bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic targeting and resistance to PARP inhibition in DNA damage repair-deficient pancreatic cancer
Authors: Gout Johann , Perkhofer Lukas , Morawe Mareen , Arnold Frank , Ihle Michaela , Biber Stephanie , Lange Sebastian , Roger Elodie , Kraus Johann M , Stifter Katja , Hahn Stephan A , Zamperone Andrea , Engleitner Thomas , Müller Martin , Walter Karolin , Rodriguez-Aznar Eva , Sainz Jr Bruno , Hermann Patrick C , Hessmann Elisabeth , Müller Sebastian , Azoitei Ninel , Lechel André , Liebau Stefan , Wagner Martin , Simeone Diane M , Kestler Hans A , Seufferlein Thomas , Wiesmüller Lisa , Rad Roland , Frappart Pierre-Olivier , Kleger Alexander 
Published: September 2020

ObjectiveATM serine/threonine kinase (ATM) is the most frequently mutated DNA damage response gene, involved in homologous recombination (HR), in pancreatic ductal adenocarcinoma (PDAC).DesignCombinational synergy screening was performed to endeavour a genotype-tailored targeted therapy.ResultsSynergy was found on inhibition of PARP, ATR and DNA-PKcs (PAD) leading to synthetic lethality in ATM-deficient murine and human PDAC. Mechanistically, PAD-induced PARP trapping, replication fork stalling and mitosis defects leading to P53-mediated apoptosis. Most importantly, chemical inhibition of ATM sensitises human PDAC cells toward PAD with long-term tumour control in vivo. Finally, we anticipated and elucidated PARP inhibitor resistance within the ATM-null background via whole exome sequencing. Arising cells were aneuploid, underwent epithelial-mesenchymal-transition and acquired multidrug resistance (MDR) due to upregulation of drug transporters and a bypass within the DNA repair machinery. These functional observations were mirrored in copy number variations affecting a region on chromosome 5 comprising several of the upregulated MDR genes. Using these findings, we ultimately propose alternative strategies to overcome the resistance.ConclusionAnalysis of the molecular susceptibilities triggered by ATM deficiency in PDAC allow elaboration of an efficient mutation-specific combinational therapeutic approach that can be also implemented in a genotype-independent manner by ATM inhibition.
Western-type diet influences mortality from necrotising pancreatitis and demonstrates a central role for butyrate
Authors: van den Berg Fons F , van Dalen Demi , Hyoju Sanjiv K , van Santvoort Hjalmar C , Besselink Marc G , Wiersinga Willem Joost , Zaborina Olga , Boermeester Marja A , Alverdy John 
Published: September 2020

ObjectiveThe gut microbiota are the main source of infections in necrotising pancreatitis. We investigated the effect of disruption of the intestinal microbiota by a Western-type diet on mortality and bacterial dissemination in necrotising pancreatitis and its reversal by butyrate supplementation.DesignC57BL/6 mice were fed either standard chow or a Western-type diet for 4 weeks and were then subjected to taurocholate-induced necrotising pancreatitis. Blood and pancreas were collected for bacteriology and immune analysis. The cecum microbiota composition of mice was analysed using 16S rRNA gene amplicon sequencing and cecal content metabolites were analysed by targeted (ie, butyrate) and untargeted metabolomics. Prevention of necrotising pancreatitis in this model was compared between faecal microbiota transplantation (FMT) from healthy mice, antibiotic decontamination against Gram-negative bacteria and oral or systemic butyrate administration. Additionally, the faecal microbiota of patients with pancreatitis and healthy subjects were analysed.ResultsMortality, systemic inflammation and bacterial dissemination were increased in mice fed Western diet and their gut microbiota were characterised by a loss of diversity, a bloom ofEscherichia coliand an altered metabolic profile with butyrate depletion. While antibiotic decontamination decreased mortality, Gram-positive dissemination was increased. Both oral and systemic butyrate supplementation decreased mortality, bacterial dissemination, and reversed the microbiota alterations. Paradoxically, mortality and bacterial dissemination were increased with FMT administration. Finally, patients with acute pancreatitis demonstrated an increase in Proteobacteria and a decrease of butyrate producers compared with healthy subjects.ConclusionButyrate depletion and its repletion appear to play a central role in disease progression towards necrotising pancreatitis.
Adaptations to the current ECCO/ESPGHAN guidelines on the management of paediatric acute severe colitis in the context of the COVID-19 pandemic: a RAND appropriateness panel
Authors: Hansen Richard , Meade Susanna , Beattie R Mark , Auth Marcus KH , Croft Nick , Davies Philip , Devadason David , Doherty Conor , Epstein Jenny , Howarth Lucy , Kiparissi Fevronia , Muhammed Rafeeq , Shivamurthy Vinay , Spray Christine , Stanton Michael P , Torrente Franco , Urs Arun , Wilson David , Irving Peter M , Samaan Mark , Kammermeier Jochen 
Published: September 2020

