Miracle-dz/UniFAR-FTUs huggingface dataset:
Unraveling Prion Protein Interactions with Aptamers and Other PrP-Binding Nucleic Acids

Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative disorders that affect humans and other mammals. The etiologic agents common to these diseases are misfolded conformations of the prion protein (PrP). The molecular mechanisms that trigger the structural conversion of the normal cellular PrP (PrPC) into the pathogenic conformer (PrPSc) are still poorly understood. It is proposed that a molecular cofactor would act as a catalyst, lowering the activation energy of the conversion process, therefore favoring the transition of PrPC to PrPSc. Several in vitro studies have described physical interactions between PrP and different classes of molecules, which might play a role in either PrP physiology or pathology. Among these molecules, nucleic acids (NAs) are highlighted as potential PrP molecular partners. In this context, the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) methodology has proven extremely valuable to investigate PrP–NA interactions, due to its ability to select small nucleic acids, also termed aptamers, that bind PrP with high affinity and specificity. Aptamers are single-stranded DNA or RNA oligonucleotides that can be folded into a wide range of structures (from harpins to G-quadruplexes). They are selected from a nucleic acid pool containing a large number (1014–1016) of random sequences of the same size (~20–100 bases). Aptamers stand out because of their potential ability to bind with different affinities to distinct conformations of the same protein target. Therefore, the identification of high-affinity and selective PrP ligands may aid the development of new therapies and diagnostic tools for TSEs. This review will focus on the selection of aptamers targeted against either full-length or truncated forms of PrP, discussing the implications that result from interactions of PrP with NAs, and their potential advances in the studies of prions. We will also provide a critical evaluation, assuming the advantages and drawbacks of the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technique in the general field of amyloidogenic proteins.
Personality and Primary Emotional Traits: Disentangling Multiple Sclerosis Related Fatigue and Depression

Objective It remains an unresolved research objective to clarify the overlap/association between fatigue (especially its cognitive facet) and depression in People with MS (PwMS). Therefore, in this study the patterns of personality and primary emotional traits (PETs) associated with each (motoric/cognitive fatigue and depression in PwMS) were investigated and compared in order to disentangle the three constructs in PwMS. Additionally, differences in personality and PETs between PwMS and healthy controls (HC) were examined. Method Associations between motoric/cognitive fatigue, depression, personality and PETs were investigated in 52 PwMS. Personality and PETs were also assessed in a gender matched HC sample (N = 52) and results regarding these were compared between PwMS and HC. Results Low extraversion was the only significant predictor of MS related motoric fatigue (β = -.341, p = .013). High neuroticism was a predictor of both MS related cognitive fatigue (β = .426, p = .002) and depression (β = .443, p < .001). Whereas neuroticism was the only significant predictor for MS related cognitive fatigue, the cluster of (high) neuroticism, (high) SADNESS (β = .273, p = .023), and (low) extraversion (β = -.237, p = .025) predicted MS related depression. PwMS showed significantly higher scores in neuroticism and FEAR compared to HC. Conclusions MS related motoric/cognitive fatigue and depression in PwMS share variance. But the substantial amount of non-shared variance (motoric fatigue, depression: 72%; cognitive fatigue, depression: 66%) together with additional predictors for depression (SADNESS being a predictor of depression only), indicate that MS related motoric/cognitive fatigue and depression are distinguishable. Consequently, we recommend assessing especially SADNESS scores to distinguish between MS related fatigue and depression.
ATP binding cassette and cholecystokinin A receptor genetic variations in gallstone susceptibility

