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Sökning: L773:0024 3019 OR L773:2075 1729

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1.
  • Avram, Vlad Florian, et al. (författare)
  • Improvement of platelet respiration by cell-permeable succinate in diabetic patients treated with statins
  • 2021
  • Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 11:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Diabetes mellitus (DM) is the most severe metabolic disease that reached the level of a global pandemic and is associated with high cardiovascular morbidity. Statins are the first-line lipid- lowering therapy in diabetic patients with or without a history of atherosclerotic disease. Although well tolerated, chronic treatment may result in side effects that lead to treatment interruption. Mitochondrial dysfunction has emerged as a central pathomechanism in DM- and statin-induced side effects. Assessment of mitochondrial respiration in peripheral platelets has been increasingly used as a mirror of organ mitochondrial dysfunction. The present study aimed to assess the: (i) changes in mitochondrial respiration elicited by statins in patients with type 2 DM and (ii) the effects of cell-permeable succinate (NV118) on respiratory parameters in platelets harvested from these patients. No significant changes were found in global mitochondrial respiration of intact platelets isolated from diabetic patients treated with either atorvastatin or rosuvastatin. Similarly, no significant changes in mitochondrial respiration of permeabilized platelets were found between diabetic patients treated with atorvastatin and healthy controls. Acute ex vivo administration of NV118 significantly improved respiration in isolated platelets. These results prompt further research on the role of permeable succinate as a therapeutic alternative for improving mitochondrial function in metabolic pathologies and point to the role of peripheral platelets as a potential biomarker of treatment response.
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2.
  • Barbara Sahlin, K., et al. (författare)
  • Short-term effect of induced alterations in testosterone levels on fasting plasma amino acid levels in healthy young men
  • 2021
  • Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Long term effect of testosterone (T) deficiency impairs metabolism and is associated with muscle degradation and metabolic disease. The association seems to have a bidirectional nature and is not well understood. The present study aims to investigate the early and unidirectional metabolic effect of induced T changes by measuring fasting amino acid (AA) levels in a human model, in which short-term T alterations were induced. We designed a human model of 30 healthy young males with pharmacologically induced T changes, which resulted in three time points for blood collection: (A) baseline, (B) low T (3 weeks post administration of gonadotropin releasing hormone antagonist) and (C) restored T (2 weeks after injection of T undecanoate). The influence of T on AAs was analyzed by spectrophotometry on plasma samples. Levels of 9 out of 23 AAs, of which 7 were essential AAs, were significantly increased at low T and are restored upon T supplementation. Levels of tyrosine and phenylalanine were most strongly associated to T changes. Short-term effect of T changes suggests an increased protein breakdown that is restored upon T supplementation. Fasting AA levels are able to monitor the early metabolic changes induced by the T fluctuations.
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3.
  • Demi, Selina, et al. (författare)
  • Doctor at your fingertips : An exploration of digital visits from stakeholders’ perspectives
  • 2021
  • Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Technological advances and the evolution of mobile technologies enable patients to meet their doctors through their smartphones. While offering the opportunity of digital visits to patients, there are also challenges for this development. The purpose of this study is to enhance the understanding of digital visits, as perceived by experts working in telemedicine companies. To serve this purpose, the authors conducted semi-structured interviews with managers and employees in eight telemedicine companies. The analysis of the empirical data confirmed the importance of digital visits and their efficiency. The potential of digital visits is expected to increase significantly, should they make use of remote devices to transfer real-time data from patients to physicians. In such a case, digital visits are expected to cover approximately 70–75% of medical cases. However, the use of remote devices must be taken with caution and specific conditions need to be taken into account. We encourage researchers to perform research on promising technologies such as artificial intelligence and remote diagnostic devices, which could make more diagnoses and conditions possible to be treated by digital visits. This is even more important in light of the ongoing Covid-19 pandemic.
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4.
  • Jakobsson, Magnus E. (författare)
  • Structure, activity and function of the dual protein lysine and protein n‐terminal methyltransferase mettl13
  • 2021
  • Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 11:11
  • Forskningsöversikt (refereegranskat)abstract
    • METTL13 (also known as eEF1A‐KNMT and FEAT) is a dual methyltransferase reported to target the N‐terminus and Lys55 in the eukaryotic translation elongation factor 1 alpha (eEF1A). METTL13‐mediated methylation of eEF1A has functional consequences related to translation dynamics and include altered rate of global protein synthesis and translation of specific codons. Aberrant regulation of METTL13 has been linked to several types of cancer but the precise mechanisms are not yet fully understood. In this article, the current literature related to the structure, activity, and function of METTL13 is systematically reviewed and put into context. The links between METTL13 and diseases, mainly different types of cancer, are also summarized. Finally, key challenges and opportunities for METTL13 research are pinpointed in a prospective outlook.
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5.
  • Sharma, Siddhant, et al. (författare)
  • Automated exploration of prebiotic chemical reaction space: progress and perspectives
  • 2021
  • Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Prebiotic chemistry often involves the study of complex systems of chemical reactions that form large networks with a large number of diverse species. Such complex systems may have given rise to emergent phenomena that ultimately led to the origin of life on Earth. The environmental conditions and processes involved in this emergence may not be fully recapitulable, making it difficult for experimentalists to study prebiotic systems in laboratory simulations. Computational chemistry offers efficient ways to study such chemical systems and identify the ones most likely to display complex properties associated with life. Here, we review tools and techniques for modelling prebiotic chemical reaction networks and outline possible ways to identify self-replicating features that are central to many origin-of-life models.
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6.
  • Hedman, Christel, et al. (författare)
  • Deprescribing in Palliative Cancer Care
  • 2022
  • Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 12:5
  • Forskningsöversikt (refereegranskat)abstract
    • The aim of palliative care is to maintain as high a quality of life (QoL) as possible despite a life-threatening illness. Thus, the prescribed medications need to be evaluated and the benefit of each treatment must be weighed against potential side effects. Medications that contribute to symptom relief and maintained QoL should be prioritized. However, studies have shown that treatment with preventive drugs that may not benefit the patient in end-of-life is generally deprescribed very late in the disease trajectory of cancer patients. Yet, knowing how and when to deprescribe drugs can be difficult. In addition, some drugs, such as beta-blockers, proton pump inhibitors, anti-depressants and cortisone need to be scaled down slowly to avoid troublesome withdrawal symptoms. In contrast, other medicines, such as statins, antihypertensives and vitamins, can be discontinued directly. The aim of this review is to give some advice according to when and how to deprescribe medications in palliative cancer care according to current evidence and clinical praxis. The review includes antihypertensive drugs, statins, anti-coagulants, aspirin, anti-diabetics, proton pump inhibitors, histamin-2-blockers, bisphosphonates denosumab, urologicals, anti-depressants, cortisone, thyroxin and vitamins.
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7.
  • Jacobs, Rita, et al. (författare)
  • Fluid Management, Intra-Abdominal Hypertension and the Abdominal Compartment Syndrome : A Narrative Review
  • 2022
  • Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 12:9
  • Forskningsöversikt (refereegranskat)abstract
    • Background: General pathophysiological mechanisms regarding associations between fluid administration and intra-abdominal hypertension (IAH) are evident, but specific effects of type, amount, and timing of fluids are less clear. Objectives: This review aims to summarize current knowledge on associations between fluid administration and intra-abdominal pressure (IAP) and fluid management in patients at risk of intra-abdominal hypertension and abdominal compartment syndrome (ACS). Methods: We performed a structured literature search from 1950 until May 2021 to identify evidence of associations between fluid management and intra-abdominal pressure not limited to any specific study or patient population. Findings were summarized based on the following information: general concepts of fluid management, physiology of fluid movement in patients with intra-abdominal hypertension, and data on associations between fluid administration and IAH. Results: We identified three randomized controlled trials (RCTs), 38 prospective observational studies, 29 retrospective studies, 18 case reports in adults, two observational studies and 10 case reports in children, and three animal studies that addressed associations between fluid administration and IAH. Associations between fluid resuscitation and IAH were confirmed in most studies. Fluid resuscitation contributes to the development of IAH. However, patients with IAH receive more fluids to manage the effect of IAH on other organ systems, thereby causing a vicious cycle. Timing and approach to de-resuscitation are of utmost importance, but clear indicators to guide this decision-making process are lacking. In selected cases, only surgical decompression of the abdomen can stop deterioration and prevent further morbidity and mortality. Conclusions: Current evidence confirms an association between fluid resuscitation and secondary IAH, but optimal fluid management strategies for patients with IAH remain controversial.
