102 results on '"Colas C."'
Search Results
2. Proyecto INCLIASMA - inercia clínica en asma
- Author
-
Trillo-Calvo, E., Colás, C., and Vera, E.
- Published
- 2022
- Full Text
- View/download PDF
3. The physical activity experience of prostate cancer patients: a multicentre peer motivation monitoring feasibility study. The Acti-Pair study
- Author
-
Baudot, A., Barth, N., Colas, C., Garros, M., Garcin, A., Oriol, M., Roche, F., Chauvin, F., Mottet, N., and Hupin, D.
- Published
- 2022
- Full Text
- View/download PDF
4. Cancer risks by sex and variant type in PTEN hamartoma tumor syndrome.
- Author
-
Hendricks, L.A.J., Hoogerbrugge, N., Mensenkamp, A.R., Brunet, J., Lleuger-Pujol, R., Høberg-Vetti, H., Tveit Haavind, M., Innella, G., Turchetti, D., Aretz, S., Spier, I., Tischkowitz, M., Jahn, A., Links, T.P., Olderode-Berends, M.J., Blatnik, A., Leter, E.M., Evans, D.G., Woodward, E.R., Steinke-Lange, V., Anastasiadou, V.C., Colas, C., Villy, M.C., Benusiglio, P.R., Gerasimenko, A., Barili, V., Branchaud, M., Houdayer, C., Tesi, B., Yazicioglu, M.O., Post, R.S. van der, Schuurs-Hoeijmakers, J.H.M., Vos, J.R., Hendricks, L.A.J., Hoogerbrugge, N., Mensenkamp, A.R., Brunet, J., Lleuger-Pujol, R., Høberg-Vetti, H., Tveit Haavind, M., Innella, G., Turchetti, D., Aretz, S., Spier, I., Tischkowitz, M., Jahn, A., Links, T.P., Olderode-Berends, M.J., Blatnik, A., Leter, E.M., Evans, D.G., Woodward, E.R., Steinke-Lange, V., Anastasiadou, V.C., Colas, C., Villy, M.C., Benusiglio, P.R., Gerasimenko, A., Barili, V., Branchaud, M., Houdayer, C., Tesi, B., Yazicioglu, M.O., Post, R.S. van der, Schuurs-Hoeijmakers, J.H.M., and Vos, J.R.
- Abstract
Item does not contain fulltext, BACKGROUND: PTEN Hamartoma Tumor Syndrome (PHTS) is a rare syndrome with a broad phenotypic spectrum, including increased risks of breast (BC, 67%-78% at age 60 years), endometrial (EC, 19%-28%), and thyroid cancer (TC, 6%-38%). Current risks are likely overestimated due to ascertainment bias. We aimed to provide more accurate and personalized cancer risks. METHODS: This was a European, adult PHTS cohort study with data from medical files, registries, and/or questionnaires. Cancer risks and hazard ratios were assessed with Kaplan-Meier and Cox regression analyses, and standardized incidence ratios were calculated. Bias correction consisted of excluding cancer index cases and incident case analyses. RESULTS: A total of 455 patients were included, including 50.5% index cases, 372 with prospective follow-up (median 6 years, interquartile range = 3-10 years), and 159 of 281 females and 39 of 174 males with cancer. By age 60 years, PHTS-related cancer risk was higher in females (68.4% to 86.3%) than males (16.4% to 20.8%). Female BC risks ranged from 54.3% (95% confidence interval [CI] = 43.0% to 66.4%) to 75.8% (95% CI = 60.7% to 88.4%), with two- to threefold increased risks for PTEN truncating and approximately twofold for phosphatase domain variants. EC risks ranged from 6.4% (95% CI = 2.1% to 18.6%) to 22.1% (95% CI = 11.6% to 39.6%) and TC risks from 8.9% (95% CI = 5.1% to 15.3%) to 20.5% (95% CI = 11.3% to 35.4%). Colorectal cancer, renal cancer, and melanoma risks were each less than 10.0%. CONCLUSIONS: Females have a different BC risk depending on their PTEN germline variant. PHTS patients are predominantly at risk of BC (females), EC, and TC. This should be the main focus of surveillance. These lower, more unbiased and personalized risks provide guidance for optimized cancer risk management.
- Published
- 2023
5. High yield of surveillance in patients diagnosed with constitutional mismatch repair deficiency
- Author
-
Ghorbanoghli, Z., Kouwen, M.C.A. van, Versluys, B., Bonnet, D., Devalck, C., Tinat, J., Januszkiewicz-Lewandowska, D., Costas, C.C., Cottereau, E., Hardwick, J.C.H., Wimmer, K., Brugieres, L., Colas, C., Vasen, H.F.A., Ghorbanoghli, Z., Kouwen, M.C.A. van, Versluys, B., Bonnet, D., Devalck, C., Tinat, J., Januszkiewicz-Lewandowska, D., Costas, C.C., Cottereau, E., Hardwick, J.C.H., Wimmer, K., Brugieres, L., Colas, C., and Vasen, H.F.A.
- Abstract
Contains fulltext : 294692.pdf (Publisher’s version ) (Closed access), BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessively inherited syndrome that is caused by biallelic pathogenic variants of the mismatch repair genes. It is characterised by the development of multiple tumours in the first and second decade of life including brain, gastrointestinal and haematological tumours often resulting in early death. In order to improve the prognosis of these patients, the European collaborative group 'care for CMMRD' developed a surveillance programme in 2014 and established a registry of patients with CMMRD in Paris. The aim of the study was to evaluate the outcome of this programme. METHODS: Twenty-two patients with a definitive diagnosis of CMMRD and with at least one follow-up study were selected from the registry. Medical data on the outcome of surveillance were collected from these patients. RESULTS: During a mean follow-up of 4 years, the programme detected eight malignant tumours including three brain tumours, three upper gastrointestinal cancers and two colorectal cancers. Most tumours could successfully be treated. In addition, many adenomas were detected in the duodenum, and colorectum and subsequently removed. Seven patients developed a symptomatic malignancy, including two brain tumours, one small bowel cancer and four haematological malignancies. At the end of the follow-up, 16 out of 22 patients (73%) who participated in the surveillance programme were still alive. CONCLUSION: The study suggests a beneficial effect of surveillance of the digestive tract and brains.
- Published
- 2023
6. The Frequency of Germline BRCA and Non-BRCA HR-Gene-Variants in a Cohort of Pancreatic Cancer Patients
- Author
-
Baz, M., primary, Gondran-Teiller, V., additional, Bressac, B., additional, Cabaret, O., additional, Fievet, A., additional, Dimaria, M., additional, Goldbarg, V., additional, Colas, C., additional, Bonnet-Dupeyron, M. N., additional, Tinat, J., additional, Lebrun, M., additional, Mari, V., additional, Limacher, J. M., additional, Corsini, C., additional, Ginglinger, E., additional, Saurin, J. C., additional, Brahimi, A., additional, Rouzier, C., additional, Giraud, S., additional, Schuster, H., additional, Hollebecque, A., additional, Boige, V., additional, Cauchin, E., additional, Malka, D., additional, Caron, O., additional, and Rouleau, E., additional
- Published
- 2022
- Full Text
- View/download PDF
7. Bio-inspired films of crystalline calcium carbonate: 2D patterning by surface-driven liquid–liquid phase separation and hybrid amorphous-to-crystal transformation
- Author
-
Colas, C., primary, Grunewald, T., additional, Gobeaux, F., additional, Campos, A., additional, Burghammer, M., additional, Baroni, A., additional, Ferrand, P., additional, Chamard, V., additional, and Chevallard, C., additional
- Published
- 2022
- Full Text
- View/download PDF
8. Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants
- Author
-
Li, S, Silvestri, V, Leslie, G, Rebbeck, TR, Neuhausen, SL, Hopper, JL, Nielsen, HR, Lee, A, Yang, X, McGuffog, L, Parsons, MT, Andrulis, IL, Arnold, N, Belotti, M, Borg, A, Buecher, B, Buys, SS, Caputo, SM, Chung, WK, Colas, C, Colonna, S, Cook, J, Daly, MB, de la Hoya, M, de Pauw, A, Delhomelle, H, Eason, J, Engel, C, Evans, DG, Faust, U, Fehm, TN, Fostira, F, Fountzilas, G, Frone, M, Garcia-Barberan, V, Garre, P, Gauthier-Villars, M, Gehrig, A, Glendon, G, Goldgar, DE, Golmard, L, Greene, MH, Hahnen, E, Hamann, U, Hanson, H, Hassan, T, Hentschel, J, Horvath, J, Izatt, L, Janavicius, R, Jiao, Y, John, EM, Karlan, BY, Kim, S-W, Konstantopoulou, I, Kwong, A, Lauge, A, Lee, JW, Lesueur, F, Mebirouk, N, Meindl, A, Mouret-Fourme, E, Musgrave, H, Yie, JNY, Niederacher, D, Park, SK, Pedersen, IS, Ramser, J, Ramus, SJ, Rantala, J, Rashid, MU, Reichl, F, Ritter, J, Rump, A, Santamarina, M, Saule, C, Schmidt, G, Schmutzler, RK, Senter, L, Shariff, S, Singer, CF, Southey, MC, Stoppa-Lyonnet, D, Sutter, C, Tan, Y, Teo, SH, Terry, MB, Thomassen, M, Tischkowitz, M, Toland, AE, Torres, D, Vega, A, Wagner, SA, Wang-Gohrke, S, Wappenschmidt, B, Weber, BHF, Yannoukakos, D, Spurdle, AB, Easton, DF, Chenevix-Trench, G, Ottini, L, Antoniou, AC, Li, S, Silvestri, V, Leslie, G, Rebbeck, TR, Neuhausen, SL, Hopper, JL, Nielsen, HR, Lee, A, Yang, X, McGuffog, L, Parsons, MT, Andrulis, IL, Arnold, N, Belotti, M, Borg, A, Buecher, B, Buys, SS, Caputo, SM, Chung, WK, Colas, C, Colonna, S, Cook, J, Daly, MB, de la Hoya, M, de Pauw, A, Delhomelle, H, Eason, J, Engel, C, Evans, DG, Faust, U, Fehm, TN, Fostira, F, Fountzilas, G, Frone, M, Garcia-Barberan, V, Garre, P, Gauthier-Villars, M, Gehrig, A, Glendon, G, Goldgar, DE, Golmard, L, Greene, MH, Hahnen, E, Hamann, U, Hanson, H, Hassan, T, Hentschel, J, Horvath, J, Izatt, L, Janavicius, R, Jiao, Y, John, EM, Karlan, BY, Kim, S-W, Konstantopoulou, I, Kwong, A, Lauge, A, Lee, JW, Lesueur, F, Mebirouk, N, Meindl, A, Mouret-Fourme, E, Musgrave, H, Yie, JNY, Niederacher, D, Park, SK, Pedersen, IS, Ramser, J, Ramus, SJ, Rantala, J, Rashid, MU, Reichl, F, Ritter, J, Rump, A, Santamarina, M, Saule, C, Schmidt, G, Schmutzler, RK, Senter, L, Shariff, S, Singer, CF, Southey, MC, Stoppa-Lyonnet, D, Sutter, C, Tan, Y, Teo, SH, Terry, MB, Thomassen, M, Tischkowitz, M, Toland, AE, Torres, D, Vega, A, Wagner, SA, Wang-Gohrke, S, Wappenschmidt, B, Weber, BHF, Yannoukakos, D, Spurdle, AB, Easton, DF, Chenevix-Trench, G, Ottini, L, and Antoniou, AC
- Abstract
PURPOSE: To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management. METHODS: We used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment. RESULTS: BRCA1 PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers. CONCLUSION: In addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs.
