Early-onset Alzheimer's disease shows a distinct neuropsychological profile and more aggressive trajectories of cognitive decline than late-onset

Early- and late-onset Alzheimer's disease (EOAD and LOAD) share the same neuropathological traits but show distinct cognitive features. We aimed to explore baseline and longitudinal outcomes of global and domain-specific cognitive function in a well characterized cohort of patients with a biomarker-based diagnosis.In this retrospective cohort study, 195 participants were included and classified according to their age, clinical status, and CSF AD biomarker profile: 89 EOAD, 37 LOAD, 46 young healthy controls (age???65?years), and 23 old healthy controls (>65?years). All subjects underwent clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture.We found distinct neuropsychological profiles between EOAD and LOAD at the time of diagnosis. Both groups showed similar performances on memory and language domains, but the EOAD patients displayed worsened deficits in visual perception, praxis, and executive tasks (p?<?0.05). Longitudinally, cognitive decline in EOAD was more pronounced than LOAD in the global outcomes at the expense of these non-amnestic domains. We found that years of education significantly influenced the decline in most of the neuropsychological tests. Besides, the APOE ?4 status showed a significant effect on the decline of memory-related tasks within the EOAD cohort (p?<?0.05).Age of onset is a main factor shaping the cognitive trajectories in AD patients, with younger age driving to a steeper decline of the non-memory domains. Years of education are related to a transversal decline in all cognitive domains and APOE ?4 status to a specific decline in memory performance in EOAD.© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association

INPUT DEVICE RESEARCH FOR DIGITAL PATHOLOGY. AN ERGONOMIC OUTLOOK

Introduction/ Background Digital Pathology represents a technological innovation that introduces changes in the traditional work of pathologists. In this regard, an important issue that has not been enough emphasized is the image handling from an ergonomic point of view to avoid work-related musculoskeletal disorders (MSD). Aims The aim of this study was to investigate a proper input device for digital pathology. Methods Research was conducted in two phases: 1. Comparative study to find an optimal external controller. Eight medical students analyzed 11 input devices: keyboard (HP), conventional mouse (HP), vertical mouse (CLS), touchpad (Logitech), 3 trackballs (Logitech, Kensington Expert and Ulove), Rollermouse (Contour), Ergopointer (Märzhäuser Sensotech), gamepad (Logitech) and a touchless device (Leap-Motion), using them with the Image Viewer software (Ventana). The web-based Fitts´ law test (UC Berkeley) was used to objectify the accuracy of each device, randomly. 12 items were included in the questionnaire: comfort, technical aspects (cursor movement and objective achievement), prospects, overall satisfaction, prior experience, and others. 2. Evaluation by two experienced pathologists (MPR and ANO, 55 and 50 year-old, respectively) the best rated input device and comparison with a voice recognition system (Invox Medical Dictation) using a headset microphone (Plantronics), rating perceived workload using NASA Task Load Index with 28 whole slide images. Digital Image Hub (Leica) with a 4 MegaPixel display (Barco) was used. Data were processed with SPSS 21.0. Results Correlation between technical aspects of the evaluated devices and accuracy (Fitts´ law test), and comfort with overall satisfaction existed (p<0.05). The assessment concluded that vertical mouse was the best rated input device. However, it has a slightly higher perceived workload in comparison with the voice recognition system, which was the proper controller for digital pathology in this study. Conclusion: We describe a methodology that can study and compare input devices for future workstations in digital pathology. Pathologists should be involved in this process trying to find ergonomic devices that prevent MSD. Voice recognition can function as a good handsfree device for digital pathology and could be considered in physical disability situations. Further studies using electromyography, accelerometry and 3D reconstruction analysis could provide additional ergonomic information

Performance of the joint LST-1 and MAGIC observations evaluated with Crab Nebula data

Aims. Large-Sized Telescope 1 (LST-1), the prototype for the Large-Sized Telescope at the upcoming Cherenkov Telescope Array Observatory, is concluding its commissioning phase at the Observatorio del Roque de los Muchachos on the island of La Palma. The proximity of LST-1 to the two MAGIC (Major Atmospheric Gamma Imaging Cherenkov) telescopes makes it possible to carry out observations of the same gamma-ray events with both systems. Methods. We describe the joint LST-1+MAGIC analysis pipeline and used simultaneous Crab Nebula observations and Monte Carlo simulations to assess the performance of the three-telescope system. The addition of the LST-1 telescope allows for the recovery of events in which one of the MAGIC images is too dim to survive analysis quality cuts. Results. Thanks to the resulting increase in the collection area and stronger background rejection, we found a significant improvement in sensitivity, allowing for the detection of 30% weaker fluxes in the energy range between 200 GeV and 3 TeV. The spectrum of the Crab Nebula, reconstructed in the energy range between ∼60 GeV and ∼10 TeV, is in agreement with previous measurements

Joint Observation of the Galactic Center with MAGIC and CTA-LST-1

MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes (IACTs), designed to detect very-high-energy gamma rays, and is operating in stereoscopic mode since 2009 at the Observatorio del Roque de Los Muchachos in La Palma, Spain. In 2018, the prototype IACT of the Large-Sized Telescope (LST-1) for the Cherenkov Telescope Array, a next-generation ground-based gamma-ray observatory, was inaugurated at the same site, at a distance of approximately 100 meters from the MAGIC telescopes. Using joint observations between MAGIC and LST-1, we developed a dedicated analysis pipeline and established the threefold telescope system via software, achieving the highest sensitivity in the northern hemisphere. Based on this enhanced performance, MAGIC and LST-1 have been jointly and regularly observing the Galactic Center, a region of paramount importance and complexity for IACTs. In particular, the gamma-ray emission from the dynamical center of the Milky Way is under debate. Although previous measurements suggested that a supermassive black hole Sagittarius A* plays a primary role, its radiation mechanism remains unclear, mainly due to limited angular resolution and sensitivity. The enhanced sensitivity in our novel approach is thus expected to provide new insights into the question. We here present the current status of the data analysis for the Galactic Center joint MAGIC and LST-1 observations

