tbuckley/cabot-search huggingface dataset:
Phenome-wide investigation of the causal associations between childhood BMI and adult trait outcomes: a two-sample Mendelian randomization study
Authors: Shan-Shan Dong, Kun Zhang, Yan Guo, Jing-Miao Ding, Yu Rong, Jun-Cheng Feng, Shi Yao, Ruo-Han Hao, Feng Jiang, Jia-Bin Chen, Hao Wu, Xiao-Feng Chen, Tie-Lin Yang
Journal: Genome Medicine (2021)

Childhood obesity is reported to be associated with the risk of many diseases in adulthood. However, observational studies cannot fully account for confounding factors. We aimed to systematically assess the causal associations between childhood body mass index (BMI) and various adult traits/diseases using two-sample Mendelian randomization (MR).After data filtering, 263 adult traits genetically correlated with childhood BMI (P < 0.05) were subjected to MR analyses. Inverse-variance weighted, MR-Egger, weighted median, and weighted mode methods were used to estimate the causal effects. Multivariable MR analysis was performed to test whether the effects of childhood BMI on adult traits are independent from adult BMI.We identified potential causal effects of childhood obesity on 60 adult traits (27 disease-related traits, 27 lifestyle factors, and 6 other traits). Higher childhood BMI was associated with a reduced overall health rating (β = - 0.10, 95% CI - 0.13 to - 0.07, P = 6.26 × 10-11). Specifically, higher childhood BMI was associated with increased odds of coronary artery disease (OR = 1.09, 95% CI 1.06 to 1.11, P = 4.28 × 10-11), essential hypertension (OR = 1.12, 95% CI 1.08 to 1.16, P = 1.27 × 10-11), type 2 diabetes (OR = 1.36, 95% CI 1.30 to 1.43, P = 1.57 × 10-34), and arthrosis (OR = 1.09, 95% CI 1.06 to 1.12, P = 8.80 × 10-9). However, after accounting for adult BMI, the detrimental effects of childhood BMI on disease-related traits were no longer present (P > 0.05). For dietary habits, different from conventional understanding, we found that higher childhood BMI was associated with low calorie density food intake. However, this association might be specific to the UK Biobank population.In summary, we provided a phenome-wide view of the effects of childhood BMI on adult traits. Multivariable MR analysis suggested that the associations between childhood BMI and increased risks of diseases in adulthood are likely attributed to individuals remaining obese in later life. Therefore, ensuring that childhood obesity does not persist into later life might be useful for reducing the detrimental effects of childhood obesity on adult diseases.
EPR21-038: Characterizing Surgical Oncology Cases During the COVID-19 Pandemic
Authors: Youmna Ashraf Sherif, Sukriti Bansal, Rachel W. Davis, Marcia Barnett, Umang M. Parikh, Hunter Bechtold, Hudson Holmes, Ahmad N. Elhajj, Jed G. Nuchtern, Chad T. Wilson, Cary Hsu
Journal: Journal of the National Comprehensive Cancer Network (2021)
Driving Impairment Following Vaporization of Cannabis
Authors: Luke A. Downey, Amie C. Hayley
Journal: JAMA (2021)

To the Editor We read with interest the recent findings reported by Dr Arkell and colleagues1 concerning the effect of vaporized Δ9-tetrahydrocannabinol (THC)–dominant and THC/cannabidiol (CBD)–equivalent cannabis on on-road driving performance.
Covid-19 dissenters—or the virtue in being less cheerful
Authors: Kamran Abbasi
Journal: BMJ (2021)

Dissent is under threat.To disagree is to affront.To protest is to break the peace.To argue is to fight.Disagreement, protest, and argument help us get nearer to the truth, and marginalising them is against the very essence of science and democracy.This is happening today, all around us, and the pandemic has moved us further, faster, and for the worse.
Training digitally competent clinicians
Authors: Videha Sharma, Georgina Moulton, John Ainsworth, Titus Augustine
Journal: BMJ (2021)

