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The extant literature aimed at characterizing attentional capability in autistics has presented inconsistent findings. This inconsistency and uncertainty may be the product of different theoretical and methodological approaches used to define attention in autism. In the current study, we investigate whether the allocation of attentional resources to task demands, and attention resource capacity, differs between autistics with no comorbid attention-deficit diagnosis (n = 55) and age-matched neurotypicals (n = 55). We compared differences in capacity and the allocation of resources by manipulating attentional load in a Multiple Object-Tracking (MOT) task, a robust, versatile, and ecological measure of selective, sustained, and distributed attention. While autistics demonstrated lower MOT performance, this difference disappeared when we accounted for fluid reasoning intelligence. Additionally, the similarity in the trend of MOT performance at increasing levels of attentional load between autistics and neurotypicals suggests no differences in the allocation of attentional resources to task demands. Taken together, our study suggests that higher-order cognitive abilities, such as intelligence, should be considered when characterizing attention across the autistic population in research. Similarly, our findings highlight the importance of considering cognitive competence when assessing attentional capabilities in autistic individuals, which could have significant implications for clinical diagnosis, treatment, and support.

Abstract Recent research shows that emotional facial expressions impact behavioral responses only when their valence is relevant to the task. Under such conditions, threatening faces delay attentional disengagement, resulting in slower reaction times and increased omission errors compared to happy faces. To investigate the neural underpinnings of this phenomenon, we used functional magnetic resonance imaging to record the brain activity of 23 healthy participants while they completed two versions of the go/no-go task. In the emotion task (ET), participants responded to emotional expressions (fearful or happy faces) and refrained from responding to neutral faces. In the gender task (GT), the same images were displayed, but participants had to respond based on the posers’ gender. Our results confirmed previous behavioral findings and revealed a network of brain regions (including the angular gyrus, the ventral precuneus, the left posterior cingulate cortex, the right anterior superior frontal gyrus, and two face-responsive regions) displaying distinct activation patterns for the same facial emotional expressions in the ET compared to the GT. We propose that this network integrates internal representations of task rules with sensory characteristics of facial expressions to evaluate emotional stimuli and exert top-down control, guiding goal-directed actions according to the context.

Those experiencing high rapport or strong social connection are more likely to copy each other, or emulate each other's ideas, either consciously or sub-consciously. In this study, we use this phenomenon to examine whether neurotype match or mismatch impacts degree of imitation in a creative task. We asked 71 participants in neurodiverse pairs (including both autistic and non-autistic participants) and single-neurotype pairs (both autistic or both non-autistic), where one participant builds and one observes, to build the tallest possible tower from dried spaghetti and plasticine. We measured the height of each tower and photographed them to create a stimulus set. We then asked independent raters (n = 351, 62 autistic) to rate towers for degree of similarity. We hypothesised that lower similarity scores would be generated for towers created by people in neurodiverse pairs, showing positive innovation. Results showed towers built in the neurodiverse condition had least similarity, whereas towers built in the autistic and non-autistic conditions were significantly more similar. There was no difference in performance (height of tower) based on condition. Our results are the first to examine creativity within single-neurotype and neurodiverse pairs; they indicate that neurological diversity may be beneficial within a group setting. Subsequent research is required to examine how this interacts with divergent communication styles.

Consistent with research across several domains, intervention adherence is associated with desired outcomes. Our study investigates adherence, defined by participants commitment to, persistence with, and compliance with an interventions regimen, as a key mechanism underlying cognitive training effectiveness. We examine this relationship in a large and diverse sample comprising 4,775 adults between the ages of 18 and 93. We test the predictive validity of individual difference factors, such as age, gender, cognitive capability (i.e., fluid reasoning and working memory), grit, ambition, personality, self-perceived cognitive failures, socioeconomic status, exercise, and education on commitment to and persistence with a 20-session cognitive training regimen, as measured by the number of sessions completed. Additionally, we test the relationship between compliance measures: (i) spacing between training sessions, as measured by the average time between training sessions, and (ii) consistency in the training schedule, as measured by the variance in time between training sessions, with performance trajectories on the training task. Our data suggest that none of these factors reliably predict commitment to, persistence with, or compliance with cognitive training. Nevertheless, the lack of evidence from the large and representative sample extends the knowledge from previous research exploring limited, heterogenous samples, characterized by older adult populations. The absence of reliable predictors for commitment, persistence, and compliance in cognitive training suggests that nomothetic factors may affect program adherence. Future research will be well served to examine diverse approaches to increasing motivation in cognitive training to improve program evaluation and reconcile the inconsistency in findings across the field.

