1,396 results on '"M, Caputo"'
Search Results
2. Atypical cancer risk profile in carriers of Italian founder BRCA1 variant p.His1673del: Implications for classification and clinical management
- Author
-
Giovanni Innella, Cristina Fortuno, Laura Caleca, Bing‐Jian Feng, Courtney Carroll, Michael T. Parsons, Sara Miccoli, Marco Montagna, Daniele Calistri, Laura Cortesi, Barbara Pasini, Siranoush Manoukian, Daniela Giachino, Laura Matricardi, Maria Cristina Foti, Valentina Zampiga, Claudia Piombino, Elena Barbieri, Francesca Vignolo Lutati, Jacopo Azzolini, Rita Danesi, Valentina Arcangeli, Sandrine M. Caputo, Nadia Boutry‐Kryza, Vincent Goussot, Susan Hiraki, Marcy Richardson, Hereditary Breast/Ovarian Cancer IOV network (HBOC IOVnet), Simona Ferrari, Paolo Radice, Amanda B. Spurdle, and Daniela Turchetti
- Subjects
BRCA1 ,breast cancer ,cancer risk ,classification ,clinical management ,ovarian cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background BRCA1:c.5017_5019del (p.His1673del) is a founder variant relatively frequent in Northern Italy. Despite previous suggestion of pathogenicity, variant classification in public databases is still conflicting, needing additional evidence. Methods Maximum likelihood penetrance of breast/ovarian and other cancer types was estimated using full pedigree data from 53 informative Italian families. The effect of the variant on BRCA1‐ABRAXAS1 interaction was assessed using a GFP‐fragment reassembly‐based PPI assay. Results were combined with additional data from multiple sources to classify the variant according to ACMG/AMP classification rules specified for BRCA1/2. Results Variant‐carriers displayed increased risk for ovarian cancer (HR = 33.0, 95% CI = 7.0–155.0; cumulative risk at age 70 = 27.6%, 95% CI = 12.6–40.0%) but not for breast cancer (HR = 0.7, 95% CI = 0.2–2.2). An increased risk of uterine cancer (HR = 8.0, 95% CI = 1.03–61.6) emerged, warranting further evaluation. Likelihood‐ratio in favor of pathogenicity was 98898642.82 under assumption of standard BRCA1 breast and ovarian penetrance, and 104240832.84 after excluding breast cancer diagnoses (based on penetrance results). Functional analysis demonstrated that the variant abrogates the BRCA1‐ABRAXAS1 binding, supporting the PS3 code assignment within the ACMG/AMP rule‐based model. Collectively, these findings allowed to classify the variant as pathogenic. Conclusion Pathogenicity of BRCA1:c.5017_5019del(p.His1673del) has been confirmed; however, breast cancer risk in Italian families is not increased, unlike in families from other countries and in carriers of most BRCA1 pathogenic variants. The knowledge of atypical risk profiles for this and other variants will pave the way for personalized management based on specific genotype.
- Published
- 2024
- Full Text
- View/download PDF
3. Acoustic detections and sightings of blue whales Balaenoptera musculus in the Seychelles, western tropical Indian Ocean (2020-2022)
- Author
-
KM Stafford, G Boussarie, M Caputo, L Irvine, S Laing, E Nancy, H Pearson, and JJ Kiszka
- Subjects
Zoology ,QL1-991 ,Botany ,QK1-989 - Abstract
Historically, the Seychelles archipelago was an opportunistic whaling ground for fleets en route to and from the Antarctic. Soviet whalers illegally killed 500 blue whales near the Seychelles in the 1960s. Since then, no dedicated research has occurred to understand the ecological importance of this region for blue whales. Based on opportunistic sightings, we undertook 2 expeditions to assess the occurrence of blue whales. The overall goals were to determine blue whale distribution, obtain photo-identification data and collect the first acoustic data on this species in this region using a hydrophone deployed for a year. The expeditions consisted of vessel-based visual surveys that focused on the slope habitat (500-2000 m) off the northern portion of the Mahé Plateau. Over the 2 expeditions, a total of 5 sightings of up to 10 animals were seen. The results of our acoustic monitoring off Seychelles demonstrate that blue whales occur there regularly, primarily from December to April, and that the acoustic population identity matches that from near Sri Lanka. Published records and the results of our work suggest that blue whales from the northwestern Indian Ocean are seasonally present in the western equatorial Indian Ocean.
- Published
- 2023
- Full Text
- View/download PDF
4. Male breast cancer: No evidence for mosaic BRCA1 promoter methylation involvement
- Author
-
Mathias Schwartz, Sabrina Ibadioune, Sophie Vacher, Marie-Charlotte Villy, Olfa Trabelsi-Grati, Jessica Le Gall, Sandrine M. Caputo, Hélène Delhomelle, Mathilde Warcoin, Virginie Moncoutier, Christine Bourneix, Nadia Boutry-Kryza, Antoine De Pauw, Marc-Henri Stern, Bruno Buecher, Emmanuelle Mouret-Fourme, Chrystelle Colas, Dominique Stoppa-Lyonnet, Julien Masliah-Planchon, Lisa Golmard, and Ivan Bieche
- Subjects
HBOC syndrome ,Breast neoplasm ,Genetic testing ,Homologous recombination ,DNA methylation ,Epigenomics ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - 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.
- Published
- 2024
- Full Text
- View/download PDF
5. What internal medicine attendings talk about at morning report: a multicenter study
- Author
-
Jeffrey W. Redinger, Daniel B. Heppe, Tyler J. Albert, Paul B. Cornia, Kirsha S. Gordon, Cherinne Arundel, Joel M. Bradley, Laura M. Caputo, Jonathan W. Chun, Jessica E. Cyr, Erik T. Ehlers, Michelle M. Guidry, Anand D. Jagannath, Brian K. Kwan, James D. Laudate, Christine A. Mitchell, Andrea C. Smeraglio, Joseph R. Sweigart, Matthew G. Tuck, and Craig G. Gunderson
- Subjects
Medical education ,Graduate medical education ,Morning report ,Internal medicine residency ,Special aspects of education ,LC8-6691 ,Medicine - Abstract
Abstract Background Morning report is a core educational activity in internal medicine resident education. Attending physicians regularly participate in morning report and influence the learning environment, though no previous study has described the contribution of attending physicians to this conference. This study aims to describe attending comments at internal medicine morning reports. Methods We conducted a prospective, observational study of morning reports conducted at 13 internal medicine residency programs between September 1, 2020, and March 30, 2021. Each attending comment was described including its duration, whether the comment was teaching or non-teaching, teaching topic, and field of practice of the commenter. We also recorded morning report-related variables including number of learners, report format, program director participation, and whether report was scripted (facilitator has advance knowledge of the case). A regression model was developed to describe variables associated with the number of attending comments per report. Results There were 2,344 attending comments during 250 conferences. The median number of attendings present was 3 (IQR, 2–5). The number of comments per report ranged across different sites from 3.9 to 16.8 with a mean of 9.4 comments/report (SD, 7.4). 66% of comments were shorter than one minute in duration and 73% were categorized as teaching by observers. The most common subjects of teaching comments were differential diagnosis, management, and testing. Report duration, number of general internists, unscripted reports, and in-person format were associated with significantly increased number of attending comments. Conclusions Attending comments in morning report were generally brief, focused on clinical teaching, and covered a wide range of topics. There were substantial differences between programs in terms of the number of comments and their duration which likely affects the local learning environment. Morning report stakeholders that are interested in increasing attending involvement in morning report should consider employing in-person and unscripted reports. Additional studies are needed to explore best practice models of attending participation in morning report.
- Published
- 2023
- Full Text
- View/download PDF
6. A Perplexing case of isolated abducens nerve palsy in a primigravida woman: A case report
- Author
-
Johnna M. Caputo, Marianna Catege, Ishani Dev, Benjamin Souferi, and Adele El Kareh
- Subjects
Sixth cranial nerve palsy ,Abducens nerve palsy ,Pregnancy ,Surgery ,RD1-811 ,Gynecology and obstetrics ,RG1-991 - Abstract
Isolated abducens nerve palsy is a rare presentation in women during pregnancy. When an abducens nerve palsy is elicited in a pregnant woman, work-up should start with labs and neuroimaging to rule out mechanical and organic causes such as tumors, preeclampsia, and multiple sclerosis. This case report highlights a 35-year-old woman, gravida 1, para 0, who was sent to the local medical center by her ophthalmologist at 37 weeks of gestation due to a left-sided headache and blurry vision. Upon admission, work-up was negative for preeclampsia. Tick-borne disease panel and lumbar puncture were unrevealing. No other mechanical or lab abnormalities were elicited. Magnetic resonance venography revealed a diminutive left transverse sinus, left sigmoid sinus, and left internal jugular vein in comparison with the right, indicating a possible congenital variant. Labor was induced to see if this would alleviate the patient's abducens nerve palsy. After induction of labor and initiation of dexamethasone, the patient's sixth cranial nerve palsy began to improve.
- Published
- 2023
- Full Text
- View/download PDF
7. Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study
- Author
-
Sanne A E Peters, Mark Woodward, Fw Asselbergs, Folkert W Asselbergs, B Williams, GP McCann, R Zaal, Carinna Hockham, P Dark, S Prasad, A Aujayeb, A Mosterd, M Saxena, L Gabriel, CE Delsing, J De Sutter, R Pisters, P van der Meer, M Caputo, A Schut, P van der Harst, MT Kearney, YM Pinto, DP Ripley, RG Tieleman, J Redón, A Moriarty, P Woudstra, Marijke Linschoten, G Captur, Chahinda Ghossein, AK Al-Ali, FA Al-Muhanna, NYY Al-Windy, YA Almubarak, AN Alnafie, M Alshahrani, AM Alshehri, RL Anthonio, JM ten Berg, AJM van Boxem, N Charlotte, HGR Dorman, JT Drost, ME Emans, JB Ferreira, WH van Gilst, BE Groenemeijer, HE Haerkens-Arends, B Hedayat, DJ van der Heijden, E Hellou, RS Hermanides, JF Hermans-van Ast, MWJ van Hessen, SRB Heymans, ICC van der Horst, SH van Ierssel, LS Jewbali, HAM van Kesteren, Kietselaer BLJH, AMH Koning, PY Kopylov, AFM Kuijper, JM Kwakkel-vanErp, van der Linden MMJM, M Linschoten, GCM Linssen, Macias Ruiz R, FJH Magdelijns, Martens FMAC, MFL Meijs, P Messiaen, PS Monraats, L Montagna, PR Nierop, CEE van Ofwegen-Hanekamp, H Poorhosseini, AC Reidinga, MIA Ribeiro, R Salah, E Saneei, J Schaap, Schellings DAAM, A Shafiee, AC Shore, HJ Siebelink, M van Smeden, PC Smits, E Tessitore, P Timmermans, RA Tio, FVY Tjong, CA den Uil, EM Van Craenenbroeck, van Veen HPAA, T Veneman, DO Verschure, JK de Vries, RMA van de Wal, DJ van de Watering, ICD Westendorp, PHM Westendorp, C Weytjens, E Wierda, KW Wu, AG Zaman, and PM van derZee
- Subjects
Medicine - Abstract
Objective To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease.Design Registry based observational study.Setting 74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021Participants All adults (aged ≥18 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11 167 patients).Main outcome measures Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with ≥20 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease.Results Of 11 167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07).Conclusions In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.
