tbuckley/cabot-search huggingface dataset:
Performance at stair-climbing test is associated with postoperative complications after lung resection: a systematic review and meta-analysis
Authors: Fairuz Boujibar, André Gillibert, Francis Edouard Gravier, Timothée Gillot, Tristan Bonnevie, Antoine Cuvelier, Jean-marc Baste
Journal: Thorax (2020)

Thoracic surgery is the optimal treatment for early-stage lung cancer, but there is a high risk of postoperative morbidity. Therefore, it is necessary to evaluate patients' preoperative general condition and cardiorespiratory capacity to determine the risk of postoperative complications. The objective of this study was to assess whether the stair-climbing test could be used in the preoperative evaluation of lung resection patients to predict postoperative morbidity following thoracic surgery.We performed a systematic review and a meta-analysis on the association between stair-climbing test result and morbidity/mortality after thoracic surgery. We analysed all articles published until May 2020 in the following databases: Pubmed/Medline, Pedro, The Cochrane library, Embase and CINAHL. The risk of bias was assessed using the Quality in Prognosis Studies tool. This meta-analysis is registered as PROSPERO CRD42019121348.13 articles were included in the systematic review for a total of 2038 patients and 6 in the meta-analysis. There were multiple test evaluation criteria: rise time, height, desaturation and heart rate change. For the meta-analysis, we were able to pool data on the height of rise at a variable threshold: risk ratio 2.34 (95% CI 1.59 to 3.43) with I²=53% (p=0.06). The threshold for occurrence of complications was estimated at a 10 m climb.Our results indicate that the stair-climbing test could be used as a first-line functional screening test to predict postoperative morbidity following thoracic surgery and that patients with a poor test result (<10 m) should be referred to formal cardiopulmonary exercise testing.
Nitrogen Trapping as a Therapeutic Strategy in Tumors with Mitochondrial Dysfunction
Authors: Hanumantha Rao Madala, Iiro Taneli Helenius, Wen Zhou, Evanna Mills, Yiyun Zhang, Yan Liu, Ana M. Metelo, Michelle L. Kelley, Surendra Punganuru, Kyung Bo Kim, Benjamin Olenchock, Eugene Rhee, Andrew M. Intlekofer, Othon Iliopoulos, Edward Chouchani, Jing-Ruey Joanna Yeh
Journal: Cancer Research (2020)

Under conditions of inherent or induced mitochondrial dysfunction, cancer cells manifest overlapping metabolic phenotypes, suggesting that they may be targeted via a common approach. Here, we use multiple oxidative phosphorylation (OXPHOS)-competent and incompetent cancer cell pairs to demonstrate that treatment with α-ketoglutarate (aKG) esters elicits rapid death of OXPHOS-deficient cancer cells by elevating intracellular aKG concentrations, thereby sequestering nitrogen from aspartate through glutamic-oxaloacetic transaminase 1 (GOT1). Exhaustion of aspartate in these cells resulted in immediate depletion of adenylates, which plays a central role in mediating mTOR inactivation and inhibition of glycolysis. aKG esters also conferred cytotoxicity in a variety of cancer types if their cell respiration was obstructed by hypoxia or by chemical inhibition of the electron transport chain (ETC), both of which are known to increase aspartate and GOT1 dependencies. Furthermore, preclinical mouse studies suggested that cell-permeable aKG displays a good biosafety profile, eliminates aspartate only in OXPHOS-incompetent tumors, and prevents their growth and metastasis. This study reveals a novel cytotoxic mechanism for the metabolite aKG and identifies cell-permeable aKG, either by itself or in combination with ETC inhibitors, as a potential anticancer approach. SIGNIFICANCE: These findings demonstrate that OXPHOS deficiency caused by either hypoxia or mutations, which can significantly increase cancer virulence, renders tumors sensitive to aKG esters by targeting their dependence upon GOT1 for aspartate synthesis. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/17/3492/F1.large.jpg.
Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity
Authors: Jacqulyne P. Robichaux, Yasir Y. Elamin, R.S.K. Vijayan, Monique B. Nilsson, Lemei Hu, Junqin He, Fahao Zhang, Marlese Pisegna, Alissa Poteete, Huiying Sun, Shuai Li, Ting Chen, Han Han, Marcelo Vailati Negrao, Jordi Rodon Ahnert, Lixia Diao, Jing Wang, Xiuning Le, Funda Meric-Bernstam, Mark Routbort, Brent Roeck, Zane Yang, Victoria M. Raymond, Richard B. Lanman, Garrett M. Frampton, Vincent A. Miller, Alexa B. Schrock, Lee A. Albacker, Kwok-kin Wong, Jason B. Cross, John V. Heymach
Journal: Cancer Cell (2020)

(Cancer Cell 36, 444–457.e1–e7; October 14, 2019) In Figure 3E of the original article, the authors showed a western blot of different Ba/F3 cell lines expressing various HER2 exon 20 mutations. It was recently brought to the authors’ attention that there was an extra lane on the western blot and that the labels on the blot were unclearly labeled. The unintentional error was that the last lane of the western blot for HER2 (top row) contained a positive control cell line, H1781, with known expression of HER2 that was not cropped from the image, and the labels were shifted incorrectly. This error has now been corrected in the article online. While this correction does not affect the findings or the conclusions of the study, the authors would like to apologize for this error and any confusion that it may have caused for readers.Figure 3E. The Most Common HER2 Variants in the Tyrosine Kinase Domain are Activating Mutations (Original)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 ActivityRobichaux et al.Cancer CellOctober 3, 2019In BriefRobichaux et al. show that ERBB2 mutation hotspots vary across human tumor types, which affect the volume of the HER2 TKI binding pocket and dictate drug sensitivity. Poziotinib is the most potent HER2 TKI among those tested. Moreover, poziotinib enhances T-DM1 efficacy by increasing the cell-surface HER2 level. Full-Text PDF Open Archive
P-35 Prognostic value of ALBI score in patients with hepatocellular carcinoma Child-Pugh A
Authors: A. Monteiro, F. Macedo, R. Félix Soares, T. Cunha Pereira, J. Paulo, M. Marques, P. Jacinto, N. Bonito, J. Ribeiro, G. Sousa
Journal: Annals of Oncology (2020)
Gold/alpha-lactalbumin nanoprobes for the imaging and treatment of breast cancer
Authors: Jiang Yang, Tai Wang, Lina Zhao, Vinagolu K. Rajasekhar, Suhasini Joshi, Chrysafis Andreou, Suchetan Pal, Hsiao-ting Hsu, Hanwen Zhang, Ivan J. Cohen, Ruimin Huang, Ronald C. Hendrickson, Matthew M. Miele, Wenbo Pei, Matthew B. Brendel, John H. Healey, Gabriela Chiosis, Moritz F. Kircher
Journal: Nature Biomedical Engineering (2020)
Current Practices for Screening and Management of Financial Distress at NCCN Member Institutions
Authors: Nandita Khera, Jessica Sugalski, Diana Krause, Richard Butterfield, Nan Zhang, F. Marc Stewart, Robert W. Carlson, Joan M. Griffin, S. Yousuf Zafar, Stephanie J. Lee
Journal: Journal of the National Comprehensive Cancer Network (2020)

