IMPORTANCE Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US.OBJECTIVE To evaluate associations of lower eGFR... Show moreIMPORTANCE Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US.OBJECTIVE To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes.DESIGN, SETTING, AND PARTICIPANTS Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021.EXPOSURES The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR).MAIN OUTCOMES AND MEASURES The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses.RESULTS Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73m(2) (SD, 22 mL/min/1.73m(2)) and the median UACR was 11mg/g (IQR, 8-16mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73m(2) (SD, 22 mL/min/1.73m(2)) and the median UACR was 9mg/g (IQR, 6-18mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10mg/g, an eGFR of 45 to 59 mL/min/1.73m(2) based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73m(2) (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]).CONCLUSIONS AND RELEVANCE In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations. Show less
ObjectivesSocial anxiety has long been related to reduced eye contact. The present study aimed to determine whether gaze avoidance by more socially anxious individuals is a habit (related to social... Show moreObjectivesSocial anxiety has long been related to reduced eye contact. The present study aimed to determine whether gaze avoidance by more socially anxious individuals is a habit (related to social anxiety) or a momentary effect of state anxiety in a face-to-face conversation. Meanwhile, this study investigated the effect of conversational role and partner gaze direction on gaze behaviour during the conversation.MethodsParticipants (N = 61, age-range 17-30 years, 89% female) had a getting acquainted conversation with a same-sex confederate for approximately 10 minutes. We alternated conversational roles (talking vs. listening) and manipulated the confederate’s gaze direction (direct vs. averted). Participants’ gaze behaviour was registered with eye-tracking glasses. Their social anxiety and state anxiety were measured using questionnaires.ResultsThe results revealed greater state anxiety was associated with reduced eye gaze throughout the conversation whereas no effect of social anxiety was found. Furthermore, the results showed that the negative association between state anxiety and eye gaze was particularly strong when the confederate directly looked at the participant and also when the participant was talking. In addition, the study found main and interaction effects of conversational role and partner gaze direction on eye gaze behaviour during the conversation.ConclusionsTogether, the current results shed light on factors that influence eye gaze behaviour in a face-to-face social setting and provide initial evidence that, in the general population, eye gaze avoidance is more related to heightened state anxiety than to social anxiety. Show less
Social anxiety is anxiety about negative evaluation and rejection by others. Social anxiety has been long related to reduced eye contact, this feature is seen as a casual and a maintaining factor... Show moreSocial anxiety is anxiety about negative evaluation and rejection by others. Social anxiety has been long related to reduced eye contact, this feature is seen as a casual and a maintaining factor of social anxiety disorder. However, related empirical findings were equivocal. The dissertation sought to address three key questions: (1) Whether social anxiety is featured by gaze avoidance. (2) Under which conditions socially anxious individuals display gaze avoidance. (3) To what extent subjective experience of gaze avoidance corresponds with actual gaze behavior. Using the combination of naturalistic social settings and wearable eye-trackers, the dissertation provides evidence for the relationship between social anxiety and gaze avoidance particularly in naturalistic social situation, and further reveals that the relationship depends on severity of social anxiety symptoms, type of social situation and age group. Besides, gaze anxiety is moderately associated with actual gaze avoidance. Altogether, the dissertation sheds light on the nature of gaze behavior adopted by socially anxious individuals in naturalistic social interactions. Show less
Shrine, N.; Izquierdo, A.G.; Chen, J.; Packer, R.; Hall, R.J.; Guyatt, A.L.; ... ; Qatar Genome Program Res QGPR 2023
Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date,... Show moreLung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by & GE;2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.Multi-ancestry genome-wide association analyses and systematic variant-to-gene mapping strategies implicate new genes and pathways influencing lung function and chronic obstructive pulmonary disease risk. Show less
Frias Castillo, M.; Hodge, J.A.; Rybak, M.; Werf, P.P. van der; Smail, I.; Birkin, J.E.; ... ; Dannerbauer, H. 2023
Background: Social anxiety has long been related to reduced eye contact, and this feature is seen as a causal and a maintaining factor of social anxiety disorder. The present research adds to the... Show moreBackground: Social anxiety has long been related to reduced eye contact, and this feature is seen as a causal and a maintaining factor of social anxiety disorder. The present research adds to the literature by investigating the relationship between social anxiety and visual avoidance of faces in a reciprocal face-to-face conversation, while taking into account two aspects of conversations as potential moderating factors: conversational role and level of intimacy. Method: Eighty-five female students (17-25 years) completed the Leibowitz Social Anxiety Scale and had a face-to-face getting-acquainted conversation with a female confederate. We alternated conversational role (talking versus listening) and manipulated intimacy of the topics (low versus high). Participants' gaze behavior was registered with Tobii eye-tracking glasses. Three dependent measures were extracted regarding fixations on the face of the confederate: total duration, proportion of fixations, and mean duration. Results: The results revealed that higher levels of social anxiety were associated with reduced face gaze on all three measures. The relation with total fixation duration was stronger for low intimate topics. The relation with mean fixation duration was stronger during listening than during speaking. Conclusion: The results highlight the importance of studying gaze behavior in a naturalistic social interaction. Show less
