bluuebunny/crossref_metadata_2025 huggingface dataset:
Associated Risk Factors and Diagnostic Value of Fiberoptic Bronchoscopy for Protracted Bacterial Bronchitis in Children
Authors: Zhang Rong , Wang Li , Gong Chen , Gao Hui , Li Wenhong , Bian Chenrong , Zhao Jiaying , Ding Shenggang , Zhu Yulin
Published: July 2023

Objective. Untreated protracted bacterial bronchitis (PBB), a chronic wet cough prevalent in children, may lead to chronic suppurative lung disease. However, clinical diagnostic criteria are currently nonspecific; thus, PBB may be misdiagnosed. Thus, we assessed the diagnostic value of fiberoptic bronchoscopy (FOB) and the risk factors associated with PBB. Methods. Children with chronic cough at The First Affiliated Hospital of Anhui Medical University from January 2015 to May 2020 were enrolled and allocated to a suspected PBB (n = 141) or a non-PBB (n = 206) group. All children underwent extensive laboratory, chest imaging, and allergen tests. Children with suspected PBB underwent FOB with bronchoalveolar lavage; lavage and sputum samples were cultured. Results. All 347 children had a chronic wet cough for approximately 2 months. Of 141 children with suspected PBB, 140 received FOB with bronchoalveolar lavage. Visible tracheal changes included pale mucosa, mucosal congestion, edema, swelling, and increased secretions attached to the wall. Sputum was visible primarily in the left main bronchus (78.7%), left lower lobe (59.6%), right upper lobe (62.4%), and right lower lobe (64.5%). Sputum properties and amounts significantly differed between children with vs. without PBB

P
<
0.05

. Dermatophagoides (odds ratio (OR), 2.642; 95% CI, 1.283–5.369), milk protein (OR, 2.452; 95% CI, 1.243–4.836) allergies, and eczema (OR, 1.763; 95% CI, 1.011–3.075) were risk factors significantly associated with PBB. Conclusion. Dermatophagoides, milk protein, and eczema were associated with an increased risk of PBB. Sputum distribution and tracheal wall changes observed through FOB may distinguish PBB and assist in its diagnosis.
The Evolution of Polarization in Online Conversation: Twitter Users’ Opinions about the COVID-19 Pandemic Become More Politicized over Time
Authors: Zhao Weize , Walasek Lukasz , Brown Gordon D. A.
Published: July 2023

Political polarization on social media has been extensively studied. However, most research has examined polarization about topics that have preexisting associations with ideology, while few studies have tracked the onset of polarization about novel topics or the evolution of polarization over a prolonged period. The occurrence of COVID-19 provides a unique opportunity to study whether social media discourse about a novel event becomes increasingly polarized along ideological lines over time. This paper analyzes trends in Twitter polarization in relation to COVID-19 and other geopolitical events of 2020. The first two studies use topic analysis to examine the evolving difference over time in discussions of COVID-19 and other topics by liberals and conservatives on social media. COVID-19-related polarization is initially absent but gradually increases over time, in contrast to polarization related to other events. A third study examines structural polarization in retweet networks and finds that the frequency of counterpartisan retweets reduces over time. Across all three studies, we find evidence that Twitter discussion of COVID-19 has become more polarized over time.
Supplementary Table 7_Genes identified by differential expression analysis in pro vs non metastatic clones from A Rare Subset of Primary Tumor Cells with Concomitant Hyperactivation of Extracellular Matrix Remodeling and dsRNA-IFN1 Signaling Metastasizes in Breast Cancer
Authors: Roda Niccolò , Cossa Andrea , Hillje Roman , Tirelli Andrea , Ruscitto Federica , Cheloni Stefano , Priami Chiara , Dalmasso Alberto , Gambino Valentina , Blandano Giada , Polazzi Andrea , Falvo Paolo , Gatti Elena , Mazzarella Luca , Luzi Lucilla , Migliaccio Enrica , Pelicci Pier Giuseppe
Published: July 2023

Supplementary Table reporting the Genes identified by differential expression analysis in pro vs non metastatic clones
Supplementary Table 1_Primer and shRNA sequences_PCR cycles_Mycoplasma testing from A Rare Subset of Primary Tumor Cells with Concomitant Hyperactivation of Extracellular Matrix Remodeling and dsRNA-IFN1 Signaling Metastasizes in Breast Cancer
Authors: Roda Niccolò , Cossa Andrea , Hillje Roman , Tirelli Andrea , Ruscitto Federica , Cheloni Stefano , Priami Chiara , Dalmasso Alberto , Gambino Valentina , Blandano Giada , Polazzi Andrea , Falvo Paolo , Gatti Elena , Mazzarella Luca , Luzi Lucilla , Migliaccio Enrica , Pelicci Pier Giuseppe
Published: July 2023

Supplementary table including information about Primer and shRNA sequences, PCR cycles, and Mycoplasma testing strategy
Supplementary Materials and Methods from A Rare Subset of Primary Tumor Cells with Concomitant Hyperactivation of Extracellular Matrix Remodeling and dsRNA-IFN1 Signaling Metastasizes in Breast Cancer
Authors: Roda Niccolò , Cossa Andrea , Hillje Roman , Tirelli Andrea , Ruscitto Federica , Cheloni Stefano , Priami Chiara , Dalmasso Alberto , Gambino Valentina , Blandano Giada , Polazzi Andrea , Falvo Paolo , Gatti Elena , Mazzarella Luca , Luzi Lucilla , Migliaccio Enrica , Pelicci Pier Giuseppe
Published: July 2023

Supplementary Materials and Methods, including a deeper characterisation of the Methods outlined in the Main manuscript and the description of additional analyses not included in the main text
Data from Caffeine Supplementation and FOXM1 Inhibition Enhance the Antitumor Effect of Statins in Neuroblastoma
Authors: Tran Gia-Buu , Ding Jane , Ye Bingwei , Liu Mengling , Yu Yajie , Zha Yunhong , Dong Zheng , Liu Kebin , Sudarshan Sunil , Ding Han-Fei
Published: July 2023

