tbuckley/cabot-search huggingface dataset:
Abstract EP41: Relationship Between Body Mass Index And Low Total Bilirubin In US Adults
Authors: Aayush Visaria, Shivani Reddy, Akarsh Sharma, Bharath Nagaraj, Fariha Hameed
Journal: Circulation (2022)

Background: Low total bilirubin (TBili) is associated with increased cardiovascular risk, in part mediated by adipose tissue-related hormones. determined whether excess adiposity (measured by BMI) is associated with low TBili levels. Methods: Our study population consisted of 14,129 (6,902 male and 7,227 non-pregnant female) adults aged ≥20 years from the 1999-2018 National Health and Nutrition Examination Surveys. Participants with elevated liver enzymes (AST&gt;80 or ALT &gt;112 IU/L; AST/ALT &gt;5), excessive alcohol consumption (&gt;20 drinks/week for males; &gt;10 for females), iron overload (transferrin &gt;50%), anemia (hemoglobin&lt;12 g/dl if female; &lt;13 g/dl if male), elevated TBili (≥1.2 mg/dl), low albumin (&lt;3.5 g/dl), or positive hepatitis B/C serology were excluded. We categorized measured BMI into 7 categories (&lt;18.5, 18.5-22.9, 23.0-24.9, 25.0-27.4, 27.5-29.9, 30-34.9, ≥35). Low TBili, our primary outcome, was defined as &lt;0.4 mg/dl for both males and females. We used sex-stratified multivariable logistic regression, sequentially adjusting for demographics, cardiometabolic factors, and liver function. Results: Among 14,129 adults (mean age [SD] of 47 [15] years, 51% female, 69% White), nearly 32% had BMI ≥30. Both males and females with BMI ≥30 had &gt;50% odds of low TBili compared to a BMI of 23-24.9, even after adjustment for covariates (Table). There was no significant association between overweight range BMIs and low TBili. Adjustment for serum albumin most significantly attenuated the associations between obese-range BMIs and low TBili, especially in males. Further classifying each BMI category into high and normal waist circumference (WC;&lt;88cm for female, &lt;102cm for male) groups revealed that high WC individuals, even with BMI of 23-24.9, had increased odds of low TBili (OR [95% CI]: 2.35 [1.40, 3.94]). Conclusions: Obese BMI is associated with higher likelihood of low TBili. Longitudinal studies are needed to determine directionality of association and risk of downstream cardiovascular disease.
Outcome and Immune Correlates of a Phase II Trial of High-Dose Interleukin-2 and Stereotactic Ablative Radiotherapy for Metastatic Renal Cell Carcinoma
Authors: Raquibul Hannan, Osama Mohamad, Alberto Diaz de Leon, Subrata Manna, Laurentiu M. Pop, Ze Zhang, Samantha Mannala, Alana Christie, Scott Christley, Nancy Monson, Dan Ishihara, Eric J. Hsu, Chul Ahn, Payal Kapur, Mingyi Chen, Yull Arriaga, Kevin Courtney, Brandi Cantarel, Edward K. Wakeland, Yang-Xin Fu, Ivan Pedrosa, Lindsay Cowell, Tao Wang, Vitaly Margulis, Hak Choy, Robert D. Timmerman, James Brugarolas
Journal: Clinical Cancer Research (2021)

