Ethnoracial inclusion in clinical trials of psychedelics: a systematic review.

Background: Prior data indicate limited ethnoracial diversity in studies testing psychedelic-assisted treatments. Regulatory approval for psychedelic treatments may be imminent given growing evidence for safety and efficacy in a variety of psychiatric conditions. Data on racial and ethnic inclusion rates in clinical psychedelic studies since 2018 have not been systematically reported to date. With the publication of multiple new studies in the field, an update to existing ethnoracial inclusion data is needed to inform the state of the science and future directions for research. Methods: Systematic review of Pubmed/MEDLINE, EMBASE, and Web of Science for studies of any design testing a psychedelic treatment for a psychiatric or substance use disorder published between January 1, 1994 and May 24, 2024. Search terms related to serotonergic psychedelics and MDMA, psychedelic therapies, psychiatric disorders, and substance use disorders were used. References of reviewed studies were screened for inclusion. Studies were rated for quality on a five-point scale ranging from 1 (most rigorous, i.e., properly powered randomized clinical trial) to 5 (least rigorous, e.g., case reports). Separate analyses were performed for two groups of studies, one involving all included studies meeting search criteria, and the other involving only studies from the USA. Rates of inclusion of different ethnoracial groups were calculated between studies published before and after December 31, 2017. Additionally, the proportion of White vs. non-White participants was compared between studies published before and after December 31, 2017. Finally, a nonparametric Mann-Whitney U test was used to compare the relative quality ratings of studies published before and after December 31, 2017. Findings: 787 studies were screened, and 39 studies were included. This included 16 studies (n = 282) from a prior review published in 2018 with an additional 23 studies (n = 1111) that were published after 2017, consisting of 14 randomized controlled studies, 8 open-label studies, and 1 placebo-controlled, within-subject, fixed-order study. In all included studies published after 2017, 85.6% of participants identified as non-Hispanic White, 3.1% as Black, 6.8% as Latinx/Hispanic, 3.6% as Asian, 1.2% as Indigenous, 3.5% as mixed race, 1.4% as other, Pooled data from all included studies (n = 1393) found 85.0% of participants identified as non-Hispanic White, 2.9% as Black, 5.9% as Latinx/Hispanic, 3.2% as Asian, 1.9% as Indigenous, 3.7% as mixed race, 1.4% as other. In studies conducted in the USA (n = 1074), 908 (84.5%) of participants identified as White, 36 (3.4%) as Black, 80 (7.4%) as Latinx/Hispanic, 43 (4.0%) as Asian, 15 (1.4%) as Indigenous, 40 (3.7%) as Mixed, and 9 (0.8%) as Other. Differences in inclusion rates were found when comparing studies published before and after December 31, 2017 for all included studies and all studies conducted in the USA. The proportion of White to non-White participants was found to have decreased in studies conducted in the USA over the same period, but not for all included studies. Interpretation: Underrepresentation of ethnoracial minoritized populations persists in studies examining psychedelic therapies, despite growing calls for diversity. Non-Hispanic White participants remain an over-represented majority by a large margin, though, there were greater proportions of ethnic minoritized populations included in studies since 2018, particularly in studies conducted in the USA. This indicates progress towards equity in psychedelic research, though much work is needed to inform the safety and efficacy of psychedelic treatments in the general population. Funding: There was no funding source for this study.

Impact and effect of imaging referral guidelines on patients and radiology services: a systematic review.

OBJECTIVES: The objective of this systematic review was to offer a comprehensive overview and explore the associated outcomes from imaging referral guidelines on various key stakeholders, such as patients and radiologists. MATERIALS AND METHODS: An electronic database search was conducted in Medline, Embase and Web of Science to retrieve citations published between 2013 and 2023. The search was constructed using medical subject headings and keywords. Only full-text articles and reviews written in English were included. The quality of the included papers was assessed using the mixed methods appraisal tool. A narrative synthesis was undertaken for the selected articles. RESULTS: The search yielded 4384 records. Following the abstract, full-text screening, and removal of duplication, 31 studies of varying levels of quality were included in the final analysis. Imaging referral guidelines from the American College of Radiology were most commonly used. Clinical decision support systems were the most evaluated mode of intervention, either integrated or standalone. Interventions showed reduced patient radiation doses and waiting times for imaging. There was a general reduction in radiology workload and utilisation of diagnostic imaging. Low-value imaging utilisation decreased with an increase in the appropriateness of imaging referrals and ratings and cost savings. Clinical effectiveness was maintained during the intervention period without notable adverse consequences. CONCLUSION: Using evidence-based imaging referral guidelines improves the quality of healthcare and outcomes while reducing healthcare costs. Imaging referral guidelines are one essential component of improving the value of radiology in the healthcare system. CLINICAL RELEVANCE STATEMENT: There is a need for broader dissemination of imaging referral guidelines to healthcare providers globally in tandem with the harmonisation of the application of these guidelines to improve the overall value of radiology within the healthcare system. KEY POINTS: The application of imaging referral guidelines has an impact and effect on patients, radiologists, and health policymakers. The adoption of imaging referral guidelines in clinical practice can impact healthcare costs and improve healthcare quality and outcomes. Implementing imaging referral guidelines contributes to the attainment of value-based radiology.

