bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO-007: A phase 2 open-label study of conditionally active biologic, ozuriftamab vedotin (BA3021) in PD-1/L1 failure patients with recurrent or metastatic squamous cell carcinoma of the head and neck
Authors: Ho Alan L. , Adkins Douglas R. , Lorch Jochen , Thomas Jacob S. , Grewal Jaspreet S. 
Published: September 2023

Abstract
Background: Ozuriftamab vedotin (BA3021) is a conditionally active biologic (CAB) anti-receptor tyrosine kinase orphan receptor 2 (ROR2) humanized monoclonal antibody (IgG1) conjugated to monomethyl auristatin E (MMAE) using a cleavable linker (CAB ROR2 ADC) (Short, et al., 2014, Chang, et al. 2021). Conditional and reversible binding by CABs is designed to reduce off-tumor toxicity and immunogenicity, avoid tissue-mediated drug deposition, and improve pharmacokinetics (PK). ROR2 is a cell-surface transmembrane receptor protein tyrosine kinase highly expressed in several tumor types including head and neck squamous cell cancer (HNSCC). Increased ROR2 expression has been associated with tumor resistance to chemotherapy, programmed death-1 (PD-1) inhibitors, molecular targeted therapy, and radiation therapy. A pronounced unmet need exists as the majority of patients with recurrent or metastatic HNSCC experience disease progression with existing therapies (Chow 2020). Trial Design: BA3021-002 is a multi-center, open-label, single-arm Phase 2 study (n=40) designed to evaluate the efficacy and safety of BA3021 in patients previously treated with PD-(L)1 with ROR-2 expressing recurrent or metastatic HNSCC. Eligible patients include those with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria. Failure to prior treatment is defined as documented disease progression after no more than one PD-1/L1 inhibitor either administered as monotherapy or in combination therapy. Pharmacokinetic (PK), pharmacodynamic (PD), immunogenicity, and biomarker assessments will be performed. Enrollment is ongoing (NCT05271604) References Chang, H.W., Frey, G., Liu, H., Steinman, L., Boyle, W.J. and Short, J.M. Proc. Natl. Acad. Sci. 2021 Mar. 2; 118(9). Chow LQ. Head and neck cancer. N Engl J Med. 2020 Jan 2;382(1):60–72. doi: 10.1056/NEJMra1715715 Short, J.M. Nature Biotechnology 2014 Nov 8, 13(20).
Citation Format: Alan L. Ho, Douglas R. Adkins, Jochen Lorch, Jacob S. Thomas, Jaspreet S. Grewal. A phase 2 open-label study of conditionally active biologic, ozuriftamab vedotin (BA3021) in PD-1/L1 failure patients with recurrent or metastatic squamous cell carcinoma of the head and neck [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-007.
Abstract PO-018: Pathological analysis of newly established immunocompetent mice with full HPV16 genome integration
Authors: Li Xue , Kothari Aditi , Rehmani Hina , Yarbrough Wendell G. , Issaeva Natalia 
Published: September 2023

Abstract
Human papillomaviruses (HPV) are associated with both benign and malignant epithelial lesions. High-risk HPV subtype HPV 16 is the causative agent of cervical and the majority of oropharyngeal squamous cell carcinomas. Despite the continuous increase in the disease burden, mechanisms and pathways of HPV16-induced cancer growth are not fully understood, thus leading to suboptimal treatment. In the last few decades, several transgenic mouse models were developed, which helped tremendously in the study of HPV-induced carcinogenesis. However, all existent HPV transgenic mice were targeted early genes expression driven by an artificial promoter and did not encompass the functionality of the whole HPV genome, including the upstream regulatory region (URR) that contains HPV promoters, regulatory elements, and a replication origin, limited our ability to investigate HPV-associated malignant transformation and the role of host factors in this process. Therefore, we generated HPV16 transgenic mice by using CRISPR/Cas9-mediated genome editing to insert the full-length HPV16 genome into the Rosa26 locus. Two founder mice, with single HPV copy and with tandem HPV integration, were used to establish mouse colonies. Interestingly, regardless of HPV copy number, approximately 50% of the HPV knock-in mice exhibited early death during the first 2 weeks after birth, while surviving pups were significantly smaller than the same-age wild-type mice and had severe hair loss. Intriguingly, the growth retardant and hair loss phenotype in the HPV16 knock-in mice disappeared in approximately 4 weeks, most likely indicating that viral genes compromise specific stages of mouse development. We evaluated the expression of HPV genes during development, in different mouse organs, and in established fibroblasts and epithelial cell cultures. Our newly established HPV16 knock-in mouse model provides viral gene expression from natural viral promoters offering an essential basis to explore the role of cellular factors in HPV-driven pathologies.
Citation Format: Xue Li, Aditi Kothari, Hina Rehmani, Wendell G. Yarbrough, Natalia Issaeva. Pathological analysis of newly established immunocompetent mice with full HPV16 genome integration [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-018.
Abstract PO-035: Immune profiles of long-term survivors of patients with head and neck squamous carcinoma on immune checkpoint inhibitor therapy
Authors: Christensen Brock , Lee Min Kyung , Zhang Ze , Butler Rondi , Ramush Geat , Sehgal Kartik , Shirai Keisuke , Koestler Devin , Salas Lucas , Wiencke John , Haddad Robert , Kelsey Karl 
Published: September 2023

