tbuckley/cabot-search huggingface dataset:
P14.06 Radiomics for the non-invasive determination of the BRAF mutational status in patients with melanoma brain metastases
Authors: A Meissner, R Gutsche, N Galldiks, M Kocher, S T Juenger, C Wendl, C Mauch, M Proescholdt, S Grau, P Lohmann
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The BRAF V600E mutation is present in approximately 50% of patients with melanoma and is an important prerequisite for a response to targeted therapies such as BRAF inhibitors. In the majority of patients, the BRAF mutational status is based on the analysis of tissue samples from the extracranial primary tumor only. Since the extracranial and intracranial BRAF mutational status may be discrepant, the additional information on the BRAF mutational status of melanoma brain metastases would be of clinical value, e.g., for the prediction of response to targeted therapies. Here, we evaluated the potential of structural MRI radiomics for the determination of the intracranial BRAF mutational status in patients with melanoma brain metastases. MATERIAL AND METHODS Fifty-nine patients with melanoma brain metastases from two university hospitals (group 1, 45 patients; group 2, 14 patients) underwent surgery with subsequent genetic analysis of the brain metastases tissue to determine the BRAF mutational status. All patients underwent structural MRI preoperatively. Areas of contrast enhancement were manually segmented and analyzed. Group 1 was used for model training and validation, group 2 for model testing. After image preprocessing, 1,316 radiomics features were extracted using the open-source PyRadiomics package. A test-retest analysis was performed to identify robust features prior to feature selection. Finally, the best performing radiomics model was applied to the test data (group 2). Diagnostic performances were evaluated using receiver operating characteristic (ROC) analyses. RESULTS Twenty-two patients (49%) in group 1, and 6 patients (43%) in group 2 had an intrametastatic BRAF V600E mutation. Using a six parameter radiomics signature, a linear support vector machine classifier yielded an average area under the ROC curve (AUC) of 0.87 (accuracy, 85%; sensitivity, 78%; specificity, 91%) for prediction of the BRAF mutational status in the training data (group 1). Finally, the classifier achieved an AUC of 0.85 (accuracy, 86%; sensitivity, 83%; specificity, 88%) in the test data (group 2). CONCLUSION The developed radiomics classifier allows a non-invasive prediction of the intracranial BRAF V600E mutational status in patients with melanoma brain metastases and may be of value for treatment decisions.
Risk of reactivated toxoplasmosis in haematopoietic stem cell transplant recipients: a prospective cohort study in a setting withholding prophylaxis
Authors: Tijana Štajner, Dragana Vujić, Jelena Srbljanović, Neda Bauman, Željko Zečević, Marija Simić, Olgica Djurković-Djaković
Journal: Clinical Microbiology and Infection (2021)
Direct endoscopic ultrasound-guided gastroenterostomy using a feeding-tube waterjet system: a teaching video to facilitate understanding of the technique
Authors: Claudia F. Consiglieri, Daniel Luna-Rodriguez, Albert Garcia-Sumalla, Sandra Maisterra, Julio G. Velasquez-Rodriguez, Joan B. Gornals
Journal: Endoscopy (2021)

To facilitate the safe and simple introduction of an endoscopic ultrasound (EUS)-guided gastroenterostomy technique, we present a step-by-step teaching video of a variant technique for direct EUS-guided gastroenterostomy using a feeding tube ([Video 1]). The stages involved are as follows.
NCCN Guidelines® Insights: Older Adult Oncology, Version 1.2021
Authors: Efrat Dotan, Louise C. Walter, Ilene S. Browner, Katherine Clifton, Harvey Jay Cohen, Martine Extermann, Cary Gross, Sumati Gupta, Genevieve Hollis, Joleen Hubbard, Reshma Jagsi, Nancy L. Keating, Elizabeth Kessler, Thuy Koll, Beatriz Korc-Grodzicki, June M. McKoy, Sumi Misra, Dominic Moon, Tracey O’Connor, Cynthia Owusu, Ashley Rosko, Marcia Russell, Mina Sedrak, Fareeha Siddiqui, Amy Stella, Derek L. Stirewalt, Ishwaria M. Subbiah, William P. Tew, Grant R. Williams, Liz Hollinger, Giby V. George, Hema Sundar
Journal: Journal of the National Comprehensive Cancer Network (2021)

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.
