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Abstract Stroke, the second leading cause of mortality globally, predominantly results from ischemic conditions. Immediate attention and diagnosis, related to the characterization of brain lesions, play a crucial role in patient prognosis. Standard stroke protocols include an initial evaluation from a non-contrast CT to discriminate between hemorrhage and ischemia. However, non-contrast CTs lack sensitivity in detecting subtle ischemic changes in this phase. Alternatively, diffusion-weighted MRI studies provide enhanced capabilities, yet are constrained by limited availability and higher costs. Hence, we idealize new approaches that integrate ADC stroke lesion findings into CT, to enhance the analysis and accelerate stroke patient management. This study details a public challenge where scientists applied top computational strategies to delineate stroke lesions on CT scans, utilizing paired ADC information. Also, it constitutes the first effort to build a paired dataset with NCCT and ADC studies of acute ischemic stroke patients. Submitted algorithms were validated with respect to the references of two expert radiologists. The best achieved Dice score was 0.2 over a test study with 36 patient studies. Despite all the teams employing specialized deep learning tools, results reveal limitations of computational approaches to support the segmentation of small lesions with heterogeneous density.

Abstract The absence of a long COVID (LC) or post-acute sequelae of COVID-19 (PASC) diagnostic has profound implications for research and potential therapeutics given the lack of specificity with symptom-based identification of LC and the overlap of symptoms with other chronic inflammatory conditions. Here, we report a machine-learning approach to LC/PASC diagnosis on 347 individuals using cytokine hubs that are also capable of differentiating LC from chronic lyme disease (CLD). We derived decision tree, random forest, and gradient-boosting machine (GBM) classifiers and compared their diagnostic capabilities on a dataset partitioned into training (178 individuals) and evaluation (45 individuals) sets. The GBM model generated 89% sensitivity and 96% specificity for LC with no evidence of overfitting. We tested the GBM on an additional random dataset (106 LC/PASC and 18 Lyme), resulting in high sensitivity (97%) and specificity (90%) for LC. We constructed a Lyme Index confirmatory algorithm to discriminate LC and CLD.

Abstract Skin pigmentation is negatively associated with circulating vitamin D (VD) concentration. Therefore, genetic factors involved in skin pigmentation could influence the risk of vitamin D deficiency (VDD). We evaluated the impact genetic variants related to skin pigmentation on VD in Mexican population. This cross-sectional analysis included 848 individuals from the Health Worker Cohort Study (ratio males to females ~ 1:3). Eight genetic variants: rs16891982 (SLC45A2), rs12203592 (IRF4), rs1042602 and rs1126809 (TYR), rs1800404 (OCA2), rs12913832 (HERC2), rs1426654 (SLC24A5), and rs2240751 (MFSD12); involved in skin pigmentation were genotyped. Skin pigmentation was assessed by self-report. Linear and logistic regression were used to assess the association between the variants of interest and VD and VDD, as appropriate. In our study, eight genetic variants were associated with skin pigmentation. A genetic risk score built with the variants rs1426654 and rs224075 was associated with lower VD levels (β = − 1.38, 95% CI − 2.59, − 0.17, p = 0.025). Nevertheless, when examining gene–gene interactions, we observed that rs2240751 × rs12203592 were associated with VD levels (P interaction = 0.021). Whereas rs2240751 × rs12913832 (P interaction = 0.0001) were associated with VDD. Our results suggest that skin pigmentation-related gene variants are associated with lower VD levels in Mexican population. These results underscore the importance of considering genetic interactions when assessing the impact of genetic polymorphisms on VD levels.

Abstract Mortality of patients hospitalized with COVID-19 has remained high during the consecutive SARS-CoV-2 pandemic waves. Early discrimination of patients at high mortality risk is crucial for optimal patient care. Symmetric (SDMA) and asymmetric dimethylarginine (ADMA) have been proposed as possible biomarkers to improve risk prediction of COVID-19 patients. We measured SDMA, ADMA, and other L-arginine-related metabolites in 180 patients admitted with COVID-19 in four German university hospitals as compared to 127 healthy controls. Patients were treated according to accepted clinical guidelines and followed-up until death or hospital discharge. Classical inflammatory markers (leukocytes, CRP, PCT), renal function (eGFR), and clinical scores (SOFA) were taken from hospital records. In a small subgroup of 23 COVID-19 patients, sequential blood samples were available and analyzed for biomarker trends over time until 14 days after admission. Patients had significantly elevated SDMA, ADMA, and L-ornithine and lower L-citrulline concentrations than controls. Within COVID-19 patients, SDMA and ADMA were significantly higher in non-survivors (n = 41, 22.8%) than in survivors. In ROC analysis, the optimal cut-off to discriminate non-survivors from survivors was 0.579 µmol/L for SDMA and 0.599 µmol/L for ADMA (both p

