The role of visual spatial frequencies in newborns' processing of dynamic facial expressions of emotion.

Evidence on newborns' discrimination of emotional facial expressions is scarce, and the question of what is the nature of the visual information that newborns rely on to perform such discrimination remains open. Here, we manipulated the spatial frequency (SF) content of the stimuli by selectively removing low spatial frequency (LSF) and high spatial frequency bands using newborn-appropriate cutoffs to investigate what information newborns use when preferring and discriminating between dynamic displays showing happy and fearful expressions unfolding over time. Using a preferential looking paradigm, in Study 1 (N = 63, 59% females, 92% White), we showed that newborns looked longer to happy over fearful expressions in unfiltered (broad spatial frequency) and high-pass (high spatial frequency > 0.6 cycles per degree [cpd]) faces but not in low-pass (LSF < 0.5 cpd) faces. In Study 2 (N = 22, 59% females, 91% White), newborns tested in a visual habituation paradigm showed successful discrimination of the two LSF emotions. Results show that newborns can discriminate between dynamic images of happy and fearful facial expressions containing either extreme low SF (< 0.5 cpd) information or higher SF (> 0.6 cpd) bandwidth. Their preference for the happy expression was present for intact and high-pass filtered faces but not for low-pass faces. This SF effect is tentatively driven by an enhancement of attentional response to the LSF fearful face, whereas the response to the happy face is unaffected by the SF manipulation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

HER2-Low Expression in Male Breast Cancer: Results from a Multicenter Series in Italy.

In the field of breast cancer care, a significant breakthrough has occurred with the recognition of HER2-low expression as a target for novel anti-HER2 antibody-drug conjugates (ADC). This discovery is reshaping the treatment landscape, challenging previous perceptions that considered HER2-low as clinically insignificant. The ability to target HER2-low expression is expected to have substantial clinical implications, irrespective of gender, including in cases of male breast cancer (MBC). However, an estimate of the prevalence of the HER2-low subtype in MBC is missing. This retrospective, observational, multicenter study was aimed at characterizing the HER2-low subtype in MBC. For the purpose of this study, the three-tiered categorization of HER2 (HER2-0, HER2-low, and HER2-positive) was used to reclassify the HER2-negative group into HER-0 or HER2-low subtypes. In the whole series of 144 invasive MBCs, 79 (54.9%) were HER2-0 (IHC scores of 0), 39 (27.1%) HER2-low (IHC scores of 1+/2+ with negative ISH), and 26 (18.0%) HER2-positive (IHC scores of 3+/2+ with positive ISH). Specifically, among hormone receptor-positive (HR+) HER2-negative invasive MBCs, 34.8% were HER2-low and 65.2% HER2-0. Compared with HER2-0, HER2-low subtype was associated with a positive lymph node involvement (p = 0.01). Other pathologic characteristics including histology, staging, and grading did not show notable variations between the two subtypes. The presence of germline BRCA1/2 pathogenic variants (PVs) did not significantly differ between HER2-0 and HER2-low MBCs. However, about 13% of HER2-low MBCs had germline PVs in BRCA1/2 genes, mainly BRCA2, a clinically relevant observation in the context of combined target therapy. Overall, our data, which focused on the largest gender-specific breast cancer series, to our knowledge, confirm that the emerging three-tiered categorization of HER2 (HER2-0, HER2-low, and HER2-positive) can also be considered in MBC, to mitigate both the gender gap and the underrepresentation of males in clinical trials.

Gender-Specific Genetic Predisposition to Breast Cancer: BRCA Genes and Beyond.