Financial distress from medical treatment is an increasing concern. Healthcare organizations may have different levels of organizational commitment, existing programs, and expected outcomes of screening and management of patient financial distress.In November 2018, representatives from 17 (63%) of the 27 existing NCCN Member Institutions completed an online survey. The survey focused on screening and management practices for patient financial distress, perceived barriers in implementation, and leadership attitudes about such practices. Due to the lack of a validated questionnaire in this area, survey questions were generated after a comprehensive literature search and discussions among the study team, including NCCN Best Practices Committee representatives.Responses showed that 76% of centers routinely screened for financial distress, mostly with social worker assessment (94%), and that 56% screened patients multiple times. All centers offered programs to help with drug costs, meal or gas vouchers, and payment plans. Charity care was provided by 100% of the large centers (≥10,000 unique annual patients) but none of the small centers that responded (<10,000 unique annual patients; P=.008). Metrics to evaluate the impact of financial advocacy services included number of patients assisted, bad debt/charity write-offs, or patient satisfaction surveys. The effectiveness of institutional practices for screening and management of financial distress was reported as poor/very poor by 6% of respondents. Inadequate staffing and resources, limited budget, and lack of reimbursement were potential barriers in the provision of these services. A total of 94% agreed with the need for better integration of financial advocacy into oncology practice.Three-fourths of NCCN Member Institutions reported screening and management programs for financial distress, although the actual practices and range of services vary. Information from this study can help centers benchmark their performance relative to similar programs and identify best practices in this area.
Final Results of a Phase I/II Trial of the Combination Bendamustine and Rituximab With Temsirolimus (BeRT) in Relapsed Mantle Cell Lymphoma and Follicular Lymphoma
Authors: Georg Hess, Karola Wagner, Ulrich Keller, Paul La Rosee, Johannes Atta, Kai Hübel, Christian Lerchenmueller, Daniel Schoendube, Mathias Witzens‐Harig, Christian Ruckes, Christoph Medler, Christina van Oordt, Wolfram Klapper, Matthias Theobald, Martin Dreyling
Journal: HemaSphere (2020)

In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with relapsed or refractory (r/r) follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with 1 to 3 previous therapies received Bendamustine (90 mg/m2, day 1 + 2) and Rituximab (375 mg/m2, day 1) with Temsirolimus in doses from 25 to 75 mg in phase I and 50 mg Temsirolimus in phase II, added on day 1, 8, 15 of a 28 days cycle. The primary endpoint of the phase II was ORR at the end of treatment. Overall, 39 (29 MCL, 10 FL) patients were included. Median age was 71 years and median pretreatment number was 2. Grade 3/4 non-hematologic adverse events were rare and included hyperglycemia in 3 patients (7%) and angioedema in 2 patients (5%). Infectious complications grade 3/4 were observed in 9 patients (23%). Hematologic grade 3/4 events included leukopenia in 22 (56%), neutropenia in 18 (46%), lymphopenia in 16 (41%) and thrombocytopenia in 14 patients (36%). An objective response (best response) was observed in 33/39 patients (89%; 24 MCL (89%) and 9 FL (90%)), including 14 CR (38%; 12 MCL (36%) and 2 FL (20%)). Median PFS is 1.5y for MCL and 1.82 years for FL, and median OS has not been reached for either entity. This data demonstrates promising efficacy of Temsirolimus in r/r MCL and FL with acceptable toxicity. The BeRT regimen may be used as a treatment option for both entities.
Atypical Skin Manifestations During Immune Checkpoint Blockage in Coronavirus Disease 2019–Infected Patients With Lung Cancer
Authors: Christian Rolfo, Andrés F. Cardona, Alejandro Ruiz-Patiño, Santiago Ariza, Lucia Zatarain-Barron, Luis E. Pino, Lucia Viola, Alessandro Russo, Leonardo Rojas, Luisa Ricaurte, Oscar Arrieta
Journal: Journal of Thoracic Oncology (2020)
P-356 phase Ib study of irinotecan, bevacizumab and biweekly trifluridine/tipiracil in patients with metastatic colorectal cancer refractory to fluoropyrimidine and oxaliplatin: Preliminary report of MODURATE study
Authors: K. Yamazaki, T. Masuishi, T. Tsushima, K. Muro, H. Yasui, K. Mori, H. Taniguchi
Journal: Annals of Oncology (2020)
Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein
Authors: Seth J. Zost, Pavlo Gilchuk, Rita E. Chen, James Brett Case, Joseph X. Reidy, Andrew Trivette, Rachel S. Nargi, Rachel E. Sutton, Naveenchandra Suryadevara, Elaine C. Chen, Elad Binshtein, Swathi Shrihari, Mario Ostrowski, Helen Y. Chu, Jonathan E. Didier, Keith W. MacRenaris, Taylor Jones, Samuel Day, Luke Myers, F. Eun-Hyung Lee, Doan C. Nguyen, Ignacio Sanz, David R. Martinez, Paul W. Rothlauf, Louis-Marie Bloyet, Sean P. J. Whelan, Ralph S. Baric, Larissa B. Thackray, Michael S. Diamond, Robert H. Carnahan, James E. Crowe
Journal: Nature Medicine (2020)
PTEN activation contributes to tumor inhibition by trastuzumab and loss of PTEN predicts trastuzumab resistance in patients.
Authors: Keng-Hsueh Lan, Yoichi Nagata, Xiaoyan Zhou, Francisco J. Esteva, Aysegul A. Sahin, Kristine S. Klos, Brett P. Monia, Nina Nguyen, Gabriel N. Hortobagyi, Mien-Chie Hung, Dihua Yu
Journal: Cancer Research (2004)

