Miracle-dz/UniFAR-FTUs huggingface dataset:
Divisive influence of interleukin-1 receptor antagonist polymorphisms in melanoma patients.

OBJECTIVE The interleukin-1 receptor antagonist (IL-1RA) contributes to tumor survival and progression in multiple cancer entities. IL-1RA polymorphisms influence IL-1RA expression patterns and function. A known polymorphism was correlated with clinical outcomes in melanoma patients with particularly aggressive disease. METHODS DNA of 343 controls and 97 melanoma patients with poor prognostic indicators (time from diagnosis to death, nodal status, metastasis) was analyzed for a variable number of tandem repeat polymorphisms (VNTR) of the IL-1RA gene. Five alleles containing two (allele 2), three (allele 4), four (allele 1), five (allele 3) or six (allele 5) 86-bp repeats were targeted via PCR amplification. RESULTS Genotype 1/2 is less common in the melanoma patient group vs. the control (28.8% vs. 39.6%; p = 0.06). Significant was the stage of the melanoma in order to predict the survivability (p = 0.008). The 1/1 and 1/2 genotype appeared to have lower hazards ratios than the 2/2 genotype (p > 0.05). CONCLUSIONS Compared to the general population, the distribution of alleles coding for IL-1RA is different in melanoma patients. This alteration and the potential impact on tumor protein function and systemic inflammatory response may warrant further investigation.
Long-Term Outcomes of Untreated Buccal Gingival Recessions: A Systematic Review and Meta-Analysis.

BACKGROUND This review aims to: 1) assess the long-term outcomes of untreated buccal gingival recession (GR) defects and the associated reported esthetic and functional alterations; and 2) evaluate which factors influence the progression/worsening of dental and periodontal tissue conditions of untreated GR defects. METHODS Interventional and observational studies with duration of ≥24 months reporting outcomes from adult patients with localized or multiple GR defects not treated by root coverage or gingival augmentation procedures were considered eligible for inclusion. MEDLINE and EMBASE databases were searched for articles published through July 2015. Random-effects meta-analyses were performed comparing baseline versus most recent follow-up outcomes (i.e., number of patients with ≥1 GR and number of sites with GR). RESULTS Of 378 potentially eligible articles, eight (reporting six studies) met inclusion criteria. Of 1,647 GR defects with baseline and follow-up information, 78.1% experienced GR depth increase during the follow-up period, whereas the remaining experienced decrease or no change. Moreover, there was a 79.3% increase in the number of GR defects among the patients followed (i.e., new GR defects). Pooled estimates (data from four studies) showed significantly increased odds of recession development long term, regarding either number of patients (odds ratio 2.43; P = 0.03) or number of sites with GR (odds ratio 2.16; P = 0.0005). CONCLUSION Untreated recession defects in individuals with good oral hygiene have a high probability of progressing during long-term follow-up.
Sinusoidal voltage protocols for rapid characterisation of ion channel kinetics

Ion current kinetics are commonly represented by current–voltage relationships, time constant–voltage relationships and subsequently mathematical models fitted to these. These experiments take substantial time, which means they are rarely performed in the same cell. Rather than traditional square‐wave voltage clamps, we fitted a model to the current evoked by a novel sum‐of‐sinusoids voltage clamp that was only 8 s long. Short protocols that can be performed multiple times within a single cell will offer many new opportunities to measure how ion current kinetics are affected by changing conditions. The new model predicts the current under traditional square‐wave protocols well, with better predictions of underlying currents than literature models. The current under a novel physiologically relevant series of action potential clamps is predicted extremely well. The short sinusoidal protocols allow a model to be fully fitted to individual cells, allowing us to examine cell–cell variability in current kinetics for the first time.
The free fatty acid receptor 1 promotes airway smooth muscle cell proliferation through MEK/ERK and PI3K/Akt signaling pathways.

