tbuckley/cabot-search huggingface dataset:
A cross-sectional analysis of muscle density and physical function in head and neck cancer patients.
Authors: Amy L. Shaver, Andrew Ray, Mary Elizabeth Platek, Anurag K. Singh, Kayleigh Erickson, Elizabeth Wendel, Gregory Wilding, Heather Ochs-Balcom, Katia Noyes
Journal: Journal of Clinical Oncology (2021)

e18597 Background: Head and neck cancer (HNC) is a debilitating disease that affects tens of thousands each year and both the disease and its treatment can cause long-term morbidity. HNC patients with greater physical function at baseline may better withstand both disease and treatment, therefore we hypothesized that baseline physical function is associated with baseline skeletal muscle density (SMD). Methods: A cross-sectional study of existing medical records was conducted. SMD was classified using pre-treatment PET-CT scans and interpreted using Sliceomatic software, and pre-treatment physical function assessed in three ways: hand grip strength, timed up and go, and short physical performance battery. Linear regression models were utilized to assess the association between SMD and each measure of physical function, with adjustment for muscle mass, sex and cancer stage in the hand grip strength model and adjustment for muscle mass and age in both the timed up and go, and short physical performance battery models. Results: The sample of 90 HNC patients, was mostly white, male, former smokers with an average BMI of 28 kg/m2. In adjusted models that included men only, we observed that for every Hounsfield unit increase in SMD there was a 0.08 increase in SPPB score (p=0.005), a 0.31 kg increase in hand grip strength (p=0.04), and a 0.13 second decrease in timed up and go (p=0.0007). In adjusted models that included women only, we observed that for every Hounsfield unit increase in SMD there was a 0.03 decrease in SPPB score (p=0.75), a 0.12 kg increase in hand grip strength (p=0.65), and a 0.01 second increase in timed up and go (p=0.84). Conclusions: Baseline physical function is associated with higher baseline physical SMD. Larger studies involving a more women are needed to replicate these findings and to further examine the potential role of effect modification by both sex and muscle mass.
Effects of formula composed of active monomers of removing heat and phlegm prescription on malignant phenotypes and growth signaling in esophageal carcinoma cells.
Authors: Fuchun Si, Wenbin Wang
Journal: Journal of Clinical Oncology (2021)

e16051 Background: Esophageal carcinoma (EC) ranks seventh in the incidence of malignant tumors and the sixth mortality worldwide. Removing heat and phlegm prescription(RHPP, composed of Rhizoma Dioscoreae Nipponicae, Rhizoma Paridis, Saponin, Rhizoma Bolbostemmae) was an effective formula screened from 531 Chinese herbs for treating EC in our previous study. The purpose of this study is to further track, isolate, purify and identify the active monomers of RHPP, study the effect of each active monomer on Eca109, EC9706, EC-1, TE-1 four EC cells and the signaling mechanism, then optimize and compose new active monomers formula and study its mechanism on EC cells. Methods: The active monomer of RHPP was extracted, separated and identified by ethanol extractioncolumn, chromatography, recrystallization, HPLC, spectroscopic method,etc. The effects of four kinds of active monomers and their composed formula on the proliferation, migration, clone formation, cell cycle and signal pathway proteins expression of Eca109 cell, EC9706 cell and TE-1 cell were investigated by MTT assay, RTCA assay, soft agar assay, flow cytometry and western blot analysis. Results: Four active monomers were identified from Rhizoma Dioscoreae Nipponicae (CSL), Saponin (ZJ), Rhizoma Bolbostemmae (TBM), Rhizoma Paridis (CL) respectively with molecular weights of 868, 1003, 1365, 854.5, and corresponding molecular formulas of C45H72O16, C50H82O20, C64H100O31 and C44H70O16(China patient No. ZL202010136431.6). Four active monomers significantly affected the cell morphology, proliferation, migration, cloning ability, cell cycle of four EC cells. The IC50 values of the active monomer of CSL, ZJ, TBM and CL for Eca109 were 1.29±0.12, 2.42±0.09, 1.93±0.09, 3.04±0.28μg/ml respectively; for EC9706 were 1.41±0.02, 5.94±0.45, 1.97±0.09, 0.63±0.04μg/ml respectively; for TE-1 were 3.72±0.28, 35.58±0.58, 7.90±0.41, 1.85±0.09μg/ml respectively; for EC-1 were 1.11±0.14, 3.56±0.28, 1.23±0.02, 0.61±0.02μg/ml respectively. Four active monomers could downregulate EGFR, PLC-γ1, and PKCα protein expression. Using the baseline proportional increase and decrease design method to compose new removing heat prescription(RH), removing phlegm prescription(RP) and removing heat and phlegm prescription (RHPP), the ratio of each drug monomer in RH, RP and RHPP were m CSL : m CL = 6: 4, m ZJ : m TBM = 3: 7, m CSL : m CL : m ZJ : m TBM = 48: 32: 6: 14. RH, RP and RHPP all could inhibit the proliferation, migration, cloning ability, cell cycle of four EC cells. Conclusions: The four active monomers and new composed RHPP all can inhibit the proliferation of EC9706, Eca109, TE-1, EC-1 four EC cells, which have close relationship with EGFR, PLC-γ1, and PKCαproteins expression. This study provides new formula and basis for the development of anti-esophageal carcinoma drugs in traditional Chinese medicine.
Evaluating survival in patients with pancreatic adenocarcinoma and lung metastasis.
Authors: Jason Cham, Aren Ebrahimi, David Jacob Hermel, Samantha R. Spierling Bagsic, Darren Sigal
Journal: Journal of Clinical Oncology (2021)

