tbuckley/cabot-search huggingface dataset:
Immunity to childhood vaccines following high dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) for germ cell tumors (GCT) with comparison to Hodgkin lymphoma (HL).
Authors: Darren R. Feldman, Akeem Ronell Lewis, Andrea Knezevic, David Ali, Maria Bromberg, Julia Aronson, Samuel Aaron Funt, Deaglan Joseph McHugh, Robert J. Motzer, Dean F. Bajorin, Sujata Patil, Gunjan L. Shah, Monika Shah, Susan Seo, Mini Kamboj, Miguel-Angel Perales, Genofeva Papanicolaou
Journal: Journal of Clinical Oncology (2021)

5017 Background: HDCT/ASCT represents a curative salvage treatment for patients with GCT but is rarely used for other solid tumors. Patients undergoing HDCT/ASCT for hematologic neoplasms require revaccination for their childhood immunizations. Whether this is necessary in patients with GCT is unknown. Methods: In this prospective longitudinal study, patients with GCT undergoing HDCT-ASCT from 11/2010 to 5/2018 had serologies for Measles, Mumps, Rubella, Diphtheria, Tetanus, Polio, and Varicella Zoster measured before HDCT and at 3, 6, and in a subset, 12+ months after the last HDCT with results at these timepoints compared using descriptive statistics. In addition, titer levels at ≥6 months post-transplant were matched 1:1 for age and gender with HL patients who underwent HDCT/ASCT during the same time period. Immunity was compared between cohorts using the Cochran-Mantel-Haenszel test. Results: Of 80 patients with GCT (median age 30, 84% nonseminoma), 91% received 3 sequential transplants and 68 had repeat titers at ≥6 months. Immunity at baseline was &gt;95% for Diphtheria, Tetanus and Polio and 89% for Varicella Zoster but lower for Measles (74%), Mumps (85%), and Rubella (83%) (Table). Compared to baseline, proportional immunity for all infections was similar at 3, 6, and 12 months post-transplant in the GCT population (≥6 months shown in Table). Matching resulted in 58 GCT-HL pairs. One-year immunity was numerically lower for most infections in the HL vs. GCT patients and significantly decreased for Measles and Rubella (Table). Conclusions: To our knowledge, this is the first study to assess vaccine titers following HDCT/ASCT for GCT. We demonstrate that HDCT/ASCT does not result in loss of immunity to childhood vaccines and that GCT patients retain protective titers more frequently than those with HL. However, 15-31% of GCT patients lack MMR immunity at baseline and at 1-year post-ASCT. Therefore, we recommend checking MMR titers at 1-year post-ASCT with revaccination of those lacking immunity. Titer evaluation and revaccination is not necessary for other childhood immunizations.[Table: see text]
Ambient pollen and air quality on children’s lung function: is there a synergy?
Authors: Yutong Cai
Journal: Thorax (2021)

Children are particularly vulnerable to airborne pollutants due to their immature lungs and immune system. Many studies have reported deleterious effects of exposure to ambient air pollution, in acute or chronic timeframe, on respiratory health in children.1 Airborne pollen are microscopic grains that are released from trees, grasses and weeds. Ample epidemiological evidence has suggested associations between high airborne pollen count and emergency hospital visits for allergies and asthma exacerbation in children.2

The interplay between air pollutants and pollen is well described in many experimental studies. Particulate matter and gaseous pollutants (eg, nitrogen dioxide (NO2), ozone (O3)) can increase allergen absorption into the lungs by binding to pollen grains, facilitate faster release of allergens, and/or modulate pollen allergenic potency.3 In epidemiological studies, while it is clear that both ambient air pollution and pollen have independent associations with poor respiratory health, their interactive effects are less certain.3 4 These mixed results, in fact, reflect the complexity in concentration, toxicity/allergenicity and seasonality of both air pollutants and pollen in diverse geographical settings. To date, most studies in this field were of time-series or case-crossover design, and focused primarily on asthma and respiratory symptoms.