Among neoplastic diseases, breast cancer (BC) is one of the most influenced by gender. Despite common misconceptions associating BC as a women-only disease, BC can also occur in men. Additionally, transgender individuals may also experience BC. Genetic risk factors play a relevant role in BC predisposition, with important implications in precision prevention and treatment. The genetic architecture of BC susceptibility is similar in women and men, with high-, moderate-, and low-penetrance risk variants; however, some sex-specific features have emerged. Inherited high-penetrance pathogenic variants (PVs) in BRCA1 and BRCA2 genes are the strongest BC genetic risk factor. BRCA1 and BRCA2 PVs are more commonly associated with increased risk of female and male BC, respectively. Notably, BRCA-associated BCs are characterized by sex-specific pathologic features. Recently, next-generation sequencing technologies have helped to provide more insights on the role of moderate-penetrance BC risk variants, particularly in PALB2, CHEK2, and ATM genes, while international collaborative genome-wide association studies have contributed evidence on common low-penetrance BC risk variants, on their combined effect in polygenic models, and on their role as risk modulators in BRCA1/2 PV carriers. Overall, all these studies suggested that the genetic basis of male BC, although similar, may differ from female BC. Evaluating the genetic component of male BC as a distinct entity from female BC is the first step to improve both personalized risk assessment and therapeutic choices of patients of both sexes in order to reach gender equality in BC care. In this review, we summarize the latest research in the field of BC genetic predisposition with a particular focus on similarities and differences in male and female BC, and we also discuss the implications, challenges, and open issues that surround the establishment of a gender-oriented clinical management for BC.

Touch me or touch me not: Emotion regulation by affective touch in human adults.

In mammals, including humans, affective touch (AT) supports the establishment and maintenance of social connections and mitigates the effects of social conflict and ostracism. AT is used to describe slowly moving, low-forced mechanical stimulation that is frequently perceived as pleasant. In humans, AT has been addressed particularly for its role in promoting bonding and emotional regulation during early development; however, more recent studies have suggested that AT also preserves physical and emotional well-being in adulthood. Here, we investigated whether AT can buffer adults' experience of negative emotions as reflected in their behavioral and physiological responses to emotionally arousing stimuli. Participants were stimulated on their forearms using AT or tapping (T) while they viewed a series of emotionally arousing and neutral images, and we measured their skin conductance response and their explicit rating of the images' unpleasantness. We found that AT, but not T, reduced the arousal and perceived unpleasantness of the emotional stimuli but not the neutral ones, revealing the soothing role of AT in emotional contexts. The second aim of the study was to explore the possibility that AT might benefit some individuals more than others, according to their individual differences. To this aim, we assessed individuals' empathy and sensory processing sensitivity, as well as their perception of AT itself. Results revealed that while empathy did not predict changes in emotional processing irrespective of tactile stimulation, individuals with higher sensitivity reported AT as less pleasant. We discuss the possible factors mediating the observed interindividual variability in AT perception. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Mitral annular disjunction and Pickelhaube sign in children with mitral valve prolapse: A prospective cohort study.

BACKGROUND: Mitral annular disjunction (MAD) and the Pickelhaube sign are identified as risk factors for malignant ventricular arrhythmias (VAs) and sudden cardiac death in adults with mitral valve prolapse (MVP); their prevalence and consequences in children have never been studied. OBJECTIVES: To determine the proportion of MAD in children with MVP, and its potential link with VAs. METHODS: A cohort of 49 consecutive children (mean age 12.8±3.0 years; 33 females) with MVP and comprehensive clinical arrhythmia (24-hour monitoring) and Doppler echocardiographic characterization, including pulsed-wave tissue Doppler (PWTD) of the lateral mitral annulus, was identified. The relationship between clinical and echocardiographic data and presence of VAs was studied. RESULTS: MAD was common (n=25; 51%). Only five patients had significant VAs (Lown grade>2) characterized by polymorphic premature ventricular contractions or couplets. MAD was not associated with VAs on 24-hour Holter monitoring, but an association was found between VAs and spiked high-velocity midsystolic signal>16cm/s on PWTD (Pickelhaube sign) (P=0.004), myxomatous mitral valve (P=0.004) and left ventricular dilatation (P=0.01). T-wave inversion in inferolateral leads on electrocardiogram was more frequent in patients with versus without the Pickelhaube sign (P=0.03). No difference was found between patients with or without MAD regarding sex, history of palpitation, severity of mitral regurgitation, aortic root diameter and incidence of connective tissue disorders. Myocardial fibrosis was detected in two of three patients who underwent a complementary cardiac magnetic resonance examination. CONCLUSIONS: MAD is common in children with MVP; its presence was not associated with significant VAs on 24-hour Holter monitoring, but the Pickelhaube sign and presence of myxomatous mitral valve may help to detect patients prone to significant VAs. Myocardial fibrosis can be detected by cardiac magnetic resonance in children with significant VAs.