Psilocybin desynchronizes the human brain.

A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials1-4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus5-8. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.

Cardiac Arrest and Cardiopulmonary Resuscitation Outcome Reports: 2024 Update of the Utstein Out-of-Hospital Cardiac Arrest Registry Template.

The Utstein Out-of-Hospital Cardiac Arrest Resuscitation Registry Template, introduced in 1991 and updated in 2004 and 2015, standardizes data collection to enable research, evaluation, and comparisons of systems of care. The impetus for the current update stemmed from significant advances in the field and insights from registry development and regional comparisons. This 2024 update involved representatives of the International Liaison Committee on Resuscitation and used a modified Delphi process. Every 2015 Utstein data element was reviewed for relevance, priority (core or supplemental), and improvement. New variables were proposed and refined. All changes were voted on for inclusion. The 2015 domains-system, dispatch, patient, process, and outcomes-were retained. Further clarity is provided for the definitions of out-of-hospital cardiac arrest attended resuscitation and attempted resuscitation. Changes reflect advancements in dispatch, early response systems, and resuscitation care, as well as the importance of prehospital outcomes. Time intervals such as emergency medical service response time now emphasize precise reporting of the times used. New flowcharts aid the reporting of system effectiveness for patients with an attempted resuscitation and system efficacy for the Utstein comparator group. Recognizing the varying capacities of emergency systems globally, the writing group provided a minimal dataset for settings with developing emergency medical systems. Supplementary variables are considered useful for research purposes. These revisions aim to elevate data collection and reporting transparency by registries and researchers and to advance international comparisons and collaborations. The overarching objective remains the improvement of outcomes for patients with out-of-hospital cardiac arrest.

Clinical characterization and mutation spectrum of patients with hypertriglyceridemia in a German outpatient clinic.

BACKGROUND: Severe hypertriglyceridemia (HTG) has predominantly multifactorial causes (MCS). Yet a small subset of patients have the monogenetic form (FCS). It remains a challenge to distinguish patients clinically, since decompensated MCS might mimic FCS´s severity. Aim of the current study was to determine clinical criteria that could sufficiently distinguish both forms as well as to apply the FCS score proposed by Moulin and colleagues. METHODS: We retrospectively studied 72 patients who presented with severe HTG in our clinic during a time span of seven years and received genetic testing. We classified genetic variants (ACMG-criteria), followed by genetic categorization into MCS or FCS. Clinical data were gathered from the medical records and the FCS score was calculated for each patient. RESULTS: Molecular genetic screening revealed eight FCS patients and 64 MCS patients. Altogether, we found 13 pathogenic variants of which four have not been described before. The FCS patients showed a significantly higher median triglyceride level compared to the MCS. The FCS score yielded a sensitivity of 75% and a specificity of 93.7% in our cohort, and significantly differentiated between the FCS and MCS group (p<0.001). CONCLUSIONS: In our cohort we identified several variables that significantly differentiated FCS from MCS. The FCS score performed similar to the original study by Moulin, thereby further validating the discriminatory power of the FCS score in an independent cohort.

Cardiac arrest and cardiopulmonary resuscitation outcome reports: 2024 update of the Utstein Out-of-Hospital Cardiac Arrest Registry template.