To address this knowledge gap, in this issue of Thorax , Amazouz et al investigated whether recent exposure to both air pollution and pollen could affect levels of spirometric lung function and fractional exhaled nitric oxide (FeNO) among 1063 eight-year-old children from the …
Oncology clinical research landscape in Middle East and North Africa (MENA) region: Challenges and proposed solutions.
Authors: Kareem Sameh, Natasha Khalife
Journal: Journal of Clinical Oncology (2021)

e13567 Background: Similar to other regions of the world, cancer incidence in Middle East and North Africa (MENA) is rising, which has been attributed to increased life expectancy and adoption of western lifestyle habits. Conducting clinical trials in the region is important to assess efficacy and safety of oncology medications in the specific population (response to drugs can be impacted by genetics, demographics and lifestyle factors). Although the MENA comprises around 5% of the global population, the region only participates in approximately 3% of clinical trials worldwide. It is important to understand the challenges in conducting trials in MENA and identify strategies to overcome these in order to facilitate advances in clinical research in the region. Methods: A literature review was conducted (via e.g. PubMed and ClinicalTrials.gov) to understand the current oncology clinical research landscape in MENA (from Jan 2015-Dec 2020), with the aim of identifying key challenges and potential strategies to overcome these. Results: Conduct of oncology clinical trials (phases 1-4) has risen in recent years in MENA, from 47 trials in 2015 to 53 trials in 2020. Despite the presence of various research-favourable factors in MENA (large patient pool, high demand for medication, lower clinical trial operational costs, compliance with ICH-GCP standards), the region still falls behind other countries in clinical research. Key factors identified as challenges in conducting clinical trials in MENA include the research infrastructure and patient awareness/understanding of research. We propose the following strategies to support the advancement of clinical research in the region: (1) Enhance research infrastructure through bolstering national clinical research networks and supporting collaboration between healthcare institutes, academia and the pharma industry; (2) Diversify methods of patient engagement (e.g. patient advisory groups and social media networks) and provide education on pros/cons of participating in research to raise awareness and improve trial participation rates; and (3) Improve availability of comprehensive oncology registries to enhance understanding of disease burden and support clinical research. Conclusions: The conduct of oncology clinical trials in MENA is increasing, yet the region is still under-represented in the global clinical trial market, despite its significant potential. The advancement of clinical research in the region will require a multi-level approach, involving collaboration between multiple stakeholders including the pharma industry, regulators, government, and healthcare professionals.
Predicting response to chemotherapy in neuroblastoma using deep learning: A report from the International Neuroblastoma Risk Group.
Authors: Siddhi Ramesh, Diana Michael, Liu Liu, Nicholas Feinberg, Meaghan Granger, Arlene Naranjo, Susan Lerner Cohn, Samuel Louis Volchenboum, Anoop Mayampurath, Mark A. Applebaum
Journal: Journal of Clinical Oncology (2021)