Male breast cancer risk associated with pathogenic variants in genes other than BRCA1/2: an Italian case-control study.

BACKGROUND: Germline pathogenic variants (PVs) in BRCA1/2 genes are associated with breast cancer (BC) risk in both women and men. Multigene panel testing is being increasingly used for BC risk assessment, allowing the identification of PVs in genes other than BRCA1/2. While data on actionable PVs in other cancer susceptibility genes are now available in female BC, reliable data are still lacking in male BC (MBC). This study aimed to provide the patterns, prevalence and risk estimates associated with PVs in non-BRCA1/2 genes for MBC in order to improve BC prevention for male patients. METHODS: We performed a large case-control study in the Italian population, including 767 BRCA1/2-negative MBCs and 1349 male controls, all screened using a custom 50 cancer gene panel. RESULTS: PVs in genes other than BRCA1/2 were significantly more frequent in MBCs compared with controls (4.8% vs 1.8%, respectively) and associated with a threefold increased MBC risk (OR: 3.48, 95% CI: 1.88-6.44; p < 0.0001). PV carriers were more likely to have personal (p = 0.03) and family (p = 0.02) history of cancers, not limited to BC. PALB2 PVs were associated with a sevenfold increased MBC risk (OR: 7.28, 95% CI: 1.17-45.52; p = 0.034), and ATM PVs with a fivefold increased MBC risk (OR: 4.79, 95% CI: 1.12-20.56; p = 0.035). CONCLUSIONS: This study highlights the role of PALB2 and ATM PVs in MBC susceptibility and provides risk estimates at population level. These data may help in the implementation of multigene panel testing in MBC patients and inform gender-specific BC risk management and decision making for patients and their families.

Sensitivity to trustworthiness cues in own- and other-race faces: The role of spatial frequency information.

Research has shown that adults are better at processing faces of the most represented ethnic group in their social environment compared to faces from other ethnicities, and that they rely more on holistic/configural information for identity discrimination in own-race than other-race faces. Here, we applied a spatial filtering approach to the investigation of trustworthiness perception to explore whether the information on which trustworthiness judgments are based differs according to face race. European participants (N = 165) performed an online-delivered pairwise preference task in which they were asked to select the face they would trust more within pairs randomly selected from validated White and Asian broad spectrum, low-pass filter and high-pass filter trustworthiness continua. Results confirmed earlier demonstrations that trustworthiness perception generalizes across face ethnicity, but discrimination of trustworthiness intensity relied more heavily on the LSF content of the images for own-race faces compared to other-race faces. Results are discussed in light of previous work on emotion discrimination and the hypothesis of overlapping perceptual mechanisms subtending social perception of faces.

A Possible Link between Gut Microbiome Composition and Cardiovascular Comorbidities in Psoriatic Patients.