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8.
  • Luo, Cui, et al. (författare)
  • Identification and Current Palaeobiological Understanding of “Keratosa”-Type Nonspicular Demosponge Fossils in Carbonates : With a New Example from the Lowermost Triassic, Armenia
  • 2022
  • Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 12:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Structures similar to fossilized nonspicular demosponges have been reported in carbonates throughout the Phanerozoic and recently in rocks dating back to 890 Ma ago. Interpretation of these records is increasingly influential to our understanding of metazoans in multiple aspects, including their early evolution, the ecology in fossil reefs, and recovery after mass extinction events. Here, we propose six identification criteria of “Keratosa”-type nonspicular demosponge fossils based on the well-established taphonomical models and their biological characteristics. Besides, sponge fossils of this kind from the lowermost Triassic of Chanakhchi (Armenia) are described with a 3-D reconstruction to exemplify the application of these criteria in recognition of such organisms. Subsequently, the state-of-the-art understanding of the taxonomy and evolution of these fossil sponges, a previously poorly addressed topic, is summarized. The morphology of the Triassic Chanakhchi fossils indicates an affinity with verongimorphs, a group that may have evolved by Cambrian Age 3. Other than that, further efforts are encouraged to forge quantitative criteria based on the here proposed descriptive version and to explore the taxonomic diversity and evolutionary details of these fossil nonspicular demosponges.
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9.
  • Pla, Indira, et al. (författare)
  • Proteomic Alterations in Follicular Fluid of Human Small Antral Follicles Collected from Polycystic Ovaries—A Pilot Study
  • 2022
  • Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 12:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Polycystic ovaries (PCO) contain antral follicles that arrest growing around 3–11 mm in diameter, perturbing the dominant follicle’s selection and the subsequent ovulatory process. Proteomic alterations of PCO follicular fluid (FF) (i.e., microenvironment in which the oocyte develops until ovulation) have been studied from large follicles in connection with oocyte pickup during ovarian stimulation. The present study aimed to detect proteomic alterations in FF from unstimulated human small antral follicles (hSAF) obtained from PCO. After performing deep-sequencing label-free proteomics on 10 PCO and 10 non-PCO FF samples from unstimulated hSAF (4.6–9.8 mm), 1436 proteins were identified, of which 115 were dysregulated in PCO FF samples. Pathways and processes related to the immune system, inflammation, and oxidative stress appeared to be upregulated in PCO, while extracellular matrix receptors interactions, the collagens-containing extracellular matrix, and the regulation of signaling were downregulated. The secreted proteins SFRP1, THBS4, and C1QC significantly decreased their expression in PCO FF, and this downregulation was suggested to affect future oocyte competence. In conclusion, our study revealed, for the first time, evidence of proteomic alterations occurring in the FF of PCO hSAF that may be related to the dysfunction of follicular growth and subsequent oocyte competence.
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10.
  • Tsochantaridis, Ilias, et al. (författare)
  • The Concept of Cancer Stem Cells : Elaborating on ALDH1B1 as an Emerging Marker of Cancer Progression
  • 2023
  • Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 13:1
  • Forskningsöversikt (refereegranskat)abstract
    • Cancer is a multifactorial, complex disease exhibiting extraordinary phenotypic plasticity and diversity. One of the greatest challenges in cancer treatment is intratumoral heterogeneity, which obstructs the efficient eradication of the tumor. Tumor heterogeneity is often associated with the presence of cancer stem cells (CSCs), a cancer cell sub-population possessing a panel of stem-like properties, such as a self-renewal ability and multipotency potential. CSCs are associated with enhanced chemoresistance due to the enhanced efflux of chemotherapeutic agents and the existence of powerful antioxidant and DNA damage repair mechanisms. The distinctive characteristics of CSCs make them ideal targets for clinical therapeutic approaches, and the identification of efficient and specific CSCs biomarkers is of utmost importance. Aldehyde dehydrogenases (ALDHs) comprise a wide superfamily of metabolic enzymes that, over the last years, have gained increasing attention due to their association with stem-related features in a wide panel of hematopoietic malignancies and solid cancers. Aldehyde dehydrogenase 1B1 (ALDH1B1) is an isoform that has been characterized as a marker of colon cancer progression, while various studies suggest its importance in additional malignancies. Here, we review the basic concepts related to CSCs and discuss the potential role of ALDH1B1 in cancer development and its contribution to the CSC phenotype.
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11.
  • Wang, Wei, et al. (författare)
  • Simulated Microgravity Modulates Focal Adhesion Gene Expression in Human Neural Stem Progenitor Cells
  • 2022
  • Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 12:11
  • Tidskriftsartikel (refereegranskat)abstract
    • We analyzed the morphology and the transcriptomic changes of human neural stem progenitor cells (hNSPCs) grown on laminin in adherent culture conditions and subjected to simulated microgravity for different times in a random positioning machine apparatus. Low-cell-density cultures exposed to simulated microgravity for 24 h showed cell aggregate formation and significant modulation of several genes involved in focal adhesion, cytoskeleton regulation, and cell cycle control. These effects were much more limited in hNSPCs cultured at high density in the same conditions. We also found that some of the genes modulated upon exposure to simulated microgravity showed similar changes in hNSPCs grown without laminin in non-adherent culture conditions under normal gravity. These results suggest that reduced gravity counteracts the interactions of cells with the extracellular matrix, inducing morphological and transcriptional changes that can be observed in low-density cultures.
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12.
  • Aspholm, Emelie E., et al. (författare)
  • Keeping α-synuclein at bay: A more active role of molecular chaperones in preventing mitochondrial interactions and transition to pathological states?
  • 2020
  • Ingår i: Life. - : MDPI AG. - 2075-1729. ; 10:11, s. 1-19
  • Tidskriftsartikel (refereegranskat)abstract
    • The property of molecular chaperones to dissolve protein aggregates of Parkinson-related α-synuclein has been known for some time. Recent findings point to an even more active role of molecular chaperones preventing the transformation of α-synuclein into pathological states subsequently leading to the formation of Lewy bodies, intracellular inclusions containing protein aggregates as well as broken organelles found in the brains of Parkinson’s patients. In parallel, a short motif around Tyr39 was identified as being crucial for the aggregation of α-synuclein. Interestingly, this region is also one of the main segments in contact with a diverse pool of molecular chaperones. Further, it could be shown that the inhibition of the chaperone:α-synuclein interaction leads to a binding of α-synuclein to mitochondria, which could also be shown to lead to mitochondrial membrane disruption as well as the possible proteolytic processing of α-synuclein by mitochondrial proteases. Here, we will review the current knowledge on the role of molecular chaperones in the regulation of physiological functions as well as the direct consequences of impairing these interactions—i.e., leading to enhanced mitochondrial interaction and consequential mitochondrial breakage, which might mark the initial stages of the structural transition of α-synuclein towards its pathological states. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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13.
  • Blyth, Colette, et al. (författare)
  • Genomic, Habitat, and Leaf Shape Analyses Reveal a Possible Cryptic Species and Vulnerability to Climate Change in a Threatened Daisy
  • 2021
  • Ingår i: Life. - : MDPI. - 2075-1729. ; 11:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Olearia pannosa is a plant species listed as vulnerable in Australia. Two subspecies are currently recognised (O. pannosa subsp. pannosa (silver daisy) and O. pannosa subsp. cardiophylla (velvet daisy)), which have overlapping ranges but distinct leaf shape. Remnant populations face threats from habitat fragmentation and climate change. We analysed range-wide genomic data and leaf shape variation to assess population diversity and divergence and to inform conservation management strategies. We detected three distinct genetic groupings and a likely cryptic species. Samples identified as O. pannosa subsp. cardiophylla from the Flinders Ranges in South Australia were genetically distinct from all other samples and likely form a separate, range-restricted species. Remaining samples formed two genetic clusters, which aligned with leaf shape differences but not fully with current subspecies classifications. Levels of genetic diversity and inbreeding differed between the three genetic groups, suggesting each requires a separate management strategy. Additionally, we tested for associations between genetic and environmental variation and carried out habitat suitability modelling for O. pannosa subsp. pannosa populations. We found mean annual maximum temperature explained a significant proportion of genomic variance. Habitat suitability modelling identified mean summer maximum temperature, precipitation seasonality and mean annual rainfall as constraints on the distribution of O. pannosa subsp. pannosa, highlighting increasing aridity as a threat for populations located near suitability thresholds. Our results suggest maximum temperature is an important agent of selection on O. pannosa subsp. pannosa and should be considered in conservation strategies. We recommend taxonomic revision of O. pannosa and provide conservation management recommendations.
