tbuckley/cabot-search huggingface dataset:
Association of Docosahexaenoic Acid and Arachidonic Acid Serum Levels With Retinopathy of Prematurity in Preterm Infants
Authors: Ann Hellström, Aldina Pivodic, Lotta Gränse, Pia Lundgren, Ulrika Sjöbom, Anders K. Nilsson, Helena Söderling, Anna-Lena Hård, Lois E. H. Smith, Chatarina Alice Löfqvist
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) has been inconsistent in reducing the severity and incidence of retinopathy of prematurity (ROP). Furthermore, few studies have measured the long-term serum lipid levels after supplementation. <h3>Objective</h3> To assess whether ROP severity is associated with serum levels of LC-PUFA, especially docosahexaenoic acid (DHA) and arachidonic acid (AA), during the first 28 postnatal days. <h3>Design, Setting, and Participants</h3> This cohort study analyzed the Mega Donna Mega study, a randomized clinical trial that provided enteral fatty acid supplementation at 3 neonatal intensive care units in Sweden. Infants included in this cohort study were born at a gestational age of less than 28 weeks between December 20, 2016, and August 6, 2019. <h3>Main Outcomes and Measures</h3> Severity of ROP was classified as no ROP, mild or moderate ROP (stage 1-2), or severe ROP (stage 3 and type 1). Serum phospholipid fatty acids were measured through gas chromatography–mass spectrometry. Ordinal logistic regression, with a description of unadjusted odds ratio (OR) as well as gestational age– and birth weight–adjusted ORs and 95% CIs, was used. Areas under the curve were used to calculate mean daily levels of fatty acids during postnatal days 1 to 28. Blood samples were obtained at the postnatal ages of 1, 3, 7, 14, and 28 days. <h3>Results</h3> A total of 175 infants were included in analysis. Of these infants, 99 were boys (56.6%); the median (IQR) gestational age was 25 weeks 5 days (24 weeks 3 days to 26 weeks 6 days), and the median (IQR) birth weight was 785 (650-945) grams. A higher DHA proportion was seen in infants with no ROP compared with those with mild or moderate ROP or severe ROP (OR per 0.5–molar percentage increase, 0.49 [95% CI, 0.36-0.68]; gestational age– and birth weight–adjusted OR, 0.66 [95% CI, 0.46-0.93]). The corresponding adjusted OR for AA levels per 1–molar percentage increase was 0.83 (95% CI, 0.66-1.05). The association between DHA levels and ROP severity appeared only in infants with sufficient AA levels, suggesting that a mean daily minimum level of 7.8 to 8.3 molar percentage of AA was necessary for a detectable association between DHA level and less severe ROP. <h3>Conclusions and Relevance</h3> This cohort study found that higher mean daily serum levels of DHA during the first 28 postnatal days were associated with less severe ROP even after adjustment for known risk factors, but only in infants with sufficiently high AA levels. Further studies are needed to identify LC-PUFA supplementation strategies that may prevent ROP and other morbidities.
Venous Thromboembolic Disease
Authors: Lawrence D Wagman, Melissa F Baird, Charles L Bennett, Paula L Bockenstedt, Spero R Cataland, John Fanikos, Patrick F Fogarty, Samuel Z Goldhaber, Tejpal S Grover, William Haire, Hani Hassoun, Mohammad Jahanzeb, Lawrence L Leung, Michael L Linenberger, Michael M Millenson, Thomas L Ortel, Riad Salem, Judy L Smith, Michael B Streiff
Journal: Journal of the National Comprehensive Cancer Network (2006)