IntroductionThe deregulation of lncRNAs expression has been associated with neuronal damage in Alzheimer’s disease (AD), but how or whether they can influence its onset is still unknown. We investigated 2 RNA-seq datasets consisting, respectively, of the hippocampal and fusiform gyrus transcriptomic profile of AD patients, matched with non-demented controls.MethodsWe performed a differential expression analysis, a gene correlation network analysis (WGCNA) and a pathway enrichment analysis of two RNA-seq datasets.ResultsWe found deregulated lncRNAs in common between hippocampus and fusiform gyrus and deregulated gene groups associated to functional pathways related to neurotransmission and memory consolidation. lncRNAs, co-expressed with known AD-related coding genes, were identified from the prioritized modules of both brain regions.DiscussionWe found common deregulated lncRNAs in the AD hippocampus and fusiform gyrus, that could be considered common signatures of AD pathogenesis, providing an important source of information for understanding the molecular changes of AD.

Summary: Background: Research in healthy young adults shows that characteristic patterns of brain activity define individual “brain-fingerprints” that are unique to each person. However, variability in these brain-fingerprints increases in individuals with neurological conditions, challenging the clinical relevance and potential impact of the approach. Our study shows that brain-fingerprints derived from neurophysiological brain activity are associated with pathophysiological and clinical traits of individual patients with Parkinson’s disease (PD). Methods: We created brain-fingerprints from task-free brain activity recorded through magnetoencephalography in 79 PD patients and compared them with those from two independent samples of age-matched healthy controls (N = 424 total). We decomposed brain activity into arrhythmic and rhythmic components, defining distinct brain-fingerprints for each type from recording durations of up to 4 min and as short as 30 s. Findings: The arrhythmic spectral components of cortical activity in patients with Parkinson’s disease are more variable over short periods, challenging the definition of a reliable brain-fingerprint. However, by isolating the rhythmic components of cortical activity, we derived brain-fingerprints that distinguished between patients and healthy controls with about 90% accuracy. The most prominent cortical features of the resulting Parkinson’s brain-fingerprint are mapped to polyrhythmic activity in unimodal sensorimotor regions. Leveraging these features, we also demonstrate that Parkinson’s symptom laterality can be decoded directly from cortical neurophysiological activity. Furthermore, our study reveals that the cortical topography of the Parkinson’s brain-fingerprint aligns with that of neurotransmitter systems affected by the disease’s pathophysiology. Interpretation: The increased moment-to-moment variability of arrhythmic brain-fingerprints challenges patient differentiation and explains previously published results. We outline patient-specific rhythmic brain signaling features that provide insights into both the neurophysiological signature and symptom laterality of Parkinson’s disease. Thus, the proposed definition of a rhythmic brain-fingerprint of Parkinson’s disease may contribute to novel, refined approaches to patient stratification. Symmetrically, we discuss how rhythmic brain-fingerprints may contribute to the improved identification and testing of therapeutic neurostimulation targets. Funding: Data collection and sharing for this project was provided by the Quebec Parkinson Network (QPN), the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer’s Disease (PREVENT-AD; release 6.0) program, the Cambridge Centre for Aging Neuroscience (Cam-CAN), and the Open MEG Archives (OMEGA). The QPN is funded by a grant from Fonds de Recherche du Québec - Santé (FRQS). PREVENT-AD was launched in 2011 as a $13.5 million, 7-year public-private partnership using funds provided by McGill University, the FRQS, an unrestricted research grant from Pfizer Canada, the Levesque Foundation, the Douglas Hospital Research Centre and Foundation, the Government of Canada, and the Canada Fund for Innovation. The Brainstorm project is supported by funding to SB from the NIH (R01-EB026299-05). Further funding to SB for this study included a Discovery grant from the Natural Sciences and Engineering Research Council of Canada of Canada (436355-13), and the CIHR Canada research Chair in Neural Dynamics of Brain Systems (CRC-2017-00311).

