tbuckley/cabot-search huggingface dataset:
Asthma, COPD and SARS-CoV-2 infection (COVID-19): potential mechanistic insights
Authors: Peter A.B. Wark, Prabuddha S. Pathinayake, Mathew Suji Eapen, Sukhwinder Singh Sohal
Journal: European Respiratory Journal (2021)

<b>Patients with asthma are somewhat protected from COVID-19 complications compared to COPD. This may be due to variability in viral attachment protein, ICS use, smoking/vaping status, a skewed inflammatory pattern, and dysregulated endocytic machinery.</b>https://bit.ly/3qOcyNb
Biological significance of cribriform pattern in radical prostatectomy specimens: Study of its prognostic significance in biochemical recurrence
Authors: F. Gómez Palomo, G. Moreno Abenza, D. Ramos Soler, L.F. Castillo Paredes, A. Bernal Gómez, J.L. Ruiz Cerdá, F. Boronat Tormo
Journal: European Urology (2021)
The CADMUS trial: A paired cohort, blinded study comparing multiparametric ultrasound targeted biopsies with multiparametric MRI targeted biopsies in the detection of clinically significant prostate cancer
Authors: A.D.R. Grey, R. Scott, B. Shah, P. Acher, S. Liyanage, M. Pavlou, R. Omar, F. Chinegwundoh, P. Patki, T.T. Shah, S. Hamid, M. Ghei, C. Brew-Graves, N. Arumainayagam, A. Chapman, L. Mcleavy, Z. Alsaadi, A. Karatziotou, T. Collins, D. Eldred-Evans, A. Freeman, M. Winkler, M. Emberton, H.U. Ahmed
Journal: European Urology (2021)
Predicting mortality risk for preterm infants using deep learning models with time-series vital sign data
Authors: Jiarui Feng, Jennifer Lee, Zachary A. Vesoulis, Fuhai Li
Journal: npj Digital Medicine (2021)

Abstract Mortality remains an exceptional burden of extremely preterm birth. Current clinical mortality prediction scores are calculated using a few static variable measurements, such as gestational age, birth weight, temperature, and blood pressure at admission. While these models do provide some insight, numerical and time-series vital sign data are also available for preterm babies admitted to the NICU and may provide greater insight into outcomes. Computational models that predict the mortality risk of preterm birth in the NICU by integrating vital sign data and static clinical variables in real time may be clinically helpful and potentially superior to static prediction models. However, there is a lack of established computational models for this specific task. In this study, we developed a novel deep learning model, DeepPBSMonitor (Deep Preterm Birth Survival Risk Monitor), to predict the mortality risk of preterm infants during initial NICU hospitalization. The proposed deep learning model can effectively integrate time-series vital sign data and fixed variables while resolving the influence of noise and imbalanced data. The proposed model was evaluated and compared with other approaches using data from 285 infants. Results showed that the DeepPBSMonitor model outperforms other approaches, with an accuracy, recall, and AUC score of 0.888, 0.780, and 0.897, respectively. In conclusion, the proposed model has demonstrated efficacy in predicting the real-time mortality risk of preterm infants in initial NICU hospitalization.
Abstract 366: Identification of a clinically significant pan-cancer biomarker for homologous recombination deficiency
Authors: Shiro Takamatsu, JB Brown, Koji Yamanoi, Ken Yamaguchi, Junzo Hamanishi, Takashi Kobayashi, Masaki Mandai, Noriomi Matsumura
Journal: Cancer Research (2021)