Abstract Arid and semi-arid areas are among the most threatened ecosystems on the planet. The Tehuacán-Cuicatlán Biosphere Reserve (TCBR), in southeastern Mexico, is an arid and semi-arid area with high biological diversity and human settlements of eight ethnic groups. Two rivers drain the reserve, Río Grande (RG) and Río Salado (RS), which are not subject to water quality monitoring by government agencies; however, measures of water quality of these rivers are needed to focus conservation actions on this resource. This work aimed to test the effectiveness of participatory water quality monitoring with the participation of three actors: Reserve management leaders, local communities, and academics, to monitoring water quality in the rivers of the TCBR. Ninety-two residents were trained to carry out water quality biomonitoring using the Biological Monitoring Working Party (BMWP) index calibrated for the reserve. The BMWP uses macroinvertebrate families to display numerical and categorical water quality scores. Additionally, the Water Quality Index (WQI) was assessed and the Normalized Difference Vegetation Index (NDVI) of the riparian zones was estimated in each study site. The mean WQI scores were 69.24 for RS (no treatment necessary for most crops and necessary treatment for public water supply) and 75.16 for RG (minor purification for crops requiring high-quality water and necessary treatment for public water supply). The BMWP showed five water quality categories (Excellent, Very Good, Good, Fair, and Poor), showing higher water quality scores in the upper portion of the basins and capable of discriminating study sites with lower scores close to human settlements. At one study site, data from participatory monitoring impelled actions taken to address a pollution source and influenced policy focus, reaching the maximum level of participatory-based monitoring. This led to avoid the discharge of wastewater into the river to conserve and protect the water resource. WQI is closely related to BMWP; however, the latter was far more sensitive to detecting areas affected by domestic water discharges. The NDVI presented low values for the TCBR, being lower in RS (the driest area). Although the NDVI showed a weak relationship with BMWP values, areas with higher NDVI values generally achieved higher BMWP values. The results of this study highlight the high sensitivity of the BMWP to detect several water quality conditions in the rivers running through the TCBR when compared to WQI. In addition, the usefulness of biomonitoring using the BMWP index was evident, as well as the importance of the participation of local inhabitants contributing to the knowledge of water quality in biosphere reserves and carrying out timely measures that allow the rivers in these reserves to be maintained in good condition.

Abstract Rapamycin slows cystogenesis in murine models of polycystic kidney disease (PKD) but failed in clinical trials, potentially due to insufficient drug dosing. To improve drug efficiency without increasing dose, kidney-specific drug delivery may be used. Mesoscale nanoparticles (MNP) selectively target the proximal tubules in rodents. We explored whether MNPs can target cystic kidney tubules and whether rapamycin-encapsulated-MNPs (RapaMNPs) can slow cyst growth in Pkd1 knockout (KO) mice. MNP was intravenously administered in adult Pkd1KO mice. Serum and organs were harvested after 8, 24, 48 or 72 h to measure MNP localization, mTOR levels, and rapamycin concentration. Pkd1KO mice were then injected bi-weekly for 6 weeks with RapaMNP, rapamycin, or vehicle to determine drug efficacy on kidney cyst growth. Single MNP injections lead to kidney-preferential accumulation over other organs, specifically in tubules and cysts. Likewise, one RapaMNP injection resulted in higher drug delivery to the kidney compared to the liver, and displayed sustained mTOR inhibition. Bi-weekly injections with RapaMNP, rapamycin or vehicle for 6 weeks resulted in inconsistent mTOR inhibition and little change in cyst index, however. MNPs serve as an effective short-term, kidney-specific delivery system, but long-term RapaMNP failed to slow cyst progression in Pkd1KO mice.