Aim: It was aimed to assess the association of four polymorphisms and relative haplotypes in the ATP binding cassettes and cholecystokinin A receptor (rs6720173, rs11887534, rs4148217, rs1800857) with the risk of gallstone. Background: Gallstone is a multifactorial disease. Besides high penetrance genes, low or moderate penetrance polymorphisms may increase susceptibility to gallstone. Methods: 200 gallstone patients and 251 healthy controls were analyzed in a case-control association model. Genotyping was carried out by restriction fragment length polymorphism. Randomly 10% of samples underwent for direct sequencing to confirm results. Results: Heterozygote variant of rs11887534 demonstrated protective effect on the risk of gallstone susceptibility in males (P=0.013; OR=0.125; CI95%=0.048-0.325). In contrast, C/C genotype associated with gallstone susceptibility in females (P=0.004; OR=5.555 CI95%=1.975-10.632). Moreover, rs1800857 showed association only in females (P=0.019; OR=0.283; CI95%=0.099-0.811). Haplotype analysis for rs1800857 showed GC, CC and CA association with gallstone. Conclusion: The most imperative polymorphisms of contributing genes to gallstone were analyzed in this study and rs11887534 and rs1800857 appeared to be associated with gallstone, which is expected to be further veriﬁed in a larger cohort in the future.
The Role of National Immunization Technical Advisory Groups (NITAGs) in the Introduction of Inactivated Polio Vaccine: Experience of the Indonesia and Uganda NITAGs

Abstract Background. National Immunization Technical Advisory Groups (NITAGs) are established by national authorities to provide them with independent, bias-free, objective, and evidence-based advice on vaccines and immunization challenges. As of December 2015, 125 countries have reported having set up an NITAG. The Health Policy and Institutional Development Center at the Agence de Médecine Préventive, a World Health Organization (WHO) Collaborative Center for evidence-informed immunization, through its Supporting Independent Immunization and Vaccine Advisory Committees (SIVAC) Initiative project, provides assistance to low- and middle-income countries in the establishment and strengthening of their NITAGs. The Indonesian NITAG (ITAGI) was formed in December 2006 and Uganda’s (UNITAG) was formed in November 2014. Both Uganda and Indonesia have introduced inactivated polio vaccine (IPV) as part of the Global Polio Eradication and Endgame Strategic Plan (the Endgame plan). The authors reflect on the process and the role played by NITAGs in the introduction of IPV in the routine immunization program and the lessons learned. Methods. This commentary is a reflection of the authors’ experience on NITAG’s role as observed in 2 particular local settings and applied to a global public health issue, the polio eradication Endgame plan. The reflection is backed up by the relevant (policy and technical) documents on polio eradication, along with minutes and reports from countries’ ministries of health, immunization programs, WHO, and NITAGs. Results. NITAGs are valuable tools for ministries of health to ensure sustainable, evidence-informed immunization policies that are trusted and accepted by their communities. Early engagement with NITAGs also ensures that the adoption of strategies addressing global public health threats at the country level reinforces the national immunization programs. On the other end, when NITAGs are proactive and forward-thinking, they can contribute to a smooth and effective introduction of the above-mentioned strategies. Time and resources are key factors to ensure optimal performance of NITAGs.
Appropriate surgical procedure for dominant thyroid nodules of the isthmus 1 cm or larger.

HYPOTHESIS Surgeon-performed ultrasound (SUS) and fine-needle aspiration (FNA) may guide the management of dominant thyroid nodules of the isthmus. DESIGN Retrospective review of prospectively collected data. SETTING Tertiary academic referral center. PATIENTS Of 942 patients who underwent preoperative SUS and FNA, followed by thyroidectomy, between January 1, 2002, and April 10, 2010, a total of 28 patients had a dominant thyroid nodule of the isthmus. MAIN OUTCOME MEASURES Preoperative SUS features and FNA findings and final pathologic results. RESULTS Of 28 patients (3%) who had a dominant thyroid nodule of the isthmus, 16 had benign final pathologic results, with all having at least 2 benign SUS features and 9 having 3 benign SUS features; 15 of 16 patients had an FNA finding that was benign or indeterminate. Of 12 patients with malignant final pathologic results, 8 had 3 malignant SUS features, and all had an FNA finding that was malignant or suspicious for a malignant neoplasm. Among these 12 patients, final pathologic results demonstrated multifocal disease (8 patients), extracapsular invasion (4 patients), or lymph node involvement (7 patients). When 11 patients with a malignant dominant thyroid nodule of the isthmus were compared with an overall group of 270 other well-differentiated papillary thyroid carcinomas 1 cm or larger on final pathologic results, patients with isthmus nodules trended toward having higher rates of multifocal disease (P = .08), extracapsular invasion (P = .09), and lymph node involvement (P = .09). CONCLUSIONS Preoperative SUS features and FNA findings in patients with dominant thyroid nodules of the isthmus can accurately predict malignant or benign thyroid disease and direct the extent of thyroidectomy. For malignant isthmus nodules, total thyroidectomy and possible central node dissection are recommended owing to high rates of multifocal disease and lymph node involvement. For benign isthmus nodules, thyroid lobectomy with isthmusectomy or isthmusectomy alone may be appropriate.
Optimal Taxation with Private Insurance

