tbuckley/cabot-search huggingface dataset:
The human liver microenvironment shapes the homing and function of CD4<sup>+</sup>T-cell populations
Authors: Benjamin G Wiggins, Laura J Pallett, Xiaoyan Li, Scott P Davies, Oliver E Amin, Upkar S Gill, Stephanie Kucykowicz, Arzoo M Patel, Konstantinos Aliazis, Yuxin S Liu, Gary M Reynolds, Brian R Davidson, Amir Gander, Tu Vinh Luong, Gideon M Hirschfield, Patrick T F Kennedy, Yuehua Huang, Mala K Maini, Zania Stamataki
Journal: Gut (2021)

Objective Tissue-resident memory T cells (T RM ) are vital immune sentinels that provide protective immunity. While hepatic CD8 + T RM have been well described, little is known about the location, phenotype and function of CD4 + T RM . Design We used multiparametric flow cytometry, histological assessment and novel human tissue coculture systems to interrogate the ex vivo phenotype, function and generation of the intrahepatic CD4 + T-cell compartment. We also used leukocytes isolated from human leukocyte antigen (HLA)-disparate liver allografts to assess long-term retention. Results Hepatic CD4 + T cells were delineated into three distinct populations based on CD69 expression: CD69 − , CD69 INT and CD69 HI . CD69 HI CD4 + cells were identified as tissue-resident CD4 + T cells on the basis of their exclusion from the circulation, phenotypical profile (CXCR6 + CD49a + S1PR1 − PD-1 + ) and long-term persistence within the pool of donor-derived leukcoocytes in HLA-disparate liver allografts. CD69 HI CD4 + T cells produced robust type 1 polyfunctional cytokine responses on stimulation. Conversely, CD69 INT CD4 + T cells represented a more heterogenous population containing cells with a more activated phenotype, a distinct chemokine receptor profile (CX 3 CR1 + CXCR3 + CXCR1 + ) and a bias towards interleukin-4 production. While CD69 INT CD4 + T cells could be found in the circulation and lymph nodes, these cells also formed part of the long-term resident pool, persisting in HLA-mismatched allografts. Notably, frequencies of CD69 INT CD4 + T cells correlated with necroinflammatory scores in chronic hepatitis B infection. Finally, we demonstrated that interaction with hepatic epithelia was sufficient to generate CD69 INT CD4 + T cells, while additional signals from the liver microenvironment were required to generate liver-resident CD69 HI CD4 + T cells. Conclusions High and intermediate CD69 expressions mark human hepatic CD4 + T RM and a novel functionally distinct recirculating population, respectively, both shaped by the liver microenvironment to achieve diverse immunosurveillance.
Feasibility of genome-wide characterization using Affymetrix Exon and Agilent miRNA. arrays in small cell lung cancer with formalin-fixed, paraffin-embedded (FFPE) samples in a phase III clinical trial (GALES)
Authors: Scott Myrand, Edwin Sandanaraj, Mark Socinski, Paul Lorigan, Gopi Ganji, Amit Aggarwal, Susan Guba, Nicholas Thatcher, Brian Mullaney, Egbert Smit
Journal: Journal of Thoracic Oncology (2009)
Maintenance Therapy With the Lowest Effective Dose of Oral Viscous Budesonide in Children With Eosinophilic Esophagitis
Authors: Salvatore Oliva, Danila Volpe, Giusy Russo, Silvio Veraldi, Paola Papoff, Carla Giordano, Cosimo Ruggiero, Chiara Maria Trovato, Gianluca Terrin, Danilo Rossetti
Journal: Clinical Gastroenterology and Hepatology (2021)
Interim Estimates of COVID-19 Vaccine Effectiveness Against COVID-19–Associated Emergency Department or Urgent Care Clinic Encounters and Hospitalizations Among Adults During SARS-CoV-2 B.1.617.2 (Delta) Variant Predominance — Nine States, June–August 2021
Authors: Shaun J. Grannis, Elizabeth A. Rowley, Toan C. Ong, Edward Stenehjem, Nicola P. Klein, Malini B. DeSilva, Allison L. Naleway, Karthik Natarajan, Mark G. Thompson
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Data on COVID-19 vaccine effectiveness (VE) since the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating strain in the United States are limited (1-3). CDC used the VISION Network* to examine medical encounters (32,867) from 187 hospitals and 221 emergency departments (EDs) and urgent care (UC) clinics across nine states during June-August 2021, beginning on the date the Delta variant accounted for >50% of sequenced isolates in each medical facility's state. VISION Network methods have been published (4).