Obesity is a risk factor for asthma and influences airway hyperresponsiveness, which is in part modulated by airway smooth muscle proliferative remodeling. Plasma free fatty acids (FFAs) levels are elevated in obese individuals, and long-chain FFAs act as endogenous ligands for the free fatty acid receptor 1 (FFAR1), which couples to both Gq and Gi proteins. We examined whether stimulation of FFAR1 induces airway smooth muscle cell proliferation through classical MEK/ERK and/or phosphoinositide 3-kinase (PI3K)/Akt signaling pathways. The long-chain FFAs (oleic acid and linoleic acid) and a FFAR1 agonist (GW9508) induced human airway smooth muscle (HASM) cell proliferation, which was inhibited by the MEK inhibitor U0126 and the PI3K inhibitor LY294002 . The long-chain FFAs and GW9508 increased phosphorylation of ERK, Akt, and p70S6K in HASM cells and freshly isolated rat airway smooth muscle. Downregulation of FFAR1 in HASM cells by siRNA significantly attenuated oleic acid-induced phosphorylation of ERK and Akt. Oleic acid-induced ERK phosphorylation was blocked by either the Gαi-protein inhibitor pertussis toxin or U0126 and was partially inhibited by either the Gαq-specific inhibitor YM-254890 or the Gβγ signaling inhibitor gallein. Oleic acid significantly inhibited forskolin-stimulated cAMP activity, which was attenuated by pertussis toxin. Akt phosphorylation was inhibited by pertussis toxin, the ras inhibitor manumycin A, the Src inhibitor PP1, or LY294002 . Phosphorylation of p70S6K by oleic acid or GW9508 was significantly inhibited by LY294002 , U0126, and the mammalian target of rapamycin (mTOR) inhibitor rapamycin. In conclusion, the FFAR1 promoted airway smooth muscle cell proliferation and p70S6K phosphorylation through MEK/ERK and PI3K/Akt signaling pathways.
Mechanism and Implications of the Tricuspid Regurgitation: From the Pathophysiology to the Current and Future Therapeutic Options

The tricuspid valve was virtually ignored for a long time in the past. However, significant tricuspid regurgitation (TR) often accompanies left-side heart valve pathology and does not always reverse with its correction. If left untreated, TR can progress and result in progressive right ventricular failure. Current guideline recommendations still hold minor differences. Nevertheless, there is a consensus to operate on patients with severe TR undergoing left-sided valve surgery (class I) or those with mild to moderate TR with a dilated annulus (≥40 or ≥21 mm2, Class IIa). However, in case of the primary TR, surgical options is limited by a relatively high risk of mortality and morbidity. For these patients, new percutaneous approaches are becoming available but no long-term data are still available. In this review, we provide a comprehensive overview of the epidemiological and pathophysiological aspects of TR, and the current and future directions of therapy.
Reanalysis of Korean War Anthropological Records to Support the Resolution of Cold Cases

Re‐investigation of previously unidentified remains from the Korean War has yielded 55 new identifications, each with corresponding records of prior anthropological analyses. This study compares biological assessments for age at death, stature, and ancestry across (i) anthropological analyses from the 1950s, (ii) recent anthropological analyses of those same sets of remains, and (iii) the reported antemortem biological information for the identified individual. A comparison of long bone measurements from both the 1950s and during reanalysis is also presented. These comparisons demonstrate commonalities and continuing patterns of errors that are useful in refining both research on Korean War cold case records and forensic anthropological analyses performed using methods developed from the 1950s identifications.
Regular consumption of Lactobacillus reuteri‐containing lozenges reduces pregnancy gingivitis: an RCT

Abstract Aim This randomized controlled trial assessed the impact of Lactobacillus reuteri on pregnancy gingivitis in healthy women. Materials and Methods Forty‐five healthy women (24 test/21 placebo) with pregnancy gingivitis in the third trimester of pregnancy were enrolled. At baseline Gingival Index (GI) and Plaque Index (PlI) were assessed at the Ramfjord teeth and venous blood taken for TNF‐α analysis. Subsequently participants were randomly provided with lozenges to be consumed 2 × daily until birth (approx. 7 weeks) containing ≥108 CFU L. reuteri ATCC PTA 5289 and ≥108 CFU L. reuteri DSM 17938 (test) or being devoid of L. reuteri (placebo). Within 2 days after birth recording of GI, PlI and blood sampling were repeated. Results At baseline, mean GI and mean PlI did not differ significantly between both groups. In the test group mean TNF‐α serum level was significantly (p < 0.02) lower than in the placebo group. At reevaluation, mean GI and mean PlI of the test group were both significantly (p < 0.0001) lower than in the placebo group. Mean TNF‐α serum level did no longer differ significantly between the groups. Conclusions The consumption of L. reuteri lozenges may be a useful adjunct in the control of pregnancy gingivitis.
Evaluation of Project P.A.T.H.S. (Secondary 1 Program) by the Program Implementers: Findings Based on the Full Implementation Phase