Abstract Purpose: This phase II clinical trial evaluated whether the addition of stereotactic ablative radiotherapy (SAbR), which may promote tumor antigen presentation, improves the overall response rate (ORR) to high-dose IL2 (HD IL2) in metastatic renal cell carcinoma (mRCC). Patients and Methods: Patients with pathologic evidence of clear cell renal cell carcinoma (RCC) and radiographic evidence of metastasis were enrolled in this single-arm trial and were treated with SAbR, followed by HD IL2. ORR was assessed based on nonirradiated metastases. Secondary endpoints included overall survival (OS), progression-free survival (PFS), toxicity, and treatment-related tumor-specific immune response. Correlative studies involved whole-exome and transcriptome sequencing, T-cell receptor sequencing, cytokine analysis, and mass cytometry on patient samples. Results: Thirty ethnically diverse mRCC patients were enrolled. A median of two metastases were treated with SAbR. Among 25 patients evaluable by RECIST v1.1, ORR was 16% with 8% complete responses. Median OS was 37 months. Treatment-related adverse events (AE) included 22 grade ≥3 events that were not dissimilar from HD IL2 alone. There were no grade 5 AEs. A correlation was observed between SAbR to lung metastases and improved PFS (P = 0.0165). Clinical benefit correlated with frameshift mutational load, mast cell tumor infiltration, decreased circulating tumor-associated T-cell clones, and T-cell clonal expansion. Higher regulatory/CD8+ T-cell ratios at baseline in the tumor and periphery correlated with no clinical benefit. Conclusions: Adding SAbR did not improve the response rate to HD IL2 in patients with mRCC in this study. Tissue analyses suggest a possible correlation between frameshift mutation load as well as tumor immune infiltrates and clinical outcomes.
Efficacy of Antiviral Agents against the SARS-CoV-2 Omicron Subvariant BA.2
Authors: Emi Takashita, Noriko Kinoshita, Seiya Yamayoshi, Yuko Sakai-Tagawa, Seiichiro Fujisaki, Mutsumi Ito, Kiyoko Iwatsuki-Horimoto, Peter Halfmann, Shinji Watanabe, Kenji Maeda, Masaki Imai, Hiroaki Mitsuya, Norio Ohmagari, Makoto Takeda, Hideki Hasegawa, Yoshihiro Kawaoka
Journal: New England Journal of Medicine (2022)
Should Everyone With Ductal Carcinoma in Situ Receive Adjuvant Radiation?
Authors: Laura E. G. Warren, Jennifer R. Bellon
Journal: Journal of Clinical Oncology (2021)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.
106P Generation of synthetic ground glass opacities (GGOs) using generative adversarial networks (GANs)
Authors: Z. Wang, Z. Zhang, L.E.L. Hendriks, R. Miclea, H. Gietema, J. Schoenmaekers, L. Wee, A. Dekker, A. Traverso
Journal: Annals of Oncology (2022)
Adagrasib Moving Ahead in GI Cancers
Journal: Cancer Discovery (2022)

Researchers reported a 100% disease control rate in 27 evaluable patients with KRASG12C-mutant pancreatic ductal adenocarcinoma and other gastrointestinal tumors, not including colorectal cancer, who received adagrasib monotherapy. These preliminary data come from the phase II portion of the KRYSTAL-1 study, which is assessing the safety and efficacy of the KRASG12C inhibitor.
Abstract P059: Effects Of Saturated Fatty Acid On Lipoprotein(a): A Systematic Review And Meta-analysis
Authors: Terrence Riley, Philip Sapp, Kristina Petersen, Penny M Kris-Etherton
Journal: Circulation (2022)

Background: Elevated lipoprotein(a) [Lp(a)] is a significant contributor to residual CVD risk. Replacement of saturated fatty acids (SFA) with mono- and polyunsaturated fatty acids (MUFA and PUFA), carbohydrates (CHO) has established effects on traditional lipid parameters related to CVD; however, the evidence for Lp(a) is inconsistent. Moreover, some evidence suggests replacing SFA with other macronutrients increases Lp(a). Objective: The aim was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of replacing SFA with MUFA, PUFA, trans fatty acids (TFA) and CHO on Lp(a). Methods: PubMed, Cochrane Central, ClinicalTrials.gov, and Web of Science were searched for RCTs with a duration of ≥13 days that included healthy adults ages 20-65 y and examined the effect of diets differing in SFA, MUFA, PUFA, or CHO on Lp(a). Exclusion criteria included changes in protein/alcohol and &gt;10% weight loss in last 6 months. Diet comparisons were extracted from trials to assess the effect of substitution of SFA for other macronutrients. Data are presented as weighted means. Data were analyzed using a mixed model approach (SAS 9.4). Results: Twenty-seven articles met criteria for inclusion and data were available for analysis for 15 articles. There were 39 comparisons between SFA and other macronutrients. Lp(a) was measured by macra, polyclonal, or sandwich enzyme linked immunosorbent assay (ELISA), particle enhanced turbidimetric immunoassay, or radioimmunoassay. SFA was substituted for TFA ( k =6), MUFA ( k =9), and PUFA ( k =3). Five trials compared a high SFA diet with a high CHO diet. A total of 539 adults (44.7 + 31.6 y) were included in the pooled sample. Overall, the mean displacement of SFA for other macronutrients was 6.7% of kcals. Mean Lp(a) across the included studies was 100.5 + 100.3 mg/dl. Replacement of SFA with MUFA, PUFA or CHO did not significantly affect Lp(a). Lp(a) was 6.1 mg/dl (p=0.021; 95% CI: -11.3, -0.9) lower when SFA replaced TFA. Conclusions: Overall, substitution of SFA for other macronutrients did not impact Lp(a) concentrations. Lower levels of Lp(a) were observed when 5% of kcals from TFA were replaced with SFA, although the clinical relevance of this finding is unclear. Further research examining the effect of SFA replacement on Lp(a) is needed due to the methodological quality of the available data and heterogeneity in Lp(a) measurement methods utilized.
162P A CT radiomics model to predict overall survival following curative-intent radiotherapy for stage I-III non-small cell lung cancer
Authors: S. Hindocha, T.G. Charlton, K. Linton-Reid, B. Hunter, C. Chan, M. Ahmed, E. Robinson, M. Orton, J. Lunn, S. Ahmad, F. McDonald, I. Locke, D. Power, S. Doran, M. Blackledge, R.W. Lee, E. Aboagye
Journal: Annals of Oncology (2022)
Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity
Authors: Thorsten Gnad, Gemma Navarro, Minna Lahesmaa, Laia Reverte-Salisa, Francesca Copperi, Arnau Cordomi, Jennifer Naumann, Aileen Hochhäuser, Saskia Haufs-Brusberg, Daniela Wenzel, Frank Suhr, Naja Zenius Jespersen, Camilla Scheele, Volodymyr Tsvilovskyy, Christian Brinkmann, Joern Rittweger, Christian Dani, Mathias Kranz, Winnie Deuther-Conrad, Holger K. Eltzschig, Tarja Niemi, Markku Taittonen, Peter Brust, Pirjo Nuutila, Leonardo Pardo, Bernd K. Fleischmann, Matthias Blüher, Rafael Franco, Wilhelm Bloch, Kirsi A. Virtanen, Alexander Pfeifer
Journal: Cell Metabolism (2022)
Combining Ixazomib With Subcutaneous Rituximab and Dexamethasone in Relapsed or Refractory Waldenström's Macroglobulinemia: Final Analysis of the Phase I/II HOVON124/ECWM-R2 Study
Authors: Marie José Kersten, Karima Amaador, Monique C. Minnema, Josephine M. I. Vos, Kazem Nasserinejad, Marcel Kap, Efstathios Kastritis, Maria Gavriatopoulou, Willem Kraan, Martine E. D. Chamuleau, Dries Deeren, Lidwine W. Tick, Jeanette K. Doorduijn, Fritz Offner, Lara H. Böhmer, Roberto D. Liu, Steven T. Pals, Meletios A. Dimopoulos
Journal: Journal of Clinical Oncology (2021)

