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Article ; Online: Doctors in Medical Data Sciences: A New Curriculum.

Cussat-Blanc, Sylvain / Castets-Renard, Céline / Monsarrat, Paul

International journal of environmental research and public health

2022 Volume 20, Issue 1

Abstract: Machine Learning (ML), a branch of Artificial Intelligence, which is competing with human experts in many specialized biomedical fields and will play an increasing role in precision medicine. As with any other technological advances in medicine, the keys ...

Abstract	Machine Learning (ML), a branch of Artificial Intelligence, which is competing with human experts in many specialized biomedical fields and will play an increasing role in precision medicine. As with any other technological advances in medicine, the keys to understanding must be integrated into practitioner training. To respond to this challenge, this viewpoint discusses some necessary changes in the health studies curriculum that could help practitioners to interpret decisions the made by a machine and question them in relation to the patient's medical context. The complexity of technology and the inherent criticality of its use in medicine also necessitate a new medical profession. To achieve this objective, this viewpoint will propose new medical practitioners with skills in both medicine and data science: the Doctor in Medical Data Sciences.
MeSH term(s)	Humans ; Data Science ; Artificial Intelligence ; Curriculum ; Technology ; Machine Learning
Language	English
Publishing date	2022-12-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph20010675
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Article ; Online: Shifting the landscape: Dominant C-terminal rare missense FOXL2 variants in non-syndromic primary ovarian failure etiology.

Clinical genetics

2024

Abstract: Pathogenic germline variants in the FOXL2 gene are associated with Blepharophimosis, Ptosis, and Epicanthus Inversus syndrome (BPES) in humans, an autosomal dominant condition. Two forms of BPES have emerged: (i) type I (BPES-I), characterized by ocular ... ...

Abstract	Pathogenic germline variants in the FOXL2 gene are associated with Blepharophimosis, Ptosis, and Epicanthus Inversus syndrome (BPES) in humans, an autosomal dominant condition. Two forms of BPES have emerged: (i) type I (BPES-I), characterized by ocular signs and primary ovarian failure (POI), and (ii) type II (BPES-II) with no systemic associations. This study aimed to compare the distribution of FOXL2 variants in idiopathic POI/DOR (diminished ovarian reserve) and both types of BPES, and to determine the involvement of FOXL2 in non-syndromic forms of POI/DOR. We studied the whole coding region of the FOXL2 gene using next-generation sequencing in 1282 patients with non-syndromic POI/DOR. Each identified FOXL2 variant was compared to its frequency in the general population, considering ethnicity. Screening of the entire coding region of the FOXL2 gene allowed us to identify 10 different variants, including nine missense variants. Of the patients with POI/DOR, 14 (1%) carried a FOXL2 variant. Significantly, six out of nine missense variants (67%) were overrepresented in our POI/DOR cohort compared to the general or specific ethnic subgroups. Our findings strongly suggest that five rare missense variants, mainly located in the C-terminal region of FOXL2 are high-risk factors for non-syndromic POI/DOR, though FOXL2 gene implication accounts for approximately 0.54% of non-syndromic POI/DOR cases. These results support the implementation of routine genetic screening for patients with POI/DOR in clinical settings.
Language	English
Publishing date	2024-04-01
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	221209-2
ISSN	1399-0004 ; 0009-9163
ISSN (online)	1399-0004
ISSN	0009-9163
DOI	10.1111/cge.14526
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Article ; Online: Covid-19 vaccine perceptions in Senegal and in Mali: a mixed approach

Fournier-Tombs, Eleonore / Diouf, Massamba / Maiga, Abdine / Faye, Sylvain / Ndoye, Tidiane / Haidara, Lalla / Batchily, Moussa / Castets-Renard, Celine

medRxiv

Abstract: This paper presents the results of two qualitative surveys in Senegal and in Mali, which include questions about hesitancy to the COVID-19 vaccine between April and June 2021. It took place within a larger 2-year research project involving researchers in ...