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14.
  • Camartin, C, et al. (författare)
  • Palliative Sedation-The Last Resort in Case of Difficult Symptom Control: A Narrative Review and Experiences from Palliative Care in Switzerland
  • 2022
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 12:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Palliative sedation can be considered as “the last resort” in order to treat unbearable, refractory symptoms or suffering in end-of-life patients. The aim is symptom relief and not to induce death as in the case of euthanasia. The treatment might be one of the most challenging therapeutic options in the field of palliative care, involving both ethical and practical issues. Still, studies have shown that it is a safe and valuable treatment and in general does not shorten the life of the patient. Since patients in Switzerland have the legal option of assisted suicide, palliative sedation is an alternative that has become increasingly important. The use of palliative sedation was reported in 17.5% of all patients admitted to palliative care in Switzerland, making the country of those with the highest use of this treatment. The aim of this narrative review is to discuss ethical and practical issues in palliative sedation, with specific focus on experiences from Switzerland. Indications, ethical considerations, drugs of choice and duration are discussed. Decision making should be based on solid guidelines. When used correctly, palliative sedation is an important and useful tool in palliative care in order to provide good symptom relief.
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15.
  • Choi, Seong Il, et al. (författare)
  • A Conceptual Framework for Integrating Cellular Protein Folding, Misfolding and Aggregation
  • 2021
  • Ingår i: Life. - : MDPI AG. - 2075-1729. ; 11:7
  • Forskningsöversikt (refereegranskat)abstract
    •  How proteins properly fold and maintain solubility at the risk of misfolding and aggregation in the cellular environments still remains largely unknown. Aggregation has been traditionally treated as a consequence of protein folding (or misfolding). Notably, however, aggregation can be generally inhibited by affecting the intermolecular interactions leading to aggregation, independently of protein folding and conformation. We here point out that rigorous distinction between protein folding and aggregation as two independent processes is necessary to reconcile and underlie all observations regarding the combined cellular protein folding and aggregation. So far, the direct attractive interactions (e.g., hydrophobic interactions) between cellular macromolecules including chaperones and interacting polypeptides have been widely believed to mainly stabilize polypeptides against aggregation. However, the intermolecular repulsions by large excluded volume and surface charges of cellular macromolecules can play a key role in stabilizing their physically connected polypeptides against aggregation, irrespective of the connection types and induced conformational changes, underlying the generic intrinsic chaperone activity of cellular macromolecules. Such rigorous distinction and intermolecular repulsive force-driven aggregation inhibition by cellular macromolecules could give new insights into understanding the complex cellular protein landscapes that remain uncharted.
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16.
  • Frankling, MH, et al. (författare)
  • Successful Strategies and Areas of Improvement-Lessons Learned from Design and Conduction of a Randomized Placebo-Controlled Trial in Palliative Care, 'Palliative-D'
  • 2021
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Clinical trials in palliative care are challenging to design and conduct. Burden on patients should be minimized, while gatekeeping by professionals and next-of kin needs to be avoided. Clinical deterioration due to disease progression affects attrition unrelated to intervention, and different care settings complicate comparisons and reduce the generalizability of the results. The aim of this review is to provide advice for colleagues planning to perform clinical trials in palliative care based on our own experiences from performing the Palliative-D study and by a thorough literature review on this topic. The Palliative-D study was a double-blind trial with 244 randomized patients comparing the effect of vitamin D3 to placebo in patients with advanced or metastatic cancer in the palliative phase of their disease trajectory who were enrolled in specialized palliative home care teams. Endpoints were opioid and antibiotic use, fatigue, and QoL. Recruitment was successful, but attrition rates were higher than expected, and we did not reach targeted power. For the 150 patients who completed the study, the completeness of the data was exceptionally high. Rather than patient reported pain, we choose the difference in the mean change in opioid dose between groups after twelve weeks compared to baseline as the primary endpoint. In this paper we discuss challenges in palliative care research based on lessons learned from the “Palliative-D” trial regarding successful strategies as well as areas for improvement.
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17.
  • Godman, B, et al. (författare)
  • Strategies to Improve Antimicrobial Utilization with a Special Focus on Developing Countries
  • 2021
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 11:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Antimicrobial resistance (AMR) is a high priority across countries as it increases morbidity, mortality and costs. Concerns with AMR have resulted in multiple initiatives internationally, nationally and regionally to enhance appropriate antibiotic utilization across sectors to reduce AMR, with the overuse of antibiotics exacerbated by the COVID-19 pandemic. Effectively tackling AMR is crucial for all countries. Principally a narrative review of ongoing activities across sectors was undertaken to improve antimicrobial use and address issues with vaccines including COVID-19. Point prevalence surveys have been successful in hospitals to identify areas for quality improvement programs, principally centering on antimicrobial stewardship programs. These include reducing prolonged antibiotic use to prevent surgical site infections. Multiple activities centering on education have been successful in reducing inappropriate prescribing and dispensing of antimicrobials in ambulatory care for essentially viral infections such as acute respiratory infections. It is imperative to develop new quality indicators for ambulatory care given current concerns, and instigate programs with clear public health messaging to reduce misinformation, essential for pandemics. Regular access to effective treatments is needed to reduce resistance to treatments for HIV, malaria and tuberculosis. Key stakeholder groups can instigate multiple initiatives to reduce AMR. These need to be followed up.
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18.
  • Goodrose-Flores, C, et al. (författare)
  • Weight Loss in Advanced Cancer: Sex Differences in Health-Related Quality of Life and Body Image
  • 2022
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Weight maintenance is a priority in cancer care, but weight loss is common and a serious concern. This study explores if there are sex differences in the perception of weight loss and its association to health-related quality of life (HRQoL) and body image. Cancer patients admitted to Advanced Medical Home Care were recruited to answer a questionnaire, including characteristics, the HRQoL-questionnaire RAND-36, and a short form of the Body Image Scale. Linear regression analyses stratified by sex and adjusted for age were performed to examine associations between percent weight loss and separate domains of HRQoL and body image score in men and women separately. In total, 99 participants were enrolled, of which 80 had lost weight since diagnosis. In men, an inverse association between weight loss and the HRQoL-domain physical functioning, β = −1.34 (95%CI: −2.44, −0.24), and a positive association with body image distress, β = 0.22 (95%CI: 0.07, 0.37), were found. In women, weight loss was associated with improvement in the HRQoL-domain role limitations due to physical health, β = 2.02 (95%CI: 0.63, 3.41). Following a cancer diagnosis, men appear to experience weight loss more negatively than women do. Recognizing different perceptions of weight loss may be of importance in clinical practice.
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19.
  • Johansson, Markus, et al. (författare)
  • Multi-Omics Characterization of a Human Stem Cell-Based Model of Cardiac Hypertrophy
  • 2022
  • Ingår i: Life-Basel. - : MDPI AG. - 2075-1729. ; 12:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiac hypertrophy is an important and independent risk factor for the development of cardiac myopathy that may lead to heart failure. The mechanisms underlying the development of cardiac hypertrophy are yet not well understood. To increase the knowledge about mechanisms and regulatory pathways involved in the progression of cardiac hypertrophy, we have developed a human induced pluripotent stem cell (hiPSC)-based in vitro model of cardiac hypertrophy and performed extensive characterization using a multi-omics approach. In a series of experiments, hiPSC-derived cardiomyocytes were stimulated with Endothelin-1 for 8, 24, 48, and 72 h, and their transcriptome and secreted proteome were analyzed. The transcriptomic data show many enriched canonical pathways related to cardiac hypertrophy already at the earliest time point, e.g., cardiac hypertrophy signaling. An integrated transcriptome-secretome analysis enabled the identification of multimodal biomarkers that may prove highly relevant for monitoring early cardiac hypertrophy progression. Taken together, the results from this study demonstrate that our in vitro model displays a hypertrophic response on both transcriptomic- and secreted-proteomic levels. The results also shed novel insights into the underlying mechanisms of cardiac hypertrophy, and novel putative early cardiac hypertrophy biomarkers have been identified that warrant further investigation to assess their potential clinical relevance.
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20.
