Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative efficacy and safety between ablative therapies or surgery for small hepatocellular carcinoma: a network meta-analysis

ABSTRACT Background: Major treatments for small hepatocellular carcinoma (SHCC) include percutaneous ethanol injection (PEI), percutaneous acetic acid injection (PAI), radiofrequency ablation (RFA), or surgical resection (SR). We aimed to compare these therapies concerning with effectiveness and safety. Methods: Cochrane Library, PubMed, and Embase were searched for randomized controlled studies (RCTs) from inception to 30 April 2017. Odds ratios (OR) for proportion dead (PD), local recurrence (LR) and adverse events (AEs). Results: Fourteen RCTs were identified. Compared with SR, PEI (OR 2.79, CrI 1.25, 6.45, p < 0.01) provided a significantly increased risk of PD. Similarly, PEI (OR 4.29, CrI 1.18, 18.35, p < 0.01) yielded more LR than SR. Also, SR significantly conferred more AEs than RFA (OR 0.10; CrI 0.02, 0.35, p < 0.01), PEI (OR 0.06; CrI 0.01, 0.31, p < 0.01). Besides, RFA conferred the highest efficacy for survival, time to recurrence, and new development of HCC. Conclusions: SR was superior to PEI. Although SR achieved highest cumulative ranking probabilities in clinical efficacy, it obtained a low benefit-to-risk ratio for patients. RFA was superior to the other ablative therapies. For tumor sizes > 2 cm or ≤ 2 cm in diameter, SR conferred non-significant effects compared with other therapies for SHCC.
Effective Genomic Selection in a Narrow‐Genepool Crop with Low‐Density Markers: Asian Rapeseed as an Example

Efficiency in genomic selection is not particularly based on detailed genotype profiling facilitated by maximum marker density. Extensive genome‐wide linkage disequilibrium is a common characteristic of breeding pools in many crop species. Every quantitative trait locus across the genome can be captured by one or a few representative markers. Fewer representative markers selected in respect of linkage disequilibrium (LD) can capture the association between a genomic region and a phenotypic trait. Low‐density marker sets enable genomic prediction accuracies in breeding populations with strong LD comparable to those achieved with high‐density genotyping.
Hyperreflective Foci Number Correlates with Choroidal Neovascularization Activity in Angioid Streaks.

Purpose To assess the changes in hyperreflective foci (HF) by means of spectral-domain optical coherence tomography (SD-OCT) in patients undergoing anti-VEGF treatment for subfoveal choroidal neovascularization (CNV) secondary to angioid streaks (AS). Methods Fifteen eyes with diagnosis of AS-related CNV (8 males) and 15 control eyes with uncomplicated AS were consecutively recruited. Patients and controls underwent complete ophthalmologic examination and SD-OCT. Patients were subjected to a pro re nata treatment regimen, including monthly examinations and intravitreal aflibercept injection in case of fluid detection on SD-OCT. HF were measured on horizontal scans of the six-line radial SD-OCT, in the fovea and parafovea and the subdivided as retinal or choroidal. Specifically, HF were analyzed at the following time points: baseline, dry on SD-OCT, 1 month before its reactivation, and the time of CNV reactivation. Results HF numbers resulted higher in all CNV phases with respect to controls, except during inactive phase. Moreover, foveal and parafoveal HF were found significantly increased in active, prereactive, and reactive phases when compared with inactive phase (P < 0.05). A similar trend was detected for choroidal HF. Interestingly, a subanalysis revealed that only foveal choroidal HF are significantly higher in a prereactive phase if compared with an inactive phase (P = 0.03). Our correlational analysis unveiled negative associations between intraretinal HF numbers and logMAR best-corrected visual acuity. Conclusions Our findings suggest that HF represent useful markers to monitor CNV activity. Choroidal HF appear already increased in the fovea 1 month before CNV reactivation. Validation of our results might lead to earlier anti-VEGF reinjection and possibly better visual outcomes.
Toll‐like receptor 1, 2 and 6 polymorphisms: no association with 11 serum cytokine concentrations