Health consequences that persist beyond the acute infection phase of COVID-19, termed post-COVID-19 condition (also commonly known as long COVID), vary widely and represent a growing global health... Show moreHealth consequences that persist beyond the acute infection phase of COVID-19, termed post-COVID-19 condition (also commonly known as long COVID), vary widely and represent a growing global health challenge. Research on post-COVID-19 condition is expanding but, at present, no agreement exists on the health outcomes that should be measured in people living with the condition. To address this gap, we conducted an international consensus study, which included a comprehensive literature review and classification of outcomes for post-COVID-19 condition that informed a two-round online modified Delphi process followed by an online consensus meeting to finalise the core outcome set (COS). 1535 participants from 71 countries were involved, with 1148 individuals participating in both Delphi rounds. Eleven outcomes achieved consensus for inclusion in the final COS: fatigue; pain; post-exertion symptoms; work or occupational and study changes; survival; and functioning, symptoms, and conditions for each of cardiovascular, respiratory, nervous system, cognitive, mental health, and physical outcomes. Recovery was included a priori because it was a relevant outcome that was part of a previously published COS on COVID-19. The next step in this COS development exercise will be to establish the instruments that are most appropriate to measure these core outcomes. This international consensus-based COS should provide a framework for standardised assessment of adults with post-COVID-19 condition, aimed at facilitating clinical care and research worldwide. Show less
We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent)... Show moreWe assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background.Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations. Show less
Background A substantial portion of people with COVID-19 subsequently experience lasting symptoms including fatigue, shortness of breath, and neurological complaints such as cognitive dysfunction... Show moreBackground A substantial portion of people with COVID-19 subsequently experience lasting symptoms including fatigue, shortness of breath, and neurological complaints such as cognitive dysfunction many months after acute infection. Emerging evidence suggests that this condition, commonly referred to as long COVID but also known as post-acute sequelae of SARS-CoV-2 infection (PASC) or post-COVID-19 condition, could become a significant global health burden. Main text While the number of studies investigating the post-COVID-19 condition is increasing, there is no agreement on how this new disease should be defined and diagnosed in clinical practice and what relevant outcomes to measure. There is an urgent need to optimise and standardise outcome measures for this important patient group both for clinical services and for research and to allow comparing and pooling of data. Conclusions A Core Outcome Set for post-COVID-19 condition should be developed in the shortest time frame possible, for improvement in data quality, harmonisation, and comparability between different geographical locations. We call for a global initiative, involving all relevant partners, including, but not limited to, healthcare professionals, researchers, methodologists, patients, and caregivers. We urge coordinated actions aiming to develop a Core Outcome Set (COS) for post-COVID-19 condition in both the adult and paediatric populations. Show less
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here... Show moreGlycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets. Show less
Chen, J.; Bos, E. van den; Velthuizen, S.L.M.; Westenberg, P.M. 2021
Patients with social anxiety disorder appear to display aberrant gaze behavior across a variety of social situations. In contrast, the gaze behavior of high socially anxious (HSA) individuals from... Show morePatients with social anxiety disorder appear to display aberrant gaze behavior across a variety of social situations. In contrast, the gaze behavior of high socially anxious (HSA) individuals from the community seems to depend on the type of situation and the aberration might be limited to gaze avoidance. This study investigated the differential effect of social situation-a face-viewing task and a public speaking task-on gaze behavior in HSA participants from a community sample. Participants' eye movements were tracked using a wearable eye tracker. Two aspects of gaze behavior were measured: (1) gaze avoidance was assessed by total fixation time, fixation counts, and mean fixation time on faces; (2) hypervigilance was assessed by scan path length and mean distance between fixations. The results confirmed a moderating effect of task on total (though not mean) fixation time on faces and fixation counts. Compared to low socially anxious participants, HSA participants looked less frequently (hence shorter) at the audience during the speech only. This indicates that visual avoidance in HSA individuals does not occur by default, but only when risks of (negative) social consequences are perceived. High and low socially anxious participants showed no difference in hypervigilance in either situation. Show less
Zhang, Q.; Zhang, Z.; Lu, T.; Peijnenburg, W.J.G.M.; Gillings, M.; Yang, X.; ... ; Qian, H. 2020