Abstract
Background: Only 15 – 20% of patients with head and neck squamous cell carcinoma (HNSCC) have response to anti-programmed cell death (PD)-1 immunotherapy and there remain gaps in predicting which patients will respond. Method: Here, we utilized DNA methylation cytometry to sequentially delineate detailed immune profiles of six patients with HNSCC (n=38 samples), who had durable response to immunotherapy over a one-year period without disease progression. Results: During the initial 3.5 months of anti-PD-1 immunotherapy treatment, increases in levels of CD8 T memory cells and natural killer cells were observed. Compared to healthy populations in similar age ranges, CD4 T and B cell levels were lower, while monocyte levels were higher in patients with HNSCC at baseline and throughout the year of treatment with immunotherapy. Conclusions: Our results suggest monitoring changes in immune cell type levels as potential biomarkers for patients with HNSCC who respond to anti-PD-1 immunotherapy.
Citation Format: Brock Christensen, Min Kyung Lee, Ze Zhang, Rondi Butler, Geat Ramush, Kartik Sehgal, Keisuke Shirai, Devin Koestler, Lucas Salas, John Wiencke, Robert Haddad, Karl Kelsey. Immune profiles of long-term survivors of patients with head and neck squamous carcinoma on immune checkpoint inhibitor therapy [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-035.
Abstract PR03: Cholinergic modulation of tumor infiltrating lymphocytes in oral squamous cell carcinoma
Authors: White Ruth A. 
Published: September 2023

Abstract
Response to immunotherapy remains less than 20% for Oral Cavity Squamous Cell Carcinoma (OSCC). The poor response is in part due to dysfunctional cytotoxic T cell activity resulting from terminal exhaustion as a response to chronic exposure to tumor antigen. New strategies are needed to sensitize OSCC to immunotherapy to improve response rates and overall survival. Stimulation of muscarinic receptors by Acetylcholine (Ach), the primary neurotransmitter of the parasympathetic nervous system, restrains pancreatic and breast cancer but promotes gastric and late stage prostate cancer. The role of cholinergic signaling in OSCC is unknown. Ach can be secreted from non-neuronal tissues, including lymphocytes, which are abundant in the OSCC microenvironment. These lymphocytes express choline acetyltransferase (ChaT), the enzyme catalyzing the rate limiting step of Ach production and are important in maintaining chronic anti-viral immune responses. Our objective is to uncover the role of these Ach secreting T cells in mediating the anti-tumor immune response in OSCC. We utilized the 4MOSC1 and 4MOSC2 orthotopic OSCC tumor model. Orthotopic tumors were generated in recipient mice with impaired Ach-muscarinic signaling. ChaT+ CD8+ T cells were amplified in the tumor microenvironment and in vitro after activation. Inhibition of Ach-muscarinic signaling in the tumor immune microenvironment (TIME) accelerated tumor growth kinetics and was associated with loss of tumor infiltrating lymphocytes (TILs). Analysis of T cell activation states in TILs and after in vitro activation demonstrated that disruption of Ach-muscarinic signaling promotes differentiation of effector T lymphocytes at the expense of central memory. These data suggest that the Ach-muscarinic axis promotes CD8+ T cell infiltration and maintains T cell memory in the TIME supporting long term anti-tumor immune responses.
Citation Format: Ruth A. White. Cholinergic modulation of tumor infiltrating lymphocytes in oral squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PR03.
ANGPTL3 Deficiency and Risk of Hepatic Steatosis
Authors: D’Erasmo Laura , Di Martino Michele , Neufeld Thomas , Fraum Tyler J. , Kang Chul Joo , Burks Kendall H. , Di Costanzo Alessia , Minicocci Ilenia , Bini Simone , Maranghi Marianna , Pigna Giovanni , Labbadia Giancarlo , Zheng Jie , Fierro Davide , Montali Anna , Ceci Fabrizio , Catalano Carlo , Davidson Nicholas O. , Lucisano Giuseppe , Nicolucci Antonio , Arca Marcello , Stitziel Nathan O. 
Published: September 2023