Abstract
High-risk neuroblastoma exhibits transcriptional activation of the mevalonate pathway that produces cholesterol and nonsterol isoprenoids. A better understanding of how this metabolic reprogramming contributes to neuroblastoma development could help identify potential prevention and treatment strategies. Here, we report that both the cholesterol and nonsterol geranylgeranyl-pyrophosphate branches of the mevalonate pathway are critical to sustain neuroblastoma cell growth. Blocking the mevalonate pathway by simvastatin, a cholesterol-lowering drug, impeded neuroblastoma growth in neuroblastoma cell line xenograft, patient-derived xenograft (PDX), and TH-MYCN transgenic mouse models. Transcriptional profiling revealed that the mevalonate pathway was required to maintain the FOXM1-mediated transcriptional program that drives mitosis. High FOXM1 expression contributed to statin resistance and led to a therapeutic vulnerability to the combination of simvastatin and FOXM1 inhibition. Furthermore, caffeine synergized with simvastatin to inhibit the growth of neuroblastoma cells and PDX tumors by blocking statin-induced feedback activation of the mevalonate pathway. This function of caffeine depended on its activity as an adenosine receptor antagonist, and the A2A adenosine receptor antagonist istradefylline, an add-on drug for Parkinson's disease, could recapitulate the synergistic effect of caffeine with simvastatin. This study reveals that the FOXM1-mediated mitotic program is a molecular statin target in cancer and identifies classes of agents for maximizing the therapeutic efficacy of statins, with implications for treatment of high-risk neuroblastoma.
Significance:
Caffeine treatment and FOXM1 inhibition can both enhance the antitumor effect of statins by blocking the molecular and metabolic processes that confer statin resistance, indicating potential combination therapeutic strategies for neuroblastoma.

See related commentary by Stouth et al., p. 2091
Data from β-Catenin–Driven Differentiation Is a Tissue-Specific Epigenetic Vulnerability in Adrenal Cancer
Authors: Mohan Dipika R. , Borges Kleiton S. , Finco Isabella , LaPensee Christopher R. , Rege Juilee , Solon April L. , Little Donald W. , Else Tobias , Almeida Madson Q. , Dang Derek , Haggerty-Skeans James , Apfelbaum April A. , Vinco Michelle , Wakamatsu Alda , Mariani Beatriz M.P. , Amorim Larissa Costa , Latronico Ana Claudia , Mendonca Berenice B. , Zerbini Maria Claudia N. , Lawlor Elizabeth R. , Ohi Ryoma , Auchus Richard J. , Rainey William E. , Marie Suely K.N. , Giordano Thomas J. , Venneti Sriram , Fragoso Maria Candida Barisson Villares , Breault David T. , Lerario Antonio Marcondes , Hammer Gary D.
Published: July 2023

Abstract
Adrenocortical carcinoma (ACC) is a rare cancer in which tissue-specific differentiation is paradoxically associated with dismal outcomes. The differentiated ACC subtype CIMP-high is prevalent, incurable, and routinely fatal. CIMP-high ACC possess abnormal DNA methylation and frequent β-catenin–activating mutations. Here, we demonstrated that ACC differentiation is maintained by a balance between nuclear, tissue-specific β-catenin–containing complexes, and the epigenome. On chromatin, β-catenin bound master adrenal transcription factor SF1 and hijacked the adrenocortical super-enhancer landscape to maintain differentiation in CIMP-high ACC; off chromatin, β-catenin bound histone methyltransferase EZH2. SF1/β-catenin and EZH2/β-catenin complexes present in normal adrenals persisted through all phases of ACC evolution. Pharmacologic EZH2 inhibition in CIMP-high ACC expelled SF1/β-catenin from chromatin and favored EZH2/β-catenin assembly, erasing differentiation and restraining cancer growth in vitro and in vivo. These studies illustrate how tissue-specific programs shape oncogene selection, surreptitiously encoding targetable therapeutic vulnerabilities.
Significance:
Oncogenic β-catenin can use tissue-specific partners to regulate cellular differentiation programs that can be reversed by epigenetic therapies, identifying epigenetic control of differentiation as a viable target for β-catenin–driven cancers.
Data from Attenuation of Sialylation Augments Antitumor Immunity and Improves Response to Immunotherapy in Ovarian Cancer
Authors: Cao Kankan , Zhang Guodong , Yang Moran , Wang Yiying , He Mengdi , Zhang Chen , Huang Yan , Lu Jiaqi , Liu Haiou
Published: July 2023

Abstract
Aberrant sialylation functions as an important modulator of all steps of malignant transformation. Therefore, targeting sialylation regulators, such as sialyltransferases and neuraminidases, is a potential strategy for treating cancer. Here, we found that elevated α2,3-sialyltransferase III (St3gal3) was associated with dismal prognosis in high-grade serous ovarian carcinoma (HGSC). St3gal3 knockdown antagonized subcutaneous tumor growth in immunocompetent, but not immunodeficient mice, with enhanced accumulation of functional CD8+ T cells and antitumor immune gene signatures. St3gal3 knockdown inhibited intraperitoneal tumor growth and repolarized tumor-associated macrophages from a protumorigenic M2-like to a tumor-suppressive M1-like phenotype. In vitro, St3gal3 knockdown tumor cells guided bone marrow–derived macrophages (BMDM) toward the M1-like phenotype under both direct contact and distant Transwell coculture conditions. Depletion of macrophages rescued the suppressed tumor growth induced by St3gal3 knockdown and completely suppressed infiltration of functional CD8+ T cells that rely on macrophage-derived CXCL10. St3gal3 engendered an immunosuppressive HGSC microenvironment characterized by an abundance of pro-tumorigenic macrophages and reduced cytotoxic T-cell infiltration. In vivo, St3gal3 knockdown improved effectiveness of dual immune checkpoint blockade (ICB) with αPD-1 and αCTLA4 antibodies. Preclinical inhibition of sialylation with ambroxol resulted in decreased tumor growth and prolonged the survival of tumor-bearing mice, which was enhanced by the addition of dual ICB. These findings indicate that altered sialylation induced by St3gal3 upregulation promotes a tumor-suppressive microenvironment in HGSC and targeting α2,3-sialylation may reprogram the immunosuppressive tumor microenvironment and improve the efficacy of immunotherapy.
Significance:
Blocking sialylation augments antitumor immunity and enhances response to immune checkpoint blockade therapy, highlighting a potential therapeutic approach for treating patients with high-grade serous ovarian cancer.
Supplementary Table 9 from Hepatocellular Carcinoma Surveillance among Individuals with Cirrhosis: Trends by Payer, Etiology, and Calendar Year, from a Statewide, Multi-Payer Dataset, 2010–2018
Authors: Hsu Christine D. , Henderson Louise M. , Jackson Bradford E. , Baggett Christopher D. , Funk Michele Jonsson , Olshan Andrew F. , Gupta Parul , Barritt A. Sidney , Sanoff Hanna K. , Wheeler Stephanie B. , Moon Andrew M. , Lund Jennifer L.
Published: July 2023