Chronic infection of the cornea by Herpes simplex virus (HSV) continues to be an important cause of unilateral blindness. Despite considerable progress in the understanding of the virus at cellular and molecular levels, the prospect of prevention still appears to be long way off. The development of non-toxic topical antiviral agents has been an important step forward in management. However, correct diagnosis and treatment, in particular, the avoidance of inappropriate use of topical steroid remains as important as ever. This article reviews the virological and clinical aspects of HSV keratitis including the current concepts of pathogenesis and management

Abstract Background Many older adults live with the combination of multiple long-term conditions (MLTC) and frailty and are at increased risk of a deterioration in health requiring interaction with healthcare services. Low skeletal muscle strength is observed in individuals living with MLTC and is central to physical frailty. Resistance exercise (RE) is the best available treatment for improving muscle strength, but little is known about the attitudes and barriers to RE in this group of older adults. This study therefore aimed to explore the knowledge of and attitudes towards RE, as well as the barriers and enabling factors, in older adults living with MLTC, frailty and a recent deterioration in health. Methods Fourteen participants aged 69–92 years (10 women) from the Lifestyle in Later Life – Older People’s Medicine (LiLL-OPM) study were recruited from an Older People’s Medicine Day Unit in Newcastle, UK. Participants were invited to take part in a semi-structured interview exploring their knowledge and attitudes as well as barriers and enabling factors to RE. Data were analysed using thematic analysis. Results The analysis generated three themes (1) a lack of awareness and understanding of RE, (2) a self-perceived inability to perform RE; physical and psychological barriers and (3) willingness to perform RE under expert guidance. There was a general lack of awareness and understanding of RE, with most participants having never heard of the term and being unaware of its potential benefits. When RE was described, participants stated that they would be willing to try RE, but it was apparent that an individualised approach underpinned by expert guidance would be required to support engagement. Conclusions Older adults living with MLTC, frailty and a recent deterioration in health lack awareness and understanding of RE. Despite a range of barriers, this group appear willing to engage in RE if they are appropriately supported. There is a need to co-design and deliver effective strategies, including education, to raise awareness and understanding of RE, as well as promote engagement in RE, in this group of older adults.

Abstract Background The p53 gene family consists of the three genes p53, p63 and p73, which have polyhedral non-overlapping functions in pivotal cellular processes such as DNA synthesis and repair, growth arrest, apoptosis, genome stability, angiogenesis, development and differentiation. These genes encode sequence-specific nuclear transcription factors that recognise the same responsive element (RE) in their target genes. Their inactivation or aberrant expression may determine tumour progression or developmental disease. The discovery of several protein isoforms with antagonistic roles, which are produced by the expression of different promoters and alternative splicing, widened the complexity of the scenario of the transcriptional network of the p53 family members. Therefore, the identification of the genes transactivated by p53 family members is crucial to understand the specific role for each gene in cell cycle regulation. We have combined a genome-wide computational search of p53 family REs and microarray analysis to identify new direct target genes. The huge amount of biological data produced has generated a critical need for bioinformatic tools able to manage and integrate such data and facilitate their retrieval and analysis. Description We have developed the p53FamTaG database (p53 FAMily TArget Genes), a modular relational database, which contains p53 family direct target genes selected in the human genome searching for the presence of the REs and the expression profile of these target genes obtained by microarray experiments. p53FamTaG database also contains annotations of publicly available databases and links to other experimental data. The genome-wide computational search of the REs was performed using PatSearch, a pattern-matching program implemented in the DNAfan tool. These data were integrated with the microarray results we produced from the overexpression of different isoforms of p53, p63 and p73 stably transfected in isogenic cell lines, allowing the comparative study of the transcriptional activity of all the proteins in the same cellular background. p53FamTaG database is available free at http://www2.ba.itb.cnr.it/p53FamTaG/ Conclusion p53FamTaG represents a unique integrated resource of human direct p53 family target genes that is extensively annotated and provides the users with an efficient query/retrieval system which displays the results of our microarray experiments and allows the export of RE sequences. The database was developed for supporting and integrating high-throughput in silico and experimental analyses and represents an important reference source of knowledge for research groups involved in the field of oncogenesis, apoptosis and cell cycle regulation.

