176 research outputs found
Upfront Genotyping of DPYD* 2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis
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Awareness about developmental coordination disorder
Data availability statement: The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The present paper is designed to promote awareness of DCD outside the academic world. With a prevalence of 5–6% it is one of the most common disorders of child development. It is therefore surprising that so little is known about it among professionals in child healthcare and education. Parents have expressed frustration about this lack of awareness, including the general public. The general aim of this paper was to describe those critical aspects of DCD that will promote awareness.Research Foundation Flanders (FWO: 1232221N). This research of PW is supported by the Czech Science Foundation (GACR EXPRO scheme: 21-15728X). The authors are part of the “DCD Big Ideas Group” consisting of 25 key researchers in the field of DCD (from early-career to established) working to develop a clear vision for the future of research on DCD. BS and HB were supported by a grant (TRIAL) from the Dutch Research Council (NWO), grant number NWA.1160.18.249
Behavioral and Neuroimaging Research on Developmental Coordination Disorder (DCD): A Combined Systematic Review and Meta-Analysis of Recent Findings
Data Availability Statement: The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s. Supplementary Material: The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpsyg.2022.809455/full#supplementary-materialAim: The neurocognitive basis of Developmental Coordination Disorder (DCD; or motor clumsiness) remains an issue of continued debate. This combined systematic review and meta-analysis provides a synthesis of recent experimental studies on the motor control, cognitive, and neural underpinnings of DCD.
Methods: The review included all published work conducted since September 2016 and up to April 2021. One-hundred papers with a DCD-Control comparison were included, with 1,374 effect sizes entered into a multi-level meta-analysis.
Results: The most profound deficits were shown in: voluntary gaze control during movement; cognitive-motor integration; practice-/context-dependent motor learning; internal modeling; more variable movement kinematics/kinetics; larger safety margins when locomoting, and atypical neural structure and function across sensori-motor and prefrontal regions.
Interpretation: Taken together, these results on DCD suggest fundamental deficits in visual-motor mapping and cognitive-motor integration, and abnormal maturation of motor networks, but also areas of pragmatic compensation for motor control deficits. Implications for current theory, future research, and evidence-based practice are discussed.
Systematic Review Registration: PROSPERO, identifier: CRD42020185444.Australian Government Research Training Program Scholarship; Research Centre scheme, Australian Catholic University; Czech Science Foundation (GACR EXPRO scheme: 21-15728X); Knut and Alice Wallenberg Foundation (KAW 2020.0200).https://www.frontiersin.org/articles/10.3389/fpsyg.2022.809455/full#supplementary-materia
Cortical and cerebellar activation induced by reflexive and voluntary saccades
Reflexive saccades are driven by visual stimulation whereas voluntary saccades require volitional control. Behavioral and lesional studies suggest that there are two separate mechanisms involved in the generation of these two types of saccades. This study investigated differences in cerebral and cerebellar activation between reflexive and self-paced voluntary saccadic eye movements using functional magnetic resonance imaging. In two experiments (whole brain and cerebellum) using the same paradigm, differences in brain activations induced by reflexive and self-paced voluntary saccades were assessed. Direct comparison of the activation patterns showed that the frontal eye fields, parietal eye field, the motion-sensitive area (MT/V5), the precuneus (V6), and the angular and the cingulate gyri were more activated in reflexive saccades than in voluntary saccades. No significant difference in activation was found in the cerebellum. Our results suggest that the alleged separate mechanisms for saccadic control of reflexive and self-paced voluntary are mainly observed in cerebral rather than cerebellar areas
Molecular Interactions of Prodiginines with the BH3 Domain of Anti-Apoptotic Bcl-2 Family Members
Prodigiosin and obatoclax, members of the prodiginines family, are small molecules with anti-cancer properties that are
currently under preclinical and clinical trials. The molecular target(s) of these agents, however, is an open question.
Combining experimental and computational techniques we find that prodigiosin binds to the BH3 domain in some BCL-2
protein families, which play an important role in the apoptotic programmed cell death. In particular, our results indicate
a large affinity of prodigiosin for MCL-1, an anti-apoptotic member of the BCL-2 family. In melanoma cells, we demonstrate
that prodigiosin activates the mitochondrial apoptotic pathway by disrupting MCL-1/BAK complexes. Computer simulations
with the PELE software allow the description of the induced fit process, obtaining a detailed atomic view of the molecular
interactions. These results provide new data to understand the mechanism of action of these molecules, and assist in the
development of more specific inhibitors of anti-apoptotic BCL-2 proteins.Spanish government and the European Union (FIS-PI10/00338) and from the ERC-2009-Adg
25027-PELE European project
Immunotherapy: is a minor god yet in the pantheon of treatments for lung cancer?
Immunotherapy has been studied for many years in lung cancer without significant results, making the majority of oncologists quite skeptical about its possible application for non-small cell lung cancer treatment. However, the recent knowledge about immune escape and subsequent 'cancer immunoediting' has yielded the development of new strategies of cancer immunotherapy, heralding a new era of lung cancer treatment. Cancer vaccines, including both whole-cell and peptide vaccines have been tested both in early and advanced stages of non-small cell lung cancer. New immunomodulatory agents, including anti-CTLA4, anti-PD1/PDL1 monoclonal antibodies, have been investigated as monotherapy in metastatic lung cancer. To date, these treatments have shown impressive results of efficacy and tolerability in early clinical trials, leading to testing in several large, randomized Phase III trials. As these results will be confirmed, these drugs will be available in the near future, offering new exciting therapeutic options for lung cancer treatment
Local host-dependent persistence of the entomopathogenic nematode Steinernema carpocapsae used to control the large pine weevil Hylobius abietis
Entomopathogenic nematodes (EPN) applied inundatively to suppress insect pests are more likely to persist and establish in stable agroecosystems than in annual crops. We investigated a system of intermediate stability: three stumps harbouring the large pine weevil (Hylobius abietis L.; Coleoptera: Curculionidae), a major European forestry pest. We tested whether persistence of EPN Steinernema carpocapsae Weiser (Rhabditida: Steinernematidae) applied around stumps is maintained by recycling of EPN through pine weevils developing within stumps. Steinernema carpocapsae was detected in soil around and under the bark of treated tree stumps up to two years, but not 4–5 years after application. Differences in nematode presence between sites were better explained by tree species (pine or spruce) than soil type (mineral or peat). Presence of S. carpocapsae in soil was positively correlated with the number of H. abietis emerging from untreated stumps the previous year, which was greater for pine stumps than spruce stumps
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