Development of patient reported outcomes-based machine learning algorithm for the six-month mortality prediction in patients with advanced cancer.
Authors: Ishwaria Mohan Subbiah, Cai Xu, Sheng-Chieh Lu, Ali Haider, Ahsan Azhar, Amy E Swan, Jaya Sheela Amaram-Davila, Michael J Tang, Yvonne Heung, Kaoswi Karina Shih, Eduardo Bruera, Chris Sidey-Gibbons
Journal: Journal of Clinical Oncology (2021)

273 Background: To date, studies of machine learning (ML) algorithms within oncology for mortality prediction have focused on structured electronic health record (EHR) data. Given the complex symptom burden of patients with advanced cancers, ML models may be better suited to identify patterns and interactions between symptom burden and outcomes compared to traditional statistical methods. To that end, in this study, we leverage the patient reported outcomes (PRO) data together with clinical EHR-based variables to assess the performance of ML algorithms to predict mortality in patients with advanced cancers. Methods: We randomly selected 689 patients with advanced cancer who had their first Palliative Care encounter between January 2012 and December 2017. 59 patients were lost to follow-up and were excluded from this analysis. The remaining cohort of 630 patients was split 4:1 randomly into a training and validation set to develop and test a supervised ML algorithm (Extreme Gradient Boosting [XGB] tree) to predict the 6-month mortality. Candidate variables for algorithm development included gender, age, ECOG performance status (PS), number of prior systemic therapies, and scores on the Edmonton Symptom Assessment System (ESAS)-FS, a 12-item PRO measure of physical and psychosocial symptom burden include the composite Physical Symptom Score (PHS), a sum of the physical ESAS symptoms (pain, fatigue, nausea, drowsiness, shortness of breath, appetite, wellbeing, sleep). Results: Overall, 630 patients were included in this 6-month mortality prediction; mean age 59 years, 354 (56%) female; 276 (44%) male. Variables with the most significant impact on the XGB tree mortality prediction were the ESAS symptoms of shortness of breath (1-AUC, 0.295), appetite, ESAS PHS, financial distress, age, and appetite as well as ECOG PS and number of prior systemic therapies. The XGB tree algorithm demonstrated the best overall prediction performance of 6-month mortality in the independent testing set, AUC 0.716 (95% CI 0.63 - 0.81), sensitivity 0.75 (95% CI 0.66 - 0.87), and a positive predictive value 0.67 (95% CI 0.57 - 0.79). Conclusions: Our ML model leveraged PRO-based assessment of symptom burden to correctly identify the majority of patients who died within 6 months. These models are uniquely positioned to not only automatically identify patients at high risk for short-term mortality but also the specific symptoms of concern for clinical intervention. Such models can be applied to available clinical and PRO data to facilitate clinical decision-making. Futures studies on improving model performance with the inclusion of interventions to modify symptom burden are in design.
Diversifying educational resources during the COVID-19 pandemic: delivering educational dermatology podcasts and webinars for healthcare professionals
Authors: A. Paolino, A. Sears, R. Mills, J. Barker, F. Child, E. Craythorne, F. Ferguson, K. Lacy, H. McAteer, R. Morris-Jones, R. Patalay, E. Rashid, A. Salam, C. Smith, C. Stefanato, S. Walsh, L. Moorhead, K. Jackson, S. Mahil
Journal: British Journal of Dermatology (2021)
Circular RNAs’ cap-independent translation protein and its roles in carcinomas
Authors: Lian He, Changfeng Man, Shouyan Xiang, Lin Yao, Xiaoyan Wang, Yu Fan
Journal: Molecular Cancer (2021)

Abstract Circular RNAs a kind of covalently closed RNA and widely expressed in eukaryotes. CircRNAs are involved in a variety of physiological and pathological processes, but their regulatory mechanisms are not fully understood. Given the development of the RNA deep-sequencing technology and the improvement of algorithms, some CircRNAs are discovered to encode proteins through the cap-independent mechanism and participate in the important process of tumorigenesis and development. Based on an overview of CircRNAs, this paper summarizes its translation mechanism and research methods, and reviews the research progress of CircRNAs translation in the field of oncology in recent years. Moreover, this paper aims to provide new ideas for tumor diagnosis and treatment through CircRNAs translation.
Yoga therapy as a supportive care strategy for family caregivers of patients with primary brain tumor: Results of 3-arm pilot randomized controlled trial.
