A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease.

Identification and validation of supervariants reveal novel loci associated with human white matter microstructure.

As an essential part of the central nervous system, white matter coordinates communications between different brain regions and is related to a wide range of neurodegenerative and neuropsychiatric disorders. Previous genome-wide association studies (GWASs) have uncovered loci associated with white matter microstructure. However, GWASs suffer from limited reproducibility and difficulties in detecting multi-single-nucleotide polymorphism (multi-SNP) and epistatic effects. In this study, we adopt the concept of supervariants, a combination of alleles in multiple loci, to account for potential multi-SNP effects. We perform supervariant identification and validation to identify loci associated with 22 white matter fractional anisotropy phenotypes derived from diffusion tensor imaging. To increase reproducibility, we use United Kingdom (UK) Biobank White British (n = 30,842) data for discovery and internal validation, and UK Biobank White but non-British (n = 1927) data, Europeans from the Adolescent Brain Cognitive Development study (n = 4399) data, and Europeans from the Human Connectome Project (n = 319) data for external validation. We identify 23 novel loci on the discovery set that have not been reported in the previous GWASs on white matter microstructure. Among them, three supervariants on genomic regions 5q35.1, 8p21.2, and 19q13.32 have P-values lower than 0.05 in the meta-analysis of the three independent validation data sets. These supervariants contain genetic variants located in genes that have been related to brain structures, cognitive functions, and neuropsychiatric diseases. Our findings provide a better understanding of the genetic architecture underlying white matter microstructure.

The interaction effects of age, APOE and common environmental risk factors on human brain structure.

Mounting evidence suggests considerable diversity in brain aging trajectories, primarily arising from the complex interplay between age, genetic, and environmental risk factors, leading to distinct patterns of micro- and macro-cerebral aging. The underlying mechanisms of such effects still remain unclear. We conducted a comprehensive association analysis between cerebral structural measures and prevalent risk factors, using data from 36,969 UK Biobank subjects aged 44-81. Participants were assessed for brain volume, white matter diffusivity, Apolipoprotein E (APOE) genotypes, polygenic risk scores, lifestyles, and socioeconomic status. We examined genetic and environmental effects and their interactions with age and sex, and identified 726 signals, with education, alcohol, and smoking affecting most brain regions. Our analysis revealed negative age-APOE-ε4 and positive age-APOE-ε2 interaction effects, respectively, especially in females on the volume of amygdala, positive age-sex-APOE-ε4 interaction on the cerebellar volume, positive age-excessive-alcohol interaction effect on the mean diffusivity of the splenium of the corpus callosum, positive age-healthy-diet interaction effect on the paracentral volume, and negative APOE-ε4-moderate-alcohol interaction effects on the axial diffusivity of the superior fronto-occipital fasciculus. These findings highlight the need of considering age, sex, genetic, and environmental joint effects in elucidating normal or abnormal brain aging.

A new 3,4-dinorsteroid from the marine sponge Cliona sp.

A new steroid, 2a-oxa-2-oxo-5ß-hydroxy-3,4-dinor-24-methylcholesta-22E-ene (1), together with 10 known ones (2-11), was isolated from the marine sponge Cliona sp. The structures of these compounds were determined by the spectroscopic methods (UV, IR, MS, and NMR) and X-ray diffraction analysis. Compound 1 was the third example of 3,4-dinorsteroid with a hemiketal at C-5 that was isolated from the natural source. In addition, the antibacterial activities of these compounds were also evaluated. However, none of them exhibited significant inhibition effects.

Diagnostic Performance of Radiomics and Deep Learning to Identify Benign and Malignant Soft Tissue Tumors: A Systematic Review and Meta-analysis.