We derive a fully non-linear optimal income tax schedule in the presence of private insurance. We fill the gap in the literature by studying the optimal tax formula with a comprehensive structure of the private markets—including incomplete markets models—both theoretically and quantitatively. As in the standard taxation literature without private insurance, the optimal tax formula can still be expressed in terms of standard sufficient statistics. With private insurance, however, the formula involves additional terms that reflect how the private market interacts with public insurance. For example, the optimal tax formula should also consider asset distribution and pecuniary externalities as well as the welfare effects of borrowing constraints.
Australian validation of the Cancer of the Prostate Risk Assessment Post‐Surgical score to predict biochemical recurrence after radical prostatectomy

The Cancer of the Prostate Risk Assessment Post‐Surgical (CAPRA‐S) score is a simple post‐operative risk assessment tool predicting disease recurrence after radical prostatectomy, which is easily calculated using available clinical data. To be widely useful, risk tools require multiple external validations. We aimed to validate the CAPRA‐S score in an Australian multi‐institutional population, including private and public settings and reflecting community practice.
PhylOligo: a package to identify contaminant or untargeted organism sequences in genome assemblies

Motivation Genome sequencing projects sometimes uncover more organisms than expected, especially for complex and/or non‐model organisms. It is therefore useful to develop software to identify mix of organisms from genome sequence assemblies. Results Here we present PhylOligo, a new package including tools to explore, identify and extract organism‐specific sequences in a genome assembly using the analysis of their DNA compositional characteristics. Availability and implementation The tools are written in Python3 and R under the GPLv3 Licence and can be found at https://github.com/itsmeludo/Phyloligo/. Contact ludovic.mallet@inra.fr Supplementary information Supplementary data are available at Bioinformatics online.
Electrochemical MHD for Microfluidics Applications

To investigate the feasibility of using magnetic fields for flow control in microfluidic devices, we employed potential sweep and potential step voltammetry in CFD simulations of the electrochemical magnetohydrodynamics (ECMHD) of a redox system. For all cases, the faradaic current at the working electrode was computed. Using time-varying boundary conditions based on the Butler-Volmer electrode kinetics model, we studied the interplay of Lorentz force, convection and redox species concentration distribution. The concentration contours obtained show strong effect of magnetoconvection due to Lorentz force. The evolution of the flow field in a two-dimensional electrochemical cell shows gradual development of a vortex structure with time. The potential step simulations have been validated by comparing with the approximate one-dimensional analytical solution for the diffusion only case. The cyclic voltammograms obtained from the potential sweep simulation have been compared with published experimental data. The results agree well. Simulations of a channelless microfluidic cell show that ECMHD is suitable for pumping, mixing and flow control.
Valve-sparing David I procedure in acute aortic type A dissection: a 20-year experience with more than 100 patients†