Abstract In mammalian females, quiescent primordial follicles serve as the ovarian reserve and sustain normal ovarian function and egg production via folliculogenesis. The loss of primordial follicles causes ovarian aging. Cellular senescence, characterized by cell cycle arrest and production of the senescence-associated secretory phenotype (SASP), is associated with tissue aging. In the present study, we report that some quiescent primary oocytes in primordial follicles become senescent in adult mouse ovaries. The senescent primary oocytes share senescence markers characterized in senescent somatic cells. The senescent primary oocytes were observed in young adult mouse ovaries, remained at approximately 15% of the total primary oocytes during ovarian aging from 6 to 12 months, and accumulated in aged ovaries. Administration of a senolytic drug ABT263 to 3-month-old mice reduced the percentage of senescent primary oocytes and the transcription of the SASP factors in the ovary, in addition, led to increased numbers of primordial and total follicles and a higher rate of oocyte maturation. Our study provides experimental evidence that primary oocytes, a germline cell type that is arrested in meiosis, become senescent in adult mouse ovaries and that senescent cell clearance reduced primordial follicle loss and mitigated ovarian aging phenotypes.

Abstract The technique known as 4D-STEM has recently emerged as a powerful tool for the local characterization of crystalline structures in materials, such as cathode materials for Li-ion batteries or perovskite materials for photovoltaics. However, the use of new detectors optimized for electron diffraction patterns and other advanced techniques requires constant adaptation of methodologies to address the challenges associated with crystalline materials. In this study, we present a novel image-processing method to improve pattern matching in the determination of crystalline orientations and phases. Our approach uses sub-pixel adaptive image processing to register and reconstruct electron diffraction signals in large 4D-STEM datasets. By using adaptive prominence and linear filters, we can improve the quality of the diffraction pattern registration. The resulting data compression rate of 103 is well-suited for the era of big data and provides a significant enhancement in the performance of the entire ACOM data processing method. Our approach is evaluated using dedicated metrics, which demonstrate a high improvement in phase recognition. Several features are extracted from the registered data to map properties such as the spot count, and various virtual dark fields, which are used to enhance the handling of the results maps. Our results demonstrate that this data preparation method not only enhances the quality of the resulting image but also boosts the confidence level in the analysis of the outcomes related to determining crystal orientation and phase. Additionally, it mitigates the impact of user bias that may occur during the application of the method through the manipulation of parameters.

Abstract Terahertz imaging is unlocking unique capabilities for the analysis of cultural heritage artifacts. This paper uses terahertz time-domain imaging for the study of a gilded wooden artifact, providing a means to perform stratigraphic analysis, yielding information about the composition of the artifact, presence of certain materials identifiable through their THz spectral fingerprint, as well as alterations that have been performed over time. Due to the limited information that is available for many historic artifacts, the data that can be obtained through the presented technique can guide proper stewardship of the artifact, informing its long-term preservation.

Abstract The aerosol and precipitable water vapor (PW) distribution over the tropical Andes region is characterized using Aerosol Robotic Network (AERONET) observations at stations in Medellin (Colombia), Quito (Ecuador), Huancayo (Peru), and La Paz (Bolivia). AERONET aerosol optical depth (AOD) is interpreted using PM2.5 data when available. Columnar water vapor derived from ozone soundings at Quito is used to compare against AERONET PW. MERRA-2 data are used to complement analyses. Urban pollution and biomass burning smoke (BBS) dominate the regional aerosol composition. AOD and PM2.5 yearly cycles for coincident measurements correlate linearly at Medellin and Quito. The Andes cordillera’s orientation and elevation funnel or block BBS transport into valleys or highlands during the two fire seasons that systematically impact South America. The February–March season north of Colombia and the Colombian-Venezuelan border directly impacts Medellin. Possibly, the March aerosol signal over Quito has a long-range transport component. At Huancayo and La Paz, AOD increases in September due to the influence of BBS in the Amazon. AERONET PW and sounding data correlate linearly but a dry bias with respect to soundings was identified in AERONET. PW and rainfall progressively decrease from north to south due to increasing altitude. This regional diagnosis is an underlying basis to evaluate future changes in aerosol and PW given prevailing conditions of rapidly changing atmospheric composition.