A total of 207 schools (N = 35,735 students) participated in the Secondary 1 Program of Project P.A. T.H. S. in the full implementation phase (2006/07 school year). After completion of the Tier 1 Program, 1,250 instructors completed a subjective outcome evaluation form (Form B) to assess their views of the program, instructors, and perceived effectiveness of the program. Utilizing the consolidated reports submitted to the funding body, the research team aggregated the consolidated data to form an overall profile of the perceptions of the program participants. Results showed that high proportions of the respondents had positive perceptions of the program and the instructors, and roughly four-fifths of the respondents regarded the program as helpful to the program participants and the workers. These findings complement the subjective outcome evaluation findings based on the perspective of the program participants.
Periodontal conditions among employed adults in Spain.

AIM To assess the prevalence and severity of periodontal conditions among a representative sample of employed adults in Spain. MATERIAL AND METHODS A national cross-sectional study was conducted during 2008-2011. Periodontal status of 5130 workers, stratified by gender, age and occupation, was assessed based on Community Periodontal Index (CPI) and Clinical Attachment Level (CAL), following the WHO criteria. RESULTS The percentage of subjects with periodontal pockets (CPI codes 3-4) was 38.4%, [95% Confidence Interval (CI): 36.4-40.5] increasing significantly in subjects ≥45 years; 13.7% (95% CI: 12.8-14.7) of workers showed CAL 4-5 mm, while 7.7% (95% CI: 7.0-8.5) showed CAL ≥6 mm, again increasing significantly in the population ≥45 years. Prevalence of worse periodontal conditions was significantly higher in male workers, in subjects with primary school education and lower income, and in smokers and former smokers. The periodontal condition in young adults (35-44 years) was worse in comparison with those previously reported in Spanish national surveys. CONCLUSION Prevalence of destructive periodontal diseases was age-, gender-, education-, income- and tobacco smoking-related. Young adults showed worse periodontal conditions than has been previously reported in national surveys in Spain. It is suggested to include oral evaluation and preventive strategies in work-related medical check-ups.
Complete Nucleotide Sequences of Two VIM-1-Encoding Plasmids from Klebsiella pneumoniae and Leclercia adecarboxylata Isolates of Czech Origin

ABSTRACT Two multidrug resistance (MDR) plasmids, carrying the VIM-1-encoding integron In110, were characterized. Plasmid pLec-476cz (311,758 bp), from a Leclercia adecarboxylata isolate, consisted of an IncHI1 backbone, a MDR region, and two accessory elements. Plasmid pKpn-431cz (142,876 bp), from a sequence type 323 (ST323) Klebsiella pneumoniae isolate, comprised IncFIIY-derived and pKPN3-like sequences and a mosaic region. A 40,400-bp sequence of pKpn-431cz was identical to the MDR region of pLec-476cz, indicating the en bloc acquisition of the VIM-1-encoding region from one plasmid by the other.
Long‐Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia

Background Imatinib, a selective BCR‐ABL1 kinase inhibitor, improved the prognosis for patients with chronic myeloid leukemia (CML). We conducted efficacy and safety analyses on the basis of more than 10 years of follow‐up in patients with CML who were treated with imatinib as initial therapy. Methods In this open‐label, multicenter trial with crossover design, we randomly assigned patients with newly diagnosed CML in the chronic phase to receive either imatinib or interferon alfa plus cytarabine. Long‐term analyses included overall survival, response to treatment, and serious adverse events. Results The median follow‐up was 10.9 years. Given the high rate of crossover among patients who had been randomly assigned to receive interferon alfa plus cytarabine (65.6%) and the short duration of therapy before crossover in these patients (median, 0.8 years), the current analyses focused on patients who had been randomly assigned to receive imatinib. Among the patients in the imatinib group, the estimated overall survival rate at 10 years was 83.3%. Approximately half the patients (48.3%) who had been randomly assigned to imatinib completed study treatment with imatinib, and 82.8% had a complete cytogenetic response. Serious adverse events that were considered by the investigators to be related to imatinib were uncommon and most frequently occurred during the first year of treatment. Conclusions Almost 11 years of follow‐up showed that the efficacy of imatinib persisted over time and that long‐term administration of imatinib was not associated with unacceptable cumulative or late toxic effects. (Funded by Novartis Pharmaceuticals; IRIS ClinicalTrials.gov numbers, NCT00006343 and NCT00333840.)
Relationships between socioeconomic position and objectively measured sedentary behaviour in older adults in three prospective cohorts

