tbuckley/cabot-search huggingface dataset:
Relationship between changes in serum androgen level measured by LC-MS/MS and therapeutic effect after enzalutamide treatment.
Authors: Yoshiyuki Miyazawa, Toshiyuki Nakamura, Yutaka Takezawa, Nobuaki Shimizu, Yasushige Matsuo, Haruyuki Ogura, Tomoyuki Takei, Seiji Arai, Masashi Nomura, Yoshitaka Sekine, Hidekazu Koike, Hiroshi Matsui, Yasuhiro Shibata, Kazuhiro Suzuki
Journal: Journal of Clinical Oncology (2021)

88 Background: Enzalutamide (ENZ) has proven efficacy against castration-resistant prostate cancer (CRPC) and is widely used in treatment. However, no useful biomarkers have yet been reported to predict the effects of ENZ. We examined the relationship between the efficacy of ENZ and changes in serum androgen levels after ENZ administration. Methods: This exploratory research was based on the data from our prospective clinical trial. Of a total of 104 cases, 67 with confirmed changes in androgen levels after 3 months of ENZ administration, compared to pretreatment levels, were included in this study to identify prognostic factors. Serum androgen levels were measured by liquid chromatography-mass spectrometry (LC-MS/MS). This study was approved by the institutional review board of Gunma University Hospital (No.1177). Results: The study population of 67 patients had a median age of 73 years. The median serum levels of testosterone (T), dihydrotestosterone (DHT), androstenedione (A-dione), and dehydroepiandrosterone sulfate (DHEA-S) before treatment were 56.8 pg/ml, 7.8 pg/ml, 253.5 pg/ml, and 502.2 pg/ml, respectively. The median increase rate(%) of T, DHT, A-dione andDHEA-S after 3 months of ENZ administration were +55.5%, +49.5%, +25.8%, and +24.9%, respectively. T, DHT, and A-dione levels were significantly increased after 3 months (p &lt; 0.05). We performed Cox regression analysis to predict PSA-PFS and OS. Hemoglobin (Hb, ≥ 12.5 g/dl vs. &lt; 12.5 g/dl) and T increase rate ( &lt; 55.5% vs. ≥ 55.5%) were significant predictors of PSA-PFS (p &lt; 0.05). ECOG performance status (0 vs. 1 - 2, respectively) and Hb (≥ 12.5 vs. &lt; 12.5 g/dl, respectively) and T ( &lt; 55.5% vs. ≥55.5%) were significant predictors of OS (p &lt; 0.05). Conclusions: PSA-PFS and OS were significantly poor in the cases in which T increased significantly 3 months after ENZ administration. It was suggested that the change of hormonal environment after ENZ administration may be a prognostic factor.
Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group
Authors: Philippe Moreau, Shaji K Kumar, Jesús San Miguel, Faith Davies, Elena Zamagni, Nizar Bahlis, Heinz Ludwig, Joseph Mikhael, Evangelos Terpos, Fredrik Schjesvold, Thomas Martin, Kwee Yong, Brian G M Durie, Thierry Facon, Artur Jurczyszyn, Surbhi Sidana, Noopur Raje, Niels van de Donk, Sagar Lonial, Michele Cavo, Sigurdur Y Kristinsson, Suzanne Lentzsch, Roman Hajek, Kenneth C Anderson, Cristina João, Hermann Einsele, Pieter Sonneveld, Monika Engelhardt, Rafael Fonseca, Annette Vangsted, Katja Weisel, Rachid Baz, Vania Hungria, Jesus G Berdeja, Fernando Leal da Costa, Angelo Maiolino, Anders Waage, David H Vesole, Enrique M Ocio, Hang Quach, Christoph Driessen, Joan Bladé, Xavier Leleu, Eloisa Riva, Peter Leif Bergsagel, Jian Hou, Wee Joo Chng, Ulf-Henrik Mellqvist, Dominik Dytfeld, Jean-Luc Harousseau, Hartmut Goldschmidt, Jacob Laubach, Nikhil C Munshi, Francesca Gay, Meral Beksac, Luciano J Costa, Martin Kaiser, Parameswaran Hari, Mario Boccadoro, Saad Z Usmani, Sonja Zweegman, Sarah Holstein, Orhan Sezer, Simon Harrison, Hareth Nahi, Gordon Cook, Maria-Victoria Mateos, S Vincent Rajkumar, Meletios A Dimopoulos, Paul G Richardson
Journal: The Lancet Oncology (2021)
Imaging modality and frequency in surveillance of stage I seminoma testicular cancer: Results from a randomized, phase III, factorial trial (TRISST).
Authors: Johnathan K. Joffe, Fay Helen Cafferty, Laura Murphy, Gordon J. S. Rustin, Syed A Sohaib, Sarah Swift, Dipa Noor, Simona Wade, Elizabeth James, Rhian Gabe, Sally P Stenning, Marcia Hall, Anand Sharma, Jeremy Braybrooke, Jonathan Shamash, John Logue, Henry Hunter Taylor, Richard S. Kaplan, Robert A Huddart
Journal: Journal of Clinical Oncology (2021)