Cyanobacterial blooms are a global ecological problem that directly threatens human health and crop safety. Cyanobacteria have toxic effects on aquatic microorganisms, which could drive the... Show moreCyanobacterial blooms are a global ecological problem that directly threatens human health and crop safety. Cyanobacteria have toxic effects on aquatic microorganisms, which could drive the selection for resistance genes. The effect of cyanobacterial blooms on the dispersal and abundance of antibiotic-resistance genes (ARGs) of concern to human health remains poorly known. We herein investigated the effect of cyanobacterial blooms on ARG composition in Lake Taihu, China. The numbers and relative abundances of total ARGs increased obviously during a Planktothrix bloom. More pathogenic microorganisms were present during this bloom than during a Planktothrix bloom or during the non-bloom period. Microcosmic experiments using additional aquatic ecosystems (an urban river and Lake West) found that a coculture of Microcystis aeruginosa and Planktothrix agardhii increased the richness of the bacterial community, because its phycosphere provided a richer microniche for bacterial colonization and growth. Antibiotic-resistance bacteria were naturally in a rich position, successfully increasing the momentum for the emergence and spread of ARGs. These results demonstrate that cyanobacterial blooms are a crucial driver of ARG diffusion and enrichment in freshwater, thus providing a reference for the ecology and evolution of ARGs and ARBs and for better assessing and managing water quality. Show less
The recent literature has shown that vulvar squamous cell carcinoma (VSCC) can be stratified into two prognostically relevant groups based on human papillomavirus (HPV) status. The prognostic value... Show moreThe recent literature has shown that vulvar squamous cell carcinoma (VSCC) can be stratified into two prognostically relevant groups based on human papillomavirus (HPV) status. The prognostic value of p53 for further sub-stratification, particularly in the HPV-independent group, has not been agreed upon. This disagreement is likely due to tremendous variations in p53 immunohistochemical (IHC) interpretation. To address this problem, we sought to compare p53 IHC patterns with TP53 mutation status. We studied 61 VSCC (48 conventional VSCC, 2 VSCC with sarcomatoid features, and 11 verrucous carcinomas) and 42 in situ lesions (30 differentiated vulvar intraepithelial neoplasia [dVIN], 9 differentiated exophytic vulvar intraepithelial lesions [deVIL], and 3 high-grade squamous intraepithelial lesions or usual vulvar intraepithelial neoplasia [HSIL/uVIN]). IHC for p16 and p53, and sequencing of TP53 exons 4-9 were performed. HPV in situ hybridization (ISH) was performed in selected cases. We identified six major p53 IHC patterns, two wild-type patterns: (1) scattered, (2) mid-epithelial expression (with basal sparing), and four mutant patterns: (3) basal overexpression, (4) parabasal/diffuse overexpression, (5) absent, and (6) cytoplasmic expression. These IHC patterns were consistent with TP53 mutation status in 58/61 (95%) VSCC and 39/42 (93%) in situ lesions. Cases that exhibited strong scattered staining and those with a weak basal overexpression pattern could be easily confused. The mid-epithelial pattern was exclusively observed in p16-positive lesions; the basal and parabasal layers that had absent p53 staining, appeared to correlate with the cells that were positive for HPV-ISH. This study describes a pattern-based p53 IHC interpretation framework, which can be utilized as a surrogate marker for TP53 mutational status in both VSCC and vulvar in situ lesions. Show less
Although visual avoidance of faces is a hallmark feature of social anxiety disorder (SAD) on clinical and theoretical grounds, empirical support is equivocal. This review aims to clarify under... Show moreAlthough visual avoidance of faces is a hallmark feature of social anxiety disorder (SAD) on clinical and theoretical grounds, empirical support is equivocal. This review aims to clarify under which conditions socially anxious individuals display visual avoidance of faces. Through a systematic search in Web of Science and PubMed up to March 2019 we identified 61 publications that met the inclusion criteria. We discuss the influence of three factors on the extent to which socially anxious individuals avoid looking at faces: (a) severity of social anxiety symptoms (diagnosed SAD versus High Social Anxiety levels in community samples [HSA] or related characteristics [Shyness, Fear of Negative Evaluation]), (b) three types of social situation (computer facial-viewing tasks, speaking tasks, social interactions), and (c) development (age-group). Adults with SAD exhibit visual avoidance across all three types of social situations, whereas adults with HSA exhibit visual avoidance in speaking and interaction tasks but not in facial-viewing tasks. The relatively few studies with children and adolescents suggest that visual avoidance emerges during adolescence. The findings are discussed in the context of cognitive-behavioral and skills-deficit models. Suggestions for future research include the need for developmental studies and more fine-grained analyses of specific areas of the face. Show less
With the picolinyl (Pic) group as a C‐1 located directing group and N3 as versatile precursor for C5‐NH2, a novel 1‐Pic‐5‐N3 thiosialyl donor was designed and synthesized, based on which a new... Show moreWith the picolinyl (Pic) group as a C‐1 located directing group and N3 as versatile precursor for C5‐NH2, a novel 1‐Pic‐5‐N3 thiosialyl donor was designed and synthesized, based on which a new sialylation protocol was established. In comparison to conventional sialylation methods, the new protocol exhibited obvious advantages, including excellent α‐stereoselectivity in the absence of a solvent effect, broad substrate scope encompassing the challenging sialyl 8‐ and 9‐hydroxy groups of sialic acid acceptors, flexibility in sialoside derivative synthesis, high temperature tolerance and easy scalability. In particular, the applicability to the synthesis of complex and bioactive N‐glycan antennae when combined with the MPEP glycosylation protocol via the “latent‐active” strategy has been shown. Mechanistically, the excellent α‐stereoselectivity of the novel sialylation protocol could be attributed to the dramatic electron‐withdrawing effect of the protonated Pic groups, which was supported by control reactions and DFT calculations. Show less