2460  The ErbB2-targeting antibody, trastuzumab (Herceptin) has remarkable therapeutic efficacy in certain patients with ErbB2-overexpressing tumors. The overall trastuzumab response rate, however, is limited and the cause of trastuzumab resistance is poorly understood. Here we report that PTEN activation contributes to trastuzumab’s anti-tumor activity. Trastuzumab treatment quickly reduced PTEN tyrosine phosphorylation, increased PTEN membrane localization and its phosphatase activity in cancer cells. Reducing PTEN expression in breast cancer cells by antisense oligonucleotides conferred trastuzumab resistance in vitro and in vivo. Patients with PTEN-deficient breast cancers had significantly poorer responses to trastuzumab-based therapy than those with normal PTEN. Thus, PTEN deficiency is a powerful predictor of trastuzumab resistance. Additionally, PI3K inhibitors rescued PTEN loss-induced trastuzumab resistance, suggesting PI3K-targeting therapies combined with trastuzumab could overcome the resistance. Trastuzumab is an excellent model of rationally designed targeted cancer treatment. However, mechanisms underlying trastuzumab anti-tumor function and causes of trastuzumab resistance are poorly understood. Here our data introduces the new concept that a rapid PTEN activation, before downregulation of ErbB2, is a novel mechanism underlying the anti-tumor activity of trastuzumab. This indicates a functional cross talk between ErbB2 receptor tyrosine kinase signaling and PTEN tumor suppressor activity. PTEN deficiencies were reported in ∼50% of breast cancers. Our finding that PTEN deficiency is significantly associated with trastuzumab resistance in patients can directly impact the treatment of these patients. PTEN-deficiencies in patients’ tumors can predict trastuzumab resistance and serve as an indicator for requiring PI3K-targeting combination treatment targeting PI3K to overcome the trastuzumab resistance.
Letter by Messerli et al Regarding Article, “Incidence, Trends, and Outcomes of Type 2 Myocardial Infarction in a Community Cohort”
Authors: Franz H. Messerli, George C.M. Siontis, Lorenz Räber
Journal: Circulation (2020)

The authors conclude, "The incidence of T2MI is similar to that of T1MI in contemporary years."Of note, in both types of myocardial infarction, the incidence of hypertension also was similar, amounting to 68% and 71%, respectively.For type 1 myocardial infarction (T1MI), such a high incidence is not unexpected, because hypertension is known to be a powerful risk factor for coronary artery disease.In contrast, for type 2 myocardial infarction (T2MI), "a diagnosis of hypertension was found to be associated with lower all-cause mortality," 1 despite the fact that long-term mortality after T2MI was higher than after T1MI.Thus, hypertension paradoxically had a protective effect; its presence was an indicator of better prognosis in patients with T2MI.The relationship between blood pressure (BP) and T2MI is more complex than the one between BP and T1MI.For T1MI, hypertension is simply a risk factor, with its duration and severity having a cumulative effect on the occurrence of an event.In contrast, for T2MI, only excessively high or excessively low BP levels consist a definitive risk; mild hypertension is prone to mitigate the risk of hypotension and therefore, as seen in the present study, may exert a protective effect.The complexity of the relationship between BP and T1MI and T2MI may well be the culprit of the somewhat archaic thought 4 decades ago that "in severe middle-aged hypertensives, attempts at 'normalization' of high blood-pressure may precipitate as many infarctions as it prevents" and that therefore "the BP in such patients should seldom be reduced…to diastolic levels <104 to 110 mm Hg." 2 Excessive hypotension associated with inappropriate antihypertensive therapy may well give rise to T2MI, 3 particularly in older patients.In contrast to T1MI, T2MI can be triggered by hypotension or uncontrolled hypertension as well as by excessive BP variability. 4e wonder whether the authors' unique database would allow them to better elucidate the relationship between BP and T2MI.Does the protective effect of hypertension in T2MI depend on the underlying cause?What was the incidence of hypotension, and what was defined as malignant hypertension as a triggering event in the authors' T2MI population?
PD-8 Regorafenib with TAS-102 in metastatic colorectal cancer patients who progressed after at least two standard therapies: Efficacy and safety results of a multicenter phase I study (REMETY)
Authors: M. Moehler, A. Stein, J. Trojan, J. Marquardt, J. Quidde, O. Waidmann, A. Weinmann, M. Woerns, H. Schroeder, M. Mänz, A. Karatas
Journal: Annals of Oncology (2020)
Adding efficiency to proficiency: a study of trainee polypectomy efficiency metrics
Authors: Larissa Muething, Sachin Wani, Matt Hall, Violette Simon, Ezenwanyi Ezekwe, Tiffany Nguyen-Vu, Carmel Malvar, Anna Duloy, Tonya Kaltenbach, Rajesh Keswani, Swati G. Patel
Journal: Endoscopy (2020)

Abstract Background Although validated colonoscopy assessment tools exist, they do not measure efficiency. This study aimed to assess content validity of polypectomy efficiency (PE) and neoplastic polypectomy efficiency (NPE) as colonoscopy efficiency indices. Methods Data from a randomized controlled trial evaluating polypectomy among gastroenterology trainees were utilized. PE and NPE were defined as number of polyps (or neoplastic polyps) removed/withdrawal time × 100. Content validity was assessed by determining the association between efficiency indices and polypectomy times. Results 20 trainees performed 601 colonoscopies. There was a strong association between PE/NPE and actual polypectomy times: as polypectomy time increased by 1 minute, the PE decreased by 0.48 (P = 0.001) and NPE decreased by 0.24 (P = 0.03). Conclusions The study proposed and provided content validity for PE and NPE as colonoscopy efficiency indices.
<i>Staphylococcus</i> Agr virulence is critical for epidermal colonization and associates with atopic dermatitis development
Authors: Yuumi Nakamura, Hiroki Takahashi, Akiko Takaya, Yuzaburo Inoue, Yuki Katayama, Yoko Kusuya, Tatsuma Shoji, Sanami Takada, Seitaro Nakagawa, Rena Oguma, Nobuko Saito, Naoko Ozawa, Taiji Nakano, Fumiya Yamaide, Eishika Dissanayake, Shuichi Suzuki, Amer Villaruz, Saranyaraajan Varadarajan, Masanori Matsumoto, Tomoko Kobayashi, Michihiro Kono, Yasunori Sato, Masashi Akiyama, Michael Otto, Hiroyuki Matsue, Gabriel Núñez, Naoki Shimojo
Journal: Science Translational Medicine (2020)

Skin colonization at 6 months of age by S. aureus with functional Agr quorum sensing associates with later atopic dermatitis development in infants.
Abstract 16113: Pain Intensity and Variation in Pain Management Strategies in Patients With Heart Failure
Authors: Casey E Cavanagh, Eric DeRycke, Parul Gandhi, Harini Bathulapalli, Joseph L Goulet, Lori Bastian, Matthew M Burg
Journal: Circulation (2018)

Introduction: Research has found that 67% of patients with heart failure (HF) report pain. However, research examining pain intensity and pain management strategies among patients with HF is limite...
Impaired mitochondrial oxidative phosphorylation limits the self-renewal of T cells exposed to persistent antigen
Authors: Santosha A. Vardhana, Madeline A. Hwee, Mirela Berisa, Daniel K. Wells, Kathryn E. Yost, Bryan King, Melody Smith, Pamela S. Herrera, Howard Y. Chang, Ansuman T. Satpathy, Marcel R. M. van den Brink, Justin R. Cross, Craig B. Thompson
Journal: Nature Immunology (2020)
P-293 Overall survival according to mutation frequency of BRAF, NRAS genes, and MSI status in patients with wild-type KRAS metastatic colorectal cancer treated with cetuximab
Authors: F. Santos, R. Reis, L. Barroti, J. Datorre, A. Pereira, A. Carvalho, G. Berardinelli, R. Araujo
Journal: Annals of Oncology (2020)
P-278 Neutrophil-to-lymphocyte, lymphocyte-to-monocyte and platelet-to-lymphocyte ratios as predictive markers of pathological response to FLOT neoadjuvant strategy in locally advanced gastric/gastroesophageal junction cancer
Authors: T. Tomás, G. Nogueira-Costa, I. Eiriz, M. Vitorino, R. Vicente, A. Oliveira, P. Luz, M. Baleiras, A. Spencer, L. Leal da Costa, P. Liu, E. Cadavez, M. Correia, G. Atalaia, M. Silva, T. Fiúza
Journal: Annals of Oncology (2020)
P-66 Treatment with FOLFIRI-aflibercept in an elderly population (over 75 and octogenarians) with metastatic colorectal cancer after failure of an oxaliplatin-based regimen: Experience in a real-life population
Authors: G. Buccafusca, F. Cappuccio, S. Cordio, M. Mare, G. Bruera, A. Colombo, V. Formica, V. Montesarchio, G. Tonini, S. Leo, L. Antonuzzo, D. Gemma, M. Biglietto, B. Giuseppina, C. Carlomagno, P. Tralongo
Journal: Annals of Oncology (2020)
Retraction Note to: SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion
Authors: Xinling Wang, Wei Xu, Gaowei Hu, Shuai Xia, Zhiping Sun, Zezhong Liu, Youhua Xie, Rong Zhang, Shibo Jiang, Lu Lu
Journal: Cellular and Molecular Immunology (2020)
Meat plants—a new front line in the covid-19 pandemic
Authors: John Middleton, Ralf Reintjes, Henrique Lopes
Journal: BMJ (2020)

Slaughterhouses and meat packing plants have been a major risk for covid-19 infection throughout the pandemic. 1 2Now these outbreaks are centre stage. 3 They affect whole communities, have far reaching implications, and require intensive public health interventions.In Germany, public health authorities have been grappling with a huge covid-19 outbreak in Gütersloh, North Rhine-Westphalia.More than 1500 of 7000 workers tested positive for covid-19, and 640 000 residents of two affected counties were returned to lockdown conditions. 4At one of Portugal's biggest poultry slaughterhouses, at least 129 of the 300 workers contracted covid-19. 5The company was closed for a week; additional measures included screening all employees, providing new bathing areas, and strengthening disinfection.Outbreaks in England and Wales have been associated with meat processing in Anglesey, Merthyr Tydfil, Wrexham, and Kirklees.
Precision Health Analytics With Predictive Analytics and Implementation Research
Authors: Thomas A. Pearson, Robert M. Califf, Rebecca Roper, Michael M. Engelgau, Muin J. Khoury, Carmela Alcantara, Craig Blakely, Cheryl Anne Boyce, Marishka Brown, Thomas L. Croxton, Kathleen Fenton, Melissa C. Green Parker, Andrew Hamilton, Lorens Helmchen, Lucy L. Hsu, David M. Kent, Amy Kind, John Kravitz, George John Papanicolaou, Mattia Prosperi, Matt Quinn, LeShawndra N. Price, Paula K. Shireman, Sharon M. Smith, Rhonda Szczesniak, David Calvin Goff, George A. Mensah
Journal: Journal of the American College of Cardiology (2020)