The Utstein Out-of-Hospital Cardiac Arrest Resuscitation Registry Template, introduced in 1991 and updated in 2004 and 2015, standardizes data collection to enable research, evaluation, and comparisons of systems of care. The impetus for the current update stemmed from significant advances in the field and insights from registry development and regional comparisons. This 2024 update involved representatives of the International Liaison Committee on Resuscitation and used a modified Delphi process. Every 2015 Utstein data element was reviewed for relevance, priority (core or supplemental), and improvement. New variables were proposed and refined. All changes were voted on for inclusion. The 2015 domains-system, dispatch, patient, process, and outcomes-were retained. Further clarity is provided for the definitions of out-of-hospital cardiac arrest attended resuscitation and attempted resuscitation. Changes reflect advancements in dispatch, early response systems, and resuscitation care, as well as the importance of prehospital outcomes. Time intervals such as emergency medical service response time now emphasize precise reporting of the times used. New flowcharts aid the reporting of system effectiveness for patients with an attempted resuscitation and system efficacy for the Utstein comparator group. Recognizing the varying capacities of emergency systems globally, the writing group provided a minimal dataset for settings with developing emergency medical systems. Supplementary variables are considered useful for research purposes. These revisions aim to elevate data collection and reporting transparency by registries and researchers and to advance international comparisons and collaborations. The overarching objective remains the improvement of outcomes for patients with out-of-hospital cardiac arrest.

Correlative multimodal optical and X-ray fluorescence imaging of brominated fluorophores.

Imaging with multiple modalities can maximise the information gained from the analysis of a single sample. probes for optical fluorescence and X-ray fluorescence microscopy based on brominated 4-amino-1,8-naphthalimide and BODIPY scaffolds have been successfully designed and synthesised. Herein we show that these prototype probes, based on each of these scaffolds, can be imaged in two different cancer cell lines, and that the respective optical fluorescence and X-ray fluorescence signals are well correlated in these images.

Ixekizumab Demonstrates Rapid and Consistent Efficacy for Patients with Psoriatic Arthritis, Regardless of Psoriasis Severity.

INTRODUCTION: Skin involvement in patients with psoriatic arthritis (PsA) worsens the severity and burden of disease. Ixekizumab (IXE), a selective interleukin (IL)-17A antagonist, was compared to placebo (PBO) in the SPIRIT-P1 (NCT01695239) and SPIRIT-P2 (NCT02349295) studies in patients with PsA and evidence of plaque psoriasis. This post hoc analysis reports musculoskeletal, skin, and nail outcomes through week 24 in patients from SPIRIT-P1 and SPIRIT-P2, stratified by mild, moderate, or psoriasis at baseline. METHODS: This post hoc analysis pooled patients from SPIRIT-P1 and SPIRIT-P2 who were randomly assigned to PBO or IXE 80 mg every 4 weeks (Q4W) or every 2 weeks (Q2W). Efficacy outcomes were analyzed through week 24 by baseline psoriasis severity, defined by percent body surface area (BSA) affected; mild = BSA < 3%, moderate = 3% ≤ BSA ≤ 10%, severe = BSA > 10%. The primary outcomes assessed were the proportion of patients achieving American College of Rheumatology (ACR)20, ACR50, and ACR70 responses. Secondary outcomes included musculoskeletal, disease activity, skin and nail, and health-related quality-of-life measures. RESULTS: Similar proportions of patients achieved ACR20/ACR50/ACR70 over time across all severity subgroups and treatment arms. More than one-third of IXE-treated patients achieved ACR20 at week 4, or ACR50 at week 24, with no significant differences according to psoriasis severity at baseline. Disease activity outcomes were similar through week 24 with both IXEQ4W and IXEQ2W, regardless of psoriasis severity at baseline. There were no significant differences over 24 weeks in the proportions of IXE-treated patients with mild, moderate, or severe baseline psoriasis who achieved Minimal Disease Activity (MDA). Across all severity subgroups, IXE demonstrated Psoriasis Area Severity Index 100 response as early as week 4, and approximately one-third of IXE-treated patients achieved total skin clearance at week 24. CONCLUSION: IXE demonstrated rapid and consistent efficacy in joint, skin, and nail for patients with PsA, regardless of baseline psoriasis severity. TRIAL REGISTRATION: SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295).

Near-Infrared Ratiometric Fluorescent Probe for Detecting Endogenous Cu2+ in the Brain.

