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Targeted therapy for capillary-venous malformations

Signal Transduction and Targeted Therapy 2024年第7期9卷 3024-3039页

作者： Lola Zerbib Sophia Ladraa Antoine Fraissenon Charles Bayard Marina Firpion Quitterie Venot Sanela Protic Clément Hoguin Amandine Thomas Sylvie Fraitag jean-paul Duong Sophie Kaltenbach Estelle Balducci Coline Lefevre Patrick Villarese Vahid Asnafi Christine Broissand Nicolas Goudin Ivan Nemazanyy Gwennhael Autret Bertrand Tavitian Christophe Legendre Nadia Arzouk Veronique Minard-Colin Caroline Chopinet Michael Dussiot Denise MAdams Tristan Mirault Laurent Guibaud paul Isenring Guillaume Canaud UniversitéParis Cité ParisFrance INSERM U1151 Institut Necker-Enfants MaladesParisFrance Service d’Imagerie Pédiatrique Hôpital Femme-Mère-EnfantHCLBronFrance CREATIS UMR 5220 Villeurbanne 69100France Service de Radiologie Mère-Enfant Hôpital NordSaint EtienneFrance Service d’Anatomie pathologique Hôpital Necker-Enfants MaladesAP-HPParisFrance Laboratoire d’Oncohématologie Hôpital Necker-Enfants MaladesAP-HPParisFrance Pharmacie Hôpital Necker-Enfants MaladesAP-HPParisFrance Necker Bio-Image Analysis INSERM US24/CNRS UMS 3633ParisFrance Platform for Metabolic Analyses Structure Fédérative de Recherche NeckerINSERM US24/CNRS UMS 3633ParisFrance Plateforme Imageries du Vivant Universitéde ParisPARCCINSERMParisFrance Service de Néphrologie Transplantation AdultesHôpital Necker-Enfants MaladesAP-HPParisFrance Service de Transplantation Hôpital La PitiéSalpétrièreAP-HPParisFrance Department of Pediatric and Adolescent Oncology INSERM 1015Gustave RoussyUniversitéParis-SaclayVillejuifFrance Service de Physiologie&Explorations Fonctionnelles Cardiovasculaires CHU de LilleLille 59000France INSERM U1163 Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic ImplicationsLaboratoire d’Excellence GR-ExParisFrance Division of Oncology Comprehensive Vascular Anomalies ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA Service de Médecine Vasculaire hôpital Européen Georges-PompidouParisFrance Nephrology Research Group L’Hôtel-Dieu de Québec Research CenterDepartment of MedicineFaculty of MedicineLaval UniversityQuebecQC G1R2J6Canada Unitéde médecine translationnelle et thérapies ciblées Hôpital Necker-Enfants MaladesAP-HPParisFrance CNRS UMR8253 Institut Necker-Enfants MaladesParisFrance

Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through *** malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening *** authorized medical treatment exists for patients with venous ***,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient *** showed that these malformations only partially signal through AKT *** compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse *** demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging *** these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous *** assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each *** demonstrated improvement in all 25 *** malformations previously considered intractable were reduced and clinical symptoms were *** showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on *** conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.

关键词： PIK3CA malformations venous

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Surgical Management of Lumbar Spinal Canal Stenosis with Instrumentation at the Yaounde Central Hospital: Comparison of Unilateral versus Bilateral Pedicle Screw Fixation Combined with Transforaminal Lumbar Interbody Fusion

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Open Journal of Modern Neurosurgery 2024年第3期14卷 179-189页

作者： Orlane Toto Ndome Nassourou Oumarou Haman Dimitri Fogue jean Bruno Ndoumou Ronaldo Fonju Anu Indira Baboke Vincent De paul Djientcheu Faculty of Medicine and Pharmaceutical Sciences University of Douala Douala Cameroon Department of Neurosurgery Douala General Hospital Douala Cameroon Faculty of Medicine and Biomedical Sciences University of Yaounde 1 Yaounde Cameroon Department of Neurosurgery Yaounde General and Central Hospitals Yaounde Cameroon Cameroon Academy of Young Scientists Yaounde Cameroon

