Miracle-dz/UniFAR-FTUs huggingface dataset:
Female-specific risk factors of parity and menopause age and risk of carotid plaque: the multi-ethnic study of atherosclerosis.

BACKGROUND Female-specific factors of grand multiparity (≥5 births) and early menopause age are associated with an increased risk of cardiovascular disease (CVD). However, mechanisms are incompletely understood. Carotid plaque is a marker of subclinical atherosclerosis and associated with increased CVD risk. We evaluated the association of female-specific factors with plaque burden. METHODS We included 2,313 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis, free of clinical CVD, whose parity and menopause age were ascertained by questionnaires and carotid plaque measured by ultrasound at baseline and 10 years later. Parity was categorized as nulliparity (reference), 1-2, 3-4 and ≥5 live births. Menopause age was categorized as <45, 45-49, 50-54 (reference) and ≥55 years. Multivariable regression was performed to evaluate the association of parity and menopause age with carotid plaque presence (yes/no) and extent [carotid plaque score (CPS)]. RESULTS The mean age was 64±9 years; 52.3% had prevalent carotid plaque at baseline. Compared to nulliparity, grand multiparity was significantly associated with prevalent carotid plaque after adjustment for CVD risk factors (prevalence ratio 1.17 (95% CI 1.03-1.35)) and progression of CPS over 10 years [percent difference 13% (95% CI 3-23)]. There was not any significant association of menopause age with carotid plaque presence or progression in fully-adjusted models. CONCLUSION In a multiethnic cohort, grand multiparity was independently associated with carotid plaque presence and progression. Early menopause, a known risk factor for CVD, was not captured by carotid plaque in this study. These findings may have implications for refining CVD risk assessment in women.
Whose Approval Matters Most? Examining Discrepancies in Self- and Other- Perceptions of Drinking

Abstract Background Research demonstrates that perceptions of others’ attitudes toward drinking behaviors (injunctive norms) are strong predictors of alcohol consumption and problems. Personalized normative feedback (PNF) aims to reduce the discrepancy between one’s perception of others’ attitudes toward drinking and others’ actual attitudes toward drinking. An implicit assumption of PNF is that self and (perceived) other attitudes toward drinking are aligned (thus, shifting one’s perceptions of others’ attitudes shifts one’s own attitudes). However, there is minimal research on the extent to which alignment (or discrepancy) in self-other attitudes toward drinking is associated with alcohol-related outcomes. Methods College students (N = 1,494; M age = 20.11, 61.0% female, 66.4% White) who endorsed past-month heavy episodic drinking reported injunctive norms toward drinking on weekends, drinking daily, drinking to black out, and drinking and driving. Participants reported their perceptions of attitudes toward these drinking behaviors for three reference groups: close friends, typical university-affiliated peers, and parents. Outcomes included weekly drinking, alcohol problems, and alcohol-related risk. Results Response surface analyses indicated that alignment in approval (versus alignment in disapproval) of drinking demonstrated a linear association with alcohol-related outcomes. Discrepancies in self-peer and self-parent attitudes were associated with alcohol-related outcomes and one’s own attitudes (versus one’s ratings of others’ attitudes) of drinking were more strongly associated with outcomes. Conclusions Results provide evidence of how self-other discrepancies in attitudes toward drinking are associated with alcohol-related outcomes. Future work is needed to test whether self-other discrepancies in attitudes toward drinking impacts response to norms-based interventions.
The Effect of nutritional supplementation on subjective and objective measures of visual and retinal function : a random controlled trial