Objectives To investigate whether sedentary behaviour in older adults is associated with a systematic and comprehensive range of socioeconomic position (SEP) measures across the life course. SEP measures included prospective measures of social class, income, educational qualifications and parental social class and contemporaneous measures of area deprivation. Setting Glasgow and the surrounding (West of Scotland) combined with Edinburgh and the surrounding area (the Lothians). Participants Community-dwelling adults aged around 79, 83, and 64 years from, respectively, the Lothian Birth Cohort 1936 (LBC1936) (n=271) and the 1930s (n=119) and 1950s (n=310) cohorts of the West of Scotland Twenty-07 study. Primary outcome measure Sedentary behaviour was measured objectively using an activPAL activity monitor worn continuously for 7 days and used to calculate percentage of waking time spent sedentary. Results Among retired participants, for most cohort and SEP combinations, greater social disadvantage was associated with increased sedentary time. For example, in the Twenty-07 1930s cohort, those most deprived on the Carstairs measure spent 6.5% (95% CI 0.3 to 12.7) more of their waking time sedentary than the least deprived. However, for employed people, the relationship between SEP and sedentary behaviour was much weaker. For example, in terms of social class differences, among the retired, the most disadvantaged spent 5.7% more waking time sedentary (95% CI 2.6% to 87%), whereas among the employed, there was effectively no difference (−0.5%; 95% CI −9.0 to 8.0). Conclusions Diverse SEP measures were associated with increased sedentary behaviour among retired people. There was little evidence for a relationship between SEP measures and sedentary behaviour among employed older adults. Prior to retirement, the constraints of the workplace may be masking effects that are only apparent at weekends.
What Does Music Sound Like for a Cochlear Implant User?

OBJECTIVE Cochlear implant research and product development over the past 40 years have been heavily focused on speech comprehension with little emphasis on music listening and enjoyment. The relatively little understanding of how music sounds in a cochlear implant user stands in stark contrast to the overall degree of importance the public places on music and quality of life. The purpose of this article is to describe what music sounds like to cochlear implant users, using a combination of existing research studies and listener descriptions. We examined the published literature on music perception in cochlear implant users, particularly postlingual cochlear implant users, with an emphasis on the primary elements of music and recorded music. Additionally, we administered an informal survey to cochlear implant users to gather first-hand descriptions of music listening experience and satisfaction from the cochlear implant population. CONCLUSION Limitations in cochlear implant technology lead to a music listening experience that is significantly distorted compared with that of normal hearing listeners. On the basis of many studies and sources, we describe how music is frequently perceived as out-of-tune, dissonant, indistinct, emotionless, and weak in bass frequencies, especially for postlingual cochlear implant users-which may in part explain why music enjoyment and participation levels are lower after implantation. Additionally, cochlear implant users report difficulty in specific musical contexts based on factors including but not limited to genre, presence of lyrics, timbres (woodwinds, brass, instrument families), and complexity of the perceived music. Future research and cochlear implant development should target these areas as parameters for improvement in cochlear implant-mediated music perception.
Individual calibration of accelerometers in children and their health-related implications