Garlic (Allium Sativum L.) is a valuable root crop that can be utilized to season foods and is widely utilized in Ethiopia to treat many different kinds of diseases. The cloves are separated by hand for plantation and processing functions. This technique can be very exhausting and take a lot of time. To fill this gap, a garlic bulb-breaking machine was fabricated and tested with the clove variety grown in Holeta, Ethiopia. The major component of the machine is two rollers that revolve in opposing directions, and shearing the bulbs to separate the cloves. The performance test experiments were carried out in a full factorial design with feed rate as the first factor having three levels (3.7, 4.2, and 5.2 kg/min) and roller speed as a second factor with also three levels (276, 326, and 376 rpm). All tests were done at 66 % moisture content of garlic and 19 mm clearance between the breaking rollers. The interaction effect of the two factors shows an important difference (p

The hippocampus and amygdala are the first brain regions to show early signs of Alzheimer's Disease (AD) pathology. AD is preceded by a prodromal stage known as Mild Cognitive Impairment (MCI), a crucial crossroad in the clinical progression of the disease. The topographical development of AD has been the subject of extended investigation. However, it is still largely unknown how the transition from MCI to AD affects specific hippocampal and amygdala subregions. The present study is set to answer that question. We analyzed data from 223 subjects: 75 healthy controls, 52 individuals with MCI, and 96 AD patients obtained from the ADNI. The MCI group was further divided into two subgroups depending on whether individuals in the 48 months following the diagnosis either remained stable (N = 21) or progressed to AD (N = 31). A MANCOVA test evaluated group differences in the volume of distinct amygdala and hippocampal subregions obtained from magnetic resonance images. Subsequently, a stepwise linear discriminant analysis (LDA) determined which combination of magnetic resonance imaging parameters was most effective in predicting the conversion from MCI to AD. The predictive performance was assessed through a Receiver Operating Characteristic analysis. AD patients displayed widespread subregional atrophy. MCI individuals who progressed to AD showed selective atrophy of the hippocampal subiculum and tail compared to stable MCI individuals, who were undistinguishable from healthy controls. Converter MCI showed atrophy of the amygdala's accessory basal, central, and cortical nuclei. The LDA identified the hippocampal subiculum and the amygdala's lateral and accessory basal nuclei as significant predictors of MCI conversion to AD. The analysis returned a sensitivity value of 0.78 and a specificity value of 0.62. These findings highlight the importance of targeted assessments of distinct amygdala and hippocampus subregions to help dissect the clinical and pathophysiological development of the MCI to AD transition.

OBJECTIVES:. In patients with COVID-19 respiratory failure, controlled mechanical ventilation (CMV) is often necessary during the acute phases of the disease. Weaning from CMV to pressure support ventilation (PSV) is a key objective when the patient’s respiratory functions improve. Limited evidence exists regarding the factors predicting a successful transition to PSV and its impact on patient outcomes. DESIGN:. Retrospective observational cohort study. SETTING:. Twenty-four Italian ICUs from February 2020 to May 2020. PATIENTS:. Mechanically ventilated ICU patients with COVID-19-induced respiratory failure. INTERVENTION:. The transition period from CMV to PSV was evaluated. We defined it as “failure of assisted breathing” if the patient returned to CMV within the first 72 hours. MEASUREMENTS AND MAIN RESULTS:. Of 1260 ICU patients screened, 514 were included. Three hundred fifty-seven patients successfully made the transition to PSV, while 157 failed. Pao2/Fio2 ratio before the transition emerged as an independent predictor of a successful shift (odds ratio 1.00; 95% CI, 0.99–1.00; p = 0.003). Patients in the success group displayed a better trend in Pao2/Fio2, Paco2, plateau and peak pressure, and pH level. Subjects in the failure group exhibited higher ICU mortality (hazard ratio 2.08; 95% CI, 1.42–3.06; p < 0.001), an extended ICU length of stay (successful vs. failure 21 ± 14 vs. 27 ± 17 d; p < 0.001) and a longer duration of mechanical ventilation (19 ± 18 vs. 24 ± 17 d, p = 0.04). CONCLUSIONS:. Our study emphasizes that the Pao2/Fio2 ratio was the sole independent factor associated with a failed transition from CMV to PSV. The unsuccessful transition was associated with worse outcomes.