Experienced quality of care and emotional functioning of patients with advanced cancer and their relatives: Results of a multicenter observational cohort study (eQuiPe).
Authors: Janneke van Roij, Natasja Raijmakers, Laurien Ham, Marieke van den Beuken-van Everdingen, Ben van den Borne, Geert-Jan Creemers, Jarno Cornelis Hunting, Evelien Kuip, Lobke van Leeuwen, Hanneke W.M. Van Laarhoven, Caroline M. Mandigers, Peter Nieboer, Lilly-Ann van der Velden, Cornelia Van Zuijlen, John Gelissen, Myrte Zijlstra, Linda Brom, Heidi Fransen, Lonneke V van de Poll-Franse
Journal: Journal of Clinical Oncology (2021)

3 Background: Previous studies on experienced quality of care and quality of life have not addressed the reciprocal relation between patients and their relatives. For the first time we were able to include almost 700 couples (patient – relative) in a palliative oncological care context. This study aims to assess the experienced quality of care and emotional functioning (EF) of patients with advanced cancer and their relatives, including their reciprocal relation by using a dyadic approach. Methods: A prospective multicentre observational study among patients with advanced cancer and their relatives, recruited from 40 hospitals in the Netherlands or self-enrolled between November 2017 and January 2020 (eQuiPe study). Patients with metastatic cancer and their relatives were eligible to participate. Respondents completed a questionnaire and clinical data of the patient were obtained by linking the information to the Netherlands Cancer Registry (NCR). Logistic regression analyses were performed on baseline data of 1,103 patients and 831 relatives to assess the association between experienced quality of care and EF of patients and relatives separately and across dyads. Results: In total, 1,103 (65%) patients and 831 (71%) relatives completed the baseline questionnaire, including 699 unique patient-relative couples. Patients experienced lower levels of quality of life, including EF, and more symptoms compared to the normative population ( p&lt;.001). Relatives reported even clinically relevantly lower EF compared to patients (69 vs. 78, p&lt;.001) and were less satisfied with care (59 vs. 74; p&lt;.001). Being more satisfied with care in general ( p&lt;.05) and clarity about who their central health care professional ( p&lt;.05) were positively associated with high EF in patients. For relatives, perceived continuity of care ( p&lt;.01) and continuity of information for the patient ( p&lt;.05) were positively associated with high EF. Dyadic analyses showed that EF of patients ( p&lt;.001) and relatives ( p&lt;.001) was positively associated with EF of the other person and perceived continuity of care by relatives was positively associated with high EF in patients ( p&lt;.01). Conclusions: Experienced integral organisation and satisfaction with care in patients and relatives are related to their EF. The additional reciprocal relation between patients’ and their relatives’ EF and the experienced continuity of care suggests the opportunity for a family‐centered approach to optimize advanced cancer care.
Long-term outcomes in patients with severe aplastic anemia treated with immunosuppression and eltrombopag: a phase 2 study
Authors: Bhavisha A. Patel, Emma M. Groarke, Jennifer Lotter, Ruba Shalhoub, Fernanda Gutierrez-Rodrigues, Olga Rios, Diego Quinones Raffo, Colin O. Wu, Neal S. Young
Journal: Blood (2021)
Chromatin accessibility and regulatory vocabulary across indicine cattle tissues
Authors: Pâmela A. Alexandre, Marina Naval-Sánchez, Moira Menzies, Loan T. Nguyen, Laercio R. Porto-Neto, Marina R. S. Fortes, Antonio Reverter
Journal: Genome biology (2021)

Abstract Background Spatiotemporal changes in the chromatin accessibility landscape are essential to cell differentiation, development, health, and disease. The quest of identifying regulatory elements in open chromatin regions across different tissues and developmental stages is led by large international collaborative efforts mostly focusing on model organisms, such as ENCODE. Recently, the Functional Annotation of Animal Genomes (FAANG) has been established to unravel the regulatory elements in non-model organisms, including cattle. Now, we can transition from prediction to validation by experimentally identifying the regulatory elements in tropical indicine cattle. The identification of regulatory elements, their annotation and comparison with the taurine counterpart, holds high promise to link regulatory regions to adaptability traits and improve animal productivity and welfare. Results We generate open chromatin profiles for liver, muscle, and hypothalamus of indicine cattle through ATAC-seq. Using robust methods for motif discovery, motif enrichment and transcription factor binding sites, we identify potential master regulators of the epigenomic profile in these three tissues, namely HNF4, MEF2, and SOX factors, respectively. Integration with transcriptomic data allows us to confirm some of their target genes. Finally, by comparing our results with Bos taurus data we identify potential indicine-specific open chromatin regions and overlaps with indicine selective sweeps. Conclusions Our findings provide insights into the identification and analysis of regulatory elements in non-model organisms, the evolution of regulatory elements within two cattle subspecies as well as having an immediate impact on the animal genetics community in particular for a relevant productive species such as tropical cattle.
