| 1. |
- Kobel, M., et al.
(författare)
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p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study
- 2023
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Ingår i: Journal of Pathology Clinical Research. - : Wiley. - 2056-4538. ; 9:3, s. 208-222
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Tidskriftsartikel (refereegranskat)abstract
- Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
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| 2. |
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| 3. |
- Rahnev, D, et al.
(författare)
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The Confidence Database
- 2020
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Ingår i: Nature human behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 4:3, s. 317-325
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Vickman, R. E., et al.
(författare)
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Deconstructing tumor heterogeneity : The stromal perspective
- 2020
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Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 11:40, s. 3621-3632
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Tidskriftsartikel (refereegranskat)abstract
- Significant advances have been made towards understanding the role of immune cell-tumor interplay in either suppressing or promoting tumor growth, progression, and recurrence, however, the roles of additional stromal elements, cell types and/or cell states remain ill-defined. The overarching goal of this NCI-sponsored workshop was to highlight and integrate the critical functions of non-immune stromal components in regulating tumor heterogeneity and its impact on tumor initiation, progression, and resistance to therapy. The workshop explored the opposing roles of tumor supportive versus suppressive stroma and how cellular composition and function may be altered during disease progression. It also highlighted microenvironment-centered mechanisms dictating indolence or aggressiveness of early lesions and how spatial geography impacts stromal attributes and function. The prognostic and therapeutic implications as well as potential vulnerabilities within the heterogeneous tumor microenvironment were also discussed. These broad topics were included in this workshop as an effort to identify current challenges and knowledge gaps in the field. Copyright:
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| 5. |
- Ahearn, Thomas U., et al.
(författare)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 6. |
- Figueroa, D., et al.
(författare)
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Return to sport soccer after anterior cruciate ligament reconstruction: ISAKOS consensus
- 2022
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Ingår i: Journal of ISAKOS. - : Elsevier BV. - 2059-7754. ; 7:6, s. 150-161
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Many factors can affect the return to pivoting sports, after an Anterior Cruciate Ligament Reconstruction. Prehabilitation, rehabilitation, surgical and psychological aspects play an essential role in the decision to return to sports. The purpose of this study is to reach an international consensus about the best conditions for returning to sports in soccer—one of the most demanding level I pivoting sports after anterior cruciate ligament (ACL) reconstruction. Methods: 34 International experts in the management of ACL injuries, representing all the Continents were convened and participated in a process based on the Delphi method to achieve a consensus. 37 statements related to ACL reconstruction were reviewed by the experts in three rounds of surveys in complete anonymity. The statements were prepared by the working group based on previous literature or systematic reviews. Rating agreement through a Likert Scale: strongly agree, agree, neither agree or disagree, disagree and strongly disagree was used. To define consensus, it was established that the assertions should achieve a 75% of agreement or disagreement. Results: Of the 37 statements, 10 achieved unanimous consensus, 18 non-unanimous consensus and 9 did not achieve consensus. In the preoperative, the correction of the range of motion deficit, the previous high level of participation in sports and a better knowledge of the injury by the patient and compliance to participate in Rehabilitation were the statements that reached unanimous consensus. During the surgery, the treatment of associated injuries, as well as the use of autografts, and the addition of a lateral extra-articular tenodesis in some particular cases (active young athletes, <25 years old, hyperlaxity, high rotatory laxity and revision cases) obtained also 100% consensus. In the postoperative period, psychological readiness and its validation with scales, adequate physical preparation, as well as not basing the RTSS purely on the time of evolution after surgery, were the factors that reached unanimous Consensus. Conclusions: The consensus statements derived from this international ISAKOS leaders, may assist clinicians in deciding when to return to sports soccer in patients after an ACL reconstruction. Those statements that reached 100% consensus have to be strongly considered in the final decision to RTS soccer. © 2022 The Authors
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| 7. |
- Carvalho, Andre F., et al.
(författare)
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Evidence-based umbrella review of 162 peripheral biomarkers for major mental disorders
- 2020
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Ingår i: Translational Psychiatry. - : NATURE PUBLISHING GROUP. - 2158-3188. ; 10:1
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Forskningsöversikt (refereegranskat)abstract
- The literature on non-genetic peripheral biomarkers for major mental disorders is broad, with conflicting results. An umbrella review of meta-analyses of non-genetic peripheral biomarkers for Alzheimers disease, autism spectrum disorder, bipolar disorder (BD), major depressive disorder, and schizophrenia, including first-episode psychosis. We included meta-analyses that compared alterations in peripheral biomarkers between participants with mental disorders to controls (i.e., between-group meta-analyses) and that assessed biomarkers after treatment (i.e., within-group meta-analyses). Evidence for association was hierarchically graded using a priori defined criteria against several biases. The Assessment of Multiple Systematic Reviews (AMSTAR) instrument was used to investigate study quality. 1161 references were screened. 110 met inclusion criteria, relating to 359 meta-analytic estimates and 733,316 measurements, on 162 different biomarkers. Only two estimates met a priori defined criteria for convincing evidence (elevated awakening cortisol levels in euthymic BD participants relative to controls and decreased pyridoxal levels in participants with schizophrenia relative to controls). Of 42 estimates which met criteria for highly suggestive evidence only five biomarker aberrations occurred in more than one disorder. Only 15 meta-analyses had a power >0.8 to detect a small effect size, and most (81.9%) meta-analyses had high heterogeneity. Although some associations met criteria for either convincing or highly suggestive evidence, overall the vast literature of peripheral biomarkers for major mental disorders is affected by bias and is underpowered. No convincing evidence supported the existence of a trans-diagnostic biomarker. Adequately powered and methodologically sound future large collaborative studies are warranted.