In industrialised countries age-related macular disease (ARMD) is the leading cause of visual loss in older people. Because oxidative stress is purported to be associated with an increased risk of disease development the role of antioxidant supplementation is of interest. Lutein is a carotenoid antioxidant that accumulates within the retina and is thought to filter blue light. Increased levels of lutein have been associated with reduced risk of developing ARMD and improvements in visual and retinal function in eyes with ARMD. The aim of this randomised controlled trial (RCT) was to investigate the effect of a lutein-based nutritional supplement on subjective and objective measures of visual function in healthy eyes and in eyes with age-related maculopathy (ARM) – an early form of ARMD. Supplement withdrawal effects were also investigated. A sample size of 66 healthy older (HO), healthy younger (HY), and ARM eyes were randomly allocated to receive a lutein-based supplement or no treatment for 40 weeks. The supplemented group then stopped supplementation to look at the effects of withdrawal over a further 20 weeks. The primary outcome measure was multifocal electroretinogram (mfERG) N1P1 amplitude. Secondary outcome measures were mfERG N1, P1 and N2 latency, contrast sensitivity (CS), Visual acuity (VA) and macular pigment optical density (MPOD). Sample sizes were sufficient for the RCT to have an 80% power to detect a significant clinical effect at the 5% significance level for all outcome measures when the healthy eye groups were combined, and CS, VA and mfERG in the ARM group. This RCT demonstrates significant improvements in MPOD in HY and HO supplemented eyes. When HY and HO supplemented groups were combined, MPOD improvements were maintained, and mfERG ring 2 P1 latency became shorter. On withdrawal of the supplement mfERG ring 1 N1P1 amplitude reduced in HO eyes. When HO and HY groups were combined, mfERG ring 1 and ring 2 N1P1 amplitudes were reduced. In ARM eyes, ring 3 N2 latency and ring 4 P1 latency became longer. These statistically significant changes may not be clinically significant. The finding that a lutein-based supplement increases MPOD in healthy eyes, but does not increase mfERG amplitudes contrasts with the CARMIS study and contributes to the debate on the use of nutritional supplementation in ARM.
The diagnostic likelihood ratio function and modified test for trend: Identifying, evaluating, and validating nontraditional biomarkers in case‐control studies

The ROC curve and its associated summary statistic, the AUC, are used to identify informative diagnostic biomarkers under the assumption that risk of disease is a monotone function of the biomarker. We refer to biomarkers that meet this assumption as traditional, and those that do not as nontraditional. Nontraditional biomarkers most often arise when both low and high biomarker values are associated with an outcome of interest, such as blood pressure with medical complications or leukocyte count with ICU prognosis. Since nontraditional biomarkers do not meet the assumptions for ROC‐based analyses, we propose using the discrete diagnostic likelihood ratio (DLR) function to evaluate a wider class of informative biomarkers. We obtain the DLR function using the multinomial logistic regression (MLR) model to improve upon existing estimation techniques, and implement a likelihood ratio test to identify candidate informative traditional and nontraditional biomarkers. We propose a modification of the Cochran‐Armitage test for trend that separates biomarkers deemed informative into traditional and nontraditional categories. The statistical properties of the likelihood ratio test and modified test for trend are explored under simulation. Together, these methods achieve the identification, evaluation, and validation of biomarkers from early discovery research. Finally, we show that incorporating covariates into the MLR model results in a covariate‐adjusted DLR function that is useful for integrating multiple sources of information in clinical decision making. The methods are applied to gene expression data from subjects with high grade serous ovarian cancer, where stage, early stage vs late stage, is the outcome of interest.
Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein elicits antibodies targeting a membrane-proximal epitope