Abstract [Background] Genomic alterations in BRCA1/2 and the ‘genomic scar' signatures are associated with homologous recombination DNA repair deficiency (HRD) and serve as therapeutic biomarkers for sensitivity to platinum and PARP inhibitors in breast and ovarian cancers. However, the clinical significance of these biomarkers in other homologous recombination repair (HRR) pathway genes or in other cancer types is not fully understood. [Method] From the TCGA and the AACR GENIE project databases, we obtained clinical and genomic data of patients with multiple solid cancers, evaluated both locus-specific LOH in HRR pathway gene mutations and two genomic scar signature scores (HRD score and mutational signature 3), identified potential HRD cases, and examined the efficacy of DNA-damaging drugs in these HRD cases. [Results] Germline and somatic gene mutations in the HRR pathway genes with locus-specific LOH were significantly enriched in cases having high genomic scar scores, whereas those without the LOH were not enriched. Somatic mutations without the LOH were remarkably enriched in hypermutated cases and considered to be passenger mutations. The mutation rate and frequency with LOH in the HRR pathway genes varied widely by cancer type. When stratifying patients by gender and presence of TP53 mutation, the correlation between the two genomic scar scores and the resulting optimal cutoff values for biallelic HRR pathway gene alterations differed greatly. The potential HRD cases that were selected by the two genomic scar cutoffs and biallelic HRR pathway gene alterations showed significantly high gene expression-based HRD scores. In Cox proportional hazard multivariate analyses with covariates of age, stage, gender, HRD, and TP53 mutation, HRD was a good prognostic factor in the group with DNA-damaging agents, but a poor one in the group without the agents. [Conclusion] Increased attention on locus-specific LOH in HRR pathway gene alterations and the differences in genomic scar signatures stratified by gender and TP53 mutation is newly warranted in order to properly assess HRD in a pan-cancer manner. The results in the present study proved the clinical significance of HRD across cancer types and may contribute to the development of personalized medicine based on HRD. Citation Format: Shiro Takamatsu, JB Brown, Koji Yamanoi, Ken Yamaguchi, Junzo Hamanishi, Takashi Kobayashi, Masaki Mandai, Noriomi Matsumura. Identification of a clinically significant pan-cancer biomarker for homologous recombination deficiency [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 366.
Adjuvant vs. progression-triggered treatment with gemcitabine after radical cystectomy in platinum-ineligible patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (AUO-AB 22-00): Long-term follow-up of a randomized multicenter phase 3 trial
Authors: J. Heinzelbecker, N. Spieler, M. Kühn, C. Fischer, B. Volkmer, F-C. Von Rundstedt, P. Albers, E. Becht, A. Bannowsky, H.M. Weber, R. Hofmann, M. Müller, S. Langbein, G. Steiner, M. Retz, J. Kamradt, S. Wellek, J. Lehmann, M. Stöckle
Journal: European Urology (2021)
Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
Authors: Xiaojing Chu, Martin Jaeger, Joep Beumer, Olivier B. Bakker, Raul Aguirre-Gamboa, Marije Oosting, Sanne P. Smeekens, Simone Moorlag, Vera P. Mourits, Valerie A. C. M. Koeken, Charlotte de Bree, Trees Jansen, Ian T. Mathews, Khoi Dao, Mahan Najhawan, Jeramie D. Watrous, Irma Joosten, Sonia Sharma, Hans J. P. M. Koenen, Sebo Withoff, Iris H. Jonkers, Romana T. Netea-Maier, Ramnik J. Xavier, Lude Franke, Cheng-Jian Xu, Leo A. B. Joosten, Serena Sanna, Mohit Jain, Vinod Kumar, Hans Clevers, Cisca Wijmenga, Mihai G. Netea, Yang Li
Journal: Genome biology (2021)

Abstract Background Recent studies highlight the role of metabolites in immune diseases, but it remains unknown how much of this effect is driven by genetic and non-genetic host factors. Result We systematically investigate circulating metabolites in a cohort of 500 healthy subjects (500FG) in whom immune function and activity are deeply measured and whose genetics are profiled. Our data reveal that several major metabolic pathways, including the alanine/glutamate pathway and the arachidonic acid pathway, have a strong impact on cytokine production in response to ex vivo stimulation. We also examine the genetic regulation of metabolites associated with immune phenotypes through genome-wide association analysis and identify 29 significant loci, including eight novel independent loci. Of these, one locus (rs174584-FADS2) associated with arachidonic acid metabolism is causally associated with Crohn’s disease, suggesting it is a potential therapeutic target. Conclusion This study provides a comprehensive map of the integration between the blood metabolome and immune phenotypes, reveals novel genetic factors that regulate blood metabolite concentrations, and proposes an integrative approach for identifying new disease treatment targets.
Impact of Prior Local Trecepherapy (PLT) on survival in metastatic castration resistant prostate cancer (mCRPC). Results from COU-AA-302 trial
Authors: M. Rodrigo Aliaga, D. Lorente Estellés, C. Garau Perelló, A. Sánchez Llopis, M. Bosquet Sanz, C. Di Capua Sacoto, R. Villamón Fort, J.A. Blasco Maspons, M. Alonso Coscojuela, A. Sánchez Hernández
Journal: European Urology (2021)
Reduction of Myocardial Infarction and All-Cause Mortality Associated to Statins in Patients Without Obstructive CAD
Authors: Kristian A Øvrehus, Axel Diederichsen, Erik L Grove, Flemming H Steffensen, Martin B Mortensen, Jesper M Jensen, Hans Mickley, Lene H Nielsen, Martin Busk, Niels Peter R Sand, Jess Lambrechtsen, Anders H Riis, Ina Trolle Andersen, Hans E Bøtker, Bjarne L Nørgaard
Journal: JACC. Cardiovascular imaging (2021)