ObjectivePaediatric acute severe colitis (ASC) management during the novel SARS-CoV-2/COVID-19 pandemic is challenging due to reliance on immunosuppression and the potential for surgery. We aimed to provide COVID-19-specific guidance using the European Crohn’s and Colitis Organisation/European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for comparison.DesignWe convened a RAND appropriateness panel comprising 14 paediatric gastroenterologists and paediatric experts in surgery, rheumatology, respiratory and infectious diseases. Panellists rated the appropriateness of interventions for ASC in the context of the COVID-19 pandemic. Results were discussed at a moderated meeting prior to a second survey.ResultsPanellists recommended patients with ASC have a SARS-CoV-2 swab and expedited biological screening on admission and should be isolated. A positive swab should trigger discussion with a COVID-19 specialist. Sigmoidoscopy was recommended prior to escalation to second-line therapy or colectomy. Methylprednisolone was considered appropriate first-line management in all, including those with symptomatic COVID-19. Thromboprophylaxis was also recommended in all. In patients requiring second-line therapy, infliximab was considered appropriate irrespective of SARS-CoV-2 status. Delaying colectomy due to SARS-CoV-2 infection was considered inappropriate. Corticosteroid tapering over 8–10 weeks was deemed appropriate for all. After successful corticosteroid rescue, thiopurine maintenance was rated appropriate in patients with negative SARS-CoV-2 swab and asymptomatic patients with positive swab but uncertain in symptomatic COVID-19.ConclusionOur COVID-19-specific adaptations to paediatric ASC guidelines using a RAND panel generally support existing recommendations, particularly the use of corticosteroids and escalation to infliximab, irrespective of SARS-CoV-2 status. Consideration of routine prophylactic anticoagulation was recommended.
p63 expression is associated with high histological grade, aberrant p53 expression and TP53 mutation in HER2-positive breast carcinoma
Authors: Guo Shuangping , Wang Yingmei , Rohr Joseph , Shang Li , Ma Jing 
Published: September 2020