Abstract	This paper presents the results of two qualitative surveys in Senegal and in Mali, which include questions about hesitancy to the COVID-19 vaccine between April and June 2021. It took place within a larger 2-year research project involving researchers in Senegal, Mali and Canada which examines the uses of artificial intelligence technologies in the fight against COVID-19. The study involved 1000 respondents in Senegal and 555 in Mali. The researchers found that overall, 55% of respondents in Senegal and 52% of respondents in Mali did not plan to be vaccinated. Hesitancy was much higher in youth aged 15-35 in both cases, with 70% of youth in Senegal and 57% of youth in Mali not planning to be vaccinated, compared to only 42% of elderly in Senegal and 37% of elderly in Mali. The researchers did not find disparities between male and female respondents in Senegal but found some in Mali. They also found that those who had a member of the family with chronic disease (diabetes or hypertension) were slightly more likely to want to be vaccinated. Reasons for vaccine hesitancy fell in several categories, including fear of vaccine side-effects, disbelief in vaccine efficacy or usefulness, and general distrust in the public health system.
Keywords	covid19
Language	English
Publishing date	2021-10-07
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.10.06.21264664
Database	COVID19

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Article: Molecular mapping of the conductance activity linked to tAE1 expressed in Xenopus oocyte.

Borgese, Franck / Renard, Céline / Gabillat, Nicole / Pellissier, Bernard / Guizouarn, Hélène

Biochimica et biophysica acta

2004 Volume 1664, Issue 1, Page(s) 80–87

Abstract: It was previously shown that expressed in Xenopus oocyte the trout (tAE1) and the mouse (mAE1) anion exchangers behave differently: both elicit anion exchange activity but only tAE1 induces a transport of organic solutes correlated with an anion ... ...

Abstract	It was previously shown that expressed in Xenopus oocyte the trout (tAE1) and the mouse (mAE1) anion exchangers behave differently: both elicit anion exchange activity but only tAE1 induces a transport of organic solutes correlated with an anion conductance. In order to identify the structural domains involved in the induction of tAE1 channel activity, chimeras have been prepared between mouse and trout AE1. As some constructs were not expressed at the plasma membrane, skate exchanger (skAE1) was used instead of mouse exchanger to complete the structure-function analysis. The present paper shows that skAE1, highly similar to mAE1, does not induce a chloride conductance when expressed in Xenopus oocyte. Construct expression analysis showed that only tAE1 transmembrane domain is linked to the anion conductance. More precisely, we identified two regions composed of helices 6, 7 and 8 and putative helices 12 and 13 which are required for this function.
MeSH term(s)	Animals ; Anion Exchange Protein 1, Erythrocyte/chemistry ; Anion Exchange Protein 1, Erythrocyte/genetics ; Bicarbonates/chemistry ; Blotting, Western ; Cell Membrane/metabolism ; Chloride Channels/chemistry ; Electrophysiology/methods ; Mice ; Models, Biological ; Oocytes/metabolism ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA, Complementary/metabolism ; Recombinant Fusion Proteins/chemistry ; Structure-Activity Relationship ; Trout ; Xenopus laevis/metabolism
Chemical Substances	Anion Exchange Protein 1, Erythrocyte ; Bicarbonates ; Chloride Channels ; RNA, Complementary ; Recombinant Fusion Proteins
Language	English
Publishing date	2004-07-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbamem.2004.04.007
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Article: Rapid responses to steroid hormones: from frog skin to human colon. A homage to Hans Ussing.

Harvey, Brian J / Alzamora, Rodrigo / Healy, Vincent / Renard, Celine / Doolan, Christina M

Biochimica et biophysica acta

2002 Volume 1566, Issue 1-2, Page(s) 116–128

Abstract: Fifty years ago, Hans Ussing described the mechanism by which ions are actively transported across frog skin. Since then, an enormous amount of effort has been invested in determining the cellular and molecular specifics of the transport mechanisms and ... ...