- Published
- 2022
9. Additional file 1 of The physical activity experience of prostate cancer patients: a multicentre peer motivation monitoring feasibility study. The Acti-Pair study
- Author
-
Baudot, A., Barth, N., Colas, C., Garros, M., Garcin, A., Oriol, M., Roche, F., Chauvin, F., Mottet, N., and Hupin, D.
- Subjects
Data_FILES - Abstract
Additional file 1. Interview Guide for peers.
- Published
- 2022
- Full Text
- View/download PDF
10. 18P The role of CTNNA1 truncating variants in hereditary diffuse gastric cancer (HDGC).
- Author
-
Lobo, S., Dias, A., Ferreira, M., Herrera-Mullar, J., Svrcek, M., Hueneburg, R., Moreira, L., Tinschert, S., Boussemart, L., Balmaña, J., Strong, V., Lazaro, C., Katona, B., Colas, C., Coulet, F., Karam, R., Pereira, P.S., Benusiglio, P.R., and Oliveira, C.
- Subjects
- *
STOMACH cancer - Published
- 2024
- Full Text
- View/download PDF
11. Comprehensive analysis of constitutional mismatch repair deficiency-associated non-Hodgkin lymphomas in a global cohort.
- Author
-
Rigaud C, Forster VJ, Al-Tarrah H, Attarbaschi A, Bianchi V, Burke A, Burkhardt B, Colas C, Devalck C, Edwards M, Elitzur S, Garthe AK, Goldberg Y, Guerrini-Rousseau L, Horpaopan S, Januszkiewicz-Lewandowska D, Kabíčková E, Kratz CP, Loeffen J, Pérez-Alonso V, Pineda M, Minard-Colin V, Rueda D, Ruiz-Ponte C, Trinquand A, Uyttebroeck A, Wimmer K, Auperin A, Tabori U, and Brugieres L
- Abstract
Background: Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare childhood cancer predisposition syndrome associated with a broad spectrum of malignancies, including non-Hodgkin lymphomas (NHL). Most patients die due to cancer before the age of 20 years. Limited data exist on CMMRD-associated lymphomas and their outcome., Methods: We conducted a retrospective study including all CMMRD-associated NHL patients registered before 2020 in the European and North American databases or reported by members of the European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL). Events considered to define event-free survival included relapse/progression, second malignancy (SML), or death, whichever occurred first., Findings: The analysis included 74 patients, with 20 having multiple metachronous NHL. The median age at diagnosis was 9.4 years. Previous malignancies were reported in 36% of the patients, café au lait spots in 96%, and consanguinity in 54%. The initial lymphoma subtypes were 53 T-cell lymphoblastic lymphomas (T-LBL), four B-lymphoblastic lymphomas, and 17 mature B-cell non-Hodgkin lymphoma (B-NHL). All patients were treated with curative intent, with current chemotherapy regimens adapted to their subtype. The median follow-up was 8.7 years. After the first lymphoma, the 5-year event-free and overall survival rates were, respectively, 23.5% [95% confidence interval (CI): 14.9-35.1] and 61.5% [95% CI: 49.6-72.1]. The 5-year cumulative risk of progression/relapse, SML or death as a first event was 20.8%, 52.9%, and 2.7%., Interpretation: Standard treatments for sporadic NHL are effective in most CMMRD-associated NHL cases, but multiple malignancies, including lymphomas, impair prognosis. Future strategies should evaluate the potential of less genotoxic therapies, including immunotherapy, in preventing SMLs while maintaining effective control of NHL., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)
- Published
- 2024
- Full Text
- View/download PDF
12. Enhancement of Forskolin Production Using Aeroponic Cultivation of Coleus forskohlii and the Impact on the Plant Phytochemistry.
- Author
-
Le Cabec A, Campos PE, Yzebe O, Pelé R, Colas C, and Destandau E
- Subjects
- Phytochemicals chemistry, Plant Extracts chemistry, Chromatography, High Pressure Liquid, Coleus chemistry, Coleus metabolism, Coleus growth & development, Colforsin metabolism, Plectranthus chemistry, Plectranthus metabolism, Plant Roots chemistry, Plant Roots metabolism
- Abstract
Accessing plant resources to extract compounds of interest can sometimes be challenging. To facilitate access and limit the environmental impact, innovative cultivation strategies can be developed. Forskolin is a molecule of high interest, mainly found in the roots of Coleus forskohlii . The aim of this study was to develop aeroponic cultivation methods to provide a local source of Coleus forskohlii and to study the impact of abiotic stress on forskolin and bioactive metabolite production. Three cultivation itineraries (LED lighting, biostimulant, and hydric stress) along with a control itinerary were established. The forskolin content in the plant roots was quantified using HPLC-ELSD, and the results showed that LED treatment proved to be the most promising, increasing root biomass and the total forskolin content recovered at the end of the cultivation period threefold (710.1 ± 21.3 mg vs. 229.9 ± 17.7 mg). Statistical analysis comparing the LED itinerary to the control itinerary identified stress-affected metabolites, showing that LEDs positively influence mainly the concentration of phenolic compounds in the roots and diterpenes in the aerial parts of Coleus forskohlii. Moreover, to better define the phytochemical composition of Coleus forskohlii cultivated in France using aeroponic cultivation, an untargeted metabolomic analysis was conducted using UHPLC-HRMS/MS analysis and molecular networks on both the root and aerial parts. This study demonstrates that aeroponic cultivation, especially with the application of an LED treatment, could be a very promising alternative for a local source of Coleus forskohlii leading to easy access to the roots and aerial parts rich in forskolin and other bioactive compounds.
- Published
- 2024
- Full Text
- View/download PDF
13. Discovery of Potent STT3A/B Inhibitors and Assessment of Their Multipathogen Antiviral Potential and Safety.
- Author
-
Pero JE, Mueller EA, Adams AM, Adolph RS, Bagchi P, Balce D, Bantscheff M, Barauskas O, Bartha I, Bohan D, Cai H, Carabajal E, Cassidy J, Cato M, Chaudhary KW, Chen D, Chen YP, Colas C, Darwech I, Eberl HC, Fernandez B, Gordon E, Grosse J, Hansen J, Hetzler B, Hwang S, Jeyasingh S, Kowalski B, Lehmann S, Lo G, McAllaster M, McHugh C, Momont C, Newby Z, Nigro M, Oladunni F, Pannirselvam M, Park A, Pearson N, Peat AJ, Plastridge B, Ranjan R, Safabakhsh P, Shapiro ND, Soriaga L, Stokes N, Sweeney D, Talecki L, Telenti A, Terrell A, Tse W, Wang L, Wang S, Wedel L, Werner T, Dalmas Wilk D, Yim S, and Zhou J
- Subjects
- Humans, Animals, Drug Discovery, COVID-19 Drug Treatment, Glycosylation, Rats, Hexosyltransferases, Antiviral Agents pharmacology, Antiviral Agents chemistry, SARS-CoV-2 drug effects, Membrane Proteins antagonists & inhibitors, Membrane Proteins metabolism, Sialyltransferases antagonists & inhibitors, Sialyltransferases metabolism
- Abstract
In the aftermath of the COVID-19 pandemic, opportunities to modulate biological pathways common to the lifecycles of viruses need to be carefully considered. N -linked glycosylation in humans is mediated exclusively by the oligosaccharyltransferase complex and is frequently hijacked by viruses to facilitate infection. As such, STT3A/B, the catalytic domain of the OST complex, became an intriguing drug target with broad-spectrum antiviral potential. However, due to the critical role N -linked glycosylation plays in a number of fundamental human processes, the toxicological ramifications of STT3A/B inhibition required attention commensurate to that given to antiviral efficacy. Herein, we describe how known STT3A/B inhibitor NGI-1 inspired the discovery of superior tool compounds which were evaluated in in vitro efficacy and translational safety (e.g., CNS, cardiovascular, liver) studies. The described learnings will appeal to those interested in the therapeutic utility of modulating N -linked glycosylation as well as the broader scientific community.
- Published
- 2024
- Full Text
- View/download PDF
14. Genetic counselling legislation and practice in cancer in EU Member States.
- Author
-
McCrary JM, Van Valckenborgh E, Poirel HA, de Putter R, van Rooij J, Horgan D, Dierks ML, Antonova O, Brunet J, Chirita-Emandi A, Colas C, Dalmas M, Ehrencrona H, Grima C, Janavičius R, Klink B, Koczok K, Krajc M, Lace B, Leitsalu L, Mistrik M, Paneque M, Primorac D, Roetzer KM, Ronez J, Slámová L, Spanou E, Stamatopoulos K, Stoklosa T, Strang-Karlsson S, Szakszon K, Szczałuba K, Turner J, van Dooren MF, van Zelst-Stams WAG, Vassallo LM, Wadt KAW, Žigman T, Ripperger T, Genuardi M, Van den Bulcke M, and Bergmann AK
- Subjects
- Humans, Genetic Testing legislation & jurisprudence, European Union, Genetic Counseling legislation & jurisprudence, Neoplasms genetics
- Abstract
Background: Somatic and germline genetic alterations are significant drivers of cancer. Increasing integration of new technologies which profile these alterations requires timely, equitable and high-quality genetic counselling to facilitate accurate diagnoses and informed decision-making by patients and their families in preventive and clinical settings. This article aims to provide an overview of genetic counselling legislation and practice across European Union (EU) Member States to serve as a foundation for future European recommendations and action., Methods: National legislative databases of all 27 Member States were searched using terms relevant to genetic counselling, translated as appropriate. Interviews with relevant experts from each Member State were conducted to validate legislative search results and provide detailed insights into genetic counselling practice in each country., Results: Genetic counselling is included in national legislative documents of 22 of 27 Member States, with substantial variation in legal mechanisms and prescribed details (i.e. the 'who, what, when and where' of counselling). Practice is similarly varied. Workforce capacity (25 of 27 Member States) and genetic literacy (all Member States) were common reported barriers. Recognition and/or better integration of genetic counsellors and updated legislation and were most commonly noted as the 'most important change' which would improve practice., Conclusions: This review highlights substantial variability in genetic counselling across EU Member States, as well as common barriers notwithstanding this variation. Future recommendations and action should focus on addressing literacy and capacity challenges through legislative, regulatory and/or strategic approaches at EU, national, regional and/or local levels., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)
- Published
- 2024
- Full Text
- View/download PDF
15. Report of the sixth meeting of the European Consortium 'Care for CMMRD' (C 4 CMMRD), Paris, France, November 16th 2022.
- Author
-
Guerrini-Rousseau L, Gallon R, Pineda M, Brugières L, Baert-Desurmont S, Corsini C, Dangouloff-Ros V, Gorris MAJ, Haberler C, Hoarau P, Jongmans MC, Kloor M, Loeffen J, Rigaud C, Robbe J, Vibert R, Weijers D, Wimmer K, and Colas C
- Abstract
Biallelic germline pathogenic variants in one of the four mismatch repair genes (MSH2, MSH6, MLH1 and PMS2) cause a very rare, highly penetrant, childhood-onset cancer syndrome, called constitutional mismatch repair deficiency (CMMRD). The European consortium "Care for CMMRD" (C4CMMRD) was founded in Paris in 2013 to facilitate international collaboration and improve our knowledge of this rare cancer predisposition syndrome. Following initial publications on diagnostic criteria and surveillance guidelines for CMMRD, several partners collaborating within the C4CMMRD consortium have worked on and published numerous CMMRD-related clinical and biological projects. Since its formation, the C4CMMRD consortium held meetings every 1-2 years (except in 2020 and 2021 due to the Covid 19 pandemic). The sixth C4CMMRD meeting was held in Paris in November 2022, and brought together 42 participants from nine countries involved in various fields of CMMRD healthcare. The aim was to update members on the latest results and developments from ongoing research, and to discuss and initiate new study proposals. As previously done for the fifth meeting of the C4CMMRD group, this report summarizes data presented at this meeting., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
16. Oil/Water Biphasic Solvent System for the Eco-Extraction and Cosmetic Formulation of Bixa orellana L.
- Author
-
Chambaud M, Fournier A, De Saint Jores C, Caux B, Colas C, and Destandau E
- Abstract
Annatto, obtained from the seeds of achiote ( Bixa orellana L.), is a widely used orange pigment rich in bixin and other apocarotenoids. This work reports the optimisation of a green extraction method of pigments and antioxidant compounds from achiote as well as its integration in a one-step green extraction-cosmetic formulation process. A biphasic solvent system of water and oil was used to recover simultaneously polar polyphenols, and less polar compounds, such as δ-tocotrienol and bixin. The optimisation of the ultrasound assisted extraction is presented, as well as a comparison of different vegetable oils used as extraction solvents. The composition, physicochemical properties and antioxidant activity of the oils were studied and their extraction performance was compared. Refined sunflower oil proved to be a better solvent than virgin olive, jojoba, coconut and grapeseed oils. Both aqueous and oil phases displayed an interesting antioxidant capacity. The oil phase contained 0.9% of bixin, as well as minor apocarotenoids and δ-tocotrienol. Twelve compounds, mainly phenolics, were identified by UHPLC-DAD-HRMS/MS in the aqueous phase. Twenty-one volatile compounds were identified in the volatile fraction by SPME-GC-MS. Lastly, a one-step green process is proposed to combine the extraction and the cosmetic formulation of the bioactive compounds.