Introduction: The choice of adopting unilateral pedicle screw fixation or using bilateral pedicle screw fixation in lumbar spinal stenosis remains controversial. In our context, very few studies have been performed comparing the clinical effectiveness of unilateral versus bilateral fixation in the surgical management of lumbar spinal canal stenosis. Objective: Evaluate the impact on quality of life and clinical efficacy of unilateral spondylodesis compared to bilateral spondylodesis in the surgical management of lumbar spinal canal stenosis at the Yaounde Central Hospital. Methods: This was a retrospective descriptive cross-sectional study for a period of 4 years, from June 2015 to June 2019. It involved all patients operated for lumbar canal stenosis and who underwent spondylodesis or spinal fusion at the neurosurgery department of the Yaounde Central Hospital. Results: A total of 68 participants were recruited during our study period. 32 (47%) of the study population were in the 50 - 60 age group, with a mean age of 56.98 years ranging from 41 to 75 years. Females, housewives and farmers were the most affected. In our study, 72% of patients had unilateral spondylodesis and 28% had bilateral fusion. Preoperatively, 71% of patients had insurmountable pain, refractory to medical treatment. At 3 months postoperatively, 73.7% of patients with bilateral setup had moderate pain compared to 69% of those with unilateral setup. At 6 months postoperatively, 79% of patients with bilateral fusion had mild pain compared to 82% of patients with unilateral setup. At 1 year postoperatively, all patients had mild pain. Preoperatively, 66.2% of patients were unable to walk and 19.1% of patients were bedridden according to the Oswestry score. At 3 months postoperatively, 10.2% of patients with unilateral setup were unable to walk compared to 10.5% of patients with bilateral fixation, while 67.3% of patients with unilateral fixation had moderate disability compared to 52.6% of patient

关键词： Lumbar Spinal Canal Stenosis Instrumentation Surgery Quality of Life

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Geospatial Analysis of Urban Heat Island Effects and Tree Equity

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Open Journal of Forestry 2024年第1期14卷 1-18页

作者： Jillian Gorrell Sharon R. jean-Philippe paul D. Ries Jennifer K. Richards Neelam C. Poudyal Rochelle Butler School of Natural Resources University of Tennessee 203 Third Creek Building Knoxville Tennessee USA

In recent decades, Urban Heat Island Effects have become more pronounced and more widely examined. Despite great technological advances, our current societies still experience great spatial disparity in urban forest access. Urban Heat Island Effects are measurable phenomenon that are being experienced by the world’s most urbanized areas, including increased summer high temperatures and lower evapotranspiration from having impervious surfaces instead of vegetation and trees. Tree canopy cover is our natural mitigation tool that absorbs sunlight for photosynthesis, protects humans from incoming radiation, and releases cooling moisture into the air. Unfortunately, urban areas typically have low levels of vegetation. Vulnerable urban communities are lower-income areas of inner cities with less access to heat protection like air conditioners. This study uses mean evapotranspiration levels to assess the variability of urban heat island effects across the state of Tennessee. Results show that increased developed land surface cover in Tennessee creates measurable changes in atmospheric evapotranspiration. As a result, the mean evapotranspiration levels in areas with less tree vegetation are significantly lower than the surrounding forested areas. Central areas of urban cities in Tennessee had lower mean evapotranspiration recordings than surrounding areas with less development. This work demonstrates the need for increased tree canopy coverage.

关键词： Spatial Analysis Land Cover Urban Heat Island Effect (UHIE) Evapotranspiration Tree Canopy Impervious Surface GIS Prediction Model GIS Machine Learning

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Multi-Elemental Analysis and 2D Image Mapping within Roots, Leaves and Seeds from O. glaberrima Rice Plants Using Micro-PIXE Technique

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World Journal of Nuclear Science and Technology 2024年第2期14卷 97-106页

作者： Alassane Traore Anna Ndiaye Christopher Bongani Mtshali Manneh Baboucarr jean paul Latyr Faye Daouda Mbodj Kandiaba Traore Tapha Gueye Ababacar Sadikhe Ndao Département de Physique Faculté des Sciences et Techniques Université Cheikh Anta Diop Dakar Senegal Département de Chimie Faculté des Sciences et Techniques Université Cheikh Anta Diop Dakar Senegal Tandetron Laboratory IBA Group iThemba LABS Cape Town South Africa Africa Rice Center St. Louis Senegal

