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Mammograms contain information that predicts breast cancer risk. We developed two novel mammogram‐based breast cancer risk measures based on image brightness (Cirrocumulus) and texture (Cirrus). Their risk prediction when fitted together, and with an established measure of conventional mammographic density (Cumulus), is not known. We used three studies consisting of: 168 interval cases and 498 matched controls; 422 screen‐detected cases and 1197 matched controls; and 354 younger‐diagnosis cases and 944 controls frequency‐matched for age at mammogram. We conducted conditional and unconditional logistic regression analyses of individually‐ and frequency‐matched studies, respectively. We estimated measure‐specific risk gradients as the change in odds per standard deviation of controls after adjusting for age and body mass index (OPERA) and calculated the area under the receiver operating characteristic curve (AUC). For interval, screen‐detected and younger‐diagnosis cancer risks, the best fitting models (OPERAs [95% confidence intervals]) involved: Cumulus (1.81 [1.41‐2.31]) and Cirrus (1.72 [1.38‐2.14]); Cirrus (1.49 [1.32‐1.67]) and Cirrocumulus (1.16 [1.03 to 1.31]); and Cirrus (1.70 [1.48 to 1.94]) and Cirrocumulus (1.46 [1.27‐1.68]), respectively. The AUCs were: 0.73 [0.68‐0.77], 0.63 [0.60‐0.66], and 0.72 [0.69‐0.75], respectively. Combined, our new mammogram‐based measures have twice the risk gradient for screen‐detected and younger‐diagnosis breast cancer (P ≤ 10−12), have at least the same discriminatory power as the current polygenic risk score, and are more correlated with causal factors than conventional mammographic density. Discovering more information about breast cancer risk from mammograms could help enable risk‐based personalised breast screening. What's new? Mammographic density, or the area of the mammogram which appears white or bright, has well‐established associations with breast cancer risk. The authors call this Cumulus due to the computer‐assisted technique for measuring that density. Here, the authors introduce two novel measurement techniques, Cirrus and Cirrocumulus, for extracting risk information from mammograms. Cirrocumulus is based on image brightness and Cirrus is based on texture. When combined, these measures substantially improve risk prediction beyond that of Cumulus. In addition, the new risk measures outperformed the recently published polygenic risk score. By obtaining more information from mammograms, these tools could improve personalized risk recommendations for screening. [ABSTRACT FROM AUTHOR]

Interval breast cancers (those diagnosed between recommended mammography screens) generally have poorer outcomes and are more common among women with dense breasts. We aimed to develop a risk model for interval breast cancer. We conducted a nested case–control study within the Melbourne Collaborative Cohort Study involving 168 interval breast cancer patients and 498 matched control subjects. We measured breast density using the CUMULUS software. We recorded first‐degree family history by questionnaire, measured body mass index (BMI) and calculated age‐adjusted breast tissue aging, a novel measure of exposure to estrogen and progesterone based on the Pike model. We fitted conditional logistic regression to estimate odds ratio (OR) or odds ratio per adjusted standard deviation (OPERA) and calculated the area under the receiver operating characteristic curve (AUC). The stronger risk associations were for unadjusted percent breast density (OPERA = 1.99; AUC = 0.66), more so after adjusting for age and BMI (OPERA = 2.26; AUC = 0.70), and for family history (OR = 2.70; AUC = 0.56). When the latter two factors and their multiplicative interactions with age‐adjusted breast tissue aging (p = 0.01 and 0.02, respectively) were fitted, the AUC was 0.73 (95% CI 0.69–0.77), equivalent to a ninefold interquartile risk ratio. In summary, compared with using dense breasts alone, risk discrimination for interval breast cancers could be doubled by instead using breast density, BMI, family history and hormonal exposure. This would also give women with dense breasts, and their physicians, more information about the major consequence of having dense breasts—an increased risk of developing an interval breast cancer. What's new? Breast cancers that are detected between regular screening intervals are more aggressive and have poorer outcomes than screen‐detected tumors but no valid risk model exists to predict "interval" breast cancers. Here the authors combined breast density with other breast cancer risk factors such as body mass index, family history and a novel measure of age‐adjusted hormonal exposure. Applying this to more than 150 women with interval breast cancer, they find that risk discrimination can be doubled with the combination of factors as compared with just using breast density alone, thus improving risk predictions and clinical recommendations for breast screening procedures. [ABSTRACT FROM AUTHOR]