- Published
- 2024
- Full Text
- View/download PDF
17. Glioma oncogenesis in the Constitutional mismatch repair deficiency (CMMRD) syndrome.
- Author
-
Guerrini-Rousseau L, Merlevede J, Denizeau P, Andreiuolo F, Varlet P, Puget S, Beccaria K, Blauwblomme T, Cabaret O, Hamzaoui N, Bourdeaut F, Faure-Conter C, Muleris M, Colas C, Adam de Beaumais T, Castel D, Rouleau E, Brugières L, Grill J, and Debily MA
- Abstract
Background: Constitutional mismatch repair deficiency (CMMRD) is a cancer predisposition due to biallelic mutations in one of the mismatch repair (MMR) genes associated with early onset of cancers, especially high-grade gliomas. Our aim was to decipher the molecular specificities of these gliomas., Methods: Clinical, histopathological, and whole exome sequencing data were analyzed in 12 children with genetically proven CMMRD and a high-grade glioma., Results: PDL1 expression was present in immunohistochemistry in 50% of the samples. In 9 patients, the glioma harbored an ultra-hypermutated phenotype (104-635 coding single nucleotide variants (SNV) per Mb, median 204). Driver mutations in POLE and POLD1 exonuclease domains were described for 8 and 1 patients respectively and were always present in the mutation burst with the highest variant allele frequency (VAF). The mutational signatures were dominated by MMR-related ones and similar in the different mutation bursts of a same patient without subsequent enrichment of the mutation signatures with POL-driven ones. Median number of coding SNV with VAF above one of the driving polymerase mutation per Mb was 57 (17-191). Our findings suggest that somatic polymerase alterations does not entirely explain the ultra-hypermutant phenotype. SETD2 , TP53 , NF1 , EPHB2 , PRKDC, and DICER1 genes were frequently mutated with higher VAF than the deleterious somatic polymerase mutation., Conclusions: CMMRD-associated gliomas have a specific oncogenesis that does not involve usual pathways and mutations seen in sporadic pediatric or adult glioblastomas. Frequent alterations in other pathways such as MAPK may suggest the use of other targeted therapies along with PD1 inhibitors., Competing Interests: The authors have no commercial association that might pose or create the appearance of a conflict of interest with the information presented in the submitted manuscript., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
- Published
- 2024
- Full Text
- View/download PDF
18. Tezepelumab for refractory eosinophilic granulomatosis with polyangiitis-related asthma.
- Author
-
Vincent-Galtié N, Marquant Q, Catherinot E, Ackermann F, Magnan A, Tcherakian C, and Groh M
- Subjects
- Humans, Middle Aged, Female, Male, Treatment Outcome, Anti-Asthmatic Agents therapeutic use, Churg-Strauss Syndrome drug therapy, Churg-Strauss Syndrome diagnosis, Granulomatosis with Polyangiitis drug therapy, Granulomatosis with Polyangiitis diagnosis, Asthma drug therapy, Asthma diagnosis, Antibodies, Monoclonal, Humanized therapeutic use
- Abstract
Conventional immunosuppressants are ineffective for the management of EGPA-related asthma. Tezepelumab is a human monoclonal antibody that inhibits thymic stromal lymphopoietin (TLSP) that has proven efficacy in several phase 3 studies for the treatment of asthma. We treated with off-label tezepelumab the first two patients with severe refractory EPGA-related asthma. These preliminary findings suggest that targeting upstream signaling of the T2 inflammatory pathway can improve symptoms, reduce BVAS and increase Asthma Control Test scores, even in patients with refractory asthma who have failed several previous lines of treatment. Nevertheless, by analogy with dupilumab-induced IL-4/13 blockade, the persistence of sputum eosinophilia (reported in both patients) raises questions as to whether TSLP inhibition could lead to a rebound of eosinophilia and potentially to eosinophil-related symptoms in patients with EGPA., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
19. Specific brain MRI features of constitutional mismatch repair deficiency syndrome in children with high-grade gliomas.
- Author
-
Raveneau M, Guerrini-Rousseau L, Levy R, Roux CJ, Bolle S, Doz F, Bourdeaut F, Colas C, Blauwblomme T, Beccaria K, Tauziède-Espariat A, Varlet P, Dufour C, Grill J, Boddaert N, and Dangouloff-Ros V
- Abstract
Background: Children with constitutional mismatch repair deficiency (CMMRD) syndrome have an increased risk of high-grade gliomas (HGG), and brain imaging abnormalities. This study analyzes brain imaging features in CMMRD syndrome children versus those with HGG without CMMRD., Methods: Retrospective comparative analysis of brain imaging in 30 CMMRD children (20 boys, median age eight years, 22 with HGG), seven with Lynch syndrome (7 HGG), 39 with type 1 neurofibromatosis (NF1) (four with HGG) and 50 with HGG without MMR or NF1 pathogenic variant ("no-predisposition" patients)., Results: HGG in CMMRD and Lynch patients were predominantly hemispheric (versus midline) compared to NF1 and no-predisposition patients (91% and 86%, vs 25% and 54%, p = 0.004). CMMRD-associated tumors often had ill-defined boundaries (p = 0.008). All CMMRD patients exhibited at least one developmental venous anomaly (DVA), versus 14%, 10%, and 6% of Lynch, NF1, and no-predisposition patients (p < 0.0001). Multiple DVAs were observed in 83% of CMMRD patients, one NF1 patient (3%), and never in other groups (p < 0.0001). Cavernomas were discovered in 21% of CMMRD patients, never in other groups (p = 0.01). NF1-like focal areas of high T2-FLAIR signal intensity (FASI) were more prevalent in CMMRD patients than in Lynch or no-predisposition patients (50%, vs 20% and 0%, respectively, p < 0.0001). Subcortical and ill-limited FASI, possibly involving the cortex, were specific to CMMRD (p < 0.0001) and did not evolve in 93% of patients (13/14)., Conclusion: Diffuse hemispherically located HGG associated with multiple DVAs, cavernomas, and NF1-like or subcortical FASI strongly suggests CMMRD syndrome compared to children with HGG in other contexts., Clinical Relevance Statement: The radiologic suggestion of CMMRD syndrome when confronted with HGGs in children may prompt genetic testing. This can influence therapeutic plans. Therefore, imaging features could potentially be incorporated into CMMRD testing recommendations., Key Points: Using imaging to detect CMMRD syndrome early may improve patient care. CMMRD features include: hemispheric HGG with multiple developmental venous anomalies and NF1-like or subcortical areas with high T2-FLAIR intensity. We propose novel imaging features to improve the identification of potential CMMRD patients., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)
- Published
- 2024
- Full Text
- View/download PDF
20. Cerebral dural arteriovenous fistulas in patients with PTEN-related hamartoma tumor syndrome.
- Author
-
Gerasimenko A, Mignot C, Naggara O, Coulet F, Ekram S, Heide S, Sorato C, Mazowiecki M, Perrin L, Colas C, Cusin V, Caux F, Dardenne A, El Chehadeh S, Verloes A, Maurey H, Afenjar A, Petit F, Barete S, Boespflug-Tanguy O, Bourrat E, Capri Y, Ciorna V, Deb W, Doummar D, Perrier A, Guédon A, Houdart E, Isidor B, Jacquemont ML, Buffet C, Mercier S, Passemard S, Riquet A, Ruaud L, Schaefer E, Heron D, Bisdorff A, and Benusiglio PR
- Subjects
- Humans, Adult, Female, Male, Young Adult, Magnetic Resonance Imaging, Mutation, PTEN Phosphohydrolase genetics, Central Nervous System Vascular Malformations genetics, Central Nervous System Vascular Malformations complications, Central Nervous System Vascular Malformations diagnostic imaging, Central Nervous System Vascular Malformations diagnosis, Hamartoma Syndrome, Multiple genetics, Hamartoma Syndrome, Multiple complications
- Abstract
Central nervous system (CNS) dural arteriovenous fistulas (DAVF) have been reported in PTEN-related hamartoma tumor syndrome (PHTS). However, PHTS-associated DAVF remain an underexplored field of the PHTS clinical landscape. Here, we studied cases with a PTEN pathogenic variant identified between 2007 and 2020 in our laboratory (n = 58), and for whom brain imaging was available. Two patients had DAVF (2/58, 3.4%), both presenting at advanced stages: a 34-year-old man with a left lateral sinus DAVF at immediate risk of hemorrhage, and a 21-year-old woman with acute intracranial hypertension due to a torcular DAVF. Interestingly, not all patients had 3D TOF/MRA, the optimal sequences to detect DAVF. Early diagnosis of DAVF can be lifesaving, and is easier to treat compared to developed, proliferative, or complex lesions. As a result, one should consider brain MRI with 3D TOF/MRA in PHTS patients at genetic diagnosis, with subsequent surveillance on a case-by-case basis., (© 2024 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
21. Correction to: Balancing Ambitions and Realities: Stakeholder Perspectives on Jurisdictional Approach Outcomes in Sabah's Forests.
- Author
-
Ng JSC, Chervier C, Carmenta R, Samdin Z, Azhar B, and Karsenty A
- Published
- 2024
- Full Text
- View/download PDF
22. Impact of spa therapy on physical activity, sleep and heart rate variability among individuals with fibromyalgia: Results of an ancillary study.