Supplementary Table 9 includes two-year cumulative incidences for HCC surveillance overall and by insurance type, by calendar year of cirrhosis diagnosis (% and 95% confidence intervals).
Supplementary Materials and Methods from Circulating Sex Hormone Levels and Risk of Gastrointestinal Cancer: Systematic Review and Meta-Analysis of Prospective Studies
Authors: Liu Zhiqiang , Zhang Yingfan , Lagergren Jesper , Li Shanshan , Li Jingru , Zhou Zhixian , Hu Zhijian , Xie Shao-Hua
Published: July 2023

This supplementary materials and methods section shows the detailed literature search strategies.
Supplementary Figure S2 from Circulating Sex Hormone Levels and Risk of Gastrointestinal Cancer: Systematic Review and Meta-Analysis of Prospective Studies
Authors: Liu Zhiqiang , Zhang Yingfan , Lagergren Jesper , Li Shanshan , Li Jingru , Zhou Zhixian , Hu Zhijian , Xie Shao-Hua
Published: July 2023

Supplementary Figure S2 shows forest plots (1), sensitivity analysis (2) and funnel plots (3) of the associations between prediagnostic circulating sex hormone levels and gastric cancer risk.
Supplementary Table S7 from Associations of Post-Diagnosis Lifestyle with Prognosis in Women with Invasive Breast Cancer
Authors: Troeschel Alyssa N. , Hartman Terryl J. , McCullough Lauren E. , Ergas Isaac J. , Collin Lindsay J. , Kwan Marilyn L. , Ambrosone Christine B. , Flanders W. Dana , Bradshaw Patrick T. , Cespedes Feliciano Elizabeth M. , Roh Janise M. , Wang Ying , Valice Emily , Kushi Lawrence H.
Published: July 2023

Subdistribution hazard ratios (sdHR) and 95% confidence intervals (95% CI) for the association of 2-year post-diagnosis lifestyle with breast cancer-specific mortality (n=1,736) and breast cancer recurrence (n=1,705).
Data from Tobacco Smoke Is a Major Source of Aromatic Amine Exposure in U.S. Adults: 2013–2014 National Health and Nutrition Examination Survey (NHANES)
Authors: Seyler Tiffany , Mazumder Shrila , Ahamed Rayaj , Zhu Wanzhe , Blount Benjamin C. , Apelberg Benjamin J. , Wang Lanqing
Published: July 2023

AbstractBackground:
Cigarette smoking increases the risk of cancer, cardiovascular diseases, and premature death. Aromatic amines (AA) are found in cigarette smoke and are well-established human bladder carcinogens.
Methods:
We measured and compared total urinary levels of 1-aminonaphthalene (1AMN), 2-aminonaphthalene (2AMN), and 4-aminobiphenyl (4ABP) in adults who smoked cigarettes exclusively and in adult nonusers of tobacco products from a nationally representative sample of non-institutionalized U.S. population in the 2013–2014 National Health and Nutrition Examination Survey.
Results:
Sample-weighted geometric mean concentrations of AAs in adults who smoked cigarettes exclusively compared with adult nonusers were 30 times higher for 1AMN and 4 to 6 times higher for 2AMN and 4ABP. We evaluated the association of tobacco-smoke exposure with urinary AAs using sample-weighted multiple linear regression models to control for age, sex, race/ethnicity, diet, and urinary creatinine. Secondhand smoke exposure status was categorized using serum cotinine (SCOT) among adult nonusers (SCOT ≤ 10 ng/mL). The exposure for adults who smoked cigarettes exclusively (SCOT > 10 ng/mL) was categorized on the basis of the average number of self-reported cigarettes smoked per day (CPD) in the five days prior to urine collection. The regression models show AAs concentration increased with increasing CPD (P < 0.001). Dietary-intake variables derived from the 24-hours recall questionnaire were not consistently significant predictors of urinary AAs.
Conclusions:
This is the first characterized total urinary AA concentrations of the U.S. adult non-institutionalized population. Our analyses show that smoking status is a major contributor to AA exposures.
Impact:
These data provide a crucial baseline for exposure to three AAs in U.S. non-institutionalized adults.
Data from Updated Review of Major Cancer Risk Factors and Screening Test use in the United States, with a Focus on Changes During the COVID-19 Pandemic
Authors: Star Jessica , Bandi Priti , Nargis Nigar , Islami Farhad , Yabroff K. Robin , Minihan Adair K. , Smith Robert A. , Jemal Ahmedin
Published: July 2023

Abstract
We present national and state representative prevalence estimates of modifiable cancer risk factors, preventive behaviors and services, and screening, with a focus on changes during the COVID-19 pandemic. Between 2019 and 2021, current smoking, physical inactivity, and heavy alcohol consumption declined, and human papillomavirus vaccination and stool testing for colorectal cancer screening uptake increased. In contrast, obesity prevalence increased, while fruit consumption and cervical cancer screening declined during the same timeframe. Favorable and unfavorable trends were evident during the second year of the COVID-19 pandemic that must be monitored as more years of consistent data are collected. Yet disparities by racial/ethnic and socioeconomic status persisted, highlighting the continued need for interventions to address suboptimal levels among these population subgroups.
Data from Associations of Post-Diagnosis Lifestyle with Prognosis in Women with Invasive Breast Cancer
Authors: Troeschel Alyssa N. , Hartman Terryl J. , McCullough Lauren E. , Ergas Isaac J. , Collin Lindsay J. , Kwan Marilyn L. , Ambrosone Christine B. , Flanders W. Dana , Bradshaw Patrick T. , Cespedes Feliciano Elizabeth M. , Roh Janise M. , Wang Ying , Valice Emily , Kushi Lawrence H.
Published: July 2023