Finnish newborns were vaccinated with Bacillus Callmette-Guerin (BCG) vaccine from 1940s until 2006. The diagnostics of severe complications after vaccination was centralised until 1988, and 222 children presented with BCG osteitis from 1960 to 1988 (1). Pattern-recognition receptors (PRR), such as toll-like receptors (TLR), recognise surface structures of pathogens and initiate inflammatory and immune responses in the host (2) Cytokines, such as tumor necrosis factor (TNF), interferons (IFN) and interleukins (IL) are important mediators in these responses. TLR1 and TLR6 work as co-receptors to TLR2, and the group is called the TLR2 subfamily (2). This article is protected by copyright. All rights reserved.
Optimal biopsy strategy for prostate cancer detection by performing a Bayesian network meta-analysis of randomized controlled trials

Objective: With the increasing recognition of the over-diagnosis and over-treatment of prostate cancer (PCa), the choice of a better prostate biopsy strategy had confused both the patients and clinical surgeons. Hence, this network meta-analysis was conducted to clarify this question. Methods: In the current network meta-analysis, twenty eligible randomized controlled trials (RCTs) with 4,571 participants were comprehensively identified through Pubmed, Embase and Web of Science databases up to July 2017. The pooled odds ratio (OR) with 95% credible interval (CrI) was calculated by Markov chain Monte Carlo methods. A Bayesian network meta-analysis was conducted by using R-3.4. 0 software with the help of package “gemtc” version 0.8. 2. Results: Six different PCa biopsy strategies and four clinical outcomes were ultimately analyzed in this study. Although, the efficacy of different PCa biopsy strategies by ORs with corresponding 95% CrIs had not yet reached statistical differences, the cumulative rank probability indicated that overall PCa detection rate from best to worst was FUS-GB plus TRUS-GB, FUS-GB, CEUS, MRI-GB, TRUS-GB and TPUS-GB. In terms of clinically significant PCa detection, CEUS, FUS-GB or FUS-GB plus TRUS-GB had a higher, whereas TRUS-GB or TPUS-GB had a relatively lower significant detection rate. Meanwhile, TPUS-GB or TRUS-GB had a higher insignificant PCa detection rate. As for TRUS-guided biopsy, the general trend was that the more biopsy cores, the higher overall PCa detection rate. As for targeted biopsy, it could yield a comparable or even a better effect with fewer cores, compared with traditional random biopsy. Conclusion: Taken together, in a comprehensive consideration of four clinical outcomes, our outcomes shed light on that FUS-GB or FUS-GB plus TRUS-GB showed their superiority, compared with other puncture methods in the detection of PCa. Moreover, TPUS or TRUS-GB was more easily associated with the over-diagnosis and over-treatment of PCa. In addition, targeted biopsy was obviously more effective than traditional random biopsy. The subsequent RCTs with larger sample sizes were required to validate our findings.
Use of rheumatology-specific patient navigators to understand and reduce barriers to medication adherence: Analysis of qualitative findings

Objective Adherence to medications among patients with rheumatic diseases is often suboptimal. Patient navigators, individuals trained in care coordination, motivational interviewing and basic rheumatology and pharmacology, have not been employed to explore and address this issue. We piloted a single-site, single arm intervention to determine the feasibility and acceptability of using rheumatology-specific navigators to understand and reduce barriers to adherence to oral disease modifying anti-rheumatic drugs (DMARDs). We analyzed our qualitative findings from navigator-patient interactions as well as patient satisfaction with the intervention. Methods We recruited patients ≥18 years with a systemic rheumatic disease who initiated an oral DMARD within the prior 6 months. Navigators conducted baseline needs assessments and 2–4 week follow-up calls to understand and address issues related to medication adherence. We analyzed patient-navigator encounters qualitatively using content analysis to identify key themes related to barriers to adherence and navigator actions performed in response to the barriers described. We also categorized intentional and unintentional nonadherent behavior and assessed satisfaction with the navigator experience (range 0–5, 5 = most satisfied). Results 107 rheumatology patients were followed for up to 6 months. Mean patient age was 55 years (+17) and 93% were female; 36% described one or more episode of intentional or unintentional nonadherence. The three most common themes identified as barriers to adherence were fear of adverse events (raised by 54%), concerns about medication effectiveness (43%), and challenges with medication acquisition (32%). 86% of participants described at least one adherence-related barrier. Frequent navigator actions included facilitation of patient-doctor communication (38%), medication and diagnosis education (27%), and development of individualized strategies to improve adherence (16%). Patients were satisfied with the navigator experience (mean 4.4 + 0.9). Conclusion Navigators uncovered and addressed a number of medication adherence-related concerns and patients were satisfied with the services provided.
Stabilization benefits of single and multi-layer self-nanoemulsifying pellets: A poorly-water soluble model drug with hydrolytic susceptibility