- Author
-
Colas C, Hodaj E, Pichot V, Roche F, and Cracowski C
- Abstract
Spa therapy is recommended to manage symptoms of fibromyalgia, but the physiological mechanisms underlying this improvement have been poorly studied. In an original study, we explored the effect of a 3-week rheumatology spa treatment for fibromyalgia patients on quality of life and with a symptom severity questionnaire. We present here the results of an ancillary study which explored three secondary criteria using objective measurement methods: diurnal actimetry for physical activity analysis, nocturnal actimetry for sleep analysis and heart rate variability. Eighty-three fibromyalgia patients were randomized to participate in an immediate 3-week rheumatological spa therapy, either a start within 6 weeks after inclusion (interventional group, n = 39) or a delayed, start 6 months after inclusion (control group, n = 44). Patients were asked to wear an actimeter (n = 56) to assess diurnal physical activity and sleep quality and a 24-h Holter ECG (n = 60) to assess nocturnal heart rate variability at baseline, 3 months and 6 months after inclusion. Time spent in sedentary and light physical activity was reduced to ∼30 min at 6 months in the interventional group (P = 0.027). Sleep quality and heart rate variability were not improved. Spa therapy made it possible to reduce sedentary activities in patients' daily life for up to 6 months afterwards, concomitant with the improvement in quality of life, pain and fatigue as highlighted in the original Thermalgi study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
23. Phonological neighbors cooperate during spoken-sentence processing: Evidence from a nonword detection task.
- Author
-
Dufour S, Fournet C, Mirault J, and Grainger J
- Abstract
We used a novel nonword detection task to examine the lexical competition principle postulated in most models of spoken word recognition. To do so, in Experiment 1 we presented sequences of spoken words with half of the sequences containing a nonword, and the target nonword (i.e., press a response key whenever you detect a nonword in the sequence) could either be phonologically related (a phonological neighbor) or unrelated to the immediately preceding word. We reasoned that the reactivation of a phonological neighbor during target nonword processing should delay the moment at which a nonword decision can be made. Contrary to our hypothesis, participants were faster at detecting nonwords when they were preceded by a phonological neighbor compared with an unrelated word. In Experiment 2, an inhibitory effect of phonological relatedness on nonword decisions was observed in a classic priming situation using the same set of related and unrelated word-nonword pairs. We discuss the implications of these findings in regard to the main models of spoken word recognition, and conclude that our specific experimental set-up with phonological neighbors embedded in spoken sentences is more sensitive to cooperative interactions between co-activated sublexical representations than lexical competition between co-activated lexical representations, with the latter being modulated by whether or not the words compete for the same slot in time., (© 2024. The Psychonomic Society, Inc.)
- Published
- 2024
- Full Text
- View/download PDF
24. Constitutional mismatch repair deficiency mimicking Lynch syndrome is associated with hypomorphic mismatch repair gene variants.
- Author
-
Gallon R, Brekelmans C, Martin M, Bours V, Schamschula E, Amberger A, Muleris M, Colas C, Dekervel J, De Hertogh G, Coupier J, Colleye O, Sepulchre E, Burn J, Brems H, Legius E, and Wimmer K
- Abstract
Lynch syndrome (LS) and constitutional mismatch repair deficiency (CMMRD) are distinct cancer syndromes caused, respectively, by mono- and bi-allelic germline mismatch repair (MMR) variants. LS predisposes to mainly gastrointestinal and genitourinary cancers in adulthood. CMMRD predisposes to brain, haematological, and LS-spectrum cancers from childhood. Two suspected LS patients with first cancer diagnosis aged 27 or 38 years were found to be homozygous for an MMR (likely) pathogenic variant, MSH6 c.3226C>T (p.(Arg1076Cys)), or variant of uncertain significance (VUS), MLH1 c.306G>A (p.(Glu102=)). MLH1 c.306G>A was shown to cause leaky exon 3 skipping. The apparent genotype-phenotype conflict was resolved by detection of constitutional microsatellite instability in both patients, a hallmark feature of CMMRD. A hypomorphic effect of these and other variants found in additional late onset CMMRD cases, identified by literature review, likely explains a LS-like phenotype. CMMRD testing in carriers of compound heterozygous or homozygous MMR VUS may find similar cases and novel hypomorphic variants. Individualised management of mono- and bi-allelic carriers of hypomorphic MMR variants is needed until we better characterise the associated phenotypes., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
25. Severe asthma care trajectories: the French RAMSES cohort.
- Author
-
Perotin JM, Gauquelin L, Just N, Devouassoux G, Chenivesse C, Bourdin A, Garcia G, Saint Raymond C, Boudjemaa A, Bonniaud P, Chanez P, Barnig C, Beurnier A, Maurer C, Freymond N, Didi T, Tcherakian C, Russier M, Drucbert M, Guillo S, Estellat C, and Taillé C
- Abstract
Background: The French RAMSES study is an observational prospective multicentre real-life cohort including severe asthmatic subjects. The objective of the study was to compare the characteristics of patients, in terms of phenotype and asthma care trajectories, between those managed by tertiary referral centres (TRCs) or secondary care centres (SCCs)., Methods: Patients were prospectively recruited and enrolled for a 5-year follow-up. Patients' characteristics were analysed at inclusion and compared between TRCs and SCCs., Results: 52 centres (24 TRCs and 28 SCCs) included 2046 patients: 1502 (73.4%) were included by a TRC and 544 (26.6%) by a SCC. Patients were mainly women (62%), 53±15 years old, 67% with Asthma Control Test <20; at inclusion, 14% received oral corticosteroids (OCS) and 66% biologics. Compared with the SCC group, the TRC group had more frequent comorbidities and lower blood eosinophil counts (262 versus 340 mm
-3 ; p=0.0036). OCS and biologics use did not differ between groups, but patients in the TRC group benefited more frequently from an educational programme (26% versus 18%; p=0.0008) and received more frequently two or more sequential lines of biologics (33% versus 24%; p=0.0105). In-depth investigations were more frequently performed in the TRC group (allergy tests: 74% versus 62%; p<0.0001; exhaled nitric oxide fraction: 56% versus 21%; p<0.0001; induced sputum: 6% versus 3%; p=0.0390)., Conclusions: Phenotypes and care trajectories differed in the RAMSES cohort between SCCs and TRCs, probably related to different levels of asthma severity and differences in medical resources and practices among centres. This highlights the need for standardisation of severe asthma care., Competing Interests: Conflict of interest: J-M. Perotin reports lecture honoraria from AstraZeneca, support for attending meetings from AstraZeneca and Chiesi, and membership of working groups and associations receiving financial support from AstraZeneca, Chiesi, Novartis and Sanofi; outside the submitted work. N. Just participated or participates as an investigator in clinical trials with Chiesi, and reports honoraria from Chiesi and AstraZeneca. G. Devouassoux reports lecture honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mundi Pharma, Novartis Pharma, Vivisol, Sanofi, ALK and Menarini; consultancy fees from AGIR Adom, ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Meda, MSD, Novartis Pharma, Orkyn, Takeda, TEVA, Sanofi and Cipla; has served as a principal investigator and/or study coordinator for AB Science, ALK, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Lilly, Novartis Pharma, Roche, Regeneron Pharmaceuticals Inc., Sanofi, TEVA, VitalAire, Gossamer and Zambon; and reports research grants from AGIR Adom, ALLP, Chiesi, GlaxoSmithKline, MSD, Novartis Pharma, Orkyn, Takeda and Vivisol. C. Chenivesse reports grants from AstraZeneca, GlaxoSmithKline, Novartis and Santelys, personal fees from ALK-Abello, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Sanofi, and congress support from AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis and Sanofi. C. Saint Raymond reports lecture honoraria, support for attending meetings, and membership of working groups and associations receiving financial support from AstraZeneca, Novartis, GlaxoSmithKline and Sanofi. A. Bourdin reports grants from Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, AB Science, Celltrion, Cipla, Areteia, Novartis, Sanofi Regeneron and Chiesi, consulting fees, lecture fees and support for meetings from Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, AB Science, Celltrion, Cipla, Novartis, Sanofi Regeneron and Chiesi, and participation on an advisory board for AB Science. G. Garcia reports personal fees from AstraZeneca, Sanofi, Novartis, Chiesi and GlaxoSmithKline, and congress support from Sanofi and Oxyvie. A. Boudjemaa reports personal fees from AstraZeneca, Sanofi, Chiesi and GlaxoSmithKline, and congress support from GlaxoSmithKline and Oxyvie. P. Bonniaud reports research grants from AstraZeneca, personal fees from AstraZeneca, Boehringer Ingelheim, Sanofi, Novartis and GlaxoSmithKline, and congress support from AstraZeneca, Sanofi, Boehringer Ingelheim, Stallergenes and Novartis. P. Chanez reports grants, consulting fees, lectures fees and support for meetings from ALK, AstraZeneca, Biopharm, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Sanofi-Aventis. C. Barnig reports support for attending meetings from AstraZeneca, GlaxoSmithKline, Sanofi, ALK and Chiesi. A. Beurnier reports lecture fees from AstraZeneca and Sanofi. N. Freymond reports lecture honoraria from AstraZeneca, Sanofi and GlaxoSmithKline, and support for attending meetings from AstraZeneca and Sanofi; outside the submitted work. C. Tcherakian reports a grant from Air Liquide Foundation, lecture fees from AstraZeneca, GlaxoSmithKline, Chiesi, Novartis and Sanofi, and meeting support from Sanofi and GlaxoSmithKline. M. Drucbert reports lecture honoraria from GlaxoSmithKline and AstraZeneca, and membership of working group receiving financial support from AstraZeneca; outside the submitted work. S. Guillo reports no personal fees, congress support or research grants with conflicting interests to disclose other than the funding of the RAMSES cohort. C. Estellat reports no personal fees, congress support or research grants with conflicting interests to disclose other than the funding of the RAMSES cohort. C. Taillé reports lecture or advisory board fees and grants from AstraZeneca, Sanofi, GlaxoSmithKline, Chiesi, Stallergenes and Novartis. All other authors have nothing to declare. There are no further conflicting interests to disclose., (Copyright ©The authors 2024.)- Published
- 2024
- Full Text
- View/download PDF
26. A novel small molecule inhibitor of CD73 triggers immune-mediated multiple myeloma cell death.
- Author
-
Ray A, Du T, Wan X, Song Y, Pillai SC, Musa MA, Fang T, Moore J, Blank B, Du X, Chen X, Warne R, Sutimantanapi D, Lui F, Zavorotinskaya T, Colas C, Friedman L, Junttila MR, Chauhan D, and Anderson KC
- Subjects
- Humans, Cell Line, Tumor, Cell Death, Multiple Myeloma drug therapy
- Published
- 2024
- Full Text
- View/download PDF
27. Familial uveal melanoma and other tumors in 25 families with monoallelic germline MBD4 variants.
- Author
-
Villy MC, Le Ven A, Le Mentec M, Masliah-Planchon J, Houy A, Bièche I, Vacher S, Vincent-Salomon A, Dubois d'Enghien C, Schwartz M, Piperno-Neumann S, Matet A, Malaise D, Bubien V, Lortholary A, Ait Omar A, Cavaillé M, Stoppa-Lyonnet D, Cassoux N, Stern MH, Rodrigues M, Golmard L, and Colas C
- Subjects
- Humans, Adult, Female, Genetic Predisposition to Disease, Germ-Line Mutation, Endodeoxyribonucleases genetics, Melanoma epidemiology, Melanoma genetics, Melanoma pathology, Skin Neoplasms epidemiology, Skin Neoplasms genetics, Breast Neoplasms epidemiology, Breast Neoplasms genetics, Uveal Neoplasms
- Abstract
Background: Monoallelic germline MBD4 pathogenic variants were recently reported to cause a predisposition to uveal melanoma, associated with a specific tumor mutational signature and good response to immunotherapy. Monoallelic tumor pathogenic variants have also been described in brain tumors, breast cancers, and myxofibrosarcomas, whereas biallelic germline MBD4 pathogenic variants have been involved in a recessive hereditary adenomatous polyposis and a specific type of acute myeloid leukemia., Methods: We analyzed MBD4 for all patients with a diagnosis of uveal melanoma at Institut Curie since July 2021 and in the 3240 consecutive female probands explored at the Institut Curie for suspicion of predisposition to breast cancer between July 2021 and February 2023., Results: We describe 25 families whose probands carry a monoallelic germline pathogenic variant in MBD4. Eighteen of these families presented with uveal melanoma (including a case patient with multiple uveal melanoma), and 7 families presented with breast cancer. Family histories showed the first familial case of uveal melanoma in monoallelic MBD4 pathogenic variant carriers and other various types of cancers in relatives, especially breast, renal, and colorectal tumors., Conclusions: Monoallelic MBD4 pathogenic variant may explain some cases of familial and multiple uveal melanoma as well as various cancer types, expanding the tumor spectrum of this predisposition. Further genetic testing in relatives combined with molecular tumor analyses will help define the tumor spectrum and estimate each tumor's risk., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
28. Features of colorectal adenomas among young patients with Lynch syndrome according to path_MMR: Results from the PRED-IdF registry.