AbstractBackground:
Lifestyle habits can impact breast cancer development, but its impact on breast cancer prognosis remains unclear. We investigated associations of post-diagnosis lifestyle with mortality and recurrence in 1,964 women with invasive breast cancer enrolled in the Kaiser Permanente Northern California Pathways Study shortly after diagnosis with lifestyle information at baseline (2005–2013) and the 2-year follow-up.
Methods:
We calculated a post-diagnosis lifestyle score (range, 0–18) based on 9 diet, physical activity, and body weight recommendations from the American Cancer Society/American Society of Clinical Oncology (ACS/ASCO) using follow-up data (body weight also included baseline data); higher scores indicate greater guideline concordance. Similarly, we calculated a pre-diagnosis lifestyle score using baseline data to investigate pre- to post-diagnosis changes. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazard models, with follow-up through December 2018 (observing 290 deaths and 176 recurrences).
Results:
The 2-year post-diagnosis lifestyle score was inversely associated with all-cause mortality (ACM; HR per 2-point increase = 0.90; 95% CI, 0.82–0.98), and breast cancer–related mortality (HR, 0.79; 95% CI, 0.67–0.95), but not recurrence. Relative to women who maintained low concordance with recommendations at both time points, women who maintained high concordance had a lower risk of ACM (HR, 0.61, 95% CI, 0.37–1.03). Improved concordance with some specific recommendations (particularly PA) may be associated with a lower hazard of ACM (HRPA, 0.52; 95% CI, 0.35–0.78).
Conclusions:
Results suggest that women with breast cancer may benefit from a post-diagnosis lifestyle aligned with ACS/ASCO guidelines.
Impact:
This information may potentially guide lifestyle recommendations for breast cancer survivors to reduce mortality risk.
Data from Recent Mortality Patterns and Time Trends for the Major Cancers in 47 Countries Worldwide
Authors: Sedeta Ephrem , Sung Hyuna , Laversanne Mathieu , Bray Freddie , Jemal Ahmedin
Published: July 2023

AbstractBackground:
Most prior studies have reported cancer mortality trends across countries for specific cancer types. Herein, we examine recent patterns and trends in cancer mortality rates for the eight common forms of cancer in 47 countries across five continents (except Africa) based on the World Health Organization mortality database.
Methods:
Rates were age-standardized to the 1966 Segi-Doll world population, and trends in the age-standardized rates for the most recent 10 years of data were examined using Joinpoint regression.
Results:
Cancer-specific mortality rates vary substantially across countries, with rates of infection-related (cervix and stomach) and tobacco-related cancers (lung and esophagus) varying by 10-fold. Recent mortality rates for all major cancers decreased in most of the studied countries except lung cancer in females and liver cancer in males, where increasing rates were observed in most countries. Rates decreased or stabilized in all countries for lung cancer in men and stomach cancer in both sexes.
Conclusions:
The findings reinforce the importance of implementing and strengthening resource-stratified and targeted cancer prevention and control programs in all parts of the world to further reduce or halt the rising cancer burden.
Impact:
The results may inform cancer prevention and treatment strategies and in so doing, reduce the marked global cancer disparities observed today.
Data from Circulating Sex Hormone Levels and Risk of Gastrointestinal Cancer: Systematic Review and Meta-Analysis of Prospective Studies
Authors: Liu Zhiqiang , Zhang Yingfan , Lagergren Jesper , Li Shanshan , Li Jingru , Zhou Zhixian , Hu Zhijian , Xie Shao-Hua
Published: July 2023

AbstractBackground:
Sex hormones may influence the development of gastrointestinal cancer, but evidence is inconsistent.
Methods:
We systematically searched MEDLINE and Embase databases to identify prospective studies examining associations between prediagnostic circulating levels of sex hormones and risk of five gastrointestinal cancers: esophageal, gastric, liver, pancreatic, and colorectal cancer. Pooled ORs and 95% confidence intervals (95% CI) were calculated using random-effects models.
Results:
Among 16,879 identified studies, 29 were included (11 cohort, 15 nested case–control, and three case–cohort studies). Comparing the highest versus lowest tertiles, levels of most sex hormones were not associated with the studied tumors. Higher levels of sex hormone binding globulin (SHBG) were associated with increased risk of gastric cancer (OR = 1.35; 95% CI, 1.06–1.72), but such associations were restricted in men only (OR = 1.43; 95% CI, 1.10–1.85) when stratified by sex. Higher SHBG levels were associated with increased risk of liver cancer (OR = 2.07; 95% CI, 1.40–3.06). Higher testosterone levels were associated with increased risk of liver cancer overall (OR = 2.10; 95% CI, 1.48–2.96), particularly in men (OR = 2.63; 95% CI, 1.65–4.18), Asian populations (OR = 3.27; 95% CI, 1.57–6.83), and in hepatitis B surface antigen-positive individuals (OR = 3.90; 95% CI, 1.43–10.64). Higher levels of SHBG and testosterone were associated with decreased risk of colorectal cancer in men (OR = 0.89; 95% CI, 0.80–0.98 and OR = 0.88; 95% CI, 0.80–0.97, respectively) but not in women.
Conclusions:
Circulating levels of SHBG and testosterone may influence the risk of gastric, liver, and colorectal cancer.
Impact:
Further clarifying the role of sex hormones in the development of gastrointestinal cancer may unravel future novel targets for prevention and treatment.
Data from Hepatocellular Carcinoma Surveillance among Individuals with Cirrhosis: Trends by Payer, Etiology, and Calendar Year, from a Statewide, Multi-Payer Dataset, 2010–2018
Authors: Hsu Christine D. , Henderson Louise M. , Jackson Bradford E. , Baggett Christopher D. , Funk Michele Jonsson , Olshan Andrew F. , Gupta Parul , Barritt A. Sidney , Sanoff Hanna K. , Wheeler Stephanie B. , Moon Andrew M. , Lund Jennifer L.
Published: July 2023