Cardiovascular disease (CVD) is one of the most common comorbidities that may affect psoriatic patients. Several exogenous and endogenous factors are involved in the etiology and progression of both psoriasis and CVD. A potential genetic link between the two diseases has emerged; however, some gaps remain in the understanding of the CVD prevalence in psoriatic patients. Recently, the role of the gut microbiome dysbiosis was documented in the development and maintenance of both diseases. To investigate whether gut microbiome dysbiosis might influence the occurrence of CVD in psoriatic patients, 16S rRNA gene sequencing was performed to characterize the gut microbiome of 28 psoriatic patients, including 17 patients with and 11 without CVD. The comparison of the gut microbiome composition between patients with and without CVD showed a higher prevalence of Barnesiellaceae and Phascolarctobacterium in patients with CVD. Among patients with CVD, those undergoing biologic therapy had lower abundance levels of Barnesiellaceae, comparable to those found in patients without CVD. Overall, these findings suggest that the co-occurrence of psoriasis and CVD might be linked to gut microbiome dysbiosis and that therapeutic strategies could help to restore the intestinal symbiosis, potentially improving the clinical management of psoriasis and its associated comorbidities.

Germline Aberrations in Pancreatic Cancer: Implications for Clinical Care.

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis and represents a major public health issue, as both its incidence and mortality are expecting to increase steeply over the next years. Effective screening strategies are lacking, and most patients are diagnosed with unresectable disease precluding the only chance of cure. Therapeutic options for advanced disease are limited, and the treatment paradigm is still based on chemotherapy, with a few rare exceptions to targeted therapies. Germline variants in cancer susceptibility genes-particularly those involved in mechanisms of DNA repair-are emerging as promising targets for PDAC treatment and prevention. Hereditary PDAC is part of the spectrum of several syndromic disorders, and germline testing of PDAC patients has relevant implications for broad cancer prevention. Germline aberrations in BRCA1 and BRCA2 genes are predictive biomarkers of response to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor olaparib and platinum-based chemotherapy in PDAC, while mutations in mismatch repair genes identify patients suitable for immune checkpoint inhibitors. This review provides a timely and comprehensive overview of germline aberrations in PDAC and their implications for clinical care. It also discusses the need for optimal approaches to better select patients for PARP inhibitor therapy, novel therapeutic opportunities under clinical investigation, and preclinical models for cancer susceptibility and drug discovery.

Distribution of Interferon Lambda 4 Single Nucleotide Polymorphism rs11322783 Genotypes in Patients with COVID-19.

Type III interferons (IFN-III), also known as IFN-Lambda, have a pivotal role during SARS-CoV-2 infection. IFN-Lambda response among individuals is heterogeneous and its association with COVID-19 symptoms severity needs to be further clarified. We analyzed the genotype frequencies of IFNL4 single nucleotide polymorphism (SNP) rs11322783 in patients with COVID-19 (n = 128), in comparison with a validated data set of European healthy controls (n = 14152). The IFNL4 SNP was also analyzed according to the haematological and clinical parameters of patients with COVID-19. The distributions of IFNL4 genotypes among SARS-CoV-2 positive patients [TT/TT 41.4% (n = 53), TT/ΔG 47.7% (n = 61) and ΔG/ΔG 10.9% (n = 14)] and healthy controls were comparable. Different levels of white blood cells (p = 0.036) and neutrophils (p = 0.042) were found in the IFNL4 different genotypes in patients with COVID-19; the ΔG/ΔG genotype was more represented in the groups with low white blood cells and neutrophils. There were no differences in major inflammation parameters (C-reactive protein, D-dimer, Albumin, and Lactate-dehydrogenase (LDH)] and survival rate according to the IFNL4 genotypes. In conclusion, although patients with COVID-19 did not exhibit a different distribution of the IFNL4 SNP, the ΔG/ΔG genotype was associated with a lower count of immune cell populations. These findings need to be confirmed in larger groups of patients with COVID-19 and the role of IFNL4 SNP needs to be also investigated in other respiratory viral infections.

Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants.

PURPOSE: To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management. METHODS: We used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment. RESULTS: BRCA1 PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers. CONCLUSION: In addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs.

Face in collision: emotional looming stimuli modulate interpersonal space across development and gender.