Despite its great potential, high-throughput functional genomic data are rarely integrated and applied to characterizing the genomic basis of fertility. We obtained and reprocessed over 30 functional genomics datasets from human and mouse germ cells to perform genome-wide prediction of genes underlying various reproductive phenotypes in both species. Genes involved in male fertility are easier to predict than their female analogs. Of the multiple genomic data types examined, protein--protein interactions are by far the most informative for gene prediction, followed by gene expression, and then epigenetic marks. As an application of our predictions, we show that copy number variants (CNVs) disrupting predicted fertility genes are more strongly associated with gonadal dysfunction in male and female case--control cohorts when compared to all gene-disrupting CNVs (OR = 1.64, p < 1.64 9 10-8 vs. OR = 1.25, p < 4 9 10-6). Using gender-specific fertility gene annotations further increased the observed associations (OR = 2.31, p < 2.2 9 10-16). We provide our gene predictions as a resource with this article. [ABSTRACT FROM AUTHOR]

A universal and facile approach to modifying proteins so that they can rapidly form hydrogel upon mixing with crosslinkers is presented. The concept of it is to introduce maleimide, which is highly reactive with dithiol-containing crosslinkers via thiol-ene click chemistry, onto proteins. Bovine serum albumin (BSA) is used as a model protein due to its good stability and low cost. The results here show that a protein hydrogel can be readily formed by blending modified BSA and resilin-related peptide crosslinker solutions at a proper ratio. The hydrogel exhibits good elasticity and tunable mechanical as well as biochemical properties. Moreover, it allows convenient 3D cell encapsulation and shows good biocompatibility. Muscle cells embedded in the hydrogel are promoted to spread by incorporating arginyl-glycyl-aspartic acid (RGD)-containing peptide into the system, thus warranting a bright future of it in regenerative medicine. [ABSTRACT FROM AUTHOR]

Summary: A 9‐year‐old show pony mare became acutely lame following removal of a bone sequestrum of the distal phalanx of the right thoracic limb. The mare also suffered from ongoing right dorsal colitis secondary to previous long‐term nonsteroidal anti‐inflammatory drug (NSAID) use. To avoid further NSAID use, a protocol for caudal epidural administration of morphine and detomidine in an increased volume was used to provide analgesia to the thoracic limbs. A total volume of 50 mL (0.2 mL/kg bwt) was administered over approximately 90 s. Immediately following the injection, the pony collapsed into lateral recumbency and experienced an apparent generalised seizure characterised by loss of consciousness and frantic paddling of all four limbs. The pony recovered rapidly without intervention, and no residual neurological deficits were noted. The epidural analgesia resulted in a marked improvement in comfort levels. The speed of injection is thought to have caused a change in epidural and intracranial pressures resulting in a generalised seizure and highlights the importance of administering large volumes slowly. [ABSTRACT FROM AUTHOR]

We have shown the efficacies of translationally fused gene (cry1Ab-1B) under the control of maize ubiquitin promoter and hybrid Bt gene (cry1A/cry1Ac) driven by rice Actin-1 promoter against the yellow stem borer (Scirpophaga incertulas Walker, YSB) insect in rice (Oryza sativa L.). The integration, expression, and functionality of the transgenes were confirmed by Southern, western, and insect bioassay. The bioassay results correlated with the molecular data. The amount of Bt protein (within the range of 0.8–1.3% of the total soluble protein) in the transgenics was sufficient to cause 100% mortality of the neonate larvae of YSB within 1 wk of infestation. The transgenic plants expressing the foreign Bt protein were normal in phenotype with as good seed setting as the nontransgenic control plants. [ABSTRACT FROM AUTHOR]

