tbuckley/cabot-search huggingface dataset:
Overcoming gender bias in STEM
Authors: Nicole Boivin, Susanne Täuber, Morteza Mahmoudi
Journal: Trends in Immunology (2024)

Despite prevalent diversity and inclusion programs in STEM, gender biases and stereotypes persist across educational and professional settings. Recognizing this enduring bias is crucial for achieving transformative change on gender equity and can help orient policy toward more effective strategies to address ongoing disparities.
I<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si18.svg" display="inline" id="d1e3125"><mml:msup><mml:mrow/><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msup></mml:math>U-Net: A dual-path U-Net with rich information interaction for medical image segmentation
Authors: Duwei Dai, Caixia Dong, Qingsen Yan, Yongheng Sun, Chunyan Zhang, Zongfang Li, Songhua Xu
Journal: Medical Image Analysis (2024)
Hierarchical online contrastive anomaly detection for fetal arrhythmia diagnosis in ultrasound
Authors: Xin Yang, Lian Liu, Zhongnuo Yan, Junxuan Yu, Xindi Hu, Xuejuan Yu, Caixia Dong, Ju Chen, Hongmei Liu, Zhuan Yu, Xuedong Deng, Dong Ni, Xiaoqiong Huang, Zhongshan Gou
Journal: Medical Image Analysis (2024)
Risk of Second Tumors and T-Cell Lymphoma after CAR T-Cell Therapy
Authors: Mark P. Hamilton, Takeshi Sugio, Troy Noordenbos, Shuyu Shi, Philip L. Bulterys, Chih Long Liu, Xiaoman Kang, Mari N. Olsen, Zinaida Good, Saurabh Dahiya, Matthew J. Frank, Bita Sahaf, Crystal L. Mackall, Dita Gratzinger, Maximilian Diehn, Ash A. Alizadeh, David B. Miklos
Journal: New England Journal of Medicine (2024)

The risk of second tumors after chimeric antigen receptor (CAR) T-cell therapy, especially the risk of T-cell neoplasms related to viral vector integration, is an emerging concern.
Case 18-2024: A 64-Year-Old Woman with the Worst Headache of Her Life
Authors: Jonathan A Edlow, Aneesh B Singhal, Javier M Romero
Journal: New England Journal of Medicine (2024)

A 64-year-old woman was evaluated because of a sudden onset of the worst headache of her life. Computed tomography of the head revealed a convexal subarachnoid hemorrhage. A diagnosis was made.
Indolent CD4+ CAR T-Cell Lymphoma after Cilta-cel CAR T-Cell Therapy
Authors: Metin Ozdemirli, Thomas M Loughney, Emre Deniz, Joeffrey J Chahine, Maher Albitar, Stefania Pittaluga, Sam Sadigh, Philippe Armand, Aykut Uren, Kenneth C Anderson
Journal: New England Journal of Medicine (2024)

Indolent CD4+ cytotoxic chimeric antigen receptor (CAR) T-cell lymphoma involving the small intestine was diagnosed in a patient who had previously received ciltacabtagene autoleucel (cilta-cel) CAR T-cell therapy for treatment of myeloma. Targeted messenger RNA sequencing revealed the presence of CAR gene product in tumor cells. Whole-genome sequencing of samples of tumor and peripheral blood identified a single lentiviral insertion site within the second intron of the
Near-Universal Resistance to Macrolides of <i>Treponema pallidum</i> in North America
Authors: Nicole A.P. Lieberman, Tara B. Reid, Chase A. Cannon, B. Ethan Nunley, Anna Berzkalns, Stephanie E. Cohen, Lori M. Newman, Sol Aldrete, Linda H. Xu, Clinton P. Thornlund, Kevin Pettus, Stephanie Lundy, Michael Kron, Olusegun O. Soge, Kimberly Workowski, Charlotte Perlowski, Edward W. Hook, Jodie A. Dionne, Matthew R. Golden, Joshua A. Lieberman, Min-Kuang Lee, Muhammad Morshed, Prenilla Naidu, Weiping Cao, Allan Pillay, Lorenzo Giacani, Alexander L. Greninger
Journal: New England Journal of Medicine (2024)
Brigatinib in ALK-Positive ALCL after Failure of Brentuximab Vedotin
Authors: Layla Veleanu, Laurence Lamant, David Sibon
Journal: New England Journal of Medicine (2024)