Authors: Kathrin Milbury, Jing Li, Shiao-Pei S. Weathers, Rosangela Silva, Stella Snyder, Yisheng Li, Tina Shih, Eduardo Bruera, Lorenzo Cohen
Journal: Journal of Clinical Oncology (2021)

156 Background: Seeking to address the well-documented burden of caring for a loved one with a high-grade glioma, this pilot RCT compared the feasibility and preliminary efficacy of a dyadic versus individual yoga intervention as a supportive care strategy for family caregivers. Methods: Caregivers completed self-reported assessments of QOL (SF-36) and caregiver burden (CRA) at baseline. Then, patients and caregivers were randomized to either a dyadic yoga (DY) arm in which caregivers attended the sessions together with the patient, a caregiver yoga (CY) arm in which the caregiver attended all sessions individually or a usual care (UC) arm. Both yoga programs were delivered over 15 sessions either in-person or via videoconference (Zoom) concurrently while patients were undergoing standard radiotherapy. All arms were re-assessed at the end of treatment and then again 3-months later. Results: We consented 76 patient-caregiver dyads (59%) and randomized 23 dyads to the DY, 22 to the CY, and 22 to the UC arm. Attendance in the DY was higher than in the CY group (session means, DY = 12.23, CY = 9.00; P =.06, d =.57). Caregivers (80% female; 78% non-Hispanic White; mean age = 53 yrs) reported significantly more overall subjective benefit in the CY compared to the DY arm (means, CY = 1.39, DY = 1.81, P &lt;.05, d = 1.45). Caregivers slightly favored the in-person delivery over the Zoom-based sessions (means, in person: 1.48; Zoom: 1.82, P =.10; d =.77). A clinically significant, medium effect size was found for improved QOL in favor of the CY over the DY group (means, CY = 49.45, DY = 44.45; F = 3.58, P =.07; d =.67). Caregivers in the CY group also reported less caregiving-related health declines compared to the DY group (means, CY = 2.18; DY = 2.48; F = 4.23, P &lt;.05; d =.42). Caregivers in the CY group reported less caregiving-related financial burden than the UC group (means: CY = 2.79; UC = 3.21; F = 3.32, P =.08; d =.35). Conclusions: Despite lower attendance, caregivers in the CY arm reported greater subjective overall benefit, experienced better mental QOL and less caregiver burden compared with those in the DY and UC comparison arms. It appears that individual rather than dyadic delivery may be a superior supportive care approach for this vulnerable caregiver population. An adequately powered, larger efficacy trial of this intervention strategy is warranted. Clinical trial information: NCT02481349.
Biomarker testing in patients (pts) with metastatic colorectal cancer (mCRC): Survey of U.S. oncologists (ONC) in rural areas and urban clusters.
Authors: Mark Andrew Lewis, Lindsay Stansfield, John M. Kelton, Michelle L. Edwards, Christopher Hanyoung Lieu
Journal: Journal of Clinical Oncology (2021)

108 Background: In the US, rural areas have higher cancer mortality rates than urban areas. Clinical practice guidelines recommend testing for BRAF and RAS mutations, and deficient mismatch repair (dMMR)/microsatellite instability (MSI) in pts with mCRC. However, data on biomarker testing rates in rural communities are limited. We surveyed ONC in the US who practice in rural areas and urban clusters to identify biomarker testing patterns and barriers. Methods: A web-based survey was administered to board-certified ONC who spend ≥ 40% of their time providing direct care to pts in rural areas or urban clusters (US Census Bureau definition) and who treated ≥ 2 pts with stage IV mCRC in the month prior to the survey. ONC in Maine, Vermont, and West Virginia were excluded (state legislature), as were those employed by the US government, Veterans Affairs, or Kaiser Permanente. Respondents were compensated. Data were analyzed descriptively. Results: From Feb 12 to Mar 18, 2021, 99 ONC (40% medical ONC, 60% hematologists/ONC) completed the survey. Respondents spent 56% and 18% of their time (mean) practicing in urban clusters and rural areas, respectively; 33% were in the South, followed by 26%, 22%, and 18% in the Northeast, Midwest, and West, respectively. 97% of ONC had ordered biomarker tests for pts; 35% referred pts for independent genomic testing. ONC tested biomarkers most commonly for stage IV disease: 72%, 65%, 63%, 59%, and 66% for KRAS, NRAS, BRAF, PD-L1, and dMMR/MSI, respectively (Table). 41% of ONC reported performing reflex testing at their primary practice, most commonly for PD-L1 (62%), KRAS (60%), and dMMR/MSI (52%). DNA-based next-generation sequencing (NGS) was the most common testing method reported. ONC indicated they would test for an actionable biomarker if it were known to occur in ≥ 28% of pts with mCRC. The most commonly cited barriers to testing were insufficient tissue samples and lack of insurance coverage. Although &gt; 50% of ONC agreed telehealth can improve testing rates, 81% noted barriers, including pts lacking technology equipment (56%) and pts being disengaged or unwilling to use telehealth (37%). Further data on testing-related decision making and barriers will be presented. Conclusions: Biomarker testing in rural areas and urban clusters falls short of current guideline recommendations. Further exploration of rural biomarker testing practices and strategies to improve testing are needed.[Table: see text]
Impact of antibiotic (ATB) exposure prior to immune checkpoint inhibitor (ICI) treatment on overall survival (OS): A population-based study.