e16237 Background: Pancreatic adenocarcinoma most commonly metastasizes to the liver and peritoneum, yet can occasionally metastasize to the lungs in an isolated fashion. Anecdotal evidence suggests that patients who have isolated metastatic disease to the lungs have improved outcomes. We sought to investigate whether pancreatic cancer lung metastasis is associated with improved survival. Methods: We conducted a retrospective review of patients within the Scripps Health system with pathologically confirmed pancreatic adenocarcinoma from 2017 to 2020. Primary sites of metastatic disease were identified with imaging, and when available, confirmed by pathology. A subgroup of 101 patients from a total cohort of 598 patients was further refined to only include patients with lung and/or liver primary metastases (N=68). Analyses were conducted on subgroups defined by metastatic sites of disease in the liver only, lung only and combined liver+lung. Primary and secondary outcome analyses compared isolated lung versus liver/liver+lung. Overall survival (OS) was defined from the date of diagnosis to date of death or most recent follow up, and recurrence free survival (RFS) from the time of diagnosis to date of recurrence. Each survival outcome was analyzed using Cox Proportional Hazards tests. Additionally, proportions of each subgroup (lung v. liver/liver+lung) that had recurrence or were deceased were reported and compared by Fisher’s exact tests. Results: No significant differences were observed in OS (HR 1.91, CI 0.66 – 3.73; p= 0.311) or RFS (HR 0.98, CI 0.42 – 2.30; p= 0.968) between patients with primary lung metastases versus those with either liver or liver+lung metastases (reported as hazard ratios of liver/liver+lung relative to lung only). Although there was no overall statistically significant difference, the kaplan-meier curve for OS appears to show improved survival for patients with primary lung metastasis initially but then ultimately shows worse survival compared to liver only metastasis at later time points. Please see Table.Conclusions: We found no difference in survival outcomes among pancreatic cancer patients with only lung metastasis at diagnosis compared to patients with hepatic metastasis. However, we do observe that patients with lung metastases seem to have improved survival initially. This study was conducted on a small set of the total number of patients with pancreatic adenocarcinoma within the Scripps Health system. Further analysis is ongoing to confirm the trend we observe in this study.[Table: see text]
The role of C-reactive protein (CRP) as a prognostic biomarker in patients with early breast cancer (EBC) treated with neoadjuvant chemotherapy (NACT).
Authors: Hans-Christian Kolberg, Alexandra Edimiris, Oliver Hoffmann, Sarah Wetzig, Mohamed Shaheen, Miltiades Stephanou, Cornelia Kolberg-Liedtke
Journal: Journal of Clinical Oncology (2021)

