Understanding the Origins of a Pandemic Virus

Understanding the pre-pandemic conditions and the origin of infectious diseases provides scientifically based rationales for implementing public health measures that help to avoid, or at least to mitigate, future epidemics. The recent ancestors of a pandemic virus provide an invaluable information about the set of minimal genomic alterations that transformed a zoonotic agent into a full human pandemic. Since the first confirmed cases of the H1N1pdm virus in the spring of 2009 several hypotheses about the strain's origins have been proposed. However, how, where, and when it first infected humans is still far from clear. The only way to piece together such an epidemiological puzzle relies on the collective effort of the international scientific community to increase genomic sequencing of influenza isolates, especially ones collected in the months prior to the origin of the pandemic

Comparison of First-Pass Effect in Aspiration vs. Stent-Retriever for Acute Intracranial ICA Occlusion

Internal carotid artery occlusion; Revascularization; Stent retrieverOclusión de la arteria carótida interna; Revascularización; Recuperador de stentOclusió de l'artèria caròtida interna; Revascularització; Recuperador de stentThe purpose of this study is to evaluate the best endovascular approach (aspiration or stent-retriever) and the impact of stent retriever size and length on clinical and angiographic outcomes in patients with acute intracranial ICA occlusion. We conducted a retrospective analysis of a prospective database of consecutive patients with acute intracranial ICA occlusion undergoing endovascular treatment in four Comprehensive Stroke Center between June-2019 and December-2020. We include 121 patients; Stent-retriever (SR) was used as first technical approach in 107 patients (88.4%) and aspiration was used in 14 patients (11.6%). SR group had higher rate of FPE compared to aspiration group (29 vs. 0%, p = 0.02). In SR subgroup, treatment highlighted higher FPE in the 6 × 50 SR (37.7%), than in the rest of the SR which are 21.2% (4–5 mm size and 20–50 mm length SR) and 19% (6 mm size and 25–40 mm length SR), but it was not found to be statistically significant. There were no other significant differences across the groups regarding primary angiographic or clinical outcomes. In our intracranial ICA occlusion series, stent retrievers were superior to direct aspiration in obtaining FPEs and mFPEs, and longer devices achieved better results with no statistically significant difference. Further studies evaluating the effects of different ICA clot removal approaches are warranted to confirm these results

Entrenamiento por Competencias de Computación de Alto Rendimiento para Ecosistemas de Computación Avanzada

peer reviewedHigh-Performance Computing (HPC) is one of the pillars of developing modern science and disruptive technologies, uniting computer architectures and parallel programming into multidisciplinary interactions to face domain-specific problems. That is why different areas of knowledge require their future professionals (scientists or not) to acquire skills in using HPC. The Super Computing and Distributed Systems Camping School, SC-Camp, is a non-profit activity that proposes a series of courses about HPC with an important focus on practical sessions (more than half of the time) addressed to undergraduate and graduate students who could benefit from HPC by demand. It is an itinerant school, bringing the HPC knowledge to a different place every year, focusing on diversity, sustainability, and humanity.La computación de alto rendimiento (HPC) es uno de los pilares del desarrollo de la ciencia moderna y las tecnologías disruptivas, uniendo arquitecturas informáticas y programación paralela en interacciones multidisciplinarias para enfrentar problemas específicos de dominio. Es por ello que distintas áreas del conocimiento exigen a sus futuros profesionales (científicos o no) adquirir habilidades en el uso de HPC. El Camping Escuela de Super Computación y Sistemas Distribuidos, SC-Camp, es una actividad sinánimo de lucro que propone una serie de cursos sobre HPC con un importante foco en sesiones prácticas (más de la mitad del tiempo) dirigidas a estudiantes de grado y posgrado que podrían beneficiarse de HPC según la demanda. Es una escuela itinerante, quelleva el conocimiento de HPC a un lugar diferente cada año, con un enfoque importante en la diversidad, la sostenibilidad y la humanidad

