The quality of studies was generally high. The mean age of women was 48 years; 12,398 lesions (4242 malignant) were analyzed. For the 5P method, the sensitivity was 77%; specificity, 87%; positive likelihood ratio (LR), 5.3; and negative LR, 0.24. For the SR method, sensitivity was 87%; specificity, 81%; positive LR, 4.8; and negative LR, 0.16. For the E/B method, sensitivity was 96%; specificity, 88%; positive LR, 7.1; and negative LR, 0.03. Of the 3 methods, the E/B had the highest sensitivity, and the E/B and 5P had the highest specificity. With a negative LR of 0.03, the E/B method can downgrade lesions with a pretest probability of 50% to a 2% probability of malignancy.
Analysis and Reduction of the Output Voltage Error of PWM for Modular Multilevel Converters

Standard pulsewidth modulation (PWM) schemes for modular multilevel converters (MMC) have neglected deviations of the module voltages from the mean module voltage of an MMC arm as well as the dynamic change in the module voltages since their last measurement and during the switching period. This induces an output voltage error. Large output voltage errors disturb the higher level closed-loop control of the MMC, such that control targets cannot be met anymore. The output voltage error can be reduced using advanced PWM methods that predict and include the dynamic change of the individual module voltages during a switching period in the calculations for the duty cycle. This paper shows measurement results obtained from an experimental medium-voltage prototype, proving that advanced methods lead to much lower output voltage errors than the standard methods, but cannot fulfill the expectations raised by the simulations documented in the literature. In order to overcome the limitations of the old method, a new method that includes the semiconductor voltage drop and parasitic resistances is introduced and evaluated with measurements in this paper. Furthermore, simulation results showing the influence of the considered modulation methods on the closed-loop current control performance are presented.
Systemic treatments for metastatic urothelial carcinoma

ABSTRACT Introduction: Urothelial carcinoma is one of the most common cancers in the western world and, until recently, had limited therapeutic options. The contemporary advancement of immune checkpoint inhibitors (ICI) has heralded a new era for these patients and represents a major shift in the evolving treatment landscape. Areas covered: This article provides a comprehensive summary of the currently available treatments for metastatic urothelial carcinoma (mUC). The authors also review ongoing, phase-III studies with novel therapeutic targets and highlight recent insights into tumor biology that may help better understand the disease. Expert opinion: The treatment landscape for first-line therapy of mUC continues to include platinum-based chemotherapy for patients who are eligible. While the approval of ICI has changed the management in those who are post-platinum or platinum-ineligible, the wider use of ICI in the first-line setting requires further clarity given recent FDA announcements. Maintaining the remarkable progress in mUC may depend upon ongoing phase-III studies evaluating treatment options beyond ICI. Better prognostication and identification of those unlikely to respond to ICI remain important unanswered questions, particularly as this class of agents moves further along the disease spectrum of non-metastatic UC.
The influences of age, gender and geometric pattern of visual image on the verticality perception: A subjective visual vertical (SVV) study among Malaysian adults

Subjective visual vertical (SVV) is a simple, quick and reliable test for measuring utricular function. The literature on the effects of fundamental demographic variables such as age and gender on SVV is inconclusive and should be supported by research with larger samples. The aim of the present study was to determine the influences of age, gender and geometric pattern of visual image on SVV among healthy adults.
Association between handgrip strength and vascular function in patients with hypertension

ABSTRACT Background: Increased handgrip strength has been associated with lower cardiovascular and non-cardiovascular mortality in different populations. In patients with hypertension, arterial stiffness relates to cardiovascular mortality. However, whether muscle strength is associated with arterial stiffness in hypertensives is unknown. Thus, the objective of this study was to analyze the association between handgrip strength and arterial stiffness parameters in hypertensive patients. Methods: Seventy-two hypertensive patients completed all evaluations and were included in the analysis. The ambulatory arterial stiffness index (AASI) was obtained based on 24-h ambulatory blood pressure monitoring. Carotid-femoral pulse wave velocity (cfPWV), and reflected wave indicator (AIx and AIx@75) were estimated using applanation tonometry technique, whereas handgrip strength test was performed using a digital dynamometer. Crude and adjusted linear regression models were performed. Results: The crude analysis revealed a negative association between handgrip strength and AASI (b = −0.41, p = 0.002) and AIx (b = −0.49, p < 0.001), and AIx@75 (b = −0.54, p < 0.001) which remained significant after adjustments for age, sex, and body mass index, mean blood pressure, and heart rate only for AASI (b = −0.46, p = 0.028) and AIx@75 (b = −0.24, p- = 0.040). Handgrip strength was not associated with cfPWV (p > 0.05). Conclusion: Handgrip strength is negatively associated with AASI and AIx@75, but not with AIx and cfPWV in hypertensive patients.
The Association Between Race/Ethnicity and Socioeconomic Factors and the Diagnosis and Treatment of Children with Attention-Deficit Hyperactivity Disorder