Among 15 patients with relapsed ALCL after the failure of brentuximab vedotin therapy, the ALK inhibitor brigatinib led to a complete response in 73%, and progression-free survival at 2 years was 73%.
T-Cell Cancer after CAR T-Cell Therapy
Authors: Emily Mitchell, George S Vassiliou
Journal: New England Journal of Medicine (2024)

The last three decades have seen dramatic advances in the use of immunotherapies to treat cancer, primarily in the form of monoclonal antibodies targeting cancer cells directly or recruiting the immune system against them. More recently, immune cells themselves are being used as anticancer treatments, led by chimeric antigen receptor (CAR) T cells, genetically modified autologous T cells that are manufactured to express a CAR gene. CAR genes are engineered to code for a transmembrane protein with an extracellular antigen recognition and intracellular T-cell–activating domains that enable CAR T cells to recognize and attack cancer cells that express its target . . .
The Art of Finding the Right Drug Target: Emerging Methods and Strategies
Authors: Zi-Chang Jia, Xue Yang, Yi-Kun Wu, Min Li, Debatosh Das, Mo-Xian Chen, Jian Wu
Journal: Pharmacological Reviews (2024)

Drug targets are specific molecules in biological tissues and body fluids that interact with drugs. Drug target discovery is a key component of drug discovery and is essential for the development of new drugs in areas such as cancer therapy and precision medicine. Traditional <i>in vitro</i> or<i> in vivo</i> target discovery methods are time-consuming and labour-intensive, limiting the pace of drug discovery. With the development of modern discovery methods, the discovery and application of various emerging technologies have greatly improved the efficiency of drug discovery, shortened the cycle time and reduced the cost. This review provides a comprehensive overview of various emerging drug target discovery strategies, including computer-assisted approaches, drug affinity response target stability, multiomics analysis, gene editing, and NMD, and discusses the effectiveness and limitations of the various approaches, as well as their application in real cases. Through the review of the above related contents, a general overview of the development of novel drug targets and disease treatment strategies will be provided, and a theoretical basis will be provided for those who are engaged in pharmaceutical science research. <b>Significance Statement</b> Target-based drug discovery has been the main approach to drug discovery in the pharmaceutical industry for the past three decades. Traditional drug target discovery methods based on <i>in vivo</i> or <i>in vitro</i> validation are time-consuming and costly, greatly limiting the development of new drugs. Therefore, the development and selection of new methods in the drug target discovery process is crucial.
Association of patient-reported experience of care with cancer clinical trial participation.
Authors: Michelle Mollica, Timothy S. McNeel, David T Eton, Michael T. Halpern
Journal: Journal of Clinical Oncology (2024)