Abstract Dysregulation of nitric oxide (NO) production can cause ischaemic retinal injury and result in blindness. How this dysregulation occurs is poorly understood but thought to be due to an impairment in NO synthase function (NOS) and nitro-oxidative stress. Here we investigated the possibility of correcting this defective NOS activity by supplementation with the cofactor tetrahydrobiopterin, BH4. Retinal ischaemia was examined using the oxygen-induced retinopathy model and BH4 deficient Hph-1 mice used to establish the relationship between NOS activity and BH4. Mice were treated with the stable BH4 precursor sepiapterin at the onset of hypoxia and their retinas assessed 48 h later. HPLC analysis confirmed elevated BH4 levels in all sepiapterin supplemented groups and increased NOS activity. Sepiapterin treatment caused a significant decrease in neuronal cell death in the inner nuclear layer that was most notable in WT animals and was associated with significantly diminished superoxide and local peroxynitrite formation. Interestingly, sepiapterin also increased inflammatory cytokine levels but not microglia cell number. BH4 supplementation by sepiapterin improved both redox state and neuronal survival during retinal ischaemia, in spite of a paradoxical increase in inflammatory cytokines. This implicates nitro-oxidative stress in retinal neurones as the cytotoxic element in ischaemia, rather than enhanced pro-inflammatory signalling.

Abstract MBA cell-based synchrotron light sources have enabled an unprecedented increase in beam coherence and brightness, greatly benefiting the scientific disciplines that rely on X-ray techniques. However, controlling the electron dynamics is a theoretical and technological challenge, due to the large number of parameters to adjust and constraints to satisfy when designing modern synchrotrons. Having versatile tools for the description and manipulation of electron dynamics could favor the design of these accelerators and lead to progress on several fronts in the understanding of matter. In this paper, a formalism based on the use of nonlinear geometric surfaces represented by polynomial quasi-invariants, to analyze and optimize the dynamic aperture of electrons in MBA storage rings, is introduced. The formalism considers on- and off-momentum particle dynamics. Within the optimization scheme, different objective functions defined in terms of the nonlinear surfaces, which are minimized using genetic algorithm methods, are proposed. A remarkable horizontal dynamic aperture exceeding 19 mm is obtained for the design particle of a synchrotron model with 86 pm $$\cdot $$ · rad emittance along with a dynamic aperture above 5 mm for momentum deviations of ± 3 $$\%$$ % . According to the results presented, this formalism could be greatly useful for manipulating the dynamical properties of electrons in synchrotrons light sources close to the diffraction limit.

Abstract Of those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ~ 10% develop the chronic post-viral debilitating condition, long COVID (LC). Although LC is a heterogeneous condition, about half of cases have typical post-viral fatigue with onset and symptoms that are very similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A key question is whether these conditions are closely related. ME/CFS is a post-stressor fatigue condition that arises from multiple triggers. To investigate the pathophysiology of LC, a pilot study of patients (n = 6) and healthy controls (n = 5) has used quantitative proteomics to discover changes in peripheral blood mononuclear cell (PBMC) proteins. A principal component analysis separated all long COVID patients from healthy controls. Analysis of 3131 proteins identified 162 proteins differentially regulated, of which 37 were related to immune functions, and 21 to mitochondrial functions. Markov cluster analysis identified clusters involved in immune system processes, and two aspects of gene expression-spliceosome and transcription. These results were compared with an earlier dataset of 346 differentially regulated proteins in PBMC’s from ME/CFS patients (n = 9) analysed by the same methodology. There were overlapping protein clusters and enriched molecular pathways particularly in immune functions, suggesting the two conditions have similar immune pathophysiology as a prominent feature, and mitochondrial functions involved in energy production were affected in both conditions.