Understanding metal accumulation at organ level in roots, leaves and seeds in O. glaberrima (OG) is crucial for improving physiological and metabolic aspects in growing Asian and African rice in salted areas. The micro-analytical imaging techniques are required to reveal its accumulation and distribution within plant tissues. PIXE studies have been performed to determine different elements in rice plants. The existing microbeam analytical technique at the iThemba LABS will be applied for the 2D image mapping of fresh rice tissues to perform a concentration of low atomic mass elements (such as Al, Si, P, S, Cl, Ca, Ti, Mn, Fe, Cu, Br, Zn and K) with detection limits of typically 1-10 μg/g. Comparison of the distribution of the elements between leaves, root and seed samples using uptake and distribution of elements in particular environmental conditions with potential amount of salt in water have been performed. We are also expecting to indicate metal exclusion as salt tolerance strategies from leaves, root, and seed compartments using matrix correlation between samples and between elements on rice species.

关键词： PIXE 2D Mapping Rice Concentration Elemental Analysis

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On the Contribution of Wu Wen-Tsün to Algebraic Topology

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Journal of Systems Science & Complexity 2019年第1期32卷 3-36页

作者： BRASSELET jean-paul I2M (CNRS)-Aix-Marseille University

The aim of this article is to present the contribution of Wu Wen-Tsün to Algebraic Topology and more precisely to the theory of characteristic classes. Several papers provide complete and welldocumented biography and academic career of Wu Wen-Tsün, in particular, Hudecek, 2014; O'Connor and Robertson, 2006; Wen-Tsün Wu's Academic Career, 2006; Selected works of Wen-Tsun Wu, *** author does not repeat the details provided in these papers concerning the Wu Wen-Tsün's bibliography, we will just mention people involved in the Wu Wen-Tsün's period in *** addition to Wu Wen-Tsün's papers, the Dieudonné's book(Dieudonné, 1960) provides an excellent presentation of main results of Wu Wen-Tsün in Algebraic and Differential Topology. The author will use and abuse of this book(and refer to) when *** the introduction, the author recalls mainly historical facts concerning the contribution of Wu Wen-Tsün to Algebraic Topology. The second section shows speci?cally the contribution of Wu WenTsün to the Stiefel-Whitney classes and introduces the third section, dealing with the(real) Wu *** author provides de?nition, properties as well as further developments and generalizations of the Wu classes. The fourth and ?fth sections are devoted to recent applications: In Cobordism theory and in Mathematical Physics. The author notices that Wu classes have been used as well in other domains,in particular surgery theory(Madsen and Milgram, 1979). The last section concerns the complex Wu classes and shows that the more recent Mather classes coincide with the previously de?ned complex Wu classes, that is a result from Zhou(1994)(see also Liu, 1996).This article is devoted to the contribution of Wu Wen-Tsün to the theory of Characteristic Classes,which coincides with his "French period"(1947–1951). However, speaking of Algebraic Topology, it is worthwhile to mention the important contribution of Wu Wen-Tsün to the Theory of realization of complexes or manifolds in Eucl

关键词： Algebraic topology characteristic class cobordism theory mathematical physics Wu Class

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Impact of Tension-Type Headaches in the Workplace in Brazzaville

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Neuroscience & Medicine 2024年第2期15卷 77-91页

作者： Happhia Dinah Boubayi Motoula Latou Josué Euberma Diatewa Ghislain Armel Mpandzou Prince Eliot Galieni Sounga Bandzouzi jean Brice Mouendenguia Karen Lise Obondzo Aloba paul Macaire Ossou-Nguiet Faculty of Health Sciences Universit Marien Ngouabi Brazzaville Congo Department of Neurology Brazzaville University Hospital Congo Department of Neurology Loandjili General Hospital Pointe-Noire Congo