AbstractBackground:
Hepatocellular carcinoma (HCC) surveillance is underutilized, with <25% of individuals with cirrhosis receiving surveillance exams as recommended. The epidemiology of cirrhosis and HCC in the United States has also shifted in recent years, but little is known about recent trends in surveillance utilization. We characterized patterns of HCC surveillance by payer, cirrhosis etiology, and calendar year in insured individuals with cirrhosis.
Methods:
We conducted a retrospective cohort study of individuals with cirrhosis using claims data from Medicare, Medicaid, and private insurance plans in North Carolina. We included individuals ≥ 18 years with a first occurrence of an ICD-9/10 code for cirrhosis between January 1, 2010, and June 30, 2018. The outcome was HCC surveillance by abdominal ultrasound, CT, or MRI. We estimated 1- and 2-year cumulative incidences for HCC surveillance and assessed longitudinal adherence to surveillance by computing the proportion of time covered (PTC).
Results:
Among 46,052 individuals, 71% were enrolled through Medicare, 15% through Medicaid, and 14% through private insurance. The overall 1-year cumulative incidence of HCC surveillance was 49% and the 2-year cumulative incidence was 55%. For those with an initial screen in the first 6 months of their cirrhosis diagnosis, the median 2-year PTC was 67% (Q1, 38%; Q3, 100%).
Conclusions:
HCC surveillance initiation after cirrhosis diagnosis remains low, though it has improved slightly over time, particularly among individuals with Medicaid.
Impact:
This study provides insight into recent trends in HCC surveillance and highlights areas to target for future interventions, particularly among patients with nonviral etiologies.
Data from Incidence Trends and Survival in Early-Onset Esophagogastric Adenocarcinoma: A Swedish Population-Based Cohort Study
Authors: Radkiewicz Cecilia , Asplund Johannes , Lagergren Jesper
Published: July 2023

AbstractBackground:
Early-onset adenocarcinomas of different sites are increasing in high-income countries, data on esophagogastric adenocarcinoma are sparse.
Methods:
We performed a Swedish population-based cohort study over 1993 to 2019 to delineate differences in incidence and survival in early-onset (age 20–54 years) compared with later-onset (55–99 years) esophageal, cardia, and noncardia gastric adenocarcinoma. Temporal incidence trends were quantified as annual percentage changes (APC) and survival differences as excess mortality rate ratios (EMRR) using Poisson regression and including 95% confidence intervals (CI).
Results:
Among 27,854 patients with esophagogastric adenocarcinoma, 2,576 were early-onset whereof 470 were esophageal, 645 were cardia, and 1,461 were noncardia gastric. Except noncardia gastric, the male predominance was larger in early-onset compared with later-onset disease. Advanced stage and signet ring cell morphology were more common among early-onset patients. Early-onset and later-onset APC estimates were comparable and esophageal adenocarcinoma incidence increased, cardia remained stable, and noncardia gastric decreased. Early-onset patients had better survival than later-onset, which was amplified when adjusting for prognostic factors including stage [adjusted EMRR 0.73 (95% CI, 0.63–0.85) in esophageal, 0.75 (95% CI, 0.65–0.86) in cardia, and 0.67 (95% CI, 0.61–0.74) in noncardia gastric adenocarcinoma]. The early-onset survival advantage was more pronounced in localized stages 0 to II (all sites) and women (esophageal and noncardia gastric).
Conclusions:
We found no major differences in incidence trends comparing early-onset and later-onset esophagogastric adenocarcinoma. Despite unfavorable prognostic features, early-onset esophagogastric adenocarcinoma survival was better than later-onset, particularly in localized stages and women.
Impact:
Our findings suggest delayed diagnosis in younger individuals and especially men.
Supplementary Table S3 from Loss of CDKN2A Cooperates with WWTR1(TAZ)–CAMTA1 Gene Fusion to Promote Tumor Progression in Epithelioid Hemangioendothelioma
Authors: Seavey Caleb N. , Hallett Andrea , Li Shuo , Che Kepeng , Pobbati Ajaybabu V. , Ma Shuang , Burtscher Ashley , Kanai Ryan , Lamar John M. , Rubin Brian P.
Published: July 2023

Supplemental Table 3. Single cell RNA sequencing of GEMM EHE tumorsDifferentially expressed genes between normal endothelial cells and Cdkn2a WT and KO tumors by single cell RNA sequencing. Functional annotations with the gene ontology sets are displayed for the Cdkn2a KO vs WT comparison, graphically displayed in Figure 3D. Transcripts used for the EHE tumor gene set are similarly displayed.
Supplementary Table S1 from Loss of CDKN2A Cooperates with WWTR1(TAZ)–CAMTA1 Gene Fusion to Promote Tumor Progression in Epithelioid Hemangioendothelioma
Authors: Seavey Caleb N. , Hallett Andrea , Li Shuo , Che Kepeng , Pobbati Ajaybabu V. , Ma Shuang , Burtscher Ashley , Kanai Ryan , Lamar John M. , Rubin Brian P.
Published: July 2023

Supplemental Table 1. Mouse Short Tandem Repeat (STR) loci for all three cell linesShort tandem repeat analysis of each EHE cell line and using both mouse and human loci. Human defining loci were undetected in all three cell lines.
Supplementary Figure S3 from Loss of CDKN2A Cooperates with WWTR1(TAZ)–CAMTA1 Gene Fusion to Promote Tumor Progression in Epithelioid Hemangioendothelioma
Authors: Seavey Caleb N. , Hallett Andrea , Li Shuo , Che Kepeng , Pobbati Ajaybabu V. , Ma Shuang , Burtscher Ashley , Kanai Ryan , Lamar John M. , Rubin Brian P.
Published: July 2023

Validation of the EHE cell lines
Supplementary Table 3 from Clinicopathologic, Genomic, and Immunophenotypic Landscape of ATM Mutations in Non–Small Cell Lung Cancer
Authors: Ricciuti Biagio , Elkrief Arielle , Alessi Joao , Wang Xinan , Li Yvonne , Gupta Hersh , Muldoon Daniel M. , Bertram Arrien A. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Barrichello Adriana , Vaz Victor R. , Gandhi Malini , Lee Elinton , Shapiro Geoffrey I. , Park Hyesun , Nishino Mizuki , Lindsay James , Felt Kristen D. , Sharma Bijaya , Cherniack Andrew D. , Rodig Scott , Gomez Daniel R. , Shaverdian Narek , Rakaee Mehrdad , Bandlamudi Chaitanya , Ladanyi Marc , Janne Pasi A. , Schoenfeld Adam J. , Sholl Lynette M. , Awad Mark M. , Cheng Michael L.
Published: July 2023