Proteasome inhibitors are effective in Waldenström's macroglobulinemia (WM) but require parenteral administration and are associated with polyneuropathy. We investigated efficacy and toxicity of the less neurotoxic oral proteasome inhibitor ixazomib combined with rituximab, in patients with relapsed WM.We conducted a multicenter phase I/II trial with ixazomib, rituximab, and dexamethasone (IRD). Induction consisted of eight cycles IRD wherein rituximab was started in cycle 3, followed by rituximab maintenance. Phase I showed feasibility of 4 mg ixazomib. Primary end point for phase II was overall response rate (ORR [≥ minimal response]) after induction.A total of 59 patients were enrolled (median age, 69 years; range, 46-91 years). Median number of prior treatments was 2 (range, 1-7); 70% had an intermediate or high WM-IPSS (International Prognostic Scoring System for WM) score. After eight cycles, ORR was 71% (42 out of 59) (14% very good partial response [PR], 37% PR, and 20% minor response). Depth of response improved until month 12 (best ORR 85% [50 out of 59]: 15% very good PR, 46% PR, and 24% minor response). Median duration of response was 36 months. The average hematocrit level increased significantly (0.33-0.38 L/L) after induction (P < .001). After two cycles of ixazomib and dexamethasone, immunoglobulin M levels decreased significantly (median 3,700-2,700 mg/dL, P < .0001). Median time to first response was 4 months. Median progression-free survival and overall survival were not reached. After median follow-up of 24 months (range, 7.4-54.3 months), progression-free survival and overall survival were 56% and 88%, respectively. Toxicity included mostly grade 2 or 3 cytopenias, grade 1 or 2 neurotoxicity, and grade 2 or 3 infections. No infusion-related reactions or immunoglobulin M flare occurred with use of subcutaneous rituximab. Quality of life improved significantly after induction. In total, 48 patients (81%) completed at least six cycles of IRD.Combination of IRD shows promising efficacy with manageable toxicity in patients with relapsed or refractory WM.
Inhibition of estrogen signaling in myeloid cells increases tumor immunity in melanoma
Authors: Binita Chakraborty, Jovita Byemerwa, Jonathan Shepherd, Corinne N. Haines, Robert Baldi, Weida Gong, Wen Liu, Debarati Mukherjee, Sandeep Artham, Felicia Lim, Yeeun Bae, Olivia Brueckner, Kendall Tavares, Suzanne E. Wardell, Brent A. Hanks, Charles M. Perou, Ching-Yi Chang, Donald P. McDonnell
Journal: Journal of Clinical Investigation (2021)