Abstract Chromobox Protein 3 (CBX3) overexpression is a common event occurring in cancer, promotes cancer cell proliferation and represents a poor prognosis marker in a plethora of human cancers. Here we describe that a wide spectrum of human cancers harbors a co-amplification of CBX3 gene with either EGFR or RAC1, which yields a statistically significant increase of both mRNA and protein levels of CBX3, EGFR and RAC1. We also reveal that the simultaneous overexpression of CBX3, RAC1 and EGFR gene products correlates with a worse prognosis compared to the condition when CBX3, RAC1 and EGFR are singularly upregulated. Furthermore, we also show that a co-occurrence of low-grade amplification, in addition to high-grade amplification, between CBX3 and EGFR or RAC1 is associated with a reduced patient lifespan. Finally, we find that CBX3 and RAC1/EGFR genetically interact in the model organism Drosophila melanogaster, suggesting that the simultaneous overexpression as well as well the co-occurrence of high- or low-grade copy number alterations in these genes is not accidental and could reflect evolutionarily conserved functional relationships.

Introduction: Infectious intestinal diseases (diarrhea) are a major cause of morbidity and mortality worldwide. In 2015, it constituted the ninth leading cause of death for all ages. Objective: To describe the epidemiological characteristics of mortality due to infectious intestinal diseases (diarrhea) in Paraguay from 2015 to 2019. Methods: Descriptive, ecological, cross-sectional, retrospective, and non-probabilistic sampling of consecutive cases was performed. ICD-10 deaths included cholera (A01), typhoid and paratyphoid fever (A01), shigellosis (A03), other bacterial intestinal infections (A04), other bacterial food poisoning (A05), amebiasis (A06), other intestinal diseases due to protozoa (A07), intestinal infections due to viruses (A08), and diarrhea and gastroenteritis of presumed infectious origin (A09). Open access data were obtained from the WEB page of the General Directorate of Strategic Information in Health of the MSP and BS of all the Departments of the country. Crude and adjusted rates (per 100,000 inhabitants) were calculated. Excel and EPI INFO 7.0 were used. Results: 495 deaths were registered; the highest prevalence was in 2019 (adjusted rate of 1.83) and the lowest in 2017 (1.36). The months with the highest mortality rates were January and July (9.9%). 51.72% were women (256), 30.91% were over 80 years old and 28.28% (140) were under 5 years old, average age 50.8, single 56.77% (281) and without any type of education 41.82% (207). A total of 80.61% (399) of the respondents resided in urban areas. The highest rates were registered in Boquerón (33.3) and Amambay (15.2). Diarrhea and gastroenteritis of infectious origin accounted for 95.56% of the cases (473). Discussion: There was a high percentage of mortality from infectious diarrhea. Extremes of life were the most vulnerable populations.

