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The detection of rare deleterious variants is the preeminent current technical challenge in statistical genetics. Sorting the deleterious from neutral variants at a disease locus is challenging because of the sparseness of the evidence for each individual variant. Hierarchical modeling and Bayesian model uncertainty are two techniques that have been shown to be promising in pinpointing individual rare variants that may be driving the association. Interpreting the results from these techniques from the perspective of multiple testing is a challenge and the goal of this article is to better understand their false discovery properties. Using simulations, we conclude that accurate false discovery control cannot be achieved in this framework unless the magnitude of the variants' risk is large and the hierarchical characteristics have high accuracy in distinguishing deleterious from neutral variants. 相似文献
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Larisa Maria Badau Andrei Dorin Ciocoiu Cristina Marinela Oprean Nusa Alina Segarceanu Adelina Gheju Brigitha Vlaicu 《Current oncology (Toronto, Ont.)》2022,29(3):1890
The safety profile and effectiveness of existing anti-HER2-targeted therapies have not been evaluated in patients with breast cancer and visceral crisis. We report the case of a 26-year-old woman who was diagnosed with advanced HER2-positive breast cancer and initially treated with curative intent therapy in a neoadjuvant setting, using Trastuzumab and Pertuzumab in combination with Docetaxel; her cancer recurred two years later, with liver metastases and pulmonary lymphangitic carcinomatosis, causing visceral crisis. Furthermore, the patient’s clinical status worsened when she developed respiratory failure, hepatomegaly and a severe hepatocytolysis. Since the patient was free of disease more than six months, we started with Paclitaxel half dose because of the hepatic dysfunction, and we gradually reintroduced Trastuzumab and then Pertuzumab. In the meantime, the patient changed her lifestyle by increasing her consumption of fresh fruits and vegetables and fiber and reducing her intake of processed meat, dairy and sugar. As a result, the patient showed a significant improvement in her respiratory symptoms and liver tests in less than two months. Imaging reevaluation showed partial remission of liver metastases and pulmonary lymphangitic carcinomatosis. She underwent seven months of dual anti-HER2 blockade before relapsing cerebrally. Our results suggest that the sequential combination therapy with Trastuzumab, Pertuzumab and Paclitaxel presented in this study, associated with a healthy lifestyle, may be a good management for recurrent HER2-positive breast cancer with pulmonary visceral crisis and severe liver dysfunction. 相似文献
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Sebastian P. Mondaca MD Dazhi Liu PharmD BCOP Jessica R. Flynn Sandy Badson Stefan Hamaway BS Mrinal M. Gounder MD Danny N. Khalil MD PhD Alexander E. Drilon MD Bob T. Li MD MPH Komal L. Jhaveri MD Alison M. Schram MD Katherine E. Kargus RN Mary Kate Kasler DNP MSN Natalie M. Blauvelt Neil H. Segal MD PhD Marinela Capanu PhD Margaret K. Callahan MD PhD David M. Hyman MD Maya Gambarin-Gelwan MD James J. Harding MD 《Cancer》2020,126(22):4967-4974
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Caitlin A. McIntyre MD Sharon A. Lawrence MD Allison L. Richards PhD Joanne F. Chou MPH Winston Wong MD Marinela Capanu PhD Michael F. Berger PhD Mark T. A. Donoghue PhD Kenneth H. Yu MD Anna M. Varghese MD David P. Kelsen MD Wungki Park MD Vinod P. Balachandran MD T. Peter Kingham MD Michael I. D’Angelica MD Jeffrey A. Drebin MD PhD William R. Jarnagin MD Christine A. Iacobuzio-Donahue MD PhD Peter J. Allen MD Eileen M. O’Reilly MD 《Cancer》2020,126(17):3939-3949
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Åke Borg Robert W. Haile Kathleen E. Malone Marinela Capanu Ahn Diep Therese Törngren Sharon Teraoka Colin B. Begg Duncan C. Thomas Patrick Concannon Lene Mellemkjaer Leslie Bernstein Lina Tellhed Shanyan Xue Eric R. Olson Xiaolin Liang Jessica Dolle Anne‐Lise Børresen‐Dale Jonine L. Bernstein 《Human mutation》2010,31(3):E1200-E1240
BRCA1 and BRCA2 screening in women at high‐risk of breast cancer results in the identification of both unambiguously defined deleterious mutations and sequence variants of unknown clinical significance (VUS). We examined a population‐based sample of young women with contralateral breast cancer (CBC, n=705) or unilateral breast cancer (UBC, n=1398). We identified 470 unique sequence variants, of which 113 were deleterious mutations. The remaining 357 VUS comprised 185 unique missense changes, 60% were observed only once, while 3% occurred with a frequency of >10%. Deleterious mutations occurred three times more often in women with CBC (15.3%) than in women with UBC (5.2%), whereas combined, VUS were observed in similar frequencies in women with CBC and UBC. A protein alignment algorithm defined 16 rare VUS, occurring at highly conserved residues and/or conferring a considerable biochemical difference, the majority located in the BRCA2 DNA‐binding domain. We confirm a multiplicity of BRCA1 and BRCA2 VUS that occur at a wide range of allele frequencies. Although some VUS inflict chemical differences at conserved residues, suggesting a deleterious effect, the majority are not associated with an increased risk of CBC. © 2010 Wiley‐Liss, Inc. 相似文献
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Larisa Daniela Sandulescu Cristiana Marinela Urhut Sarmis Marian Sandulescu Ana-Maria Ciurea Sergiu Marian Cazacu Sevastita Iordache 《World journal of hepatology》2021,13(12):1892-1908
Hepatic hemangioma is usually detected on a routine ultrasound examination because of silent clinical behaviour. The typical ultrasound appearance of hemangioma is easily recognizable and quickly guides the diagnosis without the need for further investigation. But there is also an entire spectrum of atypical and uncommon ultrasound features and our review comes to detail these particular aspects. An atypical aspect in standard ultrasound leads to the continuation of explorations with an imaging investigation with contrast substance [ultrasound/ computed tomography/or magnetic resonance imaging (MRI)]. For a clinician who practices ultrasound and has an ultrasound system in the room, the easiest, fastest, non-invasive and cost-effective method is contrast enhanced ultrasound (CEUS). Approximately 85% of patients are correctly diagnosed with this method and the patient has the correct diagnosis in about 30 min without fear of malignancy and without waiting for a computer tomography (CT)/MRI appointment. In less than 15% of patients CEUS does not provide a conclusive appearance; thus, CT scan or MRI becomes mandatory and liver biopsy is rarely required. The aim of this updated review is to synthesize the typical and atypical ultrasound aspects of hepatic hemangioma in the adult patient and to propose a fast, non-invasive and cost-effective clinical-ultrasound algorithm for the diagnosis of hepatic hemangioma. 相似文献
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THE AIM OF THIS STUDY: Is to identify two severe complications after catheterism of nasolacrimal duct. A boy, 9 months old, was treated in Clinica I Oftalmologie la?i for presptal cellulitis after catheterism of nasolacrimal duct which was performed in other Eye clinic, without general anesthesia. Also, this child presented the rupture of punctal and inferior canalicular duct. CONCLUSION: Catheterism of nasolacrimal duct must be performed by ophthalmopediatric doctors with experience, under general anesthesia, to prevent complications. 相似文献