OBJECTIVES The aortic valve-sparing David procedure has been applied to the elective treatment of patients with aortic aneurysms with excellent results. The use of this technique in patients with acute aortic dissection type A (AADA) is still a matter of debate. We present our long-term experience with 109 patients with AADA who had the valve-sparing David I procedure. METHODS Between July 1993 and October 2015, 109 patients with AADA had the valve-sparing David I procedure at our centre. We conducted a retrospective review with follow-up. RESULTS The mean age was 54 ± 12 years; 78 (72%) patients were men. Marfan syndrome was present in 6 (5%) patients and bicuspid aortic valve in 3 (3%). Only 4 (4%) patients received the isolated David procedure; 50 (46%) underwent additional proximal, 13 (12%) subtotal and 42 (39%) total aortic arch replacement. The in-hospital mortality rate was 11% ( n = 12). Intraoperative/discharge echocardiography showed aortic insufficiency ≤ I° in 93 of 97 patients (96%). Mean follow-up time was 8.3 ± 5.7 years. The survival rate after discharge at 1, 5 and 10 years was 94%, 90% and 78%, respectively. Thirteen percent ( n = 13) of patients underwent valve-related reoperation. Freedom from valve-related reoperation at 1, 5 and 10 years was 96%, 88% and 85%, respectively. Compared to patients who underwent the David I procedure for any reason other than AADA, there were no significant differences in long-term survival rates ( P = 0.29) and freedom from a valve-related reoperation ( P = 0.39). CONCLUSIONS The valve-sparing David I procedure has acceptable long-term results even in emergent operations for AADA and is not inferior when performed in elective settings.
Tubular vs Profile Plate in Peroneal or Bimalleolar Fractures: is There a Real Difference in Skin Complication? A Retrospective Study in Three Level I Trauma Center

Introduction: Not enough literature is available to evalute the wound complication rate of plates type in distal fibular fractures. Aim: The aim of our study was to compare wound complications of using a third tubular plate compared to LCP distal fibula plate. Material and Methods: This study is a retrospective single-centre study in which was performed plating of fibula in closed ankle fractures. 93 patients were included in our study and assigned in two groups, based on using of different implant : in group A 48 patients were treated with one-third tubular and in group B 45 patients were treated with LCP distal fibula plate. There were no significant differences in the baseline characterisctics. Patients received the same surgical procedure and the same post-operative care, then they were radiologically evalueted at 1-3-12 months and clinical examination was made at 12 months using AOFAS clinical rating system. Categorical data, grouped into distinct categories, were evalueted using Chi-square test. We considered a p value < 0.05 as statistically significant. Results: The wound complications rate of the overall study group was 7.6%. There were no statistical differences in the rate of wound complications between the two groups. There were no differences between both group in percentage of hardware removal at follow-up (overall 5.4%); plate removal was performed earlier in the locking plate because of wound complications. Conclusions: Our study has shown no difference in radiographic bone union rate, no significant differences in terms of clinical outcomes, in time of bone reduction and wound complication rate between the LCP distal fibula plate and conventional one-third tubular plate. Controversy still exists about the best method for the fracture reduction.
Dopamine D1 receptor‐mediated upregulation of BKCa currents modifies Müller cell gliosis in a rat chronic ocular hypertension model

Müller cell gliosis is a common response in many retinal pathological conditions. We previously demonstrated that downregulation of Kir channels contributes to Müller cell gliosis in a rat chronic ocular hypertension (COH) model. Here, the possible involvement of outward K+ currents in Müller cell gliosis was investigated. Outward K+ current densities in Müller cells isolated from COH rats, as compared with those in normal rats, showed a significant increase, which was mainly contributed by large‐conductance Ca2+‐activated K+ (BKCa) channels. The involvement of BKCa channels in Müller cell gliosis is suggested by the fact that glial fibrillary acidic protein (GFAP) levels were augmented in COH retinas when these channels were suppressed by intravitreal injections of iberiotoxin. In COH retinas an increase in dopamine (DA) D1 receptor (D1R) expression in Müller cells was revealed by both immunohistochemistry and Western blotting. Moreover, protein levels of tyrosine hydroxylase were also increased, and consistent to this, retinal DA contents were elevated. SKF81297, a selective D1R agonist, enhanced BKCa currents of normal Müller cells through intracellular cAMP‐PKA signaling pathway. Furthermore, GFAP levels were increased by the D1R antagonist SCH23390 injected intravitreally through eliminating the BKCa current upregulation in COH retinas, but partially reduced by SKF81297. All these results strongly suggest that the DA‐D1R system may be activated to a stronger extent in COH rat retinas, thus increasing BKCa currents of Müller cells. The upregulation of BKCa channels may antagonize the Kir channel inhibition‐induced depolarization of Müller cells, thereby attenuating the gliosis of these cells.
Extracting Action Sequences from Texts Based on Deep Reinforcement Learning

