bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR10: High-throughput functional and multi-omic single-cell characterization to elucidate ovarian intratumor and microenvironmental heterogeneity
Authors: Beaumont Kristin G. , Hake Austin , Wang Ying-Chih , Shah Hardik , Allette Kimaada , Hamou Wissam , Dave Arpit , Andreou Christina , Strahl Maya , Arib Hanane , Antoine Alesia , Ellis Ethan , Smith Melissa , Dottino Peter , Martignetti John , Schadt Eric E. , Sebra Robert P. 
Published: September 2020

Abstract
The genetic and functional complexity of bulk tumor tissue and its associated microenvironment, comprising heterogeneous cellular clones, has become more evident due to rapid advances in single-cell and deep-sequencing technologies. In this research, we present methods to better characterize clonal diversity from patient-derived cell lines and tumor biopsies at the single-cell level. We will profile intratumor and microenvironmental heterogeneity through single-cell selection, single-cell DNA and RNA sequencing, and real-time functional data. In addition to genetic data, single-cell real-time growth dynamics alongside CA125 secretion will be discussed as real-time functional assays. This approach uses bulk or discriminate selection of cells based on phenotype across a broad range of cellular inputs. Targeted cells from the tumor and its microenvironment were manipulated using light-induced dielectrophoresis into holding areas on the BLI Beacon platform for single-cell isolation and/or culture for monitoring growth kinetics and conducting functional screening. Hundreds to thousands of independent cells or batches were selected from resected tumor and adjacent tissue; genomic DNA was amplified and characterized using Ion Torrent AmpliSeq targeted panels and/or MissionBio Tapestri scDNA-Seq. Collectively this genomic data were used to identify cellular clonality and better address the degree of clonal heterogeneity across these tumors when compared to bulk sequencing. Specifically, growth kinetics, differential expression, and TP53 mutation profiling will be discussed in the context of several pilot primary tumor-derived samples. Orthogonal RNA-Seq data obtained using 1,500-5,000 cells per sample for 3’ mRNA scRNA-Seq on the 10X Genomics Chromium platform will also be discussed. Through the integration of these technologies, we hope to showcase an efficient and comprehensive method for assessing intratumor and microenvironmental heterogeneity.
This abstract is also being presented as Poster B53.
Citation Format: Kristin G. Beaumont, Austin Hake, Ying-Chih Wang, Hardik Shah, Kimaada Allette, Wissam Hamou, Arpit Dave, Christina Andreou, Maya Strahl, Hanane Arib, Alesia Antoine, Ethan Ellis, Melissa Smith, Peter Dottino, John Martignetti, Eric E. Schadt, Robert P. Sebra. High-throughput functional and multi-omic single-cell characterization to elucidate ovarian intratumor and microenvironmental heterogeneity [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr PR10.
Epigenetic Awakening of Viral Mimicry in Cancer
Authors: Janin Maxime , Esteller Manel 
Published: September 2020

Abstract

Summary:
In this issue, Deblois and colleagues show how taxane-resistant triple-negative breast cancer cells evade viral mimicry response as a result of metabolic alteration, DNA hypomethylation, and relocation of histone H3K27 trimethylation (H3K27me3). This adaptation confers a therapeutic vulnerability to the inhibition of the H3K27me3 methyltransferase EZH2 in resistant cells, leading to tumor growth inhibition by viral mimicry reactivation.
See related article by Deblois et al., p. 1312.
Bispecific Targeting of PD-1 and PD-L1 Enhances T-cell Activation and Antitumor Immunity
Authors: Kotanides Helen , Li Yiwen , Malabunga Maria , Carpenito Carmine , Eastman Scott W. , Shen Yang , Wang George , Inigo Ivan , Surguladze David , Pennello Anthony L. , Persaud Krishnadatt , Hindi Sagit , Topper Michael , Chen Xinlei , Zhang Yiwei , Bulaon Danielle K. , Bailey Tim , Lao Yanbin , Han Bing , Torgerson Stacy , Chin Darin , Sonyi Andreas , Haidar Jaafar N. , Novosiadly Ruslan D. , Moxham Christopher M. , Plowman Gregory D. , Ludwig Dale L. , Kalos Michael 
Published: September 2020

