Depressive symptoms in younger women and men with acute myocardial infarction:Insights from the VIRGO Study

BACKGROUND: Depression was recently recognized as a risk factor for adverse medical outcomes in patients with acute myocardial infarction (AMI). The degree to which depression is present among younger patients with an AMI, the patient profile associated with being a young AMI patient with depressive symptoms, and whether relevant sex differences exist are currently unknown. METHODS AND RESULTS: The Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study enrolled 3572 patients with AMI (67.1% women; 2:1 ratio for women to men) between 2008 and 2012 (at 103 hospitals in the United States, 24 in Spain, and 3 in Australia). Information about lifetime history of depression and depressive symptoms experienced over the past 2 weeks (Patient Health Questionnaire; a cutoff score ≥10 was used for depression screening) was collected during index AMI admission. Information on demographics, socioeconomic status, cardiovascular risk, AMI severity, perceived stress (14‐item Perceived Stress Scale), and health status (Seattle Angina Questionnaire, EuroQoL 5D) was obtained through interviews and chart abstraction. Nearly half (48%) of the women reported a lifetime history of depression versus 1 in 4 in men (24%; P<0.0001). At the time of admission for AMI, more women than men experienced depressive symptoms (39% versus 22%, P<0.0001; adjusted odds ratio 1.64; 95% CI 1.36 to 1.98). Patients with more depressive symptoms had higher levels of stress and worse quality of life (P<0.001). Depressive symptoms were more prevalent among patients with lower socioeconomic profiles (eg, lower education, uninsured) and with more cardiovascular risk factors (eg, diabetes, smoking). CONCLUSIONS: A high rate of lifetime history of depression and depressive symptoms at the time of an AMI was observed among younger women compared with men. Depressive symptoms affected those with more vulnerable socioeconomic and clinical profiles

Conceptual framework for personal recovery in patients with acute myocardial infarction

BACKGROUND: Although there has been movement in cardiology to advance patient-centered approaches to postacute myo-cardial infarction (AMI) care, work remains to be done in aligning patient preferences with clinical care. Our objective was to characterize patients’ experience of AMI and treatment to develop a new conceptual framework of patient-centered recovery in cardiology. METHODS AND RESULTS: We conducted in-depth interviews with people who previously experienced an AMI (2016–2019). The interview focused on participants’ experiences of their recovery, which were audio-recorded, transcribed verbatim, and analyzed using a phenomenological framework. The overarching theme described by the 42 participants was feeling like a “different person” after the AMI. This shift manifested itself in both losses and gains, each of which posed new challenges to everyday life. The experience appeared to be an active process requiring people to take responsibility for their health. In terms of loss, participants describe how the AMI threatened their sense of safety and security and led to social isolation, fragility, uncertainty about the future, and difficulty expressing emotions accompanied this new fear. A conceptual framework describ-ing the relationship between AMI, identity change, and functioning was developed. CONCLUSIONS: Participants experienced the AMI as an unexpected disruption in their lives that had far-reaching effects on their daily functioning, and were resolved in numerous ways. The conceptual framework may assist in providing a theoretical basis for future interventions in cardiology that not only engage and retain patients in care but also improve long-term adherence to secondary prevention and other aspects of self-care

Perceived Stress After Acute Myocardial Infarction: A Comparison Between Young and Middle-Aged Women Versus Men

Objective: The aim of the study was to examine how psychological stress changes over time in young and middle-aged patients after experiencing an acute myocardial infarction (AMI) and whether these changes differ between men and women. Methods: We analyzed data obtained from 2358 women and 1151 men aged 18 to 55 years hospitalized for AMI. Psychological stress was measured using the 14-item Perceived Stress Scale (PSS-14) at initial hospitalization and at 1 month and 12 months after AMI. We used linear mixed-effects models to examine changes in PSS-14 scores over time and sex differences in these changes, while adjusting for patient characteristics and accounting for correlation among repeated observations within patients. Results: Overall, patients' perceived stress decreased over time, especially during the first month after AMI. Women had higher levels of perceived stress than men throughout the 12-month period (difference in PSS-14 score = 3.63, 95% confidence interval = 3.08 to 4.18, p < .001), but they did not differ in how stress changed over time. Adjustment for patient characteristics did not alter the overall pattern of sex difference in changes of perceived stress over time other than attenuating the magnitude of sex difference in PSS-14 score (difference between women and men = 1.74, 95% confidence interval = 1.32 to 2.16, p < .001). The magnitude of sex differences in perceived stress was similar in patients with versus without post-AMI angina, even though patients with angina experienced less improvement in PSS-14 score than those without angina. Conclusions: In young and middle-aged patients with AMI, women reported higher levels of perceived stress than men throughout the first 12 months of recovery. However, women and men had a similar pattern in how perceived stress changed over time

Health status outcomes after spontaneous coronary artery dissection and comparison with other acute myocardial infarction: The VIRGO experience.