11117 Background: Few individuals diagnosed with cancer participate in clinical trials. Patient-reported experience of care (PEC), assessing patients’ perspectives on interactions with healthcare providers and systems, is important in evaluating quality of care. To help identify patient-centered strategies that may enhance trial enrollment, we examined whether PEC may predict enrollment in clinical trials. Methods: This study utilized Surveillance, Epidemiology, and End Results-Consumer Assessment of Healthcare Providers and Systems (SEER-CAHPS) linked data, including SEER registry data, CAHPS PEC surveys, and Medicare claims. Individuals in SEER-CAHPS who were diagnosed with lung cancer 2000-2018 and completed a CAHPS survey ≥6 months following diagnosis were included. The study outcome, clinical trial enrollment after cancer diagnosis, was determined using Medicare claims; among individuals who enrolled in clinical trials, only those completing a CAHPS survey before trial enrollment were included. PEC was assessed using 5 global ratings (Overall Care, Personal Doctor, Specialist, Health Plan, and Prescription Drug Plan) and 6 composite measures (Doctor Communications, Getting Needed Care, Getting Care Quickly, Getting Needed Drugs, Care Coordination, and Customer Service); all were scored 0 (worse PEC) to 10 (best PEC). Associations of trial participation and PEC were assessed using multivariable logistic regression, controlling for age, race/ethnicity, dual Medicaid status, fee-for-service vs Medicare Advantage plan at diagnosis, and physical problems limiting activities, and were weighted to correspond to the overall SEER population. Results: The study included 5,361 individuals diagnosed with lung cancer; 4.8% of the weighted population enrolled in a clinical trial. Patients with higher PEC ratings for their Specialist (odds ratio [OR] for a 1-point higher PEC score 0.86, 95% CI 0.76, 0.98); for their Health Plan (OR 0.87, 95% CI 0.80, 0.96); and for Getting Needed Care (OR 0.89, 95% CI 0.81, 0.98) had significantly (p&lt;0.05) lower oddsof having enrolled in a clinical trial. Among individuals without physical limitations, association of PEC and trial enrollment were similar. Among individuals with physical limitations, higher PEC ratings for Getting Care Quickly were associated with higher odds (OR 1.20, 95% CI 1.03, 1.39) of having enrolled in a trial. Conclusions: In this population, reporting worse PEC in certain domains was significantly associated with increased clinical trial enrollment. This suggests patients less happy with their clinical care may be more likely to enroll in trials, perhaps to receive different types of care and/or from different providers. PEC associations with trial enrollment differ between patients with vs without physical limitations, suggesting different strategies may be effective for increasing trial enrollment among these two sub-groups.
Variant of uncertain significance (VUS) genetic testing results and mastectomy choice in lumpectomy-eligible patients.
Authors: Osvaldo Nunez Jr., Vasanth Govind, Tizeta M. Wolde, Rainya Heath, Talia R. Donenberg, Rachel Silva-Smith, Marie B. Jeanjean, Jessica Firdman Moore, Jessica S. Crystal, Susan Kesmodel, Kristin E. Rojas
Journal: Journal of Clinical Oncology (2024)

10601 Background: Germline variants of uncertain significance (VUS) should not change surgical decision-making in breast cancer (BC) patients based on current guidelines. We sought to evaluate whether VUS may drive surgical choice in lumpectomy-eligible BC patients. Methods: A single-institution retrospective analysis included breast surgery patients (2020-2021). ‘Lumpectomy-eligible’ was defined as unilateral cT0-2 BC, excluding those with pathogenic mutations. Descriptive analyses compared those undergoing lumpectomy or bilateral mastectomy (BLMast), accounting for testing results. Multivariate analysis to predict the likelihood mastectomy receipt was limited to tested patients without pathogenic mutations using binomial logistic regression. Results: Of 741 patients, 549 (74%) were lumpectomy-eligible and 326 received genetic testing (235 negative, 91 VUS). Median age was 55.0 (26 - 84). Of those tested, 206 underwent lumpectomy, and 58 underwent BLMast. Insurance type, race, ethnicity, language, tobacco use, marital status, and axillary management did not differ between groups. Compared to lumpectomy patients, a higher proportion with a VUS (40% vs 25%, p=0.026), AJCC Stage 2 disease (41% vs 31%, p=0.023), or with ≥ 2 MRI-recommended biopsies (31.3% vs 13.8%, p=0.021) underwent BLMast. Multivariate analysis found that VUS patients were twice as likely to undergo BLMast compared to those with negative testing (OR 2.213 95% CI 1.113-4.400, p=0.023) (Table). Young patients and those with more advanced disease were also more likely to undergo BLMast. Conclusions: VUS genetic testing results may significantly influence lumpectomy-eligible patient decision-making. In an era of expanded genetic testing access, the present analysis informs the implementation of robust but accessible genetic counseling education initiatives in breast surgical oncology to decrease unnecessary mastectomies in patients with VUS. [Table: see text]
Implementation of universal germline testing in underserved patients with young onset gastrointestinal cancer.
Authors: Kaysia Ludford, Elias Awad, Anjali R. Lankford, Hilary Yu-heng Ma, Y. Nancy You
Journal: Journal of Clinical Oncology (2024)