374 Background: Survival after orchiectomy in stage I seminoma is almost 100%. CT surveillance is an international standard of care, and avoids adjuvant therapy. In this young population, who are unlikely to die from testicular cancer, minimizing irradiation is vital. The Trial of Imaging and Surveillance in Seminoma Testis (TRISST, NCT00589537), assessed whether CTs can safely be reduced, or replaced with MRI, without an unacceptable increase in advanced relapses. Methods: TRISST is a phase III, multicenter, non-inferiority, factorial trial. Eligible men had undergone orchiectomy for stage I seminoma with no adjuvant therapy planned. Randomization was to: 7 CTs (6, 12, 18, 24, 36, 48, 60 months (m) after randomization); 7 MRIs (same schedule); 3 CTs (6, 18, 36m); or 3 MRIs (same schedule). Follow-up was for 6 years. The primary outcome is 6-year incidence of RMH stage ≥IIC relapse, aiming to exclude an increase ≥5.7% (from 5.7% to 11.4%) with MRI (vs CT) or 3 scans (vs 7); target n=660, all contributing to both comparisons. Secondary outcomes include relapse ≥3cm, disease-free and overall survival (DFS, OS). Results: 669 men enrolled from 35 UK centers (2008-2014); mean tumor size 2.9cm, 358 (54%) were low risk (≤4cm, no rete testis invasion). Median follow-up was 72m. 82 (12%) patients relapsed. Incidence of stage ≥IIC relapse was low in all groups (n=10). More events occurred with 3 scans vs 7, though non-inferior based on design criteria: 9 (2.8%) vs 1 (0.3%), 2.5% increase, 90% CI 1.0% to 4.1% (intent-to-treat, ITT). 4/9 in 3-scan arms could potentially have been detected earlier with the 7-scan schedule. Fewer events occurred with MRI vs CT: 2 (0.6%) vs 8 (2.5%), 1.9% decrease, 90% CI -3.5% to -0.3% (ITT). Per protocol results were similar. Incidence of relapse ≥3cm was 3.7%; non-inferiority was shown for both comparisons. In all groups, most relapses were detected at scheduled imaging; very few occurred beyond 3 years (5 in 558 at risk, &lt;1%). Relapse treatment outcomes were good (81% complete response) with no tumor-related deaths. 5-year DFS and OS were 87% and 99%, similar across groups. Conclusions:Surveillance is a safe management approach in stage I seminoma – advanced relapse is rare, salvage treatment successful, and long-term outcomes excellent, regardless of imaging frequency or modality. Relapse beyond 3 years is rare and imaging may be unnecessary. MRI is non-inferior to CT, avoids irradiation and should be recommended. Clinical trial information: NCT00589537.
Oligometastatic Bone Disease in Castration-Sensitive Prostate Cancer Patients Treated With Stereotactic Body Radiotherapy Using 68Ga-PSMA PET/CT
Authors: Cem Onal, Gokhan Ozyigit, Zuleyha Akgun, Banu Atalar, Sefik Igdem, Ezgi Oymak, Fulya Agaoglu, Ugur Selek, Ozan Cem Guler, Pervin Hurmuz, Teuto Zoto Mustafayev, Fadil Akyol
Journal: Clinical Nuclear Medicine (2021)