The role of the thalamus in mediating the effects of lysergic acid diethylamide (LSD) was recently proposed in a model of communication and corroborated by imaging studies. However, a detailed analysis of LSD effects on nuclei-resolved thalamocortical connectivity is still missing. Here, in a group of healthy volunteers, we evaluated whether LSD intake alters the thalamocortical coupling in a nucleus-specific manner. Structural and resting-state functional Magnetic Resonance Imaging (MRI) data were acquired in a placebo-controlled study on subjects exposed to acute LSD administration. Structural MRI was used to parcel the thalamus into its constituent nuclei based on individual anatomy. Nucleus-specific changes of resting-state functional MRI (rs-fMRI) connectivity were mapped using a seed-based approach. LSD intake selectively increased the thalamocortical functional connectivity (FC) of the ventral complex, pulvinar, and non-specific nuclei. Functional coupling was increased between these nuclei and sensory cortices that include the somatosensory and auditory networks. The ventral and pulvinar nuclei also exhibited increased FC with parts of the associative cortex that are dense in serotonin type 2A receptors. These areas are hyperactive and hyper-connected upon LSD intake. At subcortical levels, LSD increased the functional coupling among the thalamus's ventral, pulvinar, and non-specific nuclei, but decreased the striatal-thalamic connectivity. These findings unravel some LSD effects on the modulation of subcortical-cortical circuits and associated behavioral outputs.

Objectives The prevalence of dementia in both community and hospital settings requires a clinical workforce that is skilled in diagnosis and management of the condition to competently care for patients. Though evidence of successful educational interventions about dementia exists, effective translation into medical school curricula is the exception rather than the norm.Design We adopted a realist synthesis approach following Realist And MEta-narrative Evidence Syntheses: Evolving Standards (RAMESES) guidelines to answer the following questions: (1) what are the barriers to integrating effective interventions about dementia into medical school curricula and (2) where they are successfully delivered, what are the contextual factors that allow for this enactment?Data sources We searched PubMed, Embase, CINAHL and PsycINFO using the MesH terms Schools, Medical; Students, Medical; Education, Medical AND Neurocognitive disorders or the closest possible set of terms within each database.Eligibility criteria Undergraduate or graduate entry medical school programme, teaching and learning focussing on dementia, evaluating student outcomes (satisfaction, knowledge, skills, attitudes or behaviours), interventions described clearly enough to classify teaching method, any research design (quantitative and qualitative), English language.Data extraction and synthesis We used a shared spreadsheet to enter key information about eligible studies and the reasons for excluding studies that did not fit eligibility criteria. We extracted descriptive data about the nature of educational interventions and narrative information as to barriers and facilitators to implementing those interventions.Results Our initial literature search identified 16 relevant papers for review. Systematic extraction of data informed the development of an initial programme theory (IPT) structured around four contextual barriers: ‘culture’, ‘concern for patient welfare’, ‘student attitudes’ and ‘logistics’ with associated facilitatory mechanisms embed medical education about dementia.Conclusions We outline the process of generating our IPT, including overlap with Cultural Historical Activity Theory. We outline our intention to refine our programme theory through ongoing review of the evidence base and collaboration with stakeholders, with the aim of finalising a model for successful integration of dementia education.

Abstract Background Many evidences report that alternative splicing, the mechanism which produces mRNAs and proteins with different structures and functions from the same gene, is altered in cancer cells. Thus, the identification and characterization of cancer-specific splice variants may give large impulse to the discovery of novel diagnostic and prognostic tumour biomarkers, as well as of new targets for more selective and effective therapies. Results We present here a genome-wide analysis of the alternative splicing pattern of human genes through a computational analysis of normal and cancer-specific ESTs from seventeen anatomical groups, using data available in AspicDB, a database resource for the analysis of alternative splicing in human. By using a statistical methodology, normal and cancer-specific genes, splice sites and cassette exons were predicted in silico. The condition association of some of the novel normal/tumoral cassette exons was experimentally verified by RT-qPCR assays in the same anatomical system where they were predicted. Remarkably, the presence in vivo of the predicted alternative transcripts, specific for the nervous system, was confirmed in patients affected by glioblastoma. Conclusion This study presents a novel computational methodology for the identification of tumor-associated transcript variants to be used as cancer molecular biomarkers, provides its experimental validation, and reports specific biomarkers for glioblastoma.

