tbuckley/cabot-search huggingface dataset:
Childhood OSA is an independent determinant of blood pressure in adulthood: longitudinal follow-up study
Authors: Kate Ching-ching Chan, Chun Ting Au, Lai Ling Hui, Yun Kwok Wing, Albert Martin Li
Journal: Thorax (2020)

Background Current literature supports cross-sectional association between childhood obstructive sleep apnoea (OSA) and elevated blood pressure (BP). However, long-term cardiovascular outcomes in children with OSA remain unexplored. Objective To evaluate the associations of childhood OSA with BP parameters in a prospective 10 year follow-up study. Methods Participants were recruited from a cohort established for our previous OSA epidemiological study. They were invited to undergo clinical examination, overnight polysomnography and 24-hour ambulatory BP monitoring. Multivariate linear regression was used to assess the associations of baseline childhood OSA with BP outcomes at follow-up. Multivariable log-binomial regression was used with inverse probability weighting to assess the adjusted associations of childhood OSA with hypertension and non-dipping of nocturnal BP in adulthood. Results 243 participants (59% male) attended the follow-up visit. The mean age was 9.8 (SD ±1.8) and 20.2 (SD ±1.9) years at baseline and follow-up respectively, with a mean follow-up duration of 10.4 (SD ±1.1) years. Childhood moderate-to-severe OSA was associated with higher nocturnal systolic blood pressure (SBP) (difference from normal controls: 6.5 mm Hg, 95% CI 2.9 to 10.1) and reduced nocturnal dipping of SBP (−4.1%, 95% CI −6.3% to 1.8%) at follow-up, adjusted for age, sex, Body Mass Index and height at baseline, regardless of the presence of OSA at follow-up. Childhood moderate-to-severe OSA was also associated with higher risk of hypertension (relative risk (RR) 2.5, 95% CI 1.2 to 5.3) and non-dipping of nocturnal SBP (RR 1.3, 95% CI 1.0 to 1.7) at follow-up. Conclusion Childhood OSA was found to be an independent risk factor for adverse BP outcomes in adulthood.
Abstract P1-01-10: Positron emission mammography in assessment of the clinicopathological characteristics of breast cancers
Authors: Jun Ito, Toshihiko Sato
Journal: Cancer Research (2020)

Abstract Background: Breast cancer is the most prevalent malignant neoplasm in women. Early detection and personalized treatment are very important to decrease mortality. Positron emission mammography(PEM) is a newly developed breast imaging technology using the positron emission tomography(PET) radiopharmaceutical 18F-fluoro-deoxy-D-glucose(18FDG). We investigated the correlation between PEM and known prognostic markers, including estrogen receptor(ER), progesterone receptor(PR), human epidermal growth factor receptor(HER2) status, tumor histology, nuclear grade, and the number of Ki-67-positive tumor cells/10 HPF(Ki-67 index). Methods: Fifty-eight patients were included in this study. PEM imaging was performed on a commercially available PEM unit. Maximum PEM uptake value(PUVmax) and lesion-to-background(LTB) ratio were determined. All resected specimens were evaluated by our institution’s pathology department. PUVmax and LTB ratios were compared with ER and PR status, tumor histology, and nuclear grades. The correlation coefficients between maximum PEM uptake value or LTB and the Ki-67 index were calculated. Results: PUVmax values were significantly different between ductal carcinoma in situ and invasive ductal carcinoma(P = 0.033). PUVmax and LTB showed significant differences between nuclear grade 1 and nuclear grade 3(PUVmax: P = 0.027, LTB: 0.0043). PUVmax, LTB, and Ki-67 index correlated significantly; PUVmax and Ki-67 index: correlation coefficient = 0.558, P = 0.000125; LTB and Ki-67 index: correlation coefficient = 0.572, P = 0.000075. Conclusions: PUVmax and LTB showed remarkable correlation with nuclear grades and the Ki-67 index, suggesting PEM’s utility in assessing the clinicopathological characteristics of breast cancer. Citation Format: Jun Ito, Toshihiko Sato. Positron emission mammography in assessment of the clinicopathological characteristics of breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-01-10.
Abstract P2-09-03: Spectrum, prevalence and clinical outcomes of germline mutations in PALB2 genes in 16501 unselected BRCA1/2-negative breast cancer patients: A multi-center analysis
Authors: Jiaojiao Zhou, Honglian Wang, Fangmeng Fu, Zhanwen Li, Yun Liu, Qingjian Feng, Weizhu Wu, Hongxia Wang, Chuan Wang, Yiding Chen
Journal: Cancer Research (2020)