Solidified self-nanoemulsifying drug delivery systems (SNEDDS) offer strong option to enhance both drug aqueous solubility and stability. The current study was designed to evaluate the potential stabilization benefits of solidifying cinnarizine (CN) liquid SNEDDS into single and multi-layer self-nanoemulsifying pellets (SL-SNEP and ML-SNEP, respectively). The selected formulations were enrolled into accelerated, intermediate and long-term stability studies. The chemical stability was assessed based on the % of intact CN remaining in formulation. The physical stability was assessed by monitoring the in-vitro dissolution and physical appearance of the formulations. The degradation pathway of CN within lipid-based formulation was proposed to involve a hydroxylation reaction of CN molecule. The chemical stability study revealed significant CN degradation in liquid SNEDDS, SL-SNEP and ML-SNEP (lacking moisture-sealing) within all the storage conditions. In contrast, the moisture sealed ML-SNEP showed significant enhancement of CN chemical stability within the formulation. In particular, ML-SNEP coated with Kollicoat Smartseal 30D showed superior CN stabilization and no significant decrease in dissolution efficiency, at all the storage conditions. The observed stability enhancement is owing to the complete isolation between CN and SNEDDS layer as well as the effective moisture protection provided by Kollicoat Smartseal 30D. Hence, the degradation problem could be eradicated completely. The incorporation of silicon dioxide had an important role in the inhibition of pellet agglomeration upon storage. Accordingly, ML-SNEP coated with Kollicoat Smartseal 30D and/or silicon dioxide could be an excellent dosage form that combine dual enhancement of CN solubilization and stabilization.
Structure of monomeric full-length ARC sheds light on molecular flexibility, protein interactions, and functional modalities

The activity-regulated cytoskeleton-associated protein (ARC) is critical for long-term synaptic plasticity and memory formation. Acting as a protein interaction hub, ARC regulates diverse signalling events in postsynaptic neurons. A protein interaction site is present in the ARC C-terminal domain (CTD), a bilobar structure homologous to the retroviral Gag capsid domain. However, knowledge of the 3-dimensional structure of full-length ARC is required to elucidate its molecular function. We purified recombinant monomeric full-length ARC and analyzed its structure using small-angle X-ray scattering and synchrotron radiation circular dichroism spectroscopy. In solution, monomeric ARC has a compact, closed structure, in which the oppositely charged N-terminal domain (NTD) and CTD are juxtaposed, and the flexible linker between them is not extended. The modelled structure of ARC is supported by intramolecular live-cell FRET imaging in rat hippocampal slices. Peptides from several postsynaptic proteins, including stargazin, bind to the N-lobe, but not to the C-lobe, of the bilobar CTD. This interaction does not induce large-scale conformational changes in the CTD or flanking unfolded regions. The ARC NTD contains long helices, predicted to form an anti-parallel coiled coil; binding of ARC to phospholipid membranes requires the NTD. Our data support a role for the ARC NTD in oligomerization as well as lipid membrane binding. These findings have important implications for the structural organization of ARC in distinct functional modalities, such as postsynaptic signal transduction and virus-like capsid formation.
Trait-Based Profiles of ADHD in Adolescents and Young Adults