Supplementary Table 3. Baseline clinicopathologic features of patients with ATMMUT and ATMWT NSCLC at the Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center.
Supplementary Figure 28 from Clinicopathologic, Genomic, and Immunophenotypic Landscape of ATM Mutations in Non–Small Cell Lung Cancer
Authors: Ricciuti Biagio , Elkrief Arielle , Alessi Joao , Wang Xinan , Li Yvonne , Gupta Hersh , Muldoon Daniel M. , Bertram Arrien A. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Barrichello Adriana , Vaz Victor R. , Gandhi Malini , Lee Elinton , Shapiro Geoffrey I. , Park Hyesun , Nishino Mizuki , Lindsay James , Felt Kristen D. , Sharma Bijaya , Cherniack Andrew D. , Rodig Scott , Gomez Daniel R. , Shaverdian Narek , Rakaee Mehrdad , Bandlamudi Chaitanya , Ladanyi Marc , Janne Pasi A. , Schoenfeld Adam J. , Sholl Lynette M. , Awad Mark M. , Cheng Michael L.
Published: July 2023

Supplementary Figure 28. (A) Box-plot showing the distribution of tumor-infiltrating lymphocytes assessed using computational pathology algorithm in ATMMUT and ATMWT NSCLCs. (B) Box-plot showing the distribution of tumor-infiltrating lymphocytes assessed using computational pathology algorithm in according to ATM/TP53 co-mutation status in NSCLC.
Supplementary Figure 25 from Clinicopathologic, Genomic, and Immunophenotypic Landscape of ATM Mutations in Non–Small Cell Lung Cancer
Authors: Ricciuti Biagio , Elkrief Arielle , Alessi Joao , Wang Xinan , Li Yvonne , Gupta Hersh , Muldoon Daniel M. , Bertram Arrien A. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Barrichello Adriana , Vaz Victor R. , Gandhi Malini , Lee Elinton , Shapiro Geoffrey I. , Park Hyesun , Nishino Mizuki , Lindsay James , Felt Kristen D. , Sharma Bijaya , Cherniack Andrew D. , Rodig Scott , Gomez Daniel R. , Shaverdian Narek , Rakaee Mehrdad , Bandlamudi Chaitanya , Ladanyi Marc , Janne Pasi A. , Schoenfeld Adam J. , Sholl Lynette M. , Awad Mark M. , Cheng Michael L.
Published: July 2023

Supplementary Figure 25. (A) Intratumoral, (B) tumor-stroma interface, and (C) total CD8+ PD1+ T cells according to ATM/TP53 co-mutation status. (D) Intratumoral, (E) tumor-stroma interface, and (F) total FOXP3+ immune cells according to ATM/TP53 co-mutation status.
Supplementary Figure 20 from Clinicopathologic, Genomic, and Immunophenotypic Landscape of ATM Mutations in Non–Small Cell Lung Cancer
Authors: Ricciuti Biagio , Elkrief Arielle , Alessi Joao , Wang Xinan , Li Yvonne , Gupta Hersh , Muldoon Daniel M. , Bertram Arrien A. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Barrichello Adriana , Vaz Victor R. , Gandhi Malini , Lee Elinton , Shapiro Geoffrey I. , Park Hyesun , Nishino Mizuki , Lindsay James , Felt Kristen D. , Sharma Bijaya , Cherniack Andrew D. , Rodig Scott , Gomez Daniel R. , Shaverdian Narek , Rakaee Mehrdad , Bandlamudi Chaitanya , Ladanyi Marc , Janne Pasi A. , Schoenfeld Adam J. , Sholl Lynette M. , Awad Mark M. , Cheng Michael L.
Published: July 2023

Supplementary Figure 20. (A) Intratumoral, (B) tumor-stroma interface, and (C) total CD8+ T cells in ATMMUT and ATMWT NSCLCs. (D) Intratumoral, (E) tumor-stroma interface, and (F) total PD1+ immune cells in ATMMUT and ATMWT NSCLCs.
Supplementary Figure 14 from Clinicopathologic, Genomic, and Immunophenotypic Landscape of ATM Mutations in Non–Small Cell Lung Cancer
Authors: Ricciuti Biagio , Elkrief Arielle , Alessi Joao , Wang Xinan , Li Yvonne , Gupta Hersh , Muldoon Daniel M. , Bertram Arrien A. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Barrichello Adriana , Vaz Victor R. , Gandhi Malini , Lee Elinton , Shapiro Geoffrey I. , Park Hyesun , Nishino Mizuki , Lindsay James , Felt Kristen D. , Sharma Bijaya , Cherniack Andrew D. , Rodig Scott , Gomez Daniel R. , Shaverdian Narek , Rakaee Mehrdad , Bandlamudi Chaitanya , Ladanyi Marc , Janne Pasi A. , Schoenfeld Adam J. , Sholl Lynette M. , Awad Mark M. , Cheng Michael L.
Published: July 2023

Supplementary Figure 14. (A) Objective response rate, (B) progression-free survival, and (C) overall survival to PD-(L)1 immune checkpoint blockade monotherapy among patients with advanced/metastatic PD-L1 negative (<1%) NSCLC, according to ATM mutation status. (D) Objective response rate, (E) progression-free survival, and (F) overall survival to PD-(L)1 immune checkpoint blockade monotherapy among patients with advanced/metastatic PD-L1 intermediate (1-49%) NSCLC, according to ATM mutation status. (G) Objective response rate, (H) progression-free survival, and (I) overall survival to PD-(L)1 immune checkpoint blockade monotherapy among patients with advanced/metastatic PD-L1 high (≥50%) NSCLC, according to ATM mutation status.
Supplementary Figure 11 from Clinicopathologic, Genomic, and Immunophenotypic Landscape of ATM Mutations in Non–Small Cell Lung Cancer
Authors: Ricciuti Biagio , Elkrief Arielle , Alessi Joao , Wang Xinan , Li Yvonne , Gupta Hersh , Muldoon Daniel M. , Bertram Arrien A. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Barrichello Adriana , Vaz Victor R. , Gandhi Malini , Lee Elinton , Shapiro Geoffrey I. , Park Hyesun , Nishino Mizuki , Lindsay James , Felt Kristen D. , Sharma Bijaya , Cherniack Andrew D. , Rodig Scott , Gomez Daniel R. , Shaverdian Narek , Rakaee Mehrdad , Bandlamudi Chaitanya , Ladanyi Marc , Janne Pasi A. , Schoenfeld Adam J. , Sholl Lynette M. , Awad Mark M. , Cheng Michael L.
Published: July 2023