10602 Background: Universal germline testing (UGT) in solid cancer patients increases the detection of pathogenic germline variants (PGVs) over guideline-based testing. There is a rising incidence of young onset (YO) gastrointestinal (GI) cancers (50 years and under). PGV rates in this population can be as high as 20%, highlighting the benefit of UGT. Underserved populations experience significant disparities in germline testing. The primary aim of this study is to evaluate rates of germline testing among patients with young onset (YO) GI cancers in a large safety net population and identify barriers and facilitators of testing in order to improve the process. Methods: In this retrospective study, we identified 202 patients ages 18-50 diagnosed with GI cancers between January 2019 and December 2022 at the Lyndon B. Johnson Hospital. Demographic and clinical data were collected and the rate, outcome and process of standard of care germline testing evaluated. Paired T-tests were used to identify factors associated with timeliness and completion of germline. Results: The majority of patients had colorectal (68%) followed by gastro-esophageal cancers (16%). Median age at diagnosis was 42 years. One third were diagnosed with stage IV disease. Half of all patients were recipients of financial assistance based on household income less than 150% of the Federal Poverty Level. Spanish was the primary language spoken by 58% of patients. Among all patients, 148 (73%) were referred to a genetics counselor with germline testing offered in 111 (55%) and completed in 99 (49%). PGVs were identified in 17% of patients tested while variants of uncertain significance were found in 19%. Patients with colon cancer (p&lt;0.001), microsatellite instability on immunohistochemistry (p&lt;0.001), and those with a first-degree relative with cancer (p&lt;0.001) were more likely to complete genetic testing. The average time from initial oncology visit to genetics referral was 20 weeks while that from referral to genetics appointment was 22.5 weeks. The average time from genetics appointment to completion of testing was 14.5 weeks. Patients with private insurance had a significantly shorter time to genetics referral (p&lt;0.05) while English-speakers had a longer time from referral to initial genetics appointment (p 0.019) and to completion of testing (p 0.044). Uninsured patients had significantly lengthier times to test completion (p 0.013). Conclusions: PGVs were detected in 17% of patients with YO GI cancers. Along the genetics services care delivery continuum, patient selection for genetic counselor referral, uptake of genetic testing and timeliness of testing were identified as key barriers to germline testing. Given the high detection rate and barriers to testing identified in this underserved population, we have designed a multilevel intervention aimed at optimizing the implementation of UGT in patients with YO GI cancers.
Glucagon-like peptide-1 (GLP-1) agonist use and weight change among patients with breast cancer.
Authors: Sherry Shen, Bethina Liu, Chad Fanti, Maria Bromberg, Yuan Chen, Cassandra Chang, Neil M. Iyengar
Journal: Journal of Clinical Oncology (2024)