Copper participates in a range of critical functions in the nervous system and human brain. Disturbances in brain copper content is strongly associated with neurological diseases. For example, changes in the level and distribution of copper are reported in neuroblastoma, Alzheimer's disease, and Lewy body disorders, such as Parkinson disease and dementia with Lewy bodies (DLB). There is a need for more sensitive techniques to measure intracellular copper levels to have a better understanding of the role of copper homeostasis in neuronal disorders. Here, we report a reaction-based near-infrared (NIR) ratiometric fluorescent probe CyCu1 for imaging Cu2+ in biological samples. High stability and selectivity of CyCu1 enabled the probe to be deployed as a sensor in a range of systems, including SH-SY5Y cells and neuroblastoma tumors. Furthermore, it can be used in plant cells, reporting on copper added to Arabidopsis roots. We also used CyCu1 to explore Cu2+ levels and distribution in post-mortem brain tissues from patients with DLB. We found significant decreases in Cu2+ content in the cytoplasm, neurons, and extraneuronal space in the degenerating substantia nigra in DLB compared with healthy age-matched control tissues. These findings enhance our understanding of Cu2+ dysregulation in Lewy body disorders. Our probe also shows promise as a photoacoustic imaging agent, with potential for applications in bimodal imaging.

Sex and statin-related genetic associations at the PCSK9 gene locus: results of genome-wide association meta-analysis.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key player of lipid metabolism with higher plasma levels in women throughout their life. Statin treatment affects PCSK9 levels also showing evidence of sex-differential effects. It remains unclear whether these differences can be explained by genetics. METHODS: We performed genome-wide association meta-analyses (GWAS) of PCSK9 levels stratified for sex and statin treatment in six independent studies of Europeans (8936 women/11,080 men respectively 14,825 statin-free/5191 statin-treated individuals). Loci associated in one of the strata were tested for statin- and sex-interactions considering all independent signals per locus. Independent variants at the PCSK9 gene locus were then used in a stratified Mendelian Randomization analysis (cis-MR) of PCSK9 effects on low-density lipoprotein cholesterol (LDL-C) levels to detect differences of causal effects between the subgroups. RESULTS: We identified 11 loci associated with PCSK9 in at least one stratified subgroup (p < 1.0 × 10-6), including the PCSK9 gene locus and five other lipid loci: APOB, TM6SF2, FADS1/FADS2, JMJD1C, and HP/HPR. The interaction analysis revealed eight loci with sex- and/or statin-interactions. At the PCSK9 gene locus, there were four independent signals, one with a significant sex-interaction showing stronger effects in men (rs693668). Regarding statin treatment, there were two significant interactions in PCSK9 missense mutations: rs11591147 had stronger effects in statin-free individuals, and rs11583680 had stronger effects in statin-treated individuals. Besides replicating known loci, we detected two novel genome-wide significant associations: one for statin-treated individuals at 6q11.1 (within KHDRBS2) and one for males at 12q24.22 (near KSR2/NOS1), both with significant interactions. In the MR of PCSK9 on LDL-C, we observed significant causal estimates within all subgroups, but significantly stronger causal effects in statin-free subjects compared to statin-treated individuals. CONCLUSIONS: We performed the first double-stratified GWAS of PCSK9 levels and identified multiple biologically plausible loci with genetic interaction effects. Our results indicate that the observed sexual dimorphism of PCSK9 and its statin-related interactions have a genetic basis. Significant differences in the causal relationship between PCSK9 and LDL-C suggest sex-specific dosages of PCSK9 inhibitors.

The protein "proprotein convertase subtilisin/kexin type 9" (PCSK9) regulates the levels of low-density lipoprotein cholesterol (LDL-C) in blood, and thus, contributes to the risk of cardio-vascular diseases. Women tend to have higher PCSK9 plasma levels throughout their life, although the difference is smaller in patients under LDL-C lowering medication (e.g., statins). We investigated the interplay of genetics, statin-treatment and sex, using combined data from six European studies. We detected 11 genetic regions associated with PCSK9 levels, of which one was specific for women (at SLCO1B3, a statin-transporter gene), and three were specific for men (e.g., ALOX5, encoding a protein linked to chronic inflammatory diseases such as atherosclerosis). We also tested if statin use changed the genetic effect and found five genes only associated with PCSK9 levels in untreated participants. Variants in the gene encoding PCSK9 were most strongly associated and had heterogeneous effects in dependence on statin treatment and sex: On one hand, there were genetic variants with stronger effects in men than women. Those variants are also linked to sex-differential gene expression of PCSK9. On the other hand, there were also variants with treatment-depending effects, linked to protein structure and functionality of PCSK9. This indicates that the observed sexual and treatment-related effects on PCSK9 levels have a genetic basis. In addition, we compared the causal effects of PCSK9 on LDL-C levels between men and women and found a different response to statin treatment. This highlights the need for sex-sensitive dosages of lipid-lowering medication.

LiMOX-A Point Cloud Lidar Model Toolbox Based on NVIDIA OptiX Ray Tracing Engine.