Basic visual functions have evolved to allow for rapid detection of dynamic stimuli in our surrounding environment. In particular, looming stimuli are of relevance because they are expected to enter the individual's interpersonal space representing a potential threat. Different studies showed that emotions can modulate the perception of visual looming stimuli and the borders of interpersonal space, defined as the area around the body that individuals maintain between themselves and others during social interactions. Here, we investigated how emotions modulate the perception and the physiological correlates of interpersonal space and whether such indexes change across age and gender. Children and adults were asked to quickly react to emotional looming stimuli while measuring their skin conductance response (SCR). We found that emotional looming stimuli shrink the borders of interpersonal space of males more than females, and that this pattern does not change with age. In addition, adults reacted faster to angry than happy and neutral faces, which is in line with the notion that threatening stimuli capture attention more quickly than other types of emotional stimuli. However, this was not observed in children, suggesting that experience with negative stimuli, rather than the evolutionary meaning they possess, may influence the boundaries of interpersonal space. Overall, our study suggests that interpersonal space is modulated by emotions, but this appears to be modulated by gender and age: while behavioural responses to emotional looming stimuli refine with age, physiological responses are adult-like as early as 5 years of age.

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores.

BACKGROUND: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. METHODS: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. RESULTS: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. CONCLUSIONS: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.

Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology.

Introduction: Compared with breast cancer (BC) in women, BC in men is a rare disease with genetic and molecular peculiarities. Therapeutic approaches for male BC (MBC) are currently extrapolated from the clinical management of female BC, although the disease does not exactly overlap in males and females. Data on specific molecular biomarkers in MBC are lacking, cutting out male patients from more appropriate therapeutic strategies. Growing evidence indicates that Next Generation Sequencing (NGS) multigene panel testing can be used for the detection of predictive molecular biomarkers, including Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI). Methods: In this study, NGS multigene gene panel sequencing, targeting 1.94 Mb of the genome at 523 cancer-relevant genes (TruSight Oncology 500, Illumina), was used to identify and characterize somatic variants, Copy Number Variations (CNVs), TMB and MSI, in 15 Formalin-Fixed Paraffin-Embedded (FFPE) male breast cancer samples. Results and discussion: A total of 40 pathogenic variants were detected in 24 genes. All MBC cases harbored at least one pathogenic variant. PIK3CA was the most frequently mutated gene, with six (40.0%) MBCs harboring targetable PIK3CA alterations. CNVs analysis showed copy number gains in 22 genes. No copy number losses were found. Specifically, 13 (86.7%) MBCs showed gene copy number gains. MYC was the most frequently amplified gene with eight (53.3%) MBCs showing a median fold-changes value of 1.9 (range 1.8-3.8). A median TMB value of 4.3 (range 0.8-12.3) mut/Mb was observed, with two (13%) MBCs showing high-TMB. The median percentage of MSI was 2.4% (range 0-17.6%), with two (13%) MBCs showing high-MSI. Overall, these results indicate that NGS multigene panel sequencing can provide a comprehensive molecular tumor profiling in MBC. The identification of targetable molecular alterations in more than 70% of MBCs suggests that the NGS approach may allow for the selection of MBC patients eligible for precision/targeted therapy.

Bone density and genomic analysis unfold cold adaptation mechanisms of ancient inhabitants of Tierra del Fuego.

The Fuegians, ancient inhabitants of Tierra del Fuego, are an exemplary case of a cold-adapted population, since they were capable of living in extreme climatic conditions without any adequate clothing. However, the mechanisms of their extraordinary resistance to cold remain enigmatic. Brown adipose tissue (BAT) plays a crucial role in this kind of adaptation, besides having a protective role on the detrimental effect of low temperatures on bone structure. Skeletal remains of 12 adult Fuegians, collected in the second half of XIX century, were analyzed for bone mineral density and structure. We show that, despite the unfavorable climate, bone mineral density of Fuegians was close to that seen in modern humans living in temperate zones. Furthermore, we report significant differences between Fuegians and other cold-adapted populations in the frequency of the Homeobox protein Hox-C4 (HOXC4) rs190771160 variant, a gene involved in BAT differentiation, whose identified variant is predicted to upregulate HOXC4 expression. Greater BAT accumulation might therefore explain the Fuegians extreme cold-resistance and the protection against major cold-related damage. These results increase our understanding of how ecological challenges have been important drivers of human-environment interactions during Humankind history.

