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Background: The aim of the current investigation was to explore predisposing factors for food protein induced allergic proctocolitis (FPIAP) in Greek infants relevant in the maternal diet, during pregnancy and breastfeeding, as relevant knowledge is limited. Methods: A multicenter retrospective case-control study was conducted in 6 regions in Greece, with 96 mothers of infants with and 141 mothers of infants without a history of FPIAP. Maternal dietary habits during pregnancy and breastfeeding were evaluated with validated questionnaires: a) The Mediterranean Diet (MedDiet) Score, and b) The Mediterranean Oriented Culture Specific Semi-Quantitative Food Frequency Questionnaire. Statistical tests, modeling and exploration of the FPIAP risk in relation to the maternal diet using elastic net regression models were performed with R software and Studio. Results: FPIAP was associated with cow’s milk (83.6%), egg (7.3 %), and wheat, beef (6.4%) in the maternal diet. Adherence to MedDiet was similar among the mothers, but mothers of FPIAP infants consumed more vegetables (p=0.018) and olive oil (p=0.003). Elastic net prediction models showed that, in this Mediterranean population, increased consumption during pregnancy and lactation of common allergens, whole grain products, homemade food, fish and shellfish, fruit offered protection; conversely, high intake of vegetables, sugar and total fat, and non-stick/grilled cooking, increased the risk of FPIAP, as did high intake of salt and white flour during lactation. Conclusions: Components of a maternal Mediterranean diet can protect against FPIAP when traditional cooking methods are adopted and fish, fruit and whole wheat products are consumed frequently.

Luciana Veronez

and 16 more

Pediatric adrenocortical tumors (ACT) are rare aggressive neoplasms with heterogeneous prognosis. Despite extensive efforts, identifying reliable prognostic factors for pediatric patients with ACT remains a challenge. MicroRNA (miRNA) signatures have been associated with cancer diagnosis, treatment response, and prognosis of several types of cancer. However, the role of miRNAs has been poorly explored in pediatric ACT. In this study, we performed miRNA microarray profiling on a cohort of 37 pediatric ACT and nine non-neoplastic adrenal (NNA) samples and evaluated the prognostic significance of abnormally expressed miRNAs using Kaplan-Meier plots, log-rank test and Cox regression analysis. We identified a total of 98 abnormally expressed miRNAs, which expression profile discriminated ACT from NNAs. Among the 98 deregulated miRNAs, 17 presented significant associations with patients’ survival. In addition, higher expression levels of hsa-miR-630, -139-3p, -125a-3p, -574-5p, -596, -564, -1321, and -423-5p and lower expression levels of hsa-miR-377-3p, -126-3p, -410, -136-3p, -29b-3p, -29a-3p, -337-5p, -143-3p, and 140-5p were significantly associated with poor prognosis, tumor relapse, and/or death. Importantly, the expression profile of these 17 miRNAs stratified patients into two groups of ACTs with different clinical outcomes. Although some individual miRNAs exhibit potential prognostic values in ACTs, only the 17 miRNA-based expression clustering was considered an independent prognostic factor for five-year event-free survival (EFS) compared to other clinicopathological features. In conclusion, our study reports for the first time associations between miRNA profiles and childhood ACT prognosis, providing evidence that miRNAs could be useful biomarkers to discriminate patients with favorable and unfavorable clinical outcomes.

Franziska Uhl

and 2 more

Background and Purpose: Heart failure (HF) affects 64 million people worldwide. Despite advancements in prevention and therapy, quality of life remains poor for many HF patients due to target organ damage. Pulmonary manifestations of HF are well-established. However, difficulties in the treatment of HF patients with chronic lung phenotypes remain, as standard therapies are often complicated by contraindications. Here, we verify the downregulation of the cystic fibrosis transmembrane regulator (CFTR) in the HF lung, a concept that may provide new mechanism-based therapies for HF patients with pulmonary complications. Experimental Approach: Ligation of the left anterior descending coronary artery in mice was used to induce myocardial infarction (MI). At 10 weeks post-MI, pharmacological CFTR corrector therapy (Lumacaftor (Lum)) was applied systemically or lung-specific for 2 weeks, and the lungs were analysed using histology, flow cytometry, Western blotting, and qPCR. Key Results: Experimental HF associated with an apparent lung phenotype characterized by reduction of pulmonary CFTR+ cells, vascular remodelling, and pronounced tissue inflammation as evidenced by infiltration of pro-inflammatory monocytes and elevation of classically-activated macrophages in the lung. PharmacologicalCFTR correction with Lum mitigated the HF-induced downregulation of pulmonary CFTR expression, increased the proportion of CFTR+ cells in the lung, and diminished the HF-associated elevation of classically-activated non-alveolar macrophages within the lungs with implication for vessel wall thickness. Conclusion and Implications: Collectively, our data suggest that pharmacological CFTR correction possesses the capacity to alleviate HF-induced inflammation in the lung and may emerge as treatment option for HF patients with chronic lung phenotypes.