Objective: Assessing race/ethnicity and socioeconomic status (SES) relationships with Attention-Deficit/Hyperactivity Disorder (ADHD) diagnosis, treatment, and access to care has yielded inconsistent results often based only on parent-report. In contrast, this study used broader ADHD diagnostic determination including case-definition to examine these relationships in a multisite elementary-school-based sample. Method: Secondary analysis of children with and without ADHD per parent and teacher-reported Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria evaluated SES, race/ethnicity, and other variables through simple bivariate/multivariable models within and across: parent-reported diagnosis, medication treatment, and meeting ADHD study case-definition. Results: The total sample included 51.9% male, 51.3% White, and 53.1% with private insurance; 10% had parent-reported ADHD diagnoses while 8.3% met ADHD study case-definition. In multivariable models, White children had higher odds of parent-reported diagnoses than Black, Hispanic, and Other Race/Ethnicity children (p < 0.05), but only Hispanic children had lower odds of being case-positive (<0.05); males and children in single-parent households had higher odds of parent-reported diagnoses and being case-positive (p < 0.05); and children who were White, male, and had health insurance had higher odds of taking medication (p < 0.05). Among children who were case-positive, those with Medicaid, White, and 2-parent statuses had higher odds of parent-reported diagnoses (p < 0.05). Conclusion: Children with underlying ADHD appear more likely to have assessment/medication treatment access if they are White, male, have health insurance (particularly Medicaid), and live in 2-parent households. While boys and children raised by single parents may have higher rates of ADHD diagnoses, false-positive diagnostic risk also appeared higher, inviting further investigation.
Knockdown of FOXP1 promotes the development of lung adenocarcinoma

ABSTRACT Lung cancer is one of the most common cancers in the world, which accounts for about 27% of all cancer deaths. However, the mechanisms underlying the pathogenesis of lung cancer cells remain largely elusive. In this study, we examined the role of the Forkhead box protein P1 (FOXP1) in lung cancer development. Our Oncomine analysis shows that FOXP1 is downregulated in lung adenocarcinoma compared with normal lung tissue. Knockdown of FOXP1 promotes the growth and invasion of PC9 and A549 cells by regulating genes of chemokine signaling molecules, including CCR1, ADCY5, GNG7, VAV3, and PLCB1. Simultaneous knockdown of CCR1 and FOXP1 attenuated FOXP1 knockdown-induced increase of lung cancer cell growth. Finally, knockdown of FOXP1 in PC9 cells promotes the tumorigenesis via CCR1 signaling in xenograft mouse model. Taken together, our data suggest that FOXP1 plays important roles in preventing lung adenocarcinoma development via suppressing chemokine signaling pathways.
Improved Brute-Force Search Strategies for Single-Trace and Few-Traces Template Attacks on the DES Round Keys

We present an improved search strategy for a template attack on the secret DES key of a widely–used smart card, which is based on a Common–Criteria certified chip. We use the logarithm of the probability function as returned by the template attack itself, averaged over all 28 template positions along the rings representing the C and D Registers of the DES key schedule, as the sorting criteria for the key candidates. For weak keys — which in this attack model have a minimal rest entropy of only two bits — we find that on average only 37.75 bits need to be recovered by brute force when using only a single trace in the Exploitation Phase. This effort goes down to just a few bits for a single DES key when using only a few traces in Exploitation Phase.
An NP-complete number-theoretic problem

Systems of nonlinear equations of the form D: Ay = σ. (x), where A is an m×n matrix of rational constants and y = (Y1,.,yn), σ(x) = (σ1(x),. , σm (x)) are column vectors are considered. Each σi(x) is of the form ri(x) or @@@@ri(x)@@@@, where ri(x) is a rational function of x with rational coefficients. It is shown that the problem of determining for a given system D whether there exists a nonnegative integral solution (y1,.,yn,X) satisfying D is decidable. In fact, the problem is NP-complete when restricted to systems D in which the maximum degree of the polynomials defining the σi(x)'s is bounded by some fixed polynomial in the length of the representation of D. Some recent results connecting Diophantine equations and counter machines are briefly mentioned.
Carbon monoxide attenuates amyloidogenesis via down‐regulation of NF‐κB‐mediated BACE1 gene expression

Amyloid‐β (Aβ) peptides, the major constituent of plaques, are generated by sequential proteolytic cleavage of the amyloid precursor protein (APP) via β‐secretase (BACE1) and the γ‐secretase complex. It has been proposed that the abnormal secretion and accumulation of Aβ are the initial causative events in the development of Alzheimer's disease (AD). Drugs modulating this pathway could be used for AD treatment. Previous studies indicated that carbon monoxide (CO), a product of heme oxygenase (HO)‐1, protects against Aβ‐induced toxicity and promotes neuroprotection. However, the mechanism underlying the mitigative effect of CO on Aβ levels and BACE1 expression is unclear. Here, we show that CO modulates cleavage of APP and Aβ production by decreasing BACE1 expression in vivo and in vitro. CO reduces Aβ levels and improves memory deficits in AD transgenic mice. The regulation of BACE1 expression by CO is dependent on nuclear factor‐kappa B (NF‐κB). Consistent with the negative role of SIRT1 in the NF‐κB activity, CO fails to evoke significant decrease in BACE1 expression in the presence of the SIRT1 inhibitor. Furthermore, CO attenuates elevation of BACE1 level in brains of 3xTg‐AD mouse model as well as mice fed high‐fat, high‐cholesterol diets. CO reduces the NF‐κB‐mediated transcription of BACE1 induced by the cholesterol oxidation product 27‐hydroxycholesterol or hydrogen peroxide. These data suggest that CO reduces the NF‐κB‐mediated BACE1 transcription and consequently decreases Aβ production. Our study provides novel mechanisms by which CO reduces BACE1 expression and Aβ production and may be an effective agent for AD treatment.