Purpose To evaluate the outcomes of metastasis-directed treatment (MDT) using stereotactic body radiotherapy (SBRT) for bone-only oligometastasis (OM) detected with gallium prostate-specific membrane antigen ( 68 Ga-PSMA) PET/CT in castration-sensitive prostate cancer (PC) patients. Methods In this multi-institutional study, clinical data of 74 PC patients with 153 bone lesions who were undergoing MDT were retrospectively evaluated. Twenty-seven patients (36.5%) had synchronous, and 47 (63.5%) had metachronous OM. All patients had PC with 5 metastases or fewer detected by 68 Ga-PSMA PET/CT and treated using SBRT with a median dose of 20 Gy. The prognostic factors for PC-specific survival (PCSS) and progression-free survival (PFS) were analyzed. Results The median follow-up was 27.3 months. Patients with synchronous OM were older and received higher rates of androgen deprivation therapy after SBRT compared with patients with metachronous OM. The 2-year PCSS and PFS rates were 92.0% and 72.0%, respectively. A prostate-specific antigen (PSA) decline was observed in 56 patients (75.7%), and 48 (64.9%) had a PSA response defined as at least 25% decrease of PSA after MDT. The 2-year local control rate per lesion was 95.4%. In multivariate analysis, single OM and PSA response after MDT were significant predictors for better PCSS and PFS. In-field recurrence was observed in 4 patients (6.5%) with 10 lesions at a median of 13.1 months after MDT completion. No serious late toxicity was observed. Conclusions We demonstrated that SBRT is an efficient and well-tolerated treatment option for PC patients with 5 bone-only oligometastases or fewer detected with 68 Ga-PSMA PET/CT.
Long-term Clinical and Echocardiographic Outcomes in Young and Middle-aged Adults Undergoing the Ross Procedure
Authors: Jamie L. R. Romeo, Grigorios Papageorgiou, Francisco F. D. da Costa, Hans H. Sievers, Ad J. J. C. Bogers, Ismail el-Hamamsy, Peter D. Skillington, Rochelle Wynne, Stefano Mastrobuoni, Gebrine El Khoury, Johanna J. M. Takkenberg, Mostafa M. Mokhles
Journal: JAMA Cardiology (2021)

There is no ideal valve substitute for young adults requiring aortic valve replacement. Multicenter data supporting use of the Ross procedure with respect to long-term postoperative valve-related mortality and reintervention, as well as function of the autograft and pulmonary homograft, are needed.To determine the long-term clinical and echocardiographic outcomes in young and middle-aged patients undergoing the Ross procedure.A retrospective multicenter international cohort study with a median follow-up period of 9.2 years was conducted in 5 experienced centers regularly performing the Ross procedure. Consecutive patients aged 18 to 65 years were included by each center between 1991 and 2018.Survival and autograft-related and homograft-related reintervention. Serial echocardiographic measurements of valve function were analyzed using mixed-effects modeling.During the study period, 1431 patients (74.3% men; n = 1063) were operated on at a median age of 48.5 years (mean [SD], 47.7 [9.5]; range, 18.1-65; interquartile range, 42.7-54.0). Implantation techniques were root inclusion in 355 (24.9%), root replacement in 485 (34.0%), and subcoronary implantation in 587 (41.1%). Right ventricular outflow tract reconstruction was performed with homografts in 98.6% (n = 1189) and bioprostheses in 1.4% (n = 17). Ten patients (0.7%) died before discharge. Median follow-up was 9.2 years (13 015 total patient-years). Survival after 10 and 15 years was 95.1% (95% CI, 93.8%-96.5%) and 88.5% (95% CI, 85.9%-91.1%), respectively. Freedom from autograft and homograft reintervention after 15 years was 92.0% and 97.2%, respectively. Late events were autograft endocarditis in 14 patients (0.11% per patient-year), homograft endocarditis in 11 patients (0.08% per patient-year), and stroke in 37 patients (0.3% per patient-year).Given its excellent short-term and long-term outcome in young and middle-aged adults in this study, the Ross procedure should be considered in young and middle-aged adults who require aortic valve replacement. Patients should be referred to an experienced center with a program dedicated to the Ross procedure.
Recurrent Hematochezia in a Returning Traveler
Authors: Shana E. Gleeson, Xuchen Zhang, Marwan M. Azar
Journal: JAMA (2021)