BACKGROUND:
ANGPTL3 (angiopoietin-like 3) is a therapeutic target for reducing plasma levels of triglycerides and low-density lipoprotein cholesterol. A recent trial with vupanorsen, an antisense oligonucleotide targeting hepatic production of ANGPTL3, reported a dose-dependent increase in hepatic fat. It is unclear whether this adverse effect is due to an on-target effect of inhibiting hepatic ANGPTL3.

METHODS:

We recruited participants with ANGPTL3 deficiency related to
ANGPTL3
loss-of-function (LoF) mutations, along with wild-type (WT) participants from 2 previously characterized cohorts located in Campodimele, Italy, and St. Louis, MO. Magnetic resonance spectroscopy and magnetic resonance proton density fat fraction were performed to measure hepatic fat fraction and the distribution of extrahepatic fat. To estimate the causal relationship between ANGPTL3 and hepatic fat, we generated a genetic instrument of plasma ANGPTL3 levels as a surrogate for hepatic protein synthesis and performed Mendelian randomization analyses with hepatic fat in the UK Biobank study.

RESULTS:

We recruited participants with complete (n=6) or partial (n=32) ANGPTL3 deficiency related to
ANGPTL3
LoF mutations, as well as WT participants (n=92) without LoF mutations. Participants with ANGPTL3 deficiency exhibited significantly lower total cholesterol (complete deficiency, 78.5 mg/dL; partial deficiency, 172 mg/dL; WT, 188 mg/dL;
P
<0.05 for both deficiency groups compared with WT), along with plasma triglycerides (complete deficiency, 26 mg/dL; partial deficiency, 79 mg/dL; WT, 88 mg/dL;
P
<0.05 for both deficiency groups compared with WT) without any significant difference in hepatic fat (complete deficiency, 9.8%; partial deficiency, 10.1%; WT, 9.9%;
P
>0.05 for both deficiency groups compared with WT) or severity of hepatic steatosis as assessed by magnetic resonance imaging. In addition, ANGPTL3 deficiency did not alter the distribution of extrahepatic fat. Results from Mendelian randomization analyses in 36 703 participants from the UK Biobank demonstrated that genetically determined ANGPTL3 plasma protein levels were causally associated with low-density lipoprotein cholesterol (
P
=1.7×10
-17
) and triglycerides (
P
=3.2×10
-18
) but not with hepatic fat (
P
=0.22).

CONCLUSIONS:

ANGPTL3 deficiency related to LoF mutations in
ANGPTL3
, as well as genetically determined reduction of plasma ANGPTL3 levels, is not associated with hepatic steatosis. Therapeutic approaches to inhibit ANGPTL3 production in hepatocytes are not necessarily expected to result in the increased risk for hepatic steatosis that was observed with vupanorsen.
Atoms for Industry: The Early Nuclear Activities of Fiat and the Atoms for Peace Program in Italy, 1956–1959
Authors: Curli Barbara 
Published: September 2023