10039 Background: Metaiodobenzylguanidine (MIBG) scans are a radionucleotide imaging modality used to evaluate neuroblastoma stage at diagnosis and also determine disease response following therapy. Curie scoring is used to semi-quantitatively assess disease burden from an MIBG scan on a scale from none (0) to widespread throughout the body (30). While a Curie score ≤2 after six cycles of induction chemotherapy has been shown to be prognostic of outcome, there is no established correlation between diagnostic Curie score and outcome. Deep learning models, such as convolutional neural networks (CNN), have been shown to learn generalizable patterns within images for successful classification of metastases and detection of multiple adult cancers. We hypothesized a CNN could be developed to predict response to induction chemotherapy, a proxy for outcome, using diagnostic MIBG scans. Methods: DICOM MIBG scans and associated clinical data from a Children’s Oncology Group (COG) pilot study for children diagnosed with high-risk neuroblastoma (ANBL12P1; NCT1798004) were deidentified and linked to clinical data by the Pediatric Cancer Data Commons and obtained from the International Neuroblastoma Risk Group Data Commons. Patients were defined as having a poor response to induction chemotherapy if their Curie score after four cycles of induction chemotherapy was ≥2. An independent external validation cohort was comprised of 29 images from 26 high-risk patients treated at the University of Chicago with clinically-annotated diagnostic and post-cycle six induction DICOM MIBG scans. The CNN was trained using 2D whole body MIBG scans obtained at diagnosis. We developed the CNN using a transfer learning approach using the Xception architecture as the base layer. Hyperparameter optimization was performed using an 80%-20% train-validation strategy. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC). Results: Among 146 patients with high-risk neuroblastoma enrolled on ANBL12P1, 104 had available diagnostic and end-induction MIBG scans. There were no differences in clinical or biological characteristics between included and excluded patients. The base model CNN was able to predict which patients had a poor response to induction chemotherapy with an AUROC of 0.72 in the validation set from the ANBL12P1 cohort. Additionally, the CNN was able to predict patient response to therapy with an AUROC of 0.64 in an independent external dataset from University of Chicago. Conclusions: Our study suggests it is feasible to apply machine learning of diagnostic MIBG scans to predict response to chemotherapy for high-risk neuroblastoma patients. Given these promising results, further work to improve AUROC and performance within larger datasets is ongoing.
Re: Meghji J, Mortimer K, Agusti A, et al. Improving lung health in low-income and middle-income countries: from challenges to solutions. Lancet 2021:397(10277):928- 940
Authors: Tracey Lonergan, Ee Ming Khoo, Donald Kt Li, Mehmet Ungan, Hilary Pinnock, Rachel Jordan
Journal: The Lancet (2021)
Patterns in cancer management changes for patients with COVID-19 in northern California.
Authors: Michael Glover, Julie Wu, Daniel H Kwon, Sylvia Zhang, Solomon Henry, Douglas Wood, Daniel Rubin, Hala Borno, Eric Jay Small, Lidia Schapira, Vadim S Koshkin, Sumit Shah
Journal: Journal of Clinical Oncology (2021)

1535 Background: The COVID-19 pandemic affected oncology practice in ways that are still evolving. In particular, COVID-19 has led to changes in cancer treatment for patients (pts) infected with COVID, which may have long-term implications for both COVID and cancer-related outcomes. In this retrospective analysis, we describe changes in cancer management over time for cancer pts diagnosed with COVID-19 at two academic institutions in Northern California. Methods: Adult and pediatric pts diagnosed with COVID-19 receiving active cancer management, defined as therapy/surgery/diagnostics within 3 weeks of COVID diagnosis, were identified through the EMR. Patients whose care was affected by COVID-19 were identified and analyzed for significant intra-group differences with regards to management type, treatment intent, and the time of COVID-19 diagnosis (“early” was defined as March to June 2020 and “late” as July 2020 to January 2021). The duration and characteristics of such changes were compared across subgroups. Chi-squared test was used to compare the incidence of delays between subgroups. Results: Among 134 COVID-positive pts on active cancer management, 83 (62%) had significant changes in management that consisted primarily of treatment delays. More delays were identified in patients treated with curative intent earlier in the course of the pandemic compared to later (OR 4.1, p=0.022). This difference was not seen among pts treated with palliative intent. In addition, pts on oral (PO) therapy were significantly less likely to have treatment changes than those on IV/IM therapy (OR 0.32, p=0.005). This difference was driven by a decrease in management changes for those on PO therapy in the later time period (OR 0.27, p=0.026). Pts diagnosed later were more likely to have delays due to clinical reasons rather than institutional policy (OR 6.2, P&lt;.005). The median delay in both time frames was 21 days. Comparison of subgroups is shown in the table. Conclusions: We found significant changes in management of cancer pts with COVID-19 that evolved over time. Oncologists have become increasingly willing to continue therapy for cancer pts treated with curative intent and pts on oral therapy. Changes in cancer therapy have become more frequently related to patient clinical status, and less so due to institutional policies. It will be important to analyze how these changes in management are ultimately reflected in cancer outcomes in order to equip patients and oncologists to react to the next pandemic.[Table: see text]
The use of machine learning for predicating complications of free flap head and neck reconstruction.
Authors: Malke Asaad, Sheng-Chieh Lu, Praneeth Kambhampati, Jun Liu, Edward I Chang, Peirong Yu, Matthew Hanasono, Chris Sidey-Gibbons
Journal: Journal of Clinical Oncology (2021)