Nídia de Sousa

and 9 more

Spinal cord injury (SCI) leads to severe motor and sensory functional impairments that affect personal and social behaviors. With no effective treatment, deficits in motor function are the most visible consequence of SCI. However, other complications produce a significant impact on SCI patient’s welfare. Spasticity is a neurological impairment that affects the control of muscle tone as a consequence of an insult in the central nervous system (e.g., SCI). Baclofen, a GABA agonist, is the most effective drug for spasticity treatment. This drug activates GABAB receptors decreasing the neurotransmitters release and neuronal hyperpolarization, which results in spasticity relief. Interestingly, emerging data reveals that Baclofen can also play a role on neuroprotection and regeneration after SCI. Our goal is to highlight the role of Baclofen as a potential treatment to promote recovery from SCI. We used a compression SCI mouse model with the administration of Baclofen at different time-points after injury. Our data showed that Baclofen is more effective when a single dose is administered acutely, leading to locomotor improvements in mice. Moreover, Baclofen administration also led to improved bladder function control in all experimental groups. Interestingly, acute Baclofen administration modulates microglia activation state and levels of circulating cytokines, suggesting a role of Baclofen in the modulation of the immune response. Although deeper studies must be performed to understand the cellular/molecular mechanisms that underlie the functional improvements produced by Baclofen, our data shed light into the pharmacological potential of Baclofen to promote recovery in a SCI context.

Silvia Fontana

and 3 more

On-anong Juntit

and 12 more

Assembly and budding in the late-stage of human immunodeficiency virus type 1 (HIV-1) production relies on the polymerization of Gag protein at the inner leaflet of the plasma membrane. We previously generated an ankyrin repeat protein (Ank1D4) that specifically interacts with the CAp24 protein. This study aimed to improve the binding activity of Ank1D4 by generating two platforms for the Ank1D4 dimer. The design of these constructs featured a distinct orientation of monomeric Ank1D4 connected by a linker peptide (G 4S) 4. The binding surfaces in either dimer generated from the C-terminus of the Ank1D4 monomer linked with the N-terminus of another monomer (Ank1D4 NC-NC) or its inverted form (Ank1D4 NC-CN), similar to monomeric Ank1D4. The interaction of Ank1D4 NC-CN with CAp24 from capture ELISA was significantly greater than that of Ank1D4 NC-NC and the parental Ank1D4. The bifunctional characteristic of Ank1D4 NC-CN was further demonstrated using sandwich ELISA. The binding kinetics of these ankyrins were evaluated using bio-layer interferometry analysis. The K D of Ank1D4 NC-CN, Ank1D4 NC-NC and monomeric Ank1D4 was 3.5 nM, 53.7 nM, and 126.2 nM, respectively. The dynamics of the interdomain linker and the behavior of ankyrin dimers were investigated in silico. Upon the binding distance calculation from the candidate structures, the achievement in obtaining double active sites is more possible in Ank1D4 NC-CN. The CD spectroscopic data indicated that secondary structure of dimer forms resemble Ank1D4 monomer α-helical content. This finding confers the strategy to generate dimer from rigid scaffold for acquiring the binding avidity.