Fluorescence liquid biopsy for cancer detection is improved by using cationic dendronized hyperbranched polymer

22 pags., 14 figs., 9 tabs. 1 sch. -- This article belongs to the Special Issue Nanostructures Applied to Drug Delivery and Diagnosis(1) Background: Biophysical techniques applied to serum samples characterization could promote the development of new diagnostic tools. Fluorescence spectroscopy has been previously applied to biological samples from cancer patients and differences from healthy individuals were observed. Dendronized hyperbranched polymers (DHP) based on bis(hydroxymethyl)propionic acid (bis-MPA) were developed in our group and their potential biomedical applications explored. (2) Methods: A total of 94 serum samples from diagnosed cancer patients and healthy individuals were studied (20 pancreatic ductal adenocarcinoma, 25 blood donor, 24 ovarian cancer, and 25 benign ovarian cyst samples). (3) Results: Fluorescence spectra of serum samples (fluorescence liquid biopsy, FLB) in the presence and the absence of DHP-bMPA were recorded and two parameters from the signal curves obtained. A secondary parameter, the fluorescence spectrum score (FSscore), was calculated, and the diagnostic model assessed. For pancreatic ductal adenocarcinoma (PDAC) and ovarian cancer, the classification performance was improved when including DHP-bMPA, achieving high values of statistical sensitivity and specificity (over 85% for both pathologies). (4) Conclusions: We have applied FLB as a quick, simple, and minimally invasive promising technique in cancer diagnosis. The classification performance of the diagnostic method was further improved by using DHP-bMPA, which interacted differentially with serum samples from healthy and diseased subjects. These preliminary results set the basis for a larger study and move FLB closer to its clinical application, providing useful information for the oncologist during patient diagnosis.This research was funded by the Spanish Ministry of Economy and Competitiveness and European ERDF Funds (MCIU/AEI/FEDER, EU) (BFU2016-78232-P to A.V.C.); Projects funded by Instituto de Salud Carlos III and co-funded by European Union (ESF, “Investing in your future”): “PI15/00663 (FIS project to O.A.)”, “PI18/00349 (FIS project to O.A.)”, “FI19/00146 (PFIS contract for SHD)”; Gobierno de Aragón-ESF (Predoctoral Research Contract FEDER 2014-2020 “Construyendo Europa desde Aragón”) to V.M.-V., Protein Targets and Bioactive Compounds Group E45_17R to A.V.C., Digestive Pathology Group B25_17R to S.H.-D., O.A. and CLIP group E47_20R, to V.M.-V. and T.S.); and the Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd

Mapping of Candidate Genes Involved in Bud Dormancy and Flowering Time in Sweet Cherry (Prunus avium)

The timing of flowering in perennial plants is crucial for their survival in temperate climates and is regulated by the duration of bud dormancy. Bud dormancy release and bud break depend on the perception of cumulative chilling during endodormancy and heat during the bud development. The objectives of this work were to identify candidate genes involved in dormancy and flowering processes in sweet cherry, their mapping in two mapping progenies 'Regina' × 'Garnet' and 'Regina' × 'Lapins', and to select those candidate genes which co-localized with quantitative trait loci (QTLs) associated with temperature requirements for bud dormancy release and flowering. Based on available data on flowering processes in various species, a list of 79 candidate genes was established. The peach and sweet cherry orthologs were identified and primers were designed to amplify sweet cherry candidate gene fragments. Based on the amplified sequences of the three parents of the mapping progenies, SNPs segregations in the progenies were identified. Thirty five candidate genes were genetically mapped in at least one of the two progenies and all were in silico mapped. Co-localization between candidate genes and QTLs associated with temperature requirements and flowering date were identified for the first time in sweet cherry. The allelic composition of the candidate genes located in the major QTL for heat requirements and flowering date located on linkage group 4 have a significant effect on these two traits indicating their potential use for breeding programs in sweet cherry to select new varieties adapted to putative future climatic conditions

Mapping of Candidate Genes Involved in Bud Dormancy and Flowering Time in Sweet Cherry (Prunus avium).

The timing of flowering in perennial plants is crucial for their survival in temperate climates and is regulated by the duration of bud dormancy. Bud dormancy release and bud break depend on the perception of cumulative chilling during endodormancy and heat during the bud development. The objectives of this work were to identify candidate genes involved in dormancy and flowering processes in sweet cherry, their mapping in two mapping progenies 'Regina' × 'Garnet' and 'Regina' × 'Lapins', and to select those candidate genes which co-localized with quantitative trait loci (QTLs) associated with temperature requirements for bud dormancy release and flowering. Based on available data on flowering processes in various species, a list of 79 candidate genes was established. The peach and sweet cherry orthologs were identified and primers were designed to amplify sweet cherry candidate gene fragments. Based on the amplified sequences of the three parents of the mapping progenies, SNPs segregations in the progenies were identified. Thirty five candidate genes were genetically mapped in at least one of the two progenies and all were in silico mapped. Co-localization between candidate genes and QTLs associated with temperature requirements and flowering date were identified for the first time in sweet cherry. The allelic composition of the candidate genes located in the major QTL for heat requirements and flowering date located on linkage group 4 have a significant effect on these two traits indicating their potential use for breeding programs in sweet cherry to select new varieties adapted to putative future climatic conditions