Immune checkpoint blockade (ICB) therapies have significantly prolonged patient survival across multiple tumor types, particularly in melanoma. Interestingly, sex-specific differences in response to ICB have been observed, with males receiving a greater benefit from ICB than females, although the mechanism or mechanisms underlying this difference are unknown. Mining published transcriptomic data sets, we determined that the response to ICBs is influenced by the functionality of intratumoral macrophages. This puts into context our observation that estrogens (E2) working through the estrogen receptor α (ERα) stimulated melanoma growth in murine models by skewing macrophage polarization toward an immune-suppressive state that promoted CD8+ T cell dysfunction and exhaustion and ICB resistance. This activity was not evident in mice harboring macrophage-specific depletion of ERα, confirming a direct role for estrogen signaling within myeloid cells in establishing an immunosuppressed state. Inhibition of ERα using fulvestrant, a selective estrogen receptor downregulator (SERD), decreased tumor growth, stimulated adaptive immunity, and increased the antitumor efficacy of ICBs. Further, a gene signature that determines ER activity in macrophages predicted survival in patients with melanoma treated with ICB. These results highlight the importance of E2/ER signaling as a regulator of intratumoral macrophage polarization, an activity that can be therapeutically targeted to reverse immune suppression and increase ICB efficacy.
Abstract 10380: Differences in Cardiac Magnetic Resonance Native T1 Values Demonstrate Utility in Identifying Acute Cellular Rejection and Assessing Graft Health
Authors: Devika Patel, Nyshidha Gurijala, Jason Mandell, Karin Hamann, Christopher Rossi, Russell Cross, Joshua Kanter, John T Berger, Laura Olivieri
Journal: Circulation (2021)

Introduction: Cardiac Magnetic Resonance (CMR) is an emerging tool for cardiac graft assessment in heart transplant recipients, with native T1 mapping directed at identifying both rejection and graft fibrosis to predict and guide management of graft dysfunction. Hypothesis: CMR native T1 values may identify acute rejection, predict graft dysfunction, and in secondary analysis, correlate with fibrosis percentage from right ventricle (RV) endomyocardial biopsy (EMB). Methods: Pediatric subjects (n=34, age 12.4±4.9 y, graft age 5.4±4.3 y, LVEF 62.9±5.6%) underwent simultaneous EMB and 1.5T CMR with breath-held T1 mapping via Modified Look-Locker Inversion recovery in 8 short-axis slices, from which global mean and peak native T1 values were quantified. EMB analyzed for histopathological fibrosis% using digital analysis of Maisson’s trichrome stained slides. Patients were stratified into three groups by decision to treat: acute rejection with new treatment initiated, ongoing treatment modified, or no change in treatment. In patients without acute rejection, linear regression was used to compare T1 values with clinical markers of right atrial (RA) mean pressure and brain natriuretic peptide (BNP). Results: Mean T1 values were higher in patients with acute rejection compared to those without, with stratified groups demonstrating a monotonic trend; peak T1 values trended towards significance. In patients without acute rejection, peak T1 values correlated with BNP (r=0.53, p=0.004) and RA mean pressure (r=0.39, p=0.046). Fibrosis% from random RV EMB did not correlate with native T1 values or clinical markers of graft dysfunction. Conclusion: In pediatric heart transplant patients, T1 values from comprehensive CMR identified acute rejection requiring initiation of treatment and graft dysfunction, with regional analysis key to capturing correlation with clinical markers. CMR shows promise as an important tool for evaluation of graft health in children.
Analysis of human brain tissue derived from DBS surgery
Authors: Salla M. Kangas, Jaakko Teppo, Maija J. Lahtinen, Anu Suoranta, Bishwa Ghimire, Pirkko Mattila, Johanna Uusimaa, Markku Varjosalo, Jani Katisko, Reetta Hinttala
Journal: Translational Neurodegeneration (2022)