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| 8. |
- Grossmann, Igor, et al.
(författare)
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Insights into the accuracy of social scientists' forecasts of societal change
- 2023
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Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7, s. 484-501
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Tidskriftsartikel (refereegranskat)abstract
- How well can social scientists predict societal change, and what processes underlie their predictions? To answer these questions, we ran two forecasting tournaments testing the accuracy of predictions of societal change in domains commonly studied in the social sciences: ideological preferences, political polarization, life satisfaction, sentiment on social media, and gender-career and racial bias. After we provided them with historical trend data on the relevant domain, social scientists submitted pre-registered monthly forecasts for a year (Tournament 1; N = 86 teams and 359 forecasts), with an opportunity to update forecasts on the basis of new data six months later (Tournament 2; N = 120 teams and 546 forecasts). Benchmarking forecasting accuracy revealed that social scientists' forecasts were on average no more accurate than those of simple statistical models (historical means, random walks or linear regressions) or the aggregate forecasts of a sample from the general public (N = 802). However, scientists were more accurate if they had scientific expertise in a prediction domain, were interdisciplinary, used simpler models and based predictions on prior data. How accurate are social scientists in predicting societal change, and what processes underlie their predictions? Grossmann et al. report the findings of two forecasting tournaments. Social scientists' forecasts were on average no more accurate than those of simple statistical models.
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| 9. |
- Meredith, S. J., et al.
(författare)
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Return to sport after anterior cruciate ligament injury: Panther Symposium ACL Injury Return to Sport Consensus Group
- 2020
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 28, s. 2403-2414
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Tidskriftsartikel (refereegranskat)abstract
- Purpose A precise and consistent definition of return to sport (RTS) after anterior cruciate ligament (ACL) injury is lacking, and there is controversy surrounding the process of returning patients to sports and their previous activity level. The aim of the Panther Symposium ACL Injury RTS Consensus Group was to provide a clear definition of RTS and description of the RTS continuum, as well as to provide clinical guidance on RTS testing and decision-making. Methods An international, multidisciplinary group of ACL experts convened as part of a consensus meeting. Consensus statements were developed using a modified Delphi method. Literature review was performed to report the supporting evidence. Results Key points include that RTS is characterized by achievement of the pre-injury level of sport and involves a criteria-based progression from return to participation to return to sport, and ultimately return to performance. Purely time-based RTS decision-making should be abandoned. Progression occurs along a RTS continuum with decision-making by a multidisciplinary group that incorporates objective physical examination data and validated and peer-reviewed RTS tests, which should involve functional assessment as well as psychological readiness. Consideration should be given to biological healing, contextual factors and concomitant injuries. Conclusion The resultant consensus statements and scientific rationale aim to inform the reader of the complex process of RTS after ACL injury that occurs along a dynamic continuum. Research is needed to determine the ideal RTS test battery, the best implementation of psychological readiness testing and methods for the biologic assessment of healing and recovery.
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| 10. |
- Meredith, S. J., et al.
(författare)
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Return to sport after anterior cruciate ligament injury: Panther Symposium ACL Injury Return to Sport Consensus Group
- 2021
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Ingår i: Journal of Isakos Joint Disorders & Orthopaedic Sports Medicine. - : Elsevier BV. - 2059-7754. ; 6:3, s. 138-146
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Tidskriftsartikel (refereegranskat)abstract
- Objectives A precise and consistent definition of return to sport (RTS) after anterior cruciate ligament (ACL) injury is lacking, and there is controversy surrounding the process of returning patients to sports and their previous activity level. The aim of the Panther Symposium ACL Injury RTS Consensus Group was to provide a clear definition of RTS after ACL injury and description of the RTS continuum, as well as provide clinical guidance on RTS testing and decision-making. Methods An international, multidisciplinary group of ACL experts convened as part of a consensus meeting. Consensus statements were developed using a modified Delphi method. Literature review was performed to report the supporting evidence. Results Key points include that RTS is characterised by achievement of the preinjury level of sport and involves a criteria-based progression from return to participation to RTS, and ultimately return to performance. Purely time-based RTS decision-making should be abandoned. Progression occurs along an RTS continuum with decision-making by a multidisciplinary group that incorporates objective physical examination data and validated and peer-reviewed RTS tests, which should involve functional assessment as well as psychological readiness. Consideration should be given to biological healing, contextual factors and concomitant injuries. Conclusion The resultant consensus statements and scientific rationale aim to inform the reader of the complex process of RTS after ACL injury that occurs along a dynamic continuum. Research is needed to determine the ideal RTS test battery, the best implementation of psychological readiness testing and methods for the biological assessment of healing and recovery.
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