  • Kalmar, Peter Janos, et al. (författare)
  • Comparing endovascular treatment methods in acute ischemic stroke Due to tandem occlusion focusing on clinical aspects
  • 2021
  • Ingår i: Life. - : MDPI. - 2075-1729. ; 11:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Acute ischemic strokes (AIS) due to tandem occlusion (TO) of intracranial anterior large vessel and concomitant extracranial internal carotid artery (EICA) are represent in 15-20% of all ischemic strokes. The endovascular treatment (EVT) strategy for those patients is still unclear. Although the intracranial mechanical thrombectomy (MT) is considered as a standard treatment approach, the EICA lesion stent necessity remains a matter of debate. We sought to assess the efficacy and safety of EVT in tandem lesions, particularly the EICA stenting management.Methods: We retrospectively analyzed all patients with anterior circulation stroke associated with EICA lesion and receiving EVT in the three participated stroke centers between November 2017 and December 2020. Patients' data were collected from our prospective stroke registry (STAY ALIVE). Patients enrolled in our study were divided into two groups depending on whether acute carotid stenting (ACS) or balloon angioplasty only (BAO) technique was used. Our primary outcome was the 90-day functional outcome assessed by modified Rankin scale (mRS). Mortality at 90 days and symptomatic intracranial hemorrhage (sICH) were considered as secondary outcomes.Results: A total of 101 patients (age: 67 ± 10 years, 38.6% female) were enrolled in our study, including 29 (28.3%) BAO cases, and 72 (71.3%) patients treated with ACS. Patients in the BAO group were slightly older (70 ± 9 years vs. 66 ± 10 years, p = 0.054), and had higher prevalence of comorbidities such as hypertension (100.0% vs. 59.4%, p < 0.001). There was no significant difference in favorable outcomes (51.7% vs. 54.4%, p = 0.808) between the groups. However, we observed a trend towards higher rates of sICH (8.3% vs. 3.4%, p = 0.382) and 90-day mortality (23.5% vs. 13.8%, p = 0.278) with significantly higher frequency of distal embolization (39.1% vs. 17.9%, p = 0.043) in patients with ACS. In the overall population age (p = 0.013), atrial fibrillation (AF) (p = 0.008), National Institutes of Health Stroke Scale (NIHSS) baseline (p = 0.029), and successful recanalization (p = 0.023) were associated with favorable outcome.Conclusion: Endovascular approach of EICA in addition to MT was safe and effective in tandem occlusion of anterior circulation. Furthermore, our results suggest that balloon angioplasty technique without acute stenting shows a comparable favorable outcome rate to ACS with moderately less hemorrhagic events and mortality rates.
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21.
  • Kay, Catherine M, et al. (författare)
  • Evolution of Microbial “Streamer” Growths in an Acidic, Metal-Contaminated Stream Draining an Abandoned Underground Copper Mine
  • 2013
  • Ingår i: Life. - : MDPI AG. - 2075-1729. ; 3:1, s. 189-210
  • Tidskriftsartikel (refereegranskat)abstract
    • A nine year study was carried out on the evolution of macroscopic “acid streamer” growths in acidic, metal-rich mine water from the point of construction of a new channel to drain an abandoned underground copper mine. The new channel became rapidly colonized by acidophilic bacteria: two species of autotrophic iron-oxidizers (Acidithiobacillus ferrivorans and “Ferrovum myxofaciens”) and a heterotrophic iron-oxidizer (a novel genus/species with the proposed name “Acidithrix ferrooxidans”). The same bacteria dominated the acid streamer communities for the entire nine year period, with the autotrophic species accounting for ~80% of the micro-organisms in the streamer growths (as determined by terminal restriction enzyme fragment length polymorphism (T-RFLP) analysis). Biodiversity of the acid streamers became somewhat greater in time, and included species of heterotrophic acidophiles that reduce ferric iron (Acidiphilium, Acidobacterium, Acidocella and gammaproteobacterium WJ2) and other autotrophic iron-oxidizers (Acidithiobacillus ferrooxidans and Leptospirillum ferrooxidans). The diversity of archaea in the acid streamers was far more limited; relatively few clones were obtained, all of which were very distantly related to known species of euryarchaeotes. Some differences were apparent between the acid streamer community and planktonic-phase bacteria. This study has provided unique insights into the evolution of an extremophilic microbial community, and identified several novel species of acidophilic prokaryotes.
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22.
  • Konatham, Samuel, et al. (författare)
  • The Impact of the Spectral Radiation Environment on the Maximum Absorption Wavelengths of Human Vision and Other Species
  • 2021
  • Ingår i: Life. - : MDPI. - 2075-1729. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Since the earliest development of the eye (and vision) around 530 million years ago (Mya), it has evolved, adapting to different habitats, species, and changing environmental conditions on Earth. We argue that a radiation environment determined by the atmosphere played a determining role in the evolution of vision, specifically on the human eye, which has three vision regimes (photopic-, scotopic-, and mesopic vision) for different illumination conditions. An analysis of the irradiance spectra, reaching the shallow ocean depths, revealed that the available radiation could have determined the bandwidth of the precursor to vision systems, including human vision. We used the radiative transfer model to test the existing hypotheses on human vision. We argue that, once on the surface, the human photopic (daytime) and scotopic (night-time) vision followed different evolutionary directions, maximum total energy, and optimum information, respectively. Our analysis also suggests that solar radiation reflected from the moon had little or no influence on the evolution of scotopic vision. Our results indicate that, apart from human vision, the vision of only a few birds, rodents, and deep-sea fish are strongly correlated to the available radiation within their respective habitats.
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23.
  • Kovalevska, L, et al. (författare)
  • A Comparative Study on the Viability of Normal and Cancerous Cells upon Irradiation with a Steady Beam of THz Rays
  • 2022
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 12:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Terahertz (THz) electromagnetic radiation is commonly used in astronomy, security screening, imaging, and biomedicine, among other applications. Such approach has raised the question of the influence of THz irradiation on biological objects, especially the human body. However, the results obtained to date are quite controversial. Therefore, we performed a comparative study on the viability of normal cells and cancer cells upon irradiation with a steady beam of THz rays. We used human peripheral blood mononuclear cells and cancer cell lines. Primary human mononuclear blood cells (monocytes, and B-, and T-cells) showed an increased death rate, determined by cell counting and fluorescence microscopy, upon 0.14 THz irradiation. The effect of THz radiation was different among malignant cells of B- and T-cell origin (Ramos and Jurkat cells) and epithelial cancer cells (MCF7 and LNCaP). This was demonstrated by cell counting and by the alamarBlue assay. In conclusion, THz radiation can result in the death of human primary and malignant cells. However, the mechanism of this phenomenon is largely unknown. Hence, more work should be done to shed some light on the mechanism of action of THz irradiation in living organisms to enhance technologic developments.
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24.
  • Lin, Chun-Yu, et al. (författare)
  • Lipopolysaccharide-Induced Nitric Oxide and Prostaglandin E2 Production Is Inhibited by Tellimagrandin II in Mouse and Human Macrophages
  • 2021
  • Ingår i: Life. - : MDPI. - 2075-1729. ; 11:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Sepsis develops from a serious microbial infection that causes the immune system to go into overdrive. The major microorganisms that induce sepsis are Gram-negative bacteria with lipopolysaccharide (LPS) in their cell walls. Nitric oxide (NO) and cyclooxygenase-2 (COX-2) are the key factors involved in the LPS-induced pro-inflammatory process. This study aimed to evaluate the effects of polyphenol Tellimagrandin II (TGII) on anti-inflammatory activity and its underlying basic mechanism in murine macrophage cell line RAW 264.7 and human monocyte-derived macrophages. Macrophages with more than 90% cell viability were found in the cytotoxicity assay under 50 mu M TGII. Pre- or post-treatment with TGII significantly reduced LPS-induced inducible nitric oxide synthase (NOS2) protein and mRNA expression, reducing LPS-induced COX-2 protein. Downstream of NOS2 and COX-2, NO and prostaglandin E2 (PGE2) were significantly inhibited by TGII. Upstream of NOS2 and COX-2, phospho-p65, c-fos and phospho-c-jun were also reduced after pre-treatment with TGII. Mitogen-activated protein kinases (MAPKs) are also critical to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) stimulation, and phospho-p38 expression was found to have been blocked by TGII. TGII efficiently reduces LPS-induced NO production and its upstream regulatory factors, suggesting that TGII may be a potential therapeutic agent for sepsis and other inflammatory diseases.
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25.
