This study examined the factor structure of the Self-Compassion Scale (SCS) using secondary data drawn from 20 samples (N = 11,685)-7 English and 13 non-English-including 10 community, 6 student, 1 ...mixed community/student, 1 meditator, and 2 clinical samples. Self-compassion is theorized to represent a system with 6 constituent components: self-kindness, common humanity, mindfulness and reduced self-judgment, isolation and overidentification. There has been controversy as to whether a total score on the SCS or if separate scores representing compassionate versus uncompassionate self-responding should be used. The current study examined the factor structure of the SCS using confirmatory factor analyses (CFA) and Exploratory Structural Equation Modeling (ESEM) to examine 5 distinct models: 1-factor, 2-factor correlated, 6-factor correlated, single-bifactor (1 general self-compassion factor and 6 group factors), and 2-bifactor models (2 correlated general factors each with 3 group factors representing compassionate or uncompassionate self-responding). Results indicated that a 1- and 2-factor solution to the SCS had inadequate fit in every sample examined using both CFA and ESEM, whereas fit was excellent using ESEM for the 6-factor correlated, single-bifactor and correlated 2-bifactor models. However, factor loadings for the correlated 2-bifactor models indicated that 2 separate factors were not well specified. A general factor explained 95% of the reliable item variance in the single-bifactor model. Results support use of the SCS to examine 6 subscale scores (representing the constituent components of self-compassion) or a total score (representing overall self-compassion), but not separate scores representing compassionate and uncompassionate self-responding.
Public Significance Statement
This study examined the factor structure of the Self-Compassion Scale (SCS) in 20 diverse samples (N = 11,685), and excellent fit was found in every sample for an Exploratory Structural Equation Modeling (ESEM) single-bifactor model (with 95% of item variance explained by a general factor) and an ESEM 6-factor correlated model. Results support use of a total SCS score or 6 subscale scores, but not 2 separate scores representing compassionate and uncompassionate self-responding.
Accurate risk assessment is essential for the success of population screening programs in breast cancer. Models with high sensitivity and specificity would enable programs to target more elaborate ...screening efforts to high-risk populations, while minimizing overtreatment for the rest. Artificial intelligence (AI)-based risk models have demonstrated a significant advance over risk models used today in clinical practice. However, the responsible deployment of novel AI requires careful validation across diverse populations. To this end, we validate our AI-based model, Mirai, across globally diverse screening populations.
We collected screening mammograms and pathology-confirmed breast cancer outcomes from Massachusetts General Hospital, USA; Novant, USA; Emory, USA; Maccabi-Assuta, Israel; Karolinska, Sweden; Chang Gung Memorial Hospital, Taiwan; and Barretos, Brazil. We evaluated Uno's concordance index for Mirai in predicting risk of breast cancer at one to five years from the mammogram.
A total of 128,793 mammograms from 62,185 patients were collected across the seven sites, of which 3,815 were followed by a cancer diagnosis within 5 years. Mirai obtained concordance indices of 0.75 (95% CI, 0.72 to 0.78), 0.75 (95% CI, 0.70 to 0.80), 0.77 (95% CI, 0.75 to 0.79), 0.77 (95% CI, 0.73 to 0.81), 0.81 (95% CI, 0.79 to 0.82), 0.79 (95% CI, 0.76 to 0.83), and 0.84 (95% CI, 0.81 to 0.88) at Massachusetts General Hospital, Novant, Emory, Maccabi-Assuta, Karolinska, Chang Gung Memorial Hospital, and Barretos, respectively.
Mirai, a mammography-based risk model, maintained its accuracy across globally diverse test sets from seven hospitals across five countries. This is the broadest validation to date of an AI-based breast cancer model and suggests that the technology can offer broad and equitable improvements in care.
Comparative analysis of RNA sequences is the basis for the detailed and accurate predictions of RNA structure and the determination of phylogenetic relationships for organisms that span the entire ...phylogenetic tree. Underlying these accomplishments are very large, well-organized, and processed collections of RNA sequences. This data, starting with the sequences organized into a database management system and aligned to reveal their higher-order structure, and patterns of conservation and variation for organisms that span the phylogenetic tree, has been collected and analyzed. This type of information can be fundamental for and have an influence on the study of phylogenetic relationships, RNA structure, and the melding of these two fields.
We have prepared a large web site that disseminates our comparative sequence and structure models and data. The four major types of comparative information and systems available for the three ribosomal RNAs (5S, 16S, and 23S rRNA), transfer RNA (tRNA), and two of the catalytic intron RNAs (group I and group II) are: (1) Current Comparative Structure Models; (2) Nucleotide Frequency and Conservation Information; (3) Sequence and Structure Data; and (4) Data Access Systems.
This online RNA sequence and structure information, the result of extensive analysis, interpretation, data collection, and computer program and web development, is accessible at our Comparative RNA Web (CRW) Site http://www.rna.icmb.utexas.edu. In the future, more data and information will be added to these existing categories, new categories will be developed, and additional RNAs will be studied and presented at the CRW Site.