Venous thromboembolic disease is a common and life-threatening condition in cancer patients. Results from a recent retrospective study of 66,106 hospitalized adult neutropenic cancer patients showed that 2.74% to 12.10% of these patients, depending on the type of malignancy, experienced a venous thromboembolism (VTE) during first hospitalization. These guidelines specifically outline strategies to prevent and treat VTE in adult inpatients with either a diagnosis of cancer or for whom cancer is clinically suspected. These guidelines evaluate the therapeutic advantages of implementing pharmacologic anticoagulation measures based on both the perceived risk for bleeding (i.e., contraindications to anticoagulation) and the status of the cancer. For the most recent version of the guidelines, please visit NCCN.org
P27.02 Associating Cardiac Plaque Accumulation With Cardiac Toxicity and Overall Survival In Locally Advanced Non-Small Cell Lung Cancer
Authors: J. Haseltine, A. Apte, A. Jackson, E. Yorke, A. Yu, A. Wu, A. Peleg, M. Al-Sadawi, M. Iocolano, D. Gelblum, N. Shaverdian, C. Simone, Ii, A. Rimner, D. Gomez, A. Shepherd
Journal: Journal of Thoracic Oncology (2021)
Relax and focus on brain tumor segmentation
Authors: Pei Wang, Albert C.S. Chung
Journal: Medical Image Analysis (2021)

In this paper, we present a Deep Convolutional Neural Networks (CNNs) for fully automatic brain tumor segmentation for both high- and low-grade gliomas in MRI images. Unlike normal tissues or organs that usually have a fixed location or shape, brain tumors with different grades have shown great variation in terms of the location, size, structure, and morphological appearance. Moreover, the severe data imbalance exists not only between the brain tumor and non-tumor tissues, but also among the different sub-regions inside brain tumor (e.g., enhancing tumor, necrotic, edema, and non-enhancing tumor). Therefore, we introduce a hybrid model to address the challenges in the multi-modality multi-class brain tumor segmentation task. First, we propose the dynamic focal Dice loss function that is able to focus more on the smaller tumor sub-regions with more complex structures during training, and the learning capacity of the model is dynamically distributed to each class independently based on its training performance in different training stages. Besides, to better recognize the overall structure of the brain tumor and the morphological relationship among different tumor sub-regions, we relax the boundary constraints for the inner tumor regions in coarse-to-fine fashion. Additionally, a symmetric attention branch is proposed to highlight the possible location of the brain tumor from the asymmetric features caused by growth and expansion of the abnormal tissues in the brain. Generally, to balance the learning capacity of the model between spatial details and high-level morphological features, the proposed model relaxes the constraints of the inner boundary and complex details and enforces more attention on the tumor shape, location, and the harder classes of the tumor sub-regions. The proposed model is validated on the publicly available brain tumor dataset from real patients, BRATS 2019. The experimental results reveal that our model improves the overall segmentation performance in comparison with the state-of-the-art methods, with major progress on the recognition of the tumor shape, the structural relationship of tumor sub-regions, and the segmentation of more challenging tumor sub-regions, e.g., the tumor core, and enhancing tumor.
GlioCova: Treatment and hospital admissions for patients with GBM in England
Authors: Radvile Mauricaite, Kerlann Le Calvez, Matthew Williams
Journal: Neuro-Oncology (2021)