The aim of this work was to evaluate the prognostic impact of statin therapy in symptomatic patients without obstructive CAD.Information on the prognostic impact of post-coronary computed tomographic angiography (CTA) statin use in patients with no or nonobstructive coronary artery disease (CAD) is sparse.Patients undergoing CTA with suspected CAD in western Denmark from 2008 to 2017 with <50% coronary stenoses were identified. Information on post-CTA use of statin therapy and cardiovascular events were obtained from national registries.The study included 33,552 patients, median aged 56 years, 58% female, with no (n = 19,669) or nonobstructive (n = 13,883) CAD and a median follow-up of 3.5 years. The absolute risk of the combined end point of myocardial infarction (MI) or all-cause mortality was directly associated with the CAD burden with an event rate/1,000 patient-years of 4.13 (95% CI: 3.69-4.61) in no, 7.74 (95% CI: 6.88-8.71) in mild (coronary artery calcium score [CACS] 0-99), 13.72 (95% CI: 11.61-16.23) in moderate (CACS 100-399), and 32.47 (95% CI: 26.25-40.16) in severe (CACS ≥400) nonobstructive CAD. Statin therapy was associated with a multivariable adjusted HR for MI and death of 0.52 (95% CI: 0.36-0.75) in no, 0.44 (95% CI: 0.32-0.62) in mild, 0.51 (95% CI: 0.34-0.75) in moderate, and 0.52 (95% CI: 0.32-0.86) in severe nonobstructive CAD. The estimated numbers needed to treat to prevent the primary end point were 92 (95% CI: 61-182) in no, 36 (95% CI: 26-58) in mild, 24 (95% CI: 15-61) in moderate, and 13 (95% CI: 7-86) in severe nonobstructive CAD. Residual confounding may persist, but not to an extent explaining all of the observed risk reduction associated with statin treatment.The risk of MI and all-cause mortality in patients without obstructive CAD is directly associated with the CAD burden. Statin therapy is associated with a reduction of MI and all-cause death across the spectrum of CAD, however, the absolute benefit of treatment is directionally proportional with the CAD burden.
Is partial cistectomy safe for non-urologic malignant tumors invading bladder wall? A ten year follow-up report
Authors: G. dos Anjos Silva, D.K. Abe, F.F.A. Batista, R.S. Nunes, F.G.M. Areas, M.D. Cordeiro, R.F. Coelho, W.C. Nahas
Journal: European Urology (2021)
Abstract 1711: Induction of anti-tumor immunity by intratumoral delivery of mRNA encoding cytokines and TNFRSF agonists
Authors: Julie-Ann Gavigan, Chaomei Shi, Michael Lampa, Natalia Malkova, Qunyan Yu, Hui Qu, Mikhail Levit, Timothy Wagenaar, Christian Hotz, Xiangming Li
Journal: Cancer Research (2021)

