277 research outputs found
Hand, foot and mouth disease in an immunocompetent adult due to Coxsackievirus A6
Hand, foot and mouth disease most commonly occurs in children less than 10 years old, but can occur in immunocompetent adults. We describe a 37-year-old immunocompetent man who presented with multiple painful papules and vesicles on his palms and feet together with vesicles inside the mouth. Real-time polymerase chain reaction revealed Coxsackievirus A6 in the vesicle fluid from the feet, throat swab, and rectal swab. Since the disease is highly contagious, to contain the infection it is prudent to recognise that hand, foot and mouth disease can occur in immunocompetent adults.published_or_final_versio
Searching for Exoplanets Using a Microresonator Astrocomb
Detection of weak radial velocity shifts of host stars induced by orbiting
planets is an important technique for discovering and characterizing planets
beyond our solar system. Optical frequency combs enable calibration of stellar
radial velocity shifts at levels required for detection of Earth analogs. A new
chip-based device, the Kerr soliton microcomb, has properties ideal for
ubiquitous application outside the lab and even in future space-borne
instruments. Moreover, microcomb spectra are ideally suited for astronomical
spectrograph calibration and eliminate filtering steps required by conventional
mode-locked-laser frequency combs. Here, for the calibration of astronomical
spectrographs, we demonstrate an atomic/molecular line-referenced,
near-infrared soliton microcomb. Efforts to search for the known exoplanet HD
187123b were conducted at the Keck-II telescope as a first in-the-field
demonstration of microcombs
Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19.
BACKGROUND
Prior studies of therapeutic-dose anticoagulation in patients with COVID-19 have reported conflicting results.
OBJECTIVES
We sought to determine the safety and effectiveness of therapeutic-dose anticoagulation in noncritically ill patients with COVID-19.
METHODS
Patients hospitalized with COVID-19 not requiring intensive care unit treatment were randomized to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary outcome was the 30-day composite of all-cause mortality, requirement for intensive care unit-level of care, systemic thromboembolism, or ischemic stroke assessed in the combined therapeutic-dose groups compared with the prophylactic-dose group.
RESULTS
Between August 26, 2020, and September 19, 2022, 3,398 noncritically ill patients hospitalized with COVID-19 were randomized to prophylactic-dose enoxaparin (n = 1,141), therapeutic-dose enoxaparin (n = 1,136), or therapeutic-dose apixaban (n = 1,121) at 76 centers in 10 countries. The 30-day primary outcome occurred in 13.2% of patients in the prophylactic-dose group and 11.3% of patients in the combined therapeutic-dose groups (HR: 0.85; 95% CI: 0.69-1.04; P = 0.11). All-cause mortality occurred in 7.0% of patients treated with prophylactic-dose enoxaparin and 4.9% of patients treated with therapeutic-dose anticoagulation (HR: 0.70; 95% CI: 0.52-0.93; P = 0.01), and intubation was required in 8.4% vs 6.4% of patients, respectively (HR: 0.75; 95% CI: 0.58-0.98; P = 0.03). Results were similar in the 2 therapeutic-dose groups, and major bleeding in all 3 groups was infrequent.
CONCLUSIONS
Among noncritically ill patients hospitalized with COVID-19, the 30-day primary composite outcome was not significantly reduced with therapeutic-dose anticoagulation compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation and fewer died (FREEDOM COVID [FREEDOM COVID Anticoagulation Strategy]; NCT04512079).Dr Stone has received speaker honoraria from Medtronic, Pulnovo,
Infraredx, Abiomed, and Abbott; has served as a consultant to
Daiichi-Sankyo, Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Ancora, Elucid Bio, Occlutech,
CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore,
Amgen, Adona Medical, and Millennia Biopharma; and has equity/
options from Ancora, Cagent, Applied Therapeutics, Biostar family of
funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix,
and Xenter; his daughter is an employee at IQVIA; and his employer,
Mount Sinai Hospital, receives research support from Abbott,
Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, BiosenseWebster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Dr
Farkouh has received institutional research grants from Amgen,
AstraZeneca, Novo Nordisk, and Novartis; has received consulting
fees from Otitopic; and has received honoraria from Novo Nordisk. Dr
Lala has received consulting fees from Merck and Bioventrix; has
received honoraria from Zoll Medical and Novartis; has served on an
advisory board for Sequana Medical; and is the Deputy Editor for the
Journal of Cardiac Failure. Dr Moreno has received honoraria from
Amgen, Cuquerela Medical, and Gafney; has received payment for
expert testimony from Koskoff, Koskoff & Dominus, Dallas W. Hartman, and Riscassi & Davis PC; and has stock options in Provisio. Dr
Goodman has received institutional research grants from Bristol
Myers Squibb/Pfizer Alliance, Bayer, and Boehringer Ingelheim; has
received consulting fees from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL
Behring, Ferring Pharmaceuticals, HLS Therapeutics, Novartis, Pendopharm/Pharmascience, Pfizer, Regeneron, and Sanofi; has received
honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim,
Bristol Myers Squibb, Eli Lilly, Ferring Pharmaceuticals, HLS Therapeutics, JAMP Pharma, Merck, Novartis, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, and Servier; has served on Data
Safety and Monitoring boards for Daiichi-Sankyo/American Regent
and Novo Nordisk A/C; has served on advisory boards for Amgen,
AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL
Behring, Eli Lilly, Ferring Pharmaceuticals, HLS Therapeutics, JAMP
Pharma, Merck, Novartis, Pendopharm/Pharmascience, Pfizer,
Regeneron, Sanofi, Servier, and Tolmar Pharmaceuticals; has a leadership role in the Novartis Council for Heart Health (unpaid); and
otherwise has received salary support or honoraria from the Heart
and Stroke Foundation of Ontario/University of Toronto (Polo) Chair,
Canadian Heart Failure Society, Canadian Heart Research Centre and
MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating
Centre for Clinical Research, Duke Clinical Research Institute, New
York University Clinical Coordinating Centre, PERFUSE Research
Institute, and the TIMI Study Group (Brigham Health). Dr Ricalde has
received consulting fees from Medtronic, Servier, and Boston Scientific; has received honoraria from Medtronic, Pfizer, Merck, Boston
Scientific, Biosensors, and Bayer; has served on an advisory board for
Medtronic; and has leadership roles in SOLACI and Kardiologen. Dr
Payro has received consulting fees from Bayer Mexico; has received
honoraria from Bayer, Merck, AstraZeneca, Medtronic, and Viatris;
has received payments for expert testimony from Bayer; has received
travel support from AstraZeneca; has served on an advisory board for
Bayer; and his institution has received equipment donated from
AstraZeneca. Dr Castellano has received consulting fees and honoraria from Ferrer International, Servier, and Daiichi-Sankyo; and has
received travel support from Ferrer International. Dr Hung has served
as an advisory board member for Pfizer, Merck, AstraZeneca, Fosun,
and Gilead. Dr Nadkarni has received consulting fees from Renalytix,
Variant Bio, Qiming Capital, Menarini Health, Daiichi-Sankyo, BioVie,
and Cambridge Health; has received honoraria from Daiichi-Sankyo
and Menarini Health; has patents for automatic disease diagnoses
using longitudinal medical record data, methods, and apparatus for
diagnosis of progressive kidney function decline using a machine
learning model, electronic phenotyping technique for diagnosing
chronic kidney disease, deep learning to identify biventricular
structure and function, fusion models for identification of pulmonary
embolism, and SparTeN: a novel spatio-temporal deep learning
model; has served on a Data Safety and Monitoring Board for CRIC
OSMB; has leadership roles for Renalytix scientific advisory board,
Pensive Health scientific advisory board, and ASN Augmented Intelligence and Digital Health Committee; has ownership interests in
Renalytix, Data2Wisdom LLC, Verici Dx, Nexus I Connect, and Pensieve Health; and his institution receives royalties from Renalytix. Dr
Goday has received the Frederick Banting and Charles Best Canada
Graduate Scholarship (Doctoral Research Award) from the Canadian
Institutes of Health Research. Dr Furtado has received institutional
research grants from AstraZeneca, CytoDin, Pfizer, Servier, Amgen,
Alliar Diagnostics, and the Brazilian Ministry of Health; has received
consulting fees from Biomm and Bayer; has received honoraria from
AstraZeneca, Bayer, Servier, and Pfizer; and has received travel support from Servier, AstraZeneca, and Bayer. Dr Granada has received
consulting fees, travel support, and stock from Cogent Technologies
Corp; and has received stock from Kutai. Dr Contreras has served as a
consultant for Merck, CVRx, Novodisk, and Boehringer Ingelheim;
and has received educational grants from Alnylam Pharmaceuticals
and AstraZeneca. Dr Bhatt has received research funding from Abbott,
Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen,
AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific,
Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi,
Cincor, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring
Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly,
Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo
Nordisk, Owkin, Pfizer Inc, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The
Medicines Company, Youngene, and 89bio; has received royalties
from Elsevier; has received consultant fees from Broadview Ventures
and McKinsey; has received honoraria from the American College of
Cardiology, Baim Institute for Clinical Research, Belvoir Publications,
Boston Scientific, Cleveland Clinic, Duke Clinical Research Institute,
Mayo Clinic, Mount Sinai School of Medicine, Novartis, Population
Health Research Institute, Rutgers University, Canadian Medical and
Surgical Knowledge Translation Research Group, Cowen and Company, HMP Global, Journal of the American College of Cardiology, K2P,
Level Ex, Medtelligence/ReachMD, MJH Life Sciences, Oakstone CME,
Piper Sandler, Population Health Research Institute, Slack Publications, WebMD, Wiley, Society of Cardiovascular Patient Care; has
received fees from expert testimony from the Arnold and Porter law
firm; has received travel support from the American College of Cardiology, Society of Cardiovascular Patient Care, American Heart Association; has a patent for otagliflozin assigned to Brigham and
Women’s Hospital who assigned to Lexicon; has participated on a
data safety monitoring board or advisory board for Acesion Pharma,
Assistance Publique-Hôpitaux de Paris, AngioWave, Baim Institute,
Bayer, Boehringer Ingelheim, Boston Scientific, Cardax, CellProthera,
Cereno Scientific, Cleveland Clinic, Contego Medical, Duke Clinical
Research Institute, Elsevier Practice Update Cardiology, Janssen,
Level Ex, Mayo Clinic, Medscape Cardiology, Merck, Mount Sinai
School of Medicine, MyoKardia, NirvaMed, Novartis, Novo Nordisk,
PhaseBio, PLx Pharma, Regado Biosciences, Population Health
Research Institute, and Stasys; serves as a trustee or director for
American College of Cardiology, AngioWave, Boston VA Research
Institute, Bristol Myers Squibb, DRS.LINQ, High Enroll, Society of
Cardiovascular Patient Care, and TobeSoft; has ownership interests in
AngioWave, Bristol Myers Squibb, DRS.LINQ, and High Enroll; has
other interests in Clinical Cardiology, the NCDR-ACTION Registry
Steering Committee; has conducted unfunded research with FlowCo
and Takeda, Contego Medical, American Heart Association Quality
Oversight Committee, Inaugural Chair, VA CART Research and Publications Committee; and has been a site co-investigator for Abbott,
Biotronik, Boston Scientific, CSI, St Jude Medical (now Abbott),
Phillips SpectraWAVE, Svelte, and Vascular Solutions. Dr Fuster declares that he raised $7 million from patients for this study granted to
Mount Sinai Heart, unrelated to industry. All other authors have reported that they have no relationships relevant to the contents of this
paper to disclose.S
Recommended from our members
Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.
We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition
Estimating Infection Attack Rates and Severity in Real Time during an Influenza Pandemic: Analysis of Serial Cross-Sectional Serologic Surveillance Data
This study reports that using serological data coupled with clinical surveillance data can provide real-time estimates of the infection attack rates and severity in an emerging influenza pandemic
Abnormalities in Oxygen Sensing Define Early and Late Onset Preeclampsia as Distinct Pathologies
BACKGROUND:
The pathogenesis of preeclampsia, a serious pregnancy disorder, is still elusive and its treatment empirical. Hypoxia Inducible Factor-1 (HIF-1) is crucial for placental development and early detection of aberrant regulatory mechanisms of HIF-1 could impact on the diagnosis and management of preeclampsia. HIF-1α stability is controlled by O(2)-sensing enzymes including prolyl hydroxylases (PHDs), Factor Inhibiting HIF (FIH), and E3 ligases Seven In Absentia Homologues (SIAHs). Here we investigated early- (E-PE) and late-onset (L-PE) human preeclamptic placentae and their ability to sense changes in oxygen tension occurring during normal placental development.
METHODS AND FINDINGS:
Expression of PHD2, FIH and SIAHs were significantly down-regulated in E-PE compared to control and L-PE placentae, while HIF-1α levels were increased. PHD3 expression was increased due to decreased FIH levels as demonstrated by siRNA FIH knockdown experiments in trophoblastic JEG-3 cells. E-PE tissues had markedly diminished HIF-1α hydroxylation at proline residues 402 and 564 as assessed with monoclonal antibodies raised against hydroxylated HIF-1α P402 or P564, suggesting regulation by PHD2 and not PHD3. Culturing villous explants under varying oxygen tensions revealed that E-PE, but not L-PE, placentae were unable to regulate HIF-1α levels because PHD2, FIH and SIAHs did not sense a hypoxic environment.
CONCLUSION:
Disruption of oxygen sensing in E-PE vs. L-PE and control placentae is the first molecular evidence of the existence of two distinct preeclamptic diseases and the unique molecular O(2)-sensing signature of E-PE placentae may be of diagnostic value when assessing high risk pregnancies and their severity
Grb2 depletion under non-stimulated conditions inhibits PTEN, promotes Akt-induced tumor formation and contributes to poor prognosis in ovarian cancer
In the absence of extracellular stimulation the adaptor protein growth factor receptor-bound protein (Grb2) and the phospholipase Plcγ1 compete for the same binding site on fibroblast growth factor receptor 2 (FGFR2). Reducing cellular Grb2 results in upregulation of Plcγ1 and depletion of the phospholipid PI(4,5)P2. The functional consequences of this event on signaling pathways are unknown. We show that the decrease in PI(4,5)P2 level under non-stimulated conditions inhibits PTEN activity leading to the aberrant activation of the oncoprotein Akt. This results in excessive cell proliferation and tumor progression in a xenograft mouse model. As well as defining a novel mechanism of Akt phosphorylation with important therapeutic consequences, we also demonstrate that differential expression levels of FGFR2, Plcγ1 and Grb2 correlate with patient survival. Oncogenesis through fluctuation in the expression levels of these proteins negates extracellular stimulation or mutation and defines them as novel prognostic markers in ovarian cancer
Fast Growth Increases the Selective Advantage of a Mutation Arising Recurrently during Evolution under Metal Limitation
Understanding the evolution of biological systems requires untangling the molecular mechanisms that connect genetic and environmental variations to their physiological consequences. Metal limitation across many environments, ranging from pathogens in the human body to phytoplankton in the oceans, imposes strong selection for improved metal acquisition systems. In this study, we uncovered the genetic and physiological basis of adaptation to metal limitation using experimental populations of Methylobacterium extorquens AM1 evolved in metal-deficient growth media. We identified a transposition mutation arising recurrently in 30 of 32 independent populations that utilized methanol as a carbon source, but not in any of the 8 that utilized only succinate. These parallel insertion events increased expression of a novel transporter system that enhanced cobalt uptake. Such ability ensured the production of vitamin B12, a cobalt-containing cofactor, to sustain two vitamin B12–dependent enzymatic reactions essential to methanol, but not succinate, metabolism. Interestingly, this mutation provided higher selective advantages under genetic backgrounds or incubation temperatures that permit faster growth, indicating growth-rate–dependent epistatic and genotype-by-environment interactions. Our results link beneficial mutations emerging in a metal-limiting environment to their physiological basis in carbon metabolism, suggest that certain molecular features may promote the emergence of parallel mutations, and indicate that the selective advantages of some mutations depend generically upon changes in growth rate that can stem from either genetic or environmental influences
Search for a singly produced third-generation scalar leptoquark decaying to a tau lepton and a bottom quark in proton-proton collisions at root s=13 TeV
A search is presented for a singly produced third-generation scalar leptoquark decaying to a tau lepton and a bottom quark. Associated production of a leptoquark and a tau lepton is considered, leading to a final state with a bottom quark and two tau leptons. The search uses proton-proton collision data at a center-of-mass energy of 13 TeV recorded with the CMS detector, corresponding to an integrated luminosity of 35.9 fb(-1). Upper limits are set at 95% confidence level on the production cross section of the third-generation scalar leptoquarks as a function of their mass. From a comparison of the results with the theoretical predictions, a third-generation scalar leptoquark decaying to a tau lepton and a bottom quark, assuming unit Yukawa coupling (lambda), is excluded for masses below 740 GeV. Limits are also set on lambda of the hypothesized leptoquark as a function of its mass. Above lambda = 1.4, this result provides the best upper limit on the mass of a third-generation scalar leptoquark decaying to a tau lepton and a bottom quark.Peer reviewe
Constraints on models of scalar and vector leptoquarks decaying to a quark and a neutrino at root s=13 TeV
The results of a previous search by the CMS Collaboration for squarks and gluinos are reinterpreted to constrain models of leptoquark (LQ) production. The search considers jets in association with a transverse momentum imbalance, using the M-T2 variable. The analysis uses proton-proton collision data at root s = 13 TeV, recorded with the CMS detector at the LHC in 2016 and corresponding to an integrated luminosity of 35.9 fb(-1). Leptoquark pair production is considered with LQ decays to a neutrino and a top, bottom, or light quark. This reinterpretation considers higher mass values than the original CMS search to constrain both scalar and vector LQs. Limits on the cross section for LQ pair production are derived at the 95% confidence level depending on the LQ decay mode. A vector LQ decaying with a 50% branching fraction to t nu, and 50% to b tau, has been proposed as part of an explanation of anomalous flavor physics results. In such a model, using only the decays to t nu, LQ masses below 1530 GeV are excluded assuming the Yang-Mills case with coupling kappa = 1, or 1115 GeV in the minimal coupling case kappa = 0, placing the most stringent constraint to date from pair production of vector LQs.Peer reviewe
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