Virtual testing and validation are building blocks in the development of autonomous systems, in particular autonomous driving. Perception sensor models gained more attention to cover the entire tool chain of the sense-plan-act cycle, in a realistic test setup. In the literature or state-of-the-art software tools various kinds of lidar sensor models are available. We present a point cloud lidar sensor model, based on ray tracing, developed for a modular software architecture, which can be used stand-alone. The model is highly parametrizable and designed as a toolbox to simulate different kinds of lidar sensors. It is linked to an infrared material database to incorporate physical sensor effects introduced by the ray-surface interaction. The maximum detectable range depends on the material reflectivity, which can be covered with this approach. The angular dependence and maximum range for different Lambertian target materials are studied. Point clouds from a scene in an urban street environment are compared for different sensor parameters.

A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels.

ABSTRACT: Coagulation factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single-variant meta-analysis, including up to 45 289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified 3 candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells. Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P < 5 × 10-9) at 7 new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and 1 for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multiphenotype analysis of FVIII and VWF identified another 3 new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, whereas silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and 1 for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro.

Effects of large-scale gold mining on habitat use and selection by American pronghorn.

Anthropogenic disturbances, including extraction of natural resources and development of alternative energy, are reducing and fragmenting habitat for wildlife across the globe. Effects of those disturbances have been explored by studying populations that migrate through oil and gas fields or alternative energy facilities. Extraction of minerals, including precious metals and lithium, is increasing rapidly in remote areas, which results in dramatically altered landscapes in areas of resident populations of wildlife. Our goal was to examine how a resident population of American pronghorn (Antilocapra americana) in the Great Basin ecosystem selected resources near a large-scale disturbance year around. We investigated how individuals selected resources around a large, open-pit gold mine. We classified levels of disturbance associated with the mine, and used a random forest model to select ecological covariates associated with habitat selection by pronghorn. We used resource selection functions to examine how disturbances affected habitat selection by pronghorn both annually and seasonally. Pronghorn strongly avoided areas of high disturbance, which included open pits, heap leach fields, rock disposal areas, and a tram. Pronghorn selected areas near roads, although selection was strongest about 2 km away. We observed relatively broad variation among individuals in selection of resources, and how they responded to the mine. The Great Basin is a mineral-rich area that continues to be exploited for natural resources, especially minerals. Sagebrush-dependent species, including pronghorn, that rely on this critical habitat were directly affected by that transformation of the landscape, which is likely to increase with expansion of the mine. As extraction of minerals from remote landscapes around the world continues to fragment habitats for wildlife, increasing our understanding of impacts of those changes on behaviors of wildlife before populations decline, may assist in the mitigation and minimization of negative impacts on mineral-rich landscapes and on wildlife populations.

Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer's disease and aging.

Alzheimer's disease (AD) is characterized by progressive neurodegeneration, but the specific events that cause cell death remain poorly understood. Death Induced by Survival gene Elimination (DISE) is a cell death mechanism mediated by short (s) RNAs acting through the RNA-induced silencing complex (RISC). DISE is thus a form of RNA interference, in which G-rich 6mer seed sequences in the sRNAs (position 2-7) target hundreds of C-rich 6mer seed matches in genes essential for cell survival, resulting in the activation of cell death pathways. Here, using Argonaute precipitation and RNAseq (Ago-RP-Seq), we analyze RISC-bound sRNAs to quantify 6mer seed toxicity in several model systems. In mouse AD models and aging brain, in induced pluripotent stem cell-derived neurons from AD patients, and in cells exposed to Aß42 oligomers, RISC-bound sRNAs show a shift to more toxic 6mer seeds compared to controls. In contrast, in brains of "SuperAgers", humans over age 80 who have superior memory performance, RISC-bound sRNAs are shifted to more nontoxic 6mer seeds. Cells depleted of nontoxic sRNAs are sensitized to Aß42-induced cell death, and reintroducing nontoxic RNAs is protective. Altogether, the correlation between DISE and Aß42 toxicity suggests that increasing the levels of nontoxic miRNAs in the brain or blocking the activity of toxic RISC-bound sRNAs could ameliorate neurodegeneration.

The brainstem's red nucleus was evolutionarily upgraded to support goal-directed action.

