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  • 1
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    Online Resource
    Diagnosis and Management of Glioblastoma: A Comprehensive Perspective
    MDPI AG ; 2021
    In:  Journal of Personalized Medicine Vol. 11, No. 4 ( 2021-04-01), p. 258-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 11, No. 4 ( 2021-04-01), p. 258-
    Abstract: Glioblastoma is the most common malignant brain tumor in adults. The current management relies on surgical resection and adjuvant radiotherapy and chemotherapy. Despite advances in our understanding of glioblastoma onset, we are still faced with an increased incidence, an altered quality of life and a poor prognosis, its relapse and a median overall survival of 15 months. For the past few years, the understanding of glioblastoma physiopathology has experienced an exponential acceleration and yielded significant insights and new treatments perspectives. In this review, through an original R-based literature analysis, we summarize the clinical presentation, current standards of care and outcomes in patients diagnosed with glioblastoma. We also present the recent advances and perspectives regarding pathophysiological bases as well as new therapeutic approaches such as cancer vaccination and personalized treatments.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm11040258
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662248-8
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  • 2
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    Precision Neurosurgery: A Path Forward
    MDPI AG ; 2021
    In:  Journal of Personalized Medicine Vol. 11, No. 10 ( 2021-10-12), p. 1019-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 11, No. 10 ( 2021-10-12), p. 1019-
    Abstract: Since the inception of their profession, neurosurgeons have defined themselves as physicians with a surgical practice. Throughout time, neurosurgery has always taken advantage of technological advances to provide better and safer care for patients. In the ongoing precision medicine surge that drives patient-centric healthcare, neurosurgery strives to effectively embrace the era of data-driven medicine. Neuro-oncology best illustrates this convergence between surgery and precision medicine with the advent of molecular profiling, imaging and data analytics. This convenient convergence paves the way for new preventive, diagnostic, prognostic and targeted therapeutic perspectives. The prominent advances in healthcare and big data forcefully challenge the medical community to deeply rethink current and future medical practice. This work provides a historical perspective on neurosurgery. It also discusses the impact of the conceptual shift of precision medicine on neurosurgery through the lens of neuro-oncology.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm11101019
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662248-8
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  • 3
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    Integrative Metabolomics Reveals Deep Tissue and Systemic Metabolic Remodeling in Glioblastoma
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 20 ( 2021-10-14), p. 5157-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 20 ( 2021-10-14), p. 5157-
    Abstract: (1) Background: Glioblastoma is the most common malignant brain tumor in adults. Its etiology remains unknown in most cases. Glioblastoma pathogenesis consists of a progressive infiltration of the white matter by tumoral cells leading to progressive neurological deficit, epilepsy, and/or intracranial hypertension. The mean survival is between 15 to 17 months. Given this aggressive prognosis, there is an urgent need for a better understanding of the underlying mechanisms of glioblastoma to unveil new diagnostic strategies and therapeutic targets through a deeper understanding of its biology. (2) Methods: To systematically address this issue, we performed targeted and untargeted metabolomics-based investigations on both tissue and plasma samples from patients with glioblastoma. (3) Results: This study revealed 176 differentially expressed lipids and metabolites, 148 in plasma and 28 in tissue samples. Main biochemical classes include phospholipids, acylcarnitines, sphingomyelins, and triacylglycerols. Functional analyses revealed deep metabolic remodeling in glioblastoma lipids and energy substrates, which unveils the major role of lipids in tumor progression by modulating its own environment. (4) Conclusions: Overall, our study demonstrates in situ and systemic metabolic rewiring in glioblastoma that could shed light on its underlying biological plasticity and progression to inform diagnosis and/or therapeutic strategies.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13205157