Abstract Aims Data on the treatment and outcomes of patients with primary brain tumours in England is sparse. The GlioCova project uses linked national data from England to explore the incidence, treatment, outcomes, and treatment costs of all adult brain tumour patients in all 50,000 patients in England from 2013 – 2018. Here we present initial results from patients with glioblastoma (GBM). Method We used a linked dataset from the national cancer registration system in England including all adult patients diagnosed with a malignant or benign brain tumour between 2013 and 2018 (51,775 patients in total). Glioblastoma patients were selected based on ICD-10 codes (C70, C71, C72), morphology codes (9440, 9441, 9442), and grade (G4, G3, GX and NA) from the national cancer registry. We extracted data on treatment (radiotherapy, chemotherapy, brain surgery or biopsy) and measured how many patients who had adjuvant Temozolomide completed 6 cycles. Results We identified 15,294 glioblastoma patients. Most had glioblastoma morphology (14,924), followed by gliosarcoma (264) and giant cell glioblastoma (106). Almost all had a cranial tumour (C71) while 17 had a tumour originating in the spinal cord, cranial nerves or other part of central nervous system (C72). Median age was 66 (IQR=17) and 60% were male. 51.9% (7,935) underwent surgery; an additional 18.2% (2,784) had a biopsy; 3,701 (24.2%) out of 15,294 patients received radiotherapy (only) and 316 (2.1%) received chemotherapy (only). 5,520 (36.1%) received both radiotherapy and chemo. Out of 4,101 GBM patients receiving temozolomide after radiotherapy, only 1,535 (37.4%) completed 6 cycles. The 7,935 GBM patients who had surgery had a median length of stay in hospital of 5 days (IQR=6) while those that had a biopsy had a median of 3 days (IQR=6). Conclusion We have presented a description of treatment of all GBM patients in England over a five-year period. This is the first time we have been able to understand detailed treatment patterns at a national scale, and significantly extends previous analyses. Further work will look at patient safety indicators, variation across centres and costs of treatment. Acknowledgements We would like to thank the GlioCova Expert Advisory Group for their input and discussion. This work uses data provided by patients and collected by the NHS as part of their care and support.
The key role of NLRP3 and STING in APOL1-associated podocytopathy
Authors: Junnan Wu, Archana Raman, Nathan J. Coffey, Xin Sheng, Joseph Wahba, Matthew J. Seasock, Ziyuan Ma, Pazit Beckerman, Dorottya Laczkó, Matthew B. Palmer, Jeffrey B. Kopp, Jay J. Kuo, Steven S. Pullen, Carine M. Boustany-Kari, Andreas Linkermann, Katalin Susztak
Journal: Journal of Clinical Investigation (2021)

Coding variants in apolipoprotein L1 (APOL1), termed G1 and G2, can explain most excess kidney disease risk in African Americans; however, the molecular pathways of APOL1-induced kidney dysfunction remain poorly understood. Here, we report that expression of G2 APOL1 in the podocytes of Nphs1rtTA/TRE-G2APOL1 (G2APOL1) mice leads to early activation of the cytosolic nucleotide sensor, stimulator of interferon genes (STING), and the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. STING and NLRP3 expression was increased in podocytes from patients with high-risk APOL1 genotypes, and expression of APOL1 correlated with caspase-1 and gasdermin D (GSDMD) levels. To demonstrate the role of NLRP3 and STING in APOL1-associated kidney disease, we generated transgenic mice with the G2 APOL1 risk variant and genetic deletion of Nlrp3 (G2APOL1/Nlrp3 KO), Gsdmd (G2APOL1/Gsdmd KO), and STING (G2APOL1/STING KO). Knockout mice displayed marked reduction in albuminuria, azotemia, and kidney fibrosis compared with G2APOL1 mice. To evaluate the therapeutic potential of targeting NLRP3, GSDMD, and STING, we treated mice with MCC950, disulfiram, and C176, potent and selective inhibitors of NLRP3, GSDMD, and STING, respectively. G2APOL1 mice treated with MCC950, disulfiram, and C176 showed lower albuminuria and improved kidney function even when inhibitor treatment was initiated after the development of albuminuria.
Initiation of long-acting cabotegravir plus rilpivirine as direct-to-injection or with an oral lead-in in adults with HIV-1 infection: week 124 results of the open-label phase 3 FLAIR study
Authors: Chloe Orkin, Enrique Bernal Morell, Darrell H S Tan, Harold Katner, Hans-Jürgen Stellbrink, Elena Belonosova, Rebecca DeMoor, Sandy Griffith, Shanker Thiagarajah, Rodica Van Solingen-Ristea, Susan L Ford, Herta Crauwels, Parul Patel, Amy Cutrell, Kimberly Y Smith, Kati Vandermeulen, Eileen Birmingham, Marty St Clair, William R Spreen, Ronald D'Amico
Journal: The Lancet HIV (2021)
P64.04 Hypo-Fractionated Versus Conventionally Fractionated Radiotherapy for Patients with LS-SCLC: An Open-Label, Randomized, Phase 3 Trial
Authors: N. Bi, X. Hu, K. Zhao, Y. Yang, L. Zhang, M. E, J. Cao, H. Ge, X. Zhu, L. Zhao, Y. Di, W. Jiang, J. Ran, H. Zhang, T. Zhang, W. Shen, C. Deng, C. Hu, M. Chen, L. Wang
Journal: Journal of Thoracic Oncology (2021)
Covid-19: Protect healthcare workers with vaccines, urges WHO after 115 000 die worldwide
Authors: Luke Taylor
Journal: BMJ (2021)