Aimp63, a member of the p53 family, is a myoepithelial cell marker usually expressed in metaplastic breast carcinoma and its expression suggests a myoepithelial phenotype. However, its expression and association with clinicopathological features of human epidermal growth factor receptor 2 (HER 2)-positive breast carcinoma is poorly investigated.Materials and methodsSixty-seven patients with oestrogen receptor-negative and progesterone receptor-negative, HER2-positive breast carcinoma who received anti-HER2-based neoadjuvant±adjuvant therapy was retrospectively analysed.ResultsTwenty cases were p63-positive and 47 cases were p63-negative. The clinicopathological features and tumour responses after neoadjuvant therapy and outcomes were analysed. Among HER2-positive tumours, expression of p63 was significantly associated with younger age (42.5 vs 55.9; p=0.010). Expression of p63 was also significantly associated with histological grade 3 (11/20 (55%) vs 11/47 (23.4%); p=0.012) and negatively associated with grade 2 (9/20 (45%) vs 36/47 (76.6%); p=0.012). Intriguingly, p63-positive breast carcinomas showed significant aberrant p53 expression by immunohistochemistry (16/18 (88.9%) vs 29/47 (61.7%); p=0.03) and ofTP53mutation by Sanger sequencing (15/16 (93.8%) vs 12/22 (54.5%); p=0.009). No significant difference in tumour response after anti-HER2 neoadjuvant therapy nor in survival were found between p63-positive and p63-negative breast carcinomas.ConclusionExpression of p63 in HER2-positive breast carcinoma is significantly associated with younger age, poor differentiation, high histological grade and aberrant expression of p53 and ofTP53mutation. HER2-positive breast carcinoma with a myoepithelial immunophenotype shows distinctive clinicopathological features representing a distinct subtype of HER2-positive breast carcinoma. Further, these findings suggest an interaction between p63 and mutant p53 in the tumorigenesis of HER2-positive breast carcinomas.
Collaborative leadership: organisational structure and institutional investment to multiply innovative educational efforts among trainees
Authors: Do Albert , Li Luming , Heller Danielle R , Abou Ziki Maen D , Glaser Daniel H , Kumar Sumit P , Huot Stephen J 
Published: September 2020

BackgroundTrainees comprise a substantial employee population worldwide and there is increasing perspective of leadership as a foundational skill of physician development. In the USA, the Accreditation Council for Graduate Medical Education mandates a ‘Resident/Fellow Forum’ to facilitate cross-institutional engagement and communication with the Graduate Medical Education Committee.InterventionsTo increase effectiveness, we conceived a ‘Senate’ in place of a forum, incorporating broader housestaff representation and partnerships with faculty and hospital executive leadership. The ‘Yale-New Haven Hospital Resident and Fellow Senate’ was supported by hospital financial resources and faculty mentorship. It provided leadership development, enhanced interdepartmental, connected multiple medical specialties, and improved housestaff engagement with institutional leaders. The Senate comprised an elected Executive Board and five councils in areas of common interest with appointed Chairs and members at large.ConclusionsWe summarise the Senate’s conception, structure, election process, lessons learnt and associated impact. We conclude that the creation of an institutionally supported Senate with interest-specific councils and faculty mentorship leads to qualitatively positive downstream effects on housestaff social interactions, institutional engagement and leadership opportunities.
Subleading EW corrections and spin-correlation effects in $$t\bar{t}W$$ multi-lepton signatures
Authors: Frederix Rikkert , Tsinikos Ioannis 
Published: September 2020

AbstractRecently a slight tension between data and predictions has been reported in $$t\bar{t}W$$

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production by both the CMS and ATLAS collaborations. We revisit the theoretical predictions for this process, focussing on the following two effects. We disentangle various effects that lead to asymmetries among the leptonic decay products of the (anti-)top quarks and W bosons, for which we find that the spin correlations in the top-quark pair are the dominant source. We also discuss the impact of the large, formally subleading, electroweak corrections to $$t\bar{t}W$$

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production at the LHC. We find that this effect changes the $$t\bar{t}W$$

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cross section significantly in the signature phase-space regions, and should therefore be included differentially in the theory to data comparisons.
AN EFFICIENT MAXIMUM LIKELIHOOD ESTIMATOR FOR TWO-DIMENSIONAL FRACTIONAL BROWNIAN MOTION
Authors: CHANG YEN-CHING 
Published: September 2020

For pattern recognition, natural scenes and medical images are often modeled as two-dimensional fractional Brownian motion (2D FBM), which can be easily described by the Hurst exponent ([Formula: see text], a real number between 0 and 1. The Hurst exponent is directly related to the fractal dimension ([Formula: see text]) by [Formula: see text]–[Formula: see text], and hence it very suitably serves as a characteristic index. Therefore, how to estimate the Hurst exponent effectively and efficiently is very important in pattern recognition. In this paper, a partially iterative algorithm, simply called an iterative maximum likelihood estimator (MLE) for 2D DFBM is first proposed and then a more sufficiently iterative algorithm, simply called an efficient MLE for 2D DFBM, is further proposed via a perfect structure of the log-likelihood function related to the Hurst exponent. Except for theoretical knowledge, two practical algorithms are also correspondingly provided for easy applications. Experimental results show that the MLE for 2D DFBM is effective and workable; its accuracy gets higher as the image size increases, and hence its recognition resolution is much finer to identify small difference among patterns. Furthermore, the efficient MLE is much quicker than the iterative MLE, especially at larger image sizes.
Abstract A028: Perceptions of the nursing role in cancer survivorship among aging African American cancer survivors and caregivers
Authors: Cobb Sharon , Ume Ebere 
Published: September 2020