  • Lopez-Dominguez, R, et al. (författare)
  • Transcription Factor Activity Inference in Systemic Lupus Erythematosus
  • 2021
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 11:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with diverse clinical manifestations. Although most of the SLE-associated loci are located in regulatory regions, there is a lack of global information about transcription factor (TFs) activities, the mode of regulation of the TFs, or the cell or sample-specific regulatory circuits. The aim of this work is to decipher TFs implicated in SLE. Methods: In order to decipher regulatory mechanisms in SLE, we have inferred TF activities from transcriptomic data for almost all human TFs, defined clusters of SLE patients based on the estimated TF activities and analyzed the differential activity patterns among SLE and healthy samples in two different cohorts. The Transcription Factor activity matrix was used to stratify SLE patients and define sets of TFs with statistically significant differential activity among the disease and control samples. Results: TF activities were able to identify two main subgroups of patients characterized by distinct neutrophil-to-lymphocyte ratio (NLR), with consistent patterns in two independent datasets—one from pediatric patients and other from adults. Furthermore, after contrasting all subgroups of patients and controls, we obtained a significant and robust list of 14 TFs implicated in the dysregulation of SLE by different mechanisms and pathways. Among them, well-known regulators of SLE, such as STAT or IRF, were found, but others suggest new pathways that might have important roles in SLE. Conclusions: These results provide a foundation to comprehend the regulatory mechanism underlying SLE and the established regulatory factors behind SLE heterogeneity that could be potential therapeutic targets.
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26.
  • Lundin, Daniel, 1965-, et al. (författare)
  • The Origin and Evolution of Ribonucleotide Reduction
  • 2015
  • Ingår i: Life. - : MDPI. - 2075-1729. ; 5:1, s. 604-636
  • Tidskriftsartikel (refereegranskat)abstract
    • Ribonucleotide reduction is the only pathway for de novo synthesis of deoxyribonucleotides in extant organisms. This chemically demanding reaction, which proceeds via a carbon-centered free radical, is catalyzed by ribonucleotide reductase (RNR). The mechanism has been deemed unlikely to be catalyzed by a ribozyme, creating an enigma regarding how the building blocks for DNA were synthesized at the transition from RNA- to DNA-encoded genomes. While it is entirely possible that a different pathway was later replaced with the modern mechanism, here we explore the evolutionary and biochemical limits for an origin of the mechanism in the RNA + protein world and suggest a model for a prototypical ribonucleotide reductase (protoRNR). From the protoRNR evolved the ancestor to modern RNRs, the urRNR, which diversified into the modern three classes. Since the initial radical generation differs between the three modern classes, it is difficult to establish how it was generated in the urRNR. Here we suggest a model that is similar to the B12-dependent mechanism in modern class II RNRs.
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27.
  • Magnuson, Ann (författare)
  • Heterocyst Thylakoid Bioenergetics
  • 2019
  • Ingår i: Life. - : MDPI. - 2075-1729. ; 9:1
  • Forskningsöversikt (refereegranskat)abstract
    • Heterocysts are specialized cells that differentiate in the filaments of heterocystous cyanobacteria. Their role is to maintain a microoxic environment for the nitrogenase enzyme during diazotrophic growth. The lack of photosynthetic water oxidation in the heterocyst puts special constraints on the energetics for nitrogen fixation, and the electron transport pathways of heterocyst thylakoids are slightly different from those in vegetative cells. During recent years, there has been a growing interest in utilizing heterocysts as cell factories for the production of fuels and other chemical commodities. Optimization of these production systems requires some consideration of the bioenergetics behind nitrogen fixation. In this overview, we emphasize the role of photosynthetic electron transport in providing ATP and reductants to the nitrogenase enzyme, and provide some examples where heterocysts have been used as production facilities.
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28.
  • Marchand, A, et al. (författare)
  • Use of Quantitative Dried Blood Spots to Evaluate the Post-Vaccination Level of Neutralizing Antibodies against SARS-CoV-2
  • 2021
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • To combat the COVID-19 pandemic, vaccines against SARS-CoV-2 are now given to protect populations worldwide. The level of neutralizing antibodies following the vaccination will evolve with time and vary between individuals. Immunoassays quantifying immunoglobulins against the viral spike (S) protein in serum/plasma have been developed, but the need for venous blood samples could limit the frequency and scale of control in populations. The use of a quantitative dried blood spot (DBS) that can be self-collected would simplify this monitoring. The objective of this study was to determine whether a quantitative DBS device (Capitainer qDBS 10 µL) could be used in combination with an Elecsys anti-SARS-CoV-2 S immunoassay from Roche to follow the development and persistence of anti-S antibodies. This objective was carried out through two clinical studies. The first study investigated 14 volunteers who received two doses of the Comirnaty (Pfizer) vaccine. The levels of anti-S antibodies and the progression over time post-vaccination were studied for three months. The level of produced antibodies varied between subjects, but a similar trend was observed. The anti-S antibodies were highly stimulated by the second dose (×100) and peaked two weeks later. The antibody levels subsequently decreased and three months later were down to 65%. DBS proved to be sufficiently sensitive for use in evaluating the immune status against SARS-CoV-2 over a prolonged time. The second cohort was composed of 200 random patients from a clinical chemistry department in Stockholm. In this cohort, we had no information on previous COVID-19 infections or vaccination. Nevertheless, 87% of the subjects had anti-S immunoglobulins over 0.8 U/mL, and the bias between plasma and DBS proved to be variable, as was also seen in the first vaccination study.
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29.
  • Nikolova, M, et al. (författare)
  • Coupling miR/isomiR and mRNA Expression Signatures Unveils New Molecular Layers of Endometrial Receptivity
  • 2021
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Embryo implantation depends on endometrial receptivity (ER). To achieve ER, the preparation of the uterine lining requires controlled priming by ovarian hormones and the expression of numerous genes in the endometrial tissue. microRNAs (miRs) have emerged as critical genetic regulators of ER in fertility and of the diseases that are associated with infertility. With the rapid development of next-generation sequencing technologies, it has become clear that miR genes can produce canonical miRs and variants—isomiRs. Here, we describe miR/isomiR expression dynamics across the four time points of natural chorionic gonadotropin (hCG)-administered cycles. Sequencing of the small RNAs (sRNA-seq) revealed that the most significant expression changes during the transition from the pre-receptive to the receptive phase occurred in the isomiR families of miR-125a, miR-125b, miR-10a, miR-10b, miR-449c, miR-92a, miR-92b, and miR-99a. Pairing the analysis of the differentially expressed (DE) miRs/isomiRs and their predicted DE mRNA targets uncovered 280 negatively correlating pairs. In the receptive endometrium, the 5′3′-isomiRs of miR-449c, which were among the most highly up-regulated isomiRs, showed a negative correlation with their target, transcription factor (TF) MYCN, which was down-regulated. Joint analysis of the miR/isomiR and TF expression identified several regulatory interactions. Based on these data, a regulatory TF-miR/isomiR gene-target circuit including let7g-5p and miR-345; the isomiR families of miR-10a, miR-10b, miR-92a, and miR-449c; and MYCN and TWIST1 was proposed to play a key role in the establishment of ER. Our work uncovers the complexity and dynamics of the endometrial isomiRs that can act cooperatively with miRs to control the functionally important genes that are critical to ER. Further studies of miR/isomiR expression patterns that are paired with those of their target mRNAs may provide a more in-depth picture of the endometrial pathologies that are associated with implantation failure.
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30.
  • Otreba, Michal, et al. (författare)
  • A small molecule targeting human MEK1/2 enhances ERK and p38 phosphorylation under oxidative stress or with phenothiazines.
  • 2021
  • Ingår i: Life (Basel). - : MDPI AG. - 2075-1729. ; 11:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Small molecules are routinely used to inhibit protein kinases, but modulators capable of enhancing kinase activity are rare. We have previously shown that the small molecule INR119, designed as an inhibitor of MEK1/2, will enhance the activity of its fission yeast homologue, Wis1, under oxidative stress. To investigate the generality of these findings, we now study the effect of INR119 in human cells under similar conditions. Cells of the established breast cancer line MCF-7 were exposed to H2O2 or phenothiazines, alone or combined with INR119. In line with the previous results in fission yeast, the phosphorylation of the MAPKs ERK and p38 increased substantially more with the combination treatment than by H2O2 or phenothiazines, whereas INR119 alone did not affect phosphorylation. We also measured the mRNA levels of TP53 and BAX, known to be affected by ERK and p38 activity. Similarly, the combination of INR119 and phenothiazines increased both mRNAs to higher levels than for phenothiazines alone. In conclusion, the mechanism of action of INR119 on its target protein kinase may be conserved between yeast and humans.