Naringenin nanocrystals for improving anti-rheumatoid arthritis activity
Authors: Guangshuai Zhang, Guangyuan Sun, Haishan Guan, Mo Li, Yanhua Liu, Baocheng Tian, Zhonggui He, Qiang Fu
Journal: Asian Journal of Pharmaceutical Sciences (2021)

Naringenin (NAR) is recognized for its anti-inflammatory activity. However, the clinical application of NAR is limited by low bioavailability, which is attributed to its poor aqueous solubility. In this study, we aimed to improve the therapeutic efficacy of NAR by formulating it into nanocrystals (NCs) via wet milling. The obtained NARNCs exhibited superior dissolution behaviors, increased cellular uptake, and enhanced transcellular diffusion relative to those of bulk NAR. Oral administration of NARNCs also significantly improved bioavailability in rats. In addition, the NARNCs effectively improved rheumatoid arthritis treatment in collagen-induced arthritic rats by reducing inflammatory cell infiltration and synovial damage. These results indicate that NARNCs provides a promising strategy for rheumatoid arthritis treatment.
P14.78 Comparison of progression-free survival after reirradiation of local and distant glioblastoma’s relapses
Authors: A Belyashova, G Pavlova, N Antipina, A Nikolaeva, E Savchenko, D Panteleev, G Kobyakov, Y Trunin, A Golanov
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Despite using of modern comprehensive approaches to the treatment of patients with glioblastomas (GB) it invariably recur after a median interval of less than 7 months. Relapses are inevitable and is often the leading cause of death in patients. About 80–90% of recurrences are local, distant relapses are 5–20%. The optimal treatment strategy of recurrent GB have not yet been determined. MATERIAL AND METHODS The analysis included 130 patients with 160 lesions after primary combined treatment. Progression was assessed based on the RANO criteria. All patients have been re-irradiated in various regimens: 26 pts with median dose 60 Gy/30 fr, 20 pts with median dose 45 Gy/15 fr, 74 pts with dose 24-35Gy for 3–7 fr., 10 pts with median dose 22Gy/1fr. The scheme and regimen of fractionation were determined by tumor volume, localization and functional status of patient. Chemotherapy was changed to a regimen with Bevacizumab (BVZ) before the re-irradiation. According to the EORTC criteria lesions were divided as local (n=112) and distant (n=48) progression with median volume 23.6 cc and 14.7 cc respectively. RESULTS The median progression-free survival in the whole group was 8.2 months(95% CI 7–8.7). Progression-free survival at 6; 12 and 24 months was 65.8%; 21.9% and 4% respectively. Progression-free median survival after treatment of local and distant glioblastoma recurrences was different: 7.6 and 9.2 months, respectively (p = 0.048). In 17.4% radiation necrosis was detected according to MRI and 11C-methionine PET-CT data. Steroid and BVZ therapy were effective in these cases, no one of them was reoperated. CONCLUSION Re-irradiation for GB recurrences is effective and safe way for improvement of outcomes in patients with progression. In the group of patients with local relapses, local control is lower than in the group of distant ones. It may associated with the increasing of the radioresistance of tumor cells after the initial combined treatment. Further studies are needed to compare and assess the role of radiobiological and others factors in the development of local and distant recurrence.The research was supported financially by RFBR (Project No. 18-29-01061).
Ibrutinib induces durable remissions in treatment-naïve patients with CLL and 17p deletion and/or <i>TP53</i> mutations
Authors: Mariela Sivina, Ekaterina Kim, William G. Wierda, Alessandra Ferrajoli, Nitin Jain, Philip Thompson, Hagop Kantarjian, Michael Keating, Jan A. Burger
Journal: Blood (2021)
Determinants of urologists’ adherence to active surveillance follow-up protocol for low-risk prostate cancer.