Abstract
Introduction: Oncology nurses are recognized globally for enhancing health outcomes, improving care coordination, and providing quality care. However, few studies have addressed the role expectations of a nurse among underserved cancer survivors and caregivers (CSCs), especially those who belong to a minority group. The purpose of this study was to explore the role expectations of nurses among aging African American cancer survivors and caregivers. Methods: A qualitative approach was utilized, using purposeful and theoretical sampling. Semi-structured qualitative interviews were conducted with 40 aging and community-dwelling African American cancer survivors and caregivers. Data was analyzed using a descriptive approach and thematic content analysis. Results: The results suggest that nurses should have a greater awareness of life events and challenges that can affect cancer survivorship, such as body image issues, financial hardship, and low social support. The following three themes that emerged that describe the perception of the nursing role and minority CSCs include: (1) adequate health education and nursing skill demonstration related to CSC, (2) increased advocacy for the underserved cancer survivors and caregivers, including resource identification and sharing, and (3) assessment and management of the biopsychosocial needs of CSCs. Implications: The role of nurses in these communities managing cancer survivorship among both survivors and caregivers is critical as these specific populations may have unique care needs. The results can be used to inform the development of culturally relevant and nursing-led interventions targeted towards CSCs to improve the cancer survivorship experience for aging minority populations.
Citation Format: Sharon Cobb, Ebere Ume. Perceptions of the nursing role in cancer survivorship among aging African American cancer survivors and caregivers [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A028.
Abstract A031: Karmanos Cancer Institute Prostate Cancer Advocacy Program
Authors: Hardy Fred 
Published: September 2020

Abstract
A multifaceted training expanding the realm and scope of the meaning of advocacy and what advocacy can be.
Citation Format: Fred Hardy. Karmanos Cancer Institute Prostate Cancer Advocacy Program [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A031.
Abstract A049: Socioeconomic disparities in treatment delays and survival for anal cancer patients
Authors: Ahmad Tessnim R , Susko Matthew , Lindquist Karla , Anwar Mekhail 
Published: September 2020

Abstract
Background: Socioeconomic status (SES) is associated with treatment delays and survival in multiple cancers, but less data exist for anal squamous cell carcinoma (ASCC). This study investigated the association between SES and outcomes for patients undergoing definitive chemoradiation therapy for ASCC. Methods: Patients diagnosed with non-metastatic ASCC between 2005 and 2018 were retrospectively reviewed. Socioeconomic predictor variables included primary payer, race, income, employment, and partnership status. Outcomes included tumor-node (TN) stage at diagnosis, the interval from diagnosis to treatment initiation, relapse-free survival (RFS), and overall survival (OS). Age, gender, TN stage, and HIV status were analyzed as covariates in survival analysis. Results: Over the study period, 111 patients met inclusion criteria. SES was not associated with the TN stage at diagnosis. SES factors associated with treatment delays were Medicaid payer (p = 0.016) and single partnership status (p = 0.016). Compared to privately insured patients, Medicaid patients had lower two-year RFS (64.4% vs. 93.8%, p = 0.021) and OS (82.9% vs. 93.5%, p = 0.038). Similarly, relative to patients in the racial majority, racial minority patients had lower two-year RFS (53.3% vs. 93.5%, p = 0.001) and OS (73.7% vs. 92.6%, p = 0.008). Race was an independent predictor for both RFS (p = 0.027) and OS (p = 0.047). Conclusions: These results highlight the impact of social contextual factors on health. Interventions targeted at socioeconomically vulnerable populations are needed to reduce disparities in ASCC outcomes.
Citation Format: Tessnim R Ahmad, Matthew Susko, Karla Lindquist, Mekhail Anwar. Socioeconomic disparities in treatment delays and survival for anal cancer patients [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A049.
Abstract A056: A study of race and socioeconomic status impacting therapeutic clinical trial enrollment in adult gliomas patients
Authors: Reihl Sheantel J , Morshed Ramin A , Kakaizada Sofia , Zhang Eric , Young Jacob S , Clarke Jennifer , Butowski Nicholas , Taylor Jennie , Bush Nancy Ann , Aghi Manish K , Berger Mitchel S , Chang Susan , Hervey-Jumper Shawn L 
Published: September 2020