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 4
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    Prenatal Alcohol Exposure Impairs the Placenta–Cortex Transcriptomic Signature, Leading to Dysregulation of Angiogenic Pathways
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 17 ( 2023-08-30), p. 13484-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 17 ( 2023-08-30), p. 13484-
    Abstract: Although alcohol consumption during pregnancy is a major cause of behavioral and learning disabilities, most FASD infants are late- or even misdiagnosed due to clinician’s difficulties achieving early detection of alcohol-induced neurodevelopmental impairments. Neuroplacentology has emerged as a new field of research focusing on the role of the placenta in fetal brain development. Several studies have reported that prenatal alcohol exposure (PAE) dysregulates a functional placenta–cortex axis, which is involved in the control of angiogenesis and leads to neurovascular-related defects. However, these studies were focused on PlGF, a pro-angiogenic factor. The aim of the present study is to provide the first transcriptomic “placenta–cortex” signature of the effects of PAE on fetal angiogenesis. Whole mouse genome microarrays of paired placentas and cortices were performed to establish the transcriptomic inter-organ “placenta–cortex” signature in control and PAE groups at gestational day 20. Genespring comparison of the control and PAE signatures revealed that 895 and 1501 genes were only detected in one of two placenta–cortex expression profiles, respectively. Gene ontology analysis indicated that 107 of these genes were associated with vascular development, and String protein–protein interaction analysis showed that they were associated with three functional clusters. PANTHER functional classification analysis indicated that “intercellular communication” was a significantly enriched biological process, and 27 genes were encoded for neuroactive ligand/receptors interactors. Protein validation experiments involving Western blot for one ligand–receptor couple (Agt/AGTR1/2) confirmed the transcriptomic data, and Pearson statistical analysis of paired placentas and fetal cortices revealed a negative correlation between placental Atg and cortical AGTR1, which was significantly impacted by PAE. In humans, a comparison of a 38WG control placenta with a 36WG alcohol-exposed placenta revealed low Agt immunolabeling in the syncytiotrophoblast layer of the alcohol case. In conclusion, this study establishes the first transcriptomic placenta–cortex signature of a developing mouse. The data show that PAE markedly unbalances this inter-organ signature; in particular, several ligands and/or receptors involved in the control of angiogenesis. These data support that PAE modifies the existing communication between the two organs and opens new research avenues regarding the impact of placental dysfunction on the neurovascular development of fetuses. Such a signature would present a clinical value for early diagnosis of brain defects in FASD.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241713484
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
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    Intraventricular Hemorrhage in Very Preterm Infants: A Comprehensive Review
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 8 ( 2020-07-31), p. 2447-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 8 ( 2020-07-31), p. 2447-
    Abstract: Germinal matrix-intraventricular-intraparenchymal hemorrhage (GMH-IVH-IPH) is a major complication of very preterm births before 32 weeks of gestation (WG). Despite progress in clinical management, its incidence remains high before 27 WG. In addition, severe complications may occur such as post-hemorrhagic hydrocephalus and/or periventricular intraparenchymal hemorrhage. IVH is strongly associated with subsequent neurodevelopmental disabilities. For this review, an automated literature search and a clustering approach were applied to allow efficient filtering as well as topic clusters identification. We used a programmatic literature search for research articles related to intraventricular hemorrhage in preterms that were published between January 1990 and February 2020. Two queries ((Intraventricular hemorrhage) AND (preterm)) were used in PubMed. This search resulted in 1093 articles. The data manual curation left 368 documents that formed 12 clusters. The presentation and discussion of the clusters provide a comprehensive overview of existing data on the pathogenesis, complications, neuroprotection and biomarkers of GMH-IVH-IPH in very preterm infants. Clinicians should consider that the GMH-IVH-IPH pathogenesis is mainly due to developmental immaturity of the germinal matrix and cerebral autoregulation impairment. New multiomics investigations of intraventricular hemorrhage could foster the development of predictive biomarkers for the benefit of very preterm newborns.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9082447