e18633 Background: The use of machine learning (ML) in plastic and reconstructive surgery has increased over the last decade. However, its use to predict surgical outcomes in head and neck reconstruction has not been well studied. The goal of this study is to assess the performance of ML algorithms trained to predict surgical outcomes of head and neck free flap reconstruction. Methods: Our study cohort included routinely collected data from 4000 patients who underwent free flaps for reconstruction of head and neck defects between January 2005 and December 2018. We developed and tested nine supervised ML algorithms to predict three outcomes of a.) any complication, b.) any major recipient-site complication, and c.) total flap loss. Results: In our sample, 33.7% of patients experienced any complication, 26.5% experienced a major complication at the recipient site and 1.7% experienced total flap loss. The k-nearest neighbors algorithm demonstrated the best overall performance for predicting any complication (AUROC = .61, sensitivity = .60). Regularized regression had the best performance for predicting major recipient site complication (AUROC=.68, sensitivity = .66), and decision trees were the best predictors of total flap loss (AUROC = .66, sensitivity = .50). Conclusions: We demonstrated that ML models trained using routinely collected data can make clinical useful predictions about who will experience complications. Our models correctly identified between half and two-thirds of patients who experienced post-surgical complications including total flap loss. These models can be applied to readily available clinical and perioperative data to facilitate decision making. Further performance improvements are likely possible with the inclusion of additional variables related to patient health and behavior.
Tumor suppressor function of <i>Gata2</i> in acute promyelocytic leukemia
Authors: Casey D. S. Katerndahl, Olivia R. S. Rogers, Ryan B. Day, Michelle A. Cai, Timothy P. Rooney, Nichole M. Helton, Mieke Hoock, Sai Mukund Ramakrishnan, Sridhar Nonavinkere Srivatsan, Lukas D. Wartman, Christopher A. Miller, Timothy J. Ley
Journal: Blood (2021)
Endoscopic resection of a rectal gastrointestinal stromal tumor using the submucosal tunneling endoscopic resection (STER) technique
Authors: Timothée Wallenhorst, Jérémie Jacques, Astrid Lièvre, Mael Pagenault, Guillaume Bouguen, Mathieu Pioche, Charlène Brochard
Journal: Endoscopy (2021)

The optimal treatment for a gastrointestinal stromal tumor (GIST) of the rectum is controversial owing to its extremely low incidence [1]. The submucosal tunneling endoscopic resection (STER) technique is a so-called "nonexposed" full-thickness endoscopic resection technique developed to remove upper gastrointestinal submucosal tumors (SMTs) arising from the muscularis propria [2] [3]. This technique allows a very interesting exposure of a GIST, as the axis of the knife is more tangential than when using an "exposed ESD technique", which features a perpendicular axis that carries a risk of R1 resection. We believe that it could also be interesting for the resection of rectal SMTs. We report here the first successful use of this technique, with an accompanying video ([Video 1]), for the removal of a 15-mm rectal GIST.
Hematology/medical oncology fellow responses to the initial development of an antiracism curriculum.
Authors: Erica C. Nakajima, Marcus Messmer, Jennifer Marie Jones, Luckson Mathieu, Tanyanika Phillips, Colin D. Weekes, Catherine Handy Marshall, Honor Sanderford, Ross C. Donehower, Kristen Marrone, Victor M. Moyo
Journal: Journal of Clinical Oncology (2021)