Supplementary Figure 11. Overall survival since the date of initial diagnosis among patients with stage IV NSCLC according to ATM mutation status.
Supplementary Figure S8 from Phase I Study of SYNB1891, an Engineered E. coli Nissle Strain Expressing STING Agonist, with and without Atezolizumab in Advanced Malignancies
Authors: Luke Jason J. , Piha-Paul Sarina A. , Medina Theresa , Verschraegen Claire F. , Varterasian Mary , Brennan Aoife M. , Riese Richard J. , Sokolovska Anna , Strauss James , Hava David L. , Janku Filip
Published: July 2023

Supplemental Figure 8. Representative immunofluorescence images for patient 200-003 and 100-005.
Supplementary Table 5 from RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
Authors: Compadre Amanda J. , van Biljon Lillian N. , Valentine Mark C. , Llop-Guevara Alba , Graham Emily , Fashemi Bisiayo , Herencia-Ropero Andrea , Kotnik Emilee N. , Cooper Isaac , Harrington Shariska P. , Kuroki Lindsay M. , McCourt Carolyn K. , Hagemann Andrea R. , Thaker Premal H. , Mutch David G. , Powell Matthew A. , Sun Lulu , Mosammaparast Nima , Serra Violeta , Zhao Peinan , Lomonosova Elena , Khabele Dineo , Mullen Mary M.
Published: July 2023

Patient characteristics of FFPE validation cohort
Supplemental Table S7 from Clonal Hematopoiesis in Young Women Treated for Breast Cancer
Authors: Gibson Christopher J. , Fell Geoffrey , Sella Tal , Sperling Adam S. , Snow Craig , Rosenberg Shoshana M. , Kirkner Greg , Patel Ashka , Dillon Deborah , Bick Alexander G. , Neuberg Donna , Partridge Ann H. , Miller Peter G.
Published: July 2023

Possible germline mutations (VAF > 0.35) predicted to impair protein function via premature stop (nonsense), splicing alterations, or a frameshift
Supplementary Table 2 from RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
Authors: Compadre Amanda J. , van Biljon Lillian N. , Valentine Mark C. , Llop-Guevara Alba , Graham Emily , Fashemi Bisiayo , Herencia-Ropero Andrea , Kotnik Emilee N. , Cooper Isaac , Harrington Shariska P. , Kuroki Lindsay M. , McCourt Carolyn K. , Hagemann Andrea R. , Thaker Premal H. , Mutch David G. , Powell Matthew A. , Sun Lulu , Mosammaparast Nima , Serra Violeta , Zhao Peinan , Lomonosova Elena , Khabele Dineo , Mullen Mary M.
Published: July 2023

Patient characteristics of patient-derived ovarian cancer cells
Supplementary Figure S2 from RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
Authors: Compadre Amanda J. , van Biljon Lillian N. , Valentine Mark C. , Llop-Guevara Alba , Graham Emily , Fashemi Bisiayo , Herencia-Ropero Andrea , Kotnik Emilee N. , Cooper Isaac , Harrington Shariska P. , Kuroki Lindsay M. , McCourt Carolyn K. , Hagemann Andrea R. , Thaker Premal H. , Mutch David G. , Powell Matthew A. , Sun Lulu , Mosammaparast Nima , Serra Violeta , Zhao Peinan , Lomonosova Elena , Khabele Dineo , Mullen Mary M.
Published: July 2023

γH2AX score in established and patient-derived ovarian cancer cell lines and patient-derived organoids
Supplementary Figure S1 from RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
Authors: Compadre Amanda J. , van Biljon Lillian N. , Valentine Mark C. , Llop-Guevara Alba , Graham Emily , Fashemi Bisiayo , Herencia-Ropero Andrea , Kotnik Emilee N. , Cooper Isaac , Harrington Shariska P. , Kuroki Lindsay M. , McCourt Carolyn K. , Hagemann Andrea R. , Thaker Premal H. , Mutch David G. , Powell Matthew A. , Sun Lulu , Mosammaparast Nima , Serra Violeta , Zhao Peinan , Lomonosova Elena , Khabele Dineo , Mullen Mary M.
Published: July 2023

Flow diagram of HGSOC patient-derived samples used for RAD51 foci assay
Supplementary Figure S2 from A Phase II Redifferentiation Trial with Dabrafenib-Trametinib and 131I in Metastatic Radioactive Iodine Refractory BRAF p.V600E-Mutated Differentiated Thyroid Cancer
Authors: Leboulleux Sophie , Do Cao Christine , Zerdoud Slimane , Attard Marie , Bournaud Claire , Lacroix Ludovic , Benisvy Danielle , Taïeb David , Bardet Stéphane , Terroir-Cassou-Mounat Marie , Anizan Nadège , Bouvier-Morel Emilie , Lamartina Livia , Lion Georges , Betrian Sarah , Sajous Christophe , Schiazza Aurélie , Garcia Marie-Eve , Ciappuccini Renaud , Schlumberger Martin , Al Ghuzlan Abir , Godbert Yann , Borget Isabelle
Published: July 2023

Swimmer plot of central RECIST response
Supplementary Table S1 from Patient-Reported Outcomes as Interradiographic Predictors of Response in Non–Small Cell Lung Cancer
Authors: Bhatt Ambika , Schabath Matthew B. , Hoogland Aasha I. , Jim Heather S.L. , Brady-Nicholls Renee
Published: July 2023

Patient demographics table
Data from Loss of CDKN2A Cooperates with WWTR1(TAZ)–CAMTA1 Gene Fusion to Promote Tumor Progression in Epithelioid Hemangioendothelioma
Authors: Seavey Caleb N. , Hallett Andrea , Li Shuo , Che Kepeng , Pobbati Ajaybabu V. , Ma Shuang , Burtscher Ashley , Kanai Ryan , Lamar John M. , Rubin Brian P.
Published: July 2023