AbstractThe programmed cell death protein 1 receptor (PD-1) and programmed death ligand 1 (PD-L1) coinhibitory pathway suppresses T-cell–mediated immunity. We hypothesized that cotargeting of PD-1 and PD-L1 with a bispecific antibody molecule could provide an alternative therapeutic approach, with enhanced antitumor activity, compared with monospecific PD-1 and PD-L1 antibodies. Here, we describe LY3434172, a bispecific IgG1 mAb with ablated Fc immune effector function that targets both human PD-1 and PD-L1. LY3434172 fully inhibited the major inhibitory receptor–ligand interactions in the PD-1 pathway. LY3434172 enhanced functional activation of T cells in vitro compared with the parent anti–PD-1 and anti–PD-L1 antibody combination or respective monotherapies. In mouse tumor models reconstituted with human immune cells, LY3434172 therapy induced dramatic and potent antitumor activity compared with each parent antibody or their combination. Collectively, these results demonstrated the enhanced immunomodulatory (immune blockade) properties of LY3434172, which improved antitumor immune response in preclinical studies, thus supporting its evaluation as a novel bispecific cancer immunotherapy.
The Origins of Sovereign Risk Ratings
Authors: Pinheiro Diogo L. 
Published: September 2020

Abstract
Sovereign Risk Ratings are controversial measures used to determine a country’s creditworthiness. They are supposed to measure not only a country’s ability, but willingness to repay its debts. Much has been said about what it is that is actually measured by these ratings. But relatively little attention has been paid to who gets rated. That is, there is substantially less research on the issue of the when and the why a nation gets rated by one of the leading Credit Rating Agencies. The objective of this article is to try to understand that, and to sort through different theories for the emergence and spread of sovereign risk ratings. We find that institutional and political aspects matter just as much as economic ones, and that therefore sovereign risk ratings may play a role in political and social issues.
Pedagogies of Solidarity
Authors: Heidemann Kai A. 
Published: September 2020

Abstract
Sociological scholarship on social movements has shed important light on the role of knowledge production for processes of collective action and mobilization. However, much of this research overlooks the question of how movement-based knowledge emerges from within institutionalized settings of formal education. Drawing on a qualitative case study, this article examines the repertoire of knowledge-building practices mobilized from within a state-based system of adult education in francophone Belgium. Building on social movement theory, it is shown how formalized sites of adult education can empower the presence of social movements in society when they adopt counter-hegemonic principles of popular education that allow them to act as free spaces which facilitate the construction of strategic capacities and collective identities.
The Sinonasal Outcome Test–22 or European Position Paper: Which Is More Indicative of Imaging Results?
Authors: Zhou Allen S. , Prince Anthony A. , Maxfield Alice Z. , Corrales C. Eduardo , Shin Jennifer J. 
Published: September 2020

ObjectiveThe 22‐item Sinonasal Outcome Test (SNOT‐22) is a trusted measure of symptom severity in chronic rhinosinusitis. The European Position Paper on Rhinosinusitis (EPOS) provides widely accepted diagnostic criteria, which include sinonasal symptoms, their duration, and imaging results. Our objective was to compare these approaches to assessing symptoms to determine if either was more indicative of radiologic findings, to support decisions in telehealth.Study DesignObservational outcomes study.SettingTertiary care center.MethodsIn total, 162 consecutive patients provided a structured sinonasal history, completed the SNOT‐22, and underwent sinus computed tomography (CT) within 1 month. SNOT‐22 scores, EPOS‐defined symptom sets, and Lund‐Mackay results were assessed. To facilitate direct comparisons, we performed stepwise evaluations of sinonasal symptoms alone and combined with duration. The discriminatory capacity for imaging results was determined through areas under the receiver operating characteristic curves (ROC‐AUC) for dichotomous outcomes and ordinal regression for multilevel outcomes.ResultsIn ROC‐AUC analyses, SNOT‐22 and EPOS‐defined symptoms had similar discriminatory capacity for Lund‐Mackay scores, regardless of duration. Within ordinal regression analyses, SNOT‐22 nasal scores were significantly associated with Lund‐Mackay scores, while EPOS‐defined nasal symptoms were not statistically significantly related.ConclusionsSNOT‐22 nasal scores and EPOS‐defined nasal symptoms may have similar associations with imaging results when assessed via ROC‐AUC, while SNOT‐22 may have more association within ordinal data. Understanding the implications of discrete patterns of symptoms may confer benefit, particularly when in‐person and fiberoptic exams are limited.
Serum cystatin C is closely associated with euthyroid Hashimoto’s thyroiditis in adult female Chinese patients
Authors: Qin Qiaojing , Yang Min , Ke Wencai , Zhao Jinying , Ding Heyuan 
Published: September 2020