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The potential role of frailty in modifying quality-of-life related outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel, abiraterone, enzalutamine, and radium 223.
Authors: Seungyeon Kim, Henriette Breunis, Narhari Timilshina, Helen Yang, Shabbir M.H. Alibhai
Journal: Journal of Clinical Oncology (2021)

63 Background: As the arsenal of therapeutic agents for mCRPC expands, frailty-informed care is emerging as a strategy for tailoring management decisions. Yet, data to guide this approach and to ascertain its impact on the mood, fatigue, pain, and quality of life (QoL) experienced by older men with mCRPC remain lacking. We examined patient-reported outcomes, stratified by a validated frailty index (FI), for mCRPC treatment with docetaxel chemotherapy (CHEMO), abiraterone (ABI), enzalutamide (ENZA), or radium 223 (RAD). Methods: Older (aged 65+) men starting one of four approved therapies for mCRPC were enrolled in a multicenter prospective cohort study. Assessing their mood, fatigue, pain, and QoL with PHQ-9, ESAS tiredness, ESAS pain, and FACT-G total as well as subscale scores, we used linear mixed effect models to determine change in each outcome over time (0, 3, 6 months). At end of treatment, we administered the Decisional Regret Scale. We then constructed a FI from 34 variables that span laboratory abnormalities, geriatric syndromes, instrumental activities of daily living, social support, as well as emotional, cognitive, and physical deficits. Following established cut-offs, we categorized patients as non-, pre-, and frail, then performed stratified linear mixed effects regression analyses to identify differences in outcomes by frailty status. Results: A total of 198 men (mean age 75.1) starting CHEMO (n = 70), ABI (n = 38), ENZA (n = 67), and RAD (n = 29) were included, of which 9.6%, 1.5%, 5.6%, and 2.5%, respectively, were determined frail. Frailty correlated only modestly with age (Pearson r = 0.27). Independent of frailty status, patients across treatment cohorts were similar in terms of baseline QoL-related measures, with the exceptions of mood (p = 0.033) and pain (p = 0.034). Over time, no significant change in QoL was reported, although all four therapies resulted in generally low levels of decisional regret and similar trends of improved pain but worsened mood (p = 0.006 and 0.02, respectively). At baseline, frailty status correlated with worse FACT-G total (p &lt; 0.001) and functional well-being (p &lt; 0.001), as well as worse depression scores (p &lt; 0.001). According to FI-stratified analysis, frail patients experienced similar QoL-related outcomes to fit patients for all measures aside from mood (p &lt; 0.001). Contrary to our hypotheses, frailty was not associated with significant worsening in emotional well-being or functional well-being in response to mCRPC treatment. Conclusions: Of the older men receiving care for mCRPC, frail patients may experience generally similar trends in QoL as fit patients. Interestingly, frailty status, rather than treatment modality, may play more of a contributory role to changes in QoL-related outcomes over time.
Abstract IA-26: Artificial intelligence for regulatory science research
Authors: Weida Tong
Journal: Clinical Cancer Research (2021)

Abstract Artificial Intelligence (AI) has impacted a board range of scientific disciplines that are important to public health, ranging from clinical diagnosis and prognosis, drug and food safety, disease prevention, precision medicine and nutrition. The rise of AI has also offered both opportunities and challenges to regulatory agencies with questions such as (1) how to assess and evaluate AI-based products and (2) how to develop and implement AI-based application to improve the agencies functions. In this presentation, the current thinking and on-going efforts at FDA in the area of AI will be discussed with examples from drug safety and biomarker discovery and development. The guiding principle and best practice of applying AI in regulatory science research will also be discussed with respect to a proposed framework, called TRIAL, for AI transparency, reproducibility, interpretability, applicability and liability. Citation Format: Weida Tong. Artificial intelligence for regulatory science research [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr IA-26.
Hemagglutinin Functionalized Liposomal Vaccines Enhance Germinal Center and Follicular Helper T Cell Immunity
Authors: Mai N. Vu, Hannah G. Kelly, Hyon‐Xhi Tan, Jennifer A. Juno, Robyn Esterbauer, Thomas P. Davis, Nghia P. Truong, Adam K. Wheatley, Stephen J. Kent
Journal: Advanced Healthcare Materials (2021)