Abstract	Fifty years ago, Hans Ussing described the mechanism by which ions are actively transported across frog skin. Since then, an enormous amount of effort has been invested in determining the cellular and molecular specifics of the transport mechanisms and their regulatory pathways. Ion transport in high-resistance epithelia is regulated by a variety of hormonal and non-hormonal factors. In vertebrates, steroid hormones such as mineralocorticoids, glucocorticoids and estrogens are major regulators of ion and water transport and hence are central to the control of extracellular fluid volume and blood pressure. Steroid hormones act through nuclear receptors to control the transcriptional activity of specific target genes, such as ion channels, ion transporters and ion pumps. These effects are observed after a latency of several hours and can last for days leading to cellular differentiation that allows a higher transport activity. This pathway is the so-called genomic phase. However, in the past 10 years, it has become apparent that steroid hormones can regulate electrolyte and water transport in tight epithelia independently of the transcription of these ion channels and transporters by regulating ion transporter activity in a non-genomic fashion via modulation of various signal transduction pathways. The molecular mechanisms underlying the steroid hormone-induced activation of signal transduction pathways such as protein kinase C (PKC), protein kinase A (PKA), intracellular calcium, intracellular pH and mitogen-activated protein kinases (MAPKs) and how non-genomic activation of these pathways influences epithelial ion transport will be discussed in this review.
MeSH term(s)	Animals ; Anura ; Chlorides/metabolism ; Colon/drug effects ; Colon/metabolism ; Enzyme Activation/drug effects ; Epithelium/drug effects ; Epithelium/metabolism ; Estrogens/pharmacology ; Glucocorticoids/pharmacology ; Hormones/pharmacology ; Humans ; Ion Transport/drug effects ; Mineralocorticoids/pharmacology ; Protein Kinase C/metabolism ; Sex Factors ; Signal Transduction/drug effects ; Skin/drug effects ; Skin/metabolism ; Sodium/metabolism ; Sodium-Hydrogen Exchangers/drug effects
Chemical Substances	Chlorides ; Estrogens ; Glucocorticoids ; Hormones ; Mineralocorticoids ; Sodium-Hydrogen Exchangers ; Sodium (9NEZ333N27) ; Protein Kinase C (EC 2.7.11.13)
Language	English
Publishing date	2002-09-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/s0005-2736(02)00589-8
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Article: Non-genomic convergent and divergent signalling of rapid responses to aldosterone and estradiol in mammalian colon.

Harvey, Brian J / Doolan, Christina M / Condliffe, Steven B / Renard, Celine / Alzamora, Rodrigo / Urbach, Valerie

Steroids

2002 Volume 67, Issue 6, Page(s) 483–491

Abstract: Studies from our laboratory have demonstrated rapid ( < 1 min) non-genomic activation of Na(+)-H(+) exchange, K(+) recycling, PKC activity and a PKC-dependent Ca(2+) entry through L-type Ca(2+) channels specifically by mineralocorticoids in distal colon. ...

Abstract	Studies from our laboratory have demonstrated rapid ( < 1 min) non-genomic activation of Na(+)-H(+) exchange, K(+) recycling, PKC activity and a PKC-dependent Ca(2+) entry through L-type Ca(2+) channels specifically by mineralocorticoids in distal colon. Aldosterone directly stimulates the activity of the PKC alpha isoform (but not PKC delta, PKC epsilon and PKC zeta) in a cell-free assay system containing only purified commercially available enzyme, appropriate substrate peptide, co-factors and lipid vesicles. The primary ion transport target of the non-genomic signal transduction cascade elicited by aldosterone in epithelia is the Na(+)-H(+) exchanger. In isolated colonic crypts, aldosterone produced a PKC alpha sensitive intracellular alkalinisation within 1 min of hormone addition. Intracellular alkalinisation upregulates an ATP-dependent K(+) channel, which is involved in K(+) recycling to maintain the electrical driving force for Na(+) absorption, while inhibiting a Ca(2+) -dependent K(+) channel, which generates the charge balance for Cl(-) secretion. The non-genomic response to aldosterone in distal colon appears to enhance the capacity for absorption while down-regulating the potential for secretion. We have also demonstrated rapid (< 1 min) non-genomic activation of Na(+)-H(+) exchange, K(+) recycling, PKC alpha activity, and a PKC delta- and PKA-dependent Ca(2+) entry through di-hydropyridine-blockable Ca(2+) channels specifically by 17beta-estradiol in distal colon. These rapid effects are female gender specific and are insensitive to inhibitors of the classical estrogen receptor (ER). 17 beta-Estradiol directly stimulated the activity of both PKC delta and PKC alpha (but not PKC epsilon or PKC zeta) in a cell-free assay system. E2 rapidly inhibited basolateral K(Ca) channel activity which would be expected to result in an acute inhibition of Cl(-) secretion. Physiological concentrations of E2 (0.1-10 nM) reduced both basal and secretagogue-induced Cl(-) secretion. This anti-secretory effect of E2 is sensitive to PKC inhibition, intracellular Ca(2+) chelation, and is female gender specific and insensitive to inhibitors of the classical ER. These observations link rapid non-genomic activation of second messengers with a rapid gender-specific physiological effect in the whole tissue. Aldosterone and E2 differ in their protein kinase signal transduction and both hormones stimulate specific PKC isoforms indicating both common and divergent signalling systems for salt-retaining steroid hormones. The physiological function of non-genomic effects of aldosterone and estradiol is to shift the balance from net secretion to net absorption in a pluripotential epithelium.
MeSH term(s)	Aldosterone/pharmacology ; Animals ; Calcium Channels/drug effects ; Calcium Channels/metabolism ; Colon/metabolism ; Enzyme Activation/drug effects ; Epithelium/metabolism ; Estradiol/pharmacology ; Female ; Humans ; Isoenzymes/metabolism ; Male ; Mammals ; Phospholipases A/metabolism ; Protein Kinase C/metabolism ; Protein Kinase C-alpha ; Rats ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Sodium-Hydrogen Exchangers/drug effects ; Sodium-Hydrogen Exchangers/metabolism
Chemical Substances	Calcium Channels ; Isoenzymes ; Sodium-Hydrogen Exchangers ; Aldosterone (4964P6T9RB) ; Estradiol (4TI98Z838E) ; PRKCA protein, human (EC 2.7.11.13) ; Protein Kinase C (EC 2.7.11.13) ; Protein Kinase C-alpha (EC 2.7.11.13) ; Phospholipases A (EC 3.1.1.32)
Language	English
Publishing date	2002-08-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80312-1
ISSN	1878-5867 ; 0039-128X
ISSN (online)	1878-5867
ISSN	0039-128X
DOI	10.1016/s0039-128x(01)00169-6
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Article: Effect of two new PBN-derived phosphorylated nitrones against postischaemic ventricular dysrhythmias.

