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  • Springer Science and Business Media LLC  (20)
  • 1
    Online Resource
    Online Resource
    Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial
    Springer Science and Business Media LLC ; 2021
    In:  Intensive Care Medicine Vol. 47, No. 8 ( 2021-08), p. 867-886
    Details
    In: Intensive Care Medicine, Springer Science and Business Media LLC, Vol. 47, No. 8 ( 2021-08), p. 867-886
    Type of Medium: Online Resource
    ISSN: 0342-4642 , 1432-1238
    URL: Article
    DOI: 10.1007/s00134-021-06448-5
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1459201-0
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  • 2
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    Time-Restricted Eating in Metabolic Syndrome–Focus on Blood Pressure Outcomes
    Springer Science and Business Media LLC ; 2022
    In:  Current Hypertension Reports Vol. 24, No. 11 ( 2022-11), p. 485-497
    Details
    In: Current Hypertension Reports, Springer Science and Business Media LLC, Vol. 24, No. 11 ( 2022-11), p. 485-497
    Type of Medium: Online Resource
    ISSN: 1522-6417 , 1534-3111
    URL: Article
    DOI: 10.1007/s11906-022-01219-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2094165-1
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  • 3
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    Precision gestational diabetes treatment: a systematic review and meta-analyses
    Springer Science and Business Media LLC ; 2023
    In:  Communications Medicine Vol. 3, No. 1 ( 2023-10-05)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2023-10-05)
    Abstract: Gestational Diabetes Mellitus (GDM) affects approximately 1 in 7 pregnancies globally. It is associated with short- and long-term risks for both mother and baby. Therefore, optimizing treatment to effectively treat the condition has wide-ranging beneficial effects. However, despite the known heterogeneity in GDM, treatment guidelines and approaches are generally standardized. We hypothesized that a precision medicine approach could be a tool for risk-stratification of women to streamline successful GDM management. With the relatively short timeframe available to treat GDM, commencing effective therapy earlier, with more rapid normalization of hyperglycaemia, could have benefits for both mother and fetus. Methods We conducted two systematic reviews, to identify precision markers that may predict effective lifestyle and pharmacological interventions. Results There was a paucity of studies examining precision lifestyle-based interventions for GDM highlighting the pressing need for further research in this area. We found a number of precision markers identified from routine clinical measures that may enable earlier identification of those requiring escalation of pharmacological therapy (to metformin, sulphonylureas or insulin). This included previous history of GDM, Body Mass Index and blood glucose concentrations at diagnosis. Conclusions Clinical measurements at diagnosis could potentially be used as precision markers in the treatment of GDM. Whether there are other sensitive markers that could be identified using more complex individual-level data, such as omics, and if these can feasibly be implemented in clinical practice remains unknown. These will be important to consider in future studies.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00371-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 3096949-9
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  • 4
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    Precision subclassification of type 2 diabetes: a systematic review
    Springer Science and Business Media LLC ; 2023
    In:  Communications Medicine Vol. 3, No. 1 ( 2023-10-05)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2023-10-05)
    Abstract: Heterogeneity in type 2 diabetes presentation and progression suggests that precision medicine interventions could improve clinical outcomes. We undertook a systematic review to determine whether strategies to subclassify type 2 diabetes were associated with high quality evidence, reproducible results and improved outcomes for patients. Methods We searched PubMed and Embase for publications that used ‘simple subclassification’ approaches using simple categorisation of clinical characteristics, or ‘complex subclassification’ approaches which used machine learning or ‘omics approaches in people with established type 2 diabetes. We excluded other diabetes subtypes and those predicting incident type 2 diabetes. We assessed quality, reproducibility and clinical relevance of extracted full-text articles and qualitatively synthesised a summary of subclassification approaches. Results Here we show data from 51 studies that demonstrate many simple stratification approaches, but none have been replicated and many are not associated with meaningful clinical outcomes. Complex stratification was reviewed in 62 studies and produced reproducible subtypes of type 2 diabetes that are associated with outcomes. Both approaches require a higher grade of evidence but support the premise that type 2 diabetes can be subclassified into clinically meaningful subtypes. Conclusion Critical next steps toward clinical implementation are to test whether subtypes exist in more diverse ancestries and whether tailoring interventions to subtypes will improve outcomes.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00360-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 5