Objective The aim of our study was to explore the association between serum cystatin C (CysC) and euthyroid Hashimoto’s thyroiditis. Methods There were 119 female euthyroid Hashimoto’s thyroiditis patients and 225 healthy controls who were recruited. Serum CysC, thyroid function, thyroid autoantibodies, fasting glucose, liver enzymes, and lipid profile were determined. Clinical parameters were compared between two groups. Results Serum CysC levels were significantly higher in euthyroid Hashimoto’s thyroiditis patients compared with controls. In the lowest, middle, and highest tertile groups of CysC, the percentage of Hashimoto’s thyroiditis was 15.9%, 34.2%, and 53.5%, respectively. The percentage of Hashimoto’s thyroiditis was significantly higher in the highest tertile than in the lowest and middle tertiles. Spearman’s correlation analysis showed that serum CysC levels were negatively correlated with free triiodothyronine (FT3), and positively correlated with serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb). Logistic regression analysis showed that serum CysC was independently related to the status of euthyroid Hashimoto’s thyroiditis. Conclusions The present study shows the first evidence suggesting that serum CysC levels are positively correlated with TPOAb and TGAb. Serum CysC might underlie the pathophysiologic features of euthyroid Hashimoto’s thyroiditis.
A case of different gene mutations in primary and metastatic lesions after EGFR-TKI treatment of lung cancer
Authors: Xie Shaonan , Deng Huiyan , Liu Guangjie , Liu Qingyi 
Published: September 2020

Background: It remains controversial whether patients with EGFR-mutant lung adenocarcinoma should stop using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) after progression during treatment. Case report: We report a 35-year-old man with poorly differentiated adenocarcinoma of the left upper lobe and an exon 19 deletion (Ex19Del) mutation found by large-panel next-generation sequencing. The patient underwent video-assisted thoracoscopic surgery 12 months after oral administration of icotinib 125 mg tid, and the left upper lobe and surrounding lymph nodes were removed. Postoperative pathology supported a diagnosis of left upper lobe adenocarcinoma and subcarinal (1/2), main pulmonary artery window (1/2), and left hilar (1/2) lymph node metastases. The EGFR mutations in the residual lesions had disappeared, and Ex19Del mutations were still visible in the mediastinal lymph node metastasis. Conclusion: Spatial heterogeneity of the resistance mechanism may explain why patients who continue to receive EGFR-TKIs in combination with local therapies (e.g., radiotherapy) for progressing lesions may benefit even after progression during EGFR-TKI therapy. The loss of the EGFR mutation allele as a putative resistance mechanism requires additional preclinical and clinical confirmation.
SUNCT/SUNA in children and adolescents: Application of ICHD-3 criteria and treatment response: Case series of 13 SUNCT/SUNA pediatric cases
Authors: Qaiser Sharoon , Hershey Andrew D , Kacperski Joanne 
Published: September 2020

Introduction Trigeminal autonomic cephalalgias (TACs) are characterized by paroxysmal attacks of unilateral primary headaches associated with ipsilateral craniofacial autonomic symptoms. In this pediatric case series, 13 cases of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)/short-lasting unilateral neuralgiform headache with autonomic symptoms (SUNA), including children ages 3–18 years, are discussed. This paper reviews the application of International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria especially in children presenting with SUNCT or SUNA. This is the largest pediatric case series of SUNCT/SUNA reported in the literature. Background Trigeminal autonomic cephalalgias are rare in children and adolescents, with SUNCT/SUNA having the least reported cases. We will discuss the application of ICHD-3 criteria to diagnose SUNCT/SUNA in children and review overlapping cases and their response to different treatment options including indomethacin, which is typically reserved for specific subtypes of TACs; for example, paroxysmal hemicrania. Conclusion This case series presents a unique opportunity to aid in the diagnosis and treatment of similar pediatric cases in the future. It helps us to broaden the ICHD-3 criteria to diagnose and treat different overlapping trigeminal autonomic cephalalgia cases in children.
A pain like no other: From cluster to headache to Eagle’s syndrome, a case report
Authors: Diab Eva , Masmoudi Ines , Leclercq Claire , Flores Clara , Louin Loïc , Bettoni Jérémie , Godefroy Olivier 
Published: September 2020