Sea turtles represent an ancient lineage of marine vertebrates that evolved from terrestrial ancestors over 100 Mya. The genomic basis of the unique physiological and ecological traits enabling these ...species to thrive in diverse marine habitats remains largely unknown. Additionally, many populations have drastically declined due to anthropogenic activities over the past two centuries, and their recovery is a high global conservation priority. We generated and analyzed high-quality reference genomes for the leatherback (
) and green (
) turtles, representing the two extant sea turtle families. These genomes are highly syntenic and homologous, but localized regions of noncollinearity were associated with higher copy numbers of immune, zinc-finger, and olfactory receptor (OR) genes in green turtles, with ORs related to waterborne odorants greatly expanded in green turtles. Our findings suggest that divergent evolution of these key gene families may underlie immunological and sensory adaptations assisting navigation, occupancy of neritic versus pelagic environments, and diet specialization. Reduced collinearity was especially prevalent in microchromosomes, with greater gene content, heterozygosity, and genetic distances between species, supporting their critical role in vertebrate evolutionary adaptation. Finally, diversity and demographic histories starkly contrasted between species, indicating that leatherback turtles have had a low yet stable effective population size, exhibit extremely low diversity compared with other reptiles, and harbor a higher genetic load compared with green turtles, reinforcing concern over their persistence under future climate scenarios. These genomes provide invaluable resources for advancing our understanding of evolution and conservation best practices in an imperiled vertebrate lineage.
The current heightened social awareness and anxiety triggered by escalating violence against Black Americans in the United States demands a safe space for reflection, education, and civil discourse ...within the academic setting. Too often there is an unmet need paired with a collective urgent desire to better understand the chronic existing structural, social, educational, and health inequities affecting disadvantaged populations, particularly Black Americans. In this perspective, the authors provide insight into a shared learning approach that provided a forum to discuss Perspectives Against Racism (PAR). Unlike existing top-down approaches, faculty, trainees, and staff were engaged in leading a series of focused discussions to examine unconscious bias, promote awareness of implicit biases, and reflect on individual and collective roles and responsibilities in working toward becoming antiracist. An existing 1-h graduate elective seminar course was dedicated to creating a space for learning, discussion, and exchange of ideas related to the experience and existence of racism (personal and institutional/systemic). A goal of each session was to go beyond didactics and identify mechanisms to implement change, at the level of the individual, department, and institution. This perspective of the shared experience may provide an adaptable framework that can be implemented in an academic setting at the departmental, center, or institutional level.
The bacterial microbiome of human body sites, previously considered sterile, remains highly controversial because it can be challenging to isolate signal from noise when low-biomass samples are being ...analyzed. We tested the hypothesis that stochastic sequencing noise, separable from reagent contamination, is generated during sequencing on the Illumina MiSeq platform when DNA input is below a critical threshold. We first purified DNA from serial dilutions of
and from negative controls using three DNA purification kits, quantified input using droplet digital PCR, and then sequenced the 16S rRNA gene in four technical replicates. This process identified reproducible contaminant signal that was separable from an irreproducible stochastic noise, which occurred as bacterial biomass of samples decreased. This approach was then applied to authentic respiratory samples from healthy individuals (
= 22) that ranged from high to ultralow bacterial biomass. Using oral rinse, bronchoalveolar lavage (BAL) fluid, and exhaled breath condensate (EBC) samples and matched controls, we were able to demonstrate (i) that stochastic noise dominates sequencing in real-world low-bacterial-biomass samples that contain fewer than 10
copies of the 16S rRNA gene per sample, (ii) that critical examination of the community composition of technical replicates can be used to separate signal from noise, and (iii) that EBC is an irreproducible sampling modality for sampling the microbiome of the lower airways. We anticipate that these results combined with suggested methods for identifying and dealing with noisy communities will facilitate increased reproducibility while simultaneously permitting characterization of potentially important low-biomass communities.
DNA contamination from external sources (reagents, environment, operator, etc.) has long been assumed to be the main cause of spurious signals that appear under low-bacterial-biomass conditions. Here, we demonstrate that contamination can be separated from another, random signal generated during low-biomass-sample sequencing. This stochastic noise is not reproduced between technical replicates; however, results for any one replicate taken alone could look like a microbial community different from the controls. Using this information, we investigated respiratory samples from healthy humans and determined the narrow range of bacterial biomass where samples transition from producing reproducible microbial sequences to ones dominated by noise. We present a rigorous approach to studies involving low-bacterial-biomass samples to detect this source of noise and provide a framework for deciding if a sample is likely to be dominated by noise. We anticipate that this work will facilitate increased reproducibility in the characterization of potentially important low-biomass communities.
Expanding visceral adiposity is associated with increased inflammation and increased risk for developing obesity-related comorbidities. The goal of this study was to examine high fat diet ...(HFD)-induced differences in adipocyte size and cytokine/chemokine expression in visceral and subcutaneous adipose depots in obesity-prone (OP) and obesity-resistant (OR) rats.