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    Integrating protein copy numbers with interaction networks to quantify stoichiometry in clathrin-mediated endocytosis
    Springer Science and Business Media LLC ; 2022
    In:  Scientific Reports Vol. 12, No. 1 ( 2022-03-30)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-03-30)
    Abstract: Proteins that drive processes like clathrin-mediated endocytosis (CME) are expressed at copy numbers within a cell and across cell types varying from hundreds (e.g. auxilin) to millions (e.g. clathrin). These variations contain important information about function, but without integration with the interaction network, they cannot capture how supply and demand for each protein depends on binding to shared and distinct partners. Here we construct the interface-resolved network of 82 proteins involved in CME and establish a metric, a stoichiometric balance ratio (SBR), that quantifies whether each protein in the network has an abundance that is sub- or super-stoichiometric dependent on the global competition for binding. We find that highly abundant proteins (like clathrin) are super-stoichiometric, but that not all super-stoichiometric proteins are highly abundant, across three cell populations (HeLa, fibroblast, and neuronal synaptosomes). Most strikingly, within all cells there is significant competition to bind shared sites on clathrin and the central AP-2 adaptor by other adaptor proteins, resulting in most being in excess supply. Our network and systematic analysis, including response to perturbations of network components, show how competition for shared binding sites results in functionally similar proteins having widely varying stoichiometries, due to variations in both abundance and their unique network of binding partners.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-022-09259-w
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 6
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    Refining the diagnosis of gestational diabetes mellitus: a systematic review and meta-analysis
    Springer Science and Business Media LLC ; 2023
    In:  Communications Medicine Vol. 3, No. 1 ( 2023-12-18)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2023-12-18)
    Abstract: Perinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review and meta-analysis of potential precision markers for GDM. Methods Systematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m 2 ) with offspring macrosomia or large-for-gestational age (LGA). Results A total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies [ n = 28,763]; odds ratio [OR] 2.65; 95% Confidence Interval [CI] 1.91, 3.68), and LGA (10 studies [ n = 20,070]; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers. Conclusions Maternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00393-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 3096949-9
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  • 7
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    Effective interventions in preventing gestational diabetes mellitus: A systematic review and meta-analysis
    Springer Science and Business Media LLC ; 2024
    In:  Communications Medicine Vol. 4, No. 1 ( 2024-04-20)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 4, No. 1 ( 2024-04-20)
    Abstract: Lifestyle choices, metformin, and dietary supplements may prevent GDM, but the effect of intervention characteristics has not been identified. This review evaluated intervention characteristics to inform the implementation of GDM prevention interventions. Methods Ovid, MEDLINE/PubMed, and EMBASE databases were searched. The Template for Intervention Description and Replication (TIDieR) framework was used to examine intervention characteristics ( who, what, when, where, and how ). Subgroup analysis was performed by intervention characteristics. Results 116 studies involving 40,940 participants are included. Group-based physical activity interventions (RR 0.66; 95% CI 0.46, 0.95) reduce the incidence of GDM compared with individual or mixed (individual and group) delivery format (subgroup p -value = 0.04). Physical activity interventions delivered at healthcare facilities reduce the risk of GDM (RR 0.59; 95% CI 0.49, 0.72) compared with home-based interventions (subgroup p -value = 0.03). No other intervention characteristics impact the effectiveness of all other interventions. Conclusions Dietary, physical activity, diet plus physical activity, metformin, and myoinositol interventions reduce the incidence of GDM compared with control interventions. Group and healthcare facility-based physical activity interventions show better effectiveness in preventing GDM than individual and community-based interventions. Other intervention characteristics (e.g. utilization of e-health) don’t impact the effectiveness of lifestyle interventions, and thus, interventions may require consideration of the local context.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-024-00491-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
    detail.hit.zdb_id: 3096949-9
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  • 8
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    A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial
    Springer Science and Business Media LLC ; 2022
    In:  Critical Care Vol. 26, No. 1 ( 2022-08-25)
    Details
    In: Critical Care, Springer Science and Business Media LLC, Vol. 26, No. 1 ( 2022-08-25)
    Abstract: Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%] , − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation.
