Miracle-dz/UniFAR-FTUs huggingface dataset:
Comment on: The Geographic Diversity of Spinocerebellar Ataxias (SCAs) in the Americas

We have read with interest the review by Teive and colleagues that described the prevalence and clinical phenotypes of spinocerebellar ataxias (SCAs) across the Americas. The authors showed, based on the results of the so far only study published from a single center in Argentina including 20 patients, that in Argentina the most frequent SCAs were SCA2 (8 cases; 40%) followed by SCA1 and SCA3 (5 cases; 25% for each subtype), SCA6 (1 case; 5%), and SCA7 (1 case; 5%). We would like to add unpublished data obtained from the largest genetic and molecular biology center in Argentina from 2008 to 2019. A total of 272 patients with progressive ataxia were tested for SCA1, SCA2, SCA3, SCA6, SCA7, or SCA8. Among the 48 (18%) cases that proved positive for SCA, the most frequent was SCA2 (22 cases; 46%) followed by SCA3 (13 cases; 27%), SCA1 (10 cases; 21%), SCA6 (2 cases; 4%), and SCA7 (1 case; 2%). These results based on a larger cohort confirm Teive and colleagues’ report that SCA2 is the most frequent genetic subtype in our country, in concordance with Cuba, but different to most countries of the Americas where SCA3 is the most prevalent SCA subtype. An explanation for the higher frequency of SCA2 in Argentina in comparison with other SCAs could be because the majority of its people have a European ancestry, mainly from Spain and Italy, where SCA2 is highly prevalent. Knowing which SCA subtypes are the most prevalent in different countries or regions is critical for genetic testing when diagnostic resources, such as comprehensive gene panels, are not universally available or affordable.
LRRK2 mediates tubulation and vesicle sorting from membrane damaged lysosomes

Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are a cause of familial and sporadic Parkinson’s disease (PD). Nonetheless, the biological functions of LRRK2 remain incompletely understood. Here, we observed that LRRK2 is recruited to lysosomes that have a ruptured membrane. Using unbiased proteomics, we observed that LRRK2 is able to recruit the motor adaptor protein JIP4 to permeabilized lysosomes in a kinase-dependent manner through the phosphorylation of RAB35 and RAB10. Super-resolution live cell imaging microscopy and FIB-SEM revealed that once at the lysosomal membrane, JIP4 promotes the formation of LAMP1-negative lysosomal tubules that release membranous content from ruptured lysosomes. Released vesicular structures are able to interact with other lysosomes. Thus, we described a new process that uses lysosomal tubulation to release vesicular structures from permeabilized lysosomes. LRRK2 orchestrates this process that we name LYTL (LYsosomal Tubulation/sorting driven by LRRK2) that, given the central role of the lysosome in PD, is likely to be disease relevant.
The Operating Performance of Firms Conducting Seasoned Equity Offerings: Evidence from the Nordics

This thesis focuses on the operating performance and the stock returns of companies conducting seasoned equity offerings (SEOs) in Sweden, Denmark, Norway and Finland between 2005 and 2015. Using a variety of operating performance measures, I find that the issuing companies consistently underperform their peers both before and after the issue. This is reflected on poor post-issue stock returns. An individual significant negative issuer effect is found on stock returns.
In-Situ Synthesis of Polymer–Clay Nanocomposites: Exfoliation of Organophilic Montmorillonite Nanolayers in Poly 2-ThiozylMethacrylamide

The aim of this work is the preparation and properties of poly 2-thiozyl methacrylamidevinylbenzyldimethyloctadecylammonium/montmorillonite (TMAAm-VBOA/MMT) nanocomposites. Firstly 2-thiozyl methacrylamide (TMAAm) monomer was synthesized by reacting 2-amino thiazole with methacryloyl chloride in the presence of triethylamine. Synthesis of nanocomposites were performed in three steps which are; purification and cation exchange capacity (CEC) determination of clay, preparation of organoclay and synthesis of nanocomposites. Nanocomposites with various amounts of TMAAm and VBOA/MMT were synthesized through in-situ and free radical polymerization using benzoyl peroxide as an initiator. Changes in the structure of the nanocomposites were examined through Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD) and scanning electron microscopy (SEM). Additionally, thermogravimetric analysis and BET analysis were conducted to investigate the thermal properties and particle size distribution of the nanocomposites. The results of X-ray and SEM analysis suggest that the exfoliated structure of the new nanocomposite materials. In addition, the thermal decomposition temperatures of nanocomposites were found to be higher than that of pure organoclay and poly(TMAAm) and thermally degradation rate decreased.
Incorporating Unstructured Free Play into Organized Sports