Abstract
Fiat's nuclear activities began in the immediate postwar period, when the company financed initiatives meant to reconstruct applied and theoretical research on nuclear physics in Italy. However, its actual industrial involvement originated in the framework of the Atoms for Peace initiative, which provided the opportunity for the purchase of an American Machine and Foundry pool-type reactor for a research center founded by Società Ricerche Impianti Nucleari (SORIN), a joint-venture created in 1956 by Fiat and the Italian chemical company Montecatini. SORIN developed know-how and technology in the electromechanical and biomedical industries. The SORIN center was the first private initiative within the Atoms for Peace framework. This article is a first attempt to assess Fiat's involvement in the nuclear sector, shedding light on the reception of Atoms for Peace in Italy and the way various actors on the Italian nuclear scene used it to pursue their own objectives during the Cold War.
Morphological and molecular characterization of the Makran Glossogobius cf. giuris (Teleostei: Gobiidae) and the Glossogobius giuris species complex taxonomy
Authors: ZAREI FATAH , KOVAČIĆ MARCELO , ESMAEILI HAMID REZA , GHANBARIFARDI MEHDI 
Published: September 2023

The Indo-West Pacific Glossogobius giuris (Hamilton, 1822) species complex has four spatially circumscribed independent lineages, partially taxonomically resolved. A sample of gobies from the G. giuris species complex was recently collected from the Makran River System, south-eastern Iran, which drains into the northern Oman Sea. The taxonomic status of this population was clarified using a molecular and morphological framework. Molecular and morphological data both revealed that the examined sample from the Makran River System is conspecific with G. giuris B which is widely distributed in the coastal habitats and basins of the Indian Ocean. In addition, consensus from different molecular species delimitations, K2P genetic distance, and tree topologies confirmed the four lineages of the G. giuris species complex as distinct taxonomic entities, hereby highlighting the necessity of an integrative morphological and molecular approach to complete the clarification of taxonomic diversity within this group. Glossogobius giuris species complex taxonomy is discussed and solution recommended.
Left ventricular remodelling in rheumatic heart disease – trends over time and implications for follow-up in childhood
Authors: MacDonald Bradley , Tarca Adrian , Causer Louise , Maslin Katie , Bruce Di , Schreiber-Wood Rachel , Kumar Mohit , Ramsay James , Andrews David , Budgeon Charley , Katzenellenbogen Judith , Bowen Asha C. , Carapetis Jonathan , Friedberg Mark K. , Yim Deane 
Published: September 2023

Abstract
Background
Rheumatic heart disease (RHD) is the most common form of acquired heart disease worldwide. In RHD, volume loading from mitral regurgitation leads to left ventricular (LV) dilatation, increased wall stress, and ultimately LV dysfunction. Improved understanding of LV dynamics may contribute to refined timing of intervention. We aimed to characterize and compare left ventricular remodelling between rheumatic heart disease (RHD) severity groups by way of serial echocardiographic assessment of volumes and function in children.

Methods
Children with RHD referred to Perth Children’s Hospital (formally Princess Margaret Hospital) (1987–2020) were reviewed. Patients with longitudinal pre-operative echocardiograms at diagnosis, approximately 12 months and at most recent follow-up, were included and stratified into RHD severity groups. Left ventricular (LV) echocardiographic parameters were assessed. Adjusted linear mixed effect models were used to compare interval changes.

Results
146 patients (median age 10 years, IQR 6–14 years) with available longitudinal echocardiograms were analysed. Eighty-five (58.2%) patients had mild, 33 (22.6%) moderate and 28 (19.2%) severe RHD at diagnosis. Mean duration of follow-up was 4.6 years from the initial diagnosis. Severe RHD patients had significantly increased end-systolic volumes (ESV) and end-diastolic volumes (EDV) compared to mild/moderate groups at diagnosis (severe versus mild EDV mean difference 27.05 ml/m2, p < 0.001, severe versus moderate EDV mean difference 14.95 ml/m2, p = 0.006). Mild and moderate groups experienced no significant progression of changes in volume measures. In severe RHD, LV dilatation worsened over time. All groups had preserved cardiac function.

Conclusions
In mild and moderate RHD, the lack of progression of valvular regurgitation and ventricular dimensions suggest a stable longer-term course. Significant LV remodelling occurred at baseline in severe RHD with progression of LV dilatation over time. LV function was preserved across all groups. Our findings may guide clinicians in deciding the frequency and timing of follow-up and may be of clinical utility during further reiterations of the Australia and New Zealand RHD Guidelines.
Giant coronary aneurysm of Behcet’s disease with sudden syncope: a case report
Authors: Feng Jingwei , Miao Qi , Zhang Chaoji 
Published: September 2023

