tbuckley/cabot-search huggingface dataset:
Abstract P5-15-09: A LINE Bot mobile app module to augment long-term and real-time follow-up of patients with breast cancer
Authors: Pei-Ju Lien, Chi-Cheng Huang, Ling-Ming Tseng
Journal: Cancer Research (2022)

Abstract Purpose: Female breast cancer is one of the most frequent cancer types in Taiwan, and several novel therapeutic options have been introduced in recent years. Patients usually received a combination of treatment modalities based on the pathological type, cancer staging and personal preferences. Due to the complexity of treatment involved, specifically associated adverse reactions and variable treatment duration, assessment of quality of life (QoL), long-term and real-time surveillance are difficult to achieve. To overcome the above limitations, we developed a LINE Bot module to augment the follow-up of patients with breast cancer. Materials and Methods: The LINE Bot is comprised of personal information including disease characteristics, therapeutic timeframe, a quality-of-life measuring instrument, the EORTC QLQ-C30 and QLQ-BR23, knowledge and guidance concerning breast cancer. The mobile app also serves as a platform for the patients to interact with their conducting physicians. Results: During the nine-month enrollment period, 108 patients who had received breast cancer therapies at our institute were identified on hospitalization or outpatient basis. Invitation was made in person, and an access to the mobile app or a direct link to online quality-of-life questionnaire was provided. Patients with ECOG=0 reported better global health/Global quality of life status (62 versus 14, P&amp;lt;0.01), physical function (90 versus 73, P&amp;lt;0.05), cognitive function (81 versus 28, P&amp;lt;0.01), less pain (24 versus 67, P&amp;lt;0.01) and dyspnea (10 versus 67, P&amp;lt;0.01) compared to those with ECOG&amp;gt;1. Patients in the status of follow-up had better role function than those undergoing active treatment (92 versus 78, P&amp;lt;0.05). Conclusion: The establishment of the LINE Bot module could improve outcomes assessment for patients themselves and physicians in charge. It provided an opportunity to reflect quality-of-life influenced by each treatment modality and disease status as these patients could repeat the questionnaire at any timing. The platform for interaction could also contribute to enhancing the quality of care. Citation Format: Pei-Ju Lien, Chi-Cheng Huang, Ling-Ming Tseng. A LINE Bot mobile app module to augment long-term and real-time follow-up of patients with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-15-09.
Burnout: set up watchdog to protect NHS staff, says wellbeing champion
Authors: Ingrid Torjesen
Journal: BMJ (2022)

<h3>OBJECTIVE</h3> To investigate the relation between measures of pain threshold and symptoms of distress to determine if fibromyalgia is a discrete construct/disorder in the clinic. <h3>METHODS</h3> 627 patients seen at an outpatient rheumatology centre from 1993 to 1996 underwent tender point and dolorimetry examinations. All completed the assessment scales for fatigue, sleep disturbance, anxiety, depression, global severity, pain, functional disability, and a composite measure of distress constructed from scores of sleep disturbance, fatigue, anxiety, depression, and global severity—the rheumatology distress index (RDI). <h3>RESULTS</h3> In regression analyses, the RDI was linearly related to the count of tender points (<i>r</i><sup>2</sup>=0.30). Lesser associations were found between the RDI and dolorimetry measurements (<i>r</i><sup>2</sup>=0.08). The RDI was more strongly correlated with the two measures of pain threshold than any of the individual fibromyalgia symptom variables. In partial correlation analyses, all of the information relating to symptom variables was contained in the tender point count, and dolorimetry was not independently related to symptoms. <h3>CONCLUSION</h3> Tender points are linearly related to fibromyalgia variables and distress, and there is no discrete enhancement or perturbation of fibromyalgia or distress variables associated with very high levels of tender points. Although fibromyalgia is a recognisable clinical entity, there seems to be no rationale for treating fibromyalgia as a discrete disorder, and it would seem appropriate to consider the entire range of tenderness and distress in clinic patients as well as in research studies. The tender point count functions as a ‘sedimentation rate’ for distress, and is a better measure than the dolorimetry score.
Multiscale Hierarchical Architecture‐Based Bioactive Scaffolds for Versatile Tissue Engineering
Authors: Hongshi Ma, Chen Yang, Zhenjiang Ma, Xiaoyue Wei, Muhammad Rizwan Younis, Hanbo Wang, Wentao Li, Zhiyong Wang, Wenhao Wang, Yongxiang Luo, Peng Huang, Jinwu Wang
Journal: Advanced Healthcare Materials (2022)