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 6
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    Pontocerebellar Hypoplasia Type 1D: A Case Report and Comprehensive Literature Review
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 15 ( 2022-07-26), p. 4335-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 15 ( 2022-07-26), p. 4335-
    Abstract: Pontocerebellar hypoplasia (PCH) is an autosomal recessive, neurodegenerative disorder with multiple subtypes leading to severe neurodevelopmental disabilities. PCH type 1 D is linked to alterations in the EXOSC9 gene. EXOSC9 is a component of the RNA exosome, an evolutionarily conserved ribonuclease complex essential for RNA degradation and processing. The clinical phenotype is characterized by cerebellar and pontine hypoplasia associated with motor neuronopathy. To date, nine patients have been reported in the literature with PCH1D. We report the case of an infant with PCH type 1D due to two variants in the EXOCS9 gene (NM_001034194.1: c.41T 〉 C-p.Leu14Pro) and a novel variant (c.643C 〉 T-p.Arg212*). This report thoroughly reviews the literature PCH1D and highlights the crucial role of the exosome in cellular homeostasis.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11154335
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 7
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    NGLY1 Deficiency: A Rare Newly Described Condition with a Typical Presentation
    MDPI AG ; 2021
    In:  Life Vol. 11, No. 3 ( 2021-02-27), p. 187-
    Details
    In: Life, MDPI AG, Vol. 11, No. 3 ( 2021-02-27), p. 187-
    Abstract: NGLY1 deficiency is the first recognized autosomal recessive disorder of N-linked deglycosylation (NGLY1-CDDG). This severe multisystemic disease is still poorly known and, to date, most cases have been diagnosed through whole exome or genome sequencing. The aim of this study is to provide the clinical, biochemical and molecular description of the first NGLY1-CDDG patient from France along with a literature review. The index case presented with developmental delay, acquired microcephaly, hypotonia, alacrimia, feeding difficulty, and dysmorphic features. Given the complex clinical picture and the multisystemic involvement, a trio-based exome sequencing was conducted and urine oligosaccharides were assessed using mass spectrometry. The exome sequencing revealed a novel variant in the NGLY1 gene in a homozygous state. NGLY1 deficiency was confirmed by the identification of the Neu5Ac1Hex1GlcNAc1-Asn oligosaccharide in the urine of the patient. Literature review revealed the association of some key clinical and biological features such as global developmental delay—hypertransaminasemia, movement disorders, feeding difficulties and alacrima/hypolacrima.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    URL: Article
    DOI: 10.3390/life11030187
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662250-6
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  • 8
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    Parsing Fabry Disease Metabolic Plasticity Using Metabolomics
    MDPI AG ; 2021
    In:  Journal of Personalized Medicine Vol. 11, No. 9 ( 2021-09-08), p. 898-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 11, No. 9 ( 2021-09-08), p. 898-
    Abstract: Background: Fabry disease (FD) is an X-linked lysosomal disease due to a deficiency in the activity of the lysosomal α-galactosidase A (GalA), a key enzyme in the glycosphingolipid degradation pathway. FD is a complex disease with a poor genotype–phenotype correlation. FD could involve kidney, heart or central nervous system impairment that significantly decreases life expectancy. The advent of omics technologies offers the possibility of a global, integrated and systemic approach well-suited for the exploration of this complex disease. Materials and Methods: Sixty-six plasmas of FD patients from the French Fabry cohort (FFABRY) and 60 control plasmas were analyzed using liquid chromatography and mass spectrometry-based targeted metabolomics (188 metabolites) along with the determination of LysoGb3 concentration and GalA enzymatic activity. Conventional univariate analyses as well as systems biology and machine learning methods were used. Results: The analysis allowed for the identification of discriminating metabolic profiles that unambiguously separate FD patients from control subjects. The analysis identified 86 metabolites that are differentially expressed, including 62 Glycerophospholipids, 8 Acylcarnitines, 6 Sphingomyelins, 5 Aminoacids and 5 Biogenic Amines. Thirteen consensus metabolites were identified through network-based analysis, including 1 biogenic amine, 2 lysophosphatidylcholines and 10 glycerophospholipids. A predictive model using these metabolites showed an AUC-ROC of 0.992 (CI: 0.965–1.000). Conclusion: These results highlight deep metabolic remodeling in FD and confirm the potential of omics-based approaches in lysosomal diseases to reveal clinical and biological associations to generate pathophysiological hypotheses.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm11090898