Transcriptomic and proteomic profiling of human brain tissue is hindered by the availability of fresh samples from living patients. Postmortem samples usually represent the advanced disease stage of the patient. Furthermore, the postmortem interval can affect the transcriptomic and proteomic profiles. Therefore, fresh brain tissue samples from living patients represent a valuable resource of metabolically intact tissue. Implantation of deep brain stimulation (DBS) electrodes into the human brain is a neurosurgical treatment for, e.g., movement disorders. Here, we describe an improved approach to collecting brain tissues from surgical instruments used in implantation of DBS device for transcriptomics and proteomics analyses. Samples were extracted from guide tubes and recording electrodes used in routine DBS implantation procedure to treat patients with Parkinson's disease, genetic dystonia and tremor. RNA sequencing was performed in tissues extracted from the recording microelectrodes and liquid chromatography-mass spectrometry (LC-MS) performed in tissues from guide tubes. To assess the performance of the current approach, the obtained datasets were compared with previously published datasets representing brain tissues. Altogether, 32,034 RNA transcripts representing the unique Ensembl gene identifiers were detected from eight samples representing both hemispheres of four patients. By using LC-MS, we identified 734 unique proteins from 31 samples collected from 14 patients. The datasets are available in the BioStudies database (accession number S-BSST667). Our results indicate that surgical instruments used in DBS installation retain brain material sufficient for protein and gene expression studies. Comparison with previously published datasets obtained with similar approach proved the robustness and reproducibility of the protocol. The instruments used during routine DBS surgery are a useful source for obtaining fresh brain tissues from living patients. This approach overcomes the issues that arise from using postmortem tissues, such as the effect of postmortem interval on transcriptomic and proteomic landscape of the brain, and can be used for studying molecular aspects of DBS-treatable diseases.
Postobstructive Pulmonary Edema after Nonlethal Suicidal Hanging
Authors: Jerry Shu-Hung Kuo, Sheng-Yuan Ruan, Chun-Ta Huang, Wei-Ting Chen
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Postobstructive Pulmonary Edema after Nonlethal Suicidal Hanging." American Journal of Respiratory and Critical Care Medicine, 204(11), pp. e113–e114
The Spatial Landscape of Progression and Immunoediting in Primary Melanoma at Single-Cell Resolution
Authors: Ajit J. Nirmal, Zoltan Maliga, Tuulia Vallius, Brian Quattrochi, Alyce A. Chen, Connor A. Jacobson, Roxanne J. Pelletier, Clarence Yapp, Raquel Arias-Camison, Yu-An Chen, Christine G. Lian, George F. Murphy, Sandro Santagata, Peter K. Sorger
Journal: Cancer Discovery (2022)

Cutaneous melanoma is a highly immunogenic malignancy that is surgically curable at early stages but life-threatening when metastatic. Here we integrate high-plex imaging, 3D high-resolution microscopy, and spatially resolved microregion transcriptomics to study immune evasion and immunoediting in primary melanoma. We find that recurrent cellular neighborhoods involving tumor, immune, and stromal cells change significantly along a progression axis involving precursor states, melanoma in situ, and invasive tumor. Hallmarks of immunosuppression are already detectable in precursor regions. When tumors become locally invasive, a consolidated and spatially restricted suppressive environment forms along the tumor-stromal boundary. This environment is established by cytokine gradients that promote expression of MHC-II and IDO1, and by PD1-PDL1-mediated cell contacts involving macrophages, dendritic cells, and T cells. A few millimeters away, cytotoxic T cells synapse with melanoma cells in fields of tumor regression. Thus, invasion and immunoediting can coexist within a few millimeters of each other in a single specimen. The reorganization of the tumor ecosystem in primary melanoma is an excellent setting in which to study immunoediting and immune evasion. Guided by classic histopathology, spatial profiling of proteins and mRNA reveals recurrent morphologic and molecular features of tumor evolution that involve localized paracrine cytokine signaling and direct cell-cell contact. This article is highlighted in the In This Issue feature, p. 1397.
A Novel Third-generation EGFR Tyrosine Kinase Inhibitor Abivertinib for EGFR T790M-mutant Non–Small Cell Lung Cancer: a Multicenter Phase I/II Study
Authors: Qing Zhou, Lin Wu, Pei Hu, Tongtong An, Jianying Zhou, Li Zhang, Xiao-Qing Liu, Feng Luo, Xin Zheng, Ying Cheng, Nong Yang, Junling Li, Jifeng Feng, Baohui Han, Yong Song, Kai Wang, Li Zhang, Jian Fang, Hong Zhao, Yongqian Shu, Xiao-Yan Lin, Zhihong Chen, Bin Gan, Wan-Hong Xu, Wei Tang, Xiaoying Zhang, Jin-Ji Yang, Xiao Xu, Yi-Long Wu
Journal: Clinical Cancer Research (2021)

To establish recommended phase II dose (RP2D) in phase I and evaluate safety and efficacy of abivertinib in patients with EGFR Thr790Met point mutation (T790M)-positive(+) non-small cell lung cancer (NSCLC) with disease progression from prior EGFR inhibitors in phase II.