Empirical work has examined the utility of using person-centered statistical approaches emphasizing traits to parsing attention deficit/hyperactivity disorder (ADHD) heterogeneity in preschool and school-age children. However, trait-based profiles have not yet been examined in other age ranges, specifically adolescence and young adulthood. Therefore, the goal of the present study is to examine trait-based profiles in adolescents and young adults with ADHD to evaluate their similarity with trait-based profiles in preschoolers and children with ADHD and through comparison with external correlates (e.g., comorbidity). One hundred eighty-two adolescents and 287 young adults completed measures of ADHD symptoms, personality and temperament traits, and comorbid internalizing and externalizing problems. Latent profile analysis suggested at least 3 consistent trait-based profiles related to ADHD within adolescents and young adults: low extraversion, high extraversion, and high neuroticism. These profiles were largely similar to those found in preschool and middle childhood and demonstrated similar comorbidity patterns, namely, the low-extraversion profile exhibited higher internalizing problems, the high-extraversion profile exhibited higher externalizing problems, and the small high-neuroticism profile exhibited descriptively higher levels of all comorbid problems. Such profiles may have utility for personalization of intervention based on trait profiles and comorbidity patterns, as well as—more speculatively—possible prognostic utility.
The Effect of Transient Location on the Resolution of Bistable Visual and Audiovisual Motion Sequences

We examined the attention and inference accounts of audiovisual perception using the stream/bounce display, a visual stimulus wherein two identical objects move toward each other, completely superimpose, then move apart. This display has two candidate percepts: stream past each other or bounce off each other. Presented without additional visual or auditory transients, the motion sequence tends to yield the streaming percept, but when coupled with a tone or flash at the point of coincidence, the response bias flips toward bouncing. We explored two competing accounts of this effect: the attentional hypothesis and the inference hypothesis. Participants watched a series of motion sequences where a transient, when present, occurred at the moment of coincidence either colocalised with the motion sequence (congruent presentation) or on the opposite side of the display (incongruent presentation). Assuming the spotlight or zoom lens metaphor, an attentional account predicts that incongruent presentations should be associated with a higher percentage of bouncing responses than congruent presentations, while the inferential account predicts the opposite effect. No effect was found for tone-only trials. However, in trials containing a visual transient, results showed higher proportions of bounce responses within congruent over incongruent presentations, favouring the inference hypothesis over a spotlight or zoom lens attentional account.
Correlation between biomarkers of creatine metabolism and serum indicators of peripheral muscle fatigue during exhaustive exercise in active men

ABSTRACT Exhaustive exercise induces various disturbances of homeostasis, with impaired bioenergetics often associated with strenuous muscular work. However, no study so far validated serum biomarkers of creatine metabolism vs. traditional markers of exhaustive exercise and fatigue. Here, we investigated how well changes in serum guanidinoacetic acid (GAA), creatine and creatinine correlate with responses in blood lactate, creatine kinase, interleukin-6 and cortisol in 11 young active men (age 23.2 ± 3.7 years; VO2max 49.5 ± 5.4 ml/kg/min) exposed to exhaustive exercise. All participants were subjected to running at individual running speed at anaerobic threshold until exhaustion, with venous blood drawn at baseline and during an exercise session at 5-min intervals. Running-to-exhaustion markedly affected serum GAA and creatine levels, with circulating GAA increased for 5.3 ± 8.5%(95% CI, −0.4 to 11.0), and serum creatine elevated by 33.9 ± 21.8% (95% CI, 19.3 to 48.6) compared to baseline levels (P ≤ 0.05). In addition, moderate-to-strong positive linear correlations were found between exhaustive exercise-induced changes in serum cortisol and GAA levels (r = 0.79; P = 0.03), and cortisol and creatine concentrations (r = 0.81; P = 0.03). This suggests a link between cortisol and heavy exercise-induced impaired bioenergetics, with future studies needed to evaluate a cause-and-effect interconnection between cortisol and GAA-creatine axis.
Drivers of women’s sanitation practices in informal settlements in sub-Saharan Africa: a qualitative study in Mathare Valley, Kenya

ABSTRACT Despite evidence suggesting women are disproportionately affected by the lack of adequate and safe sanitation facilities around the world, there is limited information about the factors that influence women’s ability to access and utilize sanitation, especially in sub-Saharan Africa. The purpose of this study was to explore factors influencing women’s sanitation practices in informal settlements in Nairobi, Kenya. Information from 55 in-depth interviews conducted in 2016 with 55 women in Mathare Valley Informal Settlement in Nairobi was used to carry out cross-case, thematic analysis of women’s common sanitation routines. Women identified neighborhood disorganization, fear of victimization, lack of privacy, and cleanliness/dirtiness of facilities as important factors in the choices they make about their sanitation practices. This suggests that future sanitation-related interventions and policies may need to consider strategies that focus not only on toilet provision or adoption but also on issues of space and community dynamics.
Improvement of bone microarchitecture in methylprednisolone induced rat model of osteoporosis by using thiolated chitosan-based risedronate mucoadhesive film