Abstract In the recent decade several immune checkpoint inhibitors, such as anti-PD1/PD-L1 antibodies, have been approved by regulatory authorities and are actively used in oncology clinical practice. However, these antibodies exhibit durable anti-tumor benefits in only a small fraction of cancer patients. A major unmet medical need in immune oncology (IO) is extending the benefits of these therapies to patients who never experience tumor regression (primary resistance) and those who derive initial benefit before experiencing tumor progression (acquired resistance). Novel IO combinations have the potential to both sensitize primary resistant tumors and combat the acquisition of resistance to checkpoint inhibition. Synthetic, in vitro transcribed messenger RNA (mRNA) is an emerging therapeutic modality that offers the ability to express a broad range of therapeutic combinations. In this project, we proposed to ignite anti-tumor immunity locally through intratumoral (i.t.) delivery of a mixture of mRNAs encoding cytokines and a TNF receptor superfamily (TNFRSF) agonist. Using in vitro and in vivo screening, we identified a combination therapy consisting of three cytokines IFNα, IL-7, and a fusion protein of IL-15 with its receptor alpha chain as well as one TNFRSF agonist, an Fc fusion hexameric OX40L for enhanced receptor clustering. The mRNA mixture enhanced human antigen-specific T cell responses in vitro and displayed potent anti-tumor efficacy in syngeneic tumor models when injected i.t., demonstrating the induction of protective immunity. Importantly, in a preclinical dual-flank syngeneic tumor model, we demonstrated that this protective immunity extended beyond tumors injected with the lead mRNA mixture to control growth of distant untreated lesions. Mechanistically, the lead candidate induced anti-tumor immunity by recruiting dendritic cells to the tumor, leading to activation and expansion of tumor specific CD8 T cells. In summary, this mRNA mixture, encoding IFNα, IL-7, IL-15 and OX40L, induced potent anti-tumor immunity in mice and will be further investigated as a combination partner to overcome resistance mechanisms to immune checkpoint inhibition. Citation Format: Julie-Ann Gavigan, Chaomei Shi, Michael Lampa, Natalia Malkova, Qunyan Yu, Hui Qu, Mikhail Levit, Timothy Wagenaar, Christian Hotz, Xiangming Li. Induction of anti-tumor immunity by intratumoral delivery of mRNA encoding cytokines and TNFRSF agonists [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1711.
Primary cutaneous anaplastic large‐cell lymphoma with marked spontaneous regression of organ manifestation after SARS‐CoV‐2 vaccination
Authors: T. Gambichler, S. Boms, S. Hessam, I. Tischoff, A. Tannapfel, T. Lüttringhaus, J. Beckman, R. Stranzenbach
Journal: British Journal of Dermatology (2021)

Primary cutaneous anaplastic large cell lymphoma (pcALCL) belongs to the primary cutaneous CD30+ T cell lymphoproliferative disorders.1 Systemic involvement is relatively rare and rather confined to the regional lymph nodes.1 We describe a patient with recurrent pcALCL and diffuse lung manifestation which spontaneously regressed after one SARS-CoV-2 vaccination. We report a 57-year-old male patient with a 10-year history of biopsy-proven (CD30+, CD3+, CD4+, ALK-, clonal T cell receptor gamma chain rearrangement) pcALCL with frequent local relapses predominantly affecting his scalp and neck.
177P Efficacy of S-1 after pemetrexed in patients with non-small cell lung cancer: A retrospective multi-institutional analysis
Authors: S. Takemoto, T. Suyama, N. Honda, Y. Umeyama, Y. Dostu, G. Hiroshi, H. Yamaguchi, M. Fukuda, H. Mukae
Journal: Journal of Thoracic Oncology (2021)
Management of cut wounds and lacerations in the Gaza Strip: a prospective clinical audit
Authors: Amira Al-Azar, Asma Alnaami, Aya Abed, Suheir Shaat, Doha Alagha, Reham Ismail, Rawan Tabash, Asmaa Bensaid, Batool Abu Tailakh, Najlaa abu Jamie, Bettina Böttcher
Journal: The Lancet (2021)
Abstract 780: Racial disparities in death from cardiovascular disease for patients with prostate cancer: A population-based study
Authors: Nikita Nikita, Joshua Banks, Scott Keith, Kosj Yamoah, Ulhas P. Naik, Felix J. Kim, David M. Shipon, Wm Kevin Kelly, Timothy R. Rebbeck, Grace Lu Yao
Journal: Cancer Research (2021)