An estimated 115 000 healthcare workers around the world have died from covid-19 so far, said senior WHO officials on 21 October as they called for governments to better protect such workers.1

If surplus vaccines stored by wealthier nations are not expedited to vulnerable healthcare professionals abroad their death toll will continue to grow by the thousand, WHO warned, adding to a looming healthcare crisis due to a global shortage of healthcare professionals.

“It’s a moral catastrophe of historic proportions that will shock future generations,” said Gordon Brown, former UK prime minister and WHO’s ambassador for global health financing. Global vaccine inequities mean that many healthcare workers in the global south have not yet received a first or second dose of a covid-19 vaccine, while booster shots are being rolled out to the general population in the global north.

Rich nations have promised to donate vaccines to poorer ones but have failed to deliver, said Brown. Only two in five health and …
Air Pollution and Coronary Plaque Vulnerability and Instability
Authors: Rocco A Montone, Massimiliano Camilli, Michele Russo, Claudio Termite, Giulia La Vecchia, Giulia Iannaccone, Riccardo Rinaldi, Filippo Gurgoglione, Marco Giuseppe Del Buono, Tommaso Sanna, Carlo Trani, Giovanna Liuzzo, Filippo Crea, Giampaolo Niccoli
Journal: JACC. Cardiovascular imaging (2021)
P63.01 Lurbinectedin in Pre-Treated Patients With Small Cell Lung Cancer and Malignant Pleural Mesothelioma in a Real World Setting
Authors: D. Dumoulin, R. Cornelissen, N. Tebayna, J.m. Mankor, S.j. Baart, L. Cantini, A. Dingemans, J. Aerts
Journal: Journal of Thoracic Oncology (2021)
Combined presentation and immunogenicity analysis reveals a recurrent RAS.Q61K neoantigen in melanoma
Authors: Aviyah Peri, Erez Greenstein, Michal Alon, Joy A. Pai, Tamir Dingjan, Shlomit Reich-Zeliger, Eilon Barnea, Chaya Barbolin, Ronen Levy, Claudia Arnedo-Pac, Shelly Kalaora, Bareket Dassa, Ester Feldmesser, Ping Shang, Polina Greenberg, Yishai Levin, Gil Benedek, Mitchell P. Levesque, David J. Adams, Michal Lotem, James S. Wilmott, Richard A. Scolyer, Göran B. Jönsson, Arie Admon, Steven A. Rosenberg, Cyrille J. Cohen, Masha Y. Niv, Nuria Lopez-Bigas, Ansuman T. Satpathy, Nir Friedman, Yardena Samuels
Journal: Journal of Clinical Investigation (2021)

Neoantigens are now recognized drivers of the antitumor immune response. Recurrent neoantigens, shared among groups of patients, have thus become increasingly coveted therapeutic targets. Here, we report on the data-driven identification of a robustly presented, immunogenic neoantigen that is derived from the combination of HLA-A*01:01 and RAS.Q61K. Analysis of large patient cohorts indicated that this combination applies to 3% of patients with melanoma. Using HLA peptidomics, we were able to demonstrate robust endogenous presentation of the neoantigen in 10 tumor samples. We detected specific reactivity to the mutated peptide within tumor-infiltrating lymphocytes (TILs) from 2 unrelated patients, thus confirming its natural immunogenicity. We further investigated the neoantigen-specific clones and their T cell receptors (TCRs) via a combination of TCR sequencing, TCR overexpression, functional assays, and single-cell transcriptomics. Our analysis revealed a diverse repertoire of neoantigen-specific clones with both intra- and interpatient TCR similarities. Moreover, 1 dominant clone proved to cross-react with the highly prevalent RAS.Q61R variant. Transcriptome analysis revealed a high association of TCR clones with specific T cell phenotypes in response to cognate melanoma, with neoantigen-specific cells showing an activated and dysfunctional phenotype. Identification of recurrent neoantigens and their reactive TCRs can promote "off-the-shelf" precision immunotherapies, alleviating limitations of personalized treatments.
A Review of Wearable Multi-Wavelength Photoplethysmography
Authors: Daniel Ray, Tim Collins, Sandra Woolley, Prasad Ponnapalli
Journal: IEEE Reviews in Biomedical Engineering (2021)