Extracting action sequences from texts is challenging, as it requires commonsense inferences based on world knowledge. Although there has been work on extracting action scripts, instructions, navigation actions, etc., they require either the set of candidate actions be provided in advance, or action descriptions are restricted to a specific form, e.g., description templates. In this paper we aim to extract action sequences from texts in \emph{free} natural language, i.e., without any restricted templates, provided the set of actions is unknown. We propose to extract action sequences from texts based on the deep reinforcement learning framework. Specifically, we view ``selecting'' or ``eliminating'' words from texts as ``actions'', and texts associated with actions as ``states''. We build Q-networks to learn policies of extracting actions and extract plans from the labeled texts. We demonstrate the effectiveness of our approach on several datasets with comparison to state-of-the-art approaches.
Inflammatory and metabolic responses to an intramammary lipopolysaccharide challenge in early lactating cows supplemented with conjugated linoleic acid

Supplementation of dairy cows with trans-10, cis-12 conjugated linoleic acid (CLA) allows nutrient repartitioning despite an energy deficiency in early lactation, which might be a benefit for the immune system, too. In this study, we investigated potential nutrient sparing effects of CLA in early lactating cows with low plasma glucose concentrations exposed to an intramammary lipopolysaccharide (LPS) challenge. Fifteen multiparous Holstein cows were exposed to an intramammary LPS challenge in week 4 p.p. Eight cows (CLA) were supplemented daily with 70 g of lipid-encapsulated CLA (6.8 g trans-10, cis-12 and 6.6 g of the cis-9, trans-11 CLA isomer; CLA) and seven cows with 56 g of control fat (CON). Blood samples were obtained every 30 min along with rectal temperature, heart and respiratory rate, and milk samples were taken hourly until 10 hr after the LPS application. Plasma was analysed for concentrations of glucose, free fatty acids, beta-hydroxybutyrate (BHB), cortisol, insulin and glucagon. In milk, somatic cell count and activity of lactate dehydrogenase were determined. Initial plasma glucose concentration was lower in CLA than in CON. During the immunostimulation, CLA had higher glucose concentrations than CON, and BHB decreased distinctly in CLA, whereas CON cows maintained BHB concentration at a lower level. Body temperature in CLA increased earlier, the difference between peak and basal temperature was higher, and the decline thereafter occurred earlier. In conclusion, CLA supplementation of early lactating cows exposed to an intramammary LPS challenge affected local and systemic immune responses. We assume that CLA supplementation triggered glycogen storage. Cows supplemented with CLA provided more glucose and preferentially used BHB as an energy source during the immune response. The more intense metabolic and more concentrated endocrine responses support an immunomodulatory effect of CLA supplementation.
Crowd Detection from Still Images

The analysis of human crowds has widespread uses from law enforcement to urban engineering and traffic management. All of these require a crowd to first be detected, which is the problem addressed in this paper. Given an image, the algorithm we propose segments it into crowd and non-crowd regions. The main idea is to capture two key properties of crowds: (i) on a narrow scale, its basic element should look like a human (only weakly so, due to low resolution, occlusion, clothing variation etc.), while (ii) on a larger scale, a crowd inherently contains repetitive appearance elements. Our method exploits this by building a pyramid of sliding windows and quantifying how “crowd-like” each level of the pyramid is using an underlying statistical model based on quantized SIFT features. The two aforementioned crowd properties are captured by the resulting feature vector of window responses, describing the degree of crowd-like appearance around an image location as the surrounding spatial extent is increased.
Treating anxiety without SSRIs

CASE 1   Brad S, a 39-year-old lawyer, is in your offi ce for a follow-up visit. A month ago, you diagnosed him with generalized anxiety disorder and prescribed paroxetine. Brad reports that the medication worked “like a miracle,” rapidly resolving his constant worry and rumination. Unfortunately, though, he is experiencing a bothersome side effect—sexual dysfunction. He’s having diffi culty achieving ejaculation during intercourse and wants to know if you can give him “something else that works just as well. ” What would you recommend?