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Background Mammogram risk scores based on texture and density defined by different brightness thresholds are associated with breast cancer risk differently and could reveal distinct information about breast cancer risk. We aimed to investigate causal relationships between these intercorrelated mammogram risk scores to determine their relevance to breast cancer aetiology. Methods We used digitised mammograms for 371 monozygotic twin pairs, aged 40–70 years without a prior diagnosis of breast cancer at the time of mammography, from the Australian Mammographic Density Twins and Sisters Study. We generated normalised, age-adjusted, and standardised risk scores based on textures using the Cirrus algorithm and on three spatially independent dense areas defined by increasing brightness threshold: light areas, bright areas, and brightest areas. Causal inference was made using the Inference about Causation from Examination of FAmilial CONfounding (ICE FALCON) method. Results The mammogram risk scores were correlated within twin pairs and with each other ( r  = 0.22–0.81; all P  < 0.005). We estimated that 28–92% of the associations between the risk scores could be attributed to causal relationships between the scores, with the rest attributed to familial confounders shared by the scores. There was consistent evidence for positive causal effects: of Cirrus, light areas, and bright areas on the brightest areas (accounting for 34%, 55%, and 85% of the associations, respectively); and of light areas and bright areas on Cirrus (accounting for 37% and 28%, respectively). Conclusions In a mammogram, the lighter (less dense) areas have a causal effect on the brightest (highly dense) areas, including through a causal pathway via textural features. These causal relationships help us gain insight into the relative aetiological importance of different mammographic features in breast cancer. For example our findings are consistent with the brightest areas being more aetiologically important than lighter areas for screen-detected breast cancer; conversely, light areas being more aetiologically important for interval breast cancer. Additionally, specific textural features capture aetiologically independent breast cancer risk information from dense areas. These findings highlight the utility of ICE FALCON and family data in decomposing the associations between intercorrelated disease biomarkers into distinct biological pathways.

ObjectivesTo assess the current status of injury prevention (IP) core competency among medical students majoring in public health in China and to advocate for incorporating IP in the medical curriculum.MethodsThe study used purposive sampling in eight medical universities in China in 2017, including 420 undergraduates and 763 graduates, using self-administered questionnaires based on the core competency instrument for IP with five domains (31 items): A) injury analysis and assessment (8 items), B) IP project planning and implementation (7 items), C) communication (6 items), D) community practice (5 items), and E) leadership and systematic thinking (5 items). The higher score indicated the higher level of proficiency of the ability (scores ranged from 1 to 5). We used linear regression model to test the effect of IP course experience on the core competency mean score after adjusting for potential confounders.ResultsThe total mean score was 2.78 (SD=0.76, median=2.9, range=1–4.55) and 2.68 (SD=0.75, median=2.81, range=1–4.45) for undergraduates and graduates, respectively. There were 60% and 36% of undergraduates and graduates who have ever taken IP course, respectively. IP course class hours were positively associated with core competency level (P<0.05) across five domains (except for domain D) and the total.ConclusionThe core competency level is relatively low among public health students in China. Setting IP courses should be considered as an effective way to improve students’ core competency. It is a step moving towards the IP education promotion, and further boosting the field of public health.

Cumulus, Altocumulus, and Cirrocumulus are measures of mammographic density defined at increasing pixel brightness thresholds, which, when converted to mammogram risk scores (MRSs), predict breast cancer risk. Twin and family studies suggest substantial variance in the MRSs could be explained by genetic factors. For 2559 women aged 30 to 80 years (mean 54 years), we measured the MRSs from digitized film mammograms and estimated the associations of the MRSs with a 313-SNP breast cancer polygenic risk score (PRS) and 202 individual SNPs associated with breast cancer risk. The PRS was weakly positively correlated (correlation coefficients ranged 0.05–0.08; all p < 0.04) with all the MRSs except the Cumulus-white MRS based on the “white but not bright area” (correlation coefficient = 0.04; p = 0.06). After adjusting for its association with the Altocumulus MRS, the PRS was not associated with the Cumulus MRS. There were MRS associations (Bonferroni-adjusted p < 0.04) with one SNP in the ATXN1 gene and nominally with some ESR1 SNPs. Less than 1% of the variance of the MRSs is explained by the genetic markers currently known to be associated with breast cancer risk. Discovering the genetic determinants of the bright, not white, regions of the mammogram could reveal substantial new genetic causes of breast cancer.