<h3>Abstract</h3> <h3>Background</h3> Up to 74% of patients with cervical cancer (CC) may experience recurrence after their treatment, and most of them are identified late when only the clinical parameters are used, which decreases their chances of recovery. Molecular markers can improve the prediction of clinical outcome and identify therapeutic targets in CC. Glycolysis is altered in 70% of CCs, so it could be a metabolic pathway in which molecular markers associated with the aggressiveness of CC can be identified. <h3>Methods</h3> The expression of 14 glycolytic genes was analyzed in 118 CC samples by microarrays, and only LDHA and PFKP were validated by qRT–PCR (n=58) and in second and third replicates by Western blotting (n=69) and immunohistochemistry (n=18). <h3>Results</h3> LDHA and PFKP were associated with poor overall survival [OS: LDHA HR=3.0 (95% CI= 1.1-8.2); <i>p=2</i>.<i>9 × 10</i><sup><i>-2</i></sup>; PFKP HR=3.4 (95% CI= 1.1-10.5); <i>p= 3</i>.<i>5 × 10</i><sup><i>-2</i></sup>] and disease-free survival [DFS: LDHA HR=2.7 (95% CI= 1.6-6.3); <i>p=2</i>.<i>6 × 10</i><sup><i>-2</i></sup>] independent of FIGO clinical stage. The risk of death was greater when both biomarkers were overexpressed than when using only FIGO stage [HR =7 (95% CI 1.6-31.1, <i>p=1</i>.<i>0 × 10</i><sup><i>-2</i></sup>) versus HR=8.1 (95% CI=2.6-26.1; <i>p=4</i>.<i>3 × 10</i><sup><i>-4</i></sup>)] and increased exponentially as the expression of LDHA and PFKP increased. <h3>Conclusions</h3> LDHA and PFKP at the mRNA and protein levels were associated with poor overall survival, disease-free survival and increased risk of death of patients with CC regardless of FIGO stage. The measurement of expression of these two markers could be very useful to evaluate the clinical evolution and the risk of death from CC and to make better therapeutic decisions at the beginning of treatment.
More holistic approach is needed to treat rise in sexually transmitted infections in the US, says report
Authors: Bob Roehr
Journal: BMJ (2021)

A change in attitudes towards sexually transmitted infections (STIs), patients, and the infrastructure that treats them will be as important as increased funding to counter the rising incidence of infections, according to a new report from the US National Academies of Science, Engineering, and Medicine.1

The report, commissioned by the US Centers for Disease Control and Prevention (CDC), called for a shift in “the professional healthcare paradigm.” The number of STIs among Americans has continued to increase, with an estimated 68 million infections in 2018, …
Inferring Macroscale Brain Dynamics via Fusion of Simultaneous EEG-fMRI
Authors: Marios G. Philiastides, Tao Tu, Paul Sajda
Journal: Annual Review of Neuroscience (2021)

Advances in the instrumentation and signal processing for simultaneously acquired electroencephalography and functional magnetic resonance imaging (EEG-fMRI) have enabled new ways to observe the spatiotemporal neural dynamics of the human brain. Central to the utility of EEG-fMRI neuroimaging systems are the methods for fusing the two data streams, with machine learning playing a key role. These methods can be dichotomized into those that are symmetric and asymmetric in terms of how the two modalities inform the fusion. Studies using these methods have shown that fusion yields new insights into brain function that are not possible when each modality is acquired separately. As technology improves and methods for fusion become more sophisticated, the future of EEG-fMRI for noninvasive measurement of brain dynamics includes mesoscale mapping at ultrahigh magnetic resonance fields, targeted perturbation-based neuroimaging, and using deep learning to uncover nonlinear representations that link the electrophysiological and hemodynamic measurements.
COVID-19 transmission following outpatient endoscopy during pandemic acceleration phase involving SARS-CoV-2 VOC 202012/01 variant in UK
Authors: Bu'Hussain Hayee, Pradeep Bhandari, Colin J Rees, Ian Penman
Journal: Gut (2021)

Infection prevention and control (IPC) measures put in place during the first phases of the COVID-19 pandemic were effective in reducing endoscopy-related transmission while allowing recovery of activity.