- Published
- 2023
- Full Text
- View/download PDF
8. Value of the loss of heterozygosity to BRCA1 variant classification
- Author
-
Elizabeth Santana dos Santos, Amanda B. Spurdle, Dirce M. Carraro, Adrien Briaux, Melissa Southey, Giovana Torrezan, Ambre Petitalot, Raphael Leman, Philippe Lafitte, kConFab Investigators, Didier Meseure, Keltouma Driouch, Lucy Side, Carole Brewer, Sarah Beck, Athalie Melville, Alison Callaway, Françoise Revillion, Maria A. A. Koike Folgueira, Michael T. Parsons, Heather Thorne, Anne Vincent-Salomon, Dominique Stoppa-Lyonnet, Ivan Bieche, Sandrine M. Caputo, and Etienne Rouleau
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract At least 10% of the BRCA1/2 tests identify variants of uncertain significance (VUS) while the distinction between pathogenic variants (PV) and benign variants (BV) remains particularly challenging. As a typical tumor suppressor gene, the inactivation of the second wild-type (WT) BRCA1 allele is expected to trigger cancer initiation. Loss of heterozygosity (LOH) of the WT allele is the most frequent mechanism for the BRCA1 biallelic inactivation. To evaluate if LOH can be an effective predictor of BRCA1 variant pathogenicity, we carried out LOH analysis on DNA extracted from 90 breast and seven ovary tumors diagnosed in 27 benign and 55 pathogenic variant carriers. Further analyses were conducted in tumors with PVs yet without loss of the WT allele: BRCA1 promoter hypermethylation, next-generation sequencing (NGS) of BRCA1/2, and BRCAness score. Ninety-seven tumor samples were analyzed from 26 different BRCA1 variants. A relatively stable pattern of LOH (65.4%) of WT allele for PV tumors was observed, while the allelic balance (63%) or loss of variant allele (15%) was generally seen for carriers of BV. LOH data is a useful complementary argument for BRCA1 variant classification.
- Published
- 2022
- Full Text
- View/download PDF
9. Identification of a large intra-exonic deletion in exon 18 in a pancreatic ductal adenocarcinoma
- Author
-
Inès Debbabi, Sophie Vacher, Cindy Neuzillet, Jérome Cros, Françoise Revillon, Ambre Petitalot, Anthony Turpin, Samantha Antonio, Elodie Girard, Célia Dupain, Maud Kamal, Pascal Hammel, Ivan Bièche, Julien Masliah-Planchon, and Sandrine M. Caputo
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
By 2030, pancreatic cancer will become the second leading cause of cancer-related deaths in the United States and in Europe. The management of patients with advanced pancreatic cancer relies on chemotherapy and poly (ADP-ribose) polymerase inhibitors for patients who carry BRCA1/2 inactivating alterations. Some variants, such as large insertion/deletions (Indels), inactivating BRCA1/2 and therefore of clinical relevance can be hard to detect by next-generation sequencing techniques. Here we report a 47-year-old patient presenting with pancreatic cancer whose tumour harbours a large somatic intra-exonic deletion of BRCA2 of 141 bp. This BRCA2 deletion, located in the C-terminal domain, can be considered as pathogenic and consequently affect tumorigenesis because it is involved in the interaction between the DSS1 protein and DNA. Thanks to the optimized bioinformatics algorithm, this intermediate size deletion in BRCA2 was identified, enabling personalized patient management via the inclusion of the patients in a clinical trial.
- Published
- 2023
- Full Text
- View/download PDF
10. A new hybrid record linkage process to make epidemiological databases interoperable: application to the GEMO and GENEPSO studies involving BRCA1 and BRCA2 mutation carriers
- Author
-
Yue Jiao, Fabienne Lesueur, Chloé-Agathe Azencott, Maïté Laurent, Noura Mebirouk, Lilian Laborde, Juana Beauvallet, Marie-Gabrielle Dondon, Séverine Eon-Marchais, Anthony Laugé, GEMO Study Collaborators, GENEPSO Study Collaborators, Catherine Noguès, Nadine Andrieu, Dominique Stoppa-Lyonnet, and Sandrine M. Caputo
- Subjects
Record linkage ,Hybrid process ,Probabilistic linkage ,Supervised machine learning ,Medicine (General) ,R5-920 - Abstract
Abstract Background Linking independent sources of data describing the same individuals enable innovative epidemiological and health studies but require a robust record linkage approach. We describe a hybrid record linkage process to link databases from two independent ongoing French national studies, GEMO (Genetic Modifiers of BRCA1 and BRCA2), which focuses on the identification of genetic factors modifying cancer risk of BRCA1 and BRCA2 mutation carriers, and GENEPSO (prospective cohort of BRCAx mutation carriers), which focuses on environmental and lifestyle risk factors. Methods To identify as many as possible of the individuals participating in the two studies but not registered by a shared identifier, we combined probabilistic record linkage (PRL) and supervised machine learning (ML). This approach (named “PRL + ML”) combined together the candidate matches identified by both approaches. We built the ML model using the gold standard on a first version of the two databases as a training dataset. This gold standard was obtained from PRL-derived matches verified by an exhaustive manual review. Results The Random Forest (RF) algorithm showed a highest recall (0.985) among six widely used ML algorithms: RF, Bagged trees, AdaBoost, Support Vector Machine, Neural Network. Therefore, RF was selected to build the ML model since our goal was to identify the maximum number of true matches. Our combined linkage PRL + ML showed a higher recall (range 0.988–0.992) than either PRL (range 0.916–0.991) or ML (0.981) alone. It identified 1995 individuals participating in both GEMO (6375 participants) and GENEPSO (4925 participants). Conclusions Our hybrid linkage process represents an efficient tool for linking GEMO and GENEPSO. It may be generalizable to other epidemiological studies involving other databases and registries.
- Published
- 2021
- Full Text
- View/download PDF
11. Inositols and metabolic disorders: From farm to bedside
- Author
-
M. Caputo, E. Bona, I. Leone, M.T. Samà, A. Nuzzo, A. Ferrero, G. Aimaretti, P. Marzullo, and F. Prodam
- Subjects
Inositol ,Diet ,Food supplement ,Metabolism ,Microbiota ,Type 2 diabetes ,Medicine - Abstract
Inositol and its derivates are catching interest in metabolism since taking part in several physiological processes, including endocrine modulation. Through several mechanisms mostly mediated by insulin signaling, these compounds regulate the activities of several hormones and are essential in oocytes maturation. It is interesting to point out the contribution of an inositol deficiency in the development of several diseases, mainly in the metabolic and endocrine setting. Inositols derive from both diet and endogenous production; among causes of inositol deficiency reduced dietary intake, increased catabolism and/or excretion, decreased biosynthesis, inhibition of gut and cellular uptake and altered microbiota could be considered. Mounting direct and indirect evidence suggests that the two main isoforms (Myo-inositol-inositol, D-chiro-inositol) are implied in glycemic and lipidic metabolism and supplementation yield a beneficial effect on these parameters without hazards for health. Moreover, they have a role in polycystic ovary syndrome, acting as insulin-sensitizing agents and free radical scavengers, helping to regulate metabolism and promoting ovulation. The aim of this narrative review is to discuss the role of inositols in metabolic function disorders paying attention to whether these compounds could be efficacious and safe as a therapeutic agent with a focus on dietary intake and the role of gut microbiota.
- Published
- 2020
- Full Text
- View/download PDF
12. Prosthetic forefoot and heel stiffness across consecutive foot stiffness categories and sizes
- Author
-
Anne T. Turner, Elizabeth G. Halsne, Joshua M. Caputo, Carl S. Curran, Andrew H. Hansen, Brian J. Hafner, and David C. Morgenroth
- Subjects
Medicine ,Science - Abstract
Prosthetic foot stiffness plays a key role in the functional mobility of lower limb prosthesis users. However, limited objective data exists to guide selection of the optimal prosthetic foot stiffness category for a given individual. Clinicians often must rely solely on manufacturer recommendations, which are typically based on the intended user’s weight and general activity level. Availability of comparable forefoot and heel stiffness data would allow for a better understanding of differences between different commercial prosthetic feet, and also between feet of different stiffness categories and foot sizes. Therefore, this study compared forefoot and heel linear stiffness properties across manufacturer-designated stiffness categories and foot sizes. Mechanical testing was completed for five types of commercial prosthetic feet across a range of stiffness categories and three foot-sizes. Data were collected for 56 prosthetic feet, in total. Testing at two discrete angles was conducted to isolate loading of the heel and forefoot components, respectively. Each prosthetic foot was loaded for six cycles while force and displacement data were collected. Forefoot and heel measured stiffness were both significantly associated with stiffness category (p = .001). There was no evidence that the relationships between stiffness category and measured stiffness differed by foot size (stiffness category by size interaction p = .80). However, there were inconsistencies between the expected and measured stiffness changes across stiffness categories (i.e., magnitude of stiffness changes varied substantially between consecutive stiffness categories of the same feet). While statistical results support that, on average, measured stiffness is positively correlated with stiffness category, force-displacement data suggest substantial variation in measured stiffness across consecutive categories. Published objective mechanical property data for commercial prosthetic feet would likely therefore be helpful to clinicians during prescription.