Abstract
Introduction: Under-enrollment in clinical trials significantly limits valid analyses of clinical interventions and generalizability of findings. It can also result in premature study termination, with estimates of 22% to 50% of clinical trials being terminated due to poor accrual. Currently, there are limited reports addressing the influence of race, ethnicity and socioeconomic status on clinical trial enrollment in patients with adult glioma. The goal of this study was to determine if race and socioeconomic status impacts clinical trial participation for glioma patients. Methods: A search within the UCSF Tumor Board Registry identified 852 adult patients discussed over a 2-year period. This cohort was analyzed to determine the rate of therapeutic clinical trial consideration, tumor board recommendation, and study enrollment based on clinical reports available through the electronic medical record. Results: At the time of initial diagnosis, 30.7% and 18.0% of glioma patients were recommended and enrolled in a therapeutic clinical trial, respectively. At the time of recurrence, 38.7% and 25.3% of patient were recommended and enrolled in a clinical trial, respectively. Nineteen percent of the study population belonged to a NIH designated underrepresented minority group, with Asian/Pacific Islander patients comprising 10.3% of the total patient cohort. Percentage of patients who enrolled in a clinical trial was comparable between subgroups. On univariate analysis, only in-state location, distance to the hospital, and WHO grade were associated with consideration, recommendation, and enrollment at initial diagnosis and recurrence. Minority status, insurance type, median household income, and percent below poverty line based on county of residence were not associated with clinical trial recommendation or enrollment. Conclusion: Race and socioeconomic status did not impact clinical trial consideration, tumor board recommendation, or study enrollment. Our results do not support the premise that provider decisions are impacted by biases based on minority or socioeconomic status.
Citation Format: Sheantel J Reihl, Ramin A Morshed, Sofia Kakaizada, Eric Zhang, Jacob S Young, Jennifer Clarke, Nicholas Butowski, Jennie Taylor, Nancy Ann Bush, Manish K Aghi, Mitchel S Berger, Susan Chang, Shawn L Hervey-Jumper. A study of race and socioeconomic status impacting therapeutic clinical trial enrollment in adult gliomas patients [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A056.
Abstract A127: Medicare restricts coverage of genetic testing
Authors: Hobbs Verinda 
Published: September 2020

Abstract
This poster will discuss the Medicare to National Coverage Determinations (NCD) for Next Generation Sequencing (NGS) for Medicare Beneficiaries with Advanced Cancer. The change to NCD will impact access to necessary screenings of people within specific communities most at risk for hereditary cancers; all age groups, men and women but specifically people of color with BRCA 1 and BRCA 2 gene mutations. Germline mutations are associated with increased risk of a variety of cancers and confer significant risk of increased morbidity and additional primary cancers. Without access to genetic testing, the possibility of identifying the “familial component” of cancer increases, resulting in late diagnoses, complicating and creating difficult treatment decisions and potentially affecting the prognosis. The NCD should strive to provide reasonable and necessary care that aligns with current evidence based guidelines and medicine. Germline tests should be covered, are important diagnostic tools that identify specific mutations’ this knowledge can provide physicians the benefit of clinically actionable interventions.
Citation Format: Verinda Hobbs. Medicare restricts coverage of genetic testing [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A127.