Optical pulse detection ‘photoplethysmography’ (PPG) provides a means of low cost and unobtrusive physiological monitoring that is popular in many wearable devices. However, the accuracy, robustness and generalizability of single-wavelength PPG sensing are sensitive to biological characteristics as well as sensor configuration and placement; this is significant given the increasing adoption of single-wavelength wrist-worn PPG devices in clinical studies and healthcare. Since different wavelengths interact with the skin to varying degrees, researchers have explored the use of multi-wavelength PPG to improve sensing accuracy, robustness and generalizability. This paper contributes a novel and comprehensive state-of-the-art review of wearable multi-wavelength PPG sensing, encompassing motion artifact reduction and estimation of physiological parameters. The paper also encompasses theoretical details about multi-wavelength PPG sensing and the effects of biological characteristics. The review findings highlight the promising developments in motion artifact reduction using multi-wavelength approaches, the effects of skin temperature on PPG sensing, the need for improved diversity in PPG sensing studies and the lack of studies that investigate the combined effects of factors. Recommendations are made for the standardization and completeness of reporting in terms of study design, sensing technology and participant characteristics.
All-<i>trans</i> retinoic acid plus low-dose rituximab vs low-dose rituximab in corticosteroid-resistant or relapsed ITP
Authors: Ye-Jun Wu, Hui Liu, Qiao-Zhu Zeng, Yi Liu, Jing-Wen Wang, Wen-Sheng Wang, None Jia-Feng, He-Bing Zhou, Qiu-Sha Huang, Yun He, Hai-Xia Fu, Xiao-Lu Zhu, Qian Jiang, Hao Jiang, Ying-Jun Chang, Lan-Ping Xu, Xiao-Jun Huang, Xiao-Hui Zhang
Journal: Blood (2021)
Ancestral diversity is limited in published T cell receptor sequencing studies
Authors: Yu-Ning Huang, Kerui Peng, Alice B. Popejoy, Jieting Hu, Theodore Scott Nowicki, Stefan M. Gold, Lluis Quintana-Murci, Macarena Fuentes-Guajardo, Mikhail Shugay, Victor Greiff, Amanda M. Burkhardt, Houda Alachkar, Serghei Mangul
Journal: Immunity (2021)
P48.07 Real-World Impact of Upfront Osimertinib in Reducing Health Resource Utilization by Preventing Brain Metastases
Authors: F. Simionato, F. Pancheri, S. Scarparo, P. Frugoni, C. Marco, A.G. Menin, S. Ave, L. Capparotto, A. Lupi, L. Volpin, G. Aprile, L. Calvetti
Journal: Journal of Thoracic Oncology (2021)
Antithrombotic Therapy in Patients Undergoing Transcatheter Interventions for Structural Heart Disease
Authors: Paolo Calabrò, Felice Gragnano, Giampaolo Niccoli, Rossella Marcucci, Marco Zimarino, Carmen Spaccarotella, Giulia Renda, Giuseppe Patti, Giuseppe Andò, Elisabetta Moscarella, Massimo Mancone, Arturo Cesaro, Gennaro Giustino, Raffaele De Caterina, Roxana Mehran, Davide Capodanno, Marco Valgimigli, Stephan Windecker, George D. Dangas, Ciro Indolfi, Dominick J. Angiolillo
Journal: Circulation (2021)