Background Eagle’s syndrome, also called stylohyoid complex syndrome, is a rare syndrome pathology characterised by latero-cervical pain radiating to the face, linked to an abnormal enlargement of the styloid or calcification of the stylo-hyoid ligament. Case We report here the case of a young man of 25 suffering from cluster headache resistant to treatments, revealing Eagle’s syndrome. Conclusion Only surgery led to a real improvement of his condition.
Chemokine receptors on peripheral blood T lymphocytes in children on peritoneal dialysis
Authors: Szczepańska Maria , Sędek Łukasz , Bulsa Joanna , Mazur Bogdan , Zwolińska Danuta , Tkaczyk Marcin , Karpe Jacek , Szczepański Tomasz 
Published: September 2020

Background: Immune cell dysfunction is listed among complications resulting from chronic kidney disease (CKD). It could be associated with T-cells, which play a role in the lymphocytic migration and infiltration. However, the data on chemokine receptors expression on T-cells in patients with CKD particularly treated with peritoneal dialysis (PD) are still limited. Methods: The study aimed at multiparameter flow-cytometric analysis of the absolute numbers and percentage of T-cell subsets with surface chemokine receptors (CCR4, CCR5, CCR7, CXCR3, and CXCR4) or receptors’ combinations in 47 children treated with PD. Results: We found lower absolute numbers of total T lymphocytes, lymphocytes with surface CCR5, CXCR4+CCR5, CXCR3+CCR5 antigens and T-cells with CCR4, CCR4+CD4, CXCR3, CXCR3+CD4, and CD8 receptors. Lymphocytes T with CD4, CCR7, CD28+CCR7, CXCR3+CD8 antigens showed higher percentage in children on PD as compared to healthy children and opposite percentage values of CCR4+, CCR4+CD4+, CXCR3+ T lymphocytes were diminished. Mean fluorescent intensity for CCR7+, CCR7+CD45RO+, CCR7+CD28+, CXCR4+CD4+, CCR5+CD4+, CCR4+, CCR4+CD4+ T-cells was lower in the PD group than in healthy children. The analysis of correlation between T lymphocyte subpopulations with chemokine receptors and other parameters revealed positive correlation of CCR7+ and CCR7+CD28+ T-cells and weekly creatinine clearance, negative correlation between the percentage of CD45RO+CCR7 antigen positive T-cells and KT/Vurea. Summary: In conclusion, we could not confirm the phenomenon of earlier senescence of T-cells in children with CKD on PD treatment. This still requires further investigation. The higher percentage of T-cells with CCR7 surface receptor could be responsible for the increase of proliferation activity in this group of children.
How Midlife Chronic Stress Combines with Stressful Life Events to Influence Later Life Mental and Physical Health for Husbands and Wives in Enduring Marriages
Authors: Wickrama Kandauda A. S. , Klopack Eric T. , O’Neal Catherine W. 
Published: September 2020

Objectives: To investigate how midlife chronic stress (40–50 years) and subsequent acute stressful events (50–65 years) influence husbands’ and wives’ later life mental and physical health (65+ years). Methods: Dyadic structural equation modeling was used with prospective data over 25 years from 256 husbands and wives in enduring marriages. Results: For both spouses, midlife chronic stress influenced the occurrence of subsequent acute stressful life events, which in turn influenced both depressive symptoms and poor physical health in later years. For both spouses, midlife chronic stress also directly influenced depressive symptoms. Wives’ midlife chronic stress also directly influenced their own poor physical health and husbands’ depressive symptoms in later years. Discussion: These findings enhance our knowledge about the long-term joint influence of midlife chronic stress and acute stressful life events on health outcomes of husbands and wives in later years and identify dependencies between spouses, which can inform health preventive intervention programs.
The effectiveness of human papillomavirus load, reflected by cycle threshold values, for the triage of HPV-positive self-samples in cervical cancer screening
Authors: Song Fangbin , Du Hui , Wang Chun , Huang Xia , Qu Xinfeng , Wei Lihui , Belinson Jerome L , Wu Ruifang ,   CHIMUST team
Published: September 2020