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31.
  • Pattanaik, Bagmi, et al. (författare)
  • Terpenoids and their biosynthesis in cyanobacteria.
  • 2015
  • Ingår i: Life. - : MDPI AG. - 2075-1729. ; 5:1, s. 269-93
  • Tidskriftsartikel (refereegranskat)abstract
    • Terpenoids, or isoprenoids, are a family of compounds with great structural diversity which are essential for all living organisms. In cyanobacteria, they are synthesized from the methylerythritol-phosphate (MEP) pathway, using glyceraldehyde 3-phosphate and pyruvate produced by photosynthesis as substrates. The products of the MEP pathway are the isomeric five-carbon compounds isopentenyl diphosphate and dimethylallyl diphosphate, which in turn form the basic building blocks for formation of all terpenoids. Many terpenoid compounds have useful properties and are of interest in the fields of pharmaceuticals and nutrition, and even potentially as future biofuels. The MEP pathway, its function and regulation, and the subsequent formation of terpenoids have not been fully elucidated in cyanobacteria, despite its relevance for biotechnological applications. In this review, we summarize the present knowledge about cyanobacterial terpenoid biosynthesis, both regarding the native metabolism and regarding metabolic engineering of cyanobacteria for heterologous production of non-native terpenoids.
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32.
  • Preiner, Martina, et al. (författare)
  • Serpentinization : Connecting Geochemistry, Ancient Metabolism and Industrial Hydrogenation
  • 2018
  • Ingår i: Life. - : MDPI AG. - 2075-1729.
  • Forskningsöversikt (refereegranskat)abstract
    • Rock-water-carbon interactions germane to serpentinization in hydrothermal vents have occurred for over 4 billion years, ever since there was liquid water on Earth. Serpentinization converts iron(II) containing minerals and water to magnetite (Fe3O4) plus H-2. The hydrogen can generate native metals such as awaruite (Ni3Fe), a common serpentinization product. Awaruite catalyzes the synthesis of methane from H-2 and CO2 under hydrothermal conditions. Native iron and nickel catalyze the synthesis of formate, methanol, acetate, and pyruvate-intermediates of the acetyl-CoA pathway, the most ancient pathway of CO2 fixation. Carbon monoxide dehydrogenase (CODH) is central to the pathway and employs Ni-0 in its catalytic mechanism. CODH has been conserved during 4 billion years of evolution as a relic of the natural CO2-reducing catalyst at the onset of biochemistry. The carbide-containing active site of nitrogenase-the only enzyme on Earth that reduces N(2)is probably also a relic, a biological reconstruction of the naturally occurring inorganic catalyst that generated primordial organic nitrogen. Serpentinization generates Fe3O4 and H-2, the catalyst and reductant for industrial CO2 hydrogenation and for N-2 reduction via the Haber-Bosch process. In both industrial processes, an Fe3O4 catalyst is matured via H-2-dependent reduction to generate Fe5C2 and Fe2N respectively. Whether serpentinization entails similar catalyst maturation is not known. We suggest that at the onset of life, essential reactions leading to reduced carbon and reduced nitrogen occurred with catalysts that were synthesized during the serpentinization process, connecting the chemistry of life and Earth to industrial chemistry in unexpected ways.
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33.
  • Ruíz-Bermejo, Marta, et al. (författare)
  • Simple organics and biomonomers identified in HCN polymers : An overview
  • 2013
  • Ingår i: Life. - : MDPI AG. - 2075-1729. ; 3:3, s. 421-448
  • Tidskriftsartikel (refereegranskat)abstract
    • Hydrogen cyanide (HCN) is a ubiquitous molecule in the Universe. It is a compound that is easily produced in significant yields in prebiotic simulation experiments using a reducing atmosphere. HCN can spontaneously polymerise under a wide set of experimental conditions. It has even been proposed that HCN polymers could be present in objects such as asteroids, moons, planets and, in particular, comets. Moreover, it has been suggested that these polymers could play an important role in the origin of life. In this review, the simple organics and biomonomers that have been detected in HCN polymers, the analytical techniques and procedures that have been used to detect and characterise these molecules and an exhaustive classification of the experimental/environmental conditions that favour the formation of HCN polymers are summarised. Nucleobases, amino acids, carboxylic acids, cofactor derivatives and other compounds have been identified in HCN polymers. The great molecular diversity found in HCN polymers encourages their placement at the central core of a plausible protobiological system
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34.
  • Santos, Marina, et al. (författare)
  • CRISPRi as a Tool to Repress Multiple Copies of Extracellular Polymeric Substances (EPS)-Related Genes in the Cyanobacterium Synechocystis sp. PCC 6803
  • 2021
  • Ingår i: Life. - : MDPI AG. - 2075-1729. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of the versatile cyanobacterial extracellular polymeric substances (EPS) for biotechnological/biomedical applications implies an extensive knowledge of their biosynthetic pathways to improve/control polymer production yields and characteristics. The multiple copies of EPS-related genes, scattered throughout cyanobacterial genomes, adds another layer of complexity, making these studies challenging and time-consuming. Usually, this issue would be tackled by generating deletion mutants, a process that in cyanobacteria is also hindered by the polyploidy. Thus, the use of the CRISPRi multiplex system constitutes an efficient approach to addressing this redundancy. Here, three putative Synechocystis sp. PCC 6803 kpsM homologues (slr0977, slr2107, and sll0574) were repressed using this methodology. The characterization of the 3-sgRNA mutant in terms of fitness/growth and total carbohydrates, released and capsular polysaccharides, and its comparison with previously generated single knockout mutants pointed towards Slr0977 being the key KpsM player in Synechocystis EPS production. This work validates CRISPRi as a powerful tool to unravel cyanobacterial complex EPS biosynthetic pathways expediting this type of studies.
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35.
  • Smith, Hillary H., et al. (författare)
  • The grayness of the origin of life
  • 2021
  • Ingår i: Life. - : MDPI AG. - 2075-1729. ; 11:6
  • Tidskriftsartikel (refereegranskat)abstract
    • In the search for life beyond Earth, distinguishing the living from the non-living is paramount. However, this distinction is often elusive, as the origin of life is likely a stepwise evolutionary process, not a singular event. Regardless of the favored origin of life model, an inherent “grayness” blurs the theorized threshold defining life. Here, we explore the ambiguities between the biotic and the abiotic at the origin of life. The role of grayness extends into later transitions as well. By recognizing the limitations posed by grayness, life detection researchers will be better able to develop methods sensitive to prebiotic chemical systems and life with alternative biochemistries.
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36.
  • Tomita, Y., et al. (författare)
  • Metabolism in Retinopathy of Prematurity
  • 2021
  • Ingår i: Life-Basel. - : MDPI AG. - 2075-1729. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Retinopathy of prematurity is defined as retinal abnormalities that occur during development as a consequence of disturbed oxygen conditions and nutrient supply after preterm birth. Both neuronal maturation and retinal vascularization are impaired, leading to the compensatory but uncontrolled retinal neovessel growth. Current therapeutic interventions target the hypoxia-induced neovessels but negatively impact retinal neurons and normal vessels. Emerging evidence suggests that metabolic disturbance is a significant and underexplored risk factor in the disease pathogenesis. Hyperglycemia and dyslipidemia correlate with the retinal neurovascular dysfunction in infants born prematurely. Nutritional and hormonal supplementation relieve metabolic stress and improve retinal maturation. Here we focus on the mechanisms through which metabolism is involved in preterm-birth-related retinal disorder from clinical and experimental investigations. We will review and discuss potential therapeutic targets through the restoration of metabolic responses to prevent disease development and progression.
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37.
  • Tsai, CH, et al. (författare)
  • Effects of Electronic Health Record Implementation and Barriers to Adoption and Use: A Scoping Review and Qualitative Analysis of the Content
  • 2020
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 10:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite the great advances in the field of electronic health records (EHRs) over the past 25 years, implementation and adoption challenges persist, and the benefits realized remain below expectations. This scoping review aimed to present current knowledge about the effects of EHR implementation and the barriers to EHR adoption and use. A literature search was conducted in PubMed, Web of Science, IEEE Xplore Digital Library and ACM Digital Library for studies published between January 2005 and May 2020. In total, 7641 studies were identified of which 142 met the criteria and attained the consensus of all researchers on inclusion. Most studies (n = 91) were published between 2017 and 2019 and 81 studies had the United States as the country of origin. Both positive and negative effects of EHR implementation were identified, relating to clinical work, data and information, patient care and economic impact. Resource constraints, poor/insufficient training and technical/educational support for users, as well as poor literacy and skills in technology were the identified barriers to adoption and use that occurred frequently. Although this review did not conduct a quality analysis of the included papers, the lack of uniformity in the use of EHR definitions and detailed contextual information concerning the study settings could be observed.