Abstract Background: PALB2 (Partner and Localizer of BRCA2) is a breast cancer predisposition gene, which plays a critical role in homologous recombination via interacting with BRCA1/2 and RAD51 when DNA break. However, the clinical relevance of PALB2 germline mutations in Chinese breast cancer patients remains unknown. We attempted to illustrate the full prevalence and spectrum of PALB2 germline mutations in Chinese breast cancer population, and to investigate the clinical outcomes of PALB2 germline mutations. Patients and methods: A total of 21216 unselected breast cancer patients were enrolled from multiple clinical centers in China. After evaluation of the DNA quality and clinical information, 16501 eligible BRCA1/2-negative breast cancer patients were analyzed. A group of 5890 Chinese women without cancer was enrolled as healthy controls. PALB2 screening was based on next-generation sequencing, by screening complete coding sequence and intron-exon boundaries of PALB2. Clinical information was synchronously collected. Results: The 79 PALB2 deleterious germline mutations included 25 nonsense mutations, 47 frameshift mutations, and 7 splicing mutations. The hotspot region for PALB2 mutations was exon4. A total of 41 novel mutations were identified in PALB2. Among the 16501 BRCA1/2-negative breast cancer patients and 5890 healthy women, PALB2 deleterious mutation carriers account for 0.97% (n=160) and 0.19% (n=11) separately. PALB2 mutations were significantly associated with increased breast cancer risk (OR: 5.23, 95% CI 2.89-9.49; P&amp;lt;0.0001), and especially in women aged 30 or younger (OR: 11.97, 95% CI 3.76-34.39; P&amp;lt;0.0001). PALB2 mutation carriers were significantly more likely to be triple negative breast cancers and have bigger tumors, positive axillary lymph nodes, bilateral breast cancers, family history of breast and/or ovarian cancer and family history of any other cancer, than noncarriers. Conclusions: The PALB2 mutations confer a moderately increased breast cancer risk in women, but relatively highly increased breast cancer risk in those aged 30 or younger. PALB2 mutation status is associated with distinct clinical characteristics in breast cancer. Key words:PALB2, breast cancer, germline mutations, next-generation sequencing Citation Format: Jiaojiao Zhou, Honglian Wang, Fangmeng Fu, Zhanwen Li, Yun Liu, Qingjian Feng, Weizhu Wu, Hongxia Wang, Chuan Wang, Yiding Chen. Spectrum, prevalence and clinical outcomes of germline mutations in PALB2 genes in 16501 unselected BRCA1/2-negative breast cancer patients: A multi-center analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-09-03.
Abstract C12: Lipids signaling contributes to glucose-independent metabolic adaptation in pancreatic ductal adenocarcinoma
Authors: Ziheng Chen, Jintan Liu, I-Lin Ho, Johnathan Rose, Liang Yan, Wantong Yao, Andrea Viale, Alessandro Carugo, Haoqiang Ying, Giulio Draetta
Journal: Cancer Research (2019)

Abstract Increasing researches verify that mitochondrial oxidase phosphorylation (OXPHOS) plays remarkable roles in cancer initiation, development, and drug resistance. Our previous study identified that preclinic OXPHOS inhibitor IACS-010759 significantly suppressed cancer cell growth in brain cancer and acute myeloid leukemia (AML) in vivo and in vitro with very low compound concentration. In pancreatic ductal adenocarcinoma (PDAC), there were actually different responses to OXPHOS inhibition in glucose-independent conditions. Using patient-derived xenograft (PDX) model, we identified sensitive and resistant groups to IACS-010759, and there were dramatic metabolic changes to feed-back compound resistance. By metabolomics analysis, we found a novel lipids-signaling activation mechanism that is responsible for the adaptive metabolic resistance. Furthermore, combination of OXPHOS inhibitor and specific lipids pathway inhibitor showed significant cancer cell growth suppression in resistant PDAC types. Our findings uncovered a novel adaptive metabolism in drug resistance and provide new thoughts on therapy strategy in PDAC. Citation Format: Ziheng Chen, Jintan Liu, I-Lin Ho, Johnathan Rose, Liang Yan, Wantong Yao, Andrea Viale, Alessandro Carugo, Haoqiang Ying, Giulio Draetta. Lipids signaling contributes to glucose-independent metabolic adaptation in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C12.
Abstract P5-05-12: Small molecule targeting regulated cell death pathways in treating triple negative breast cancer
Authors: Venkata Mahidhar Yenugonda, Ariana Waters, Sivaramakrishna Yadavalli, Diego Marzese, Surojeet Senugupta, Elmar Nurmammadov, Yueqin Quan, Natsuko Nomura, Annamarie Allnutt, Santosh Kesari
Journal: Cancer Research (2020)