Introduction: Tension-type headaches are the most widespread of the primary headache disorders. Due to their high prevalence, tension-type headaches represent a major public health problem with an enormous socio-economic burden. Determining their impact remains a challenge. Objective: To assess the impact of occupational tension-type headache in Brazzaville and identify associated factors. Population and Methods: This was an analytical case-control study conducted in public and private companies in the city of Brazzaville over a period of four (04) months. The case population consisted of cephalalgic employees;the control population was drawn from the same companies and was free of tension-type headaches. Study variables were divided into socio-professional, clinical and individual impact variables. Individual impact variables were represented by: the HIT-6 score, which incorporates a very broad conception of disability, covering several domains, namely: severity of pain during attacks and the restrictive and limiting nature of attacks. Results: Individual impact was severe in 18 (62.1%) men and 11 (37.9%) women. Mean age was 36.3 6.14 years for cases with severe impact. The mean duration of headache was 40.3 32.7 months for cases with severe impact. Tension headache evolved in attacks in 22 (75.9%) cases with severe impact, and continuously in seven (24.1%) cases. The average number of attacks per month was 2.52 1.04 for cases with severe impact. Cases with severe impact included 14 (48.3%) with chronic headache and 15 (51.7%) with episodic headache. Pain of severe intensity present in 48.3% of cases was associated with a severe impact of tension-type headache: OR = 151.66 [2.36 - 44245.95] and p-value = 0.037. At least one days absence from work per year was observed in 47.4% of our cases. The number of days off work per year due to tension-type headache had an interquartile range between 0 and 3 days and extremes from 0 to 14 days. It was the consequence of a sev

关键词： Impact Tension Headache Workplace

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Enhancing Precision in Radiotherapy Delivery: Validating Monte Carlo Simulation Models for 6 MV Elekta Synergy Agility LINAC Photon Beam Using Two Models of the GAMOS Code

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World Journal of Nuclear Science and Technology 2024年第2期14卷 146-163页

作者： Nogaye Ndiaye Oumar Ndiaye Papa Macoumba Faye Kodjo Joël Fabrice N’Guessan Djicknack Dione Khady Sy Moussa Hamady Sy jean paul Latyr Faye Alassane Traoré Ababacar Sadikhe Ndao Institute of Applied Nuclear Technology University Cheikh Anta Diop Dakar Senegal International Cancer Center of Dakar Dakar Senegal Department of Physics Faculty of Sciences and Technology University Cheikh Anta Diop Dakar Senegal

The most crucial requirement in radiation therapy treatment planning is a fast and accurate treatment planning system that minimizes damage to healthy tissues surrounding cancer cells. The use of Monte Carlo toolkits has become indispensable for research aimed at precisely determining the dose in radiotherapy. Among the numerous algorithms developed in recent years, the GAMOS code, which utilizes the Geant4 toolkit for Monte Carlo simula-tions, incorporates various electromagnetic physics models and multiple scattering models for simulating particle interactions with matter. This makes it a valuable tool for dose calculations in medical applications and throughout the patient’s volume. The aim of this present work aims to vali-date the GAMOS code for the simulation of a 6 MV photon-beam output from the Elekta Synergy Agility linear accelerator. The simulation involves mod-eling the major components of the accelerator head and the interactions of the radiation beam with a homogeneous water phantom and particle information was collected following the modeling of the phase space. This space was po-sitioned under the X and Y jaws, utilizing three electromagnetic physics mod-els of the GAMOS code: Standard, Penelope, and Low-Energy, along with three multiple scattering models: Goudsmit-Saunderson, Urban, and Wentzel-VI. The obtained phase space file was used as a particle source to simulate dose distributions (depth-dose and dose profile) for field sizes of 5 × 5 cm2 and 10 × 10 cm2 at depths of 10 cm and 20 cm in a water phantom, with a source-surface distance (SSD) of 90 cm from the target. We compared the three electromagnetic physics models and the three multiple scattering mod-els of the GAMOS code to experimental results. Validation of our results was performed using the gamma index, with an acceptability criterion of 3% for the dose difference (DD) and 3 mm for the distance-to-agreement (DTA). We achieved agreements of 94% and 96%, respective

关键词： GAMOS Monte Carlo LINAC Radiotherapy Dose Distribution Phase Space Gamma Index 6 MV Photon Beam

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Microbiota-host interplay at the gut epithelial level,health and nutrition

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Journal of Animal Science and Biotechnology 2017年第2期8卷 327-334页

作者： jean-paul Lallès Division of Human Nutrition Division INRA Clermont-Ferrand France Human Nutrition Research Center-West Nantes France