AbstractPurpose:
Epithelioid hemangioendothelioma (EHE) is a vascular sarcoma caused by the WWTR1(TAZ)–CAMTA1 (TC) gene fusion. This fusion gene has been observed in almost all reported EHE cases and functions as a constitutively activated TAZ. Sequencing of human tumors has, however, identified additional secondary mutations in approximately 50% of EHE, most commonly the loss of tumor suppressor CDKN2A. In this study, the effect of loss of CDKN2A in EHE tumorigenesis was evaluated.
Experimental Design:
Mice bearing a conditional TC allele were paired with a conditional Cdkn2a knockout allele and an endothelial-specific Cre. Histologic characterization and single-cell RNA-seq of the resultant tumors were performed. EHE cell lines were established through ex vivo culture of tumor cells and evaluated for sensitivity to TEAD inhibition and trametinib.
Results:
Loss of Cdkn2a within EHE was associated with more aggressive disease, as displayed by earlier tumor-related morbidity/mortality and enhanced tumor cell proliferation. As no previous EHE cell lines exist, we attempted, successfully, to expand EHE tumor cells ex vivo and produced the first EHE cell lines. These cell lines are “addicted” to the TC oncoprotein, replicate the EHE transcriptional profile, and generate EHE tumors when injected into immunodeficient mice.
Conclusions:
CDKN2A loss enhances the tumorigenicity of EHE in vivo and enabled the generation of the first cell lines of this disease. These cell lines replicate key facets of the human disease phenotype. Therefore, these cell lines and allograft tumors generated after implantation serve as robust model systems for therapeutic testing of compounds directed at either EHE or other TAZ-driven cancers.
Data from Anticoagulants Enhance Molecular and Cellular Immunotherapy of Cancer by Improving Tumor Microcirculation Structure and Function and Redistributing Tumor Infiltrates
Authors: Wei Fang , Su Yuling , Quan Yibo , Li Xiaojia , Zou Qi , Zhang Liuxi , Li Shu , Jiang Mengmeng , Lin Guohuan , Liang Ping , He Jie , Xie Keping
Published: July 2023

AbstractPurpose:
Pancreatic ductal adenocarcinoma (PDA) resists immunotherapy of adoptive cell transfer (ACT) and immune checkpoint inhibitors. Understanding the mechanisms underlying this resistance will improve PDA immunotherapy. This study investigated therapeutic effects and underlying mechanisms of anticoagulants on immunotherapy in PDA.
Experimental Design:
The antitumor activity of immunotherapy was evaluated in mouse models of desert, excluded, and inflamed tumors. The underlying mechanisms were investigated by analyzing immune cell infiltration by immunofluorescence imaging and tumor microcirculation by interstitial fluid pressure and coagulation status measurement.
Results:
Combined use of heparin and ACT inhibited tumor growth and metastasis, whereas neither heparin nor ACT had any therapeutic effect. The combination of heparin and ACT significantly increased the intratumor infiltration of CD8+ T cells and M1 macrophages and reduced the infiltration of immunosuppressive M2 macrophages and FOXP3+/CD4+ regulatory T cells (Treg). Assessments of tumor microenvironment revealed that heparin promoted tumor vascular regression and normalized the remaining blood vessels, facilitating the extravasation and perivascular accumulation of activated CD8+ T cells in tumors. Mechanistically, tumor microvessel hemodynamic properties were significantly improved by heparin, which is consistent with its inhibitory effects on tumor angiogenesis. Similarly, the combination of heparin and anti-PD1 also produced a pronounced antitumor activity, whereas neither heparin nor anti-PD1 treatment had appreciable antitumor activity.
Conclusions:
Combined treatment of heparin and ACT or anti-PD1 produced synergistic antitumor effects, which were at least in part through tumor vascular normalization, hence increased antitumor T-cell responses due to reduced Treg infiltration and increased M1 macrophage polarization. This synergistic combination therapy warrants clinical evaluation.

See related commentary by Korc, p. 2348
Data from Increased Nerve Density Adversely Affects Outcome in Oral Cancer
Authors: Perez-Pacheco Cindy , Schmitd Ligia B. , Furgal Allison , Bellile Emily L. , Liu Min , Fattah Aya , Gonzalez-Maldonado Laura , Unsworth Shelby P. , Wong Sunny Y. , Rozek Laura S. , Rao Arvind , Wolf Gregory T. , Taylor Jeremy M.G. , Casper Keith , Mierzwa Michelle , D'Silva Nisha J.
Published: July 2023

AbstractPurpose:
Perineural invasion (PNI) in oral cavity squamous cell carcinoma (OSCC) is associated with poor survival. Because of the risk of recurrence, patients with PNI receive additional therapies after surgical resection. Mechanistic studies have shown that nerves in the tumor microenvironment promote aggressive tumor growth. Therefore, in this study, we evaluated whether nerve density (ND) influences tumor growth and patient survival. Moreover, we assessed the reliability of artificial intelligence (AI) in evaluating ND.
Experimental Design:
To investigate whether increased ND in OSCC influences patient outcome, we performed survival analyses. Tissue sections of OSCC from 142 patients were stained with hematoxylin and eosin and IHC stains to detect nerves and tumor. ND within the tumor bulk and in the adjacent 2 mm was quantified; normalized ND (NND; bulk ND/adjacent ND) was calculated. The impact of ND on tumor growth was evaluated in chick chorioallantoic-dorsal root ganglia (CAM-DRG) and murine surgical denervation models. Cancer cells were grafted and tumor size quantified. Automated nerve detection, applying the Halo AI platform, was compared with manual assessment.
Results:
Disease-specific survival decreased with higher intratumoral ND and NND in tongue SCC. Moreover, NND was associated with worst pattern-of-invasion and PNI. Increasing the number of DRG, in the CAM-DRG model, increased tumor size. Reduction of ND by denervation in a murine model decreased tumor growth. Automated and manual detection of nerves showed high concordance, with an F1 score of 0.977.
Conclusions:
High ND enhances tumor growth, and NND is an important prognostic factor that could influence treatment selection for aggressive OSCC.

See related commentary by Hondermarck and Jiang, p. 2342