Authors: Lawson Eng, Rinku Sutradhar, Yue Niu, Ning Liu, Ying Liu, Yosuf Kaliwal, Melanie Lynn Powis, Geoffrey Liu, Jeffrey M. Peppercorn, Philippe L. Bedard, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2021)

303 Background: ICIs are a common therapeutic option for many solid tumors. While prior studies have shown that ATB exposure may negatively impact ICI outcomes through gut microbiome changes, many were small studies with heterogeneity in ATB classes and exposure windows. Here, we performed a population level retrospective cohort study to evaluate the impact of ATB exposure prior to ICI on OS. Methods: We used administrative data to identify a cohort of cancer patients &gt; 65 years of age receiving ICIs from June 2012 to October 2018 in Ontario, Canada and deterministically linked with databases to obtain socio-demographic and clinical co-variates and ATB prescription claims. Multivariable cox-proportional hazard models evaluated the impact of ATB exposure both within 1 year and 60 days prior to starting ICI on OS, adjusted for age, gender, body mass index, comorbidities, autoimmune history, hospitalization in the past year and treatment facility level at start of ICI therapy. Results: Among 2737 patients, median age 73; 43% received Nivolumab, 41% Pembrolizumab and 13% Ipilimumab; 53% were lung cancer, 34% melanoma. Median ATB treatment duration for patients receiving ATB within 1 year (59%) and 60 days (19%) prior to ICI were 14 days (SD = 32) and 9 days (SD = 13) respectively. Median OS estimate was 306 days. Any ATB exposure within 1 year prior to ICI was associated with worse OS (aHR = 1.12 95% CI [1.12-1.23] p = 0.03). A non significant dose effect was seen based on weeks of ATB exposure 1 year prior to ICI (aHR = 1.01 per week [1.00-1.02] p = 0.10). ATB class analysis identified fluoroquinolone exposure within 1 year (aHR = 1.26 [1.13-1.40] p &lt; 0.001) and 60 days before ICI (aHR = 1.20 [0.99-1.45] p = 0.06) were associated with worse OS; with a dose effect based on total weeks of exposure over 1 year (aHR = 1.07 per week [1.03-1.11] p &lt; 0.001) and 60 days (aHR = 1.12 per week [1.03-1.23] p = 0.01). Subgroup analysis showed similar results for patients receiving anti-PD1 ICIs, where patients exposed to fluoroquinolone both 1 year (aHR = 1.28 [1.15-1.44] p &lt; 0.001) and 60 days (aHR = 1.19 [0.98-1.44] p = 0.08) before ICIs had poorer OS with dose effects observed based on weeks of fluoroquinolone exposure. Similarly, subgroup analyses based on disease site identified that lung cancer patients exposed to fluoroquinolones 1 year before starting ICIs (aHR = 1.22 [1.06-1.39] p = 0.005) and melanoma patients exposed to fluoroquinolones 60 days before starting ICIs (aHR = 1.66 [1.12-2.47] p = 0.01) had poorer OS. Conclusions: Exposure to ATBs and specifically fluoroquinolones prior to ICI therapy is associated with worse OS. Interventions aimed at altering the gut microbiome may be required to help improve outcomes for patients on ICIs with prior ATB exposure.
