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  • 1
    Online Resource
    Online Resource
    Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection
    American Medical Association (AMA) ; 2023
    In:  JAMA Vol. 329, No. 22 ( 2023-06-13), p. 1934-
    Details
    In: JAMA, American Medical Association (AMA), Vol. 329, No. 22 ( 2023-06-13), p. 1934-
    Abstract: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID . Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure SARS-CoV-2 infection. Main Outcomes and Measures PASC and 44 participant-reported symptoms (with severity thresholds). Results A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%] ) were PASC positive at 6 months. Conclusions and Relevance A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.
    Type of Medium: Online Resource
    ISSN: 0098-7484
    URL: Article
    DOI: 10.1001/jama.2023.8823
    RVK:
    XA 10000
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 2
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    Metabolic control of nitrogen fixation in rhizobium-legume symbioses
    American Association for the Advancement of Science (AAAS) ; 2021
    In:  Science Advances Vol. 7, No. 31 ( 2021-07-30)
    Details
    In: Science Advances, American Association for the Advancement of Science (AAAS), Vol. 7, No. 31 ( 2021-07-30)
    Abstract: Rhizobia induce nodule formation on legume roots and differentiate into bacteroids, which catabolize plant-derived dicarboxylates to reduce atmospheric N 2 into ammonia. Despite the agricultural importance of this symbiosis, the mechanisms that govern carbon and nitrogen allocation in bacteroids and promote ammonia secretion to the plant are largely unknown. Using a metabolic model derived from genome-scale datasets, we show that carbon polymer synthesis and alanine secretion by bacteroids facilitate redox balance in microaerobic nodules. Catabolism of dicarboxylates induces not only a higher oxygen demand but also a higher NADH/NAD + ratio than sugars. Modeling and 13 C metabolic flux analysis indicate that oxygen limitation restricts the decarboxylating arm of the tricarboxylic acid cycle, which limits ammonia assimilation into glutamate. By tightly controlling oxygen supply and providing dicarboxylates as the energy and electron source donors for N 2 fixation, legumes promote ammonia secretion by bacteroids. This is a defining feature of rhizobium-legume symbioses.
    Type of Medium: Online Resource
    ISSN: 2375-2548
    URL: Article
    DOI: 10.1126/sciadv.abh2433
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2021
    detail.hit.zdb_id: 2810933-8
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  • 3
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    Gestational Glucose Intolerance and Birth Weight–Related Complications
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Obstetrics & Gynecology Vol. 142, No. 3 ( 2023-09), p. 594-602
    Details
    In: Obstetrics & Gynecology, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. 3 ( 2023-09), p. 594-602
    Abstract: To evaluate the risks of large-for-gestational-age birth weight (LGA) and birth weight–related complications in pregnant individuals with gestational glucose intolerance, an abnormal screening glucose loading test result without meeting gestational diabetes mellitus (GDM) criteria. METHODS: In a retrospective cohort study of 46,989 individuals with singleton pregnancies who delivered after 28 weeks of gestation, those with glucose loading test results less than 140 mg/dL were classified as having normal glucose tolerance. Those with glucose loading test results of 140 mg/dL or higher and fewer than two abnormal values on a 3-hour 100-g oral glucose tolerance test (OGTT) were classified as having gestational glucose intolerance. Those with two or more abnormal OGTT values were classified as having GDM. We hypothesized that gestational glucose intolerance would be associated with higher odds of LGA (birth weight greater than the 90th percentile for gestational age and sex). We used generalized estimating equations to examine the odds of LGA in pregnant individuals with gestational glucose intolerance compared with those with normal glucose tolerance, after adjustment for age, body mass index, parity, health insurance, race and ethnicity, and marital status. In addition, we investigated differences in birth weight–related adverse pregnancy outcomes. RESULTS: Large for gestational age was present in 7.8% of 39,685 pregnant individuals with normal glucose tolerance, 9.5% of 4,155 pregnant individuals with gestational glucose intolerance and normal OGTT, 14.5% of 1,438 pregnant individuals with gestational glucose intolerance and one abnormal OGTT value, and 16.0% of 1,711 pregnant individuals with GDM. The adjusted odds of LGA were higher in pregnant individuals with gestational glucose intolerance than in those with normal glucose tolerance overall (adjusted odds ratio [aOR] 1.35, 95% CI 1.23–1.49, P 〈 .001). When compared separately with pregnant individuals with normal glucose tolerance, those with either gestational glucose intolerance subtype had higher adjusted LGA odds (gestational glucose intolerance with normal OGTT aOR 1.21, 95% CI 1.08–1.35, P 〈 .001; gestational glucose intolerance with one abnormal OGTT value aOR 1.77, 95% CI 1.52–2.08, P 〈 .001). The odds of birth weight–related adverse outcomes (including cesarean delivery, severe perineal lacerations, and shoulder dystocia or clavicular fracture) were higher in pregnant individuals with gestational glucose intolerance with one abnormal OGTT value than in those with normal glucose tolerance. CONCLUSION: Gestational glucose intolerance in pregnancy is associated with birth weight–related adverse pregnancy outcomes. Glucose lowering should be investigated as a strategy for lowering the risk of these outcomes in this group.