Abstract Introduction: Prostate cancer (PCa) is the most common cancer diagnosis among men in the United States. However, a vast majority of patients with PCa die of causes other than PCa, the most common being cardiovascular disease (CVD). We hypothesize that CVD-related mortality in PCa patients is disproportionately higher among Blacks as compared to Whites. Methods: We identified patients with PCa from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked files between 1/1/2004 and 12/31/2015. The PCa risk groups were created based on the National Comprehensive Cancer Network criteria: low, intermediate, and high risk. The primary endpoint was CVD-related mortality. The following CVD conditions were included in the CVD-specific mortality: acute myocardial infarction, stroke, congestive heart failure, atrial fibrillation, and ischemic heart disease. A proportional hazards model that considered the competing risks was fitted to address the hypothesis. The model was adjusted for age, year of diagnosis, marital status, income level, SEER-region, state buy-in, radiation, surgery, and education level. Results: We identified 394,323 patients with PCa. Among these 80% were Whites, 15% were Blacks, and 5% were other races. The median age at diagnosis for Whites, Blacks, and other races was 69, 66, and 70 years, respectively. The incidence of CVD-related mortality was 5.6%, 6.6%, and 5% among Whites, Blacks, and Other races, respectively. Compared to Whites, Blacks had a significantly higher risk of mortality due to CVD across all PCa risk groups (Table). Similar results were not seen when the Other races was compared to Whites. Conclusion: Blacks with PCa have a significantly higher risk of mortality due to CVD as compared to Whites across all PCa risk groups. Our study highlights the importance of cardio-oncology in the setting of PCa. Further studies are warranted to confirm the findings. Table: Risk of CVD-related mortality among PCa patients; stratified by PCa risk group.Low-Risk (N=84,367)Intermediate-Risk(N=146,411)High-Risk(N=96,502)HR (95%CI); p-valueHR (95%CI); p-valueHR (95%CI); p-valueWhites(N=316,803)RefRefRefBlacks(N=58,046)1.23 (1.09-1.39); p&amp;lt;0.0011.24 (1.14-1.34); p&amp;lt;0.0011.09 (1.01-1.20); p=0.029Other Races(N=19,474)0.79 (0.60-1.04); p=0.0890.87 (0.74-1.03); p=0.1120.79 (0.69-0.91); p&amp;lt;0.001 Citation Format: Nikita Nikita, Joshua Banks, Scott Keith, Kosj Yamoah, Ulhas P. Naik, Felix J. Kim, David M. Shipon, Wm Kevin Kelly, Timothy R. Rebbeck, Grace Lu Yao. Racial disparities in death from cardiovascular disease for patients with prostate cancer: A population-based study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 780.
Abstract CT239: ENVASARC: A Pivotal Trial of Envafolimab, and Envafolimab in Combination with Ipilimumab, in Patients with Advanced or Metastatic Undifferentiated Pleomorphic Sarcoma or Myxofibrosarcoma who have Progressed on Prior Chemotherapy
Authors: Sandra D'Angelo, Steven Robinson, Joelle Lam, Bonne Adams, James Freddo, Charles P. Theuer, Robert Maki
Journal: Cancer Research (2021)

Abstract Background: Metastatic undifferentiated pleomorphic sarcoma (UPS) and the genetically related myxofibrosarcoma (MFS) are soft tissue sarcoma (STS) subtypes with poor prognoses. While responses to front line chemotherapy can approach 20%, in the 2nd line setting and beyond, efficacy remains limited. Pazopanib, the only approved treatment in the refractory setting has demonstrated an objective response rate (ORR) of 4%. Envafolimab is a single domain PD-L1 antibody administered rapidly by subcutaneous (SQ) injection that is being studied in two additional pivotal trials: MSI-H cancer and biliary tract cancer. The activity of envafolimab is similar to other PD-1 antibodies administered intra-venously. Envafolimab demonstrated a 32% ORR in MSI-H colorectal cancer that failed three approved chemotherapeutics, similar to the ORR of 28% and 33%, with nivolumab and pembrolizumab, respectively. The rationale for the ENVASARC trial is based on the previously reported efficacy of checkpoint inhibition in UPS/MFS. Single agent pembrolizumab demonstrated a 23% ORR, while the combination of nivolumab and ipilimumab demonstrated a 29% ORR in refractory UPS/MFS. Methods: ENVASARC (NCT 04480502) is a pivotal multicenter (at ~25 U.S. centers) open-label, randomized, non-comparative, parallel cohort study of treatment with envafolimab 300 mg every 3 weeks by SQ injection (cohort A; n=80) or envafolimab 300 mg every 3 weeks by SQ injection combined with ipilimumab 1 mg/kg every 3 weeks intra-venously for four doses (cohort B; n=80) in patients with locally advanced, unresectable or metastatic UPS/MFS who have progressed on one or two lines of prior therapy. The primary objective of each of parallel cohort is to demonstrate an ORR with a lower limit of the 95% confidence interval that excludes 5.0% in each cohort. If ≥ 9 responders are observed of the 80 patients enrolled in each cohort, then the lower bound of the 95% confidence interval will exclude 5.0%. Secondary endpoints include duration of response (DOR), PFS and OS. Key inclusion criteria: ≤ 2 prior lines of therapy (neoadjuvant and adjuvant therapy excluded), ECOG ≤ 1. Citation Format: Sandra D'Angelo, Steven Robinson, Joelle Lam, Bonne Adams, James Freddo, Charles P. Theuer, Robert Maki. ENVASARC: A Pivotal Trial of Envafolimab, and Envafolimab in Combination with Ipilimumab, in Patients with Advanced or Metastatic Undifferentiated Pleomorphic Sarcoma or Myxofibrosarcoma who have Progressed on Prior Chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT239.