Vergely, Catherine / Renard, Céline / Moreau, Daniel / Perrin- Sarrado, Caroline / Roubaud, Valérie / Tuccio, Béatrice / Rochette, Luc

Fundamental & clinical pharmacology

2003 Volume 17, Issue 4, Page(s) 433–442

Abstract: Spin traps might exert antioxidant cardioprotective effects during myocardial ischaemia-reperfusion where free radicals are thought to be responsible for the occurrence of reperfusion injury. The aim of our study was to investigate the effects of two new ...

Abstract	Spin traps might exert antioxidant cardioprotective effects during myocardial ischaemia-reperfusion where free radicals are thought to be responsible for the occurrence of reperfusion injury. The aim of our study was to investigate the effects of two new alpha-phenyl N-tert-butylnitrone (PBN)-derived beta-phosphorylated nitrones: 2-N-oxy-N-[benzylidène amino] diéthyl propyl-2-phosphate (PPN) and 1-diethoxyphosphoryl-1-methyl-N-[(1-oxido-pyridin-1-ium-4-yl) methylidene] ethylamine N-oxide (4-PyOPN) compared with PBN on (1) the evolution of cardiovascular parameters and (2) the postischaemic recovery. Anaesthetized rats were injected with 120 micro mol/kg of the nitrones or 14 micro mol/kg of amiodarone, used as a reference antidysrhythmic drug. Ischaemia was induced in vivo through ligation of the left anterior descending coronary artery for 5 min followed by 15 min of reperfusion after release. Cardiovascular parameters and occurrence of ventricular premature beats (VPB), ventricular tachycardia (VT) and fibrillation (VF) were recorded throughout the experiment. Under nonischaemic conditions, none of the three spin traps was shown to modify cardiovascular parameters during the 25-min measurement period. Solvent-treated (NaCl 0.9%) animals challenged with ischaemia-reperfusion exhibited 39 +/- 10 VPB, 156 +/- 39 s of VT and 60% mortality caused by sustained VF. Nitrones improved slightly postischaemic recovery, reducing the occurrence of VF and mortality to 33% whereas amiodarone injection totally suppressed rhythm disturbances and mortality. Our study has shown only limited antidysrhythmic cardioprotective effects of PBN-derived beta-phosphorylated nitrones during reperfusion after a regional myocardial ischaemia but also minor antioxidant properties of these spin trapping agents.
MeSH term(s)	Amiodarone/therapeutic use ; Animals ; Anti-Arrhythmia Agents/therapeutic use ; Arrhythmias, Cardiac/drug therapy ; Cyclic N-Oxides/therapeutic use ; Dose-Response Relationship, Drug ; Imines/therapeutic use ; Male ; Myocardial Reperfusion Injury/drug therapy ; Nitrogen Oxides/therapeutic use ; Organophosphonates/therapeutic use ; Rats ; Rats, Wistar
Chemical Substances	1-diethoxyphosphoryl-1-methyl-N-((1-oxidopyridin-1-ium-4-yl)methylidene)ethylamine N-oxide ; Anti-Arrhythmia Agents ; Cyclic N-Oxides ; Imines ; N-benzylidene-1-diethoxyphosphoryl-1-methylethylamine N-oxide ; Nitrogen Oxides ; Organophosphonates ; phenyl-N-tert-butylnitrone (3I91332OPG) ; Amiodarone (N3RQ532IUT)
Language	English
Publishing date	2003-12-02
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639134-5
ISSN	1472-8206 ; 0767-3981
ISSN (online)	1472-8206
ISSN	0767-3981
DOI	10.1046/j.1472-8206.2003.00158.x
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Article: Vitamin C deficiency exerts paradoxical cardiovascular effects in osteogenic disorder Shionogi (ODS) rats.