- Author
-
Alric H, Coffin E, Lekhal C, Benusiglio PR, Dhooge M, Colas C, Caron O, Cusin V, Becq A, Perez Cuadrado Robles E, Leenhardt R, Perkins G, Buecher B, Bellanger J, Rahmi G, Malka D, Laurent-Puig P, Chaussade S, Benamouzig R, Parc Y, Cellier C, and Perrod G
- Subjects
- Humans, Male, Adult, Middle Aged, Female, Colonoscopy, Germ-Line Mutation, DNA Mismatch Repair, Colorectal Neoplasms, Hereditary Nonpolyposis epidemiology, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Colorectal Neoplasms, Hereditary Nonpolyposis diagnosis, Colorectal Neoplasms epidemiology, Colorectal Neoplasms genetics, Colorectal Neoplasms diagnosis, Adenoma epidemiology, Adenoma genetics, Adenoma diagnosis
- Abstract
Background: Lynch syndrome (LS) is the most frequent inherited colorectal cancer syndrome., Aim: To assess the burden of adenoma in LS patients under 50 years-old followed in the PRED-IdF network., Methods: From January 2010 to January 2019, all patients under 50 years of age with a confirmed LS germline mutation were included. The main objective was the description of adenomas characteristics according to path_MMR., Results: We analyzed data from 708 patients (mean age 34.8 ± 8.6), of which 41.8 % were male. Among these patients, 37.6% had path_MLH1, 45.4% path_MSH2, 13.9% path_MSH6, 2.9% path_PMS2, and 1.2% path_EpCAM. The analysis included 1721 (70.9%) follow-up colonoscopies. A total of 682 adenomas were detected, including 140 (20.5%) advanced adenomas. The adenoma detection rates during the first and follow-up colonoscopies were 19.2% and 20.5%, respectively. Most adenomas were <10 mm (57.9%), located in the proximal colon (334, 48.9%), and presented as non-polypoid lesions (493, 72.3%). The median growth time for adenomas was 23 months (range 9-114) irrespective of the path_MMR mutation (p = 0.62)., Conclusion: LS patients under 50 years of age have a high burden of adenomas, particularly small non-polypoid adenomas located in the proximal colon. These results highlight the need for intensive screening, with a particular focus on the proximal colon., Competing Interests: Declaration of Competing Interest Authors declare no Conflict of Interests for this article., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
29. Mosaic BRCA1 promoter methylation contribution in hereditary breast/ovarian cancer pedigrees.
- Author
-
Schwartz M, Ibadioune S, Chansavang A, Vacher S, Caputo SM, Delhomelle H, Wong J, Abidallah K, Moncoutier V, Becette V, Popova T, Suybeng V, De Pauw A, Stern MH, Colas C, Mouret-Fourme E, Stoppa-Lyonnet D, Golmard L, Bieche I, and Masliah-Planchon J
- Subjects
- Humans, Female, BRCA1 Protein genetics, Pedigree, BRCA2 Protein genetics, Methylation, Germ-Line Mutation genetics, Genetic Predisposition to Disease, DNA Methylation genetics, Breast Neoplasms genetics, Breast Neoplasms pathology, Ovarian Neoplasms genetics, Ovarian Neoplasms diagnosis
- Abstract
Purpose: Mosaic BRCA1 promoter methylation ( BRCA1 meth) increases the risk of early-onset breast cancer, triple-negative breast cancer and ovarian cancer. As mosaic BRCA1 meth are believed to occur de novo, their role in family breast/ovarian cancer has not been assessed., Patients: Blood-derived DNA from 20 unrelated affected cases from families with aggregation of breast/ovarian cancer, but with no germline pathogenic variants in BRCA1 / 2 , PALB2 or RAD51C/D , were screened by methylation-sensitive high-resolution melting. CpG analysis was performed by pyrosequencing on blood and buccal swab. Two probands carried a pathogenic variant in a moderate-penetrance gene ( ATM and BARD1 ), and 8 of 18 others (44%) carried BRCA1 meth (vs none of the 20 age-matched controls). Involvement of BRCA1 in tumourigenesis in methylated probands was demonstrated in most tested cases by detection of a loss of heterozygosity and a homologous recombination deficiency signature. Among the eight methylated probands, two had relatives with breast cancer with detectable BRCA1 meth in blood, including one with high methylation levels in two non-tumour tissues., Conclusions: The high prevalence of mosaic BRCA1 meth in patients with breast/ovarian cancer with affected relatives, as well as this first description of a family aggregation of mosaic BRCA1 meth, shows how this de novo event can contribute to hereditary breast/ovarian cancer pedigrees., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
- Full Text
- View/download PDF
30. Male breast cancer: No evidence for mosaic BRCA1 promoter methylation involvement.
- Author
-
Schwartz M, Ibadioune S, Vacher S, Villy MC, Trabelsi-Grati O, Le Gall J, Caputo SM, Delhomelle H, Warcoin M, Moncoutier V, Bourneix C, Boutry-Kryza N, De Pauw A, Stern MH, Buecher B, Mouret-Fourme E, Colas C, Stoppa-Lyonnet D, Masliah-Planchon J, Golmard L, and Bieche I
- Subjects
- Humans, Male, Female, DNA Methylation, BRCA1 Protein genetics, Genetic Predisposition to Disease, Breast Neoplasms genetics, Breast Neoplasms pathology, Breast Neoplasms, Male genetics, Triple Negative Breast Neoplasms genetics
- Abstract
Breast cancers (BC) are rare in men and are often caused by constitutional predisposing factors. In women, mosaic BRCA1 promoter methylations (MBPM) are frequent events, detected in 4-8% of healthy subjects. This constitutional epimutation increases risk of early-onset and triple-negative BC. However, the role of MBPM in male BC predisposition has never been assessed. We screened 40 blood samples from men affected by BC, and performed extensive tumour analysis on MBPM-positive patients. We detected two patients carrying MBPM. Surprisingly, tumour analysis revealed that neither of these two male BCs were caused by the constitutional BRCA1 epimutations carried by the patients., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
31. Branched pegylated linker-auristatin to control hydrophobicity for the production of homogeneous minibody-drug conjugate against HER2-positive breast cancer.
- Author
-
Douez E, Allard-Vannier E, Amar IAM, Jolivet L, Boursin F, Maisonial-Besset A, Witkowski T, Chezal JM, Colas C, Letast S, Auvert E, Denevault-Sabourin C, Aubrey N, and Joubert N
- Subjects
- United States, Mice, Humans, Animals, Female, Pharmaceutical Preparations, Tissue Distribution, Cell Line, Tumor, Ado-Trastuzumab Emtansine, Hydrophobic and Hydrophilic Interactions, Polyethylene Glycols, Breast Neoplasms drug therapy, Immunoconjugates therapeutic use, Oligopeptides, Aminobenzoates
- Abstract
Trastuzumab emtansine (Kadcyla®) was the first antibody-drug conjugate (ADC) approved by the Food and Drug Administration in 2013 against a solid tumor, and the first ADC to treat human epidermal growth factor receptor 2 positive (HER2+) breast cancer. However, this second generation ADC is burden by several limitations included heterogeneity, limited activity against heterogeneous tumor (regarding antigen expression) and suboptimal tumor penetration. To address this, different development strategies are oriented towards homogeneous conjugation, new drugs, optimized linkers and/or smaller antibody formats. To reach better developed next generation ADCs, a key parameter to consider is the management of the hydrophobicity associated with the linker-drug, increasing with and limiting the drug-to-antibody ratio (DAR) of the ADC. Here, an innovative branched pegylated linker was developed, to control the hydrophobicity of the monomethyl auristatin E (MMAE) and its cathepsin B-sensitive trigger. This branched pegylated linker-MMAE was then used for the efficient generation of internalizing homogeneous ADC of DAR 8 and minibody-drug conjugate of DAR 4, targeting HER2. Both immunoconjugates were then evaluated in vitro and in vivo on breast cancer models. Interestingly, this study highlighted that the minibody-MMAE conjugate of DAR 4 was the best immunoconjugate regarding in vitro cellular internalization and cytotoxicity, gamma imaging, ex vivo biodistribution profile in mice and efficient reduction of tumor size in vivo. These results are very promising and encourage us to explore further fragment-drug conjugate development., Competing Interests: Declaration of competing interest All authors have no relevant conflict of interest with the subject matter or materials discussed in the manuscript., (Copyright © 2023. Published by Elsevier B.V.)
- Published
- 2024
- Full Text
- View/download PDF
32. Clinical implications of incorporating genetic and non-genetic risk factors in CanRisk-based breast cancer risk prediction.
- Author
-
Tüchler A, De Pauw A, Ernst C, Anota A, Lakeman IMM, Dick J, van der Stoep N, van Asperen CJ, Maringa M, Herold N, Blümcke B, Remy R, Westerhoff A, Stommel-Jenner DJ, Frouin E, Richters L, Golmard L, Kütting N, Colas C, Wappenschmidt B, Rhiem K, Devilee P, Stoppa-Lyonnet D, Schmutzler RK, and Hahnen E
- Subjects
- Female, Humans, Young Adult, Adult, Middle Aged, Aged, BRCA1 Protein genetics, BRCA2 Protein genetics, Genetic Testing, Risk Factors, Genetic Predisposition to Disease, Breast Neoplasms pathology
- Abstract
Background: Breast cancer (BC) risk prediction models consider cancer family history (FH) and germline pathogenic variants (PVs) in risk genes. It remains elusive to what extent complementation with polygenic risk score (PRS) and non-genetic risk factor (NGRFs) data affects individual intensified breast surveillance (IBS) recommendations according to European guidelines., Methods: For 425 cancer-free women with cancer FH (mean age 40·6 years, range 21-74), recruited in France, Germany and the Netherlands, germline PV status, NGRFs, and a 306 variant-based PRS (PRS
306 ) were assessed to calculate estimated lifetime risks (eLTR) and estimated 10-year risks (e10YR) using CanRisk. The proportions of women changing country-specific European risk categories for IBS recommendations, i.e. ≥20 % and ≥30 % eLTR, or ≥5 % e10YR were determined., Findings: Of the women with non-informative PV status, including PRS306 and NGRFs changed clinical recommendations for 31·0 %, (57/184, 20 % eLTR), 15·8 % (29/184, 30 % eLTR) and 22·4 % (41/183, 5 % e10YR), respectively whereas of the women tested negative for a PV observed in their family, clinical recommendations changed for 16·7 % (25/150), 1·3 % (2/150) and 9·5 % (14/147). No change was observed for 82 women with PVs in high-risk genes (BRCA1/2, PALB2). Combined consideration of eLTRs and e10YRs identified BRCA1/2 PV carriers benefitting from IBS <30 years, and women tested non-informative/negative for whom IBS may be postponed., Interpretation: For women who tested non-informative/negative, PRS and NGRFs have a considerable impact on IBS recommendations. Combined consideration of eLTRs and e10YRs allows personalizing IBS starting age., Funding: Horizon 2020, German Cancer Aid, Federal Ministry of Education and Research, Köln Fortune., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
33. Statistical inference with a manifold-constrained RNA velocity model uncovers cell cycle speed modulations.
- Author
-
Lederer AR, Leonardi M, Talamanca L, Herrera A, Droin C, Khven I, Carvalho HJF, Valente A, Mantes AD, Arabí PM, Pinello L, Naef F, and Manno G
- Abstract
Across a range of biological processes, cells undergo coordinated changes in gene expression, resulting in transcriptome dynamics that unfold within a low-dimensional manifold. Single-cell RNA-sequencing (scRNA-seq) only measures temporal snapshots of gene expression. However, information on the underlying low-dimensional dynamics can be extracted using RNA velocity, which models unspliced and spliced RNA abundances to estimate the rate of change of gene expression. Available RNA velocity algorithms can be fragile and rely on heuristics that lack statistical control. Moreover, the estimated vector field is not dynamically consistent with the traversed gene expression manifold. Here, we develop a generative model of RNA velocity and a Bayesian inference approach that solves these problems. Our model couples velocity field and manifold estimation in a reformulated, unified framework, so as to coherently identify the parameters of an autonomous dynamical system. Focusing on the cell cycle, we implemented VeloCycle to study gene regulation dynamics on one-dimensional periodic manifolds and validated using live-imaging its ability to infer actual cell cycle periods. We benchmarked RNA velocity inference with sensitivity analyses and demonstrated one- and multiple-sample testing. We also conducted Markov chain Monte Carlo inference on the model, uncovering key relationships between gene-specific kinetics and our gene-independent velocity estimate. Finally, we applied VeloCycle to in vivo samples and in vitro genome-wide Perturb-seq, revealing regionally-defined proliferation modes in neural progenitors and the effect of gene knockdowns on cell cycle speed. Ultimately, VeloCycle expands the scRNA-seq analysis toolkit with a modular and statistically rigorous RNA velocity inference framework.