RATIONALE AND OBJECTIVES: To systematically evaluate the application value of radiomics and deep learning (DL) in the differential diagnosis of benign and malignant soft tissue tumors (STTs). MATERIALS AND METHODS: A systematic review was conducted on studies published up to December 11, 2023, that utilized radiomics and DL methods for the diagnosis of STTs. The methodological quality and risk of bias were evaluated using the Radiomics Quality Score (RQS) 2.0 system and Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool, respectively. A bivariate random-effects model was used to calculate the summarized sensitivity and specificity. To identify factors contributing to heterogeneity, meta-regression and subgroup analyses were performed to assess the following covariates: diagnostic modality, region/volume of interest, imaging examination, study design, and pathology type. The asymmetry of Deeks' funnel plot was used to assess publication bias. RESULTS: A total of 21 studies involving 3866 patients were included, with 13 studies using independent test/validation sets included in the quantitative statistical analysis. The average RQS was 21.31, with substantial or near-perfect inter-rater agreement. The combined sensitivity and specificity were 0.84 (95% CI: 0.76-0.89) and 0.88 (95% CI: 0.69-0.96), respectively. Meta-regression and subgroup analyses showed that study design and the region/volume of interest were significant factors affecting study heterogeneity (P < 0.05). No publication bias was observed. CONCLUSION: Radiomics and DL can accurately distinguish between benign and malignant STTs. Future research should concentrate on enhancing the rigor of study designs, conducting multicenter prospective validations, amplifying the interpretability of DL models, and integrating multimodal data to elevate the diagnostic accuracy and clinical utility of soft tissue tumor assessments.

Two new diketopiperazines from the marine sponge Dysidea sp.

A chemical investigation on the marine sponge Dysidea sp. resulted in the isolation of a series of diketopiperazines, including two new compounds, dysidines A (1) and B (2) as well as six known ones (3-8). Their structures with absolute configurations were determined on the basis of UV, IR, HRMS, NMR and calculated ECD method. Additionally, the cytotoxic, anti-inflammatory, antibacterial and antiviral activities of 1-8 were also tested. However, none of them exhibited significant bioactivities.

Analyzing bivariate cross-trait genetic architecture in GWAS summary statistics with the BIGA cloud computing platform.

As large-scale biobanks provide increasing access to deep phenotyping and genomic data, genome-wide association studies (GWAS) are rapidly uncovering the genetic architecture behind various complex traits and diseases. GWAS publications typically make their summary-level data (GWAS summary statistics) publicly available, enabling further exploration of genetic overlaps between phenotypes gathered from different studies and cohorts. However, systematically analyzing high-dimensional GWAS summary statistics for thousands of phenotypes can be both logistically challenging and computationally demanding. In this paper, we introduce BIGA (https://bigagwas.org/), a website that aims to offer unified data analysis pipelines and processed data resources for cross-trait genetic architecture analyses using GWAS summary statistics. We have developed a framework to implement statistical genetics tools on a cloud computing platform, combined with extensive curated GWAS data resources. Through BIGA, users can upload data, submit jobs, and share results, providing the research community with a convenient tool for consolidating GWAS data and generating new insights.

The value of ultrasound in combination with 99mTc-MIBI imaging department of ultrasound medicine, for the diagnosis of ectopic parathyroid glands in the thyroid gland in patients with secondary hyperparathyroidism.

To investigate the value of preoperative ultrasound combined with 99mTc-MIBI imaging for the diagnosis of ectopic intrathyroid parathyroid gland (ETPG) in patients with secondary hyperparathyroidism (SHPT). One hundred and eleven patients with SHPT who underwent total parathyroidectomy plus forearm transplantation from January 2015 to January 2022 in the Third Hospital of Hebei Medical University were selected. All patients underwent routine preoperative ultrasonography and 99mTc-MIBI imaging, and with pathological diagnosis as the gold standard, the clinical data of ETPG patients were selected, including clinical manifestations, laboratory tests, preoperative ultrasonography and 99mTc-MIBI imaging for localization and diagnosis, intraoperative exploration and postoperative pathology, and postoperative follow-up. To analyze the ultrasound manifestations of preoperative parathyroid hyperplasia and the results of 99mTc-MIBI imaging in patients with ETPG. Among 111 patients with SHPT, there were 5 patients with ETPG, 1 male and 4 females with a mean age of (45.00 ±â€…5.05) years, and 6 ectopic parathyroid glands were located in the thyroid gland. The incidence of ETPG was 4.5% (5/111), 4 were detected by ultrasound, 2 were not detected with a diagnostic accuracy of 66.7% (4/6), 3 were positive for 99mTc-MIBI imaging, 3 were negative with a diagnostic accuracy of 50.0% (3/6). Among them, one was not detected by ultrasound, but was positive for 99mTc-MIBI imaging, 2 with negative 99mTc-MIBI imaging, but all were detected by ultrasound, and one with negative 99mTc-MIBI imaging was detected by ultrasound but misdiagnosed as a thyroid nodule. A total of 5 ETPGs were detected by ultrasound combined with 99mTc-MIBI imaging, with a diagnostic accuracy of 83.3% (5/6). Patients' postoperative serum calcium and serum parathyroid hormone (PTH) levels were normalized or significantly decreased from preoperative levels. Ultrasound combined with 99mTc-MIBI imaging can achieve higher accuracy than either examination alone in the preoperative localization and diagnosis of ETPG in SHPT patients.