10607 Background: Elevated body mass index (BMI) and post-diagnosis weight gain increase the risk of breast cancer recurrence and all-cause mortality. Chemotherapy and endocrine therapy can worsen metabolic dysfunction and are associated with weight gain. GLP-1 agonists mimic the action of endogenous GLP-1 and stimulate insulin secretion, delay gastric emptying, and promote satiety. In addition to diabetes treatment, several of these agents induce substantial (8-15%) weight loss and are indicated for obesity weight management. The efficacy of GLP-1 agonists during or after breast cancer treatment is unclear. Methods: Patients with breast cancer and prescribed a GLP-1 agonist from 2015-2023 with follow-up weight data (pre- and on/post-GLP-1 agonist) were included in this retrospective cohort study. A linear mixed effects model with a random intercept for baseline patient weight was used to assess mean weight change at each available follow-up timepoint. Relative weight change from baseline to approximately 12 months after GLP-1 agonist initiation was also computed and a multivariable linear regression was used to assess the association of baseline covariates with relative weight change. Results: 75 patients were included; median age was 52 (range 27-74), 4 (5%) had carcinoma in situ, 64 (85%) had stage I – III, and 4 (5%) had stage IV breast cancer. 62 (83%) had hormone receptor-positive tumors; 14 (19%) had HER2-positive and 8 (11%) had triple negative tumors. 40 (53%) received an aromatase inhibitor concurrently with GLP-1 agonist whereas 3 (4%) received tamoxifen concurrently. Chemotherapy was administered to 56 (75%), and 44 (59%) received radiation. 59 (79%) had a diagnosis of diabetes. Median time from breast cancer diagnosis to GLP-1 agonist prescription was 4.3 years (range -4.4 to 29.5). Median weight at breast cancer diagnosis was 85 kg (range 52-163), median BMI was 32 kg/m 2 (range 20-53). Median weight upon GLP-1 agonist initiation was 90 kg (range 58-151) and median BMI was 34 kg/m 2 (range 23-50). Median duration of GLP-1 agonist use was 20 months (range 6-111). At 12 months after GLP-1 agonist initiation, mean relative weight change was -5% (SD 6%). Mean weight change from GLP-1 agonist initiation was -2.8 kg (95% CI -0.9 to -4.7) at 6 months, -4.2 kg (95% CI -2.1 to -6.2) at 12 months, and -6.2 kg (95% CI -3.7 to -8.7) post-GLP-1 agonist treatment. Baseline BMI, concurrent anti-estrogen therapy, duration of GLP-1 agonist therapy, and comorbid diabetes were not associated with relative weight change in multivariate models. Conclusions: The use of GLP-1 agonists in this cohort of patients treated for breast cancer was efficacious and associated with modest (5%) weight loss. Based on this observed activity, prospective trials are warranted.
The contribution of rare and common genetic variants to risk of prostate cancer and second primary cancer after prostate in the UK Biobank.
Authors: Jennifer Lynn Beebe-Dimmer, Nathan Snyder, Ann G. Schwartz, Jun Wei, Zhuqing Shi, Huy Tran, Lily Zheng, Jeffrey Shevach, Kathleen A. Cooney, Jianfeng Xu
Journal: Journal of Clinical Oncology (2024)

10604 Background: It has been estimated that up to 40% of prostate cancer may be attributed to inherited genetic susceptibility, yet very few variants have been consistently associated with risk and/or adverse outcomes after diagnosis. Moreover, because prostate cancer survival is generally good, risk of developing a second primary cancer (SPC) is an important concern. Identifying men at greater genetic risk of developing an SPC will lead to improved post-diagnostic cancer surveillance practices and lifestyle behavior modifications. Methods: The current investigation leverages genetic and phenotypical data from the UK Biobank (UKB) to examine inherited genetic factors, including rare pathogenic mutations (RPMs) and polygenic risk scores (PRS) with prostate cancer risk and SPC. The individual and joint contribution of (RPM in 26 cancer susceptibility genes and trans-ethnic PRS previously derived for 11 different cancer sites with both risk of prostate cancer and also SPCs among men diagnosed after primary prostate cancer. Cox regression models were used to estimate Hazard Ratio (HR) for prostate cancer, adjusted for age and ancestry. Cumulative incidence of SPC by person-year among prostate cancer patients was estimated from the age of diagnosis and compared with that in men without cancer. Results: Among 228,472 men in the UKB, 17,547 were diagnosed with prostate cancer. RPMs in five genes ( ATM, BRCA2, CHEK2, HOXB13 and PTEN) were significantly associated with prostate cancer risk. The rate of prostate cancer among RPM carriers was 15.59% compared with 7.72% in non-carriers (HR=2.26, 95% CI=1.97-2.59). The top decile of PRS Prostate was associated with a 9.99-fold increase in risk of prostate cancer (95% CI=9.08-11). Having a diagnosis of prostate cancer had a significantly increased risk for two SPCs (bladder and kidney) and reduced risk for lung cancer, p&lt;0.001. Those that developed SPC of bladder cancer had significantly higher PRS Bladder , p=5.91E-06. The number of RPM carriers (n=77) among SPC bladder cancers was prohibitively small to precisely estimate risk. Conclusions: In this large population-based cohort, both RPMs in largely DNA damage repair genes and PRS contribute to risk of prostate cancer and PRS with second primary bladder cancer among men with prostate cancer. These data both contribute to our understanding of the genetic susceptibility to prostate cancer and reinforce the need for refinement of genetic screening panels.
Clinically significant variant classification resulting from the addition of RNA sequencing: Experience at high-volume cancer genetics center.
Authors: Sydney Rudowski, Alexis Gallant, Ana Stupar, Ashley Reeves, Sarah Campian, Dana Zakalik
Journal: Journal of Clinical Oncology (2024)