Tsubasa Toji

and 4 more

Geographic differences in floral traits may reflect geographic differences in effective pollinator assemblages. Independent local adaptation to pollinator assemblages in multiple regions would be expected to cause parallel floral trait evolution, although sufficient evidence for this is still lacking. In this study, we investigated the relationship between flower spur length and pollinator size in 16 populations of Aquilegia buergeriana var. buergeriana distributed in four mountain regions in the Japanese Alps. We also examined the genetic relationship between yellow- and red-flowered individuals, to see if color differences caused genetic differentiation by pollinator isolation. Genetic relationships among 16 populations were analyzed based on genome-wide single-nucleotide polymorphisms. Even among populations within the same mountain region, pollinator size varied widely, and the average spur length of A. buergeriana var. buergeriana in each population was strongly related to the average visitor size of that population. Genetic relatedness between populations was not related to the similarity of spur length between populations; rather, it was related to the geographic proximity of populations in each mountain region. Our results indicate that spur length in each population evolved independently of the population genetic structure but in parallel in different mountain regions. Further, yellow- and red-flowered individuals of A. buergeriana var. buergeriana were not genetically differentiated. Unlike other Aquilegia species in Europe and America visited by hummingbirds and hawkmoths, this species is consistently visited by bumblebees in Japan. As a result, genetic isolation by flower color has not occurred.

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Sangjun Yoo

and 7 more

Introduction: We assessed the effects of preoperative bladder compliance on the long-term functional outcomes, especially focused on postoperative storage symptom changes, after laser prostatectomy. Materials and Methods: From January 2008 to March 2014, 1608 men who underwent laser prostatectomy, including holmium laser enucleation or photo-vaporization of the prostate, were included in the analysis. We divided patients into 3 groups according to bladder compliance on a baseline urodynamic study: < 12.5; 12.5–25.0; ≥25 mL/cm H2O. A multivariable analysis was performed to determine the impact of bladder compliance on long-term functional outcomes after laser prostatectomy. Results: Bladder compliance was less than 12.5 ml/cm H2O in 50 (3.1%), 12.5-25 ml/cm H2O in 232 (14.4%) patients. As bladder compliance decreased, the baseline International Prostate Symptom (I-PSS) total score and storage sub-score were increased; the voiding sub-score remain unchanged. At postoperative 36 months, improvements in the I-PSS total score and storage sub-score were significantly higher in < 12.5 mL/cm H2O group compared to other groups, although those were equivalent at postoperative 1 and 12 months. On the multivariable analysis, decreased bladder compliance < 12.5 mL/cm H2O was significantly associated with superior improvement in storage sub-score at postoperative 36 months, although it was not associated with voiding sub-score. Conclusion: In patients with preoperative bladder compliance < 12.5 mL/cm H2O, storage symptoms could be further improved at 36 months after laser prostatectomy compared to others. Thus, laser prostatectomy could be a considerable treatment option for patients with severely decreased bladder compliance

Colum Keohane

and 6 more

Abstract Objective To determine whether the introduction of a one-stop see and treat clinic offering early reflux ablation for Venous Leg Ulcer (VLU) patients in July 2016 has affected rates of unplanned inpatient admissions due to venous ulceration. Design Review of inpatient admission data and analysis of related costs. Materials The Hospital Inpatient Enquiry collects data from acute public hospitals in Ireland on admissions and discharges, coded by diagnosis and acuity. This was the primary source of all data relating to admissions and length of stay. Costs were calculated from data published by the Health Service Executive in Ireland on average costs per inpatient stay for given diagnosis codes. Methods Data were collected on admission rates, length of stay, overall bed day usage, and costs across a four-year period; the two years since the introduction of the rapid access clinic, and the two years immediately prior as a control. Results 218 patients admitted with VLUs accounted for a total of 2,529 inpatient bed-days, with 4.5(2-6) unplanned admissions, and a median hospital stay of 7(4-13) days per month. Median unplanned admissions per month decreased from 6(2.5-8.5) in the control period, to 3.5(2-5) after introduction of the clinic p=.040. Bed-day usage was significantly reduced from median 62.5(27-92.5), to 36.5(21-44) bed-days per month (p=.035), though length of stay remained unchanged (p=.57). Cost of unplanned inpatient admissions fell from median \euro33,336.25(\euro14,401.26-\euro49,337.65) per month to \euro19,468.37(\euro11,200.98-\euro22,401.96) (p=.03). Conclusions Admissions for inpatient management of VLUs have fallen after beginning aggressive endovenous treatment of venous reflux in a dedicated one-stop see-and-treat clinic for these patients. As a result, bed-day usage has also fallen, leading to cost savings.