Contemporary evidence supports device-based transcatheter interventions for the management of patients with structural heart disease. These procedures, which include aortic valve implantation, mitral or tricuspid valve repair/implantation, left atrial appendage occlusion, and patent foramen ovale closure, profoundly differ with respect to clinical indications and procedural aspects. Yet, patients undergoing transcatheter cardiac interventions require antithrombotic therapy before, during, or after the procedure to prevent thromboembolic events. However, these therapies are associated with an increased risk of bleeding complications. To date, challenges and controversies exist regarding balancing the risk of thrombotic and bleeding complications in these patients such that the optimal antithrombotic regimens to adopt in each specific procedure is still unclear. In this review, we summarize current evidence on antithrombotic therapies for device-based transcatheter interventions targeting structural heart disease and emphasize the importance of a tailored approach in these patients.
Lipoic acid supplementation associated with neural epidermal growth factor-like 1 (NELL1)–associated membranous nephropathy
Authors: Rebecca I. Spain, Nicole K. Andeen, Pamela C. Gibson, Mary H. Samuels, Cynthia D. Morris, Andrew J. Solomon, Richard Solomon, Carin Waslo, Rupali S. Avasare
Journal: Kidney International (2021)
The dynamic, combinatorial cis-regulatory lexicon of epidermal differentiation
Authors: Daniel S. Kim, Viviana I. Risca, David L. Reynolds, James Chappell, Adam J. Rubin, Namyoung Jung, Laura K. H. Donohue, Vanessa Lopez-Pajares, Arwa Kathiria, Minyi Shi, Zhixin Zhao, Harsh Deep, Mahfuza Sharmin, Deepti Rao, Shin Lin, Howard Y. Chang, Michael P. Snyder, William J. Greenleaf, Anshul Kundaje, Paul A. Khavari
Journal: Nature Genetics (2021)
Integrating thousands of PTEN variant activity and abundance measurements reveals variant subgroups and new dominant negatives in cancers
Authors: Kenneth A. Matreyek, Jason J. Stephany, Ethan Ahler, Douglas M. Fowler
Journal: Genome Medicine (2021)

Abstract Background PTEN is a multi-functional tumor suppressor protein regulating cell growth, immune signaling, neuronal function, and genome stability. Experimental characterization can help guide the clinical interpretation of the thousands of germline or somatic PTEN variants observed in patients. Two large-scale mutational datasets, one for PTEN variant intracellular abundance encompassing 4112 missense variants and one for lipid phosphatase activity encompassing 7244 variants, were recently published. The combined information from these datasets can reveal variant-specific phenotypes that may underlie various clinical presentations, but this has not been comprehensively examined, particularly for somatic PTEN variants observed in cancers. Methods Here, we add to these efforts by measuring the intracellular abundance of 764 new PTEN variants and refining abundance measurements for 3351 previously studied variants. We use this expanded and refined PTEN abundance dataset to explore the mutational patterns governing PTEN intracellular abundance, and then incorporate the phosphatase activity data to subdivide PTEN variants into four functionally distinct groups. Results This analysis revealed a set of highly abundant but lipid phosphatase defective variants that could act in a dominant-negative fashion to suppress PTEN activity. Two of these variants were, indeed, capable of dysregulating Akt signaling in cells harboring a WT PTEN allele. Both variants were observed in multiple breast or uterine tumors, demonstrating the disease relevance of these high abundance, inactive variants. Conclusions We show that multidimensional, large-scale variant functional data, when paired with public cancer genomics datasets and follow-up assays, can improve understanding of uncharacterized cancer-associated variants, and provide better insights into how they contribute to oncogenesis.
FP05.02 A Biomarker-Directed, Multi-Center Phase II Study of Molecular Response Adaptive Immuno-Chemotherapy in Lung Cancer
Authors: V. Anagnostou, C. Ho, P. Wheatley-Price, S. Laurie, J. Taylor, A. Sacher, J. Brahmer, L. Gallinaro, K. Ding, J. Dancey
Journal: Journal of Thoracic Oncology (2021)