- Published
- 2022
13. Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- Author
-
T Richards, S Shaikh, S Rehman, A Khan, J Shah, C Smith, A Brown, S Singh, A P Arnaud, A Young, D Bowen, P Patel, S Williams, J Dunn, J John, M Loubani, A Hainsworth, A Kolias, PJ Hutchinson, R Singh, S Sinha, S Shaw, J Edwards, S Mukherjee, AAB Jamjoom, A Singh, S Saeed, J Martin, S Smith, S Ross, M Mohan, P Hutchinson, G James, RDC Moon, P Brennan, A Williams, S Brown, A Ward, M Lee, K Thompson, S Ali, J Williams, S Reid, U Khan, J Lambert, A Smith, B Singh, M Hassan, N Sharma, J Reynolds, N Wright, T Williams, H Smith, M Ng, M Rahman, A Taylor, P Shah, D Saxena, J Evans, I Omar, M Ali, A Hanson, Z Li, R Andrade, P Cardoso, H Jeong, P Sharma, M Arrieta, J Clark, L Pearce, J McVeigh, V Sharma, B Kim, J Singh, S Newman, J Byrne, A Hassan, A Persad, A Gardner, H Liu, K Shah, I Hughes, S Davison, A Balakrishnan, K Patel, J Hall, S Mistry, J Parry, R Baumber, N McGrath, E Ross, R Mannion, S Murphy, FL Wright, A Rogers, B Rai, M Thomas, R Ribeiro, E Hamilton, J Teixeira, B Davidson, L Carvalho, R Garrido, A Puppo, A Guimarães, E Santos, M Kamal, M Denning, M Elhadi, J E Fitzgerald, D Miller, M Gowda, C Morris, A Phillips, H Yang, Y Zhang, N Machairas, A Fisher, A Kaufmann, A Aggarwal, L Hansen, M Otify, H Soleymani Majd, A Jones, M Rodrigues, S Sundar, C Jones, R Edmondson, A Sharkey, L Smith, G Williams, J Dunning, E Belcher, D Stavroulias, V Zamvar, M Patel, M Baker, R Evans, M Sherif, J Hopkins, R Mohammed, A Hill, H Jackson, G Jones, K George, J Dixon, A Tong, S Jallad, Deborah S Keller, A Pereira, L Elliott, D Ford, A Sermon, M Almond, Andrew Metcalfe, C Peluso, T White, S Shah, A Witek, Chetan Khatri, A Tiwari, T Lo, K Agarwal, C Sweeney, C Hart, T Holme, S Green, I Ahmed, A Sobti, C Anderson, N Modi, R Campbell, C Magee, M Mirza, D Jones, N Stylianides, X Luo, C Kang, J Ribeiro, L Kumar, J Diaz, A Bhalla, R Young, C Perkins, A James, A Walters, J Reid, R Pereira, C McDonald, A Aujayeb, K Jackson, M Allen, D Ghosh, M Chan, C Price, K Khan, R Moore, M Ibrahim, A Marchbank, M Silva, M Baig, J De Coster, J Castellanos, S Saxena, M Duque, E Li, E Martin, A Isik, J González, RJ Davies, B Smith, R Owen, K Lakhoo, M Rogers, MA Akhtar, K Mellor, S Agrawal, L Foster, G Harris, J McIntyre, M Garner, R West, R Cuthbert, D Johnson, H Gomes, C Roy, N Spencer, D Mehta, J Freedman, J Blair, K Rajput, K Williams, J Wall, A Soliman, F Chen, A Mokhtari, I Mohamed, J Pascoe, M Khalifa, R Das, A Lara, M Costa, A Mahmoud, K Roberts, J Lane, S Robertson, J P Evans, E Krishnan, I Haq, S Rogers, J Knowles, M Chowdhury, A Ghanbari, L Macdonald, S Powell, J Hunt, J Cornish, J Engel, S Page, I Blake, A Rolls, H Ross, D Simpson, J Hammond, A Goyal, K Parkins, A Desai, A Gaunt, A Salim, Y Yousef, A Schache, H Mohan, SR Brown, R Nair, M Flatman, J Lord, RJ Egan, R Harries, N Judkins, K Sugand, T Hine, J Luck, C Johnson, G Salerno, AW Phillips, R Houston, A Volpe, C Walker, C Steele, M Rela, C Barry, R Alves, L Ramsay, A Turnbull, A Daniele, C S Jones, P Gallagher, G Gradinariu, A Oliveira, C Hardie, H Ferguson, S Bhattacharya, E Davies, P Joshi, C Mellor, E Griffiths, A Bhangu, R Mahoney, F Kashora, G Ruiz, K Wong, G Hill, V Testa, S Ford, C Park, P Gomez, C Lopes, A Lázaro, A Shabana, A Agarwal, C Chung, C Politis, G Martin, E Chung, M Ismail, C Cunha, S Correia, I Santos, A Tang, A Robson, T Collier, G Baltazar, M Quintana, C English, M Ip, K Newton, J Kahn, C Tan, D Cheng, R Woods, M Ho, A ABBAS, A Henry, F Rivas, M Mohammed, N Parsons, T Board, S Madan, A Osorio, M Jarvis, M Hashem, A Egglestone, E Halliday, A Ridgway, G Gallo, J Gilliland, W Marx, R Shaw, A Mahmood, K Gohil, B Gallagher, D Alderson, A Karim, G D Stewart, G Peck, L Majkowski, J Carter, H Ishii, L HUMPHREYS, J Khan, S Abbott, C Newton, F Borghi, A Sud, K Bhatia, H Cao, V Vijay, L Sanderson, E Holler, N Hanna, D Ferguson, P Miranda, L Pickering, T Singhal, T Newman, K Ghosh, C Camacho, D Manning, C Lipede, R Clifford, S Higgs, C Menakaya, S Shankar, K Booth, M Abdalla, T Nelson, T Farrell, H Naseem, J Johnstone, A Wilkins, A Brunt, A Nogués, A Patience, D Jeevan, M Vatish, G Stables, S Adegbola, I Hunt, K Dickson, W Matthews, N Dunne, M Maher, G Faulkner, E Hernandez, R Sofat, K Sahnan, A Brunelli, M Raza, K Chui, C Brennan, P Vaughan, H Chu, R Hagger, ASD Liyanage, R Perkins, S Duff, C Gill, H Dean, S Bandyopadhyay, K Ragupathy, Y Cunningham, A Bateman, V Brown, B Ho, E Britton, H Ikram, R Hasan, A Colquhoun, S Handa, A Maqsood, M Caputo, J Torkington, G Fusai, N Hossain, DJ Lin, S Stefan, IR Daniels, D Pournaras, A Askari, P Nisar, S Moug, J Sagar, N Yassin, G Minto, Z Hamady, JR O'Neill, S Chowdhury, R Cresner, D Vimalachandran, FD Mcdermott, RP Jones, P Zerbib, L Sreedharan, S Wahed, SS Gisbertz, MI van Berge Henegouwen, R Preece, I Liew, S McCluney, D Watts, D Nehra, B Dean, D Chaudhry, L Ross, F Solari, S Chatterji, B Barmayehvar, S Lourenco, L Onos, F Mansour, A Radhakrishnan, M Varcada, M Richmond, I Hernández, A Spinelli, H Pham, J Shalhoub, F Wells, K Bevan, A Peckham-Cooper, N Campain, J Steinke, R Wilkin, K McEvoy, S Mastoridis, N Fine, J Bayer, Y Joshi, A Yener, S C McKay, NS Kalson, S Horvath, H Fu, A Parente, SE Lewis, Y Ahmad, G Seidel, M Dunstan, U von Oppell, J Vatish, H Hirsch, K Breen, C Dott, D Mathieu, J Hardie, K Aldridge, A Doorgakant, P Petrone, R Tansey, M El Amrani, C Branco, Y Viswanath, A Meagher, B Keeler, N Tewari, A Gabr, J Kinross, M Longhi, E M Harrison, P Daliya, P Asaad, F Langlands, N Misra, S Kristinsson, S Di Saverio, C Conso, H Roy, E Massie, L Masterson, D Baskaran, A Hannah, O Ismail, S URBAN, J Domenech, S Ranjit, L Massey, S Mannan, D Rutherford, F Colombo, R Kulkarni, D Kearney, Neil J Smart, G Bourke, D Shrestha, P Nankivell, O Breik, R Exley, D Zakai, AK Abou-Foul, P Naredla, R Vidya, G Mundy, H Marin, A E Ward, A Sudarsanam, W Singleton, M Ganau, F Moura, J Blanco, R Myatt, S Sousa, H Zahid, S Garrido, A Fell, E Caruana, D Nepogodiev, F Dhaif, B Bankhad-Kendall, H Kaafarani, C Bretherton, L Marais, K Siaw-Acheampong, B E Dawson, J C Glasbey, R R Gujjuri, E Heritage, S K Kamarajah, J M Keatley, S Lawday, G Pellino, J F F Simoes, I M Trout, M L Venn, R J W Wilkin, A O Ademuyiwa, E Al Ameer, O Alser, K M Augestad, B Bankhead-Kendall, R A Benson, S Chakrabortee, R Blanco-Colino, A Brar, A Minaya Bravo, K A Breen, I Lima Buarque, M F Cunha, G H Davidson, S Farik, M Fiore, G M A Gomes, C Halkias, I Lawani, H Lederhuber, S Leventoglu, M W Loffler, H Mashbari, D Mazingi, D Moszkowicz, J S Ng-Kamstra, S Metallidis, M Niquen, F Ntirenganya, O Outani, F Pata, T D Pinkney, P Pockney, D Radenkovic, A Ramos-De la Medina, A Schnitzbauer, S Shu, K Soreide, S Tabiri, P Townend, G Tsoulfas, G van Ramshorst, Mak JKC, F Tirotta, A Kisiel, LD Cato, AM Pathanki, A Chebaro, K Lecolle, S Truant, FR Pruvot, E Surmei, L Mattei, J Dudek, S El-Hasani, J Cuschieri, GH Davidson, RG Wade, H Elkadi, C Pompili, JR Burke, E Bagouri, Z Abual-Rub, S Munot, M Kowal, SC Winter, F Di Chiara, K Wallwork, A Qureishi, M Lami, S Sravanam, S Chidambaram, R Smillie, AV Shaw, C Cernei, D Jeyaretna, RJ Piper, E Duck, C Jelley, SC Tucker, G Bond-Smith, XL Griffin, GD Tebala, N Neal, TM Noton, H Ghattaura, OBF Risk, H Kharkar, C Verberne, A Senent-Boza, A Sánchez-Arteaga, I Benítez-Linero, F Manresa-Manresa, L Tallón-Aguilar, L Melero-Cortés, MR Fernández-Marín, VM Durán-Muñoz-Cruzado, I Ramallo-Solís, P Beltrán-Miranda, F Pareja-Ciuró, BT Antón-Eguía, AC Dawson, A Drane, F Oliva Mompean, J Gomez-Rosado, J Reguera-Rosal, J Valdes-Hernandez, L Capitan-Morales, del Toro Lopez, A Alanbuki, O Usman, AJ Beamish, D Bosanquet, D Magowan, H Nassa, G Mccabe, D Holroyd, NB Jamieson, NM Mariani, V Nicastro, D Motter, C Jenvey, T Minto, DR Sarma, C Godbole, W Carlos, A Khajuria, H Connolly, G Di Taranto, S Shanbhag, J Skillman, M Sait, H Al-omishy, B Heer, R Lunevicius, ARG Sheel, M Sundhu, AJA Santini, Fathelbab MSAT, KMA Hussein, QM Nunes, K Shahzad, Baig MMAS, JL Hughes, A Kattakayam, SB Shah, AL Clynch, N Georgopoulou, HM Sharples, AA Apampa, IC Nzenwa, D Podolsky, NL Coleman, MP Callahan, P Beak, I Gerogiannis, A Ebrahim, A Alwadiya, C Demetriou, E Grimley, E Theophilidou, E Ogden, FL Malcolm, G Davies-Jones, Ng JCK, N Elmaleh, Z Chia, J A'Court, A Konarski, R Talwar, P S Jambulingam, A Maity, C Hatzantonis, S Kudchadkar, N Cirocchi, CH Chan, H Eberbach, B Erdle, R Sandkamp, G Velmahos, LR Maurer, M El Moheb, A Gaitanidis, L Naar, MA Christensen, C Kapoen, K Langeveld, M El Hechi, B Main, T Maccabe, NS Blencowe, DP Fudulu, D Bhojwani, M Baquedano, F Rapetto, O Flannery, D Tadross, C Blundell, S Forlani, S Guha, CJ Kelty, G Chetty, G Lye, SP Balasubramanian, N Sureshkumar Shah, A Al-mukhtar, E Whitehall, A Giblin, A Adamec, J Konsten, M Van Heinsbergen, A Sou, J Jimeno Fraile, D Morales-Garcia, M Carrillo-Rivas, E Toledo Martínez, Pascual À, A Landaluce-olavarria, M Gonzalez De miguel, Fernández Gómez Cruzado L, E Begoña, D Lecumberri, A Calvo Rey, GM Prada hervella, L Dos Santos Carregal, MI Rodriguez Fernandez, M Freijeiro, S El Drubi Vega, J Van den Eynde, W Oosterlinck, R Van den Eynde, A Boeckxstaens, A Cordonnier, J Jaekers, M Miserez, M Galipienso Eri, JD Garcia Montesino, J Dellonder Frigolé, D Noriego Muñoz, V Lizzi, F Vovola, A Arminio, A Cotoia, AL Sarni, M Bekheit, BS Kamera, M Elhusseini, A Ahmeidat, W Cymes, G Mignot, J Agilinko, A Sgrò, MM Rashid, K Milne, KE Stewart, MSJ Wilson, K McGivern, BC Brown, B Wadham, IA Aneke, J Collis, H Warburton, DM Fountain, R Laurente, KV Sigamoney, M Dasa, Z Naqui, M Galhoum, MT Hasan, R Kalenderov, O Pathmanaban, R