Mürşide Zengin

and 2 more

Aim: The aim of this study was to determine the anxiety levels of parents with children aged 3-6 years due to the Coronavirus Disease-2019 (COVID-19) pandemic and to examine the effects of Solution-Focused Support Program (SFSP) applied to parents with high level of anxiety. Methods: The study was conducted as a parallel-group, randomized controlled design. The sample of the study consisted of 77 parents who were randomly assigned to the experimental and control groups (control group n = 40; intervention group n = 37). One session of online SFSP was applied to the intervention group each week and 4 sessions were applied in total. No intervention was applied to the control group. The data were collected using introductory information form and State-Trait Anxiety Inventory (STAI). Statistical Package for the Social Sciences (SPSS) programme and Analysis of Moment Structures (AMOS) 23 application were used in the analysis of the data.  Structural Equation Modeling (SEM) was used to examine a hypothesized model that SFSP has both direct and indirect effects on anxiety levels of parents.Results: The state and trait anxiety mean scores of the intervention group decreased compared to the pre-intervention mean scores after the implemented programme. While this difference between state anxiety scores was statistically significant (p≤ .001), the difference between trait anxiety scores was not statistically significant (p> .05). There was no statistically significant difference between the pre-test and post-test STAI total scores of the control group.Conclusions: In the study, it has been found that SFSP applied to parents with high level of anxiety is an effective method in reducing the state anxiety levels of parents. Clinical trial number: NCT04609722 (Registration date: 30.10.2020)

Mohammed Al-Sadawi

and 7 more

Abstract: Background: This meta-analysis assessed the relationship between Obstructive Sleep Apnea (OSA) and echocardiographic parameters of diastolic dysfunction (DD), which are used in the assessment of Heart Failure with Preserved Ejection Fraction (HFpEF). Methods: We searched the databases including Ovid MEDLINE, Ovid Embase Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from inception up to December 26th, 2020. The search was not restricted to time, publication status or language. Comparisons were made between patients with OSA, diagnosed in-laboratory polysomnography (PSG) or home sleep apnea testing (HSAT), and patients without OSA in relation to established markers of diastolic dysfunction. Results: Primary search identified 2512 studies. A total of 18 studies including 2509 participants were included. The two groups were free of conventional cardiovascular risk factors. Significant structural changes were observed between the two groups. Patients with OSA exhibited greater LAVI (3.94 CI [0.8, 7.07]; p=0.000) and left ventricular mass index (11.10 CI [2.56,19.65]; p=0.000) as compared to control group. The presence of OSA was also associated with more prolonged DT (10.44 ms CI [0.71,20.16]; p=0.04), IVRT (7.85 ms CI[4.48, 11.22]; p=0.000), and lower E/A ratio (-0.62 CI [-1,-0.24]; p=0.001) suggestive of early DD. The E/e’ ratio (0.94 CI[0.44, 1.45]; p=0.000) was increased. Conclusion: An association between OSA and echocardiographic parameters of DD was detected that was independent of conventional cardiovascular risk factors. OSA may be independently associated with DD perhaps due to higher LV mass. Investigating the role of CPAP therapy in reversing or ameliorating diastolic dysfunction is recommended.