Dislocation substructure in hot-pressed hexagonal BaTiO3 ceramics was analysed by transmission electron microscopy. Two dislocation networks each consisting of dissociated half-partials were determined for the Burgers vectors ( b) using the g · b = 0 effective invisibility criteria, and the true directions ( u) by trace analysis. Each of the networks contains three partial nodes that are in the form: 1/3[ 010]+1/3[10 0]+1/3[1 00]+1/3[ 100] = 0, where four partials meet at a point and the Burgers vectors are conserved, as analysed by the weak-beam dark field technique. Basal dislocation with bb = 1/3<11 0> is dissociated into two prism plane half-partials with bhp = 1/3<10 0> by: 1/3<11 0> → 1/3<01 0> + 1/3<10 0>. Dissociation of basal dislocation by a glide mechanism creates a stacking fault when shear occurs along <10 0> in the c-layer of (000 l), where l = 1, 3, 4 and 6, of the (chc)1(chc)2 (or (CBC)(ABA)) stacking sequence. The slip system of 1/3<11 0>(0001) in hexagonal BaTiO3 has been activated at 1300 °C by hot-pressing under ∼25.8 MPa. Plastic flow contributing to the densification of hexagonal BaTiO3 ceramics occurs through glide of half-partials in the basal plane by a glide-controlled dislocation glide mechanism. Dislocation motion governed by the Peierls mechanism, where velocity is determined by both correlated and uncorrelated double-kink nucleation on two half-partials, is discussed. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Sharp et al paper. To view this article visit https://doi.org/10.1111/apt.13944. [ABSTRACT FROM AUTHOR]

Cytokine release syndrome (CRS) is a significant side-effect of conventional chimeric antigen receptor (CAR) T-cell therapy. To facilitate patient accessibility, short-term (st) CAR T cells, which are administered to patients only 24 h after vector exposure, are in focus of current investigations. Their impact on the incidence and severity of CRS has been poorly explored. Here, we evaluated CD19-specific stCAR T cells in preclinical models. In co-culture with tumor cells and monocytes, stCAR T cells exhibited anti-tumoral activity and potent release of CRS-related cytokines (IL-6, IFN-γ, TNF-α, GM-CSF, IL-2, IL-10). When administered to NSG-SGM3 mice, stCAR T cells, but not conventional CAR T cells, induced severe acute adverse events within 24 h, including hypothermia and weight loss, as well as high body scores, independent of the presence of tumor target cells. Human (IFN-γ, TNF-α, IL-2, IL-10) and murine (MCP-1, IL-6, G-CSF) cytokines, typical for severe CRS, were systemically elevated. Our data highlight potential safety risks of rapidly manufactured CAR T cells and suggest NSG-SGM3 mice as sensitive model for their preclinical safety evaluation., (© 2024. The Author(s).)

Aim: Young people with common mood disorders face the prospect of shortened life expectancy largely due to premature cardiovascular disease. Metabolic dysfunction is a risk factor for premature cardiovascular disease. There is an ongoing debate whether metabolic dysfunction can be simply explained by weight gain secondary to psychotropic medications or whether shared genetic vulnerability, intrinsic immune-metabolic disturbances or other system perturbations (e.g. dysregulated sympathetic nervous system, circadian dysfunction) are more relevant determinants of premature cardiovascular disease. Thus, we aimed to investigate underlying drivers of metabolic dysfunction and premature cardiovascular disease in young people in the early phases of common mood disorders., Methods: We evaluated the relationships between insulin resistance (assessed by HOMA2-IR) and body mass index (BMI), sex, diagnosis, medication, inflammatory markers and hormonal factors in 327 inpatients with emerging affective and major mood disorders admitted to the Young Adult Mental Health Unit, St Vincent's Private Hospital, Sydney., Results: While HOMA2-IR scores were positively associated with BMI (r s  = 0.465, p < .001), they were also higher in those prescribed mood stabilizers (p = .044) but were not associated with specific diagnoses, other medication types or the number of prescribed medications. Further, high-sensitivity C-reactive protein levels (but not thyroid-stimulating hormone and ferritin levels) were positively associated with HOMA2-IR (r s  = 0. 272, p < .001) and BMI (r s  = . 409, p < .001)., Conclusions: In addition to BMI, other non-specific markers of inflammation are associated with early metabolic dysfunction in young people with emerging affective and major mood disorders., (© 2021 John Wiley & Sons Australia, Ltd.)