- Published
- 2024
- Full Text
- View/download PDF
34. Neurofibromatosis type 1 mosaicism in patients with constitutional mismatch repair deficiency.
- Author
-
Guerrini-Rousseau L, Pasmant E, Muleris M, Abbou S, Adam-De-Beaumais T, Brugieres L, Cabaret O, Colas C, Cotteret S, Decq P, Dufour C, Guillerm E, Rouleau E, Varlet P, Zili S, Vidaud D, and Grill J
- Subjects
- Female, Humans, Mosaicism, Retrospective Studies, Mismatch Repair Endonuclease PMS2 genetics, DNA Mismatch Repair genetics, Neurofibromatosis 1 diagnosis, Neurofibromatosis 1 genetics, Neoplastic Syndromes, Hereditary genetics, Brain Neoplasms genetics, Colorectal Neoplasms genetics
- Abstract
Differential diagnosis between constitutional mismatch repair deficiency (CMMRD) and neurofibromatosis type 1 (NF1 ) is crucial as treatment and surveillance differ. We report the case of a girl with a clinical diagnosis of sporadic NF1 who developed a glioblastoma. Immunohistochemistry for MMR proteins identified PMS2 loss in tumour and normal cells and WES showed the tumour had an ultra-hypermutated phenotype, supporting the diagnosis of CMMRD. Germline analyses identified two variants (one pathogenic variant and one classified as variant(s) of unknown significance) in the PMS2 gene and subsequent functional assays on blood lymphocytes confirmed the diagnosis of CMMRD. The large plexiform neurofibroma of the thigh and the freckling were however more compatible with NF1. Indeed, a NF1 PV (variant allele frequencies of 20%, 3% and 9% and in blood, skin and saliva samples, respectively) was identified confirming a mosaicism for NF1. Retrospective analysis of a French cohort identified NF1 mosaicism in blood DNA in 2 out of 22 patients with CMMRD, underlining the existence of early postzygotic PV of NF1 gene in patients with CMMRD whose tumours have been frequently reported to exhibit somatic NF1 mutations. It highlights the potential role of this pathway in the pathogenesis of CMMRD-associated gliomas and argues in favour of testing MEK inhibitors in this context., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
- Full Text
- View/download PDF
35. The Acti-Pair program helps men with prostate cancer increase physical activity with peer support: a mixed method pilot study.
- Author
-
Baudot A, Barth N, Colas C, Garros M, Garcin A, Oriol M, Collange F, Bongue B, Roche F, Chauvin F, Bourmaud A, and Hupin D
- Subjects
- Male, Humans, Pilot Projects, Cognition, Data Accuracy, Exercise, Prostatic Neoplasms therapy
- Abstract
Background: Although the health benefits of physical activity (PA) are recognized, prostate cancer patients do not follow PA recommendations. Barriers to PA, whether physical, environmental or organizational, are known. Furthermore, even when these barriers are overcome, this achievement is not systematically accompanied by lifestyle change. Many strategies have shown to be effective in increasing patient adherence to PA. This study aims to assess the feasibility and the viability of the Acti-Pair program which combines three strategies: peer support, a personalized and realistic PA project, and support from health and adapted physical activity professionals in a local context., Methods and Analysis: We conducted a pilot study utilizing a mixed qualitative and quantitative methodology, employing feasibility and viability assessments. Quantitative assessments included recruitment, retention adherence rates, process and potential effectiveness (PA and motivation) indicators; while qualitative methods were used to evaluate the program's practicality, suitability and usefulness. Indicators of potential effectiveness were assessed before and after the intervention using a Wilcoxon test for matched data. Qualitative data were collected through semistructured interviews conducted by two researchers with various program stakeholders. The study lasted for 3 years., Results: Twenty-four patients were recruited over a 25-month period. Forty-two percent of patients completed the program 3 months after the beginning. We recruited 14 peers and trained nine peers over a 10-month period. The program was coordinated extensively by adapted PA professionals, while health professionals were involved in recruiting patients and peers. Self-reporting of moderate to vigorous PA was increased after the Acti-Pair program initiation [42.86 (30.76) at baseline to 53.29 (50.73)]. Intrinsic motivation significantly increased after participation in the Acti-Pair program [1.76 (1.32) before the intervention vs. 2.91 (1.13) after the intervention]. The key player to support the Acti-Pair program in the field has been the PA support system. The main challenge has been the difficulty of health professionals in promoting PA., Discussion: This pilot study has shown that the Acti-Pair program is feasible and viable. It will allow us to extend the peer support intervention to other contexts and assess the effectiveness of this intervention and its generalization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Baudot, Barth, Colas, Garros, Garcin, Oriol, Collange, Bongue, Roche, Chauvin, Bourmaud and Hupin.)
- Published
- 2024
- Full Text
- View/download PDF
36. Balancing Ambitions and Realities: Stakeholder Perspectives on Jurisdictional Approach Outcomes in Sabah's Forests.
- Author
-
Ng JSC, Chervier C, Carmenta R, Samdin Z, Azhar B, and Karsenty A
- Subjects
- Humans, Malaysia, Palm Oil, Conservation of Natural Resources, Forests
- Abstract
The jurisdictional approach concept emerged in response to the widespread failure of sectoral forest conservation projects. Despite its increasing popularity, understanding jurisdictional approach outcomes is challenging, given that many remain in either the formation or implementation stage. Furthermore, diverse stakeholders hold different perspectives on what exactly a jurisdictional approach is intended to pursue. These different perspectives are important to unravel, as having a shared understanding of the outcomes is important to build the critical support needed for it. This study aims to add to the limited evidence with a case study in Sabah, Malaysia, which is committed to addressing a leading deforestation driver (palm oil) through sustainability certification in a jurisdiction. We used Q-methodology to explore stakeholder perceptions, revealing three distinct perspectives regarding what outcomes jurisdictional approaches should pursue. We asked about outcomes achievable within ten years (2022-2032) and considering real-world constraints. We found different perspectives regarding economic, environmental, governance, and smallholders' welfare outcomes. However, we found consensus among stakeholders about some outcomes: (i) that achieving zero-deforestation is untenable, (ii) that issuing compensation or incentives to private land owners to not convert forests into plantations is unrealistic, (iii) that the human well-being of plantation workers could improve through better welfare, and (iv) the free, prior and informed consent given by local communities being required legally. The findings offer insights into key stakeholders' perceptions of the deliverables of jurisdictional approaches and the difficulty of achieving its objectives under real-world constraints., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
37. Benralizumab for eosinophilic granulomatosis with polyangiitis: a retrospective, multicentre, cohort study.
- Author
-
Bettiol A, Urban ML, Padoan R, Groh M, Lopalco G, Egan A, Cottin V, Fraticelli P, Crimi C, Del Giacco S, Losappio L, Moi L, Cinetto F, Caminati M, Novikov P, Berti A, Cameli P, Cathébras P, Coppola A, Durel CA, Folci M, Lo Gullo A, Lombardi C, Monti S, Parronchi P, Rivera CM, Solans R, Vacca A, Espígol-Frigolé G, Guarnieri G, Bianchi FC, Marchi MR, Tcherakian C, Kahn JE, Iannone F, Venerito V, Desaintjean C, Moroncini G, Nolasco S, Costanzo GAML, Schroeder JW, Ribi C, Tesi M, Gelain E, Mattioli I, Bello F, Jayne D, Prisco D, Vaglio A, and Emmi G
- Subjects
- Male, Humans, Female, Adult, Middle Aged, Retrospective Studies, Cohort Studies, Prednisone, Interleukin Inhibitors, Pathologic Complete Response, Churg-Strauss Syndrome diagnosis, Granulomatosis with Polyangiitis drug therapy, Leukocyte Disorders, Antibodies, Monoclonal, Humanized
- Abstract
Background: Interleukin-5 (IL-5) inhibitors represent novel therapies for eosinophilic granulomatosis with polyangiitis (EGPA). This study assessed the effectiveness and safety of the IL-5 receptor inhibitor benralizumab in a European cohort of patients with EGPA., Methods: This retrospective cohort study included patients with EGPA from 28 European referral centres of the European EGPA Study Group across six countries (Italy, France, UK, Russia, Spain, and Switzerland) who received benralizumab as any line of treatment between Jan 1, 2019, and Sep 30, 2022. We assessed the rates of complete response, defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] of 0) and a prednisone dose of up to 4 mg/day, in contrast to partial response, defined as a BVAS of 0 and a prednisone dose greater than 4 mg/day. Active disease manifestations, pulmonary function, variation in glucocorticoid dose, and safety outcomes were also assessed over a 12-month follow-up., Findings: 121 patients with relapsing-refractory EGPA treated with benralizumab at the dose approved for eosinophilic asthma were included (64 [53%] women and 57 [47%] men; median age at the time of beginning benralizumab treatment 54·1 years [IQR 44·2-62·2]). Complete response was reported in 15 (12·4%, 95% CI 7·1-19·6) of 121 patients at month 3, 25 (28·7%, 19·5-39·4) of 87 patients at month 6, and 32 (46·4%, 34·3-58·8) of 69 patients at month 12; partial response was observed in an additional 43 (35·5%, 27·0-44·8) patients at month 3, 23 (26·4%, 17·6-37·0) at month 6, and 13 (18·8%, 10·4-30·1) at month 12. BVAS dropped from 3·0 (IQR 2·0-8·0) at baseline to 0·0 (0·0-2·0) at months 3 and 6, and to 0·0 (0·0-1·0) at month 12. The proportion of patients with systemic manifestations, active peripheral neurological disease, ear, nose, and throat involvement, and pulmonary involvement decreased, with an improvement in lung function tests. Six patients relapsed after having a complete response. The oral prednisone (or equivalent) dose decreased from 10·0 mg/day (5·0-12·5) at baseline to 5·0 mg/day (3·6-8·5) at month 3 (p<0·01), to 5·0 mg/day (2·5-6·3) at month 6, and to 2·5 mg/day (0·0-5·0) at month 12 (p<0·0001). 19 (16%) of 121 patients had adverse events and 16 (13%) discontinued benralizumab., Interpretation: These data suggest that benralizumab could be an effective treatment for EGPA in real-life clinical practice. Further clinical trials are required to confirm the efficacy of benralizumab in patients with a higher baseline disease activity., Funding: None., Competing Interests: Declaration of interests ABer and RP report receiving consulting fees from GSK outside the current work. PCam reports receiving research grants and consulting fees from GSK and AstraZeneca outside the current work. FC reports being invited as a speaker or advisory board member by Grifols, Kedrion, GSK, Takeda, and CSL Behring outside the current work. CC reports receiving honoraria for lectures from GSK, Sanofi, AstraZeneca, Novartis, ResMed, and Fisher & Paykel outside the current work. GE reports receiving consultation honoraria from GSK and AstraZeneca outside the current work. GE-F reports receiving advisory fees from GSK outside the current work. J-EK and VC report receiving consulting fees from GSK and AstraZeneca outside the current work. CT reports receiving grants and consulting fees from GSK, Novartis, Sanofi, and AstraZeneca outside the current work. PP reports receiving consultation honoraria from GSK and Novartis outside the current work. AVag reports receiving consultation honoraria from GSK outside the current work. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