Hans Fangohr

and 2 more

Guest Editors’ IntroductionNotebook interfaces – documents combining executable code with output and notes – first became popular as part of computational mathematics software such as Mathematica and Maple. The Jupyter Notebook, which began as part of the IPython project in 2012, is an open source notebook that can be used with a wide range of general-purpose programming languages.Before notebooks, a scientist working with Python code, for instance, might have used a mixture of script files and code typed into an interactive shell. The shell is good for rapid experimentation, but the code and results are typically transient, and a linear record of everything that was tried would be long and not very clear. The notebook interface combines the convenience of the shell with some of the benefits of saving and editing code in a file, while also incorporating results, including rich output such as plots, in a document that can be shared with others.The Jupyter Notebook is used through a web browser. Although it is often run locally, on a desktop or a laptop, this design means that it can also be used remotely, so the computation occurs, and the notebook files are saved, on an institutional server, a high performance computing facility or in the cloud. This simplifies access to data and computational power, while also allowing researchers to work without installing any special software on their own computer: specialized research software environments can be provided on the server, and the researcher can access those with a standard web browser from their computer.These advantages have led to the rapid uptake of Jupyter notebooks in many kinds of research. The articles in this special issue highlight this breadth, with the authors representing various scientific fields. But more importantly, they describe different aspects of using notebooks in practice, in ways that are applicable beyond a single field.We open this special issue with an invited article by Brian Granger and Fernando Perez – two of the co-founders and leaders of Project Jupyter. Starting from the origins of the project, they introduce the main ideas behind Jupyter notebooks, and explore the question of why Jupyter notebooks have been so useful to such a wide range of users. They have three key messages. The first is that Notebooks are centered around the humans using them and building knowledge with them. Next, notebooks provide a write-eval-think loop that lets the user have a conversation with the computer and the system under study, which can be turned into a persistent narrative of computational exploration. The third idea is that Project Jupyter is more than software: it is a community that is nourished deliberately by its members and leaders.The following five articles in this special issue illustrate the key features of Project Jupyter effectively. They show us a small sample of where researchers can go when empowered by the tool, and represent a range of scientific domains.Stephanie Juneau et al. describe how Jupyter has been used to ‘bring the compute to the data’ in astrophysics, allowing geographically distributed teams to work efficiently on large datasets. Their platform is also used for education & training, including giving school students a realistic taste of modern science.Ryan Abernathey et al. , of the Pangeo project, present a similar scenario with a focus on data from the geosciences. They have enabled analysis of big datasets on public cloud platforms, facilitating a more widely accessible ‘pay as you go’ style of analysis without the high fixed costs of buying and setting up powerful computing and storage hardware. Their discussion of best practices includes details of the different data formats required for efficient access to data in cloud object stores rather than local filesystems.Marijan Beg et al. describe features of Jupyter notebooks and Project Jupyter that help scientists make their research reproducible. In particular, the work focuses on the use of computer simulation and mathematical experiments for research. The self-documenting qualities of the notebook—where the response to a code cell can be archived in the notebook—is an important aspect. The paper addresses wider questions, including use of legacy computational tools, exploitation of HPC resources, and creation of executable notebooks to accompany publications.Blaine Mooers describes the use of a snippet library in the context of molecular structure visualization. Using a Python interface, the PyMOL visualization application can be driven through commands to visualize molecular structures such as proteins and nucleic acids. By using those commands from the Jupyter notebook, a reproducible record of analysis and visualizations can be created. The paper focuses on making this process more user-friendly and efficient by developing a snippet library, which provides a wide selection of pre-composed and commonly used PyMOL commands, as a JupyterLab extension. These commands can be selected via hierarchical pull-down menus rather than having to be typed from memory. The article discusses the benefits of this approach more generally.Aaron Watters describes a widget that can display 3D objects using webGL, while the back-end processes the scene using a data visualization pipeline. In this case, the front-end takes advantage of the client GPU for visualization of the widget, while the back-end takes advantage of whatever computing resources are accessible to Python.The articles for this special issue were all invited submissions, in most cases from selected presentations given at JupyterCon in October 2020. Each article was reviewed by three independent reviewers. The guest editors are grateful to Ryan Abernathey, Luca de Alfaro, Hannah Bruce MacDonald, Christopher Cave-Ayland, Mike Croucher, Marco Della Vedova, Michael Donahue, Vidar Fauske, Jeremy Frey, Konrad Hinsen, Alistair Miles, Arik Mitschang, Blaine Mooers, Samual Munday, Chelsea Parlett, Prabhu Ramachandran, John Readey, Petr Škoda and James Tocknell for their work as reviewers, along with other reviewers who preferred not to be named. The article by Brian Granger and Fernando Perez was invited by the editor in chief, and reviewed by the editors of this special issue.Hans Fangohr is currently heading the Computational Science group at the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and is a Professor of Computational Modelling at the University of Southampton, UK. A physicist by training, he received his PhD in Computer Science in 2002. He authored more than 150 scientific articles in computational science and materials modelling, several open source software projects, and a text book on Python for Computational Science and Engineering. Contact him at hans.fangohr@mpsd.mpg.deThomas Kluyver is currently a software engineer at European XFEL. Since gaining a PhD in plant sciences from the University of Sheffield in 2013, he has been involved in various parts of the open source & scientific computing ecosystems, including the Jupyter & IPython projects. Contact him at thomas.kluyver@xfel.euMassimo Di Pierro is a Professor of Computer Science at DePaul University. He has a PhD in Theoretical Physics from the University of Southampton and is an expert in Numerical Algorithms, High Performance Computing, and Machine Learning. Massimo is the lead developer of many open source projects including web2py, py4web, and pydal. He has authored more than 70 articles in Physics, Computer Science, and Finance and has published three books. Contact him at massimo.dipierro@gmail.com