Chelva, K Subba, M Khalefa, F Hossain, T Moores, J Anthoney, O Emmerson, R Makin-Taylor, CS Ong, R Callan, O Bloom, G Chauhan, J Kaur, A Burahee, S Bleibleh, N Pigadas, D Snee, S Bhasin, A Crichton, A Habeebullah, AS Bodla, M Mondragon, V Dewan, MC Giuffrida, A Marano, S Palagi, S Di Maria Grimaldi, A Simonato, M D'Agruma, R Chiarpenello, L Pellegrino, F Maione, D Cianflocca, Pruiti Ciarello, G Giraudo, E Gelarda, E Dalmasso, A Abrate, V Ciriello, F Rosato, A Garnero, L Leotta, M Chiozza, G Anania, A Urbani, M Koleva Radica, P Carcoforo, M Portinari, M Sibilla, JE Archer, A Odeh, N Siddaiah, H Carmichael, CG Velopulos, RC McIntyre, TJ Schroeppel, EA Hennessy, L Zier, C Parmar, JM Muñoz Vives, CJ Gómez Díaz, CA Guariglia, C Soto Montesinos, L Sanchon, M Xicola Martínez, N Guàrdia, P Collera, R Diaz Del Gobbo, R Sanchez Jimenez, R Farre Font, R Flores Clotet, CEM Brathwaite, H Hakmi, AH Sohail, R Heckburn, D Townshend, N McLarty, A Shenfine, K Madhvani, M Hampton, AP Hormis, V Miu, K Sheridan, C Luney, MA Williams, A Alqallaf, A Ben-Sassi, R Crichton, J Sonksen, GR Layton, B Karki, S Pankhania, S Asher, A Folorunso, J Winyard, J Mangwani, BHB Babu, C Weerasinghe, M Ballabio, P Bisagni, T Armao, M Madonini, A Gagliano, P Pizzini, A Älgå, M Nordberg, G Sandblom, J El Kafsi, K Logishetty, A Saadya, R Midha, H Subbiah Ponniah, T Stockdale, T Bacarese-Hamilton, N Anjarwalla, D Marujo Henriques, R Hettige, C Baban, A Tenovici, F Anazor, SD King, S Kazzaz, S HKruijff, De Vries JPPM, PJ Steinkamp, PKC Jonker, WY Van der Plas, W Bierman, Y Janssen, ABJ Borgstein, D Enjuto, M Perez Gonzalez, P Díaz Peña, M Marqueta De Salas, P Martinez Pascual, L Rodríguez Gómez, R Garcés García, A Ramos Bonilla, N Herrera-Merino, P Fernández Bernabé, EP Cagigal Ortega, García de Castro Rubio E, I Cervera, MH Siddique, C Barmpagianni, A Basgaran, A Basha, V Okechukwu, A Bartsch, CA Leo, HK Ubhi, N Zafar, H Abdul-Jabar, F Mongelli, M Bernasconi, M Di Giuseppe, D Christoforidis, D La Regina, M Arigoni, A Al-Sukaini, S Mediratta, O Brown, M Boal, S Stanger, H Abdalaziz, J Constable, G Dovell, R Gopi reddy, A Dehal, HB Shah, GWV Cross, P Seyed-Safi, YW Smart, A Kuc, M Al-Yaseen, B Jayasankar, D Balasubramaniam, K Abdelsaid, N Mundkur, RE Soulsby, O Ryska, T Raymond, P Hawkin, G Kinnaman, I Sharma, K Freystaetter, JN Hadfield, A Hilley, S Arkani, M Youssef, I Shaikh, K Seebah, V Kouritas, D Chrastek, G Maryan, DF Gill, F Khatun, J Parakh, V Sarodaya, A Daadipour, KD Bosch, V Bashkirova, LS Dvorkin, VK Kalidindi, A Choudhry, M Espino Segura-Illa, G Sánchez Aniceto, AM Castaño-Leon, L Jimenez-Roldan, J Delgado Fernandez, A Pérez Núñez, A Lagares, D Garcia Perez, M Santas, I Paredes, O Esteban Sinovas, L Moreno-Gomez, E Rubio, V Vega, A Vivas Lopez, M Labalde Martinez, O García Villar, PM Pelaéz Torres, J Garcia Borda, E Ferrero Herrero, C Eiriz Fernandez, C Ojeda-Thies, JM Pardo Garcia, H Wynn Jones, H Divecha, C Whelton, E Powell-Smith, M Alotaibi, A Maashi, A Zowgar, M Alsakkaf, O Izquierdo, D Ventura, D Escobar, U Garcia de cortazar, Villamor Garcia, A Cioci, K Rakoczy, W Pavlis, R Saberi, A Khaleel, A Unnithan, K Memon, RR Pala Bhaskar, F Maqboul, F Kamel, A Al-Samaraee, R Madani, H Llaquet Bayo, N Duchateau, C De Gheldere, A Fayad, ML Wood, G Groot, I Hakami, C Boeker, J Mall, AF Haugstvedt, ML Jönsson, P Caja Vivancos, Villalabeitia Ateca, M Prieto Calvo, P Martin Playa, A Gainza, EJ Aragon Achig, A Rodriguez Fraga, Melchor Corcóstegui, G Mallabiabarrena Ormaechea, JJ Garcia Gutierrez, L Barbier, MA Pesántez Peralta, M Jiménez Jiménez, JA Municio Martín, J Gómez Suárez, G García Operé, LA Pascua Gómez, M Oñate Aguirre, A Fernandez-Colorado, M De la Rosa-Estadella, A Gasulla-Rodriguez, M Serrano-Martin, A Peig-Font, S Junca-Marti, M Juarez-Pomes, S Garrido-Ondono, L Blasco-Torres, M Molina-Corbacho, Y Maldonado-Sotoca, A Gasset-Teixidor, J Blasco-Moreu, V Turrado-Rodriguez, AM Lacy, FB de Lacy, X Morales, A Carreras-Castañer, P Torner, M Jornet-Gibert, M Balaguer-Castro, M Renau-Cerrillo, P Camacho-Carrasco, M Vives-Barquiel, B Campuzano-Bitterling, I Gracia, R Pujol-Muncunill, M Estaire Gómez, D Padilla-Valverde, S Sánchez-García, D Sanchez-Pelaez, E Jimenez Higuera, R Picón Rodríguez, Fernández Camuñas À, C Martínez-Pinedo, EP Garcia Santos, V Muñoz-Atienza, A Moreno Pérez, CA Cano, D Crego-Vita, M Huecas-Martinez, A Roselló Añón, MJ Sangüesa, JC Bernal-Sprekelsen, JC Catalá Bauset, P Renovell Ferrer, C Martínez Pérez, O Gil-Albarova, J Gilabert Estellés, K Aghababyan, R Rivas, J Escartin, JL Blas Laina, B Cros, Talal El-Abur, J Garcia Egea, C Yanez, JH Kauppila, E Sarjanoja, S Tzedakis, PA Bouche, S Gaujoux, D Gossot, A Seguin-Givelet, D Fuks, M Grigoroiu, R Sanchez Salas, X Cathelineau, P Macek, Y Barbé, F Rozet, E Barret, A Mombet, N Cathala, E Brian, F Zadegan, AJ Baldwin, E Gammeri, A Catton, S Marinos Kouris, J Pereca, M Kaushal, A Kler, V Reghuram, S Tezas, V Oktseloglou, F Mosley, MFI De La Cruz Monroy, P Bobak, S Ahad, E Lostis, GK Ambler, J Manara, M Doe, T Jichi, GD Stewart, J Ramzi, AA Singh, J Ashcroft, OJ Baker, P Coughlin, Durst AZED, A Abood, A Habeeb, VE Hudson, B Lamb, L Luke, S Mitrasinovic, Ngu AWT, S Waseem, F Georgiades, XS Tan, J Pushpa-rajah, I Abu-Nayla, S Rooney, E Irune, MHV Byrne, A Durrani, A Sethuraman Venkatesan, T Combellack, G Tahhan, M Kornaszewska, V Valtzoglou, I Deglurkar, M Koutentakis, Syed Nong Chek SAH, M Shinkwin, F Ayeni, H Tustin, M Bordenave, N Manu, N Eardley, OL Serevina, S Roy Mahapatra, K Mohankumar, I Khawaja, A Palepa, T Doulias, Y Premakumar, Y Jauhari, Z Koshnow, A Uberai, F Hirri, BM Stubbs, J Manickavasagam, S Dalgleish, R Kanitkar, CJ Payne, Ng CE, DE Henshall, T Drake, EM Harrison, A Tambyraja, RJE Skipworth, G Linder, R McGregor, J Mayes, R Pasricha, A Razik, S Thrumurthy, D Howden, Z Baxter, L Osagie, M Bence, GE Fowler, N Rajaretnam, A Goubran, JS McGrath, JRA Phillips, DA Raptis, JM Pollok, F Soggiu, S Xyda, C Hidalgo Salinas, H Tzerbinis, T Pissanou, R Mirnezami, N Angamuthu, T Shakir, H Capitelli-McMahon, L Hitchman, A Andronic, A Aboelkassem Ibrahim, J Totty, S Tayeh, T Chase, J Ayorinde, T Cuming, A Trompeter, C Hing, P Tsinaslanidis, MW Benjamin, A Leyte, J Smelt, G Santhirakumaran, A Labib, O Lyons, S Onida, KM Sarraf, S Erridge, S Yalamanchili, A Abuown, D Davenport, S Wheatstone, SM Andreani, MF Bath, A Sahni, L Rigueros Springford, C Sohrabi, J Bacarese-Hamilton, FG Taylor, P Patki, C Tanabalan, ME Alexander, CJ Smart, L Abdeh, M Zeiton, R Advani, S Nikolaou, T Oni, N Ilahi, K Ballantyne, Z Woodward, R Merh, B Robertson-Smith, P Ameerally, JG Finch, C Gnanachandran, I Pop, D Dass, G Thiruchandran, Toh SKC, A Allana, C Bellis, O Babawale, YC Phan, U Lokman, T Koc, L Duggleby, S Shamoon, H Clancy, A Mansuri, A Thakrar, L Wickramarachchi, S Sivayoganathan, E Karam, HV Colvin, A Badran, A Cadersa, A Cumpstey, R Aftab, F Wensley, V Morrison-Jones, GK Sekhon, H Shields, Z Shakoor, T Talbot, A Alzetani, J Rooney, M Rudic, A Aladeojebi, M Kitchen, R Lefroy, P Nanjaiah, AD Rajgor, RJ Scurrah, LJ Watson, T Royle, B Steel, Luk ACO, VG Thiruvasagam, W Marlow, C Konstantinou, D Yershov, A Denning, E Mangos, T Nambirajan, I Flindall, V Mahendran, J De Marchi, NF Davis, A Picciariello, V Papagni, DF Altomare, S Granieri, C Cotsoglou, A Cabeleira, P Serralheiro, T Teles, C Canhoto, J Simões, AC Almeida, O Nogueira, R Athayde Nemésio, MJ Amaral, A Valente da Costa, R Martins, P Guerreiro, A Ruivo, D Breda, JM Oliveira, AL De Oliveira Lopez, M Colino, J De Barros, AP Soares, H Morais, T Revez, MI Manso, JC Domingues, P Henriques, Cardoso N Ribeiro VI, G Martins dos Santos, M Peralta Ferreira, J Ascensão, B Costeira, L Rio Rodrigues, M Sousa Fernandes, P Azevedo, I Lourenço, G Mendinhos, A Nobre Pinto, H Taflin, H Abdou, L O'Meara, Z Cooper, SA Hirji, BU Okafor, V Roxo, CP Raut, JS Jolissaint, DA Mahvi, C Reinke, S Merola, A Ssentongo, P Ssentongo, Oh JS, J Hazelton, J Maines, N Gusani, RCG Martin, N Bhutiani, R Choron, F Soliman, MD E Dauer, E Renza-Stingone, E Gokcen, E Kropf, H Sufrin, J Sewards, J Poggio, K Sanserino, L Rae, M Philp, M Metro, P McNelis, R Petrov, T Pazionis, DB Lumenta, SP Nischwitz, E Richtig, M Pau, P Srekl-Filzmaier, N Eibinger, B Michelitsch, M Fediuk, A Papinutti, TU Cohnert, E Kantor, J Kahiu, S Hosny, A Sultana, M Taggarsi, L Vitone, OP Vaz, I Sarantitis, S Timbrell, A Shugaba, GP Jones, SS Tripathi, MS Greenhalgh, H Emerson, K Vejsbjerg, W McCormick, K Singisetti, Y Aawsaj, R Vanker, M Ghobrial, S Kanthasamy, H Fawi, M Awadallah, J Cheung, S Tingle, F Abbadessa, A Sachdeva, CD Chan, I McPherson, F Mahmoud Ali, S Pandanaboyana, T Grainger, S Nandhra, N Dawe, C McCaffer, J Riches, J Moir, H Elamin Ahmed, C Saleh, RM Koshy, LJ Rogers, PL Labib, N Hope, K Emslie, P Panahi, E Clough, I Enemosah, J Natale, N Raza, JI Webb, M Antar, J Noel, R Nunn, F Eriberto, R Tanna, S Lodhia, C Osório, J Antunes, P Balau, and M Godinho
- Subjects
Medicine - Abstract
Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.Setting Prospective, international, multicentre, observational cohort study.Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration number NCT04323644
- Published
- 2021
- Full Text
- View/download PDF
14. Effectiveness of alternative means for controlling pomegranate postharvest pathogens
- Author
-
A. Mincuzzi, S.M. Sanzani, M. Caputo, P. D’Ambrosio, L. Palou, M. Ragni, and A. Ippolito
- Subjects
Horticulture - Published
- 2023
- Full Text
- View/download PDF
15. Gestational Diabetes Mellitus: Clinical Characteristics and Perinatal Outcomes in a Multiethnic Population of North Italy
- Author
-