Abstract X chromosome was reported to be a major contributor to isolation between closely related species—the ‘large X’ effect (LXE). The causes of LXE are not clear, but the leading theory is that it is caused by recessive species incompatibilities exposed in the phenotype due to the hemizygosity of X-linked genes in the heterogametic sex. However, the LXE was also reported in species with relatively recently evolved sex chromosomes where Y chromosome is not completely degenerate and X-linked genes are not hemizygous, such as the plant Silene latifolia. Recent genome sequencing and detailed genetic mapping in this species revealed a massive (> 330 Mb) non- or rarely-recombining pericentromeric region on the X chromosome (Xpr) that comprises ~ 90% of the chromosome and over 13% of the entire genome. If any of the Xpr genes are involved in species incompatibilities, this would oppose interspecific gene flow for other genes tightly linked in the Xpr. Here we test the hypothesis that the previously reported LXE in S. latifolia is caused by the lack of recombination on most of the X chromosome. Based on genome-wide analysis of DNA polymorphism and gene expression in S. latifolia and its close cross-compatible relative S. dioica, we report that the rarely-recombining regions represent a significant barrier for interspecific gene flow. We found little evidence for any additional factors contributing to the LXE, suggesting that extensive pericentromeric recombination suppression on the X-chromosome is the major if not the only cause of the LXE in S. latifolia and S. dioica.

Abstract Several observational studies have investigated the association between cannabis use and intraocular pressure, but its association with primary open-angle glaucoma (POAG) remains unclear. In this study, we leveraged human genetic data to assess through Mendelian randomization (MR) whether cannabis use affects POAG. We used five single-nucleotide polymorphisms (SNPs) associated with lifetime cannabis use (P-value

Abstract SARS-CoV-2 undergoes frequent mutations, affecting COVID-19 diagnostics, transmission and vaccine efficacy. Here, we describe the genetic diversity of 49 SARS-CoV-2 samples from Uganda, collected during the COVID-19 waves of 2020/2021. Overall, the samples were similar to previously reported SARS-CoV-2 from Uganda and the Democratic Republic of Congo (DRC). The main lineages were AY.46 and A.23, which are considered to be Delta SARS-CoV-2 variants. Further, a total of 268 unique single nucleotide variants and 1456 mutations were found, with more than seventy percent mutations in the ORF1ab and S genes. The most common mutations were 2042C>G (83.4%), 14143C>T (79.5%), 245T>C (65%), and 1129G>T (51%), which occurred in the S, ORF1ab, ORF7a and N genes, respectively. As well, 28 structural variants—21 insertions and 7 deletions, occurred in 16 samples. Our findings point to the possibility that most SARS-CoV-2 infections in Uganda at the time arose from local spread and were not newly imported. Moreover, the relatedness of variants from Uganda and the DRC reflects high human mobility and interaction between the two countries, which is peculiar to this region of the world.

Abstract The fibrogenic process plays a significant pathophysiological role in the progression of chronic kidney disease. Inhibition of the renin-angiotensin system (RAS) is one strategy to delay disease progression but does not reverse established fibrosis. In this context, induced pluripotent stem cells (iPSCs) have been considered an alternative due to their regenerative potential. iPSCs exert their effects through paracrine signaling, which releases specific biomolecules into the extracellular environment, either directly or within extracellular vesicle (EVs), that can reach target cells. This study aims to evaluate the potential beneficial effects of iPSC-derived EVs (EV-iPSCs) in an in vitro model of fibrosis using mouse mesangial cells (MMCs) stimulated with TGF-β. EV-iPSCs were obtained by differentially ultracentrifuging iPSCs culture medium. MMCs were stimulated with 5 ng/mL of TGF-β and simultaneously treated with or without EV-iPSCs for 24 h. Markers of inflammation, fibrosis, and RAS components were assessed using RT-PCR, western blotting, and immunofluorescence. Under TGF-β stimulus, MMCs exhibited increased expression of inflammation markers, RAS components, and fibrosis. However, these changes were mitigated in the presence of EV-iPSCs. EV-iPSCs effectively reduced inflammation, RAS activation, and fibrogenesis in this fibrosis model involving mesangial cells, suggesting their potential as a strategy to reduce glomerular sclerosis.

Abstract Rectal cancer is an increasing disease worldwide. The outcomes of its treatment are related to the preoperative characteristics of the patient. The objective of this study was to describe sociodemographic, clinical and surgical characteristics and outcomes of patients operated on for rectal cancer at Hospital Universitario Mayor Méderi (HUM) during the period within 2013–2017.A retrospective descriptive cohort-type study was carried out by consulting the clinical records of patients above the age of 18 years with a clinical/histopathological diagnosis of rectal cancer and an institutional follow-up in those who underwent surgery with laparoscopic anterior resection of the rectum carried out by the coloproctology service of the HUM between 2013 and 2017. For statistical analysis, the SPSS V22 program was used.Data from 133 patients were collected during the study period, most of them male, with more frequent involvement of the lower rectum. Complications occurred in 25% of the patients. Conversion rate to open surgery was 8.6%, in-hospital death was associated with cardiovascular comorbidity, corticosteroid uses and with the presence of complications. Sociodemographic characteristics of the patients were similar to the world population. The institution has a low prevalence of anastomotic dehiscence, global complications are comparable with international statistics.