Aim: Risk algorithms predicting personal mental ill-health will form an important component of digital and personalized preventive interventions, yet it is unknown whether informing people of personal risk may cause unintended harm. This trial evaluated the comparative effect of communicating personal mental ill-health risk profiles on psychological distress., Methods: Australian participants using a mood-monitoring app were randomly allocated to receiving their current personal mental ill-health risk profile (n = 119), their achievable personal risk profile (n = 118) or to a control group (n = 118) in which no risk information was communicated, in a non-inferiority trial design. The primary outcome was psychological distress at four-weeks as assessed on the Kessler Psychological Distress Scale., Results: There was high attrition in the trial with 64% of data missing at follow up. Per-protocol (completer) analysis found that the lower bounds of the confidence intervals of the estimated mean change of the current risk (m = 0.19, 95% CI: -2.59- 2.98) and achievable risk (m = -0.09, 95% CI: -2.84 to 2.66) groups were within the non-inferiority margin of the control group's mean at follow up. Supplementary intention-to-treat analysis using Multivariate Imputation by Chained Equations (MICE) found that 98/100 imputed datasets of the current risk profile group, and all imputed datasets of the achievable risk profile group showed non-inferiority to the control group., Conclusions: This study provides preliminary support that providing personal mental health risk profiles does not lead to unacceptable worsening of distress compared to no risk feedback, although this needs to be replicated in a fully powered RCT., (© 2020 John Wiley & Sons Australia, Ltd.)

The inhibitory effects of furfural and acetic acid on the fermentation of xylose and glucose to ethanol in YEPDX medium by a recombinant Saccharomyces cerevisiae strain (LNH-ST 424A) were investigated. Initial furfural concentrations below 5 g/L caused negligible inhibition to glucose and xylose consumption rates in batch fermentations with high inoculum (4.5-6.0 g/L). At higher initial furfural concentrations (10-15 g/L) the inhibition became significant with xylose consumption rates especially affected. Interactive inhibition between acetic acid and pH were observed and quantified, and the results suggested the importance of conditioning the pH of hydrolysates for optimal fermentation performance. Poplar biomass pretreated by various CAFI processes (dilute acid, AFEX, ARP, SO(2)-catalyzed steam explosion, and controlled-pH) under respective optimal conditions was enzymatically hydrolyzed, and the mixed sugar streams in the hydrolysates were fermented. The 5-hydroxymethyl furfural (HMF) and furfural concentrations were low in all hydrolysates and did not pose negative effects on fermentation. Maximum ethanol productivity showed that 0-6.2 g/L initial acetic acid does not substantially affect the ethanol fermentation with proper pH adjustment, confirming the results from rich media fermentations with reagent grade sugars., ((c) 2009 American Institute of Chemical Engineers Biotechnol.)

Numerous case reports in the literature describe adverse drug events associated with immediate-release nifedipine (IRN). In addition, several publications alerted health care professionals regarding the agent. However, it is still administered, and adverse reactions are still reported. Our patient suffered IRN-induced hypotension, myocardial ischemia, and mental status changes. We recommend that the use of IRN in treatment of hypertension should be either totally prohibited or severely restricted. The product should not be readily available for indiscriminate administration. Also, continuing education and training are required to alert all health care professionals to the serious dangers associated with this drug.