M. Caputo, V. Bullara, C. Mele, M. T. Samà, M. Zavattaro, A. Ferrero, T. Daffara, I. Leone, G. Giachetti, V. Antoniotti, D. Longo, A. De Pedrini, P. Marzullo, V. Remorgida, F. Prodam, and G. Aimaretti
- Subjects
Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Aim. To evaluate clinical characteristics and perinatal outcomes in a heterogeneous population of Caucasians born in Italy and High Migration Pressure Countries (HMPC) women with GDM living in Piedmont, North Italy. Methods. We retrospectively analyzed data from 586 women referring to our unit (2015–2020). Epidemiological (age and country of origin) and clinical-metabolic features (height, weight, family history of DM, parity, previous history of GDM, OGTT results, and GDM treatment) were collected. The database of certificates of care at delivery was consulted in relation to neonatal/maternal complications (rates of caesarean sections, APGAR score, fetal malformations, and neonatal anthropometry). Results. 43.2% of women came from HMPC; they were younger p
- Published
- 2021
- Full Text
- View/download PDF
16. Transition in endocrinology: predictors of drop-out of a heterogeneous population on a long-term follow-up
- Author
-
F. Prodam, M. Caputo, M. Romanisio, S. Brasili, M. Zavattaro, M. T. Samà, A. Ferrero, S. Costelli, F. R. Lenzi, A. Petri, E. Basso, S. Bellone, and G. Aimaretti
- Subjects
Endocrinology ,Endocrinology, Diabetes and Metabolism - Published
- 2022
- Full Text
- View/download PDF
17. Metal Nanoclusters with Synergistically Engineered Optical and Buffering Activity of Intracellular Reactive Oxygen Species by Compositional and Supramolecular Design
- Author
-
B. Santiago-Gonzalez, A. Monguzzi, M. Caputo, C. Villa, M. Prato, C. Santambrogio, Y. Torrente, F. Meinardi, and S. Brovelli
- Subjects
Medicine ,Science - Abstract
Abstract Metal nanoclusters featuring tunable luminescence and high biocompatibility are receiving attention as fluorescent markers for cellular imaging. The recently discovered ability of gold clusters to scavenge cytotoxic reactive oxygen species (ROS) from the intracellular environment extends their applicability to biomedical theranostics and provides a novel platform for realizing multifunctional luminescent probes with engineered anti-cytotoxic activity for applications in bio-diagnostics and conceivably cellular therapy. This goal could be achieved by using clusters of strongly reactive metals such as silver, provided that strategies are found to enhance their luminescence while simultaneously enabling direct interaction between the metal atoms and the chemical surroundings. In this work, we demonstrate a synergic approach for realizing multifunctional metal clusters combining enhanced luminescence with strong and lasting ROS scavenging activity, based on the fabrication and in situ protection of Ag nanoclusters with a supramolecular mantle of thiolated-Au atoms (Ag/Au-t). Confocal imaging and viability measurements highlight the biocompatibility of Ag/Au-t and their suitability as fluorescent bio-markers. ROS concentration tests reveal the remarkable scavenging activity of Ag-based clusters. Proliferation tests of cells in artificially stressed culture conditions point out their prolonged anti-cytotoxic effect with respect to gold systems, ensuring positive cell proliferation rates even for long incubation time.
- Published
- 2017
- Full Text
- View/download PDF
18. Intrinsic Disorder and Phosphorylation in BRCA2 Facilitate Tight Regulation of Multiple Conserved Binding Events
- Author
-
Manon Julien, Rania Ghouil, Ambre Petitalot, Sandrine M. Caputo, Aura Carreira, and Sophie Zinn-Justin
- Subjects
disorder ,phosphorylation ,cancer ,DNA repair ,mitosis ,meiosis ,Microbiology ,QR1-502 - Abstract
The maintenance of genome integrity in the cell is an essential process for the accurate transmission of the genetic material. BRCA2 participates in this process at several levels, including DNA repair by homologous recombination, protection of stalled replication forks, and cell division. These activities are regulated and coordinated via cell-cycle dependent modifications. Pathogenic variants in BRCA2 cause genome instability and are associated with breast and/or ovarian cancers. BRCA2 is a very large protein of 3418 amino acids. Most well-characterized variants causing a strong predisposition to cancer are mutated in the C-terminal 700 residues DNA binding domain of BRCA2. The rest of the BRCA2 protein is predicted to be disordered. Interactions involving intrinsically disordered regions (IDRs) remain difficult to identify both using bioinformatics tools and performing experimental assays. However, the lack of well-structured binding sites provides unique functional opportunities for BRCA2 to bind to a large set of partners in a tightly regulated manner. We here summarize the predictive and experimental arguments that support the presence of disorder in BRCA2. We describe how BRCA2 IDRs mediate self-assembly and binding to partners during DNA double-strand break repair, mitosis, and meiosis. We highlight how phosphorylation by DNA repair and cell-cycle kinases regulate these interactions. We finally discuss the impact of cancer-associated variants on the function of BRCA2 IDRs and more generally on genome stability and cancer risk.
- Published
- 2021
- Full Text
- View/download PDF
19. Informing ankle-foot prosthesis prescription through haptic emulation of candidate devices.
- Author
-
Joshua M. Caputo, Peter G. Adamczyk, and Steven H. Collins
- Published
- 2015
- Full Text
- View/download PDF
20. Real-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients
- Author
-
P. Marzullo, T. Daffara, C. Mele, M. Zavattaro, A. Ferrero, M. Caputo, F. Prodam, and G. Aimaretti
- Subjects
Endocrinology ,Endocrinology, Diabetes and Metabolism - Abstract
Purpose Registered trials and real-world evidence (RWE) studies provided evidence on the efficacy of once-weekly (OW) semaglutide on hyperglycaemia and cardiovascular risk factors as add-on or de-novo treatment in type 2 diabetes (T2D). Methods In a retrospective analysis of electronic data files from 258 T2D patients, this RWE study aimed to explore the impact of OW semaglutide on biochemical and anthropometric outcomes after 6 and 12 months in patients receiving at least one prescription of OW semaglutide between September 2019 and May 2021. Results During the study period, 154 and 56 consecutive patients completed the 6 and 12 months of OW semaglutide treatment. HbA1c levels decreased by -1.02±0.1% after 6 months and -1.1±0.1% after 12 months of OW semaglutide (ppppp Conclusions Real-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients.
- Published
- 2022
- Full Text
- View/download PDF
21. Three mutations at a Y-STR haplotype defy a paternal half-brothers kinship case analysis
- Author
-
A. Sala, M. Caputo, and D. Corach
- Subjects
Pathology and Forensic Medicine - Published
- 2023
- Full Text
- View/download PDF
22. Supplementary Figure 1 (A). from Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact of BRCA1 BRCT Variants on Cancer Risk
- Author
-
Sandrine M. Caputo, Sophie Zinn-Justin, Bernard S. Lopez, Rosette Lidereau, Etienne Rouleau, Catherine Noguès, Jean-Christophe Aude, Philippe Lafitte, Jeff A. Schnell, Jean Feunteun, Dorine Bonte, Isslam Bouazzaoui, Patrick Julien, Josée Guirouilh-Barbat, Naima Nhiri, Eric Jacquet, Elodie Dardillac, and Ambre Petitalot
- Abstract
Plot of the HR efficiencies measured after expression of either WT BRCA1 or VUS normalized to the HR efficiency after expression of WT BRCA1. The HR efficiencies are here plotted as a function of the position of the mutation in the BRCA1 sequence. Statistical significance was calculated using a one-side paired student t-test. To account for the multiple testing, the p-values were adjusted using the Benjamini-Horchberg method at a level a=0.05. HR efficiencies significantly different from the WT value are marked by asterisks. They are indicated by * if p < 0.05 and ** if p < 0.01. All 7 (likely) causal (noted LC or C) variants (in red) caused a significantly decreased HR efficiency whereas all 6 (likely) neutral (noted LN or N) variants (in blue) caused no significant HR difference. Twenty-four VUS of class 3 could not provide WT HR efficiency.
- Published
- 2023
- Full Text
- View/download PDF
23. Supplementary Data Index from NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation
- Author
-
Cory Abate-Shen, Aditya Dutta, Antonina Mitrofanova, Mark A. Rubin, Michael M. Shen, James M. McKiernan, Hanina Hibshoosh, Sven Wenske, Guarionex Joel De Castro, Vinson Wang, Christopher Haas, Joseph M. Caputo, Elvis A. Maliza, Alanna B. Williams, Matteo Di Bernardo, Jaime Y. Kim, Luis Pina Martina, Teresa A. Milner, Renu K. Virk, Elizabeth Margolskee, Sukanya Panja, Antonio Rodriguez-Calero, and Alexandros Papachristodoulou
- Abstract
List of all supplementary items included with the manuscript.
- Published
- 2023
- Full Text
- View/download PDF
24. Supplementary Figure 4. (A-D) from Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact of BRCA1 BRCT Variants on Cancer Risk
- Author
-
Sandrine M. Caputo, Sophie Zinn-Justin, Bernard S. Lopez, Rosette Lidereau, Etienne Rouleau, Catherine Noguès, Jean-Christophe Aude, Philippe Lafitte, Jeff A. Schnell, Jean Feunteun, Dorine Bonte, Isslam Bouazzaoui, Patrick Julien, Josée Guirouilh-Barbat, Naima Nhiri, Eric Jacquet, Elodie Dardillac, and Ambre Petitalot
- Abstract
Isothermal Titration Calorimetry curves obtained by adding the different phosphopeptides at (A-B) 200 mM onto the WT BRCT domains at 20 mM and (C-D) 100 mM onto the WT BRCT domains at 10 mM .