Thymoquinone regulates microglial M1/M2 polarization after cerebral ischemia-reperfusion injury via the TLR4 signaling pathway.

Acute ischemic stroke followed by microglia activation, and the regulation of neuroinflammatory responses after ischemic injury involves microglia polarization. microglia polarization is involved in the regulation of neuroinflammatory responses and ischemic stroke-related brain damage. Thymoquinone (TQ) is an anti-inflammatory agent following ischemic stroke onset. However, the significance of TQ in microglia polarization following acute ischemic stroke is still unclear. We predicted that TQ might have neuroprotective properties by modulating microglia polarization. In this work, we mimicked the clinical signs of acute ischemic stroke using a mouse middle cerebral artery ischemia-reperfusion (I/R) model. It was discovered that TQ treatment decreased I/R-induced infarct volume, cerebral oedema, and promoted neuronal survival, as well as improved the histopathological changes of brain tissue. The sensorimotor function was assessed by the Garica score, foot fault test, and corner test, and it was found that TQ could improve the motor deficits caused by I/R. Secondly, real-time fluorescence quantitative PCR, immuno-fluorescence, ELISA, and western blot were used to detect the expression of M1/M2-specific markers in microglia to explore the role of TQ in the modulation of microglial cell polarization after cerebral ischemia-reperfusion. We found that TQ was able to promote the polarization of microglia with extremely secreted inflammatory factors from M1 type to M2 type. Furthermore, TQ could block the TLR4/NF-κB signaling pathway via Hif-1α activation which subsequently may attenuate microglia differentiation following the cerebral ischemia, establishing a mechanism for the TQ's beneficial effects in the cerebral ischemia-reperfusion model.

Hybridization of bimetallic cobalt-molybdenum oxide multihole nanosheets with selenium adulteration as advanced bifunctional electrocatalysts for boosting overall water splitting.

Electrocatalytic water splitting produces green and pollution-free hydrogen as a clean energy carrier, which can effectively alleviate energy crisis. In this paper, bimetallic and selenium doped cobalt molybdate (Se-CoMoO4) nanosheets with rough surface are resoundingly prepared. The multihole Se-CoMoO4 nanosheets display ultrathin and rectangular architecture with the dimensions of âˆ¼ 3.5 µm and 700 nm for length and width, respectively. The Se-CoMoO4 electrocatalyst shows remarkable water electrolysis activity and stability. The overpotentials of oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) are 270 and 63.3 mV at 10 mA cm-2, along with low Tafel slopes of 51.6 and 62.0 mV dec-1. Furthermore, the Se-CoMoO4 couple electrolyzer merely requires a cell voltage of 1.48 V to achieve 10 mA cm-2 current density and presents no apparent attenuation for 30 h. This investigation declares that the hybridization of transition bimetallic oxide with nonmetallic adulteration can afford a tactic for the preparation of bifunctional non-precious metal-based electrocatalysts.

Three-dimensional aortic geometry: clinical correlates, prognostic value and genetic architecture.

Aortic structure and function impact cardiovascular health through multiple mechanisms. Aortic structural degeneration increases left ventricular afterload, pulse pressure and promotes target organ damage. Despite the impact of aortic structure on cardiovascular health, aortic 3D-geometry has yet to be comprehensively assessed. Using a convolutional neural network (U-Net) combined with morphological operations, we quantified aortic 3D-geometric phenotypes (AGPs) from 53,612 participants in the UK Biobank and 8,066 participants in the Penn Medicine Biobank. AGPs reflective of structural aortic degeneration, characterized by arch unfolding, descending aortic lengthening and luminal dilation exhibited cross-sectional associations with hypertension and cardiac diseases, and were predictive for new-onset hypertension, heart failure, cardiomyopathy, and atrial fibrillation. We identified 237 novel genetic loci associated with 3D-AGPs. Fibrillin-2 gene polymorphisms were identified as key determinants of aortic arch-3D structure. Mendelian randomization identified putative causal effects of aortic geometry on the risk of chronic kidney disease and stroke.