The red nucleus is a large brainstem structure that coordinates limb movement for locomotion in quadrupedal animals (Basile et al., 2021). The humans red nucleus has a different pattern of anatomical connectivity compared to quadrupeds, suggesting a unique purpose (Hatschek, 1907). Previously the function of the human red nucleus remained unclear at least partly due to methodological limitations with brainstem functional neuroimaging (Sclocco et al., 2018). Here, we used our most advanced resting-state functional connectivity (RSFC) based precision functional mapping (PFM) in highly sampled individuals (n = 5) and large group-averaged datasets (combined N ~ 45,000), to precisely examine red nucleus functional connectivity. Notably, red nucleus functional connectivity to motor-effector networks (somatomotor hand, foot, and mouth) was minimal. Instead, red nucleus functional connectivity along the central sulcus was specific to regions of the recently discovered somato-cognitive action network (SCAN; (Gordon et al., 2023)). Outside of primary motor cortex, red nucleus connectivity was strongest to the cingulo-opercular (CON) and salience networks, involved in action/cognitive control (Dosenbach et al., 2007; Newbold et al., 2021) and reward/motivated behavior (Seeley, 2019), respectively. Functional connectivity to these two networks was organized into discrete dorsal-medial and ventral-lateral zones. Red nucleus functional connectivity to the thalamus recapitulated known structural connectivity of the dento-rubral thalamic tract (DRTT) and could prove clinically useful in functionally targeting the ventral intermediate (VIM) nucleus. In total, our results indicate that far from being a 'motor' structure, the red nucleus is better understood as a brainstem nucleus for implementing goal-directed behavior, integrating behavioral valence and action plans.

Clinical and genetic diagnosis of familial hypercholesterolaemia in patients undergoing coronary angiography: the Ludwigshafen Risk and Cardiovascular Health Study.

AIMS: To investigate the prevalence of familial hypercholesterolaemia (FH) and compare the performance of clinical criteria and genetic testing in patients undergoing coronary angiography. METHODS: The prevalence of FH was determined with the Dutch Lipid Clinical Network (DLCN), US-MEDPED, Simon Broome (SB) criteria, the 'Familial Hypercholesterolaemia Case Ascertainment Tool' (FAMCAT), and a clinical algorithm. Genetic screening was conducted with a custom array from Affymetrix (CARRENAL array) harboring 944 FH mutations. RESULTS: The study cohort consisted of 3267 patients (78.6% with coronary artery disease [CAD]). FH was diagnosed in 2.8%, 2.2%, 3.9%, and 7.9% using the DLCN, US-MEDPED, SB criteria, and the FAMCAT. The clinical algorithm identified the same patients as the SB criteria. Pathogenic FH mutations were found in 1.2% (1.2% in patients with CAD, 1.0% in patients without CAD). FH was more frequently diagnosed in younger patients. With genetic testing as reference, the clinical criteria achieved areas under the ROC curve (AUCs) in the range of 0.56-0.68. Using only LDL-C corrected for statin intake, an AUC of 0.68 was achieved. CONCLUSION: FH is up to fourfold more prevalent in patients undergoing coronary angiography than in contemporary cohorts representing the general population. Different clinical criteria yield substantially different diagnosis rates, overestimating the prevalence of FH compared to genetic testing. LDL-C testing alone may be sufficient to raise the suspicion of FH, which then needs to be corroborated by genetic testing.

Combining methods to conduct a systematic review and propose a conceptual and theoretical framework in socio-environmental research.

This study aims to present a combination of methods and propose robust theoretical and conceptual frameworks for solving socio-environmental issues. This proposal included the Problem, Intervention, Context, and Outcome (PICO) framework and Protocol and Reporting result with Search, Appraisal, Synthesis, and Analysis framework, and develop (PSALSAR) method through SODIP steps: (i) Systematic review and meta-analysis defining the study from guiding questions; (ii) Open-source related to software and data; (iii) Data visualization and design information; (iv) Identification of gaps, challenges and trends through automation and lexicometric analysis; and (v) Proposal of theoretical and conceptual frameworks. This proposal defines the steps as support to combine and systematize information necessary to facilitate the production of this type of document using open-access software in the visualization and design of information. All these steps are replicable and essential to propose a conceptual and theoretical framework to contribute to the construction of knowledge in socio-environmental research and to propose solutions by filling in the gaps. In summary, this combination of methods shows:•The use of SODIP steps provides robustness and efficiency in carrying out review studies, facilitating the way to propose theoretical or conceptual frameworks.•Choosing to use open-source tools is essential for better evaluation and visualization of qualitative and quantitative data in review studies.•The combination of methods and data in the systematic review (scientific, political documents. and databases) supports the proposal of robust theoretical and conceptual frameworks.