The aim of this meta-analysis, based on individual participant data from several studies, was to investigate the influence of patient-, materials-, and tooth-related variables on the survival of ...posterior resin composite restorations. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a search resulting in 12 longitudinal studies of direct posterior resin composite restorations with at least 5 years’ follow-up. Original datasets were still available, including placement/failure/censoring of restorations, restored surfaces, materials used, reasons for clinical failure, and caries-risk status. A database including all restorations was constructed, and a multivariate Cox regression method was used to analyze variables of interest patient (age; gender; caries-risk status), jaw (upper; lower), number of restored surfaces, resin composite and adhesive materials, and use of glass-ionomer cement as base/liner (present or absent). The hazard ratios with respective 95% confidence intervals were determined, and annual failure rates were calculated for subgroups. Of all restorations, 2,816 (2,585 Class II and 231 Class I) were included in the analysis, of which 569 failed during the observation period. Main reasons for failure were caries and fracture. The regression analyses showed a significantly higher risk of failure for restorations in high-caries-risk individuals and those with a higher number of restored surfaces.
The LIFE study is a two-phase randomized clinical trial comparing two approaches to maintaining weight loss following guided weight loss. Phase I provided a nonrandomized intensive 6-month behavioral ...weight loss intervention to 472 obese (body mass index 30-50) adult participants. Phase II is the randomized weight loss maintenance portion of the study. This paper focuses on Phase I measures of sleep, screen time, depression and stress.
The Phase I intervention consisted of 22 group sessions led over 26 weeks by behavioral counselors. Recommendations included reducing dietary intake by 500 calories per day, adopting the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and increasing physical exercise to at least 180 min per week. Measures reported here are sleep time, insomnia, screen time, depression and stress at entry and post-weight loss intervention follow-up.
The mean weight loss for all participants over the intensive Phase I weight loss intervention was 6.3 kg (s.d. 7.1). Sixty percent (N=285) of participants lost at least 4.5 kg (10 lbs) and were randomized into Phase II. Participants (N=472) attended a mean of 73.1% (s.d. 26.7) of sessions, completed 5.1 (s.d. 1.9) daily food records/week, and reported 195.1 min (s.d. 123.1) of exercise per week. Using logistic regression, sleep time (quadratic trend, P=0.030) and lower stress (P=0.024) at entry predicted success in the weight loss program, and lower stress predicted greater weight loss during Phase I (P=0.021). In addition, weight loss was significantly correlated with declines in stress (P=0.048) and depression (P=0.035).
Results suggest that clinicians and investigators might consider targeting sleep, depression and stress as part of a behavioral weight loss intervention.
Abstract The structure and dynamics of the star-forming disk of the Small Magellanic Cloud (SMC) have long confounded us. The SMC is widely used as a prototype for galactic physics at low ...metallicity, and yet we fundamentally lack an understanding of the structure of its interstellar medium (ISM). In this work, we present a new model for the SMC by comparing the kinematics of young, massive stars with the structure of the ISM traced by high-resolution observations of neutral atomic hydrogen (H i ) from the Galactic Australian Square Kilometre Array Pathfinder survey. Specifically, we identify thousands of young, massive stars with precise radial velocity constraints from the Gaia and APOGEE surveys and match these stars to the ISM structures in which they likely formed. By comparing the average dust extinction toward these stars, we find evidence that the SMC is composed of two structures with distinct stellar and gaseous chemical compositions. We construct a simple model that successfully reproduces the observations and shows that the ISM of the SMC is arranged into two superimposed, star-forming systems with similar gas mass separated by ∼5 kpc along the line of sight.
In a phase 2 study, rucaparib, an inhibitor of poly(ADP-ribose) polymerase (PARP), showed a high level of activity in patients who had metastatic, castration-resistant prostate cancer associated with ...a deleterious
alteration. Data are needed to confirm and expand on the findings of the phase 2 study.
In this randomized, controlled, phase 3 trial, we enrolled patients who had metastatic, castration-resistant prostate cancer with a
,
, or
alteration and who had disease progression after treatment with a second-generation androgen-receptor pathway inhibitor (ARPI). We randomly assigned the patients in a 2:1 ratio to receive oral rucaparib (600 mg twice daily) or a physician's choice control (docetaxel or a second-generation ARPI abiraterone acetate or enzalutamide). The primary outcome was the median duration of imaging-based progression-free survival according to independent review.
Of the 4855 patients who had undergone prescreening or screening, 270 were assigned to receive rucaparib and 135 to receive a control medication (intention-to-treat population); in the two groups, 201 patients and 101 patients, respectively, had a
alteration. At 62 months, the duration of imaging-based progression-free survival was significantly longer in the rucaparib group than in the control group, both in the BRCA subgroup (median, 11.2 months and 6.4 months, respectively; hazard ratio, 0.50; 95% confidence interval CI, 0.36 to 0.69) and in the intention-to-treat group (median, 10.2 months and 6.4 months, respectively; hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001 for both comparisons). In an exploratory analysis in the ATM subgroup, the median duration of imaging-based progression-free survival was 8.1 months in the rucaparib group and 6.8 months in the control group (hazard ratio, 0.95; 95% CI, 0.59 to 1.52). The most frequent adverse events with rucaparib were fatigue and nausea.