ABSTRACT PLAY IS AN ESSENTIAL ELEMENT OF POSITIVE YOUTH DEVELOPMENT. YOUTH SHOULD ENGAGE IN ALL 3 TYPES OF PLAY (UNSTRUCTURED, SEMISTRUCTURED, AND STRUCTURED) TO BEST PROMOTE PHYSICAL LITERACY, MOTOR SKILL PROFICIENCY AND MUSCLE STRENGTH, LONG-TERM ATHLETIC DEVELOPMENT, AND FUN. UNFORTUNATELY, HOWEVER, EMPHASIS IS TOO OFTEN PLACED ON STRUCTURED PLAY, SUCH AS PLAYING ON A SPORTS TEAM, POTENTIALLY AT THE EXPENSE OF MOTOR SKILL MASTERY. OVERUSE, INJURY, AND DROPPING OUT OF SPORTS ARE POSSIBLE CONSEQUENCES OF SPORTS SPECIALIZATION. THIS ARTICLE DESCRIBES HOW PLAY POSITIVELY INFLUENCES ATHLETICISM AND LIFETIME PARTICIPATION IN PHYSICAL ACTIVITY AND RECOMMENDS HOW TO BALANCE AND INTEGRATE FREE PLAY INTO SPORTS PRACTICE.
Scatter signatures in SFDI data enable breast surgical margin delineation via ensemble learning

Margin assessment in gross pathology is becoming feasible as various explanatory deep learning-powered methods are able to obtain models for macroscopic textural information, tissue microstructure, and local surface optical properties. Unfortunately, each different method seems to lack enough diagnostic power to perform an adequate classification on its own. This work proposes using several separately trained deep convolutional networks, and averaging their responses, in order to achieve a better margin assessment. Qualitative leave-one-out cross-validation results are discussed for a cohort of 70 samples.
Diabetes mellitus : economic and health burden, treatment and the therapeutical effects of Hypoxis hemerrocallidea plant

Diabetes mellitus (DM) is becoming one of the leading causes of death worldwide because of its adverse complications that include cardiovascular related diseases and chronic kidney disease. DM is considered a menace to public health due to the unavailability of adequate drugs to manage this condition, especially in poor developing countries such as those in the African continent. Proper management and treatment of this is lacking, which possibly explains escalating percentages of morbidity and mortality associated with it. In Africa, as a result of poor socio-economic conditions, it is nearly impossible to properly monitor and manage DM. Globally, the commercially available drugs used in diabetes treatment regimens have been associated with drastic side effects and are also mostly unaffordable in some developing countries (particularly in Africa), hence the need to investigate cheap and readily available medicinal plants such as Hypoxis hemerocallidea . It is important to thoroughly investigate the activities of medicinal plants in animal models to identify both their therapeutic and toxic effects. This review paper examines the potential anti-diabetic benefits of Hypoxis hemerocallidea based on experimental studies done on this plant between the years 2000 and 2016. The authors recommend that further studies on the different extracts of the plant be undertaken to discover the exact mechanisms of their action.
All the News That’s Fit to Click: The Economics of Clickbait Media

The news media industry has changed as the internet and social media have matured and become integral to modern life. I describe these changes through a theoretical analysis of the economic structure of the industry and explore the implications for scholars of online media and politics. The crux of my argument is that social media simultaneously serves as a distribution platform and reputation builder, as social recommendations take the place of expensive investments in high-quality journalism. This development rendered crucial portions of previous models of the market for news inaccurate due to the declining importance of firm reputation. This mechanism interacts with the massive heterogeneity in digital literacy and growing animosity toward the news media among conservatives to create “credibility cascades,” which I argue are a necessary condition for Fake News to flourish.
Nitric Oxide Consumption and Pulmonary Hypertension in Patients with Paroxysmal Nocturnal Hemoglobinuria.