Artificial construction from tendon to bone remains a formidable challenge in tissue engineering owing to their structural complexity. In this work, bioinspired calcium silicate nanowires and alginate composite hydrogels are utilized as building blocks to construct multiscale hierarchical bioactive scaffolds for versatile tissue engineering from tendon to bone. By integrating 3D printing technology and mechanical stretch post-treatment in a confined condition, the obtained composite hydrogels possess bioinspired reinforcement architectures from nano- to submicron- to microscale with significantly enhanced mechanical properties. The biochemical and topographical cues of the composite hydrogel scaffolds provide much more efficient microenvironment to the rabbit bone mesenchymal stem cells and rabbit tendon stem cells, leading to ordered alignment and improved differentiation. The composite hydrogels markedly promote in vivo tissue regeneration from bone to tendon, especially fibrocartilage transitional tissue. Therefore, such calcium silicate nanowires/alginate composite hydrogels with multiscale hierarchical structures have potential application for tissue regeneration from tendon to bone. This work provides an innovative strategy to construct multiscale hierarchical architecture-based scaffolds for tendon/bone engineering.
31P Molecular testing, treatment and outcome of patients with advanced solid tumors harboring a NTRK1, NTRK2 or NTRK3 gene fusion: Study design and first results of the REALTRK registry
Authors: C. Vannier, A. Völkel, U.M. Martens, T. Decker, G. Köchling, S. Lange, E. Von der Heyde, T-O. Emde, A. Wortmann, R. Grunewald, M. Frank, B. Niemeier, M. Flum, B. Kasenda
Journal: Annals of Oncology (2022)
FK506 BINDING PROTEIN 51 COLOCALIZES WITH MICROTUBULES AND MAY CONTRIBUTE TO METABOLIC ABNORMALITIES BY DIRECTING GLUCOCORTICOID RECEPTOR LOCALIZATION IN PULMONARY ARTERY ENDOTHELIAL CELLS ISOLATED FROM THE SUGEN RAT MODEL OF PULMONARY ARTERIAL HYPERTENSION
Authors: Marcus J. Kwon, Caleb L. Hamilton, Jonathan R. Brown, Emily A. Snyder, Audrey A. Vasauskas
Journal: Journal of the American College of Cardiology (2022)
Four-Year Disease-Free Remission in a Patient With POLE Mutation–Associated Colorectal Cancer Treated Using Anti–PD-1 Therapy
Authors: Michael L. Durando, Sanjay V. Menghani, Jessica L. Baumann, Danny G. Robles, Tovah A. Day, Cyrus Vaziri, Aaron J. Scott
Journal: Journal of the National Comprehensive Cancer Network (2022)

The stability of the human genome depends upon a delicate balance between replication by high- and low-fidelity DNA polymerases. Aberrant replication by error-prone polymerases or loss of function of high-fidelity polymerases predisposes to genetic instability and, in turn, cancer. DNA polymerase epsilon (Pol ε) is a high-fidelity, processive polymerase that is responsible for the majority of leading strand synthesis, and mutations in Pol ε have been increasingly associated with various human malignancies. The clinical significance of Pol ε mutations, including how and whether they should influence management decisions, remains poorly understood. In this report, we describe a 24-year-old man with an aggressive stage IV high-grade, poorly differentiated colon carcinoma who experienced a dramatic response to single-agent checkpoint inhibitor immunotherapy after rapidly progressing on standard chemotherapy. His response was complete and durable and has been maintained for more than 48 months. Genetic testing revealed a P286R mutation in the endonuclease domain of POLE and an elevated tumor mutational burden of 126 mutations per megabase, both of which have been previously associated with response to immunotherapy. Interestingly, tumor staining for PD-L1 was negative. This case study highlights the importance of genetic profiling of both early and late-stage cancers, the clinical significance of POLE mutations, and how the interplay between genetic instability and immune-checkpoint blockade can impact clinical decision-making.
CARDIAC MAGNETIC RESONANCE IMAGING AND ECHOCARDIOGRAPHY IN MORBIDLY OBESE PATIENTS: AN ASSESSMENT OF IMAGE QUALITY
Authors: Akash Goyal, Christopher D. Crabtree, Thura T. Harfi, Haikady Nagaraja, Bryan Lee, Saurabh Rajpal, Orlando P. Simonetti, Matthew S. Tong
Journal: Journal of the American College of Cardiology (2022)
Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico
Authors: Lisa M. Dunkle, Karen L. Kotloff, Cynthia L. Gay, Germán Áñez, Jeffrey M. Adelglass, Alejandro Q. Barrat Hernández, Wayne L. Harper, Daniel M. Duncanson, Monica A. McArthur, Diana F. Florescu, R. Scott McClelland, Veronica Garcia-Fragoso, Robert A. Riesenberg, David B. Musante, David L. Fried, Beth E. Safirstein, Mark McKenzie, Robert J. Jeanfreau, Jeffrey K. Kingsley, Jeffrey A. Henderson, Dakotah C. Lane, Guillermo M. Ruíz-Palacios, Lawrence Corey, Kathleen M. Neuzil, Robert W. Coombs, Alex L. Greninger, Julia Hutter, Julie A. Ake, Katherine Smith, Wayne Woo, Iksung Cho, Gregory M. Glenn, Filip Dubovsky
Journal: New England Journal of Medicine (2021)

NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b–3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America.
Abstract P3-09-01: A ubiquitination cascade regulating the integrated stress response and survival in carcinomas
Authors: Lisa D Cervia, Tsukasa Shibue, Benjamin Gaeta, Ashir A Borah, Lisa Leung, Naomi Li, Nancy Dumont, Alfredo Gonzalez, Nolan Bick, Mariya Kazachkova, Joshua M Dempster, John M Krill-Burger, Federica Piccioni, Namrata D Udeshi, Meagan E Olive, Steven A Carr, David E Root, James M McFarland, Francisca Vazquez, William C Hahn
Journal: Cancer Research (2022)

Abstract Targeting of mutated oncogenes has led to the identification of new targeted therapies. However, druggable oncogenes do not occur in most cancers. Systematic identification of signaling pathways required for the fitness of cancer cells will facilitate the development of new cancer therapies. We used gene essentiality measurements in 793 cancer cell lines to identify selective co-essentiality modules and found that a ubiquitination ligase complex composed of UBA6, BIRC6, KCMF1 and UBR4, which encode an E1, E2 and two heterodimeric E3 subunits, respectively, is required for the survival of a subset of epithelial tumors, particularly subtypes of breast cancer. Suppressing BIRC6 in cell lines that are dependent on this complex led to a substantial reduction in cell fitness in vitro and potent tumor regression in vivo. Mechanistically, BIRC6 suppression resulted in selective activation of the integrated stress response (ISR) by stabilization and upregulation of the heme-regulated inhibitor (HRI), a direct ubiquitination target of the UBA6/BIRC6/KCMF1/UBR4 complex. These observations uncover a novel ubiquitination cascade that regulates ISR and highlight the potential of ISR activation as a new therapeutic strategy. Citation Format: Lisa D Cervia, Tsukasa Shibue, Benjamin Gaeta, Ashir A Borah, Lisa Leung, Naomi Li, Nancy Dumont, Alfredo Gonzalez, Nolan Bick, Mariya Kazachkova, Joshua M Dempster, John M Krill-Burger, Federica Piccioni, Namrata D Udeshi, Meagan E Olive, Steven A Carr, David E Root, James M McFarland, Francisca Vazquez, William C Hahn. A ubiquitination cascade regulating the integrated stress response and survival in carcinomas [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-09-01.
DES STRUT THICKNESS AND CLINICAL OUTCOMES AFTER CTO RECANALIZATION: INSIGHTS FROM LATAM CTO REGISTRY
Authors: Sérgio Câmara, Carlos Campos, Rodrigo Daghlawi, Lucio Padilla, João Tinoco, Antônio Carlos Botelho, Ricardo Santiago, Mauro Echavarria, Felix de los Santos, Marcos Danillo Oliveira, Anibal Pereira Abelin, Pedro Oliveira, Luis Pino, Marcelo Harada, Emmanouil S. Brilakis, Alexandre Abizaid, Alexandre Schaan Quadros
Journal: Journal of the American College of Cardiology (2022)
Algorithms for Ethical Decision-Making in the Clinic: A Proof of Concept
Authors: Lukas J. Meier, Alice Hein, Klaus Diepold, Alena Buyx
Journal: The American Journal of Bioethics (2022)