Objective The performance of Cobas4800 cycle threshold value (Ct-value, reflecting viral load) combined with human papillomavirus (HPV) 16/18 genotyping was explored as a method of risk stratification to triage patients after primary HPV screening of self-collected samples. Methods The Chinese Multi-site Screening Trial database was reviewed, with focus on self-collected samples, using the results of Cobas4800 HPV assay. Quartiles of Ct-values of each genotype were used for grouping and developing screening algorithms. Diagnostic accuracy for paired comparisons between algorithms was obtained using McNemar’s test. Results A total of 10,498 women were included. The Ct-values of HPV16 and other high-risk HPV were inversely correlated with the severity of cervical lesions ( p < 0.001). Risks for cervical intraepithelial neoplasia (CIN2+/CIN3+) were significantly stratified by Ct-values from channels detecting HPV16 and other high-risk HPV types. “HPV with HPV16/18 and reflex Ct <33.7” (algorithm G) achieved a favorable sensitivity to “HPV with atypical squamous cells of undetermined significance or worse (≥ASCUS)” (81.9% vs. 70.1% for CIN2+, p < 0.001), a comparable sensitivity to “HPV with HPV16/18 reflex cytology ≥ASCUS” (81.9% vs. 81.3% for CIN2+, p > 0.05), and resulted in a slightly lower specificity than the latter two algorithms (92.6% vs. 97.4% and 95.4% respectively for CIN2+, p < 0.05). However, algorithm G achieved a comparable sensitivity to HPV testing alone for CIN3+, and reduced the colposcopy referral rate from 13.7% for HPV testing alone to 8.4%. Conclusions HPV viral loads reflected by Ct-values are associated with the severity of cervical lesions. Ct-values with an appropriate cut-off of 33.7, combined with HPV16/18 genotyping, represent a promising triage of HPV-positive women particularly for self-collected samples.
Radiographic and Clinical Outcomes of Hallux Valgus and Metatarsus Adductus Treated With a Modified Lapidus Procedure
Authors: Conti Matthew S. , Caolo Kristin C. , Ellis Scott J. , Cody Elizabeth A. 
Published: September 2020

Background: Previous studies have found an increased rate of deformity recurrence in hallux valgus (HV) patients with concomitant metatarsus adductus (MA) undergoing metatarsal osteotomies. The purpose of this paper was to determine if there were radiographic or clinical outcome differences between HV patients with and without MA undergoing a modified Lapidus procedure. Methods: One hundred forty-seven feet that underwent a modified Lapidus procedure for HV were divided into 2 groups based on their preoperative modified Sgarlato’s angle: (1) the MA group had an angle ≥20 degrees and (2) the HV-only group had an angle <20 degrees. HV angle (HVA) and intermetatarsal angle (IMA) were measured on preoperative and ≥5-month postoperative weightbearing radiographs. Patient-Reported Outcome Measurement Information System (PROMIS) physical function (PF) and pain interference (PI) scores were obtained preoperatively and postoperatively. Results: Patients in the MA group had a significantly higher mean postoperative HVA (10.8 vs 7.5 degrees; P = .038). There was a trend toward higher PROMIS PI scores in the MA group at 1 year postoperatively (51.9 vs 47.6; P = .088). Patients in the MA group were more likely to have a revision surgery (7.3% vs 0%; P = .021), and there was a trend toward those patients having a higher recurrence rate (17.1% vs 6.6%; P = .064). Conclusion: Despite potentially worse postoperative outcomes in patients with HV and MA who undergo a modified Lapidus procedure, the recurrence rates reported here are lower than those reported in the literature for patients with MA undergoing metatarsal osteotomies, indicating that a modified Lapidus procedure may be an acceptable choice in these patients. Level of Evidence: Level III, retrospective comparative series.