The Interaction Effects of Age, Sex, APOE and Common Health Risk Factors on Human Brain Functions.

Recent studies have shed light on the complex nonlinear changes in brain functions across the lifespan, demonstrating the variability in the individual cognitive and neural development during aging. This variability is influenced by factors such as sex, age, genetics, and modifiable health risk factors (MHRFs), which collectively shape unique patterns of brain functional connectivities (FCs) across different regions. However, their joint effects and underlying mechanisms remain unclear. We conduct a comprehensive analysis to jointly examine the association of common risk factors with brain functional measures, using data from 36,630 UK Biobank participants aged 44-81. Participants were assessed for age, sex, Apolipoprotein E ( APOE ) genotypes, ten common MHRFs, and brain FCs measured via resting-state functional magnetic resonance imaging. Using the fine-grained HCP-MMP parcellation and Ji-12 network atlases, we identified 91 associations with network functional connectivity (NFC) and 102 associations with network edge strength (NES) measures. Hypertension, BMI, and education emerged as the top three influential factors across networks. Notably, a negative interaction between sex and APOE-ε4 ( APOE4 ) genotype was observed, with male APOE4 carriers showing greater reductions in NFC between the cingulo- opercular (CON) and posterior multimodal (PMN) networks. Additionally, a negative age-BMI interaction on NES between the visual and dorsal attention (DAN) networks suggested that higher BMI accelerates the decline in visual-DAN connectivity. A positive age-hypertension interaction between the frontoparietal (FPN) and default mode (DMN) networks indicated a more rapid decrease in functional segregation associated with hypertension. We also identified sex- education interactions, showing more pronounced positive effects on CON-FPN networks in females and PMN-DMN networks in males. Further interactions involving sex and other MHRFs, such as smoking, alcohol consumption, diabetes, and BMI, revealed that smoking, alcohol, and BMI had more detrimental effects in males, while diabetes had a more pronounced negative impact in females within specific networks. These findings underscore the necessity of jointly considering sex, age, genetic factors, and MHRFs to accurately delineate the multifactorial alterations in the FCs during brain aging.

Associations between Longitudinal Changes in Sleep Stages and Risk of Cognitive Decline in Older Men.

STUDY OBJECTIVES: To investigate the relationships between longitudinal changes in sleep stages and the risk of cognitive decline in older men. METHODS: This study included 978 community-dwelling older men who participated in the first (2003-2005) and second (2009-2012) sleep ancillary study visits of the Osteoporotic Fractures in Men Study. We examined the longitudinal changes in sleep stages at the initial and follow-up visits, and the association with concurrent clinically relevant cognitive decline during the 6.5-year follow-up. RESULTS: Men with low to moderate (quartile 2, Q2) and moderate increase (Q3) in N1 sleep percentage had a reduced risk of cognitive decline on the Modified Mini-Mental State Examination compared to those with a substantial increase (Q4) in N1 sleep percentage. Additionally, men who experienced a low to moderate (Q2) increase in N1 sleep percentage had a lower risk of cognitive decline on the Trails B compared with men in the reference group (Q4). Furthermore, men with the most pronounced reduction (Q1) in N2 sleep percentage had a significantly higher risk of cognitive decline on the Trails B compared to those in the reference group (Q4). No significant association was found between changes in N3 and rapid eye movement sleep and the risk of cognitive decline. CONCLUSIONS: Our results suggested that a relatively lower increase in N1 sleep showed a reduced risk of cognitive decline. However, a pronounced decrease in N2 sleep was associated with concurrent cognitive decline. These findings may help identify older men at risk of clinically relevant cognitive decline.

The genetic architecture of biological age in nine human organ systems.