Machine intelligence already helps medical staff with a number of tasks. Ethical decision-making, however, has not been handed over to computers. In this proof-of-concept study, we show how an algorithm based on Beauchamp and Childress' prima-facie principles could be employed to advise on a range of moral dilemma situations that occur in medical institutions. We explain why we chose fuzzy cognitive maps to set up the advisory system and how we utilized machine learning to train it. We report on the difficult task of operationalizing the principles of beneficence, non-maleficence and patient autonomy, and describe how we selected suitable input parameters that we extracted from a training dataset of clinical cases. The first performance results are promising, but an algorithmic approach to ethics also comes with several weaknesses and limitations. Should one really entrust the sensitive domain of clinical ethics to machine intelligence?
Impaired neutralisation of SARS-CoV-2 delta variant in vaccinated patients with B cell chronic lymphocytic leukaemia
Authors: Helen Parry, Graham McIlroy, Rachel Bruton, Sarah Damery, Grace Tyson, Nicola Logan, Chris Davis, Brian Willett, Jianmin Zuo, Myah Ali, Manjit Kaur, Christine Stephens, Dawn Brant, Ashley Otter, Tina McSkeane, Hayley Rolfe, Sian Faustini, Alex Richter, Sophie Lee, Farooq Wandroo, Salim Shafeek, Guy Pratt, Shankara Paneesha, Paul Moss
Journal: Journal of Hematology & Oncology (2022)

Immune suppression is a clinical feature of chronic lymphocytic leukaemia (CLL), and patients show increased vulnerability to SARS-CoV-2 infection and suboptimal antibody responses. We studied antibody responses in 500 patients following dual COVID-19 vaccination to assess the magnitude, correlates of response, stability and functional activity of the spike-specific antibody response with two different vaccine platforms. Spike-specific seroconversion post-vaccine was seen in 67% of patients compared to 100% of age-matched controls. Amongst responders, titres were 3.7 times lower than the control group. Antibody responses showed a 33% fall over the next 4 months. The use of an mRNA (n = 204) or adenovirus-based (n = 296) vaccine platform did not impact on antibody response. Male gender, BTKi therapy, prophylactic antibiotics use and low serum IgA/IgM were predictive of failure to respond. Antibody responses after CD20-targeted immunotherapy recovered 12 months post treatment. Post-vaccine sera from CLL patients with Spike-specific antibody response showed markedly reduced neutralisation of the SARS-CoV-2 delta variant compared to healthy controls. Patients with previous natural SARS-CoV-2 infection showed equivalent antibody levels and function as healthy donors after vaccination. These findings demonstrate impaired antibody responses following dual COVID-19 vaccination in patients with CLL and further define patient risk groups. Furthermore, humoural protection against the globally dominant delta variant is markedly impaired in CLL patients and indicates the need for further optimisation of immune protection in this patient cohort.
Corrigendum to “Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up”
Authors: A. Vogel, A. Cervantes, I. Chau, B. Daniele, J.M. Llovet, T. Meyer, J.-C. Nault, U. Neumann, J. Ricke, B. Sangro, P. Schirmacher, C. Verslype, C.J. Zech, D. Arnold, E. Martinelli
Journal: Annals of Oncology (2022)
Abstract P2-10-04: Breast cancer risk assessment tool (BCRAT) predicted breast cancer incidence and breast cancer mortality in the women's health initiative
Authors: Rebecca Nelson, Kathy Pan, Rowan Chlebowski, Thomas E Rohan, Joanne Mortimer, Jean Wactawski-Wende, Dorothy Lane, Laura Kruper
Journal: Cancer Research (2022)