e12545 Background: C-reactive protein (CRP) is an acute phase reactant influenced by inflammation and tissue damage. It has been demonstrated that elevated CRP levels are associated with poor outcome of cancer including metastatic breast cancer. However, evidence regarding an impact of CRP levels on outcome in early breast cancer (EBC) are missing. Methods: Patients after neoadjuvant chemotherapy (NACT) for EBC and with available data regarding CRP levels before therapy, pathologic complete remission (pCR) and follow-up were included. The association between CRP at baseline and outcome parameters was analyzed. Results: 156 women were included in this analysis, median follow up was 5.8 years. No association between CRP at baseline and pCR rates could be detected. 6.4% of the patients developed a local recurrence, 10.3% developed a distant recurrence and 5.1% died from breast cancer. A negative correlation (Spearman-Rho) between CRP at baseline and overall survival (OS) (Correlation coefficient (CC) -0.255; p = 0.45), disease free survival (DFS)(CC -0.348; p = 0.075), local recurrence free survival (LRFS)(CC -0.245; p = 0.327) and distant disease free survival (DDFS)(CC -0.422; p = 0.057) was not statistically significant, although especially in DFS and DDFS a strong trend was detected. The probability of death from breast cancer was 2% if the CRP was &lt; 0.08 mg/dl and 40% if the CRP was &gt; 2.08 m/dl, this association was highly statistically significant (Chi Square; p &lt; 0.001). These results were independent from age, estrogen and progesterone receptor status, HER2 status and grading. Conclusions: CRP at baseline is not predictive for pCR in EBC after NACT in our patient dataset. However, an association of parameters of long-term prognosis with CRP could be demonstrated. Although the correlations of higher CRP at baseline and shorter OS, DFS, LRFS and DDFS were not significant, a strong trend could be detected that was reproduced in the analysis of different cut-offs for CRP and the probability of breast cancer mortality. Higher CRP-levels are indicating a worse prognosis in early breast cancer after NACT in this retrospective analysis. These results justify further investigation of CRP as a biomarker of long-term prognosis in early breast cancer in prospective trials.
Effect of vitamin D supplementation on total and allergen-specific IgE in children with asthma and low vitamin D levels
Authors: Franziska J. Rosser, Yueh-Ying Han, Erick Forno, Leonard B. Bacharier, Wanda Phipatanakul, Theresa W. Guilbert, Michael D. Cabana, Kristie Ross, Joshua Blatter, Sandy Durrani, James Luther, Stephen R. Wisniewski, Juan C. Celedón
Journal: Journal of Allergy and Clinical Immunology (2021)
Optimal Timing of Initial Treatment in Severe Kawasaki Disease: A sub-analysis of the RAISE Study
Authors: Ikeda Kazuyuki, Saji Tsutomu, Kobayashi Tohru, Yahata Tomoyo, Hamaoka Akiko, Kato Taichi, Ogawa Shunichi, Miura Masaru, Nomura Yuichi, Hamaoka Kenji
Journal: Circulation (2013)
BUTTERFLY: addressing the pooled amplification paradox with unique molecular identifiers in single-cell RNA-seq
Authors: Johan Gustafsson, Jonathan Robinson, Jens Nielsen, Lior Pachter
Journal: Genome biology (2021)

Abstract The incorporation of unique molecular identifiers (UMIs) in single-cell RNA-seq assays makes possible the identification of duplicated molecules, thereby facilitating the counting of distinct molecules from sequenced reads. However, we show that the naïve removal of duplicates can lead to a bias due to a “pooled amplification paradox,” and we propose an improved quantification method based on unseen species modeling. Our correction called BUTTERFLY uses a zero truncated negative binomial estimator implemented in the kallisto bustools workflow. We demonstrate its efficacy across cell types and genes and show that in some cases it can invert the relative abundance of genes.
The role of PTEN and TP53 co-mutations in immunotherapy of lung cancer.
Authors: Xiaolong Ma, Ding Zhang, Shiqing Chen
Journal: Journal of Clinical Oncology (2021)