Active wetting of epithelial tissues

Development, regeneration and cancer involve drastic transitions in tissue morphology. In analogy with the behavior of inert fluids, some of these transitions have been interpreted as wetting transitions. The validity and scope of this analogy are unclear, however, because the active cellular forces that drive tissue wetting have been neither measured nor theoretically accounted for. Here we show that the transition between 2D epithelial monolayers and 3D spheroidal aggregates can be understood as an active wetting transition whose physics differs fundamentally from that of passive wetting phenomena. By combining an active polar fluid model with measurements of physical forces as a function of tissue size, contractility, cell-cell and cell-substrate adhesion, and substrate stiffness, we show that the wetting transition results from the competition between traction forces and contractile intercellular stresses. This competition defines a new intrinsic lengthscale that gives rise to a critical size for the wetting transition in tissues, a striking feature that has no counterpart in classical wetting. Finally, we show that active shape fluctuations are dynamically amplified during tissue dewetting. Overall, we conclude that tissue spreading constitutes a prominent example of active wetting --- a novel physical scenario that may explain morphological transitions during tissue morphogenesis and tumor progression

Observing the Evolution of the Universe

How did the universe evolve? The fine angular scale (l>1000) temperature and polarization anisotropies in the CMB are a Rosetta stone for understanding the evolution of the universe. Through detailed measurements one may address everything from the physics of the birth of the universe to the history of star formation and the process by which galaxies formed. One may in addition track the evolution of the dark energy and discover the net neutrino mass. We are at the dawn of a new era in which hundreds of square degrees of sky can be mapped with arcminute resolution and sensitivities measured in microKelvin. Acquiring these data requires the use of special purpose telescopes such as the Atacama Cosmology Telescope (ACT), located in Chile, and the South Pole Telescope (SPT). These new telescopes are outfitted with a new generation of custom mm-wave kilo-pixel arrays. Additional instruments are in the planning stages.Comment: Science White Paper submitted to the US Astro2010 Decadal Survey. Full list of 177 author available at http://cmbpol.uchicago.ed

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Exploring low-energy neutrino physics with the Coherent Neutrino Nucleus Interaction Experiment

The Coherent Neutrino-Nucleus Interaction Experiment (CONNIE) uses low-noise fully depleted charge-coupled devices (CCDs) with the goal of measuring low-energy recoils from coherent elastic scattering ( CE ν NS ) of reactor antineutrinos with silicon nuclei and testing nonstandard neutrino interactions (NSI). We report here the first results of the detector array deployed in 2016, considering an active mass 47.6 g (eight CCDs), which is operating at a distance of 30 m from the core of the Angra 2 nuclear reactor, with a thermal power of 3.8 GW. A search for neutrino events is performed by comparing data collected with the reactor on (2.1 kg-day) and reactor off (1.6 kg-day). The results show no excess in the reactor-on data, reaching the world record sensitivity down to recoil energies of about 1 keV (0.1 keV electron equivalent). A 95% confidence level limit for new physics is established at an event rate of 40 times the one expected from the standard model at this energy scale. The results presented here provide a new window to low-energy neutrino physics, allowing one to explore for the first time the energies accessible through the low threshold of CCDs. They will lead to new constraints on NSI from the CEνNS of antineutrinos from nuclear reactors.Fil: Aguilar Arevalo, Alexis. Universidad Nacional Autónoma de México; MéxicoFil: Bertou, Xavier Pierre Louis. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Bonifazi, Carla Brenda. Universidade Federal do Rio de Janeiro; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cancelo, Gustavo Indalecio. Fermi National Accelerator Laboratory; Estados UnidosFil: Castañeda, Alejandro. Universidad Nacional Autónoma de México; MéxicoFil: Cervantes Vergara, Brenda. Universidad Nacional Autónoma de México; MéxicoFil: Chavez, Claudio. Universidad Nacional de Asunción; ParaguayFil: D’Olivo, Juan C.. Universidad Nacional Autónoma de México; MéxicoFil: Dos Anjos, João C.. Centro Brasileiro de Pesquisas Físicas; BrasilFil: Estrada, Juan. Fermi National Accelerator Laboratory; Estados UnidosFil: Fernandes Neto, Aldo R.. Centro Federal de Educacão Tecnológica Celso Suckow Da Fonseca; BrasilFil: Fernández Moroni, Guillermo. Fermi National Accelerator Laboratory; Estados Unidos. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Foguel, Ana. Universidade Federal do Rio de Janeiro; BrasilFil: Ford, Richard. Fermi National Accelerator Laboratory; Estados UnidosFil: Gonzalez Cuevas, Juan. Universidad Nacional de Asunción; ParaguayFil: Hernández, Pamela. Universidad Nacional Autónoma de México; MéxicoFil: Hernandez, Susana. Fermi National Accelerator Laboratory; Estados UnidosFil: Izraelevitch, Federico Hernán. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional de San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kavner, Alexander R.. University of Michigan; Estados UnidosFil: Kilminster, Ben. Universitat Zurich; SuizaFil: Kuk, Kevin. Fermi National Accelerator Laboratory; Estados UnidosFil: Lima, H.P.. Centro Brasileiro de Pesquisas Físicas; BrasilFil: Makler, Martín. Centro Brasileiro de Pesquisas Físicas; BrasilFil: Molina, Jorge. Universidad Nacional de Asunción; ParaguayFil: Mota, Philipe. Centro Brasileiro de Pesquisas Físicas; BrasilFil: Nasteva, Irina. Universidade Federal do Rio de Janeiro; BrasilFil: Paolini, Eduardo Emilio. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; ArgentinaFil: Romero, Carlos. Universidad Nacional de Asunción; ParaguayFil: Sarkis, Y.. Universidad Nacional Autónoma de México; MéxicoFil: Sofo Haro, Miguel Francisco. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional de Cuyo; Argentina. Fermi National Accelerator Laboratory; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - Patagonia Norte. Unidad de Adm.territorial; ArgentinaFil: Souza, Iruatã M. S.. Centro Brasileiro de Pesquisas Físicas; BrasilFil: Tiffenberg, Javier Sebastian. Fermi National Accelerator Laboratory; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wagner, Stefan. Centro Brasileiro de Pesquisas Físicas; Brasil. Pontifícia Universidade Católica do Rio de Janeiro; Brasi