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38.
  • Vimarlund, Vivian, et al. (författare)
  • Advances in E-Health
  • 2021
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 11:6
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • E-health offers new ways to access health information, to deliver health and social care and to perform self-management [...]
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39.
  • Åberg, Daniel, 1973, et al. (författare)
  • Insulin-Like Growth Factor-II and Ischemic Stroke-A Prospective Observational Study
  • 2021
  • Ingår i: Life-Basel. - : MDPI AG. - 2075-1729. ; 11:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Insulin-like growth factor-II (IGF-II) regulates prenatal brain development, but the role in adult brain function and injury is unclear. Here, we determined whether serum levels of IGF-II (s-IGF-II) are associated with mortality and functional outcome after ischemic stroke (IS). The study population comprised ischemic stroke cases (n = 492) and controls (n = 514) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months and 2 years using the modified Rankin Scale (mRS), and additionally, survival was followed at a minimum of 7 years or until death. S-IGF-II levels were higher in IS cases both in the acute phase and at 3-month follow-up compared to controls (p < 0.05 and p < 0.01, respectively). The lowest quintile of acute s-IGF-II was, compared to the four higher quintiles, associated with an increased risk of post-stroke mortality (median follow-up 10.6 years, crude hazard ratio (HR) 2.34, 95% confidence interval (CI) 1.56-3.49, and fully adjusted HR 1.64, 95% CI 1.02-2.61). In contrast, crude associations with poor functional outcome (mRS 3-6) lost significance after full adjustment for covariates. In conclusion, s-IGF-II was higher in IS cases than in controls, and low acute s-IGF-II was an independent risk marker of increased mortality.
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40.
  • Almowallad, S, et al. (författare)
  • NF-kB in Signaling Patterns and Its Temporal Dynamics Encode/Decode Human Diseases
  • 2022
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 12:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Defects in signaling pathways are the root cause of many disorders. These malformations come in a wide variety of types, and their causes are also very diverse. Some of these flaws can be brought on by pathogenic organisms and viruses, many of which can obstruct signaling processes. Other illnesses are linked to malfunctions in the way that cell signaling pathways work. When thinking about how errors in signaling pathways might cause disease, the idea of signalosome remodeling is helpful. The signalosome may be conveniently divided into two types of defects: phenotypic remodeling and genotypic remodeling. The majority of significant illnesses that affect people, including high blood pressure, heart disease, diabetes, and many types of mental illness, appear to be caused by minute phenotypic changes in signaling pathways. Such phenotypic remodeling modifies cell behavior and subverts normal cellular processes, resulting in illness. There has not been much progress in creating efficient therapies since it has been challenging to definitively confirm this connection between signalosome remodeling and illness. The considerable redundancy included into cell signaling systems presents several potential for developing novel treatments for various disease conditions. One of the most important pathways, NF-κB, controls several aspects of innate and adaptive immune responses, is a key modulator of inflammatory reactions, and has been widely studied both from experimental and theoretical perspectives. NF-κB contributes to the control of inflammasomes and stimulates the expression of a number of pro-inflammatory genes, including those that produce cytokines and chemokines. Additionally, NF-κB is essential for controlling innate immune cells and inflammatory T cells’ survival, activation, and differentiation. As a result, aberrant NF-κB activation plays a role in the pathogenesis of several inflammatory illnesses. The activation and function of NF-κB in relation to inflammatory illnesses was covered here, and the advancement of treatment approaches based on NF-κB inhibition will be highlighted. This review presents the temporal behavior of NF-κB and its potential relevance in different human diseases which will be helpful not only for theoretical but also for experimental perspectives.
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41.
  • Anifanti, M, et al. (författare)
  • Right Ventricular Morphology and Function after Exercise Training in People with Systemic Sclerosis: A Randomized Controlled Pilot Study
  • 2023
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 13:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Vascular dysfunction and its concomitant multi-organ involvement, including cardiac involvement, affects prognosis in systemic sclerosis (SSc) patients. Regular exercise has demonstrated to be able to improve vascular function in SSc. However, the effects of an exercise program on the heart and specifically in right ventricular (RV) morphology and function in SSc have yet to be explored. The study aimed to examine whether a 3-month combined exercise program can affect RV morphology and function in SSc patients. Methods: Twenty-eight SSc patients were randomly allocated to either the exercise training (ET) or the control (CON) group. Baseline and follow-up assessments consisted of a cardiopulmonary exercise test along with both a conventional and a two-dimensional speckle tracking echocardiography (2DSTE) focused on RV morphology and function. Following the baseline assessments, Group ET participated in a supervised combined exercise program for 12 weeks, while group CON received their usual care. Results: The ET group demonstrated increases in peak oxygen consumption by 25.1% (p < 0.001), global RV free wall longitudinal systolic strain by 6.69% (p < 0.03), RV free wall longitudinal systolic strain of the basal segment by 13.5% (p < 0.001), and global RV four-chamber longitudinal systolic strain by 6.76% (p < 0.03) following the exercise program. No differences were observed in group CON. Conclusions: Combined exercise improved cardiorespiratory efficiency and indices of RV systolic function, as assessed by the 2DSTE, in SSc patients.
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42.
  • Balato, A, et al. (författare)
  • The Impact of Psoriasis and Atopic Dermatitis on Quality of Life: A Literature Research on Biomarkers
  • 2022
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 12:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Psoriasis (PSO) and Atopic dermatitis (AD) are common inflammatory skin diseases that affect people of all ages globally. They negatively impact the quality of life (QoL) of patients in health-related aspects such as physical, psychological and mental functioning. Here, we conducted a review of studies relating to candidate biomarkers and indicators associated with QoL impairment in PSO and AD. Data research was performed using PUBMED and SCOPUS databases from inception to September 2022. Most of the included studies reported genomic or proteomic biomarkers associated with disease activity and QoL outcomes. Sociodemographic, clinical and therapeutic factors have also been implicated in deterioration of life quality in these patients. The inclusion of clinical characteristics, QoL impairment and co-diagnosis should be considered in drug development programs, since processing biomarkers based on an increased number of features in addition to drug class and disease will intensify the value of the biomarker itself, thereby maximizing the future clinical utility as a stratification tool.
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43.
  • Baranova, E, et al. (författare)
  • Sputum Microbiome Composition in Patients with Squamous Cell Lung Carcinoma
  • 2022
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 12:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Recent findings indicate that the host microbiome can have a significant impact on the development of lung cancer by inducing an inflammatory response, causing dysbiosis, and generating genome damage. The aim of this study was to search for bacterial communities specifically associated with squamous cell carcinoma (LUSC). Methods: In this study, the taxonomic composition of the sputum microbiome of 40 men with untreated LUSC was compared with that of 40 healthy controls. Next-Generation sequencing of bacterial 16S rRNA genes was used to determine the taxonomic composition of the respiratory microbiome. Results: There were no differences in alpha diversity between the LUSC and control groups. Meanwhile, differences in the structure of bacterial communities (β diversity) among patients and controls differed significantly in sputum samples (pseudo-F = 1.53; p = 0.005). Genera of Streptococcus, Bacillus, Gemella, and Haemophilus were found to be significantly enriched in patients with LUSC compared to the control subjects, while 19 bacterial genera were significantly reduced, indicating a decrease in beta diversity in the microbiome of patients with LUSC. Conclusions: Among other candidates, Streptococcus (Streptococcus agalactiae) emerges as the most likely LUSC biomarker, but more research is needed to confirm this assumption.
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44.
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45.