Pulmonary hypertension (PHT) is an emerging common complication of hereditary hemolytic anemias. It has been mechanistically and epidemiologically linked to intravascular hemolysis and decreased nitric oxide (NO) bioavailability. While this complication has been described in approximately 30% of adult patients with sickle cell disease and thalassemia, the prevalence of PHT in patients with paroxysmal nocturnal hemoglobinuria (PNH), an acquired disease with the highest levels of intravascular hemolysis observed, has never been determined. PNH patients frequently have symptoms consistent with both hemolysis and PHT including severe fatigue and dyspnea on exertion. Therefore, we examined for the presence of PHT in PNH and explored potential mechanisms associated with its development by measuring the ability of plasma to instantaneously consume NO using ozone-based chemiluminescence. Doppler echocardiography was performed in 24 hemolytic PNH patients to estimate pulmonary artery systolic pressures. Systolic PHT was defined by a tricuspid regurgitant jet velocity (TRV) ≥ 2.5m/s at rest. Eleven (46%) patients had elevated pulmonary artery systolic pressures (mean TRV 2.7m/s ± 0.08) and one (4%) had severely elevated pressures (TRV 3.5m/s). Plasma from PNH patients (n=28) consumed 32.26 ± 8. 74μM NO while normal subjects (n=9) consumed 2.42 ± 0. 77μM NO (p=0.03). LDH levels correlated with NO consumption (p
Counselling and the kink community: a thematic analysis

ABSTRACT Limited research indicates that people from the kink community may not find talking therapies accessible. Findings are presented from a thematic analysis of five semi-structured interviews with adults who self-identify as kinky. Participants reported self-censorship as a risk-management strategy to avoid encountering (i) social stigma, (ii) medicalisation and (iii) conflation of true BDSM with abuse or self-harm. Interviewees required counsellors to be better informed, and for services to be more inclusive and proactive. They regarded the kink community as therapeutically minded, harbouring a population motivated and appropriately skilled to engage with counselling and psychotherapy. Findings recommend potential changes to counsellor training and service provision aiming to enable practitioners to work more effectively and ethically with sexually diverse clients.
ADMINISTRATION OF SYSTEMIC PROPOLIS VERSUS MOXIFLOXACIN AS ADJUNCTIVE TREATMENT OF SEVERE GENERALIZED PERIODONTITIS

To-date, emerging bacterial resistance to the commonly prescribed antibiotics in the management of periodontitis has become a challenging problem making scientists continually seek for new agents. In the present study, propolis (PRO) (natural bee glue) and moxifloxacin (MXF) (new quinolone antibiotic) were evaluated in the treatment of severe generalized periodontitis (gP) as adjuncts to scaling and root planing (SRP). Fifty four subjects with severe gP were randomly assigned into three groups (3 subjects did not complete the study after participation). Group I in which SRP alone was performed to gP patients (SRP group; n=17); group II in which SRP was done to gP patients combined with orally administered propolis 400 mg once daily for 7 days (PRO group; n=16); and group III in which SRP was performed to gP patients combined with oral moxifloxacin 400 mg once daily for 7 days (MXF group; n=18). Pocket depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), plaque (PI) and gingival (GI) indices were recorded at baseline, after 6 and 12 weeks of SRP. Salivary interleukin-1 beta (IL-1β) was evaluated at the same time points for all groups. All three procedures led to significant reductions in PD, CAL, BOP, PI and GI after 6 and 12 weeks. PD reduction and CAL gain were significantly greater in the PRO and MXF groups compared to SRP group at 6 and 12 weeks after therapy (p 0.05). Likewise, in PRO and MXF groups, the salivary inflammatory marker (IL-1β) was significantly reduced in comparison to SRP group (p < 0.01). In all groups, salivary IL-1β levels were decreased at 6 and 12 weeks compared to baseline values. It was concluded that the adjunctive use of PRO and MXF to SRP had significantly improved the treatment outcomes in subjects with severe gP comparable to SRP alone. Thus, PRO and MXF showed promising results in the treatment of periodontal disease. KEYWORDS Propolis, Moxifloxacin, Adjunctive treatment, Periodontitis.
Impact of a probiotic-based hospital sanitation on antimicrobial resistance and HAI-associated antimicrobial consumption and costs: a multicenter study