Quantificação de células dos túbulos seminíferos e rendimento da espermatogênese em cutias (Dasyprocta aguti) criadas em cativeiros

This study has as objective to evaluate the spermatogenesis yield of Agoutis rised in captivity, through the rates found between cellular types of the seminiferous epithelium. The results showed that the spermatogenesis yield of the Agoutis since 9 to 14 months of age did not reach the stabilization point. The coefficient of efficiency of the spermatogonium mitoses, did not increase with the age. The meiotic yield, usual spermatogenesis yield and the Sertoli cells index didn't showed numeric variation at function of the age, however, it was not detected by statistic data.O presente estudo teve como objetivo avaliar o rendimento da espermatogênese de cutias criadas em cativeiro, por intermédio das razões encontradas entre tipos celulares do epitélio seminífero. Os resultados apontaram que o rendimento da espermatogênese da cutia dos nove aos quatorze meses de idade não chegou a um ponto de estabilização. O coeficiente de eficiência de mitoses espermatogoniais não aumentou com a idade. O rendimento meiótico, o rendimento geral da espermatogênese e o índice de células de Sertoli mostraram variações numéricas em função da idade, entretanto, não detectadas estatisticamente

A Prospective, Multicenter, Real-World Registry of Coronary Lithotripsy in Calcified Coronary Arteries

BACKGROUND Intravascular lithotripsy (IVL) has demonstrated effectiveness in the treatment of calcified lesions in selected patients with stable coronary disease. OBJECTIVES The authors sought to assess the performance of coronary IVL in calcified coronary lesions in a real-life, all comers, setting. METHODS The REPLICA-EPIC18 study prospectively enrolled consecutive patients treated with IVL in 26 centers in Spain. An independent core laboratory performed the angiographic analysis and event adjudication. The primary effectiveness endpoint assessed procedural success (successful IVL delivery, final diameter stenosis <20%, and absence of in- hospital major adverse cardiovascular events [MACE]). The primary safety endpoint measured freedom from MACE at 30 days. A predefined substudy compared outcomes between acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients. RESULTS A total of 426 patients (456 lesions) were included, 63% of the patients presenting with ACS. IVL delivery was successful in 99% of cases. Before IVL, 49% of lesions were considered undilatable. The primary effectiveness endpoint was achieved in 66% of patients, with similar rates among CCS patients (68%) and ACS patients (65%). Likewise, there were no significant differences in angiographic success after IVL between CCS and ACS patients. The rate of MACE at 30 days (primary safety endpoint) was 3% (1% in CCS and 5% in ACS patients [P = 0.073]). CONCLUSIONS Coronary IVL proved to be a feasible and safe procedure in a real-life setting, effectively facilitating stent implantation in severely calcified lesions. Patients with ACS on admission showed similar angiographic success rates but showed a trend toward higher 30-day MACE compared with patients with CCS. (REPLICA-EPIC18 study [Registry of Coronary Lithotripsy in Spain]; NCT04298307) (c) 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts