tbuckley/cabot-search huggingface dataset:
426P Impact of preoperative chemoradiotherapy on tumor infiltrating lymphocytes in locally advanced rectal cancer: The SMART-STAR study
Authors: F. Negri, L. Gnetti, L. Bottarelli, N. Campanini, F. Bergamo, S. Siena, M. Frisinghelli, M. Petric, G. Chiaulon, S. Mosconi, F. Gelsomino, C. Azzoni, E.M. Silini, F. Gaiani, G.L. de Angelis, F. Leonardi, C. Aschele
Journal: Annals of Oncology (2020)
638P Meningeal metastases (MM) in patients with metastatic castration resistant prostate cancer (mCRPC)
Authors: M. Aldea, L. Cerbone, M. Tiako Meyo, E. Colomba-Blameble, P. Lavaud, A.C. Fuerea, R. Flippot, D. Edoh, C. Massard, Y. Loriot, L. Albiges, G. Baciarello, K. Fizazi
Journal: Annals of Oncology (2020)
852P Exploring the correlation between AXL expression and gene expression molecular subtyping (GEMS) in high grade serous ovarian cancer (HGSOC)
Authors: N.Y.L. Ngoi, T.Z. Tan, N.M. Lee, D. Micklem, A. Rayford, J. Nautiyal, D.G. Lim, S. Wong, L. Johnson, A. Jackson, J.B. Lorens, H. Gabra, R. Huang, D.S. Tan
Journal: Annals of Oncology (2020)
298P Differences in the mutational profile between primary breast carcinomas and their cutaneous metastasis
Authors: S. González Martínez, B. Pérez Mies, T. Caniego Casas, J.M. Rosa Rosa, J.L. Rodríguez Peralto, G. Curigliano, P. Schmid, S. Kümmel, J.M. Perez Garcia, E. Lopez Miranda, M. Gion Cortes, J. Palacios Calvo, J. Cortés
Journal: Annals of Oncology (2020)
631P Darolutamide (D), enzalutamide (E) and apalutamide (A), the risk of adverse events (AEs) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC): Number needed to harm (NNH)
Authors: D.J. George, A.R. Waldeck, H. Guo, A.J. Upton
Journal: Annals of Oncology (2020)
LBA34 Single-agent anti-PD-1 balstilimab or in combination with anti-CTLA-4 zalifrelimab for recurrent/metastatic (R/M) cervical cancer (CC): Preliminary results of two independent phase II trials
Authors: D.M. O'Malley, A. Oaknin, B.J. Monk, A. Leary, F. Selle, J. Alexandre, L.M. Randall, C. Rojas, M. Neffa, A. Kryzhanivska, L. Gladieff, D. Berton, T. Meniawy, I. Lugowska, I. Bondarenko, K.N. Moore, W.I. Ortuzar Feliu, M. Ancukiewicz, I. Shapiro, I.L. Ray-Coquard
Journal: Annals of Oncology (2020)
1125P A phase Ib study of rose bengal disodium and anti-PD-1 in metastatic cutaneous melanoma: Results in patients naïve to immune checkpoint blockade
Authors: S.S. Agarwala, M. Ross, J.S. Zager, A.S. Sarnaik, K. Shirai, G. Lu, R. Essner, B. Smithers, V. Victoria Atkinson, E. Wachter
Journal: Annals of Oncology (2020)
354TiP Unraveling trastuzumab emtansine resistance in HER2-positive advanced breast cancer: GEICAM KATIA study
Authors: F. Rojo Todo, A. Stradella, J.A. García-Sáenz, B. Bermejo De Las Heras, J.L. Alfonso Romero, A. Barnadas, Y. Izarzugaza Peron, E. Alba, S. López-Tarruella, F. Henao-Carrasco, E. Carrasco, R. Caballero, M. Del Campo
Journal: Annals of Oncology (2020)
Young Adults as a Tobacco Control Priority Population in the US
Authors: Ollie Ganz, Cristine D. Delnevo
Journal: JAMA Network Open (2020)

Jessica L. Barrington-Trimis, PhD; Jessica L. Braymiller, PhD; Jennifer B. Unger, PhD; Rob McConnell, MD; Andrew Stokes, PhD; Adam M. Leventhal, PhD; James D. Sargent, MD; Jonathan M. Samet, MD; Renee D. Goodwin, PhD
Interaction of bacterial metagenome and virome in patients with cirrhosis and hepatic encephalopathy
Authors: Jasmohan S Bajaj, Masoumeh Sikaroodi, Amirhossein Shamsaddini, Zachariah Henseler, Tasha Santiago-Rodriguez, Chathur Acharya, Andrew Fagan, Phillip B Hylemon, Michael Fuchs, Edith Gavis, Tonya Ward, Dan Knights, Patrick M Gillevet
Journal: Gut (2020)

Altered bacterial composition is associated with disease progression in cirrhosis but the role of virome, especially phages, is unclear.Cross-sectional and pre/post rifaximin cohorts were enrolled. Cross-sectional: controls and cirrhotic outpatients (compensated, on lactulose (Cirr-L), on rifaximin (Cirr-LR)) were included and followed for 90-day hospitalisations. Pre/post: compensated cirrhotics underwent stool collection pre/post 8 weeks of rifaximin. Stool metagenomics for bacteria and phages and their correlation networks were analysed in controls versus cirrhosis, within cirrhotics, hospitalised/not and pre/post rifaximin.Cross-sectional: 40 controls and 163 cirrhotics (63 compensated, 43 Cirr-L, 57 Cirr-LR) were enrolled. Cirr-L/LR groups were similar on model for end-stage liver disease (MELD) score but Cirr-L developed greater hospitalisations versus Cirr-LR (56% vs 30%, p=0.008). Bacterial alpha/beta diversity worsened from controls through Cirr-LR. While phage alpha diversity was similar, beta diversity was different between groups. Autochthonous bacteria linked negatively, pathobionts linked positively with MELD but only modest phage-MELD correlations were seen. Phage-bacterial correlation network complexity was highest in controls, lowest in Cirr-L and increased in Cirr-LR. Microviridae and Faecalibacterium phages were linked with autochthonous bacteria in Cirr-LR, but not Cirr-L hospitalised patients had greater pathobionts, lower commensal bacteria and phages focused on Streptococcus, Lactococcus and Myoviridae. Pre/post: No changes in alpha/beta diversity of phages or bacteria were seen postrifaximin. Phage-bacterial linkages centred around urease-producing Streptococcus species collapsed postrifaximin.Unlike bacteria, faecal phages are sparsely linked with cirrhosis characteristics and 90-day outcomes. Phage and bacterial linkages centred on urease-producing, ammonia-generating Streptococcus species were affected by disease progression and rifaximin therapy and were altered in patients who experienced 90-day hospitalisations.
Is the jejunum the fulcrum of glucose metabolism?
Authors: Jose Manuel Fernández-Real, Jordi Mayneris-Perxachs
Journal: Gut (2020)

Jejunum is derived from the Latin word jējūnus, from modern Latin noun use of Latin ‘ieiunum’, neuter of ieiunus ‘empty’ and also with the meaning of ‘fasting’. The jejunum is typically found empty during dissections, perhaps because it would tend to drain in a body laid on its back and is void of food following death (‘fasting’), due to its intensive peristaltic activity relative to the duodenum and ileum. In modern Italian ( digiuno ), Catalan ( dejuni ) and Galician ( xexun ), fasting is still named using similar words.

Since the observation by Rubino et al in 2004 that variations in circulating hormone levels occurred early after bariatric surgery in parallel to improvement of glucose metabolism before substantial weight modifications,1 the search for the factors responsible for these effects after bariatric surgery has been intensively pursued.

The surface of the intestine is critical in the rate of nutrition absorption. Small bowel length (SBL) has been claimed to determine the caloric absorptive capacity. Some authors have described a positive and statistically significant correlation between the Total SBL (TSBL) and both weight (p=0.01) and height (p<0.001) but not with body mass index (BMI) of the subjects.2 Other authors found that TSBL was positively linked to the weight of the subjects but not to height.3 …
Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies
Authors: Yoshiaki Nakamura, Hiroya Taniguchi, Masafumi Ikeda, Hideaki Bando, Ken Kato, Chigusa Morizane, Taito Esaki, Yoshito Komatsu, Yasuyuki Kawamoto, Naoki Takahashi, Makoto Ueno, Yoshinori Kagawa, Tomohiro Nishina, Takeshi Kato, Yoshiyuki Yamamoto, Junji Furuse, Tadamichi Denda, Hisato Kawakami, Eiji Oki, Takako Nakajima, Naohiro Nishida, Kensei Yamaguchi, Hisateru Yasui, Masahiro Goto, Nobuhisa Matsuhashi, Koushiro Ohtsubo, Kentaro Yamazaki, Akihito Tsuji, Wataru Okamoto, Katsuya Tsuchihara, Takeharu Yamanaka, Izumi Miki, Yasutoshi Sakamoto, Hiroko Ichiki, Masayuki Hata, Riu Yamashita, Atsushi Ohtsu, Justin I. Odegaard, Takayuki Yoshino
Journal: Nature Medicine (2020)
PHLPPing the Script: Emerging Roles of PHLPP Phosphatases in Cell Signaling
Authors: Timothy R. Baffi, Ksenya Cohen-Katsenelson, Alexandra C. Newton
Journal: The Annual Review of Pharmacology and Toxicology (2020)

Whereas protein kinases have been successfully targeted for a variety of diseases, protein phosphatases remain an underutilized therapeutic target, in part because of incomplete characterization of their effects on signaling networks. The pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) is a relatively new player in the cell signaling field, and new roles in controlling the balance among cell survival, proliferation, and apoptosis are being increasingly identified. Originally characterized for its tumor-suppressive function in deactivating the prosurvival kinase Akt, PHLPP may have an opposing role in promoting survival, as recent evidence suggests. Additionally, identification of the transcription factor STAT1 as a substrate unveils a role for PHLPP as a critical mediator of transcriptional programs in cancer and the inflammatory response. This review summarizes the current knowledge of PHLPP as both a tumor suppressor and an oncogene and highlights emerging functions in regulating gene expression and the immune system. Understanding the context-dependent functions of PHLPP is essential for appropriate therapeutic intervention.
Usefulness of PAX8 Immunohistochemistry in Adult Intraocular Tumor Diagnosis
Authors: Hardeep Singh Mudhar, Tatyana Milman, Ralph C. Eagle, Tracy Sanderson, Leanne Pheasey, Simon Paine, Sachin Salvi, Ian G. Rennie, Paul Rundle, Carol L. Shields, Jerry A. Shields
Journal: Ophthalmology (2020)
Beyond quality of life: A call for patients' own willingness to pay in chronic skin disease to assess psychosocial burden—A multicenter, cross-sectional, prospective survey
Authors: Jung Min Bae, Jung Eun Kim, Ro Woo Lee, Hyun Jeong Ju, Ju Hee Han, Joo Hee Lee, Yu Ri Woo, Ji Hae Lee, Chul Hwan Bang, Chul Jong Park, Khaled Ezzedine, Miri Kim
Journal: Journal of the American Academy of Dermatology (2020)
AB0053 Rheumatoid lung disease as a presenting feature of rheumatoid arthritis
Authors: P Borman, G Ak, N Barca, H Bodur
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Pulmonary involvement is a common extraarticular feature of rheumatoid arthritis (RA) but early symptomatic manifestations of RA are uncommon. We present 2 male RA patients with all characteristic features of pulmonary involvement which preceded the articular symptoms and occurred concurrently. Case1; A 32-year-old male presented with severe pulmonary involvement due to the rheumatoid nodules, pleurisy, atelectasis, interstitial fibrosis which preceded the articular symptoms. Case 2; A 54-year-old male presented with articular manifestations of RA associated with typical pulmonary findings of rheumatoid lung including paranchimal nodules, pleurisy, interstitial fibrosis and honey-comb appearance simultaneously. In both cases the diagnosis were made after exclusion of other causes of pulmonary disease and depending on the findings of pleural biopsy. In conclusion the onset of RA with severe typical pulmonary findings are not uncommon and physicians must be aware of this extraarticular finding as a presenting feature of RA. <h3>Objectives</h3> <h3>Methods</h3> <h3>Results</h3> <h3>Conclusion</h3>
Correspondence on ‘EULAR recommendations for the management of antiphospholipid syndrome in adults’
Authors: Rui Gao, Lang Qin
Journal: Annals of the Rheumatic Diseases (2021)

Correspondence on 'EULAR recommendations for the management of antiphospholipid syndrome in adults' 2019 European Alliance of Associations for Rheumatology (EULAR) recommendations for the management of antiphospholipid syndrome (APS) has been successfully launched, 1 with recommendations on obstetric APS for obstetricians to refer to.However, the recommendations for obstetric APS are incomplete, which weakens the application of this guideline in clinical practice of obstetrics.First, the definition of obstetric APS is limited.In the practice, many patients come to see doctors because of threatened abortion or threatened premature delivery, with no history of delivery <34th week of gestation and <10th week spontaneous miscarriage, but the results of laboratory tests show that antiphospholipid antibodies (aPLs) are positive and other pathogenesis is not found.According to 'EULAR recommendations for the management of APS in adults', they are difficult to be diagnosed as obstetric APS, but they are at risk of becoming patients with obstetric APS and cannot get treatment recommendations from the guideline.How to manage these patients?Under what circumstances can low dose aspirin (LDA) and prophylactic doses of low molecular weight heparin (LMWH) be used in these pregnant women?Is it possible to include recommendations for the management of 'aPLs-related adverse pregnancy outcome' in the future guideline?In addition, the management recommendations for patients with obstetric APS before pregnancy are lacking.For example, is it necessary to start using LDA before pregnancy for patients at high risk of aPLs?And in refractory obstetric APS women with recurrent pregnancy complications despite receiving combination treatment with LDA and LMWH at prophylactic dosage, addition of hydroxychloroquine (HCQ) in the first trimester are considered.We know that HCQ needs to be used 3 months in advance to reach the effective concentration.For these patients, is it necessary to start using HCQ 3 months before the next pregnancy?Moreover, recommendations for the dynamic management during pregnancy of patients with obstetric APS are lacking in the guideline.For patients with obstetric APS or 'non criteria' obstetric APS, obstetricians tend to intensify monitoring and detect aPLs regularly during pregnancy.Studies have shown that the aPLs level will change dynamically during pregnancy, 2 does these changes have any effect on our prescription?In addition, studies have shown that decreased platelet count may be an indicator of poor prognosis in APS patients, 3 is it necessary to monitor platelet changes during pregnancy?Maybe these questions need more evidence and more clear explanation from experts.
Comparative Effectiveness of Generic vs Brand-Name Levothyroxine in Achieving Normal Thyrotropin Levels
Authors: Juan P. Brito, Joseph S. Ross, Lindsey Sangaralingham, Sarah K. Dutcher, David J. Graham, Zhong Wang, Yute Wu, Xiaoxi Yao, Robert C. Smallridge, Victor Bernet, Nilay D. Shah, Kasia J. Lipska
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Whether the use of generic vs brand levothyroxine affects thyrotropin levels remains unclear. <h3>Objective</h3> To compare the effectiveness of generic vs brand levothyroxine in achieving and maintaining normal thyrotropin levels among new users. <h3>Design, Setting, and Participants</h3> This retrospective, 1:1 propensity score–matched longitudinal cohort study used the OptumLabs Data Warehouse administrative claims database linked to laboratory results from commercially insured and Medicare Advantage enrollees throughout the United States. Eligible patients were adults (aged ≥18 years) with thyrotropin levels ranging from 4.5 to 19.9 mIU/L who initiated use of generic or brand-name levothyroxine from January 1, 2008, to October 1, 2017. Data were analyzed from August 13, 2018, to October 25, 2019. <h3>Exposure</h3> Patients received generic or brand-name levothyroxine. <h3>Main Outcomes and Measures</h3> Proportion of patients with normal vs markedly abnormal thyrotropin levels (&lt;0.1 or &gt;10 mIU/L) within 3 months and with stable thyrotropin levels within 3 months after the thyrotropin value fell into the normal range. <h3>Results</h3> A total of 17 598 patients were included (69.0% female; 74.0% White; mean [SD] age, 55.1 [16.0] years), of whom 15 299 filled generic and 2299 filled brand-name levothyroxine prescriptions during the study period. Among 4570 propensity score–matched patients (mean [SD] age, 50.3 [13.8] years; 3457 [75.6%] female; 3510 [76.8%] White), the proportion with normal thyrotropin levels within 3 months of filling levothyroxine prescriptions was similar for patients who received generic vs brand-name levothyroxine (1722 [75.4%; 95% CI, 71.9%-79.0%] vs 1757 [76.9%; 95% CI, 73.4%-80.6%];<i>P</i> = .23), as was the proportion with markedly abnormal levels (94 [4.1%; 95% CI, 3.4%-5.0%] vs 88 [3.9%; 95% CI, 3.1%-4.7%];<i>P</i> = .65). Among 1034 propensity score–matched patients who achieved a normal thyrotropin value within 3 months of initiation of levothyroxine, the proportion maintaining subsequent normal thyrotropin levels during the next 3 months was similar for patients receiving generic vs brand-name levothyroxine (427 [82.6%] vs 433 [83.8%];<i>P</i> = .62). <h3>Conclusions and Relevance</h3> Initiation of generic vs brand-name levothyroxine formulations was associated with similar rates of normal and stable thyrotropin levels. These results suggest that generic levothyroxine as initial therapy for mild thyroid dysfunction is as effective as brand-name levothyroxine.
Diagnosis of Hepatopulmonary Syndrome in a Large Integrated Health System
Authors: Shoma Bommena, Richard D. Gerkin, Sumit Agarwal, Sarah Raevens, Marilyn K. Glassberg, Michael B. Fallon
Journal: Clinical Gastroenterology and Hepatology (2020)

Data on the accuracy of the diagnosis of hepatopulmonary syndrome (HPS) in cirrhosis is limited. We evaluated the clinical characteristics of patients with International Classification of Diseases (ICD) codes for hepatopulmonary syndrome (HPS) in a large integrated health system.A retrospective review of encounters was performed of all patients with ICD-9-CM and/or ICD-10-CM diagnosis of cirrhosis and HPS from 2014-2019 in a multi-state health system. Demographics and cardiopulmonary testing closest to the time of HPS diagnosis were recorded. HPS was defined using standard criteria.A total of 42,749 unique individuals with cirrhosis were identified. An ICD diagnosis of HPS was found in 194 patients (0.45%), of which 182 had clinically confirmed cirrhosis. 143 (78.5%) underwent contrast-enhanced transthoracic echocardiography, and 98 (54%) had delayed shunting. Among them, 61 patients had a documented arterial blood gas, with 53 showing abnormal oxygenation (A-a gradient of >15 mm Hg). 12 were excluded due to significant pulmonary function test abnormalities and abnormal oxygenation from other cardiopulmonary diseases. Ultimately, 41 (22.5%) fulfilled the criteria for HPS. When stratifying those with an ICD code diagnosis of HPS into HPS, no HPS and indeterminate HPS groups, based on standard diagnostic criteria for HPS, we found that the confirmed HPS patients had similar complications except for less portopulmonary hypertension, worse gas exchange, less cardiopulmonary disease and were more often diagnosed in transplant centers.The diagnosis of HPS by ICD code is made in an extremely small subset of a sizeable cirrhotic cohort. When made, only a minority of these patients meet diagnostic criteria. Our findings highlight the need for improved education and more effective screening algorithms.