ABSTRACT Respiratory syncytial virus (RSV) causes tens of millions of acute lower respiratory tract infections and millions of hospital admissions globally each year. An antibody repertoire analysis of a human vaccine trial investigating a prefusion-stabilized RSV fusion (F) glycoprotein antigen (DS-Cav1) identified several neutralizing antibody public clonotypes (PCs) in multiple vaccine recipients. Of these, PCs 1 and 2 were found in six out of six and five out of six vaccine recipients, respectively. Whereas PC1 was shown to bind antigenic site V, the binding site and mechanism of action for PC2 were not defined. Here, we expressed and characterized six antibodies from PC2 and one PC2-like antibody, which we found to be prefusion-specific, possess nanomolar affinity for RSV F, and display neutralization IC50s of 20–81 ng/mL. Cryo-EM studies for the RSV F:PC2 Fab complex resulted in a 2.7 Å resolution reconstruction, which shows that this clonotype simultaneously recognizes antigenic site I and an uncharacterized, prefusion-F-specific antigenic site consisting of the membrane-proximal stalk of RSV F. Taken together, our results suggest that immunization with DS-Cav1 boosts the production of neutralizing antibodies that target a previously uncharacterized epitope in a newly designated antigenic site VI. IMPORTANCE Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants, infecting all children by age 5. RSV also causes substantial morbidity and mortality in older adults, and a vaccine for older adults based on a prefusion-stabilized form of the viral F glycoprotein was recently approved by the FDA. Here, we investigate a set of antibodies that belong to the same public clonotype and were isolated from individuals vaccinated with a prefusion-stabilized RSV F protein. Our results reveal that these antibodies are highly potent and recognize a previously uncharacterized antigenic site on the prefusion F protein. Vaccination with prefusion RSV F proteins appears to boost the elicitation of these neutralizing antibodies, which are not commonly elicited by natural infection. Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants, infecting all children by age 5. RSV also causes substantial morbidity and mortality in older adults, and a vaccine for older adults based on a prefusion-stabilized form of the viral F glycoprotein was recently approved by the FDA. Here, we investigate a set of antibodies that belong to the same public clonotype and were isolated from individuals vaccinated with a prefusion-stabilized RSV F protein. Our results reveal that these antibodies are highly potent and recognize a previously uncharacterized antigenic site on the prefusion F protein. Vaccination with prefusion RSV F proteins appears to boost the elicitation of these neutralizing antibodies, which are not commonly elicited by natural infection.
Cell‐free protein synthesis system: A new frontier for sustainable biotechnology‐based products

Cell‐free protein synthesis (CFPS) system is an innovative technology with a wide range of potential applications that could challenge current thinking and provide solutions to environmental and health issues. CFPS system has been demonstrated to be a successful way of producing biomolecules in a variety of applications, including the biomedical industry. Although there are still obstacles to overcome, its ease of use, versatility, and capacity for integration with other technologies open the door for it to continue serving as a vital instrument in synthetic biology research and industry. In this review, we mainly focus on the cell‐free based platform for various product productions. Moreover, the challenges in the bio‐therapeutic aspect using cell‐free systems and their future prospective for the improvement and sustainability of the cell free systems.
Mediation effect of anxious attachment on relationship between childhood trauma and suicidal ideation sensitive to psychological pain levels

Abstract Background Childhood trauma (CT), depression, and psychological pain are known predictors of suicidal ideation. Recent literature additionally highlights the importance of the attachment system. Methods We aimed to predict suicidal ideation through CT, attachment, and psychological and social pain by using mediation models aiming to predict suicidal ideation through CT (predictor) and attachment (mediator). In the same models, we introduced psychological or social pain as a moderator of the relationship between attachment, CT, and suicidal ideation. We included 161 depressed patients and assessed depression, attachment, CT, suicidal ideation, psychological pain, and social pain. Results We found (1) a complete mediating effect of anxious attachment (a2b2 = 0.0035, CI95% = [0.0010; 0.0069]) on the relationship between CT on suicidal ideation, and (2) a significant complete conditional mediating effect of anxious attachment and psychological pain (index of moderated mediation VAS: 0.0014; CI95% = [0.0002; 0.0032]) but not social pain on the relationship between CT and suicidal ideation. Both models were controlled for history of suicidal attempt, depression severity, and sex. Conclusions Our results suggest a developmental profile of suicidal ideation in mood disorder that is characterized by the presence of CT and insecure attachment, especially anxious attachment, that is sensitive to experiences of psychological pain. Nevertheless, we cannot conclude that avoidantly attached individuals do not present the same mechanism, as they may not disclose those ideas.
Seafood-Associated Outbreak of ctx-Negative Vibrio mimicus Causing Cholera-Like Illness, Florida, USA