Investigating the genetic underpinnings of human aging is essential for unraveling the etiology of and developing actionable therapies for chronic diseases. Here, we characterize the genetic architecture of the biological age gap (BAG; the difference between machine learning-predicted age and chronological age) across nine human organ systems in 377,028 participants of European ancestry from the UK Biobank. The BAGs were computed using cross-validated support vector machines, incorporating imaging, physical traits and physiological measures. We identify 393 genomic loci-BAG pairs (P < 5 × 10-8) linked to the brain, eye, cardiovascular, hepatic, immune, metabolic, musculoskeletal, pulmonary and renal systems. Genetic variants associated with the nine BAGs are predominantly specific to the respective organ system (organ specificity) while exerting pleiotropic links with other organ systems (interorgan cross-talk). We find that genetic correlation between the nine BAGs mirrors their phenotypic correlation. Further, a multiorgan causal network established from two-sample Mendelian randomization and latent causal variance models revealed potential causality between chronic diseases (for example, Alzheimer's disease and diabetes), modifiable lifestyle factors (for example, sleep duration and body weight) and multiple BAGs. Our results illustrate the potential for improving human organ health via a multiorgan network, including lifestyle interventions and drug repurposing strategies.

Multi-organ imaging-derived polygenic indexes for brain and body health.

The UK Biobank (UKB) imaging project is a crucial resource for biomedical research, but is limited to 100,000 participants due to cost and accessibility barriers. Here we used genetic data to predict heritable imaging-derived phenotypes (IDPs) for a larger cohort. We developed and evaluated 4,375 IDP genetic scores (IGS) derived from UKB brain and body images. When applied to UKB participants who were not imaged, IGS revealed links to numerous phenotypes and stratified participants at increased risk for both brain and somatic diseases. For example, IGS identified individuals at higher risk for Alzheimer's disease and multiple sclerosis, offering additional insights beyond traditional polygenic risk scores of these diseases. When applied to independent external cohorts, IGS also stratified those at high disease risk in the All of Us Research Program and the Alzheimer's Disease Neuroimaging Initiative study. Our results demonstrate that, while the UKB imaging cohort is largely healthy and may not be the most enriched for disease risk management, it holds immense potential for stratifying the risk of various brain and body diseases in broader external genetic cohorts.

The Janus face of HIF-1α in ischemic stroke and the possible associated pathways.

Stroke is the most devastating disease, causing paralysis and eventually death. Many clinical and experimental trials have been done in search of a new safe and efficient medicine; nevertheless, scientists have yet to discover successful remedies that are also free of adverse effects. This is owing to the variability in intensity, localization, medication routes, and each patient's immune system reaction. HIF-1α represents the modern tool employed to treat stroke diseases due to its functions: downstream genes such as glucose metabolism, angiogenesis, erythropoiesis, and cell survival. Its role can be achieved via two downstream EPO and VEGF strongly related to apoptosis and antioxidant processes. Recently, scientists paid more attention to drugs dealing with the HIF-1 pathway. This review focuses on medicines used for ischemia treatment and their potential HIF-1α pathways. Furthermore, we discussed the interaction between HIF-1α and other biological pathways such as oxidative stress; however, a spotlight has been focused on certain potential signalling contributed to the HIF-1α pathway. HIF-1α is an essential regulator of oxygen balance within cells which affects and controls the expression of thousands of genes related to sustaining homeostasis as oxygen levels fluctuate. HIF-1α's role in ischemic stroke strongly depends on the duration and severity of brain damage after onset. HIF-1α remains difficult to investigate, particularly in ischemic stroke, due to alterations in the acute and chronic phases of the disease, as well as discrepancies between the penumbra and ischemic core. This review emphasizes these contrasts and analyzes the future of this intriguing and demanding field.

Eye-brain connections revealed by multimodal retinal and brain imaging genetics.

The retina, an anatomical extension of the brain, forms physiological connections with the visual cortex of the brain. Although retinal structures offer a unique opportunity to assess brain disorders, their relationship to brain structure and function is not well understood. In this study, we conducted a systematic cross-organ genetic architecture analysis of eye-brain connections using retinal and brain imaging endophenotypes. We identified novel phenotypic and genetic links between retinal imaging biomarkers and brain structure and function measures from multimodal magnetic resonance imaging (MRI), with many associations involving the primary visual cortex and visual pathways. Retinal imaging biomarkers shared genetic influences with brain diseases and complex traits in 65 genomic regions, with 18 showing genetic overlap with brain MRI traits. Mendelian randomization suggests bidirectional genetic causal links between retinal structures and neurological and neuropsychiatric disorders, such as Alzheimer's disease. Overall, our findings reveal the genetic basis for eye-brain connections, suggesting that retinal images can help uncover genetic risk factors for brain disorders and disease-related changes in intracranial structure and function.