    Type of Medium: Online Resource
    ISSN: 0029-7844
    URL: Article
    DOI: 10.1097/AOG.0000000000005278
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2012791-1
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  • 4
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    Genome-Scale Metabolic Modelling of Lifestyle Changes in Rhizobium leguminosarum
    American Society for Microbiology ; 2022
    In:  mSystems Vol. 7, No. 1 ( 2022-02-22)
    Details
    In: mSystems, American Society for Microbiology, Vol. 7, No. 1 ( 2022-02-22)
    Abstract: Biological nitrogen fixation in rhizobium-legume symbioses is of major importance for sustainable agricultural practices. To establish a mutualistic relationship with their plant host, rhizobia transition from free-living bacteria in soil to growth down infection threads inside plant roots and finally differentiate into nitrogen-fixing bacteroids. We reconstructed a genome-scale metabolic model for Rhizobium leguminosarum and integrated the model with transcriptome, proteome, metabolome, and gene essentiality data to investigate nutrient uptake and metabolic fluxes characteristic of these different lifestyles. Synthesis of leucine, polyphosphate, and AICAR is predicted to be important in the rhizosphere, while myo- inositol catabolism is active in undifferentiated nodule bacteria in agreement with experimental evidence. The model indicates that bacteroids utilize xylose and glycolate in addition to dicarboxylates, which could explain previously described gene expression patterns. Histidine is predicted to be actively synthesized in bacteroids, consistent with transcriptome and proteome data for several rhizobial species. These results provide the basis for targeted experimental investigation of metabolic processes specific to the different stages of the rhizobium-legume symbioses. IMPORTANCE Rhizobia are soil bacteria that induce nodule formation on plant roots and differentiate into nitrogen-fixing bacteroids. A detailed understanding of this complex symbiosis is essential for advancing ongoing efforts to engineer novel symbioses with cereal crops for sustainable agriculture. Here, we reconstruct and validate a genome-scale metabolic model for Rhizobium leguminosarum bv. viciae 3841. By integrating the model with various experimental data sets specific to different stages of symbiosis formation, we elucidate the metabolic characteristics of rhizosphere bacteria, undifferentiated bacteria inside root nodules, and nitrogen-fixing bacteroids. Our model predicts metabolic flux patterns for these three distinct lifestyles, thus providing a framework for the interpretation of genome-scale experimental data sets and identifying targets for future experimental studies.
    Type of Medium: Online Resource
    ISSN: 2379-5077
    URL: Article
    DOI: 10.1128/msystems.00975-21
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2844333-0
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  • 5
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    Regulation strategies for two-output biomolecular networks
    The Royal Society ; 2023
    In:  Journal of The Royal Society Interface Vol. 20, No. 205 ( 2023-08)
    Details
    In: Journal of The Royal Society Interface, The Royal Society, Vol. 20, No. 205 ( 2023-08)
    Abstract: Feedback control theory facilitates the development of self-regulating systems with desired performance which are predictable and insensitive to disturbances. Feedback regulatory topologies are found in many natural systems and have been of key importance in the design of reliable synthetic bio-devices operating in complex biological environments. Here, we study control schemes for biomolecular processes with two outputs of interest, expanding previously described concepts based on single-output systems. Regulation of such processes may unlock new design possibilities but can be challenging due to coupling interactions; also potential disturbances applied on one of the outputs may affect both. We therefore propose architectures for robustly manipulating the ratio/product and linear combinations of the outputs as well as each of the outputs independently. To demonstrate their characteristics, we apply these architectures to a simple process of two mutually activated biomolecular species. We also highlight the potential for experimental implementation by exploring synthetic realizations both in vivo and in vitro . This work presents an important step forward in building bio-devices capable of sophisticated functions.