38. MSH3 : a confirmed predisposing gene for adenomatous polyposis.
- Author
-
Villy MC, Masliah-Planchon J, Schnitzler A, Delhomelle H, Buecher B, Filser M, Merchadou K, Golmard L, Melaabi S, Vacher S, Blanluet M, Suybeng V, Corsini C, Dhooge M, Hamzaoui N, Farelly S, Ait Omar A, Benamouzig R, Caumette V, Bahuau M, Cucherousset J, Allory Y, Stoppa-Lyonnet D, Bieche I, and Colas C
- Subjects
- Humans, Female, Microsatellite Repeats genetics, Genetic Predisposition to Disease, MutS Homolog 3 Protein genetics, MutS Homolog 3 Protein metabolism, Adenomatous Polyposis Coli genetics, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Colorectal Neoplasms, Hereditary Nonpolyposis genetics
- Abstract
Background: The MSH3 gene is part of the DNA mismatch repair system, but has never been shown to be involved in Lynch syndrome. A first report of four patients from two families, bearing biallelic MSH3 germline variants, with a phenotype of attenuated colorectal adenomatous polyposis raised the question of its involvement in hereditary cancer predisposition. The patients' tumours exhibited elevated microsatellite alterations at selected tetranucleotide repeats (EMAST), a hallmark of MSH3 deficiency., Methods: We report five new unrelated patients with MSH3 -associated polyposis. We describe their personal and familial history and study the EMAST phenotype in various normal and tumour samples, which are relevant findings based on the rarity of this polyposis subtype so far., Results: All patients had attenuated colorectal adenomatous polyposis, with duodenal polyposis in two cases. Both women had breast carcinomas. EMAST phenotype was present at various levels in different samples of the five patients, confirming the MSH3 deficiency, with a gradient of instability in polyps depending on their degree of dysplasia. The negative EMAST phenotype ruled out the diagnosis of germline MSH3 deficiency for two patients: one homozygous for a benign variant and one with a monoallelic large deletion., Conclusion: This report lends further credence to biallelic MSH3 germline pathogenic variants being involved in colorectal and duodenal adenomatous polyposis. Large-scale studies may help clarify the tumour spectrum and associated risks. Ascertainment of EMAST may help with the interpretation of variants of unknown significance. We recommend adding MSH3 to dedicated diagnostic gene panels., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
- Full Text
- View/download PDF
39. Adaptive nanopore sequencing to determine pathogenicity of BRCA1 exonic duplication.
- Author
-
Filser M, Schwartz M, Merchadou K, Hamza A, Villy MC, Decees A, Frouin E, Girard E, Caputo SM, Renault V, Becette V, Golmard L, Servant N, Stoppa-Lyonnet D, Delattre O, Colas C, and Masliah-Planchon J
- Subjects
- Female, Humans, Virulence, Genetic Predisposition to Disease, BRCA1 Protein genetics, BRCA2 Protein genetics, Genes, BRCA2, Exons, Germ-Line Mutation genetics, High-Throughput Nucleotide Sequencing methods, Nanopore Sequencing, Breast Neoplasms genetics
- Abstract
BRCA1 and BRCA2 are tumour suppressor genes that have been characterised as predisposition genes for the development of hereditary breast and ovarian cancers among other malignancies. The molecular diagnosis of this predisposition syndrome is based on the detection of inactivating variants of any type in those genes. But in the case of structural variants, functional consequences can be difficult to assess using standard molecular methods, as the precise resolution of their sequence is often impossible with short-read next generation sequencing techniques. It has been recently demonstrated that Oxford Nanopore long-read sequencing technology can accurately and rapidly provide genetic diagnoses of Mendelian diseases, including those linked to pathogenic structural variants. Here, we report the accurate resolution of a germline duplication event of exons 18-20 of BRCA1 using Nanopore sequencing with adaptive sampling target enrichment. This allowed us to classify this variant as pathogenic within a short timeframe of 10 days. This study provides a proof-of-concept that nanopore adaptive sampling is a highly efficient technique for the investigation of structural variants of tumour suppressor genes in a clinical context., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
- Full Text
- View/download PDF
40. Autoregressive modeling for lossless compression of holograms.
- Author
-
Kizhakkumkara Muhamad R, Schretter C, Blinder D, and Schelkens P
- Abstract
The large number of pixels to be processed and stored for digital holographic techniques necessitates the development of effective lossless compression techniques. Use cases for such techniques are archiving holograms, especially sensitive biomedical data, and improving the data transmission capacity of bandwidth-limited data transport channels where quality loss cannot be tolerated, like display interfaces. Only a few lossless compression techniques exist for holography, and the search for an efficient technique well suited for processing the large amounts of pixels typically encountered is ongoing. We demonstrate the suitability of autoregressive modeling for compressing signals with limited spatial bandwidth content, like holographic images. The applicability of such schemes for any such bandlimited signal is motivated by a mathematical insight that is novel to our knowledge. The devised compression scheme is lossless and enables decoding architecture that essentially has only two steps. It is also highly scalable, with smaller model sizes providing an effective, low-complexity mechanism to transmit holographic data, while larger models obtain significantly higher compression ratios when compared to state-of-the-art lossless image compression solutions, for a wide selection of both computer-generated and optically-acquired holograms. We also provide a detailed analysis of the various methods that can be used for determining the autoregressive model in the context of compression.
- Published
- 2023
- Full Text
- View/download PDF
41. Trend in respiratory viruses' activity in the COVID-19 area.
- Author
-
Farfour É, Rouabah L, Bargain P, Lecuru M, Picard C, Tcherakian C, Maneglier B, Juillet SM, and Vasse M
- Subjects
- Humans, Infant, Retrospective Studies, SARS-CoV-2, Influenza, Human epidemiology, COVID-19 diagnosis, COVID-19 epidemiology, Viruses, Respiratory Tract Infections diagnosis, Respiratory Tract Infections epidemiology
- Abstract
Objectives: SARS-CoV-2 has impacted the detection of seasonal respiratory viruses. We retrospectively assessed the trend in the detection of 10 viruses in the COVID-19 area in 2 hospitals located in the Paris area., Methods: All patients positive for a respiratory virus in two hospitals from September 2016 to August 2021 were retrospectively included. The rate of RT-PCR positive for each virus was calculated for the 2020-2021 season and the 2019-2020 season in comparison to a baseline of 3 seasons, i.e. 2016-2017, 2017-2018, and 2018-2019., Results: Overall, 7,835 patients were tested positive from September 2016 to August 2021. The detection of respiratory virus dramatically falls on week-11 of 2020, as the number of RT-PCR performed. Then, 3 trends were identified: a) almost a disappearance for influenza; b) a 10-weeks delay in the seasonal outbreak for RSV; c) a persistence of circulation with variable activity for other viruses. In comparison to a baseline of three seasons (2016-2019), the rate of positive patients was lower during the 2020-2021 season for coronavirus (4.51% vs. 1.26%, P < 0.0001), adenovirus (1.93% vs. 1.34%, P = 0.14), bocavirus (0.58% vs. 0.11%, P = 0.08), and enterovirus (0.28% vs. 0.0%, P = 0.12). In contrast, the rate of hMPV-positive (1.92% vs. 2.83%, P = 0.03) and hPIV-positive (2.17% vs. 2.99%, P = 0.06) patients increased., Conclusions: The fall in the number of respiratory viruses detected might be related to the lower number of tests performed and the implementation of non pharmaceutical intervention (NPI). Then, all viruses except influenza are detected, probably as a consequence of high adherence to influenza vaccines. Despite, a lower number of tests being performed, the rate of hMPV-positive and hPIV-positive patients increased suggesting an active circulation of these viruses. Altogether, these findings suggest a persistent circulation of common respiratory viruses all over the COVID-19 era.
- Published
- 2023
- Full Text
- View/download PDF
42. Reliability of the Modified Frenchay Scale for the Assessment of Upper Limb Function in Adults With Hemiparesis.
- Author
-
Laclergue Z, Ghédira M, Gault-Colas C, Billy L, Gracies JM, and Baude M
- Subjects
- Humans, Adult, Female, Middle Aged, Reproducibility of Results, Hand, Paresis, Upper Extremity, Stroke complications
- Abstract
Objectives: To investigate the reliability of the Modified Frenchay Scale (MFS) in adults with hemiparesis., Design: Prospective analysis of videos., Setting: Study conducted in a Neurorehabilitation Unit of a University Hospital., Participants: Fifty-one patients (17 women [33%], age 46±15, time since injury 5.2±6.7 years) with hemiparesis secondary to stroke (N=47), tumor (N=3), or spinal cord injury (N=1) were enrolled., Intervention: The MFS measures active upper limb function in spastic hemiparesis based on a video recording of 10 daily living tasks, each rated from 0 to 10. Six tasks are bimanual and 4 are unimanual with the paretic hand. MFS videos performed in routine care of patients with hemiparesis between 2015 and 2021 were collected. After a 3-hour group training session, each MFS video was assessed twice, 1 week apart by 4 rehabilitation professionals with various levels of experience in using the scale., Main Outcome Measures: Internal consistency was determined using Cronbach's alpha. Intra- and inter-rater reliability was measured using intraclass correlation coefficients (ICC, mean [95% CI]), mean differences between ratings and minimal detectable change (MDC). Bland-Altman plots were also performed for inter-rater assessments., Results: The mean overall MFS score was 4.95±1.20 with no floor or ceiling effect. Cronbach's α was 0.97. For the overall MFS score, intra- and inter-rater ICCs were 0.99[0.99;1.00] and 0.97[0.95;0.98], respectively; mean intra- and inter-rater differences were 0.10±0.04 and 0.24±0.12, respectively; and MDC were 0.17 and 0.37, respectively., Conclusions: The MFS is an internally consistent and reliable scale to assess upper limb function in adults with hemiparesis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
43. Effects of alternating letter case on processing sequences of written words.
- Author
-
Fournet C, Mirault J, Perea M, and Grainger J
- Subjects
- Humans, Writing, Language, Reading
- Abstract
In three grammatical decision experiments, we examined the impact of alternating letter case on sentence reading to determine the locus of case-alternation effects. Experiments 1 and 2 compared grammatical decision responses ("Is this a grammatically correct sequence of words or not?") in three different conditions: (1) SAME CASE/same case; (2) alternating CASE between WORDS; and (3) aLterNaTing cAsE wItHin WoRdS. For the grammatically correct sequences, we observed significantly faster responses in the same-case conditions compared with the between-word case manipulation, as well as a significant advantage for the between-word condition compared with within-word alternating case. These results confirm that case-alternation deteriorates sentence reading, but more so at the level of single word processing (within-word alternation) than at the sentence level (between-word alternation). Experiment 3 demonstrated that between-word case-alternation facilitates sentence processing compared with an all-lowercase condition when betweenWORDspacesAREremoved. Therefore, in the absence of between-word spacing, case changes across words facilitate sentence processing, possibly by guiding readers' eyes to optimal locations for word identification.