OP and OR rats were fed either a low fat diet (LFD, 10% kilocalories from fat) or HFD (60% kilocalories from fat) for 7 weeks. Adipocyte size and the presence of crown-like structures in epididymal and inguinal adipose tissue were determined. A multiplex cytokine/chemokine panel was used to assess the expression of inflammatory markers in epididymal and inguinal adipose tissues.
A higher percentage of large adipocytes (>5000 μm
) was detected in the epididymal and inguinal adipose tissues of OP rats and a higher percentage of small adipocytes (<4000 μm
) was detected in the epididymal and inguinal adipose tissues of OR rats. More crown-like structures were identified in epididymal adipose tissue of OP rats fed a LFD, compared to OR rats. Consumption of a HFD increased the number of crown-like structures in OR, but not OP rats. Epididymal expression of pro-inflammatory cytokines (IL-1β and TNF-α) was higher in OP rats, compared to OR rats fed LFD. HFD consumption increased epididymal expression of GM-CSF, IL-1α, IL-1β, IL-6, MIP-2 and TNF-α in OP and OR rats. Inguinal expression of pro-inflammatory cytokines (IL-1α, IL-1β and TNF-α) was higher in OP rats, compared to OR rats.
Overall, these data suggest that a higher susceptibility to developing obesity is characterized by large adipocytes and increased visceral adipose inflammation. Interestingly, in OR rats, the detrimental effects of HFD consumption on visceral adipose inflammation are evident with only small increases in weight and adiposity, suggesting that HFD also increases the risk for obesity-related comorbidities in OR rats.
A positive perception of motor skills is important for physical activity participation. The aim was to investigate which modifiable factors predict children's perceived motor skills. Mothers ...completed questionnaires when their child was 3.5 and 5 years old. At 5 years old, the children's perceived motor competence (PMC) was assessed. Separate linear regression models (up to 300 children) examined which factors at each time point predicted children's PMC, adjusted for relevant confounders. Multivariate models were then run with factors associated (
< 0.10) with perception. At 3.5 years, the time spent with same age and older children (both higher tertiles) and parental physical activity facilitation (sum of facilitation in last month, e.g., taking child to park) were initially associated with higher perception. Dance/gymnastics participation were associated with lower perceptions. Other child behaviours, maternal beliefs, play equipment, and swimming lessons were non-significant. In the final prospective model (
= 226), parental physical activity facilitation when child was 3.5 years old was the only factor to predict PMC. No factors were significant for the cross-sectional analyses at 5 years. Perceptions are formed based on past experiences which may explain why factors at 3.5 years rather than current experiences (when children were 5 years old) were associated with childhood perceptions.
Summary Background Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) progressing after first-line platinum regimens have a poor prognosis and few treatment ...options. Afatinib, an irreversible ERBB family blocker, has shown efficacy in a phase 2 study in this setting. We aimed to assess the efficacy and safety of afatinib compared with methotrexate as second-line treatment in patients with recurrent or metastatic HNSCC progressing on or after platinum-based therapy. Methods In this open-label, phase 3, randomised controlled trial conducted in 101 centres in 19 countries, we enrolled patients aged 18 years or older with histologically or cytologically confirmed HNSCC that was recurrent, metastatic, or both who had progressed on or after first-line platinum-based therapy, were not amenable for salvage surgery or radiotherapy, and who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Previous treatment with more than one systemic regimen in this setting was not allowed; previous treatment with EGFR-targeted antibody therapy (but not EGFR-targeted tyrosine-kinase inhibitors) was allowed. We randomly assigned eligible patients in a 2:1 ratio to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m2 per week), stratified by ECOG performance status and previous EGFR-targeted antibody therapy for recurrent or metastatic disease. Randomisation was done centrally with an interactive voice or web-based response system. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. The primary endpoint was progression-free survival as assessed by an independent, central imaging review committee. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov , number NCT01345682. Findings Between Jan 10, 2012, and Dec 12, 2013, we enrolled 483 patients and randomly assigned 322 to afatinib and 161 to methotrexate. After a median follow-up of 6·7 months (IQR 3·1–9·0), progression-free survival was longer in the afatinib group than in the methotrexate group (median 2·6 months 95% CI 2·0–2·7 for the afatinib group vs 1·7 months 1·5–2·4 for the methotrexate group; hazard ratio HR 0·80 95% CI 0·65–0·98, p=0·030). The most frequent grade 3 or 4 drug-related adverse events were rash or acne (31 10% of 320 patients in the afatinib group vs none of 160 patients in the methotrexate group), diarrhoea (30 9% vs three 2%), stomatitis (20 6% vs 13 8%), fatigue (18 6% vs five 3%), and neutropenia (1 <1% vs 11 7%); serious adverse events occurred in 44 (14%) of afatinib-treated patients and 18 (11%) of methotrexate-treated patients. Interpretation Afatinib was associated with significant improvements in progression-free survival and had a manageable safety profile. These findings provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in HNSCC. Funding Boehringer Ingelheim.
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