Vibrio mimicus caused a seafood-associated outbreak in Florida, USA, in which 4 of 6 case-patients were hospitalized; 1 required intensive care for severe diarrhea. Strains were ctx-negative but carried genes for other virulence determinants (hemolysin, proteases, and types I–IV and VI secretion systems). Cholera toxin–negative bacterial strains can cause cholera-like disease.
Current Issues in Evaluating Structural Reforms within the Lisbon Process; comments and recommendations about the Lisbon Methodology (LIME) Working Group. Bruegel Policy Contribution/February 2007

In 2005, shortly after taking office, the Barroso Commission replaced the failed Lisbon process initiated in 2000 (Lisbon 1) by a new one (Lisbon 2) which gave centre stage to the National Reform Programmes (NRPs). A year later, in a paper written at the request of the Austrian Presidency, Jean Pisani-Ferry and I critically reviewed the new process and concluded that “the outcome is mixed at best”. In particular, we emphasised that “There is no explicit methodology behind the evaluation of the NRPs by the Commission. ”
Regulatory circuits of mitophagy restrict distinct modes of cell death during memory CD8+ T cell formation

Mitophagy, a central process guarding mitochondrial quality, is commonly impaired in human diseases such as Parkinson’s disease, but its impact in adaptive immunity remains unclear. The differentiation and survival of memory CD8+ T cells rely on oxidative metabolism, a process that requires robust mitochondrial quality control. Here, we found that Parkinson’s disease patients have a reduced frequency of CD8+ memory T cells compared with healthy donors and failed to form memory T cells upon vaccination against COVID-19, highlighting the importance of mitochondrial quality control for memory CD8+ T cell formation. We further uncovered that regulators of mitophagy, including Parkin and NIX, were up-regulated in response to interleukin-15 (IL-15) for supporting memory T cell formation. Mechanistically, Parkin suppressed VDAC1-dependent apoptosis in memory T cells. In contrast, NIX expression in T cells counteracted ferroptosis by preventing metabolic dysfunction resulting from impaired mitophagy. Together, our results indicate that the mitophagy machinery orchestrates survival and metabolic dynamics required for memory T cell formation, as well as highlight a deficit in T cell–mediated antiviral responses in Parkinson’s disease patients. Description Parkin and NIX coordinate mitochondrial dynamics and function to prevent cell death during memory T cell formation. Editor’s summary During an immune response, T cells rely on mitochondria to support their evolving metabolic demands. Maintenance of mitochondrial health requires removal of damaged mitochondria via mitophagy, which can occur through PINK1/Parkin- or BNIP3L/NIX-mediated pathways. Using peripheral blood from patients with Parkinson’s disease and LCMV-infected mice, Franco et al. examined the function of mitochondrial quality control in memory T cell responses. Patients with Parkinson’s disease, which is associated with impairments in mitophagy, had fewer CD8+ memory T cells and impaired SARS-CoV-2–specific responses after vaccination. In LCMV-infected mice, Parkin suppressed VDAC1-dependent apoptosis of memory T cells, whereas NIX restrained ferroptosis by preventing metabolic dysfunction. These results demonstrate that key pathways of mitophagy support memory T cell responses by limiting distinct forms of cell death. —Claire Olingy
Shorter-acting glucagon-like peptide-1 receptor agonists are associated with increased development of gastro-oesophageal reflux disease and its complications in patients with type 2 diabetes mellitus: a population-level retrospective matched cohort study