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 9
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    The Neurobehavioral Phenotype of School-Aged, Very Prematurely Born Children with No Serious Neurological Sequelae: A Quality of Life Predictor
    MDPI AG ; 2021
    In:  Children Vol. 8, No. 11 ( 2021-10-20), p. 943-
    Details
    In: Children, MDPI AG, Vol. 8, No. 11 ( 2021-10-20), p. 943-
    Abstract: School-aged extremely preterm (EPT) children have multiple specific neurocognitive/behavioral disorders that are often associated with other disorders; this manifests a true neurobehavioral “phenotype” of prematurity. To determine a profile of cognitive/behavioral impairments in a population of school-aged EPT children (7–10 years-old) without major disabilities, a cross-sectional study was conducted in five medical centers. An algorithm distributed the study population according to four WISC-IV subtests, five NEPSY-2 subtests, and two variables of figure of Rey. The behavior (SDQ), anxiety (Spielberg STAI-C), and generic QoL (Kidscreen 10 and VSP-A) were also evaluated. The study included 231 school-aged EPT children. Three neurobehavioral “phenotypes” were defined according to their severity: 1 = moderately, 2 = minor, and 3 = unimpaired. In all the profiles, the working memory, perceptual reasoning, as well as mental flexibility, were close to or below average, and their emotional behavior was always troubled. Self-esteem and school-work were the most impacted QoL areas. The unimpaired neurobehavior exhibited emotional behavioral impairment and executive dysfunction. The profile analysis defined distinct outcome groups and provided an informative means of identifying factors related to developmental outcomes. The QoL deterioration is determined by the severity of the three neurobehavioral “phenotypes”, which is defined as well as by dysexecutive and/or behavioral disorders.
    Type of Medium: Online Resource
    ISSN: 2227-9067
    URL: Article
    DOI: 10.3390/children8110943
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2732685-8
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  • 10
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    Effects of MgSO4 Alone or Associated with 4-PBA on Behavior and White Matter Integrity in a Mouse Model of Cerebral Palsy: A Sex- and Time-Dependent Study
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 24 ( 2022-12-15), p. 15947-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 24 ( 2022-12-15), p. 15947-
    Abstract: Cerebral palsy (CP) is defined as permanent disorders of movement and posture. Prematurity and hypoxia–ischemia (HI) are risk factors of CP, and boys display a greater vulnerability to develop CP. Magnesium sulfate (MgSO4) is administered to mothers at risk of preterm delivery as a neuroprotective agent. However, its effectiveness is only partial at long term. To prolong MgSO4 effects, it was combined with 4-phenylbutyrate (4-PBA). A mouse model of neonatal HI, generating lesions similar to those reported in preterms, was realized. At short term, at the behavioral and cellular levels, and in both sexes, the MgSO4/4-PBA association did not alter the total prevention induced by MgSO4 alone. At long term, the association extended the MgSO4 preventive effects on HI-induced motor and cognitive deficits. This might be sustained by the promotion of oligodendrocyte precursor differentiation after HI at short term, which led to improvement of white matter integrity at long term. Interestingly, at long term, at a behavioral level, sex-dependent responses to HI were observed. This might partly be explained by early sex-dependent pathological processes that occur after HI. Indeed, at short term, apoptosis through mitochondrial pathways seemed to be activated in females but not in males, and only the MgSO4/4-PBA association seemed to counter this apoptotic process.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232415947
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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