    Type of Medium: Online Resource
    ISSN: 1364-8535
    URL: Article
    DOI: 10.1186/s13054-022-04120-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2051256-9
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  • 9
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    Impact of individual and environmental factors on dietary or lifestyle interventions to prevent type 2 diabetes development: a systematic review
    Springer Science and Business Media LLC ; 2023
    In:  Communications Medicine Vol. 3, No. 1 ( 2023-10-05)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2023-10-05)
    Abstract: The variability in the effectiveness of type 2 diabetes (T2D) preventive interventions highlights the potential to identify the factors that determine treatment responses and those that would benefit the most from a given intervention. We conducted a systematic review to synthesize the evidence to support whether sociodemographic, clinical, behavioral, and molecular factors modify the efficacy of dietary or lifestyle interventions to prevent T2D. Methods We searched MEDLINE, Embase, and Cochrane databases for studies reporting on the effect of a lifestyle, dietary pattern, or dietary supplement interventions on the incidence of T2D and reporting the results stratified by any effect modifier. We extracted relevant statistical findings and qualitatively synthesized the evidence for each modifier based on the direction of findings reported in available studies. We used the Diabetes Canada Clinical Practice Scale to assess the certainty of the evidence for a given effect modifier. Results The 81 publications that met our criteria for inclusion are from 33 unique trials. The evidence is low to very low to attribute variability in intervention effectiveness to individual characteristics such as age, sex, BMI, race/ethnicity, socioeconomic status, baseline behavioral factors, or genetic predisposition. Conclusions We report evidence, albeit low certainty, that those with poorer health status, particularly those with prediabetes at baseline, tend to benefit more from T2D prevention strategies compared to healthier counterparts. Our synthesis highlights the need for purposefully designed clinical trials to inform whether individual factors influence the success of T2D prevention strategies.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00363-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 10
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    The alternatively-included 11a sequence modifies the effects of Mena on actin cytoskeletal organization and cell behavior
    Springer Science and Business Media LLC ; 2016
    In:  Scientific Reports Vol. 6, No. 1 ( 2016-10-17)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2016-10-17)
    Abstract: During tumor progression, alternative splicing gives rise to different Mena protein isoforms. We analyzed how Mena11a, an isoform enriched in epithelia and epithelial-like cells, affects Mena-dependent regulation of actin dynamics and cell behavior. While other Mena isoforms promote actin polymerization and drive membrane protrusion, we find that Mena11a decreases actin polymerization and growth factor-stimulated membrane protrusion at lamellipodia. Ectopic Mena11a expression slows mesenchymal-like cell motility, while isoform-specific depletion of endogenous Mena11a in epithelial-like tumor cells perturbs cell:cell junctions and increases membrane protrusion and overall cell motility. Mena11a can dampen membrane protrusion and reduce actin polymerization in the absence of other Mena isoforms, indicating that it is not simply an inactive Mena isoform. We identify a phosphorylation site within 11a that is required for some Mena11a-specific functions. RNA-seq data analysis from patient cohorts demonstrates that the difference between mRNAs encoding constitutive Mena sequences and those containing the 11a exon correlates with metastasis in colorectal cancer, suggesting that 11a exon exclusion contributes to invasive phenotypes and leads to poor clinical outcomes.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/srep35298
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2615211-3
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