Abstract A key limitation in assessing the therapeutic impact of non-pharmacological approaches to treating hypertension is the method of reporting outcomes. Reducing the medications required to achieve the same blood pressure may be reported separately to a reduction in the blood pressure without change in medication, and thus lessen the reported beneficial impact of treatment. This study aims to derive a novel scoring system to gauge the therapeutic impact of non-drug treatment of hypertension by utilising a combination of excessive blood pressure and the number of anti-hypertensives into a combined score—the hypertensive index (HTi). The hypertensive index was empirically derived based on the systolic blood pressure and number of antihypertensive drugs, and applied retrospectively to a cohort undergoing intervention for renovascular hypertension. Subgroup and receiver operating characteristic analyses were used to compare the HTi to traditional methods of reporting outcomes. Following intervention (99 patients), 46% had improvement in both medication load and blood pressure, 29% had benefit in blood pressure without reduction in medication load, 15% had reduction in medication load without significant change in blood pressure and 9% showed no benefit in either parameter. The HTi was superior in detecting benefit from intervention compared with measuring blood pressure or medication load alone (AUC 0.94 vs 0.85;0.84). The hypertensive index may be a more sensitive marker of treatment effect than assessing blood pressure measurements alone. The use of such scoring systems in future trial design may allow more accurate reporting of the effects of interventions for hypertension.

Abstract Intrahepatic cholangiocarcinoma (iCCA) is a rare, understudied primary hepatic malignancy with dismal outcomes. Aiming to identify prognostically relevant single-nucleotide polymorphisms, we analyzed 11 genetic variants with a role in tumor-promoting inflammation (VEGF, EGF, EGFR, IL-1B, IL-6, CXCL8 (IL-8), IL-10, CXCR1, HIF1A and PTGS2 (COX-2) genes) and their association with disease-free (DFS) and overall survival (OS) in patients undergoing curative-intent surgery for iCCA. Genomic DNA was isolated from 112 patients (64 female, 48 male) with iCCA. Germline polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism protocols. The IL-1B +3954 C/C (73/112, hazard ratio (HR) = 1.735, p = 0.012) and the IL-8 -251 T/A or A/A (53/112 and 16/112, HR = 2.001 and 1.1777, p = 0.026) genotypes were associated with shorter OS in univariable and multivariable analysis. The IL-1B +3954 polymorphism was also associated with shorter DFS (HR = 1.983, p = 0.012), but this effect was not sustained in the multivariable model. A genetic risk model of 0, 1 and 2 unfavorable alleles was established and confirmed in multivariable analysis. This study supports the prognostic role of the IL-1B C+3954T and the IL-8 T-251A variant as outcome markers in iCCA patients, identifying patient subgroups at higher risk for dismal clinical outcomes.

Abstract Chronic pain alters the experience of owning a body and leads to disturbances in bodily perception. We tested whether women with fibromyalgia (FM) are receptive to bodily illusions of owning a visible and progressively invisible body in immersive virtual reality (VR), and what modulates this experience. Twenty patients participated in two experimental sessions; each session included two conditions in a counterbalanced order. We found that patients with FM could indeed experience virtual embodiment. Sentiment analysis revealed significantly more positive reactions to the progressively invisible body, yet twice as many patients declared they preferred the illusion of a visible virtual body. A linear mixed model revealed that the strength of embodiment was positively associated with body perception disturbances and negatively associated with FM symptoms intensity. No effect of pain during the VR experience nor interoception awareness on embodiment was found. The results indicated that patients with FM are receptive to virtual bodily illusions and that the impact of the embodiment depends on affective reactions, the level of cognitive body distortions, and the intensity of symptoms. Importantly, there is a large variation among patients which should be considered in future VR-based interventions.