Purpose Antimicrobial resistance (AMR) is one of the major threats to human health, and the high frequency of resistant pathogens in the hospital environment can contribute to the transmission of difficult-to-treat health care-associated infections (HAIs). We recently reported that, compared with conventional chemical cleaning, the use of a microbial-based sanitation strategy (Probiotic Cleaning Hygiene System [PCHS]) was associated with remodulation of hospital microbiota and reduction of HAI incidence. Here, we aimed to analyze the impact of PCHS on AMR and related effects, such as HAI-associated antimicrobial drug consumption and costs. Patients and methods Five Italian hospitals, enrolled in a multicenter study where conventional sanitation methods were replaced with PCHS, were included in the analysis. The study period included a 6-month observation for each sanitation type. Surface microbiota AMR was analyzed using microarray, nested PCR, antibiogram, and microdilution tests. Drug consumption data and related costs were obtained from the medical records of all hospitalized patients affected by HAIs. Results PCHS use was associated with up to 99% decrease of the AMR genes harbored by surface hospital microbiota, independently of the resistance types originally present in each individual setting (Pc<0.01). Functional assays confirmed the molecular data, demonstrating a 33%–100% decrease of resistant strains depending on the antibiotic type. Antimicrobial drug consumption associated with HAI onset showed a global 60.3% decrease, with a 75.4% decrease of the associated costs. Conclusion The spread of AMR in the hospital environment can be limited by the use of sanitation methods to remodulate the hospital microbiota, leading to lower antimicrobial consumption and costs. This approach might be considered as part of broader infection prevention and control strategies.
Efficacy and safety of tacrolimus in induction therapy of patients with lupus nephritis

Background The purpose of this study was to detect the efficacy and safety of tacrolimus (TAC) in induction therapy of patients with lupus nephritis. Methods Associated studies were extracted from the PubMed and the Cochrane Library on July 10, 2018, and applicable investigations were pooled and analyzed by meta-analysis. Data on complete remission (CR), total remission (TR; complete plus partial remission), proteinuria levels, urine erythrocyte number, albumin, glomerular filtration rate, negative rate of ds-DNA, C3 levels, C4 levels, systemic lupus erythematosus disease activity index (SLE-DAI), etc, were extracted and pooled using RevMan 5.3. Results In the therapeutic regimen of TAC + glucocorticoids (GC) vs cyclophosphamide (CYC) + GC, the results indicated that the TAC group had high values of CR, TR, albumin, and negative rate of ds-DNA, and low values of proteinuria levels and SLE-DAI when compared with those in CYC group (all P<0.05). In the therapeutic regimen comprising TAC + GC vs mycophenolate mofetil (MMF) + GC, the results indicated that the difference of CR, TR, proteinuria levels, and albumin between TAC group and MMF group were not significant (all P>0.05). In the therapeutic regimen comprising TAC + MMF + GC vs CYC + GC, multitarget therapy group showed higher values of CR, TR, urinary protein decline, and rise of serum albumin when compared with CYC group (all P<0.05). Conclusion TAC is an effective and safe agent in induction therapy of patients with lupus nephritis.
Framing by the Flock: Collective Issue Definition and Advocacy Success

The framing of issues is part of the tool kit used by lobbyists in modern policy making, yet the ways in which framing works to affect lobbying success across issues remain underexplored. Analyzing a new dataset of lobbying in the news on 50 policy issues in five European countries, we demonstrate that it is not individual but collective framing that matters: Emphasis frames that enjoy collective backing from lobbying camps of like-minded advocates affect an advocate’s success, rather than frames being voiced by individual advocates. Crucially, it matters for advocacy success whether the advocate’s camp frames its policy goals on an issue in unity with “one voice” and whether the actor’s camp wins the contest of framing the issue vis-à-vis the opposing camp. Our results emphasize the need to consider the collective mechanisms behind the power of framing and have implications for future research on framing as an advocacy tool.
The Relative Power of Negativity: The Influence of Language Intensity on Perceived Strength