The genetic architecture of multimodal human brain age.

The complex biological mechanisms underlying human brain aging remain incompletely understood. This study investigated the genetic architecture of three brain age gaps (BAG) derived from gray matter volume (GM-BAG), white matter microstructure (WM-BAG), and functional connectivity (FC-BAG). We identified sixteen genomic loci that reached genome-wide significance (P-value < 5×10-8). A gene-drug-disease network highlighted genes linked to GM-BAG for treating neurodegenerative and neuropsychiatric disorders and WM-BAG genes for cancer therapy. GM-BAG displayed the most pronounced heritability enrichment in genetic variants within conserved regions. Oligodendrocytes and astrocytes, but not neurons, exhibited notable heritability enrichment in WM and FC-BAG, respectively. Mendelian randomization identified potential causal effects of several chronic diseases on brain aging, such as type 2 diabetes on GM-BAG and AD on WM-BAG. Our results provide insights into the genetics of human brain aging, with clinical implications for potential lifestyle and therapeutic interventions. All results are publicly available at https://labs.loni.usc.edu/medicine .

Secondary hyperparathyroidism combined with thyroid disease.

To retrospectively analyze the diagnosis and treatment of secondary hyperparathyroidism (SHPT) combined with thyroid disease, and to investigate the correlation between SHPT and papillary thyroid carcinoma (PTC), SHPT and thyroid disease, and the importance of preoperative localization diagnosis in patients with SHPT. Clinical data of 101 patients who underwent surgical treatment for SHPT at the Third Hospital of Hebei Medical University were collected from August 2014 to May 2023, and patients were divided into SHPT without PTC group (n = 94) and SHPT with PTC group (n = 7) according to their postoperative pathology. Patients were divided into SHPT without thyroid disease group (n = 32) and SHPT with thyroid disease group (n = 69) according to their preoperative ultrasound diagnosis and postoperative pathology. The differences between the 2 groups were compared to explore the association between SHPT and PTC and between SHPT and thyroid disease. Of the 101 patients with SHPT, 65 were male and 36 were female with a mean age of (44.26 ±â€…11.16) years. There were 69 patients (68.32%) with concomitant thyroid disease and 32 patients (31.68%) without concomitant thyroid disease, including 7 patients (6.93%) with PTC. The results of univariate analysis showed that the differences in age and preoperative PTH levels between the SHPT without PTC group and the SHPT with PTC group were statistically significant (P < 0. 05),There were no significant differences in age, gender, preoperative PTH, preoperative alkaline phosphatase, preoperative serum calcium, preoperative serum phosphorus, preoperative serum creatinine, duration of dialysis disease, and whether they were accompanied by hypertension or not between the SHPT without thyroid disease group and the SHPT with thyroid disease group (P > 0. 05), logistic regression analysis showed that there was a correlation between the age of patients with SHPT and the level of preoperative PTH with PTC. In patients with SHPT, concomitant thyroid disease is more common, so patients with SHPT should be screened for thyroid disease at the same time as routine preoperative ultrasonography combined with nuclear scan for localized diagnosis, and surgical resection is preferred if concomitant PTC is present.

An atlas of trait associations with resting-state and task-evoked human brain functional organizations in the UK Biobank.

Functional magnetic resonance imaging (fMRI) has been widely used to identify brain regions linked to critical functions, such as language and vision, and to detect tumors, strokes, brain injuries, and diseases. It is now known that large sample sizes are necessary for fMRI studies to detect small effect sizes and produce reproducible results. Here we report a systematic association analysis of 647 traits with imaging features extracted from resting-state and task-evoked fMRI data of more than 40,000 UK Biobank participants. We used a parcellation-based approach to generate 64,620 functional connectivity measures to reveal fine-grained details about cerebral cortex functional organizations. The difference between functional organizations at rest and during task was examined, and we have prioritized important brain regions and networks associated with a variety of human traits and clinical outcomes. For example, depression was most strongly associated with decreased connectivity in the somatomotor network. We have made our results publicly available and developed a browser framework to facilitate the exploration of brain function-trait association results (http://fmriatlas.org/).