Abstract We develop a novel global perspective of the complexity of the relationships between three COVID-19 datasets, the standardised per-capita growth rate of COVID-19 cases and deaths, and the Oxford Coronavirus Government Response Tracker COVID-19 Stringency Index (CSI) which is a measure describing a country’s stringency of lockdown policies. We use a state-of-the-art heterogeneous intrinsic dimension estimator implemented as a Bayesian mixture model, called Hidalgo. Our findings suggest that these highly popular COVID-19 statistics may project onto two low-dimensional manifolds without significant information loss, suggesting that COVID-19 data dynamics are generated from a latent mechanism characterised by a few important variables. The low dimensionality imply a strong dependency among the standardised growth rates of cases and deaths per capita and the CSI for countries over 2020–2021. Importantly, we identify spatial autocorrelation in the intrinsic dimension distribution worldwide. The results show how high-income countries are more prone to lie on low-dimensional manifolds, likely arising from aging populations, comorbidities, and increased per capita mortality burden from COVID-19. Finally, the temporal stratification of the dataset allows the examination of the intrinsic dimension at a more granular level throughout the pandemic.

Abstract Imaginary worlds are present and often central in many of the most culturally successful modern narrative fictions, be it in novels (e.g., Harry Potter), movies (e.g., Star Wars), video games (e.g., The Legend of Zelda), graphic novels (e.g., One Piece) and TV series (e.g., Game of Thrones). We propose that imaginary worlds are popular because they activate exploratory preferences that evolved to help us navigate the real world and find new fitness-relevant information. Therefore, we hypothesize that the attraction to imaginary worlds is intrinsically linked to the desire to explore novel environments and that both are influenced by the same underlying factors. Notably, the inter-individual and cross-cultural variability of the preference for imaginary worlds should follow the inter-individual and cross-cultural variability of exploratory preferences (with the personality trait Openness-to-experience, age, sex, and ecological conditions). We test these predictions with both experimental and computational methods. For experimental tests, we run a pre-registered online experiment about movie preferences (N = 230). For computational tests, we leverage two large cultural datasets, namely the Internet Movie Database (N = 9424 movies) and the Movie Personality Dataset (N = 3.5 million participants), and use machine-learning algorithms (i.e., random forest and topic modeling). In all, consistent with how the human preference for spatial exploration adaptively varies, we provide empirical evidence that imaginary worlds appeal more to more explorative people, people higher in Openness-to-experience, younger individuals, males, and individuals living in more affluent environments. We discuss the implications of these findings for our understanding of the cultural evolution of narrative fiction and, more broadly, the evolution of human exploratory preferences.

Individuals diagnosed with colorectal adenomas with high-risk features during screening colonoscopy have increased risk for the development of subsequent adenomas and colorectal cancer. While US guidelines recommend surveillance colonoscopy at 3 years in this high-risk population, surveillance uptake is suboptimal. To inform future interventions to improve surveillance uptake, we sought to assess surveillance rates and identify facilitators of uptake in a large integrated health system. We utilized a cohort of patients with a diagnosis of ≥ 1 tubular adenoma (TA) with high-risk features (TA ≥ 1 cm, TA with villous features, TA with high-grade dysplasia, or ≥ 3 TA of any size) on colonoscopy between 2013 and 2016. Surveillance colonoscopy completion within 3.5 years of diagnosis of an adenoma with high-risk features was our primary outcome. We evaluated surveillance uptake over time and utilized logistic regression to detect factors associated with completion of surveillance colonoscopy. The final cohort was comprised of 405 patients. 172 (42.5%) patients successfully completed surveillance colonoscopy by 3.5 years. Use of a patient reminder (telephone, electronic message, or letter) for due surveillance (adjusted odds = 1.9; 95%CI = 1.2-2.8) and having ≥ 1 gastroenterology (GI) visit after diagnosis of an adenoma with high-risk features (adjusted odds = 2.6; 95%CI = 1.6-4.2) significantly predicted surveillance colonoscopy completion at 3.5 years. For patients diagnosed with adenomas with high-risk features, surveillance colonoscopy uptake is suboptimal and frequently occurs after the 3-year surveillance recommendation. Patient reminders and visitation with GI after index colonoscopy are associated with timely surveillance completion. Our findings highlight potential health system interventions to increase timely surveillance uptake for patients diagnosed with adenomas with high-risk features.