Background Shorter half-life glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying (DGE) more than GLP-1 RAs with longer half-lives. DGE is a known risk factor for gastro-oesophageal reflux disease (GERD) and its complications. Aim To determine whether short-acting or long-acting GLP-1 RAs are associated with an increased risk of new GERD or GERD-related complications Design We used the TriNetX global database to identify adult patients with type 2 diabetes mellitus and generated two cohorts totalling 1 543 351 patients on (1) GLP-1 RA or (2) other second-line diabetes medication. Using propensity-score matching, Kaplan-Meier Analysis and Cox-proportional hazards ratio (HR), we analysed outcomes and separately examined outcomes in patients starting short-acting (≤1 day) and long-acting (≥5 days) GLP-1 RAs. Results 177 666 patients were in each propensity-matched cohort. GLP-1 RA exposure was associated with an increased risk (HR 1.15; 95% CI 1.09 to 1.22) of erosive reflux disease (ERD). However, this was solely due to short-acting (HR 1.215; 95% CI 1.111 to 1.328), but not long-acting (HR 0.994; 95% CI 0.924 to 1.069) GLP-1 RA exposure. Short-acting GLP-1 RAs were also associated with increased risk of oesophageal stricture (HR 1.284; 95% CI 1.135 to 1.453), Barrett’s without dysplasia (HR 1.372; 95% CI 1.217 to 1.546) and Barrett’s with dysplasia (HR 1.505; 95% CI 1.164 to 1.946) whereas long-acting GLP-1 RAs were not. This association persisted in sensitivity analyses, and when individually examining the short-acting GLP-1 RAs liraglutide, lixisenatide and exenatide. Conclusion Starting shorter-acting GLP-1 RAs is associated with increased risks of GERD and its complications.
Study protocol for development and validation of a single tool to assess risks of stroke, diabetes mellitus, myocardial infarction and dementia: DemNCD-Risk

Introduction Current efforts to reduce dementia focus on prevention and risk reduction by targeting modifiable risk factors. As dementia and cardiometabolic non-communicable diseases (NCDs) share risk factors, a single risk-estimating tool for dementia and multiple NCDs could be cost-effective and facilitate concurrent assessments as compared with a conventional single approach. The aim of this study is to develop and validate a new risk tool that estimates an individual’s risk of developing dementia and other NCDs including diabetes mellitus, stroke and myocardial infarction. Once validated, it could be used by the public and general practitioners. Methods and analysis Ten high-quality cohort studies from multiple countries were identified, which met eligibility criteria, including large representative samples, long-term follow-up, data on clinical diagnoses of dementia and NCDs, recognised modifiable risk factors for the four NCDs and mortality data. Pooled harmonised data from the cohorts will be used, with 65% randomly allocated for development of the predictive model and 35% for testing. Predictors include sociodemographic characteristics, general health risk factors and lifestyle/behavioural risk factors. A subdistribution hazard model will assess the risk factors’ contribution to the outcome, adjusting for competing mortality risks. Point-based scoring algorithms will be built using predictor weights, internally validated and the discriminative ability and calibration of the model will be assessed for the outcomes. Sensitivity analyses will include recalculating risk scores using logistic regression. Ethics and dissemination Ethics approval is provided by the University of New South Wales Human Research Ethics Committee (UNSW HREC; protocol numbers HC200515, HC3413). All data are deidentified and securely stored on servers at Neuroscience Research Australia. Study findings will be presented at conferences and published in peer-reviewed journals. The tool will be accessible as a public health resource. Knowledge translation and implementation work will explore strategies to apply the tool in clinical practice.
Attentive Notifications: Minimizing Distractions of Mobile Notifications through Gaze Tracking

Notifications on smartphones typically appear at the top of the screen, resulting in interruptions caused by content overlaps of toolbars and potential accidental activation of a notification. As returning to a workflow which got interrupted proves difficult for the general user, interface designers should thoughtfully design the visual disruption caused by notifications. We explore possible designs of gaze-attentive notifications to overcome this issue. By placing the notification banner as far from the user’s current gazing point as possible they result in less visual overlap and our study participants experienced them as less distracting.
User-Centered Privacy to Improve User Quantification using Smartphone Sensing

Mobile sensing technologies enable adaptive and context-aware applications. At the same time, they raise a range of privacy concerns. Thus, to reduce privacy concerns today apps are restricted from accessing certain information hindering to deliver full personalization and novel adaptive use cases. I investigate this issue by shedding light on the privacy concerns that arise from state-of-the-art mobile sensing data, studying the users’ perspective on mobile smartphone privacy, and proposing concepts that protect the users’ privacy while keeping the resulting data usable. I found that there is a lack of user-centered privacy design and that control features play a key role to give the users more agency. My results motivate the proliferation of control-enhancing privacy features in mobile applications. I show that the benefits of trust and system adoption surpass any impairments that control features might bring to the data.