Data on health status outcomes after spontaneous coronary artery dissection (SCAD) are limited. Using the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study we compared patients with SCAD and other acute myocardial infarction (AMI) at presentation (baseline), 1-month, and-12 months using standardized health status instruments. Among 3572 AMI patients ≤ 55 years, 67 had SCAD. SCAD patients were younger (median age (IQR) 45 (40.5-51) years vs. 48 (44-52) in other AMI, p = 0.003), more often female (92.5% vs. 66.6%), have college education (73.1% vs. 51.7%) and household income >$100,000 (43.3% vs. 17.7% (All p<0.001). SCAD patients at baseline had higher mean ± SD Short Form-12 [SF-12] physical component scores [PCS] (48.7±10.2 vs. 43.8±12.1, p<0.001) and mental component scores [MCS] (49.6±12.4 vs. 45.4±12.5, p = 0.008), and at 12-months [PCS (50.1±9.0 vs. 44.3±12.3, p<0.001) and MCS (53±10.1 vs 50.2±11.0, p = 0.045)]. The Euro-Quality of Life Scale [EQ-5D] VAS and EQ-5D index scores were similar at baseline, but higher at 12-months for SCAD (EQ-5D VAS: 82.2±10.2 vs. 72.3±21.0, p<0.001; EQ-5D index scores; 90.2±15.3 vs. 83.7±19.8, p = 0.012). SCAD patients had better baseline Seattle Angina Questionnaire [SAQ] physical limitation (88.8±20.1 vs. 81.2±25.4, p = 0.017). At 12-months SCAD patients had better physical limitation (98.0±8.5 vs. 91.4±18.8, p = 0.007), angina frequency (96.4±8.8 vs. 91.3±16.8, p = 0.018) and quality of life scores (80.7±14.7 vs 72.2±23.2, p = 0.005). Magnitude of change in health status from baseline to 12-months was not statistically different between the groups. After adjustment for time and comorbidities there remained no difference in most health status outcomes. SCAD patients fare marginally better than other AMI patients on most health status instruments and have similar 12-month health status recovery. Better pre-event health status suggests a need to modify exercise prescriptions and cardiac rehabilitation protocols to better assist this physically active population to recover.The VIRGO study was supported by a 4-year National Heart, Lung, and Blood Institute grant [number 5R01HL081153). IMJOVEN was supported in Spain by grant PI 081614 from the Fondo de Investigaciones Sanitarias del Instituto Carlos III, Ministry of Science and Technology, and additional funds from the Centro Nacional de Investigaciones Cardiovasculares (CNIC).S

Can hysterosalpingo-foam sonography replace hysterosalpingography as first-choice tubal patency test? A randomized non-inferiority trial

Funding Information: The FOAM study was an investigator-initiated study funded by ZonMw, The Netherlands organization for Health Research and Development (project number 837001504). ZonMw funded the whole project. IQ Medical Ventures provided the ExEm-foamVR kits free of charge. The funders had no role in study design, collection, analysis and interpretation of the data. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.Peer reviewedPublisher PD

HNF4A and GATA6 loss reveals therapeutically actionable subtypes in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) can be divided into transcriptomic subtypes with two broad lineages referred to as classical (pancreatic) and squamous. We find that these two subtypes are driven by distinct metabolic phenotypes. Loss of genes that drive endodermal lineage specification, HNF4A and GATA6, switch metabolic profiles from classical (pancreatic) to predominantly squamous, with glycogen synthase kinase 3 beta (GSK3β) a key regulator of glycolysis. Pharmacological inhibition of GSK3β results in selective sensitivity in the squamous subtype; however, a subset of these squamous patient-derived cell lines (PDCLs) acquires rapid drug tolerance. Using chromatin accessibility maps, we demonstrate that the squamous subtype can be further classified using chromatin accessibility to predict responsiveness and tolerance to GSK3β inhibitors. Our findings demonstrate that distinct patterns of chromatin accessibility can be used to identify patient subgroups that are indistinguishable by gene expression profiles, highlighting the utility of chromatin-based biomarkers for patient selection in the treatment of PDAC

Bi-fractional transforms in phase space

The displacement operator is related to the displaced parity operator through a two dimensional Fourier transform. Both operators are important operators in phase space and the trace of both with respect to the density operator gives the Wigner functions (displaced parity operator) and Weyl functions (displacement operator). The generalisation of the parity-displacement operator relationship considered here is called the bi-fractional displacement operator, O(α, β; θα, θβ). Additionally, the bi-fractional displacement operators lead to the novel concept of bi-fractional coherent states. The generalisation from Fourier transform to fractional Fourier transform can be applied to other phase space functions. The case of the Wigner-Weyl function is considered and a generalisation is given, which is called the bi-fractional Wigner functions, H(α, β; θα, θβ). Furthermore, the Q−function and P−function are also generalised to give the bi-fractional Q−functions and bi-fractional P−functions respectively. The generalisation is likewise applied to the Moyal star product and Berezin formalism for products of non-commutating operators. These are called the bi-fractional Moyal star product and bi-fractional Berezin formalism. Finally, analysis, applications and implications of these bi-fractional transforms to the Heisenberg uncertainty principle, photon statistics and future applications are discussed

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P &lt; 0.001) and PARP inhibitor therapy (P &lt; 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P &lt; 0.018) and WEE1 inhibitor (P &lt; 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P &lt; 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe