427 research outputs found
The double-edged sword effect of warming on the soil predatory mite Cosmolaelaps brevistilis (Karg, 1978) (Mesostigmata: Laelapidae)
In this study we used the average annual temperature in Brazil and four warming predictions to propose a maximum thermal threshold for the predatory mite Cosmolaelaps brevistilis (Karg, 1978) (Mesostigmata: Laelapidae) as an experimental model. Then, we evaluated the effects of warming on the biological parameters of C. brevistilis for conservation biological control. We observed higher rates of oviposition and predation of the prey Tyrophagus putrescentiae (Schrank, 1781) (Astigmatina: Acaridae) under warmer conditions at 75 ± 10% RH. The highest rates of prey consumption and oviposition were observed at 28°C compared to the others tested (22, 24, and 26°C). However, the egg viability of C. brevistilis was reduced at the same temperature. Therefore, temperature increases both positive and negative effects on the biological parameters of C. brevistilis which are important for the ecological interactions that are essential for biological control programs
palaeoverse: A community‐driven R package to support palaeobiological analysis
1. The open-source programming language ‘R' has become a standard tool in the
palaeobiologist's toolkit. Its popularity within the palaeobiological community
continues to grow, with published articles increasingly citing the usage of R and R
packages. However, there are currently a lack of agreed standards for data preparation and available frameworks to support the implementation of such standards.
Consequently, data preparation workflows are often unclear and not reproducible, even when code is provided. Moreover, due to a lack of code accessibility and
documentation, palaeobiologists are often forced to ‘reinvent the wheel’ to find
solutions to issues already solved by other members of the community.
2. Here, we introduce palaeoverse, a community-driven R package to aid data preparation and exploration for quantitative palaeobiological research. The package is
freely available and has three core principles: (1) streamline data preparation and
analyses; (2) enhance code readability; and (3) improve reproducibility of results.
To develop these aims, we assessed the analytical needs of the broader palaeobiological community using an online survey, in addition to incorporating our own
experiences.
3. In this work, we first report the findings of the survey, which shaped the development of the package. Subsequently, we describe and demonstrate the functionality available in palaeoverse and provide usage examples. Finally, we discuss the resources we have made available for the community and our future plans for the
broader Palaeoverse project.
4. palaeoverse is a community-driven R package for palaeobiology, developed with
the intention of bringing palaeobiologists together to establish agreed standards
for high-quality quantitative research. The package provides a user-friendly platform for preparing data for analysis with well-documented open-source code to
enhance transparency. The functionality available in palaeoverse improves code
reproducibility and accessibility, which is beneficial for both the review process
and future research
Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress
Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions
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
Draft genome sequence of Wickerhamomyces anomalus LBCM1105, isolated from cachaça fermentation
Wickerhamomyces anomalus LBCM1105 is a yeast isolated from cachaça distillery fermentation vats, notable for exceptional glycerol consumption ability. We report its draft genome with 20.5x in-depth coverage and around 90% extension and completeness. It harbors the sequences of proteins involved in glycerol transport and metabolism.The authors gratefully acknowledge Laboratorio Nacional de Ciencia e Tecnologia do Bioetanol (CTBE) and the Centro Nacional de Pesquisa em Energia e Materiais (CNPEM) for support with the sequencing of LBCM1105. This work was supported by CAPES/Brazil (PNPD 2755/2011; PCF-PVE 021/2012), by CNPq (Brazil), processes 304815/2012 (research grant) and 305135/2015-5, and by AUXPE-PVES 1801/2012 (Process 23038.015294/2016-18) from Brazilian Government and by UFOP. C.L. is supported by the strategic program UID/BIA/04050/2013 [POCI-01-0145-FEDER-007569] funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional de Competitividade e Internacionalizacao (POCI). DMRP is a fellow from the CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) - Brazil (310080/2018-5)
Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).
Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)
Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.
OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)
Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.
BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362
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