Abstract The absence of hormone and Her2 receptor expression in triple negative breast cancer (TNBC) precludes the use of targeted therapy available for other breast cancer subtypes, and cytotoxic chemotherapy such as paclitaxel and doxorubicin remains the mainstay of treatment for TNBC. However, patients with TNBC have higher relapse rates, with residual disease after chemotherapy and shorter overall survival, leaving space for further improvement beyond these cytotoxic chemotherapies. We have identified a new chemical entity, VMY- BC-1, that potently blocks growth in TNBC cell lines compared to other breast cancer subgroups or normal-like breast epithelial cells. Our molecule reduces invasion and induces apoptosis in TNBC cell lines. VMY-BC-1 is orally bioavailable and has promising pharmacological properties, and has demonstrated TNBC growth inhibition in vivo. Quantitative proteomics with tandem mass tag (TMT) and Ingenuity Pathway Analysis (IPA) identified significantly altered pathways upon treatment with VMY-BC-1 in the human TNBC cell line, MDA-MB-231. These include activation of the apoptosis, autophagy, and DNA damage pathways, and inhibition of the mTOR1, PI3K, and AKT pathways (Z score = 0.156, p value =1.97E-10). Thermal proteome profiling (TPP) analysis identified proteins interacting with VMY-BC-1 that relate to activated autophagy and DNA damage pathways, such as UNC-51 like kinase 1 (ULK1) and ataxia-telangiectasia mutated (ATM). Importantly, in line with our in vitro observations, in addition to a significantly lower expression of ULK1 on TNBC (T-test; p value = 2.127E-10), we observed that patients with tumors with high ULK1 expression have a larger relapse-free survival (n=3,951; HR=0.77 [0.69-0.86]; log rank; p=5.1E-06). Moreover, our small molecules activated autophagy mediated signaling pathways through ULK1 phosphorylation. These data suggest that autophagy and DNA damage pathways could be therapeutically targeted in TNBC. Citation Format: Venkata Mahidhar Yenugonda, Ariana Waters, Sivaramakrishna Yadavalli, Diego Marzese, Surojeet Senugupta, Elmar Nurmammadov, Yueqin Quan, Natsuko Nomura, Annamarie Allnutt, Santosh Kesari. Small molecule targeting regulated cell death pathways in treating triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-05-12.
Prediction of hepatocellular carcinoma recurrence after liver transplantation by preoperative F-18-FDG PET/CT
Authors: Birkan Bozkurt, Ender Anilir, Tolga Sahin, Refik Bilgin, Ayfer Serin, Pinar Yazici, Yildiray Yuzer, Yaman Tokat
Journal: International Journal of Surgery (2020)
Supervised pulmonary tele-rehabilitation versus pulmonary rehabilitation in severe COPD: a randomised multicentre trial
Authors: Henrik Hansen, Theresa Bieler, Nina Beyer, Thomas Kallemose, Jon Torgny Wilcke, Lisbeth Marie Østergaard, Helle Frost Andeassen, Gerd Martinez, Marie Lavesen, Anne Frølich, Nina Skavlan Godtfredsen
Journal: Thorax (2020)