Vergely, Catherine / Goirand, Françoise / Ecarnot-Laubriet, Aline / Renard, Céline / Moreau, Daniel / Guilland, Jean-Claude / Dumas, Monique / Rochette, Luc

The Journal of nutrition

2003 Volume 134, Issue 4, Page(s) 729–735

Abstract: Vitamin C is considered to be a very efficient water-soluble antioxidant, for which several new cardiovascular properties were recently described. The aim of this study was to determine in vivo the effects of a severe depletion of vitamin C on cardiac ... ...

Abstract	Vitamin C is considered to be a very efficient water-soluble antioxidant, for which several new cardiovascular properties were recently described. The aim of this study was to determine in vivo the effects of a severe depletion of vitamin C on cardiac and vascular variables and reperfusion arrhythmias. For this purpose, we used a mutant strain of Wistar rats, osteogenic disorder Shionogi (ODS). After 15 d of consuming a vitamin C-deficient diet, ODS rats had a 90% decrease in plasma and tissue levels of ascorbate compared with ODS vitamin C-supplemented rats and normal Wistar rats. However, plasma antioxidant capacity, proteins, alpha-tocopherol, urate, catecholamines, lipids, and nitrate were not influenced by the vitamin C deficiency in ODS rats. Moreover, there was no difference between ODS vitamin C-deficient and -supplemented rats in heart rate and arterial pressure. After 5 min of an in vivo regional myocardial ischemia, various severe arrhythmias were observed, but their intensities were not modified by vitamin C in vitamin C-deficient ODS rats. The vascular reactivity, measured in vitro on thoracic arteries, was not altered by ascorbate deficiency in ODS rats. These unexpected results suggest that unidentified compensatory mechanisms play a role in maintaining normal cardiac function and vascular reactivity in vitamin C-deficient rats.
MeSH term(s)	Acetylcholine/pharmacology ; Animals ; Aorta ; Arrhythmias, Cardiac/etiology ; Ascorbic Acid/administration & dosage ; Ascorbic Acid Deficiency/complications ; Ascorbic Acid Deficiency/physiopathology ; Blood Pressure ; Bone Diseases/genetics ; Bone Diseases/physiopathology ; Cardiovascular Diseases/drug therapy ; Cardiovascular Diseases/etiology ; Diet ; Epinephrine/blood ; Heart Rate ; Male ; Muscle Contraction/drug effects ; Myocardial Ischemia/physiopathology ; Myocardial Reperfusion/adverse effects ; Norepinephrine/blood ; Osteogenesis ; Phenylephrine/pharmacology ; Rats ; Rats, Mutant Strains ; Rats, Wistar ; alpha-Tocopherol/blood
Chemical Substances	Phenylephrine (1WS297W6MV) ; alpha-Tocopherol (H4N855PNZ1) ; Acetylcholine (N9YNS0M02X) ; Ascorbic Acid (PQ6CK8PD0R) ; Norepinephrine (X4W3ENH1CV) ; Epinephrine (YKH834O4BH)
Language	English
Publishing date	2003-05-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.1093/jn/134.4.729
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