  • Berciano-Guerrero, MA, et al. (författare)
  • Treatment of Metastatic Melanoma at First Diagnosis: Review of the Literature
  • 2022
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 12:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Metastatic melanoma (MM) is a pathological entity with a very poor prognosis that, until a few decades ago, had a low response rate to systemic treatments. Fortunately, in the last few years, new therapies for metastatic melanoma have emerged. Currently, targeted therapy and immunotherapy are the mainstays of the therapeutic arsenal available for patients with unresectable or metastatic melanoma. However, both clinical evolution and drug efficacy in melanoma patients are very different depending on the stage at which it is diagnosed. In fact, the aggressiveness of melanoma is different depending on whether it debuts directly as metastatic disease or if what occurs is a relapse after a first diagnosis at an early stage, although the biological determinants are largely unknown. Another key aspect in the clinical management of metastatic melanoma at first diagnosis strives in the different prognosis of melanoma of unknown primary (MUP) compared to melanoma of known primary (MPK). Understanding the mechanisms behind this, and the repercussion of implementing targeted and immune therapies in this specific form is crucial for designing diagnosis and treatment decision algorithms that optimize the current strategies. In this review article, we recapitulate the information available thus far regarding the epidemiology and response to immunotherapy treatments or targeted therapy in patients diagnosed with metastatic melanoma as a first diagnosis, with especial emphasis on the emerging specific information of the subpopulation formed by MUP patients.
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46.
  • Dahlen, E, et al. (författare)
  • Comparison of Creatinine and Cystatin C to Estimate Renal Function in Geriatric and Frail Patients
  • 2022
  • Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 12:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to compare estimated glomerular filtration rate (eGFR) with creatinine (eGFRcrea) and cystatin C (eGFRcys) in geriatric and frail patients. A retrospective, cross-sectional study was performed at a geriatric clinic in Stockholm (n = 95). The revised Lund–Malmö equation was used to calculate eGFRcrea and the Caucasian-Asian-Pediatric-Adult (CAPA) equation was used for eGFRcys. The absolute mean percentage difference between eGFRcrea and eGFRcys was used as a surrogate measure for accuracy in eGFR. Other outcome measures were consistency expressed in Lin’s concordance correlation coefficient and the proportion of consistent staging of renal failure. Subgroup analyses were performed with regard to frailty (according to Clinical Frailty Scale) and age. eGFRcys estimated lower GFR than eGFRcrea across the entire study population as well as in all subgroups (p < 0.05). Difference between the estimates increased with increasing frailty (r2 = 0.15, p < 0.01), but was not significantly affected by age (r2 = 0.004, p = 0.55). In conclusion, eGFRcys was significantly lower compared to eGFRcrea in geriatric and frail patients. Moreover, frailty had greater impact than age on the accuracy of eGFR. However, this study cannot determine if any of the estimates are preferable over the other in this patient group.
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47.
  • Dawod, Ahmed, et al. (författare)
  • Efficacy of Ficus sycomorus (Sycamore Fig) Extract on Intestinal Coccidiosis in Experimentally Infected Rabbits
  • 2022
  • Ingår i: Life. - : MDPI. - 2075-1729. ; 12:6
  • Tidskriftsartikel (refereegranskat)abstract
    • This study was conducted to investigate the effect of the Ficus sycomorus extract on Eimeria intestinalis in experimentally infected rabbits. For this purpose, forty male 30-day-old rabbits (Blanc de Bouscat) were divided into four groups (n = 10 in each group). Rabbits kept in the first group served as negative control (non-treated-non-infected). Rabbits kept in the second, third, and fourth groups were challenged at 10 weeks old with 3 x 10(4) E. intestinalis sporulated oocysts. The third and fourth groups were treated orally with diclazuril 10% (0.05 mg/kg body weight) and F. sycomorus (100 mg/Kg) for three consecutive days, respectively. The efficacy was assessed based on the growth performance parameters, clinical symptoms, oocyst shedding, histopathological findings, and hematological parameters for 16 days post challenge. The study revealed that rabbits treated with F. sycomorus methanolic extract and diclazuril showed mild clinical symptoms with a significant decrease in oocyst shedding compared with the positive control. Moreover, the diclazuril-treated group showed the highest leukocytic count and the lowest monocytes percentage compared with other groups. Furthermore, the lowest lymphocytes percentage was recorded in the control positive group. Histopathologically, moderate coccidia infestation in the intestinal mucosa and moderate hydropic degeneration of hepatocytes were observed in the diclazuril treated group compared with the negative control. However, mild coccidia infestation in the intestinal mucosa and slight coagulative necrosis of hepatocytes was found in the F. sycomorus treated group. In conclusion, F. sycomorus methanolic extract had promising effects on the live performance, oocyst count, and blood variables, while it possesses adverse consequences on the hepatic tissues. Further studies are required to optimize the dose and extraction method to mitigate its side effects.
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48.
  • De Luca, Mariarosaria, et al. (författare)
  • Endothelial Dysfunction and Heart Failure with Preserved Ejection Fraction-An Updated Review of the Literature.
  • 2023
  • Ingår i: Life (Basel, Switzerland). - 2075-1729. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Heart failure (HF) is a clinical syndrome consisting of typical symptoms and signs due to structural and/or functional abnormalities of the heart, resulting in elevated intracardiac pressures and/or inadequate cardiac output. The vascular system plays a crucial role in the development and progression of HF regardless of ejection fraction, with endothelial dysfunction (ED) as one of the principal features of HF. The main ED manifestations (i.e., impaired endothelium-dependent vasodilation, increased oxidative stress, chronic inflammation, leukocyte adhesion, and endothelial cell senescence) affect the systemic and pulmonary haemodynamic and the renal and coronary circulation. The present review is aimed to discuss the contribution of ED to HF pathophysiology-in particular, HF with preserved ejection fraction-ED role in HF patients, and the possible effects of pharmacological and non-pharmacological approaches. For this purpose, relevant data from a literature search (PubMed, Scopus, EMBASE, and Medline) were reviewed. As a result, ED, assessed via venous occlusion plethysmography or flow-mediated dilation, was shown to be independently associated with poor outcomes in HF patients (e.g., mortality, cardiovascular events, and hospitalization due to worsening HF). In addition, SGLT2 inhibitors, endothelin antagonists, endothelial nitric oxide synthase cofactors, antioxidants, and exercise training were shown to positively modulate ED in HF. Despite the need for future research to better clarify the role of the vascular endothelium in HF, ED represents an interesting and promising potential therapeutic target.
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49.
  • Dedicova, Beata (författare)
  • Modulation of Tropane Alkaloids' Biosynthesis and Gene Expression by Methyl Jasmonate in Datura stramonium L.: A Comparative Analysis of Scopolamine, Atropine, and Hyoscyamine Accumulation
  • 2024
  • Ingår i: Life. - 2075-1729. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Scopolamine and atropine are two medicinal alkaloids derived from Datura stramonium L. with anticholinergic properties. This study explored how methyl jasmonate (MJ), a plant growth regulator, affects the biosynthesis and accumulation of these alkaloids in different plant tissues. The expression levels of putrescine N-methyltransferase (PMT), tropinone reductase I (TR1), and hyoscyamine 6 beta-hydroxylase (h6h), three critical enzymes in the biosynthetic pathway, were also analyzed. The results indicated that MJ at 150 mu M increased the production of scopolamine and atropine in both leaves and roots, while MJ at 300 mu M had an adverse effect. Furthermore, MJ enhanced the expression of PMT, TR1, and h6h genes in the roots, the primary site of alkaloid synthesis, but not in the leaves, the primary site of alkaloid storage. These results imply that MJ can be applied to regulate the biosynthesis and accumulation of scopolamine and atropine in D. stramonium, thereby improving their production efficiency.
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50.
  • Delfin, Carl, et al. (författare)
  • A Federated Database for Obesity Research : An IMI-SOPHIA Study
  • 2024
  • Ingår i: Life. - 0024-3019. ; 14:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is considered by many as a lifestyle choice rather than a chronic progressive disease. The Innovative Medicines Initiative (IMI) SOPHIA (Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy) project is part of a momentum shift aiming to provide better tools for the stratification of people with obesity according to disease risk and treatment response. One of the challenges to achieving these goals is that many clinical cohorts are siloed, limiting the potential of combined data for biomarker discovery. In SOPHIA, we have addressed this challenge by setting up a federated database building on open-source DataSHIELD technology. The database currently federates 16 cohorts that are accessible via a central gateway. The database is multi-modal, including research studies, clinical trials, and routine health data, and is accessed using the R statistical programming environment where statistical and machine learning analyses can be performed at a distance without any disclosure of patient-level data. We demonstrate the use of the database by providing a proof-of-concept analysis, performing a federated linear model of BMI and systolic blood pressure, pooling all data from 16 studies virtually without any analyst seeing individual patient-level data. This analysis provided similar point estimates compared to a meta-analysis of the 16 individual studies. Our approach provides a benchmark for reproducible, safe federated analyses across multiple study types provided by multiple stakeholders.
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