AbstractBehcet’s disease(BD) is a chronic inflammatory vasculitis that rarely affects the arteries, making myocardial infarction unlikely. We report a 28-year-old patient who was admitted to our hospital with multiple sudden syncope. Cardiovascular risk factors such as hypertension (HT), diabetes and obesity were not found in her. Preoperatively, imaging examinations suggested thrombosis of the inferior and superior vena cava and right heart combined with coronary artery aneurysm. The patient was finally diagnosed with a huge coronary artery aneurysm proximal to the left anterior descending artery. Syncope is considered to be caused right ventricular outflow tract obstruction. The patient received a successful aneurysm resection and had an uneventful postoperative recovery.
SASE, Success and Adverse event Score in Endoscopic Retrograde Cholangiopancreatography: a Novel Grading System
Authors: Maieron Andreas , Duller Christine , Püspök Andreas , Steiner Emanuel , Kapral Christine 
Published: September 2023

Abstract
Background
Validated, accepted grading tools for preprocedural complexity assessment in ERCP are lacking. We therefore created a grading system for ERCP based on the classification used by the American Society for Gastrointestinal Endoscopy (ASGE).

Methods
Data on ERCP adverse events (AE) and success were collected in a multicenter, prospective uncontrolled study. Multiple logistic regressions were applied to success and AEs in accordance with the ASGE classification. Each procedure suggested by ASGE was tested against different outcomes. Results were used to create a score and were evaluated in a control cohort.

Results
16,327 ERCPs were documented in 27 centers. Analysis of ASGE categorization (10,904 cases) showed that this model fails to adequately predict parameters of complexity; only for cardiopulmonary AEs and perforation was no significant variance evident. Depending on the specific clinical circumstances, probability of success of the intervention sometimes varied significantly in risk, implying a twofold score, one part for probability of success and one for risk. A split score with three levels each was designed and tested in a validation cohort (5,423 procedures). Achieving therapeutic targets / post-ERCP pancreatitis could be correctly predicted in 87.0%/95.3%.

Conclusions
Grading ERCP success and AEs have to be considered independently. Onefold grading systems appear incomplete and unable to provide an adequate classification of severity. SASE (Success and Adverse Event Score in Endoscopic Retrograde Cholangiopancreatography) was created to incorporate these findings. Showing high predictive value, this score could be a potent tool for planning ERCP and training in endoscopy.
Predictors and impact of trust on vaccine decisions in parents of 2-year-old children in Canada: findings from the 2017 Childhood National Immunization Coverage Survey (cNICS)
Authors: N Schellenberg , M Dietrich Leurer , P Petrucka , AM Crizzle 
Published: September 2023

AbstractTrust is known to be an important factor in vaccine decisions for parents of young children, but there has been a lack of Canadian data measuring the determinants and impact of trust. Using data from the 2017 Canadian Childhood National Immunization Coverage Survey (cNICS), this study analyzed the relationships between sources that parents trust for vaccine information and demographics, parental knowledge, attitudes, and beliefs (KAB) and vaccine decisions (refusal, delay or reluctance) in parents of 2-year-old children who had accepted at least one vaccine for their child (n = 6125). The findings show that 83% of parents trust doctors for vaccine information; 70–80% trust pharmacists, PMH, nurses and HC/PHAC; 34% trust family and 23% trust friends and CAM HCPs. However, parents found to have poor or moderate KAB were less likely to trust doctors, nurses, pharmacists, PMH and HC/PHAC. Parents were also less likely to trust the PMH or HC/PHAC if they had high school education or less or trade/college education, or were widowed, separated, or divorced. Parents who had never been reluctant to vaccinate their 2-year-old child were over 2 times more likely to trust doctors, nurses, pharmacists, PMH and HC/PHAC while parents who trusted family and friends were less likely to delay or refuse vaccines. There was also significant regional variation within Canada, with parents from Quebec most likely to trust doctors, nurses, pharmacists, friends, PMH and HC/PHAC. Parents from the Territories were less likely to trust doctors, nurses and pharmacists, but more likely to trust family. Parents were less likely to trust doctors if they were from the Prairies, and pharmacists if they were from BC, and parents from the Prairies and BC were less likely to trust HC/PHAC. Parents from Ontario were less likely to trust family or friends, but more likely to trust the PMH. Tailored vaccine campaigns are needed to account for educational, marital, and regional differences across Canada to improve vaccine uptake.