In late 2020 a novel, more infectious, SARS-CoV-2 variant (VOC 202012/01) was associated with a second ’surge' or acceleration phase in the UK. We sought to measure whether pre-existing IPC guidance would be sufficient to prevent transmission in this scenario. Prospective data were collected from eight UK centres for n=2440 procedures. Pre-endoscopy, nine (0.37%) asymptomatic patients were positive for SARS-CoV-2 by nasopharyngeal swab (NPS) testing and their procedures deferred. Post endoscopy, 30 (1.27%) developed symptoms suspicious for COVID-19, with 15 (0.65%) testing positive on NPS. Three (0.12%) cases were attributed to potential transmission from endoscopy attendance. All 15 patients recovered fully requiring only community treatment.

Although we report cases potentially transmitted by endoscopy attendance in this latest study, the risk of COVID-19 transmission following outpatient endoscopy remains very low. Thus, IPC measures developed in earlier pandemic phases appear robust, but our data emphasise the need for vigilance and strict adherence to these measures in order to optimally protect both patients and staff.

The effects of the COVID-19 pandemic continue to extend beyond direct care of affected patients,1 particularly impacting outpatient diagnostics including GI endoscopy. Considerable concerns remain around the potential impact on detection of, and survival from, significant disease such as cancer.2 3 In mid-2020, a pandemic deceleration phase4 in the UK led to a period of intense ‘restart and recovery’ activity in endoscopy to mitigate the effects of delayed or cancelled procedures. This was supported by professional society guidance on the development of ‘COVID-minimised’ or ‘green’ pathways with NPS testing of patients before their attendance for the procedure.5–7 Activity was limited by the impact on endoscopy staff …
Abstract 12678: Oral Anticoagulation Use in High Risk Atrial Fibrillation Patients is Much Higher Than Previously Reported
Authors: Mohammed Ruzieh, Gerald V Naccarelli, Deborah Wolbrette, Mauricio Sendra-Ferrer, John v Harskamp, Barbara Bentz, Gregory Caputo, Nathaniel McConkey, Kevin Mills, Stephen Wasemiller, Jovan Plamenac, Douglas Leslie, Frendy D Glasser, Thomas W Abendroth
Journal: Circulation (2020)

Introduction: Guidelines recommend oral anticoagulants (OAC) in high risk atrial fibrillation (HRAF) patients. It has been reported that &gt;40% of such patients are not taking an OAC. We observed that active AF often was not present in patients labeled as having AF (either because of wrong diagnosis or no AF in last 5 years). Hypothesis: We undertook a systematic electronic medical record (EMR) review to determine the presence or absence of active AF to accurately identify HRAF patients requiring an OAC. Methods: We reviewed 6514 patients with presumed AF and 2 or more outpatient visits documented by at least one of: billing diagnosis, EMR encounter diagnosis, EMR problem list, or EKG interpretation. Results: Active AF was noted in 4555/6514 patients (69.7%) after 1959 patients with no prior history of AF or inactive AF were withdrawn from further analysis. In active AF patients, 3869 had HRAF with CHA 2 DS 2 -VASc ≥2. OAC use was statistically higher (p&lt;0.0001 by McNamer’s test) in the active HRAF group [3090/3869 (79.9%) compared to the presumed HRAF group (62.9%)], Figure 1. There was no statistically significant difference in the use of OAC between men (80.7%) and women (78.8%), even in women with a CHA 2 DS 2 -VASc ≥3 (79.9%). In HRAF patients not taking an OAC (20.1%), expert review frequently disagreed with that recommendation suggesting that OACs can be taken in up to 92% of HRAF patients. Conclusions: 1) Current registries with un-adjudicated EMR diagnoses over-report the number of HRAF patients not taking an OAC; 2) Expert adjudication of active AF diagnosis identifies a smaller OAC treatment gap than previously described; 3) absolute contraindication or repeated refusal to take an OAC exists in less than 10% of HRAF patients; and, 4) there were no gender differences in OAC use.
MA05.03 Differential Frequency of Blood Immune Cells as Biomarkers for Risks Assessment in bioMILD Lung Cancer Screening Trial
Authors: G. Sozzi, V. Huber, O. Fortunato, M. Boeri, A. Cova, P. Squarcina, P. Suatoni, U. Pastorino, L. Rivoltini
Journal: Journal of Thoracic Oncology (2021)
Assessment of the Frequency of Dual Allergy to Penicillins and Cefazolin
Authors: Bernardo Sousa-Pinto, Kimberly G. Blumenthal, Lindsay Courtney, Christian M. Mancini, Meghan N. Jeffres
Journal: JAMA Surgery (2021)