Abstract B01: Genome-scale shRNA screen provides insight into the role of CUL3 in adaptive mechanisms of resistance to mutant BRAF inhibition
Authors: Marion Vanneste, Eliot Zhu, Charlotte Feddersen, Afshin Varzavand, Tyler Foley, Lei Zhao, Rob Piper, Christopher Stipp, Adam Dupuy, Michael Henry
Journal: Cancer Research (2020)

Abstract MAPK inhibition with targeted BRAF inhibitors has revolutionized the treatment of BRAF-mutant melanoma. However, in most cases, the effects of mutant BRAF inhibition are transient, owing to the acquisition of drug resistance. To resolve mechanisms that drive resistance to mutant BRAF inhibition, we performed a genome-scale shRNA screen capable of revealing genes whose loss of function confers resistance to vemurafenib (VEM). We validated ten of our top candidates with independent lentiviral shRNA constructs. We found that knockdown of NF1 and CUL3 confers resistance to VEM. This result is consistent with previous genome-scale loss-of-function screens that have also identified NF1 and CUL3 as drivers of resistance to mutant BRAF inhibition. NF1 encodes a protein that hydrolyzes Ras-GTP. Not surprisingly, it has been shown that loss of NF1 results in increased Ras-GTP levels that lead to reactivation of MAPK in the presence of VEM. However, little is known about the mechanistic changes that underlie CUL3-mediated resistance. Here, we show that unlike the classical reactivation of MAPK that is seen with the loss of NF1, loss of CUL3 results in increased signaling through a Rac1-dependent focal-adhesion-like process that is accompanied by sustained MAPK activity in the presence of VEM. Furthermore, we show that this mechanism of resistance can be abrogated by inhibiting the Src kinase family, a nine-member protein family that critically mediates integrin signaling. In relation to other known drivers of resistance to mutant BRAF inhibition, loss of NF1 reactivates MAPK in a manner much like RAS mutations or BRAF alterations/amplification. By contrast, loss of CUL3 leads to resistance reminiscent of a reversible therapy-resistant state that lacks the key genomic alterations in MAPK signaling proteins. Citation Format: Marion Vanneste, Eliot Zhu, Charlotte Feddersen, Afshin Varzavand, Tyler Foley, Lei Zhao, Rob Piper, Christopher Stipp, Adam Dupuy, Michael Henry. Genome-scale shRNA screen provides insight into the role of CUL3 in adaptive mechanisms of resistance to mutant BRAF inhibition [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B01.
Utility of repeating bone marrow biopsy for confirmation of complete response in multiple myeloma
Authors: Marcella A. Tschautscher, Dragan Jevremovic, Francis K. Buadi, Martha Q. Lacy, Morie A. Gertz, Angela Dispenzieri, Prashant Kapoor, David Dingli, Lisa Hwa, Amie Fonder, Miriam Hobbs, Suzanne Hayman, John Lust, Stephen J. Russell, Nelson Leung, Ronald S. Go, Yi Lin, Wilson Gonsalves, Taxiarchis Kourelis, Rahma Warsame, Robert A. Kyle, S. Vincent Rajkumar, Shaji Kumar
Journal: Blood Cancer Journal (2020)
Sex Differences in Rates of Change and Burden of Metabolic Risk Factors Among Adults Who Did and Did Not Go On to Develop Diabetes: Two Decades of Follow-up From the Tehran Lipid and Glucose Study
Authors: Azra Ramezankhani, Fereidoun Azizi, Farzad Hadaegh
Journal: Diabetes Care (2020)

OBJECTIVE We investigated the cumulative burden and linear rates of change of major metabolic risk factors (MRFs) among Iranian adults in whom type 2 diabetes did and did not develop. RESEARCH DESIGN AND METHODS We included 7,163 participants (3,069 men) aged 20–70 years at baseline with at least three examinations during 1999–2018. Individual growth curve modeling was used for data analysis. Statistical interactions for sex by diabetes status were adjusted for age, family history of diabetes, smoking status, and physical activity level. RESULTS Study sample included 743 (316 men) new case subjects with diabetes. In both men and women, compared with individuals in whom diabetes did not develop, individuals in whom diabetes developed had a higher burden of all MRFs and a greater rate of change in BMI, fasting plasma glucose (FPG), systolic blood pressure (SBP), and diastolic blood pressure; however, the differences in burden and rate of change between those who did and did not develop diabetes were greater in women than in men. During the transition to diabetes, women experienced more adverse change in BMI, FPG, triglyceride, and HDL cholesterol (HDL-C) (diabetes-sex interaction P values &amp;lt;0.05) and faster rates of change in BMI, FPG, HDL-C, and total cholesterol (interaction P values &amp;lt;0.01) and SBP (interaction P = 0.055) than men. CONCLUSIONS The greater exposure of women to and burden of MRFs before onset of diabetes may have implications for implementing sex-specific strategies in order to prevent or delay diabetes complications.