Abstract Research on the contribution of the ipsilateral hemisphere to unilateral movements, and how it is mediated by transcallosal connections, has so far provided contradictory findings. By using dynamic causal modelling (DCM) and Parametric Empirical Bayes analyses applied to fMRI data, we sought to describe effective connectivity during pantomimed and imagined right-hand grasping within the grasping network, namely the anterior intraparietal sulcus, ventral and dorsal (PMd) premotor cortex, supplementary motor area and primary motor cortex (M1). The two-fold aim of the present work was to explore a) whether right and left parieto-frontal areas show similar connectivity couplings, and b) the interhemispheric dynamics between these regions across the two hemispheres. We detected a network architecture comparable across hemispheres during executed but not imagined grasping movements. Furthermore, during pantomimed grasping the interhemispheric crosstalk was mainly driven by premotor areas: we found an inhibitory influence from the right PMd toward the left premotor and motor areas and excitatory couplings between homologous ventral premotor and supplementary motor regions. Overall, our results support the view that dissociable components of unilateral grasping execution are encoded by a non-lateralized set of brain areas complexly intertwined by interhemispheric dynamics, whereas motor imagery obeys different principles.

Abstract Introduction Accumulating evidence indicates that the amygdala exhibits early signs of Alzheimer's disease (AD) pathology. However, it is still unknown whether the atrophy of distinct subfields of the amygdala also participates in the transition from healthy cognition to mild cognitive impairment (MCI). Methods Our sample was derived from the AD Neuroimaging Initiative 3 and consisted of 97 cognitively healthy (HC) individuals, sorted into two groups based on their clinical follow‐up: 75 who remained stable (s‐HC) and 22 who converted to MCI within 48 months (c‐HC). Anatomical magnetic resonance (MR) images were analyzed using a semi‐automatic approach that combines probabilistic methods and a priori information from ex vivo MR images and histology to segment and obtain quantitative structural metrics for different amygdala subfields in each participant. Spearman's correlations were performed between MR measures and baseline and longitudinal neuropsychological measures. We also included anatomical measurements of the whole amygdala, the hippocampus, a key target of AD‐related pathology, and the whole cortical thickness as a test of spatial specificity. Results Compared with s‐HC individuals, c‐HC subjects showed a reduced right amygdala volume, whereas no significant difference was observed for hippocampal volumes or changes in cortical thickness. In the amygdala subfields, we observed selected atrophy patterns in the basolateral nuclear complex, anterior amygdala area, and transitional area. Macro‐structural alterations in these subfields correlated with variations of global indices of cognitive performance (measured at baseline and the 48‐month follow‐up), suggesting that amygdala changes shape the cognitive progression to MCI. Discussion Our results provide anatomical evidence for the early involvement of the amygdala in the preclinical stages of AD. Highlights Amygdala's atrophy marks elderly progression to mild cognitive impairment (MCI). Amygdala's was observed within the basolateral and amygdaloid complexes. Macro‐structural alterations were associated with cognitive decline. No atrophy was found in the hippocampus and cortex.

Objective According to the 2019 European Society of Cardiology (ESC) guidelines on pulmonary embolism (PE), prognosis is calculated using the Pulmonary Embolism Severity Index (PESI), a complex score with debated validity, or simplified PESI (sPESI). We have developed and validated a new risk score for in-hospital mortality (IHM) of patients with PE in the emergency department. Methods This retrospective, dual-center cohort study was conducted in the emergency departments of two third-level university hospitals. Patients aged >18 years with a contrast-enhanced computed tomography-confirmed PE were included. Clinical variables and laboratory tests were evaluated blindly to IHM. Multivariable logistic regression was performed to identify the new score’s predictors, and the new score was compared with the PESI, sPESI, and shock index. Results A total of 1,358 patients were included in this study: 586 in the derivation cohort and 772 in the validation cohort, with a global 10.6% of IHM. The PATHOS scores were developed using independent variables to predict mortality: platelet count, age, troponin, heart rate, oxygenation, and systolic blood pressure. The PATHOS score showed good calibration and high discrimination, with an area under the receiver operating characteristics curve of 0.83 (95% confidence interval [CI], 0.77–0.89) in the derivation population and 0.74 (95% CI, 0.68–0.80) in the validation cohort, which is significantly higher than the PESI, sPESI, and shock index in both cohorts (P