| 1. |
|
|
| 2. |
- Demichev, Vadim, et al.
(författare)
-
A time-resolved proteomic and prognostic map of COVID-19
- 2021
-
Ingår i: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
-
Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
|
|
| 3. |
- Galluzzi, Lorenzo, et al.
(författare)
-
Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer
- 2012
-
Ingår i: Cell Reports. - Cambridge : Cell press. - 2211-1247. ; 2:2, s. 257-269
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct types of physical and chemical stress, including multiple chemotherapeutics. This effect requires pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. In line with a general role of vitamin B6 in stress responses, low PDXK expression levels were found to be associated with poor disease outcome in two independent cohorts of patients with NSCLC. These results indicate that PDXK expression levels constitute a biomarker for risk stratification among patients with NSCLC.
|
|
| 4. |
- Geisen, Christof, et al.
(författare)
-
An HPA-1a–positive platelet–depleting agent for prevention of fetal and neonatal alloimmune thrombocytopenia : a randomized, single-blind, placebo–controlled, single-center, phase 1/2 proof-of-concept study
- 2023
-
Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 21:4, s. 838-849
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a rare and potentially life-threatening bleeding disorder of the fetus/newborn. Antibodies against human platelet antigen 1a (HPA-1a) are associated with the most frequent FNAIT cases. There are no approved therapies for FNAIT prevention or treatment. RLYB211 is a polyclonal HPA-1a hyperimmune IgG being developed to prevent FNAIT. Objectives: To investigate whether a single dose of anti–HPA-1a (1000 IU) could markedly accelerate the elimination of HPA-1ab platelets transfused into healthy, HPA-1a–negative participants as compared with placebo. Methods: This randomized, single-blind, placebo–controlled, single-center, phase 1/2 proof-of-concept study (EudraCT: 2019-003459-12) included HPA-1a– and HLA-A2–negative healthy men. Cohort 1 received intravenous RLYB211 or placebo 1 hour after transfusion of HPA-1ab platelets. Cohort 1B received RLYB211 or placebo, followed by platelet transfusion 1 week later. Primary endpoint was the half-life of transfused platelets in circulation after administration of RLYB211 or placebo, determined by flow cytometry. Proof of concept was ≥90% reduction of half-life relative to placebo. Results: Twelve participants were allocated to cohort 1 or 1B and randomized to receive RLYB211 (n = 9) or placebo (n = 3). RLYB211 markedly accelerated the elimination of HPA-1ab platelets in all participants vs placebo. In cohort 1B, this effect was observed 7 days after RLYB211 administration. Two treatment–emergent adverse events were possibly related to treatment, both in RLYB211–treated participants. No participants developed HPA-1a antibodies at 12 or 24 weeks. Conclusion: These data support the hypothesis that anti–HPA-1a could be used as prophylaxis in women at risk of having an FNAIT–affected pregnancy.
|
|
| 5. |
- Shaw, Emily, et al.
(författare)
-
AMEE Consensus Statement : Planetary health and education for sustainable healthcare.
- 2021
-
Ingår i: Medical teacher. - 0142-159X .- 1466-187X. ; 43:3, s. 272-286
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this Consensus Statement is to provide a global, collaborative, representative and inclusive vision for educating an interprofessional healthcare workforce that can deliver sustainable healthcare and promote planetary health. It is intended to inform national and global accreditation standards, planning and action at the institutional level as well as highlight the role of individuals in transforming health professions education. Many countries have agreed to 'rapid, far-reaching and unprecedented changes' to reduce greenhouse gas emissions by 45% within 10 years and achieve carbon neutrality by 2050, including in healthcare. Currently, however, health professions graduates are not prepared for their roles in achieving these changes. Thus, to reduce emissions and meet the 2030 Sustainable Development Goals (SDGs), health professions education must equip undergraduates, and those already qualified, with the knowledge, skills, values, competence and confidence they need to sustainably promote the health, human rights and well-being of current and future generations, while protecting the health of the planet. The current imperative for action on environmental issues such as climate change requires health professionals to mobilize politically as they have before, becoming strong advocates for major environmental, social and economic change. A truly ethical relationship with people and the planet that we inhabit so precariously, and to guarantee a future for the generations which follow, demands nothing less of all health professionals. This Consensus Statement outlines the changes required in health professions education, approaches to achieve these changes and a timeline for action linked to the internationally agreed SDGs. It represents the collective vision of health professionals, educators and students from various health professions, geographic locations and cultures. 'Consensus' implies broad agreement amongst all individuals engaged in discussion on a specific issue, which in this instance, is agreement by all signatories of this Statement developed under the auspices of the Association for Medical Education in Europe (AMEE). To ensure a shared understanding and to accurately convey information, we outline key terms in a glossary which accompanies this Consensus Statement (Supplementary Appendix 1). We acknowledge, however, that terms evolve and that different terms resonate variably depending on factors such as setting and audience. We define education for sustainable healthcare as the process of equipping current and future health professionals with the knowledge, values, confidence and capacity to provide environmentally sustainable services through health professions education. We define a health professional as a person who has gained a professional qualification for work in the health system, whether in healthcare delivery, public health or a management or supporting role and education as 'the system comprising structures, curricula, faculty and activities contributing to a learning process'. This Statement is relevant to the full continuum of training - from undergraduate to postgraduate and continuing professional development.
|
|