    Type of Medium: Online Resource
    ISSN: 1742-5662
    URL: Article
    DOI: 10.1098/rsif.2023.0174
    Language: English
    Publisher: The Royal Society
    Publication Date: 2023
    detail.hit.zdb_id: 2156283-0
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  • 6
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    How Rhizobia Adapt to the Nodule Environment
    American Society for Microbiology ; 2021
    In:  Journal of Bacteriology Vol. 203, No. 12 ( 2021-05-20)
    Details
    In: Journal of Bacteriology, American Society for Microbiology, Vol. 203, No. 12 ( 2021-05-20)
    Abstract: Rhizobia are a phylogenetically diverse group of soil bacteria that engage in mutualistic interactions with legume plants. Although specifics of the symbioses differ between strains and plants, all symbioses ultimately result in the formation of specialized root nodule organs that host the nitrogen-fixing microsymbionts called bacteroids. Inside nodules, bacteroids encounter unique conditions that necessitate the global reprogramming of physiological processes and the rerouting of their metabolism. Decades of research have addressed these questions using genetics, omics approaches, and, more recently, computational modeling. Here, we discuss the common adaptations of rhizobia to the nodule environment that define the core principles of bacteroid functioning. All bacteroids are growth arrested and perform energy-intensive nitrogen fixation fueled by plant-provided C 4 -dicarboxylates at nanomolar oxygen levels. At the same time, bacteroids are subject to host control and sanctioning that ultimately determine their fitness and have fundamental importance for the evolution of a stable mutualistic relationship.
    Type of Medium: Online Resource
    ISSN: 0021-9193 , 1098-5530
    URL: Article
    DOI: 10.1128/JB.00539-20
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 1481988-0
    SSG: 12
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  • 7
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    LAB-STEM CELLS
    Oxford University Press (OUP) ; 2012
    In:  Neuro-Oncology Vol. 14, No. suppl 6 ( 2012-10-01), p. vi142-vi152
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 14, No. suppl 6 ( 2012-10-01), p. vi142-vi152
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/nos239
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2012
    detail.hit.zdb_id: 2094060-9
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  • 8
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    Swarm Learning for decentralized and confidential clinical machine learning
    Springer Science and Business Media LLC ; 2021
    In:  Nature Vol. 594, No. 7862 ( 2021-06-10), p. 265-270
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 594, No. 7862 ( 2021-06-10), p. 265-270
    Abstract: Fast and reliable detection of patients with severe and heterogeneous illnesses is a major goal of precision medicine 1,2 . Patients with leukaemia can be identified using machine learning on the basis of their blood transcriptomes 3 . However, there is an increasing divide between what is technically possible and what is allowed, because of privacy legislation 4,5 . Here, to facilitate the integration of any medical data from any data owner worldwide without violating privacy laws, we introduce Swarm Learning—a decentralized machine-learning approach that unites edge computing, blockchain-based peer-to-peer networking and coordination while maintaining confidentiality without the need for a central coordinator, thereby going beyond federated learning. To illustrate the feasibility of using Swarm Learning to develop disease classifiers using distributed data, we chose four use cases of heterogeneous diseases (COVID-19, tuberculosis, leukaemia and lung pathologies). With more than 16,400 blood transcriptomes derived from 127 clinical studies with non-uniform distributions of cases and controls and substantial study biases, as well as more than 95,000 chest X-ray images, we show that Swarm Learning classifiers outperform those developed at individual sites. In addition, Swarm Learning completely fulfils local confidentiality regulations by design. We believe that this approach will notably accelerate the introduction of precision medicine.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-021-03583-3
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 9
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    DataSheet1.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Molecular Biosciences Vol. 8 ( 2021-5-10)
    Details
    In: Frontiers in Molecular Biosciences, Frontiers Media SA, Vol. 8 ( 2021-5-10)
    Abstract: The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com , we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
    Type of Medium: Online Resource
    ISSN: 2296-889X
    URL: Article
    URL: Article
    DOI: 10.3389/fmolb.2021.653148
    DOI: 10.3389/fmolb.2021.653148.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2814330-9
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