- Published
- 2023
- Full Text
- View/download PDF
25. Data from Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact of BRCA1 BRCT Variants on Cancer Risk
- Author
-
Sandrine M. Caputo, Sophie Zinn-Justin, Bernard S. Lopez, Rosette Lidereau, Etienne Rouleau, Catherine Noguès, Jean-Christophe Aude, Philippe Lafitte, Jeff A. Schnell, Jean Feunteun, Dorine Bonte, Isslam Bouazzaoui, Patrick Julien, Josée Guirouilh-Barbat, Naima Nhiri, Eric Jacquet, Elodie Dardillac, and Ambre Petitalot
- Abstract
BRCA1 mutations have been identified that increase the risk of developing hereditary breast and ovarian cancers. Genetic screening is now offered to patients with a family history of cancer, to adapt their treatment and the management of their relatives. However, a large number of BRCA1 variants of uncertain significance (VUS) are detected. To better understand the significance of these variants, a high-throughput structural and functional analysis was performed on a large set of BRCA1 VUS. Information on both cellular localization and homology-directed DNA repair (HR) capacity was obtained for 78 BRCT missense variants in the UMD-BRCA1 database and measurement of the structural stability and phosphopeptide-binding capacities was performed for 42 mutated BRCT domains. This extensive and systematic analysis revealed that most characterized causal variants affect BRCT-domain solubility in bacteria and all impair BRCA1 HR activity in cells. Furthermore, binding to a set of 5 different phosphopeptides was tested: all causal variants showed phosphopeptide-binding defects and no neutral variant showed such defects. A classification is presented on the basis of mutated BRCT domain solubility, phosphopeptide-binding properties, and VUS HR capacity. These data suggest that HR-defective variants, which present, in addition, BRCT domains either insoluble in bacteria or defective for phosphopeptide binding, lead to an increased cancer risk. Furthermore, the data suggest that variants with a WT HR activity and whose BRCT domains bind with a WT affinity to the 5 phosphopeptides are neutral. The case of variants with WT HR activity and defective phosphopeptide binding should be further characterized, as this last functional defect might be sufficient per se to lead to tumorigenesis.Implications:The analysis of the current study on BRCA1 structural and functional defects on cancer risk and classification presented may improve clinical interpretation and therapeutic selection.
- Published
- 2023
- Full Text
- View/download PDF
26. Supplementary Materials and Methods from NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation
- Author
-
Cory Abate-Shen, Aditya Dutta, Antonina Mitrofanova, Mark A. Rubin, Michael M. Shen, James M. McKiernan, Hanina Hibshoosh, Sven Wenske, Guarionex Joel De Castro, Vinson Wang, Christopher Haas, Joseph M. Caputo, Elvis A. Maliza, Alanna B. Williams, Matteo Di Bernardo, Jaime Y. Kim, Luis Pina Martina, Teresa A. Milner, Renu K. Virk, Elizabeth Margolskee, Sukanya Panja, Antonio Rodriguez-Calero, and Alexandros Papachristodoulou
- Abstract
Detailed materials and methods including references.
- Published
- 2023
- Full Text
- View/download PDF
27. Supplementary Figures from NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation
- Author
-
Cory Abate-Shen, Aditya Dutta, Antonina Mitrofanova, Mark A. Rubin, Michael M. Shen, James M. McKiernan, Hanina Hibshoosh, Sven Wenske, Guarionex Joel De Castro, Vinson Wang, Christopher Haas, Joseph M. Caputo, Elvis A. Maliza, Alanna B. Williams, Matteo Di Bernardo, Jaime Y. Kim, Luis Pina Martina, Teresa A. Milner, Renu K. Virk, Elizabeth Margolskee, Sukanya Panja, Antonio Rodriguez-Calero, and Alexandros Papachristodoulou
- Abstract
Supplementary Figures and Figure legends
- Published
- 2023
- Full Text
- View/download PDF
28. Supplementary Figure 3. Classification of the 42 purified mutated BRCT domains as a function of their thermostability as measured using a high throughput fluorescence assay. from Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact of BRCA1 BRCT Variants on Cancer Risk
- Author
-
Sandrine M. Caputo, Sophie Zinn-Justin, Bernard S. Lopez, Rosette Lidereau, Etienne Rouleau, Catherine Noguès, Jean-Christophe Aude, Philippe Lafitte, Jeff A. Schnell, Jean Feunteun, Dorine Bonte, Isslam Bouazzaoui, Patrick Julien, Josée Guirouilh-Barbat, Naima Nhiri, Eric Jacquet, Elodie Dardillac, and Ambre Petitalot
- Abstract
The black bar corresponds to WT BRCA1, the blue bars to VUS of classes 1 and 2, the grey bars to VUS of class 3 and the red bars to VUS of classes 4 and 5. Bars boxed in green correspond to mutants that are defective in phosphopeptide-binding, as observed using fluorescence based thermal shift assays. HR- marks VUS that are HR-defective.
- Published
- 2023
- Full Text
- View/download PDF
29. Supplementary Datasets from NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation
- Author
-
Cory Abate-Shen, Aditya Dutta, Antonina Mitrofanova, Mark A. Rubin, Michael M. Shen, James M. McKiernan, Hanina Hibshoosh, Sven Wenske, Guarionex Joel De Castro, Vinson Wang, Christopher Haas, Joseph M. Caputo, Elvis A. Maliza, Alanna B. Williams, Matteo Di Bernardo, Jaime Y. Kim, Luis Pina Martina, Teresa A. Milner, Renu K. Virk, Elizabeth Margolskee, Sukanya Panja, Antonio Rodriguez-Calero, and Alexandros Papachristodoulou
- Abstract
Datasets reported in the manuscript including gene expression, pathway analyses, and mass spectrometry data.
- Published
- 2023
- Full Text
- View/download PDF
30. Supplementary Figure 6. (A) from Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact of BRCA1 BRCT Variants on Cancer Risk
- Author
-
Sandrine M. Caputo, Sophie Zinn-Justin, Bernard S. Lopez, Rosette Lidereau, Etienne Rouleau, Catherine Noguès, Jean-Christophe Aude, Philippe Lafitte, Jeff A. Schnell, Jean Feunteun, Dorine Bonte, Isslam Bouazzaoui, Patrick Julien, Josée Guirouilh-Barbat, Naima Nhiri, Eric Jacquet, Elodie Dardillac, and Ambre Petitalot
- Abstract
FBTSA assay revealing that binding of the WT BRCA1 BRCT domains to ACC1-P, BACH1-P, CtiP-P, AB-1P and AB-2P induce a measurable increase in the BRCT thermostability that raises with peptide concentration.
- Published
- 2023
- Full Text
- View/download PDF
31. Supplementary Tables from NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation
- Author
-
Cory Abate-Shen, Aditya Dutta, Antonina Mitrofanova, Mark A. Rubin, Michael M. Shen, James M. McKiernan, Hanina Hibshoosh, Sven Wenske, Guarionex Joel De Castro, Vinson Wang, Christopher Haas, Joseph M. Caputo, Elvis A. Maliza, Alanna B. Williams, Matteo Di Bernardo, Jaime Y. Kim, Luis Pina Martina, Teresa A. Milner, Renu K. Virk, Elizabeth Margolskee, Sukanya Panja, Antonio Rodriguez-Calero, and Alexandros Papachristodoulou
- Abstract
This files contains all of the supplementary tables included in the manuscript.
- Published
- 2023
- Full Text
- View/download PDF
32. Supplementary Figure 2. Classification of the VUS as a function of the impact of the corresponding missense variations on BRCT domain expression in E. coli. from Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact of BRCA1 BRCT Variants on Cancer Risk
- Author
-
Sandrine M. Caputo, Sophie Zinn-Justin, Bernard S. Lopez, Rosette Lidereau, Etienne Rouleau, Catherine Noguès, Jean-Christophe Aude, Philippe Lafitte, Jeff A. Schnell, Jean Feunteun, Dorine Bonte, Isslam Bouazzaoui, Patrick Julien, Josée Guirouilh-Barbat, Naima Nhiri, Eric Jacquet, Elodie Dardillac, and Ambre Petitalot
- Abstract
Mutated BRCT domains fused to GST were expressed in E. coli and purified by affinity chromatography using glutathione beads. This figure shows a SDS-PAGE gel with samples from the bacterial pellet (P), supernatant (S) and the glutathione beads (G) after incubation with the supernatant and washing. VUS were classified into 3 groups as a function of the amount of (1) soluble and (2) purified protein obtained from bacterial cultures. Lanes corresponding to a typical insoluble fusion protein, a typical poorly soluble fusion protein and a typical fusion protein as soluble as the WT fusion protein are boxed in orange, grey and black, respectively (colors are as in Figure 4 excepted for mutations that cause aggregation during purification, which are in yellow on Figure 4 even if they displayed a "grey-like" profile at the expression and first affinity purification stages).
- Published
- 2023
- Full Text
- View/download PDF
33. Supplementary Figure 5. (A-B) from Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact of BRCA1 BRCT Variants on Cancer Risk
- Author
-
Sandrine M. Caputo, Sophie Zinn-Justin, Bernard S. Lopez, Rosette Lidereau, Etienne Rouleau, Catherine Noguès, Jean-Christophe Aude, Philippe Lafitte, Jeff A. Schnell, Jean Feunteun, Dorine Bonte, Isslam Bouazzaoui, Patrick Julien, Josée Guirouilh-Barbat, Naima Nhiri, Eric Jacquet, Elodie Dardillac, and Ambre Petitalot
- Abstract
Size Exclusion Chromatography profiles obtained on BRCA1 BRCT domains free (red curve) or in complex with BACH1-P (purple), AB-1P (green), AB-2P (blue). The experiment was performed using a Superdex-75 10/300 GL column (GE Healthcare) pre-equilibrated with 50mM Tris-HCl pH 7.5, 150 mM NaCl, 10 mM β-mercaptoethanol and protease inhibitors (Roche).
- Published
- 2023
- Full Text
- View/download PDF
34. Data from NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation
- Author
-
Cory Abate-Shen, Aditya Dutta, Antonina Mitrofanova, Mark A. Rubin, Michael M. Shen, James M. McKiernan, Hanina Hibshoosh, Sven Wenske, Guarionex Joel De Castro, Vinson Wang, Christopher Haas, Joseph M. Caputo, Elvis A. Maliza, Alanna B. Williams, Matteo Di Bernardo, Jaime Y. Kim, Luis Pina Martina, Teresa A. Milner, Renu K. Virk, Elizabeth Margolskee, Sukanya Panja, Antonio Rodriguez-Calero, and Alexandros Papachristodoulou
- Abstract
Mitochondria provide the first line of defense against the tumor-promoting effects of oxidative stress. Here we show that the prostate-specific homeoprotein NKX3.1 suppresses prostate cancer initiation by protecting mitochondria from oxidative stress. Integrating analyses of genetically engineered mouse models, human prostate cancer cells, and human prostate cancer organotypic cultures, we find that, in response to oxidative stress, NKX3.1 is imported to mitochondria via the chaperone protein HSPA9, where it regulates transcription of mitochondrial-encoded electron transport chain (ETC) genes, thereby restoring oxidative phosphorylation and preventing cancer initiation. Germline polymorphisms of NKX3.1 associated with increased cancer risk fail to protect from oxidative stress or suppress tumorigenicity. Low expression levels of NKX3.1 combined with low expression of mitochondrial ETC genes are associated with adverse clinical outcome, whereas high levels of mitochondrial NKX3.1 protein are associated with favorable outcome. This work reveals an extranuclear role for NKX3.1 in suppression of prostate cancer by protecting mitochondrial function.Significance:Our findings uncover a nonnuclear function for NKX3.1 that is a key mechanism for suppression of prostate cancer. Analyses of the expression levels and subcellular localization of NKX3.1 in patients at risk of cancer progression may improve risk assessment in a precision prevention paradigm, particularly for men undergoing active surveillance.See related commentary by Finch and Baena, p. 2132.This article is highlighted in the In This Issue feature, p. 2113
- Published
- 2023
- Full Text
- View/download PDF
35. Supplementary Figure 6. (B-C) from Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact of BRCA1 BRCT Variants on Cancer Risk
- Author
-
Sandrine M. Caputo, Sophie Zinn-Justin, Bernard S. Lopez, Rosette Lidereau, Etienne Rouleau, Catherine Noguès, Jean-Christophe Aude, Philippe Lafitte, Jeff A. Schnell, Jean Feunteun, Dorine Bonte, Isslam Bouazzaoui, Patrick Julien, Josée Guirouilh-Barbat, Naima Nhiri, Eric Jacquet, Elodie Dardillac, and Ambre Petitalot
- Abstract
FBTSA assays performed to measure binding of the mutated BRCA1 BRCT domains to ACC1-P, BACH1-P, CtiP-P, AB-1P and AB-2P.