Growing evidence suggests the implication of the gut microbiota in various facets of health and disease. In this review, the focus is put on microbiota-host molecular cross-talk at the gut epithelial level with special emphasis on two defense systems： intestinal alkaline phosphatase（IAP） and inducible heat shock proteins（iHSPs）. Both IAP and iHSPs are induced by various microbial structural components（e.g. lipopolysaccharide, flagellin, CpG DNA motifs）,metabolites（e.g. n-butyrate） or secreted signal molecules（e.g., toxins, various peptides, polyphosphate）. IAP is produced in the small intestine and secreted into the lumen and in the interior milieu. It detoxifies microbial components by dephosphorylation and, therefore, down-regulates microbe-induced inflammation mainly by inhibiting NF-κB pro-inflammatory pathway in enterocytes. IAP gene expression and enzyme activity are influenced by the gut microbiota. Conversely, IAP controls gut microbiota composition both directly, and indirectly though the detoxification of pro-inflammatory free luminal adenosine triphosphate and inflammation inhibition. Inducible HSPs are expressed by gut epithelial cells in proportion to the microbial load along the gastro-intestinal tract. They are also induced by various microbial components, metabolites and secreted molecules. Whether iHSPs contribute to shape the gut microbiota is presently unknown. Both systems display strong anti-inflammatory and anti-oxidant properties that are protective to the gut and the host. Importantly, epithelial gene expressions and protein concentrations of IAP and iHSPs can be stimulated by probiotics, prebiotics and a large variety of dietary components, including macronutrients（protein and amino acids, especially L-glutamine, fat, fiber）, and specific minerals（e.g. calcium）and vitamins（e.g. vitamins K1 and K2）. Some food components（e.g. lectins, soybean proteins, various polyphenols） may inhibit or disturb these systems. The general cel ular and molecula

关键词： Diet Gut Inducible heat shock protein Inflammation Intestinal alkaline phosphatase Microbiota

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Acceptance and Experience of HIV-Infected Adolescents in Two Hospitals in Yaoundé

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Open Journal of Pediatrics 2024年第2期14卷 435-443页

作者： Isabelle Mekone Nkwele Nelly Kamgaing Pierrette Amanda Emah Manga jeannette Épée Ngoué Hélène Kamo Sélangai Claude Audrey Meguieze Nsoh Ndeh-Fofang Serge Tchoukoua jean-Baptiste Fotso Djemo paul Koki Ndombo Department of Pediatrics Faculty of Medicine and Biomedical Sciences University of Yaoundé I Yaoundé Cameroon Institut Supérieur des Sciences de la Santé de Bangangté Université des Montagnes Bangangté Cameroon Faculty of Medicine and Biomedical Sciences University of Garoua Garoua Cameroon

Introduction: Access to antiretroviral drugs has improved the survival of children infected with the Human Immunodeficiency Virus (HIV). As they reach adolescence, they are confronted with various constraints related to the infection and its treatment, in addition to those of the growth period they are going through. The main aim of the study was to assess the acceptance and describe the experience of HIV infection by infected adolescents but also to investigate the factors associated with good acceptance and a positive experience. Methodology: The cross-sectional analytic study concerned HIV-infected adolescents aged 15 to 19 followed up at the Chantal Biya Foundation-Mother and Child Centre (CME-FCB) and the Yaoundé University Hospital Centre (CHUY) between February 2020 and June 2020. The study saw participants complete a questionnaire containing socio-demographic data and assessing acceptance and experience with the infection. Data analysis was accomplished using Epi info software version 7.***.2.6. Results: One hundred and thirteen HIV-infected adolescents were included in the study. The sex ratio was 0.68 and the mean age was 17 years. More than half of the adolescents had a good acceptance and positive experience with the infection. Related factors were the adolescent’s perception of good health and participation in an association with other infected adolescents. Conclusion: Emphasizing the psychological and educational follow-up of infected adolescents and encouraging their participation in associations for adolescents living with HIV could reduce the consequences of poor acceptance and ensure a better transition to adulthood. .

关键词： HIV Adolescent Acceptance Experience

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Single-particle cryo-EM: beyond the resolution

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National Science Review 2019年第5期6卷 864-866页

作者： jean-paul Armache Yifan Cheng Department of Biochemistry and Molecular Biology and the Huck Institutes of the Life Sciences Pennsylvania State University Howard Hughes Medical Institute University of California San Francisco Department of Biochemistry and Biophysics University of California San Francisco

Structural biology aims to provide structural insights into our understandings of biological processes at the atomic *** structures of biological macromolecules are often determinedby one of the three major methods:Xr... 详细信息

关键词： Single-particle cryo-EM beyond the resolution

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