Negative utterances and words have been found to be stronger than positive utterances and words, but what happens if positive and negative utterances are intensified? Two online experiments were carried out in which participants judged the strength of (un)intensified positive and negative evaluations in written dialogues. Both studies showed intensified language was perceived as stronger than unmarked language (i.e., language that was not intensified), and negative evaluations were stronger than positive evaluations. What is more, intensification and polarity interact; the increment of perceived strength for intensified positive adjectives (Study 1) and purely intensified adverbs (really, very; Study 2) was bigger than the increment in perceived strength of intensified negative adjective and adverbs. When a meaningful intensifier (deliciously, disgustingly) was used, the negativity effect remained. The findings were discussed within cognitive frameworks such as relevance theory, theory of mind, and theory on verbal aggression.
Acid-responsive nanoparticles as a novel oxidative stress-inducing anticancer therapeutic agent for colon cancer

Objective Nanoparticles can efficiently carry and deliver anticancer agents to tumor sites. Mounting evidence indicates that many types of cancer cells, including colon cancer, have a weakly acidic microenvironment and increased levels of reactive oxygen species. The construction of nano drug delivery vehicles “activatable” in response to the tumor microenvironment is a new antitumor therapeutic strategy. Methods Cinnamaldehyde (CA) was designed to link directly with dextran to form a polymer through an acid cleavable acetal bond. Herein, a novel pH-sensitive drug delivery system was constructed with co-encapsulated 10-hydroxy camptothecin (HCPT). Dynamic light scattering (DLS) analysis, transmission electron microscopy (TEM) analysis, and release kinetics analysis of HCPT-CA-loaded nanoparticles (PCH) were conducted to investigate the physical and chemical properties. The cellular uptake signatures of the nanoparticles were observed by confocal microscopy and flow cytometry. Cell viability, cell scratch assay, apoptosis assay, and colony formation assay were performed to examine the potent antiproliferative and apoptotic effects of the PCH. The antitumor mechanism of the treatment with PCH was evaluated by Western blotting, flow cytometry, and TEM analysis. The pharmacokinetics of PCH were examined in healthy Sprague Dawley rats within 6 hours after sublingual vein injection. We lastly examined the biodistribution and the in vivo anticancer activity of PCH using the xenograft mouse models of HCT116 cells. Results Both HCPT and CA were quickly released by PCH in an acidic microenvironment. PCH not only induced cancer cell death through the generation of intracellular reactive oxygen species in vitro but also facilitated the drug uptake, effectively prolonged drug circulation, and increased accumulation of drug in tumor sites. More attractively, PCH exhibited excellent therapeutic performance and better in vivo systemic safety. Conclusion Overall, PCH not only utilized the tumor microenvironment to control drug release, improve drug pharmacokinetics, and passively target the drug to the tumor tissue, but also exerted a synergistic anticancer effect. The acid-responsive PCH has enormous potential as a novel anticancer therapeutic strategy.
Preparation of sustained release apremilast-loaded PLGA nanoparticles: in vitro characterization and in vivo pharmacokinetic study in rats

Background Apremilast (APM) is a novel, orally administered small molecule drug approved for treatment of psoriasis or psoriatic arthritis. Due to its low solubility and permeability, it is classified as a class IV drug according to BCS classification. Dose titration is recommended during APM treatment due to its tolerability and twice-daily dosing regimen issues. Materials and Methods In this study, three different APM-loaded PLGA nanoparticles (F1–F3) were prepared by single emulsion and evaporation method. Based on particle size, PDI, zeta potential (ZP), entrapment efficiency (%EE), drug loading (%DL), and spectral characterization, the nanoparticles (F3) were optimized. The F3 nanoparticles were further evaluated for in vitro release and in vivo pharmacokinetic studies in rats. Results The optimized nanoparticles (F3) had particles size 307.3±8.5 nm with a low PDI value 0.317, ZP of −43.4±2.6 mV, EE of 61.1±1.9% and DL of 1.9±0.1%. The in vitro release profile showed a sustained release pattern of F3 nanoparticles of APM. The pharmacokinetic results showed 2.25 times increase in bio-availability of F3 nanoparticles compared to normal APM suspension. Moreover, significant increase in half-life and mean residence time confirms long-term retention of F3 nanoparticles. Conclusion Bioavailability enhancement along-with long-term retention of the APM-loaded PLGA nanoparticles might be helpful for the once-daily regimen treatment.