e21161 Background: Patients with non-small cell lung cancer (NSCLC) harboring PTEN mutations have a worse prognosis of immunotherapy in research with small sample size and case reports. However, the role of PTEN and TP53 co-mutations in immunotherapy of NSCLC has not been fully studied. Methods: Patients with NSCLC from our dataset were enrolled in this study. For the genomic profiling, only the pathogenic mutations and likely pathogenic mutations in clinical significance were rolled. The efficiency of immunotherapy was analyzed in a public cohort of 240 NSCLC patients by Rizvi. Patients with EGFR/ALK mutation were excluded in our analysis. Results: In our dataset, 1,428 patients were included in the analysis. 25 (1.75%) patients have PTEN mutations and 429 (30.04%) patients have TP53 mutations. In all patients with PTEN mutations, 84% with TP53 co-mutations. Median tumor mutational burden (TMB) was 12.29 mutations/MB (range, 3.35-36.87) and 6.98mutations/MB (range, 0.56-9.50) in patients harboring PTEN mutations with TP53 co-mutations and without TP53 co-mutations, respectively ( p= 0.02). In 240 NSCLC patients of Rizvi, the overall response rate (ORR) of the PTEN and TP53 co-mutations group, the PTEN mutations without TP53 mutations group and PTEN wild-type group was 33.33%, 0% and 20.26%, respectively. The disease control rate (DCR) was 83.33%, 0% and 54.74%, respectively. The median progression-free survival (PFS) in the PTEN and TP53 co-mutations group was the longest (7.5 months), while the median PFS in the PTEN mutations without TP53 mutations group was only 2.5 months. However, No significant differences of PFS were observed. Conclusions: Our findings suggested that patients with NSCLC harboring PTEN and TP53 co-mutations might benefit more from immunotherapy compare to those harboring PTEN mutation without TP53 mutations and PTEN wild-type. TMB may be an important factor that lead to the results. Further studies need to be explore in cohorts with larger sample sizes.
An AIB1 Isoform Alters Enhancer Access and Enables Progression of Early-Stage Triple-Negative Breast Cancer
Authors: Ghada M. Sharif, Moray J. Campbell, Apsra Nasir, Surojeet Sengupta, Garrett T. Graham, Max H. Kushner, William B. Kietzman, Marcel O. Schmidt, Gray W. Pearson, Olivier Loudig, Susan Fineberg, Anton Wellstein, Anna T. Riegel
Journal: Cancer Research (2021)

Abstract AIB1Δ4 is an N-terminally truncated isoform of the oncogene amplified in breast cancer 1 (AIB1) with increased expression in high-grade human ductal carcinoma in situ (DCIS). However, the role of AIB1Δ4 in DCIS malignant progression has not been defined. Here we CRISPR-engineered RNA splice junctions to produce normal and early-stage DCIS breast epithelial cells that expressed only AIB1Δ4. These cells showed enhanced motility and invasion in 3D cell culture. In zebrafish, AIB1Δ4-expressing cells enabled invasion of parental cells when present in a mixed population. In mouse xenografts, a subpopulation of AIB1Δ4 cells mixed with parental cells enhanced tumor growth, recurrence, and lung metastasis. AIB1Δ4 chromatin immunoprecipitation sequencing revealed enhanced binding to regions including peroxisome proliferator-activated receptor (PPAR) and glucocorticoid receptor (GR) genomic recognition sites. H3K27ac and H3K4me1 genomic engagement patterns revealed selective activation of breast cancer-specific enhancer sites by AIB1Δ4. AIB1Δ4 cells displayed upregulated inflammatory response genes and downregulated PPAR signaling gene expression patterns. In the presence of AIB1Δ4 enabler cells, parental cells increased NF-κB and WNT signaling. Cellular cross-talk was inhibited by the PPARγ agonist efatutazone but was enhanced by treatment with the GR agonist dexamethasone. In conclusion, expression of the AIB1Δ4-selective cistrome in a small subpopulation of cells triggers an “enabler” phenotype hallmarked by an invasive transcriptional program and collective malignant progression in a heterogeneous tumor population. Significance: A minor subset of early-stage breast cancer cells expressing AIB1Δ4 enables bulk tumor cells to become invasive, suggesting that selective eradication of this population could impair breast cancer metastasis.
Spatiotemporal loco-regional recurrence patterns after breast-conserving surgery.
Authors: Feilin Qu, Rui Mao, Zhebin Liu, Caijin Lin, Junjie Li, Zhiming Shao
Journal: Journal of Clinical Oncology (2021)