Transcriptome of Male Breast Cancer Matched with Germline Profiling Reveals Novel Molecular Subtypes with Possible Clinical Relevance.

Male breast cancer (MBC) is a rare and understudied disease compared with female BC. About 15% of MBCs are associated with germline mutation in BC susceptibility genes, mainly BRCA1/2 and PALB2. Hereditary MBCs are likely to represent a subgroup of tumors with a peculiar phenotype. Here, we performed a whole transcriptome analysis of MBCs characterized for germline mutations in the most relevant BC susceptibility genes in order to identify molecular subtypes with clinical relevance. A series of 63 MBCs, including 16 BRCA2, 6 BRCA1, 2 PALB2, 1 RAD50, and 1 RAD51D germline-mutated cases, was analyzed by RNA-sequencing. Differential expression and hierarchical clustering analyses were performed. Module signatures associated with central biological processes involved in breast cancer pathogenesis were also examined. Different transcriptome profiles for genes mainly involved in the cell cycle, DNA damage, and DNA repair pathways emerged between MBCs with and without germline mutations. Unsupervised clustering analysis revealed two distinct subgroups, one of which was characterized by a higher expression of immune response genes, high scores of gene-expression signatures suggestive of aggressive behavior, and worse overall survival. Our results suggest that transcriptome matched with germline profiling may be a valuable approach for the identification and characterization of MBC subtypes with possible relevance in the clinical setting.

60-S Retrogated Compressed Sensing 2D Cine of the Heart: Sharper Borders and Accurate Quantification.

BACKGROUND AND OBJECTIVE: Real-time compressed sensing cine (CSrt) provides reliable quantification for both ventricles but may alter image quality. The aim of this study was to assess image quality and the accuracy of left (LV) and right ventricular (RV) volumes, ejection fraction and mass quantifications based on a retrogated segmented compressed sensing 2D cine sequence (CSrg). METHODS: Thirty patients were enrolled. Each patient underwent the reference retrogated segmented steady-state free precession cine sequence (SSFPref), the real-time CSrt cine and the segmented retrogated prototype CSrg sequence providing the same slices. Functional parameters quantification and image quality rating were performed on SSFPref and CSrg images sets. The edge sharpness, which is an estimate of the edge spread function, was assessed for the three sequences. RESULTS: The mean scan time was: SSFPref = 485.4 ± 83.3 (SD) s (95% CI: 454.3-516.5) and CSrg = 58.3 ± 15.1 (SD) s (95% CI: 53.7-64.2) (p < 0.0001). CSrg subjective image quality score (median: 4; range: 2-4) was higher than the one provided by CSrt (median: 3; range: 2-4; p = 0.0008) and not different from SSFPref overall quality score (median: 4; range: 2-4; p = 0.31). CSrg provided similar LV and RV functional parameters to those assessed with SSFPref (p > 0.05). Edge sharpness was significantly better with CSrg (0.083 ± 0.013 (SD) pixel-1; 95% CI: 0.078-0.087) than with CSrt (0.070 ± 0.011 (SD) pixel-1; 95% CI: 0.066-0.074; p = 0.0004) and not different from the reference technique (0.075 ± 0.016 (SD) pixel-1; 95% CI: 0.069-0.081; p = 0.0516). CONCLUSIONS: CSrg cine provides in one minute an accurate quantification of LV and RV functional parameters without compromising subjective and objective image quality.

Pre-diagnostic DNA methylation patterns differ according to mammographic breast density amongst women who subsequently develop breast cancer: a case-only study in the EPIC-Florence cohort.