Cefazolin is the preoperative antibiotic of choice because it is safer and more efficacious than second-line alternatives. Surgical patients labeled as having penicillin allergy are less likely to prophylactically receive cefazolin and more likely to receive clindamycin or vancomycin, which results in higher rates of surgical site infections.
P60.10 Tumor Neoantigen Burden and Immune Environment in Driver Alteration-Positive Lung Adenocarcinoma.
Authors: B. Leibowitz, L. Kujtan, L. Shunyakov, A. Schwarzbach, A.K. Ganti, A. Masood, J. Subramanian
Journal: Journal of Thoracic Oncology (2021)
P20.03 Impact of Radiotherapy Timing After Induction Chemotherapy on Survival of Patients With Locally Advanced Non Small Cell Lung Cancer
Authors: D. Scepanovic, M. Dzongov, A. Hanicova, M. Lukacovicova Kolarcikova, M. Fekete, M. Pobijakova, A. Masarykova
Journal: Journal of Thoracic Oncology (2021)
P50.13 A Nomogram for Assessing Survival in Extensive-stage SCLC patients with SVCS Referred To Thoracic Radiotherapy: Upfront vs. Consolidative ?
Authors: T. Mei, W. Xiu, X. Yang, Y. Yu, J. Zhu, Y. Xu, M. Huang, J. Xue, L. Zhou, X. Zhou, Y. Liu, Y. Lu, Y. Gong
Journal: Journal of Thoracic Oncology (2021)
P21.13 Durvalumab in Locally-Advanced NSCLC in LATAM: Real World Data from Patients Included in the Early Access Program
Authors: F. Tsou, M. Angel, F. Reinhold, C. Gabay, M. Bonet, M.V. Bluthgen, J. Minatta, B. Bustos, C. Novas, M. Rizzo, R. Kowalyszyn, J. Cundom, E. Richardet, G. Ferreira, D. Gomez Bradley, G. Roa, M. Tatangelo, C. Caglevic, A. Pini, M. Paskevicius, M. Flores, C. Pupareli, C. Martin
Journal: Journal of Thoracic Oncology (2021)
Join us at The Lancet Clinic
Authors: Sabine Kleinert, Richard Horton, Elena Becker-Barroso, Niall Boyce, David Collingridge, Justine Davies, Emma Grainger, Peter Hayward, John McConnell, Zoë Mullan, Lan-Lan Smith
Journal: The Lancet Diabetes & Endocrinology (2015)