e12580 Background: Loco-regional recurrence (LRR) following breast-conserving surgery (BCS) represents a heterogeneous class of disease that has significant variation in its biological behavior and prognosis. Herein we report for the first time the spatiotemporal patterns of LRR post-lumpectomy in a Chinese population-based cohort. Methods: This retrospective study analyzed the single institutional patient-level data of breast cancer patients who underwent BCS between January 2006 and December 2016 at Shanghai Cancer Hospital of Fudan University. The enrolled patients were followed up regularly after initial surgery. Multivariate Cox regression models were performed to identify independent risk factors for LRR events. Recurrence patterns were scrutinized based on recurrence type and recurrence-free interval (RFI). Annual recurrence rates (ARR) were compared according to recurrence type and molecular subtype. Results: 4,325 patients were included, with a median follow-up of 66 months. A total of 120 (2.8%) LRRs were recorded as the first site of failure. Age at onset, pathologic stage, and molecular subtype were identified as predictors of loco-regional relapse. The major type of LRR was ipsilateral breast tumour recurrence (IBTR), which mainly (83.6%) occurred ≤5y post surgery. ARR curves showed that relapse peaked in the first 2.5 years in the overall population. Patients with regional nodal recurrence (RNR), shorter RFI, and synchronous distant metastasis were associated with a poorer prognosis. HER2+ positive disease had a higher rate of LRR events, more likely to have in-breast recurrence, and had an earlier relapse peak in the first 2 years after surgery. Conclusions: Currently, the LRR rate is generally low. Different recurrence patterns after BCS were related to distinct clinical outcomes. Management of LRR should be largely individualized and tailored to the extent of disease, the molecular profile of the recurrence, and to baseline clinical variables.
The Effect of Bioactive Phospholipids on Normal and Malignant Hematopoiesis—Modulation of Their Effects By Downregulating the Activities of Heme Oxygenase 1 (HO-1) and Inducible Nitric Oxygenase Synthase (iNOS)
Authors: Ahmed Abdelbaset-Ismail, Magdalena Kucia, Janina Ratajczak, Mariusz Z Ratajczak
Journal: Blood (2017)
EPCT-12. NATIONAL MULTICENTERED RETROSPECTIVE REVIEW OF DEMOGRAPHIC, TUMOUR AND INTRAOPERATIVE FEATURES ASSOCIATED WITH THE DEVELOPMENT OF CEREBELLAR MUTISM AFTER PEDIATRIC POSTERIOR FOSSA TUMOUR RESECTION
Authors: Michelle Kameda-Smith, Cameron Elliott, Hannna Moore, Nicholas Sader, Michael Tso, Mosaab Alsuwaihel, Ayoub Dakson, Olufemi Ajani, Blake Yarascavitch, Adam Fleming, Vivek Mehta, Forough Farrokhyar, Ali Yikilmaz, Nina Stein, Sheila Singh
Journal: Neuro-Oncology (2021)

Abstract Background Cerebellar mutism (CM) is a condition characterized by a significant lack or loss of speech in children following posterior fossa (PF) surgery. The biological origin of CM remains largely unclear and remains the subject of ongoing debate. Despite multidisciplinary rehabilitative interventions, the outcome is less favorable than initially described. Given the treatment refractory nature of CM, central to its management is prevention. Methods A national multi-centered retrospective review of all the children undergoing posterior fossa resection at 4 Canadian academic pediatric institutions was undertaken. Patient, tumour, surgical features suggested to be associated with the post-operative development of CM were reviewed to identify pre-operative and intra-operative factors that may predict post-operative CM occurrence. Results 258 pediatric patients were identified after posterior fossa lesion resection. Mean age at surgery was 6.74 years (SD 4.60) and 42.2% were female. Frozen section was available in 90.3% of cases. The majority of final tumour histology was medulloblastoma (35.7%), pilocytic astrocytoma (32.6%), ependymoma (17.1%) and exophytic glioma (1.2%). Intra-operative impression of adherence to the floor of the 4th ventricle was negative in 47.7%, positive in 36.8% of cases. The extent of resection assessed intraoperatively as gross total resection was 69.8% of cases. Intra-operative abrupt changes in blood pressure and/or heart rate was identified in 19.4% and 17.8% of cases. CM was experienced in 19.5% of patients (N=50), with the majority of cases identified by post-operative day 7. The clinical resolution of CM as mainly assessed by a neurosurgeon (86%) and was complete, significantly resolved, slight improvement, no improvement or deterioration in 56.0%, 8.0%, 20.0%, 14.0%, 2.0% respectively. Conclusion As a devastating surgical complication, identifying and understanding the biological origin of CM is the first step to complication avoidance. Maximal safe resection irrespective of intra-operative pathology remains the goal to avoid the devastating complication of CM.