P04.20 The role of YAP in Glioblastoma cell lines
Authors: G Casati, L Giunti, A Iorio, A Marturano, I Sardi
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastoma (GBM) is a primary human malignant brain tumor, the most common in adults. Several studies have highlighted the Hippo-pathway as a cancer signalling network. The Hippo pathway is an evolutionarily conserved signal cascade, which is involved in the control of organ growth. Dysregulations among this pathway have been found in lung, ovarian, liver and colorectal cancer. The key downstream effector of the Hippo-pathway is the Yes-associated protein (YAP); in the nucleus, its function as transcription co-activator is to interact with transcription factors, resulting in the expression of target genes involved in pro-proliferating and anti-apoptotic programs. MATERIAL AND METHODS Using western blotting analysis, we determined the nuclear expression of YAP on three GBM cell lines (U87MG, T98G and A172). To investigate which inhibitors against the Hippo-pathway were the most efficient, we performed a cytotoxic assay: we treated all the three cell lines with different inhibitors such as Verteporfin (VP), Cytochalasin D (CIT), Latrunculin A (LAT), Dobutamine (DOB) and Y27632. Afterwards, we performed a treatment using Doxorubicin (DOX) combined with the inhibitors, evaluating its cytotoxic effect on our cell lines, through cell viability experiments. More western blotting experiments were performed to investigate the oncogenic role of YAP at nucleus level. Furthermore, preliminary experiments have been conducted in order to investigate the apoptosis, senescence and autophagy modulation due to the Hippo-pathway. RESULTS We showed our cell lines express nuclear YAP. We assessed the efficiency of the main inhibitors against Hippo-pathway, proving that VP, LAT A and CIT show a strong cytostatic effect, linked to time increase; plus we saw a cytotoxic effect on T98G. The association of DOX with selected inhibitors is able to reduce cell viability and nuclear YAP expression rate in all three GBM lines. Finally, preliminary experiments were set up to assess how and if the mechanisms of apoptosis, autophagy and senescence were affected by the Hippo-pathway. The combination of DOX with inhibitors promotes resistance to apoptosis. CONCLUSION Our results show that nuclear YAP is present in all tumor lines, thus confirming that this molecular pathway is functioning in GBM lines. Nuclear YAP is more highly expressed after DOX administration. Moreover, the combined treatment (DOX with Hippo-pathway inhibitors) reduces both cell proliferation and viability, and increases the rate of apoptosis. Preliminary experiments on senescence and autophagy were used to determine the best Hippo-pathway inhibitor. These data demonstrate that the Hippo-pathway plays a crucial role in GBM proliferation and resistance to apoptosis. Inhibiting this pathway and in particular the transcription factor YAP, in association with DOX, might be an excellent therapeutic target.
Resolving transportation disparity in cancer care.
Authors: Rachel Marquez, Matthew A. Manning, Mohamed K. Mohamed
Journal: Journal of Clinical Oncology (2021)

96 Background: Improving healthcare value requires new models of care including higher utilization of outpatient services. A significant social determinant of health in this mode of care is transportation, and the most vulnerable segments of society are disproportionately affected. Transportation disparity is especially troubling in radiation oncology, due to the protracted daily treatment schedule. Disruptions in treatment adversely impact clinical outcomes and survivals. This study is a pilot trial of a novel virtual logistics hub, capable of managing rideshare, taxis, wheelchair accessible vehicles, vehicles with car seats for children and stretcher vehicles in radiation oncology to measure utilization, patient satisfaction and financial impact. Methods: Over 4 months, using predictive analytics, patients with transportation barriers in a community cancer center were enrolled in a rideshare program. Those who received rides for radiation treatment were included in this study. Each patient's personal historic no-show rate in the health system was recorded. The estimated cost per no-show for a radiation treatment was set at $250. The opportunity cost was calculated as the product of the no-show rate, the no-show cost per treatment and the number of treatments. In addition, the cost of the transportation was recorded and subtracted from the opportunity cost to calculate the return on investment ROI. Qualitative data were also collected through patient surveys after each ride. Results: 29 subjects were included in this IRB-approved pilot study for a total of 419 rides. The most common diagnoses were Breast (27.6%), Lung (17.2%) and Prostate (17.2%). Most patients were racial minorities (70.0%) and had non-metastatic disease (75.9%). The median number of radiation treatments was 10 (3-40). The historic average no-show rate was 7% (0%-36%). The average expected no show cost per patient was $219.14 ($0.00-$1,837.50). The opportunity cost representing the benefit to the health system was $6,355.00. Per patient, the average transportation cost was $325.81 ($13.26-$1,034.39). The total cost of rides was $11,864.77. The ROI was -$5,509.77. When asked 'How would you rate your transportation experience today?' 82% responded Above Average. To the question 'Would you have been able to attend your appointment today if this program did not exist?' 92% answered No. Conclusions: This study shows that the cost of rideshare transportation can partially offset the cost of no-shows. This suggests that a proactive virtual transportation hub can help address transportation barriers, drive patient satisfaction and reduce the waste of no-shows. Radiation therapy represents an ambulatory medicine crucible for patients with limited transportation and social support. Scaling up rideshare innovations from radiation oncology has the potential to drive broader ambulatory strategy.