Authors: Soohyun Hwang, Sarah A. Birken
Journal: Journal of Clinical Oncology (2021)

12 Background: The National Comprehensive Cancer Network (NCCN) guideline offers a guideline for follow-up care for patients with low-risk prostate cancer on active surveillance (AS). However, in practice, 70% of patients receive follow-up care that is not guideline-adherent, characterized by insufficient or excessive surveillance testing, potentially diminishing AS effectiveness and contributing to poor patient outcomes. The objective of this study is to identify provider- and organization-level determinants of guideline-adherent AS follow-up care. Methods: We used in-depth semi-structured qualitative interviews with 13 United States urologists to examine determinants of urologists’ adherence to the active surveillance follow-up guideline. Guided by the combined use of the Consolidated Framework for Implementation Research, which focuses on organization-level determinants, and the Theoretical Domains Framework, which focuses on provider-level determinants, we used template analysis to identify multilevel determinants of urologists’ adherence to guideline-recommended AS follow-up care. Results: Relevant determinants were comfort with varied utilization behaviors of the guideline, perspectives on the prostate biopsy procedure, and the degree of structure within the practice setting. At the provider level, there was variation in how urologists provided AS follow-up care. All urologists referred to the NCCN guideline; however, most urologists adapted the guidelines to their needs and/or comfort level (e.g., following a subset of recommendations; adapting the interval/frequency of serial tests). Most providers felt that strictly adhering to the repeated biopsy aspect of the guideline was difficult because of concerns about fitting everybody to one type of frequency that does not stratify patients by risk. Others reflected on patients expressing physical discomfort and concerns of infection stemming from the biopsy procedure. At the organization level, urologists in a structured practice environment had the tendency towards providing NCCN guideline-adherent care whereas urologists practicing in settings with less organization relied more on individual discretion, which created room for flexibility with the care that they provide. Conclusions: Both provider- and organization-level determinants affected urologists’ provision of NCCN guideline-adherent follow-up care which may partially explain why patients eventually fail to receive guideline-adherent AS follow-up care. Findings call on the need for multilevel strategies to increase adherence or to modify existing guidelines to reflect the need at multiple levels.
David Oliver: Social care plan furthers inequality and unfairness
Authors: David Oliver
Journal: BMJ (2021)

In my last column I discussed the lack of detail or meaningful change in the government's Build Back Better plan for health and social care in England. 1 2 I did not, however, touch on the inherent inequality of the changes, between rich and poor, young and old.The "health and social care levy" is a planned 1.25 percentage point rise in national insurance contributions from April 2022.But this applies only to people in employment and younger than the state retirement age.From 2023 people still working beyond retirement age will also have to pay the levy.
P02.02 Modeling of response to irradiation in recurrence glioblastoma’s cells culture
Authors: N Antipina, A Belyashova, G Pavlova, A Nikolaeva, E Savchenko, A Ovechkina, D Shamadykova, A Golanov
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Radiosensitivity of glioblastoma (GB) cells of local relapses may be markedly different from the primary tumor. Optimal doses and regimes of re-irradiation GB recurrence is not determined yet. MATERIAL AND METHODS GO1 primary GB cell culture was obtained during removal of a recurrent tumor after combined treatment, including irradiation of the surgical bed. Сell’s culture was irradiated by photon beams with energy 6 MeV and dose rate 600 MU/min. Irradiation performed in 1, 3 and 5 fractions, by 10 different doses for each regime. The dose range was determined experimentally for one fraction (5–250 Gy); for other regimes it was calculated according to the biological equivalent dose conception (3 fractions: 5–450 Gy, 5 fractions: 5–550 Gy). The proliferative activity of cells was investigate by MTT test. The results were normalized to the control. Dose-effect curves were plotted for each irradiation regime.The experimental data were approximated by calculated curves obtained by selecting the optimal parameters of the LQ-model and it’s modification. RESULTS Irradiation of GO1 by 1 fraction with the dose 5–250 Gy, causes a slow decrease in proliferative activity, which reaches a minimum value of 23% at 150 Gy and then remains constant. After irradiation by 3 fractions, proliferative activity of the GO1 gradually decrease only at a total dose over 120 Gy and reaches 37% after 450 Gy. When GO1 was irradiated in 5 fractions, a similar dose-effect curve was obtained, gradual decrease was observed to a value of 52% in the range of 250–500 Gy. Thus, the experimental dose-effect curves for irradiation of recurrence GB cells for 3 and 5 fractions have the appreciable “shoulder”, which could be explained by increased radioresistance. When approximating the experimental data by fitting the parameters of the LQ-model, the use of α/β = 8 provided the slope of the curve, close to the experimental data. For reflecting the “shoulder” an additional summand was introduced into the mathematical expression for the number of proliferating cells - a 105 Gy for 3 fractions and 255 Gy for 5 fractions. CONCLUSION Modified LQ-model could be used for an adequate mathematical description of the effectiveness of fractionated irradiation in relapsed GB culture cells in vitro. It’s necessary to introduce a summand into the formula that determines the formation of a “shoulder” on the dose-effect curve for this. The research was supported financially by RFBR (Project No. 18-29-01061).