Cumulus, Cumulus-percent, Altocumulus, Cirrocumulus, and Cumulus-white are mammogram risk scores (MRSs) for breast cancer based on mammographic density defined in effect by different levels of pixel brightness and adjusted for age and body mass index. We measured these MRS from digitized film mammograms for 593 monozygotic (MZ) and 326 dizygotic (DZ) female twin pairs and 1592 of their sisters. We estimated the correlations in relatives (r) and the proportion of variance due to genetic factors (heritability) using the software FISHER and predicted the familial risk ratio (FRR) associated with each MRS. The ρ estimates ranged from: 0.41 to 0.60 (standard error [SE] 0.02) for MZ pairs, 0.16 to 0.26 (SE 0.05) for DZ pairs, and 0.19 to 0.29 (SE 0.02) for sister pairs (including pairs of a twin and her non-twin sister), respectively. Heritability estimates were 39% to 69% under the classic twin model and 36% to 56% when allowing for shared non-genetic factors specific to MZ pairs. The FRRs were 1.08 to 1.17. These MRSs are substantially familial, due mostly to genetic factors that explain one-quarter to one-half as much of the familial aggregation of breast cancer that is explained by the current best polygenic risk score.

Background: Objective to investigate the needs of junior high school students for injury prevention awareness and emergency skills education, so as to provide reference basis for junior high school students to carry out injury prevention work. Methods: A total of 1079 vocational middle school students were selected by stratified cluster sampling. The content of the questionnaire includes: basic demographic information, cognition of injury-related risk factors, demand for injury prevention education, mastery of first aid skills, etc. Results: 76.2% believed that there were potential risk factors leading to injury accidents in life, 397 (36.8%) chose yes, rarely, 303 (28.1%) chose yes, generally, and 122 (11.3%) chose yes, many .Among the places considered most vulnerable to injury, the top five were road/street, off-campus sports ground, business district, school and residential district, with 79.1%, 41.6%, 33.1%, 29.2% and 19.6% respectively. The potential risk factors considered by students are divided into four aspects. The proportion of vocational middle school students in the judgment and selection of potential risk factors are lack of safety awareness (54.9%) and excessive learning pressure (41.2%) respectively. Parents ignore their children (34.0%) and family relationship is not harmonious (31.3%) were the top two risk factors for potential injury to the family. The top two risk factors for potential injury in schools were bad school atmosphere (37.7%) and lack of school safety education (36.9%).For potential hazardous environmental factors, unsafe road environment (64.8%) and unsafe sports facilities (44.8%) ranked top two.89.0% of the students think it necessary to attend schools or other institutions to carry out safety education or activity, hope schools provide injury prevention education aspect, the top six were bullying (85.6%), food hygiene (80.3%), traffic injuries (74.4%), fraud (65.1%), electric shock (65.1%) and first aid (63.5%), especially the bullying of these safety education.78.9% of the students said they had received first aid training, and CPR (86.5%), first aid for drowning (49.4%), bandaging (42.2%) and hemostasis (42.0%) were the top four first aid skills of the middle school students surveyed. The most common reasons for not mastering first aid skills were forgetting after learning (33.5%) and too short training time (29.7%). Conclusion: Junior high school students need to improve their education on potential injury risk factors in life and emergency treatment in the face of injury.It is necessary to carry out injury prevention and emergency skills education among high school students in vocational schools.