Jumpei Ogura

and 9 more

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) infection has a significant clinical impact on both pregnant women and neonates. The aim of this study was to accurately assess the vertical transmission rate of MRSA and its clinical impacts on both pregnant mothers and neonates.Material and Methods: We conducted a prospective observational cohort study of 898 pregnant women who were admitted to our department and 905 neonates from August 2016 to December 2017. MRSA was cultured from  nasal and vaginal samples taken from the mothers at enrollment and from nasal and umbilical surface swabs taken from neonates at the time of delivery. We examined the vertical transmission rate of MRSA in mother-neonate pairs. We used multivariable logistic regression to identify risk factors for maternal MRSA colonization and maternal/neonatal adverse outcomes associated with maternal MRSA colonization.Results: The prevalence of maternal MRSA colonization was 6.1% (55 out of 898) at enrollment. The independent risk factors were multiparity and occupation (healthcare provider) (OR: 2.35, 95% CI: 1.25-4.42, OR: 2.58, 95% CI: 1.39-4.79, respectively). The prevalence of neonatal MRSA colonization at birth was 12.7% (7 out of 55 mother-neonate pairs) in the maternal MRSA-positive group, whereas it was only 0.12% (one out of 843 pairs) in the maternal MRSA-negative group (OR: 121, 95% CI: 14.6-1000). When maternal vaginal samples were MRSA positive, vertical transmission was observed in four out of nine cases (44.4%) in this study. Skin and soft tissue infections (SSTIs) developed more frequently in neonates in the maternal MRSA-positive group than in the MRSA-negative group (OR: 7.47, 95% CI: 2.50-22.3).Conclusions: The prevalence of MRSA in pregnant women was approximately 6%. Vertical transmission caused by maternal vaginal MRSA colonization was observed in four out of nine cases (44.4%). Although our study includes limited number of maternal MRSA positive cases, the vertical transmission of MRSA may occur in up to 44% of neonates of mothers with vaginal MRSA colonization. Maternal MRSA colonization may associate with increased development of SSTIs in neonates via vertical transmission.
Many societal opportunities and challenges, both current and future, are either inter- or transdisciplinary in nature. Focus and action to cut across traditional academic boundaries has increased in research and, to a less extent, teaching. One successful collaboration has been the augmentation of fields within the Humanities, Social Sciences, and Arts by integrating complementary tools and methods originated from STEM. This trend is gradually materializing in formal undergraduate and secondary education.The proven effectiveness of Jupyter notebooks for teaching and learning STEM practices gives rise to a nascent case for education seeking to replicate this interdisciplinary design to adopt notebook technology as the best pedagogical tool for this job. This article presents two sets of data to help argue this case.The first set of data demonstrates the art of the possible. A sample of undergraduate and secondary level courses showcases existing or recent work of educational stakeholders in the US and UK who are already pioneering instruction where computational and data practices are integrated into the study of the Humanities, Social Sciences, and Arts, with Jupyter notebooks chosen as a central pedagogical tool. Supplementary data providing an overview of the types of technical material covered by each course syllabi further evidences what interdisciplinary education is perceived to be or is already feasible using this Jupyter technology with student audiences of these levels.The second set of data provides more granular, concrete insight derived from user experiences of a handful of the courses from the sample. Four instructors and one student describe a range of pedagogical benefits and value they attribute to the use of Jupyter notebooks in their course(s).In presenting this nascent case, the article aims to stimulate the development of Jupyter notebook-enabled, computational data-driven interdisciplinary education within undergraduate and secondary school programs.

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