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Simple Summary: Early detection of breast cancer in asymptomatic women through screening is an important strategy in reducing the burden of breast cancer. In current organized breast screening programs, age is the predominant risk factor. Breast cancer risk assessment tools are numerical models that can combine information on various risk factors to estimate the risk of being diagnosed with breast cancer within a certain time period. These tools could be used to offer risk-based screening. This systematic review assessed, using a variety of methods, how accurately breast cancer risk assessment tools can group women eligible for screening within a population, into risk groups, so that each group could potentially be offered a screening protocol with more benefits and less harms compared to current age-based screening. Background: The benefits and harms of breast screening may be better balanced through a risk-stratified approach. We conducted a systematic review assessing the accuracy of questionnaire-based risk assessment tools for this purpose. Methods: Population: asymptomatic women aged ≥40 years; Intervention: questionnaire-based risk assessment tool (incorporating breast density and polygenic risk where available); Comparison: different tool applied to the same population; Primary outcome: breast cancer incidence; Scope: external validation studies identified from databases including Medline and Embase (period 1 January 2008–20 July 2021). We assessed calibration (goodness-of-fit) between expected and observed cancers and compared observed cancer rates by risk group. Risk of bias was assessed with PROBAST. Results: Of 5124 records, 13 were included examining 11 tools across 15 cohorts. The Gail tool was most represented (n = 11), followed by Tyrer-Cuzick (n = 5), BRCAPRO and iCARE-Lit (n = 3). No tool was consistently well-calibrated across multiple studies and breast density or polygenic risk scores did not improve calibration. Most tools identified a risk group with higher rates of observed cancers, but few tools identified lower-risk groups across different settings. All tools demonstrated a high risk of bias. Conclusion: Some risk tools can identify groups of women at higher or lower breast cancer risk, but this is highly dependent on the setting and population. [ABSTRACT FROM AUTHOR]

Recognition of RNA by receptors of the innate immune system is regulated by various posttranslational modifications. Different single 2′-O-ribose (2′-O-) methylations have been shown to convert TLR7/TLR8 ligands into specific TLR8 ligands, so we investigated whether the position of 2′-O-methylation is crucial for its function. To this end, we designed different 2′-O-methylated RNA oligoribonucleotides (ORN), investigating their immune activity in various cell systems and analyzing degradation under RNase T2 treatment. We found that the 18S rRNA-derived TLR7/8 ligand, RNA63, was differentially digested as a result of 2′-O-methylation, leading to variations in TLR8 and TLR7 inhibition. The suitability of certain 2′-O-methylated RNA63 derivatives as TLR8 agonists was further demonstrated by the fact that other RNA sequences were only weak TLR8 agonists. We were thus able to identify specific 2′-O-methylated RNA derivatives as optimal TLR8 ligands. [ABSTRACT FROM AUTHOR]

As a result of a viral infection, viral genomes are not only recognized by RIG-I, but also lead to the activation of RNase L, which cleaves cellular RNA to generate the endogenous RIG-I ligand (eRL). The eRL was previously identified as a specific sequence derived from the internal transcribed spacer region 2, which bears a 2′3′ cyclic phosphate instead of the common 5′ triphosphate. By now, the generation of the eRL and its immunostimulatory effect were shown both in vitro and in reporter systems. In this work, we aimed to elucidate whether the eRL is also generated in Influenza A (IAV) and vesicular stomatitis virus (VSV) infected cells. RNA was extracted from virus-infected cells and used for immunostimulations as well as specific PCR-strategies to detect eRL cleavage. We show that the eRL is generated in IAV infected HEK293 cells, but we could not detect specific eRL fragments in VSV infected cells. Further, RIG-I mediated IFN-response depends not only on viral genomes but also on the eRL, as immunostimulatory properties remain present under 5′triphosphate degrading conditions. In summary, we prove the IAV infection induced eRL generation in HEK293 cells, amplifying the innate immune response. [ABSTRACT FROM AUTHOR]

Objective: Afghanistan is one of the countries with the highest prevalence of spousal violence (56%) and a low prevalence of contraceptive use (23%), yet there is no study assessing how spousal violence is related to contraceptive use, and what methods are most used by women. Therefore, this study examined the association between the number of types of spousal violence and contraceptive use., Method: Using data from 18,985 Afghan married women, aged 15 to 49, who responded to the 2015 Afghanistan Demographic and Health Survey, the current contraceptive method was grouped into five categories: male-involved methods, pills, injectables, long-acting reversible contraception, female sterilization, and Lactation Amenorrhea Method. The number of types of spousal violence in the past 12 months was categorized as none, one type, or two or more types, based on women's experiences with verbal, physical, and sexual violence. For analysis, binary and multinomial logistic regression were used., Results: After adjusting for the covariates, the experience of any spousal violence was associated with contraception use (adjusted odds ratio (aOR) = 1.93, 95% CI: 1.64-2.27, p = 0.0001). Among those using contraception, experiencing two or three types of spousal violence was associated with using pills (adjusted risk ratio (aRRR) = 2.12, 95% CI: 1.63-2.77, p = 0.0001), injections (aRRR = 1.75, 95% CI: 1.26-2.41, p = 0.001), and LAM (aRRR = 3.27, 95% CI: 2.05-5.20, p = 0.0001), compared to male-involved methods., Conclusions: The findings of this study may inform policymakers and program implementers in designing interventions to address the pervasive problem of violence against women, and make pills and injectables more accessible to Afghan women, since these methods are under women's control and more often used in Afghanistan.