On Oct 5, 2015, we launch the first 45 disease-specific pages of a major new online initiative involving all Lancet journals that will bring together an overview Seminar and relevant Reviews, Clinical Series, Commissions, research, Case Reports, and Clinical Pictures. Over the next 18 months or so when The Lancet Clinic is complete, there will be online pages for 135 diseases, which we have identified by a combination of global burden of disease data and clinical practice needs. We hope that The Lancet Clinic will help practising doctors make better informed decisions that ultimately lead to better lives of people worldwide, and help others who want to educate or update themselves keep abreast of the evolving evidence base. Importantly, these pages will be updated at regular intervals. The authors of newly commissioned Seminars have agreed to provide regular summaries of important new evidence for 4 years. Individual clinical editors will pull together newly published material from across the Lancet journals and post links to these on the page regularly. In addition, we are continuing our regular editorial policies of commissioning more specialised Clinical Reviews and Series across The Lancet Group to provide a more focused and in-depth assessment for key diseases. And beyond providing knowledge and information, we want to encourage academic and practising clinicians to use this knowledge for advocacy and change. In 2014, The Lancet published the first Clinical Commission on liver disease in the UK and in February, 2015, we launched our first Clinical Campaign based on this Commission. A Cancer Campaign as a joint effort between The Lancet and The Lancet Oncology followed in April. Clinical Campaigns aim to effect change based on data, knowledge, and expert interpretation in partnership with others. Further Clinical Commissions on asthma, hypertension, dementia, tuberculosis, traumatic brain injury, psychotherapy, chronic obstructive pulmonary disease, and others are underway across all Lancet journals. With these Clinical Commissions and Campaigns, we hope to extend our goal to publish the best science for better lives to being an active partner in using this science for actual change. Commissions and Campaigns will be part of the disease pages to encourage engagement and actions. The Lancet Clinic invites you to be part of this endeavour.
Effectiveness of right heart catheterization: Time for a randomized trial (multiple letters) [1]
Authors: J. K. Baxter, G. J. Beilman, J. H. Abrams, R. J. Jackson, R. P. Lewis, J. D. Punch, J. L. Kaufman, R. J. Beale, D. Wyncoll, A. McLuckie, D. Heyl, S. Aitken, J. Drover, O. Boyd, H. S. Friedman, S. W. Sharkey, C. W. Hanson, D. B. Coursin, C. G. Durbin, M. J. Murray, J. W. Hoyt, R. Schlichtig, E. D. Robin, D. H. Spodick, A F Jr Connors, F E Jr Harrell, W. A. Knaus, D. Wagner, R. C. Bone, J. E. Dalen
Journal: JAMA (1997)
Anti-GD2 antibody dinutuximab inhibits triple-negative breast tumor growth by targeting GD2<sup>+</sup> breast cancer stem-like cells
Authors: Stanley Ly, Vivek Anand, Fouad El-Dana, Khoa Nguyen, Yiming Cai, Shirong Cai, Helen Piwnica-Worms, Debasish Tripathy, Aysegul A Sahin, Michael Andreeff, Venkata Lokesh Battula
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no effective standard therapy. Breast cancer stem-like cells (BCSCs) in primary TNBCs are reported to be responsible for metastatic spread of the disease and resistance to chemotherapy, but no available therapeutic tools target BCSCs. We previously reported that the ganglioside GD2 is highly expressed on BCSCs and that inhibition of its expression hampers TNBC growth. We therefore hypothesized that the anti-GD2 antibody dinutuximab (ch14.18) targets GD2 + BCSCs and inhibits TNBC growth. Method To test our hypothesis, we first determined GD2 expression via immunohistochemistry in frozen primary tumor samples from patients with TNBC (n=89). Then, we examined the effects of dinutuximab on TNBC cell adhesion, migration, and mammosphere formation in vitro and on tumor growth in vivo using TNBC cell-line and patient-derived xenograft (PDX) models. Results We found that GD2 was expressed in around 60% of primary TNBC tumors at variable levels and was associated with worse overall survival of patients with TNBC (p=0.002). GD2 was found to be expressed in tumors and stroma, but normal ducts and lobules in adjacent tissues have shown low or no GD2 staining, indicating that GD2 is potentially a novel biomarker for tumor and its microenvironment. Treatment with dinutuximab significantly decreased adhesion and migration of MDA-MB-231 and SUM159 TNBC cells. Moreover, dinutuximab treatment inhibited mTOR signaling, which has been shown to be regulated by GD2 in BCSCs. Dinutuximab also reduced tumor growth in nude mice bearing TNBC cell-line xenografts. Finally, dinutuximab in combination with activated natural killer cells inhibited tumor growth in a TNBC PDX model and improved overall survival of tumor-bearing mice. Conclusions Dinutuximab successfully eliminated GD2 + cells and reduced tumor growth in both in vivo models. Our data provide proof-of-concept for the criticality of GD2 in BCSCs and demonstrate the potential of dinutuximab as a novel therapeutic approach for TNBC.
P59.03 Intratumoral Heterogeneity and Clonal Evolution in Large Non-Small Cell Lung Cancer (>7cm) Delineated by Multiregion Sequencing
Authors: J. Zhang, S. Dong, Q. Zhu, G. Zhao, P. Li, Q. Zhou, J. Yang, X. Zhang, Y. Guan, X. Xia, X. Yang, W. Zhong, Y. Wu
Journal: Journal of Thoracic Oncology (2021)
P76.07 Metformin Enhances the Efficacy of EGFR-TKIs in Advanced Non-Small Cell Lung Cancer Patients With Type 2 Diabetes Mellitus
Authors: R. Han, Y. Jia, X. Li, C. Zhao, S. Zhao, S. Liu, Y. Liu, M. Qiao, J. Li, G. Gao, C. Su, S. Ren, C. Zhou
Journal: Journal of Thoracic Oncology (2021)
Abstract P01: Development of a TMB classifier on NSCLC H&amp;E images
Authors: Alan Jerusalmi
Journal: Clinical Cancer Research (2021)