ABSTRACT This study compared children’s physical activity (PA) levels, the prevalence of children meeting current guidelines of ≥60 minutes of daily moderate to vigorous PA (MVPA), and PA-health associations using individually calibrated (IC) and empirical accelerometer cutpoints. Data from 75 (n = 32 boys) 10–12 year old children were included in this study. Clustered cardiometabolic (CM) risk, directly measured cardiorespiratory fitness (CRF), anthropometric and 7 day accelerometer data were included within analysis. PA data were classified using Froude anchored IC, Evenson et al. (Evenson, K. R., Catellier, D. J., Gill, K., Ondrak, K. S., & McMurray, R. G. (2008). Calibration of two objective measures of physical activity for children. Journal of Sports Sciences, 26(14), 1557–1565. doi:10.1080/02640410802334196) (Ev) and Mackintosh et al. (Mackintosh, K. A., Fairclough, S. J., Stratton, G., & Ridgers, N. D. (2012). A calibration protocol for population-specific accelerometer cutpoints in children. PLoS One, 7(5), e36919. doi:10.1371/journal.pone. 0036919) (Mack) cutpoints. The proportion of the cohort meeting ≥60mins MVPA/day ranged from 37%-56% depending on the cutpoints used. Reported PA differed significantly across the cutpoint sets. IC LPA and MPA were predictors of CRF (LPA: standardised β = 0.32, p = 0.002, MPA: standardised β = 0.27 p = 0.013). IC MPA also predicted BMI Z-score (standardised β = −0.35, p = 0.004). Ev VPA was a predictor of BMI Z-score (standardised β = −0.33, p = 0.012). Cutpoint choice has a substantial impact on reported PA levels though no significant associations with CM risk were observed. Froude IC cutpoints represent a promising approach towards classifying children’s PA data.
Static dielectric constant of water within a bilayer using recent water models: a molecular dynamics study

The water confined within a surfactant bilayer is studied using different water models via molecular dynamics simulations. We considered four representative rigid models of water: the SPC/E and the TIP4P/2005, which are commonly used in numerical calculations and the more recent TIP4Q and SPC/ε models, developed to reproduce the dielectric behaviour of pure water. The static dielectric constant of the confined water was analyzed as a function of the temperature for the four models. In all cases it decreases as the temperature increases. Additionally, the static dielectric constant of the bilayer-water system was estimated through its expression in terms of the fluctuations in the total dipole moment, usually applied for isotropic systems. The estimated dielectric was compared with the available experimental data. We found that the TIP4Q and the SPC/ε produce closer values to the experimental data than the other models, particularly at room temperature. It was found that the probability of finding the sodium ion close to the head of the surfactant decreases as the temperature increases, thus the head of the surfactant is more exposed to the interaction with water when the temperature is higher.
Two adjacent inversions maintain genomic differentiation between migratory and stationary ecotypes of Atlantic cod.

Atlantic cod is composed of multiple migratory and stationary populations widely distributed in the North Atlantic Ocean. The Northeast Arctic cod (NEAC) population in the Barents Sea undertakes annual spawning migrations to the northern Norwegian coast. Although spawning occurs sympatrically with the stationary Norwegian coastal cod (NCC), phenotypic and genetic differences between NEAC and NCC are maintained. In this study, we resolve the enigma by revealing the mechanisms underlying these differences. Extended linkage disequilibrium (LD) and population divergence were demonstrated in a 17.4-Mb region on linkage group 1 (LG1) based on genotypes of 494 SNPs from 192 parents of farmed families of NEAC, NCC or NEACxNCC crosses. Linkage analyses revealed two adjacent inversions within this region that repress meiotic recombination in NEACxNCC crosses. We identified a NEAC-specific haplotype consisting of 186 SNPs that was fixed in NEAC sampled from the Barents Sea, but segregating under Hardy-Weinberg equilibrium in eight NCC stocks. Comparative genomic analyses determine the NEAC configuration of the inversions to be the derived state and date it to ~1.6-2.0 Mya. The haplotype block harbours 763 genes, including candidates regulating swim bladder pressure, haem synthesis and skeletal muscle organization conferring adaptation to long-distance migrations and vertical movements down to large depths. Our results suggest that the migratory ecotype experiences strong directional selection for the two adjacent inversions on LG1. Despite interbreeding between NEAC and NCC, the inversions are maintaining genetic differentiation, and we hypothesize the co-occurrence of multiple adaptive alleles forming a 'supergene' in the NEAC population.
Characterization of the Spatial and Temporal Distribution of Nipah Virus Spillover Events in Bangladesh, 2007–2013

Nipah virus is a zoonotic virus harbored by bats and lethal to humans. Bat-to-human spillovers occur every winter in Bangladesh. However, there is significant heterogeneity in the number of spillovers detected by district and year that remains unexplained. We analyzed data from all 57 spillovers during 2007-2013 and found that temperature differences explained 36% of the year-to-year variation in the total number of spillovers each winter and that distance to surveillance hospitals explained 45% of spatial heterogeneity. Interventions to prevent human infections may be most important during colder winters. Further work is needed to understand how dynamics of bat infections explains spillover risk.