- Published
- 2023
- Full Text
- View/download PDF
44. Unlocking secrets of microbial ecotoxicology: recent achievements and future challenges.
- Author
-
Hellal J, Lise B, Annette B, Aurélie C, Giulia C, Simon C, Cristiana CL, Caroline C, Nicolas G, Marina H, Fabrice ML, Jean M, Soizic M, Carmen P, Stéphane P, Agnès R, and Stéphane V
- Subjects
- Ecotoxicology, Environmental Pollution, Risk Assessment, Environmental Pollutants toxicity, Environmental Restoration and Remediation
- Abstract
Environmental pollution is one of the main challenges faced by humanity. By their ubiquity and vast range of metabolic capabilities, microorganisms are affected by pollution with consequences on their host organisms and on the functioning of their environment. They also play key roles in the fate of pollutants through the degradation, transformation, and transfer of organic or inorganic compounds. Thus, they are crucial for the development of nature-based solutions to reduce pollution and of bio-based solutions for environmental risk assessment of chemicals. At the intersection between microbial ecology, toxicology, and biogeochemistry, microbial ecotoxicology is a fast-expanding research area aiming to decipher the interactions between pollutants and microorganisms. This perspective paper gives an overview of the main research challenges identified by the Ecotoxicomic network within the emerging One Health framework and in the light of ongoing interest in biological approaches to environmental remediation and of the current state of the art in microbial ecology. We highlight prevailing knowledge gaps and pitfalls in exploring complex interactions among microorganisms and their environment in the context of chemical pollution and pinpoint areas of research where future efforts are needed., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)
- Published
- 2023
- Full Text
- View/download PDF
45. Lynch syndrome: influence of additional susceptibility variants on cancer risk.
- Author
-
Vibert R, Hasnaoui J, Perrier A, Lefebvre A, Colas C, Dhooge M, Basset N, Chansavang A, Desseignes C, Duval A, Farelly S, Hamzaoui N, Laurent-Puig P, Metras J, Moliere D, Muleris M, Netter J, Touat M, Bielle F, Labreche K, Nicolle R, Perkins G, Warcoin M, Coulet F, and Benusiglio PR
- Subjects
- Humans, Germ-Line Mutation, Risk, Phenotype, Colorectal Neoplasms, Hereditary Nonpolyposis diagnosis, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Colorectal Neoplasms, Hereditary Nonpolyposis pathology
- Abstract
Some patients with Lynch syndrome (LS) have extreme phenotypes, i.e. cancer before the recommended screening age, or cancer for which there are no screening guidelines. We made the hypothesis that additional germline variants in cancer susceptibility genes (CSG) could explain some of these phenotypes. We compared the prevalence of additional CSG variants in LS patients with a cancer diagnosis before age 30 (early-onset, EO group) and after 40 (usual-onset, UO group). While there was no overall difference, we did find an excess of pathogenic variants and variants of unknown significance in EO cases when only gastrointestinal CSG were considered (OR 2.25; 95% CI: 1.01-5.06, p value = 0.04). Four EO cases stood out: two with POLE/POLD1 variants in the key exonuclease domain, one with a BMPR1A duplication and one with an EPCAM deletion. Additional germline variants should be considered in future screening recommendations, as they might influence cancer risk., (© 2023. The Author(s), under exclusive licence to European Society of Human Genetics.)
- Published
- 2023
- Full Text
- View/download PDF
46. Targeting SLC transporters: small molecules as modulators and therapeutic opportunities.
- Author
-
Schlessinger A, Zatorski N, Hutchinson K, and Colas C
- Subjects
- Humans, Membrane Transport Proteins chemistry, Biological Transport physiology, Drug Discovery methods, Solute Carrier Proteins chemistry, Solute Carrier Proteins metabolism, Neoplasms metabolism
- Abstract
Solute carrier (SLCs) transporters mediate the transport of a broad range of solutes across biological membranes. Dysregulation of SLCs has been associated with various pathologies, including metabolic and neurological disorders, as well as cancer and rare diseases. SLCs are therefore emerging as key targets for therapeutic intervention with several recently approved drugs targeting these proteins. Unlocking this large and complex group of proteins is essential to identifying unknown SLC targets and developing next-generation SLC therapeutics. Recent progress in experimental and computational techniques has significantly advanced SLC research, including drug discovery. Here, we review emerging topics in therapeutic discovery of SLCs, focusing on state-of-the-art approaches in structural, chemical, and computational biology, and discuss current challenges in transporter drug discovery., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
47. Paralog-dependent isogenic cell assay cascade generates highly selective SLC16A3 inhibitors.
- Author
-
Dvorak V, Casiraghi A, Colas C, Koren A, Tomek T, Offensperger F, Rukavina A, Tin G, Hahn E, Dobner S, Frommelt F, Boeszoermenyi A, Bernada V, Hannich JT, Ecker GF, Winter GE, Kubicek S, and Superti-Furga G
- Subjects
- Membrane Transport Proteins genetics, Carrier Proteins, Drug Discovery
- Abstract
Despite being considered druggable and attractive therapeutic targets, most of the solute carrier (SLC) membrane transporters remain pharmacologically underexploited. One of the reasons for this is a lack of reliable chemical screening assays, made difficult by functional redundancies among SLCs. In this study we leveraged synthetic lethality between the lactate transporters SLC16A1 and SLC16A3 in a screening strategy that we call paralog-dependent isogenic cell assay (PARADISO). The system involves five isogenic cell lines, each dependent on various paralog genes for survival/fitness, arranged in a screening cascade tuned for the identification of SLC16A3 inhibitors. We screened a diversity-oriented library of ∼90,000 compounds and further developed our hits into slCeMM1, a paralog-selective and potent SLC16A3 inhibitor. By implementing chemoproteomics, we showed that slCeMM1 is selective also at the proteome-wide level, thus fulfilling an important criterion for chemical probes. This study represents a framework for the development of specific cell-based drug discovery assays., Competing Interests: Declaration of interests V.D., A.C., and G.S.-F. are co-authors of patent applications related to presented study. S.K., G.E.W., and G.S.-F. are co-founders of company related to SLCs. G.S.-F. is the Academic Project Coordinator of the IMI RESOLUTE/Resolution consortium in partnership with Pfizer, Novartis, Bayer, Sanofi, Boehringer Ingelheim and Vifor Pharma. G.S.-F., G.E.W., and S.K. laboratories receive funds from Pfizer., (Copyright © 2023 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences GmbH. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
48. Physical Activity in Long COVID: A Comparative Study of Exercise Rehabilitation Benefits in Patients with Long COVID, Coronary Artery Disease and Fibromyalgia.
- Author
-
Colas C, Le Berre Y, Fanget M, Savall A, Killian M, Goujon I, Labeix P, Bayle M, Féasson L, Roche F, and Hupin D
- Subjects
- Humans, Post-Acute COVID-19 Syndrome, Hand Strength, Exercise Therapy, Exercise, Exercise Test, Coronary Artery Disease, Fibromyalgia, COVID-19
- Abstract
Exercise in long COVID is poorly studied. Nevertheless, exerciserehabilitation could improve cardiorespiratory, muscular and autonomic functions. We aimed to investigate improvement in physical and autonomic performances of long COVID patients ( n = 38) after a 4-week exercise rehabilitation program (3 sessions/week) compared to two control groups composed of coronary artery disease ( n = 38) and fibromyalgia patients ( n = 38), two populations for whom exercise benefits are well known. Efficacy of exercise training was assessed by a cardiopulmonary exercise test, a handgrip force test, and a supine heart rate variability recording at rest before and after the rehabilitation program. Cardiorespiratory and muscular parameters were enhanced after exercise rehabilitation in the three groups ( p < 0.001). No significant difference was observed for the autonomic variables. Through this comparative study with control groups, we confirm and reinforce the interest of caring for long COVID patients without post-exertional symptom exacerbation by exercise rehabilitation of both strength and endurance training, by personalizing the program to the patient and symptoms.
- Published
- 2023
- Full Text
- View/download PDF
49. First report of medulloblastoma in a patient with MUTYH-associated polyposis.
- Author
-
Villy MC, Warcoin M, Filser M, Buecher B, Golmard L, Suybeng V, Schwartz M, Bieche I, Vacher S, Laurence V, Bourdeaut F, Bernier M, Gutman T, Stoppa-Lyonnet D, Masliah-Planchon J, and Colas C
- Subjects
- Humans, Genetic Predisposition to Disease, Mutation, Carcinogenesis, Medulloblastoma genetics, Adenomatous Polyposis Coli genetics, Adenomatous Polyposis Coli pathology, Cerebellar Neoplasms genetics, Colorectal Neoplasms genetics
- Abstract
Aims: The mutY DNA glycosylase encoded by the MUTYH gene prevents G:C → T:A transversions through the base excision repair DNA repair system. Germline biallelic pathogenic variants in MUTYH cause an adenomatous polyposis called MUTYH-associated polyposis (MAP), an autosomal recessive disease (OMIM: 608456), with an increased risk of colorectal cancer. Digestive lesions in this context show an excess of G:C → T:A transversions, individualising a specific mutational signature associated with MUTYH deficiency called signature SBS36. Predisposition to other tumours in patients with germline biallelic pathogenic variants in MUTYH is suspected but remains unclear. We report the first case of medulloblastoma in a patient with MAP, carrying the homozygous pathogenic variant c.1227_1228dup, p.(Glu410Glyfs*43) in MUTYH., Methods: Whole exome sequencing was performed on the medulloblastoma to enlighten single nucleotide variants of interest, microsatellite status and mutational signature. The objective was to determine the involvement of MUTYH deficiency in the oncogenesis of this medulloblastoma., Results: The medulloblastoma has the mutational signature SBS36 and driver pathogenic variants in CTNNB1, PTCH1 and KDM6A corresponding to G:C → T:A transversions, suggesting a role of MUTYH deficiency in oncogenesis., Conclusions: Therefore, medulloblastoma could be a rare manifestation associated with germline biallelic pathogenic variants in MUTYH., (© 2023 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)
- Published
- 2023
- Full Text
- View/download PDF
50. STAT3 mutation-associated airway epithelial defects in Job syndrome.
- Author
-
Zhang Y, Lin T, Leung HM, Zhang C, Wilson-Mifsud B, Feldman MB, Puel A, Lanternier F, Couderc LJ, Danion F, Catherinot E, Salvator H, Tcherkian C, Givel C, Xu J, Tearney GJ, Vyas JM, Li H, Hurley BP, and Mou H
- Subjects
- Humans, Mice, Animals, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, Cell Differentiation, Epithelial Cells metabolism, Mutation, Job Syndrome genetics
- Abstract
Background: Job syndrome is a disease of autosomal dominant hyper-IgE syndrome (AD-HIES). Patients harboring STAT3 mutation are particularly prone to airway remodeling and airway infections., Objectives: Airway epithelial cells play a central role as the first line of defense against pathogenic infection and express high levels of STAT3. This study thus interrogates how AD-HIES STAT3 mutations impact the physiological functions of airway epithelial cells., Methods: This study created human airway basal cells expressing 4 common AD-HIES STAT3 mutants (R382W, V463del, V637M, and Y657S). In addition, primary airway epithelial cells were isolated from a patient with Job syndrome who was harboring a STAT3-S560del mutation and from mice harboring a STAT3-V463del mutation. Cell proliferation, differentiation, barrier function, bacterial elimination, and innate immune responses to pathogenic infection were quantitatively analyzed., Results: STAT3 mutations reduce STAT3 protein phosphorylation, nuclear translocation, transcription activity, and protein stability in airway basal cells. As a consequence, STAT3-mutated airway basal cells give rise to airway epithelial cells with abnormal cellular composition and loss of coordinated mucociliary clearance. Notably, AD-HIES STAT3 airway epithelial cells are defective in bacterial killing and fail to initiate vigorous proinflammatory responses and neutrophil transepithelial migration in response to an experimental model of Pseudomonas aeruginosa infection., Conclusions: AD-HIES STAT3 mutations confer numerous abnormalities to airway epithelial cells in cell differentiation and host innate immunity, emphasizing their involvement in the pathogenesis of lung complications in Job syndrome. Therefore, therapies must address the epithelial defects as well as the previously noted immune cell defects to alleviate chronic infections in patients with Job syndrome., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.