- Published
- 2023
- Full Text
- View/download PDF
36. Supplementary Data Tables S1-S4 from Skipping Nonsense to Maintain Function: The Paradigm of BRCA2 Exon 12
- Author
-
Pascaline Gaildrat, Alexandra Martins, Maaike P.G. Vreeswijk, Thierry Frebourg, Claude Houdayer, Dominique Stoppa-Lyonnet, Harry Vrieling, Lisa Golmard, Fabienne M.G.R. Calléja, Charlotte Grout, Aurélie Drouet, Maud Privat, Paul Vilquin, Sarab Lizard, Violaine Bourdon, Myriam Bronner, Virginie Guibert, Françoise Bonnet-Dorion, Omar Soukarieh, Hélène Tubeuf, Capucine Delnatte, Françoise Révillion, Johanna Sokolowska, Nadia Boutry-Kryza, Mélanie Léone, Virginie Caux-Moncoutier, Marine Guillaud-Bataille, Sophie Krieger, Sandrine M. Caputo, Romy L.S. Mesman, and Laëtitia Meulemans
- Abstract
Supplementary Tables S1-S4. Table S1. Description of primers used in this study. Table S2. Variants selected in BRCA2 exon 12 and its flanking intronic regions. Table S3. Overview of bioinformatics predictions and experimental data obtained for the 40 selected BRCA2 exon 12 variants. Table S4. Clinical and family data of patients carrying BRCA2 exon 12 spliceogenic variants.
- Published
- 2023
- Full Text
- View/download PDF
37. Supplementary Tables from Calibration of Pathogenicity Due to Variant-Induced Leaky Splicing Defects by Using BRCA2 Exon 3 as a Model System
- Author
-
Alexandra Martins, Shyam K. Sharan, Pascaline Gaildrat, Thierry Frebourg, Claude Houdayer, Dominique Stoppa-Lyonnet, Angela R. Solano, Laurence Venat-Bouvet, Chrystelle Colas, Séverine Audebert-Bellanger, Fátima Vaz, Pascal Pujol, Danièle Muller, Hélène Larbre, Violaine Bourdon, Françoise Bonnet-Dorion, Myriam Vezain, Daniela Di Giacomo, Aurélie Drouet, Omar Soukarieh, Eileen Southon, Susan Reid, Linda Cleveland, Marine Guillaud-Bataille, Capucine Delnatte, Nadia Boutry-Kryza, Mélanie Léoné, Françoise Révillion, Laëtitia Meulemans, Alice Fiévet, Gaia Castelain, Julie Hauchard, Virginie Caux-Moncoutier, Sophie Krieger, Julie Rondeaux, Teresa Sullivan, Sandrine M. Caputo, and Hélène Tubeuf
- Abstract
Supp Tables S1-S6 (including variant classification, bioinformatics predictions versus experimental data, primer sequences, summary of biological, clinical, tumoral, familial and multifactorial data, and description of statistical analysis approaches)
- Published
- 2023
- Full Text
- View/download PDF
38. Data from Calibration of Pathogenicity Due to Variant-Induced Leaky Splicing Defects by Using BRCA2 Exon 3 as a Model System
- Author
-
Alexandra Martins, Shyam K. Sharan, Pascaline Gaildrat, Thierry Frebourg, Claude Houdayer, Dominique Stoppa-Lyonnet, Angela R. Solano, Laurence Venat-Bouvet, Chrystelle Colas, Séverine Audebert-Bellanger, Fátima Vaz, Pascal Pujol, Danièle Muller, Hélène Larbre, Violaine Bourdon, Françoise Bonnet-Dorion, Myriam Vezain, Daniela Di Giacomo, Aurélie Drouet, Omar Soukarieh, Eileen Southon, Susan Reid, Linda Cleveland, Marine Guillaud-Bataille, Capucine Delnatte, Nadia Boutry-Kryza, Mélanie Léoné, Françoise Révillion, Laëtitia Meulemans, Alice Fiévet, Gaia Castelain, Julie Hauchard, Virginie Caux-Moncoutier, Sophie Krieger, Julie Rondeaux, Teresa Sullivan, Sandrine M. Caputo, and Hélène Tubeuf
- Abstract
BRCA2 is a clinically actionable gene implicated in breast and ovarian cancer predisposition that has become a high priority target for improving the classification of variants of unknown significance (VUS). Among all BRCA2 VUS, those causing partial/leaky splicing defects are the most challenging to classify because the minimal level of full-length (FL) transcripts required for normal function remains to be established. Here, we explored BRCA2 exon 3 (BRCA2e3) as a model for calibrating variant-induced spliceogenicity and estimating thresholds for BRCA2 haploinsufficiency. In silico predictions, minigene splicing assays, patients' RNA analyses, a mouse embryonic stem cell (mESC) complementation assay and retrieval of patient-related information were combined to determine the minimal requirement of FL BRCA2 transcripts. Of 100 BRCA2e3 variants tested in the minigene assay, 64 were found to be spliceogenic, causing mild to severe RNA defects. Splicing defects were also confirmed in patients' RNA when available. Analysis of a neutral leaky variant (c.231T>G) showed that a reduction of approximately 60% of FL BRCA2 transcripts from a mutant allele does not cause any increase in cancer risk. Moreover, data obtained from mESCs suggest that variants causing a decline in FL BRCA2 with approximately 30% of wild-type are not pathogenic, given that mESCs are fully viable and resistant to DNA-damaging agents in those conditions. In contrast, mESCs producing lower relative amounts of FL BRCA2 exhibited either null or hypomorphic phenotypes. Overall, our findings are likely to have broader implications on the interpretation of BRCA2 variants affecting the splicing pattern of other essential exons.Significance:These findings demonstrate that BRCA2 tumor suppressor function tolerates substantial reduction in full-length transcripts, helping to determine the pathogenicity of BRCA2 leaky splicing variants, some of which may not increase cancer risk.
- Published
- 2023
- Full Text
- View/download PDF
39. Supplementary Data from Skipping Nonsense to Maintain Function: The Paradigm of BRCA2 Exon 12
- Author
-
Pascaline Gaildrat, Alexandra Martins, Maaike P.G. Vreeswijk, Thierry Frebourg, Claude Houdayer, Dominique Stoppa-Lyonnet, Harry Vrieling, Lisa Golmard, Fabienne M.G.R. Calléja, Charlotte Grout, Aurélie Drouet, Maud Privat, Paul Vilquin, Sarab Lizard, Violaine Bourdon, Myriam Bronner, Virginie Guibert, Françoise Bonnet-Dorion, Omar Soukarieh, Hélène Tubeuf, Capucine Delnatte, Françoise Révillion, Johanna Sokolowska, Nadia Boutry-Kryza, Mélanie Léone, Virginie Caux-Moncoutier, Marine Guillaud-Bataille, Sophie Krieger, Sandrine M. Caputo, Romy L.S. Mesman, and Laëtitia Meulemans
- Abstract
Fig. S1 to S10. Figure S1. Variant selection from human variation databases; Figure S2. Capillary electrophoresis analyses of BRCA2 exon 12 splicing patterns in minigene assays of presumed LoF variants; Figure S3. Bioinformatics predictions of 3'/5' ss alterations for variants located at position IVS{plus minus}1/2 of BRCA2 exon 12; Figure S4. Bioinformatics analysis of variants predicted to alter 3'/5' ss of BRCA2 exon 12 (â^†MES {less than or equal to} -15%); Figure S5. Capillary electrophoresis analyses of BRCA2 exon 12 splicing patterns in minigene assays of variants predicted to alter 3'/5' ss (A) or ESR (B); Figure S6. Capillary electrophoresis analyses of BRCA2 exon 12 splicing patterns in control and patient lymphoblastoid cell lines; Figure S7. RT-PCR analysis of BRCA2 exon 12 splicing patterns in puromycin- or mock-treated lymphoblastoid cell lines of control individuals and patients carrying the c.6844G>T or c.6901G>T nonsense variants; Figure S8. Capillary electrophoresis analyses of BRCA2 exon 12 splicing patterns in variant-expressing mESC; Figure S9. Quantitation of BRCA2 protein expression in mESC; Figure S10. Sensitivity of BRCA2 variants to cisplatin and PARP inhibitors.
- Published
- 2023
- Full Text
- View/download PDF
40. Data from Skipping Nonsense to Maintain Function: The Paradigm of BRCA2 Exon 12
- Author
-
Pascaline Gaildrat, Alexandra Martins, Maaike P.G. Vreeswijk, Thierry Frebourg, Claude Houdayer, Dominique Stoppa-Lyonnet, Harry Vrieling, Lisa Golmard, Fabienne M.G.R. Calléja, Charlotte Grout, Aurélie Drouet, Maud Privat, Paul Vilquin, Sarab Lizard, Violaine Bourdon, Myriam Bronner, Virginie Guibert, Françoise Bonnet-Dorion, Omar Soukarieh, Hélène Tubeuf, Capucine Delnatte, Françoise Révillion, Johanna Sokolowska, Nadia Boutry-Kryza, Mélanie Léone, Virginie Caux-Moncoutier, Marine Guillaud-Bataille, Sophie Krieger, Sandrine M. Caputo, Romy L.S. Mesman, and Laëtitia Meulemans
- Abstract
Germline nonsense and canonical splice site variants identified in disease-causing genes are generally considered as loss-of-function (LoF) alleles and classified as pathogenic. However, a fraction of such variants could maintain function through their impact on RNA splicing. To test this hypothesis, we used the alternatively spliced BRCA2 exon 12 (E12) as a model system because its in-frame skipping leads to a potentially functional protein. All E12 variants corresponding to putative LoF variants or predicted to alter splicing (n = 40) were selected from human variation databases and characterized for their impact on splicing in minigene assays and, when available, in patient lymphoblastoid cell lines. Moreover, a selection of variants was analyzed in a mouse embryonic stem cell–based functional assay. Using these complementary approaches, we demonstrate that a subset of variants, including nonsense variants, induced in-frame E12 skipping through the modification of splice sites or regulatory elements and, consequently, led to an internally deleted but partially functional protein. These data provide evidence, for the first time in a cancer-predisposition gene, that certain presumed null variants can retain function due to their impact on splicing. Further studies are required to estimate cancer risk associated with these hypomorphic variants. More generally, our findings highlight the need to exercise caution in the interpretation of putative LoF variants susceptible to induce in-frame splicing modifications.Significance:This study presents evidence that certain presumed loss-of-function variants in a cancer predisposition gene can retain function due to their direct impact on RNA splicing.