Pulmonary rehabilitation (PR) is an effective, key standard treatment for people with COPD. Nevertheless, low participant uptake, insufficient attendance and high drop-out rates are reported. Investigation is warranted of the benefits achieved through alternative approaches, such as pulmonary tele-rehabilitation (PTR).To investigate whether PTR is superior to conventional PR on 6 min walk distance (6MWD) and secondarily on respiratory symptoms, quality of life, physical activity and lower limb muscle function in patients with COPD and FEV1 <50% eligible for routine hospital-based, outpatient PR.In this single-blinded, multicentre, superiority randomised controlled trial, patients were assigned 1:1 to 10 weeks of groups-based PTR (60 min, three times weekly) or conventional PR (90 min, two times weekly). Assessments were performed by blinded assessors at baseline, end of intervention and at 22 weeks' follow-up from baseline. The primary analysis was based on the intention-to-treat principle.The primary outcome was change in 6MWD from baseline to 10 weeks; 134 participants (74 females, mean±SD age 68±9 years, FEV1 33%±9% predicted, 6MWD 327±103 metres) were included and randomised. The analysis showed no between-group differences for changes in 6MWD after intervention (9.2 metres (95% CI: -6.6 to 24.9)) or at 22 weeks' follow-up (-5.3 metres (95% CI: -28.9 to 18.3)). More participants completed the PTR intervention (n=57) than conventional PR (n=43) (χ2 test p<0.01).PTR was not superior to conventional PR on the 6MWD and we found no differences between groups. As more participants completed PTR, supervised PTR would be relevant to compare with conventional PR in a non-inferiority design. Trial registration number ClinicalTrials.gov (NCT02667171), 28 January 2016.
Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility — King County, Washington, March 2020
Authors: Anne Kimball, Kelly M. Hatfield, Melissa Arons, Allison James, Joanne Taylor, Kevin Spicer, Ana C. Bardossy, Lisa P. Oakley, Sukarma Tanwar, Zeshan Chisty, Jeneita M. Bell, Mark Methner, Josh Harney, Jesica R. Jacobs, Christina M. Carlson, Heather P. McLaughlin, Nimalie Stone, Shauna Clark, Claire Brostrom-Smith, Libby C. Page, Meagan Kay, James Lewis, Denny Russell, Brian Hiatt, Jessica Gant, Jeffrey S. Duchin, Thomas A. Clark, Margaret A. Honein, Sujan C. Reddy, John A. Jernigan, Atar Baer, Leslie M. Barnard, Eileen Benoliel, Meaghan S. Fagalde, Jessica Ferro, Hal Garcia Smith, Elysia Gonzales, Noel Hatley, Grace Hatt, Michaela Hope, Melinda Huntington-Frazier, Vance Kawakami, Jennifer L. Lenahan, Margaret D. Lukoff, Emily B. Maier, Shelly McKeirnan, Patricia Montgomery, Jennifer L. Morgan, Laura A. Mummert, Sargis Pogosjans, Francis X. Riedo, Leilani Schwarcz, Daniel Smith, Steve Stearns, Kaitlyn J. Sykes, Holly Whitney, Hammad Ali, Michelle Banks, Arun Balajee, Eric J. Chow, Barbara Cooper, Dustin W. Currie, Jonathan Dyal, Jessica Healy, Michael Hughes, Temet M. McMichael, Leisha Nolen, Christine Olson, Agam K. Rao, Kristine Schmit, Noah G. Schwartz, Farrell Tobolowsky, Rachael Zacks, Suzanne Zane
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Following identification of a case of coronavirus disease 2019 (COVID-19) in a health care worker, 76 of 82 residents of a long-term care skilled nursing facility were tested for SARS-CoV-2; 23 (30.3%) had positive test results, approximately half of whom were asymptomatic or presymptomatic on the day of testing.
Abstract P2-13-21: Predicting symptoms and diseases after breast cancer treatment: Development of a nomogram
Authors: Marianne J. Heins, Kelly M. De Ligt, Janneke Verloop, Sabine Siesling, Joke C. Korevaar
Journal: Cancer Research (2020)

Abstract Background: Women with breast cancer can experience a variety of late adverse effects, depending on age, treatment and time since diagnosis. We developed a nomogram that predicts which symptoms and diseases are likely to occur in breast cancer survivors up to 15 years after diagnosis. Methods: Data from the Netherlands Cancer Registry and NIVEL Primary Care Database were combined in the Primary-Secondary Cancer Care Registry, containing data about the cancer diagnosis/treatment and data from the primary care electronic health records of 12.850 Dutch women diagnosed with breast cancer between 2000-2016. From Nivel Primary Care Database 25.700 control women without breast cancer were obtained. First, Cox regression models were built, stratified by 4 age groups and 2 time windows (1-5 and 5-15 years after diagnosis), in order to determine which symptoms and diseases were more frequently experienced in cases compared to controls (p-value&amp;lt;.05). Second, for each significant symptom and disease, relevant treatment variables (chemo therapy (yes/no), radio therapy (yes/no, and lateralisation), hormone therapy (yes/no), axillary dissection (yes/no)) were added stepwise to the models. Variables with a p-value &amp;lt;.10 were included in a multivariate model and all variables with a p-value &amp;lt;.05 were retained in the final model. Findings: In total, 635 models were constructed, forming the basis for the nomogram. Late effects occurring more frequently in cases compared to controls independent of age and time since diagnosis were chest symptoms, lymphedema/arm symptoms, redness/infections of the skin, nausea, cystitis, insomnia and discussing euthanasia. Others were predominantly relevant 1-5 years after diagnosis, including vomiting and side-effects of medication. Interpretation: This nomogram can provide clinicians and women with breast cancer insight in which symptoms and diseases she has an increased risk to experience in the upcoming years, which is both applicable when making treatment decisions and at follow-up initiation. Besides, it may be a starting point to develop effective preventive measures to limit late side-effects of breast cancer and improve after care for women with breast cancer. Citation Format: Marianne J. Heins, Kelly M. De Ligt, Janneke Verloop, Sabine Siesling, Joke C. Korevaar. Predicting symptoms and diseases after breast cancer treatment: Development of a nomogram [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-21.
Prenatal and perinatal risk and protective factors for psychosis: a systematic review and meta-analysis
Authors: Cathy Davies, Giulia Segre, Andrés Estradé, Joaquim Radua, Andrea De Micheli, Umberto Provenzani, Dominic Oliver, Gonzalo Salazar de Pablo, Valentina Ramella-Cravaro, Maria Besozzi, Paola Dazzan, Maddalena Miele, Gianluigi Caputo, Cecilia Spallarossa, Georgia Crossland, Athif Ilyas, Giulia Spada, Pierluigi Politi, Robin M Murray, Philip McGuire, Paolo Fusar-Poli
Journal: The Lancet Psychiatry (2020)
Correction to: Circular RNA circNHSL1 promotes gastric cancer progression through the miR-1306-3p/SIX1/Vimentin axis
Authors: Zhonglin Zhu, Zeyin Rong, Zai Luo, Zhilong Yu, Jing Zhang, Zhengjun Qiu, Chen Huang
Journal: Molecular Cancer (2020)