Despite remarkable successes of immunization in protecting public health, safe and effective vaccines against a number of life-threatening pathogens such as HIV, ebola, influenza, and SARS-CoV-2 remain urgently needed. Subunit vaccines can avoid potential toxicity associated with traditional whole virion-inactivated and live-attenuated vaccines; however, the immunogenicity of subunit vaccines is often poor. A facile method is here reported to produce lipid nanoparticle subunit vaccines that exhibit high immunogenicity and elicit protection against influenza virus. Influenza hemagglutinin (HA) immunogens are functionalized on the surface of liposomes via stable metal chelation chemistry, using a scalable advanced microfluidic mixing technology (NanoAssemblr). Immunization of mice with HA-liposomes elicits increased serum antibody titers and superior protection against highly pathogenic virus challenge compared with free HA protein. HA-liposomal vaccines display enhanced antigen deposition into germinal centers within the draining lymph nodes, driving increased HA-specific B cell, and follicular helper T cell responses. This work provides mechanistic insights into highly protective HA-liposome vaccines and informs the rational design and rapid production of next generation nanoparticle subunit vaccines.
Direct Comparative Analyses of 10X Genomics Chromium and Smart-Seq2
Authors: Xiliang Wang, Yao He, Qiming Zhang, Xianwen Ren, Zemin Zhang
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Single-cell RNA sequencing (scRNA-seq) is generally used for profiling transcriptome of individual cells. The droplet-based 10X Genomics Chromium (10X) approach and the plate-based Smart-seq2 full-length method are two frequently used scRNA-seq platforms, yet there are only a few thorough and systematic comparisons of their advantages and limitations. Here, by directly comparing the scRNA-seq data generated by these two platforms from the same samples of CD45− cells, we systematically evaluated their features using a wide spectrum of analyses. Smart-seq2 detected more genes in a cell, especially low abundance transcripts as well as alternatively spliced transcripts, but captured higher proportion of mitochondrial genes. The composite of Smart-seq2 data also resembled bulk RNA-seq data more. For 10X-based data, we observed higher noise for mRNAs with low expression levels. Approximately 10%−30% of all detected transcripts by both platforms were from non-coding genes, with long non-coding RNAs (lncRNAs) accounting for a higher proportion in 10X. 10X-based data displayed more severe dropout problem, especially for genes with lower expression levels. However, 10X-data can detect rare cell types given its ability to cover a large number of cells. In addition, each platform detected distinct groups of differentially expressed genes between cell clusters, indicating the different characteristics of these technologies. Our study promotes better understanding of these two platforms and offers the basis for an informed choice of these widely used technologies.
Maintaining homeostatic control of periodontal bone tissue
Authors: Jessica D. Hathaway‐Schrader, Chad M. Novince
Journal: Periodontology 2000 (2021)

Abstract Alveolar bone is a unique osseous tissue due to the proximity of dental plaque biofilms. Periodontal health and homeostasis are mediated by a balanced host immune response to these polymicrobial biofilms. Dysbiotic shifts within dental plaque biofilms can drive a proinflammatory immune response state in the periodontal epithelial and gingival connective tissues, which leads to paracrine signaling to subjacent bone cells. Sustained chronic periodontal inflammation disrupts “coupled” osteoclast‐osteoblast actions, which ultimately result in alveolar bone destruction. This chapter will provide an overview of alveolar bone physiology and will highlight why the oral microbiota is a critical regulator of alveolar bone remodeling. The ecology of dental plaque biofilms will be discussed in the context that periodontitis is a polymicrobial disruption of host homeostasis. The pathogenesis of periodontal bone loss will be explained from both a historical and current perspective, providing the opportunity to revisit the role of fibrosis in alveolar bone destruction. Periodontal immune cell interactions with bone cells will be reviewed based on our current understanding of osteoimmunological mechanisms influencing alveolar bone remodeling. Lastly, probiotic and prebiotic interventions in the oral microbiota will be evaluated as potential noninvasive therapies to support alveolar bone homeostasis and prevent periodontal bone loss.