- Published
- 2023
- Full Text
- View/download PDF
41. Photoinduced renormalization and electronic screening of quasi-two-dimensional Dirac states in BaNiS_{2}
- Author
-
N. Nilforoushan, M. Casula, M. Caputo, E. Papalazarou, J. Caillaux, Z. Chen, L. Perfetti, A. Amaricci, D. Santos-Cottin, Y. Klein, A. Gauzzi, and M. Marsi
- Subjects
Physics ,QC1-999 - Abstract
By means of time- and angle-resolved photoelectron spectroscopy, we give evidence of a remarkable reduction of the Fermi velocity of out-of-equilibrium Dirac bands in the quasi-two-dimensional semimetal BaNiS_{2}. This effect is accompanied by a nonrigid shift of the bands at the center of the Brillouin zone. Analytical and first-principles calculations indicate that this band renormalization is ascribed to a change in nonlocal electron correlations driven by a photoinduced enhancement of screening properties. Our results are explained by a scaling relation between inverse screening length and electronic temperature that is of general relevance for the description of out-of-equilibrium dynamics and screening effects in all layered Dirac materials.
- Published
- 2020
- Full Text
- View/download PDF
42. GEMO, a National Resource to Study Genetic Modifiers of Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Pathogenic Variant Carriers
- Author
-
Fabienne Lesueur, Noura Mebirouk, Yue Jiao, Laure Barjhoux, Muriel Belotti, Maïté Laurent, Mélanie Léone, Claude Houdayer, Brigitte Bressac-de Paillerets, Dominique Vaur, Hagay Sobol, Catherine Noguès, Michel Longy, Isabelle Mortemousque, Sandra Fert-Ferrer, Emmanuelle Mouret-Fourme, Pascal Pujol, Laurence Venat-Bouvet, Yves-Jean Bignon, Dominique Leroux, Isabelle Coupier, Pascaline Berthet, Véronique Mari, Capucine Delnatte, Paul Gesta, Marie-Agnès Collonge-Rame, Sophie Giraud, Valérie Bonadona, Amandine Baurand, Laurence Faivre, Bruno Buecher, Christine Lasset, Marion Gauthier-Villars, Francesca Damiola, Sylvie Mazoyer, Sandrine M. Caputo, Nadine Andrieu, Dominique Stoppa-Lyonnet, and GEMO Study Collaborators
- Subjects
breast cancer ,BRCA1/2 mutation carriers ,pathogenic variant (PV) ,DNA banking ,genetic epidemiology ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2018
- Full Text
- View/download PDF
43. An experimental robotic testbed for accelerated development of ankle prostheses.
- Author
-
Joshua M. Caputo and Steven H. Collins
- Published
- 2013
- Full Text
- View/download PDF
44. Clinical and radiological presentation of parasellar ectopic pituitary adenomas: case series and systematic review of the literature
- Author
-
C. Campana, F. Nista, L. Castelletti, M. Caputo, E. Lavezzi, P. Marzullo, A. Ferrero, G. Gaggero, F. R. Canevari, D. C. Rossi, G. Zona, A. Lania, D. Ferone, and F. Gatto
- Subjects
Endocrinology ,Endocrinology, Diabetes and Metabolism - Published
- 2022
- Full Text
- View/download PDF
45. Novel germline MET pathogenic variants in French patients with papillary renal cell carcinomas type I
- Author
-
Molka Sebai, David Tulasne, Sandrine M. Caputo, Virginie Verkarre, Marie Fernandes, Célia Guérin, Fanny Reinhart, Séverine Adams, Christine Maugard, Olivier Caron, Marine Guillaud‐Bataille, Pascaline Berthet, Yves‐Jean Bignon, Brigitte Bressac‐de Paillerets, Nelly Burnichon, Jean Chiesa, Sophie Giraud, Sophie Lejeune, Jean‐Marc Limacher, Antoine Pauw, Dominique Stoppa‐Lyonnet, Hélène Zattara‐Cannoni, Sophie Deveaux, Rosette Lidereau, Stéphane Richard, and Etienne Rouleau
- Subjects
Male ,Germ Cells ,Phenotype ,Neoplastic Syndromes, Hereditary ,Genetics ,Humans ,Female ,Proto-Oncogene Proteins c-met ,Carcinoma, Renal Cell ,Kidney Neoplasms ,Genetics (clinical) - Abstract
Hereditary papillary renal cell carcinoma (HPRC) is a rare inherited renal cancer syndrome characterized by bilateral and multifocal papillary type 1 renal tumors (PRCC1). Activating germline pathogenic variants of the MET gene were identified in HPRC families. We reviewed the medical and molecular records of a large French series of 158 patients screened for MET oncogenic variants. MET pathogenic and likely pathogenic variants rate was 12.4% with 40.6% among patients with familial PRCC1 and 5% among patients with sporadic PRCC1. The phenotype in cases with MET pathogenic and likely pathogenic variants was characteristic: PRCC1 tumors were mainly bilateral (84.3%) and multifocal (87.5%). Histologically, six out of seven patients with MET pathogenic variant harbored biphasic squamoid alveolar PRCC. Genetic screening identified one novel pathogenic variant MET c.3389TC, p.(Leu1130Ser) and three novel likely pathogenic variants: MET c.3257AT, p.(His1086Leu); MET c.3305TC, p.(Ile1102Thr) and MET c.3373TG, p.(Cys1125Gly). Functional assay confirmed their oncogenic effect as they induced an abnormal focus formation. The genotype-phenotype correlation between MET pathogenic variants and PRCC1 presentation should encourage to widen the screening, especially toward nonfamilial PRCC1. This precise phenotype also constitutes a strong argument for the classification of novel missense variants within the tyrosine kinase domain when functional assays are not accessible.
- Published
- 2022
- Full Text
- View/download PDF
46. Robotic Emulation of Candidate Prosthetic Foot Designs May Enable Efficient, Evidence-Based, and Individualized Prescriptions
- Author
-
Joshua M, Caputo, Evan, Dvorak, Kate, Shipley, Mary Ann, Miknevich, Peter G, Adamczyk, and Steven H, Collins
- Subjects
Rehabilitation ,Biomedical Engineering ,Orthopedics and Sports Medicine - Abstract
The design and selection of lower-limb prosthetic devices is currently hampered by a shortage of evidence to drive the choice of prosthetic foot parameters. We propose a new approach wherein prostheses could be designed, specified, and provided based on individualized measurements of the benefits provided by candidate feet. In this manuscript, we present a pilot test of this evidence-based and personalized process.We previously developed a "prosthetic foot emulator," a wearable robotic system that provides users with the physical sensation of trying on different prosthetic feet before definitive fitting. Here we detail preliminary demonstrations of two possible approaches to personalizing foot design: 1) an emulation and test-drive strategy of representative commercial foot models, and 2) a prosthetist-driven tuning procedure to optimize foot parameters.The first experiment demonstrated large and sometimes surprising differences in optimal prosthetic foot parameters across a variety of subjects, walking conditions, and outcome measures. The second experiment demonstrated a quick and effective simple manual tuning procedure for identifying preferred prosthetic foot parameters.Emulator-based approaches could improve individualization of prosthetic foot prescription. The present results motivate future clinical studies of the validity, efficacy, and economics of the approach across larger and more diverse subject populations.Today, emulator technology is being used to accelerate research and development of novel prosthetic and orthotic devices. In the future, after further refinement and validation, this technology could benefit clinical practice by providing a means for rapid test-driving and optimal selection of clinically available prosthetic feet.
- Published
- 2021
- Full Text
- View/download PDF
47. Effects of shear force reduction during mechanical testing and day-to-day variation on stiffness of commercial prosthetic feet: a technical note
- Author
-
Elizabeth G. Halsne, Anne T. Turner, Carl S. Curran, Andrew H. Hansen, Brian J. Hafner, Joshua M. Caputo, and David C. Morgenroth
- Subjects
Foot ,Rehabilitation ,Mechanical Tests ,Humans ,Artificial Limbs ,Prosthesis Design ,Gait ,Health Professions (miscellaneous) ,Biomechanical Phenomena - Abstract
Mechanical testing is the principal method used to quantify properties of commercial prosthetic feet in a controlled and standardized manner. To test feet in a mechanical testing machine without overconstraining the system, tangential shear forces must be minimized. However, there is scant published information comparing techniques for reducing shear forces during mechanical testing. Furthermore, there are no data on variability in linear stiffness across testing sessions.To compare techniques for reducing shear forces during mechanical testing of prosthetic feet and to evaluate variation in linear stiffness across testing sessions.Repeated measures.Force-displacement data were collected at two pylon progression angles, one for the forefoot and one for the heel, and compared across three conditions: roller plate (RoPl), low-friction interface on the shoe (SB), and no method for reducing shear forces (NoSB). Data were collected for a range of commercial prosthetic foot models and sizes. Select data were collected over multiple days to assess variation over test sessions.Differences in stiffness between RoPl and SB test conditions ranged from -0.9% to +2.6% across foot models. By contrast, differences between RoPl and no method for reducing shear conditions ranged from -2.9% to +14.6%. Differences in linear stiffness between test sessions ranged from -2.2% to +3.6%.Methods for reducing shear force in this study demonstrated roughly equivalent effects. Thus, a low-friction interface may be used as a less expensive and less complex method for reducing shear force in prosthetic foot testing. In addition, mechanical testing results were relatively consistent across multiple test sessions, lending confidence to test consistency.
- Published
- 2021
- Full Text
- View/download PDF
48. Trans-Amazon Drilling Project (TADP): origins and evolution of the forests, climate, and hydrology of the South American tropics
- Author
-
P. A. Baker, S. C. Fritz, C. G. Silva, C. A. Rigsby, M. L. Absy, R. P. Almeida, M. Caputo, C. M. Chiessi, F. W. Cruz, C. W. Dick, S. J. Feakins, J. Figueiredo, K. H. Freeman, C. Hoorn, C. Jaramillo, A. K. Kern, E. M. Latrubesse, M. P. Ledru, A. Marzoli, A. Myrbo, A. Noren, W. E. Piller, M. I. F. Ramos, C. C. Ribas, R. Trnadade, A. J. West, I. Wahnfried, and D. A. Willard
- Subjects
Geology ,QE1-996.5 - Abstract
This article presents the scientific rationale for an ambitious ICDP drilling project to continuously sample Late Cretaceous to modern sediment in four different sedimentary basins that transect the equatorial Amazon of Brazil, from the Andean foreland to the Atlantic Ocean. The goals of this project are to document the evolution of plant biodiversity in the Amazon forests and to relate biotic diversification to changes in the physical environment, including climate, tectonism, and the surface landscape. These goals require long sedimentary records from each of the major sedimentary basins across the heart of the Brazilian Amazon, which can only be obtained by drilling because of the scarcity of Cenozoic outcrops. The proposed drilling will provide the first long, nearly continuous regional records of the Cenozoic history of the forests, their plant diversity, and the associated changes in climate and environment. It also will address fundamental questions about landscape evolution, including the history of Andean uplift and erosion as recorded in Andean foreland basins and the development of west-to-east hydrologic continuity between the Andes, the Amazon lowlands, and the equatorial Atlantic. Because many modern rivers of the Amazon basin flow along the major axes of the old sedimentary basins, we plan to locate drill sites on the margin of large rivers and to access the targeted drill sites by navigation along these rivers.
- Published
- 2015
- Full Text
- View/download PDF
49. First mutation rate analysis Of 24 autosomal STRs in Argentina
- Author
-
A, Sala, M, Caputo, and D, Corach
- Published
- 2019
- Full Text
- View/download PDF
50. Integrating care: the experience of a US healthcare organization
- Author
-
Coniglio, Ray, M. Caputo, Lisa, D. Sanddal, Nels, Salottolo, Kristin, Sabin, Margaret, W. Bourg, Pamela, and W. Mains, Charles
- Published
- 2014
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.