PURPOSE: Mammographic breast density (MBD) is a marker of increased breast cancer (BC) risk, yet much remains to be clarified about the underlying mechanisms. We investigated whether DNA methylation patterns differ between high- vs. low-MBD women who developed BC during an 8.9-year median follow-up in the Florence section of the European Prospective Investigation into Cancer and Nutrition. METHODS: We analysed 96 pairs of women with BC arising on high- vs. low-MBD breasts (BI-RADS category III-IV vs. I). DNA methylation was determined on pre-diagnostic blood samples using the Illumina Infinium MethylationEPIC BeadChip assay. The statistical analysis was conducted by performing an epigenome-wide association study (EWAS), by searching differentially methylated regions (DMRs) in gene promoters (followed by functional enrichment and gene annotation analysis); and through a "candidate pathways" approach focusing on pre-defined inflammation-related pathways. RESULTS: In EWAS, no single CpG site was differentially methylated between high- and low-MBD women after correction for multiple testing. A total of 140 DMRs were identified, of which 131 were hyper- and 9 hypo-methylated amongst high-MBD women. These DMRs encompassed an annotation cluster of 35 genes coding for proteins implicated in transcription regulation and DNA binding. The "apoptosis signalling" was the only inflammation-related candidate pathway differentially methylated between high- and low-MBD women. CONCLUSION: Pre-diagnostic methylation patterns differ between high- vs. low-MBD women who subsequently develop BC, particularly, in genes involved in the regulation of DNA transcription and cell apoptosis. Our study provides novel clues about the mechanisms linking MBD and BC.

Right Ventricular Volume and Function Assessment in Congenital Heart Disease Using CMR Compressed-Sensing Real-Time Cine Imaging.

BACKGROUND AND OBJECTIVE: To evaluate the reliability of compressed-sensing (CS) real-time single-breath-hold cine imaging for quantification of right ventricular (RV) function and volumes in congenital heart disease (CHD) patients in comparison with the standard multi-breath-hold technique. METHODS: Sixty-one consecutive CHD patients (mean age = 22.2 ± 9.0 (SD) years) were prospectively evaluated during either the initial work-up or after repair. For each patient, two series of cine images were acquired: first, the reference segmented multi-breath-hold steady-state free-precession sequence (SSFPref), including a short-axis stack, one four-chamber slice, and one long-axis slice; then, an additional real-time compressed-sensing single-breath-hold sequence (CSrt) providing the same slices. Two radiologists independently assessed the image quality and RV volumes for both techniques, which were compared using the Wilcoxon test and paired Student's t test, Bland-Altman, and linear regression analyses. The visualization of wall-motion disorders and tricuspid-regurgitation-related signal voids were also analyzed. RESULTS: The mean acquisition time for CSrt was 22.4 ± 6.2 (SD) s (95% CI: 20.8-23.9 s) versus 442.2 ± 89.9 (SD) s (95% CI: 419.2-465.2 s) for SSFPref (p < 0.001). The image quality of CSrt was diagnostic in all examinations and was mostly rated as good (n = 49/61; 80.3%). There was a high correlation between SSFPref and CSrt images regarding RV ejection fraction (49.8 ± 7.8 (SD)% (95% CI: 47.8-51.8%) versus 48.7 ± 8.6 (SD)% (95% CI: 46.5-50.9%), respectively; r = 0.94) and RV end-diastolic volume (192.9 ± 60.1 (SD) mL (95% CI: 177.5-208.3 mL) versus 194.9 ± 62.1 (SD) mL (95% CI: 179.0-210.8 mL), respectively; r = 0.98). In CSrt images, tricuspid-regurgitation and wall-motion disorder visualization was good (area under receiver operating characteristic curve (AUC) = 0.87) and excellent (AUC = 1), respectively. CONCLUSIONS: Compressed-sensing real-time cine imaging enables, in one breath hold, an accurate assessment of RV function and volumes in CHD patients in comparison with standard SSFPref, allowing a substantial improvement in time efficiency.