Abstract Objective: In this study, we investigated the potential of thiolated chitosan-based mucoadhesive film, loaded with risedronate sodium in the treatment of osteoporosis. Significance: Risedronate sodium is a bisphosphonate derivative having very low bioavailability when administered through the oral route. Moreover, the adverse effects associated with the drug when administered through GIT necessitate an alternative and feasible route which can improve its bioavailability and therapeutic efficacy. Methods: Thiolation of chitosan was interpreted by different analytical techniques. The mucoadhesive films were prepared by the solvent evaporation method and evaluated for drug content analysis, swelling degree, mucoadhesive parameters, and permeation characterization. For the screening of preclinical efficacy and pharmacodynamic parameters, a methylprednisolone induced osteoporotic rat model was used. The trabecular microarchitecture and biochemical markers were evaluated for determination of bone resorption. Results: The different analytical characterization of synthesized thiolated chitosan revealed that chitosan was successfully incorporated with thiol groups. The formulation containing 2:1 ratio of thiolated chitosan and HPMC-4KM was found to have the maximum swelling degree, mucoadhesive strength with a good force of adhesion and better in vitro permeability compared to the marketed formulation. With respect to trabecular microarchitecture, the drug-loaded film formulation showed superior and promising results. Furthermore, the film formulation also improved the serum level of biomarkers better than the marketed formulation. Conclusions: The results significantly suggest that risedronate loaded novel mucoadhesive film formulation could be a logical approach in the therapeutic intervention of osteoporosis.
Association of Transforming Growth Factor &bgr; Polymorphism C−509T With Radiation-Induced Fibrosis Among Patients With Early-Stage Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial

Importance Whether genetic factors can identify patients at risk for radiation-induced fibrosis remains unconfirmed. Objective To assess the association between the C−509T variant allele in the promoter region of TGFB1 and breast fibrosis 3 years after radiotherapy. Design, Setting, and Participants This is an a priori–specified, prospective, cohort study nested in an open-label, randomized clinical trial, which was conducted in community-based and academic cancer centers to compare hypofractionated whole-breast irradiation (WBI) (42.56 Gy in 16 fractions) with conventionally fractionated WBI (50 Gy in 25 fractions) after breast-conserving surgery. In total, 287 women 40 years or older with pathologically confirmed stage 0 to IIA breast cancer treated with breast-conserving surgery were enrolled from February 2011 to February 2014. Patients were observed for a minimum of 3 years. Outcomes were compared using the 1-sided Fisher exact test and multivariable logistic regression. Exposures A C-to-T single-nucleotide polymorphism at position −509 relative to the first major transcription start site (C−509T) of the TGFB1 gene. Main Outcomes and Measures The primary outcome was grade 2 or higher breast fibrosis as assessed using the Late Effects Normal Tissue/Subjective, Objective, Medical Management, Analytic scale (range, 0 to 3) three years after radiotherapy. Results Among 287 women enrolled in the trial, TGFB1 genotype and 3-year radiotherapy-induced toxicity data were available for 174 patients, of whom 89 patients (51%) with a mean (SD) age of 60 (8) years had at least 1 copy of C−509T. Grade 2 or higher breast fibrosis was present in 12 of 87 patients with C−509T (13.8%) compared with 3 of 80 patients without the allele variant (3.8%) (absolute difference, 10.0%; 95% CI, 1.7%-18.4%; P = .02). The results of multivariable analyses indicated that only C−509T (odds ratio, 4.47; 95% CI, 1.25-15.99; P = .02) and postoperative cosmetic outcome (odds ratio, 7.09; 95% CI, 2.41-20.90; P < .001) were significantly associated with breast fibrosis risk. Conclusions and Relevance To date, this study seems to be the first prospective validation of a genomic marker for radiation fibrosis. The C−509T allele in TGFB1 is a key determinant of breast fibrosis risk. Assessing TGFB1 genotype may facilitate a more personalized approach to locoregional treatment decisions in breast cancer. Trial Registration ClinicalTrials.gov identifier: NCT01266642