The development of epoxy (EP) nanocomposites has emerged as a prominent research area across diverse sectors, including automotive, construction, and aerospace industries. Recently, adopting biomimetic strategies for the preparation of nanomaterials to design multifunctional epoxy resins has emerged as a prominent research hotspot. Inspired by the growth pattern of coral reefs, this study successfully engineered a novel hierarchical nanostructured material (Fe-NiPS-PBA) with the aim of creating EP nanocomposites that exhibit highly flame-retardant efficiency, exceptional mechanical strength, and distinguished wear-resisting property even at low additive concentrations. With a 3 ​wt% addition of Fe-NiPS-PBA, the limiting oxygen index of the EP/3Fe-NiPS-PBA nanocomposite increased from 23.5 to 25.9, achieving a UL-94 V-0 rating. Compared to pure EP, EP/3Fe-NiPS-PBA nanocomposite reduced the peak heat release rate (PHRR), total heat release (THR), peak smoke production rate (PSPR), total smoke production (TSP), and maximum CO emission (MCO) by 44.1 ​%, 66.7 ​%, 47.0 ​%, 67.8 ​%, and 51.7 ​%, respectively. Moreover, the incorporation of a 1 ​wt% additive resulted in significant enhancements of tensile strength from 76.7 ​MPa to 96.9 ​MPa, while the wear rate demonstrated a remarkable reduction of 77.8 ​%. The Fe-NiPS-PBA significantly enhanced the fire performance and mechanical strength of EP nanocomposites, demonstrating exceptional overall performance in various applications. A novel hierarchical Fe-NiPS-PBA architecture was fabricated using a bio-inspired strategy based on the growth pattern of coral reefs. Subsequently, Fe-NiPS-PBA was incorporated into epoxy resin (EP) through a solution blending method to produce EP nanocomposites exhibiting exceptional flame retardancy, mechanical strength, and wear-resisting performance. The phase structure and layered morphology of Fe-NiPS-PBA were analyzed, and the positive effects on the flame retardancy, mechanical strength and wear-resisting performance of EP nanocomposites were evaluated in detail. [Display omitted] •A coral reefs-inspired hierarchical Fe-NiPS-PBA was innovatively synthesized.•3.0 ​wt% of Fe-NiPS-PBA enabled EP to achieve a UL-94 V-0 rating.•EP/3Fe-NiPS-PBA nanocomposite exhibited significant decrease in PHRR, THR, PSPR, TSP, MCO and MCO2.•The mechanical strength and wear-resisting properties of EP were greatly enhanced.

Abstract Microtubule, composed of αβ-tubulin heterodimers, remains as one of the most popular anticancer targets for decades. To date, anti-microtubule drugs are mainly functionally divided into microtubule-destabilizing and microtubule-stabilizing agents while microtubule- or tubulin-degradation agents are rarely reported. Six known binding sites on tubulin dimer are identified with five sites on β-tubulin and only one site on α-tubulin (pironetin site), hinting compounds binding to α-tubulin are less well characterized. Cevipabulin, a microtubule-active antitumor clinical candidate, is widely accepted as a microtubule-stabilizing agent by binding to the vinblastine site. Our X-ray crystallography study reveals that, in addition binding to the vinblastine site, cevipabulin also binds to a novel site on α-tubulin (named the seventh site) which located near the nonexchangeable GTP. Interestingly, we find the binding of cevipabulin to the seventh site induces tubulin degradation. As the non-exchangeable GTP has structural role and is important for the stability of tubulin dimers, we propose and confirm the tubulin degradation mechanism as: Cevipabulin at the seventh site puts the αT5 loop outward to make the non-exchangeable GTP exchangeable, which reduces the stability of tubulin and results in its destabilization and degradation. Our results confirm a novel agent binding site on α-tubulin and shed light on the development of tubulin degraders as a new generation of anti-microtubule drugs targeting this novel site. Competing Interest Statement The authors have declared no competing interest.