Abstract A number of immunotherapy treatments in cancer can be guided by a patient’s tumor mutation burden (TMB) status. However typical TMB determination is performed via next generation sequencing which is problematic due to its high cost, low availability worldwide and operational challenges. The ability to screen patients for TMB determination using alternative methodologies is of interest, particularly in the use of H&amp;E slides which are readily available for most cancer patients. Bio-AI Health has developed a machine learning (ML) classifier model capable of identifying TMB status in patients using H&amp;E slides only. Our automated model is unique in that it uses an enriched signal from samples consisting of tumor region only while generating unique visualizers that provide an insight into the performance and mode of action of the model itself. This visualizer allows the pathologist a unique view into the ML performance therefore eliminating the black box concept and providing a crucial QC step to ensure proper algorithm performance. This test can increase the sensitivity of detection providing significant clinical utility. The dataset for model development was obtained from TCGA cohort and TMB status was calculated using whole exome sequencing data. We further developed automated ML segmentation models to accurately segment the tissue into multiple compartments and filter our all necrotic and non-neoplastic tissue regions. Taking into account only tumor regions, the classifier ML model uses an ensemble approach which integrates the prediction of multiple convolutional network probabilities and achieves an accuracy of 0.76 with a sensitivity of .79 and F1 score of .82 towards the classification of the tissue as TMB high or Low. Citation Format: Alan Jerusalmi. Development of a TMB classifier on NSCLC H&amp;E images [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr P01.
P46.07 An Extended Targeted RNA Sequencing for Fusion Detection with Oncomine Comprehensive Assay Plus
Authors: A. Marcovitz, R. Gottimukkala, G. Bee, J. Kilzer, V. Mital, E. Wong-Ho, C. Yang, Y. Tseng, S. Myrand, P. Williams, A.V.H. Teoh, S. Sadis, F. Hyland
Journal: Journal of Thoracic Oncology (2021)
Rendezvous therapy with endoscopic and endovascular treatments for rectal arteriovenous malformation: A case report
Authors: Takashi Matsuda, Tsuyoshi Ishikawa, Takashi Oono, Ryo Sasaki, Isao Hidaka, Munemasa Okada, Isao Sakaida
Journal: Endoscopy (2021)

An 84-year-old man was admitted to our hospital with recurring hematochezia. Six months earlier, he had undergone transcatheter arterial embolization using platinum coils for hemorrhagic rectal arteriovenous malformation.