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1.
Nature ; 616(7958): 691-695, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36848931

RESUMO

Spontaneous symmetry breaking underlies much of our classification of phases of matter and their associated transitions1-3. The nature of the underlying symmetry being broken determines many of the qualitative properties of the phase; this is illustrated by the case of discrete versus continuous symmetry breaking. Indeed, in contrast to the discrete case, the breaking of a continuous symmetry leads to the emergence of gapless Goldstone modes controlling, for instance, the thermodynamic stability of the ordered phase4,5. Here, we realize a two-dimensional dipolar XY model that shows a continuous spin-rotational symmetry using a programmable Rydberg quantum simulator. We demonstrate the adiabatic preparation of correlated low-temperature states of both the XY ferromagnet and the XY antiferromagnet. In the ferromagnetic case, we characterize the presence of a long-range XY order, a feature prohibited in the absence of long-range dipolar interaction. Our exploration of the many-body physics of XY interactions complements recent works using the Rydberg-blockade mechanism to realize Ising-type interactions showing discrete spin rotation symmetry6-9.

2.
Genet Med ; 24(11): 2380-2388, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36057905

RESUMO

PURPOSE: Health care professionals are expected to take on an active role in the implementation of risk-based cancer prevention strategies. This study aimed to explore health care professionals' (1) self-reported familiarity with the concept of polygenic risk score (PRS), (2) perceived level of knowledge regarding risk-stratified breast cancer (BC) screening, and (3) preferences for continuing professional development. METHODS: A cross-sectional survey was conducted using a bilingual-English/French-online questionnaire disseminated by health care professional associations across Canada between November 2020 and May 2021. RESULTS: A total of 593 professionals completed more than 2 items and 453 responded to all questions. A total of 432 (94%) participants were female, 103 (22%) were physicians, and 323 (70%) were nurses. Participants reported to be unfamiliar with (20%), very unfamiliar (32%) with, or did not know (41%) the concept of PRS. Most participants reported not having enough knowledge about risk-stratified BC screening (61%) and that they would require more training (77%). Online courses and webinar conferences were the preferred continuing professional development modalities. CONCLUSION: The study indicates that health care professionals are currently not familiar with the concept of PRS or a risk-stratified approach for BC screening. Online information and training seem to be an essential knowledge transfer modality.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Masculino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Conhecimentos, Atitudes e Prática em Saúde , Estudos Transversais , Detecção Precoce de Câncer , Pessoal de Saúde/educação , Inquéritos e Questionários , Fatores de Risco
3.
Cell Rep ; 14(3): 429-439, 2016 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-26774475

RESUMO

High-grade serous ovarian carcinomas (HGSOCs) with BRCA1/2 mutations exhibit improved outcome and sensitivity to double-strand DNA break (DSB)-inducing agents (i.e., platinum and poly(ADP-ribose) polymerase inhibitors [PARPis]) due to an underlying defect in homologous recombination (HR). However, resistance to platinum and PARPis represents a significant barrier to the long-term survival of these patients. Although BRCA1/2-reversion mutations are a clinically validated resistance mechanism, they account for less than half of platinum-resistant BRCA1/2-mutated HGSOCs. We uncover a resistance mechanism by which a microRNA, miR-622, induces resistance to PARPis and platinum in BRCA1 mutant HGSOCs by targeting the Ku complex and restoring HR-mediated DSB repair. Physiologically, miR-622 inversely correlates with Ku expression during the cell cycle, suppressing non-homologous end-joining and facilitating HR-mediated DSB repair in S phase. Importantly, high expression of miR-622 in BRCA1-deficient HGSOCs is associated with worse outcome after platinum chemotherapy, indicating microRNA-mediated resistance through HR rescue.


Assuntos
Antineoplásicos/farmacologia , Proteína BRCA1/metabolismo , MicroRNAs/metabolismo , Compostos Organoplatínicos/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Animais , Antígenos Nucleares/genética , Antígenos Nucleares/metabolismo , Proteína BRCA1/genética , Sequência de Bases , Linhagem Celular Tumoral , Reparo do DNA por Junção de Extremidades/efeitos dos fármacos , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Intervalo Livre de Doença , Feminino , Recombinação Homóloga/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Autoantígeno Ku , Camundongos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Oligonucleotídeos Antissenso/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Interferência de RNA , Alinhamento de Sequência , Proteína 1 de Ligação à Proteína Supressora de Tumor p53
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