After publication of the article [1], the authors reported errors of inter-duplication in Figure 3.
In addition to mTOR and JAK/STAT, NLRP3 inflammasome is another key pathway activated in sarcoidosis
Authors: Nicolas Riteau, Jean-François Bernaudin
Journal: European Respiratory Journal (2020)

<b>The study of Huppertz and co-workers addresses the role of the NLRP3 inflammasome in sarcoidosis. Employing both mouse model and human samples, they provide evidence of NLPR3 inflammasome activation and increased IL-1β production in lung granulomas.</b>http://bit.ly/32a4GsI
Abstract P2-04-05: Loss of Ste20-like kinase induces a basal/stem-like phenotype in HER2-positive breast cancers
Authors: Khalid N Al-Zahrani, John Abou-Hamad, Ben Pryce, David P Cook, Johnathan Hodgins, Cedrik Labreche, Pascale Robineau-Charette, Christiano de Souza, John Bell, Rebecca Auer, Michele Ardolino, Barbara Vanderhyden, Daniel Schramek, Luc Sabourin
Journal: Cancer Research (2020)

Abstract Over the past two decades, the mammalian Ste20-like kinase (SLK) has been characterized for its role in regulating cellular migration, proliferation and apoptosis in fibroblasts and myoblasts. In mammary epithelial cells, SLK has been shown to be required for efficient epithelial-to-mesenchymal transition and to be activated downstream of the HER2/Neu-oncogene to control chemotactic cellular migration. Here, we assessed the role of SLK in HER2/Neu-induced mammary tumorigenesis in vivo. As SLK is activated downstream of HER2/Neu, we hypothesized that the loss of SLK would significantly delay tumor progression in a mouse model of HER2-positive breast cancer. As we have shown that global attenuation of SLK kinase activity results in embryonic lethality, a conditional SLK knockout mouse model was generated. To study the role of SLK in HER2-positive breast cancer, we crossed these conditional SLK knockout mice with mice expressing HER2/Neu linked to Cre recombinase in the mammary luminal epithelium. Unexpectedly, we have demonstrated that conditional deletion of SLK significantly accelerates Neu-induced mammary tumor onset and decreases overall survival. SLK deletion results in the induction of Sox10 which drives mammary stem/progenitor activity and cooperates with HER2/Neu to drive tumor growth. Using the Cancer Genome Atlas, we have supported previous findings and validated Sox10 as a potential biomarker of the Triple-negative Breast Cancer subtype. Furthermore, we have uncovered that SLK deletion results in enhanced activation of AKT. We provide evidence that Sox10 induction requires signaling through a novel AKT/Sox9-dependent pathway following SLK deletion. Taken together, our data suggests that SLK may be required to maintain cells in a fully differentiated state and that loss of SLK in HER2/Neu-induced breast cancer drives a more basal/stem-like phenotype through the induction of Sox10. Citation Format: Khalid N Al-Zahrani, John Abou-Hamad, Ben Pryce, David P Cook, Johnathan Hodgins, Cedrik Labreche, Pascale Robineau-Charette, Christiano de Souza, John Bell, Rebecca Auer, Michele Ardolino, Barbara Vanderhyden, Daniel Schramek, Luc Sabourin. Loss of Ste20-like kinase induces a basal/stem-like phenotype in HER2-positive breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-04-05.