Abstract Purpose Commonly used breast cancer risk models estimate breast cancer incidence. However, such model performance, re-purposed to predict breast cancer mortality, are largely unknown. Therefore, we examined whether the BCRAT model predicts long-term breast cancer mortality in postmenopausal women in the WHI. Participants and Methods Of 161,808 WHI participants aged 50-79 years, after exclusions,145,408 were in the analysis. BCRAT risk was calculated, with incident breast cancers verified by central medical record review. Breast cancer mortality was related to BCRAT 5-year risk groups (&amp;lt; 1%, 1-2.99%, ≥ 3%) using unadjusted Cox proportional hazard models and in age-stratified, multi-variable models. An addition analysis compared proportion of participants with BCRAT risk ≥ 1.67% and ≥ 3% (former and current prevention thresholds). Results Of 145,408 participants, the ≥1.67% and the ≥3.0% risk groups included 40% and 9% of participants, respectively. Compared to women with BCRAT&amp;lt;1% risk, women with BCRAT ≥ 3% risk had more common breast cancer family history and lower BMI. After 20 years median follow-up, with 8,849 breast cancers and 1,076 deaths from breast cancer, risk of death from breast cancer in BCRAT risk group ≥ 3% was not higher compared to BCRAT risk group &amp;lt;1%. (Hazard Ratio [HR] 1.06 95% Confidence Interval [CI] 0.80-1.40, P = 0.76). Similarly, risk of death from breast cancer in BCRAT risk group 1-2.99% was not higher compared to BCRAT risk group &amp;lt;1 (HR 1.15 95% CI 0.93-1.43). Conclusions Current guideline recommendation for threshold for endocrine-targeted interventions substantially reduces postmenopausal prevention candidates from 40% to &amp;lt;10%. The BCRAT prediction model, even at the ≥ 3% 5-year risk threshold, does not identify women at significantly increased risk of death from breast cancer. Citation Format: Rebecca Nelson, Kathy Pan, Rowan Chlebowski, Thomas E Rohan, Joanne Mortimer, Jean Wactawski-Wende, Dorothy Lane, Laura Kruper. Breast cancer risk assessment tool (BCRAT) predicted breast cancer incidence and breast cancer mortality in the women's health initiative [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-10-04.
Improving the Affordability of Anticancer Medicines Demands Evidence-Based Policy Solutions
Authors: Nora Franzen, Giorgia Romagnoli, Andreas Ziegler, Valesca P. Retèl, Theo J.S. Offerman, Wim H. van Harten
Journal: Cancer Discovery (2022)

The high cost of many new anticancer medicines significantly impedes breakthrough discoveries from reaching patients. A commonly heard refrain is that high prices are necessary to compensate for the high costs of research and development (R&D). Yet, there are promising policy proposals aimed at improving affordability without compromising innovation. In seeking new policy solutions, we argue for a shift away from entrenched opinion toward an evidence-based discourse that is grounded in experiments and real-world pilot studies. We offer a novel perspective and practical recommendations on how empirical evidence could and should be gathered to inform evidence-based policy interventions that lead to sustainable medicine prices in oncology.See related article by Franzen et al. (Cancer Res Commun 2022;2:39-47).
Ferrous iron–activatable drug conjugate achieves potent MAPK blockade in <i>KRAS</i>-driven tumors
Authors: Honglin Jiang, Ryan K. Muir, Ryan L. Gonciarz, Adam B. Olshen, Iwei Yeh, Byron C. Hann, Ning Zhao, Yung-hua Wang, Spencer C. Behr, James E. Korkola, Michael J. Evans, Eric A. Collisson, Adam R. Renslo
Journal: The Journal of Experimental Medicine (2022)

KRAS mutations drive a quarter of cancer mortality, and most are undruggable. Several inhibitors of the MAPK pathway are FDA approved but poorly tolerated at the doses needed to adequately extinguish RAS/RAF/MAPK signaling in the tumor cell. We found that oncogenic KRAS signaling induced ferrous iron (Fe2+) accumulation early in and throughout mutant KRAS-mediated transformation. We converted an FDA-approved MEK inhibitor into a ferrous iron–activatable drug conjugate (FeADC) and achieved potent MAPK blockade in tumor cells while sparing normal tissues. This innovation allowed sustainable, effective treatment of tumor-bearing animals, with tumor-selective drug activation, producing superior systemic tolerability. Ferrous iron accumulation is an exploitable feature of KRAS transformation, and FeADCs hold promise for improving the treatment of KRAS-driven solid tumors.
New Deputy Editor—March 2022
Authors: Melina R. Kibbe
Journal: JAMA Surgery (2022)

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