The duration of imaging-based progression-free survival was significantly longer with rucaparib than with a control medication among patients who had metastatic, castration-resistant prostate cancer with a
alteration. (Funded by Clovis Oncology; TRITON3 ClinicalTrials.gov number, NCT02975934.).
Myocardial fibrosis confers an almost threefold mortality risk in heart disease. There are no prognostic therapies and novel therapeutic targets are needed. Many thousands of unannotated small open ...reading frames (smORFs) have been identified across the genome with potential to produce micropeptides (< 100 amino acids). We sought to investigate the role of smORFs in myocardial fibroblast activation.
Analysis of human cardiac atrial fibroblasts (HCFs) stimulated with profibrotic TGFβ1 using RNA sequencing (RNA-Seq) and ribosome profiling (Ribo-Seq) identified long intergenic non-coding RNA LINC01013 as TGFβ1 responsive and containing an actively translated smORF. Knockdown of LINC01013 using siRNA reduced expression of profibrotic markers at baseline and blunted their response to TGFβ1. In contrast, overexpression of a codon-optimised smORF invoked a profibrotic response comparable to that seen with TGFβ1 treatment, whilst FLAG-tagged peptide associated with the mitochondria.
Together, these data support a novel LINC01013 smORF micropeptide-mediated mechanism of fibroblast activation.
Graphical Abstract
TGFβ1 stimulation of atrial fibroblasts induces expression of LINC01013, whose knockdown reduces fibroblast activation. Overexpression of a smORF contained within LINC01013 localises to mitochondria and activates fibroblasts
Enteroviruses show a high degree of sequence variation both between and within serotypes due to the lack of proofreading of the viral RNA-dependent RNA polymerase. In addition, recombination is known ...to occur not only within but also between different serotypes. We have previously shown that capsid coding sequences of coxsackievirus B4 (CVB4) cluster in several coexisting genotypes (intergenotypic nucleotide difference of 12 % or more) whereas a single lineage of echovirus 30 (EV30) has been prevailing and evolving throughout the last two decades. In the major capsid gene, VP1, clustering of both nucleotide and amino acid sequences correlates with serotype. We have now determined a 501 nucleotide sequence in the non-structural 3CD region of CVB4 and EV30 field strains. Phylogenetic analysis revealed that sequences of Human enterovirus B (HEV-B) were segregated in the 3CD region into three distinct clusters without the VP1-associated serotype/genotype correlation. One of the clusters comprised the E2 strain of CVB4, the EV30 prototype and five other CVB4 field strains whereas the other two clusters, in addition to CVB4 and EV30 strains, also included other HEV-B serotypes. We believe that intertypic recombination is the most likely explanation for the observed incongruence. Similarity analysis based on complete genomes of the CVB4 and EV30 prototypes and the CVB4 E2 strain revealed that a putative recombination spot was mapped within the 2B gene. The incongruence observed in the two genomic domains (P1 and P3) suggests a certain degree of independent evolution, which may be explained by interserotypic recombination within an enterovirus species. It is thus difficult to exclude recombination in the history of any given strain.
Abstract
A long-standing question in nuclear physics is whether chargeless nuclear systems can exist. To our knowledge, only neutron stars represent near-pure neutron systems, where neutrons are ...squeezed together by the gravitational force to very high densities. The experimental search for isolated multi-neutron systems has been an ongoing quest for several decades
1
, with a particular focus on the four-neutron system called the tetraneutron, resulting in only a few indications of its existence so far
2–4
, leaving the tetraneutron an elusive nuclear system for six decades. Here we report on the observation of a resonance-like structure near threshold in the four-neutron system that is consistent with a quasi-bound tetraneutron state existing for a very short time. The measured energy and width of this state provide a key benchmark for our understanding of the nuclear force. The use of an experimental approach based on a knockout reaction at large momentum transfer with a radioactive high-energy
8
He beam was key.
Objective
Determine the association between key dental outcomes and added sugar intake using a survey instrument to assess added sugars, which was specifically tailored to immigrant and US‐born ...adults of Mexican origin.
Methods
Hispanic adults of Mexican origin (n = 326; 36.2 ± 12.1 years) completed a self‐administered survey to gather acculturation, self‐reported dental experiences and self‐care practices (eg brushing, flossing, pain, bleeding gums), and socio‐demographic information. The survey included a culturally tailored 22‐item Added Sugar Intake Estimate (ASIE) that assessed added sugar intake from processed foods and sugar‐sweetened beverages in a semiquantitative food frequency questionnaire format. Linear regression, 2‐sample t test, and ANOVA were used to evaluate associations of demographic and dental outcomes with daily added sugar intake.
Results
Of the mean total daily added sugar intake (99.6 ± 94.6 g), 36.5 ± 44.4 g was derived from sugar‐containing foods and snacks, and 63.1 ± 68.2 g from beverages. Participants who reported greater added sugar intake were more likely to have reported the presence of a toothache in the preceding 12 months, having been prescribed antibiotics for dental reasons, being less likely to floss daily, have reported eating or drinking within 1 hour before bed and have lower psychological acculturation (P < .05 for all). Results were comparable when assessing intake from sugar‐containing foods/snacks and sugar‐sweetened beverages.
Conclusions
This study confirmed the association between added sugar intake and self‐reported dental outcomes among adults of Mexican origin and points to an urgent need to improve dietary behaviours in this population.
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