11042 Background: While the American Council on Graduate Medical Education (ACGME) set up a Planning Committee for Diversity in GME in 2018, no formalized milestones or training mandates have been announced. The nation-wide protests for racial justice following the senseless killings of Breonna Taylor, Ahmaud Arbery and George Floyd further brought to the forefront the need for immediate action to address widespread inequities across graduate medical education, our healthcare system and society as a whole. Therefore, the Johns Hopkins Hematology/Medical Oncology Fellowship Program focused on creating an anti-racism curriculum to foster dialogue on systemic racism and discrimination, grounded in the institutional and geographic context of our training program. Methods: Using the Kern six step curriculum development method, we created a comprehensive anti-racism initiative, which included virtual townhalls with Black alumni of the fellowship, book clubs, readings, and lectures. We sought to deepen the fellowship’s awareness of the impact of racism and inequity upon trainees, underrepresented minority oncologists and hematologists, and patients in order to develop initiatives to confront them productively. Trainees received a survey 6 months after the start of the curriculum to assess the impact of the initiatives upon trainees, and inform iterative changes to the curriculum. Results: 25 of 34 fellows across all post-graduate years (PGY) completed the survey. Fellows agreed that the curriculum was helpful (68%) and encouraging (60%). Collectively, fellows reported that the curriculum increased their awareness of instances of racism in medicine, caused them to think about next steps that the fellowship could take to address racism, and enabled them to identify available resources for support and further education. Respondents selected community engagement and recruitment of diverse fellowship classes as the most pressing priorities for the program. Conclusions: Social justice and anti-racism education belong in the formalized training of our hematology/medical oncology fellows. To this end, our ongoing curricular expansion is focusing on anti-racism training, diverse recruitment and youth mentorship. Collectively, a comprehensive yet program-specific approach facilitates opportunities for learning, engagement and development of the skills necessary to engage in this life-long work for ourselves, our communities and our patients.
Extracellular circular RNAs to promote the growth and metastasis of triple-negative breast cancer through remodeling the tumor immune microenvironment.
Authors: Sujin Yang, Jinhai Tang
Journal: Journal of Clinical Oncology (2021)

e13047 Background: Triple-negative breast cancer (TNBC) has been confirmed to have a high degree of heterogeneity of breast cancer, which is more common in young women, with a high degree of malignancy, lack of effective clinical treatment and poor prognosis. Recently, many studies have also found that immune microenvironment (IME) can remarkablely affect the occurrence and metastasis of TNBC through exosome-mediated molecular transmission. Therefore, there is an urgent need to find new immune-related molecules as therapeutic targets and to predict the progress of TNBC and prognosis of treatment. Methods: Using RNA-sequencing and bioinformatics analysis, we found the differential-expressed circular RNAs (circRNAs) in exosomes from TNBC cell lines (BT549 and MDA-MB-231), non-TNBC cell lines (MCF-7 and MCF-10A) and tissues from breast cancer patients. Then, we used CIBERSORT and ESTIMATE algorithm to explore the tumor-infiltrating immune cells (TICs) or stromal components in IME, and identified the significant differential-expressed mRNAs in the immune cells between TNBC and non-TNBC samples. RT-qPCR was used to confirm the expression level of selected circRNAs and mRNAs in TNBC cell lines. Results: We profiled the circRNAs in the exosomes from TNBC cell lines and breast cancer patients by RNA sequencing and detected 27 significantly differentially-expressed circRNAs. After bioinformatic analysis and RT-qPCR, circRELB and circANXA1 were chose to further study. TICs and IME scores were found to associated with the survival and clinicopathological characteristics of TNBC patients and IME remodeling. Interestingly, 92 differentially-expressed genes were found to be enriched in the NF-kB signaling pathway and mTOR signaling pathway. Moreover, we identified 33 target genes of circRELB and circANXA1 by cross-analysis. Based on the predicted miRNAs and the corresponding mRNAs and circRNAs, we have established an IME-related circRNA-miRNA-mRNA network. Then, Kaplan-Meier plots showed the expression levels of certain targeted genes (PTEN, CCND1, IL6, CDKN1A, AKT1, TNF and WNT1) were connected to prognosis in TNBC metastasis patients. Conclusions: The expression levels of circRELB and circANXA1 was found significantly upregulated in exosomes from TNBC cell lines and tumor tissues from breast cancer patients. In addition, circRELB and circANXA1could affect the expression of downstream target genes by competing for endogenous RNA (ceRNAs), and ultimately promote the metastasis of TNBC and remodeling of IME. In summary, this study analyzes the mechanisms of exosome-contained circRNAs in TNBC and these targets from the IME-related circRNA-miRNA-mRNA network may be new potential prognostic biomarkers and immune treatment strategies to prevent the development and metastasis of TNBC.
A Variant Noncoding Region Regulates <i>Prrx1</i> and Predisposes to Atrial Arrhythmias
Authors: Fernanda M. Bosada, Mathilde R. Rivaud, Jae-Sun Uhm, Sander Verheule, Karel van Duijvenboden, Arie O. Verkerk, Vincent M. Christoffels, Bastiaan J. Boukens
Journal: Circulation Research (2021)

[Figure: see text].