Surveillance for Colonization, Transmission, and Infection With Methicillin-Susceptible <i>Staphylococcus aureus</i> in a Neonatal Intensive Care Unit
Authors: Dennis Nurjadi, Vanessa M. Eichel, Patrik Tabatabai, Sabrina Klein, Katharina Last, Nico T. Mutters, Johannes Pöschl, Philipp Zanger, Klaus Heeg, Sébastien Boutin
Journal: JAMA Network Open (2021)

<h3>Importance</h3> <i>Staphylococcus aureus</i>is one of the leading causes of infections in neonatal intensive care units (NICUs). Most studies in this patient group focus on methicillin-resistant<i>S aureus</i>or the outbreak setting, whereas data for methicillin-susceptible<i>S aureus</i>are limited. <h3>Objectives</h3> To identify risk factors for<i>S aureus</i>colonization and infections in hospitalized newborns and to investigate<i>S aureus</i>transmission and its dynamics in a nonoutbreak setting. <h3>Design, Setting, and Participants</h3> This monocentric cohort study in a tertiary NICU in Heidelberg, Germany, enrolled all hospitalized neonates (n = 590) with at least 1 nasal screening swab positive for<i>S aureus</i>. Data were collected from January 1, 2018, to December 31, 2019. <h3>Exposures</h3> Weekly screening for<i>S aureus</i>colonization was performed for all newborns until discharge. <h3>Main Outcomes and Measures</h3> The primary end point was any<i>S aureus</i>infection until hospital discharge. Transmission of<i>S aureus</i>and performance of routine typing to detect transmissions were defined as the secondary outcomes of the study. <h3>Results</h3> In total, 590 newborns were enrolled (276 [46.8%] female and 314 [53.2%] male; 220 [37.3%] with birthweight &lt;1500 g; 477 [80.8%] preterm; 449 [76.1%] singletons; 419 [71.5%] delivered via cesarean section). The median length of stay was 26 (range, 10-62) days. Overall, 135 infants (22.9%) were colonized by<i>S aureus</i>at some time during their hospital stay. The median time to first detection was 17 (interquartile range, 11-37) days. The overall incidence of<i>S aureus</i>infection was 1.7% (10 of 590). Low birth weight (&lt;1500 g [odds ratio, 9.3; 95% CI, 5.9-14.6;<i>P</i>&lt; .001]) and longer hospital stay (odds ratio, 2.3; 95% CI, 1.9-2.7;<i>P</i>&lt; .001) were associated with colonization. Nasal carriage was significantly associated with<i>S aureus</i>infection (odds ratio, 8.2; 95% CI, 2.1-32.3;<i>P</i> = .002). A total of 123 of 135 colonization isolates were sequenced. All recoverable infection isolates (4 of 7) of newborns with colonization were genetically identical to the colonizing isolate. Whole-genome sequencing indicated 23 potential transmission clusters. <h3>Conclusions and Relevance</h3> The findings of this cohort study suggest that nasal colonization is a relevant risk factor for<i>S aureus</i>infection in a nonoutbreak NICU setting. In colonized newborns, infection and colonization isolates were genetically identical, suggesting that eradication of colonization may be a useful measure to prevent infection. Further investigations are necessary to validate and assess the generalizability of our findings.