10603 Background: Germline cancer genetic testing plays an important role in prevention, early detection, and targeted therapy1. The increasing use of multi-gene panel testing (MGPT) underscores the importance of accurate variant classification. We report on the significant contribution of RNA analysis to variant classification with impact on clinical care. Methods: A total of 6343 patients who presented to the Nancy &amp; James Grosfeld Cancer Genetics Center between 2019 to 2023 and underwent MGPT at a laboratory with RNA sequencing were evaluated. Patients underwent MGPT using standard DNA technology with added RNA sequencing. We analyzed these patients for clinically significant variant reclassification which includes upgrades from non-actionable variants of uncertain significance (VUS) to pathogenic/likely pathogenic (P/LP) or P/LP to VUS as a significant downgrade. Results: A total of 177 patients (2.8%) had a variant classification significantly impacted by RNA sequencing. Of those 177 patients 45 (25.4%) had clinically relevant change due to their reclassification which resulted in a change in medical or surgical management. The majority of these 45 patients were upgraded from a non-actionable result to P/LP and 14 were downgraded to non-actionable. The clinically significant upgrades included the following genes: BRCA1/2 (5), MSH2 (4), MSH6 (1), PMS2 (1), ATM (5), CHEK2 (5), RAD51C (5), CDH1 (2), and PALB2 (3), which lead to evidence-based early detection and prevention. The clinically significant downgrades included the following genes: BRCA2 (5), RAD50 (1), and RAD51D (8), which allowed for a reduction in medical burden. Of the 177 cases impacted by RNA sequencing, 61 uncertain variants (34.4%) were downgraded to benign polymorphisms, helping to reduce uncertainty regarding management. Conclusions: Our study demonstrates the importance and added benefit of RNA sequencing in variant classification for patients undergoing multigene panel testing for hereditary cancer. The addition of RNA sequencing improved identification of individuals at increased risk, while lowering the number of uncertain variants. This improved technology will allow for a more precise approach to cancer screening, treatment and prevention.
Upfront Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Bevacizumab With or Without Atezolizumab for Patients With Metastatic Colorectal Cancer: Updated and Overall Survival Results of the ATEZOTRIBE Study
Authors: Carlotta Antoniotti, Daniele Rossini, Filippo Pietrantonio, Lisa Salvatore, Sara Lonardi, Stefano Tamberi, Federica Marmorino, Roberto Moretto, Michele Prisciandaro, Emiliano Tamburini, Giampaolo Tortora, Alessandro Passardi, Francesca Bergamo, Alessandra Raimondi, Giuliana Ritorto, Beatrice Borelli, Veronica Conca, Clara Ugolini, Giuseppe Aprile, Lorenzo Antonuzzo, Fabio Gelsomino, Erika Martinelli, Nicoletta Pella, Gianluca Masi, Luca Boni, Jerome Galon, Chiara Cremolini
Journal: Journal of Clinical Oncology (2024)

JCO